A randomized trial of open lung protective ventilation compared to conventional mechanical ventilation in deceased organ donors.
Ware, L. B., et al.Journal of Heart & Lung Transplantation 2025 [record in progress].
Aims
They aim to determine whether an open-lung protective ventilation (OLPV) strategy (lower tidal volume + higher positive end-expiratory pressure (PEEP) + protocolised recruitment manoeuvres) increases donor-lung utilisation for transplantation compared with conventional ventilation (CV) during the 48-h donor-management period.
Interventions
The intervention, OLPV arm had core ventilator settings of Vt 8 ml kg⁻¹ predicted body weight (PBW); PEEP 10 cm H₂O (could drop to 8 if haemodynamically required), with recruitment manoeuvres of 30-s inspiratory hold at 30 cm H₂O every 8 hours and after any disconnection/bronchoscopy. The control arm core ventilator settings of Vt 10 ml kg⁻¹ PBW; PEEP 5 cm H₂O, with recruitment manoeuvres only after circuit disconnect (extra 8-hourly allowed if severe hypoxaemia).
Participants
153 donation after brain death (DBD) donors in Northern California from july 2018 to January 2020 (aged >13 years, BMI <40, haemodynamically stable and ratio of arterial to inspired oxygen tension (PaO₂/FiO₂) 150-400 mm Hg).
Outcomes
The primary outcome was lung transplantation rate. The donor secondary outcomes included: delta PaO₂/FiO₂ to procurement, delta static compliance, radiographic assessment of lung edema (RALE) oedema score, atelectasis score, need ≥ 1 vasopressor and organ retrieval rate. The exploratory biomarkers were plasma & tumor necrosis factor receptor-1 (TNFR1), interleukin-6 (IL-6), interleukin-8 (IL-8), receptor for advanced glycation endproducts (RAGE), Syndecan-1, surfactant protein-D (SP-D) and immunoglobulin M (IgM). The recipient outcomes recorded were: primary graft dysfunction (PGD)-3 at 48/72
Follow-up
6 months
CET Conclusions
The investigators have conducted a robustly designed trial of an open-lung protective ventilation (OLPV) strategy versus conventional ventilation (CV) in a US donor cohort. They found in this cohort with moderate baseline oxygenation (many with infiltrates/smoking history) a sustained OLPV strategy did not improve lung transplant rate (23% vs 22%) or gas-exchange relative to standard CV, though it modestly reduced radiographic atelectasis There were no biomarker or early recipient outcomes differences either. The study was randomised with a multi-centre donor pool, strict protocol adherence with partial blinding, biomarker assessment and safety evaluation. Unfortunately, recruitment was terminated early with only 153 donors evaluated from a target of 400.Hhowever, this was not due to any safety signal or an interim analysis finding. The sponsor-OPO (Donor Network West) changed its routine donor-management protocols while the trial was in progress, adopting a new individualized “lung-focused resuscitation” strategy that no longer matched either of the two randomized ventilator arms, hence it was no longer possible to continue randomising donors to the prespecified open-lung-protective or conventional protocols. Their data suggest routine escalation to PEEP 10 cm H₂O and lower Vt throughout donor management does not confer additional benefit over contemporary US “standard” practice for donors with PaO₂/FiO₂ 150-400 mm Hg, while appearing safe. Donor-management guidelines may remain permissive rather than prescriptive on high-PEEP OLPV, the certainty of their outcome is limited by the reduction in power because of incomplete recruitment. Larger multi-organ procurement organisation studies, perhaps targeting donors with severe atelectasis or integrating lung ultrasound-guided PEEP titration, are needed before this could carry any weight towards changing practice.
Data analysis
Strict intention-to-treat analysis
Trial registration
EudraCT - 2018-003300-39; ClinicalTrials.gov - NCT03699254