Pelayanan Prima

DIAGNOSIS & MANAGMENT OF
Acute Respiratory Distress Syndrome
vitrag24 - www.medicalgeek.com
DR. VITRAG SHAH
FIRST YEAR FNB RESIDENT,
DEPARTMENT OF CCEM,
SGRH, DELHI
MODERATOR
DR.RAHUL
SYMPTOMS…………
• Fever/chills
• Headache, myalgia
• Sore throat
• Cough
• Coryza
• Prostration
• Range of symptoms differs by age
– Vomiting & diarrhea in children/elderly
– Fever alone in infants
– May be atypical in elderly
• Serious complications can occur among high risk groups
OUTLINE
 What is ARDS
 Berlin vs AECC definition & LIS
 Risk Factors
 Etiology
 Clinical course & Pathophysiology
 Differential diagnosis
 Management
 General management & nursing care
 Role of NIV
 Ventilatory management
 Management of Refractory hypoxemia
 Non-Ventilatory management
 Other drugs/therapies
 Prognosis
 Future/Research & Role of stem cells
 References
WHAT IS ARDS??
 A type of inflammatory lung injury that is
neither a primary disease or a single entity.
 Rather, it is an expression of myriad other
diseases that produce diffuse inflammation in the
lungs, often accompanied by inflammatory injury
in other organs & it is also the leading cause of
acute respiratory failure.
 Physicians think they do a lot for a patient when
they give his disease a name --Immanuel Kant
 First described as clinical syndrome in 1967 by

Ashbaugh & Petty .
 Synonyms: Sponge Lung, Shock lung, Non-
cardiogenic pulmonary edema, Capillary leak
syndrome, Traumatic wet Lung, Adult hyaline
membrane disease, ALI & ARDS, and most recently,
Only ARDS.
THE BERLIN DEFINITION:-
 The Berlin Definition of ARDS (published in 2012) replace
the American-European Consensus Conference‘s definition of
ARDS (published in 1994).
 The European society of intensive care medicine endorsed by
The American Thoracic Society and The Society of Critical
Care Medicine developed the Berlin definition in 2012.
 The major changes to the Berlin Definition are that the

term “acute lung injury” has been eliminated, the
pulmonary capillary wedge pressure (ie, pulmonary
artery occlusion pressure) criteria has been removed,
and minimal ventilator settings have been added.
SpO2 can be substituted for the PaO2 to calculate the SpO2/FIO2 ratio, which may
be more a feasible method of identifying severely ill patients in these resource-
limited environments.
WHAT‘S NOT INCLUDED…..
 The draft definition of severe ARDS included the
more extensive involvement on the frontal chest
radiograph (3 or 4 quadrants) { from those with the
minimal criterion of ―bilateral opacities‖ (2
quadrants) }, respiratory system compliance (40
mL/cm H2O), positive end expiratory pressure (10
cm H2O), and corrected expired volume per minute
(10 L/min).
 These variables were identified for further study

during the evaluation phase & not included in
present criteria.
PCWP:
 The problem is that the wedge pressure is not a
measure of capillary hydrostatic pressure,
 The PCWP is a measure of LAP and LAP cannot be the

same as the pulmonary capillary pressure in presence of
blood flow .
 If the wedge (left-atrial) pressure were equivalent to the
pressure in the pulmonary capillaries, there would be no
pressure gradient for flow in the pulmonary veins. Thus,
the capillary hydrostatic pressure must be higher than
the wedge pressure.So PCWP will underestimate the
actual capillary hydrostatic pressure.
 This difference is small in the normal lung, but in severe

ARDS, the capillary hydrostatic pressure can be double
the wedge pressure.
 Because of this discrepancy, the wedge pressure should

be abandoned as a diagnostic criterion for ARDS.
MURRAY LUNG INJURY SCORE
(LIS)
 Radiography
 Oxygenation
 Compliance
 PEEP
 But doesn‘t exclude left heart failure

 Risk Factors
 Older age
 Chronic alcohol abuse
 Metabolic acidosis
Critical illness.

 Trauma patients
 >80% of cases are caused by:

 Sepsis
 Bacterial pneumonia
 Trauma
 Multiple transfusions
 Gastric acid aspiration
 Drug overdose
CLINICAL DISORDERS ASSOCIATED WITH THE
DEVELOPMENT OF ARDS
Direct insult  Indirect insult
 Common
 Common  Sepsis
 Aspiration pneumonia  Severe trauma
 Pneumonia  Shock
 Less common
Less common  Acute pancreatitis
 Inhalation injury  Cardiopulmonary bypass
 Pulmonary contusions  Transfusion-related TRALI
 Fat emboli  DIC
 Near drowning  Burns
 Reperfusion injury  Head injury
 Drug overdose
CLINICAL COURSE AND
PATHOPHYSIOLOGY
The natural history of ARDS is marked by three phases
1. Exudative (First 7 days)
2. Proliferative (After 7-21 days)
3. Fibrotic (After 3-4 weeks)
Each with characteristic clinical and pathologic features

Alveolar
Damage
Hypoxic Capillary
Vasoconstriction Damage
Leakage
↑Dead Space Oedema
Fluid
Hypoxia
Inflammatory
↓Thoracic
Cellular
Compliance
Infiltrates
V/Q
Atelectasis
Mismatch
ARDS– PROBLEMS & CONCERNS
 Strain (stretch) due to over distension of compliant
alveoli leading to volutrauma.
 High inspiratory pressures (Pplat) leading to barotrauma.
 Release of inflammatory mediators from lung

(biotrauma)
 Shear stress due to complete closure & re-opening of

non-compliant alveoli (atelectrauma).
 Earliest clinical signs of ARDS are tachypnea &
progressive hypoxemia usually refractory to oxygen ,
which usually leads to diffuse pulmonary infiltrates in
chest x-ray within 24 hours & leading to respiratory
failure requiring mechanical ventilation within 48
hours of illness.
PROGRESSION OF ARDS:
If the injurious factor is not
removed, the amount of
inflammatory mediators released by
the lungs in ARDS may results in
 SIRS - Systemic inflammatory

response syndrome
 MODS - multi organ

dysfunction syndrome
This adds up to impaired

oxygenation which is the central
problem of ARDS, which further
impairs oxygen delivery.
DIFFERENTIAL DIAGNOSIS
 Most common
 Cardiogenic pulmonary edema
 Diffuse pneumonia
 Alveolar hemorrhage
 Less frequent
 Acute interstitial lung diseases(e.g., acute interstitial
pneumonitis)
 Acute immunologic injury (e.g., hypersensitivity
pneumonitis)
 Toxin injury (e.g., radiation pneumonitis)
 Neurogenic pulmonary edema
ARDS vs Cardiogenic Pulmonary Edema
1. CHEST X- RAY .
 A homogeneous infiltrate and the absence
of pleural effusions is more characteristic
of ARDS.
 Patchy infiltrates from the hilum,
prominent pleural effusions, cardiomegaly
& cephalization is more characteristic of
cardiogenic pulmonary edema.
 However, , pleural effusions can appear in

ARDS, and the view is that CXR are not
reliable for distinguishing ARDS from
cardiogenic pulmonary edema
2. Severity of Hypoxemia:
 In the early stages of ARDS, the hypoxemia is often more

pronounced than the CXR abnormality
 In the early stages of cardiogenic pulmonary edema, the
CXR abnormalities are often more pronounced than the
hypoxemia.
 However, there are exceptions, and severe hypoxemia can

occur in cardiogenic pulmonary edema from a low cardiac
output
3. BNP
 In patients with hypoxic respiratory failure :
 An BNP level of less than 100 pg/mL in a patient
with bilateral infiltrates and hypoxemia favors
the diagnosis of ARDS/acute lung injury (ALI)
rather than cardiogenic pulmonary edema.
4. Bronchoalveolar Lavage:
The most reliable method for confirming or

excluding the diagnosis of ARDS .
A.) Neutrophils
 In normal subjects, neutrophils make up
less than 5% of the cells recovered in lung
lavage fluid, whereas in patients with
ARDS, as many as 80% of the recovered
cells are neutrophils.
 A low neutrophil count in lung lavage

fluid can be used to exclude the diagnosis
of ARDS, while a high neutrophil count is
considered evidence of ARDS .
B.) Total Protein:
 Because inflammatory exudates are rich in proteinaceous

material, lavage fluid similarly rich in protein→ evidence
of lung inflammation.
 When the protein concentration in lung lavage fluid is
expressed as a fraction of the total protein concentration,
the following criteria can be applied
 Protein (lavage/serum) <0.5 = Hydrostatic edema
 Protein (lavage/serum) >0.7 = Lung inflammation
 Lung inflammation is expected to produce a protein

concentration that is greater than 70% of the protein
concentration in serum.
 Although not specific, BAL can be used as evidence of
ARDS if other causes of lung inflammation (e.g.,
pneumonia) can be excluded on clinical grounds.
 BAL has not gained widespread acceptance as a diagnostic

tool for ARDS, because most ICU physicians use the
diagnostic criteria to evaluate possible ARDS.
MANAGEMENT OF ARDS
 General principles & supportive care
 Role of NIV
 Lung-Protective Ventilation Protocol
• LVV & VILI
• Permissive hypercapnia
PEEP & Open lung ventilation
•
• Lung Recruitment - Recruitment maneuvers
• Mode of ventilator
• Approach to patient-ventilator dyssynchrony
• Role of Neuromuscular blockers
 Management of Refractory Hypoxemia
• Prone Position
• Other Modes of ventilation
• IRV
• Inhaled Nitric Oxide
• ECMO
 Non Ventilatory Management
 Fluid management
 Diuretics
 Steroids
 Blood Transfusion cut-off
 Choice of Inotropic agent
 Other drugs/Therapies
 Prognosis
 Future/Research & Role of stem cell
Management of ARDS:-
General Principles:
(1) Early recognition and treatment of the underlying

medical and surgical disorders (e.g., sepsis, aspiration,
trauma);
(2) Minimizing procedures and their complications;
(3) Prophylaxis against venous thromboembolism,
gastrointestinal bleeding, and central venous catheter
infections;
(4) Prompt recognition of nosocomial infections; and
provision of adequate nutrition, Glucose control.
(5) Use of sedatives and neuromuscular blockade
(6) Hemodynamic management
(7) Ventilatory strategies to decrease tidal volume (Vt)
while maintaining adequate oxygenation
MANAGEMENT OF HYPOXEMIA
 Decrease oxygen consumption
 Increase oxygen delivery
 Ventilatory strategies (LPV)
DECREASE OXYGEN CONSUMPTION
 In diseases with severe pulmonary shunting,
increasing the saturation of mixed venous blood
(SvO2 ) may increase the SaO2 . Therapies that
decrease oxygen consumption may improve SvO2
(and SaO2 subsequently) by decreasing the
amount of oxygen extracted from the blood.
 Common causes of increased oxygen

consumption include fever, anxiety and pain, and
use of respiratory muscles; therefore, arterial
saturation may improve after treatment with
anti-pyretics, sedatives, analgesics, or
paralytics
INCREASE OXYGEN DELIVERY
 DO 2 = 10 x CO x (1.34 x Hgb x SaO 2 + 0.003 x
PaO 2 )
 where DO 2 is oxygen delivered, CO is cardiac
output, Hgb is hemoglobin concentration, SaO 2 is
the arterial oxygen saturation, and PaO 2 is the
partial pressure of oxygen in arterial blood. As a
result, in addition to low SaO 2 , DO 2 may be
decreased by a low Hgb and a low CO. In turn, a
low DO 2 may decrease SvO 2 .
ROLE OF NIV
 No trials have compared NIV to invasive mechanical
ventilation, and the only evidence at present is studies
such as that by ―Ferrer et al‖ in which NIPPV is
compared with supplemental oxygen by face mask alone.
In this particular trial, NIPPV was associated with
decreased need for intubation compared with oxygen by
face mask in the overall study population, but among
patients with ARDS, there were no differences in
outcomes.
 Their use should only be considered in patients with mild
disease (PaO2/FIO2 > 200 and no other organ
dysfunction) and immunocompromised patients who are
hemodynamically stable, able to tolerate wearing a face
mask, and able to maintain a patent airway.
PaO2 55-80 mmhg
The slope of this relationship represents the compliance of the respiratory system, and the goal
should be to ventilate patients on the steepest portion of the relationship where smaller pressure
changes are necessary to achieve the desired tidal volume. Lowering the tidal volume helps avoid
the upper, flat portion of this relationship (A), where large changes in pressure are necessary to
achieve small volume changes. Application of positive end-expiratory pressure helps avoid the
lower, flat portion of this relationship (B) by preventing repetitive opening and closing of the
alveoli.
Lung-Protective Ventilation:
 Since the introduction of positive-pressure mechanical

ventilation, large inflation volumes(TV) were used to
↓ tendency for atelectasis during MV.
 The standard tidal volumes were 10 to 15 mL/kg,
which are twice the size of tidal volumes used during
quiet breathing (6 to 7 mL/kg).
 In patients with ARDS, these large inflation volumes

are delivered into lungs that have a marked ↓in
functional volume. → VOLUTRAUMA.
 CXR in ARDS show homogeneous
pattern of lung infiltration.
 CT images reveal that the lung

infiltration in ARDS is not spread evenly
throughout the lungs, but rather is
confined to dependent lung regions
 The remaining area of uninvolved lung is

the functional portion of the lungs in
ARDS.( baby lungs)
 The large inflation volumes delivered by

mechanical ventilation cause
overdistention and rupture of BABY
LUNG→ Ventilator-induced lung
injury.
Ventilator-Induced Lung Injury
MECHANISM
 The following mechanisms of lung injury have been described:
1) Atelectrauma : collapse of alveoli and surfactant depletion. Ventilation with high FiO2
aggravates alveolar collapse due to absorption atelectasis
2) Oxygen toxicity : While this is well known, it is not clear what concentration of oxygen is
toxic over what period of time. It is generally assumed that FiO2 <0.6 is not toxic, however
an attempt must be made to maintain the FiO2 as low as possible.
3)Volutrauma : Ventilation at high volumes and pressures can lead to alveolar

overdistension, causing increased permeability pulmonary edema in the uninjured lung and
enhanced edema in the injured lung.
4)Cyclical shear stress injury : Cyclic opening and closing of atelectatic alveoli during
mechanical ventilation create tremendous shear stress at their junctions with open alveoli.
This results in damage to the capillary endothelium and the alveolar membrane.
5)Biotrauma : Alveolar over-distension along with the repeated collapse and reopening of
the alveoli can result in a whole cascade of proinflammatory cytokines which induce both a
pulmonary and systemic cytokine response, aggravating lung injury and causing systemic
multiorgan dysfunction.
6)Barotrauma : Pneumothorax, pneumomediastinum, interstitital emphysema.

Lung-Protective Ventilation:
Low-Volume Ventilation(LVV)
LVV protocol is designed to achieve

three goals :
 Maintain a tidal volume of 6 mL/kg using
predicted body weight,
 Keep the end-inspiratory plateau

pressure below 30 cm H2O, and
 Avoid severe respiratory acidosis.

MEDIAN ORGAN
FAILURE FREE DAYS
6ml/kg.
12ml/k
g.
Permissive Hypercapnia
 One of the consequences of low volume ventilation is a

reduction in CO2 elimination via the lungs leading to
hypercapnia and respiratory acidosis. Allowing
hypercapnia to persist in favor of maintaining lung-
protective low-volume ventilation is known as permissive
hypercapnia.
 The degree of hypercapnia can be minimized by using the

highest respiratory rate that does not induce auto-
PEEP and shortening the ventilator tubing to
decrease dead space. In addition, changing from a
heat and moisture exchanger to a heated humidifier
appears to decrease hypercapnia by decreasing dead space
ventilation
 One of the more troublesome side effects of
hypercapnia is brainstem respiratory stimulation with
subsequent hyperventilation, which often requires
neuromuscular blockade to prevent ventilator
asynchrony.
 Data from clinical trials of permissive hypercapnia
show that arterial PCO2 levels of 60 to 70 mm Hg
and arterial pH levels of 7.2 to 7.25 are safe for
most patients .
OPEN LUNG VENTILATION
 It is a stratergy that combines low tidal volume ventilation &
enough applied PEEP to maximize alveolar recruitment. The LTVV
aims to mitigate alveolar overdistention, while the applied
PEEP seeks to minimize cyclic atelectasis. Togather , these
effects are expected to decrese the risk of ventilator associated lung
injury.
 LTVV is applied as described and applied PEEP is set at least 2
cm above the lower inflection point of the pressure volume
curve are used. Applied PEEP of 16 cm H 2 O is used if the lower
inflection point is uncertain.
 Alternative approach : PEEP set at a high level following a

recruitment maneuver and then incrementally decreased until both
the static lung compliance decreased and the sPO2 decreased by 2%
from the previous measurement. The PEEP is then set 2 cm H 2 O
above this level.
 PEEP adjustment based on the PEEP–FIO2 protocol used in ARMA

is likely the most feasible approach until more data are available.
STRATEGY………..?
Aerated
Non aerated
recruitable
Non aerated
Non recruitable
(or decrease in PaCO2 at constant minute ventilation and
tidal volume)
Titration of PEEP by oxygenation after assessment of lung recruitability.

PEEP/FIO2 tables are from the ALVEOLI Trial. Adjust PEEP and FIO2 using the
two tables as guidelines to maintain PaO2 between 55 and 80 mmHg or SpO2
between 88% and 95%.
*Consider the using lower PEEP table as a guideline for PEEP titration for
patients who have active barotrauma or adverse PEEP-induced cardiovascular
changes.
Positive End-Expiratory Pressure:
The high PEEP approach is a type of open lung
ventilation that does not require pressure-volume
curves. This is advantageous because pressure-volume
curves are difficult to construct and generally require
neuromuscular blockade.
Significance of PEEP:
Applied PEEP opens collapsed alveoli, which decreases
alveolar overdistension because the volume of each
subsequent tidal breath is shared by more open alveoli.
If the alveoli remain open throughout the respiratory
cycle, cyclic atelectasis is also reduced. Alveolar
overdistension and cyclic atelectasis are the principal
causes of ventilator-associated lung injury.
TITRATING PEEP BY ESOPHAGEAL PRESSURE
 Esophageal pressure is an estimate of pleural
pressure. It can be measured with an esophageal
balloon catheter and then used to calculate the
transpulmonary pressure.
 Transpulmonary pressure = airway pressure -
pleural pressure
 The transpulmonary pressure can then be adjusted by
titrating applied PEEP, since airway pressure is
related to applied PEEP. Titrating applied PEEP to
an end-expiratory transpulmonary pressure between 0
and 10 cm H 2 O may reduce cyclic alveolar collapse,
while maintaining an end-inspiratory
transpulmonary pressure ≤25 cm H 2 O may reduce
alveolar overdistension.
• PEEP by acting as a “stent” to keep small airways open
at the end of expiration and ↓ shear forces.
• Advantages of PEEP:
• PEEP ↑arterial oxygenation by ↓ intra pulmonary
shunting.
• Allows reduction in (FiO2) to safer levels hence
↓oxygen toxicity.
• PEEP can also open collapsed alveoli and reverse

atelectasis - known as lung recruitment, and it
increases the available surface area in the lungs
for gas exchange
―High applied peep should be administered to
the patients with refractory hypoxemia before
implimenting other rescue interventions because
ARDS patients are a heterogenous group , some of
whom may have large areas of recruitable lung that
will respond to applied PEEP.‖
Pitfalls of PEEP:
 Increased applied PEEP has the potential to
cause pulmonary barotrauma or ventilator-
associated lung injury by increasing the plateau
airway pressure and causing alveolar
overdistension. It also has the potential to
decrease blood pressure by reducing cardiac
output.
LUNG RECRUITMENT
 If there is recruitable lung, then PEEP will have a
favorable effect and will improve gas exchange in the lungs.
However if there is no recruitable lung, PEEP can
overdistend the lungs (because the lung volume is lower if
areas of atelectasis cannot be aerated) and produce an
injury similar to ventilator-induced lung injury.
 Areas of atelectasis that contain pockets of aeration are

most likely to represent recruitable lung, whereas areas of
atelectasis that are airless are unlikely to be recruitable.
 The impact of routine recruitment maneuvers on clinical

outcomes is unclear, although one meta-analysis found that
recruitment maneuvers did not affect mortality, length of
hospital stay, or the incidence of barotrauma, despite
improving the PaO 2 .
RECRUITMENT MANEUVERS (RMS)
Current evidence suggests that that RMs should not be routinely used on all
ARDS patients unless severe hypoxemia persists or as a rescue maneuver to
overcome severe hypoxemia, to open the lung when setting PEEP, or following
evidence of acute lung derecruitment such as a ventilator circuit disconnect
• Vital capacity maneuver (inflation of the lungs up to 40 cm H2O,

maintained for 15 - 26 seconds)
• Intermittent sighs
• Intermittent increase of PEEP
• Continuous positive airway pressure (CPAP) of 35-40cm of H20
for 40 seconds.
• Increasing the ventilatory pressures to a plateau pressure of 50 cm
H2O for 1-2 minutes .
• One study found that most of the alveolar recruitment occurred
during the first ten seconds of the maneuver . This was followed by
a decrease in the blood pressure, which recovered within 30 seconds
after the recruitment maneuver. Significant airway overdistention
does not occur while single recruitment manuevre and recruited
alveoli tend to remain open when lower pressure are instituted.
RECRUITMENT MANEUVERS
CPAP : 35-40 cm H20 for 30-40 seconds
Anesthesiology 2002, 96:795–802.

RECRUITMENT MANEUVERS
Intermittent Sigh
Intermittent PEEP
Progressive PEEP
Anesthesiology 2002, 96:795–802.

Curr Opin Crit Care 2003; 9:22–27
Crit Care Med 2004; 32: 2371–77
MODE OF VENTILATOR
Randomized, controlled trials demonstrating superiority of volume
assist control over other modes in the management of ARDS are
lacking at this time, but it is the mode used in the majority of major
clinical trials in patients with ARDS and was the mode used in the
ARMA trial, which, as noted above, showed a clear mortality
benefit.
PCV : Variable flow, so more comfortable if dyssynchrony, prolong i

time for oxygenation, control peak pressures
NEUROMUSCULAR BLOCKERS
 Administration of short-term (up to 48 hours)
neuromuscular blockade to patients with ARDS who
have severe gas exchange abnormalities (eg, PaO 2
/FiO 2 ≤120 mmHg) is probably safe and potentially
beneficial.
 Improvements in patient–ventilator synchrony and

elimination of muscle activity and the associated
oxygen consumption,
 Papazian L, Forel JM, Gacouin A, et al.

Neuromuscular blockers in early acute respiratory
distress syndrome. N Engl J Med 2010; 363:1107.
REFRACTORY HYPOXEMIA
 Following modalities are used for Refractory

Hypoxemia apart from N-M Blockers, High
PEEP & other recruitment maneuvers
 Prone Position
 Other modes of ventilator
 IRV
 Inhaled Nitric Oxide
 ECMO
Prone position:
 In several trials, MV in the prone position improves

oxygenation. Other purported benefits include
improvements in secretion clearance, increased end-
expiratory volume, and decreased mechanical compression
of the lungs by the heart.
 Switching from the supine to prone position can improve

pulmonary gas exchange by diverting blood away from
poorly aerated lung regions in the posterior thorax and
increasing blood flow in aerated lung regions in the
anterior thorax.
 The latest PROSEVA (Proning Severe ARDS Patients)

trial confirmed these benefits in a formal randomized
study. The bulk of data indicates that in severe acute
respiratory distress syndrome, carefully performed prone
positioning offers an absolute survival advantage of 10–
17%, making this intervention highly recommended in
this specific population subset.
 Can be hazardous, leading to accidental endotracheal

extubation, loss of central venous catheters, and
orthopedic injury, pressure sores etc.
POSSIBLE MECHANISMS
 Recruitment of dependent lung zones,
 Increased functional residual capacity (FRC)
 Improved diaphragmatic excursion
 Increased cardiac output
 Improved ventilation-perfusion matching
 Relief of compression of the lung by the heart and
Mediastinal structures
OTHER MODES OF MV :
 AIRWAY PRESSURE RELEASE VENTILATION
(APRV):
 Another “open lung” approach
 It is a pressure control mode with spoteneous breaths;
CPAP released periodicaly.
 Two CPAP levels Higher CPAP is baseline pressure
 Intermittent, brief release of Paw from higher CPAP
level to lower CPAP level
 Decrease in Paw augments TV
 Spontaneous breathing at both upper & lower CPAP
 Available on few ventilators
 Like BiPAP/BiLevel but time at the lower pressure
(“release time”) is usually short  0.6-1sec
APRV
Airway Pressure Release Ventilation
From Mosby’s R. C. Equip. 6th ed. 1999.
Inverse ratio ventilation (IRV)
 Oxygenation can also be improved by increasing mean airway

pressure with "inverse ratio ventilation."
 The inspiratory (I) time is lengthened so that it is longer than
the expiratory (E) time (I:E ratio as high as 7:1 have been
used).
 When the inspiratory time is increased, there is an

obligatory decrease in the expiratory time. This can lead to
air trapping, auto-PEEP, barotrauma, hemodynamic
instability, and decreased oxygen delivery.
 ↓ FIO2 to 0.60 to avoid possible oxygen toxicity,
 But no mortality benefit in ARDS has been demonstrated.

o There are potential side effects associated with
prolonging the inspiratory time that should be
considered.
o In addition, a prolonged inspiratory time may

require significant sedation or neuromuscular
blockage, particulary if the inspiratory time
surpasses the expiratory time.
 High-frequency ventilation (HFV) –
 High frequency oscillatory ventilation (HFOV)

delivers small tidal volumes (1–2 mL/kg) using
rapid pressure oscillations (300 cycles/min). The
small tidal volumes limit the risk of volutrauma,
and the rapid pressure oscillations create a mean
airway pressure that prevents small airway
collapse and limits the risk of atelectrauma.
 HFOV requires a specialized ventilator
 Partial liquid ventilation (PLV) with

perfluorocarbon, an inert, high-density liquid that
easily solubilizes oxygen and carbon dioxide, has
revealed promising preliminary data on pulmonary
function in patients with ARDS, but no survival
benefit.
INHALED NITRIC OXIDE
 Inhaled nitric oxide (5–10 ppm) is a selective

pulmonary vasodilator that can improve arterial
oxygenation in ARDS by increasing flow to areas
of high dead space ventilation. iNO flows only
into well ventilated areas, so improves shunt.
 However, the increase in arterial oxygenation is
temporary (1–4 days), and there is no associated
survival benefit
 Adverse effects of inhaled nitric oxide include
methemoglobinemia (usually mild) and renal
dysfunction.
EXTRA CORPOREAL MEMBRANE
OXYGENATION:-
 Extracorporeal membrane oxygenation (ECMO) is the use
of a modified heart–lung machine to provide respiratory,
circulatory, or both support at the bedside, usually for at
least a number of days or even weeks.
 Extracorporeal membrane oxygenation (ECMO) uses
technology derived from cardiopulmonary bypass (CPB)
that allows gas exchange outside the body. In addition,
circulatory support can also be provided.
 ECMO is a valuable option for the management of severe
but reversible causes of respiratory failure or cardiogenic
shock refractory to conventional treatment.
 Veno-venous ECMO is designed to provide gas exchange,
while veno-arterial ECMO provides both gas exchange and
haemodynamic support.
 Acute respiratory distress syndrome associated with
pneumonia (viral or bacterial) is the most common cause of
refractory hypoxemia that requires ECMO support.
NON-VENTILATORY MANAGEMENT
 Fluid management
 Diuretics
 Steroids
 Blood Transfusion cut-off
 Choice of Inotropic agent

Fluids management:
 Patients with ARDS should receive intravenous
fluids only sufficient to achieve an adequate
cardiac output, tissue oxygen delivery, and organ
function, as assessed by urine output, acid-base
status, and arterial pressure.
 Once the patient is beyond the early, resuscitative

phase of their illness, efforts should be made to
decrease the amount of volume administered and
maintain an even balance between the volume of
fluid administered to and eliminated from the
patient, referred to as ―euvolemia‖. The benefits of
this approach were demonstrated in the Fluid and
Catheter Treatment Trial (FACTT) .There were no
differences in 60-day mortality between the two
groups, but the conservative approach was
associated with improved gas exchange and
shorter duration of mechanical ventilation without
increasing the incidence of acute kidney injury or
other non-pulmonary organ failures.
 Goal: MAP ≥ 65mmHg, avoid hypoperfusion

ROLE OF DIURETICS
 Fluid management in ARDS is usually aimed at
reducing extravascular lung water with diuretics. While
this approach has shown modest benefits in clinical
measures like lung compliance, gas exchange, and
length of time on the ventilator, but little survival
benefit.
 The first problem with the use of diuretic therapy in
ARDS is the nature of the lung infiltration. While
diuretics can remove the watery edema fluid that forms
as a consequence of heart failure, the lung infiltration in
ARDS is an inflammatory process, and diuretics don't
reduce inflammation.
 Diuretic therapy can be tailored to achieve the lowest
cardiac filling pressures that do not compromise cardiac
output and systemic oxygen transport.
 The golden rule is that hydrostatic pressures should
be kept as low as possible, provided that oxygen
delivery to the tissues is not compromised .
 As techniques to monitor the regional circulation
become available, titration of fluid requirements will
become more precise.
 There is no place for systematic fluid restriction and

diuretics to eliminate edema, as the function of other
tissues may deteriorate with inadequate perfusion.
ROLE OF STEROIDS
IN UNRESOLVING ARDS
Because of apparent benefit in small trials, it was thought that
there might be a role for high-dose corticosteroid therapy in
patients with late (fibroproliferative phase) ARDS. However, an
ARDS Study Network trial of methylprednisolone for patients
with ARDS persisting for at least 7 days demonstrated no
benefit in terms of 60-day mortality.Patients treated later in the
course of ARDS, 14 days after onset, had worsened mortality
with corticosteroid therapy.
The benefit of steroids in ARDS may be explained by the

ability of steroids to promote collagen breakdown and inhibit
fibrosis
One of the successful regimens involved methylprednisolone in

a dose of 1-2 mg/kg/day.
1.Steinberg KP, Hudson LD, Goodman RB, et al found
that in the subgroup of patients randomized 7 to 13
days after the onset of ARDS, methylprednisolone
caused a non-statistically significant reduction in 60-
day mortality (27 versus 36 percent) and 180-day
mortality (27 versus 39 percent). In contrast, among
patients randomized more than 14 days after the onset
of ARDS, methylprednisolone increased 60-day
mortality (35 versus 8 percent) and 180-day mortality
(44 versus 12 percent). Methylprednisolone increased
ventilator-free days, shock-free days, oxygenation, lung
compliance, and blood pressure, but also increased
neuromuscular weakness.
2. In a double-blind trial, patients with early ARDS

(defined as ≤72 hours), Meduri GU, Golden E, Freire
AX, et al found that glucocorticoid therapy reduced the
duration of mechanical ventilation, length of ICU stay,
and ICU mortality (21 versus 43 percent).
HEMOGLOBIN
 Transfusion is often recommended to keep the Hb
above 10 g/dL, but this practice has no scientific
basis or documented benefit, even in ventilator-
dependent patients.
 Considering that blood transfusions can cause
ARDS, it is wise to avoid transfusing blood
products in patients with ARDS AND threshold
should be 7 g/dL.
 If there is no evidence of tissue dysoxia or
impending dysoxia (e.g., an oxygen extraction
ratio >50%), there is no need to correct anemia
with blood transfusions.
INOTROPIC AGENT
 Cardiac output may be augmented by raising filling
pressures if they are low (if pulmonary edema is not
exacerbated) or by using inotropic agents. However,
raising oxygen delivery to supernormal levels is not
clinically useful and may be harmful in some
circumstances.
 If volume infusion is not indicated, dobutamine is

preferred over vasodilators for augmenting the
cardiac output because vasodilators will increase
intrapulmonary shunt and will add to the gas
exchange abnormality in ARDS. Dopamine should be
avoided in ARDS because it constricts pulmonary
veins, and this will cause an exaggerated rise in the
pulmonary capillary hydrostatic pressure.
OTHER DRUG THERAPY – UNPROVEN BENIFIT
INHALED VASODILATORS : PGE1 (pulmonary
vasodilatation and anti-inflammatory effects on
neutrophils/macrophages) , Aerosolized PGI2 (selective
pulmonary vasodilatation of ventilated lung areas), NO
GM-CSF
Almitrine (selective pulmonary vasoconstrictor of
nonventilated lung areas)
Surfactant (prevents alveolar collapse and protects against

intrapulmonary injury and infection)
Antioxidants - dietary oil supplementation – Omega-3 fatty

acid, N-acetylcysteine (protect the lung from free oxygen
radical production)
Anti-inflammatory drugs (Lisofylline, Ibuprofen,

ketoconazole, Statin)
No recommendation can be made for their use - Rescue

modality in the patient with refractory hypoxia?
Mortality:
 Recent mortality estimates for ARDS range
from 26 to 58% with substantial variability.
 The underlying cause of the ARDS is the most
common cause of death among patients who die
early. In contrast, nosocomial pneumonia and
sepsis are the most common causes of death
among patients who die later in their clinical
course . Patients uncommonly die from
respiratory failure.
 Thus, improvement in survival is likely

secondary to advances in the care of
septic/infected patients and those with
multiple organ failure.
Functional Recovery in ARDS
Survivors
o ARDS pts experience prolonged

respiratory failure and remain dependent
on mechanical ventilation for survival.
o Patients usually recover their max lung
function within 6 mnths.
o One year after endotracheal extubation,

over a 1/3 of ARDS survivors have normal
spirometry values and diffusion capacity.
o Most of the remaining patients have only

mild abnormalities in their pulmonary
function.
 Recovery of lung function is strongly associated with
the extent of lung injury in early ARDS
 When caring for ARDS survivors it is important to be
aware of the burden of emotional and respiratory
symptoms.
 There are significant rates of depression and

posttraumatic stress disorder in ARDS survivors
FUTURE DIRECTIONS:
 With the high mortality rates associated
with ARDS and sepsis, the search
continues to identify targets.
 Effective anti-sepsis interventions may
reduce the incidence of ARDS and
improve outcomes from it.
 1) Antibodies against macrophage

migration inhibitory factor (MIF),
 2) Antibodies against high-mobility

group B-1 protein (HMGB1),
 3.) Stem cell therapy (MSC)

ROLE OF STEM CELLS – PHASE-I CLINICAL
TRAIL GOING ON
 Stem cells constitute a promising therapeutic strategy for
patients suffering from ALI/ARDS.
 MSCs appear closest to clinical translation, given the evidence
that they may favourably modulate the immune response to
reduce lung injury, while maintaining host immune-
competence and also facilitating lung regeneration and repair.
 However, gaps remain in our knowledge regarding the
mechanisms of action of MSCs, the optimal MSC
administration and dosage regimens, and the safety of MSCs
in critically ill patients. It is anticipated that these remaining
knowledge deficits will be addressed in ongoing and future
studies.
 Other stem cells, such as ESCs and iPCs, are at an earlier
stage in the translational process, but offer the hope of directly
replacing injured lung tissue.
 Ultimately, lung-derived stem cells may offer the greatest
hope for lung diseases, given their role in replacing and
repairing the native damaged lung tissues.
 JAMA, June 20, 2012—Vol 307, No. 23 : Berlin Definition
 Harrison‗s Principles Of Internal Medicine 19th Edition
 The ICU Book, 3rd Edition - Paul L. Marino
 UpToDate : www.uptodate.com
 eMedicine : www.medscape.com
 Mechanical ventilation 3rd Edition - David W Chang
 Susen Pilbeam Text Book Of Mechanical Ventiltor
 Human Mesenchymal Stem Cells For Acute Respiratory
Distress Syndrome (START)Clinicaltrial :
http://clinicaltrials.gov/show/NCT01775774
 M, Luks Andrew. 2013. "Ventilatory strategies and supportive
care in acute respiratory distress syndrome." Influenza and other
respiratory viruses 7 Suppl 3: 8-17. doi:10.1111/irv.12178.
 Carl F. Haas, MLS, RRT “Mechanical Ventilation with Lung
Protective Strategies: What Works?” Crit Care Clin 27 (2011) 469–
486
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DIAGNOSIS & MANAGMENT OF

Acute Respiratory Distress Syndrome

 First described as clinical syndrome in 1967 by

 The major changes to the Berlin Definition are that the

 These variables were identified for further study

 The PCWP is a measure of LAP and LAP cannot be the

 This difference is small in the normal lung, but in severe

 Because of this discrepancy, the wedge pressure should

 But doesn‘t exclude left heart failure

 >80% of cases are caused by:

Direct insult  Indirect insult

Each with characteristic clinical and pathologic features

 Release of inflammatory mediators from lung

 Shear stress due to complete closure & re-opening of

 SIRS - Systemic inflammatory

 MODS - multi organ

This adds up to impaired

 However, , pleural effusions can appear in

 In the early stages of ARDS, the hypoxemia is often more

 However, there are exceptions, and severe hypoxemia can

The most reliable method for confirming or

 A low neutrophil count in lung lavage

 Because inflammatory exudates are rich in proteinaceous

 Protein (lavage/serum) >0.7 = Lung inflammation

 Lung inflammation is expected to produce a protein

 BAL has not gained widespread acceptance as a diagnostic

(1) Early recognition and treatment of the underlying

 Common causes of increased oxygen

 Since the introduction of positive-pressure mechanical

 In patients with ARDS, these large inflation volumes

 CT images reveal that the lung

 The remaining area of uninvolved lung is

 The large inflation volumes delivered by

3)Volutrauma : Ventilation at high volumes and pressures can lead to alveolar

6)Barotrauma : Pneumothorax, pneumomediastinum, interstitital emphysema.

LVV protocol is designed to achieve

 Keep the end-inspiratory plateau

 Avoid severe respiratory acidosis.

 One of the consequences of low volume ventilation is a

 The degree of hypercapnia can be minimized by using the

 Alternative approach : PEEP set at a high level following a

 PEEP adjustment based on the PEEP–FIO2 protocol used in ARMA

Titration of PEEP by oxygenation after assessment of lung recruitability.

• PEEP can also open collapsed alveoli and reverse

 Areas of atelectasis that contain pockets of aeration are

 The impact of routine recruitment maneuvers on clinical

• Vital capacity maneuver (inflation of the lungs up to 40 cm H2O,

Anesthesiology 2002, 96:795–802.

Anesthesiology 2002, 96:795–802.

PCV : Variable flow, so more comfortable if dyssynchrony, prolong i

 Improvements in patient–ventilator synchrony and

 Papazian L, Forel JM, Gacouin A, et al.

 Following modalities are used for Refractory

 In several trials, MV in the prone position improves

 Switching from the supine to prone position can improve

 The latest PROSEVA (Proning Severe ARDS Patients)

 Can be hazardous, leading to accidental endotracheal

 Oxygenation can also be improved by increasing mean airway

 When the inspiratory time is increased, there is an

 ↓ FIO2 to 0.60 to avoid possible oxygen toxicity,

 But no mortality benefit in ARDS has been demonstrated.

o In addition, a prolonged inspiratory time may

 High frequency oscillatory ventilation (HFOV)