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Vaso-occlusive events in sickle cell disease are managed with opioids, but there are several side effects. Ketamine is proposed as an adjunctive therapy that may reduce the need for high-dose opioids.

  • Sickle cell disease causes vaso-occlusive pain episodes, typically managed with opioids and NSAIDs
  • Ketamine might be an effective therapy to add to VOE management plans
  • Patients who received ketamine infusions also reduced their opioid dose and experienced few side effects
  • More research is needed to fully elucidate long-term effects of opioids, especially in pediatric patients.

Patients with sickle cell disease (SCD) experience painful vaso-occlusive episodes (VOEs), which are traditionally managed with opioids. Even with continuous opioid treatment, VOEs are difficult to manage, and side effects are common in children. Moreover, ongoing opioid use can lead to tolerance and opioid-induced hyperalgesia, making their use less effective over time.

Current VOE Management Strategies and Limitations

The American Society of Hematology currently suggests tailored opioid therapy and short-course non-steroidal anti-inflammatory drugs (NSAIDs) for VOE management. However, NSAIDs often are not effective at reducing pain and can lead to kidney damage when overused.

Potential Benefits of Ketamine for Pain Management in SCD

Researchers are investigating low-dose ketamine as a potential management strategy for VOEs in pediatric patients with SCD. Ketamine blocks NMDA receptors in the brain to reduce neuropathic pain and modulate opioid-induced pain sensitivity and tolerance.

In a retrospective study published in Pediatric Blood & Cancer, patients who received ketamine as an adjuvant to opioids were evaluated for opioid adjustments and side effects. Of patients who received ketamine infusion, 79.3% had a reduction in either patient-controlled analgesia,  continuous opioid infusion, or both, showing a potential benefit of ketamine infusion. Additionally, most patients who received ketamine did not experience short-term side effects. The most common side effects were altered mental status, dizziness, hallucinations, and dissociative symptoms.

Considerations for Personalized Pain Management Plans

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These findings show initial potential for effective adjunct treatment of VOEs with ketamine. Ketamine infusion therapy may be taken into consideration when developing personalized pain management plans for patients with SCD. For individuals who have had insufficient pain relief from opioids in the past or experienced dose-limiting opioid side effects, ketamine infusion therapy may be particularly beneficial. 

The long-term effects, particularly in children, must be further studied. In addition, more research is needed to determine long-term safety, optimal dosing, and individualized treatment plans.


Harris, E. M., Vilk, E., Donado, C., Williams, A., Heeney, M. M., Solodiuk, J., Greco, C., & Archer, N. M. (2023). Ketamine use for management of vaso-occlusive pain in pediatric sickle cell disease. Pediatric Blood & Cancer, e30254. https://doi.org/10.1002/pbc.30254