Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
Br J Anaesth. 2023 Oct;131(4):682-686. doi: 10.1016/j.bja.2023.06.063. Epub 2023 Aug 2.
Use of sodium-glucose transporter-2 (SGLT2) inhibitors has dramatically increased over the past decade. This medication class predisposes patients to euglycaemic diabetic ketoacidosis, particularly during times of physiologic stress, including fasting and surgery. Beyond case reports and series, a systematic description of perioperative metabolic effects of SGLT2 inhibitors is lacking.
We examined the degree of anion gap acidosis, controlling for non-ketone anions, in patients undergoing surgery at Massachusetts General Hospital in 2016-22. We constructed a multivariable regression model incorporating known non-ketone contributors to the postoperative anion gap (albumin, lactate, estimated glomerular filtration rate, and preoperative anion gap), hold time, and interaction terms between hold time and three previously suggested risk factors for euglycaemic diabetic ketoacidosis: emergency surgery, cardiac surgery, and insulin use.
In 463 patients on SGLT2 inhibitors, we observed a strong association between decreased hold time and postoperative anion gap (P<0.001 in a univariable analysis; -0.43, 95% confidence interval [-0.76 to -0.11] change in anion gap per day held, P=0.01 in a multivariable analysis). A significant interaction between hold time and emergency surgery was observed, whereas there was no apparent interaction with insulin use or cardiac surgery.
These findings provide the first evidence that an anion gap acidosis, likely from ketoacids, develops in all patients who do not hold SGLT2 inhibitors before surgery rather than in an idiosyncratic few. If an SGLT2 inhibitor is unable to be stopped, postoperative monitoring of anion gap and serum ketones can help detect clinically significant euglycaemic diabetic ketoacidosis, particularly in those undergoing emergency surgery.
在过去十年中，钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂的使用显著增加。这种药物类别使患者易发生血糖正常的糖尿病酮症酸中毒，尤其是在生理应激期间，包括禁食和手术期间。除病例报告和系列研究外，缺乏 SGLT2 抑制剂围手术期代谢影响的系统描述。
我们检查了 2016 年至 2022 年在马萨诸塞州综合医院接受手术的患者的阴离子间隙酸中毒程度，同时控制了非酮阴离子。我们构建了一个多变量回归模型，其中包括已知的术后阴离子间隙的非酮体贡献因素（白蛋白、乳酸、估计肾小球滤过率和术前阴离子间隙）、保持时间以及三个先前提出的与血糖正常的糖尿病酮症酸中毒相关的风险因素（紧急手术、心脏手术和胰岛素使用）之间的交互项。
在 463 名服用 SGLT2 抑制剂的患者中，我们观察到保持时间减少与术后阴离子间隙之间存在很强的关联（单变量分析中 P<0.001；多变量分析中 P=0.01，每天保持时间阴离子间隙变化 -0.43，95%置信区间[-0.76 至-0.11]）。观察到保持时间与紧急手术之间存在显著的交互作用，而与胰岛素使用或心脏手术之间没有明显的交互作用。
这些发现首次提供了证据，表明所有未在手术前停止 SGLT2 抑制剂的患者都会发生阴离子间隙酸中毒，而不是在少数患者中发生。如果无法停止 SGLT2 抑制剂，如果无法停止 SGLT2 抑制剂，则可以通过监测阴离子间隙和血清酮体来帮助发现临床上明显的血糖正常的糖尿病酮症酸中毒，特别是在接受紧急手术的患者中。
