Ketamine is an antagonist at the N-methyl-D-aspartate receptor and has analgesic properties that may be important in the modulation of central sensitization to nociceptive stimulation. This class of drug may be useful for prevention and treatment of acute postoperative pain. Some clinical studies have described an analgesic effect of systemic ketamine [1-3]. The purpose of this study was to assess the analgesic effect of intravenous (i.v.) ketamine on postoperative morphine consumption.
After Ethics Committee approval and written informed consent, ASA I-II patients, aged 20-75, scheduled for lower abdominal surgery and requiring morphine for postoperative analgesia were included in a prospective, double-blinded, placebo-controlled, randomized study. Exclusion criteria were morbid obesity, psychiatric disorder, chronic opioid use or prescription of an opioid within 12 h before surgery, allergy to opioids or any other drug used in the study, alcohol intoxication, pregnancy or breastfeeding, hypertension, or severe respiratory insufficiency. On the evening before surgery, patients were instructed about the use of a 10 cm visual analogue scale (0: no pain to 10: worst possible pain) and a patient-controlled analgesia device (Pain management provider 5500, Abbott, USA).
Patients were allocated using a random number table to one of two groups, a control group and a ketamine group. Patients in the control group received i.v. isotonic sodium chloride 10 mL. Patients in the ketamine group received i.v. ketamine 150 μg kg−1 diluted with isotonic sodium chloride to a volume of 10 mL.
Anaesthesia was induced with i.v. remifentanil 1 μg kg−1 and propofol 1.5 mg kg−1. Tracheal intubation was facilitated with 0.1 mg kg−1 vecuronium. Anaesthesia was maintained with propofol 70 μg kg−1 min−1 and remifentanil 0.5 μg kg−1 min−1. Patients received the study drugs before the surgical incision. Propofol was discontinued 10 min before the anticipated end of surgery and remifentanil was stopped at skin closure. Patients received morphine 0.1 mg kg−1 i.v. approximately 30 min before the end of surgery. Muscle relaxation was antagonized at the end of operation with neostigmine 3 mg and atropine sulphate 1 mg.
After emerging from anaesthesia, patients were transferred to the recovery room where they stayed for at least 1 h, and were then discharged to the ward. Upon arrival in the recovery room, visual analogue scores were measured and patients were connected to the patient-controlled analgesia device. The time to first analgesic demand was recorded. The patient-controlled analgesia device was programmed to deliver a bolus of 1 mg of morphine, with a lockout interval of 12 min and no background infusion. Patients continued to use the system on the ward for until 48 h after surgery during which time no other analgesics were administered. Morphine requirement, pain intensity, heart rate (HR), systolic blood pressure (BP) and respiratory rate were recorded at 30 min and at 2, 12, 24 and 48 h after surgery. Adverse effects (nausea, urinary retention, sedation and pruritus) were recorded.
Statistical analysis was performed using SPSS 8.0 for windows. Age, weight and length of surgery were analysed with Student's t-test. For opioid consumption, we used the Mann-Whitney U-test to compare the doses consumed by the two groups. Visual analogue scores were analysed using the Kruskal-Wallis test. A P-value <0.05 was considereds statistically significant. Data are expressed as mean ± SE.
Sixty patients gave informed consent to participate in the study. There were no exclusions resulting in 30 patients in each group. There were no differences between the groups with respect to age (45.2 ± 3.0 yr vs. 47.2 ± 4.2 yr), weight (66.1 ± 3.1 kg vs. 66.2 ± 2.8 kg), gender (male: female - 14:16 vs. 17:13) and duration of operation (210.8 ± 20.5 min vs. 213.4 ± 21.3 min) in control and ketamine groups, respectively.
The pain scores were statistically significantly different between the two groups at 30 min and at 48 h (Table 1). Time to first analgesic request was 17.7 ± 2.2 min in the ketamine group and 11.4 ± 1.2 min in controls (P < 0.05). In the ketamine group, morphine consumption was decreased compared with the control group; after 24 h, cumulative morphine consumption was 44.2 ± 4.1 mg in the ketamine group and 53.9 ± 4.0 mg in the control group (P < 0.05) (Fig. 1). Between 24 and 48 h, cumulative morphine consumption was 25.6 ± 3.9 mg with ketamine and 32.8 ± 4.4 mg in controls (P < 0.05) (Fig. 1).
There were no statistically significant differences between the groups in respect of HR, respiratory rate and systolic BP. No patient suffered central excitatory phenomena or respiratory depression. Two controls and four from the ketamine group had urinary retention. Two controls and one patient from the ketamine group were nauseous or vomited, none requiring treatment.
The major finding of this study was the reduced postoperative morphine requirement in the ketamine group. Our results also indicate that a small preoperative dose of ketamine delays the first postoperative request for analgesia by about 6 min (11.4 vs. 17.7 min).
Many studies have investigated the effect of a systemic co-administration of low-dose ketamine on postoperative morphine consumption [1,2,4-7]. Several studies have described an analgesic effect with ketamine [2,4,7] although the results are conflicting. Roytblat and colleagues  and Fu and colleagues  found reduced morphine requirements in the ketamine group. Menigaux and colleagues , Adam and colleagues , Holthusen and colleagues  and Gilabert and Sanchez  were unable to demonstrate any difference. Our study supports the view that a small dose of ketamine administered preoperatively can reduce postoperative morphine requirements without significant adverse effects.
Department of Anesthesiology; Cumhuriyet University School of Medicine; Sivas, Turkey
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6. Gilabert MA, Sanchez PC. Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy. Rev Esp Anestesiol Reanim
© 2004 European Academy of Anaesthesiology
7. Aida S, Yamakura T, Baba H, Taga K, Fukuda S, Shimoji K. Preemptive analgesia by intravenous low-dose ketamine and epidural morphine in gastrectomy: a randomized double-blind study. Anesthesiology