By Samuel Nadler, MD, PhD

Critical Care, Pulmonary Medicine, The Polyclinic Madison Center, Seattle; Clinical Instructor, University of Washington, Seattle

SYNOPSIS: In patients on venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome, prone positioning is safe and feasible. Prone positioning appears to improve survival but increases length of stay.

SOURCE: Giani M, Martucci G, Madotto F, et al. Prone positioning during venovenous extracorporeal membrane oxygenation in acute respiratory distress syndrome. A multicenter cohort study and propensity-matched analysis. Ann Am Thorac Soc 2021;18:495-501.

Prone positioning (PP) has shown benefits in patients with refractory hypoxemia from acute respiratory distress syndrome (ARDS).1 The EOLIA trial demonstrated extracorporeal membrane oxygenation (ECMO) can be used for patients with progressive hypoxemia or hypercarbia despite PP and other therapies for ARDS.2 The current paper is a retrospective, multicenter cohort study to assess the feasibility and efficacy of PP in patients on venovenous ECMO (VV-ECMO). The authors compared patients from four centers where PP is performed routinely on VV-ECMO patients with patients from two other centers where VV-ECMO patients remain supine. All patients underwent lung protective ventilation with driving pressures < 10 cm H2O to 12 cm H2O, respiratory rate < 20 breaths/minute, and moderate positive end-expiratory pressures (PEEP).

Of the 240 patients on VV-ECMO studied, 107 underwent PP and 133 remained supine. Patients were mostly male (65%) with an average age of 48-49 years. Pneumonia was the predominant cause of ARDS (91% to 92.5%). The partial pressure of oxygen to fraction of inspired oxygen (P/F) ratio of patients before ECMO in the PP and supine groups was 73 and 76, respectively, and each group had undergone an average of two days of mechanical ventilation before being placed on ECMO. The PP group first underwent proning on average four days from the start of ECMO. Notable differences between the two groups included a higher rate of acute kidney injury requiring dialysis in the PP group (15.9% vs. 6.8%), while the supine group had higher rates of hypertension (34.6%), immunodeficiency (22.6%), and asthma-chronic obstructive pulmonary disease (12.78%) than the PP group (20.6%, 14%, and 6.4%, respectively).

The study endpoints included evaluation of the safety of PP in ECMO patients as well as effects on gas exchange, respiratory mechanics, mortality, and length of stay. In the 107 PP patients, there were 21 reported complications, including eight desaturations, four bleeding episodes, and four decreases of ECMO blood flows, as well as one episode each of thigh swelling, face swelling, and vomiting. The most notable changes in respiratory and hemodynamic parameters with PP included improvements in P/F ratio and partial pressure of arterial oxygen (PaO2), and a decrease in pulmonary shunt fraction. Plateau pressure (Pplat), driving pressure, and PEEP were not statistically different before and after prone positioning, although tidal volumes increased 12 mL and respiratory system compliance (Crs) increased from 23 ± 14 mL to 25 ± 15 mL/cm H2O (P = 0.038). Mortality at hospital discharge decreased significantly in the PP group compared with supine patients (34% vs. 49.6%; P = 0.017). In contrast, the median duration of ECMO support and intensive care unit (ICU) length of stay (LOS) increased in patients in the PP group compared with supine patients (six days vs. nine days, respectively).

COMMENTARY

When considered in the context of other studies, this report adds to our understanding of the optimal management of patients with severe ARDS. The interpretation of this study by itself is limited by its retrospective and multicenter cohort design. As discussed by the authors, patients in the PP and supine groups were located in separate institutions. While all belonged to the Italian National Network for the Treatment of Acute Respiratory Failure, there were no strict ventilatory protocols within the trial, which raises the potential for confounding variables. The two groups differed in important parameters, as discussed earlier, including large differences in the rates of immunosuppression and active malignancy. To reduce this confounding, the authors performed a propensity-matched analysis of a smaller cohort of patients within the trial and re-demonstrated a mortality benefit of PP vs. supine position (30% vs. 53%; P = 0.024). The rates of complications were low, and the use of PP in VV-ECMO patients appears safe.

Other studies have evaluated the effect of PP on mortality and LOS in patients with severe ARDS with mixed results. One retrospective analysis of 158 patients failed to demonstrate significant differences in hospital survival or rates of ECMO weaning.3 This study had significantly higher rates of fungal and pneumocystis infection within the PP group, implying differences in immunosuppression that might confound the analysis. Early prone positioning (within 17 hours of ECMO) was associated with improved outcomes in this study, although the PP group tended to be on mechanical ventilation longer before ECMO than the supine group. Retrospective re-analysis of the randomized EOLIA trial comparing outcomes of patients on VV-ECMO who underwent PP demonstrated significantly improved 30- and 60-day survival compared to patients who remained supine (43% vs. 71%; P < 0.001; and 40% vs. 62%; P = 0.004, respectively).4 Most recently, a retrospective study of patients with SARS-CoV-2-induced ARDS showed a mortality benefit of PP vs. supine position (56% vs. 78.6%, respectively; P = 0.02).5 None of these studies reported significant changes in Pplat, driving pressures, or Crs, raising the question of how PP improves mortality. However, a growing body of retrospective evidence supports the use of PP in ARDS patients treated on VV-ECMO.

Overall, this study suggests PP may be safe for patients undergoing VV-ECMO for the treatment of ARDS. Mechanistically, the reason for improved outcomes with PP remains unclear. The apparent improvement in mortality in patients proned on VV-ECMO for ARDS must be weighed against the clear increase in ECMO resource utilization and hospital LOS that would increase strain on the healthcare system as a whole. 

REFERENCES

  1. Guérin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013;368:2159-2168.
  2. Combes A, Hajage D, Capellier G, et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. N Engl J Med 2018;378:1965-1975.
  3. Rilinger J, Zotzmann V, Bemtgen X, et al. Prone positioning in severe ARDS requiring extracorporeal membrane oxygenation. Crit Care 2020;24:397.
  4. Guervilly C, Prud’homme E, Pauly V, et al. Prone positioning and extracorporeal membrane oxygenation for severe acute respiratory distress syndrome: Time for a randomized trial? Intensive Care Med 2019;45:1040-1042.
  5. Garcia B, Cousin N, Bourel C, et al. Prone positioning under VV-ECMO in SARS-CoV-2-induced acute respiratory distress syndrome. Crit Care 2020;24:428.