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V SHAHAPURKAR SIR
DEFINITION
Multiple
World War One Circulatory failure, hypovolemic shock World War Two Korean War Post-traumatic acute renal Viet Nam War insufficiency Post-traumatic acute respiratory insufficiency
ORIGIN
Originally patients were classified as having sepsis or
the sepsis syndrome. This resulted in two concepts: Systemic inflammatory response syndrome (SIRS) and
AIMS
Identify the patient at risk from developing MODS
give an account of possible preventative measures recognise progressive organ dysfunction as it is
occurring outline the treatment options available put surgical intervention into context describe the importance of good communication with the ICU team, and of early referral with a view to preventing organ failure becoming established
Causes
Sepsis
Trauma Shock due to any cause- cardiovascular/hemorrhagic Severe derangement in any particular organ system Other:
Burns Pancreatitis Massive blood transfusion Poisoning Eclampsia Acute CTDs, severe vasculitis Atrial myxoma, cholesterol emboli, SJS-TEN
Classification
Primary : Dysfunction is happened simultaneously in two or more organs due to primary disease. Secondary : Dysfunction happened in a organ, other organs sequentially happened dysfunction or failure.
INTRODUCTION
Multiple
Organ Dysfunction Syndrome (MODS) describes the progressive dysfunction and ultimate failure of organs in response to a noxious stimulus. This may be infection, trauma or inflammation, or some combination of these. MODS is common in the Intensive Care Unit (ICU), and carries a high mortality. It is easy to recognise when fully established, but more difficult to appreciate whilst it is developing, which is the time when prompt action may prevent further progression.
Identifying that a patient has MODS does not remove the requirement to diagnose and treat the underlying cause. Multiple Organ Dysfunction Syndrome is a specific term arising from the American College of Chest Physicians/Society of Critical Care Medicine
AETIOLOGY
The condition usually results from infection, injury
primary
cause
triggers
an
uncontrolled
inflammatory response.
In operative and non-operative patients sepsis is the most
common cause.
Sepsis may result in septic shock.
ROLE OF INFECTION
Since infection has such a pivotal role in the development of MODS, it is important to consider possible sources. Primary infective causes that may lead to MODS include: primary pneumonia (community acquired). intra-abdominal surgical emergency (e.g. faecal peritonitis). meningococcal disease. gram positive toxic shock (Streptococcal or Staphylococcal). severe forms of food poisoning (e.g. Salmonella, E. coli 0157).
abscess).
Other new infection (e.g. acalculous cholecystitis, urinary
the ICU, have a different pattern from those acquired in the community. Today, about 40% of ICU-acquired infections are Grampositive and a similar number are Gram-negative, with fungal infections comprising the next largest group. Staphylococcus aureus is the most common Grampositive organism, followed by Coagulase Negative Staphylococci and Enterococci.
now methicillin (flucloxacillin) resistant (MRSA), and an increasing number of Enterococci are becoming resistant to vancomycin (VRE). The most common Gram-negative is still Pseudomonas aeruginosa, with various coliforms also being seen frequently. It is recognised that the patient is usually the source of the bacteria, having become colonised whilst in hospital, especially if broad spectrum antibiotics have been given.
colonisation of the upper gastrointestinal (GI) tract with bacteria is a well-recognised phenomenon in critically-ill patients.
All intubated patients suffer chronic low-grade aspiration
Mechanism
Uncontrolled inflammatory response Microcirculatory hypo-perfusion Ischemia/reperfusion injury
Inflammation
Inflammatory cells
Inflammatory cytokines
Pro-inflammatory reaction TNF-a, IL-1, IL-6, IFN TXA2, PAF Cell activation
CLASSIFICATION
Primary MODS describes a situation in which multiple
organ dysfunction is directly attributable to the initiating insult, as in the case of multiple trauma.
Secondary MODS describes a situation where the organ
but
is
consequence
of
the
host
response,
characterised by a generalised activation of the inflammatory response in organs remote from the
initial insult.
MODS may exist in the same patient, but it is secondary MODS which has become such a familiar sight in modern ICUs.
Pathogenesis
Theories put forward: Gut hypothesis Endotoxin macrophage hypothesis Tissue hypoxia-microvascular hypothesis Integrated hypothesis
mucosal ischaemia there are structural changes and alterations in cellular function.
immune
function
of
the
gut
and
increased
translocation of bacteria.
Hepatic dysfunction leads to toxins escaping into the
response.
This results in tissue injury and organ dysfunction
tissue in the body (gut-associated lymphoid tissue, GALT), and may be a source of cytokine release even without translocation. Surface mucosal immunity, which is mediated by IgA, seems to operate in a common fashion in both the gut and the respiratory tree. Failure to protect the gut by failing to provide enteral feeding and ensuring adequate gut perfusion diminishes the effectiveness of the GALT and the gastrointestinal IgA, and also of the respiratory mucosal IgA, so potentially predisposing to respiratory infection.
common, hence endotoxins have been advanced as principal mediator in this disorder.
It is thought that following the initial event cytokines are
Tumour
necrosis
factor-alpha
A2,
(TNF-),
interleukin-1,
platelet
interleukin-6,
thromboxane
prostacyclin,
Integrated hypothesis
Since in most cases no primary cause is found, the condition
Infection/ injury
Inflammatory stimulator
Local inflammatory Systemic inflammatory cell cell activated activated (M (M ,PMN,VEC,) ,PMN,VEC,)
Tissue injury
An uncontrolled inflammation process Pro-inflammatory signals exceed its normal domain or degree
Pro-inflammatory reaction TNF-a, IL-1, IL-6, IFN TXA2, PAF Cell Result inactivation end-organ damage
and multi-system
failure.
Definitions of systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and multiple organ dysfunction syndrome (American College of Chest Physicians, 1992)
Systemic inflammatory response syndrome Two or more of the following clinical signs of systemic response to endothelial inflammation: Temperature >38C or <36C Heart rate >90 beats/min
Sepsis Systemic response to infection manifested by two or more of the following: Temperature >38C or <36C
Raised heart rate >90/min Tachypnoea (respiratory rate >20 breaths/min or hyperventilation (PaCO2<4.25 kPa))
White blood cell count >12109/l or <4109/l or the presence of more than 10% immature neutrophils
Tachypnoea (respiratory rate >20 breaths/min or hyperventilation (PaCO2<4.25 kPa)) White blood cell count >12109/l or <4109/l or the presence of more than 10% immature neutrophils In the setting (or strong suspicion) of a known cause of endothelial inflammation such as:
Septic shock
Sepsis induced hypotension (systolic blood pressure <90 mm Hg or a reduction of 40 mm Hg from baseline) despite adequate fluid resuscitation Multiple organ dysfunction syndrome Presence of altered organ function in an acutely ill patient such that homoeostasis cannot be maintained without intervention
Ischaemia Multiple trauma and tissue injury Haemorrhagic shock Immune mediated organ injury Absence of any other known cause for such clinical abnormalities
Definition
An uncontrolled Anti-inflammatory signals exceed its normal domain or degree Result in end-organ damage and multi-system failure. Pro-inflammatory reaction
TNF-a, IL-1, IL-6, IFN TXA2, PAF Cell activation
Anti-inflammatory reaction IL-10, IL-4, TGF- IL-1ra ,Lipoxin Cell eliminate anti-inflammation process
Immune paralysis
Infection/Injury
MODS
Infection/injur y controlled
Chronology of dysfunction
The progressive dysfunction of organ systems that
characterize MODS usually occurs in a predictable manner. During the first 72 hours of the original insult, respiratory failure commonly occurs. This is followed by
hepatic failure (5 to 7 days), gastrointestinal bleeding (10 to 15 days), and finally
DIAGNOSIS
The European Society of Intensive Care organized a
SOFA SCORE
Organ parameters
Respiratory PaO2/FiO2
>400
1
</= 400
2
</= 300
3
</=200 with support
4
</=100 with support
> 150
< 1.2 no
</=20
6.0-11.9 >12
Dopamine >5 or epi <0.1 or norepi< 0.1 Dopamine >15 or epi >0.1 or norepi> 0.1
15 <1.2
13-14
10-12
6-9
1.2-1.9 2.0-3.4
Four clinical phases have been suggested: Stage 1 the patient has increased volume requirements and mild respiratory alkalosis which is accompanied by oliguria, hyperglycemia and increased insulin requirements. Stage 2 the patient is tachypneic, hypocapnic and hypoxemic. Moderate liver dysfunction and possible hematologic abnormalities. Stage 3 the patient develops shock with azotemia and acid-base disturbances. Significant coagulation abnormalities. Stage 4 the patient is vasopressor dependent and oliguric or anuric. Ischemic colitis and lactic acidosis follow.
SYSTEMS INVOLVED
There are various systems involves such as:1) Cardiovascular dysfunction:-
Cardiovascular dysfunction is a key component of MODS, and can be both a cause and a consequence. The key components of cardiovascular function are: cardiac function vascular tone vascular permeability.
Cardiac output is determined by: cardiac filling (preload) cardiac contractility heart rate vascular resistance (afterload). Blood pressure is generated by: cardiac output vascular resistance.
The pattern of cardiac dysfunction typically seen in sepsis and MODS is: Pathological vasodilatation Leading to hypotension and reduced cardiac filling, and a relative reduction in cardiac output. The reduced vascular tone also tends to increase cardiac output by reducing resistance to forward blood flow (afterload). The net effect of these opposing phenomena depends on the overall volume status. The mechanism for the vasodilatation is an increased production of nitric oxide by the vascular endothelium, resulting in vascular relaxation.
the interstitium, oedema formation and hypovolaemia. In the lung the oedema contributes to impaired gas exchange. The hypovolaemia contributes to a fall in cardiac output. Many cytokines have direct myocardial depressing effects, resulting in impaired contractility and reduced stroke volume, so limiting the compensatory increase in cardiac output in response to a fall in vascular resistance. Heart rate is generally increased in response to the inflammatory mediators and increased sympathetic drive, resulting in an increase in cardiac output.
which predominate, on the volume status of the patient, and on the degree of pre-existing cardiac dysfunction which determines the cardiac reserve.
In a patient with a healthy heart who has been volume
resuscitated, the typical hyperdynamic pattern appears, in which there is a higher than normal cardiac output and a lower than normal vascular tone and blood pressure.
If blood pressure is inadequate there will be reduced perfusion of vital organs, manifested by:
confusion
a falling urine output
Oxygen consumption (VO2) is the difference between the amount of oxygen being despatched by the arterial supply and returning via the venous system. V02 - Hb x 1.39 x (Sa02 - Sv02) x 10 x CO If oxygen delivery is inadequate and tissue hypoxia develops, the signs of anaerobic metabolism will be present: worsening metabolic acidosis, with an increasingly negative base excess rising blood lactate level splanchnic ischaemia measured with a gastric tonometer (which measures CO2 production by the gastric mucosa, which increases as perfusion worsens).
2) Respiratory dysfunction :-Respiratory dysfunction is a key feature of MODS and arises for a number of reasons. Lung damage may be primary or secondary.Primary lung damage include:
pneumonia pulmonary contusion aspiration smoke inhalation.
acute, although there may be pre-existing lung disease. The term Acute Respiratory Distress Syndrome (ARDS) is used in this context but, just as with the terms relating to sepsis. The key principle that emerged was that an acute lung injury occurs in critically-ill patients in response to a number of different injuries. Conceptually, this is exactly the same principle as that which underpins MODS itself. Less severe damage would be known as Acute Lung Injury (ALI) and more severe damage as Acute Respiratory Distress Syndrome (ARDS).
The definitions of Acute Lung Injury and Adult (Acute) Respiratory Distress syndrome have several features in common:
An appropriate clinical setting with one or more recognised
risk factors
Bilateral diffuse fluffy infiltrates on the chest X-ray No clinical evidence of heart failure or fluid overload
seen in MODS, ALI and ARDS may be triggered or exacerbated by overenthusiastic fluid resuscitation in patients where there is already pulmonary capillary damage with increased permeability and therefore a tendency to develop pulmonary oedema. Recently, there have been two more important conceptual advances. The first is that a considerable proportion of the lung injury seen in MODS patients with ALI or ARDS is probably caused by the sheer stresses imposed upon the lung by the mechanical ventilator. This has led to the term ventilator-induced lung injury (VILI).
realisation that the injured lung can contribute to the development or progression of MODS through the release of cytokines, even in the absence of pulmonary infection. A severe lung injury also has haemodynamic consequences. Pulmonary hypertension develops acutely and can be very severe, leading ultimately to right heart failure, with a rising central venous pressure and liver congestion. Forward blood flow through the injured lung also becomes impaired, and left ventricular filling and systemic blood flow fall.
arterio-venous
perfusion gradients across various organ beds, so further contributing to end-organ damage and the progression of MODS.
Finally, severe hypoxaemia due to ARDS also contributes to
Pressure-volume curve of the lung - demonstrating potential for lung damage with inadequate recruitment or overdistension
At low total lung volume many alveoli are collapsed and the curve is flat. A large increase in pressure is required to generate a small change in lung volume, and so compliance is low. If the lung is ventilated at these volumes there is cyclical opening and closing of alveoli, causing damage. At high lung volumes the lung becomes over-distended and compliance is also poor. Ventilating here causes damage through overstretching alveoli.
lung volumes where compliance is good and ventilation more efficient and less damaging. The two points where the curve changes shape are known as the lower and upper inflection points. The aim, therefore, is to stay between these two points throughout the respiratory cycle. Typically, this can be achieved by setting a positive endexpiratory pressure (PEEP) of 12-15 cm H20, which will approximate to the lower inflection point, and limiting tidal ventilation to 5-7 ml/kg, therefore remaining below the upper inflection point.
3) Aute renal dysfunction:Acute renal dysfunction and failure is a common feature of MODS. As with other organs, the kidney is a victim of the systemic process, but the pattern of renal impairment and subsequent failure and recovery owes much to the
due to hypovolaemia or hypotension. Renal failure implies direct renal damage. Post-renal failure implies obstruction to urine outflow.
In the context of MODS there are numbers of insults to
the kidney occurring at the same time rather than a single injury, and this classification is less useful. The haemodynamic changes contribute to reduced perfusion and local hypoxia, which is exacerbated by hypoxaemia secondary to the lung injury.
nephrotoxic drugs.
The renal response to injury consists of three phases: Oliguria - conservation of salt and water by a reduction in urine output. Urea and creatinine levels rise. At this stage, urine output can still be restored if the patient is resuscitated successfully. Anuria - renal failure becomes established, urine output becomes minimal or ceases for a period of days or weeks even if renal blood flow is restored and the initiating insult resolved. During this period renal support techniques are required.
and there is often a period of polyuria before full recovery of function occurs. Occasionally, there is no anuric period,
biochemical abnormalities, but management of fluid balance remains possible with appropriate fluid replacement regimens.
The major pathological consequences of acute renal failure are: rising urea and creatinine. rising potassium. Worsening metabolic acidosis, usually associated with a normal lactate. Fluid balance abnormalities (depending upon the cause of the renal failure), followed by a tendency to become fluid overloaded easily if anuric, and fluid depleted if polyuric. The impact of acute renal failure upon the outcome of patients with MODS is often debated, since the mortality of this group of patients is so high; of the order of 5070%.
4) Acute liver dysfunction:- The liver is fundamental to many metabolic and immune functions, and has a rich blood supply via
relatively lacking.
Traditional liver function tests (liver enzymes, bilirubin, albumin and clotting) are often non-specifically deranged in critically-ill patients,
More specific tests of dynamic liver function are available for research purposes, and these include:
measurements of liver blood flow using a hepatic vein catheter
they have revealed that there is often very severe acute liver dysfunction in patients with MODS which is not apparent from conventional tests, and that the degree of liver dysfunction may predict outcome.
If bacteria, endotoxin or cytokines are released into the
portal blood from a leaky gut, an immune response in the liver results.
What subsequent role this might have in causing the
systemic response seen in MODS is still unclear, but this mechanism has often been suggested as one possible stimulus for the development of MODS as part of the gutorigin of MODS theory.
GIT DYSFUNCTION
Apart from a possible role in the genesis of MODS, the
gut is directly involved in two more straightforward ways, both of which might be regarded as being gutfailure, i.e.: failure to tolerate enteral feeding stress ulceration and gastrointestinal bleeding. Failure to tolerate enteral feeding Critically-ill patients all require tube feeding when they are intubated and ventilated, and may be difficult to feed enterally.
Haematological dysfunction
Haematological dysfunction is an area that is readily overlooked, but
abnormalities are commonplace in the patient with MODS. The patterns seen are usually due to systemic consumption of blood components or bone marrow depression, i.e.:
Peripheral consumption (disseminated intravascular coagulation, DIC)
due to activation of the coagulation pathways as part of the inflammatory response seen in MODS features include prolonged clotting, low platelets, low fibrinogen, low antithrombin III and low protein C, with bleeding and anaemia in severe cases.
low white cell count in the face of severe infection, and a low platelet count.
Both syndromes, which often occur at the same time,
Cerebral dysfunction
Cerebral dysfunction is very difficult to quantify and assess
in critically-ill patients. In the acute phases of severe illness patients become obtunded, often for a variety of reasons.
Most common are the global effects of hypoxia and
context is severely unwell, and should have his/her airway protected as soon as possible.
Once intubated and sedated, patients with MODS become
much
more
difficult
to
assess,
but
non-specific
Barr Syndrome, and peripheral demyelination and axonal damage are sometimes seen, as well as muscle wasting and necrosis.
microvascular occlusion and effects of drugs, especially non-depolarising neuromuscular blockers (and
TREATMENT
Having recognised that a patient is developing MODS,
the first principle is to resuscitate and make safe. This means referring to the ICU and usually:
establishing good intravenous access instituting invasive arterial monitoring (central venous
providing
cardiovascular support with fluids, vasopressors and inotropes guided by invasive haemodynamic monitoring. Unfortunately, no single treatment for MODS will reverse the associated high mortality. Survival is more likely when the cause of MODS can be found and eliminated. Further measures include: infection screen taking blood, sputum and urine cultures
full
haematological (including clotting) and biochemical screen commencing broad-spectrum antibiotics providing renal and nutritional support as necessary identifying the source of the sepsis that has led to MODS and treating it. If there is a surgical cause, this should be remedied surgically as soon as the patient has been stabilised, since there is unlikely to be improvement otherwise.
supportive measures to correct hypoxia, hypotension, and impaired tissue oxygenation. Identify the source of infection and treat with antimicrobial therapy, surgery, or both. Maintain adequate organ system function guided by cardiovascular monitoring and interrupt the pathogenesis of multiorgan system dysfunction.
Features of therapy
Largely supportive: Etiology control Maintenance of oxygen transport Use of activated protein C Corticosteroids Metabolic support Organ support
Etiology control
Infection - antibiotics
Trauma - wound care/amputation if required Abscess: - drainage
Oxygen support
Objective is to achieve supramarginal oxygen level in
Hemoglobin at 11g/dl
Corticosteroids
Intravenous corticosteroids (hydrocortisone 200-
300mg/day, for 7days in three or four divided doses or by continuous infusion) are recommended inpatients with septic shock who, despite adequate fluid replacement, require vasopressor therapy to maintain adequate blood pressure.
----- surviving sepsis guidelines SCCM
2004
Metabolic support
Calorie around 30-50 cal/kg/day with no more than 5
gm/kg/day of glucose
Increased carbohydrate causes excessive lipolysis and
CO2 production
increased
infection
rate,
because
of
direct
immunosuppressive effects due to the fat preparations used, and due to the requirement for central venous access
gut atrophy leading to increased gut permeability, since
SUMMARY
MODS is the extreme end of an infective or
inflammatory process. The mortality is high, and MODS is a major cause of death after surgery. All organ systems are involved. Early recognition and treatment in an ICU are essential. This is often an expensive and timeconsuming process. Successful care is multidisciplinary in nature.
features at the earliest and intervene We should not have a hopeless attitude towards patients having various organ involvement Critical care can be truly rewarding if the principles are followed diligently.. -------------------
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THANK-YOU.