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

Prone positioning has been used for

many years to improve oxygenation in

patients with ARDS.

Background

Prone Position As A Rescue

Therapy For Severe

Hypoxemia

By increased aeration of dorsal lung

regions, prone position improves V/Q

matching and arterial oxygenation.

Improved Oxygenation

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

Prone Position As A

Recruitment Maneuver

Prone Position:

●Recruits nonaerated lung regions.

● Provides uniform distribution of delivered VT.

● Prevents regional overinflation.

CT in supine position shows bilateral nonaerated dorsal areas

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

Prone Position As A Lung

Protective Strategy

Right Lung

Left Lung

Avoidance of Alveolar Overdistension

Prone Position

More Uniform Distribution of Aeration

Prone Position

Increased PaO2 Decreased VILI

Does Prone Position

Improve Outcome Of ARDS?

Several randomized controlled

trials failed to show survival benefit

of prone position.

Gattinoni L et al. NEJM 2001;568-573

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

Mancebo et al. AJRCCM 2006;173:1233-1239

ICU Mortality: 58% Supine vs. 43% Prone, P=0.12

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%

In contrast, several meta-analyses

have suggested that prone position

may improve survival of severely

hypoxic patients with ARDS.

Sud et al. ICM 2010; 36:585-599

RR = 0.84 (95% CI, 0.74 - 0.96) P = 0.01

Abroug et al. Critical care 2011, 15:R6

Research Question

Does early application of prone

positioning improve survival among

patients with severe ARDS?

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.

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).

● 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.

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).

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

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.

Baseline characteristics were similar

between the two study groups except for

the SOFA score and the use of

vasopressors and neuromuscular

blockers.

● 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.

The primary end point was the

28-day mortality.

● 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.

● 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.

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).

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).

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.

● 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.

The incidence of complications did not differ

significantly between the groups, except for

cardiac arrest, which was higher in the

supine group.

In patients with severe ARDS, early

application of prolonged prone position

significantly decreased 28-day and 90-

day mortality.

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).

Baseline characteristics between the groups

were different in SOFA score and the use of

vasopressors and neuromuscular blockers

which could have influenced the results.

Can We Apply The Valid,

Important Results Of PROSEVA

Trial To Our Patients?

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.

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?

Thank You