COMMENTARY

A Negative APRV Trial in ARDS

Aaron B. Holley, MD

Disclosures

June 29, 2018

Recently, I reviewed a randomized, controlled trial (RCT)[1] comparing acute respiratory distress syndrome (ARDS) management with protocolized airway pressure release ventilation (APRV) with low-tidal-volume (LTV) ventilation. APRV showed superiority for the primary outcome, ventilator-free days, and a number of secondary outcomes. Mortality in the intensive care unit and hospital days were not significantly different, but both showed trends toward improvement with APRV. I saw this trial, in conjunction with previously published physiologic data, as a major step forward in supporting APRV for ARDS outside the setting of "rescue therapy."

An RCT published online recently found that APRV dramatically increased mortality in children with ARDS when compared with LTV.[2] The study was stopped early, after only 52 children were enrolled, because of the mortality difference (53.8% versus 26.9% among controls; relative risk, 3.2 [1.0-10.1]; P = .089).

This prompted two pediatricians to write an editorial.[3] While they conclude their piece by advising caution before using APRV in children, they use data applicable to adults to help make their case.

So, should the pediatric RCT or the accompanying editorial influence our opinion of APRV for ARDS in adults?

Looking closely at the pediatric RCT, it seems the groups were unbalanced at baseline. Patients randomized to APRV had a significantly lower PaO2:FiO2 and higher oxygenation index, suggesting they had worse disease at enrollment. The authors of the editorial suggest that this imbalance is not enough to account for the large 28-day mortality difference—ergo, it must be due to APRV.

I have two issues with this logic:

  1. It seems even less likely that APRV could generate such a large increase in mortality; and

  2. The authors of the editorial criticize the positive APRV adult trial[1] for having similar imbalances at baseline (in this case, the APRV group had a lower burden of comorbid disease and less pressor use).

So how do we reconcile the disparate results between these two RCTs?

The APRV titration strategies were slightly different, there were some imbalances at baseline, and one enrolled adults and the other enrolled children. More important, though, they were both small, single-center studies. The most likely reason for the discrepant results is type I error. In fact, this should be expected given the sample sizes. When it comes to biologic plausibility, I do not believe APRV, when compared with LTV, could dramatically increase ventilator-free days or double mortality at the 28-day mark.

We will keep waiting for that large RCT we all want. Until then, I would recommend sticking with LTV. If you have experienced physicians and respiratory therapists, APRV could be considered a first-line treatment for ARDS. If you are a physician, do not consider yourself "experienced" unless you are using APRV on a regular basis and understand the physiology outlined in the review by Habashi.[4]

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