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

Abstract

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: CRPS; acute pain; cancer pain; chronic pain; postoperative pain; sickle cell disease.

Figure 1

Flowchart indicating patient selection and exclusion criteria.

Figure 2

Differential effect of ketamine on pain scores and opioid intake. Notes: The box plots show median and 25^th and 75^th percentiles, and the whiskers 10^th and 90^th percentiles. (A) Box plots of the changes in pain scores from baseline to the day after ketamine discontinuation according to primary clinical diagnosis. Ketamine infusions yielded greater reductions in pain scores in patients with cancer-associated pain and patients with IFD (including pancreatitis and Crohn’s disease) and the lowest in patients with FGID and other (cystic fibrosis, diabetes mellitus, neurofibromatosis 1, and postural orthostatic tachycardia syndrome), overall difference, p=0.011. (B) Effect of ketamine infusions on pain scores also varied according to the duration of ketamine infusion as longer ketamine infusions yielded greater reductions in pain scores (p=0.004). (C) The ketamine effect on opioid intake also varied according to clinical diagnosis (p=0.030) as greater reductions in opioid intake were observed in patients with cancer pain and patients with sickle cell disease, whereas lesser reductions were observed in patients with accidental trauma and postoperative pain due to surgical trauma (p=0.030). (D) Similar to the observation for pain scores, longer ketamine infusions yielded greater reductions in oral morphine-equivalent intake (p=0.022). Abbreviations: CA, cancer; IFD, inflammatory disease; SCD, sickle cell disease; POP, postoperative pain; AT, accidental trauma; FGID, functional gastrointestinal disease.

Figure 3

Proportion of ketamine infusions associated with a clinically meaningful reduction in pain scores. Notes: The stacked bars show the proportion of infusions associated with meaningful (≥20% reduction, white bars) and nonmeaningful reductions (<20% reduction, dotted bars). We defined a clinically meaningful reduction as a ≥20% reduction in pain scores from baseline to the day after ketamine discontinuation. The proportion of infusions that yielded a meaningful reduction varied according to clinical diagnosis (A, overall effect, p=0.003), pain location (B, p=0.012), age (C, p=0.039), and duration of infusion (D, p=0.017). Abbreviations: CA, cancer; IFD, inflammatory disease; SCD, sickle cell disease; POP, postoperative pain; AT, accidental trauma; OT, other; FGID, functional gastrointestinal disease; UE, upper extremity; Abd, abdominal; Gen, generalized; LE, lower extremity.