The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial
The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial
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DOI：
10.1111/bcp.13263
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发表时间：
2017-08-01
影响因子：
3.4
通讯作者：
Loke, Yoon K.
中科院分区：
文献类型：
--
作者：
Chan, Wei Yee;Clark, Allan B.;Loke, Yoon K.
目的复方新诺明在治疗耶氏肺孢子虫和弓形虫以及尿路感染方面保持着既定的作用。观察性研究报告高钾血症与复方新诺明有关，这可能源于阿米洛利样保钾作用。目前的研究调查了没有急性感染的患者血清钾的变化，以及合并使用的抗利尿药对此效果的影响。方法对间质性肺疾病患者进行了一项随机对照试验，这些患者被分配到安慰剂组或960mg复方新诺明治疗组，每天两次。在基线、6周、6、9和12个月时测量血清钾和肌酐。主要结局是 6 周时复方新诺明与安慰剂之间平均血清钾浓度的差异。结果基线时平均血清钾水平相似：87 名复方新诺明组参与者为 4.24 (0.44) mmol l(-1)，83 名对照参与者为 4.25 (+/- 0.39) mmol l(-1)。复方新诺明在 6 周时显着增加平均血清钾水平，与安慰剂相比，平均值之间的差异为 0.21mmol l(-1) [95% 置信区间 (CI) 0.09, 0.34； P=0.001）。即使在排除使用抗利尿药物的患者后，仍可检测到血清钾的显着升高，复方新诺明与安慰剂相比的平均值差异为 0.23mmol l(-1) (95% CI 0.09, 0.38；P=0.002)。研究期间，有5/87（5.7%）服用复方新诺明的患者血清钾浓度达到5.5mmol l(-1)。结论复方新诺明显着增加血清钾浓度，即使在未使用抗利尿药的受试者中也是如此。虽然增加的幅度通常很小，但我们门诊队列中的一小部分患者出现了具有临床意义的高钾血症。
AimsCo-trimoxazole maintains a well-established role in the treatment of Pneumocystis jirovecii and Toxoplasma gondii, as well as urinary tract infections. Observational studies report hyperkalaemia to be associated with co-trimoxazole, which may stem from an amiloride-like potassium-sparing effect. The current study investigated changes in serum potassium in patients without acute infections, and the influence of concomitant antikaliuretic drugs on this effect.MethodsA post hoc analysis was carried out of a randomized controlled trial in patients with interstitial lung disease who were assigned to placebo or 960mg co-trimoxazole twice daily. Serum potassium and creatinine were measured at baseline, 6weeks, and 6, 9 and 12months. The primary outcome was the difference in mean serum potassium concentrations between co-trimoxazole and placebo at 6weeks.ResultsMean serum potassium levels were similar at baseline: 4.24 ( 0.44) mmol l(-1) in the 87 co-trimoxazole group participants and 4.25 (+/- 0.39) mmol l(-1) in the 83 control participants. Co-trimoxazole significantly increased mean serum potassium levels at 6weeks, with a difference between means compared with placebo of 0.21mmol l(-1) [95% confidence interval (CI) 0.09, 0.34; P=0.001). This significant increase in serum potassium was detectable even after exclusion of patients on antikaliuretic drugs, with a difference between means for co-trimoxazole compared with placebo of 0.23mmol l(-1) (95% CI 0.09, 0.38; P=0.002). There were 5/87 (5.7%) patients on co-trimoxazole whose serum potassium concentrations reached 5.5mmol l(-1) during the study period.ConclusionsCo-trimoxazole significantly increases serum potassium concentration, even in participants not using antikaliuretic drugs. While the magnitude of increase was often minor, a small proportion in our outpatient cohort developed hyperkalaemia of clinical importance.