加拿大安大略省临床评价科学研究所Amit X. Garg小组近日取得一项新成果。他们的最新研究分析了慢性肾病患者服用巴氯芬与脑病的关系。相关论文发表在2019年11月9日出版的《美国医学会杂志》上。

目前，至少有30例报告认为肌肉松弛剂巴氯芬与慢性肾病（CKD）患者的脑病有关。

研究组在加拿大安大略省进行了一项基于人群的回顾性队列研究，对2007-2018年间的相关医疗数据进行分析。参与者包括15942名CKD老年患者，中位年龄为77岁，9707例每日服用巴氯芬≥20mg，6235例每日服用巴氯芬<20mg。脑病定义为谵妄、定向障碍、短暂意识改变、短暂性脑缺血发作或不明原因的痴呆。

治疗30天后，巴氯芬≥20mg组中有1.11%的患者因脑病住院，而巴氯芬<20mg组为0.42%。在亚组分析中，当肾小球滤过率（eGFR）较低时，脑病的绝对风险增加，eGFR为30-44时风险为1.23%，eGFR<30时风险升至2.90%。与284263名未服用巴氯芬的人群进行比较，服用巴氯芬的患者脑病风险显著增加，<20mg组的加权风险比为5.90，≥20mg组的加权风险比为19.8。

综上，老年CKD患者服用高剂量巴氯芬30天脑病的发病率显著高于低剂量组。医务人员在使用巴氯芬时需权衡利弊。

附：英文原文

Title: Association of Baclofen With Encephalopathy in Patients With Chronic Kidney Disease

Author: Flory T. Muanda, Matthew A. Weir, Lavanya Bathini, Peter G. Blake, Kianna Chauvin, Stephanie N. Dixon, Eric McArthur, Jessica M. Sontrop, Louise Moist, Amit X. Garg

Issue&Volume: November 9, 2019

Abstract:

Importance  

At least 30 case reports have linked the muscle relaxant baclofen to encephalopathy in patients with chronic kidney disease (CKD).

Objective  

To compare the 30-day risk of encephalopathy in patients with CKD and newly prescribed baclofen at greater than or equal to 20 mg per day vs less than 20 mg per day. The secondary objective was to compare the risk of encephalopathy in baclofen users vs nonusers.

Design, Setting, and Participants

Retrospective population-based cohort study in Ontario, Canada (2007-2018) using linked health care data. Participants comprised 15942 older adults (aged 66 years or older) with CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 but not receiving dialysis). The primary cohort was restricted to patients who were newly prescribed baclofen; participants in the secondary cohort were new users and nonusers.

Exposures  

Prescription for oral baclofen greater than or equal to 20 mg per day vs less than 20 mg per day.

Main Outcomes and Measures

Hospital admission with encephalopathy, defined as a main diagnosis of delirium, disorientation, transient alteration of awareness, transient cerebral ischemic attack, or unspecified dementia within 30 days of starting baclofen. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RRs) were obtained using modified Poisson regression and weighted risk differences (RDs) using binomial regression. Prespecified subgroup analyses were conducted by eGFR category.

Results  

The primary cohort comprised 15942 patients with CKD (9699 [61%] women; median age, 77 years [interquartile range, 71-82]; 9707 [61%] patients started baclofen at ≥20 mg/d and 6235 [39%] at <20 mg/d). The primary outcome, hospitalization with encephalopathy, occurred in 108/9707 (1.11%) patients who started baclofen at greater than or equal to 20 mg per day and in 26/6235 (0.42%) who started baclofen at less than 20 mg per day; weighted RR, 3.54 (95% CI, 2.24 to 5.59); weighted RD, 0.80% (95% CI, 0.55% to 1.04%). In subgroup analysis, the absolute risk increased progressively at lower eGFR (weighted RD eGFR 45-59, 0.42% [95% CI, 0.19%-0.64%]; eGFR 30-44, 1.23% [95% CI, 0.62%-1.84%]; eGFR <30, 2.90% [95% CI, 1.30%-4.49%]; P for interaction, <.001]). In the secondary comparison with 284263 nonusers, both groups of baclofen users had a higher risk of encephalopathy (<20 mg/d weighted RR, 5.90 [95% CI, 3.59 to 9.70] and ≥20 mg/d weighted RR, 19.8 [95% CI, 14.0 to 28.0]).

Conclusions and Relevance  

Among older patients with CKD who were newly prescribed baclofen, the 30-day incidence of encephalopathy was increased among those prescribed higher doses compared with lower doses. If verified, these risks should be balanced against the benefits of baclofen use.

DOI: 10.1001/jama.2019.17725

Source: https://jamanetwork.com/journals/jama/fullarticle/2754806