Ibach Bethany W, Miller Jamie L, Woo Sukyung, Harrison Donald, Standifer Kelly M, Hagemann Tracy, Johnson Peter N
Department of Pharmacy Practice, Texas Tech University Health Sciences Center School of Pharmacy, Abilene, Texas, United States.
Department of Pharmacy: Clinical and Administrative Sciences, The University of Oklahoma College of Pharmacy, Oklahoma City, Oklahoma, United States.
J Pediatr Intensive Care. 2017 Jun;6(2):83-90. doi: 10.1055/s-0036-1584909. Epub 2016 Jun 29.
Tolerance is a complication of fentanyl continuous infusions (CINs) in critically ill children, but the incidence and time of onset are lacking. The primary objective was to identify the incidence of tolerance. Secondary objectives were to determine the onset time and compare risk factors between children with tolerance versus no tolerance and between children with early (< 24 hours) versus late tolerance. Children aged 0 to 17 years, receiving fentanyl CIN > 3 days from May 1, 2012 to June 30, 2013 were included. Tolerance was defined as a doubling of the fentanyl CIN dose. Descriptive and inferential statistics were performed. A logistic regression model was used to assess the relationship between the development of tolerance and independent variables. A total of 59 CINs were included. Tolerance occurred in 46 CINs (78%), with median time to tolerance of 26 hours (range: 1-160 hours). Early tolerance was identified in 21 CINs (45.7%). Patients with tolerance had higher peak CIN doses ( < 0.001), final CIN doses ( = 0.031), and cumulative exposure ( = 0.017). No significant differences were noted between those with early versus late tolerance. The regression model noted factors associated with the odds of development of tolerance were lower initial fentanyl dose ( = 0.007; odds ratio [OR]: 0.011, 95% confidence interval [CI]: 0.0004-0.29) and higher cumulative exposure ( = 0.009; OR: 1.01, 95% CI: 1.001-1.01). Tolerance developed in 78% of children, and half developed it within 24 hours. Lower initial opioid dose and higher cumulative exposure were independently associated with tolerance.
耐受性是重症儿童芬太尼持续输注（CIN）的一种并发症，但目前尚缺乏其发生率和发病时间的数据。主要目的是确定耐受性的发生率。次要目的是确定发病时间，并比较有耐受性与无耐受性儿童之间以及早期（<24小时）与晚期耐受性儿童之间的危险因素。纳入2012年5月1日至2013年6月30日期间接受芬太尼CIN治疗超过3天的0至17岁儿童。耐受性定义为芬太尼CIN剂量加倍。进行了描述性和推断性统计分析。采用逻辑回归模型评估耐受性发展与自变量之间的关系。共纳入59例CIN病例。46例CIN（78%）出现耐受性，耐受性的中位时间为26小时（范围：1 - 160小时）。21例CIN（45.7%）出现早期耐受性。有耐受性的患者CIN峰值剂量更高（P<0.001）、最终CIN剂量更高（P = 0.031）以及累积暴露量更高（P = 0.017）。早期与晚期耐受性患者之间未观察到显著差异。回归模型显示，与耐受性发生几率相关的因素为初始芬太尼剂量较低（P = 0.007；比值比[OR]：0.011，95%置信区间[CI]：0.0004 - 0.29）和累积暴露量较高（P = 0.009；OR：1.01，95% CI：1.001 - 1.01）。78%的儿童出现耐受性，其中半数在24小时内出现。初始阿片类药物剂量较低和累积暴露量较高与耐受性独立相关。
