Valdes Eduard, Fang Taolin, Boffa Michael, Frontera Jennifer A
Department of Neurology, Columbia University Irving Medical Center, New York, NY.
Department of Neurology, New York University Grossman School of Medicine, New York, NY.
Crit Care Med. 2024 Jan 1;52(1):e1-e10. doi: 10.1097/CCM.0000000000006065. Epub 2023 Sep 20.
Critically ill patients eliminate levetiracetam (LEV) more rapidly than healthy controls, yet low doses are commonly used for seizure prophylaxis in the ICU setting. We compared the rates of achievement of target serum levels and new onset seizure (clinical and/or electrographic) among patients who received low (500 mg bid) versus high (750-1,000 mg bid) dose LEV.
Prospective, observational study.
Tertiary care, academic center.
We included patients who received prophylactic LEV following traumatic brain injury, intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, or supratentorial neurosurgery between 2019 and 2021. Patients with a history of seizure, antiseizure medication use, or renal failure requiring dialysis were excluded.
None.
LEV levels were obtained at steady state. The impact of low-dose versus high-dose LEV on the primary outcome of target LEV levels (12-46 μg/mL), and the secondary outcome of clinical and/or electrographic seizure, were assessed using multivariable logistic regression analyses adjusting for age, LEV loading dose, BMI, primary diagnosis and creatinine clearance (CrCl).
Of the 205 subjects included in analyses, n = 106 (52%) received LEV 500 mg bid (median 13 mg/kg/d), and n = 99 (48%) received LEV 750-1,000 mg bid (median 25 mg/kg/d). Overall, 111 of 205 patients (54%) achieved target levels: 48 (45%) from the low-dose group versus 63 (64%) from the high-dose group (odds ratio [OR] 2.1; 95% CI, 1.1-3.7; p = 0.009). In multivariable analyses, high-dose LEV predicted target levels (adjusted OR [aOR] 2.23; 95% CI, 1.16-4.27; p = 0.016), and was associated with lower seizure odds (aOR 0.32; 95% CI, 0.13-0.82; p = 0.018) after adjusting for age, loading dose, BMI, diagnosis, and CrCl.
Underdosing of LEV was common, with only 54% of patients achieving target serum levels. Higher doses (750-1,000 mg bid) were more than twice as likely to lead to optimal drug levels and reduced the odds of seizure by 68% compared with low-dose regimens (500 mg bid).
重症患者比健康对照者更快地清除左乙拉西坦（LEV），然而在重症监护病房（ICU）环境中，低剂量常用于预防癫痫发作。我们比较了接受低剂量（500mg，每日两次）与高剂量（750 - 1000mg，每日两次）LEV的患者达到目标血清水平和新发癫痫（临床和/或脑电图）的发生率。
前瞻性观察性研究。
三级医疗学术中心。
我们纳入了2019年至2021年间因创伤性脑损伤、脑出血、自发性蛛网膜下腔出血或幕上神经外科手术而接受预防性LEV治疗的患者。排除有癫痫病史、使用抗癫痫药物或需要透析的肾衰竭患者。
无。
在稳态时获取LEV水平。使用多变量逻辑回归分析评估低剂量与高剂量LEV对目标LEV水平（12 - 46μg/mL）这一主要结局以及临床和/或脑电图癫痫发作这一次要结局的影响，并对年龄、LEV负荷剂量、体重指数（BMI）、主要诊断和肌酐清除率（CrCl）进行校正。
在纳入分析的205名受试者中，n = 106（52%）接受500mg，每日两次的LEV（中位数13mg/kg/d），n = 99（48%）接受750 - 1000mg，每日两次的LEV（中位数25mg/kg/d）。总体而言，205名患者中有111名（54%）达到目标水平：低剂量组48名（45%），高剂量组63名（64%）（优势比[OR]2.1；95%置信区间[CI]，1.1 - 3.7；p = 0.009）。在多变量分析中，高剂量LEV可预测目标水平（校正后OR[aOR]2.23；95%CI，1.16 - 4.27；p = 0.016），并且在对年龄、负荷剂量、BMI、诊断和CrCl进行校正后，与较低的癫痫发作几率相关（aOR 0.32；95%CI，0.13 - 0.82；p = 0.018）。
LEV剂量不足很常见，只有54%的患者达到目标血清水平。与低剂量方案（500mg，每日两次）相比，较高剂量（每日两次750-1000mg）达到最佳药物水平的可能性高出两倍多，且癫痫发作几率降低了68%。
