儿童重症监护病房镇痛镇静治疗撤药模式对戒断综合征的影响

Effect of sedation weaning pattern on withdrawal syndrome in pediatric intensive care unit

目的调查儿童重症监护病房(PICU)机械通气患儿镇痛镇静治疗情况,探讨不同撤药模式对戒断综合征的影响。方法单中心前瞻性队列研究。以2016年4月1日至2017年4月30日入住上海儿童医学中心PICU需机械通气并连续使用苯二氮类药物和(或)阿片类药物≥5 d的112例患儿为研究对象,根据患儿撤药开始后每日镇痛镇静药物剂量是否较前1日增加≥50%,分为不稳定撤药模式20例(17.9%)、稳定撤药模式92例(82.1%)。收集患儿人口统计学特征、临床特征、镇痛镇静药物暴露等指标,以Mann-Whitney U检验等方法比较不同撤药模式组患儿临床特征及发生与未发生戒断综合征患儿的临床特征,并通过Logistic回归探索戒断综合征发生的危险因素。结果纳入112例患儿,戒断综合征发生率41.1%(46/112)。不稳定撤药组患儿的第3代小儿死亡危险评分(PRISM-Ⅲ)[10.0(3.5,12.0)比6.0(2.0,10.0),U=654.50,P=0.043]、撤机后再插管比例[35.0%(7/20)比7.6%(7/92),P=0.003]均明显高于稳定撤药模式组。发生戒断综合征患儿总镇痛镇静时间更长[19.5(16.8,24.3)比10.0(7.0,17.3)d,U=743.50,P<0.01]、不稳定撤药发生率更高[32.6%(15/46)比7.6%(5/66),χ^2=11.58,P=0.001]、PICU住院时间更长[19.0(15.8,25.3)比12.0(8.8,17.0)d,U=755.00,P<0.01]、住院总费用更高[8.9(5.7,10.9)比5.3(3.2,7.9)万元,U=804.00,P<0.01]。多因素Logistic回归分析发现不稳定撤药[比值比(OR)=4.85,95%可信区间(CI)1.39~16.91,P=0.013]、肝移植围手术期(OR=6.97,95%CI 1.25~39.04,P=0.027)和总咪达唑仑剂量≥34.7mg/kg(OR=8.12,95%CI 3.09~21.37,P<0.01)是发生戒断综合征的危险因素。结论不稳定撤药患儿更容易发生戒断综合征,避免不稳定撤药可能使镇痛镇静治疗患儿获益。

Objective To investigate the sedation weaning strategies in critically ill patients with mechanical ventilation in pediatric intensive care unit(PICU)and to explore the effect of different sedative weaning patterns on withdrawal syndrome.Methods A single-center prospective cohort study was conducted from April 1,2016 to April 30,2017.One hundred and twelve patients who required mechanical ventilation and benzodiazepines and(or)opioids for at least 5 consecutive days in PICU of Shanghai Children's Medical Center were enrolled.Twenty patients(17.9%)had an intermittent weaning pattern,defined as a 50%or greater increase in daily benzodiazepine and(or)opioid dose after the start of weaning,and the remaining 92 cases(82.1%)had a steady weaning pattern.The demographic and clinical features,duration and dose of sedative and analgesics,and the incidence of withdrawal syndrome were evaluated.Mann-Whitney U test was used for comparison about clinical features between different weaning pattern groups and children with withdrawal syndrome or not.Logistic regression was used to explore the risk factors of withdrawal syndrome.Results Among the 112 patients,46(41.1%)had withdrawal syndrome.The patients with the intermittent weaning pattern had a high score of pediatric risk of mortalityⅢ(PRISM-Ⅲ)(10.0(3.5,12.0)vs.6.0(2.0,10.0),U=654.50,P=0.043)and were prone to re-intubation(35.0%(7/20)vs.7.6%(7/92),P=0.003).The patients with withdrawal syndrome had longer duration of sedation(19.5(16.8,24.3)vs.10.0(7.0,17.3)days,U=743.50,P<0.01),higher incidence of intermittent weaning pattern(32.6%(15/46)vs.7.6%(5/66),χ^2=11.58,P=0.001),longer PICU hospitalization(19.0(15.8,25.3)vs.12.0(8.8,17.0)days,U=755.00,P<0.01)and higher cost(89(57,109)vs.53(32,79)thousand yuan,U=804.00,P<0.01).Logistic regression showed that intermittent weaning pattern(odds ratio(OR)=4.85,95%confidence interval(CI)1.39-16.91,P=0.013),perioperative period of liver transplantation(OR=6.97,95%CI 1.25-39.04,P=0.027)and a cumulative dose of midazolam≥34.7 mg/kg(OR=8.12,95%CI 3.09-21.37,P<0.01)were risk factors of withdrawal syndrome.Conclusions Withdrawal syndrome is more likely to occur in children who are intermittently weaned from sedation.Steady weaning strategy may help prevent iatrogenic withdrawal syndrome.