Ketamine Sickle Cell Disease

Summary

Sickle cell disease (SCD) often results in acute vaso-occlusive crisis (VOC), an obstruction of blood vessels resulting in ischemic injury and pain. The pain experienced during these episodes is due to a wide range of pathophysiological processes. Though recent studies have begun to unravel the underlying mechanisms of these processes, literature focused on pain management for sickle cell disease is scarce. Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) remain the predominate treatment for VOC. However, the efficacy of these treatments has come into question. A large sub-set of patients with SCD report continued pain despite treatment with opioids. Tolerance and opioid-induced hyperalgesia (OIH) may be responsible for unresponsiveness to opioid-centric treatment modalities. New classes of drugs are being tested to prevent and treat acute pain associated with SCD, but in the meantime physicians are looking to existing therapies to bridge the gap. 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. Ketamine utilized as a low dose continuous infusion could benefit patients with SCD related pain that are unresponsive to opioid analgesics. 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.

Timeline

Start

2018-09-01

Primary completion

2019-09-01

Completion

2019-11-01

Publications

• Background Puri L, Nottage KA, Hankins JS, Anghelescu DL. State of the Art Management of Acute Vaso-occlusive Pain in Sickle Cell Disease. Paediatr Drugs. 2018 Feb;20(1):29-42. doi: 10.1007/s40272-017-0263-z.
• Background Neri CM, Pestieau SR, Darbari DS. Low-dose ketamine as a potential adjuvant therapy for painful vaso-occlusive crises in sickle cell disease. Paediatr Anaesth. 2013 Aug;23(8):684-9. doi: 10.1111/pan.12172. Epub 2013 Apr 9.
• Background Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006 Aug;60(7):341-8. doi: 10.1016/j.biopha.2006.06.021. Epub 2006 Jul 5.
• Background Aguado D, Abreu M, Benito J, Garcia-Fernandez J, Gomez de Segura IA. Ketamine and remifentanil interactions on the sevoflurane minimum alveolar concentration and acute opioid tolerance in the rat. Anesth Analg. 2011 Sep;113(3):505-12. doi: 10.1213/ANE.0b013e318227517a. Epub 2011 Jul 21.
• Background Sun J, Lin H, Feng X, Dong J, Ansong E, Xu X. A comparison of intrathecal magnesium and ketamine in attenuating remifentanil-induced hyperalgesia in rats. BMC Anesthesiol. 2016 Sep 6;16(1):74. doi: 10.1186/s12871-016-0235-9.

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