According to the results of a small phase 2 trial, there was no superior benefit of an open lung mechanical ventilation strategy in patients with moderate to severe acute respiratory distress syndrome (ARDS). Findings from this study were published in the American Journal of Respiratory and Critical Care Medicine.
Researchers conducted the clinical trial, Permissive Hypercapnia Alveolar Recruitment and Low Airway Pressure (PHARLAP; ClinicalTrials.gov Identifier: NCT01667146), enrolling adult patients with moderate to severe ARDS (N=115). Patients were randomly assigned to either maximal lung recruitment, titrated positive end-expiratory pressure (PEEP), and further tidal volume (n=58) or control “protective” ventilation (n=57), with 1 patient from each group withdrawing their consent to use data.
The number of ventilator-free days (VFDs) at 28 days following randomization comprised the primary outcome. Additional outcomes included physiologic outcomes (eg, arterial partial pressure of carbon dioxide, arterial partial pressure of oxygen/fraction of inspired oxygen, PEEP, driving pressure, and plateau pressure to day 7), mortality, use of new hypoxemic adjuvant therapies, hospital length of stay, and various safety outcomes.
There was no difference at 28 days between the maximal lung recruitment and control ventilation groups with regard to the number of VFDs (median, 16 [interquartile range (IQR), 0-21] vs 14.5 [IQR, 0-21.5], respectively; P =.95), mortality (24.6% vs 26.8%, respectively; P =.79), or barotrauma rate (5.2% vs 10.7%, respectively; P =.32). The intervention was associated with a reduction in the use of new hypoxemic adjuvant agents, such as inhaled nitric oxide and extracorporeal membrane oxygenation (median change from baseline, 0 [IQR, 0-1] vs 1 [IQR, 0-1]; P =.004). The intervention group also had increased rates of new cardiac arrhythmia (29% vs 13%; P =.03).
Trial limitations included the small sample size, as well as the early termination, which may limit the interpretation of the findings.
The researchers concluded that future trials “should consider identifying individual patients or phenotypes who may benefit from an open lung approach using predictive enrichment prior to randomization.”
Hodgson CL, Cooper DJ, Arabi Y, et al; for the PHARLAP Study Investigators and the ANZICS Clinical Trials Group. Maximal recruitment open lung ventilation in acute respiratory distress syndrome (PHARLAP): a phase II, multicenter, randomized, controlled trial [published online July 29, 2019]. Am J Respir Crit Care Med. doi:10.1164/rccm.201901-0109OC