Abstract
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.
Keywords
fentanyl - opioid - continuous infusion - tolerance - critically ill - child
