Ventilator Management for Patients With Acute Respiratory Failure Supported With Venovenous ECMO: A Prospective, Pragmatic, Cluster-crossover Pilot Study

Rationale: The optimal ventilator management strategy for patients with acute respiratory failure (ARF) requiring venovenous extracorporeal membrane oxygenation (VV-ECMO) is unknown. Current guidelines recommend “ultra-lung protective ventilation (U-LPV)” due to a theoretical reduction in the risk of ventilator-induced lung injury. However, there is little evidence comparing U-LPV to more standard “lung protective ventilation (S-LPV)” in this population. We performed a prospective study comparing S-LPV to U-LPV in patients with ARF requiring ECMO. We hypothesized that compared to S-LPV, U-LPV would prolong time to eligibility for an ECMO weaning trial as well as time to having a weaning trial performed. Methods: We performed a single-center, open label, pragmatic cluster-crossover pilot trial comparing U-LPV to S-LPV for management of patients with ARF requiring VV-ECMO. The trial was conducted in the medical ICU at our institution which was treated as the study cluster. For 18 months, the cluster was assigned in alternating two-month blocks to either an S-LPV or an U-LPV protocol as the recommended ventilator management for patients supported with VV-ECMO. All patients supported with VV-ECMO during an intervention block were eligible. There were no exclusion criteria. All eligible patients were enrolled under a waiver of consent. The feasibility outcome was the percentage of patients whose ventilator settings were adherent to their assigned protocol >80% of the time receiving ECMO. Exploratory clinical outcomes included cumulative incidence of objective ECMO weaning trial eligibility, weaning trial performance, and ECMO decannulation at 14 days. Results: From March 1st, 2023 to July 31st, 2024, 18 patients were enrolled, 8 in the S-LPV arm and 8 in the U-LPV arm. For the feasibility outcome, 61% of patients’ ventilator settings adhered to their assigned protocol >80% of their time on ECMO. The cumulative incidence of objective weaning trial eligibility and weaning trial performance at day 14 was significantly higher in the S-LPV arm compared to the U-LPV arm [CIF (95% CI): 66.7%(23.6-89.2%) vs. 22.2% (2.4-54.4%), p = 0.02, and 66.7% (23.6-89.2%) vs. 12.5% (0.3%-36.9%), p=0.008, respectively]. A similar trend was seen in the cumulative incidence of ECMO decannulation, but the result was not statistically significant (Table 1). Conclusion: Despite only moderate protocol adherence, we observed a higher cumulative incidence of weaning trial eligibility and weaning trial performance at day 14 in patients with ARF requiring VV-ECMO with S-LPV compared to U-LPV. Sample size and methodology limit these findings. A larger trial comparing U-LPV and S-LPV in this population is warranted.

Duke Scholars

Author Christopher Ethan Cox Medicine, Pulmonary, Allergy, and Critical Care Medicine

Author Daniel Lee Gilstrap Medicine, Pulmonary, Allergy, and Critical Care Medicine

Author Elias Pratt Medicine, Pulmonary, Allergy, and Critical Care Medicine

Author Craig Rackley Medicine, Pulmonary, Allergy, and Critical Care Medicine

Author Cynthia Lea Green Biostatistics & Bioinformatics, Division of Biostatistics