1) This study evaluated the effects of early prone positioning on outcomes in patients with severe acute respiratory distress syndrome (ARDS). 2) Patients with ARDS who required mechanical ventilation within 36 hours and had a PaO2/FiO2 ratio <150 were randomized to either remain in the supine position or be placed in the prone position for at least 16 consecutive hours. 3) The primary outcome was 28-day mortality. Mortality at 28 days was lower in the prone position group compared to the supine position group, suggesting prone positioning improves survival in severe ARDS.

1. Prone Positioning in
Severe Acute Respiratory
Distress Syndrome
Claude Guerin, et al (for the PROSEVA Study Group)
Published in the NEJM on May 20, 2013
Dr Nitish Gupta
Moderator: Lt Col Nikahat
Jahan

2. BACKGROUND
Previous trials involving patients with ARDS have
failed to prove an outcome benefit of prone
positioning during mechanical ventilatory support
This study evaluates the effect of early application
of prone positioning on outcomes in patients with
Severe ARDS

3. 1.
2.
3.
INCLUSION CRITERIA
ARDS (as defined by the American-European
Consensus Conference criteria)
Endotracheal intubation and mechanical
ventilation for ARDS, <36 hours
Severe ARDS (as defined by the authors)
Pao2:Fio2 < 150mmHg
Fio2 ≥ 0.6
PEEP ≥ 5 cm of water
Tidal volume ≈ 6 ml per Kg

4. Non-inclusion criteria
1.
Contraindication for prone positioning
a. Intracranial pressure >30 mm Hg or cerebral perfusion pressure
<60 mmHg
b. Massive hemoptysis requiring an immediate surgical or
interventional radiology procedure
c. Tracheal surgery or sternotomy during the previous 15 days
d. Serious facial trauma or facial surgery during the previous 15
days
e. Deep venous thrombosis treated for less than 2 days
f. Cardiac pacemaker inserted in the last 2 days
g. Unstable spine, femur, or pelvic fractures
h. Mean arterial pressure lower than 65 mm Hg

5. 2. Clinical context
a. Lung transplantation
b. Burns on >20 % of the body surface
c. Chronic respiratory failure requiring oxygen therapy
or NIV
d. Underlying disease with a life expectancy of <1 year
e. NIV delivered for >24 hours before inclusion

6. 3. Other non-inclusion criteria
a. End-of-life decision before inclusion
b. Inclusion in another research protocol in the
previous 30 days with mortality as the main
end-point
c. Previous inclusion in the present study
d. Prone positioning before inclusion
e. Subject deprived of freedom, minor, subject
under a legal protective measure
f. Opposition from next of kin

7. TRIAL DESIGN
1.
2.
3.
4.
26 ICUs in France and 1 in Spain, which have
used prone positioning in daily practice for
more than 5 years.
Randomization computer-generated and
stratified according to ICU.
Written informed consent was obtained
Data collectors were aware of the studygroup assignments, but outcomes assessors
were not.

8. PROTOCOL

10. No dropouts
after initial
assessment

11. 1.
1.
After a patient was determined to be
eligible, a stabilization period of 12 to 24
hours was mandated.
Patients assigned to the prone group had to
be turned within the first hour following
randomization. They were placed in prone
position for at least 16 consecutive hours.

12. 3. Mechanical ventilation was delivered:
–
In a volume-controlled mode
–
With constant inspiratory flow
–
Tidal volume ≈ 6 ml/kg
–
PEEP level selected from a PEEP–Fio2 table
4. The goal was to maintain:

Ppeak ≤ 30 cm of water, and

pH of 7.20 to 7.45.

13. 5. Measurements were performed:

In the supine group, every 6 hours

In the prone group,




Just before the patient was turned to the prone
position
After 1 hour of prone positioning
Just before the patient was turned back to the supine
position, and
4 hours after the patient was returned to the supine
position

14. 6. The criteria for stopping prone treatment
were ANY of the following:
a.
Improvement in oxygenation (defined as:

Pao2:Fio2 ratio of ≥150 mm Hg

with a PEEP of ≤10 cm of water, and

an Fio2 of ≤0.6 )

15. b. A decrease in the Pao2:Fio2 ratio of more
than 20%, relative to the ratio in the supine
position, before two consecutive prone sessions
c. Complications occurring during a prone
session, such as….

16. Complications leading to the immediate
interruption of prone treatment included :
•
nonscheduled extubation
•
main-stem bronchus intubation
•
endotracheal-tube obstruction
•
hemoptysis

17. Contd.
•
sPO2 < 85%, or a Pao2 < 55 mm Hg for more
than 5 minutes when the Fio2 was 1.0
•
cardiac arrest
•
HR < 30 bpm, for more than 1 minute
•
SBP < 60 mm Hg for more than 5 minutes

18. 8. Patients in the supine group could not be
crossed over to the prone group except as a
rescue measure in case of life-threatening
hypoxemia when all the following criteria were
met simultaneously:
•
Pao2:Fio2 < 55 mm Hg with an Fio2 of 1.0
•
maximal PEEP according to the PEEP–Fio2 table
•
Performance of respiratory recruitment
maneuvers to increase the amount of aerated
lung

19. 9. Weaning from mechanical ventilation was
conducted in the same way for both groups
10. The investigators assessed patients at least
every morning until day 28 or discharge from the
ICU
11. The prone-positioning strategy was applied

22. DATA COLLECTION
At the time of admission, they recorded:
Age, sex, the setting from which the patient was
admitted to the ICU, the context for admission
to the ICU,
Ventilator settings, time from intubation to
randomization, height, predicted body weight,

23. Contd..
The number of lung quadrants involved on chest
radiography
Arterial blood gases,
Ppeak,
arterial blood lactate levels,
the cause of ARDS,
the SOFA score

24. The following events were recorded daily until day
28:
–
Attempts at extubation
–
Administration of inhaled nitric oxide
–
Infusion of almitrine bis- mesylate
–
Use of ECMO
–
Infusion of sedatives and neuro- muscular blockers
–
Complications
–
SOFA score

25. OUTCOME MEASURES
PRIMARY END-POINT
Mortality at day 28
SECONDARY END-POINTS
Mortality at day 90
Rate of & Time to successful extubation
The length of stay in the ICU
Complications
The use of NIV

26. •
Successful extubation
•
In patients who had undergone a tracheotomy

27. STATISTICAL ANALYSIS
1. Data were compared between groups with
the use of the chi-square test or Fisher’s exact
test and analysis of variance as indicated.
2. Patient survival was analyzed with the use of
the Kaplan–Meier method

28. 3. The statistical analysis was performed with
the use of SPSS software (SPSS for Windows,
version 17.0).
4. A P value < 0.05 was considered to indicate
statistical significance.

30. RESULTS

31. Prone Positioning
–
Patients in the prone group underwent their first
prone-positioning session within 55±55 minutes
after randomization.
–
The average number of sessions was 4±4 per
patient, and the mean duration per session was
17±3 hours.
–
In the prone group, patients were ventilated in
the prone position for 73% of the 22,334 patienthours spent in the ICU from the start of the first
session to the end of the last session.

34. COMPLICATIONS

35. DISCUSSION
•
•
Survival after severe ARDS was significantly
higher in the prone group than in the supine
group.
Results are consistent with findings from
previous meta-analyses
(1. Sud S, Friedrich JO, Taccone P, et al. Prone ventilation
reduces mortality in patients with acute respiratory failure and
severe hypoxemia: systematic review and meta-analysis.
Intensive Care Med 2010; 36:585-99.
2. Gattinoni L, Carlesso E, Taccone P, Polli F, Guérin C, Mancebo
J. Prone posi- tioning improves survival in severe ARDS: a
pathophysiologic review and individual patient meta-analysis.

36. and an observational study,
(Charron C, Bouferrache K, Caille V, et al. Routine prone
positioning in patients with severe ARDS: feasibility and impact on
prognosis. Intensive Care Med 2011; 37:785-90.)
even though prior randomized trials have failed

37. •
Meta-analyses of ARDS studies
(1. Sud S, Friedrich JO, Taccone P, et al. Prone ventilation reduces mortality in
patients with acute respiratory failure and severe hypoxemia: systematic
review and meta-analysis. Intensive Care Med 2010; 36:585-99.
2. Gattinoni L, Carlesso E, Taccone P, Polli F, Guérin C, Mancebo J. Prone positioning improves survival in severe ARDS: a pathophysiologic review and
individual patient meta-analysis. Minerva Anestesiol 2010;76:448-54. )
have suggested that the outcomes with prone
positioning are better in the subgroup of
patients with severe hypoxemia.

38. LIMITATIONS
1.
Only a few ICUs complied with the request to
record the data of patients who were eligible but
not included, making it impossible to fully
appreciate the physiological condition of the
excluded patients
2. Fluid balance and the cumulative dose of
catecholamines were not assessed
3. The imbalance between the groups in baseline
SOFA score, vasopressor use, and the use of
neuromuscular blockers could also have influenced

39. CONCLUSION
This trial showed that patients with ARDS and
severe hypoxemia (as confirmed by a Pao2:Fio2
ratio of <150 mm Hg, with an Fio2 of ≥0.6 and a
PEEP of ≥5 cm of water) can benefit from prone
treatment when it is used early and in relatively
long sessions

40. (N Engl J Med
2001;345:568-73.)
Conclusions Although placing patients with acute
respiratory failure in a prone position improves their
oxygenation, it does not improve survival

42. In ARDS patients in supine position, alveolar
ventilation is shifted preferentially to the nondependent part of the lung. Dependent lung regions
continuously collapse and inflate during mechanical

43. EDITORIAL
In Prone Ventilation, One Good Turn Deserves
Another
Guy W. Soo Hoo, M.D., M.P.H.

44. Compelling enough to change practice
patterns?

45. Prone ventilation is a conceptually simple
intervention but can seem technically
challenging

46. Nevertheless,
Prone ventilation in selected patients with
severe ARDS has arrived and is ready for its turn
in the management of the disease !!

47. THANK YOU