1. Acute Respiratory Distress Syndrome
Dr Samir Sahu
Consultant Intensivist
BBSR

2. ARDS
First described
Adult Respiratory Distress Syndrome - Ashbaugh
Acute Respiratory Distress Syndrome
ATS & European consensus Conference

3. ARDS- INTRODUCTION Incidence-86.2cases/100,000 p/y Rubenfeld NEJM 2005
Incidence of 7.2/100,000/year
The ALIEN study, Intensive Care Med 2011
Cause - variety of insults
Most common cause - SEPSIS
Mortality – 60-70%(late 1980s) % (last 2 decades) – Mild(27%), Mod(32%), Severe(45%) JAMA 2012
Higher mortality in Sepsis

4. Incidence and Outcomes of Acute Lung Injury Rubenfeld GD, Caldwell E, Peabody E, et al N Engl J Med. 2005;353:
The incidence of ALI was 80 cases per 100,000 person-years, with an associated in hospital mortality rate of 38% & 41% in ARDS.
The incidence of ALI increased with age, as did mortality.
Approximately 75% of identified patients met the more severe hypoxemia criteria for ARDS.

5. ARDS - Diagnosis Bilateral infiltrates on CXR
Hypoxaemia - PAO2/FIO2 <200
No elevation of LAP (PAP <18)
One or more underlying disease process known to cause ARDS
American European Consensus Conference on ARDS -
1994

6. ARDS Berlin Definition JAMA, 2012
Mild
Moderate
Severe
Timing
Acute onset <1 wk
Hypoxemia
PaO2 /FiO with PEEP > 5
PaO2 /FiO2 < 200 with PEEP > 5
PaO2 / FiO2 < 100 with PEEP > 10
Origin of Edema
Respiratory failure or fluid overload*
not fully explained
by cardiac failure
Radiological Abnormalities
Bilateral opacities**
Opacities involving at least 3 quadrants
Additional Physiological Derangement
N/A
VE CORR >10 L/min or CRS < 40 ml/cm H2O

7. ARDS Berlin Definition
** Not fully explained by effusions, nodules, masses, or lobar/lung collapse;
* Need objective assessment if no risk factor present
VE corr = VE X PaCO2/ (corrected for Body Surface Area)
VE corr = Corrected minute ventilation; (an indirect assessment of lung dead space)
CRS = Lung compliance at rest

8. ARDS - Radiology CXR - widespread involvement of all lung fields
Stage I (1-24h)-latent stage
Stage II(24-36h)-dense airspace
consolidation
Stage III(>72h)airspace consolidn
decreases

10. ARDS - Radiology CT: Consolidation & Collapse in dependant areas
- Recruitable
- Non recruitable
Normal
Bilateral-92%,Dependant-86%
Basilar-68%,Patchy-75%
Gatinoni 1986

12. ARDS
Heterogenous
Low compliance
High Pressures
Baby Lung
VILI

14. ARDS-Lung Injury Score
CXR
Hypoxaemia PAO2/FIO2 >
<
PEEP <5mm - 0
>15mm - 4
Compliance >80ml/c - 0
<19ml/c - 4
>2.5 - Severe Lung Injury
Murray 1983

15. ARDS - Clinical suspicion
A disease known to cause ARDS
Tachypnoea
Hypoxia SpO2
CXR - bilateral infiltrates
Shift patient to ICU for monitoring
Early intubation (before the pt gets tired or collapses)

16. ARDS - VILI
Ventilator Induced Lung Injury (VILI) has become a major concern in Mechanical Ventilation in ARDS
Causes
- End inspiratory overdistension (volutrauma)
- Insufficient alveolar recruitment
- Frank derecruitment at end expiration (atelectrauma) – Ventilator induced release of proinflammatory mediators inducing systemic damage to end organs (Biotrauma)

20. ARDS - Ventilatory Strategy
To improve outcome & limit VILI
- reduce Tidal Volume
- keep Pplat below 30-35cmH2O
-sufficient PEEP
International Consensus Conference
1999.

21. Ventilatory Strategy Goals TV – 6 ml/Kg ideal body weight
Pplat - < 30 cm H2O (the mean Pplat of the non beneficial trials was 32)
pH – 7.45

22. ARDS Network Low VT Trial
Patients with ALI/ARDS (NAECC definitions) of < 36 hours
Ventilator procedures
Volume-assist-control mode
RCT of 6 vs. 12 ml/kg of predicted body weight PBW Tidal Volume
(PBW/Measured body weight = 0.83)
Plateau pressure  30 vs.  50 cmH2O
Ventilator rate setting 6-35 (breaths/min) to achieve a pH goal
of 7.3 to 7.45
I/E ratio:1.1 to 1.3
Oxygenation goal: PaO mmHg/SpO %
Allowable combination of FiO2 and PEEP:
FiO
PEEP
The trial was stopped early after the fourth interim analysis (n = 861
for efficacy; p = for the difference in mortality between groups)
ARDS Network. N Engl J Med

23. ARDSnet Ventilatory Strategy
First Stage
Calculate predicted body weight x(height in cm-152.4)+50/45.5
Set Mode - VC/AC
Set initial TV to 8 ml/Kg PBW
Add PEEP of 5-7 cm H2O
Reduce TV by 1 ml/kg every 2 hours until TV = 6 ml/Kg PBW

24. ARDSnet Ventilatory Strategy
Second Stage
When TV 6 ml/kg measure inspiratory plateau pressure with 0.5s pause
Target Pplat < 30 cm H2O
Measure Pplat 4hourly & after every change in PEEP or TV
If Pplat > 30 reduce TV 1 ml/kg until Pplat < 30 or TV 4ml/kg
Pplat < 25 & TV < 6ml/Kg increase TV

25. ARDSnet Ventilatory Strategy
Third Stage
Monitor ABG for respiratory acidosis
Target pH = 7.3 – 7.45
If pH 7.15 – 7.30 increase RR until pH > 7.30 or RR > 35/min
If pH < 7.15 increase RR to 35
If pH still < 7.15 increase TV at 1 ml/kg increments till pH > 7.15
Do not increase RR if PCO2 < 25
If pH < 7.30 & RR 35/min consider Bicarb inf
pH > 7.45 & patient not triggering decrease RR (> 6/min)

26. ARDSnet Ventilatory Strategy
Oxygenation goal: PaO mmHg/ SpO %
FiO2 <70%
Allowable combination of FiO2 and PEEP:
FiO
PEEP
FiO
PEEP

28. Low Tidal Volume RCTs Amato 1998 6.0-12.0 ml
ARDS Network ml
Brochard ml
Brower ml
Stewart ml
Villar (5-8)-(9-11) ml

30. Monitoring
Stress Index – (<0.9 tidal recruitment >1 tidal hyperinflation Ranieri Anaesthiology 2000
CT – Analysis of pulmonary CT images during mechanical ventilation

35. Tidal Hyperinflation during low TV in ARDS. Terragni,2007
The lung-protective strategy might not be protective for all patients with ALI
Patients with large amounts of collapsed lung might be exposed to VILI despite TV & Pplat limitations

38. Pplat at Low TV Hager 2005

39. Summary
Ventilation with lower tidal volume (6 ml/Kg PBW) in unselected cases of ARDS can be very effective for short-term lung recovery.
Ventilation with higher tidal volume and higher plateau pressure is associated with increased risk of death.
Lower the Pplat, better the outcome.

40. Summary
The belief that an intermediate VT of 8–10 mL/kg in conjunction with a Pplat 32 cm H2O is relatively safe is not supported by credible evidence.
We still do not know what level of Pplat is safe.

41. Summary
Further data are required to assess long-term health-related quality of life, long-term cognitive outcomes and cost.
The best ventilatory strategy should be ideally adapted to the size of aerated lung.
Individual titration of ventilation is crucial.

42. Prognosis Hypoxemia is the most relevant prognostic variable
Median duration of mechanical ventilation in survivors:
Mild – 5 days
Moderate – 7 days
Severe – 9 days

43. ARDS - Management Haemodynamic - Vasopressors Treat Inciting cause
Prevent & treat coexisting other Organ Failure
Nutrition
Prevent Thromboembolism & GI bleed
Manage Infections - VAP-30-50%
Steroids - Late stage ARDS

44. PEEP
The optimal level of PEEP & best method used to set PEEP have not been definitively established

45. Steroids in ARDS Meduri. Am J Respir Crit Care Med(165). 983–991, 2002
58 patients in the methylprednisolone group and 30 from patients in the placebo group.
Corticoid treatment at moderate doses was administered late (9+3 d) in the course of ARDS to patients failing to improve.
A loading dose of 2 mg/kg was followed by 2 mg/kg/day from Day 1 to 14, 1 mg/kg/day from Day 15 to 21, 0.5 mg/kg/day from Day 22 to 28, 0.25 mg/kg/day on Days 29 & 30, and mg/kg/day on Days 31 & 32.

46. Steroids in ARDS ARDSnet, N Engl J Med 2006;
A single dose of 2 mg of methylprednisolone/kg of PBW was followed by a dose of 0.5 mg/Kg PBW every 6 hours for 14 days, a dose of 0.5 mg/kg PBW every 12 hours for 7 days, & then tapering of the dose.
Conclusions These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death.

47. Methylprednisolone Infusion in Early Severe ARDS Meduri. CHEST 2007;
Adult intubated patients receiving mechanical ventilation were eligible if, within 72 h of study entry, they met diagnostic criteria for ARDS by the American-European Consensus definition while receiving PEEP.

48. Methylprednisolone Infusion in Early Severe ARDS Meduri. CHEST 2007;
Methylprednisolone or normal saline solution placebo was mixed in 240 mL of normal saline solution and administered daily as an infusion at 10 mL/h and changed to a single oral dose when enteral intake was restored.
A loading dose of 1 mg/kg was followed by an infusion of 1 mg/kg/d from day 1 to day 14,
0.5 mg/kg/d from day 15 to day 21,
0.25 mg/kg/d from day 22 to day 25,
0.125 mg/kg/d from day 26 to day 28.

49. Methylprednisolone Infusion in Early Severe ARDS Meduri. CHEST 2007;
If the patient was extubated between days 1 and 14, the patient was advanced to day 15 of drug therapy and tapered according to schedule.
Diagnostic fiberoptic bronchoscopy with bilateral BAL was performed prior to study entry, and then every 5 to 7 days

50. Methylprednisolone Infusion in Early Severe ARDS Meduri. CHEST 2007;
If the patient failed to improve LIS between study days 7 and 9, the patient left the treatment arm of the study to receive unblinded methylprednisolone therapy (2 mg/kg/d) for unresolving ARDS following a previously reported protocol

51. Recruitment in ARDS Indications – PO2 < 60 with FiO2 > 60
Maneuver – PC 45 + PEEP 15 for 2 min
Other maneuvers – CPAP 40 for 40 sec, Intermittent PEEP for 2 breaths, sighs/min (PC inflations at cm H2O
-Decremental PEEP
In ARDS, the percentage of potentially recruitable lung is extremely variable and is strongly associated with the response to PEEP Gattinino et al,NEJM,2006

52. Recommendations in Practice
Principle of precaution
Limited VT 6 mL/kg PBW to avoid alveolar distension
End-inspiratory plateau pressure < cm H2O
Adequate end-expiratory lung volumes utilizing PEEP and higher mean airway pressures to minimize atelectrauma and improve oxygenation
Consider recruitment maneuvers
Avoid oxygen toxicity: FiO2 < 0.7 whenever possible
Monitor hemodynamics, mechanics, and gas exchange
Address deficits of intravascular volume
Prioritize patient comfort and safety

53. Prone Positioning Improves oxygenation & decreases incidence of VAP
Might be considered for patients with refractory hypoxemia in ARDS

54. Prone ventilation reduces mortality in patients with acute respiratory failure and severe hypoxemia: systematic review and meta-analysis Intensive Care Med (2010)
Prone ventilation reduces mortality in patients with severe hypoxemia.
Given associated risks, this approach should not be routine in all patients with AHRF, but may be considered for severely hypoxemic patients.

55. Intensive Care Med (2010)
Prone ventilation reduced mortality in patients with PaO2/FiO2<100 mmHg; but not in patients with PaO2/FiO2 >100 mmHg.
Prone ventilation improved oxygenation by 27–39% over the first 3 days of therapy but increased the risks of pressure ulcers, endotracheal tube obstruction, and chest tube dislodgement.

56. NMBA in ARDS Papazian et al. N Engl J Med Sept 16, 2010
Cis-atracurium infusion for first 48 hours if P/F < 120.
The mortality rate was about 41% in the patients randomized to placebo vs about 32% or 31% in the patients randomized to the active intervention.
The absolute risk reduction was about 10%. A number needed to treat of only 10

57. NIV
PaO2/FiO2 ratio of 146 or less after one hour of NIV was an independent risk factor for intubation (odds ratio 2.51)
Antonelli et al. Intensive Care Med 2001
Mean PaO2/FiO2 in the NIV success group was 147 and 112 in the failure group
Rana et al. Crit Care 2006
NIV should be avoided in patients with shock, severe hypoxemia or acidosis.

58. NIV
APACHE II score of more than 17 and a respiratory rate of more than 25/min after 1 h of NIV predicts the need for endotracheal intubation in ALI patients treated with NIV Yoshida Y et al.J Anaes, 2008.
Patients should be closely monitored in an intensive care unit setting and, if there is no improvement in oxygenation (PaO2/FiO2 into the range of 150), pH or vital signs within the first 1 to 2 hours, intubated.
Erik Garpestad and Nicholas S HillCritical Care 2006,

59. Antonelli M et al, A multiple-center survey on the use in clinical practice of noninvasive ventilation as a first line intervention for acute respiratory distress syndrome Crit Care Med 2007
Antonelli’s study found that patients who ultimately ended-up intubated had PaO2/FiO2 ratio less than 175 mm Hg after 1 hour of NIV.
The hospital mortality rate of those patients was quite high : something like 50%.
Most of those patients were intubated within 8 to 12 hours for hypoxemia and dyspnea.
Should have a shorter cut-off time for NIV in those patients whose oxygenation doesn’t improve very quickly.

60. ALI/ARDS
Antonelli’s study of NIV in hypoxemic respiratory failure excluded patients in shock or with 2-organ failure,
People who did okay with NIV had a low mortality rate, but those who failed NIV had a higher mortality rate.

61. ALI/ARDS Antonelli, the cut-off was after 1 to 2 hours,
Check blood gases after 1 or 2 hours and the PaO2/FiO2 ratio does not improve to over 175 mm Hg, NIV failure is very likely.
Experienced centers may be able to treat sicker patients successfully with NIV than those with less experience.

62. Outcome-NIV in ARDS Number – 38 cases Success – 22 (57.8%)
Failure (42.2%)
Intubated – 13
Delay in intub. – 3
DNI – 2
Death – 10
Survival after intubation - 5
Duration(success) –
Median – 3 days
(IQR1-2, IQR3-6)
Duration(failure) –
Median 19.5 hrs
(IQR1-9, IQR3-72)
Wean – 2
H1N1 – 4(2death)

63. High Frequency Oscillatory Ventilation
May be an effective rescue therapy for severe adult ARDS patients Mehta et al Chest 2004

64. H1N1/ARDS
Patients should be managed with a low VT (target VT, 6 mL/kg), open-lung strategy of ventilation, with PEEP titrated based on FiO2 for goal PPLAT 30 to 35 cm H2O and SpO2 88% to 90% per the ARDS Network protocol.
PEEP levels higher than usually used may be necessary

65. H1N1 ARDS
Given the high failure rate and the duration of ventilatory support often required in patients with H1N1-related respiratory failure, routine use of NIV should be avoided.

66. H1N1 /ARDS
Alternative modes of ventilation, such as APRV and HFOV, were used in small numbers of patients with no obvious adverse effects. These modes, if available, may be considered in the setting of persistent hypoxemia (SpO2 88–90%, with high PEEP and FiO2 0.8) or when the goals of lung-protective ventilation cannot be met (PPLAT 30–35; VT 8 mL/kg), particularly in the setting of progressive patient decline.

67. H1N1 /ARDS
Rescue therapies such as Recruitment Man., neuromuscular blockade, and prone ventilation can be considered if oxygenation goals cannot be met (SpO2 88–90%, with
high PEEP and FiO2 0.8) with the aforementioned ventilatory strategy, particularly in the setting of progressive patient decline.

68. Extracorporeal Support
Considered only in patients with severe hypoxemia & hypercapnia which was unresponsive to optimal management

69. Inhaled Nitric Oxide
Cannot be recommended for routine treatment of ARDS but may be useful as rescue therapy in patients with refractory hypoxemia

70. Conservative Fluid Management FACTT Study, NEJM, 2006
Early goal-directed therapy with intravenous fluids and medications for patients with septic shock improves mortality and acidosis but may not improve the overall length of hospital stay or duration of mechanical ventilation.
The current study demonstrates that liberal and conservative fluid management strategies yield similar 60-day mortality rates among patients with acute lung injury, although conservative fluid management was associated with improved oxygenation, number of ventilator-free days, and central nervous system function

71. PA & CV in ARDS FACTT Study, NEJM, 2006
Conclusions PAC-guided therapy did not improve survival or organ function but was associated with more complications than CVC-guided therapy. These results, when considered with those of previous studies, suggest that the PAC should not be routinely used for the management of acute lung injury.

72. Red Blood Cell Transfusions and the Risk of Acute Respiratory Distress Syndrome Among the Critically Ill: A Cohort Study
pRBC use independently correlates with the development of ARDS in ICU patients at risk for this process. The link between transfusion administration follows a dose-response relationship, suggesting that exposure to any pRBC transfusion volume increases the probability for the onset of this severe complication. We urge clinicians to consider this information as they weigh the risks and benefits of transfusion in individual patients and to acknowledge that the burden of proof is shifting to suggest that transfusion avoidance may be the safer paradigm.
Crit Care.  2007;11(3) 

73. Prediction of Death and Prolonged Mechanical Ventilation in Acute Lung Injury
The presence of persistent shock, renal failure, age, immunosuppression, underlying cause of ALI, severity of illness were previously identified as important nonpulmonary outcome determinants
Overall nonpulmonary organ failures (creatinine, platelet count, bilirubin, and Glasgow Coma Scale score) did not contribute to the discriminative power of our model

74. Prediction of Death and Prolonged Mechanical Ventilation in Acute Lung Injury
In the ARDS-net low tidal volume study,
Age,
APACHE II score,
Plateau pressure,
The number of organ failures (using the Brussels Organ Failure Classification),
Number of hospital days before enrollment,
Arterial-alveolar oxygen gradient
were found to be independent prognostic factors, and were used in the mortality adjustments reported in the recent ARDS-net study

75. Prediction of Death and Prolonged Mechanical Ventilation in Acute Lung Injury: Second International Study of Mechanical Ventilation and ARDS-net Investigators
A majority of patients with ALI are at risk for death or prolonged mechanical ventilation. A model derived from
age,
oxygenation index,
cardiovascular failure
three days after intubation predicts death or prolonged mechanical ventilation and may inform decisions regarding specific interventions such as tracheostomy, particularly in terms of clinical trial design.
Crit Care.  2007;11(3) ©2007 

76. Mortality & Cost Canadian Critical Care Trials Group
75% of the costs associated with adult respiratory distress syndrome (ARDS) are due to the initial hospitalization. The bulk of the remaining healthcare costs are from hospital readmissions and inpatient rehabilitation
Overall, two-year mortality was 49%. Forty percent died before discharge during the initial hospitalization. However, of those surviving to discharge, 85% were surviving at two years.
Am J Respir Crit Care Med 2006;174:

77. The ALIEN study Intensive Care Med (2011)
The overall ICU and hospital mortality rates (42.7 and 47.8%, respectively)
The incidence and mortality of ARDS have not changed in Europe 10 years after the original ARDSnet study.
Recent systematic review of 53 observational studies by Phua et al. in which they found that the pooled mortality for ARDS from 1994 to 2006 was 44%. Am J Respir Crit Care Med 2009

78. Prospective cohort study
Lung-Protective Ventilation Yields Improved Survival in Acute Lung Injury BMJ. March 27, 2012.
Prospective cohort study
tidal volume equal to or less than 6.5 mL/kg of predicted body weight,
plateau pressure equal to or less than 30 cm of water,
Of the 485 patients included in the study, 311 (64%) died within 2 years.
For each 1 mL/kg predicted body weight increase in average tidal volume, there was an associated 18% increase in risk for death during the subsequent 2 years.

79. the authors, estimated absolute risk reduction in mortality for a typical patient with 50% adherence to lung-protective ventilation was 4.0% (95% CI, 0.8% - 7.2%; P = .012).
With full, 100% adherence, risks were reduced even further, by 7.8% (95% CI, 1.6% %; P = .011).

80. Quality of Life Canadian Critical Care Trials Group
Survivors of ARDS gradually adapt and return to work by two years.
65% were able to return to work, although nearly all of the cohort had significant exercise limitations which did not improve during the two years of follow-up.
Quality of life was significantly and persistently lower than before initial hospitalization
Am J Respir Crit Care Med 2006;174:

81. Functional Disability 5 Years after ARDS, Canadian Critical Care Trials Group N Engl J Med 2011
The median 6-minute walk distance was 436 m (76% of predicted distance)
Younger patients had a greater rate of recovery than older patients, but neither group returned to normal predicted levels of physical function at 5 years.
A constellation of other physical and psychological problems developed or persisted in patients and family caregivers for up to 5 years.

82. The EDEN Randomized Trial ARDSnet, JAMA. 2012;
This large study is relatively definitive in showing that for patients with ALI, a delay in initiating enteral nutritional support for up to 6 days does not result in worse outcomes.
In fact, it suggests that there may be benefits in terms of gastrointestinal symptoms.

83. ARDS – Causes-2010 Sepsis - 209(112)*AMI - 2(1)
Malaria (51) *Post-PPI-1(1)
Fat Emb (3) *Leptosp- 1
Post-CABG - 3(2) *En/My/Ra-1(1)
Pnuemonia – 9(5) *Trauma -2
Peurp/Ecla. – *Drowning-1(1)
Post-op (2) Tetanus – 1(1)
TRALI (1) Aspiration-1(1)
Mortality 178/338(52.6%)
Withdrawal - 10

84. ARDS - Conclusion ARDS is a Multisystem Disease in most cases
Management is Essentially Supportive
Outcome depends on
-Underlying Disease
-Severity of ARDS
-Other Organ Dysfunction