Use of Airway Pressure Release Ventilation in Patients With Acute Respiratory Failure Due to COVID-19: Results of a Single-Center Randomized Controlled Trial*

Abstract

OBJECTIVES: Airway pressure release ventilation is a ventilatory mode characterized by a mandatory inverse inspiratory:expiratory ratio with a very short expiratory phase, aimed to avoid derecruitment and allow spontaneous breathing. Recent basic and clinical evidence suggests that this mode could be associated with improved outcomes in patients with acute respiratory distress syndrome. The aim of this study was to compare the outcomes between airway pressure release ventilation and traditional ventilation targeting low tidal volume, in patients with severe coronavirus disease 2019. DESIGN: Single-center randomized controlled trial. SETTING: ICU of a Mexican referral center dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019. PATIENTS: Ninety adult intubated patients with acute respiratory distress syndrome associated with severe coronavirus disease 2019. INTERVENTIONS: Within 48 hours after intubation, patients were randomized to either receive ventilatory management with airway pressure release ventilation or continue low tidal volume ventilation. MEASUREMENTS AND MAIN RESULTS: Forty-five patients in airway pressure release ventilation group and 45 in the low tidal volume group were included. Ventilator-free days were 3.7 (0–15) and 5.2 (0–19) in the airway pressure release ventilation and low tidal volume groups, respectively ( p = 0.28). During the first 7 days, patients in airway pressure release ventilation had a higher Pa o 2 /F io 2 (mean difference, 26 [95%CI, 13–38]; p < 0.001) and static compliance (mean difference, 3.7 mL/cm H 2 O [95% CI, 0.2–7.2]; p = 0.03), higher mean airway pressure (mean difference, 3.1 cm H 2 O [95% CI, 2.1–4.1]; p < 0.001), and higher tidal volume (mean difference, 0.76 mL/kg/predicted body weight [95% CI, 0.5–1.0]; p < 0.001). More patients in airway pressure release ventilation had transient severe hypercapnia, defined as an elevation of P co 2 at greater than or equal to 55 along with a pH less than 7.15 (42% vs 15%; p = 0.009); other outcomes were similar. Overall mortality was 69%, with no difference between the groups (78% in airway pressure release ventilation vs 60% in low tidal volume; p = 0.07). CONCLUSIONS: In conclusion, when compared with low tidal volume, airway pressure release ventilation was not associated with more ventilator-free days or improvement in other relevant outcomes in patients with severe coronavirus disease 2019.

The authors reply

“…However, many of the current studies, including ours, present specific details on how APRV is being applied and as such do contain information that so far highlight its challenges. We share the interpretation of Ghosh et al ( 1 ) and suggest that readers do not deem our study ( 2 ) as negative; we prefer to consider our results as a step forward in order to increase the awareness of APRV characteristics and pitfalls. As far as we are concerned, the door is still wide open for further research.…”

“…As found in a recent secondary analysis of multicenter randomized controlled trials (RCTs) of critically ill adults published in high-impact journals ( 3 ), we are aware that an overly optimistic assumption of unrealistic treatment effects at calculation of sample size is one of the main reasons for biased results toward the null (type II error). However, as described in the methods of our study ( 2 ), we calculated the sample size with an expected difference of 4 days in ventilator-free days (VFDs), considering a mean of 14 VFD according to the experience in our center; this yields an a priori minimal clinically important difference of 28.5%, which is not far from the 25% reported in the Prospective, Randomized, Multi-Center Trial of 12 mL/kg vs. 6 mL/kg Tidal Volume Positive Pressure Ventilation for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome, and is even more realistic than the results observed in the largest RCT of APRV, which reported a significant difference in VFD of 19 and 2 days in APRV and control groups, respectively (an 89% increase in VFD with APRV) ( 4 ). More importantly, questioning the calculation of sample size in our study ( 2 ) is a moot point, as the sample size was not reached.…”

“…We thank Ghosh et al ( 1 ) for their interest in our study ( 2 ), addressing the use of airway pressure release ventilation (APRV) in patients with COVID-19.…”

Airway Pressure Release Ventilation in Acute Respiratory Failure Due to COVID-19: When One Door Closes

“…We read with great interest the article by Ibarra-Estrada et al ( 1 ) published in a recent issue of Critical Care Medicine on a randomized controlled trial using airway pressure release ventilation in acute respiratory failure due to coronavirus disease 2019 (COVID-19). While the authors present many important results, we would like to emphasize several statistical issues that should be taken under consideration when interpreting the findings of this clinical trial.…”

A Ventilator Mode Cannot Set Itself, Nor Can It Be Solely Responsible for Outcomes*

“…The Ibarra-Estrada et al (1) method for initial APRV settings were: P High set at the plateau pressure measured during an inspiratory pause in VCV (maximum 30 cm H 2 O); P Low set to 0 cm H 2 O; T High 4–6 seconds; and T Low 0.4–0.6 seconds. The methods to change these settings were to adjust T Low to E FT /E FP = 75% or 50%, with 50% used to increase Pa co 2 removal and 75% to increase oxygenation and P High adjusted to keep expiratory V t as close to 6 mL/kg as possible.…”