title: Low-dose ketamine as a potential adjuvant therapy for painful vaso-occlusive crises in sickle cell disease.
abstract: 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.
authors.affiliation: Children's National Medical Center, Center for Cancer and Blood Disorders, Washington, DC 20010, USA. cneri@cnmc.org
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Neri
authors.forename: Sophie R
authors.initials: SR
authors.lastname: Pestieau
authors.forename: Deepika S
authors.initials: DS
authors.lastname: Darbari
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications*; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001157:Arterial Occlusive Diseases / Q000150:complications*; D004361:Drug Tolerance; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010148:Intractable Pain / Q000188:drug therapy
chemical_list: D000778:Anesthetics, Dissociative; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine
keywords: analgesics; anemia; hyperalgesia; ketamine; opioid; pain; sickle cell/drug therapy; tolerance