Department of Cardiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Paediatr Drugs. 2023 Nov;25(6):709-718. doi: 10.1007/s40272-023-00587-6. Epub 2023 Aug 7.
Dexmedetomidine (DEX) is frequently used as an adjunct agent for prolonged sedation in the intensive care unit (ICU), though its effect on concomitant opioids or benzodiazepines infusions is unclear. We explored the impact of DEX on concomitant analgosedation in a cohort of ventilated pediatric patients in a cardiac ICU, with stratification of patients according to duration of ventilation (< 5 versus ≥ 5 days) following DEX initiation.
We conducted a retrospective analysis on ventilated patients receiving a DEX infusion ≥ 24 h and at least one other sedative/analgesic infusion (January 2011-June 2021). We evaluated trends of daily doses of opioids and benzodiazepines from 24 h before to 72 h following DEX initiation, stratifying patients based on ventilation duration after DEX initiation (< 5 versus ≥ 5 days).
After excluding 1146 patients receiving DEX only, 1073 patients were included [median age 234 days (interquartile range 90, 879)]. DEX was associated with an opioid infusion in 99% of patients and a benzodiazepine infusion in 62%. Among patients ventilated for < 5 days (N = 761), opioids increased in the first 24 h following DEX initiation [+ 1.12 mg/kg/day (95% CI 0.96, 1.23), P < 0.001], then decreased [- 0.90 mg/kg/day (95% CI - 0.89, - 0.71), P < 0.001]; benzodiazepines slowly decreased [- 0.20 mg/kg/day (95% CI - 0.21, - 0.19), P < 0.001]. Among patients ventilated for ≥ 5 days (N = 312), opioid administration doubled [+ 2.09 mg/kg/day (95% CI 1.82, 2.36), P < 0.001] in the first 24 h, then diminished minimally [- 0.18 mg/kg/day (95% CI - 0.32, - 0.04), P = 0.015] without returning to baseline; benzodiazepine administration decreased minimally [- 0.03 mg/kg/day (95% CI - 0.05, - 0.01), P = 0.010]. Similar trends were confirmed when adjusting for age, gender, surgical complexity, recent major invasive procedures, duration of mechanical ventilation before DEX initiation, extubation within 72 h following DEX initiation, mean hourly DEX dose, and use of neuromuscular blocking infusion.
While in patients ventilated < 5 days opioids initially increased and then quickly decreased in the 72 h following DEX initiation, among patients ventilated ≥ 5 days opioids doubled, then decreased only minimally; benzodiazepines decreased minimally in both groups, although more slowly in the long-ventilation cohort. These findings may inform decision-making on timing of DEX initiation in ventilated patients already being treated with opioid or benzodiazepine infusions.
右美托咪定（DEX）常用于重症监护病房（ICU）的长时间镇静辅助治疗，但它对同时给予的阿片类药物或苯二氮䓬类药物输注的影响尚不清楚。我们在心脏 ICU 中对接受 DEX 输注超过 24 小时且至少同时接受另一种镇静/镇痛药物输注的通气患儿进行了一项队列研究，并根据 DEX 起始后通气时间（<5 天与≥5 天）对患者进行分层。
我们对 2011 年 1 月至 2021 年 6 月期间接受 DEX 输注超过 24 小时且至少同时接受一种其他镇静/镇痛药物输注的通气患者进行了回顾性分析。我们评估了 DEX 起始后 72 小时内，24 小时前至 DEX 起始后 72 小时内，每日阿片类药物和苯二氮䓬类药物剂量的趋势，根据 DEX 起始后通气时间（<5 天与≥5 天）对患者进行分层。
排除仅接受 DEX 治疗的 1146 例患者后，纳入了 1073 例患者[中位年龄 234 天（四分位间距 90，879）]。DEX 与 99%的患者的阿片类药物输注和 62%的患者的苯二氮䓬类药物输注有关。在通气时间<5 天的患者（N=761）中，DEX 起始后 24 小时内阿片类药物输注量增加[+1.12mg/kg/天（95%CI 0.96，1.23），P<0.001]，然后减少[-0.90mg/kg/天（95%CI -0.89，-0.71），P<0.001]；苯二氮䓬类药物缓慢减少[-0.20mg/kg/天（95%CI -0.21，-0.19），P<0.001]。在通气时间≥5 天的患者（N=312）中，阿片类药物输注量在 24 小时内增加了一倍[+2.09mg/kg/天（95%CI 1.82，2.36），P<0.001]，然后略有减少[-0.18mg/kg/天（95%CI -0.32，-0.04），P=0.015]，但未恢复至基线水平；苯二氮䓬类药物输注量略有减少[-0.03mg/kg/天（95%CI -0.05，-0.01），P=0.010]。在调整年龄、性别、手术复杂性、近期重大侵入性操作、DEX 起始前机械通气时间、DEX 起始后 72 小时内拔管、平均每小时 DEX 剂量和使用神经肌肉阻滞剂输注等因素后，也得到了相似的趋势。
在通气时间<5 天的患者中，DEX 起始后 72 小时内，阿片类药物初始增加，然后迅速减少，而在通气时间≥5 天的患者中，阿片类药物增加一倍，然后仅略有减少；两组患者的苯二氮䓬类药物输注量均略有减少，尽管在通气时间较长的患者中减少速度较慢。这些发现可能为正在接受阿片类药物或苯二氮䓬类药物输注治疗的通气患者决定何时开始 DEX 治疗提供信息。
