title: Ketamine Infusion as a Counter Measure for Opioid Tolerance in Mechanically Ventilated Children: A Pilot Study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Drug rotation with ketamine in mechanically ventilated children with opioid tolerance is feasible and seems to reduce the rate of fentanyl infusion.
authors.affiliation: 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.
authors.forename: Felix
authors.initials: F
authors.lastname: Neunhoeffer
authors.affiliation: Department of Paediatric Cardiology, Pulmology and Intensive Care Medicine, University Children's Hospital Tübingen, Hoppe-Seyler Str. 1, 72076, Tübingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Hanser
authors.affiliation: Department of Paediatric Cardiology, Pulmology and Intensive Care Medicine, University Children's Hospital Tübingen, Hoppe-Seyler Str. 1, 72076, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Esslinger
authors.affiliation: Department of Paediatric Cardiology, Pulmology and Intensive Care Medicine, University Children's Hospital Tübingen, Hoppe-Seyler Str. 1, 72076, Tübingen, Germany.
authors.forename: Vanja
authors.initials: V
authors.lastname: Icheva
authors.affiliation: Department of Paediatric Cardiology, Pulmology and Intensive Care Medicine, University Children's Hospital Tübingen, Hoppe-Seyler Str. 1, 72076, Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kumpf
authors.affiliation: Department of Paediatric Cardiology, Pulmology and Intensive Care Medicine, University Children's Hospital Tübingen, Hoppe-Seyler Str. 1, 72076, Tübingen, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Gerbig
authors.affiliation: Department of Paediatric Cardiology, Pulmology and Intensive Care Medicine, University Children's Hospital Tübingen, Hoppe-Seyler Str. 1, 72076, Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hofbeck
authors.affiliation: Department of Paediatric Cardiology, Pulmology and Intensive Care Medicine, University Children's Hospital Tübingen, Hoppe-Seyler Str. 1, 72076, Tübingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Michel
mesh_terms: D000293:Adolescent; D000700:Analgesics / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D057915:Drug Substitution; D004361:Drug Tolerance; D005240:Feasibility Studies; D005260:Female; D005283:Fentanyl / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D015278:Intensive Care Units, Pediatric; D007649:Ketamine / Q000627:therapeutic use*; D008297:Male; D008874:Midazolam / Q000627:therapeutic use; D010865:Pilot Projects; D012121:Respiration, Artificial; D012189:Retrospective Studies
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D007649:Ketamine; D008874:Midazolam; D005283:Fentanyl