Association Between Preoperative Metformin Exposure and Postoperative Outcomes in Adults With Type 2 Diabetes
Association Between Preoperative Metformin Exposure and Postoperative Outcomes in Adults With Type 2 Diabetes
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DOI：
10.1001/jamasurg.2020.0416
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发表时间：
2020-06-01
期刊：
影响因子：
16.9
通讯作者：
Neal, Matthew D.
中科院分区：
文献类型：
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作者：
Reitz, Katherine M.;Marroquin, Oscar C.;Neal, Matthew D.
具有合并症的成人在大手术干预压力后生理储备较少，术后死亡率和再入院率增加。目的评估术前有或没有二甲双胍处方的糖尿病患者的术后死亡率和再入院率。设计、环境和参与者本队列研究从宾夕法尼亚州一个多中心、单一医疗保健系统的电子健康记录中获取数据。纳入的对象是2010年1月1日至2016年1月1日在该系统内的15家社区和学术医院接受大手术并入院的成人糖尿病患者。没有二甲双胍治疗临床指征的个体被排除在外。随访一直持续到2018年12月18日。术前二甲双胍暴露定义为手术前180天内服用1张或更多的二甲双胍处方。主要结局和测量方法比较术前未开二甲双胍和开二甲双胍两组患者的术后全因死亡率、出院90天内再入院率和术前中性粒细胞与白细胞比值测量的炎症情况。在倾向评分匹配的队列中计算相应的绝对风险降低率（ARR）和校正风险比（HR） （95% CI）。结果在10088例接受大手术干预的糖尿病患者中，5962例（59%）术前有二甲双胍处方。共有5460例患者符合倾向评分，其中平均（SD）年龄为67.7（12.2）岁，女性2866例（53%）。在倾向评分匹配的队列中，术前二甲双胍处方与降低90天死亡率（调整后危险度，0.72 [95% CI, 0.55-0.95]； ARR, 1.28% [95% CI, 0.26-2.31]）和再入院风险相关，死亡率在30天（ARR, 2.09% [95% CI, 0.35-3.82]；亚危险度，0.84 [95% CI, 0.72-0.98]）和90天（ARR, 2.78% [95% CI, 0.62-4.95]；亚危险度，0.86 [95% CI, 0.77-0.97]）均为竞争风险。术前使用二甲双胍的患者与未使用二甲双胍的患者相比炎症减轻（平均中性粒细胞与白细胞比值，4.5 [95% CI, 4.3-4.6] vs 5.0 [95% CI, 4.8-5.3]; P < .001）。e值分析显示对未测量的混杂具有稳健性。结论和相关性本研究发现，在大手术前给2型糖尿病患者开二甲双胍处方与降低手术后风险调整死亡率和再入院率之间存在关联。这种联系值得进一步调查。
IMPORTANCE Adults with comorbidity have less physiological reserve and an increased rate of postoperative mortality and readmission after the stress of a major surgical intervention.OBJECTIVE To assess postoperative mortality and readmission among individuals with diabetes with or without preoperative prescriptions for metformin.DESEGN, SETTING, AND PARTICIPANTS This cohort study obtained data from the electronic health record of a multicenter, single health care system in Pennsylvania. Included were adults with diabetes who underwent a major operation with hospital admission from January 1, 2010, to January 1, 2016, at 15 community arid academic hospitals within the system. Individuals without a clinical indication for metformin therapy were excluded. Follow-up continued until December 18, 2018.EXPOSURES Preoperative metformin exposure was defined as 1 or more prescriptions for metformin in the 180 days before the surgical procedure.MAIN OUTCOMES AND MEASURES All-cause postoperative mortality, hospital readmission within 90 days of discharge, and preoperative inflammation measured by the neutrophil to leukocyte ratio were compared between those with and without preoperative prescriptions for metformin. The corresponding absolute risk reduction (ARR) and adjusted hazard ratio (HR) with 95% CI were calculated in a propensity score-matched cohort.RESULTS Among the 10 088 individuals with diabetes who underwent a major surgical intervention, 5962 (59%) had preoperative metformin prescriptions. A total of 5460 patients were propensity score-matched, among whom the mean (SD) age was 67.7 (12.2) years, and 2866 (53%) were women. In the propensity score-matched cohort, preoperative metformin prescriptions were associated with a reduced hazard for 90-day mortality (adjusted HR, 0.72 [95% CI, 0.55-0.95]; ARR, 1.28% [95% CI, 0.26-2.31]) and hazard of readmission, with mortality as a competing risk at both 30 days (ARR, 2.09% [95% CI, 0.35-3.82]; sub-HR, 0.84 [95% CI, 0.72-0.98]) and 90 days (ARR, 2.78% [95% CI, 0.62-4.95]; sub-HR, 0.86 [95% CI, 0.77-0.97]). Preoperative inflammation was reduced in those with metformin prescriptions compared with those without (mean neutrophil to leukocyte ratio, 4.5 [95% CI, 4.3-4.6] vs 5.0 [95% CI, 4.8-5.3]; P < .001). E-value analysis suggested robustness to unmeasured confounding.CONCLUSIONS AND RELEVANCE This study found an association between metformin prescriptions provided to individuals with type 2 diabetes before a major surgical procedure and reduced risk-adjusted mortality and readmission after the operation. This association warrants further investigation.