Increased recovery of thoracic organs after hormonal resuscitation therapy.

Division of Cardiothoracic Surgery, University School of Medicine, St. Louis, Missouri.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation (Impact Factor: 5.61). 03/2010; 29(5):594-6. DOI: 10.1016/j.healun.2009.12.001
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    ABSTRACT: To review all published clinical studies of thyroid hormone administration to brain-dead potential organ donors. A search of PubMed using multiple search terms retrieved 401 publications including 35 original reports describing administration of thyroid hormone to brain-dead potential organ donors. Detailed review of the 35 original reports led to identification of two additional publications not retrieved in the original search. The 37 original publications reported findings from 16 separate case series or retrospective audits and seven randomized controlled trials, four of which were placebo-controlled. Meta-analysis was restricted to the four placebo-controlled randomized controlled trials. Whereas all case series and retrospective audits reported a beneficial effect of thyroid hormone administration, all seven randomized controlled trials reported no benefit of thyroid hormone administration either alone or in combination with other hormonal therapies. In four placebo-controlled trials including 209 donors, administration of thyroid hormone (n=108) compared with placebo (n=101) had no significant effect on donor cardiac index (pooled mean difference, 0.15 L/min/m²; 95% confidence interval -0.18 to 0.48). The major limitation of the case series and retrospective audits was the lack of consideration of uncontrolled variables that confound interpretation of the results. A limitation of the randomized controlled trials was that the proportion of donors who were hemodynamically unstable or marginal in other ways was too small to exclude a benefit of thyroid hormone in this subgroup. The findings of this systematic review do not support a role for routine administration of thyroid hormone in the brain-dead potential organ donor. Existing recommendations regarding the use of thyroid hormone in marginal donors are based on low-level evidence.
    Critical care medicine 05/2012; 40(5):1635-44. DOI:10.1097/CCM.0b013e3182416ee7 · 6.15 Impact Factor
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    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; 28(1). DOI:10.1016/j.jcrc.2012.04.015 · 2.19 Impact Factor
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    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.
    Transplantation 08/2012; 94(5):425-41. DOI:10.1097/TP.0b013e3182547537 · 3.78 Impact Factor