Evaluation of Free Valproate Concentration in Critically Ill Patients.
Evaluation of Free Valproate Concentration in Critically Ill Patients.
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评估重症患者的游离丙戊酸盐浓度。
DOI：
10.1097/cce.0000000000000746
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发表时间：
2022-09
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丙戊酸的蛋白结合在 ICU 患者中是可变的，即使在校正白蛋白时，总丙戊酸浓度也不能预测游离丙戊酸浓度。我们试图量化 ICU 患者的游离丙戊酸浓度，确定与游离丙戊酸浓度增加相关的危险因素，并评估游离丙戊酸浓度与潜在不良药物反应之间的关联。回顾性多中心队列研究。两个学术医疗中心。 ICU 中收集的年龄大于或等于 18 岁且伴有游离丙戊酸和总丙戊酸浓度的患者。没有任何。该研究纳入了 256 名患者，中位年龄为 56 岁（42-70 岁），其中 65% 的患者为男性。丙戊酸总浓度中位数为 53 µg/mL (38–70 µg/mL)，游离丙戊酸浓度为 12 µg/mL (7–20 µg/mL)，游离比例为 23.6% (17.0–33.9%)。 70% 的患者出现游离丙戊酸浓度和总丙戊酸浓度之间的治疗不一致。在多变量分析中，游离丙戊酸浓度的增加与较高的总丙戊酸浓度（每增加 5 µg/mL，增加 1.72 µg/mL，95% CI，1.48–1.96）和较低的血清白蛋白（每减少 1 g/dL，增加 4.60 µg/mL，95% CI，2.71–6.49）相关。游离丙戊酸浓度与不良反应之间没有关联。大多数患者（70%）的丙戊酸总浓度和游离浓度不一致。丙戊酸游离浓度增加与低白蛋白血症和总丙戊酸浓度相关。对于许多 ICU 患者来说，基于丙戊酸总浓度的临床决策可能是不正确的。需要进行前瞻性对照研究来证实这些发现及其临床相关性。
Protein binding of valproate is variable in ICU patients, and the total valproate concentration does not predict the free valproate concentration, even when correcting for albumin. We sought to quantify valproate free concentration among ICU patients, identify risk factors associated with an increasing free valproate concentration, and evaluate the association between free valproate concentration with potential adverse drug effect. Retrospective multicenter cohort study. Two academic medical centers. Patients greater than or equal to 18 years of age with concomitant free and total valproate concentrations collected in the ICU. None. Two-hundred fifty-six patients were included in the study, with a median age of 56 years (42–70) and 65% of patients were male. The median total valproate concentration was 53 µg/mL (38–70 µg/mL), the free valproate concentration was 12 µg/mL (7–20 µg/mL), and the free fraction was 23.6% (17.0–33.9%). Therapeutic discordance between the free and total valproate concentration occurred in 70% of patients. On multivariable analysis, increased free valproate concentration was associated with higher total valproate concentration (per 5 µg/mL increase, increase 1.72 µg/mL, 95% CI, 1.48–1.96) and lower serum albumin (per 1 g/dL decrease, increase 4.60 µg/mL, 95% CI, 2.71–6.49). There was no association between free valproate concentration and adverse effects. The valproate total and free concentration was discordant in the majority of patients (70%). Increased valproate free concentration was associated with hypoalbuminemia and total valproate concentration. Clinical decisions based on total valproate concentration may be incorrect for many ICU patients. Prospective, controlled studies are needed to confirm these findings and their clinical relevance.