Extended Duration Ketamine Infusions in Critically Ill Children: A Case Report and Review of the Literature

Abstract

Ketamine is an N-methyl-D-aspartate receptor antagonist that has been used as an adjunct analgesic and sedative in critically ill children. Previous reports noted that ketamine has been used for a variable duration of 12 to 408 hours for this indication. We report on the use of ketamine infusions for >720 hours as a second-line sedative in addition to an opioid and dexmedetomidine infusion in a 2-month old and 17-month old. The purpose of this case report and review of the literature is to highlight the prolonged ketamine exposure of these two patients and to provide awareness to clinicians on the potential of withdrawal with extended ketamine administration. These children were started on initials doses of 5 and 15 µg/kg/min and titrated to peak doses of 20 and 25 µg/kg/min, respectively. They were continued for a total of 987 and 792 hours, respectively. No adverse events were noted during the ketamine infusions. One patient developed possible withdrawal symptoms 17 hours after ketamine discontinuation despite tapering of the infusion. These symptoms resolved with administration of as needed intravenous opioids and benzodiazepines, and the agitation normalized within 24 hours after ketamine discontinuation. Clinicians should consider tapering ketamine infusions in children receiving >72 hours of a continuous infusion by 5 µg/kg/min every 8 to 12 hours. Patients should be monitored for potential withdrawal symptoms including anxiety, allodynia, hyperalgesia, sweating, and drowsiness.

Keywords

ketamine - withdrawal - children

Publication History

Received: 03 April 2020

Accepted: 07 May 2020

Article published online:
10 June 2020

• References

• 1 Golding CL, Miller JL, Gessouroun MR, Johnson PN. Ketamine continuous infusions in critically ill infants and children. Ann Pharmacother 2016; 50 (03) 234-241
• 2 Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Ther 2013; 19 (06) 370-380
• 3 Heiberger AL, Ngorsuraches S, Olgun G. et al. Safety and utility of continuous ketamine infusion for sedation in mechanically ventilated pediatric patients. J Pediatr Pharmacol Ther 2018; 23 (06) 447-454
• 4 Neunhoeffer F, Hanser A, Esslinger M. et al. Ketamine infusion as a counter measure for opioid tolerance in mechanically ventilated children: a pilot study. Paediatr Drugs 2017; 19 (03) 259-265
• 5 Tobias JD, Martin LD, Wetzel RC. Ketamine by continuous infusion for sedation in the pediatric intensive care unit. Crit Care Med 1990; 18 (08) 819-821
• 6 Barbi E, Rizzello E, Taddio A. Use of ketamine continuous infusion for pediatric sedation in septic shock. Pediatr Emerg Care 2010; 26 (09) 689-690
• 7 Ito H, Sobue K, Hirate H. et al. Use of ketamine to facilitate opioid withdrawal in a child. Anesthesiology 2006; 104 (05) 1113
• 8 Rock MJ, Reyes de la Rocha S, L'Hommedieu CS, Truemper E. Use of ketamine in asthmatic children to treat respiratory failure refractory to conventional therapy. Crit Care Med 1986; 14 (05) 514-516
• 9 Nehama J, Pass R, Bechtler-Karsch A, Steinberg C, Notterman DA. Continuous ketamine infusion for the treatment of refractory asthma in a mechanically ventilated infant: case report and review of the pediatric literature. Pediatr Emerg Care 1996; 12 (04) 294-297
• 10 Agrawal A, Shrivastava J. Intravenous ketamine for refractory bronchospasm precipitated by H1N1 infection. Front Pediatr 2014; 2: 24
• 11 Youssef-Ahmed MZ, Silver P, Nimkoff L, Sagy M. Continuous infusion of ketamine in mechanically ventilated children with refractory bronchospasm. Intensive Care Med 1996; 22 (09) 972-976
• 12 Park S, Choi AY, Park E. et al. Effects of continuous ketamine infusion on hemodynamics and mortality in critically ill children. PLoS One 2019; 14 (10) e0224035
• 13 Mitchell AC. Generalized hyperalgesia and allodynia following abrupt cessation of subcutaneous ketamine infusion. Palliat Med 1999; 13 (05) 427-428
• 14 Ketamine Hydrochloride [package insert]. Chestnut Ridge, NY: Par Pharmaceutical; 2017
• 15 Klepstad P, Borchgrevink P, Hval B, Flaat S, Kaasa S. Long-term treatment with ketamine in a 12-year-old girl with severe neuropathic pain caused by a cervical spinal tumor. J Pediatr Hematol Oncol 2001; 23 (09) 616-619
• 16 Franck LS, Scoppettuolo LA, Wypij D, Curley MA. Validity and generalizability of the withdrawal assessment tool-1 (WAT-1) for monitoring iatrogenic withdrawal syndrome in pediatric patients. Pain 2012; 153 (01) 142-148
• 17 Johnson PN. Drug withdrawal. In: Mastropietro CW, Mack EH. eds. Pediatric Current Concepts. Prospect. IL: Society of Critical Care Medicine; 2018: e23-42
• 18 Flint RB, Brouwer CNM, Kränzlin ASC, Lie-A-Huen L, Bos AP, Mathôt RAA. Pharmacokinetics of S-ketamine during prolonged sedation at the pediatric intensive care unit. Paediatr Anaesth 2017; 27 (11) 1098-1107