Schweizer Thilo, Nossen Caroline M, Galova Barbara, Schild Christof, Huber Markus, Bally Lia, Vogt Andreas, Siepe Matthias, Nagler Michael, Fischer Kady, Guensch Dominik P
From the Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department of Cardiac Surgery, Inselspital, Bern University Hospital, University of Bern, Bern Switzerland.
Anesth Analg. 2025 Aug 1;141(2):267-272. doi: 10.1213/ANE.0000000000007106. Epub 2024 Jun 11.
Hyperglycemia is common in patients undergoing cardiovascular surgery with cardiopulmonary bypass. We hypothesize that intraoperative hyperglycemia may be, at least partially, attributable to insulin loss due to adhesion on artificial surfaces and/or degradation by hemolysis. Thus, our primary aim was to investigate the loss of insulin in 2 different isolated extracorporeal circulation circuits (ECCs), that is, a conventional ECC (cECC) with a roller pump, and a mini-ECC (MiECC) system with a centrifugal pump. The secondary aim was to assess and compare the relationship between changes in insulin concentration and the degree of hemolysis in our 2 ECC models.
Six cECC and 6 MiECC systems were primed with red packed blood cells and thawed fresh-frozen plasma (1:1). Four additional experiments were performed in cECC using only thawed fresh-frozen plasma. Human insulin (Actrapid) was added, targeting a plasma insulin concentration of 400 mU/L. Insulin concentration and hemolysis index were measured at baseline and hourly thereafter. The end points were the change in insulin level after 4 hours compared to baseline and hemolysis index after 4 hours. The insulin concentration and hemolysis index were analyzed by means of a saturated linear mixed-effect regression model with a random offset for each experiment to account for the repeated measure design of the study, resulting in mean estimates and 95% confidence intervals (CIs) of the primary end points as well as of pairwise contrasts with respect to ECC type.
Insulin concentration decreased by 63% (95% CI, 48%-77%) in the MiECC and 92% (95% CI, 77%-106%) in the cECC system that contained red blood cells. Insulin loss was significantly higher in the cECC system compared to the MiECC ( P = .022). In the cECC with only plasma, insulin did not significantly decrease (-4%; 95% CI, -21% to 14%). Hemolysis index in MiECC increased from 68 (95% CI, 46-91) to 76 (95% CI, 54-98) after 4 hours, in cECC from 81 (95% CI, 59-103) to 121 (95% CI, 99-143). Hemolysis index and percent change of insulin showed an excellent relationship (r = -0.99, P < .01).
Our data showed that insulin levels substantially decreased during 4 hours of simulated cardiopulmonary bypass only in the ECC that contained hemoglobin. The decrease was more pronounced in the cECC, which also exhibited a greater degree of hemolysis. Our results suggest that insulin degradation by hemolysis products may be a stronger contributor to insulin loss than adhesion of insulin molecules to circuit surfaces.
在接受体外循环心脏手术的患者中，高血糖很常见。我们推测术中高血糖可能至少部分归因于胰岛素因黏附于人工表面和/或因溶血而降解导致的损失。因此，我们的主要目的是研究胰岛素在两种不同的体外循环回路（ECC）中的损失情况，即配备滚压泵的传统ECC（cECC）和配备离心泵的微型ECC（MiECC）系统。次要目的是评估和比较我们的两种ECC模型中胰岛素浓度变化与溶血程度之间的关系。
用红细胞和解冻的新鲜冰冻血浆（1:1）预充6个cECC和6个MiECC系统。在cECC中仅使用解冻的新鲜冰冻血浆进行了另外4次实验。加入人胰岛素（Actrapid），目标血浆胰岛素浓度为400 mU/L。在基线时及之后每小时测量胰岛素浓度和溶血指数。终点是4小时后与基线相比胰岛素水平的变化以及4小时后的溶血指数。通过饱和线性混合效应回归模型分析胰岛素浓度和溶血指数，每个实验有一个随机偏移量以考虑研究的重复测量设计，得出主要终点以及关于ECC类型的成对对比估计值和均值及95%置信区间（CI）。
在含有红细胞的MiECC中，胰岛素浓度下降了63%（95%CI，48%-77%），在cECC系统中下降了92%（95%CI，77%-106%）。与MiECC相比，cECC系统中的胰岛素损失显著更高（P = 0.022）。在仅含血浆的cECC中，胰岛素没有显著下降（-4%；95%CI，-21%至14%）。4小时后，MiECC中的溶血指数从68（95%CI，46-91）增加到76（95%CI，54-98），cECC中从81（95%CI，59-103）增加到121（95%CI，99-143）。溶血指数与胰岛素百分比变化显示出极好的相关性（r = -0.99，P < 0.01）。
我们的数据表明，仅在含有血红蛋白（此处疑为红细胞，原文hemoglobin有误）的ECC中，在4小时模拟体外循环期间胰岛素水平大幅下降。cECC中的下降更为明显，其溶血程度也更高。我们的结果表明，溶血产物对胰岛素的降解可能比胰岛素分子黏附于回路表面对胰岛素损失的影响更大。
