Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial
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Critical shortages of organs for transplantation jeopardize many lives. Observational data suggest that better fluid management for deceased organ donors could increase organ recovery. We conducted the first large multicenter randomized trial in brain-dead donors to determine whether protocolized fluid therapy increases the number of organs transplanted.
We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A “protocol-guided fluid therapy” algorithm targeting the cardiac index, mean arterial pressure and pulse pressure variation was used. Our primary outcome was the number of organs transplanted per donor, and our primary analysis was intention to treat. Secondary analyses included: (1) modified intention to treat where only subjects able to receive the intervention were included and (2) 12-month survival in transplant recipients. The study was stopped early.
We enrolled 556 donors: 279 protocolized care and 277 usual care. Groups had similar characteristics at baseline. The study protocol could be implemented in 76 % of subjects randomized to the intervention. There was no significant difference in mean number of organs transplanted per donor: 3.39 organs per donor (95 % CI 3.14–3.63) with protocolized care compared to 3.29 usual care (95 % CI 3.04–3.54; mean difference, 0.1, 95 % CI −0.25 to 0.45; p = 0.56). In modified intention-to-treat analysis the mean number of organs increased (3.52 organs per donor, 95 % CI 3.23–3.8), but not statistically significantly (mean difference, 0.23, 95 % CI −0.15 to 0.61; p = 0.23). Among the 1,430 recipients of organs from study subjects with data available, 56 deaths (7.8 %) occurred in the protocolized care arm and 56 (7.9 %) in the usual care arm in the first year (hazard ratio: 0.97, p = 0.86).
In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor.
KeywordsOrgan donation Clinical trial Transplantation Functional hemodynamic monitoring Fluid management Brain death
MOnIToR was supported by a grant (R38OT1058) from the Health Resources and Services Administration (HRSA) with additional support from LiDCO Products (London, UK) in the form of personnel training and loaning of equipment. Additional support for John Kellum was provided by a grant (R01DK083961) from the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) and for Raghavan Murugan from the National Institute of Health through grant nos. UL1 RR024153 and UL1TR000005. The data reported here have been supplied by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplant Recipients (SRTR). The agencies listed had no role in the design and conduct of the study; the collection, analysis and interpretation of the data; or the preparation or approval of the paper. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the US government, specifically of HRSA, NIDDK or NIH.
Conflicts of interest
Rupert Pearse reports receiving research funding from LiDCO Ltd including equipment for research. No other authors report any competing interests.
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