Khan Attiya, DeMott Joshua M, Varughese Christy, Hammond Drayton A
Department of Pharmacy, Rush University Medical Center, 1653 W. Congress Pkwy, Chicago, IL.
Department of Pharmacy, Rush University Medical Center, 1653 W. Congress Pkwy, Chicago, IL; Department of Internal Medicine, Rush Medical College, Chicago, IL.
Chest. 2020 Jul;158(1):157-163. doi: 10.1016/j.chest.2020.01.051. Epub 2020 Mar 6.
Pharmacodynamic and pathophysiologic changes in critically ill adults receiving cefepime may increase the risk of adverse events.
What is the impact of cefepime exposure on neurotoxicity development in critically ill adults with renal dysfunction?
Critically ill adults with creatinine clearance < 60 mL/min who received cefepime for ≥ 48 hours between January 1, 2014 and July 31, 2018 were evaluated for cefepime-associated neurotoxicity (CAN) development. Higher- and lower-dose cefepime exposure groups stratified by moderate (≥ 8 g vs < 8 g in first 48 hours) or severe (≥ 4 g vs < 4 g in first 48 hours) renal dysfunction were compared. Between-group comparisons were performed using Fisher exact tests. CAN-free survival was evaluated using Kaplan-Meier curves and log-rank tests.
Cefepime total dose in the first 48 hours was greater in the higher-dose cefepime group (3.7 ± 1.6 g vs 7.7 ± 2.2 g; P < .001). Cefepime-associated neurotoxicity occurred infrequently in both lower- (n = 108) and higher-dose (n = 92) cefepime groups (4% vs 10%, OR 2.82, 95% CI, 0.84-9.48, P = .093). The frequencies of cefepime-associated neurotoxicity were similar between lower- and higher-dose cefepime groups when moderate renal dysfunction subgroups were compared (5% vs 7%, OR 1.42, 95% CI, 0.34-5.92, P = .72) and numerically greater in the higher-dose cefepime group in the severe renal dysfunction subgroup (0 vs 16%, P = .064). Times to cefepime-associated neurotoxicity development and resolution were similar between lower- and higher-dose groups. Durations of CAN-free survival were similar between lower- and higher-dose groups. Most patients who developed cefepime-associated neurotoxicity displayed altered mental status (n = 12, 92%).
Cefepime-associated neurotoxicity is an uncommon occurrence in critically ill adults. Patients with severe renal dysfunction receiving higher-dose cefepime may be at greater risk of cefepime-associated neurotoxicity, although this requires additional investigation.
接受头孢吡肟的重症成年患者的药效学和病理生理学变化可能会增加不良事件的风险。
头孢吡肟暴露对肾功能不全的重症成年患者神经毒性发展有何影响？
对2014年1月1日至2018年7月31日期间肌酐清除率<60 mL/分钟且接受头孢吡肟≥48小时的重症成年患者进行头孢吡肟相关神经毒性（CAN）发展情况评估。比较按中度（前48小时≥8 g vs <8 g）或重度（前48小时≥4 g vs <4 g）肾功能不全分层的高剂量和低剂量头孢吡肟暴露组。组间比较采用Fisher精确检验。使用Kaplan-Meier曲线和对数秩检验评估无CAN生存期。
高剂量头孢吡肟组前48小时的头孢吡肟总剂量更高（3.7±1.6 g vs 7.7±2.2 g；P<.001）。低剂量（n = 108）和高剂量（n = 92）头孢吡肟组中头孢吡肟相关神经毒性的发生均不常见（4% vs 10%，OR 2.82，95%CI，0.84 - 9.48，P =.093）。比较中度肾功能不全亚组时，低剂量和高剂量头孢吡肟组的头孢吡肟相关神经毒性发生率相似（5% vs 7%，OR 1.42，95%CI，0.34 - 5.92，P =.72），而在重度肾功能不全亚组中，高剂量头孢吡肟组的发生率在数值上更高（0 vs 16%，P =.064）。低剂量和高剂量组之间头孢吡肟相关神经毒性发展和消退的时间相似。低剂量和高剂量组之间无CAN生存期的持续时间相似。大多数发生头孢吡肟相关神经毒性的患者表现为精神状态改变（n = 12，92%）。
头孢吡肟相关神经毒性在重症成年患者中并不常见。接受高剂量头孢吡肟的重度肾功能不全患者可能发生头孢吡肟相关神经毒性的风险更高，尽管这需要进一步研究。
