Intra-aortic balloon pump

From Wikipedia, the free encyclopedia

An intra-aortic balloon pump

The Intra-aortic balloon pump (IABP) is a mechanical device that increases myocardial oxygen perfusion while at the same time increasingcardiac output. Increasing cardiac output increases coronary blood flow and therefore myocardial oxygen delivery. It consists of a cylindrical polyethylene balloon that sits in the aorta, approximately 2 centimeters (0.79 in) from the left subclavian artery[1] and counterpulsates. That is, it actively deflates in systole, increasing forward blood flow by reducing afterload through a vacuum effect. It actively inflates in diastole, increasing blood flow to the coronary arteries via retrograde flow. These

actions combine to decrease myocardial oxygen demand and increase myocardial oxygen supply.[2] [3] [4] A computer-controlled mechanism inflates the balloon with helium from a cylinder during diastole, usually linked to either an electrocardiogram(ECG) or a pressure transducer at the distal tip of the catheter; some IABPs, such as the Datascope System 98XT, allow asynchronous counterpulsation at a set rate, though this setting is rarely used. Helium is used because its low viscosity allows it to travel quickly through the long connecting tubes, and has a lower risk than air of causing an embolism should the balloon rupture.
Contents [hide]

1 History 2 Indications 3 Contraindications

o o

3.1 Absolute contraindication 3.2 Relative contraindication

4 Complications 5 See also 6 References 7 External links

History[edit]
The IABP device was pioneered at Grace Sinai Hospital in Detroit during the early 1960s by Dr. Adrian Kantrowitz and his team.[3] The first publication of intra-aortic balloon counter-pulsation appeared in the American Heart Journal of May 1962; 63: 669-675 by S. Moulopoulos, S. Topaz and W. Kolff. The device was developed for use in heart surgery by Dr. David Bregman in 1976 at NewYork-Presbyterian Hospital in New York City.[5] The first clinical implant was performed at Maimonides Medical Center, Brooklyn, N.Y. in Oct., 1967. The patient, a 48 year old woman, was in cardiogenic shock and unresponsive to traditional therapy. An IABP was

inserted by a cut down on the left femoral artery. Pumping was performed for approximately 6 hours. Shock reversed and the patient was discharged. The size of the original balloon was 15 French but eventually 9 and 8 French balloons were developed.[6] A second operation removed the balloon. Since 1979 the placement of the balloon has been modified using the Seldinger technique.[6][7]

Indications[edit]
The following situations may benefit from this device.[2][3][4]

Cardiogenic shock when used alone as treatment for myocardial infarction. 9-22% survive the first year. Reversible intracardial mechanical defects complicating infarction, i.e. acute mitral regurgitation and septal perforation. Unstable angina pectoris benefits from counterpulsation. Post cardiothoracic surgerymost common and useful is counterpulsation in weaning patients from cardiopulmonary bypass after continued perioperative injury to myocardial tissue.

Preoperative use is suggested for high-risk patients such as those with unstable angina with stenosis greater than 70% of main coronary artery, in ventricular dysfunction with an ejection fraction less than 35%.

Percutaneous coronary angioplasty In high risk coronary artery bypass graft surgery where cardiopulmonary bypass time was shortened, as well as during intubation period and hospital stay.[8]

Thrombolytic therapy of acute myocardial infarction.[6]

Contraindications[edit]

Aortic pressure curve in the presence of an intra-aortic balloon pump

Absolute contraindication[edit]

The following conditions will always exclude patients for treatment:[2] [3] [4]

Severe aortic valve insufficiency Aortic dissection

Severe aortoiliac occlusive disease Relative contraindication[edit] The following conditions make IABP therapy inadvisable except under pressing circumstances:[2]

Prosthetic vascular grafts in the aorta Aortic aneurysm Aortofemoral grafts

Complications[edit]
Since the device is placed in the femoral artery and aorta it could provoke ischemia, and compartment syndrome. The leg is at highest risk of becoming ischemic if the femoral artery it is supplied by becomes obstructed. Placing the balloon too distal from the arcus aortae may induce occlusion of the renal artery and subsequent renal failure. Other possible complications are cerebral embolism during insertion, infection, dissection of the aorta or iliac artery, perforation of the artery and hemorrhage in the mediastinum. Mechanical failure of the balloon itself is also a risk which entails vascular surgery to remove under that circumstance. After balloon removal there is also a risk of 'embolic shower' from micro clots that have formed on the surface of the balloon, and can lead to peripheral thrombosis, myocardial ischemia, hemodynamic decompensation, and latepseudoaneurysm.[2] [3] [4]

See also[edit]

Artificial heart valve

From Wikipedia, the free encyclopedia

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This article needs additional citations for verification. (November 2008) This article includes a list of references, but its sources remain unclear bec
2011)

This article possibly contains original research. (November 2013) An artificial heart valve is a device implanted in the heart of a patient with valvular heart disease.[1][2] When one of the four heart valves malfunctions, the medical choice may be to replace the natural valve with an artificial valve. This requires open-heart surgery. Valves are integral to the normal physiological functioning of the human heart. Natural heart valves are evolved to forms that perform the functional requirement of inducing unidirectional blood flow through the valve structure from one chamber of the heart to another. Natural heart valves become dysfunctional for a variety of pathological causes. Some pathologies may require complete surgical replacement of the natural heart valve with a heart valve prosthesis.[3]
Contents [hide]

1 Types of heart valve prostheses 2 Mechanical valves

o o o o o

2.1 Types of mechanical heart valves 2.2 Durability 2.3 Cavitation 2.4 Fluid mechanics 2.5 Blood damage

3 Tissue (biological) valves 4 Functional requirements of heart valve prostheses 5 Design challenges of heart valve prostheses 6 Replaceable models of heart valve prostheses 7 Typical configuration of a heart valve prosthesis 8 Additional images 9 See also 10 References 11 Sources 12 External links

Types of heart valve prostheses[edit]

There are three main types of artificial heart valves: the mechanical,the biological, and the tissue engineered valves.

Mechanical heart valve Percutaneous implantation Stent framed Not framed Sternotomy/Thoracotomy implantation Ball and cage Tilting disk Bi-leaflet Tri-leaflet Tissue (biological) heart valves Allograft/isograft Xenograft Tissue Engineered heart valves

Mechanical valves[edit]

A mechanical artificial heart valve with a pivoting disc.

Mechanical heart valves (MHV) are prosthetics designed to replicate the function of the natural valves of the human heart. The human heart contains four valves: tricuspid valve, pulmonic valve, mitral valve and aortic valve. Their main purpose is to maintain unimpeded forward flow through the heart and from the heart into the major blood vessels connected to the heart, the pulmonary artery and the aorta. As a result of a number of disease processes, both acquired and congenital, any one of the four heart valves may malfunction and result in either stenosis (impeded forward flow) and/or backward flow (regurgitation). Either process burdens the heart and may lead to serious problems including heart failure. A mechanical heart valve is intended to replace a diseased heart valve with its prosthetic equivalent.

There are two basic types of valves that can be used for valve replacement, mechanical and tissue valves. Modern mechanical valves can last indefinitely (the equivalent of over 50,000 years in an accelerated valve wear tester).[citation needed] However, current mechanical heart valves all require lifelong treatment with anticoagulants (blood thinners), e.g. warfarin, which requires monthly blood tests to monitor.[citation needed] This process of thinning the blood is called anticoagulation. Tissue heart valves, in contrast, do not require the use of anticoagulant drugs due to the improved blood flow dynamics resulting in less red cell damage and hence less clot formation.[citation
needed]

Their main weakness however, is their limited lifespan. Traditional tissue before they require replacement (but typically less in younger patients).

valves, made of pig heart valves, will last on average 15 years[citation

needed]

Types of mechanical heart valves[edit]

Starr-Edwards-Mitral-Valve (Caged ball valve).

1. Starr-Edwards Valve 2. Starr-Edwards Valve 3. Smeloff-Cutter Valve

There are three major types of mechanical valves caged-ball, tiltingdisk and bileaflet with many modifications on these designs. The first artificial heart valve was the caged-ball, which utilizes a metal cage to house a silicone elastomer ball. When blood pressure in the chamber of the heart exceeds that of the pressure on the outside of the chamber the ball is pushed against the cage and allows blood to flow. At the completion of the heart's contraction, the pressure inside the chamber drops and is lower than beyond the valve, so the ball moves back against the base of the valve forming a seal. In 1952, Dr. Charles A. Hufnagel implanted caged-ball heart valves in ten patients (six survived the operation), marking the first long-term success in prosthetic heart valves.[citation needed] A similar valve was invented by Miles "Lowell" Edwards and Albert Starrin 1960 (commonly referred to as the Starr-Edwards Silastic Ball Valve).[citation needed] The first human implant was on Sept 21, 1960.[citation needed] It consisted of a silicone ball enclosed in a cage formed by wires originating from the valve housing. Caged ball valves have a high tendency to forming blood clots, so the patient must have a high degree

of anti-coagulation, usually with a target INR of 2.5-3.5.[citation needed] Edwards Lifesciencesdiscontinued production of the Starr-Edwards valve in 2007.[citation
needed]

Soon after came tilting-disc valves. The first clinically available tilting disk valve was the Bjork-Shiley valve and has undergone several significant design changes since its introduction in 1969.[citation needed] Tilting disk valves have a single circular occluder controlled by a metal strut. They are made of a metal ring covered by an ePTFE fabric, into which the suture threads are stitched in order to hold the valve in place. The metal ring holds, by means of two metal supports, a disc which opens and closes as the heart pumps blood through the valve. The disc is usually made of an extremely hard carbon material (pyrolytic carbon), in order to allow the valve to function for years without wearing out. The Medtronic-Hall model is the most common tilting-disc design in the US. In some models of mechanical valves, the disc is divided into two parts, which open and close as a door. Bileaflet heart valves consist of two semicircular leaflets that rotate about struts attached to the valve housing. This design was introduced in 1979[citation
needed]

and while they take care of some of the issues that were seen in the

other models, bileaflets are vulnerable to backflow and so they cannot be considered as ideal. Bileaflet valves do, however, provide much more natural blood flow than caged-ball or tilting-disc implants. One of the main advantages of these valves is that they are well tolerated by the body. Only a small amount of blood thinner is needed to be taken by the patient each day in order to prevent clotting of the blood when flowing through the valve. These bileaflet valves have the advantage that they have a greater effective opening area (2.43.2 square cm c.f. 1.52.1 for the single-leaflet valves).[citation needed] Also, they are the least thrombogenic of the artificial valves. Mechanical heart valves are today very reliable and allow the patient to live a normal life. Most mechanical valves last for at least 20 to 30 years.[citation needed]
Durability[edit]

Mechanical heart valves have been traditionally considered to be more durable in comparison to their bioprosthetic counterparts. The struts and

occluders are made out of either pyrolytic carbon or titanium coated with pyrolytic carbon,[citation needed] and the sewing ring cuff is Teflon (PTFE), polyester or dacron.[citation needed] The major load arises from transvalvular pressure generated at and after valve closure, and in cases where structural failure does happen, it is usually as a result of occluder impact on the components. Impact wear and friction wear dictate the loss of material in MHV. Impact wear usually occurs in the hinge regions of bileaflets, between the occluder and ring in tilting-discs, and between the ball and cage in caged-ball valves. Friction wear occurs between the occluder and strut in tilting-discs, and between the leaflet pivots and hinge cavities in bileaflets.[citation needed] MHV, made out of metal are also susceptible to fatigue failure owing to the polycrystalline characteristic of metals, but this is not an issue with pyrolytic carbon MHV because this material is not crystalline in nature.[citation
needed]

Cavitation[edit]

Cavitation is an event that can lead to MHV failure. While this has been a relatively rare occurrence, in 1988 the Edwards-Duramedics bileaflet had 46 reported failures in 20,000 implants related to cavitation damage.[citation
needed]

Since then, manufacturers have made cavitation testing an essential

part of the design verification process. Cavitation is the rapid formation of vaporous microbubbles in the fluid due to a local drop of pressure below the vaporization pressure at a given temperature. When conditions for cavitation are present bubbles will form and at the time of pressure recovery they will collapse or implode. This event will cause pressure or thermal shockwaves and fluid microjets which can damage a surface. These thermodynamic conditions are known to be the cause of MHV related erosion.[citation needed] The valvular event that causes such cavitating conditions to exist is the closing mechanics of the MHV. Several causes of cavitation relating to valve closure have been identified. Squeeze flow is cavitation that is said to occur as the occluder approaches the housing during closure and fluid is squeezed between the occluder and the valve housing causing a low pressure formation. Water hammer is cavitation caused by the sudden stop of the valve occluder as it contacts the valve housing. This sudden retardation of the fluid

retrograde inertia is said to put the fluid under tension causing cavitation. Squeeze flow is said to form a cloud of bubbles at the circumferential lip of the occluder whereas water hammer is said to be seen as transient bubbles at the occlude housing.[citation needed] For either event, cavitation occurs on the upstream side of valve. Clinically, cavitation is of primary concern in the mitral position. This position is especially harsh due to the sudden ventricular pressure rise which drives the valve closure against a low left atrial pressure which is said to be the worst case condition thus position for cavitation to occur. Cavitation is also suspected as a contributing factor in blood cell damage and increased risk of thromboembolic complications.[citation needed] The temporal rate of change of the left ventricular, measured as a slope of the ventricular pressure curve (dP/dt) is regarded as the best indicator for cavitation potential. Most MHV investigated generate cavitation only when the dP/dt is well above the physiological range. However investigations have found that several tilting disc valves and only one bileaflet valve, the EdwardsDuromedics, generate cavitation within the physiological range. Investigations have repeatedly demonstrated that bileaflet valves, with the exception of the Edwards Duramedics design, cavitate only at dP/dt levels well above the physiological range.[citation needed]
Fluid mechanics[edit]

Many of the complications associated with MHV can be explained through fluid mechanics. For example, thrombus formation is a debilitating side effect of high shear stresses created by the design of the valves. An ideal heart valve from an engineering perspective would produce minimal pressure drops, have small regurgitation volumes, minimize turbulence, reduce prevalence of high stresses, and not create flow separations in the vicinity of the valve.[citation
needed]

One measure of the quality of a valve is the effective orifice area (EOA), which can be calculated as follows:

where and

is the root mean square systolic/diastolic flow rate (cm/s) is the mean systolic/diastolic pressure drop (mmHg). This is a

measure of how much the prosthesis impedes blood flow through the valve. A higher EOA corresponds to a smaller energy loss. The performance index (PI) normalizes the EOA by valve size and is a size-independent measure of the valves resistance characteristics. Bileaflet valves typically have higher PIs than tilted-disc models, which in turn have higher PIs than caged-ball models.[citation needed] As blood flows through a prosthetic heart valve, a sudden pressure drop occurs across the valve due to the reduction in cross-sectional area within the valve housing. This can be quantified through the continuity equation and Bernoullis equation:

where A represents the cross-sectional area, P is pressure, and V is the velocity.

[citation needed]

is density,

As cross-sectional area decreases in the

valve, velocity increases and pressure drops as a result. This effect is more dramatic in caged-ball valves than in tilting-disc and bileaflet valves. A larger systolic pressure is required to drive flow forward in order to compensate for a large pressure drop, so it should be minimized.[citation needed] Regurgitation is the sum of retrograde flow during the closing motion of the valve and leakage flow after closure. It is directly proportional to valve size and is also dependent on valve type. Typically, caged-ball valves have a low amount of regurgitation as there is very little leakage. Tilting-disc and bileaflet valves are comparable, with the bileaflet valves have a slightly larger regurgitation volume. Bioprosthetics prevail over MHV in this case, as they have virtually no regurgitation volume.[citation needed] Turbulence and high shear stresses are also major issues with MHV, as they can fracture the valve housing or components, or induce blood damage. A large flow gradient can lead to these factors, so flow separation and stagnation should be as small as possible. High stresses are created at the edges of the annular jet in caged-ball valves, in narrow regions at the edges of the major orifice jet in tilting-disc valves, and in regions immediately distal to

the valve leaflets in bileaflet valves. The implications of blood damage from these stresses are discussed in the next section.[citation needed] The cavitation phenomenon can also be described using fluid mechanics. This can result from pressure oscillations, flow deceleration, tip vortices, streamline contraction, and squeeze jets. This last cause is the most contributive factor to cavitation. The squeeze jets are formed when the valve is closing and the blood between the occluder and valve housing is squeezed out to create a high-speed jet. This in turn creates intense vortices with very low pressures that can lead to cavitation.[citation needed]
Blood damage[edit]

One of the major drawbacks of mechanical heart valves is that patients with these implants require consistent anti-coagulation therapy. Clots formed by red blood cell (RBC) and platelet damage can block up blood vessels and lead to very serious consequences. Clotting occurs in one of three basic pathways: tissue factor exposure, platelet activation, or contact activation by foreign materials, and in three steps: initiation, amplification, and propagation.[citation
needed]

In the tissue factor exposure path, initiation begins when cells are ruptured and expose tissue factor (TF). Plasma Factor (f) VII binds to TF and sets off a chain reaction which activates fXa and fVa which bind to each other to produce thrombin which in turn activates platelets and fVIII. The platelets activate by binding to the damaged tissue in the initiation phase, and fibrin stabilizes the clot during the propagation phase.[citation needed] The platelet activation pathway is triggered when stresses reach a level above 6 to 8 Pa (6080 dyn/cm). The steps involved with this are less clearly understood, but initiation begins with the binding of vWF from the plasma to GPIb on the platelet. This is followed by a large influx of Ca2+ ions, which activates the platelets. GPIIb-IIIa facilitates platelet-platelet adhesion during amplification. The propagation step is still under study.[citation needed] Contact activation begins when fXII binds to a procoagulant surface. This in turn activates prekallikrein (PK) and high-molecular-weight kininogen (HK). Eventually, HKa-PK and HKa-fXI complexes form on the surface. In amplification, Hka-FXIa complexes activate fIX to fIXa, which in turn forms

thrombin and platelets. Proteins buildup on the surface and facilitate platelet adhesion and tissue growth in the propagation stage.[citation needed] All MHV models are vulnerable to thrombus formation due to high shear stress, stagnation, and flow separation. The caged-ball designs experience high stresses at the walls that can damage cells, as well as flow separation due to high-velocity reverse flow surrounded by stagnant flow. Tilting-disc valves have flow separation behind the valve struts and disc as a result of a combination of high velocity and stagnant flows. The bileaflet models have high stresses during forward and leakage flows as well as adjacent stagnant flow in the hinge area. As it turns out, the hinge area is the most critical part of bileaflets and is where the thrombus formation usually prevails.[citation needed] In general, blood damage affects valves in both the mitral and aortic positions. High stresses during leakage flow in aortal valves result from higher transvalvular pressures, and high stresses occur during forward flow for mitral valves. Valvular thrombosis is most common in mitral prosthetics. The cagedball model is better than the other two models in terms of controlling this problem, because it is at a lower risk for thrombosis and it is gradual when it does happen. The bileaflet is more adaptable to this problem than the tiltingdisc model because if one leaflet stops working, the other can still function. However, if the hinge is blocked, both leaflets will stop functioning.[citation needed] Because all models experience high stresses, patients with mechanical heart valve implants require anti-coagulation therapy. Bioprosthetics are less prone to develop blood clotting, but the trade-off concerning durability generally favors their use in patients older than age 55.[citation needed] Mechanical heart valves can also cause mechanical hemolytic anemia with hemolysis of the red blood cells as they pass through the valve.[citation needed]

Tissue (biological) valves[edit]

Biological valves are valves of animals, like pigs, which undergo several chemical procedures in order to make them suitable for implantation in the human heart. The porcine (or pig) heart is most similar to the human heart, and therefore represents the best anatomical fit for replacement. Implantation of a porcine valve is a type of xenotransplantation, also known as a xenograft, which means a transplant from one species (in this case a pig) to another.

There are some risks associated with a xenograft such as the human body's tendency to reject foreign material. Medication can be used to retard this effect, but is not always successful.[citation needed] Another type of biological valve utilizes biological tissue to make leaflets that are sewn into a metal frame. This tissue is typically harvested from the Pericardial Sac of either Bovine (cows) or Equine (horses). The pericardial sac is particularly well suited for a valve leaflet due to its extremely durable physical properties. This type of biological valve is extremely effective means of valve replacement. The tissue is sterilized so that the biological markers are removed, eliminating a response from the host's immune system. The leaflets are flexible and durable and do not require the patient to take blood thinners for the rest of their life.[citation needed] The most used heart valves in the US and EU are those utilizing tissue leaflets. Mechanical valves are more commonly used in Asia and Latin America.[citation needed] The following companies manufacture tissue heart valves: Edwards Lifesciences, Medtronic, St. Jude Medical, Sorin, Medtronic ATS Medical, 3F Therapeutics, CryoLife, and LifeNet Health.[citation needed]

Functional requirements of heart valve prostheses[edit]

The functioning of natural heart valves is characterized by many advantages:

Minimal regurgitation This means that the amount of blood lost upstream as the valve closes is small. For example, closure regurgitation through the mitral valve would result in some blood loss from the left ventricle to the left atrium as the mitral valve closes. Some degree of valvular regurgitation is inevitable and natural, up to around 5ml per beat.[4] However, several heart valve pathologies (e.g. rheumatic endocarditis) may lead to clinically significant valvular regurgitation. A desirable characteristic of heart valve prostheses is that regurgitation is minimal over the full range of physiological heart function (i.e. complete functional envelope of cardiac output vs. heart rate).

Minimal transvalvular pressure gradient Whenever a fluid flows through a restriction, such as a valve, a pressure gradient arises over the restriction. This pressure gradient is a result of the increased resistance to flow through the restriction. Natural heart valves have a low transvalvular

pressure gradient as they present little obstruction to the flow through themselves, normally less than 16 mmHg. A desirable characteristic of heart valve prostheses is that their transvalvular pressure gradient is as small as possible.

Non-thrombogenic As natural heart valves are lined with an endothelium continuous with the endothelium lining the heart chambers they are not normally thrombogenic. This is important as should thrombi form on the heart valve leaflets and become seeded with bacteria, so called "bacterial vegetations" will form. Such vegetations are difficult for the body to deal with as the normal physiological defense mechanisms are not present within the valve leaflets because they are avascular and largely composed ofconnective tissue (Fixme: Create article discussing the pathgonesis of leaflet bacterial vegetations.). Should bacterial vegetations form on the valve leafets they may continually seed bacteria into the arterial tree which may lead to bacteremia or septicaemia. Portions of the vegetation may also break off forming septic emboli. Septic emboli can lodge anywhere in the arterial tree (e.g. brain, bowel, lungs) causing local infectious foci. Even dislodged fragments from uninfected thrombi can be hazardous as they can lodge in, and block, downstream arteries (e.g. coronary arteries leading to myocardial infarction, cerebral arteries leading to stroke, see embolism). A desirable characteristic of heart valve prostheses is that they are non or minimally thrombogenic.

Self-repairing Although of limited extent compared to well vascularised tissue (e.g. muscle), the valve leaflets do retain some capacity for repair due to the presence of regenerative cells (e.g. fibroblasts) in the connective tissue from which the leaflets are composed. As the human heart beats approximately 3.4x109 times during a typical human lifespan this limited but nevertheless present repair capacity is critically important. No heart valve prostheses can currently self-repair but replacement tissues grown using stem cell technology may eventually offer such capabilities.[citation needed]

Rapid dynamic response STD

Design challenges of heart valve prostheses[edit]

A replaceable model of Cardiac Biological Valve Prosthesis.[5] [6]

Thrombogenesis / haemocompatibility Mechanisms: Forward and backward flow shear Static leakage shear Presence of foreign material (i.e. intrinsic coagulation cascade) Cellular maceration Valve-tissue interaction Wear Blockage Getting stuck Dynamic responsiveness Failure safety Valve orifice to anatomical orifice ratio Trans-valvular pressure gradient Minimal leakages Detachable And Replaceable Models Of Heart Valve Prostheses

Replaceable models of heart valve prostheses[edit]

Mechanical or biological (bioprostheses or "tissue valves"), the replaceable models of implantable heart valve prostheses are made by two or three mechanical components. The gear attachment mechanism usually uses the coil effect or the bayonet coupling system.[citation needed] The replaceable models of implantable heart valve prostheses are typically supplied with a sewing or suturing ring surrounding the valve body or stent that is to be sutured by the surgeon to the valvar rim.[citation needed]

The biggest challenge in this type of prostheses is the difficulty in its future removal. This is due to the formation of pannus fibrotic around the valve body and sewing ring. To separate the parts is very laborious, keeping intact the sewing ring, which will be used in the coupling of the new valve. To easily remove the old replaceable bioprostheses, its "stent" can be sectioned to dismount its framework and so facilitate its removal from the sewing ring.[citation needed]

Time line of the detachable and replaceable models of heart valve prostheses:

1984 Martin, J. R [7] 1984 Martin, J. R [8] 1984 Martin, J. R [9] 1987 Fernandez J [10] 1988 Cooper DK [11] 1992 Lyra,R M [5] 1992 Lyra,R M [6] 1992 Jansen J [12]

Typical configuration of a heart valve prosthesis[edit]

Anchor Leaflets

Additional images[edit]

3D Rendering of Mechanical Valve

3D Rendering of Mechanical Valve (St. Francis model)

See also[edit]

Vascular grafting
From Wikipedia, the free encyclopedia

It has been suggested that this article be merged with Vascular bypass. (Discuss) Proposed since March 2014.

Vascular grafting
Intervention ICD-9-CM MeSH 39.2 D058017

Vascular grafting is the use of transplanted or prosthetic blood vessels in surgical procedures. PTFE and Dacron are some of the most commonly used grafts. Grafts can be used for the aorta, femoral artery or in the forearm. Coronary artery bypass graft is used for people with occluded coronary arteries, and often the saphenous vein or left internal thoracic artery are used in this procedure.

See also[edit]

JOINT IMPLANT

Hip replacement

From Wikipedia, the free encyclopedia

Hip replacement
Intervention

In this X-ray, the patients right hip (left of image) has been replaced, with the ball of this ball-andsocket joint replaced by a metal head that is set in the thighbone or femur and the socket replaced by a white plastic cup (clear in this Xray). Pelvic anatomy consistent with that of a female (large infrapubic angle, large pelvic opening). ICD-9-CM MeSH MedlinePlus 81.5181.53 D019644 002975

Hip replacement is a surgical procedure in which the hip joint is replaced by a prosthetic implant. Hip replacement surgery can be performed as a total replacement or a hemi (half) replacement. Such joint replacement orthopaedic surgery is generally conducted to relieve arthritis pain or fix severe physical joint damage as part of hip fracture treatment. A total hip replacement (total hip arthroplasty) consists of replacing both the acetabulum and the femoral head while hemiarthroplasty generally only replaces the femoral head. Hip

replacement is currently the most common orthopaedic operation, though patient satisfaction short and long term varies widely.
Contents [hide]

1 Medical uses 2 Risks

o o o o o o o o o

2.1 Vein thrombosis 2.2 Dislocation 2.3 Osteolysis 2.4 Metal sensitivity 2.5 Metal toxicity 2.6 Nerve palsy 2.7 Chronic pain 2.8 Death 2.9 Leg length inequality

3 Modern process 4 Techniques

o o o o o

4.1 Posterior approach 4.2 Lateral approach 4.3 Antero-lateral approach 4.4 Anterior approach 4.5 Minimally invasive approach 5.1 Acetabular Cup 5.2 Femoral Component 5.3 Articular Interface

5 Implants
o o o

6 Metal-on-metal hip implant failure 7 Alternatives and variations

o o o o

7.1 Conservative management 7.2 Hemiarthroplasty 7.3 Hip resurfacing 7.4 Viscosupplementation

8 History 9 See also 10 References

11 External links

Medical uses[edit]
Total hip replacement is most commonly used to treat joint failure caused by osteoarthritis. Other indications include rheumatoid arthritis, avascular necrosis, traumatic arthritis,protrusio acetabuli, certain hip fractures, benign and malignant bone tumors, arthritis associated with Paget's disease, ankylosing spondylitis and juvenile rheumatoid arthritis. The aims of the procedure are pain relief and improvement in hip function. Hip replacement is usually considered only after other therapies, such as physical therapy and pain medications, have failed.

Risks[edit]

Dislocated artificial hip

Hip prosthesis displaying aseptic loosening (arrows)

Risks and complications in hip replacement are similar to those associated with all joint replacements. They can include dislocation, loosening, impingement, infection, osteolysis, metal sensitivity, nerve palsy, pain and death.
Vein thrombosis[edit]

Venous thrombosis such as deep vein thrombosis and pulmonary embolism are relatively common following hip replacement surgery. Standard treatment with anticoagulants is for 710 days; however treatment for more than 21 days may be superior.[1]
Dislocation[edit]

Dislocation is the most common complication of hip replacement surgery. At surgery the femoral head is taken out of the socket, hip implants are placed and the hip put back into proper position. It takes eight to twelve weeks for the soft tissues injured or cut during surgery to heal. During this period, the hip ball can come out of the socket. The chance of this is diminished if less tissue is cut, if the tissue cut is repaired and if large diameter head balls are used. Surgeons who perform more of the operations each year tend to have fewer patients dislocate. Doing the surgery from an anterior approach seems to lower dislocation rates when small diameter heads are used, but the benefit has not been shown when compared to modern posterior incisions with the

use of larger diameter heads. Patients can decrease the risk further by keeping the leg out of certain positions during the first few months after surgery. Use of alcohol by patients during this early period is also associated with an increased rate of dislocation.
Osteolysis[edit]

Many long-term problems with hip replacements are the result of osteolysis. This is the loss of bone caused by the body's reaction to polyethylene wear debris, fine bits of plastic that come off the cup liner over time. An inflammatory process causes bone resorption that may lead to subsequent loosening of the hip implants and even fractures in the bone around the implants. In an attempt to eliminate the generation of wear particles, ceramic bearing surfaces are being used in the hope that they will have less wear and less osteolysis with better long term results. Metal cup liners joined with metal heads (metal-on-metal hip arthroplasty) were also developed for similar reasons. In the lab these show excellent wear characteristics and benefit from a different mode of lubrication. At the same time that these two bearing surfaces were being developed, highly cross linked polyethylene plastic liners were also developed. The greater cross linking significantly reduces the amount of plastic wear debris given off over time. The newer ceramic and metal prostheses do not always have the long term track record of established metal on poly bearings. Ceramic pieces can break leading to catastrophic failure. This occurs in about 2% of the implants placed. They may also cause an audible, high pitched squeaking noise with activity. Metal-on-metal arthroplasty releases metal debris into the body raising concerns about the potential dangers of these accumulating over time. Highly cross linked polyethylene is not as strong as regular polyethylene. These plastic liners can crack or break free of the metal shell that holds them.
Metal sensitivity[edit]

Concerns are being raised about the metal sensitivity and potential dangers of metal particulate debris. New publications[2][3] have demonstrated development of pseudotumors, soft tissue masses containing necrotic tissue, around the hip joint. It appears these masses are more common in women and these patients show a higher level of iron in the blood. The cause is unknown and is probably multifactorial. There may be a toxic reaction to an

excess of particulate metal wear debris or a hypersensitivity reaction to a normal amount of metal debris. Metal hypersensitivity is a well-established phenomenon and is common, affecting about 1015% of the population.[4] Contact with metals can cause immune reactions such as skin hives, eczema, redness and itching. Although little is known about the short and long term pharmacodynamics and bioavailability of circulating metal degradation products in vivo, there have been many reports of immunologic type responses temporally associated with implantation of metal components. Individual case reports link hypersensitivity immune reactions with adverse performance of metallic clinical cardiovascular, orthopedic and plastic surgical and dental implants.[4]
Metal toxicity[edit]

Most hip replacements consist of cobalt and chromium alloys, or titanium. Stainless steel is no longer used. All implants release their constituent ions into the blood. Typically these are excreted in the urine, but in certain individuals the ions can accumulate in the body. In implants which involve metal-on-metal contact, microscopic fragments of cobaltand chromium can be absorbed into the patient's bloodstream. There are reports of cobalt toxicity with hip replacement patients.[5][6]
Nerve palsy[edit]

Post operative sciatic nerve palsy is another possible complication. The incidence of this complication is low. Femoral nerve palsy is another but much more rare complication. Both of these will typically resolve over time, but the healing process is slow. Patients with pre-existing nerve injury are at greater risk of experiencing this complication and are also slower to recover.
Chronic pain[edit]

A few patients who have had a hip replacement suffer chronic pain after the surgery. Groin pain can develop if the muscle that raises the hip (iliopsoas) rubs against the edge of the acetabular cup. Bursitis can develop at the trochanter where a surgical scar crosses the bone, or if the femoral component used pushes the leg out to the side too far. Also some patients can experience pain in cold or damp weather.[citation needed] Incision made in the front of the hip (anterior approach) can cut a nerve running down the thigh

leading to numbness in the thigh and occasionally chronic pain at the point where the nerve was cut (a neuroma).
Death[edit]

Rates of death for elective hip replacements are much less than 1%.[7][8]
Leg length inequality[edit]

The leg can be lengthened or shortened during surgery. Unequal legs are the most common complaint by patients after surgery with over lengthening the most common problem. Sometimes the leg seems long immediately after surgery when in fact both are equal length. An arthritic hip can develop contractures that make the leg behave as if it is short. When these are relieved with replacement surgery and normal motion and function are restored, the body feels that the limb is now longer than it was. If the legs are truly equal, the sense of inequality resolves within a month or two of surgery. If the leg is unequal, it will not. A shoe lift for the short leg, or in extreme cases, a corrective operation may be needed. True leg length inequality may sometimes be caused by improper implant selection. The femoral component may be too large and stick out of the femur further than needed. The head ball selected may sit too proud on the stem. Stiffness in the lower back from arthritis or previous fusion surgery seems to magnify the perception of leg length inequality.

Modern process[edit]

A titanium hip prosthesis, with a ceramichead and polyethylene acetabular cup

The modern artificial joint owes much to the work of Sir John Charnley at Wrightington Hospital; his work in the field of tribologyresulted in a design that

almost completely replaced the other designs by the 1970s. Charnley's design consisted of three parts: 1. stainless steel one-piece femoral stem and head 2. polyethylene (originally teflon), acetabular component, both of which were fixed to the bone using 3. PMMA (acrylic) bone cement The replacement joint, which was known as the Low Friction Arthroplasty, was lubricated with synovial fluid. The small femoral head (7/8" (22.2 mm)) was chosen for Charnley's belief that it would have lower friction against the acetabular component and thus wear out the acetabulum more slowly. Unfortunately, the smaller head dislocated more easily. Alternative designs with larger heads such as the Mueller prosthesis were proposed. Stability was improved, but acetabular wear and subsequent failure rates were increased with these designs. The Teflon acetabular components of Charnley's early designs failed within a year or two of implantation. This prompted a search for a more suitable material. A German salesman showed a polyethylene gear sample to Charnley's machinist, sparking the idea to use this material for the acetabular component. The Ultra High Molecular Weight Polyethylene or UHMWPEacetabular component was introduced in 1962. Charnley's other major contribution was to use polymethylmethacrylate (PMMA) bone cement to attach the two components to the bone. For over two decades, the Charnley Low Friction Arthroplasty, and derivative designs were the most used systems in the world. It formed the basis for all modern hip implants. The Exeter hip stem was developed in the United Kingdom during the same time as the Charnley device. This is also a cemented device, but with a slightly different stem geometry. Both designs have shown excellent long-term durability when properly placed and are still widely used in slightly modified versions. Early implant designs had the potential to loosen from their attachment to the bones, typically becoming painful ten to twelve years after placement. In addition, erosion of the bone around the implant was seen on x-rays. Initially, surgeons believed this was caused by an abnormal reaction to the cement

holding the implant in place. That belief prompted a search for an alternative method to attach the implants. The Austin Moore device had a small hole in the stem into which bone graft was placed before implanting the stem. It was hoped bone would then grow through the window over time and hold the stem in position. Success was unpredictable and the fixation not very robust. In the early 1980s, surgeons in the United States applied a coating of small beads to the Austin Moore device and implanted it without cement. The beads were constructed so that gaps between beads matched the size of the pores in native bone. Over time, bone cells from the patient would grow into these spaces and fix the stem in position. The stem was modified slightly to fit more tightly into the femoral canal, resulting in the Anatomic Medullary Locking (AML) stem design. With time, other forms of stem surface treatment and stem geometry have been developed and improved. Initial hip designs were made of a one-piece femoral component and a onepiece acetabular component. Current designs have a femoral stem and separate head piece. Using an independent head allows the surgeon to adjust leg length (some heads seat more or less onto the stem) and to select from various materials from which the head is formed. A modern acetabulum component is also made up of two parts: a metal shell with a coating for bone attachment and a separate liner. First the shell is placed. Its position can be adjusted, unlike the original cemented cup design which are fixed in place once the cement sets. When proper positioning of the metal shell is obtained, the surgeon may select a liner made from various materials. To combat loosening caused by polyethylene wear debris, hip manufacturers developed improved and novel materials for the acetabular liners. Ceramic heads mated with regular polyethylene liners or a ceramic liner were the first significant alternative. Metal liners to mate with a metal head were also developed. At the same time these designs were being developed, the problems that caused polyethylene wear were determined and manufacturing of this material improved. Highly-crosslinked UHMWPE was introduced in the late 1990s. The most recent data comparing the various bearing surfaces has shown no clinically significant differences in their performance. Potential early problems with each material are discussed below. Performance data after 20 or 30 years may be needed to demonstrate

significant differences in the devices. All newer materials allow use of larger diameter femoral heads. Use of larger heads significantly decreases the chance of the hip dislocating, which remains the greatest complication of the surgery. When currently available implants are used, cemented stems tend to have a better longevity than uncemented stems. No significant difference is observed in the clinical performance of the various methods of surface treatment of uncemented devices. Uncemented stems are selected for patients with good quality bone that can resist the forces needed to drive the stem in tightly. Cemented devices are typically selected for patients with poor quality bone who are at risk of fracture during stem insertion. Cemented stems are less expensive due to lower manufacturing cost, but require good surgical technique to place them correctly. Uncemented stems can cause pain with activity in up to 20% of patients during the first year after placement as the bone adapts to the device. This is rarely seen with cemented stems. Once an uncommon operation reserved for frail patients with a limited life expectancy, hip replacement is now common, even among active athletes including race car driversBobby Labonte and Dale Jarrett, and British Open runner-up, golfer Tom Watson.

Techniques[edit]
There are several incisions, defined by their relation to the gluteus medius. The approaches are posterior (Moore), lateral (Hardinge or Liverpool),[9] antero-lateral (Watson-Jones),[10] anterior (SmithPetersen)[11] and greater trochanter osteotomy. There is no compelling evidence in the literature for any particular approach, but consensus of professional opinion favours either modified anterolateral (Watson-Jones) or posterior approach.[citation needed]
Posterior approach[edit]

The posterior (Moore or Southern) approach accesses the joint and capsule through the back, taking piriformis muscle and the short external rotators off the femur. This approach gives excellent access to the acetabulum and femur and preserves the hip abductors and thus minimises the risk of abductor dysfunction post operatively. It has the advantage of becoming a more

extensile approach if needed. Critics cite a higher dislocation rate, although repair of the capsule, piriformis and the short external rotators along with use of modern large diameter head balls reduces this risk.
Lateral approach[edit]

The lateral approach is also commonly used for hip replacement. The approach requires elevation of the hip abductors (gluteus medius and gluteus minimus) to access the joint. The abductors may be lifted up by osteotomy of the greater trochanter and reapplying it afterwards using wires (as per Charnley),[citation needed] or may be divided at their tendinous portion, or through the functional tendon (as per Hardinge) and repaired using sutures. Although this approach has a lower dislocation risk than the posterior approach, critics note that occasionally the abductor muscles do not heal back on, leading to pain and weakness which is often very difficult to treat.
Antero-lateral approach[edit]

The anterolateral approach develops the interval between the tensor fasciae latae and the gluteus medius.
Anterior approach[edit]

The anterior approach uses an interval between the sartorius muscle and tensor fascia latae. Dr. Joel Matta has adapted this approach, which was commonly used for pelvic fracture repair surgery, for use when performing hip replacement. When used with older hip implant systems that had a small diameter head, dislocation rates were reduced compared to surgery performed through a posterior approach. With modern implant designs, dislocation rates are lower because supporting muscle tissue, Including the iliotibial tract, receives very little damage during the surgery. There is a 10% rate of numbness in the thigh following this approach, due to injury to the lateral femoral cutaneous nerve. The anterior approach results in a quicker and less painful recovery. Immediately following surgery patients are instructed to go about their normal hip function, including weight bearing activity and bending their hip freely.[citation needed]
Minimally invasive approach[edit]

The double incision surgery and minimally invasive surgery seeks to reduce soft tissue damage through reducing the size of the incision. However, component positioning accuracy and visualization of the bone structures is

significantly impaired. This can result in unintended fractures and soft tissue injury. Surgeons using these approaches are advised to use intraoperative xray fluoroscopy or computer guidance systems.[citation needed] Computer Assisted Surgery techniques are also available to guide the surgeon to provide enhanced accuracy. Several commercial CAS systems are available for use worldwide.HipNav was the first system developed specifically for total hip replacement, and included navigation and preoperative planning based on a preoperative CT scan of the patient. Improved patient outcomes and reduced complications have not been demonstrated when these systems are used when compared to standard techniques.

Implants[edit]

Cement free implant 16 days after surgery. Femoral component is cobalt chromium combined with titanium which induces bone growth into the implant. Ceramic head. Acetabular cup coated with bone growth inducing material and held temporarily in place with a single screw.

The prosthetic implant used in hip replacement consist of different parts, the acetabular cup, the femoral component and the articular interface. Options exist for different patients and indications. Correct selection of the prosthesis is important.

Acetabular Cup[edit]

The Acetabular cup is the component which is placed into the acetabulum (hip socket). Cartilage and bone are removed from the acetabulum and the acetabular cup is attached using friction or cement. Some acetabular cups are one piece, while others are modular. One piece (monobloc) shells are either UHMWPE (ultra high molecular weight polyethylene) or metal, they have their articular surface machined on the inside surface of the cup and do not rely on a locking mechanism to hold a liner in place. A monobloc polyethylene cup is cemented in place while a metal cup is held in place by a metal coating on the outside of the cup. Modular cups consist of two pieces, a shell and liner. The shell is made of metal, the outside has a porous coating while the inside contains a locking mechanism designed to accept a liner. Two types of porous coating used to form a friction fit are sintered beads or a foam metal design to mimic the trabeculae of cancellous bone. Additional fixation is achieved as bone grows onto or into the porous coating. Screws can be used to lag the shell to the bone providing even more fixation. Polyethylene liners are placed into the shell and connected by a rim locking mechanism, ceramic and metal liners are attached with a Morse taper.[citation needed]
Femoral Component[edit]

The femoral component is the component that fits in the femur (thigh bone). Bone is removed and the femur is shaped to accept the femoral stem with attached prosthetic femoral head (ball). There are two types of fixation: cemented and uncemented. Cemented stems use acrylic bone cement to form a mantle between the stem and to the bone. Uncemented stems use friction, shape and surface coatings to stimulate bone to remodel and bond to the implant. Stems are made of multiple materials (titanium, cobalt chromium, stainless steel, and polymer composites) and they can be monolithic or modular. Modular components consist of different head dimensions and/or modular neck orientations; these attach via a taper similar to a Morse taper. These options allow for variability in leg length, offset and version. Femoral heads are made of metal or ceramic material. Metal heads, made of cobalt chromium for hardness, are machined to size and then polished to reduce wear of the socket liner. Ceramic heads are more smooth than polished metal heads, have a lower coefficient of friction than a cobalt chrome head, and in theory will wear down the socket liner more slowly. As of early 2011, follow up

studies in patients have not demonstrated significant reductions in wear rates between the various types of femoral heads on the market. Ceramic implants are more brittle and may break after being implanted.
Articular Interface[edit]

The articular interface is not actually part of either implant, rather it is the area between the acetabular cup and femoral component. The articular interface of the hip is a simple ball and socket joint. Size, material properties and machining tolerances at the articular interface can be selected based on patient demand to optimise implant function and longevity whilst mitigating associated risks. The interface size is measured by the outside diameter of the head or the inside diameter of the socket. Common sizes of femoral heads are 28 mm, 32 mm and 36 mm. While a 22.25 mm was common in the first modern prostheses, now even larger sizes are available 3854+. Larger diameter heads lead to increased stability and range of motion whilst lowering the risk of dislocation. At the same time they are also subject to higher stresses such as friction and inertia. Different combinations of materials have different physical properties which can be coupled to reduce the amount of wear debris generated by friction. Typical pairings of materials include metal on polyethylene (MOP), metal on crosslinked polyethylene (MOXP), ceramic on ceramic (COC), ceramic on crosslinked polyethylene (COXP) and metal on metal (MOM). Each combination has different advantages and disadvantages.

Metal-on-metal hip implant failure[edit]

See also: Implant failure By 2010, reports in the orthopaedic literature have increasingly cited the problem of early failure of metal on metal prostheses in a small percentage of patients.[12] Failures may relate to release of minute metallic particles or metal ions from wear of the implants, causing pain and disability severe enough to require revision surgery in 13% of patients.[13]Design deficits of some prothesis models, especially with heat-treated alloys and a lack of special surgical experience accounts for most of the failures. Surgeons at leading medical centers such as the Mayo Clinic have reported reducing their use of metal-on-metal implants by 80 percent over the last year in favor of those made from other materials, like combinations of metal and plastic.[14] The cause of these failures remain controversial, and may include both design

factors, technique factors, and factors related to patient immune responses (allergy type reactions). In the United Kingdom the Medicines and Healthcare Products Regulatory Agency commenced an annual monitoring regime for metal-on-metal hip replacement patients from May 2010.[15] Data which is shown in The Australian Orthopaedic Association's 2008 National Joint Replacement Registry, a record of nearly every hip implanted in that country over the previous 10 years, tracked 6,773 BHR (Birmingham Hip Resurfacing) Hips and found that less than one-third of one percent may have been revised due to the patient's reaction to the metal component.[16] Other similar metalon-metal designs have not fared as well, where some reports show 76% to 100% of the people with these metal-on-metal implants and have aseptic implant failures requiring revision also have evidence of histological inflammation accompanied by extensive lymphocyte infiltrates, characteristic of delayed type hypersensitivity responses.[17] It is not clear to what extent this phenomenon negatively affects orthopedic patients. However for patients presenting with signs of an allergic reactions, evaluation for sensitivity should be conducted. Removal of the device that is not needed should be considered, since removal may alleviate the symptoms. Patients who have allergic reactions to cheap jewelry are more likely to have reactions to orthopedic implants. There is increasing awareness of the phenomenon of metal sensitivity and many surgeons now take this into account when planning which implant is optimal for each patient. On March 12, 2012, The Lancet published a study, based on data from the National Joint Registry of England and Wales, finding that metal-on-metal hip implants failed at much greater rates than other types of hip implants and calling for a ban on all metal-on-metal hips.[18] The analysis of 402,051 hip replacements showed that 6.2% of metal-on-metal hip implants had failed within five years, compared to 1.7% of metal-on-plastic and 2.3% of ceramicon-ceramic hip implants. Each 1mm increase in head size of metal-on-metal hip implants was associated with a 2% increase of failure.[19] Surgeons of the British Hip Society are recommending that large head metal-on-metal implants should no longer be performed.[20] On February 10, 2011, the U.S. FDA issued a patient advisory on metal-metal hip implants, stating it was continuing to gather and review all available

information about metal-on-metal hip systems.[21] On June 2728, 2012, an advisory panel met to decide whether to impose new standards, taking into account the The Lancet findings.[6][22][23] No new standards, such as routine checking of blood metal ion levels, were set, but guidance was updated.[24] Currently, FDA has not required hip implants to be tested in clinical trials before they can be sold in the U.S.[25] Instead, companies making new hip implants only need to prove that they are "substantially equivalent" to other hip implants already on the market. The exception is metal-on-metal implants, which were not tested in clinical trials but because of the high revision rate of metal-on-metal hips, in the future the FDA has stated that clinical trials will be required for approval and that post-market studies will be required to keep metal on metal hip implants on the market.[26]

Alternatives and variations[edit]

Conservative management[edit]

The first line approach as an alternative to hip replacement is conservative management which involves a multimodal approach of medication, activity modification and physical therapy.[27] Conservative management can prevent or delay the need for hip replacement.
Hemiarthroplasty[edit]

Hemiarthroplasty is a surgical procedure which replaces one half of the joint with an artificial surface and leaves the other part in its natural (pre-operative) state. This class of procedure is most commonly performed on the hip after a subcapital (just below the head) fracture of the neck of the femur (a hip fracture). The procedure is performed by removing the head of the femur and replacing it with a metal or composite prosthesis. The most commonly used prosthesis designs are the Austin Moore prosthesis and the Thompson Prosthesis. More recently a composite of metal and HDPE which forms two interphases (bipolar prosthesis) has also been used. The bipolar prosthesis has not been shown to have any advantage over monopolar designs. The procedure is recommended only for elderly and frail patients, due to their lower life expectancy and activity level. This is because with the passage of time the prosthesis tends to loosen or to erode the acetabulum.[28]
Hip resurfacing[edit]

Hip resurfacing is an alternative to hip replacement surgery. It has been used in Europe for over 17 years and become a common procedure. The minimally invasive hip resurfacing procedure is a further refinement to hip resurfacing.
Viscosupplementation[edit]

Current alternatives also include viscosupplementation, or the injection of artificial lubricants into the joint.[29] Use of these medications in the hip is off label. The cost of treatment is typically not covered by health insurance organizations. Some believe that the future of osteoarthritis treatment is bioengineering, targeting the growth and/or repair of the damaged, arthritic joint. Centeno et al. have reported on the partial regeneration of an arthritic human hip joint using mesenchymal stem cells in one patient.[30] It is yet to be shown that this result will apply to a larger group of patients and result in significant benefits. The FDA has stated that this procedure is being practiced without conforming to regulations, but Centeno claims that it is exempt from FDA regulation. It has not been shown in controlled clinical trials to be effective, and costs over $7,000.

History[edit]
The earliest recorded attempts at hip replacement (Gluck T, 1891), which were carried out in Germany, used ivory to replace the femoral head (the ball on the femur).[31] On September 28, 1940 at Columbia Hospital in Columbia, South Carolina, Dr. Austin T. Moore (18991963), an American surgeon, reported and performed the first metallic hip replacement surgery. The original prosthesis he designed was a proximal femoral replacement, with a large fixed head, made of the Cobalt-Chrome alloy Vitallium. It was about a foot in length and it bolted to the resected end of the femoral shaft (hemiarthroplasty). A later version of Dr. Moore's prosthesis, the so-called Austin Moore, developed in Columbia, SC was introduced in 1952 is still in use today, although rarely. Like modern hip implants it is inserted into the medullary canal of the femur. It depends on bone growth through a hole in the stem for long term attachment.

In 1960 a Burmese orthopaedic surgeon, Dr. San Baw (29 June 1922 7 December 1984), pioneered the use of ivory hip prostheses to replace ununited fractures of the neck offemur when he first used an ivory prosthesis to replace the fractured hip bone of an 83 year old Burmese Buddhist nun, Daw Punya.[32] This was done while Dr. San Baw was the chief of orthopaedic surgery at Mandalay General Hospital in Mandalay, Burma. Dr. San Baw used over 300 ivory hip replacements from the 1960s to 1980s. He presented a paper entitled "Ivory hip replacements for ununited fractures of the neck of femur" at the conference of the British Orthopaedic Association held in London in September 1969. An 88% success rate was discerned in that Dr. San Baw's patients ranging from the ages of 24 to 87 were able to walk, squat, ride a bicycle and play football a few weeks after their fractured hip bones were replaced with ivory prostheses. Ivory may have been used because it was cheaper than metal at that time in Burma and also was thought to have good biomechanical properties including biological bonding of ivory with the human tissues nearby. An extract from Dr San Baw's paper, which he presented at the British Orthopaedic Association's Conference in 1969, is published in Journal of Bone and Joint Surgery (British edition), February 1970. With modern hip replacement surgery, one can expect to walk immediately postoperation.

See also[edit]

Metallosis
From Wikipedia, the free encyclopedia

This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be removed. (August 2012)
Metallosis is the putative medical condition involving deposition and build-up of metal debris in the soft tissues of the body.[1] Metallosis has been hypothesized to occur when metallic components in medical implants, specifically joint replacements, abrade against one another.[2] Metallosis has also been observed in some patients either sensitive to the implant or for unknown reasons even in the absence of malpositioned prosthesis. Though rare, metallosis has been observed at an estimated incidence

of 5% of metal joint implant patients over the last 40 years. Women may be at slightly higher risk than men. If metallosis occurs, it may involve the hip andknee joints, the shoulder,[3] wrist,[4] or elbow joints.[5] The abrasion of metal components may cause metal ions to be solubilized. The hypothesis that the immune system identifies the metal ions as foreign bodies and inflames the area around the debris may be incorrect because of the small size of metal ions may prevent them from becoming haptens.[6] Poisoning from metallosis is rare, but cobaltism is an established health concern. The involvement of the immune system in this putative condition has also been theorized but has never been proven.[7] Purported symptoms of metallosis generally include pain around the site of the implant, pseudotumors (a mass of inflamed cells that resembles a tumor but is actually collected fluids), and a noticeable rash that indicates necrosis.[8] The damaged and inflamed tissue can also contribute to loosening the implant or medical device. Metallosis can cause dislocation of noncemented implants as the healthy tissue that would normally hold the implant in place is weakened or destroyed.[9] Metallosis has been demonstrated to cause osteolysis.[10] Women, those who are small in stature, and the obese are at greater risk for metallosis because their body structure causes more tension on the implant, quickening the abrasion of the metal components and the subsequent build-up of metallic debris.

Contents [hide]

1 Physical effects and symptoms 2 Side effects 3 DePuy hip replacement recall 4 References

Physical effects and symptoms[edit]

Persons suffering from metallosis can experience any of the following symptoms:

Extreme pain (even when not moving); Swelling and inflammation; Loosening of the implant; Dislocation; Bone deterioration; Aseptic fibrosis, local necrosis;[11] Hip replacement failure;

Metal toxicity from grinding metal components; and Necessary subsequent hip replacement revision or surgeries.

Side effects[edit]
This section does not cite any references or sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (August 2012)
As the grinding components cause metal flakes to shed from the system, the implant wears down. Metallosis results in numerous additional side effects:

Confusion; Feelings of malaise; Gastrointestinal problems; Emotional disturbance; Recurring infections; Dizziness; Headaches; Problems in the nervous system (feelings of burning, tingling, or numbness of the extremities); and

Cobalt poisoning (skin rashes, cardiomyopathy, problems with hearing, sight or cognition, tremors, and hypothyroidism).

DePuy hip replacement recall[edit]

Main article: 2010 DePuy Hip Recall In August 2010, DePuy recalled its hip replacement systems ASR XL Acetabular Hip Replacement System and ASR Hip Resurfacing System due to failure rates and side effects including metallosis. The recalls triggered a large number of lawsuits against DePuy and its parent company Johnson & Johnson upon claims that the companies knew about the dangers of the implants before they went on the market in the United States.

References[edit]
1. Jump up^

2.Shoulder replacement
3. From Wikipedia, the free encyclopedia

Shoulder replacement
Intervention

X-ray of a shoulder prosthesis ICD-9-CM MedlinePlus 81.80-81.81 007387

4. Shoulder replacement is a surgical procedure in which all or part of the glenohumeral joint is replaced by a prosthetic implant. Such joint replacement surgery generally is conducted to relieve arthritis pain or fix severe physical joint damage.[1] 5. Shoulder replacement surgery is an option for treatment of severe arthritis of the shoulder joint. Arthritis is a condition that affects the cartilage of the joints. As the cartilage lining wears away, the protective lining between the bones is lost. When this happens, painful bone-onbone arthritis develops. Severe shoulder arthritis is quite painful, and can cause restriction of motion. While this may be tolerated with some medications and lifestyle adjustments, there may come a time when surgical treatment is necessary.

6. Treatment[edit]

7. The main source of shoulder pain, shoulder arthritis, is first managed in early stages with physical therapy and non-steroidal anti-inflammatory (NSAID) drugs.[2] Surgery is considered if pain worsens. There are two primary methods for shoulder replacement; total shoulder replacement and reverse shoulder replacement. Total shoulder replacement involves a replacement of the ball and socket joint. A metal ball is used to replace the humeral head and a plastic socket replaces the cartilage on the glenoid cavity. Once complete this method looks and functions like the original joint.[3] 8. A reverse shoulder replacement is used to treat patients with severe damage or arthritis of the shoulder joint, and particularly patients with severe rotator cuff tears.[4] It involves the insertion of a hemispherical implant in place of the glenoid instead of the humerus and the cup section being added to the humerus. This method allows the arm to be moved primarily by the deltoid instead of the rotator cuff. An important complication following reverse shoulder replacement is known as scapular notching, in which erosion of the scapular neck is caused by repetitive contact between the humeral component and the inferior scapular neck during adduction.[5] Scapular notching may be more likely in patients with shorter scapular neck lengths.[6] 9. Non surgery options are preferred treatment for a variety of reasons. Besides not wanting to risk the usual risks of surgery such as infection, shoulder replacement can lead to a variety of complications including rotator cuff tear and glenohumeral instability. However despite these risks, shoulder replacement shows promise with a low rate of complication which depending on the type of surgery is close to 5%.[7]

10.

External links[edit]

List of orthopedic implants

From Wikipedia, the free encyclopedia
An orthopedic implant is a medical device manufactured to replace a missing joint or bone or to support a damaged bone.[1] Internal fixation is an operation in orthopedics that involves the surgical implementation of implants for the purpose of repairing a bone.[2][3] Among the most common types of medical implants are the pins, rods, screws and plates used to anchor fractured bones while they heal.[4]

Contents [hide]

1 Implants and their uses 2 Image gallery 3 References 4 See also

Implants and their uses[edit]

Austin-Moore prosthesis : for fracture of the neck of femur[5] Baksi's prosthesis : for elbow replacement[6] Buttress plate : for condylar fractures of tibia [7] Charnley prosthesis : for total hip replacement[8] Condylar blade plate : for condylar fractures of femur[9] Dynamic compression plate Ender's nail : for fixing inter-trochanteric fracture[10] Grosse-Kempf (GK) nail : for tibial or femoral shaft fracture [11] Gamma nail : for peri-trochanteric fractures[12] Harrington rod: for fixation of the spine [13] Hartshill rectangle : for fixation of the spine[14] Insall Burstein prosthesis : for total knee replacement [15] Interlocking nail : for femoral or tibial shaft fractures[16] Kirschner wire : for fixation of small bones [17] Kuntscher nail : for fracture of the shaft of femur[18] Luque rod : for fixation of the spine[19] Moore's pin : for fracture of the neck of femur Neer's prosthesis : for shoulder replacement[20] Rush nail : for diaphyseal fractures of long bone [21] Smith Peterson (SP) nail : for fracture of the neck of femur Smith Peterson nail with McLaughlin's plate : for inter-trochanteric fracture Seidel nail : for fracture of the shaft of humerus [22] Souter's prosthesis : for elbow replacement[23] Steffee plate : for fixation of the spine[24] Steinmann pin : for skeletal traction[25] Swanson prosthesis : for the replacement of joints of the fingers[26] Talwalkar nail : for fracture of radius and ulna[27]

Thompson prosthesis : for fracture of the neck of femur[28] Unicompartmental knee : for partial knee replacement[29]

Image gallery[edit]
This section contains a gallery of images. Galleries containing indiscriminate images of the article subject are discouraged; please improve or remove the section accordingly, moving freely licensed images to Wikimedia Commons if not already hosted there. (August 2012)

Moore's pin

Austin Moore prostheses

Steinman pins

Shans pin

Rush nail

Butress plates

References[edit]
1. Jump up^

Implant (medicine)
From Wikipedia, the free encyclopedia

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (June 2009)

Orthopedic implants to repair fractures to the radius and ulna. Note the visible break in the ulna. (right forearm)
An implant is a medical device manufactured to replace a missing biological structure, support a damaged biological structure, or enhance an existing biological structure. Medical implants are man-made devices, in contrast to a transplant, which is a transplantedbiomedical tissue. The surface of implants that contact the body might be made of a biomedical material such as titanium, silicone orapatite depending on what is the most functional. In some cases implants contain electronics e.g. artificial pacemaker and cochlear implants. Some implants are bioactive, such as subcutaneous drug delivery devices in the form of implantable pills or drug-eluting stents.

Contents [hide]

1 Applications 2 Classification
o

2.1 United States classification

3 Complications 4 Failures 5 See also 6 References 7 External links

Applications[edit]
Among the most common types of medical implants are the pins, rods, screws, and plates used to anchor fractured bones while they heal.[citation needed]

Classification[edit]
United States classification[edit]
Medical devices are classified by the US Food and Drug Administration (FDA) under three different classes depending on the risks the medical device may impose on the user. Class I devices are considered to pose the least amount of risk to the user and require the least amount of control. Class I devices include simple devices such as arm slings and hand-held surgical instruments. Class II devices are considered to need more regulation than Class I devices and are required to undergo specific requirements before FDA approval. Class II devices include Xray systems and physiological monitors. Class III devices require the most regulatory controls since the device supports or sustains human life or may not be well tested. Class III devices include replacement heart valves and implanted cerebellar stimulators. Many implants typically fall under Class II and Class III devices. [1]

Complications[edit]
Under ideal conditions, implants should initiate the desired host response. Ideally, the implant should not cause any undesired reaction from neighboring or distant tissues. However, the interaction between the implant and the tissue surrounding the implant can lead to complications. [2] The process of implantation of medical devices is subjected to the same complications that other invasive medical procedures can have during or after surgery along with several different complications. Common complications includeinfection, inflammation, and pain. Other complications that can occur include risk of rejection from implantinduced coagulation and allergic foreign body response. Depending on the type of implant, the complications may vary. When the site of an implant becomes infected during or after surgery, the surrounding tissue becomes infected by microorganisms. Three main categories of infection can occur after operation. Superficial immediate infections arecaused by organisms that commonly grow near or on skin. The infection usually occurs at the surgical opening. Deep immediate infection, the

second type, occurs immediately after surgery at the site of the implant. Skin-dwelling and airborne bacteria cause deep immediate infection. These bacteria enter the body by attaching to the implants surface prior to implantation. Though not common, deep immediate infections can also occur from dormant bacteria from previous infections of the tissue at the implantation site that have been activated from being disturbed during the surgery. The last type, late infection, occurs months to years after the implantation of the implant. Late infections are caused by dormant blood-borne bacteria attached to the implant prior to implantation. The blood-borne bacteria colonize on the implant and eventually get released from it. Depending on the type of material used to make the implant, it may be infused with antibiotics to lower the risk of infections during surgery. However, only certain types of materials can be infused with antibiotics, the use of antibiotic-infused implants runs the risk of rejection by the patient since the patient may develop a sensitivity to the antibiotic, and the antibiotic may not work on the bacteria. [3] Inflammation, a common occurrence after any surgical procedure, is the bodys response to tissue damage as a result of trauma, infection, intrusion of foreign materials, or local cell death, or as a part of an immune response. Inflammation starts with the rapid dilation of local capillaries to supply the local tissue with blood. The inflow of blood causes the tissue to become swollen and may cause cell death. The excess blood, or edema, can activate pain receptors at the tissue. The site of the inflammation becomes warm from local disturbances of fluid flow and the increased cellular activity to repair the tissue or remove debris from the site. [4] Implant-induced coagulation is similar to the coagulation process done within the body to prevent blood loss from damaged blood vessels. However, the coagulation process is triggered from proteins that become attached to the implant surface and lose their shapes. When this occurs, the protein chances conformation and different activation sites become exposed, which may trigger an immune system response where the body attempts to attack the implant to remove the foreign material. The trigger of the immune system response can be accompanied by inflammation. The immune system response may lead to chronic inflammation where the implant is rejected and has to be removed from the body. The immune system may encapsulate the implant as an attempt to remove the foreign material from the site of the tissue by encapsulating the implant in fibrogen and platelets. The encapsulation of the implant can lead to further complications, since the thick layers of fibrous capsulation may prevent the implant from performing the desired functions. Bacteria may attack the fibrous encapsulation and become embedded into the fibers. Since the layers of fibers are thick, antibiotics may not be able to reach the bacteria and the bacteria may grow and infect the surrounding tissue. In order to remove the bacteria, the implant would have to be removed. Lastly, the immune system may accept the presence of the implant and repair and remodel the surrounding tissue. Similar responses occur when the body initiates an allergic foreign body response. In the case of an allergic foreign body response, the implant would have to be removed. ([5]

Failures[edit]
Main article: Implant failure The many examples of implant failures include rupture of silicone breast implants, hip replacement joints, and artificial heart valves, such as the BjorkShiley valve, all of which have caused FDA intervention. The consequences of implant failure depend on the nature of the implant and its position in the body. Thus, heart valve failure is likely to threaten the life of the individual, while breast implant or hip joint failure is less likely to be life-threatening.

Oxygenator
From Wikipedia, the free encyclopedia

This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (May 2007) An oxygenator is a medical device that is capable of exchanging oxygen and carbon dioxide in the blood of human patient during surgical procedures that may necessitate the interruption or cessation of blood flow in the body, a critical organ or great blood vessel. These organs can be the heart, lungs or liver, while the great vessels can be the aorta,pulmonary artery, pulmonary veins or vena cava. An oxygenator is typically utilized by a perfusionist in cardiac surgery in conjunction with the heart-lung machine. However, oxygenators can also be utilized in extracorporeal membrane oxygenation in neonatal intensive care units by nurses. For most cardiac operations such as coronary artery bypass grafting, the cardiopulmonary bypass is performed using a heart-lung machine (or cardiopulmonary bypass machine). The heart-lung machine serves to replace the work of the heart during the open bypass surgery. The machine replaces both the heart's pumping action and the lungs' gas exchange function. Since the heart is stopped during the operation, this permits the surgeon to operate on a bloodless, stationary heart. One component of the heart-lung machine is the oxygenator. The oxygenator component serves as the lung, and is designed to expose the blood to oxygen and remove carbon dioxide. It is disposable and contains about 24 m of a

membrane permeable to gas but impermeable to blood, in the form of hollow fibers. Blood flows on the outside of the hollow fibers, while oxygen flows in the opposite direction on the inside of the fibers. As the blood passes through the oxygenator, the blood comes into intimate contact with the fine surfaces of the device itself. Gas containing oxygen and medical air is delivered to the interface between the blood and the device, permitting the blood cells to absorb oxygen molecules directly.
Contents [hide]

1 Heparin-coated blood oxygenator

o o

1.1 Rationale 1.2 Surgical outcomes

2 See also 3 Footnotes

Heparin-coated blood oxygenator[edit]

Rationale[edit]

Operations which involve uncoated CPB circuits require a high dose of systemic heparin. Although the effects of heparin are reversible by administering protamine, there are a number of side effects associated with this. Side effects can include allergic reaction to heparin resulting in thrombocytopenia, various reactions to the administration of protamine and post-operative hemorrhage due to inadequate reversal of the anticoagulation. Systemic heparin does not completely prevent clotting or the activation of complement,neutrophils, and monocytes, which are the principal mediators of the inflammatory response. This response produces a wide range of cytotoxins, and cell-signaling proteins that circulate throughout the patient's body during surgery and disrupt homeostasis. The inflammatory responses can produce microembolic particles. A greater source of such microemboli are caused by the suction of surgical debris and lipids into the CPB circuit.[1] Microparticles obstruct arterioles that supply small nests of cells throughout the body and, together with cytotoxins, damage organs and tissues and temporarily disturb organ function. All aspects of cardiopulmonary bypass, including manipulation of the aorta by the surgeon, may be associated with

neurological symptoms following perfusion. Physicians refer to such temporary neurological deficits as pumphead syndrome. Heparin-coated blood oxygenators are one option available to a surgeon and a perfusionist to decrease morbidity associated with CPB to a limited degree. Heparin-coated oxygenators are thought to:

Improve overall biocompatibility and host homeostasis Mimic the natural endothelial lining of the vasculature Reduce the need for systemic anticoagulation Better maintain platelet count Reduce adhesion of plasma proteins Prevent denaturation and activation of adhered proteins and blood cells Avoid complications resulting from an abnormal pressure gradient across

the oxygenator Surgical outcomes[edit] Heparin coating is reported to result in similar characteristics to the native endothelium. It has been shown to inhibit intrinsic coagulation, inhibit host responses to extracorporeal circulation, and lessen postperfusion, or pumphead, syndrome. Several studies have examined the clinical efficacy of these oxygenators. Mirow et al. 2001 examined the effects of heparin-coated cardiopulmonary bypass systems combined with full and low dose systemic heparinization in coronary artery bypass patients. The researchers concluded that:

Heparin-coated extracorporeal circuits with reduced systemic heparinization lead to significantly increased thrombin generation. Postoperative bleeding was reduced with low systemic heparinization, but the reduction was not significant.

Ovrum et al. 2001 compared the clinical outcomes of 1336 patients with the Carmeda Bioactive Surface and Duraflo II coatings. The researchers concluded that:

Duraflo II patients required less heparin to keep the target activated clotting time

Effects on renal function and platelets were similar Incidences of perioperative MI, stroke, and hospital mortality were similar Reduced incidence of postoperative atrial fibrillation compared to identical uncoated controls Overall clinical results were favorable in both groups

Statistics and conclusions from more studies are available here. Clearly, heparin-coated blood oxygenators exhibit some advantages over non-coated oxygenators. Some hospitals use heparin-coated oxygenators for the large majority of their cases requiring cardiopulmonary bypass. It is unclear whether most surgeons actually reduce the amount of systemic heparin used when their patients are being perfused with heparin-coated oxygenators. Ultimately, each surgeon makes this decision based upon the needs of individual patient. Although they offer advantages, these oxygenators are not widely regarded by surgeons as revolutionary breakthroughs in cardiopulmonary bypass. This is attibutable to the fact that most of the morbidity associated with CPB is not caused by the contact between the blood with the oxygenator. The leading cause of hemolysis and microemboli is the return of blood suctioned from the surgical field to the CPB circuit. This blood has come into contact with air, lipids and debris that can significantly increase system inflammatory response. Surgeons are instead looking to off-pump cardiac procedures, wherein surgery is performed on beating hearts, as the next big thing in open heart surgery. Coated circuits have not been proven to alter surgical outcomes in any statistically significant manner. Furthermore, coated circuits are significantly more expensive than conventional circuits.

See also[edit]

BLOOD BAGS

Operacin Puerto doping case

From Wikipedia, the free encyclopedia

Part of a series on

Doping in sport
Substances and types[show] Terminology[show] History[show] Doping-related lists[show] Anti-doping bodies[show]

V T E

Operacin Puerto (Operation Mountain Pass)[1] is the code name of a Spanish Police operation against the doping network of Doctor Eufemiano Fuentes, started in May 2006, which resulted in a scandal that involved several of the world's most famous cyclists at the time. Media attention has focused on the small number of professional road cyclists named, however sportspeople from other disciplines including football and tennis have also been connected with the scandal.[2] Fifteen had been acquitted by May 2007, while three had admitted doping or evidence of blood doping was found.[3][4]
Contents
[hide]

1 Timeline
o o o o o o

1.1 Revelations by Jess Manzano 1.2 Police action 1.3 Suspensions 1.4 Additional leaks 1.5 Legal repercussions 1.6 Admissions and evidence of doping

1.7 Trial

2 List of athletes named

o

2.1 Cyclists

2.1.1 Teams 2.1.2 Others 2.1.3 Already retired or suspended

2.2 Other athletes

3 See also 4 References

Timeline[edit]
Revelations by Jess Manzano[edit]

In March 2004 in an interview with the Spanish newspaper Diario AS, Jess Manzano exposed systematic doping in his former cycling team, Kelme. He detailed blood doping[5] as well as the performance-enhancing drugs he used while on the team.[6] The investigation and the allegations he made led to questioning of several members of the team in April 2004. These included Eufemiano Fuentes who was the Kelme team doctor, Walter Vir the doctor before Fuentes, and Alfredo Crdova who was working for Liberty Seguros-Wrth but involved with Kelme in 2003.[7] An investigation began into the practices of Fuentes in early 2006 by the anti-drug trafficking arm of the Spanish Guardia Civil.[8]
Police action[edit]

On 23 May 2006, Spanish Guardia Civil arrested the directeur sportif of the Liberty Seguros-Wrth team, Manolo Saiz, and four others including Fuentes, accused of dopingpractices with riders.[9] Spanish police raided residences. In one, belonging to Fuentes, they found a thousand doses of anabolic steroids, 100 packets of blood products, and machines to manipulate and transfuse them.[10] The Guardia Civil found a list naming other cyclists involved . Liberty Seguros withdrew their sponsorship, which left Wrth as sole sponsor.[11]
Suspensions[edit]

As more names leaked to the press, T-Mobile Team asked riders to sign a statement that they had never worked with Fuentes,[12] while the Phonak team suspended Santiago Botero and Jos Enrique Gutirrez, who had finished

second in the 2006 Giro d'Italia.[13] Tour de France organisers ASO considered withdrawing invitations to Wrth andComunidad Valenciana.[14] On 1 June, the director of Valenciana, Jos Ignacio Labarta, resigned.[15] Wrth found a new sponsor, five Kazakh companies united under the name of the capital, Astana, and became Astana-Wrth.[16] ASO withdrew Comunitat Valenciana's invitation, moving riders to send blood samples to be analysed to prove their innocence.[17] The Vuelta a Espaa considered expelling the team.[18] After El Pas published details of Operacin Puerto, Spanish riders boycotted the Spanish National Road Race Championships, which was cancelled after 500 metres.[19] ASO wrote asking Astana-Wrth not to take part in the Tour de France, which the team ignored. Jan Ullrich, linked to Fuentes by the newspaper, threatened to sue El Pas. The Court of Arbitration for Sport (CAS) said Astana-Wrth were to be accepted in the Tour. The Spanish authorities lifted the secret of summary two days before the start of the 2006 Tour, formally involving all 56 riders found in Fuentes' lists. Because Ullrich and scar Sevilla were in the lists, T-Mobile suspended them.[20] The example was followed by Ivan Basso's Team CSC and Francisco Mancebo's AG2R Prvoyance. ASO demanded all riders involved be withdrawn by their teams, even though Astana-Wrth had received the support of the CAS. The day before the Tour, Astana-Wrth yielded to pressure. Five of their riders had been excluded by ASO for involvement in the scandal, leaving only four of the six riders required. Francisco Mancebo, fourth the previous year and involved in the case, ended his career, according to his directeur sportif Vincent Lavenu. As a result, none of the riders who finished in the top 5 of the 2005 Tour de France started in the 2006 edition. On 3 July, Wrth also withdrew sponsorship of the Astana team. They had planned sponsorship only if it were not excluded from a race. Six days later, T-Mobile fired Rudy Pevenage, directeur sportif, because he was also involved. On 21 July, the team suspended Ullrich and Sevilla,

effectively sacking them. On the same day, Spanish cycling newspaper Meta2Mil listed codenames used by Fuentes which had not been deciphered by police.
Additional leaks[edit]

In November 2006, El Mundo[citation needed] claimed that an anti-doping laboratory in Barcelona which analyzed 99 bags of blood plasma seized in Operacin Puerto found "high levels of erythropoietin (EPO)". This suggested athletes working with Fuentes had been boosting their performance in ways other than blood doping. El Mundo suggested those implicated had delegated their cheating to Fuentes, and would not have been able to control the level of EPO they were taking. After studying the Barcelona lab's report, El Mundo described Fuentes's program as: riders would visit Fuentes a few weeks before a race and have blood removed. Fuentes would run the blood through a centrifuge, separating the blood plasma from the red blood cells. The cells would be re-injected shortly before competition, boosting resistance to fatigue. If haematocrit levels (volume of red blood cells) got dangerously high, they would re-inject plasma as well, enhanced with EPO, to dilute the red blood cells and avoid detection. The Barcelona lab did not identify any athlete responsible for any of the 99 tested bags of blood.[21]
Legal repercussions[edit]

On 26 July 2006, five Astana riders were cleared by Spanish courts. The five Joseba Beloki, Isidro Nozal, Srgio Paulinho, Allan Davis and Alberto Contador - received a document clearing them of links to Operacin Puerto, the Spanish newspaper El Diario Vasco reported.[22] On 8 October, the Madrid court in charge of the case told the Spanish cycling federation, the Real Federacin Espaola de Ciclismo (RFEC), that court documents could not be used in the federation's investigations.[23] On 13 October, Ivan Basso was cleared by Italian authorities due to lack of evidence. Ullrich was cleared by the Spanish courts on 25 October. The judge ruled that Ullrich and Basso were put under investigation without proof of involvement.[24]

On 28 October, the RFEC closed disciplinary files against cyclists in the investigation. However, the RFEC will initiate disciplinary investigations on Manolo Siz.[25] UCI president Pat McQuaid was reported to feel let down by authorities in Spain. He hoped teams would require cyclists to submit DNA samples to clear their names.[26] The investigations into Spanish riders were suspended.[27] On 7 March 2007, the case was dropped through lack of evidence of crime.[28]
Admissions and evidence of doping[edit]

On 3 April 2007, the German news agency sid said nine bags of blood marked Jan, number 1 or Hijo Rudicio (Son of Rudy) matched Jan Ullrich's saliva DNA.[4] On 7 May, Basso admitted involvement with the scandal to the Italian National Olympic Committee (CONI).[3] On 9 May, Michele Scarponi admitted he was Zapatero in Fuentes' files.[29] And on 30 June, Jrg Jaksche admitted he was Bella.[30]
Trial[edit]

In January 2013, the Operacion Puerto trial went underway, and Eufemiano Fuentes offered to reveal the names of all the athletes who were his clients. Julia Santamaria, the judge presiding the trial, told Fuentes that he was not under obligations to name any athlete other than the cyclists implicated. Fuentes stated that he supplied athletes in other sports with drugs and said: I could identify all the samples [of blood]. If you give me a list I could tell you who corresponds to each code on the [blood] packs.[31] On the 30 April 2013 Fuentes was found guilty and given a one year suspended prison sentence. The judge also ruled on a request to hand over blood bags to the Spanish anti-doping agency. The judge ordered the blood bags destroyed, but the anti-doping agency has appealed.[32] Additional appeals where filed by the International Cycling Union, theItalian National Olympic Committee and the World Anti-Doping Agency, as well as by the prosecution.[33]

List of athletes named[edit]

According to the Guardia Civil,[20][34][35] the following athletes have been named.
Cyclists[edit]

Teams[edit] Astana-Wrth Alberto Contador removed from the case by Spanish courts (26 July 2006).[22] Allan Davis removed from the case by Spanish courts (26 July 2006),[22] investigation closed by the Australian Sports Anti-Doping Authority (14 December).[36] Joseba Beloki removed from the case by Spanish courts (26 July 2006).[22] David Etxebarra Isidro Nozal removed from the case by Spanish courts (26 July 2006).[22] Unai Osa Srgio Paulinho removed from the case by Spanish courts (26 July 2006).[22] Michele Scarponi - admitted he is Zapatero in Fuentes' files.[29] Scarponi was suspended on 16 May 2007.[37] Marcos Serrano ngel Vicioso Comunidad Valenciana

Vicente Ballester removed from the case by Spanish courts (28 July 2006).[38] David Bernabeu removed from the case by Spanish courts (28 July 2006).[38] David Blanco removed from the case by Spanish courts (28 July 2006).[38] Jos Adrin Bonilla removed from the case by Spanish courts (28 July 2006).[38] Juan Gomis removed from the case by Spanish courts (28 July 2006).[38] Eladio Jimnez removed from the case by Spanish courts (28 July 2006).[38] David Latasa removed from the case by Spanish courts (28 July 2006).[38] Javier Pascual Rodrguez removed from the case by Spanish courts (28 July 2006).[38]

Rubn Plaza removed from the case by Spanish courts (28 July 2006).[38] Others[edit]

AG2R Prvoyance Francisco Mancebo initially retired from cycling,[39] but having severed ties with AG2R,[40] joined Spanish professional continental team Relax-Gam.[41] In 2009 he raced with USA-based Rock Racing. Caisse d'Epargne-Illes Balears

Constantino Zaballa Alejandro Valverde the source of blood marked VALV.(PITI) (Piti being believed to be the name of Valverde's dog at the time).[42] Valverde was suspended from racing in Italy from May 2009, and in May 2010 a two year suspension, backdated to 1 January 2010, was applied. Team CSC Ivan Basso Basso's contract with CSC was terminated by mutual agreement on 18 October 2006.[43] On 27 October 2006 the case was dropped by the Federazione Ciclistica Italiana due to lack of evidence,[44] and he was then employed in December 2006 by Discovery Channel.[45] On 24 April 2007 Basso was suspended by Discovery Channel when the Italian National Olympic Committee (CONI) reopened his case. On 1 May 2007 Basso requested to be released from his Discovery Channel contract. This was granted.[46] Basso attended a hearing on 2 May,[47] and on 7 May 2007, admitted that he was Birillo.[3] Basso was suspended on 16 May 2007.[37] Frnk Schleck - Schleck admitted transferring nearly 7000 euros to a bank account held by Dr. Fuentes, but denied any doping or personal contact with Fuentes.[48] Phonak Hearing Systems

Jos Ignacio Gutirrez Jos Enrique Gutirrez Santiago Botero case dropped by disciplinary committee of the Federacin Colombiana de Ciclismo (2 October 2006).[49]

Saunier Duval-Prodir Carlos Zrate Koldo Gil T-Mobile Team scar Sevilla - codename Sevillano. Jan Ullrich - DNA tests confirmed that the 9 bags that were marked Jan, number 1 or Hijo Rudicio (Son of Rudy) all contained Jan Ullrich's blood.[4] An alleged doping plan was published in the newspaper, Sddeutsche Zeitung, where Ullrich's suspected doping during the first week of the 2005 Tour de France was described. In 2012, Ullrich admitting to cooperate with Dr.Fuentes saying it was a mistake.[50] Tinkoff Credit Systems Tyler Hamilton - at the time of the initial investigation, Hamilton was suspended for a prior doping offence. Politiken, a Danish newspaper, published details of alleged doping diary of Hamilton during the 2003 season when he rode for Team CSC. It described intake of EPO, growth hormones, testosterone and insulin on 114 days during the 200 day season of 2003.[51] According to allegations originally published in El Pas, Hamilton is to have paid over 43,000 to Fuentes and that in 2003 Hamilton took erythropoietin, blood transfusions, growth hormone, a hormone taken by menopausal women and anabolic steroids.[52] Jrg Jaksche - at the time of the initial investigation, Jaksche rode for Astana-Wrth. On 30 June 2007, Jaksche admitted to Der Spiegel that he used Fuentes' services. He said that he was Bella, or number 20. Jaksche had been under suspension by Tinkoff Credit Systems since May.[30] Unibet

Carlos Garca Quesada Already retired or suspended[edit]

Michele Bartoli - on 25 May 2007 La Gazzetta dello Sport reported that Bartoli was connected to Fuentes with the code

name Sansone. Bartoli has not commented on this accusation.[53]

ngel Casero Roberto Heras Santiago Prez Marco Pantani (deceased) Corriere della Sera reported that Pantani was connected to Fuentes with the code name PTNI in 2003.[54]

Mario Cipollini, codename "Maria"

according to the Gazzetta dello Sport.[55] Other athletes[edit] On 5 July 2006, Fuentes was indignant that only cyclists had been named and said he also worked with tennis and football players.[2] On 27 July 2006, IAAF was assured by Spanish prosecutors that no track and field athletes were involved.[56] On 23 September 2006, former cyclist Jess Manzano told reporters from France 3 that he had seen "wellknown footballers" from La Liga visit the offices of Dr Fuentes.[57] In May 2007 Sepp Blatter, president of FIFA, at a World Anti-Doping Agency meeting in Montreal, was reportedly interested in the contents "of the Puerto file".[58] Le Monde had reported in December 2006 that they had possession of documents of Fuentes detailing "seasonal preparation plans" for Spanish football clubs FC Barcelona and Real Madrid. These plans did not specifically name any players.[59] This news seem to be only rumors, since the

French journal lost its trials in 2009 and 2011 against the FC Barcelona because he could not produce any proof of its allegations. In the ultimate judgement, on 14 November 2011, it was condemned to pay 15,000 euros of indemnity for "using false and unverified facts".[60] No other athletes had been named.

See also[edit]

Terumo Penpol
From Wikipedia, the free encyclopedia

Terumo Penpol Limited

Industry Founded

Medical Technology 1987 (as Peninsula Polymers Limited - Penpol)

Headquarters Thiruvananthapuram, India Key people Kimura Yoshihiro, Chairman; C. Balagopal, Senior advisor;C. Padmakumar Executive Director Products Blood-bags, Medical Electronic Products Employees Parent Website 822[1] Terumo Corporation, Japan trumopenpol.com

Terumo Penpol Limited (TPL) is a subsidiary of Terumo Corp., Japan, and is India's largest blood bag manufacturer. It is also the largest producers of blood bags in Asia, outside of Japan.

Contents [hide]

1 Origins 2 Operations 3 References 4 External links

Origins[edit]
The original company - Peninsula Polymers Limited (Penpol Ltd.) - was established in 1987[1] by C. Balagopal, a former Indian Administrative Service (IAS, 1977 Batch) officer from the Manipur Cadre.[2] It was established as joint venture with Sree Chitra Thirunal Institute of Medical Sciences and Technology and soon became the first company in India to produce blood bags using indigenous technology. In 1989, Penpol started exporting and followed it up it by setting up an R&D centre. In 1999, Tokyo-based Terumo Corporation signed a contract to acquire a 74% share of Peninsula Polymers Limited, and the new joint venture was renamed as Terumo Penpol Limited (TPL). The stake of financial institutions and other investors bought over by Terumo, leaving only the promoters and itself as shareholders.[3]

Operations[edit]
Terumo Penpol has its headquarters in Thiruvananthapuram, Kerala and employs 1200 people.[4] Terumo Penpol Blood Bags are sold in over 64 countries across the world and its medical equipment division has commissioned more than 25000 installations. TPL has entered its 25 year of operations in 2010, with an enhanced production capacity of 22 million blood bags per annum.[5] TPL has been winning the top exporter award or the second best exporter award for medical disposables every year from 1994 onwards.[5]

References[edit]
1. ^ Jump up to:a b

Plasma Economy
From Wikipedia, the free encyclopedia

This article contains TraditionalChinese text. Without properrendering support, you may seequestion marks, boxes, or other symbols instead of Chinese characters.

Plasma Economy (Chinese:) was a 19911995 plasmapheresis campaign by the Henan provincial government in China, in which blood plasma were extracted in exchange for money. The campaign attracted 3 million donors of mostly rural Chinese, and it is estimated at least 40% of the blood donors subsequently contracted AIDS.[1] The Plasma Economy campaign boomed due to demand by biotech companies, and became a lucrative source of income for middlemen. The campaign had low health and safety standards, and lacked proper sterilization procedures; needles, blood bags, and other equipment in contact with blood were often recycled and reused. It is estimated that by 2003, over 1.2 million people had contracted AIDS in Henan Province alone.[1]
Contents [hide]

1 History 2 See also 3 External links 4 References

History[edit]
Caijing noted that China's blood donation system is largely monetarily driven, and while attempts had been made in the 1980s to move to a voluntary system, they were mostly unsuccessful. [2]In the early 1990s, China restricted the import of blood products, while called for local investment by foreign pharmaceutical companies, especially to the province of Henan, where numerous plasmapheresis stations were built. The selling of blood plasma were seen by locals as a method to reduce poverty. In plasmapheresis, blood plasma is taken from donors, while the remaining blood constituents such as red blood cells are returned to the donor. The

blood plasma is then sold to pharmaceutical companies to produce bloodbased products. As a cost-cutting measure, some stations mixed several bloods in the same centrifuge, resulting in large-scale blood contamination.[2] As a result, by 1995, such stations were shut down in Henan province, while blood collection was restricted by area, although demand for blood plasma still remained strong. The impact of the Plasma Economy campaign had a long lasting effect. It is estimated that by 1999, the Caixian County in Henan had 43% of its blood donors being infected with AIDS,[2] while in the village of Wenlou, over 65% of its residents had contracted HIV.[3] HIV/AIDS activist Yan Lianke wrote the book The Dream of Ding Village in 2005 based on the incident.[4]

See also[edit]

Blood transfusion
From Wikipedia, the free encyclopedia

Blood transfusion
Intervention

Plastic bag with 0.5 - 0.7 liters containingpacked

red blood cells in citrate, phosphate,dextrose, and adenine (CPDA) solution ICD-9-CM MeSH OPS-301 code: MedlinePlus 99.0 D001803 8-80 000431

Illustration depicting intravenous blood transfusion

Blood transfusion is generally the process of receiving blood products into one's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but modern medical practice commonly uses only components of the blood, such as red blood cells, white blood cells, plasma, clotting factors, andplatelets. Units of packed red blood cells are typically only recommended when either a patient's hemoglobin level falls below 10g/dL orhematocrit falls below 30%; recently, this 'trigger' level has been decreased to 7-8g/dL, as a more restrictive strategy has been shown to have better patient outcomes.[1] This is in part due to the increasing evidence that there are cases where patients have worse outcomes when transfused.[2] One may consider transfusion for people with symptoms of cardiovascular disease such as chest pain or shortness of breath.[1] Globally around 85 million units of red blood cells are

transfused in a given year.[1] In cases where patients have low levels of hemoglobin but are cardiovascularly stable, parenteral iron is increasingly a preferred option based on both efficacy and safety.[3] Other blood products are given where appropriate, such as clotting deficiencies. When a patient's own blood is salvaged and reinfused during a surgery (e.g. using a cell salvage machine such as a Cell Saver), this can be considered a form of autotransfusion (and thus a form of transfusion) even though no "blood product" is actually created. Before this was possible, autotransfusion had referred only to pre-donating one's own blood autologously, which still occurs as well.
Contents [hide]

1 Pre-transfusion procedures
o o o o

1.1 Blood donation 1.2 Processing and testing of blood products after donation 1.3 Compatibility testing 1.4 Neonatal transfusion 2.1 Massive transfusion protocol 2.2 Epidemiology 3.1 Immunologic reaction 3.2 Infection 3.3 Inefficacy 3.4 Other 4.1 Early attempts with animal blood

2 Procedures
o o

3 Adverse effects
o o o o

4 History
o

4.1.1 Jean-Baptiste Denys 4.1.2 Richard Lower

o o o

4.2 Early efforts to transfuse human blood 4.3 Development of blood banking 4.4 The modern era 5.1 Religious

5 Ethical issues
o

6 Between animals 7 Blood substitutes 8 Alternative treatment options 9 See also 10 References 11 External links

Pre-transfusion procedures[edit]
Before a blood transfusion is given, there are many steps taken to ensure quality of the blood products, compatibility, and safety to the recipient.
Blood donation[edit]

Main article: Blood donation Blood transfusions typically use sources of blood: one's own (autologous transfusion), or someone else's (allogeneic or homologous transfusion). The latter is much more common than the former. Using another's blood must first start with donation of blood. Blood is most commonly donated as whole blood intravenously and collecting it with ananticoagulant. In developed countries, donations are usually anonymous to the recipient, but products in a blood bank are always individually traceable through the whole cycle of donation, testing, separation into components, storage, and administration to the recipient. This enables management and investigation of any suspected transfusion related disease transmission or transfusion reaction. In developing countries the donor is sometimes specifically recruited by or for the recipient, typically a family member, and the donation occurs immediately before the transfusion.
Processing and testing of blood products after donation[edit]

The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. Please improve this article and discuss the issue on the talk page. (June 2011)

A bag containing one unit of fresh frozen plasma

Donated blood is usually subjected to processing after it is collected, to make it suitable for use in specific patient populations. Collected blood is then separated into blood components by centrifugation: red blood cells, plasma, platelets, albumin protein, clotting factor concentrates, cryoprecipitate, fibrinogen concentrate, and immunoglobulins (antibodies). Red cells, plasma and platelets can also be donated individually via a more complex process called apheresis.

All donated blood is tested for infections.[citation needed] The current protocol tests donated blood for HIV-1, HIV-2, HTLV-1, HTLV-2,Hepatitis B, Hepatitis C, Syphilis (Treponema pallidum), Chagas disease (Trypanosoma cruzi), and West Nile Virus. In addition, platelet products are also tested for bacterial infections due to its higher inclination for contamination due to storage at room temperature. Presence of Cytomegalovirus (CMV) is also tested because of risk to certain immunocompromised recipients if given, such as those with organ transplant or HIV. However, not all blood is tested for CMV because only a certain amount of CMV-negative blood needs to be available to supply patient needs. Other than positivity for CMV, any products tested positive for infections are not used.

All donated blood is also tested for ABO and Rh groups, along with the presence of any red blood cell antibodies.

Leukoreduction is the removal of white blood cells by filtration. Leukoreduced blood products are less likely to cause HLAalloimmunization (development of antibodies against specific blood types), febrile non-hemolytic transfusion reaction, cytomegalovirus infection, and platelet-transfusion refractoriness.

Pathogen Reduction treatment that involves, for example, the addition of riboflavin with subsequent exposure to UV light has been shown to be effective in inactivating pathogens (viruses, bacteria, parasites and white blood cells) in blood products.[4][5][6] By inactivating white blood cells in donated blood products, riboflavin and UV light treatment can also replace gamma-irradiation as a method to prevent graft-versus-host disease (TA-

GvHD).[7][8][9] Compatibility testing[edit]

Illustration of labeled blood bag.

Main articles: ABO blood group system and Rh blood group system Before a recipient receives a transfusion, compatibility testing between donor and recipient blood must be done. The first step before a transfusion is given is to Type and Screen the recipient's blood. Typing of recipient's blood determines the ABO and Rh status. The sample is then Screened for any alloantibodies that may react with donor blood.[10] It takes about 45 minutes to complete (depending on the method used). The blood bank scientist also checks for special requirements of the patient (e.g. need for washed, irradiated or CMV negative blood) and the history of the patient to see if they have a previously identified antibodies and any other serological anomalies;.

A positive screen warrants an antibody panel/investigation to determine if it is clinically significant. An antibody panel consists of commercially prepared group O red cell suspensions from donors that have been phenotyped for antigens that correspond to commonly encountered and clinically significant alloantibodies. Donor cells may have homozygous (e.g. K+k-), heterozygous (K+k+) expression or no expression of various antigens (K-k-). The phenotypes of all the donor cells being tested are shown in a chart. The patient's serum is tested against the various donor cells. Based on the reactions of the patient's serum against the donor cells, a pattern will emerge to confirm the presence of one or more antibodies. Not all antibodies are clinically significant (i.e. cause transfusion reactions, HDN, etc.). Once the patient has developed a clinically significant antibody it is vital that the patient receive antigen-negative red blood cells to prevent future transfusion reactions. A direct antiglobulin test (Coombs test) is also performed as part of the antibody investigation.[11] If there is no antibody present, an immediate spin crossmatch or computer assisted crossmatch is performed where the recipient serum and donor rbc are incubated. In the immediate spin method, two drops of patient serum are tested against a drop of 3-5% suspension of donor cells in a test tube and spun in a serofuge. Agglutination or hemolysis (i.e., positive Coombs test) in the test tube is a positive reaction and the unit should not be transfused. If an antibody is suspected, potential donor units must first be screened for the corresponding antigen by phenotyping them. Antigen negative units are then tested against the patient plasma using an antiglobulin/indirect crossmatch technique at 37 degrees Celsius to enhance reactivity and make the test easier to read. In urgent cases where crossmatching cannot be completed, and the risk of dropping hemoglobin outweighs the risk transfusing uncrossmatched blood, O-negative blood is used, followed by crossmatch as soon as possible. Onegative is also used for children and women of childbearing age. It is preferable for the laboratory to obtain a pre-transfusion sample in these cases so a type and screen can be performed to determine the actual blood group of the patient and to check for alloantibodies.
Neonatal transfusion[edit]

To ensure the safety of blood transfusion to pediatric patients, hospitals are taking additional precaution to avoid infection and prefer to use specially tested pediatric blood units that are guaranteed negative for Cytomegalovirus. Most guidelines recommend the provision of CMV-negative blood components and not simply leukoreduced components for newborns or low birthweight infants in whom the immune system is not fully developed.[12] These specific requirements place additional restrictions on blood donors who can donate for neonatal use. vnv Neonatal transfusions typically fall into one of two categories:

"Top-up" transfusions, to replace losses due to investigational losses and correction of anemia. Exchange (or partial exchange) transfusions are done for removal of bilirubin, removal of antibodies and replacement of red cells (e.g., for anemia secondary to thalassemiasand other hemoglobinopathies).[13]

Procedures[edit]
Massive transfusion protocol[edit]

A massive transfusion protocol is typically defined as when it is anticipated that more than ten units of packed red blood cells will be needed.[14] Typically higher ratios of fresh frozen plasma and platelets are given relative to packed red blood cells.[14]
Epidemiology[edit]

In the United States, blood transfusions were performed nearly 3 million times during hospitalizations in 2011, making it the most common procedure performed. The rate of hospitalizations with a blood transfusion nearly doubled from 1997, from a rate of 40 stays to 95 stays per 10,000 population. It was the most common procedure performed for patients 45 years of age and older in 2011, and among the top five most common for patients between the ages of 1 and 44 years.[15]

Adverse effects[edit]
In the same way that the safety of pharmaceutical products are overseen by pharmacovigalence, the safety of blood and blood products are overseen by Haemovigilance. This is defined by the World Health Organization (WHO) as a

system "...to identify and prevent occurrence or recurrence of transfusion related unwanted events, to increase the safety, efficacy and efficiency of blood transfusion, covering all activities of the transfusion chain from donor to recipient." The system should include monitoring, identification, reporting, investigation and analysis of adverse events near-misses and reactions related to transfusion and manufacturing.[16] In the UK this data is collected by a charity called SHOT (Serious Hazards Of Transfusion).[17] Transfusions of blood products are associated with several complications, many of which can be grouped as immunological or infectious. There is also increasing focus (and controversy) on complications arising directly or indirectly from potential quality degradation during storage.[18] Overall, adverse events from transfusions in the US account for about $17 Billion - and in effect add more to the cost of each transfusion than acquisition and procedure costs combined.[19] While some complication risks depend on patient status or specific transfusion quantity involved, a baseline risk of complications simply increases in direct proportion to the frequency and volume of transfusion.
Immunologic reaction[edit]

Acute hemolytic reactions occur with transfusion of red blood cells, and occurs in about 0.016 percent of transfusions, with about 0.003 percent being fatal.[citation needed] This is due to destruction of donor erythrocytes by preformed recipient antibodies. Most often this occurs due to clerical errors or improper typing and crossmatching. Symptoms include fever, chills, chest pain, back pain, hemorrhage, increased heart rate, shortness of breath, and rapid drop in blood pressure. When suspected, transfusion should be stopped immediately, and blood sent for tests to evaluate for presence of hemolysis. Treatment is supportive. Kidney injury may occur due to the effects of the hemolytic reaction (pigment nephropathy).

Delayed hemolytic reactions occur more frequently (about 0.025 percent of transfusions) and are due to the same mechanism as in acute hemolytic reactions. However, the consequences are generally mild and a great proportion of patients may not have symptoms. However, evidence of hemolysis and falling hemoglobin levels may still occur. Treatment is

generally not needed, but due to the presence of recipient antibodies, future compatibility may be affected.

Febrile nonhemolytic reactions are due to recipient antibodies to donor white blood cells, and occurs in about 7% of transfusions. This may occur after exposure from previous transfusions. Fever is generally short lived and is treated with antipyretics, and transfusions may be finished as long as an acute hemolytic reaction is excluded. This is a reason for the nowwidespread use of leukoreduction - the filtration of donor white cells from red cell product units.

Allergic reactions may occur when the recipient has preformed antibodies to certain chemicals in the donor blood, and does not require prior exposure to transfusions. Symptoms include urticaria, pruritus, and may proceed to anaphylactic shock. Treatment is the same as for any other type 1 hypersensitivity reactions. A small population (0.13%) of patients are deficient in the immunoglobin IgA, and upon exposure to IgAcontaining blood, may develop an anaphylactic reaction.

Posttransfusion purpura is a rare complication that occurs after transfusion containing platelets that express a surface protein HPA-1a. Recipients who lack this protein develop sensitization to this protein from prior transfusions, and develop thrombocytopenia about 710 days after subsequent transfusions. Treatment is with intravenous immunoglobulin, and recipients should only receive future transfusions with washed cells or HPA-1a negative cells.

Transfusion-associated acute lung injury (TRALI) is an increasingly recognized adverse event associated with blood transfusion. TRALI is a syndrome of acute respiratory distress, often associated with fever, noncardiogenic pulmonary edema, and hypotension, which may occur as often as 1 in 2000 transfusions.[20] Symptoms can range from mild to lifethreatening, but most patients recover fully within 96 hours, and the mortality rate from this condition is less than 10%.[21] Although the cause of TRALI is not clear, it has been consistently associated with antiHLA antibodies. Because these types of antibodies are commonly formed

during pregnancy, several transfusion organisations have decided to use only plasma from men for transfusion.[22] TRALI is typically associated with plasma components rather than packed red blood cells (RBCs), though there is some residual plasma in RBC units.[22] Infection[edit] On rare occasion, blood products are contaminated with bacteria. This can result in life-threatening infection, also known as transfusion-transmitted bacterial infection. The risk of severe bacterial infection is estimated, as of 2002, at about 1 in 50,000 platelet transfusions, and 1 in 500,000 red blood cell transfusions.[23] It is important to note that blood product contamination, while rare, is still more common than actual infection. The reason platelets are more often contaminated than other blood products is that they are stored at room temperature for short periods of time. Contamination is also more common with longer duration of storage, especially when exceeding 5 days. Sources of contaminants include the donor's blood, donor's skin, phlebotomist's skin, and from containers. Contaminating organisms vary greatly, and include skin flora, gut flora, or environmental organisms. There are many strategies in place at blood donation centers and laboratories to reduce the risk of contamination. A definite diagnosis of transfusiontransmitted bacterial infection includes the identification of a positive culture in the recipient (without an alternative diagnosis) as well as the identification of the same organism in the donor blood. Since the advent of HIV testing of donor blood in the 1980s, the transmission of HIV during transfusion has dropped dramatically. Prior testing of donor blood only included testing for antibodies to HIV. However, due to latent infection (the "window period" in which an individual is infectious, but has not had time to develop antibodies), many cases of HIV seropositive blood were missed. The development of a nucleic acid test for the HIV-1 RNA has dramatically lowered the rate of donor blood seropositivity to about 1 in 3 million units. As transmittance of HIV does not necessarily mean HIV infection, the latter could still occur, at an even lower rate. The transmission of hepatitis C via transfusion currently stands at a rate of about 1 in 2 million units. As with HIV, this low rate has been attributed to the

ability to screen for both antibodies as well as viral RNA nucleic acid testing in donor blood. Other rare transmissible infections include hepatitis B, syphilis, Chagas disease, cytomegalovirus infections (in immunocompromised recipients), HTLV, and Babesia.
Inefficacy[edit]

Transfusion inefficacy or insufficient efficacy of a given unit(s) of blood product, while not itself a "complication" per se, can nonetheless indirectly lead to complications - in addition to causing a transfusion to fully or partly fail to achieve its clinical purpose. This can be especially significant for certain patient groups such as critical-care or neonatals. For red blood cells (RBC), by far the most commonly transfused product, poor transfusion efficacy can result from units damaged by the socalled storage lesion - a range of biochemical and biomechanical changes that occur during storage. With red cells, this can decrease viability and ability for tissue oxygenation.[24] Although some of the biochemical changes are reversible after the blood is transfused,[25] the biomechanical changes are less so,[26] and rejuvenation products are not yet able to adequately reverse this phenomenon.[27] There has been increasing controversy about whether a given product unit's age is a factor in transfusion efficacy, specifically about whether "older" blood directly or indirectly increases risks of complications.[28][29] Studies have not been consistent on answering this question,[30] with some showing that older blood is indeed less effective but with others showing no such difference; these developments are being closely followed by hospital blood bankers - who are the physicians, typically pathologists, who collect and manage inventories of tranfusable blood units. Certain regulatory measures are in place to minimize RBC storage lesion including a maximum shelf life (currently 42 days), a maximum auto-hemolysis threshold (currently 1% in the US, 0.8% in Europe), and a minimum level of post-transfusion RBC survival in vivo (currently 75% after 24 hours).[31] However, all of these criteria are applied in a universal manner that does not account for differences among units of product.[32] For example, testing for the post-transfusion RBC survival in vivo is done on a sample of healthy volunteers, and then compliance is presumed for all RBC units based

on universal (GMP) processing standards (of course, RBC survival by itself does not guarantee efficacy, but it is a necessary prerequisite for cell function, and hence serves as a regulatory proxy). Opinions vary as to the "best" way to determine transfusion efficacy in a patient in vivo.[33]In general, there are not yet any in vitro tests to assess quality or predict efficacy for specific units of RBC blood product prior to their transfusion, though there is exploration of potentially relevant tests based on RBC membrane properties such as erythrocyte deformability[34] and erythrocyte fragility (mechanical).[35] Many physicians have adopted a so-called "restrictive protocol" - whereby transfusion is held to a minimum - due in part to the noted uncertainties surrounding storage lesion, in addition to the very high direct and indirect costs of transfusions,[19] along with the increasing view that many transfusions are inappropriate or use too many RBC units.[36][37] Of course, restrictive protocol is not an option with some especially vulnerable patients who may require the best possible efforts to rapidly restore tissue oxygenation. Although tranfusions of platelets are far less numerous (relative to RBC), platelet storage lesion and resulting efficacy loss is also a concern.[38]
Other[edit]

Transfusion-associated volume overload is a common complication simply due to the fact that blood products have a certain amount of volume. This is especially the case in recipients with underlying cardiac or kidney disease. Red cell transfusions can lead to volume overload when they must be repeated due to insufficient efficacy (see above). Plasma transfusion is especially prone to causing volume overload due to its hypertonicity.

Hypothermia can occur with transfusions with large quantities of blood products which normally are stored at cold temperatures. Core body temperature can go down as low as 32 C and can produce physiologic disturbances. Prevention should be done with warming the blood to ambient temperature prior to transfusions.

Transfusions with large amounts of red blood cells, whether due to severe hemorrhaging and/or transfusion inefficacy (see above), can lead to an

inclination for bleeding. The mechanism is thought to be due to disseminated intravascular coagulation, along with dilution of recipient platelets and coagulation factors. Close monitoring and transfusions with platelets and plasma is indicated when necessary.

Metabolic alkalosis can occur with massive blood transfusions due to the breakdown of citrate stored in blood into bicarbonate

Hypocalcemia can also occur with massive blood transfusions due to the complex of citrate with serum calcium

Blood doping is often used by athletes, drug addicts or military personnel for reasons such as to increase physical stamina, to fake a drug detection test or simply to remain active and alert during the duty-times respectively. However a lack of knowledge and insufficient experience can turn a blood transfusion into a sudden death. For example, when individuals run the frozen blood sample directly in their veins this cold blood rapidly reaches the heart, where it disturbs the heart's original pace leading to cardiac arrest and sudden death.

History[edit]
Early attempts with animal blood[edit]

World War II Russian syringe for direct inter-human blood transfusion

Beginning with Harvey's experiments with circulation of the blood, research into blood transfusion began in the 17th century, with successful experiments in transfusion between animals. However, successive attempts by physicians to transfuse animal blood into humans gave variable, often fatal, results.

Jean-Baptiste Denys[edit] The first fully documented human blood transfusion was administered by Dr. Jean-Baptiste Denys, eminent physician to King Louis XIV of France, on June 15, 1667.[39] He transfused the blood of a sheep into a 15-year-old boy, who survived the transfusion.[40] Denys performed another transfusion into a labourer, who also survived. Both instances were likely due to the small amount of blood that was actually transfused into these people. This allowed them to withstand the allergic reaction. Denys' third patient to undergo a blood transfusion was Swedish Baron Gustaf Bonde. He received two transfusions. After the second transfusion Bonde died.[41] In the winter of 1667, Denys performed several transfusions on Antoine Mauroy with calf's blood, who on the third account died.[42] Much controversy surrounded his death. Mauroy's wife asserted Denys was responsible for her husband's death; she was accused as well, though it was later determined that Mauroy actually died from arsenic poisoning, Denys' experiments with animal blood provoked a heated controversy in France.[41] Finally, in 1670 the procedure was banned. In time, the British Parliament and the Vatican followed suit. Blood transfusions fell into obscurity for the next 150 years. Richard Lower[edit] Richard Lower examined the effects of changes in blood volume on circulatory function and developed methods for cross-circulatory study in animals, obviating clotting by closed arteriovenous connections. His newly devised instruments eventually led to actual transfusion of blood. "Many of his colleagues were present. Towards the end of February 1665 [when he] selected one dog of medium size, opened its jugular vein, and drew off blood, until ... its strength was nearly gone. Then, to make up for the great loss of this dog by the blood of a second, I introduced blood from the cervical artery of a fairly large mastiff, which had been fastened alongside the first, until this latter animal showed ... it was overfilled ... by the inflowing blood." After he "sewed up the jugular veins," the animal recovered "with no sign of discomfort or of displeasure." Lower had performed the first blood transfusion between animals. He was then "requested by the Honorable [Robert] Boyle ... to acquaint the Royal

Society with the procedure for the whole experiment," which he did in December 1665 in the Society's Philosophical Transactions.[citation needed] Six months later in London, Lower performed the first human transfusion of animal blood in Britain. At a meeting of the Royal Society, Lower stated he had "superintended the introduction in [a patient's] arm at various times of some ounces of sheep's blood at , and without any inconvenience to him." The recipient was Arthur Coga, "the subject of a harmless form of insanity." Sheep's blood was used because of speculation about the value of blood exchange between species; it had been suggested that blood from a gentle lamb might quiet the tempestuous spirit of an agitated person and that the shy might be made outgoing by blood from more sociable creatures. Lower wanted to treat Coga several times, but his patient refused. No more transfusions were performed. Shortly before, Lower had moved to London, where his growing practice soon led him to abandon research.[43]
Early efforts to transfuse human blood[edit]

James Blundell, pioneer of blood transfusion

The science of blood transfusion dates to the first decade of the 20th century, with the discovery of distinct blood types leading to the practice of mixing some blood from the donor and the receiver before the transfusion (an early form of cross-matching). In the early 19th century, British obstetrician Dr. James Blundell made efforts to treat hemorrhage by transfusion of human blood using a syringe. In 1818 following experiments with animals, he performed the first successful

transfusion of human blood to treat postpartum hemorrhage. Blundell used the patient's husband as a donor, and extracted four ounces of blood from his arm to transfuse into his wife. During the years 1825 and 1830, Blundell performed 10 transfusions, five of which were beneficial, and published his results. He also invented a number of instruments for the transfusion of blood.[44] He made a substantial amount of money from this endeavour, roughly $2 million ($50 million real dollars).[citation needed] In 1840, at St George's Hospital Medical School in London, Samuel Armstrong Lane, aided by Dr. Blundell, performed the first successful whole blood transfusion to treat haemophilia. George Washington Crile is credited with performing the first surgery using a direct blood transfusion in 1906 at St. Alexis Hospital in Cleveland while a professor of surgery at Case Western Reserve University.[when?][45] Early transfusions were risky and many resulted in the death of the patient. It was not until 1901, when the Austrian Karl Landsteinerdiscovered human blood groups, that blood transfusions became safer. Jan Jansk also discovered the human blood groups in which he classified blood into four groups I, II, III, IV. William Lorenzo Moss's blood typing technique was widely used throughout the world until World War II.[46] Mixing blood from two incompatible individuals can lead to an immune response, and the destruction of red blood cells releases free hemoglobin into the bloodstream, which can have fatal consequences. Karl Landsteiner discovered that when incompatible types are mixed, the red blood cells clump, and that this immunological reaction occurs when the receiver of a blood transfusion has antibodies against the donor blood cells. His work made it possible to determine blood type and allowed a way for blood transfusions to be carried out much more safely. For this discovery he was awarded the Nobel Prize in Physiology and Medicine in 1930, and many other blood groups have been discovered since.
Development of blood banking[edit]

Main article: Blood bank

Dr. Luis Agote (2nd from right) overseeing one of the first safe and effective blood transfusion in 1914

While the first transfusions had to be made directly from donor to receiver before coagulation, in the 1910s it was discovered that by adding anticoagulant and refrigerating the blood it was possible to store it for some days, thus opening the way for blood banks. The first non-direct transfusion was performed on March 27, 1914 by the Belgian doctor Albert Hustin, though this was a diluted solution of blood. The Argentine doctor Luis Agote used a much less diluted solution in November of the same year. Both used sodium citrate as an anticoagulant.[47] The First World War acted as a catalyst for the rapid development of blood banks and transfusion techniques. The first blood transfusion using blood that had been stored and cooled was performed on January 1, 1916.[citation needed] Geoffrey Keynes, a British surgeon, developed a portable machine that could store blood to enable transfusions to be carried out more easily. His work was recognized as saving thousands of lives during the war. Oswald Hope Robertson, a medical researcher and U.S. Army officer, is generally credited with establishing the first blood bank while serving in France during World War I.[48] The first academic institution devoted to the science of blood transfusion was founded by Alexander Bogdanov in Moscow in 1925. Bogdanov was motivated, at least in part, by a search for eternal youth, and remarked with satisfaction on the improvement of his eyesight, suspension of balding, and other positive symptoms after receiving 11 transfusions of whole blood. In fact, following the death of Vladimir Lenin, Bogdanov was entrusted with the study of Lenin's brain, with a view toward resuscitating the deceased Bolshevik leader. Bogdanov died in 1928 as a result of one of his experiments, when the blood of a student suffering from malaria and tuberculosis was given to him in a transfusion. Some

scholars (e.g. Loren Graham) have speculated that his death may have been a suicide, while others attribute it to blood type incompatibility, which was not completely understood at the time.[49] Today, Red Blood Cells (RBC) can be stored for up to 42 days / 6 weeks from the time of collection, assuming proper storage solutions and conditions. While this particular shelf life has little evidentiary basis and persists primarily for historical reasons, it remains the default metric in the absence of any direct means for measuring actual quality degradation of product units. Likewise, inventory is managed essentially on a "first-in-first-out" basis, due to the need to rely upon storage time as a rough indicator of quality (with many controversies surrounding the extent to which this is reliable).
The modern era[edit]

Charles R. Drew

Following Bogdanov's lead, the Soviet Union set up a national system of blood banks in the 1930s. News of the Soviet experience traveled to America, where in 1937 Bernard Fantus, director of therapeutics at the Cook County Hospital in Chicago, established the first hospital blood bank in the United States. In creating a hospital laboratory that preserved and stored donor blood, Fantus originated the term "blood bank". Within a few years, hospital and community blood banks were established across the United States. In the late 1930s and early 1940s, Dr. Charles R. Drew's research led to the discovery that blood could be separated into blood plasmaand red blood cells,

and that the plasma could be frozen separately. Blood stored in this way lasted longer and was less likely to become contaminated. Another important breakthrough came in 1939-40 when Karl Landsteiner, Alex Wiener, Philip Levine, and R.E. Stetson discovered theRhesus blood group system, which was found to be the cause of the majority of transfusion reactions up to that time. Three years later, the introduction by J.F. Loutit and Patrick L. Mollison of acid-citrate-dextrose (ACD) solution, which reduces the volume of anticoagulant, permitted transfusions of greater volumes of blood and allowed longer term storage. Carl Walter and W.P. Murphy, Jr. introduced the plastic bag for blood collection in 1950. Replacing breakable glass bottles with durable plastic bags allowed for the evolution of a collection system capable of safe and easy preparation of multiple blood components from a single unit of whole blood. In the field of cancer surgery replacement of massive blood loss became a major problem. The cardiac arrest rate was high. In 1963, C. Paul Boyan and Willam Howland discovered that the temperature of the blood and the rate of infusion greatly affected survival rates, and introduced blood warming to surgery.[50][51] Further extending the shelf life of stored blood was an anticoagulant preservative, CPDA-1, introduced in 1979, which increased the blood supply and facilitated resource-sharing among blood banks. As of 2006, there were about 15 million units of blood products transfused per year in the United States.[52]

Ethical issues[edit]
Religious[edit]

Objections to blood transfusions may arise for personal, medical, or religious reasons. For example, Jehovah's Witnesses object to blood transfusion primarily on religious groundsthey believe that blood is sacred, the Bible says "abstain from blood" (Acts 15:28,29) they have also highlighted complications associated with transfusion.[53]

Between animals[edit]
Main article: Blood type (non-human)

Veterinarians also administer transfusions to other animals. Various species require different levels of testing to ensure a compatible match. For example, cats have 3 known blood types, cattle have 11, dogs have 12, pigs 16 and horses have 34. However, in many species (especially horses and dogs), cross matching is not required before the firsttransfusion, as antibodies against non-self cell surface antigens are not expressed constitutively - i.e. the animal has to be sensitized before it will mount an immune response against the transfused blood. The rare and experimental practice of inter-species blood transfusions is a form of xenograft.

Blood substitutes[edit]
Main article: Blood substitutes Thus far, there are no available oxygen-carrying blood substitutes, which is the typical objective of a blood (RBC) transfusion; however, there are widely available non-bloodvolume expanders for cases where only volume restoration is required. These are helping doctors and surgeons avoid the risks of disease transmission and immune suppression, address the chronic blood donor shortage, and address the concerns of Jehovah's Witnesses and others who have religious objections to receiving transfused blood. A number of blood substitutes have been explored (and still are), but thus far they all suffer from many challenges. Most attempts to find a suitable alternative to blood thus far have concentrated on cell-free hemoglobin solutions. Blood substitutes could make transfusions more readily available in emergency medicine and in pre-hospital EMS care. If successful, such a blood substitute could save many lives, particularly in trauma where massive blood loss results. Hemopure, a hemoglobin-based therapy, is approved for use inSouth Africa.

Alternative treatment options[edit]

Although there are clinical situations where transfusion with red blood cells is the only clinically appropriate option, increasingly clinicians are looking at alternatives. This can be due to several reasons, such as patient safety, economic burden or scarcity of blood. Increasingly guidelines recommend

blood transfusions should be reserved for patients with or at risk of cardiovascular instability due to the degree of their anaemia[54][55] In these cases parenteral iron is recommended.

See also[edit]

HLL Lifecare
From Wikipedia, the free encyclopedia

HLL Lifecare Limited

Type Industry Founded

Public Health Care 1966, Thiruvananthapuram

Headquarters Thiruvananthapuram, Kerala,India Key people Dr. M. Ayyappan, Chairman & Managing Director Products Condoms Hormonal contraception Surgical Equipment Revenue INR 244 crores (FY 2005-2006) Website www.lifecarehll.com

HLL Lifecare Limited (formerly Hindustan Latex Limited) (HLL) is an Indian healthcare products manufacturing company based

inThiruvananthapuram, Kerala, India. A Government of India -owned corporation (Public-sector undertaking), it produces health care products, including condoms,Surgical Sutures, Hydrocephalus Shunts, Tissue Expanders, blood bags, and contraceptive pills. One of HLL's contraceptive products is ormeloxifene, branded as Saheli, a non-hormonal non-steroid weekly oral contraceptive.[1] In 2012, HLL announced a polymerase chain reaction based duplex test kit for chikungunya and dengue fever tests in collaboration with the Rajiv Gandhi Centre for Biotechnology, Trivandrum.[2]
Contents [hide]

1 History 2 See also 3 References 4 External links

History[edit]
Earlier Hindustan Lever Limited, had the same acronym HLL. But Hindustan Lever Limited changed their name as Hindustan Unilever Limited with acronym as HUL. Today HLL means HLL Lifecare Limited. In 2005, it established LifeSpring Hospitals, a 50-50 joint venture with the Acumen Fund, a U.S.-based nonprofit global venture philanthropy fund, to provide low-cost maternity services, starting at Hyderabad, today it has nine hospitals across Andhra Pradeshstate today.[3][4][5][6] In February 2014, HLL acquired 74% Equity in Goa Antibiotics and Pharmaceuticals Ltd.[7]

See also[edit]

Plateletpheresis
From Wikipedia, the free encyclopedia

Plateletpheresis
Intervention

A 250 mL bag of newly collected platelets. ICD-10-PCS ICD-9-CM MeSH 6A550Z2, 6A551Z2 99.05 D010983

Plateletpheresis
Intervention

A 250 mL bag of newly collected platelets. ICD-10-PCS MeSH 6A550Z2, 6A551Z2 D010983

Plateletpheresis (more accurately called thrombocytapheresis or thrombapheresis, though these names are rarely used) is the process of collecting thrombocytes, more commonly called platelets, a component of blood involved in blood clotting. The term specifically refers to the method of collecting the platelets, which is performed by a device used in blood donation that separates the platelets and returns other portions of the blood to the donor. Platelet transfusion can be a lifesaving procedure in preventing or treating serious complications from bleeding and hemorrhage in patients who have disorders manifesting as thrombocytopenia (low platelet count) or platelet dysfunction. This process may also be used therapeutically to treat disorders resulting in extraordinarily high platelet counts such as essential thrombocytosis.
Contents
[hide]

1 Platelet transfusion
o o o o o o

1.1 Plateletpheresis and whole blood platelets 1.2 Thrombocytopenia due to underproduction 1.3 Immune thrombocytopenia 1.4 Altered platelet functions 1.5 Cardiopulmonary bypass surgery 1.6 Drug-induced platelet dysfunction

2 Expected platelet increase after transfusion 3 Platelet collection

o o

3.1 Leukoreduction 3.2 Apheresis

4 Platelet donation
o

4.1 Adverse events

4.1.1 Vein scarring

5 See also 6 References 7 External links

Platelet transfusion[edit]
Platelet transfusions are traditionally given to those undergoing chemotherapy for leukemia, multiple myeloma, those with aplastic anemia, AIDS, hypersplenism, ITP, sepsis, bone marrow transplant, radiation treatment, organ transplant or surgeries such ascardiopulmonary bypass. Platelet transfusions should be avoided in those with TTP because it can worsen neurologic symptoms and acute renal failure, presumably due to creation of new thrombi as the platelets are consumed. It should also be avoided in those withheparin-induced thrombocytopenia (HIT) or disseminated intravascular coagulation (DIC).[1]
Plateletpheresis and whole blood platelets[edit]

Not all platelet transfusions use platelets collected by automated apheresis. The platelets can also be separated from donations ofwhole blood collected in a traditional blood donation, but there are several advantages to separating the platelets at the time of collection. The first advantage is that the wholeblood platelets, sometimes called "random" platelets, from a single donation are not numerous enough for a dose to give to an adult patient. They must be pooled from several donors to create a single transfusion, and this complicates processing and increases the risk of diseases that can be spread in transfused blood, such as human immunodeficiency virus.[citation needed] Collecting the platelets from a single donor also simplifies human leukocyte antigen (HLA) matching, which improves the chance of a successful transfusion. Since it is time-consuming to find even a single compatible donor for HLA-matched transfusions, being able to collect a full dose from a single donor is much more practical than finding multiple compatible donors. Plateletpheresis products are also easier to test for bacterial contamination, a leading cause of transfusion-associated deaths.[citation needed] Pooling of whole blood platelets is often done in an "open" system where the platelet containers are connected in a way that could expose the platelets to air, and pooled

platelets must be transfused promptly so that any contamination does not have time to grow. Problems with apheresis include the expense of the equipment used for collection. Whole blood platelets also do not require any additional donor recruitment, as they can be made from blood donations that are also used for packed red blood cells and plasma components.
Thrombocytopenia due to underproduction [edit]

Recipients in this category include those undergoing chemotherapy, those with myelophthisic anemia, AIDS, or with aplastic anemia. If indicated, transfusions (one thrombapheresis concentrate) should be given until recovery of platelet function, generally approximately twice weekly. Surgical bleeding due solely to thrombocytopenia occurs when platelets < 50,000/L while spontaneous bleeding occurs when platelets < 10,000/L. Thrombocytopenic patients can develop "dry" bleeding, that is, petechiae andecchymoses only. They will not suffer fatal hemorrhagic events unless they first have extensive mucosal bleeding, or "wet" bleeding. Therefore, in those with no bleeding or only "dry" bleeding, the threshold for transfusion should be between 5,000 to 10,000/L. A more conservative threshold of 20,000/L should be used in those with a fever or other risk factors for bleeding. Those with active bleeding or prior to surgery should have a threshold of 50,000/L. An unconfirmed, but helpful, way to determine whether a patient is recovering from chemotherapy-induced thrombocytopenia is to measure "reticulated" platelets, or young RNA-containing platelets, which signifies that the patient is starting to make new platelets.
Immune thrombocytopenia[edit]

Recipients in this category include those with ITP or drug-induced thrombocytopenia. Platelet transfusions are generally not recommended for this group of patients because the underlying cause involves antibodies that destroy platelets, therefore any newly transfused platelets will also be destroyed. More studies need to be done.
Altered platelet functions[edit]

Disorders of platelet function can be congenital or acquired. Most of these disorders are mild and may respond to therapy with desmopressin (dDAVP). Transfusion is not necessarily required. However, with some more severe

disorders such as Glanzmann thrombasthenia, transfusions with large amount of platelets may be needed. The number of transfusions may be reduced if these patients are given recombinant human factor VIIa since the underlying cause are antibodies to platelet glycoproteins IIb/IIIa.
Cardiopulmonary bypass surgery[edit]

This surgery can result in destruction of a large proportion of the patient's platelets and may render the remaining viable platelets to be dysfunctional. The indications for transfusion in such patients is controversial. General guidelines recommend not transfusing patients prophylactically but only when they are bleeding excessively, while also giving desmopressin.
Drug-induced platelet dysfunction[edit]

The most common of these is aspirin, and its similar drug class, the NSAIDs. Other antiplatelet drugs are commonly prescribed for patients with acute coronary syndromes such as clopidogrel and ticlopidine. When surgery is undertaken following the administration of these drugs, bleeding can be serious. Transfusion under these circumstances is not clear-cut and one has to use clinical judgment in these cases.

Expected platelet increase after transfusion[edit]

Platelet count increase as well as platelet survival after transfusion is related to the dose of platelets infused and to the patient's body surface area (BSA). Usually these values are less than what would be expected.

Corrected platelet count increment (CCI) = platelet increment at one hr x BSA (m2) / # platelets infused x 1011 Expected platelet increase (per L) = platelets infused x CCI / BSA (m2)

The theoretical value of the CCI is 20,000/L but clinically, the value is closer to 10,000/L. If the CCI is less than 5,000/L, patients are said to have "refractoriness" to platelet transfusion.

Platelet collection[edit]

A single line cartridge based, centrifuge machine. Collecting a 'double unit' in this instance.

The separation of individual blood components is done with a specialized centrifuge (see apheresis). The earliest manual forms of thrombapheresis are done by the separation of platelets from multiple bags of whole blood collected from donors or blood sellers. Since each blood bag (usually 250 mL or 500 mL) contains a relatively small number of platelets, it can take as many as a dozen blood bags (usually from 5 to 10 bags, depending on the size of the blood bags and each donor's platelet count) to accumulate a single unit of platelets (enough for one patient). This greatly increases the risks of the transfusion. Each unit of platelets separated from donated whole blood is called a "platelet concentrate". Modern automatic thrombapheresis allows blood donors to give a portion of their platelets, while keeping their red blood cells and at least a portion of blood plasma. Therefore, no more than three units of platelets are generally harvested in any one sitting from a donor. Most donors will donate a "single" or "double" unit, however the occurrence of "triples" has been increasing as more suitable donors are recruited. Because platelets have a shelf life of just 5 days, more platelet donors are always needed. Some centers are experimenting with 7 day platelets, but this requires additional testing and the lack of any preservative solutions means that the product is far more effective when fresh. Even though red blood cells can also be collected in the process, most blood donation organizations do not do so because it takes much longer for the human body to replenish their loss. If the donor donates both red blood cells and platelets, it takes months, rather than days or weeks, before they are

allowed to donate again (the guidelines regarding blood donation intervals are country-specific). In most cases, blood plasma is returned to the donor as well. However, in locations that have plasma processing facilities, a part of the donor's plasma can also be collected in a separate blood bag (see plasmapheresis).
Leukoreduction[edit]

Due to their higher relative density, white blood cells are collected as an unwanted component with the platelets. Since it takes up to 3 liters of whole blood (the amount of a dozen blood bags) to generate a dose of platelets, white blood cells from one or several donors will also be collected along with the platelets. A 70 kg (154 lb) man has only about 6 liters of blood. If all of the incidentally collected white blood cells are transfused with the platelets, substantial rejection problems can occur. Therefore, it is standard practice to filter out white blood cells before transfusion by the process of leukoreduction. Early platelet transfusions used a filter to remove white blood cells at the time of transfusion. It takes a trained person about 10 minutes to assemble the equipment, and this is not the safest or most efficient means of filtration because living white blood cells can release cytokines during storage and dead white blood cells can break up into smaller fragments that can still stimulate a dangerous response from the immune system. In addition, simple filtration can lead to increased risks of infection and loss of valuable platelets. Newer, more advanced thrombapheresis machines can filter white blood cells during separation. For example, with marginally acceptable whole blood (white blood cells: < 10,000/mm; platelets: > 150,000/mm), a dose (31011) of platelets comes with about 21010 white blood cells. This can seriously damage the patient's health. A dose of single-donor platelets prepared using latest filters can contain as little as 5106 white blood cells.
Apheresis[edit]

There are two types of manual platelet apheresis. Platelet-rich plasma (PRP) is widely used in North America and Buffy coat (BC) is more widely used in Europe.

Plasma can be collected simultaneously with a platelet donation.

Platelets are the clotting factor of the blood, and when donated, frequently go to cancer patients, because due tochemotherapy many cancer patients are unable to generate enough platelets of their own. The basic principles of automatic platelet apheresis are the same as in the manual procedure, but the whole procedure is performed by a computercontrolled machine. Since the donor's blood is processed in a sterile singleuse centrifuge, the unwanted components can be returned to the donor safely. This allows the apheresis machine to repeat the draw-centrifuge-return cycle to obtain more platelets. The bulk of the machine and the length of the donation process means most platelet donations are done in blood centers instead of mobile blood drives. Each country has its own rules to protect the safety of both donor and recipient. In a typical set of rules, a platelet donor must weigh at least 50 kg (110 lb) and have a platelet count of at least 150 x 109/L (150,000 platelets per mm).[1]

One unit has greater than 31011 platelets. Therefore, it takes 2 liters of blood having a platelet count of 150,000/mm to produce one unit of platelets. Some regular donors have higher platelet counts (over 300,000/mm); for those donors, it only takes about one liter of their blood to produce a unit. Since the machine used to perform the procedure uses suction to draw blood out of a donor's body, some people who can give whole blood may have veins too small for platelet donation. Blood centers evaluate each donor's veins prior to donation. Blood accounts for about 8% of body weight, so a 50 kg (110 lb) donor has about four liters of blood. No more than 50% of a donor's platelets are ever extracted in one sitting, and they can be replenished by the body in about three days. Most newer apheresis machines can separate a maximum donation of platelets in about 60 to 120 minutes depending on the donor's health condition.

Platelet donation[edit]
After a short physical examination, the donor is taken into the donation room and sits in a chair next to the machine. The technician cleans one or both arms with iodine, or other disinfectant, and inserts the catheter into a vein in the arm. With some procedures both arms are used, one to draw blood and the other to return it. The process takes about one to two hours while blood is pulled into the machine, mixed with an anticoagulant such as sodium citrate, spun around, and returned to the donor. "Double needle" procedures using both arms tend to be shorter since the blood is drawn and returned through different catheters; with "single needle" procedures a set volume is drawn and processed in the first part of the cycle and returned in the second part. The donor's blood undergoes repeated cycles of draw and return. Side effects of the donation of platelets generally fall into three categories: blood pressure changes, problems with vein access, and effects of the anticoagulant on the donor's calcium level. Blood pressure changes can sometimes cause nausea, fatigue, and dizziness. Venous access problems can cause bruising, referred to as a hematoma. While donating, a supply of calcium antacid tablets is usually kept close by to replenish the calcium lost.

Because the anticoagulant works by binding to the calcium in the blood, a donor's levels of calcium - and especially of active calcium ions - drop during the donation process. The lips may begin to tingle or there may be a metallic taste; since calcium enables the function of the nervous system, nerveending-dense areas (such as the lips) are susceptible, at least during the donation process. Unusually low calcium can cause more serious problems such as fainting, nerve irritation[citation needed] and short-duration tetany. Such an acute hypocalcaemia is usually due to low calcium levels prior to donation, aggravated by the anticoagulant. Hypocalcaemia can be curtailed by modestly increasing dietary calcium intake in the days prior to donation. Serious problems are extremely rare, but apheresis donors are typically not allowed to sleep during the long donation process so that they can be monitored.[citation
needed]

Aside from the procedure, donating platelets is different from donating blood in a few ways. Firstly, the donor must not take aspirin or other anti-platelet medications such as clopidogrel (Plavix) for anywhere from 36 to 72 hours prior to donation. (Guidelines vary by blood center.) The reason is that aspirin can prevent platelets from adhering to clot bleeding. Some blood centers also prohibit the taking of any NSAID (non-steroidal anti-inflammatory drug) for 36 hours prior. Secondly, one is generally allowed to donate platelets anywhere from every 328 days. This is a stark contrast to whole-blood donation, which has an eight-week (or longer) waiting period between donations. Along those lines, since platelet donation does temporarily remove whole blood from the body, it may be necessary to wait eight weeks after a whole blood donation to donate platelets, although one week is more common. In the US, a donor is only allowed to donate 24 times each year and may not lose more red blood cells or plasma in a year than they would from the maximum allowable number of whole blood donations.[citation needed] Thirdly, additional tests may be required before becoming a donor for the first time. These tests may establish a platelet count. Newer automated platelet pheresis machines do that as the donation begins, and adjust accordingly the quantity of platelets to be drawn. Tests may also determine the donor's compatibility with particular recipients through an HLA (Human Leukocyte

Antigen) test. Multiparous women may be excluded from becoming donors due to heightened TRALI risk. These tests usually involve nothing more involved than the drawing of several tubes of blood.
Adverse events[edit]

A hematoma caused by a patient moving their arm during a plateletpheresis donation.

Adverse conditions that can happen during a plateletpheresis donation are hypocalcemia, hematoma formation, andvasovagal reactions. The risk of these conditions happening can be reduced or prevented by pre-donation education of the donors and change of apheresis machine configuration.[2] Vein scarring[edit] Repeated platelet donations at short intervals will cause the venipuncture site to scar. While cosmetically it is virtually invisible, the scarring also occurs on the vein itself, making it harder to insert a needle on future occasions. Anecdotal reports have said that rubbing Vitamin E oil (or the insides of a Vitamin E capsule) on the venipuncture site may reduce scarring.[citation needed] Scarring of veins may also cause problems for further attempts to draw blood, such as for medical procedures. This may confuse phlebotomists who may believe they have missed the vein due to the higher pressure needed to penetrate the scar tissue.[citation needed]

See also[edit]

BLOOD DIALYSER

Artificial kidney

From Wikipedia, the free encyclopedia

This article is outdated. Please update this article to reflect recent events or newly available information. (March 2011) Artificial kidney is often a synonym for hemodialysis, but may also, more generally, refer to renal replacement therapies (with exclusion of renal transplantation) that are in use and/or in development. This article deals with bioengineered kidneys/bioartificial kidneys that are grown from renal cell lines/renal tissue.
Contents [hide]

1 Indications
o o

1.1 Renal Failure 1.2 Need for a bioartificial kidney 2.1 Artificial Kidney 2.2 Wearable artificial kidney 2.3 Bioengineered kidneys

2 Proposed Solutions
o o o

3 See also 4 References 5 External links

Indications[edit]
Renal Failure[edit]

Kidneys are paired vital organs located behind the abdominal cavity, at about the level of the bottom of the ribcage. They perform about a dozen physiologic functions, and are fairly easily damaged. Kidney failure results in the slow accumulation of nitrogenous wastes, salts, water, and disruption of the body's normal pH balance. Until the Second World War, kidney failure generally meant death for the patient. Several insights into renal function and acute renal failure were made during the war, not least of which would be Bywaters and Beall's descriptions of pigment-induced nephropathy drawn from their clinical experiences during the London Blitz.[1]
Need for a bioartificial kidney[edit]

Over 300,000 Americans are dependent on hemodialysis as treatment for renal failure, but according to data from the 2005 USRDS 452,000 Americans have end-stage renal disease (ESRD).[2] Intriguing investigations from groups in London, Ontario and Toronto, Ontario have suggested that dialysis treatments lasting two to three times as long as, and delivered more frequently than, conventional thrice weekly treatments may be associated with improved clinical outcomes[3] Implementing six-times weekly, all-night dialysis would overwhelm existing resources in most countries. This, as well as scarcity of donor organs for kidney transplantation has prompted research in developing alternative therapies, including the development of a wearable or implantable device.[4]

Proposed Solutions[edit]
Artificial Kidney[edit]

Dialyser used in hemodialysis

Hemodialysis is a method for removing waste products such as creatinine and urea,as well as free water from the blood when the kidneys are in renal failure. The mechanical device used to clean the patients blood is called a dialyser, also known as an artificial kidney. Modern dialysers typically consist of a cylindrical rigid casing enclosing hollow fibers cast or extruded from a polymer or copolymer, which is usually a proprietary formulation. The combined area of the hollow fibers is typically between 1-2 square meters. Intensive research has been conducted by many groups to optimize blood and dialysate flows

within the dialyser, in order to achieve efficient transfer of wastes from blood to dialysate.
Wearable artificial kidney[edit]

A wearable artificial kidney is a wearable dialysis machine that a person with end-stage renal disease could use daily or even continuously. As of November 2008, no wearable kidney is widely available, but many research teams are in the process of developing such devices.
Bioengineered kidneys[edit]

Currently, no viable bioengineered kidneys exist. Although a great deal of research is underway, numerous barriers exist to their creation.[5][6][7] However, manufacturing a membrane that mimics the kidney's ability to filter blood and subsequently excrete toxins while reabsorbing water and salt would allow for a wearable and/or implantable artificial kidney. Developing a membrane using microelectromechanical systems (MEMS) technology is a limiting step in creating an implantable, bioartificial kidney. The BioMEMS and Renal Nanotechnology Laboratories at the Cleveland Clinic's Lerner Research Institute have focused on advancing membrane technology to develop an implantable or wearable therapy for end-stage renal disease (ESRD). Current dialysis cartridges are too large and require superphysiologic pressures for blood circulation, and pores in current polymer membranes have too broad of a size distribution and irregular features. Manufacturing a silicon, nanoporous membrane with narrow pore size distributions improves the membrane's ability to discriminate between filtered and retained molecules. It also increases hydraulic permeability by allowing the mean pore size to approach the desired cutoff of the membrane. Using a batch-fabrication process allows for strict control over pore size distribution and geometry.[8] In recent studies, human kidney cells were harvested from donated organs unsuitable for transplantation, and grown on these membranes. The cultured cells covered the membranes and appear to retain features of adult kidney cells. The differentiated growth of renal epithelial cells on MEMS materials suggests that a miniaturized device suitable for implantation may be feasible.

A UCSF-led effort to create an implantable artificial kidney for dialysis patients has been selected as one of the first projects to undergo more timely and collaborative review at the Food and Drug Administration. The FDA announced on April 9, 2012 that it had chosen three renal device projects to pilot a new regulatory approval program called Innovation Pathway 2.0, intended to bring breakthrough medical device technologies to patients faster and more efficiently. The artificial kidney project, which is targeted for clinical trials in 2017, was selected for its transformative potential in treating end stage renal disease and for its potential to benefit from early interactions with the FDA in the approval process. The FDA effort will involve close contact between the federal agency and device developers early in the development process to identify and address potential scientific and regulatory hurdles and create a roadmap for project approval. The goal is to improve the projects overall chance of success, while reducing the time and cost of FDA review and maintaining safety. Lessons, the agency said, will inform approvals in other areas.

See also[edit]

Dialysis
From Wikipedia, the free encyclopedia

This article is about renal dialysis; for the laboratory technique, see dialysis (biochemistry); for treatment for liver failure, see liver dialysis.

Dialysis
Intervention

Patient receiving dialysis ICD-9-CM MeSH MedlinePlus 39.95 D006435 007434

In medicine, dialysis (from Greek dialusis,"", meaning dissolution, dia, meaning through, and lysis, meaning loosening or splitting) is a process for removing waste and excess water from the blood, and is used primarily as an artificial replacement for lostkidney function in people with renal failure.[1] Dialysis may be used for those with an acute disturbance in kidney function (acute kidney injury, previously acute renal failure), or progressive but chronically worsening kidney functiona state known as chronic kidney disease stage 5 (previously chronic renal failure or end-stage renal disease). The latter form may develop over months or years, but in contrast to acute kidney injury is not usually reversible, and dialysis is regarded as a "holding measure" until a renal transplant can be performed, or sometimes as the only supportive measure in those for whom a transplant would be inappropriate.[2] The kidneys have important roles in maintaining health. When healthy, the kidneys maintain the body's internal equilibrium of water and minerals (sodium, potassium, chloride, calcium, phosphorus, magnesium, sulfate). The acidic metabolism end-products that the body cannot get rid of via respiration are also excreted through the kidneys. The kidneys also function as a part of the endocrine system, producing erythropoietin and calcitriol. Erythropoietin is involved in the production of red blood cells and calcitriol plays a role in bone formation.[3] Dialysis is an imperfect treatment to replace kidney function because it does not correct the compromised endocrine functions of the kidney. Dialysis treatments replace some of these functions through diffusion (waste removal) andultrafiltration (fluid removal).[4]
Contents [hide]

1 History 2 Principle 3 Types

o o o o o

3.1 Hemodialysis 3.2 Peritoneal dialysis 3.3 Hemofiltration 3.4 Hemodiafiltration 3.5 Intestinal dialysis

4 Starting indications 5 See also

o o

5.1 Materials and methods 5.2 Medical applications

6 References 7 External links

History[edit]

Arm showing tubes

Dr. Willem Kolff, a Dutch physician, constructed the first working dialyzer in 1943 during the Nazi occupation of the Netherlands.[5] Due to the scarcity of available resources, Kolff had to improvise and build the initial machine using sausage casings, beverage cans, a washing machine, and various other items that were available at the time. Over the following two years,[1943-1945] Kolff used his machine to treat 16 patients suffering from acute kidney failure, but the results were unsuccessful. Then, in 1945, a 67-year-old comatose woman regained consciousness following 11 hours of hemodialysis with the dialyzer, and lived for another seven years before dying from an unrelated condition. She was the first-ever patient successfully treated with dialysis.[5]

Principle[edit]

A hemodialysis machine

Dialysis works on the principles of the diffusion of solutes and ultrafiltration of fluid across a semi-permeable membrane. Diffusion is a property of substances in water; substances in water tend to move from an area of high concentration to an area of low concentration.[6]Blood flows by one side of a semi-permeable membrane, and a dialysate, or special dialysis fluid, flows by the opposite side. A semipermeable membrane is a thin layer of material that contains holes of various sizes, or pores. Smaller solutes and fluid pass through the membrane, but the membrane blocks the passage of larger substances (for example, red blood cells, large proteins). This replicates the filtering process that takes place in the kidneys, when the blood enters the kidneys and the larger substances are separated from the smaller ones in the glomerulus.[6] The two main types of dialysis, hemodialysis and peritoneal dialysis, remove wastes and excess water from the blood in different ways.[2]Hemodialysis removes wastes and water by circulating blood outside the body through an external filter, called a dialyzer, that contains asemipermeable membrane. The blood flows in one direction and the dialysate flows in the opposite. The counter-current flow of the bloodand dialysate maximizes the concentration gradient of solutes between the blood and dialysate, which helps to remove more urea andcreatinine from the blood. The concentrations of solutes (for example potassium, phosphorus, and urea) are undesirably high in the blood,

but low or absent in the dialysis solution, and constant replacement of the dialysate ensures that the concentration of undesired solutes is kept low on this side of the membrane. The dialysis solution has levels of minerals like potassium and calcium that are similar to their natural concentration in healthy blood. For another solute, bicarbonate, dialysis solution level is set at a slightly higher level than in normal blood, to encourage diffusion of bicarbonate into the blood, to act as a pH buffer to neutralize the metabolic acidosis that is often present in these patients. The levels of the components of dialysate are typically prescribed by a nephrologist according to the needs of the individual patient. In peritoneal dialysis, wastes and water are removed from the blood inside the body using the peritoneal membrane of the peritoneum as a natural semipermeable membrane. Wastes and excess water move from the blood, across the peritoneal membrane, and into a special dialysis solution, called dialysate, in the abdominal cavity which has a composition similar to the fluid portion of blood.

Types[edit]
There are three primary and two secondary types of dialysis: hemodialysis (primary), peritoneal dialysis (primary), hemofiltration (primary), hemodiafiltration (secondary), andintestinal dialysis (secondary).
Hemodialysis[edit]

Hemodialysis schematic

Main articles: Hemodialysis and Home hemodialysis In hemodialysis, the patient's blood is pumped through the blood compartment of a dialyzer, exposing it to a partially permeable membrane. The dialyzer is composed of thousands of tiny synthetic hollow fibers. The fiber wall acts as the semipermeable membrane. Blood flows through the fibers, dialysis solution flows around the outside of the fibers, and water and wastes move between these two solutions.[7] The cleansed blood is then returned via the circuit back to the body. Ultrafiltration occurs by increasing the hydrostatic pressure across the dialyzer membrane. This usually is done by applying a negative pressure to the dialysate compartment of the dialyzer. This pressure gradient causes water and dissolved solutes to move from blood to dialysate, and allows the removal of several litres of excess fluid during a typical 4-hour treatment. In the US, hemodialysis treatments are typically given in a dialysis center three times per week (due in the US to Medicare reimbursement rules); however, as of 2007 over 2,500 people in the US are dialyzing at home more frequently for various treatment lengths.[8] Studies have demonstrated the clinical benefits of dialyzing 5 to 7 times a week, for 6 to 8 hours. This type of hemodialysis is usually called "nocturnal daily hemodialysis", which a study has shown a significant improvement in both small and large molecular weight clearance and decrease the requirement of taking phosphate binders.[9] These frequent long treatments are often done at home while sleeping, but home dialysis is a flexible modality and schedules can be changed day to day, week to week. In general, studies have shown that both increased treatment length and frequency are clinically beneficial.[10] Hemo-dialysis was one of the most common procedures performed in U.S. hospitals in 2011, occurring in 909,000 stays (a rate of 29 stays per 10,000 population).[11]

Peritoneal dialysis[edit]

Schematic diagram of peritoneal dialysis

Main article: Peritoneal dialysis In peritoneal dialysis, a sterile solution containing glucose (called dialysate) is run through a tube into the peritoneal cavity, the abdominalbody cavity around the intestine, where the peritoneal membrane acts as a partially permeable membrane. The peritoneal membrane or peritoneum is a layer of tissue containing blood vessels that lines and surrounds the peritoneal, or abdominal, cavity and the internal abdominal organs (stomach, spleen, liver, and intestines).[12] Diffusion and osmosis drive waste products and excess fluid through the peritoneum into the dialysate until the dialysate approaches equilibrium with the body's fluids. Then the dialysate is drained, discarded, and replaced with fresh dialysate.[13] This exchange is repeated 4-5 times per day; automatic systems can run more frequent exchange cycles overnight. Peritoneal dialysis is less efficient than hemodialysis, but because it is carried out for a longer period of time the net effect in terms of removal of waste products and of salt and water are similar to hemodialysis. Peritoneal dialysis is carried out at home by the patient, often without help. This frees patients from the routine of having to go to a dialysis clinic on a fixed schedule multiple times per week. Peritoneal dialysis can be performed with little to no specialized equipment (other than bags of fresh dialysate).
Hemofiltration[edit]

Main article: Hemofiltration

Hemofiltration is a similar treatment to hemodialysis, but it makes use of a different principle. The blood is pumped through a dialyzer or "hemofilter" as in dialysis, but no dialysate is used. A pressure gradient is applied; as a result, water moves across the very permeable membrane rapidly, "dragging" along with it many dissolved substances, including ones with large molecular weights, which are not cleared as well by hemodialysis. Salts and water lost from the blood during this process are replaced with a "substitution fluid" that is infused into the extracorporeal circuit during the treatment. Hemodiafiltration is the combining of hemodialysis and hemofiltration in one process.
Hemodiafiltration[edit]

Hemodiafiltration is a combination of hemodialysis and hemofiltration.

Intestinal dialysis[edit]

In intestinal dialysis, the diet is supplemented with soluble fibres such as acacia fibre, which is digested by bacteria in the colon. This bacterial growth increases the amount of nitrogen that is eliminated in fecal waste.[14][15][16] An alternative approach utilizes the ingestion of 1 to 1.5 liters of non-absorbable solutions of polyethylene glycol or mannitolevery fourth hour.[17]

Starting indications[edit]
The decision to initiate dialysis or hemofiltration in patients with renal failure depends on several factors. These can be divided into acute or chronic indications.

Indications for dialysis in the patient with acute kidney injury are summarized with the vowel acronym of "AEIOU":[18] 1. Acidemia from metabolic acidosis in situations in which correction with sodium bicarbonate is impractical or may result in fluid overload 2. Electrolyte abnormality, such as severe hyperkalemia, especially when combined with AKI 3. Intoxication, that is, acute poisoning with a dialyzable substance. These substances can be represented by the mnemonic SLIME: salicylic acid, lithium, isopropanol, Magnesium-containing laxatives, and ethylene glycol

4. Overload of fluid not expected to respond to treatment with diuretics 5. Uremia complications, such as pericarditis, encephalopathy, or gastrointestinal bleeding.

Chronic indications for dialysis: 1. Symptomatic renal failure 2. Low glomerular filtration rate (GFR) (RRT often recommended to commence at a GFR of less than 10-15 mls/min/1.73m2). In diabetics, dialysis is started earlier. 3. Difficulty in medically controlling fluid overload, serum potassium, and/or serum phosphorus when the GFR is very low

See also[edit]

Liver support systems

From Wikipedia, the free encyclopedia

[hide]This article has multiple issues. Please help improve it or discuss the
2013)

This article needs attention from an expert on the subject. The specific pr This article has no lead section. (June 2013)
Hepatic insufficiency implies the inability of the liver to carry out its metabolic, excretory and detoxifying functions owing to a decrease in the number of functional hepatocytes or because their normal activity is altered. Hepatic insufficiency can be acute or chronic. Acute liver failure (ALF) is produced without a previous liver disease whereas the chronic liver failure is the consequence of a liver disease evolution over a long period of time, independently of its etiology and degree. The incidence of acute liver failure is estimated to be of 1-6 cases per million of person.[1] ALF can be subclassified into hyperacute, acute and subacute based on when hepatic encephalopathy occurs following the onset of jaundice (O`Grady et al., 1993),[2] and this classification can sometimes help to identify the etiology, potential complications and patient prognosis (Table 1). Table 1: Classification for acute hepatic insufficiency

In hyperacute and acute liver failure the clinical picture develops rapidly with progressive encephalopathy and multiorgan dysfunction such as hyperdynamic circulation,coagulopathy, acute renal and respiratory insufficiency, severe metabolic alterations and cerebral edema that can lead to brain death.[3][4] In these cases the mortality withoutliver transplantation (LTx) ranges between 40-80%.[5][6] LTx is the only effective treatment for these patients although it requires a precise indication and timing to achieve good results. Nevertheless, due to the scarcity of organs to carry out liver transplantations, it is estimated that one third of patients with ALF die while waiting to be transplanted.[7] On the other hand, a patient with a chronic hepatic disease can suffer an acute decompensation of liver function following a precipitating event such as variceal bleeding, sepsis and excessive alcohol intake among others that can lead to a condition referred to as acute-on-chronic liver failure (ACLF). Both types of hepatic insufficiency, ALF and ACLF, can potentially be reversible and liver functionality can return to a level similar to that prior to the insult or precipitating event. LTx is the only treatment that has shown an improvement in the prognosis and survival with most severe cases of ALF. Nevertheless, cost and donor scarcity have prompted researchers to look for new supportive treatments that can act as bridge to the transplant procedure. By stabilizing the patients clinical state, or by creating the right conditions that could allow the recovery of native liver functions, both detoxification and synthesis can improve, after an episode of ALF or ACLF.[8] Basically, three different types of supportive therapies have been developed: bio-artificial, artificial and hybrid liver support systems (Table 2).

Table 2: Liver Support Systems

Bio-artificial ELAD[9] Extracorporeal liver assist device BLSS[12] Bioartificial Liver Support System RFB[15] Radial Flow Bioreactor AMC-BAL[18] Bioartificial Liver

Artificial MARS[10] Molecular adsorbent recirculating system Prometheus FPSA[13] Fractionated plasma separation and adsorption system SPAD[16] Single-pass albumin dialysis SEPET[19] Selective plasma filtration therapy

Hybrids

Hepat-Assist[11]

TECLA-HALSS[14] TECA-Hybrid Artificial Liver Support System MELS[17] Modular Extracorporeal Liver Support

Bio-artificial liver support systems are experimental extracorporeal devices that use living cell lines to provide detoxification and synthesis support to the failing liver. Bio-artificial liver (BAL) Hepatassist 2000 uses porcine hepatocytes11 whereas ELAD system employs hepatocytes derived from human hepatoblastoma C3A cell lines.9,[20][21] Both techniques can produce, in fulminat hepatic failure (FHF), an improvement of hepatic encephalopathy grade and biochemical parameters. Nevertheless, they are therapies with high complexity that require a complex logistic approach for implementation; a very high cost and possible inducement of important side effects such as immunological issues (porcine endogenous retrovirus transmission), infectious complications and tumor transmigration have been documented. Other biological hepatic systems are Bioartificial Liver Support (BLSS)12 and Radial Flow Bioreactor (RFB).15 Detoxification capacity of these systems is poor and therefore they must be used combined with other systems to mitigate this deficiency. Today its use is limited to centers with high experience in their application.[22] Artificial liver support systems are aimed to temporally replace native liver detoxification functions and they use albumin as scavenger molecule to clear the toxins involved in the physiopathology of the failing liver. Most of the toxins that accumulate in the plasma of patients with liver insufficiency are protein bound, and therefore conventional renal dialysistechniques, such as hemofiltration, hemodialysis or hemodiafiltration are not able to adequately eliminate them.

Between the different albumin dialysis modalities, single pass albumin dialysis (SPAD) has shown some positive results at a very high cost;[23] it has been proposed that lowering the concentration of albumin in the dialysate does not seem to affect the detoxification capability of the procedure.[24] Nevertheless, the most widely used systems today are based on hemodialysis and adsorption. These systems use conventional dialysis methods with an albumin containing dialysate that is latter regenerate by means of adsorption columns, filled with activated charcoal and ion exchange resins. At present, there are two artificial extracorporeal liver support systems: the Molecular Adsorbents Recirculating System (MARS)10 from Gambro and Fractionated Plasma Separation and Adsorption (FPSA), commercialised as Prometheus (PROM) from Fresenius Medical Care.13 Of the two therapies, MARS is the most frequently studied, and clinically used system to date.

Contents [hide]

1 The MARS System 2 MARS System Components 3 Results published in the literature with the MARS system 4 LiverNet 5 Effects of MARS treatment on Hepatic Encephalopathy (HE) 6 Effects of MARS Treatment on Unstable Hemodynamics 7 Effects of MARS Treatment on Renal Function 8 Effects of MARS Treatment on Biochemical Parameters 9 Effects of MARS Treatment on Pruritus 10 Effects of MARS Treatment on Drugs and Poisons clearance 11 Effects of MARS on Survival 12 Safety Aspects 13 Health Economics 14 MARS Therapy Indications
o o o o o

14.1 Acute on Chronic Liver Failure 14.2 Acute Liver failure 14.3 MARS in Graft Dysfucntion After Liver Transplant[116][117] 14.4 MARS in liver Failure after Liver Surgery[118] 14.5 MARS for intractable pruritus in Cholestasis[66][66][106][109][119]

15 MARS Therapy Contraindications 16 Treatment Parameters 17 FDA Clearance (US only)

18 References

The MARS System[edit]

MARS was developed by a group of researchers at the University of Rostock (Germany), in 199310 and later commercialized for its clinical use in 1999.[25] The system is able to replace the detoxification function of the liver while minimizing the inconvenience and drawbacks of previously used devices.[26][27][28] In vivo preliminary investigations indicated the ability of the system to effectively remove bilirubin, biliary salts, free fatty acids and tryptophan while important physiological proteins such as albumin, alpha-1-glicoproteine, alpha 1 antitrypsin, alpha-2-macroglobulin, transferrin, globulin tyrosine, and hormonal systems are unaffected.[29] Also, MARS therapy in conjunction with CRRT/HDF can help clear cytokines acting as inflammatory and immunological mediators in hepatocellular damage, and therefore can create the right environment to favour hepatocellular regeneration and recovery of native liver function.

MARS System Components[edit]

Combined MARS and PrismaFlex monitors

MARS is an extracorporeal hemodialysis system composed of three different circuits: blood, albumin and low flux dialysis. The Blood circuit uses a double lumen catheter and a conventional hemodialysis device to pump the patients blood into the MARS FLUX, a biocompatible polysulfone high-flux dialyser. With a membrane surface area of 2.1 m2, 100 nm of thickness and a cut-off of 50 KDa, the MARSFLUX is essential to retaining the albumin in the dialysate. Blood is dialysed against a human serum albumin (HSA) dialysate solution that allows blood detoxification of both, water soluble and protein bound toxins, by means of the presence of albumin in the

dialysate (albumin dialysis). The albumin dialysate is then regenerated in a close loop in the MARS circuit by passing through the fibres of the low-flux diaFLUX filter, to clear water soluble toxins and provide electrolyte/acid-base balance, by a standard dialysis fluid. Next, the albumin dialysate passes through two different adsorption columns; protein-bound substances are removed by the diaMARS AC250, containing activated charcoal and anionic substances are removed by the diaMARS IE250, filled with cholestyramine, an anion exchange resin. The albumin solution is then, ready to initiate another detoxifying cycle of the patients blood that can be sustained until both adsorption columns are saturated, eliminating the need to continuously infuse albumin into the system during treatment (Fig. 1).

Figure 1: The MARS system

Results published in the literature with the MARS system[edit]

A systematic review of the literature from 1999 to June 2011 was performed in the following databases: 1. Specialized in systematic reviews: Cochrane Library Plus and NHS Centre database for Reviews and Dissemination (HTA, DARE and NHSEED). 2. General databases: Medline, Pubmed and Embase. 3. On-going clinical trials and research project databases: Clinical Trials Registry (National Institutes of Health, EE.UU.) and Health Services Research Projects in Progress. 4. General web searching engines: Scholar Google.

LiverNet[edit]
The LiverNet is a database dedicated to the liver diseases treated with the support of extracorporeal therapies. To date, the most currently used system is the Molecular Adsorbent Recirculating System (MARS), which is based on the selective removal of albumin bound molecules and toxins from the blood in patients with acute and acute-on-chronic liver failure. The purpose is to register prospectively all patients treated worldwide with the MARS system in order to: 1. Improve our understanding of the clinical course, pathopysiology and treatment of these diseases 2. Evaluate the clinical impact of MARS therapy on the course of the disease in different specific indication 3. Increase the knowledge in this extremely innovative area, a basis for an improvement of liver support devices and the treatment of these patients in the next future The liverNet is an eCRF database (www.livernet.net) using a SAS plateform that allows major advantages for the centres including the automatic calculations of most liver rand ICU scoring systems, instant queries online, instant export of all patients included in the database of each centre to an Excel file for direct statistical analysis and finally instant online statistical analysis of selective data decided by the scientific committee. Therefore, the LiverNet is an important tool to progress in the knowledge of liver support therapies.

Effects of MARS treatment on Hepatic Encephalopathy (HE)[edit]

Hepatic encephalopathy (HE) represents one of the more serious extrahepatic complications associated with liver dysfunction.[30][31] Neuro-psychiatric manifestations of HE affect consciousness and behaviour. Evidence suggests that HE develops as some neurotoxins and neuro active substances, produced after hepatocellular breakdown, accumulates in the brain as a consequence of a portosystemic shunt and the limited detoxification capability of the liver. Substances involved are ammonia, manganese, aromatic aminoacids, mercaptans, phenols, medium chain fatty acids, bilirubin, endogenous benzodiazepines, etc. The relationship between ammonia neurotoxicity and HE was first described in animal studies by Pavlov et al.[32] Subsequently, several studies in either animals or humans have confirmed that, a ratio in ammonia concentration higher than 2 mM between the brain and blood stream, causes HE, and even a comatose state when the value is greater than 5 mM. Some investigators have also reported a decrease in serum ammonia following a MARS treatment (Table 3).

Table 3. Clinical studies showing some improvement in the treatment of HE following a MARS treatment

References

N patients

Age Ammonia Pre- Ammonia PostTreatment MARS MARS (years) p

[aver. SD] Hours/patient (g/dl) (g/dl)

Awad et al.[33] (1999) Novelli et al.[34] (2002) Schmidt et al.[35] (2001) Sorkyne et al.[36] (2001)

9 10 8 8

385 4212 435 4716

73.2 51.2 10.0 28.1

130 247 150 280

64 126 121 65

<0.05 <0.003 <0.05 <0.005

Manganese and copper serum levels are increased in patients with either acute or acute on chronic liver failure. Nevertheless, only in those patients with chronic hepatic dysfunction, a bilateral magnetic resonance alteration on Globos Pallidus is observed,[37] probably because this type of patients selectively shows higher cerebral membrane permeability. Imbalance between aromatic and branched chain aminoacids (Fischer index), traditionally involved in HE genesis,[38][39][40] can be normalized following a MARS treatment. The effects are noticeable even after 3 hours of treatment and this reduction in the Fisher index is accompanied with an improvement in the HE.[41] Novelli G et al.[42] published their three years experience on MARS analyzing the impact of the treatment in the cerebral level for 63 patients reporting an improvement in Glasgow Coma Score (GCS) for all observed in all patients. In the last 22 patients, cerebral perfusion pressure was monitored by Doppler (mean flow velocity in middle cerebral artery), establishing a clear relationship between a clinical improvement (especially neurological) and an improvement in arterial cerebral perfusion. This study confirms other results showing similar increments in cerebral perfusion in patients treated with MARS.[35] More recently, several studies have shown a significant improvement of HE in patients treated with MARS. In the studies by Heemann et al.[43] and Sen et al.[44] an improvement in HE was considered when encephalopathy grade was reduced by one or more grades vs. basal values; for Hassenein et al., in their randomized controlled trial, improvement was considered when a decrease of two grades was observed.[45] In the latter, 70 patients with acute on chronic liver

failure and encephalopathy grade III and IV were included. Likewise, Kramer et al.[46] estimated an HE improvement when an improvement in peak N70 latency in electroencephalograms was observed. Sen et al.44 observed a significant reduction in Child-Pugh Score (p<0,01) at 7 days following a MARS treatment, without any significant change in the controls. Nevertheles, when they looked at the Model for End-Stage Liver Disease Score (MELD), a significant reduction in both groups, MARS and controls, was recorded (p<0,01 y p<0,05, respectively). Likewise, in several case series, an improvement in HE grade with MARS therapy is also reported.[47][48][49][50][51][52][53][54][55]

Effects of MARS Treatment on Unstable Hemodynamics[edit]

Hemodynamic instability is often associated with acute liver insufficiency, as a consequence of endogenous accumulation of vasoactive agents in the blood. This is characterized by a systemic vasodilatation, a decrease of systemic vascular resistance, arterial hypotension, and an increase of cardiac output that gives rise to a hyperdynamic circulation. During MARS therapy, systemic vascular resistance index and mean arterial pressure have been shown to increase and show improvement.[47][49][51][56][57] Schmidt et al.[58] reported the treatment of 8 patients, diagnosed with acute hepatic failure, that were treated with MARS for 6 hours, and were compared with a control group of 5 patients to whom ice pads were applied to match the heat loss produced in the treatment group during the extracorporeal therapy. They analyzed hemodynamic parameters in both groups hourly. In the MARS group, a statistically significant increase of 46% on systemic vascular resistance was observed (1215 437 to 1778 710 dinas x s x cm5 x m2) compared with a 6% increase in the controls. Mean arterial pressure also increased (69 5 to 83 11 mmHg, p< 0.0001) in the MARS group, whereas no difference was observed in the controls. Cardiac output and heart rate also decreased in the MARS group as a consequence of an improvement in the hyperdynamic circulation. Therefore it was shown that a statistically significant improvement was obtained with MARS when compared with the SMT. Catalina et al.[59] have also evaluated systemic and hepatic hemodynamic changes produced by MARS therapy. In 4 patients with acute decompensation of chronic liver disease, they observed after MARS therapy, an attenuation of hyperdynamic circulation and a reduction in the portal pressure gradient was measured. Results are summarized in table 4.

Table 4: Hemodinamic parameters during MARS treatment BASE LINE AFTER 1ST TREAT. AFTER 2ND TREAT.

PARAMETER

MAP(mmHg)

77.8 11.7

82.7 11.7

84.2 8

WHVP(mmHg)

40.7 5.6

34 9.6

37.3 5.5

FHVP(mmHg)

17.7 7.4

16.7 7.5

17 3.6

HVPG(mmHg)

23 7.0

17.3 9.9

20.3 5.5

PAP(mmHg)

23.7 7.3

22 4.8

15.7 4.1

PCP(mmHg)

17.2 8.3

14.5 2.9

9.7 7.0

rPAP (mmHg)

11.2 4.6

10 4.2

7.3 7.6

CO(l/min)

11.2 1.6

10 2.8

9.4 2.1

SVRI (dinas x seg/cm5) 478.5 105

514 104.7

622 198

Abbreviations: MAP= mean arterial pressure; WHVP= wedged hepatic venous pressure;FHVP= free hepatic venous pressure; HVPG= hepatic venous pressure gradient; PAP= pulmonary arterial pressure; PCP= pulmonar capillary pressure; rPAP= right pulmonary arterial pressure; CO= cardiac output; SVRI= systemic vascular resistance index.

There are other studies also worth mentioning with similar results: Heemann et al.[43] and Pars et al.[60] among others. Dethloff T et al.[61] concluded that there is a statistically significant improvement favourable to MARS in comparison with Prometheus system (Table 5).

Table 5. Changes in hemodynamic parameters with MARS therapy

MARS System Mitzner et al.[62] (2000)

MAP NS

SVRI

CO

BR

Heemann et al.[43] (2002) Schmidt et al.[58] (2003) Laleman et al.[57] (2006) Dethloff et al.[61] (2008)

S S S NS

S S

Abbreviations: MAP: Mean arterial pressure; SVRI: Systemic vascular resistance index; CO: Cardiac output; BR: Beat rate; S: Statistically significant, p< 0.05; NS: not statistically significant. : Increase; :Decrease; : No changes.

Effects of MARS Treatment on Renal Function[edit]

Hepatorenal syndrome is one of the more serious complications in patients with an acute decompensation of cirrhosis and increased portal hypertension. It is characterized by hemodynamic changes in splanchnic, systemic and renal circulation. Splanchnic vasodilatation triggers the production of endogenous vasoactive substances that produce renal vasoconstriction and low glomerular filtration rate, leading to oliguria with a concommitant reduction in creatinine clearance. Renal insufficiency is always progressive with a very poor prognosis,[62][63] with survival at 1 and 2 months of 20 and 10% respectively. Pierre Versin[64] is one of the pioneers in the study of hepatorenal syndrome in patients with liver impairment. Great efforts have been made trying to improve the prognosis of this type of patient; however, few have solved the problem. Orthotopic liver transplantation is the only treatment that has shown to improve acute and chronic complications derived from severe liver insufficiency. Today it is possible to combine albumin dialysis with continuous veno-venous hemodialfiltration, which provides a greater expectation for these patients[65] by optimization of their clinical status. MARS treatment lowers serum urea and creatinine levels improving their clearance,[57][58][59][61] and even favors resolution of hepatorenal syndrome.[43][50][51][56][66] Results are confirmed in a randomized controlled trial published by Mitzner et al.[62] in which 13 patients diagnosed with hepatorenal syndrome type I were treated with MARS therapy. Mean survival was 25,234,6 days in the MARS group compared to 4,61,8 days observed in the controls in whom hemodiafiltration and standard care (SMT) was applied. This resulted in a statistically significance difference in survival at 7 and 30 days (p<0.05). Authors concluded that MARS therapy, applied to liver failure patients (Child-Pugh C and UNOS 2A scores) who develop hepatorenal syndrome type I, prolonged survival compared to patients treated with SMT.

Although mechanisms explaining previous findings are not yet fully understood, it has been reported that there was a decrease in plasma rennin concentrations in patients diagnosed with acute on chronic liver failure with renal impairment that were treated with MARS. Likewise, other studies have suggested some efficacy for MARS in the treatment of hepatorenal syndrome.[67][68][69] However, other references have been published that do not show efficacy in the treatment of these types of patients with MARS therapy. Khuroo et al.[70] published a metaanalysis based in 4 small RCTs and 2 non RCTs in patients diagnosed with ACLF, concluding that MARS therapy would not bring any significant increment on survival compared with SMT. Another observational study in 6 patients with cirrhosis, refractory ascitis and hepatorenal syndrome type I, not responding to vasoconstrictor therapy, showed no impact on hemodynamics following MARS therapy; however authors concluded that MARS therapy could effectively serve as bridge to liver transplantation.[52][71]

Effects of MARS Treatment on Biochemical Parameters[edit]

Total bilirubin was the only parameter analyzed in all trials that was always reduced in the groups of patients treated with MARS; Banayosy et al.[72] measured bilirubin levels 14 days after since MARS therapy was terminated and observed a consistent, significant decrease not only for bilirubin but also for creatinine and urea (Table 6).

Table 6: Biochemical parameters analysis with MARS therapy

MA RS MARS A A B MARS Contr Patholog Bilir Creati Albu Ur Amm Gro Interve L S U study ols (n) y ubin nine min ea onia up ntion T T N (n)

Mitzne r et al. (200 0)[62]

ACLF (OH)

6hx3 d

NS

Heema nn et al. (200 2)[43]

12

12

ACLF

6hx3 d

Sen et al. (200 4)[44]

ACLF+H E (OH)

8hx7 d 4 session s 6-8 h x 10 d S S -

Lalema n et al. (2006)[5

7]

SHR

Hassan ein et al. (2007)[4

5]

31

ACLF+H 6hx5 39 E (III / d IV)

Schmid t et al. (2003)[5

8]

ALF

6h

S S -

El Banayo sy et al. (2004)[7

2]

13

14

ALF

8hx3 d

Dethlof 8:8 f et al. Promet (2008)[6 heus 1] Montej o et al. (200 9)[73]

ACLF

26

19

IHA/GD/ 8 h x 3 ACLF d

S S S

Abbreviations; ALF= acute liver failure; ACLF= acute on chronic liver failure; GD= graft dysfunction; HE= hepatic encephalopathy; AST: aspartate amino transferase; BUN: blood urea nitrogen; NS: not significant; S: statistically significant (p<0,05); decrease; increase; no change; ALT: alanine amino transferase; h: hours; d: days

Primary goal in the Heemann trial was to achieve a bilirubin level beloiw 15 mg/dl during three consecutive days, which was observed in 42% of the patients treated with MARS compared to 17% in the control group.

Impact of MARS therapy on plasma biliary acids levels was evaluated in 3 studies. In the study from Stadbauer et al.,[74] that was specifically addressing the topic, it is reported that MARS and Prometheus systems lower to the same extent biliary acids plasma concentration. Heemann et al.[43] and Laleman et al.[57] have also published a significant improvement for these organic ions.

Effects of MARS Treatment on Pruritus[edit]

Pruritus is one of the most common clinical manifestations in cholestasis liver diseases and one of the most distressing symptoms in patients with chronic liver disease caused by viral hepatitis C. Many hypothesis have been formulated to explain physio pathogenesis of such manifestation, including incremental plasma concentration of biliary acids, abnormalities in the bile ducts,[75] increased central neurotransmitters coupling opioid receptors,[76][77] etc.. Despite the number of historical drugs used, individually or combined (exchange resins, hidrophilic biliary acids, antihistaminines, antibiotics, anticonvulsants, opioid antagonists), there are reported cases of intractable or refractory pruritus with a dramatic reduction in patients quality of life (i.e. sleep disorders, depression, suicide attempts).[78][79] Intractable pruritus can be an indication for liver transplantation. The MARS indication for intractable pruritus is therapeutically an option that has shown to be beneficial for patients in desperate cases, although at high cost.[80][81][82][83] In several studies, it was confirmed that after MARS treatments, patients remain free from pruritus for a period of time ranging from 6 to 9 months.[83] Nevertheless, some authors have concluded that besides the good results found in the literature, application of MARS therapy in refractory pruritus requires larger evidence.[81]

Effects of MARS Treatment on Drugs and Poisons clearance[edit]

Pharmacokinetics and pharmacodynamics for a majority of drugs can be significantly be modified with liver failure, affecting the therapeutic approach and potential toxicity of the drugs. In these type of patients, Child-Pugh score represents a poor prognostic factor to assess the metabolic capacity of the failing liver.

Metabolic performance of the liver depends on several factors: Hepatic flow rate Cytochrome P-450 enzimatic activity Albumin affinity for the drug Extrahepatic clearance for the drug

In patients with hepatic failure, drugs that are only metabolized in the liver, accumulate in the plasma right after they are administered, and therefore it is needed to modify drug dosing in both,

concentration and time intervals, to lower the risk of toxicity. It is also necessary to adjust the dosing for those drugs that are exclusively metabolized by the liver, and have low affinity for proteins and high distribution volume, such as fluoroquinolones (Levofloxacine and Ciprofloxacine).[84][85][86][87] Extracorporeal detoxification with albumin dialysis increases the clearance of drugs that are bound to plasmatic proteins (Table 7).

Table 7: Drugs Highly Bound to Proteins

NSAIDs

Antibiotic Anti-H2 s
Cephazoline Omeprazole

Statins

Antipsyc hotics
Chlorpromazi ne

Diclofenac

Clofibrate

Ibuprofen

Cefoperazone

Antifungal s

Lovastatin

Haloperidol

Indomethacine

Ceftriaxone

Amphotericine Simvastatine B

Chemoth erapy Drugs

Chlorambucil

Ketoprofen

Cloxacilin

Itraconazole

Fluvastatine

Naproxen

Oxacilin

Ketoconazole

Hypotensors

Etoposide

Phenylbutazone Clindamycin

Barbiturat es

Hydralacine

Melphalan

Piroxicam

Erythromycin Thiopental

Irbesartan

Dpenicilamine

Anaestheti cs
Bupivacaine

Teicoplanin

Benzodiaz epines
Clonazepam

Losartan

Tamoxifen

Rifampicin

Misoprostol

Opioids

Calcium Anthagoni sts

Rifabutin

Diazepam

Prazosin

Fentanyl

Nimodipine

Antidepre Flunitrazepam sants

Amitriptyline Flurazepam

Valsartan

Methadone

Nifedipine

ACE's
Fosinopropil

Antipsychotic s

Nitrendipine

Desipramine

Lorazepam

Clozapine

Antiarrhyt hmics

Imipramine

Midazolam

Quinapril

Fluoxetine

Amiodarone

Nortriptyline

Nitrazepam

Immunosupp ressors

Risperidone

Quinidine

Anticoag ulants
Warfarin

Oxacepam

Ciclosporin

Sertraline

Propafenone

Temazepam

Tacrolimus

Zolpidem

Lidocaine

Antiemeti Beta cs Blockers

Ondansetron Carvedilol

Methylprednisolone

Others
Celecoxib

Digoxin

Prednisone

Verapamil

Antiepilec Propanolol tics

Budesonide

Diphenhydra mine

Oral Antidiabet ics

Glibenclamide

Carbamazepin e

Diuretics

Ethinylestradi ol

Valproic acid Furosemide

Mefloquine

Spironolactone -

Paclitaxel

Torsemide

Effects of MARS on Survival[edit]

In the meta-analysis published by Khuroo et al.[70] which included 4 randomized trials[43][58][62][72] an improvement in survival for the patients with liver failure treated with MARS, compared with SMT, was not observed. However, neither in the extracorporeal liver support systems review by the Cochrane[88] (published in 2004), nor the meta-analysis by Kjaergard et al.[89] was a significance difference in survival found for patients diagnosed with ALF treated with extracorporeal liver support systems. Nevertheless, these reviews included all kind of liver support systems and used a heterogeneous type of publication ( abstracts, clinical trials, cohort, etc.). There is literature showing favorable results in survival for patients diagnosed with ALF, and treated with MARS., In a randomized controlled trial, Salib et al.[90] studied the impact on survival of MARS therapy for patients with ALF, waiting on the liver transplant list. Forty-nine patients received SMT and 53 were treated with MARS. They observed that patients that received 3 or more MARS sessions showed a statistically significance increase in transplant-free

survival compared with the others patients of the study. Notably, 75% of the patients underwent liver transplantation in the first 24 hours after inclusion in the waiting list, and besides the short exposure to MARS therapy, some patients showed a better survival trend compared to controls, when they were treated with MARS prior to the transplant. In a case-controlled study by Montejo et al.[73] it was reported that MARS treatment do not decrease mortality directly; however, the treatment contributed to significantly improve survival in patients that were transplanted. In studies by Mitzner et al.[62] and Heemann et al.[43] they were able to show a significance statistical difference in 30 day survival for patients in the MARS group. However, El Banayosy et al.[72] and Hassanein et al.[45] noticed a non significant improvement in survival, probably because of the short number of patients included in the trials. In the majority of available MARS studies published with patients diagnosed with ALF, either transplanted or not, survival was greater in the MARS group with some variations according to the type of trial, ranging from 20-30%,[91][92] and 60-80%.[52][93][94][95] Data is summarized in Tables 8, 9 and 10.

Table 8: Studies of MARS Therapy

Type N Level of MARS Study Pathology of Patients Evidence Study

Study Groups Analysed Variables MARS Controls

Mitzner et al..[62] (2000)

ACLF

13

RCT (LN)

III

18

5 HD

1, 3, 4

Heemann et al..[43] (2002)

ACLF

24

RCT (LN)

III

12

12 SMT

1, 2, 3, 4, 5

Sen et al.. (2004)

[44]

ACLF

18

RCT (LN)

III

9 SMT

1, 3, 4, 5

Hassanein et al..[45] (2007)

ACLF

70

RCT (HN)

II

39

31 SMT

1, 2, 3, 5

Schmidt et al..[58] (2003)

ALF

13

RCT (LN)

III

5 SMT

1, 3, 4

El Banayosy et al.[72] (2004)

ALF

27

RCT (LN)

III

14

13 HD

1, 3

Montejo et al.[73] (2009)

ACLF / ALF

45

Casecontrol

19

26 SMT

1, 2, 3, 4, 5

MARSPrometheus Studies

Evenepoel et al.[96] (2006)

ACLF

18

Case serie

VIII

Comparative series

1, 2, 3

Faenza et al.[97] (2008)

ACLF

57

Case serie

VIII

Comparative series

1, 2, 5

Krisper et al.[98] (2005)

ACLF

10

RCT (LN)

III

Crossover

1, 2, 3

Laleman et al.[57] (2006)

ACLF

18

RCT (LN)

III

2, 3, 4

Stadlbauer et al.[99] (2006)

ACLF

RCT (LN)

III

Crossover

1, 2, 3

Dethloff et al.[61] (2008)

ESLD

24

RCT (LN)

III

1, 2, 3, 4

Abbreviations; ACLF: Acute on chronic liver failure; ALF: Acute liver failure; ESLD: Endstage liver disease; RCT: Randomized controlled trial; RCT(LN): RCT, low number of patients; RCT (HN): RCT, high number of patients; HD: Hemodialysis; SMT: Standard medical treatment; 1: Survival/mortality; 2: Security; 3: Biochemical parameters; 4: hemodynamic parameters; 5: Clinical parameters.

Table 9: Survival with MARS Therapy

Study

Pathology

Controlled Study

Follow-up

Survival (%)

Bridging to LTx Faenza et al.[97] (2008) ACLF No 3 months Krisper et al.[98] (2005)

7/10 (70)

2/6 (33)

ACLF

Yes (crossover)

30 days

4/9 (44)

Stadlbauer et al.[99] (2006) Laleman et al.[57] (2006) Dethloff et al..[61] (2008)

ACLF

Yes (crossover)

30 days

4/8 (50)

ACLF

Yes

7 days

6/6 (100)

ESLD

Yes

6 months

5/8 (63)

Abbreviations; ALF: Acute liver failure; ACLF: Acute on chronic liver failure; ESLD: Endstage liver disease; Not statistically significance.

Table 10: Mortality in Selected Studies

Mortality Mortality Study N MARS (%) Controls Time

Odds Ratio (OR)

Acute on Chronic Liver Failure Mitzner et al. [62] Heemann et al. [43] 13 24 63 50 100 67 7 days 6 months 0.63 0.75

Sen et al..[44] Hassanein et al. [45] Dethloff et al. [61] Acute Liver Failure Schmidt et al. [58] El Banayosy et al.
[72]

18 70 24

56 49 25

56 55 50

3 months NR 6 months NR NR

1 0.89 0.50

13 27

38 50

40 69

0.94 0.72

Abbreviations; NR: Not reported.

For patients diagnosed with acute on chronic liver failure and treated with MARS therapy, clinical trial results showed a not statistically significant reduction in mortality (odds ratio [OR] =0,78; confident interval [CI] =95%: 0,58 1,03; p= 0,1059, Figure 3)

Figure 3: Meta-analysis showing the effect on survival of patients with ACLF treated with MARS therapy

A non-statistically significant reduction of mortality was shown in patients with ALF treated with MARS (OR = 0,75 [CI= 95%, 0,42 1,35]; p= 0,3427). (Figure 4)

Figure 4. Meta-analysis showing the effect on survival of patients with ALF treated with MARS therapy.

Combined results yielded a non-significant reduction on mortality in patients treated with MARS therapy. However, the low number of patients included in each of the studies may be responsible for not being able to achieve enough statistical power to show differences between both treatment groups. Moreover, heterogeneity for the number of MARS sessions and severity of liver disease of the patients included, make it very difficult for the evaluation of MARS impact on survival. Recently, a meta-analysis on survival in patients treated with an extra-hepatic therapy has been published.[100] Searching strategies yielded 74 clinical trials: 17 randomized controlled trials, 5 case control and 52 cohort studies. Eight studies were included in the meta-analysis: three addressing acute liver failure, one with MARS therapy[72] and five addressing acute on chronic, being four MARS related.[43][44][45][62] Authors concluded that extra-hepatic detoxifying systems improve survival for acute liver insufficiency, whereas results for acute decompensation of chronic liver diseases suggested a non significant survival benefit. Also, due to an increased demand for liver transplantation together with an augmented risk of liver failure following large resections, development of detoxifying extrahepatic systems are necessary.

Safety Aspects[edit]
Safety, defined as presence of adverse events, is evaluated in few trials. Adverse events in patients receiving MARS therapy are similar to those in the controls with the exception of

thrombocytopenia and hemorrhage that seems to occur more frequently with the MARS system.[101] Heemann et al.[43] reported two adverse events most probably MARS related: fever and sepsis, presumably originated at the catheter. In the study by Hassanein et al.,[45] two patients in the MARS group abandoned the study owing to hemodynamic instability, three patients required larger than average platelets transfusion and three more patients presented gastrointestinal bleeding. Laleman et al.[57] detected one patient with thrombocytopenia in both the MARS and Prometheus treatment groups, and an additional patient with clotting of the dialysis circuit and hypotension, only in the Prometheus group. Kramer et al. (Biologic-DT)[46] wrote about 3 cases with disseminated intravascular coagulation in the interventional group, two of them with fatal outcomes. Mitzner et al.[62] described, among patients treated with MARS, a thrombocytopenia case and a second patient with chronic hepatitis B, who underwent TIPS placement on day 44 after randomization and died on day 105 of multiorgan failure, as a concequence of complications related to the TIPS procedure. Montejo et al.[73] showed that MARS is an easy technique, without serious adverse events related to the procedure, and also easy to implement in ICU settings that are used to renal extracorporeal therapies. The MARS International Registry, with data from more than 500 patients (although sponsored by the manufacturer), shows that the adverse effects observed are similar to the control group. However, in these severely ill patients it is difficult to distinguish between complications of the disease itself and side effects attributable to the technique.

Health Economics[edit]
Only three Studies addressing cost-effectivenenss of MARS therapy have been found. Hassanein et al.[102] analysed costs of randomized patients with ACLF receiving MARS therapy or standard medical care. They used the study published in 2001 by Kim et al.[103] describing the impact of complications in hospitalization costs in patients diagnosed with alcoholic liver failure. Cost of 11 patients treated with standard medical care (SMT) were compared to those that received MARS, in addition to SMT (12 patients). In the MARS group, there was less in-hospital mortality and complications related to the disease, with a remarkable reduction in cost which compensated the MARS related expenditure (Table 11).

Table 11. Analysis of Complications According to the Modality of treatment.

MARS GROUP n=12 In-hospital mortality Worsening of hepatic encephalopathy (grade 4) Worsening of renal function (Hepatorenal Syndrome) Ascites Variceal bleeding Severe hypotension Electrolyte disorders Coagulopathy 1/12 0/12 1/12 0/12 0/12 2/12 4/12 4/12

CONTROL GROUP n=11 6/11 3/11 7/11 1/11 1/11 3/11 10/11 3/11

There were 5 survivors in the control group, with a cost per patient of $35.904, whereas in the MARS group, 11 patients out of 12 survived with a cost per patient of $32.036 which represents a $4000 savings per patient in favors of the MARS group. Hessel et al.[104] published a 3-year follow-up of a cohort of 79 patients with ACLF, of whom 33 received MARS treatments and 46 received SMT. Survival was 67% for the MARS group and 63% for the controls, that was reduced to 58 and 35% respectively at one year follow-up, and then 52 and 17% at three years. Hospitalization costs for the MARS treated group were greater than that for the controls (31.539 vs. 7.543) and similarly direct cost at 3-year follow-up (8.493 vs. 5.194). Nevertheless, after adjusting mortality rate, the annual cost per patient was 12.092 for controls and 5.827 for MARS group; also in the latter, they found an incremental cost-effectiveness ratio of 31.448 per life-year gained (LYG) and an incremental costs per QALY gained of 47171 . Two years later, same authors published the results of 149 patients diagnosed with ACLF.[105] There were 67 patients (44,9%) treated with MARS and 82 patients (55,1%) were allocated to receive SMT. Mean survival time was 692 days in the MARS group (33% at 3 years) and 453 days in the controls (15% at 3 years); the results were significant (p=0,022). Differences in average cost was 19.853 (95% IC: 13.308-25.429): 35.639 for MARS patients and 15.804 for the control group. Incremental cost per LYG was 29.985 (95% IC: 9.441-321.761) and 43.040 (95% IC: 13.551-461.856) per quality-adjusted life years (QALY). Liver support systems, such as MARS, are very important to stabilize patients with acute or acute on chronic liver failure and avoid organ dysfunction, as well as a bridge-to-transplant. Although initial in-hospital costs are high, they are worth for the favorable outcome.

MARS Therapy Indications[edit]

Acute on Chronic Liver Failure[edit]
Etiology:

Chronic viral hepatitis[106] Alcoholic liver disease[107][108] Autoimmune disease[109] Metabolic disease such as hemochromatosis Idiopathic Cirrhosis

Goals of MARS Therapy

Re-compensation of previous chronic state. Prolong survival time and bridge to urgent or elective transplant Pre-transplant optimization of the patient

MARS Therapy Indication

Bilirubin > 15 mg/dl (255 mol/l), not responding to standard medical care alter 3 days Renal dysfunction or hepatorenal syndrome. Hepatic encephalopathy II

Treatment Schedule:

3 to 5 eight-hour treatment sessions in consecutives days Continuous treatment with hemodynamic inestability (in any case, treatment kit must be replaced every 24 hours)

Acute Liver failure[edit]

Etiology:

Viral infection[34][58][110] Poisoning (paracetamol overdose, mushrooms)[93][111][112][113][114] Multiorgan dysfunction (severe sepsis) Vascular diseases (Budd Chiari syndrome) Hypoxic hepatitis[115] Liver failure during pregnancy or Reye syndrome Unknown etiology

Goals of MARS Therapy

Native liver recovery.

Bridging to liver transplant Pre-transplant optimization of the patient.

MARS Therapy Indication

Kings College or Clichy criteria for liver transplantation Hepatic encephalopathy II Increased intracraneal pressure Acute hypoxic hepatitis with bilirubin > 8 mg/dl (100 mol/l) Renal dysfunction or hepatorenal syndrome Progressive intrahepatic cholestasis Fulminant Wilson disease Acute liver dysfunction following paracetamol overdose

Treatment Schedule:

3 to 5 eight-hour treatment sessions in consecutives days Hypoxic hepatitis. 3 eight-hour treatment sessions in consecutives days Paracetamol overdose: 3 to 5 twenty four-hour treatment sessions Mushroom poisoning: 3 to 5 twenty four-hour treatment sessions Fulminant Wilson: minimum 5 twenty four-hour treatment sessions owing to copper saturation of the treatment kit

Drug overdose: 3 to 5 eight-hour treatment sessions in consecutives days

MARS in Graft Dysfucntion After Liver Transplant[116][117][edit]

Etiology:

Graft damage during preparation and transportation Infection Hepatotoxic drugs Graft rejection Technical complications (vascular, biliary) Recurrence of primary disease

Goals of MARS Therapy

Recovery and prevention of re-transplantation Prolong survival time and stabilize the patient to receive a re-transplant if the above goal is not achieved

MARS Therapy Indication

Primary graft dysfunction Hepatic encephalopathy II Increased intracranial pressure Renal dysfunction or hepatorenal syndrome. Progressive intrahepatic cholestasis

Treatment Schedule:

3 to 5 eight-hour treatment sessions in consecutives days Continuous treatment with hemodynamic inestability (in any case, treatment kit must be replaced every 24 hours)

MARS in liver Failure after Liver Surgery[118][edit]

Etiology:

Liver Resection in hepatocellular carcinoma Transarterial Chemoembolization (TACE) Partial resection in living donor transplantation Other surgical intervenctions

Goals of MARS Therapy

Recovery until hepatic regeneration

MARS Therapy Indication

Hepatic encephalopathy II Renal dysfunction or hepatorenal syndrome. Progressive intrahepatic cholestasis

Treatment Schedule:

3 to 5 eight-hour treatment sessions in consecutives days Continuous treatment with hemodynamic inestability (in any case, treatment kit must be replaced every 24 hours)

MARS for intractable pruritus in Cholestasis[66][66][106][109][119][edit]

Etiology:

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) Benign intrahepatic cholestasis (BIC) Biliary Atresia

Goals of MARS Therapy

Attenuate pruritus symptoms and improve patients quality of life

MARS Therapy Indication

Pruritus not responding to SMT

Treatment Schedule:

3 to 5 eight-hour treatment sessions in consecutives days Repeat treatment when symptoms reoccur

MARS Therapy Contraindications[edit]

Same contraindications as with any other extracorporeal treatment may be applied to MARS therapy.

Unstable hemodynamics with mean arterial pressure (MAP)< 55 mmHg despite vasoconstrictors administration

Uncontrolled hemorrhage Severe coagulopathy Severe thrombocytopenia

Treatment Parameters[edit]
Blood Flow The trend is to use high flow rates, although it is determined by the technical specifications of the combined machine and catheters size Intermittent treatments:

Without renal dysfunction, it is recommended a blood and albumin flow rates ranging from 150 to 250 ml/min

Continuous treatments:

With or without renal impairment it is recommended to use flow rates from 100 to 150 ml/min.

Dyalisate Flow Rate Intermittent treatments:

Without renal impairment: 1800 a 3000 ml/hour With renal impairment: 3000 a 6000 ml/hour

Continuous treatments:

Recommended flow rate: 1000 to 2000 ml/hour.

Replacement Flow Rate

According to medical criteria and same as in CVVHD

Heparin Anticoagulation Similarly to CVVHD, it depends of previous patients coagulation status. In many cases it will not be needed, unless the patient presents a PTT inferior to 160 seconds. In patients with normal values, a bolus of 5000 to 10000 IU of heparin could be administered at the comencement of the treatment, followed by a continuous perfusion, to keep PTT in ratios from 1,5 to 2,5 or 160 to 180 seconds. Monitoring A biochemical analysis is recommended (liver and kidney profile, ionic, glucose) together with a hemogram at the end of first session and before starting the following one. Coagulation analysis must be also performed before starting the session to adjusting heparin dose. In case that medication susceptible to be eliminated by MARS is being administered, it is also recommended to monitor their levels in blood End of the Session

Once the treatment is finalized, blood should be returned following the unit procedure,

and both catheters lumens heparinized

For the next session a new kit must be used For continuous treatments, kit must be changed by a new one every 24 hours Treatment must be stopped before schedule owing to the particular circumstances listed below: 1. MAP inferior to 40 mmHg at least for 10 minutes 2. Air embolism of the extracorporeal circuit 3. Transmembrane pressure (TMP) greater than 600 mmHg. 4. Blood leak detection in the albumin circuit 5. Disseminated intravascular coagulation (DIC) 6. Severe active hemorrhage

FDA Clearance (US only)[edit]

Federal Drug Administration (FDA) cleared, in a document dated on May 27, 2005, MARS therapy for the treatment of drug overdose and poisoning. The only requirement is that the drug or poison must be susceptible to be dialysed and removed by activated charcoal or anionic exchange resins. More recently, on December 17, 2012, MARS therapy has been cleared by the FDA for the treatment of hepatic encephalopathy due to a decompensation of a chronic liver disese Clinical trials conducted with MARS treatment in HE patients having a decompensation of chronic liver disease demonstrated a transient effect from MARS treatments to significantly decrease their hepatic encephalopathy scores by at least 2 grades compared to standard medical therapy (SMT). The MARS is not indicated as a bridge to liver transplant. Safety and efficacy has not been demonstrated in controlled, randomized clinical trials. The effectiveness of the MARS device in patients that are sedated could not be established in clinical studies and therefore cannot be predicted in sedated patients

References[edit]
1. Jump up^

Instruments used in general medicine

From Wikipedia, the free encyclopedia
Instruments used in general medicine and clinics (i.e. internal medicine and pediatrics) are as follows:[1][2]

Instrument list[edit]
Instrument Uses

Stethoscope

used to hear sounds from movements within the body, like heart beats, intestinal movement, breath sounds, etc.

Reflex testing hammer (padded)

to test motor reflexs of the body

Sphygmomanometer (Blood

to record the patient's blood pressure

pressure meter)

A thin beam electric torch

to see into the eye, body's natural orifices, etc., and to test for pupillary light reflex, etc.

A watch / stopwatch

used in recording rates like heart rate, respiratory rate, etc.; for certain tests of hearing

A measuring tape

for size measurements

A weighing machine

to record the weight

Tuning forks

to test for deafness and to categorize it

Kidney dish

as a tray for instruments, gauze, tissue, etc.

Bedpan

for patients who are unconscious or too weak to even sit up of walk to the toilet to defecate

Thermometer

to record the body temperature

Gas cylinders

supply of oxygen, nitrous oxide, carbon dioxide, etc.

Oxygen mask or tubes

delivering gases up to the nostrils to assist in oxygen intake or to administer aerosolized or gaseous drugs

Vaporizer

to produce vapors

Instrument sterilizers

Used to sterilize instruments in absence of an autoclave

Dressing drums

storage of gowns, cotton, linen, etc.

Nebulizer

to produce aerosols of drugs to be administered by respiratory route

Positive pressure ventilator

to assist or carry out the mechanical act of inspiration and expiration so that the patient who can not respire on his / her own may respire; it is a component of "life support"

Cardioverter / Defibrillator

to correct arrhythmias of the heart or to start up a heart that is not beating

Dialyser

to remove toxic materials from the blood that are generally removed by the kidneys; used in case of renal failure

Rubber catheter

to drain and collect urine directly from the bladder (primary use); also to act as a makeshift oxygen tube, etc.

Syringe of different sizes and needles

for injections and aspiration of blood or fluid from the body

Canula

a kind of a needle that is used to create a permanent pathway to a vein (or artery) for the purpose of repeated injections or infusion ofintravenous fluids

Transfusion sets

used to transfuse blood and blood products

Sucker Gastrointestinal tubes[3]

for sucking up blood or secretions)

Nasogastric tube

used for nasogastric suction (or at times introduction of food or drugs). vide link

Stomach tube Levin's tube Kehr's "T" tube Infant feeding tube

-do-

-do-

-do-

-do-; for infants

Spectacles

for protection of the eyes or for refractive error correction

Enema set

to passively evacuate the rectum of faeces; vide link

Bandage

to cover and protect certain areas of the body such as recent injury

Pipettes or droppers

to measure out doses of liquid, specially in children

Graduated spoons

to measure out doses of liquids

Ophthalmoscope

to look at the retina

Otoscope

to look into the external ear cavity

Endoscope

to look inside the oesophagus, stomach, upper intestines, bile duct, larynx, trachea, bronchi-through the mouth; anal canal, rectum, colon-

through anus; used mainly in Surgery or by surgical consultants

Proctoscope

to look inside anal canal and lower part of the rectum

Linen

for dressing and draping

Beds, bottle stands, etc.

Gauze, cotton, antiseptics,gloves etc.

This list is incomplete; you can help by expanding it.

Image gallery[edit]

Clinical mercury manometer

Stethoscope

Tuning fork

Reflex hammer

Queen square reflex hammer

Mercury thermometers

Weight scale

Kidney dish

Bedpan

Cylinder of oxygen

Nebulizer

High frequency ventilator

Defibrillator

Hemodialysis machine

Syringe and needle

Foley catheter

Intravenous cannula

Intravenous cannula (parts)

Blood infusion set

Spectacles

Enema bulb

Enema set

Bandage

Endoscope

Ophthalmoscope

References[edit]
1. Jump up^

EXTERNAL PROSTHESIS

Prosthesis
From Wikipedia, the free encyclopedia
For other uses, see Prosthesis (disambiguation). Not to be confused with Orthotic.

A man with two prosthetic arms playingtable football.

Disability
Theory and models[show] Education[show] Therapy[show] Societal implications[show] Personal / physical assistance[show] Socioeconomic assistance[show] Groups and organizations[show] Disabled sports[show] Culture[show]

Disability portal Category: Disability Category: Disability lists

V T E

In medicine, a prosthesis, (from Ancient Greek prsthesis, "addition, application, attachment")[1] is an artificial device that replaces a missing body part lost through trauma, disease, or congenital conditions. Prosthetic amputee rehabilitation is coordinated by an interdisciplinary team of health care professionals including physiatrists and prosthetists.

Contents [hide]

1 Types
o

1.1 Limb Prostheses

2 History

2.1 Lower extremity modern history 3.1 Body-powered arms

3 Current technology/manufacturing
o

3.1.1 Sockets 3.1.2 Wrists 3.1.3 Voluntary opening and voluntary closing 3.1.4 Feedback 3.1.5 Terminal devices

3.1.5.1 Hooks 3.1.5.2 Hands

3.1.6 Commercial providers, materials 3.2.1 Socket 3.2.2 Shank & Connectors 3.2.3 Foot 3.2.4 Knee-joint

3.2 Lower extremity prosthetics

3.2.4.1 Microprocessor Controlled

o o

3.3 Myoelectric 3.4 Robotic prostheses

3.4.1 Robotic arms 3.4.2 Robotic legs

4 Attachment to the body

o

4.1 Direct bone attachment / osseointegration

5 Cosmesis 6 Cognition 7 Prosthetic enhancement 8 Design considerations

o o

8.1 Performance 8.2 Other 9.1 High-cost 9.2 Low-cost 9.3 Open-source 10.1 Pole and Crutch 10.2 (Bamboo) PVC/Plaster limbs

9 Cost
o o o

10 Low-cost Prosthetics for Children

o o

o o o

10.3 Adjustable Bicycle Limb 10.4 Sathi Limb 10.5 Monolimb

11 References 12 External links

Types[edit]
A person's prosthesis sould be designed and assembled according to the patient's appearance and functional needs. For instance, a patient may need a transradial prosthesis, but need to choose between an aesthetic functional device, a myoelectric device, a body-powered device, or an activity specific device. Depending on the patient's economical capabilities, she may have the option to choose more than one device. Craniofacial prostheses include intra-oral and extra-oral prostheses. Extra-oral prostheses are further divided into hemifacial, auricular (ear), nasal, orbital and ocular. Intra-oral prostheses include dental prostheses such as dentures, obturators, and dental implants. Prostheses of the neck include larnyx substitutes, trachea and upper esophageal replacements, Somato prostheses of the torso include breast prostheses which may be either single or bilateral, full breast devices or nipple prostheses.

Limb Prostheses[edit]

A United States Marine with bilateral prosthetic legs leads a formation run.
Limb Prostheses include both upper and lower extremity prostheses.

Upper extremity prostheses are used at varying levels of amputation: shoulder disarticulation, transhumeral prosthesis, elbow disarticulation, transradial prosthesis, wrist disarticulation, full hand, partial hand, finger, partial finger. A transhumeral prosthesis is an artificial limb that replaces an arm missing above the elbow. Transhumeral amputees experience some of the same problems as transfemoral amputees, due to the similar complexities associated with the movement of the elbow. This makes mimicking the correct motion with an artificial limb very difficult. In the prosthetic industry a trans-humeral prosthesis is often referred to as a "AE" or above the elbow prothesis. A transradial prosthesis is an artificial limb that replaces an arm missing below the elbow. Two main types of prosthetics are available. Cable operated limbs work by attaching a harness and cable around the opposite shoulder of the damaged arm. The other form of prosthetics available are myoelectric arms. These work by sensing, via electrodes, when the muscles in the upper arm moves, causing an artificial hand to open or close. In the prosthetic industry a trans-radial prosthetic arm is often referred to as a "BE" or below elbow prosthesis. Lower extremity prostheses provide replacements at varying levels of amputation. These include hip disarticulation, transfemoral prosthesis, knee disarticulation, transtibial prosthesis, symes, foot, partial foot, and toe. The two main subcategories of lower extremity prosthetic devices are trans-tibial (any amputation transecting the tibia bone or a congenital anomaly resulting in a tibial deficiency) and trans-femoral (any amputation transecting the femur bone or a congenital anomaly resulting in a femoral deficiency). A transfemoral prosthesis is an artificial limb that replaces a leg missing above the knee. Transfemoral amputees can have a very difficult time regaining normal movement. In general, a transfemoral amputee must use approximately 80% more energy to walk than a person with two whole legs.[2] This is due to the complexities in movement associated with the knee. In newer and more improved designs, hydraulics, carbon fiber, mechanical linkages, motors, computer microprocessors, and innovative combinations of these technologies are employed to give more control to the user. In the prosthetic industry a trans-femoral prosthetic leg is often referred to as an "AK" or above the knee prosthesis.[3] A transtibial prosthesis is an artificial limb that replaces a leg missing below the knee. Transtibial amputees are usually able to regain normal movement more readily than someone with a transfemoral amputation, due in large part to retaining the knee, which allows for easier movement. Lower extremity prosthetics describes artificially replaced limbs located at the hip level or lower. In the prosthetic industry a trans-tibial prosthetic leg is often referred to as a "BK" or below the knee prosthesis.

History[edit]

Prosthetic toe from ancient Egypt

Prosthetics have been mentioned throughout history. The earliest recorded mention is the warrior queen Vishpala in the Rigveda.[4] The Egyptians were early pioneers of the idea, as shown by the wooden toe found on a body from the New Kingdom.[5] Roman bronze crownshave also been found, but their use could have been more aesthetic than medical.[6] Another early mention of a prosthetic comes from the Greek historian Herodotus, who tells the story of Hegesistratus, a Greek diviner who cut off his own foot to escape his Spartan captors and replaced it with a wooden one.[7] Pliny the Elder also recorded that a Roman general who had his arm cut off had an iron one made to hold his shield up when he returned to battle. A famous and quite refined[8]historical prosthetic arm was that of Gtz von Berlichingen, made at the beginning of the 16th century.

An artificial limbs factory in 1941

Around the same time, Franois de la Noue is also reported to have had an iron hand, as is, in the 1600s century, Ren-Robert Cavalier de la Salle.[9] During the Middle Ages, prosthetics remained quite basic in form. Debilitated knights would be fitted with prosthetics so they could hold up a shield. Only the wealthy could afford anything that would assist in daily life.[citation
needed]

During the Renaissance, prosthetics developed with the use of iron, steel, copper, and

wood. Functional prosthetics began to make an appearance in the 1500s.[citation needed]

Artificial iron arm owned by Gtz von Berlichingen (14801562)

Gtz von Berlichingen, a German mercenary, owned a pair of iron hands that could be moved by a series of catches and springs. An Italian surgeon recorded the existence of an amputee who had an arm that allowed him to remove his hat, open his purse, and sign his name.[10] Improvement in amputation surgery and prosthetic design came at the hands of

Ambroise Par. Among his inventions was an above-knee device that was a kneeling peg leg and foot prosthesis with a fixed position, adjustable harness, and knee lock control. The functionality of his advancements showed how future prosthetics could develop. Other major improvements before the modern era:

Pieter Verduyn First nonlocking below-knee (BK) prosthesis. James Potts Prosthesis made of a wooden shank and socket, a steel knee joint and an articulated foot that was controlled by catgut tendons from the knee to the ankle. Came to be known as Anglesey Leg or Selpho Leg.

Sir James Syme A new method of ankle amputation that did not involve amputating at the thigh. Benjamin Palmer Improved upon the Selpho leg. Added an anterior spring and concealed tendons to simulate natural-looking movement. Dubois Parmlee Created prosthetic with a suction socket, polycentric knee, and multiarticulated foot. Marcel Desoutter & Charles Desoutter First aluminum prosthesis[11]

At the end of World War II, the NAS (National Academy of Sciences) began to advocate better research and development of prosthetics. Through government funding, a research and development program was developed within the Army, Navy, Air Force, and the Veterans Administration.

Lower extremity modern history[edit]

Socket technology for lower extremity limbs saw a revolution of advancement during the 1980s when John Sabolich C.P.O., invented the Contoured Adducted Trochanteric-Controlled Alignment Method (CATCAM) socket, later to evolve into the Sabolich Socket. He followed the direction of Ivan Long and Ossur Christensen as they developed alternatives to the quadrilateral socket, which in turn followed the open ended plug socket, created from wood.[12] The advancement was due to the difference in the socket to patient contact model. Prior, sockets were made in the shape of a square shape with no specialized containment for muscular tissue. New designs thus help to lock in the bony anatomy, locking it into place and distributing the weight evenly over the existing limb as well as the musculature of the patient. Ischial containment is well known and used today by many prosthetist to help in patient care. Variations of the ischial containment socket thus exists and each socket is tailored to the specific needs of the patient. Others who contributed to socket development and changes over the years include Tim Staats, Chris Hoyt, and Frank Gottschalk. Gottschalk disputed the efficacy of the CAT-CAM socketinsisting the surgical procedure done by the amputation surgeon was most important to prepare the amputee for good use of a prosthesis of any type socket design.[13]

The first microprocessor-controlled prosthetic knees became available in the early 1990s. The Intelligent Prosthesis was first commercially available microprocessor controlled prosthetic knee. It was released by Chas. A. Blatchford & Sons, Ltd., of Great Britain, in 1993 and made walking with the prosthesis feel and look more natural.[14] An improved version was released in 1995 by the name Intelligent Prosthesis Plus. Blatchford released another prosthesis, the Adaptive Prosthesis, in 1998. The Adaptive Prosthesis utilized hydraulic controls, pneumatic controls, and a microprocessor to provide the amputee with a gait that was more responsive to changes in walking speed. Cost analysis reveals that a sophisticated above knee prosthesis will be in the neighborhood of $1 million in 45 years, given only annual cost of living adjustments.[15]

Current technology/manufacturing[edit]

Knee prosthesis manufactured usingWorkNC Computer Aided Manufacturingsoftware

Over the years there have been significant advancements in artificial limbs. New plastics and other materials, such as carbon fiber, have allowed artificial limbs to be stronger and lighter, limiting the amount of extra energy necessary to operate the limb. This is especially important for transfemoral amputees. Additional materials have allowed artificial limbs to look much more realistic, which is important to transradial and transhumeral amputees because they are more likely to have the artificial limb exposed.[16]

Manufacturing a prosthetic finger

In addition to new materials, the use of electronics has become very common in artificial limbs. Myoelectric limbs, which control the limbs by converting muscle movements to electrical signals, have become much more common than cable operated limbs. Myoelectric signals are picked up by electrodes, the signal gets integrated and once it exceeds a certain threshold, the prosthetic limb control signal is triggered which is why inherently, all myoelectric controls lag. Conversely, cable control is immediate and physical, and through that offers a certain degree of direct force feedback that myoelectric control does not. Computers are also used extensively in the manufacturing of limbs. Computer Aided Design and Computer Aided Manufacturing are often used to assist in the design and manufacture of artificial limbs.[16] Most modern artificial limbs are attached to the stump of the amputee by belts and cuffs or by suction. The stump either directly fits into a socket on the prosthetic, ormore commonly todaya liner is used that then is fixed to the socket either by vacuum (suction sockets) or a pin lock. Liners are soft and by that, they can create a far better suction fit than hard sockets. Silicone liners can be obtained in standard sizes, mostly with a circular (round) cross section, but for any other stump shape, custom liners can be made. The socket is custom made to fit the residual limb and to distribute the forces of the artificial limb across the area of the stump (rather than just one small spot), which helps reduce wear on the stump. The custom socket is created by taking a plaster cast of the stump or, more commonly today, of the liner worn over the stump, and then making a mold from the plaster cast. Newer methods include laser guided measuring which can be input directly to a computer allowing for a more sophisticated design. One problem with the stump and socket attachment is that a bad fit will reduce the area of contact between the stump and socket or liner, and increase pockets between stump skin and socket or liner. Pressure then is higher, which can be painful. Air pockets can allow sweat to accumulate that can soften the skin. Ultimately, this is a frequent cause for itchy skin rashes. Further down the road, it can cause breakdown of the skin.[2] Artificial limbs are typically manufactured using the following steps:[16] 1. Measurement of the stump 2. Measurement of the body to determine the size required for the artificial limb 3. Fitting of a silicone liner 4. Creation of a model of the liner worn over the stump 5. Formation of thermoplastic sheet around the model This is then used to test the fit of the prosthetic 6. Formation of permanent socket 7. Formation of plastic parts of the artificial limb Different methods are used, including vacuum forming and injection molding 8. Creation of metal parts of the artificial limb using die casting

9. Assembly of entire limb

Body-powered arms[edit]
Current high tech allows body powered arms to weigh around half to only a third of the weight that a myoelectric arm has.

Sockets[edit]
Current body powered arms contain sockets that are built from hard epoxy or carbon fiber. These sockets or "interfaces" can be made more comfortable by lining them with a softer, compressible foam material that provides padding for the bone prominences. A self suspending or supracondylar socket design is useful for those with short to mid range below elbow absence. Longer limbs may require the use of a locking roll-on type inner liner or more complex harnessing to help augment suspension.

Wrists[edit]
Wrist units are either screw-on connectors featuring the UNF 1/2-20 thread (USA) or quick release connector, of which there are different models.

Voluntary opening and voluntary closing[edit]

Two types of body powered systems exist, voluntary opening "pull to open" and voluntary closing "pull to close". Virtually all "split hook" prostheses operate with a voluntary opening type system. More modern "prehensors" called GRIPS utilize voluntary closing closing systems. The differences are significant. Users of voluntary opening systems rely on elastic bands or springs for gripping force, while users of voluntary closing systems rely on their own body power and energy to create gripping force. Voluntary closing users can generate prehensive forces equivalent to the normal hand, upwards to or exceeding one hundred pounds. Voluntary closing GRIPS require constant tension to grip, like a human hand, and in that property they do come closer to matching human hand performance. Voluntary opening split hook users are limited to forces their rubber or springs can generate which usually is below twenty pounds.

Feedback[edit]
An additional difference exists in the biofeedback created that allows the user to "feel" what is being held. Voluntary opening systems once engaged provide the holding force so that they operate like a passive vice at the end of the arm. No gripping feedback is provided once the hook has closed around the object being held. Voluntary closing systems provide directly proportional control and biofeedback so that the user can feel how much force that they are applying. A recent study showed that by stimulating the median and ulnar nerves, according to the information provided by the artificial sensors from a hand prosthesis, physiologically appropriate (near-natural) sensory information could be provided to an amputee. This feedback enabled the

participant to effectively modulate the grasping force of the prosthesis with no visual or auditory feedback.[17]

Terminal devices[edit]
Terminal devices contain a range of hooks, prehensors, hands or other devices.

Hooks[edit]
Voluntary opening split hook systems are simple, convenient, light, robust, versatile and relatively affordable. Hooks obviously do not match human hand in both appearance and overall versatility. However, a hook's material tolerances can also exceed and surpass the human hand for mechanical stress (one can use a hook to slice open boxes or as a hammer whereas same is not possible with a hand), for thermal stability (one can use a hook to grip items from boiling water, to turn meat on a grill, to hold a match until it has burned down completely) and for chemical hazards (as a metal hook withstands acids or lye, and does not react to solvents as a prosthetic glove or human skin does).

Hands[edit]

Actor Owen Wilson gripping the myoelectric prosthetic arm of a United States Marine
Prosthetic hands are available in both voluntary opening and voluntary closing versions and because of their more complex mechanics and cosmetic glove covering require a relatively large activation force, which, depending on the type of harness used, may be uncomfortable.[18] Researchers from cole Polytechnique Fdral De Lausanne, in Switzerland and the Scuola Superiore Sant'Anna, in Italy, implanted the electrodes into the amputee's arm in February 2013. The study, published Wednesday in Science Translational Medicine, details the first time sensory feedback has been restored allowing an amputee to control an artificial limb in real-time.[19] With wires linked to nerves in his upper arm, the Danish patient was able to handle objects and instantly receive a sense of touch through the special artificial hand that was created by Silvestro Micera and researchers both in Switzerland and Italy.[20]

Commercial providers, materials[edit]

Hosmer and Otto Bock are major commercial hook providers. Mechanical hands are sold by Hosmer and Otto Bock as well; the Becker Hand is still manufactured by the Becker family. Prosthetic hands may be fitted with standard stock or custom made cosmetic looking silicone gloves. But regular work gloves may be worn as well. Other terminal devices include the V2P Prehensor, a versatile robust gripper that allows customers to modify aspects of it, Texas Assist Devices (with a whole assortment of tools) and TRS that offers a range of terminal devices for sports. Cable harnesses can be built using aircraft steel cables, ball hinges and self lubricating cable sheaths.

Lower extremity prosthetics[edit]

A prosthetic leg worn by Ellie Cole

Lower extremity prosthetics describes artificially replaced limbs located at the hip level or lower. Concerning all ages Ephraim et al. (2003) found a worldwide estimate of all-cause lowerextremity amputations of 2.0 5.9 per 10.000 inhabitants. For birth prevalence rates of congenital limb deficiency they found an estimate between 3.5 7.1 cases per 10.000 births.[21] The two main subcategories of lower extremity prosthetic devices are 1.trans-tibial (any amputation transecting the tibia bone or a congenital anomaly resulting in a tibial deficiency) and 2.trans-femoral (any amputation transecting the femur bone or a congenital anomaly resulting in a femoral deficiency). In the prosthetic industry a trans-tibial prosthetic leg is often referred to as a "BK" or below the knee prosthesis while the trans-femoral prosthetic leg is often referred to as an "AK" or above the knee prosthesis. Other, less prevalent lower extremity cases include the following:

1. Hip disarticulations This usually refers to when an amputee or congenitally challenged patient has either an amputation or anomaly at or in close proximity to the hip joint. 2. Knee disarticulations This usually refers to an amputation through the knee disarticulating the femur from the tibia. 3. Symes This is an ankle disarticulation while preserving the heel pad.

Socket[edit]
This important part serves as an interface between the residuum and the prosthesis, allowing comfortable weight-bearing, movement control and proprioception.[22] Its fitting is one of the most challenging aspects of the entire prosthesis. The difficulties accompanied with the socket are that it needs to have a perfect fit, with total surface bearing to prevent painful pressure spots. It needs to be flexible, but sturdy, to allow normal gait movement but not bend under pressure.

Shank & Connectors[edit]

This part creates distance and support between the knee-joint and the foot (in case of upper-leg prosthesis) or between the socket and the foot. The type of connectors that are used between the shank and the knee/foot determines whether the prosthesis is modular or not. Modular means that the angle and the displacement of the foot in respect to the socket can be changed after fitting. In developing countries prosthesis mostly are non-modular, in order to reduce cost. When considering children modularity of angle and height is important because of their average growth of 1.9 cm annually.[23]

Foot[edit]
Providing contact between to the ground the foot provides shock absorption and stability during stance.[24] Additionally it influences gait biomechanics by its shape and stiffness. This is because the trajectory of the centre of pressure (COP) and the angle of the ground reaction forces is determined by the shape and stiffness of the foot and needs to match the subjects build in order to produce a normal gait pattern.[25] Andrysek (2010) found 16 different types of feet, with greatly varying results concerning durability and biomechanics. The main problem found in current feet is durability, endurance ranging from 1632 months [26] These results are for adults and will probably be worse for children due to higher activity levels and scale effects.

Knee-joint[edit]
In case of a trans-femoral amputation there also is a need for a complex connector providing articulation, allowing flexion during swing-phase but not during stance.

Microprocessor Controlled[edit]

Two different models microprocessor controlled knees (C-leg)

To mimic the knee's functionality during gait, microprocessor-controlled knee joints have been developed that control the flexion of the knee. Some examples are Otto Bocks C-leg , introduced in 1997, Ossur's Rheo Knee, released in 2005, the Power Knee byOssur, introduced in 2006, the Pli Knee from Freedom Innovations[27] and DAW Industries Self Learning Knee (SLK).[28] The idea was originally developed by Kelly James, a Canadian engineer, at the University of Alberta.[29] A microprocessor is used to interpret and analyse signals from knee-angle sensors and moment sensors. The microprocessor receives signals from its sensors to determine the type of motion being employed by the amputee. Most microprocessor controlled knee-joints are powered by a battery housed inside the prosthesis. The sensory signals are computed by the microprocessor are used to control the resistance generated by hydraulic cylinders in the knee-joint. Small valves control the amount of hydraulic fluid that can pass into and out of the cylinder, thus regulating the extension and compression of a piston connected to the upper section of the knee.[15] The main advantage of microprocessor controlled prosthesis is closer approximation to an amputees natural gait. Some even allow amputees to walk near walking speed or run. Variations in speed are also possible and are taken into account by sensors and communicated to the microprocessor, which adjusts to these changes accordingly. It also enables the amputees to walk down stairs with a step-over-step approach, rather than the one step at a time approach used with mechanical knees.[30] However, some have some significant drawbacks that impair its use. They can be susceptible to water damage and thus great care must be taken to ensure that the prosthesis remains dry.

Myoelectric[edit]
A myoelectric prosthesis uses electromyography signals or potentials from voluntarily contracted muscles within a person's residual limb on the surface of the skin to control the

movements of the prosthesis, such as elbow flexion/extension, wrist supination/pronation (rotation) or hand opening/closing of the fingers. A prosthesis of this type utilizes the residual neuro-muscular system of the human body to control the functions of an electric powered prosthetic hand, wrist or elbow. This is as opposed to an electric switch prosthesis, which requires straps and/or cables actuated by body movements to actuate or operate switches that control the movements of a prosthesis or one that is totally mechanical. It is not clear whether those few prostheses that provide feedback signals to those muscles are also myoelectric in nature. It has a self suspending socket with pick up electrodes placed over flexors and extensors for the movement of flexion and extension respectively. The first commercial myoelectric arm was developed in 1964 by the Central Prosthetic Research Institute of the USSR, and distributed by the Hangar Limb Factory of theUK.[31][32] Researchers at the Rehabilitation Institute of Chicago announced in September 2013 that they have developed a robotic leg that translates neural impulses from the user's thigh muscles into movement, which is the first prosthetic leg to do so. It is currently in testing.[33]

Robotic prostheses[edit]
Main articles: Neural prosthetics and Powered_exoskeleton#Current_exoskeletons Further information: Robotics#Touch In order for a robotic prosthetic limb to work, it must have several components to integrate it into the body's function: Biosensors detect signals from the user's nervous or muscular systems. It then relays this information to a controller located inside the device, and processes feedback from the limb and actuator (e.g., position, force) and sends it to the controller. Examples include wires that detect electrical activity on the skin, needle electrodes implanted in muscle, or solidstate electrode arrays with nerves growing through them. One type of these biosensors are employed in myoelectric prosthesis. Mechanical sensors process aspects affecting the device (e.g., limb position, applied force, load) and relay this information to the biosensor or controller. Examples include force meters and accelerometers. The controller is connected to the user's nerve and muscular systems and the device itself. It sends intention commands from the user to the actuators of the device, and interprets feedback from the mechanical and biosensors to the user. The controller is also responsible for the monitoring and control of the movements of the device. An actuator mimics the actions of a muscle in producing force and movement. Examples include a motor that aids or replaces original muscle tissue. Targeted muscle reinnervation (TMR) is a technique in which motor nerves which previously controlled muscles on an amputated limb are surgically rerouted such that they reinnervate a

small region of a large, intact muscle, such as the pectoralis major. As a result, when a patient thinks about moving the thumb of his missing hand, a small area of muscle on his chest will contract instead. By placing sensors over the reinervated muscle, these contractions can be made to control movement of an appropriate part of the robotic prosthesis.[34][35] An emerging variant of this technique is called targeted sensory reinnervation (TSR). This procedure is similar to TMR, except that sensory nerves are surgically rerouted to skinon the chest, rather than motor nerves rerouted to muscle. The patient then feels any sensory stimulus on that area of the chest, such as pressure or temperature, as if it were occurring on the area of the amputated limb which the nerve originally innervated. In the future, artificial limbs could be built with sensors on fingertips or other important areas. When a stimulus, such as pressure or temperature, activated these sensors, an electrical signal would be sent to an actuator, which would produce a similar stimulus on the "rewired" area of chest skin. The user would then feel that stimulus as if it were occurring on an appropriate part of the artificial limb.[34] Recently, robotic limbs have improved in their ability to take signals from the human brain and translate those signals into motion in the artificial limb. DARPA, the Pentagons research division, is working to make even more advancements in this area. Their desire is to create an artificial limb that ties directly into the nervous system.[36]

Robotic arms[edit]
Advancements in the processors used in myoelectric arms has allowed to make gains in fine tuned control of the prosthetic. The Boston Digital Arm is a recent artificial limb that has taken advantage of these more advanced processors. The arm allows movement in five axes and allows the arm to be programmed for a more customized feel. Recently thei-Limb hand, invented in Edinburgh, Scotland, by David Gow has become the first commercially available hand prosthesis with five individually powered digits. The hand also possesses a manually rotatable thumb which is operated passively by the user and allows the hand to grip in precision, power and key grip modes.[37] Raymond Edwards,Limbless Association Acting CEO, was the first amputee to be fitted with the i-LIMB by the National Health Service in the UK.[38] The hand, manufactured by "Touch Bionics"[39] of Scotland (a Livingston company), went on sale on 18 July 2007 in Britain.[40] It was named alongside the Large Hadron Collider in Time magazine's top fifty innovations.[41] Another neural prosthetic is Johns Hopkins University Applied Physics Laboratory Proto 1. Besides the Proto 1, the university also finished the Proto 2 in 2010.[42] Early in 2013, Max Ortiz Catalan and Rickard Brnemark of the Chalmers University of Technology, and Sahlgrenska University Hospital in Sweden, succeeded in making the first robotic arm which is mind-controlled and can be permanently attached to the body (using osseointegration).[43][44][45]

Robotic legs[edit]
Robotic legs have also been developed: the Argo Medical Technologies ReWalk is an example or a recent robotic leg, targeted to replace the wheelchair. It is marketed as a "robotic pants".[46] Walk Again project is developing a similar device.[47]

Attachment to the body[edit]

Most prostheses can be attached to the exterior of the body, in a non-permanent way. Some others however can be attached in a permanent way. One such example are exoprostheses (see below).

Direct bone attachment / osseointegration[edit]

Main article: Osseointegration Osseointegration is a new method of attaching the artificial limb to the body. This method is also sometimes referred to as exoprosthesis (attaching an artificial limb to the bone), or endoexoprosthesis. The stump and socket method can cause significant pain in the amputee, which is why the direct bone attachment has been explored extensively. The method works by inserting a titanium bolt into the bone at the end of the stump. After several months the bone attaches itself to the titanium bolt and an abutment is attached to the titanium bolt. The abutment extends out of the stump and the (removable) artificial limb is then attached to the abutment. Some of the benefits of this method include the following:

Better muscle control of the prosthetic. The ability to wear the prosthetic for an extended period of time; with the stump and socket method this is not possible.

The ability for transfemoral amputees to drive a car.

The main disadvantage of this method is that amputees with the direct bone attachment cannot have large impacts on the limb, such as those experienced during jogging, because of the potential for the bone to break.[2]

Cosmesis[edit]
Cosmetic prosthesis has long been used to disguise injuries and disfigurements. With advances in modern technology, cosmesis, the creation of lifelike limbs made from siliconeor PVC has been made possible. Such prosthetics, such as artificial hands, can now be made to mimic the appearance of real hands, complete with freckles, veins, hair, fingerprints and even tattoos. Custom-made cosmeses are generally more expensive (costing thousands of US dollars, depending on the level of detail), while standard cosmeses come ready-made in various sizes, although they are often not as realistic as their custom-made counterparts. Another option is the

custom-made silicone cover, which can be made to match a person's skin tone but not details such as freckles or wrinkles. Cosmeses are attached to the body in any number of ways, using an adhesive, suction, form-fitting, stretchable skin, or a skin sleeve.

Cognition[edit]
Main article: Neuroprosthetics Unlike neuromotor prostheses, neurocognitive prostheses would sense or modulate neural function in order to physically reconstitute or augment cognitive processes such asexecutive function, attention, language, and memory. No neurocognitive prostheses are currently available but the development of implantable neurocognitive brain-computer interfaces has been proposed to help treat conditions such as stroke, traumatic brain injury, cerebral palsy, autism, and Alzheimer's disease.[48] The recent field of Assistive Technology for Cognition concerns the development of technologies to augment human cognition. Scheduling devices such as Neuropage remind users with memory impairments when to perform certain activities, such as visiting the doctor. Micro-prompting devices such as PEAT, AbleLink and Guide have been used to aid users with memory and executive function problems perform activities of daily living.

Prosthetic enhancement[edit]
Further information: Powered exoskeleton#Research

Sgt. Jerrod Fields, a U.S. Army World Class Athlete Program Paralympic sprinter hopeful, works out at the U.S. Olympic Training Center in Chula Vista, Calif. A below-the-knee amputee, Fields won a gold medal in the 100 meters with a time of 12.15 seconds at the Endeavor Games in Edmond, Okla., on June 13, 2009

In addition to the standard artificial limb for everyday use, many amputees or congenital patients have special limbs and devices to aid in the participation of sports and recreational activities. Within science fiction, and, more recently, within the scientific community, there has been consideration given to using advanced prostheses to replace healthy body parts with artificial mechanisms and systems to improve function. The morality and desirability of such technologies are being debated.[by whom?] Body parts such as legs, arms, hands, feet, and others can be replaced. The first experiment with a healthy individual appears to have been that by the British scientist Kevin Warwick. In 2002, an implant was interfaced directly into Warwick's nervous system. The electrode array, which contained around a hundred electrodes, was placed in themedian nerve. The signals produced were detailed enough that a robot arm was able to mimic the actions of Warwick's own arm and provide a form of touch feedback again via the implant.[49] The DEKA company of Dean Kamen developed the "Luke arm", an advanced prosthesis under clinical trials in 2008.[50] Oscar Pistorius In early 2008, Oscar Pistorius, the "Blade Runner" of South Africa, was briefly ruled ineligible to compete in the 2008 Summer Olympicsbecause his transtibial prosthesis limbs were said to give him an unfair advantage over runners who had ankles. One researcher found that his limbs used twenty-five percent less energy than those of an able-bodied runner moving at the same speed. This ruling was overturned on appeal, with the appellate court stating that the overall set of advantages and disadvantages of Pistorius' limbs had not been considered. Pistorius did not qualify for the South African team for the Olympics, but went on to sweep the 2008 Summer Paralympics, and has been ruled eligible to qualify for any future Olympics. He qualified for the 2011 World Championship in South Korea and reached the semifinal where he ended last timewise, he was 14th in the first round, his personal best at 400m would have given him 5th place in the finals. At the 2012 Summer Olympics in London, Pistorius became the first amputee runner to compete at an Olympic Games.[51] He ran in the400 metres race semifinals;,[52][53][54] and the 4 400 metres relay race finals.[55] He also competed in 5 events in the 2012 Summer Paralympics in London.[56] In November 2012 new artificial muscles made from nanotech yarns and infused with paraffin wax were shown to lift more than 100,000 times their own weight, and generate 85 times more mechanical power than the natural muscle of the same dimensions, according to scientists. (Science Daily) (Science)

Design considerations[edit]

There are multiple factors to consider when designing a transtibial prosthesis. Manufacturers must make choices about their priorities regarding these factors.

Performance[edit]
Nonetheless, there are certain elements of socket and foot mechanics that are invaluable for the athlete, and these are the focus of todays high-tech prosthetics companies:

Fit athletic/active amputees, or those with bony residua, may require a carefully detailed socket fit; less-active patients may be comfortable with a 'total contact' fit and gel liner Energy storage and return storage of energy acquired through ground contact and utilization of that stored energy for propulsion Energy absorption minimizing the effect of high impact on the musculoskeletal system Ground compliance stability independent of terrain type and angle Rotation ease of changing direction Weight maximizing comfort, balance and speed Suspension how the socket will join and fit to the limb

Other[edit]
The buyer is also concerned with numerous other factors:

Cosmetics Cost Ease of use Size availability

Cost[edit]
High-cost[edit]

[hide]This section has multiple issues. Please help improve it or discuss th This section relies on references to primary sources. (October 2010) This section appears to be written like an advertisement. (October 2010)
Transradial and transtibial prostheses typically cost between US $6,000 and $8,000. Transfemoral and transhumeral prosthetics cost approximately twice as much with a range of $10,000 to $15,000 and can sometimes reach costs of $35,000. The cost of an artificial limb does recur because artificial limbs are usually replaced every 34 years due to wear and tear. In addition, if the socket has fit issues, the socket must be replaced within several months. If height is an issue components can be changed, such as the pylons.[57] [58]

Low-cost[edit]

Low cost above knee prostheses often provide only basic structural support with limited function. This function is often achieved with crude, non-articulating, unstable, or manually locking knee joints. A limited number of organizations, such as the International Committee of the Red Cross (ICRC), create devices for developing countries. Their device which is manufactured by CR Equipments is a single-axis, manually operated locking polymer prosthetic knee joint.[59] Table. List of knee joint technologies based on the literature review. [60]

Name of technology (country of origin) ICRC knee (Switzerland) ATLAS knee (UK) POF/OTRC knee (US) DAV/Seattle knee (US) LIMBS International M1 knee (US) JaipurKnee (India) LCKnee (Canada) None provided (Nepal) None provided (New Zealand) None provided (India) Friction knee (US) Wedgelock knee (Australia) SATHI friction knee (India)

Brief description Single-axis with manual lock Weight-activated friction Compliant polycentric Four-bar Four-bar

Highest level of evidence Independent field Independent field Field Field Field

Single-axis with ext. assist Field

Single-axis with automatic Field lock Single-axis Roto-molded single-axis Six-bar with squatting Weigh-activated friction Weigh-activated friction Weigh-activated friction Field Field Technical development Technical development Technical development Limited data available

Low Cost Above Knee Prosthetic Limbs: ICRC Knee (left) and LC Knee (right)
A plan for a low-cost artificial leg, designed by Sbastien Dubois, was featured at the 2007 International Design Exhibition and award show in Copenhagen, Denmark, where it won the Index: Award. It would be able to create an energy-return prosthetic leg for US $8.00, composed primarily of fiberglass.[61] Prior to the 1980s, foot prostheses merely restored basic walking capabilities. These early devices can be characterized by a simple artificial attachment connecting one's residual limb to the ground. The introduction of the Seattle Foot (Seattle Limb Systems) in 1981 revolutionized the field, bringing the concept of an Energy Storing Prosthetic Foot (ESPF) to the fore. Other companies soon followed suit, and before long, there were multiple models of energy storing prostheses on the market. Each model utilized some variation of a compressible heel. The heel is compressed during initial ground contact, storing energy which is then returned during the latter phase of ground contact to help propel the body forward. Since then, the foot prosthetics industry has been dominated by steady, small improvements in performance, comfort, and marketability.Jaipur Foot, an artificial limb from Jaipur, India, costs about US$ 40.

Open-source[edit]
There is currently an open Prosthetics design forum known as the "Open Prosthetics Project". The group employs collaborators and volunteers to advance Prosthetics technology while attempting to lower the costs of these necessary devices.[62] Another open-source prosthetics design forum is called PATCH Project. This forum is specially focussed on the development of prosthetics and tools for children in developing countries. The website is focussed on storing and spreading information and improving development of opensource low-cost solutions.[63]

Low-cost Prosthetics for Children[edit]

In the USA an estimate was found of 32,500 children (<21 years) that suffer from major paediatric amputation, with 5,525 new cases each year, of which 3,315 congenital.[64] Carr et al. (1998) investigated amputations caused by landmines for Afghanistan, Bosnia, Cambodia and Mozambique among children (<14 years), showing estimates of respectively 4.7, 0.19, 1.11 and 0.67 per 1000 children.[65] Mohan (1986) indicated in India a total of 424,000 amputees (23,500 annually), of which 10.3% had an onset of disability below the age of 14, amounting to a total of about 43,700 limb deficient children in India alone.[66]

Few low-cost solutions have been created specially for children. Underneath some of them can be found.

Artificial limbs for a thalidomidechild 19611965

Pole and Crutch[edit]

this hand-held pole with leather support band or platform for the limb is one of the simplest and cheapest solutions found. It serves well as a short-term solution, but is prone to rapid contracture formation if the limb is not stretched daily through a series of range-of motion (RoM) sets [67]

(Bamboo) PVC/Plaster limbs[edit]

this also fairly simple solution comprises a plaster socket with a bamboo or PVC pipe at the bottom, optionally attached to a prosthetic foot. This solution prevents contractures because the knee is moved through its full RoM. The David Werner Collection, an online database for the assistance of disabled village children, displays manuals of production of these solutions [68]

Adjustable Bicycle Limb[edit]

This solution is built using a bicycle seat post up side down as foot, generating flexibility and (length) adjustability. It is a very cheap solution, using locally available materials.[69]

Sathi Limb[edit]
It is an endoskeletal modular lower limb from India, which uses thermoplastic parts. Its main advantages are the small weight and adaptability.[67]

Monolimb[edit]
Monolimbs are non-modular prostheses and thus require more experienced prosthetist for correct fitting, because alignment can barely be changed after production. However, their durability on average is better than low-cost modular solutions.

References[edit]
1. Jump up^