Journal: Anesth Analg 107(4):1170-1175, 2008. 35 References
Reprint: Dept of Anesthesia, The Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8 (MW Crawford, MBBS, FRCPC)
Faculty Disclosure: Abstracted by L. Easley, who has nothing to disclose.
Anesthetic challenges presented by scoliosis surgery include the need to provide profound intraoperative analgesia and to facilitate intraoperative neurophysiologic monitoring of the spinal cord and/or wake-up testing. In a prospective randomized, placebo-controlled, double-blind trial the authors tested the hypothesis that low-dose intraoperative infusion of the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine would prevent the development of acute opioid tolerance and thereby decrease postoperative morphine consumption and improve pain scores after surgical correction of idiopathic scoliosis.
Thirty-four unpremedicated adolescents, aged 12-18 yrs, scheduled to undergo posterior instrumentation for correction of idiopathic scoliosis were studied. Patients were assigned randomly to receive ketamine as a bolus dose of 0.5 mg/kg followed by a continuous infusion of 4 mcg/kg/min or a bolus and infusion of an equal volume of placebo (saline). Cumulative postoperative morphine consumption, pain scores at rest and on coughing, and sedation scores were recorded every hour for the first 4 hr, every 4 hr for 20 hr, and then every 12 hr until completion of the study at 72 hr. Postoperative nausea, vomiting, pruritus, pyrexia, and expressions of unpleasant dreams were recorded.
Cumulative morphine consumption in the initial 36 hr after surgery was almost identical in the two groups. Mean cumulative PCA morphine consumption at 24, 48, and 72 hr after surgery did not differ significantly between groups. No significant differences between groups were found in NRS pain scores, either at rest or during cough.
Remifentanil-based anesthesia is associated with the development of clinically relevant acute opioid tolerance and/or hyperalgesia in humans, as evidenced by a reduced therapeutic benefit from a given dose of opioid. The NMDA receptor is involved in the modulation of windup, allodynia, and acute opioid tolerance. In clinical studies, ketamine has been shown to be beneficial in the management of acute postoperative pain after a variety of surgical procedures. Ketamine and other NMDA antagonists have been studied in a variety of clinical scenarios using a variety of routes and dosage regimens. The dose of ketamine used in the present study is supported by studies showing that ketamine produces effective analgesia when administered as a single bolus of >0.3 mg/kg, but has no effect on analgesia or morphine consumption when administered at infusion rates <4 mcg/kg/min.
Pharmacokinetic differences in children may explain in part, why the study results with ketamine differ from those in adults and it remains open to speculation whether a larger dose of ketamine or an extension of the infusion into the postoperative period would have suppressed the development of remifentanil-induced hyperalgesia.
In conclusion, this study does not support the use of low-dose intraoperative infusion of ketamine to prevent the development of acute opioid tolerance and/or hyperalgesia resulting from remifentanil-based anesthesia. |
