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Open lung ventilation fails to reduce ventilator-free days in ARDS
New data from the PHARLAP trial indicated that a maximal lung recruitment strategy, compared with conventional mechanical ventilation, had no effect on the number of ventilator-free days or mortality in patients with acute respiratory distress syndrome.
Investigators designed the multicenter, phase 2, randomized, controlled trial to compare the PHARLAP strategy — an open lung procedure with maximal lung recruitment — with a control protective ventilation group. The study included patients in the ICU who were mechanically ventilated for less than 72 hours and had a diagnosis of moderate to severe ARDS. The primary outcome was the number of ventilator-free days at 28 days after ventilation.
Researchers planned to enroll 340 patients with moderate to severe ARDS, but the trial was stopped in 2017 due to safety concerns and potential loss of equipoise after publication of the Alveolar Recruitment Trials.
The study comprised 115 patients randomly assigned the PHARLAP strategy (n = 58) or the control intervention (n = 57).
At 28 days, the number of ventilator-free days did not differ significantly with PHARLAP, compared with the control intervention (median, 16 vs. 14.5 days). The same was true for mortality, rate of barotrauma, rate of pneumothorax requiring chest drain and length of stay.
Additionally, results revealed no significant differences between the PHARLAP and control groups in time to first unassisted breathing trial (median, 7 vs. 7 days) or in the rate of tracheostomy (28.1% vs. 30.4%).
The researchers did note that the PHARLAP strategy, compared with the control intervention, reduced driving pressure on day 1, improved oxygenation from days 1 to 5 and decreased the use of new adjuvant therapies for hypoxemia, including inhaled nitric oxide, extracorporeal membrane oxygenation and prone positioning (median change from baseline, 0 vs. 1; P = .004); however, the rates of cardiac arrhythmia were increased with the PHARLAP strategy vs. the control intervention (29% vs. 13%; P = .03).
Patients reported 34 serious adverse events, with 56% occurring in the control group. In the PHARLAP group, none were considered to be associated with the intervention.
“An open lung mechanical ventilation strategy (PHARLAP) including maximal [recruitment maneuvers] and PEEP titration compared with conventional protective lung ventilation did not change ventilator-free days, mortality, length of stay, or rate of barotrauma in patients with moderate to severe ARDS,” the researchers wrote. “However, the power of the study was limited by lower than expected recruitment rates, early termination of the trial and treatment cross-overs. Responders with improved outcomes to the open lung intervention were identified with improved static lung compliance in the first 48 hours from randomization, however there remains no evidence for the routine use of maximal [recruitment maneuvers] in patients with moderate to severe ARDS.”
The PHARLAP strategy included pressure control mode, tidal volume of 4 mL/kg to 6 mL/kg and plateau airway pressures of 28 centimeters of water (cmH20). Patients also underwent daily recruitment maneuvers with positive end-expiratory pressure titration, which was a combined open lung procedure, for up to the first 5 days. The control intervention consisted of ventilation according to the ARDS Network’s low tidal-volume/low PEEP ventilation protocol, including volume control mode, tidal volumes of 6 mL/kg, plateau airway pressures of 30 cmH20 and the low PEEP strategy. – by Melissa Foster
Disclosures: The PHARLAP trial was funded by the National Health and Medical Research council of Australia, the Health Research Council of New Zealand, Alfred Health Foundation, the Health Research Board of Ireland and the Australian and New Zealand College of Anaesthetists. One author reports support from a Heart Foundation Future Fellowship. Another author reports support from a Health Research Board Clinical Trial Network Award. A third author reports support from an NHMRC Level II Practitioner Fellowship.