Low-Dose Intravenous Ketamine for Primary Pain Control During Naxitamab Anti-GD2 Immunotherapy Treatment

Anti-GD2 antibodies, including naxitamab, are part of standard therapy for high-risk neuroblastoma (HR-NB) and are associated with significant pain. We developed a protocol for outpatient use of low-dose intravenous ketamine (LDIVK) for pain management during naxitamab. We describe the LDIVK protocol and report on its impact on the management of naxitamab-associated pain.

Patients with HR-NB receiving naxitamab with poorly controlled pain in at least 1 cycle received LDIVK outpatient for subsequent cycles. LDIVK at 0.5 mg/kg/h was started 30 minutes before and ended 1 hour after naxitamab. A retrospective chart review of LDIVK-treated patients was completed. Intrapatient comparison of vital signs, opioid use, and adverse events between LVIDK-containing and non-containing cycles was analyzed using the Wilcoxon signed rank test.

Twenty-two pediatric patients received LDIVK at a median age of 6.3 (range, 1-16) years. Twelve patients received the same premedication for cycles with and without LDIVK, and their opioid use was analyzed. Statistically significant reduction in total opioid use in LDIVK-containing cycle (0.064 mg/kg IV hydromorphone vs. 0.054 mg/kg IV hydromorphone; p = 0.003) and rescue opioid use (0.028 mg/kg IV hydromorphone vs. 0.018 mg/kg IV hydromorphone; p = 0.0042) was noted. There was no significant difference in premedication opioid (0.046 mg/kg IV hydromorphone vs. 0.051 mg/kg IV hydromorphone; p > 0.2). Fluid boluses administered, heart rate, and blood pressure (p > 0.1 for each) between cycles were the same. One patient experienced dysphoria, which resolved with LDIVK rate reduction.

Ketamine was successfully administered in an outpatient setting and was associated with a significant opioid-sparing effect. A larger prospective study is warranted.