From the Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio.
Ohio University Heritage College of Osteopathic Medicine, Cleveland, Ohio.
Anesth Analg. 2024 Jun 1;138(6):1304-1312. doi: 10.1213/ANE.0000000000006863. Epub 2024 May 20.
The cause of postoperative delirium is unknown, but it is thought to result at least in part from inflammation. Metformin, besides its hypoglycemic properties, demonstrates anti-inflammatory effects systemically and in the brain. We tested the primary hypothesis that chronic metformin use in adults with type 2 diabetes is associated with less delirium during the first 5 days after major noncardiac surgery. Secondary outcomes were a composite of serious complications (myocardial infarction, cardiac arrest, stage 2-3 acute kidney injury [AKI], and mortality) and time to discharge alive.
We considered adults with type 2 diabetes who did or did not routinely use metformin daily and had noncardiac surgery. Delirium was assessed by Confusion Assessment Method for Intensive Care Unit (CAM-ICU) or brief Confusion Assessment Method (bCAM) for 5 postoperative days. Postoperative AKI was defined by Kidney Disease Improving Global Guidelines. Logistic regression and generalized estimating equation models accounted for within-patient correlation across multiple surgeries and explored the association between metformin use and postoperative delirium and complications. Inverse propensity score weighting and propensity score calibration (PSC) adjusted for confounding variables.
No significant difference was observed in the incidence of postoperative delirium between the 2 groups, with 260 of 4744 cases (5.5%) among metformin users and 502 of 5918 cases (8.5%) cases in nonmetformin users, for an odds ratio of 0.88 (95% confidence interval [CI], 0.73-1.05; P = .155), number-needed-to-expose = 118 patients. Similarly, there were fewer composite complications in metformin users (3.3%) than in nonusers (11.7%); However, the common-effect odds ratio of 0.67 was not statistically significant (97.5% CI, 0.39-1.17; P = .106). Discharge from the hospital was significantly faster in patients who took metformin (3 [interquartile range, IQR, 1-5] days for metformin users and 3 [IQR, 2-6] days for nonmetformin users), with a hazard ratio of 1.07 for early discharge, and tight CIs (1.01-1.13).
Chronic metformin use was associated with slightly and nonsignificantly less delirium. However, patients who used metformin had clinically meaningfully fewer major complications, mostly stage 2 to 3 kidney injury. While not statistically significant, the reduction was substantial and warrants further investigation because there is currently no effective preventive measure for perioperative renal injury. Benefit would be especially meaningful if it could be produced by acute perioperative treatment. Finally, metformin was associated with faster hospital discharge, although not by a clinically meaningful amount.
术后谵妄的病因尚不清楚，但据认为至少部分是由炎症引起的。二甲双胍除了具有降血糖作用外，还具有全身和大脑的抗炎作用。我们检验了一个主要假设，即 2 型糖尿病成年患者长期使用二甲双胍与主要非心脏手术后的前 5 天内发生谵妄的风险较低相关。次要结局是严重并发症（心肌梗死、心脏骤停、2-3 期急性肾损伤[AKI]和死亡率）的复合结果和存活出院时间。
我们考虑了有或没有常规每日使用二甲双胍且接受非心脏手术的 2 型糖尿病成年人。使用重症监护病房意识模糊评估法（CAM-ICU）或简短意识模糊评估法（bCAM）评估术后 5 天的谵妄。术后 AKI 采用肾脏病改善全球指南定义。Logistic 回归和广义估计方程模型考虑了多个手术之间的患者内相关性，并探讨了二甲双胍使用与术后谵妄和并发症之间的关系。逆倾向评分加权和倾向评分校准（PSC）调整了混杂变量。
在接受二甲双胍治疗的 4744 例病例中（5.5%）和未接受二甲双胍治疗的 5918 例病例中（8.5%），两组术后谵妄的发生率无显著差异，比值比为 0.88（95%置信区间[CI]，0.73-1.05；P =.155），需要暴露的人数=118 例。同样，在接受二甲双胍治疗的患者中，复合并发症的发生率较低（3.3%），而非使用者的发生率较高（11.7%）；然而，常见效应比值 0.67并不具有统计学意义（97.5%CI，0.39-1.17；P =.106）。服用二甲双胍的患者出院速度明显更快（二甲双胍组为 3[四分位距[IQR]，1-5]天，非二甲双胍组为 3[IQR，2-6]天），提前出院的风险比为 1.07，且置信区间（CI）较紧（1.01-1.13）。
慢性二甲双胍使用与轻微但无统计学意义的谵妄发生率降低相关。然而，使用二甲双胍的患者发生严重并发症（主要为 2-3 期 AKI）的情况明显减少。虽然没有统计学意义，但这种减少幅度较大，值得进一步研究，因为目前还没有有效的围手术期肾损伤预防措施。如果能通过围手术期急性治疗产生效果，将具有重要意义。最后，二甲双胍与更快的出院时间相关，尽管没有达到临床意义的程度。
