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Pre-Emptive Low-Dose Ketamine Does Not Improve Analgesia after Spinal Fusion Surgery in Children
Joel B. Gunter, M.D., John J. McAuliffe, M.D., M.B.A., Eileen Beckman, R.N., Richard E. Berlin, M.D., Anna M. Varughese, M.D.
Department of Anesthesia, Children's Hospital Medical Center, Cincinnati, Ohio.
One possible mechanism of pre-emptive analgesia is blockade of spinal NMDA receptors.¹ We studied the pre-emptive analgesic efficacy of ketamine, a potent NMDA antagonist, in children undergoing spinal fusion surgery.

Materials and Methods-After informed parental consent and subject assent, children 8 years and older presenting for spinal fusion surgery (posterior, anterior, or VATS/posterior) were randomized to receive in a double-blind fashion either ketamine (0.3 mg/kg bolus before incision followed by a 5 μg/kg/min infusion) or placebo. All subjects received a standardized anesthetic maintenance consisting of midazolam 0.1 mg/kg, morphine 0.5 mg/kg, and D-tubocurarine supplemented with N2O and isoflurane as needed. Esmolol and sodium nitroprusside were used for deliberate hypotension (target HR < 100/min and MAP 50-60 mmHg). The study drug infusion was stopped 30 min before the wake-up test or the end of surgery. Subjects self-administered morphine via PCA after surgery. PCA morphine usage, VAS pain scores, and analgesia satisfaction scores (1 poor, 2 fair, 3 good, 4 excellent) were recorded every 4 h postoperatively. PCA morphine was summed and VAS and satisfaction scores were averaged for the first and second postoperative days (POD). Subjects were queried at 24h, 48h, and one week after surgery regarding dysphoric symptoms. Data were compared between groups using Student's t-test (for continuous and ordinal data) or Chi-squared contingency tables with Yate's correction for continuity (for nominal data).

Results-Subject demographics are shown in Table 1. PCA morphine usage on PODs 1and 2 did not differ between subjects receiving ketamine or placebo (Table 2). VAS pain scores for PODs 1 and 2 and analgesia satisfaction scores for POD 1 also showed no difference between groups; analgesia satisfaction scores on POD 2 were higher, signifying greater satisfaction, in subjects receiving placebo. Subjects in the placebo group had a greater normalized blood loss, but the difference was not significant. Almost half (7/15) of the subjects in the ketamine group reported dysphoric symptoms in the first week after surgery, versus only a quarter (5/21) of those in the placebo group (P = 0.28)

Discussion-In contrast to our results, ketamine has shown efficacy in providing pre-emptive analgesia in adults in doses comparable to those used in this study.² Our study population was small, suggesting the possibility of a Type II error; however, the absence of any trend in morphine usage or VAS/satisfaction scores in favor of ketamine makes such an error less likely. It seems more likely that a positive association between ketamine and postoperative psychotomimetic disturbance was obscured by limited sample size. We conclude that ketamine does not confer pre-emptive analgesia in children having spinal fusion surgery.

References-1. Pain 1991;44:293. 2. Anesth Analg 1993;77:1161.

Anesthesiology 2003; 99: A1405
Table 1: Demographics
NumberAge (y)Weight (kg)
Table 2: Outcome Variables
MSO4 POD1 (mg/kg/d)MSO4 POD2 (mg/kg/d)VAS POD1VAS POD2Satisfaction POD1Satisfaction POD2EBL (ml/kg)
*P = 0.046