The use of ketamine for perioperative pain management

Corresponding author: Soo Kyung Lee, M.D., Department of Anesthesiology and Pain Medicine, Hallym University Sacred Heart Hospital, 896, Pyeongchon-dong, Dongan-gu, Anyang 431-070, Korea. Tel: 82-31-380-3945, Fax: 82-31-385-3244, E-mail: [email protected] This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. CC Ketamine is a phencyclidine derivative that was introduced into clinical use in 1965. It is a noncompetitive N-methyl-Daspartate (NMDA) receptor antagonist, and has analgesic and antihyperalgesic properties. Today, it is unusual to use ketamine as the first-line drug in general anesthesia and the role of ketamine is changing in clinical practice. Ketamine may be a useful adjunct to improve the management of perioperative pain, because the mechanism of action differs from that of opioids. The antihyperalgesic mechanism of ketamine is not fully understood. Opioid-induced hyper algesia may be associated with the influence of excitatory neuro transmission [1]. Therefore, ketamine can prevent the develop ment of tolerance and hyperalgesia by inhibition of the NMDA receptors [2,3]. Various studies have reported on the potentiation of opioidinduced analgesia and the opioid-sparing effect of ketamine [4-6]. However, the results from several clinical trials are controversial. A subanesthetic dose, intravenous intraoperative ketamine reduced mechanical hyperalgesia and improved postoperative analgesia [7], and a small dose of ketamine given before skin incision decreased postoperative pain and reduced morphine consumption after open renal surgery [8]. A small intravenous dose of ketamine before the first incision followed by a 24-h infusion had a morphine-sparing effect after total hip arthroplasty and decreased postoperative chronic pain up to 6 months after surgery [9]. Intravenous patient-controlled analgesia (PCA) with a subanesthetic ketamine and morphine following transthoracic lung and heart surgery resulted in lower pain scores, reduced morphine consumption and shorter postoperative IV-PCA dependence, associated with cardiovascular stability and better respiratory parameters [10]. The potentiation of opioid-induced analgesia and the opioid-sparing effect of ketamine were observed in pediatric patients [6,11]. In this issue of the Korean Journal of Anesthesiology [12], the authors assessed the effectiveness of ketamine, when given intravenously via a PCA pump, as an alternative to nonsteroidal anti-inflammatory drugs towards the management of acute postoperative pain. The authors concluded that a small dose of ketamine (0.5-2.5 μg/kg/min) proportional to fentanyl was not only safe, but also lowered postoperative pain intensity in patients undergoing spinal fusion; however, the opioidsparing effects of ketamine were not demonstrated. However, there was no benefit provided to patients with either small-dose ketamine combined with morphine for PCA after major orthopedic surgery [13] or the addition of a low dose of ketamine to a multimodal analgesic regimen after gynecolo gical surgery [14]. Because of their side effects, low doses of ketamine can be administered in clinical practice. Even subtherapeutic doses of ketamine can cause hallucinogenic effects. In a previous study, PCA with morphine and ketamine, in a dose ratio of 1 : 1, was safe and effective. However, it was infrequently a reason for discontinuing the regimen owing to side-effects [15]. Low-dose ketamine is defined as a bolus dose of less than 2 mg/kg when given intramuscularly, or less than 1 mg/kg when administered via the intravenous or epidural route, and an intravenous infusion rate of ≤ 20 μg/kg/min [16]. The developing rhesus macaque brain was sensitive to the apoptotic action of ketamine at both a fetal and neonatal age, and exposure duration of 5 h was sufficient to induce a significant neuroapoptotic response [17]. Therefore, it is