van Wezel H B, Zuurbier C J, de Jonge E, van Dam E W C M, van Dijk J, Endert E, de Mol B A, Fliers E
Department of Anesthesia, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
J Clin Endocrinol Metab. 2006 Oct;91(10):4144-53. doi: 10.1210/jc.2006-1199. Epub 2006 Aug 8.
Hyperglycemia in patients undergoing coronary artery bypass grafting (CABG) is associated with adverse outcome. Although insulin infusion strategies are increasingly used to improve outcome, a pathophysiological rationale is currently lacking. The present study was designed to quantify the effects of a perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress response during CABG.
Forty-four nondiabetic patients, scheduled for elective CABG, were randomized to either a control group (n = 22) receiving standard care or to a clamp group (n = 22) receiving additionally a perioperative hyperinsulinemic (regular insulin at a fixed rate of 0.1 IU.kg(-1).h(-1)) normoglycemic (plasma glucose between 3.0 and 6.0 mmol.liter(-1)) clamp during 26 h. We measured the endocrine response of the hypothalamus-pituitary-adrenal (HPA) axis, the sympathoadrenal axis, and glucagon, as well as plasma glucose and insulin at regular intervals from the induction of anesthesia at baseline through the end of the second postoperative day (POD).
There were no differences in clinical outcome between the groups. In the control group, hyperglycemia developed at the end of surgery and remained present until the final measurement point on POD2, whereas plasma insulin levels remained unchanged until the morning of POD1. In the intervention group, normoglycemia was well maintained during the clamp, whereas insulin levels ranged between 600 and 800 pmol.liter(-1). In both groups, plasma ACTH and cortisol increased from 6 h after discontinuation of cardiopulmonary bypass onward. However, during the clamp period, a marked reduction in the HPA axis response was found in the intervention group, as reflected by a 47% smaller increase in area under the curve in plasma ACTH (P = 0.035) and a 27% smaller increase in plasma cortisol (P = 0.002) compared with the control group. Compared with baseline, epinephrine and norepinephrine increased by the end of the clamp interval until POD2 in both groups. Surprisingly, the area under the curve of epinephrine levels was 47% higher (P = 0.026) after the clamp interval in the intervention group as compared with the control group.
A hyperinsulinemic normoglycemic clamp during CABG delays and attenuates the HPA axis response during the first 18 h of the myocardial reperfusion period, whereas after the clamp, plasma epinephrine is higher. The impact of delaying cortisol responses on clinical outcome of CABG remains to be elucidated.
冠状动脉旁路移植术（CABG）患者的高血糖与不良预后相关。尽管胰岛素输注策略越来越多地用于改善预后，但目前缺乏病理生理学依据。本研究旨在量化围手术期高胰岛素正常血糖钳夹对CABG期间神经体液应激反应的影响。
44例计划行择期CABG的非糖尿病患者被随机分为对照组（n = 22）接受标准治疗，或钳夹组（n = 22）在26小时内额外接受围手术期高胰岛素（正规胰岛素以0.1 IU·kg⁻¹·h⁻¹的固定速率）正常血糖（血浆葡萄糖在3.0至6.0 mmol·L⁻¹之间）钳夹。我们从基线麻醉诱导至术后第二天（POD）结束定期测量下丘脑 - 垂体 - 肾上腺（HPA）轴、交感肾上腺轴和胰高血糖素的内分泌反应，以及血浆葡萄糖和胰岛素。
两组临床结局无差异。对照组在手术结束时出现高血糖，并持续至POD2的最后测量点，而血浆胰岛素水平在POD1早晨之前保持不变。干预组在钳夹期间血糖维持正常，而胰岛素水平在600至800 pmol·L⁻¹之间。两组中，血浆促肾上腺皮质激素（ACTH）和皮质醇从体外循环停止后6小时开始升高。然而，在钳夹期间，干预组的HPA轴反应明显降低，表现为血浆ACTH曲线下面积增加比对照组小47%（P = 0.035），血浆皮质醇增加比对照组小27%（P = 0.002）。与基线相比，两组中肾上腺素和去甲肾上腺素在钳夹间隔结束至POD2时均升高。令人惊讶的是，干预组钳夹间隔后肾上腺素水平曲线下面积比对照组高47%（P = 0.026）。
CABG期间的高胰岛素正常血糖钳夹在心肌再灌注期的前18小时延迟并减弱HPA轴反应，而在钳夹后，血浆肾上腺素更高。延迟皮质醇反应对CABG临床结局的影响仍有待阐明。
