(256) Pilot Study of Immune Response and Iatrogenic Withdrawal Syndrome in Critically-Ill Children Receiving Fentanyl Infusion

Objective : To evaluate the potential of using peripheral monocyte inflammatory response as a biomarker for opioid-associated iatrogenic withdrawal syndrome (IWS) in critically-ill children receiving fentanyl infusion during early postsurgical period.

Methods: Peripheral whole blood was collected prior to surgery, as well as 24 and 72 hours after surgery began. The blood samples were stimulated with lipopolysaccharide ex vivo and the expression of intracellular proinflammatory cytokines (interleukin 1-β [IL-1β] and tumor necrosis factor-α [TNF-α]) was measured using flow cytometry. The fold changes of the intracellular IL-1β and TNF-α expression at 24 and 72 hours, relative to the baseline, were determined. The relationships among the fold changes and patient variables, such as the cumulative fentanyl dose and the development of opioid-associated IWS (withdrawal assessment tool-1 score >3), were evaluated using univariate regression analyses.

Results: Thirteen patients were enrolled, with a median age of 2 months (range: 0-11 months) and 85% female. The monocyte IL-1β and TNF-α expression was suppressed (range: 20-90%) at 24 and 72 hours after surgery compared with baseline. We observed a trend for more suppression of IL-1β (but not TNF-α) response at 24 hours in patients receiving higher fentanyl cumulative doses; however, the suppression of IL-1β and TNF-α response at 72 hours was weaker with higher 72-hour cumulative fentanyl doses. We also observed a trend for weaker IL-1β and TNF-α suppression at 24 and 72 hours among patients who developed opioid-associated IWS compared with those who did not.

Conclusions: The suppression of the monocyte inflammatory response may depend on the fentanyl dose and duration, and a weaker suppression may be associated with the development of opioid-associated IWS.