Anterior cruciate ligament repair, the procedure evaluated in this study, is associated with significant postoperative pain. Forty-five inpatients, ASA 1 or 2, mean age 26 years and mean weight 72 kilograms, underwent procedures lasting approximately two hours. Patients were premedicated with hydroxyzine 3 mg orally 1 to 2 hours before surgery and received anesthesia with propofol by target controlled infusion and vecuronium to facilitate placement of a laryngeal mask airway. Anesthesia was maintained with continuous administration of propofol and 60% nitrous oxide in oxygen. A bolus of 0.2 mg/kg sufentanil was administered 10 minutes after surgical incision, followed by a continuous infusion that was stopped 30 minutes before skin closure. The study was performed in Bolougne-Billancourt, France.

On the evening before surgery, patients were divided into 3 groups. Patients received ketamine 0.15 mg/kg or isotonic saline in identical blinded syringes. In the PRE group, the patients receive IV ketamine 10 minutes after the induction of anesthesia but before tourniquet inflation. In the POST group, the patients received 10 ml of IV ketamine at the end of surgery. In the CONT (control) group, both injections were of isotonic saline. The PRE and POST groups received placebo (saline) at the other time point. After emerging from anesthesia, patients were transferred to the PACU and then to the ward. The timing of first request for analgesic medication by the patient was recorded. In the PACU, painless control by titration of IV morphine was administered by a nurse. This titration consisted of repeated boluses of 3 mg morphine every five minutes until the 5 verbal rating scale (VRS) was less than two. Sequentially, patients were given access to a PCA device containing morphine, which was continued for 48 hours on the surgical ward. Intravenous morphine PCA was used during physical therapy sessions 24 and 48 hours after surgery. Passive and active knee flexion was recorded at the physical therapy sessions. Side effects such as nausea, vomiting, pruritus, dysphoria, and urinary retention were recorded.

The amount of propofol and sufentanil administered to all 3 groups was the same. The time from laryngeal mask airway removal and the first request for analgesics in the PACU was longer in both ketamine treated groups compared with control group: 27�23, 29�22, and 10�7 minutes for the PRE, POST, and CONT groups respectively. Accumulative morphine consumption at 24 and 48 hours was greater in the control group (CONT) than in the PRE and POST groups; there were no differences in accumulative morphine consumption between the PRE and POST groups. Incremental morphine consumption by patients on postoperative days 1 and 2 was less in the post group than in the control group for all studies. There was also a significant difference in the first 3 hours and at 19 to 24 hours. Morphine consumption was less in the first hour and similar in the second hour in the PRE group; the PRE group then followed the same time course in morphine use as the POST group with significant decrease at 19 to 24 hours.

Compared with the CONT group, significantly better first knee flexion and lower morphine consumption were noted in the ketamine groups during the first session at 24 hours; anxiety, pain scores, and the degree of maximal knee flexion were comparable in the 3 groups during this session. During the second physical therapy session at 48 hours, no inter-group differences were seen. Three cases of urinary retention were observed, one in each group. Nausea and vomiting requiring treatment occurred infrequently in all groups. No patient in any group reported sedation dysphoria, hallucinations, pruritus, or dipopia. However, it does not appear that the authors questioned all patients about these side effects; they were only noted if present.

This paper demonstrates that a single dose of ketamine 0.15 mg/kg administered intraoperatively delays the first request for analgesic. Immediate morphine consumption was lower when ketamine was injected at the end of surgery. This result is likely related to a pharmacologic action of the drug. More importantly, ketamine produced a significant 50% morphine-sparing effect during the first 48 hours after arthroscopic ACL repair, and facilitated knee mobilization at 24 hours. These effects were not related to the timing of intraoperative ketamine administration. This later beneficial effect is probably due to the action of ketamine on CNS sensitization. These authors also observed that the side effect profile was not apparently different between the treatment groups and the control. This may indicate that this low dose of ketamine does not provoke such side effects, although the subjects were not questioned thoroughly.

ABSTRACT The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair Menigaux C, Fletcher D, Dupont X, Guignard B, Guirimand F, Chauvin M. SOURCE: Anesth Analg 2000 Jan;90(1):129-35. ABSTRACT: In a randomized, double-blinded study with three parallel groups, we assessed the analgesic effect of intraoperative ketamine administration in 45 ASA physical status I or II patients undergoing elective arthroscopic anterior ligament repair under general anesthesia. The patients received either IV ketamine 0.15 mg/kg after the induction of anesthesia and before surgical incision and normal saline at the end of surgery (PRE group); normal saline after the induction of anesthesia and before surgical incision and IV ketamine at the end of surgery (POST group); or normal saline at the beginning and the end of surgery (CONT group). Anesthesia was performed with propofol (2 mg/kg for induction, 60-200 microg x kg(-1) x min(-1) for maintenance), sufentanil (0.2 microg/kg 10 min after surgical incision, followed by an infusion of 0.25 microg x kg(-1) x h(-1) stopped 30 min before skinclosure), vecuronium (0.1 mg/kg), and 60% N2O in O2 via a laryngeal mask airway. Postoperative analgesia was initially provided with IV morphine in the postanesthesia care unit, then with IV patient-controlled analgesia started before discharge from the postanesthesia care unit. Pain scores, morphine consumption, side effects, and degree of knee flexion were recorded over 48 h and during the first and second physiotherapy periods, performed on Days 1 and 2. Patients in the ketamine groups required significantly less morphine than those in the CONT group over 48 h postoperatively (CONT group 67.7+/-38.3 mg versus PRE group 34.3+/-23.2 mg and POST group 29.5+/-21.5 mg; P < 0.01). Better first knee flexion (CONT group 35+/-10 degrees versus PRE group 46+/-12 degrees and POST group 47+/-13 degrees; P < 0.05) and lower morphine consumption (CONT group 3.8+/-1.7 mg versus PRE group 1.2+/-0.4 mg and POST group 1.4+/-0.4 mg; P < 0.05) were noted at first knee mobilization. No differences were seen between the PRE and POST groups, except for an increase in morphine demand in the PRE versus the POST group (P < 0.05) in the second hour postoperatively. IMPLICATIONS: We found that intraoperative small-dose ketamine reduced postoperative morphine requirements and improved mobilization 24 h after arthroscopic anterior ligament repair. No differences were observed in the timing of administration. Intraoperative small-dose ketamine may therefore be a useful adjuvant to perioperative analgesic management.