A Randomized Controlled Trial of Naloxone for Optimization of Hypoxemia in Lung Donors after Brain Death.
Dhar R, Stahlschmidt E, et al.Transplantation, 2018; [record in progress].
Aims
To evaluate whether naloxone is able to improve oxygenation in brain dead (BD) lung donors with hypoxemia.
Interventions
Eligible donors were randomized to naloxone (8 mg IV) or saline placebo as soon as possible after the initial arterial blood gas (ABG). ABGs were collected as per standard Organ Procurement Organizations practices (approx. every 6-8 hours) with a final ABG collected prior to organ procurement.
Participants
199 lung-eligible BD donors were randomized (naloxone, n=98; placebo, n=101). Eligible patients were age 13-70 years without established lung disease who had hypoxemia, defined as PaO2:FiO2 ratio (PFR) <300 on arterial blood gas (ABG) performed after BD declaration.
Outcomes
The primary outcome was change in PFR from baseline to final ABG. The secondary efficacy outcome was proportion of donors enrolled who had lungs transplanted. Primary analyses were performed using intention-to-treat principles. Outcomes were also evaluated in a per protocol analysis.
Follow-up
Median total time from BD to procurement was 41 hours (IQR 32-47).
CET Conclusions
This muticentre, placebo-controlled study investigated the use of IV naloxone in brain-dead organ donors as a strategy to reduce neurogenic pulmonary oedema. The study demonstrated no difference in the primary outcome of improvement in PaO2:FiO2 ratio, and no difference in transplant rates from the donors recruited. The study is well designed, and it appears that there is no benefit to this intervention in this subset of donors with all-cause hypoxemia. Interestingly, reversal of hypoxemia through other donor management protocols was significantly associated with increased chance of transplant, highlighting the importance of interventions to improve this in donors. It should also be noted that no transplant outcomes were assessed: it is important that in any donor intervention the transplant rates and outcomes of all transplanted organs from the donors are documented, as what is good for one organ may be detrimental to the outcomes of another.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT02581111