An overview of adult respiratory distress syndrome with a focus on the updates in ventilatory management of this important syndrome in the intensive care

1. Adult Respiratory Distress
Syndrome
Respiratory Study Day
Royal Brompton Hospital
Dr. Hatem Aboumarie, MBBS, MSc, MRCP

2. • ESICM convened an international panel of experts, with
representation of ATS and SCCM
• The objectives were to update the ARDS definition using a
systematic analysis of:
• Current epidemiologic evidence
• Physiological concepts
• Results of clinical trials
ARDS, New Definition

3. • All modifications were based on the principle
that syndrome definitions must fulfill three
criteria:
• Feasibility
• Reliability
• Validity
ARDS, New Definition

4. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669
The Berlin definition

5. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669
The Berlin definition

6. • No change in the underlying conceptual understanding of ARDS
• “acute diffuse, inflammatory lung injury, leading to increased pulmonary vascular
permeability, increased lung weight, and loss of aerated lung tissue…[with] hypoxemia and
bilateral radiographic opacities, associated with increased venous admixture, increased
physiological dead space, and decreased lung compliance.”
• Although the authors emphasize the increased power of the new Berlin
definition to predict mortality compared to the AECC definition, in truth it’s still
poor, with an area under the curve of only 0.577, (95% CI, 0.561-0.593)
compared to 0.536, (95% CI, 0.520-0.553 ) for the old definition.
The Berlin definition

7. Pathophysiology

8. Pathological Stages
1. Exudative stage: diffuse alveolar damage within the first week
2. Proliferative stage: resolution of pulmonary edema, proliferation of
type II alveolar cells, squamous metaplasia, interstitial infiltration by
myofibroblasts, and early deposition of collagen.
3. Some patients progress to a third "fibrotic" stage, characterized by
obliteration of normal lung architecture, diffuse fibrosis, and cyst
formation

9. Pathophysiology

10. Risk Factors
• Sepsis
• Severe trauma
• Surface burns
• Multiple blood transfusions
• Drug overdose
• Following bone marrow
transplantation
• Multiple fractures
• Aspiration
• Pneumonia
• Pulmonary contusion
• Pulmonary embolism
• Inhalational injury
• Near drowning

11. Negative Pressure Pulmonary Edema
• Type of Non-Cardiogenic Pulmonary Edema
• Mechanism:
Rapid resolution of large levels of negative intra-thoracic pressures
by removal of airways obstruction  alveolar and capillary damage
 increased vascular permeability

12. Clinical Presentation
• Dyspnea, Tachypnea
• Persistent hypoxemia, despite the administration of high
concentrations of inspired oxygen
• Increase in the shunt fraction
• Decrease in pulmonary compliance
• Increase in the dead space ventilation

13. Basic Management Strategies
• Identify and treat underlying causes
• Ventilatory support
• Lung protective strategy
• Application of PEEP
• Restore and maintain hemodynamic function
• Conservative fluid replacement strategy
• Vasopressors and inotropics support
• Prevent complications of critical illness
• Ensure adequate nutrition
• Avoid oversedation
• Using weaning protocol with spontaneous breathing trials
• Continuous use of steroids for fibroproliferative phase ? questionable

14. Fluid management and vasoactive support
•SAFE trial
Resuscitation with saline is as beneficial as resuscitation with
albumin in critically ill patients with shock
•FACTT trial
• Prospective, Randomized, Multi-Center Trial
• Utility and safety of using a pulmonary artery catheter versus
central venous catheter to guide the volume replacement
• Liberal versus conservative fluid replacement

15. FACTT
• Patients were treated with the specific fluid management strategy
(to which they were randomized) for 7 days or until unassisted
ventilation, whichever occurs first.
• The study enrolled 1000 patients and showed no benefit with PAC
guided fluid therapy over the less invasive CVC guided therapy.

16. •The Use of Conservative fluid management strategy was associated
with
•Significant improvement in oxygenation index
• Significant improvement in Lung Injury score (Murray’s)
• Increase in the number of ventilator- free days
FACTT

17. Murray Lung Injury Score

18. Mechanical Ventilation
• Ventilator associated lung injury:
• Volutrauma
• Atelectotrauma
• Biotrauma
• Barotrauma
• Air embolism/translocation

19. NHLBI ARDS Network
 Compared low tidal volumes (6ml/kg of ideal body weight )
against conventional tidal volumes (12ml/kg ideal body weight )
 Significant decrease in mortality associated with the use of low
tidal volumes (39.8% versus 31%, P= 0.007)

20. NHLBI ARDS Network

21. NHLBI ARDS Network

22. Mechanical Ventilation
• Initial tidal volumes of 8 mL/kg predicted body weight in kg, calculated by:
• [2.3 *(height in inches - 60) + 45.5 for women or + 50 for men].
• Respiratory rate up to 35 breaths/min
• expected minute ventilation requirement (generally, 7-9 L /min)
• Set positive end-expiratory pressure (PEEP) to at least 5 cm H2O (but much higher is
probably better)
• FiO2 to maintain an arterial oxygen saturation (SaO2) of 88-95%  92-97% (PaO2 55-80
mm Hg, 7-10 kPa).  (70-90 mmHg, 9-11 kPa)
• Titrate FiO2 to below 60-70% when feasible.
• Over a period of less than 4 hours, reduce tidal volumes to 7 mL/kg, and then to 6 mL/kg.

23. Mechanical Ventilation

24. • Plateau pressure (measured during an inspiratory hold of 0.5-1 sec) <30 cm H2O,
• High plateau pressures vastly elevate the risk for harmful alveolar distension (Barotrauma).
• If plateau pressures remain elevated after following the above protocol, further
strategies should be tried:
• Reduce tidal volume, to as low as 4 mL/kg by 1 mL/kg stepwise decrements.
• Sedate the patient to minimize ventilator-patient dyssynchrony.
• Consider other mechanisms for the increased plateau pressure.
•    Permissive Hypercapnea
Mechanical Ventilation

25. Potential benefits of hypercapnia in
patients with ARDS
• Decrease in TNF-alpha release by alveolar macrophages
• Decrease in PMNL-endothelial cell adhesion
• Decrease in Xanthine oxiedase activity
• Decrease in NOS activity
• Reduction of IL-8

26. PEEP
Use of PEEP usually improves gas exchange and helps
reduce the need for high FiO2. In addition, appropriate
levels may limit VILI, by maintaining lung recruitment,
improving lung homogeneity and reducing so-called
atelectrauma attributed to repeated opening and closing of
alveoli

27. ARDS
High versus Low PEEP
•Higher PEEP along with low tidal volume ventilation should be
considered for patients receiving mechanical ventilation for ARDS.
• This suggestion is based on a 2010 meta-analysis of 3 randomized trials (n=2,229) testing
higher vs. lower PEEP in patients with acute lung injury or ARDS, in which ARDS
patients receiving higher PEEP had a strong trend toward improved survival.

28. •However, patients with milder acute lung injury (paO2/FiO2 ratio > 200)
receiving higher PEEP had a strong trend toward harm in that same
meta-analysis.
•Higher PEEP can conceivably cause ventilator-induced lung injury by
increasing plateau pressures, or cause pneumothorax or decreased cardiac
output.
ARDS
High versus Low PEEP

29. Mechanical Ventilation

30. Mechanical Ventilation

31. Mechanical Ventilation

32. ARDS
• Inhaled NO
• Steroids
• Prone Position
• High Frequency Oscillatory Ventilation
• ECMO

33. Inhaled Nitric Oxide
• It is a bronchial and vascular smooth muscle dilator
• Decreases the Platelets Adherence and Aggregation
• Improves Ventilation/Perfusion ratio
• Reduction in Pulmonary Artery Pressure and pulmonary Vascular
Resistance

34. • Two Prospective, Randomized, Placebo Controlled Clinical Trials
failed to demonstrate an improvement in the survival.
• However, there was improvement in the oxygenation!
Inhaled Nitric Oxide

35. This multicenter RCT of 340 patients with severe ARDS found
early use of 48 hours of neuromuscular blockade reduced mortality
compared to placebo (NNT of 11 to prevent one death at 90 days
in all patients, and a NNT of 7 in a prespecified analysis of patients
with a PaO2:FiO2 ratio less than 120).
NMBs
N Engl J Med, 2010;363:1107-16.

36. Steroids
• A protocol for steroids in late ARDS, based on the Meduri paper*
• The patient must have no demonstrable infection
• BAL may be necessary to confirm this. This includes undrained abscesses, disseminated fungal
infection and septic shock
• Steroids should not be started less than 7 days, or more than 28 days, from admission
• The patient should not have a history of gastric ulceration of active gastrointestinal
bleeding
• Patients with burns requiring skin grafting, pregnant patients, AIDS, and those in
whom life support is expected to be withdrawn, are unsuitable
*Meduri GU, Kohler G, Headley S, Tolley E, Stentz F, Postlethwaite A. Chest 1995; 108(5):1303-1314.

37. Prone Positioning
• Relieves the cardiac and abdominal compression exerted on the lower
lobes
• Makes regional Ventilation/Perfusion ratios and chest elastance more
uniform
• Facilitates drainage of secretions
• Potentiates the beneficial effect of recruitment maneuvers

41. Evidence-based Pearls

42. Pearl #1
Noninvasive support, with close monitoring, is a reasonable
initial approach in less severely ill patients with ARDS

43. PaO2 should be maintained within a normal range (e.g.,
between 70 and 90 mmHg, 9-11 kPa) or SaO2 between 92
and 97%
Pearl #2

44. Low tidal volume ventilation, about 6 ml/kg based on
predicted body weight, along with an airway plateau
pressure ≤ 30 cmH2O should be targeted in most patients
with ARDS
Pearl #3

45. The measurement of esophageal pressure, as a surrogate for
pleural pressure, enables estimation of transpulmonary
pressure (i.e., the distending pressure across the lung)
Pearl #4

46. PEEP selection should be based on various factors, including
gas exchange, hemodynamics, lung recruitability, end-
expiratory transpulmonary pressure and driving pressure
Pearl #5

47. In severe ARDS, there is no outcome advantage of using
volume-controlled compared to pressure-controlled forms
of ventilation.
However, use of VC ventilation during passive inflation
facilitates the measurement of respiratory mechanics and
driving pressure and is recommended in the early stage.
Pearl #6

48. Pressure controlled ventilation does not guarantee a fixed
tidal volume, but may result in better respiratory comfort at
a later stage during assisted breathing because it does not
limit inspiratory flow.

49. Recruitment maneuvers can be applied before PEEP selection or
in case of abrupt de-recruitment
• A transient increase in inspiratory airway pressure to 40–45 cmH2O
 Observe hemodynamics
• Routine application is not associated with a reduction in hospital
mortality
Pearl #7

50. Use of high-frequency oscillatory ventilation is not
Recommended (unless rescue therapy)
However: a recent meta-analysis suggests some potential
advantage in these patients (P/F < ~ 70 mmHg)*
Pearl #8
* Meade MO, et al. Am J Respir Crit Care Med. 2017

51. Prone positioning should be used in ARDS patients with
PaO2/FiO2 < 150 mmHg unless contraindicated
Pearl #9

52. Prone Positioning
Because of its beneficial effects on oxygenation, lung recruitment
and stress distribution—should be considered in the early phase of
ARDS in patients with PaO2/FiO2 < 150 mmHg, and when used
should be applied for 16–20 hours per day.
An important recent study by Guerin et al. showed that prone
positioning applied for at least 16 hours per day in patients with
ARDS and PaO2/FiO2 < 150 mmHg significantly reduced 28-day
mortality (16% vs 32%).

53. Contraindications: the presence of an open abdominal
wound, unstable pelvic fracture, spinal lesions and
instability, and brain injury without monitoring of
intracranial pressure. In addition, well-trained staff are
required for its safe implementation.
Prone Positioning

54. In moderate/severe ARDS, neuromuscular blocking agents
may be useful in the acute phase
Pearl #10

55. NMBs
Neuromuscular blockade requires sustained deep sedation.
Adverse effects of prolonged use of these drugs include
myopathy, deleterious effects on the diaphragm and ICU-
acquired weakness, especially in patients receiving
concomitant corticosteroids

56. Sedation should be reduced and partial ventilator support
can be used to promote respiratory muscle activity
whenever gas exchange, respiratory mechanics and
hemodynamic status have improved
Pearl #11

57. ECMO should be considered in addition to mechanical
ventilation in selected very severe cases of ARDS.
Some preliminary reports and a strong pathophysiological
rationale suggest that ventilation with very low tidal volume
(3–4 ml/kg PBW) associated with extracorporeal carbon
dioxide removal (ECCO2R) may limit the development of
VILI.
Pearl #12

58. Use and timing of tracheostomy should be individualized
Tracheotomy should not be used in every patient with
ARDS, but should be considered when prolonged
mechanical ventilation is anticipated.
Pearl #13

59. Weaning should be considered whenever PaO2/ FiO2 > 200
mmHg with PEEP < 10 cmH2O in most cases.
It has consistently been shown that the duration of mechanical
ventilation is significantly reduced in patients who have been
assessed once daily with a period of unassisted breathing (T-piece,
CPAP or low levels of pressure support ventilation)
Pearl #14

60. For patients at high risk for extubation failure, NIV is
recommended after extubation as this may significantly
reduce the ICU length of stay and mortality.
Pearl #15

61. In some specific scenarios, for patients with high risk of lung
collapse (e.g., morbid obesity or in patients after cardiac
surgery), direct extubation from CPAP levels ≥ 10 cmH2O
(or PEEP ≥ 10 cmH2O plus low levels of pressure support)
has been used with success, resulting in reduced postoperative
pulmonary complications.
Pearl #16

62. Thank You