van Gelder Thomas G, van Diem-Zaal Irene J, Dijkstra-Kersten Sandra M A, de Mul Nikki, Lalmohamed Arief, Slooter Arjen J C
Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Br J Clin Pharmacol. 2024 Jun;90(6):1471-1479. doi: 10.1111/bcp.16031. Epub 2024 Mar 14.
Knowledge of risk factors may provide strategies to reduce the high burden of delirium in intensive care unit (ICU) patients. We aimed to compare the risk of delirium after deep sedation with propofol versus midazolam in ICU patients.
In this prospective cohort study, ICU patients who were in an unarousable state for ≥24 h due to continuous sedation with propofol and/or midazolam were included. Patients admitted ≤24 h, those with an acute neurological disorder and those receiving palliative sedation were excluded. ICU patients were assessed daily for delirium during the 7 days following an unarousable state due to continuous sedation.
Among 950 included patients, 605 (64%) subjects were delirious during the 7 days after awaking. The proportion of subsequent delirium was higher after midazolam sedation (152/207 [73%] patients) and after both propofol and midazolam sedation (257/377 [68%] patients), compared to propofol sedation only (196/366 [54%] patients). Midazolam sedation (adjusted cause-specific hazard ratio [adj. cause-specific HR] 1.32, 95% confidence interval [CI] 1.05-1.66) and propofol and midazolam sedation (adj. cause-specific HR 1.29, 95% CI 1.06-1.56) were associated with a higher risk of subsequent delirium compared to propofol sedation only.
This study among sedated ICU patients suggests that, compared to propofol sedation, midazolam sedation is associated with a higher risk of subsequent delirium. This risk seems more apparent in patients with high cumulative midazolam intravenous doses. Our findings underpin the recommendations of the Society of Critical Care Medicine Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) guidelines to use propofol over benzodiazepines for sedation in ICU patients.
了解风险因素可能为降低重症监护病房（ICU）患者谵妄的高负担提供策略。我们旨在比较ICU患者使用丙泊酚与咪达唑仑进行深度镇静后发生谵妄的风险。
在这项前瞻性队列研究中，纳入了因持续使用丙泊酚和/或咪达唑仑镇静而处于不可唤醒状态≥24小时的ICU患者。入院≤24小时的患者、患有急性神经系统疾病的患者以及接受姑息性镇静的患者被排除。在因持续镇静导致不可唤醒状态后的7天内，每天对ICU患者进行谵妄评估。
在950例纳入患者中，605例（64%）在苏醒后的7天内出现谵妄。与仅使用丙泊酚镇静（196/366 [54%]例患者）相比，咪达唑仑镇静后（152/207 [73%]例患者）以及丙泊酚和咪达唑仑联合镇静后（257/377 [68%]例患者）随后发生谵妄的比例更高。与仅使用丙泊酚镇静相比，咪达唑仑镇静（调整后的特定病因风险比[adj. cause-specific HR] 1.32，95%置信区间[CI] 1.05 - 1.66）以及丙泊酚和咪达唑仑联合镇静（adj. cause-specific HR 1.29，95% CI 1.06 - 1.56）与随后发生谵妄的风险更高相关。
这项针对接受镇静的ICU患者的研究表明，与丙泊酚镇静相比，咪达唑仑镇静与随后发生谵妄的风险更高相关。这种风险在咪达唑仑静脉累积剂量高的患者中似乎更为明显。我们的研究结果支持了危重病医学学会疼痛、躁动/镇静、谵妄、活动受限（康复/活动）和睡眠（干扰）指南中关于在ICU患者镇静中使用丙泊酚而非苯二氮䓬类药物的建议。
