Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan.
Department of Infection Control and Prevention, Tokushima University Hospital, Tokushima, Japan.
Clin Ther. 2018 Feb;40(2):252-260. doi: 10.1016/j.clinthera.2017.12.006. Epub 2018 Jan 2.
Liposomal amphotericin B (L-AMB) is an essential antifungal agent for patients with hematologic diseases; however, the drug causes severe hypokalemia at a high frequency. Meanwhile, there is little evidence regarding the risk factors for L-AMB-induced severe hypokalemia, and the prevention protocol has not been established. The goal of this study was to identify the risk factors related to severe hypokalemia induced by L-AMB in hematologic patients.
Seventy-eight hematologic patients with a first administration of L-AMB were enrolled in the study. Eleven patients who had serum potassium levels <3.0 mmol/L before L-AMB administration and 12 patients who received L-AMB administration within 3 days were excluded. Patients who had a serum potassium level <3.0 mmol/L during L-AMB administration were classified into a hypokalemia group (n = 26), and those who had a serum potassium level ≥3.0 mmol/L were classified into a non-hypokalemia group (n = 29). The patient characteristics were analyzed retrospectively. In addition, the usefulness of potassium supplementation was analyzed for those patients who received potassium formulations (non-hypokalemia group, n = 15; hypokalemia group, n = 24).
Twenty-six patients had hypolalemia after L-AMB administration. Hypokalemia with serum potassium levels <3.0 mmol/L was observed ~7 days after starting L-AMB administration. The patient characteristics, L-AMB dose, and L-AMB administration period did not differ between the 2 groups. In the patients who received potassium formulations, the period between starting L-AMB administration and starting potassium supplementation was significantly shorter in the non-hypokalemia group than in the hypokalemia group (median, 0 vs 4 days, respectively; P < 0.01); the potassium dose was not different between the 2 groups. A receiver-operating characteristic curve revealed that the cutoff time for the start of potassium supplementation to reduce the incidence of L-AMB-induced hypokalemia was 3 days. Multivariate logistic regression analysis revealed that beginning potassium supplementation within 2 days from the start of L-AMB administration was an independent factor reducing the risk of L-AMB-induced hypokalemia (odds ratio, 0.094 [95% CI, 0.019-0.47]).
This study showed that starting administration of a potassium formulation within 2 days from the start of L-AMB administration was a risk reduction factor for L-AMB-induced hypokalemia. This finding indicates that early potassium supplementation should be incorporated into the regimen of hypokalemia management when L-AMB is used.
两性霉素 B 脂质体(L-AMB)是血液病患者的一种重要抗真菌药物;然而,该药会导致严重低钾血症的高频率发生。同时,关于 L-AMB 引起的严重低钾血症的危险因素的证据很少,并且尚未建立预防方案。本研究的目的是确定与血液病患者中 L-AMB 诱导的严重低钾血症相关的危险因素。
本研究纳入了 78 例首次接受 L-AMB 治疗的血液病患者。排除了 11 例 L-AMB 治疗前血清钾水平<3.0mmol/L 的患者和 12 例在 3 天内接受 L-AMB 治疗的患者。在 L-AMB 治疗期间血清钾水平<3.0mmol/L 的患者被分为低钾血症组(n=26),而血清钾水平≥3.0mmol/L 的患者被分为非低钾血症组(n=29)。回顾性分析患者特征。此外,对于接受钾制剂治疗的患者(非低钾血症组,n=15;低钾血症组,n=24),分析了钾补充的有用性。
26 例患者在 L-AMB 治疗后出现低血钾症。低钾血症伴血清钾水平<3.0mmol/L 发生在开始 L-AMB 治疗后约 7 天。两组患者特征、L-AMB 剂量和 L-AMB 治疗时间无差异。在接受钾制剂治疗的患者中,非低钾血症组开始 L-AMB 治疗至开始钾补充的时间明显短于低钾血症组(中位数分别为 0 天和 4 天,P<0.01);两组的钾剂量无差异。受试者工作特征曲线显示,开始钾补充的时间为 3 天,可以降低 L-AMB 引起的低钾血症的发生率。多变量逻辑回归分析显示,在开始 L-AMB 治疗的 2 天内开始钾补充是降低 L-AMB 诱导的低钾血症风险的独立因素(比值比,0.094[95%CI,0.019-0.47])。
本研究表明,在开始 L-AMB 治疗的 2 天内开始给予钾制剂是降低 L-AMB 诱导的低钾血症风险的因素。这一发现表明,在使用 L-AMB 时,应将早期钾补充纳入低钾血症管理方案。