Subanesthetic ketamine for pain management in hospitalized children, adolescents, and young adults: a single-center cohort study

Journal of Pain Research Dovepress open access to scientific and medical research ORIGINAL RESEARCH Journal of Pain Research downloaded from https://www.dovepress.com/ by 54.37.117.73 on 13-Jul-2018 For personal use only. Open Access Full Text Article Subanesthetic ketamine for pain management in hospitalized children, adolescents, and young adults: a single-center cohort study This article was published in the following Dove Press journal: Journal of Pain Research 5 April 2017 Number of times this article has been viewed Kathy A Sheehy 1,* Caroline Lippold 1,* Amy L Rice 1 Raissa Nobrega 1 Julia C Finkel 1 Zenaide MN Quezado 1,2 1 Division of Anesthesiology, Pain, and Perioperative Medicine, The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s Research Institute, Children’s National Health System, George Washington University School of Medicine and Health Sciences, 2Center for Neuroscience Research, Children’s Research Institute, Children’s National Health System, Washington, DC, USA *These authors contributed equally to this work Background: Subanesthetic doses of ketamine, an N-methyl-d-aspartate receptor antagonist used as an adjuvant to opioid for the treatment of pain in adults with acute and chronic pain, have been shown, in some instances, to improve pain intensity and to decrease opioid intake. However, less is known about the role of ketamine in pain management in children, adolescents, and young adults. Purpose: We examined the effects of subanesthetic ketamine on pain intensity and opioid intake in children, adolescents, and young adults with acute and chronic pain syndromes treated in an inpatient setting. Methods: This is a longitudinal cohort study of patients treated with subanesthetic ketamine infusions in regular patient care units in a tertiary pediatric hospital. Primary outcomes included changes in pain scores and morphine-equivalent intake. Results: The study cohort included 230 different patients who during 360 separate hospital admissions received subanesthetic ketamine infusions for pain management. Overall, ketamine infusions were associated with significant reductions in mean pain scores from baseline (mean pain scores 6.64 [95% CI: 6.38–6.90]) to those recorded on the day after discontinuation of ketamine (mean pain scores 4.38 [95% CI: 4.06–4.69]), p<0.001. Importantly, the effect of ketamine on pain scores varied according to clinical diagnosis (p=0.011), infusion duration (p=0.004), and pain location (p=0.004). Interestingly, greater reductions in pain scores were observed in patients with cancer pain and patients with pain associated with pancreatitis and Crohn’s disease. There were no records of psychotomimetic side effects requiring therapy. Conclusion: These data suggest that administration of subanesthetic ketamine for pain management is feasible and safe in regular inpatient care units and may benefit children, adolescents, and young adults with acute and chronic pain. This study is informative and can be helpful in determining sample and effect sizes when planning clinical trials to determine the role of subanesthetic ketamine infusions for pain management in pediatric patients. Keywords: cancer pain, sickle cell disease, CRPS, postoperative pain, chronic pain, acute pain Introduction Correspondence: Zenaide MN Quezado Department of Perioperative Medicine National Institutes of Health Clinical Center National Institutes of Health 10 Center Drive Building 10, Room 6-5561 Bethesda, MD 20892, USA Email 787 submit your manuscript | www.dovepress.com Journal of Pain Research 2017:10 787–795 Dovepress © 2017 Sheehy et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/JPR.S131156 Powered by TCPDF (www.tcpdf.org) Ketamine has been used clinically since the 1960s as a general anesthetic.1 A decade after its approval by the US Food and Drug Administration, researchers showed that ketamine reduces the excitatory response to N-methyl-d-aspartic acid (NMDA) in central neurons, thus revealing its NMDA receptor antagonism properties2 and advancing our understanding of the pharmacology of ketamine. Currently, clinicians use ketamine as a general anesthetic less frequently, given its emergence psychotomimetic effects and findings of neurotoxic effects shown in the developing brain of animals.3 Conversely, Dovepress Journal of Pain Research downloaded from https://www.dovepress.com/ by 54.37.117.73 on 13-Jul-2018 For personal use only. Sheehy et al over the past decade, researchers have explored the effect of subanesthetic doses of ketamine as an antidepressant4 and as an analgesic.5,6 The use of subanesthetic ketamine as an analgesic is supported by evidence, from both animal and human studies, implicating activation of NMDA receptors in the pathobiology of nociceptive, inflammatory, and neuropathic pain and in central sensitization.7 In addition, activation of NMDA receptors has also been shown in animals8 and in human experimental studies9 to play a role in settings where acute or chronic use of opioids is associated with tolerance or opioidinduced hyperalgesia. Therefore, based on these preclinical findings, ketamine has been examined clinically as an adjuvant to opioids for the treatment of acute and chronic pain and in settings of opioid-induced hyperalgesia.6,10 However, among clinical studies, there has been a great variability in ketamine doses and duration of administration. Additionally, the beneficial effects of ketamine have not been consistently reported, and some groups have been unable to show opioidsparing effects of ketamine in clinical settings associated with opioid-induced hyperalgesia.11,12 Similarly, in chronic pain, there are no definitive data supporting the use of ketamine for the treatment of chronic regional pain syndrome (CRPS) or other types of chronic pain.13 Further, in critical reviews of available trials, researchers can only conclude that there might be a beneficial role for ketamine as an adjuvant to opioids to treat pain in the postoperative period, cancer pain, and chronic pain.9,12,14,15 Consequently, as outlined in clinical guidelines, the evidence to support the use of ketamine for the treatment of acute and chronic pain is at best moderate.16,17 However, despite lack of conclusive clinical evidence to support its use, clinicians from various disciplines in many countri (...truncated)