Characterization of Tolerance in Children during Fentanyl Continuous Infusions

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 (p < 0.001), final CIN doses (p = 0.031), and cumulative exposure (p = 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 (p = 0.007; odds ratio [OR]: 0.011, 95% confidence interval [CI]: 0.0004-0.29) and higher cumulative exposure (p = 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.