Prone Positioning in Severe Acute Respiratory

Distress Syndrome

Dr Nitish GuptaModerator: Lt Col Nikahat

Jahan

Claude Guerin, et al (for the PROSEVA Study Group)Published in the NEJM on May 20, 2013

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

INCLUSION CRITERIA1. ARDS (as defined by the American-European

Consensus Conference criteria)

2. Endotracheal intubation and mechanical ventilation for ARDS, <36 hours

3. Severe ARDS (as defined by the authors)

Pao2:Fio2 < 150mmHg

Fio2 ≥ 0.6

PEEP ≥ 5 cm of water

Tidal volume ≈ 6 ml per Kg

(confirmed after 12-24hrs of ventilation in the ICUs)

Non-inclusion criteria1. 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 i. Pregnant women j. Single anterior chest tube with air leaks

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

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

TRIAL DESIGN

1. 26 ICUs in France and 1 in Spain, which have used prone positioning in daily practice for more than 5 years.

2. Randomization computer-generated and stratified according to ICU.

3. Written informed consent was obtained

4. Data collectors were aware of the study-group assignments, but outcomes assessors were not.

PROTOCOL

No dropouts after initial assessment

1. After a patient was determined to be eligible, a stabilization period of 12 to 24 hours was mandated.

1. 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.

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.

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

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 )

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….

Complications leading to the immediate interruption of prone treatment included :

• nonscheduled extubation

• main-stem bronchus intubation

• endotracheal-tube obstruction

• hemoptysis

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

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

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 every day up to day 28, after which it was used at the clinician’s discretion.

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,

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

The time at which the first prone session was started.

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

– Ventilator settings, Ppeak, static compliance of the respiratory system

– Results of measurements of arterial blood gases

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

The tracheotomy rate

The number of days free from organ dysfunction

Ventilator settings

Measurements of ABG,

respiratory-system mechanics during the first week after randomization

• Successful extubation

• In patients who had undergone a tracheotomy

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

STATISTICAL ANALYSIS

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.

RESULTS

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 patient-hours spent in the ICU from the start of the first session to the end of the last session.

COMPLICATIONS

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, Guerin C, Mancebo J. Prone posi- tioning improves survival in severe ARDS: a pathophysiologic review and individual patient meta-analysis.

Minerva Anestesiol 2010;76:448-54. ) to show a survival benefit with prone positioning.

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

• 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, Guerin C, Mancebo J. Prone posi- tioning 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.

LIMITATIONS1. 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 the results

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

Conclusions Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival

(N Engl J Med 2001;345:568-73.)

In ARDS patients in supine position, alveolar ventilation is shifted preferentially to the non- dependent part of the lung. Dependent lung regions continuously collapse and inflate during mechanical ventilation. While in the prone position, ventilation is probably more homogeneous and dorsally distributed, and perfusion is probably more homogeneous and not dependent on gravity.

In Prone Ventilation, One Good Turn Deserves Another

Guy W. Soo Hoo, M.D., M.P.H.

EDITORIAL

Compelling enough to change practice patterns?

Prone ventilation is a conceptually simple intervention but can seem technically

challenging

Nevertheless,

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

THANK YOU