"Pre-emptive analgesia with ketamine for major vascular surgery under remifentanil based anaesthesia. Does it matter ?"

E. Winters, D. Schmartz, A. Ducart, E. Engelman, J. Ferreira, L. Barvais

Department of Anesthesiology, Hôpital Erasme, Université Libre Bruxelles.

Introduction: After major vascular surgery under remifentanil-based anaesthesia, analgesia transition is not easy to perform because locoregional techniques are contraindicated if heparin has been used. A loading dose of a long-acting opioid drug is always required and often associated with other complementary analgesic techniques. Ketamine (0.15 mg/kg before incision) has been proposed as a pre-emptive analgesic therapy (1, 2). The aim of this study was to evaluate the effects of peroperative low doses of ketamine on the immediate postoperative pain and therapy in patients undergoing aortic abdominal aneurysm repair.

Methods: After approval of the ethical committee, 23 patients scheduled for abdominal aortic aneurysm repair give their informed written consent. Anaesthesia was performed with a TCI-technique combining remifentanil and propofol. Muscle paralysis was obtained by cis-atracurium. Patients were randomized in two groups in a double-blind fashion. In the ketamine group, they received a bolus of 0.15 mg/kg ketamine IV, 10 min before incision, followed by a continuous infusion of 3 µg/kg/min until the end of surgery. In the control group, patients received saline infusion. At the end of surgery, patients of both groups received a loading dose of 0.2 mg/kg of morphine (M⁺) and two grams of proparacetamol. TCI of remifentanil was stopped after the transfer of the patient in the ICU. Postoperative sedation was obtained by a continuous infusion of propofol (1 to 3 mg/kg/h). Postoperative analgesia was controlled by giving repeated bolus of 2 mg of morphine according to an analgesic scale. When temperature and hemodynamic parameters were stable, propofol was stopped and patients were extubated. After extubation, a PCA-pump of morphine was started. VAS at rest and at cough were regularly recorded as well as blood pressure, heart rate, respiratory rate, morphine consumption at extubation, 1, 2, 4, 8, 12 hours after extubation and regularly during the next two postoperative days. At the same time, nausea, vomiting, hallucinations and diplopia were evaluated.

Results: No statistical difference was evidenced between both groups for age, weight, duration of surgery, blood pressure, heart rate, time to extubation and total doses of propofol and remifentanil (table). Maximal mean VAS at rest were observed in both groups just after extubation and were always comparable and less than 3.5 (table). Mean VAS at cough were similar in both groups except on the morning of the first postoperative day (cough VAS: 7.5 ± 1.4 in the ketamine group and 4.2 ± 2.5 in the placebo group). Hourly and total morphine consumption were also similar. Nausea and vomiting were observed in two patients of both groups while hallucinations were recorded only once in the placebo group.

Group	N =	Time (h) to extubation	Propofol (mg)	Remifen tanil (mg)	Rest VAS extubation	Cough VAS extubation	Total M^+(mg)
Ketamine	11	5.1 ± 3.4	1283 ± 887	5.4 ± 3.3	3.5 ± 2.7	5.4 ± 2.2	64±30
Placebo	12	3.3 ± 1.6	986 ± 341	4.4 ± 1.1	3.4 ± 3.3	5.1 ± 3.1	64±41

Discussion: Pre-emptive analgesic effects of low-dose ketamine have been demonstrated during the first postoperative hours (1). In our study, low peroperative doses of ketamine has no effect on postoperative pain and morphine consumption in elderly patients after aortic abdominal aneurysm repair under remifentanil based anaesthesia technique combined with per- and postoperative morphine titration. In conclusion, pre-emptive analgesia, using low doses of ketamine is not recommended when recovery and extubation are not immediate at the end of surgery and if postoperative morphine analgesia transition is well managed.

References: 1) Royblat L. et al.: Anesth Analg 1993, 77: 1161-5

2) Tverskoy M. et al.: Anesth Analg 1994, 78: 205-9