Ketamine Infusion as a Counter Measure for Opioid Tolerance in Mechanically Ventilated Children: A Pilot Study

Drug rotation to prevent opioid tolerance is well recognized in chronic pain management. However, ketamine infusion as a counter measure for opioid tolerance is rarely described in mechanically ventilated children developing tolerance from prolonged opioid infusion.

We performed a retrospective study in a 14-bed medical-surgical-cardiac pediatric intensive care unit. Thirty-two mechanically ventilated children who had developed tolerance from prolonged intravenous infusion of opioids received a continuous intravenous infusion of ketamine as an opioid substitute for more than 2 days, scheduled in a drug rotation protocol.

Thirty-two children (median age 2.5 years, range 0.1–16.0; weight 11.2 kg [3.8–62.0]) were included. Patients had received continuous intravenous infusion of opioids and benzodiazepines for 16.0 days (4.0–34.0) when drug rotation was started. The median dose of continuous intravenous infusion of ketamine was 4.0 mg·kg⁻¹·h⁻¹ (1.8–6.0) and the median duration was 3.0 days (2.0–6.0). After having restarted opioids, fentanyl doses were significantly lower compared with the time before the drug rotation began (after, 2.9 µg·kg⁻¹·h⁻¹ [0.8–4.9] vs before, 4.15 µg·kg⁻¹·h⁻¹ [1.2–10.0]; p < 0.001). Continuous intravenous infusion of midazolam and clonidine were unchanged during drug rotation. COMFORT-B scoring was significantly lower after having started drug rotation (after, 14.5 [8–19] vs before, 16 [11–22]; p < 0.001).

Drug rotation with ketamine in mechanically ventilated children with opioid tolerance is feasible and seems to reduce the rate of fentanyl infusion.