[Show abstract][Hide abstract] ABSTRACT: PURPOSE: Corticosteroids are used to promote hemodynamic stability and reduce inflammatory organ injury after brain death. High-dose (HD) methylprednisolone has become the standard regimen based on comparisons to untreated/historical controls. However, this protocol may exacerbate hyperglycemia. Our objective was to compare a lower-dose (LD) steroid protocol (adequate for hemodynamic stabilization in adrenal insufficiency and sepsis) to the traditional HD regimen in the management of brain-dead organ donors. METHODS: We evaluated 132 consecutive brain-dead donors managed before and after changing the steroid protocol from 15 mg/kg methylprednisolone (HD) to 300 mg hydrocortisone (LD). Primary outcome measures were glycemic control, oxygenation, hemodynamic stability, and organs transplanted. RESULTS: Groups were balanced except for nonsignificantly higher baseline Pao(2) in the LD cohort. Final Pao(2) remained higher (394 mm Hg LD vs 333 mm Hg HD, P=.03); but improvement in oxygenation was comparable (+37 mm Hg LD vs +28 mm Hg HD, P=.43), as was the proportion able to come off vasopressor support (39% LD vs 47% HD, P=.38). Similar proportions of lungs (44% vs 33%) and hearts (31% vs 27%) were transplanted in both groups. After excluding diabetics, median glucose values at 4 hours (170 mmol/L vs 188 mmol/L, P=.06) and final insulin requirements (2.9 U/h vs 8.4 U/h, P=.01) were lower with LD steroids; and more patients were off insulin infusions (74% LD vs 53% HD, P=.02). CONCLUSIONS: A lower-dose corticosteroid protocol did not result in worsened donor pulmonary or cardiac function, with comparable organs transplanted compared with the traditional HD regimen. Insulin requirements and glycemic control were improved. High-dose methylprednisolone may not be required to support brain-dead donors.
Journal of critical care 07/2012; · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background}Contradictory evidence has been published on the effects of steroid treatments on the outcomes ofkidney and liver transplantation from brain dead (BD) donors. Our study aimed to evaluate thisdisparity by investigating the effect of prednisolone administration on BD rats.
Journal of translational medicine. 05/2014; 12(1):111.
[Show abstract][Hide abstract] ABSTRACT: Given the static number of deceased donors, improvements in donor management and organ preservation to increase the number and quality of organs transplanted per donor are more pressing. Because controlled trials provide the best evidence, we conducted a review of English-language literature of trials in donor management and organ preservation to provide a compendium and to promote additional discussion and studies.Eighty-seven reports were retrieved: 13 on hemodynamic and fluid management, 7 on immunosuppressants, 12 on preconditioning, 34 on preservation fluids, and 21 on pulsatile perfusion. Sixteen studies are ongoing. Although hormonal therapy is used widely, additional studies are needed to determine the benefit of thyroid hormone and insulin replacement and to optimize steroid regimens. Dopamine's success in reducing kidney delayed graft function highlights the opportunity for additional preconditioning trials of remote ischemia, gases, opioids, and others. More rapid progress requires addressing unique barriers in consent and research approval, legal constraints precluding research in cardiac death donors, and streamlining collaboration of multiple stakeholders. With little interest from industry, federal funding needs to be increased.While the University of Wisconsin solution still reigns supreme, several promising preservative solutions and additives with not only biophysical but also pharmacological effects are on the cusp of phase 1 to 2 trials. After nearly three decades of uncertainty, the recent success of a European trial has reenergized the topic not only of machine preservation of the kidney but also of other organs evident by trials in progress. However, the costs of such technical innovations merit the burden of rigorous proof from controlled trials.
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