Supplementary Material for: Associations of Pre-Transplant Prescription Narcotic Use with Clinical Complications after Kidney Transplantation

Background: The impact of narcotic use before kidney transplantation on post-transplant clinical outcomes is not well described. Methods: We examined integrated national transplant registry, pharmacy records, and Medicare billing claims to follow 16,322 kidney transplant recipients, of whom 28.3% filled a narcotic prescription in the year before transplantation. Opioid analgesic fills were normalized to morphine equivalents (ME) and expressed as mg/kg exposures (approximate quartiles: 0.1-1.7, 1.8-5.4, 5.5-23.7, and ≥23.8 mg/kg, respectively). Post-transplant cardiovascular, respiratory, neurological, accidents, substance abuse, and noncompliance events were identified using diagnosis codes on Medicare billing claims. Adjusted associations of ME level with post-transplant complications were quantified by multivariate Cox regression. Results: The incidence of complications at 3 years post-transplant among those with the highest pre-transplant ME exposure compared to no use included: ventricular arrhythmias, 1.1 vs. 0.2% (p < 0.001); cardiac arrest, 4.7 vs. 2.7% (p < 0.05); hypotension, 14 vs. 8% (p < 0.0001); hypercapnia, 1.6 vs. 0.9% (p < 0.05); mental status changes, 5.3 vs. 2.7% (p < 0.001); drug abuse/dependence, 7.0 vs. 1.7% (p < 0.0001); alcohol abuse, 1.8 vs. 0.6% (p = 0.0001); accidents, 0.9 vs. 0.3% (p < 0.05); and noncompliance, 3.5 vs. 2.3% (p < 0.05). In multivariate analyses, transplant recipients with the highest level of pre-transplant narcotic use had approximately 2 to 4 times the risks of post-transplant ventricular arrhythmias, mental status changes, drug abuse, alcohol abuse, and accidents compared with non-users, and 35-45% higher risks of cardiac arrest and hypotension. Conclusion: Although associations may reflect underlying conditions or behaviors, high-level prescription narcotic use before kidney transplantation predicts increased risk of clinical complications after transplantation.

背景：肾移植术前使用麻醉性镇痛药对移植后临床结局的影响尚未得到充分阐明。方法：本研究整合全国移植登记系统、药房处方记录以及联邦医疗保险（Medicare）结算账单数据，对16322名肾移植受者进行随访，其中28.3%的受者在移植前1年内开具过麻醉性镇痛药处方。将阿片类镇痛药（Opioid analgesic）处方量换算为吗啡当量（morphine equivalents, ME），并以mg/kg为单位表示暴露量，其近似四分位数区间分别为0.1~1.7、1.8~5.4、5.5~23.7以及≥23.8 mg/kg。借助联邦医疗保险结算账单中的诊断编码，我们识别出移植后心血管、呼吸、神经系统不良事件，意外伤害，药物滥用以及治疗不依从事件。采用多变量Cox回归分析量化吗啡当量水平与移植后并发症之间的校正后关联。结果：与未使用阿片类镇痛药的受者相比，移植前吗啡当量暴露水平最高的受者在移植后3年的各类并发症发生率如下：室性心律失常为1.1% vs 0.2%（p<0.001）；心搏骤停为4.7% vs 2.7%（p<0.05）；低血压为14% vs 8%（p<0.0001）；高碳酸血症为1.6% vs 0.9%（p<0.05）；精神状态改变为5.3% vs 2.7%（p<0.001）；药物滥用/依赖为7.0% vs 1.7%（p<0.0001）；酒精滥用为1.8% vs 0.6%（p=0.0001）；意外伤害为0.9% vs 0.3%（p<0.05）；治疗不依从为3.5% vs 2.3%（p<0.05）。多变量分析结果显示，与未使用阿片类镇痛药的受者相比，移植前高剂量使用麻醉性镇痛药的受者发生移植后室性心律失常、精神状态改变、药物滥用、酒精滥用以及意外伤害的风险约为未使用者的2~4倍，发生心搏骤停和低血压的风险则高出35%~45%。结论：尽管上述关联可能反映了受者的基础疾病或行为特征，但肾移植术前高剂量开具麻醉性镇痛药的行为可预测移植后临床并发症风险升高。