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A Randomized Controlled Trial of Naloxone for Optimization of Hypoxemia in Lung Donors After Brain Death

Dhar, Rajat MD1; Stahlschmidt, Emily BS2; Paramesh, Anil MD3,4; Marklin, Gary MD2

doi: 10.1097/TP.0000000000002511
Original Clinical Science—General
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Background. Persistent hypoxemia is the principal reason lungs from otherwise eligible brain dead (BD) organ donors are not transplanted. Experimental models and retrospective studies have suggested that naloxone attenuates neurogenic pulmonary edema and reverses hypoxemia after brain death. We undertook a multisite, randomized, placebo-controlled trial to evaluate whether naloxone is able to improve oxygenation in BD donors with hypoxemia.

Methods. BD organ donors at 4 organ procurement organizations were randomized in a blinded manner to naloxone 8 mg or saline placebo if lung were being considered for allocation but exhibited hypoxemia (partial pressure of oxygen in arterial blood to fraction of inspired oxygen ratio [PFR] below 300 mm Hg). The primary outcome was change in PFR from baseline to final arterial blood gas. Secondary outcomes included early improvement in PFR and proportion of lungs transplanted.

Results. A total of 199 lung-eligible BD donors were randomized to naloxone (n = 98) or placebo (n = 101). Groups were comparable at baseline. Both groups exhibited similar improvements in oxygenation (median improvement in PFR of 81 with naloxone versus 80 with saline, P = 0.68), with 37 (39%) versus 38 (40%) exhibiting reversal of hypoxemia. There was no difference in the rate of lungs transplanted (19% in both groups, P = 0.97) although it was significantly higher in those with reversal of hypoxemia (32/69 versus 2/111, P < 0.001).

Conclusions. Naloxone does not improve oxygenation more than placebo in hypoxemic organ donors. However, reversal of hypoxemia was a powerful predictor of lung utilization regardless of drug therapy. Further organ procurement organization–led research is needed to assess optimal interventions to improve oxygenation in BD donors with hypoxemia.

1 Division of Neurocritical Care, Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, MO.

2 Mid-America Transplant, St. Louis, MO.

3 Department of Surgery, Tulane University School of Medicine, New Orleans, LA.

4 Louisiana Organ Procurement Agency, Covington, LA.

Received 17 July 2018. Revision received 13 September 2018.

Accepted 2 October 2018.

G.M. and E.S. are employees of Mid-America Transplant, an organ procurement organization. R.D. is a consultant for Mid-America Transplant and A.P. is a consultant for Louisiana Organ Procurement Agency. R.D. is the Chair of the Organ Donation Research Council of AOPO.

The study received administrative support from Mid-America Transplant (in the form of a part-time research coordinator) but no discrete funding. Mid-America Transplant did not have any control or influence over data collection, analysis, interpretation, or decisions over publication. The full data remains in possession of the principal investigator.

R.D. contributed to study design, performance of the research, data analysis, and writing of the article. E.S. contributed to performance of the research and data analysis. A.P. contributed to the study design, performance of the research, and writing of the article. G.M. contributed to the study design, performance of the research, and writing of the article.

This study was registered at www.clinicaltrials.gov under NCT02581111.

Correspondence: Rajat Dhar, MD, Washington University in St. Louis School of Medicine, 660 S Euclid Avenue, Campus Box 8111, St. Louis, MO 63110. (dharr@wustl.edu).

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