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Current risk-adjusted models for donor lung use and lung graft survival do not include donor critical care data. We sought to identify modifiable donor physiologic and mechanical ventilation parameters that predict donor lung use and lung graft survival. This is a prospective observational study of donors after brain death (DBDs) managed by 19 Organ Procurement Organizations from 2016 to 2019. Demographics, mechanical ventilation parameters, and critical care data were recorded at standardized time points during donor management. The lungs were transplanted from 1811 (30%) of 6052 DBDs. Achieving ≥7 critical care endpoints was a positive predictor of donor lung use. After controlling for recipient factors, donor blood pH positively predicted lung graft survival (OR 1.48 per 0.1 unit increase in pH) and the administration of dopamine during donor management negatively predicted lung graft survival (OR 0.19). Tidal volumes ≤8 ml/kg predicted body weight (OR 0.65), and higher positive end-expiratory pressures (OR 0.91 per cm H2 O) predicted decreased donor lung use without affecting lung graft survival. A randomized clinical trial is needed to inform optimal ventilator management strategies in DBDs.

Solid organ transplantation continues to be constrained by a lack of suitable donor organs. Advances in donor management and evaluation are needed to address this shortage, but the performance of research studies in deceased donors is fraught with challenges. Here we discuss several of the major obstacles we faced in the conduct of the Donor Heart Study-a prospective, multi-site, observational study of donor management, evaluation, and acceptance for heart transplantation. These included recruitment and engagement of participating organ procurement organizations, ambiguities related to study oversight, obtaining authorization for donor research, logistical challenges encountered during donor management, sustaining study momentum, and challenges related to study data management. By highlighting these obstacles encountered, as well as the solutions implemented, we hope to stimulate further discussion and actions that will facilitate the design and execution of future donor research studies.

BACKGROUND: Delayed graft function (DGF), the need for dialysis in the first week following kidney transplant, affects approximately one-quarter of deceased-donor kidney transplant recipients. Donor demographics, donor serum creatinine, and graft cold ischemia time are associated with DGF. However, there is no consensus on the optimal management of hemodynamic instability in organ donors after brain death (DBDs). Our objective was to determine the relationship between vasopressor selection during donor management and the development of DGF. METHODS: Prospective observational data, including demographic and critical care parameters, were collected for all DBDs managed by seventeen Organ Procurement Organizations from nine Organ Procurement and Transplantation Network Regions between 2012 and 2018. Recipient outcome data were linked with donor data through donor identification numbers. Donor critical care parameters, including type of vasopressor and doses, were recorded at three standardized time points during donor management. The analysis included only donors who received at least one vasopressor at all three time points. Vasopressor doses were converted to norepinephrine equivalent doses and analyzed as continuous variables. Univariate analyses were conducted to determine the association between donor variables and DGF. Results were adjusted for known predictors of DGF using binary logistic regression. RESULTS: Complete data were available for 5,554 kidney transplant recipients and 2,985 DBDs. On univariate analysis, donor serum creatinine, donor age, donor subtype, kidney donor profile index, graft cold ischemia time, phenylephrine dose, and dopamine dose were associated with DGF. After multivariable analysis, increased donor serum creatinine, donor age, kidney donor profile index, graft cold ischemia time, and phenylephrine dose remained independent predictors of DGF. CONCLUSION: Higher doses of phenylephrine were an independent predictor of DGF. With the exception of phenylephrine, the selection and dose of vasopressor during donor management did not predict the development of DGF. LEVEL OF EVIDENCE: Prognostic study, level III

Study objective The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion. Methods We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in the parent trial included critically injured adult patients admitted to 1 of 12 North American Level I trauma centers who received at least 1 unit of packed RBCs and were predicted to require massive blood transfusion. The primary exposure was volume of packed RBC units transfused during the first 24 hours of hospitalization, stratified by packed RBC age category: 0 to 7 days, 8 to 14 days, 15 to 21 days, and greater than or equal to 22 days. The primary outcome was 24-hour mortality. We evaluated the association between transfused volume of each packed RBC age category and 24-hour survival, using random-effects logistic regression, adjusting for total packed RBC volume, patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, clinical site, and trial treatment group. Results The 678 patients included in the analysis received a total of 8,830 packed RBC units. One hundred patients (14.8%) died within the first 24 hours. On multivariable analysis, the number of packed RBCs greater than or equal to 22 days old was independently associated with increased 24-hour mortality (adjusted odds ratio [OR] 1.05 per packed RBC unit; 95% confidence interval [CI] 1.01 to 1.08): OR 0.97 for 0 to 7 days old (95% CI 0.88 to 1.08), OR 1.04 for 8 to 14 days old (95% CI 0.99 to 1.09), and OR 1.02 for 15 to 21 days old (95% CI 0.98 to 1.06). Results of sensitivity analyses were similar only among patients who received greater than or equal to 10 packed RBC units. Conclusion Increasing quantities of older packed RBCs are associated with increased likelihood of 24-hour mortality in trauma patients receiving massive packed RBC transfusion (≥10 units), but not in those who receive fewer than 10 units.

Background Meeting donor management goals when caring for potential organ donors has been associated with more organs transplanted per donor (OTPD). Concern persists, however, as to whether this indicates that younger/healthier donors are more likely to meet donor management goals or whether active management affects outcomes. Study Design A prospective observational study of all standard criteria donors was conducted by 10 organ procurement organizations across United Network for Organ Sharing Regions 4, 5, and 6. Donor management goals representing normal critical care end points were measured at 2 time points: when a catastrophic brain injury was recognized and a referral was made to the organ procurement organization by the DH; and after brain death was declared and authorization for organ donation was obtained. Donor management goals Bundle "met" was defined as achieving any 7 of 9 end points. A positive Bundle status change was defined as not meeting the Bundle at referral and subsequently achieving it at authorization. The primary outcomes measure was having ≥4 OTPD. Results Data were collected for 1,398 standard criteria donors. Of the 1,166 (83%) who did not meet the Bundle at referral, only 254 (22%) had a positive Bundle status change. On adjusted analysis, positive Bundle status change increased the odds of achieving ≥4 OTPD significantly (odds ratio 2.04; 95% CI 1.49 to 2.81; p Conclusions A positive donor management goal Bundle status change during donor hospital management is associated with a 2-fold increase in achieving ≥4 OTPD. Active critical care management of the potential organ donor, as evidenced by improvement in routinely measured critical care end points can be a means by which to substantially increase the number of organs available for transplantation.

Background No standard exists for the use of deceased donor liver biopsy during procurement. We sought to evaluate liver biopsy and the impact of findings on outcomes and graft utilization. Methods A prospective observational study of donors after neurologic determination of death was conducted from 02/2012-08/2017 (16 OPOs). Donor data were collected through the UNOS Donor Management Goals Registry Web Portal and linked to the Scientific Registry of Transplant Recipients (SRTR) for recipient outcomes. Recipients of biopsied donor livers (BxDL) were studied and a Cox proportional hazard analysis was used to identify independent predictors of 1-year graft survival. Results Data from 5449 liver transplant recipients were analyzed, of which 1791(33%) received a BxDL. There was no difference in graft or patient survival between the non-BxDL and BxDL recipient groups. On adjusted analysis of BxDL recipients, macrosteatosis (21%-30%[n = 148] and >30%[n = 92]) was not found to predict 1-year graft survival, whereas increasing donor age (HR1.02), donor Hispanic ethnicity (HR1.62), donor INR (HR1.18), and recipient life support (HR2.29) were. Conclusions Excellent graft and patient survival can be achieved in recipients of BxDL grafts. Notably, as demonstrated by the lack of effect of macrosteatosis on survival, donor to recipient matching may contribute to these outcomes.

In a recent trial, targeted mild hypothermia in brain-dead organ donors significantly reduced the incidence of delayed graft function after kidney transplantation. This trial was stopped early for efficacy. Here, we report long-term graft survival for all organs along with donor critical care end points.We assessed graft survival through 1 year of all solid organs transplanted from 370 donors who had been randomly assigned to hypothermia (34-35°C) or normothermia (36.5-37.5°C) before donation. Additionally, changes in standardized critical care end points were compared between donors in each group.Mild hypothermia was associated with a nonsignificant improvement in 1-year kidney transplant survival (95% versus 92%; hazard ratio, 0.61 [0.31-1.20]; P = 0.15). Mild hypothermia was associated with higher 1-year graft survival in the subgroup of standard criteria donors (97% versus 93%; hazard ratio, 0.39 [0.15 to -1.00]; P = 0.05). There were no significant differences in graft survival of extrarenal organs. There were no differences in critical care end points between groups.Mild hypothermia in the donor safely reduced the rate of delayed graft function in kidney transplant recipients without adversely affecting donor physiology or extrarenal graft survival. Kidneys from standard criteria donors who received targeted mild hypothermia had improved 1-year graft survival.

Pancreatic transplantation has become a standard of care for complicated type 1 diabetes therapy. In the United States in 2015, there were approximately 1000 patients awaiting pancreas transplant, with the percentage of active listings at 65%, the highest in decades.1 Solid organ pancreata can be transplanted individually, after a kidney transplant (pancreas-after-kidney [PAK]), or with a simultaneous pancreas-kidney (SPK) transplant. As diabetes is cited as a major, in- creasing public health burden,2 pancreas transplant has been recommended by the American Diabetes Association and other national guidelines as an accepted treatment, particularly when coupled with end-stage renal disease.3 Benefits to pancreas transplantation, SPK, and PAK are well described, having both improvements in mortality when compared to those on the waiting list4 and better overall glycemic control, reducing number of hypoglycemic episodes compared to those on insulin regimens.5 In addition, pancreas transplantation has been shown to delay secondary complications of diabetes, such as cardiovascular disease6 and nervous system complications.7 Despite these demonstrated advantages for pancreatic transplantation, only approximately 10% of available organs are recovered from donors after brain death (DBD). Additionally, there has been an overall decline in pancreatic transplantation over the past decade.8 In pancreatic transplantation, inconsistent donor management and organ acceptance practices are pervasive. Potentially contributing to this lack of consistency in donor management is the fact that the current risk-adjustment models used to predict both organ procurement organization (OPO) donor pancreas utilization and transplant center graft survival models lack detailed donor critical care data. In an effort to increase standardization and data collection, several OPOs have collaborated to develop a checklist of critical care endpoints to guide the bedside care of potential organ donors. These endpoints are also known as donor management goals (DMGs), and they represent normal hemodynamic, respiratory, renal, acid-base, and endocrine parameters for an organ donor. Multiple studies have shown improvements in both organ utilization rates9–13 and recipient graft outcomes14–16 when these goals are met. The link between optimal management of the potential organ donor after brain death (DBD) and pancreatic graft utilization and function has not yet been explored in the literature, and we sought to further elucidate this relationship using a deceased organ donor database containing demographic and critical care data at 4 time points during donor management. Given anecdotal reports of insulin requirements being used as criteria for pancreatic acceptance or denial, we also sought to determine the relationship between insulin dose and pancreatic usage and function.

Delayed graft function (DGF) in kidney transplant significantly increases inpatient and outpatient cost. Targeted, mild hypothermia in organ donors after neurologic determination of death significantly reduced the rate of DGF in a recent randomized controlled clinical trial. To assess the potential economic benefit of national implementation of donor hypothermia, rates of reduction DGF were combined with estimates of the impact of DGF on hospital cost and total health expenditure for standard and extended criteria donor organs (SCD and ECD). DGF increases the cost of the transplant episode by $9487 for ECD transplant and $10 342 for SCD transplant. Medicare recipients with DGF incur an additional $18 513 spending for ECD and $14 948 in SCD transplants over the first year. An absolute reduction in DGF rate after kidney transplantation consistent with trial results (ECD 25%, SCD 7%) has the potential to lower annual hospital cost for kidney transplant by $13 178 746 and annual Medicare spending by $20 970 706 compared to standard donor management practice using static cold storage. Targeted mild hypothermia improves care of renal transplant patients by safely reducing DGF rates in both ECD and SCD transplant. Broader application of this safe, effective, and low-cost intervention could reduce healthcare expenditures for providers and insurers.

Therapeutic hypothermia (TH) is clinically used to improve neurologic outcomes in patients with anoxic brain injury after cardiopulmonary resuscitation (CPR). For patients that regress and become organ donors after neurologic determination of death (DNDDs), the impact of TH received before determination of death on organ donation outcomes remains unknown. A prospective observational study of all adult DNDDs that received CPR and had anoxia as a cause of death from March 2013 to December 2014 was conducted across 20 organ procurement organizations (OPOs) in the United States. Main outcome measures included organs transplanted per donor (OTPD), specific organ transplantation rates, and recipient graft outcomes. One thousand ninety eight DNDDs met inclusion criteria, with 46% having received TH before determination of death. DNDDs with hypothermia before death had a similar number of OTPD (2.74 vs. 2.69

BACKGROUND: Current risk-adjusted models used to predict donor heart utilization and cardiac graft survival from organ donors after brain death (DBDs) do not include bedside critical care data. We sought to identify novel independent predictors of heart utilization and graft survival to better understand the relationship between donor management and transplant outcomes. STUDY DESIGN: Prospective observational study of DBDs managed from 2008 to 2013 by 10 organ procurement organizations. Demographic data, critical care parameters, and treatments were recorded at three standardized time points during donor management. The primary outcome measures were donor heart utilization and cardiac graft survival. RESULTS: From 3,433 DBDs, 1,134 (33%) hearts were transplanted and 969 (85%) cardiac grafts survived after 684 (± 392) days of follow-up. After multivariable analysis, independent positive predictors of heart utilization included standard criteria donor status (OR = 3.93), male sex (OR = 1.68), ejection fraction > 50% (OR = 1.64), and PaO(2):FiO(2) > 300 (OR = 1.31). Independent negative predictors of heart utilization included donor age (OR = 0.94), body mass index > 30 kg/m(2) (OR = 0.78), serum creatinine (OR = 0.83), and use of thyroid hormone (OR = 0.78). As for graft survival, after controlling for known recipient risk factors, thyroid hormone dose was the only independent predictor (OR = 1.04 per μg/hr). CONCLUSION: Modifiable critical care parameters and treatments predict donor heart utilization and cardiac graft survival. The discordant relationship between thyroid hormone and donor heart utilization (negative predictor) versus cardiac graft survival (positive predictor) warrants further investigation.

Endotheliopathy of trauma is characterized by breakdown of the endothelial glycocalyx. Elevated biomarkers of endotheliopathy, such as serum syndecan-1 (Synd-1) ≥ 40 ng/mL, have been associated with increased need for transfusions, complications, and mortality. We hypothesized that severely injured trauma patients who exhibit elevated Synd-1 levels shortly after admission have an increased likelihood of developing sepsis.We analyzed a subset of patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who survived at least 72 hours after hospital admission, and we determined elevated Synd-1 levels (≥ 40 ng/mL) 4 hours after hospital arrival. Sepsis was defined a priori as meeting systemic inflammatory response criteria and having a known or suspected infection. Univariate analysis was performed to identify variables associated with elevated Synd-1 levels and sepsis. Significant variables at a value of p0.2 in the univariate analysis were chosen by purposeful selection and analyzed in a mixed effects multivariate logistic regression model to account for the 12 different study sites.We included 512 patients. Of these, 402 (79%) had elevated Synd-1 levels, and 180 (35%) developed sepsis. Median Synd-1 levels at 4 hours after admission were 70 ng/dL (interquartile range [IQR] 36 to 157 ng/dL) in patients who did not develop sepsis, and 165 ng/dL [IQR 67 to 336 ng/dL] in those who did (p0.001). Adjusting for treatment arm and site, multivariable analyses revealed that elevated Synd-1 status, Injury Severity Score (ISS), and total blood transfused were significantly associated with an increased likelihood of developing sepsis.Elevated Synd-1 levels 4 hours after admission in severely injured adult trauma patients who survived the initial 72 hours after hospital admission are associated with subsequent sepsis.

Background A rhabdomyolysis protocol (RP) with mannitol and bicarbonate to prevent acute renal dysfunction (ARD, creatinine >2.0 mg/dL) remains controversial. Methods Patients with creatine kinase (CK) greater than 2,000 U/L over a 10-year period were identified. Shock, Injury Severity Score, massive transfusion, intravenous contrast exposure, and RP use were evaluated. RP was initiated for a CK greater than 10,000 U/L (first half of the study) or greater than 20,000 U/L (second half). Multivariable analyses were used to identify predictors of ARD and the independent effect of the RP. Results Seventy-seven patients were identified, 24 (31%) developed ARD, and 4 (5%) required hemodialysis. After controlling for other risk factors, peak CK greater than 10,000 U/L (odds ratio 8.6, P = .016) and failure to implement RP (odds ratio 5.7, P = .030) were independent predictors of ARD. Among patients with CK greater than 10,000, ARD developed in 26% of patients with the RP versus 70% without it ( P = .008). Conclusion Reduced ARD was noted with RP. A prospective controlled study is still warranted.