Women aged 26–45 yr scheduled for laparoscopic sterilization using Filshie clips were eligible for the study. Patients were not included if they were unable to cooperate, were breast feeding, had known allergy to gabapentin or morphine, a history of drug or alcohol abuse, chronic pain or daily intake of analgesics or corticosteroids, diabetes, or impaired kidney function. Patients with an intake of NSAIDs or paracetamol 24 h prior to operation or an intake of antacids 48 h prior to operation were also excluded from the study. Patients were recruited from the Day Surgical Departments of Copenhagen University Hospital, Herlev (Herlev, Denmark) and Copenhagen University Hospital, Glostrup (Glostrup, Denmark) during the period September 2002 to November 2004. Written informed consent was obtained from all patients, and the study was approved by the Regional Ethics Committee (Herlev, Denmark) and The Danish Medicine Agency (Copenhagen, Denmark).
Interventions
Patients received oral lornoxicam 8 mg, combined with oral gabapentin 1.200 mg or placebo, 30 min before surgery.
General anesthesia was induced with 1.5–2.5 mg/kg propofol, and infusion of 1 μg/kg remifentanil for 1 min.
A pro seal laryngeal mask (LMA-PS) was inserted. A nasogastric tube was introduced through the LMA-PS to drain the stomach of air. Liquid gastric content was returned through the nasogastric tube. Anesthesia was maintained with infusion of propofol at the discretion of the anesthetist, and a fixed infusion of 0.4 μg·kg-1 min-1 remifentanil. Hypotension was treated with 5 mg ephedrine intravenously in incremental doses, in order to preserve systolic blood pressure above 90 mmHg. The infusions of propofol and remifentanil were terminated at skin closure; 0.5 mg alfentanil was administered intravenously to all patients, who were then transferred to the postoperative care unit. Postoperative pain treatment consisted of patient-controlled intravenous morphine (Abbott Pain Management Provider; Abbott, Virum, Denmark). Initial bolus dose was 5 mg, supplemental bolus doses were 2.5 mg. Lock-out time was 10 min. Additional morphine, 2.5 mg intravenously, was administered by a nurse observer, if requested by the patient, during the lock-out period. Ondansetron, 4 mg intravenously, was administered on patient request. No other medications were administered during the 4-h observation period.
Outcomes and assessments
The primary outcome measure was number of patients requesting morphine during the first 4 postoperative hours.
Secondary outcome measures were: Total morphine consumption from 0 to 4 h postoperatively; pain at rest and during mobilization from the supine to the sitting position, and side effects: nausea, sedation, dizziness, and vomiting.
Before surgery, all patients were instructed in the use of patient-controlled analgesia (PCA) and the visual analogue score (VAS) (0 mm: no pain, 100 mm: worst pain imaginable). Total morphine consumption was recorded from 0 to 4 h postoperatively. Pain scores at rest and during mobilization were assessed by the patients at 2 and 4 h after surgery.
Side effects were rated on a four-point verbal scale (none, mild, moderate, severe) at 2 and 4 h after surgery.
The number of patients vomiting, as well as use of antiemetics, was recorded.
Study population size
Based on registration of morphine administration for this procedure during the year before the study 60 % of patients had morphine in the postoperative period after laparoscopic sterilization. We considered a 30 % reduction in this frequency to be clinically relevant. With a type 1 error of 5 % and a power of 90% 38 patients were required in each study group.
Blinding
The study was randomized, double-blind, and placebo controlled. Study medication was prepared by the hospital pharmacy into identical capsules containing either 300 mg gabapentin, or placebo. Study medication was marked with the name of the project, the investigator's name, and consecutive numbers according to a computer-generated block randomization schedule prepared by the hospital pharmacy. Patients were enrolled by the same investigators who also performed the assessments. Participants were assigned consecutively to their group according to their number. No person was aware of group assignment until all patients had been included and assessments were completed.
Statistical methods
The Kolmogorov-Smirnov one-sample test for normality (K-S) was performed on the data sets to examine if t-test was possible. The K-S test was significant for all data sets except total morphine consumption. Consequently total morphine consumption was compared using Students t-test, and all other variables were compared using Mann-Whitney rank sum test for unpaired data.
Bonferronis correction was used for multiple comparisons.
Data are presented as medians with lower and upper quartiles. Calculations were performed using SPSS 13.0 for Windows (SPPS, Chicago, IL). The statistical analysis was performed by the investigators.
