Shapey I M, Summers A, Yiannoullou P, Fullwood C, Augustine T, Rutter M K, van Dellen D
University of Manchester, UK.
Manchester University NHS Foundation Trust, UK.
Ann R Coll Surg Engl. 2024 Jan;106(1):19-28. doi: 10.1308/rcsann.2022.0161. Epub 2023 Mar 16.
Outcomes following pancreas transplantation are suboptimal and better donor selection is required to improve this. Vasoactive drugs (VaD) are commonly used to correct the abnormal haemodynamics of organ donors in intensive care units. VaDs can differentially affect insulin secretion positively (dobutamine) or negatively (noradrenaline). The hypothesis was that some VaDs might induce beta-cell stress or rest and therefore impact pancreas transplant outcomes. The aim of the study was to assess relationships between VaD use and pancreas transplant graft survival.
Data from the UK Transplant Registry on all pancreas transplants performed between 2004 and 2016 with complete follow-up data were included. Univariable- and multivariable-adjusted Cox regression analyses determined risks of graft failure associated with VaD use.
In 2,183 pancreas transplants, VaDs were used in the following numbers of donors: dobutamine 76 (3.5%), dopamine 84 (3.8%), adrenaline 161 (7.4%), noradrenaline 1,589 (72.8%) and vasopressin 1,219 (55.8%). In multivariable models, adjusted for covariates and the co-administration of other VaDs, noradrenaline use (vs non-use) was a strong predictor of better graft survival (hazard ratio [95% confidence interval] 0.77 [0.64-0.94], = 0.01).
Noradrenaline use was associated with better graft survival in models adjusted for donor and recipient variables - this may be related to inhibition of pancreatic insulin secretion initiating pancreatic beta-cell 'rest'. Further research is required to replicate these findings and establish whether relationships are causal. Identification of alternative methods of inducing beta-cell rest could be valuable in improving graft outcomes.
胰腺移植的效果并不理想,需要更好地选择供体以改善这一情况。血管活性药物(VaD)常用于纠正重症监护病房中器官供体的异常血流动力学。VaD对胰岛素分泌的影响可能不同,有的呈正向作用(多巴酚丁胺),有的呈负向作用(去甲肾上腺素)。研究假设是某些VaD可能会诱导β细胞应激或使其处于静息状态,从而影响胰腺移植的结果。本研究的目的是评估VaD的使用与胰腺移植移植物存活之间的关系。
纳入英国移植登记处2004年至2016年间进行的所有胰腺移植数据,并具有完整的随访数据。单变量和多变量调整的Cox回归分析确定了与使用VaD相关的移植物失败风险。
在2183例胰腺移植中,使用不同VaD的供体数量如下:多巴酚丁胺76例(3.5%),多巴胺84例(3.8%),肾上腺素161例(7.4%),去甲肾上腺素1589例(72.8%),血管加压素1219例(55.8%)。在多变量模型中,经协变量和其他VaD联合使用调整后,使用去甲肾上腺素(与未使用相比)是移植物存活更好的有力预测因素(风险比[95%置信区间]为0.77[0.64 - 0.94],P = 0.01)。
在对供体和受体变量进行调整的模型中,使用去甲肾上腺素与更好的移植物存活相关——这可能与抑制胰腺胰岛素分泌从而使胰腺β细胞“静息”有关。需要进一步研究来重复这些发现,并确定这种关系是否具有因果性。确定诱导β细胞静息的替代方法可能对改善移植物结果具有重要价值。