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.


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.

Keywords: analgesics; anemia; hyperalgesia; ketamine; opioid; pain; sickle cell/drug therapy; tolerance.

Publication types

  • Review

MeSH terms

  • Anemia, Sickle Cell / complications*
  • Anesthetics, Dissociative / administration & dosage
  • Anesthetics, Dissociative / adverse effects
  • Anesthetics, Dissociative / pharmacology
  • Anesthetics, Dissociative / therapeutic use*
  • Arterial Occlusive Diseases / complications*
  • Drug Tolerance
  • Excitatory Amino Acid Antagonists / adverse effects
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Humans
  • Ketamine / administration & dosage
  • Ketamine / adverse effects
  • Ketamine / pharmacology
  • Ketamine / therapeutic use*
  • Pain / drug therapy*
  • Pain / etiology
  • Pain, Intractable / drug therapy


  • Anesthetics, Dissociative
  • Excitatory Amino Acid Antagonists
  • Ketamine