Low-dose ketamine as a potential adjuvant therapy for painful vaso-occlusive crises in sickle cell disease

Authors

  • Caitlin M. Neri,

    Corresponding author
    1. Department of Pediatrics, School of Medicine, The George Washington University, Washington, DC, USA
    • Children's National Medical Center, Center for Cancer and Blood Disorders, Washington, DC, USA
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  • Sophie R. Pestieau,

    1. Department of Pediatrics, School of Medicine, The George Washington University, Washington, DC, USA
    2. Division of Anesthesiology and Pain Medicine, Children's National Medical Center, Washington, DC, USA
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  • Deepika S. Darbari

    1. Children's National Medical Center, Center for Cancer and Blood Disorders, Washington, DC, USA
    2. Department of Pediatrics, School of Medicine, The George Washington University, Washington, DC, USA
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Correspondence

Caitlin M. Neri, Center for Cancer and Blood Disorders, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA

Email: cneri@cnmc.org

Summary

The hallmark of sickle cell disease (SCD) is the acute painful vaso-occlusive crisis (VOC). Among SCD patients, vaso-occlusive pain episodes vary in frequency and severity. Some patients rarely have painful crises, while others are admitted to the hospital multiple times in a year for parenteral analgesics. Opioids are the mainstay of therapy for SCD-related pain. However, a subset of patients report continued pain despite escalating doses of opioids. Tolerance and opioid-induced hyperalgesia (OIH) have been considered as possible explanations for this phenomenon. The activation of the N-methyl-d-aspartate (NMDA) receptor has been implicated in both tolerance and OIH. As a NMDA receptor agonist, ketamine has been shown to modulate opioid tolerance and OIH in animal models and clinical settings. Low-dose ketamine, by virtue of its NMDA receptor agonist activity, could be a useful adjuvant to opioid therapy in patients with refractory SCD-related pain. Based on limited studies of adjuvant ketamine use for pain management, low-dose ketamine continuous infusion appears safe. Further clinical investigations are warranted to fully support the use of low-dose ketamine infusion in patients with SCD-related pain.

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