2. History
In 1967, Ashbaugh and colleagues reported the clinical
characteristics of 12 patients with sudden respiratory failure that
they called ARDS
No underlying cardiac or pulmonary disease
Rapidly developed acute hypoxemia, stiff lungs, and diffuse
bilateral alveolar infiltrates on chest x-ray a few days following
exposure to a precipitating factor.
Autopsies revealed a characteristic histological pattern of diffuse
alveolar damage (DAD) including hyaline membrane formation,
oedema, cell necrosis, or fibrosis (Ashbaugh et al. 1967)
4. FIVE KEY CLINICAL FEATURES
PRESENCE OF DEFINED RISK FACTOR
SEVERE HYPOXEMIA REFRACTORY TO SUPPLEMENTAL OXYGEN
BILATERAL PULMONARY INFILTRATES
REDUCED LUNG COMPLIANCE
ABSENCE OF CHF
5. LUNG INJURY SCORE
MURRAY 1988
P/F RATIO
PEEP
COMPLIANCE
RADIOGRAPHIC DISTRIBUTION
INVALIDATED AS A MARKER OF MORTALITY
6.
7. First clinical definition - AECC
(1994)
Acute onset of hypoxemia
PaO2 to FiO2 ratio ≤ 200 mmHg regardless of PEEP level,
Presence of bilateral infiltrates on chest radiograph, and
Pulmonary artery wedge pressure ≤ 18 mmHg or no clinical signs of
cardiogenic pulmonary oedema
ALI ( acute lung injury)
ARDS
8. CRITIQUE
VARIABILITY IN PLAIN FILM INTERPRETATION
POOR CORRELATION WITH CT
CLINICAL ARDS PATIENTS HAD ELEVATED PCWP
NO STANDARDISATION OF PEEP
ALI ARDS DISTINCTION - ? SIGNIFICANCE
10. Timing of onset
By definition, respiratory symptoms must commence within 7 days of a clinical insult
Disease processes developing over several weeks like idiopathic pulmonary fibrosis,
nonspecific interstitial pneumonitis and granulomatosis with polyangiitis can be excluded
by accurately timing the respiratory symptoms
11. Diseases with acute onset that may
mimic ARDS
CONGESTIVE HEART FAILURE
INTERSTITIAL LUNG DISEASE
CONNECTIVE TISSUE DISEASE
DIFFUSE ALVEOLAR HEMORRHAGE – ANTI GBM
DRUG INDUCED LUNG DISEASE
ENDOBRONCHIAL TUBERCULOSIS
MALIGNANCY
A complete diagnostic workup should include
Echo,BAL and chest CT scan
12. ARDS is an acute inflammatory lung condition
ARDS is not a disease
Always precipitated by an underlying process
• Pneumonia
• Aspiration of gastric contents
• Contusion,near
drowning,inhalational injury
Pulmonary
• sepsis, pancreatitis, major trauma,
transfusion-related acute lung injury,
severe burns, or drug overdose.
Extra
pulmonary
13. Pathophysioogy
ARDS is characterized by a marked reduction in lung compliance
DAD is the morphological hallmark of the lung in ARDS
Diffuse alveolar damage is defined by the presence of hyaline membranes
associated with interstitial oedema, cell necrosis and proliferation and
then fibrosis at a later stage
14. INTERSTITIAL AND ALVEOLAR EDEMA TO FIBROSIS
EXUDATIVE PHASE – INITIAL RESPONSE TO INJURY
INNATE IMMUNE CELL MEDIATED DAMAGE OF ALVEOLAR ENDOTHELIAL
AND EPITHELIAL BARRIERS – EDEMA FLUID WITHIN ALVEOLUS
PROLIFERATIVE PHASE - REPAIR PROCESS – RESTORE ALVEOLAR
ARCHITECTURE
FIBROTIC PHASE - FINAL PHASE – NOT IN ALL
PROLONGED MECHANICAL VENTILATION AND INCREASED MORTALITY
17. Mechanisms of hypoxemia in ARDS
Loss of lung volume due to alveolar
oedema and collapse
intrapulmonary shunt and marked
alteration in (VA/Q ratio)
Surfactant deficiency
impairment to the hypoxic pulmonary
vasoconstriction response
Pulmonary hypertension and positive
pressure ventilation
Opening of patent foramen ovale
intracardiac shunt
Increase in the physiological dead space
occurs
Alteration in lung diffusion
18. Traditional ventilator settings
TV 12 – 15 ml/kg
PEEP 0 - 5 CM H20
FiO2 0.8 - 1.0
PaCO2 < 50, PO2 > 80, spO2 > 98%
Ventilator induced lung
injury(VILI)
21. “Baby lung”
Using CT scan, Gattinoni found that compliance correlated with the normally aerated lung and
that the specific compliance (compliance divided by functional residual capacity) was actually
normal.
The "baby lung" is a physiological concept
The remaining normally aerated lung accessible to ventilation is considerably reduced and of
similar size as that of a baby
ARDS lung is not "stiff" but instead small, with nearly normal intrinsic elasticity
29. Oxygenation strategies
The first-line strategy in supporting hypoxemic patients is to
provide oxygen
oxygen mask
oxygen mask plus reservoir
High flow canula – 1st line strategy for
oxygenation
31. The FLORALI study
a small multicenter, open-label trial
acute hypoxaemic respiratory failure and without hypercapnia,
treatment with high-flow nasal oxygen, standard face mask oxygen, or
non-invasive ventilation did not result in a significantly different
intubation rates.
There was a significant difference in favour of high-flow nasal oxygen in
90 day mortality (Frat et al, 2015; FLORALI study)
32.
33. NIV
No strong evidence for the use of noninvasive ventilation (NIV)
Intubation rates of 40-50% in cases of moderate and severe ARDS
Risk of delaying intubation by masking signs of respiratory distress
Worsening VILI
poor tolerance of the facemask is frequent
34. When to intubate?
Whatever oxygenation strategy is used, intubation should not be
delayed.
RR > 35-40 breaths/min
Clinical signs of respiratory distress
Severe hypoxemia defined as PaO2 < 60 mm Hg or SpO2 < 90%
despite high FiO2
Respiratory acidosis, and copious secretions
Non-respiratory indications for invasive ventilation are altered
consciousness and the occurrence of shock
35. Targets of mechanical ventilation
To achieve adequate gas exchange whilst avoiding VILI
36. Lung protective ventilation
Low VTs ( 4 - 6 ml/kg of ideal body weight)
High PEEP levels ( 11- 16 cm h2O)
Strict monitoring of plateau pressure to avoid exceeding 30 cm H2O
37.
38. Mode of ventilation
Worldwide assist-control in volume-controlled ventilation
(VCV) is the most commonly used mode
No difference in outcomes between VCV and (PCV
Whatever the ventilator mode used, VTs and end-inspiratory plateau
pressure should be limited and continuously monitored.
39. Gas exchange targets
Target a PaO2 of at least 60 mm Hg and SaO2 of at least 90%
No studies have shown that increasing PaO2 improves outcome
Protective ventilation using low VTs may induce respiratory acidosis
pH should usually be maintained above 7.2.
40.
41.
42. Driving pressure
Driving pressure (plateau pressure – PEEP) major determinant of outcome
it has been suggested that the mechanical power transferred to the respiratory system
from the ventilator plays a key factor in VILI
Not only the strain (change in lung volume) but both high flow and respiratory rate are
potentially harmful to the lungs
45. Recruitment maneuvers
Transient increases in trans-pulmonary pressure in an attempt to open collapsed alveoli.
When performing a recruitment manoeuvre the pressure reached at the end of inspiration
surpasses the recommended safety thresholds for short time periods
Sigh breaths, extended sigh breaths,
Increased inspiratory pressures and PEEP,
Sustained inflation
Staircase Recruitment Manoeuvre. There is currently minimal evidence to recommend a
particular method of recruitment.
46. Recruitment maneuvers
Oxygenation benefits may be short-lived and of uncertain signifiance,
There are no studies showing patient outcome benefits,
It is uncertain how to differentiate responders from non-responders
There is no evidence for when, how often they should be performed
There is no evidence of reducing VILI
The ART trial found increased mortality with staircase recruitment manoeuvre. Experts
made recently a conditional recommendation for using recruitment maneuver (Fan et al.
2017)
Recruitment maneuvers can be considered as rescue therapy in the most
severely hypoxemic patients
No single method can be recommended.
47. Proning
Advocated for almost 40 years
Oxygenation improves dramatically
The dorsum of the lung has a larger volume than the anterior and apical areas
Better ventilating the dorsal regions of the lung in the prone position improves
ventilation, reduces intrapulmonary shunt leading to an improvement in V/Q
matching.
50. Hemodynamics of proning
Afterload to the right ventricle is reduced
Lower pulmonary vascular resistance
Reduced levels of PEEP
Improves preload
53. PROSEVA Prone positioning in severe acute respiratory
distress syndrome. N Engl J Med. 2013 Jun .
MCRCT n =466
patients with severe ARDS (PaO2/Fi02 ratio <150 mm Hg, with FiO2 of at least 0.6, PEEP at least 5 cmH2),
and VT 6 ml/kg of IBW)
prone-positioning sessions of at least 16 hours duration (n=237) with the supine position (n=229)
primary outcome: 28-day mortality lower in the prone group (16% versus 32.8%; P<0.001; hazard ratio for
death 0.39, 95% CI 0.25 to 0.63)
secondary outcomes:
— Unadjusted 90-day mortality lower with prone positioning (23.6% versus 41.0%; P<0.001; hazard ratio
0.44, 95% CI 0.29 to 0.67); NNT=6
— incidence of cardiac arrests higher in the supine group
— no difference in ICU LOS or other complications such as pneumothorax
— better oxygenation, lower oxygen requirements, and more ventilation-free days in prone group
commentary:
— highly select group: <15% of all patients with ARDS and <1/3 of screened patients with ARDS underwent
randomization, almost 60% ineligible on the basis of exclusion criteria
— benefit may be because of long duration proning
— mortality among controls (32.8%) was similar to the mortality of 25 to 40% observed in various trials
54. PROSEVA trial
PROSEVA: Prone Positioning in Severe Acute Respiratory Distress
Syndrome
Guerin et al for the PROSEVA Study Group. NEJM 2013;368:2159-68.
Proning in severe ARDS reduces mortality without an
increase in adverse outcomes. Further studies are required to confirm
these findings but in the mean time these results are difficult to ignore
55. Early application of airway pressure release ventilation may reduce
the duration of mechanical ventilation in acute respiratory
distress syndrome
Zhou. Intensive Care Medicine 2017; 43:1648-1659.
58. CESAR TRIAL 2009
180 patients – ECMO / Conventional
63% survival at 6months in ECMO group Vs 47% in conventional group
Technically flawed due to different levels of care
Summary : Mortality difference observed cannot be attributed to ECMO
59. EOLIA TRIAL 2018
NO MORTALITY DIFFERENCE – ECMO VS CONVENTIONAL VENTILATION
CONTROLS – 90% PRONE VENTILATED
PRONE VS ECMO
28% OF CONTROLS (SICKER AT RANDOMISATION) MIGRATED TO ECMO
WHICH MADE RESULTS DIFFICULT TO INTERPRET
SUMMARY(HARDIN &HIBBERT 2018,NEJM)):
TRIAL SUPPORTS USE OF ECMO WHO HAVE CLEARLY EXCEEDED
CONVENTIONAL VENTILATION AND PRONE POSITION
60. Sedation
The use of sedation improves patient tolerance of positive pressure
ventilation and allows resting of respiratory muscles and the reduction of
oxygen consumption by these muscles.
61. Neuro muscular blockers
Neuromuscular blocking agent cisatracurium used for 48 hours in severe ARDS patients
Improved oxygenation ( ACURASYS trial)
Reduced lung and systemic inflammation
Improved patient survival after adjusting for confounding factors
62.
63.
64. Steroids
Clear indications for steroid therapy for diseases that may mimic ARDS
include
Alveolar hemorrhage due to vasculitis,
Drug-induced toxic pneumonia with a lymphocytic pattern
Organized pneumonia
Acute eosinophilic pneumonia
65. Steroids in ARDS
Use of steroids in ARDS is unresolved
Mortality was significantly higher when steroid therapy was started 2 weeks after the
onset
Studies showing beneficial outcomes started low dose steroids early in the course of the
disease
High doses of steroids has been associated with either worse outcomes
66. Meduri GU et al. 1998
Effect of prolonged methylprednisolone therapy in unresolving acute respiratory
distress syndrome: a randomized controlled trial. JAMA. 1998 Jul 8;280(2):159-65.
RCT
double blind (placebo controlled)
n = 24
inclusion criteria: severe ARDS who failed to improve by day 7 of respiratory failure
methylpredisolone VS placebo
-> reduction in ICU mortality
-> reduced oxygenation requirement
-> reduction in MODS score
– criticisms: small numbers, differences in baseline characteristics between groups.
67. Steinberg KP, National Heart, Lung, and Blood Institute Acute Respiratory Distress
Syndrome (ARDS) Clinical Trials Network.
Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J
Med. 2006 Apr 20;354(16):1671-84.
MC RCT, n = 180
methylprednisolone for 14 days with taper versus placebo
results:
reduced shock symptoms
reduced ventilator days
improved pulmonary compliance
NO improvement in survival
increased mortality in patient who had had steroids > 14 days
increased neuromuscular weakness
What about steroids for ARDS prophylaxis? – increase in ARDS and subsequent mortality (weak
trend)
68. Other adjunct therapies
HFOV - High frequency oscillatory ventilation - found harmful
Inhaled nitric oxide - no proven benefit
Restricted fluid regimen - beneficial
69.
70. adults with moderate-to-severe ARDS
early application of HFOV, as compared with a ventilation strategy of low
tidal volume and high positive end-expiratory pressure,
does not reduce, and may increase, in-hospital mortality
71. OSCAR trial 2013
non-blinded intention-to-treat MC RCT
795 patients
HFOV versus usual care control group
outcomes:
-> all cause mortality at 28 days was 41.7% vs 41.1% (P=0.85 chi-square test)
Commentary and criticisms:
— less hemodynamic compromise, lower airway pressures than OSCILLATE and
more protocol variation, possibly due to physician judgement limiting the
harm from HFOV settings
— HFOV groups received more sedatives and muscle relaxants
Conclusion: no mortality difference at 1 month
72. SUMMARY
Bed side echo ,BAL and CT thorax for complete work up
HFNC is first line oxygenation method in mild ARDS
Do not delay intubation
Lung protective ventilation strategy
Recruitment during early disease as rescue oxygenation
Early proning in case of poor response
Consider early ecmo if poor response to proning
73. This Photo by Unknown Author is licensed under CC BY-NC-ND
