• Felix Neunhoeffer, Anja Hanser, Martin Esslinger, Vanja Icheva, Matthias Kumpf, Ines Gerbig, Michael Hofbeck, and Jörg Michel.
• Department of Paediatric Cardiology, Pulmology and Intensive Care Medicine, University Children's Hospital Tübingen, Hoppe-Seyler Str. 1, 72076, Tübingen, Germany. felix.neunhoeffer@med.uni-tuebingen.de.
• Paediatr Drugs. 2017 Jun 1; 19 (3): 259-265.

BackgroundDrug 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.Patients And MethodsWe 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.ResultsThirty-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).ConclusionDrug rotation with ketamine in mechanically ventilated children with opioid tolerance is feasible and seems to reduce the rate of fentanyl infusion.

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