Chan B S, Cheng S, Isoardi K Z, Chiew A, Siu W, Shulruf B, Vecellio E, Buckley N A
Department of Emergency Medicine & Clinical Toxicology, Prince of Wales Hospital, Sydney, Australia.
Faculty of Medicine, University of New South Wales, Sydney, Australia.
Clin Toxicol (Phila). 2020 Nov;58(11):1023-1027. doi: 10.1080/15563650.2020.1726376. Epub 2020 Feb 18.
Severe lithium toxicity is commonly observed in older people. We aimed to determine the extent to which age is associated with increased severity of chronic lithium poisoning and of which a range of possible factors might explain the associations. We did a retrospective review of patients aged ≥15 years old with serum lithium concentrations ≥1.3 mmol/L from three hospitals. Clinical details, treatment and outcomes were recorded. eGFR, creatinine and lithium clearance were calculated. The severity of lithium toxicity was graded into five categories (Amdisen score). ANOVA was used to quantify the association between age and severity. Spearman correlation coefficient was used to explore relationships between age and different factors expected to alter severity. Ordinal regression analysis was used to determine the interdependence of age and these factors and age on severity of lithium toxicity. From 2008-2018, there were 242 patients with a median age of 56.5 years (IQR: 41-69). There were 156 females (64%). There was a statistically significant association between Amdisen severity scores and age ( = .0004). The median calculated eGFR was 65 mL/min/1.73 m (IQR: 41-91) with a corresponding estimated lithium clearance of 18 mL/min (IQR: 13.8-22.8). There was no correlation of age with initial serum lithium concentration ( = .76). There was a strong correlation between age and estimated lithium clearance ( = -0.72, 95% CI: -0.78 to -0.66, < .001), lithium daily dose ( = -0.65, 95% CI: -0.72 to -0.57, < .0001) and lithium concentration/dose ( = 0.62, 95% CI: 0.53-0.69, < .0001). There was a weak correlation between age and infection ( = 0.18, 95% CI: 0.04-0.31, = .009) and drug interactions ( = 0.25, 95% CI: 0.11-0.37, = .0003). Ordinal regression indicated the independent predictors for severity of lithium toxicity were lithium concentration ( < .0001) and lithium clearance ( = .03) adjusted for age and dose. Despite lower lithium doses, older patients had more severe toxicity. Increased severity of lithium toxicity in the elderly is largely explainable by decreased lithium clearance from multiple factors such as age-related decline in renal function, drug interactions and infection.
严重锂中毒在老年人中较为常见。我们旨在确定年龄与慢性锂中毒严重程度增加之间的关联程度,以及一系列可能的因素如何解释这种关联。我们对三家医院中年龄≥15岁、血清锂浓度≥1.3 mmol/L的患者进行了回顾性研究。记录了临床细节、治疗情况和结局。计算了估算肾小球滤过率(eGFR)、肌酐和锂清除率。锂中毒的严重程度分为五类(阿姆迪森评分)。采用方差分析来量化年龄与严重程度之间的关联。使用斯皮尔曼相关系数来探讨年龄与预期会改变严重程度的不同因素之间的关系。采用有序回归分析来确定年龄和这些因素以及年龄与锂中毒严重程度之间的相互依存关系。2008年至2018年期间,共有242例患者,中位年龄为56.5岁(四分位间距:41 - 69岁)。有156名女性(64%)。阿姆迪森严重程度评分与年龄之间存在统计学显著关联(P = 0.0004)。计算得到的中位eGFR为65 mL/min/1.73 m²(四分位间距:41 - 91),相应的估算锂清除率为18 mL/min(四分位间距:13.8 - 22.8)。年龄与初始血清锂浓度无相关性(P = 0.76)。年龄与估算锂清除率(r = -0.72,95%可信区间:-0.78至-0.66,P < 0.001)、锂日剂量(r = -0.65,95%可信区间:-0.72至-0.57,P < 0.0001)以及锂浓度/剂量(r = 0.62,95%可信区间:0.53 - 0.69,P < 0.0001)之间存在强相关性。年龄与感染(r = 0.18,95%可信区间:0.04 - 0.31,P = 0.009)和药物相互作用(r = 0.25,95%可信区间:0.11 - 0.37,P = 0.0003)之间存在弱相关性。有序回归表明,经年龄和剂量调整后,锂中毒严重程度的独立预测因素为锂浓度(P < 0.0001)和锂清除率(P = 0.03)。尽管锂剂量较低,但老年患者的毒性更严重。老年人锂中毒严重程度增加在很大程度上可归因于多种因素导致的锂清除率降低,如与年龄相关的肾功能下降、药物相互作用和感染。