Ards and ALI

ACUTE RESPIRATORY DISTRESS
SYNDROME/ ACUTE LUNG INJURY
Dr. Mubashar Hashmi
ICU Specialist
KFHJ

objectives
 Review the pathophysiology of acute
lung injury/ARDS
 Research guiding thinking about the use
of standard ventilator approaches,
salvage, and innovative therapies in
addition to or in lieu of standard
techniques
 long term outcomes.

Historical Background
• World War-1: physicians have recognized a syndrome of
respiratory distress, diffuse lung infiltrates and respiratory
failure
• Various medical conditions including from battle trauma to
severe sepsis, pancreatitis, massive transfusions etc
• In 1967, Ashbaugh et al become the first to describe the
syndrome which they referred to as adult respiratory distress
syndrome in 12 such patients .

Historical Background
• 1971, Ashbaugh and Petty definition of ARDS
- Severe dyspnea
- Cyanosis refractory to Oxygen therapy
- Decreased pulmonary compliance
- Diffuse alveolar infiltrates on CXR
-: Autopsy FINDINGS. Atelectasis, vascular congestion,
hemorrhage, pulmonary edema and hyaline embranes

AMERICAN-EUROPEAN CONSENSUS CONFERENCE DEFINITIONS
1994
•

DIRECT LUNG INJURY
- Pneumonia
- Aspiration of gastric contents
- Inhalation injury
- Pulmonary contusion
- Fat emboli
- Near drowning
- Reperfusion pulmonary edema

INDIRECT LUNG INJURY
- Sepsis
- Sever trauma with shock or prolonged
hypotension
- Acute pancreatitis.
- Cardiopulmonary bypass.
- Sever burns
- D I C
- Drug over dose
- Cranial trauma
- Large volume blood transfusion

PATHOGENESIS
STAGES
Exudative
( Acute
Phase)
PROLIFERATI
VE Fibrotic Recovery

Phases of ARDS/ALI
 Light Microscopy: Early ARDS/ALI is characterized by flooding of the
lung with proteinaceous fluid and minimal evidence of cellular injury.
 Electron Microscopy: changes of endothelial cell swelling, widening
of intercellular junctions, increased numbers of pinocytotic vesicles, and
disruption and denudation of the basement membrane are prominent.
 Pulmonary edema and its effects & intrapulmonary shunt.
 Hyaline membrane formation in the alveolar spaces , &
inflammatory cells become more numerous.
EXUDATIVE PHASE:
DIFFUSE ALVEOLAR DAMAGE

 Diffuse alveolar collapse
 intrapulmonary shunt
 Low ventilation –perfusion ratio
 Decreased lung compliance
 Hypoxemia
 PEEP-more effective in reversing hypoxemia

Phases of ARDS/ALI
 Dominated by disordered healing.
 As early as7 to 10 days after the initial injury
 Exhibits extensive pulmonary fibrosis, which is not dissimilar
microscopically to the pathology of patients with longstanding
pulmonary fibrosis.
 Neovasularisation, microcirculatory thrombosis
PROLIFERATIVE PHASE

• Pulmonary edema may not be as prominent in this latter
phase of lung injury. Capillary damage
• Challenging large dead-space fraction and high minute
ventilation requirements.
• Progressive pulmonary hypertension, even if the
pulmonary circulation was normal at baseline.
• High V/P ratio, intrapulmonary shunt -less responsive
to PEEP.
• Further reduction in lung compliance.

Physical/ chemical
injury
Activation Innate
Inflammatory Cascade
Leakage Protein Rich
Oedema Fluid
Inflammatory Cellular
Infiltrates
Diffusion Abnormalities
V/Q Mismatch
Hypoxia
Respiratory
Failure
Physical/ chemical
injury
Activation Innate
Cellular Infiltrate
Atelectasis
Oedema Fluid
Reduced Thoracic
Compliance +
Vasoconstriction
Hypoxia
Respiratory
Failure
Physical/ chemical
injury
Activation Innate
Small Vessel Thrombosis
Increased Dead Space
Hypoxia
Respiratory
Failure

Consequences
• Impaired gas exhange .
• Decreased lung compliance .
• Pulmonary HTN .

Pathogenesis cont…
COMPLETE RESOLUTION .
FIBROPROLIFERATION. The extent of fibrosis may be
determined by the severity of the initial injury,
ongoing or repetitious lung injury, toxic oxygen
effects, and ventilator-associated lung injury.

RESOLUTION
Improvement of hypoxaemia
Improved dead space and lung compliance
Resolution radiographic abnormalities
Can take up to 1 year
Residual restrictive or obstructive
picture

ARDS:Treatment
• Oxygen therapy
• Noninvasive ventilation
• Mechanical ventilation
• Innovative approaches
• Treatment of underlying cause
– Better supportive ICU Care
• Prevention of infections
• Appropriate nutrition
• GI prophylaxis
• Thromboembolism prophylaxis

Mechanical Ventilation in ARDS
Injurious ventilator
associated lung injury
Necessary to reverse
Hypoxaemia
Ventilatory management of ALI & ARDS
LUNG PROTECTIVE STRATEGY

• Ventilator associated lung injury:(VALI)
 High inflation pressure Barotrauma
 Over distension Volutrauma
 Repetitive opening & closing of alveoli
 Atelect-trauma
 SIRS & cytokines release Biotrauma.
Ventilatory management of ALI & ARDS

Ventilatory Management of ARDS
VENTILATOR INDUCED LUNG
INJURY (VILI )
• Indistinguishable
morphologically, physiologically,
and radiologically from DAD
caused by other etiologies of
ALI.
• Unique because one can identify
that mechanical ventilation is
the cause of lung injury.
• Large tidal volumes (VT) and
high inflation pressures
• Animal studies- distending
volume > distending pressure
VENTILATOR-ASSOCIATED LUNG
INJURY (VALI)
• Resembles ARDS and occurs
in patients receiving
mechanical ventilation.
• Invariably associated with a
preexisting lung pathology
such as ARDS.
• Difficult to differentiate
from ARDS.

Clinical Studies of Ventilator Strategies for ARDS
•
 Limit VT and utilize PEEP to avoid alveolar recruitment-derecruitment
(so called open lung ventilation)
 ACV with VTs of 12 mL/kg, PEEP to keep FIO2 0.6, RR for PCO2~ 25-
38, NO control of PIP, or PPlt.(i.e conventional)
 PC inverse ratio ventilation, pressure support ventilation, or volume-
assured pressure-support ventilation with VTs of 6mL/kg, recruitment
maneuver, peak pressures of 40 cmH2O, PEEP titrated to maintain
lung inflation above the LIP (i.e, the open-lung approach).

RESULTS:
open-lung approach demonstrated a more rapid
recovery of pulmonary compliance,
LESS FIO2 requirement
 less barotrauma,
 higher rate of ventilator liberation,
decreased mortality

LIMITATIONS of this study:
 The number of patients included only 53
 Multiple treatment differences between the two groups,
including PEEP strategy, VT, PCO2,minute ventilation, lung
recruitment maneuvers, and mode of ventilation.
 Mortality rate was extremely high in the conventional
ventilation group (71%),
 Finally, patients with severe metabolic acidosis, which is a
common feature of patients with overwhelming sepsis and
ARDS, were excluded from study.
 Even if one accepts the results of this study, perhaps the
benefit was simply due to VT reduction, not to the PEEP
strategy.

CLINICAL PRACTICE
CHANGING TRIAL
2000 (NEJM)

ARDSNET Trial
 861 patients Randomized to a VT 12 or 6 mL/kg, IBW. PtP less 30 cmH2O
 The trial was stopped sooner as the findings were striking.
RESULTS:
 The mean VT on days 1 to 3 were 6.2 and 11.8 mL/kg, respectively, in the low-VT
and high-VT groups (P ,.001) and were associated with Pplat values of 25 and 33cm
H2O, respectively (P , .001).
 PEEP levels were minimally higher in the low-VT group from days 1 to 3 (averaging
,1 cmH2O, lower on day 7).
 The low-VT group - modest increase in PaCO2, very modest decrease in pH
 Respiratory acidosis between the groups was minimized by the higher respiratory
rates used in the low-VT group.

ARDS NET TRIAL CONT>>>
• Primary end point
– 28-day mortality,
• significantly improved with low-VT ventilation.
– 39.8% in the traditional group
– 31.0% with low-VT ventilation (P ¼ .007).
Number of ventilator-free days in the first 28
days was greater in the low-VT

Benchmark trial and confirms earlier studies
suggesting that low-VT ventilation can be protective
for patients with ARDS and will improve outcome.
Perhaps the best evidence-based recommendation
for the routine management of patients with ARDS
undergoing mechanical ventilation is to implement
the ARDSnet protocol.
 While questions surround other elements of
ventilatory strategy(eg, the ‘‘best PEEP’’ level, the
trade-off betweenFio2 and PEEP, the use of
recruitment maneuvers, and patient positioning),
 Current evidence strongly supports the use of the
ARDSnet Strategy.

RECOMMENDATIONS
ACCP BORAD REVIEW
2012

Practical Points for Managing the Patient With
ALI/ARDS
•
OXYGEN THERAPY
 Provide oxygen by high flow or rebreather mask.
 Rarely achieve a tracheal FIO2 > .0.6 in dyspneic, tachypneic
patients.
 Supplemental oxygen is a diagnostic as well as therapeutic
maneuver.
 Patients whose oxygenation improves dramatically with supplemental
oxygen generally have a small shunt and a larger component of
ventilation-perfusion mismatch (or hypoventilation).
 Slight improvement of PO2, BUT oxygen delivery will rise
significantly.

Role of non-invasive ventilation
• Not well established , but have been successfully used.
Generally not a good choice, and patients must be carefully
selected.
The course of ARDS is usually longer than the length of time that
patients tolerate noninvasive positive-pressure ventilation
 ARDS is so often associated with hemodynamic instability,
coma,and multiorgan system failure (including ileus).
ALL BUT EXCEPTIONAL PATIENTS SHOULD BE
ENDOTRACHEALLY INTUBATED.

Mechanical ventilation
INTUBATION should be performed early and
electively when it is clear that mechanical
ventilation will be required, rather than waiting for
frank respiratory failure.
 SEDATION AND MUSCLE RELAXATION : hypoperfusion ,
cardiovascular instability, to diminish the oxygen
requirement.
 SEDATION OR PARALYSIS: for extreme hypoxemic
ventilatory management.

VENTILATOR SETTINGS
 The initial ventilator settings as shown on table…
 Use of low VT is strongly supported by current evidence.
 Proper PEEP level is less clear.
 Some intensivists recommend a ‘‘least-PEEP’’ approach,
using PEEP only as necessary to achieve adequate oxygenation
and avoid toxic levels of FIO2 (although these thresholds are not
well established).
 Others recommend higher PEEP levels with a goal of
achieving maximal lung recruitment and avoiding mechanical
events, such as collapse-reinflation, that could lead to VALI.

Optimal PEEP??
 Some advocate the use of the PV curve of the lung measured
during the respiratory cycle as a guide to this PEEP titration.
 A trial completed by the ARDSnet comparing the PEEP strategy as
implemented in the trial of low-VT vs high VT against a higher PEEP
level did not show a difference in survival.
 A Canadian and then French trial did not demonstrate a difference
in survival based on high-PEEP vs low-PEEP strategy,
 Although the French study did demonstrate an improvement
in ventilator-free days with the high-PEEP strategy.

Optimal “PEEP”
• Positive end-expiratory
pressure should be high
enough to shift the end-
expiratory pressure above the
lower inflection point by 2-3
cm H2O (usually 12-15 cm H2O)
– Allows maximal alveolar
recruitment
– Decreases injury by
repeated opening and
closing of small airways

CAUTION……
 Regardless of specific strategy, reducing PEEP, even for
short periods of time, is often associated with alveolar
derecruitment and hence, rapid arterial hemoglobin
desaturation.
Thus, once endotracheal tube suctioning has been
accomplished for diagnostic purposes,nursing and
respiratory therapy staff should be instructed to keep
airway disconnections to a minimum or to use an in-
line suctioning generally effective for lower levels of
PEEP (ie, ,15 cm H2O) but often leak if higher levels are
attempted

ALTERNATIVE VENTILATORY APPROACHES
TO LUNG PROTECTION

ADVANTAGES:
 Decrease barotrauma, Provide better V/P matching,
 Cardiac filling Patient comfort.
Airway pressure release ventilation (APRV)

For Every Thing (Turn…Turn…Turn…)
PRONE POSITION in ARDS
Adjunctive therapies to lung-protective
Ventilation

Dorsal
VentralDorsal
Ventral
Mechanism of Prone Positioning

 PRONE POSITIONING:
– Recruitment of dorsal (nondependent) atelectatic lung, increased
FRC.
– Improved respiratory mechanics
– Decreased ventilation- perfusion mismatch, blood flow
redistribution
– Helps Increased secretion drainage
– Reduced and improved distribution of injurious mechanical forces
Adjunctive therapies to lung-protective
Ventilation

Innovative therapies for ARDS
For resistant and sever hypoxemia.
These approaches are not supported by large
prospective trials (or trials have been conducted
without seeing a benefit), but they may have
some role in individual patient management.

High-Frequency Ventilation
High frequency jet ventilation typically employs VT
of 1 to 5 mL (or higher) and respiratory rates of 60
to 300 breaths/min.
Gas exchange is complex under these conditions
and clearly not explained by bulk convective flow.
Large prospective trials are not available to compare
high-frequency jet ventilation to lung protective
ventilation as defined by the ARDSnet protocol. .

Extracorporeal Gas Exchange
The use of extracorporeal gas exchange (ie, extracorporeal
membrane oxygenation or ECMO) to adequately oxygenate
and ventilate the blood while allowing the lung to rest –
Attractive strategy for the management of patients with
ALI for decades.
In the recent past, the technologies supporting ECMO in the
ICU have become much improved, including double-lumen
catheters for conducting veno-venous ECMO and circuits
less complex and prone to interruption during extended use
outside the operating room- so wide scale application.

ECMO….
A recent trial conducted in England randomized
patients with ALI/ARDS to either remain in their
regional hospital or be transferred to a regional
center of excellence that offered ECMO
Using a combined end point of survival and
avoidance of severe neurologic injury, there was
a significant difference between the groups
favoring referral to the regional center.

ECMO…
 This study does not permit a clear conclusion of
the use of ECMO per se but does support a
comprehensive approach to care of these
patients.
 Recent publications tracking the use of ECMO
during periods of increased respiratory failure
incidence such as influenza pandemics have, not
surprisingly, shown that significant regional
differences in the use of ECMO exist.

Inhaled nitiric oxide
 Potent endogenous vasodilator
 Selectively vasodilates the pulmonary circulation.
 Inhaled NO (iNO) has several potentially salutary effects in
ARDS patients.
 selectively vasodilates pulmonary vessels, which subserve
ventilated alveoli, diverting blood flow to these alveoli (and
away from areas of shunt).
 Rapid inactivation of iNO via hemoglobin binding prevents
unwanted systemic hemodynamic side.

Inhaled nitiric oxide
 In numerous studies- approximately 50% to
70% of patients improving oxygenation.
Two prospective trials failed to demonstrate
improved long-term outcome in ARDS
Remains a salvage therapy at best.

Neuromuscular blockage for ARDS
• A recent multicenter prospective placebo-controlled trial -
use of cis-tracurium in patients with severe ARDS
• Enrolled within 48 h of the onset of the syndrome and
treated for 48 h. The primary end point —90-day - there was
significant diffrence.
• Development of neuromuscular weakness, differences were
not noted between the groups, although the study did not
report long-term follow-up of the patients studied.
• Additional studies supporting this pharmacologic therapy are
needed , but short term use of NMB is beneficial.

Fluid managment
The ARDSnet completed a large multicenter trial addressing these
questions.
Patients were randomized to receive management with either a
CVL or a right heart catheter, and then each group was
additionally randomized to receive a liberal or conservative fluid
strategy.
This study showed no discernable benefit for the use of the right
heart catheter with a protocolized management algorithm.

Fluids in ARDS…….
Conservative fluid strategy ( CVP ; PCWP 8)
Liberal fluid strategy ( CVP 10-14, PCWP 14-18))
Improvements in oxygenation index and lung
injury score , increased ventilator free days and
days not spent in the ICU.
NO DIFFRENCE IN SHOCK, RRT, AND
MORTALITY.

MANAGEMENT OF PROLIFERATIVE PHASE
• Characterized by increasing airway pressures or a
falling VT while receiving pressure control
ventilation, a further fall in lung compliance, less
response to PEEP, a ‘‘honeycomb’’ appearance on
the chest radiograph.
• Progressive pulmonary hypertension, and rising
minute ventilation requirements (.20 L/min).
• Barotrauma is a prominent feature, and multiple
organ failures often occur.

MANAGEMENT OF PROLIFERATIVE PHASE
• No increased vascular permeability- don’t reduce
preload for preventing edema- keep euvolemia.
• Increased zone I ventilation- don’t try to decrease
PCWP furthr, will increase dead space ventilation
• High dose steroids- favorable response in terms
of return to spontaneuos breathing & extubation
(Meduri et al JAMA 1998;280:159-165)
• CAUTION>>>>> ventilator associated pneumonia
after steroids… increased mortality.

LONG TERM outcomes of ARDS
Chronic Respiratory Disease,Muscle Fatigue,
Muscle Wasting ,Weakness.
 2012 retrospective analysis in JAMA:
Hypoxemia- predictor of mortality
 Reviews of ARDS outcomes :
Most people who survive ARDS recover
pulmonary function, but may remain impaired for
months or years in other domains, both physically
and psychologically.

MEET THE NEW ARDS
EXPERT PANEL ANNOUNCES NEW
DEFINITION, &SEVERITY CLASSES
(JAMA)

ARDS “The Berlin Definition “
The ARDS Definition Task Force*
JAMA. 2012;307(23):2526-2533. doi:10.1001/jam
• “ACUTE LUNG INJURY” NO LONGER EXISTS.
• ONSET OF ARDS (DIAGNOSIS) MUST BE ACUTE, as defined as within 7 days of
some defined event, Most cases of ARDS occur within 72 hours .
• BILATERAL OPACITIES consistent with pulmonary edema (CT scan /XRAY).
• NO NEED TO EXCLUDE HEART FAILURE in the new ARDS definition; patients
with high pulmonary capillary wedge pressures, or known congestive heart
failure with left atrial hypertension can still have ARDS.
• RESPIRATORY FAILURE SIMPLY BE “NOT FULLY EXPLAINED BY CARDIAC
FAILURE OR FLUID OVERLOAD.
• “OBJECTIVE ASSESSMENT“– ECHOCARDIOGRAM — if no clear risk factor
present like trauma or sepsis.

The new Berlin definition - ARDS severity classicfication
Severity PaO2/FiO2* Mortality**
Mild 200 – 300 27%
Moderate 100 – 200 32%
Severe < 100 45%
*on PEEP 5+; **observed in cohort

 Mechanical ventilation is life saving but can contribute to
patient morbidity and mortality
 Volume and pressure limited ventilation clearly leads to
improved patient survival, low tidal volume, high PEEP with or
without recruitment maneuver, target Plateau pr. Less than
30.
 Current evidence recommends lung protective strategy
 Innovative therapies- ECMO has observed role
 Careful fluids administration, followed by euvolemic strategy
in proliferative phase.
 High dose steroids beneficial in proloferative phase, risk of
VAP.
CONCLUSION

Ards and ALI

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