Neri Caitlin M, Pestieau Sophie R, Darbari Deepika S
Children's National Medical Center, Center for Cancer and Blood Disorders, Washington, DC 20010, USA.
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.
镰状细胞病（SCD）的标志是急性疼痛性血管闭塞危机（VOC）。在SCD患者中，血管闭塞性疼痛发作的频率和严重程度各不相同。一些患者很少出现疼痛危机，而另一些患者则每年多次因需要肠外镇痛药而住院。阿片类药物是治疗SCD相关疼痛的主要药物。然而，有一部分患者尽管阿片类药物剂量不断增加，但仍报告持续疼痛。耐受性和阿片类药物诱导的痛觉过敏（OIH）被认为是这一现象的可能解释。N-甲基-D-天冬氨酸（NMDA）受体的激活与耐受性和OIH均有关。作为一种NMDA受体激动剂，氯胺酮已被证明在动物模型和临床环境中可调节阿片类药物耐受性和OIH。低剂量氯胺酮凭借其NMDA受体激动剂活性，可能是治疗难治性SCD相关疼痛患者阿片类药物治疗的有用辅助药物。基于辅助使用氯胺酮进行疼痛管理的有限研究，低剂量氯胺酮持续输注似乎是安全的。有必要进行进一步的临床研究，以充分支持在SCD相关疼痛患者中使用低剂量氯胺酮输注。
