Intravenous Ketamine Significantly Reduces Pain in Refractory Pediatric Headache


The use of intravenous ketamine in pediatric patients with refractory headaches resulted in a median pain reduction of 50% at discharge and nearly two-third of patients did not need further rescue therapies 1 month posttreatment.

Scott Rosenthal, MD, a child neurology resident at Children's Hospital Colorado, University of Colorado School of Medicine

Scott Rosenthal, MD

Findings from a recent study of pediatric patients with refractory migraine demonstrated a significant reduction in pain at discharge using intravenous ketamine as a treatment with no serious adverse events. These results suggest that intravenous ketamine is an effective, safe, and well-tolerated option for treating refractory pediatric headaches and status migrainosus.1

All told, the median percent pain reduction at discharge was 50% (IQR -67% to +25%) among 58 encounters with pediatric patients with refractory migraine. Of note, 64% of patients did not have headache recurrence or exacerbation in 1 month after discharge. Notably, the median time to recurrence was 7 days (IQR, 3-12.5) for those that recurred and 9% had recurrence in 72 hours postdischarge.

"Patients with severe and refractory headaches often have few options for treatment despite ongoing pain and significant disability. While intravenous dihydroergotamine (IV DHE), an ergot derivative with 5HT agonism, is often effective for the majority of pediatric patients presenting with status migrainosus and refractory headaches, a significant proportion of patients will fail to respond or cannot receive IV DHE due to intolerability/contraindications," lead author Scott Rosenthal, MD, a child neurology resident at Children's Hospital Colorado, University of Colorado School of Medicine and colleagues wrote.1

Presented at the 2023 American Headache Society (AHS) Annual Meeting, June 15-18, in Austin, Texas, researchers conducted a retrospective chart review of patients between the ages of 5 and 21 years old. To be eligible, the patients had to be admitted to a tertiary pediatric referral center for the treatment of refractory headache. Patients were excluded if they received both ketamine and IV dihydroergotamine (DHE) in the same period, had a secondary etiology for headache, or had a pain score that was less than 3 on a verbal analogue scale at presentation.

Investigators used the percentage of pain reduction at discharge ([Discharge Pain Score - Initial Pain Score]/Initial Pain Score*100) as the primary outcome, while also observing serious adverse events, medication adverse effects, headache recurrence in 72 hours, and headache recurrence in 30 days postdischarge. Investigators defined headache recurrence if patients made a phone call or representation of care for headache requiring rescue therapy. Demographic variables from the patients were also collected.

In the analysis, 58 encounters comprised of 38 unique pediatric patients with a median age of 15.8 years (IQR 13.42-17.41), 76% of which identified as women, were included. Seventy-eight percent of patients were diagnosed as chronic migraine without aura and he median duration of headache or headache pain exacerbation at presentation was 10 days (IQR, 3-26.5). Also, the median maximum dose of intravenous ketamine was 0.28 mg/kg/hour (IQR, 0.2-0.4), with the median duration of infusion being 3 days (IQR, 2-3).

Although there were no serious adverse events reported in the analysis, the most common adverse effects were dizziness (19%), nausea (12%), hallucinations (12%), blurry vision (12%), cognitive fog (9%), dysphoria (5%) and vomiting (4%). Notably, only 7% of encounters had discontinued therapy early because of the adverse events the patients experienced.

"Ketamine, a NMDA receptor antagonist, has emerged as potential therapeutic option for this population and has demonstrated benefit in other chronic pain syndromes and refractory mood disorders. Unfortunately, there is a paucity of literature available about the efficacy and tolerability of IV ketamine in the treatment of refractory pediatric headaches and status migrainosus." Rosenthal et al noted.1

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1. Rosenthal S, Ackley E, Koehler A, Yonker M. The Safety and Efficacy of Intravenous Ketamine in the Treatment of Refractory Pediatric Headache. Presented at: AHS Annual Meeting, 2023; June 15-18; Austin, TX. P-193.
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