Low-dose Ketamine for Children and Adolescents with Acute Sickle Cell Disease Related Pain: A Single Center Experience

Abstract

Background: Opioids are the mainstay of therapy for painful vasoocclusive episodes (VOEs) in sickle cell disease (SCD). Based on limited studies, low-dose ketamine could be a useful adjuvant analgesic for refractory SCD pain, but its safety and efficacy has not been evaluated in pediatric SCD. Procedure:Using retrospective chart review we recorded and compared characteristics of hospitalizations of 33 children with SCD hospitalized with VOE who were treated with low-dose ketamine and opioid PCA vs. a paired hospitalization where the same patients received opioid PCA without ketamine. We seek to 1) describe a single center experience using adjuvant low-dose ketamine with opioid PCA for sickle cell related pain, 2) retrospectively explore the safety and efficacy of adjuvant low-dose ketamine for pain management, and 3) determine ketamine's effect on opioid consumption in children and adolescents hospitalized with VOE. Results:During hospitalizations where patients received ketamine, pain scores and opioid use were higher (6.48 vs. 5.99; p=0.002 and 0.040 mg/kg/h vs. 0.032 mg/kg/h; p=0.004 respectively) compared to hospitalizations without ketamine. In 3 patients, ketamine was discontinued due to temporary and reversible psychotomimetic effects. There were no additional short term side effects of ketamine.Conclusions: Low-dose ketamine has an acceptable short-term safety profile for patients with SCD hospitalized for VOE. Lack of an opioid sparing effect of ketamine likely represents use of low-dose ketamine for patients presenting with more severe VOE pain. Prospective randomized studies of adjuvant low-dose ketamine for SCD pain are warranted to determine efficacy and long-term safety.

NMDA receptor modulators: an updated patent review (2013 – 2014)

“…These study results suggest that blockage of the NMDA receptor could reduce tolerance and OIH, and therefore that NMDA antagonists could be useful for pain management associated with SCD [144,145]. Ketamine, used in conjunction with opiates, has been studied in small case studies for the treatment of pain associated with SCD in children, and has shown an acceptable short-term safety profile [146] in addition to the reduction of opioid use and decreased reported pain [147]. Recently a Phase II clinical trial was completed where a low-dose of ketamine in addition to treatment involving opioids was studied for pain stemming for SCD, although no results were provided [148].…”

Patient characteristics affect the response to ketamine and opioids during the treatment of vaso-occlusive episode-related pain in sickle cell disease

“…Further, intraoperative administration of ketamine to patients with chronic back pain and opioid dependence decreases opioid requirements and reduces the incidence of late postoperative pain after spinal fusion (17). Therefore, given the reported analgesic and opioid-sparing effects in acute and chronic pain as well as a favorable safety profile, researchers have argued that ketamine might have a role in modulating SCD pain (18,19).…”

“…Several groups have reported the use of intravenous (18,(20)(21)(22) and intranasal ketamine (23) in SCD patients presenting with VOEs. Here, we conducted an exploratory study on a large cohort of SCD patients who during admissions for VOEs were treated with subanesthetic doses of ketamine.…”

Dexmedetomidine as an Adjuvant to Analgesic Strategy During Vaso‐Occlusive Episodes in Adolescents with Sickle‐Cell Disease

“…For the purpose of this report, we defined high‐dose opioid as those exceeding 2 mg/kg/day of oral morphine equivalent. This definition is based on a study indicating that patients requiring those doses of opioid were often treated with ketamine . For this investigation, we examined patient demographics, SCD genotype, analgesic therapy, self‐reported pain scores (numeric rating scale 0 to 10), and treatment‐related hemodynamic changes requiring intervention.…”