PROSEVA trial - Prone position in severe ARDS. Why did prone position improve outcome of ARDS while other measures aimed at improving oxygenation such as high PEEP, RM and HFO have failed to do so?

1. ORIGINAL ARTICLE
Prone Positioning in Severe Acute
Respiratory Distress Syndrome
Claude Guérin, M.D., Ph.D., Jean Reignier, M.D., Ph.D., Jean-Christophe Richard, M.D., Ph.D., Pascal Beuret, M.D., Arnaud
Gacouin, M.D., Thierry Boulain, M.D., Emmanuelle Mercier, M.D., Michel Badet, M.D., Alain Mercat, M.D., Ph.D., Olivier Baudin ,
M.D., Marc Clavel, M.D., Delphine Chatellier, M.D., Samir Jaber, M.D., Ph.D., Sylvène Rosselli, M.D., Jordi Mancebo, M.D., Ph .D.,
Michel Sirodot, M.D., Gilles Hilbert, M.D., Ph.D., Christian Bengler, M.D., Jack Richecoeur, M.D., Marc Gainnier, M.D., Ph.D. ,
Frédérique Bayle, M.D., Gael Bourdin, M.D., Véronique Leray, M.D., Raphaele Girard, M.D., Loredana Baboi, Ph.D., and Louis
Ayzac, M.D. for the PROSEVA Study Group
N Engl J Med 2013. DOI: 10.1056/NEJMoa1214103

2. Prone positioning has been used for
many years to improve oxygenation in
patients with ARDS.
Background

4. Prone Position As A Rescue
Therapy For Severe
Hypoxemia

5. By increased aeration of dorsal lung
regions, prone position improves V/Q
matching and arterial oxygenation.

6. Improved Oxygenation
Gattinoni et al. NEJM 2001;345:568-573

7. Prone Position As A
Recruitment Maneuver

8. Prone Position:
● Recruits nonaerated lung regions.
● Provides uniform distribution of delivered VT.
● Prevents regional overinflation.

9. CT in supine position shows bilateral nonaerated dorsal areas

10. CT of the same patient shows dramatic decrease in nonaerated dorsal areas

11. Prone Position As A Lung
Protective Strategy

12. Right Lung
Left Lung
Avoidance of Alveolar Overdistension

13. Prone Position
More Uniform Distribution of Aeration

14. Prone Position
Increased PaO2 Decreased VILI

15. Does Prone Position
Improve Outcome Of ARDS?

16. Several randomized controlled
trials failed to show survival benefit
of prone position.

17. Gattinoni L et al. NEJM 2001;568-573

18. Guerine et al. JAMA. 2004;292:2379-2387

19. Mancebo et al. AJRCCM 2006;173:1233-1239
ICU Mortality: 58% Supine vs. 43% Prone, P=0.12

20. Taccone et al. JAMA 2009;302:1977-1984
P/F < 200 P/F = 100-200 P/F < 100
Mortality: 32.8% vs.31% 22.5% vs. 25.5% 46% vs. 38%

21. In contrast, several meta-analyses
have suggested that prone position
may improve survival of severely
hypoxic patients with ARDS.

22. Sud et al. ICM 2010; 36:585-599
RR = 0.84 (95% CI, 0.74 - 0.96) P = 0.01

23. Abroug et al. Critical care 2011, 15:R6

24. Research Question
Does early application of prone
positioning improve survival among
patients with severe ARDS?

25. Multicenter, prospective, randomized,
controlled trial.
Between January 1, 2008 and July 25, 2011,
patients were recruited from 26 ICUs in France
and 1 in Spain.

26. Adult patients with ARDS, as defined according to
the American-European Consensus Conference
criteria, who met the following criteria:
● Intubated and mechanically ventilated for <36 hours.
● Severe ARDS (defined by P/F ratio <150, with FiO2 ≥0.6,
and PEEP ≥5 cm of water).

27. ● Hemodynamic instability e.g. MAP< 65 mm Hg.
● ICP> 30 mm Hg or CPP< 60 mm Hg.
● Serious facial trauma or facial surgery in the last
15 days.
● Unstable spine, femur or pelvic fractures.
● Pregnancy.
● NIV for more than 24 hours.
● Underlying disease with life expectancy< 1 year.
● DVT treated for less than 2 days.

28. 466 patients with severe ARDS were
randomly assigned to undergo prone
positioning for at least 16 hours (237
patients) or to be left in the supine
position (229 patients).

29. Enrollment, Randomization, and Follow-up of the Study Participants

30. Eligible patients were included in the study after
a stabilization period of 12 to 24 hours. Patients
assigned to the prone group had to be turned to
the prone position within the first hour after
randomization and to remain in prone position
for at least 16 consecutive hours.

31. Baseline characteristics were similar
between the two study groups except for
the SOFA score and the use of
vasopressors and neuromuscular
blockers.

33. ● Volume-controlled mode.
● Tidal volume: 6 ml per kilogram of PBW.
● FIO2 and PEEP were adjusted according
to ARDS network protocol.
● Oxygenation goal: SpO2 of 88 to 95%, or
PaO2 of 55 to 80 mm Hg.

35. The primary end point was the
28-day mortality.

36. ● 90-day mortality.
● Rate of successful extubation.
● Time to successful extubation.
● Length of stay in the ICU.
● Complications.
● Number of days free from organ dysfunction.
● Ventilator settings, measurements of ABGs,
and respiratory-system mechanics during the
first week after randomization.

37. ● A total of 3449 patients with ARDS were
admitted to the participating ICUs and 474
underwent randomization.
● 8 patients were excluded.
● 466 patients were included in intention -to-
treat analysis: 229 in the supine group and
237 in the prone group.

38. The 28-day mortality was 16.0% in the
prone group and 32.8% in the supine
group (P<0.001).
The hazard ratio for death with prone
positioning was 0.39 (95% confidence interval
0.25 to 0.63).

39. Unadjusted 90-day mortality was 23.6% in
the prone group versus 41.0% in the supine
group (P<0.001), with a hazard ratio of 0.44
(95% CI, 0.29 to 0.67).

40. After adjustment for the SOFA score and
the use of neuromuscular blockers and
vasopressors, mortality remained
significantly lower in the prone group than
in the supine group.

42. ● The rate of successful extubation was
significantly higher in the prone group.
● The duration of mechanical ventilation and
length of stay in the ICU were significantly lower
in the prone group.

43. The incidence of complications did not differ
significantly between the groups, except for
cardiac arrest, which was higher in the
supine group.

45. In patients with severe ARDS, early
application of prolonged prone position
significantly decreased 28-day and 90-
day mortality.

46. Randomized (randomization was concealed).
Multicenter trial (recruiting a large number of patients from
27 ICUs).
Well defined study protocol.
Complete follow up.
Intention-to-treat analysis (all patients were analyzed in the
groups to which they were randomized).

47. Baseline characteristics between the groups
were different in SOFA score and the use of
vasopressors and neuromuscular blockers
which could have influenced the results.

48. Can We Apply The Valid,
Important Results Of PROSEVA
Trial To Our Patients?

49. Because all centers participating in the
study have used prone positioning in
daily practice for more than 5 years, the
results of PROSEVA study cannot
necessarily be generalized to centers
without such experience.

50. Why did prone positioning substantially
improve outcome of severe ARDS while
other measures used to recruit the lung
and improve oxygenation such as HFO,
high PEEP and RM failed to do so?

51. Thank You