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Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial.

ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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). CONCLUSIONS:In brain-dead organ donors, protocol-guided fluid therapy compared to usual care may not increase the number of organs transplanted per donor.

SUBMITTER: Al-Khafaji A

PROVIDER: S-EPMC4351113 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial.

Al-Khafaji Ali A Elder Michele M Lebovitz Daniel J DJ Murugan Raghavan R Souter Michael M Stuart Susan S Wahed Abdus S AS Keebler Ben B Dils Dorrie D Mitchell Stephanie S Shutterly Kurt K Wilkerson Dawn D Pearse Rupert R Kellum John A JA

Intensive care medicine 20150113 3

<h4>Background</h4>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.<h4>Methods</h4>We randomly assigned donors to either protocolized or usual care in eight organ procurement organizations. A ...[more]

PMID: 25583616

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Project description:ImportanceDelayed graft function in kidney-transplant recipients is associated with increased financial cost and patient burden. In donors with high Kidney Donor Profile Index whose kidneys are not pumped, therapeutic hypothermia has been shown to confer a protective benefit against delayed graft function.ObjectiveTo determine whether hypothermia is superior to normothermia in preventing delayed graft function in low-risk nonpumped kidney donors after brain death.Design, setting, and participantsIn a multicenter randomized clinical trial, brain-dead kidney donors deemed to be low risk and not requiring machine perfusion per Organ Procurement Organization protocol were prospectively randomized to hypothermia (34.0-35 °C) or normothermia (36.5-37.5 °C) between August 10, 2017, and May 21, 2020, across 4 Organ Procurement Organizations in the US (Arizona, Upper Midwest, Pacific Northwest, and Texas). The final analysis report is dated June 15, 2022, based on the data set received from the United Network for Organ Sharing on June 2, 2021. A total of 509 donors (normothermia: n = 245 and hypothermia: n = 236; 1017 kidneys) met inclusion criteria over the study period.InterventionDonor hypothermia (34.0-35.0 °C) or normothermia (36.5-37.5 °C).Main outcomes and measuresThe primary outcome was delayed graft function in the kidney recipients, defined as the need for dialysis within the first week following kidney transplant. The primary analysis follows the intent-to-treat principle.ResultsA total of 934 kidneys were transplanted from 481 donors, of which 474 were randomized to the normothermia group and 460 to the hypothermia group. Donor characteristics were similar between the groups, with overall mean (SD) donor age 34.2 (11.1) years, and the mean donor creatinine level at enrollment of 1.03 (0.53) mg/dL. There was a predominance of Standard Criteria Donors (98% in each treatment arm) with similar low mean (SD) Kidney Donor Profile Index (normothermia: 28.99 [20.46] vs hypothermia: 28.32 [21.9]). Cold ischemia time was similar in the normothermia and hypothermia groups (15.99 [7.9] vs 15.45 [7.63] hours). Delayed graft function developed in 87 of the recipients (18%) in the normothermia group vs 79 (17%) in the hypothermia group (adjusted odds ratio, 0.92; 95% CI, 0.64-1.33; P = .66).Conclusions and relevanceThe findings of this study suggest that, in low-risk non-pumped kidneys from brain-dead kidney donors, therapeutic hypothermia compared with normothermia does not appear to prevent delayed graft function in kidney transplant recipients.Trial registrationClinicalTrials.gov Identifier: NCT02525510.

Project description:ImportanceThe effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear.ObjectiveTo evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU).Design, setting, and participantsThe Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020.InterventionsHospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care.Main outcomes and measuresThe primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group.ResultsAmong the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006).Conclusions and relevanceThis cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist.Trial registrationClinicalTrials.gov Identifier: NCT03179020.

Project description:IntroductionIschaemia/reperfusion injuries (IRIs) are associated with poorer survival of kidney grafts from expanded criteria donors. Preclinical studies have shown that mineralocorticoid receptor antagonists (MRAs) prevent acute and chronic post-ischaemic renal dysfunction by limiting IRI. However, data concerning the safety of MRAs in brain-dead donor patients are scarce. We seek to investigate the tolerance of MRAs on the haemodynamics in this population.Methods and analysisCANREO-PMO is a randomised, controlled, single-centre, double-blind study. Brain-dead organ donors hospitalised in intensive care are randomised 1:1 after consent to receive 200 mg potassium canrenoate or its matching placebo every 6 hours until organ procurement. The primary outcome is a hierarchical composite endpoint that includes: (1) cardiocirculatory arrest, (2) the impossibility of kidney procurement, (3) the average hourly dose of norepinephrine/epinephrine between randomisation and departure to the operating room, and (4) the average hourly volume of crystalloids and/or colloids received. Thirty-six patients will be included. The secondary endpoints evaluated among the graft recipients are the: (1) vital status of the kidney graft recipients and serum creatinine level with estimated glomerular filtration rate (GFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) at 3 months after renal transplantation, (2) percentage of patients dependent on dialysis and/or with an estimated GFR <20 mL/min/1.73 m2 at 3 months, (3) vital status of the kidney graft recipients at 3 months, and (4) vital status of the kidney graft recipients and creatinine levels (in μmol/L), with the estimated GFR according to CKD-EPI (in mL/min/1.73 m2), at 1 year, 3 years and 10 years after transplantation.Ethics and disseminationThis trial has full ethical approval (Comité de Protection des Personnes: CPP Ouest II-ANGERS, France), and the written consent of relatives will be obtained. Results will be reported at conferences, peer-reviewed publications and using social media channels.Trial registration numberNCT04714710.

Project description:Background: Protocolized ventilator weaning (PW) strategies utilizing spontaneous breathing trials (SBTs) result in shorter intubation duration and intensive care unit (ICU) length of stay (LOS). We compared respiratory therapy (RT)-driven PW versus usual care (UC) as it pertains to physiologic respiratory parameters, intubation duration, extubation success/reintubation rates, and ICU LOS. Methods: prospective, multicentric, randomized controlled trial was performed in closed medical and surgical ICUs with 24/7 in-house intensivist coverage at six academic medical centers in a resource-limited setting from October 18, 2007, to May 03, 2014. Extubation readiness was determined by the attending physician (UC) or the respiratory therapist (PW) using predefined criteria and SBT. Physiologic variables, serial blood gas measurements, and weaning indices were assessed including the Rapid Shallow Breathing Index (RSBI), negative inspiratory force (NIF), occlusion pressure (P0.1), and dynamic and static compliance (Cdyn and Cs). Results: total of 5502 patients were randomized (PW 2787; UC 2715), of which 167 patients died without ventilator weaning (PW 90; UC 77) and 645 patients were excluded (PW 365; UC 280). Finally, a total of 4200 patients were analyzed (PW 2075; UC 2125). The PW group displayed improvements in minute ventilation (P < 0.001), Cs and Cdyn(both P < 0.05), P0.1 (P < 0.001), NIF (P < 0.001), and RSBI (P < 0.001). Early re-intubation (≤48 h) rates were lower in the PW group (16.7% vs. 24.8%; P < 0.0001), as were late re-intubation rates (5.2% vs. 25.8%; P < 0.0001). Intubation duration was longer in the PW group (P < 0.001), however, hospital LOS was shorter (P < 0.001). Mortality was unchanged (P = 0.19). Conclusion: PW with RT-driven extubation decisions is safe, effective, and associated with decreased re-intubation (early and late), shorter hospital stays, increased intubation duration (statistically but not clinically significant), and unchanged in-patient mortality.

Project description:BackgroundAcute kidney injury (AKI) is frequently found in deceased donors; however, few studies have reported the use of imaging to detect and identify this phenomenon. The purpose of this study was to detect renal microcirculatory perfusion in brain-dead donors using contrast-enhanced ultrasonography (CEUS), investigate the value of CEUS in identifying AKI, and analyze the correlation between CEUS and preimplantation biopsy results and early post-transplant renal function of grafts.MethodsThis prospective study recruited 94 kidneys from brain-dead donors (AKI =44, non-AKI =50) from August 2020 to November 2022. The inclusion criteria were age ≥18 years and brain death. The exclusion criteria encompassed donors maintained with extracorporeal membrane oxygenation (ECMO) and the presence of irregular kidney anatomy. The mean age of the donors was 45.1±10.4 [standard deviation (SD)] years, and the majority were male (86.2%). CEUS was performed prior to organ procurement, and time-intensity curves (TICs) were constructed. The time to peak (TTP) and peak intensity (PI) of kidney segmental artery (KA), kidney cortex (KC), and kidney medulla (KM) were calculated using TIC analysis.ResultsArrival time (AT) of KA (P<0.001) and TTP of kidney cortex (TTPKC) (P<0.001) of the non-AKI group were significantly shorter than those of the AKI group. The PI of the KA (P=0.003), KM (P=0.005), and kidney cortex (PIKC; P<0.001) of the non-AKI group were significantly higher than those of the AKI group. Multivariable logistic regression analysis showed that serum creatinine [odds ratio (OR) =1.06; 95% CI: 1.03-1.1; P<0.001], TTPKC (OR =1.38; 95% CI: 1.03-1.84; P=0.03), and PIKC (OR =0.95; 95% CI: 0.91-1; P=0.046) were the independent factors of AKI. The area under the receiver operating characteristic curve (AUC) for identifying AKI for TTPKC and PIKC was 0.73 and 0.71, respectively. TTPKC showed a weak correlation with interstitial fibrosis (r=0.23; P=0.03), PIKC showed a weak correlation with arterial intimal fibrosis ((r=-0.29; P=0.004) and arteriolar hyalinosis (r=-0.27; P=0.008), and PIKC showed the strongest correlation with eGFR on postoperative day 7 (r=-0.46; P=0.046) in the donor kidneys with AKI.ConclusionsCEUS can be used to identify AKI in brain-dead donors. Furthermore, there is a correlation between CEUS-derived parameters and pretransplant biopsy results and early preimplantation renal function of grafts.

Dataset Information

Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial.

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Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial.

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