A recent study by Cheng et al.1 investigating the postoperative analgesic effects of nicotine nasal spray coincidentally found that patients anesthetized with propofol had less postoperative pain than patients anesthetized with isoflurane over the first 24 h. Previous clinical studies investigating the recovery profile of IV propofol anesthesia compared with inhaled anesthetics have shown a tendency to better postoperative analgesia with propofol.2–4 However, none of these studies was designed and powered to detect differences in postoperative pain over time as a primary outcome.
The objective of this study was to determine (a) whether patients anesthetized with IV propofol have less pain compared with patients anesthetized with sevoflurane for laparoscopic day-case surgery, and (b) whether IV propofol anesthesia has better quality of recovery compared with sevoflurane anesthesia in the immediate postoperative period after diagnostic day-case laparoscopic surgery.
This study was approved by the hospital ethics research committee and registered with the European Clinical Trials Database (EUDRACT 2008-0010502-48). After we obtained written informed consent, 80 ASA physical status I–II patients older than 18 yr undergoing day-case diagnostic laparoscopic surgery were recruited into the study. Patients with chronic pain states, allergies, or contraindications to any of the medications and those who were pregnant were excluded from the study.
Patients were randomized into 2 groups using a computer-generated random number table: the first group was anesthetized with IV propofol (Group P) and the second group (Group S) was anesthetized with sevoflurane. Group assignment was placed in sealed opaque envelopes that were opened by the attending anesthesiologist who would administer the anesthetic and had no further involvement in assessing the patient postoperatively. The investigator was blinded to the drug administered and only assessed the patients in the postoperative care unit (PACU). All patients were instructed on the use of the visual analog scale (VAS) for pain assessment before the induction of anesthesia.
On arrival to the operating room, physiological monitoring was established before the induction of anesthesia (pulse oximetry, continuous electrocardiography, and noninvasive arterial blood pressure monitoring). An 18-gauge cannula was sited and compound sodium lactate (Hartmann's solution) was infused at 1000 mL/h, reducing to a maintenance rate of 1 mL · kg−1 · h−1 if surgery exceeded 1 h.
All patients received IV alfentanil 0.5 mg before the induction of anesthesia. In Group S, anesthesia was induced using an inhaled technique. After priming a circle breathing system with 8% sevoflurane in 100% oxygen, patients were encouraged to take deep breaths through the breathing system until loss of eyelash reflex. Tracheal intubation and positive pressure ventilation were facilitated with rocuronium 0.3 mg/kg. The patient's lungs were mechanically ventilated with a mixture of oxygen (FIO2 0.5) in air maintaining the end-tidal CO2 at 4.5–5.0 kPa. Anesthesia was maintained with sevoflurane titrated to a bispectral index (Aspect Medical Systems, Norwood, MA) value of 40.
In Group P, anesthesia was induced with 2.5 mg/kg propofol. Tracheal intubation and positive pressure ventilation were facilitated with rocuronium 0.3 mg/kg. The patients' lungs were mechanically ventilated with a mixture of oxygen (FIO2 0.5) in air maintaining the end-tidal CO2 at 4.5–5.0 kPa. Anesthesia was maintained with IV propofol infusion titrated to a bispectral index value of 40.
After induction of anesthesia, all patients received IV paracetamol 1 g and IV infusion of diclofenac 75 mg in 250 mL of normal saline. To prevent postoperative nausea and vomiting, all patients received IV dexamethasone 4 mg immediately after induction of anesthesia and IV ondansetron 4 mg at the end of surgery. Neostigmine 2.5 mg with glycopyrrolate 0.5 mg IV was administered to antagonize any residual neuromuscular blockade at the end of surgery.
In the PACU, postoperative pain was treated with 2-mg boluses of IV morphine until a VAS pain score of <4 was achieved. Postoperative nausea and vomiting were treated with IM prochlorperazine 12.5 mg. Once patients were discharged to the ward, breakthrough pain was treated with immediate release oxycodone 10 mg orally.
After emergence from anesthesia, the time the patient arrived at PACU was designated time 0. At time 0, every 10 min for 60 min, 90 min, 2 h, and 4 h, the following data were collected: VAS pain scores (0 cm = no pain and 10 cm = worst pain imaginable); sedation score measured with a 5-point scale (0 = alert and fully awake; 1 = lightly asleep, eyes open intermittently; 2 = asleep, eyes open to verbal command; 3 = responds to painful stimulus, does not respond to verbal command; and 4 = unresponsive); cumulative dose of morphine; incidence of postoperative nausea and vomiting; and incidence of demand for additional oral analgesic. A quality of recovery score, based on a structured 9-item quality of recovery questionnaire5 (QoR-9), was recorded before discharge.
Based on an audit of day-case laparoscopic surgery in our department whereby the mean VAS postoperative pain score was 6 with a standard deviation of 2, it was calculated that 72 patients (36 pairs) would be required to have an 80% power of detecting a 1.5-cm reduction in the pain VAS at a significance level of 0.05. Using these calculations, we decided to randomize 40 patients (total 80) into each group to account for protocol violations.
Statistical analyses were undertaken with PRISM 5 for Mac OS, version 5.0a (GraphPad Software, San Diego, CA). Data on patients' weight and height, duration of surgery, time to discharge, and total morphine consumption were analyzed using Student's t-test. Total overall pain VAS was analyzed by plotting VAS against time and calculating the area under curve for each group using the trapezium rule. Fisher's exact test was used to compare categorical data, and Mann-Whitney test was used to compare nonparametric data. A P value of <0.05 was considered significant.
Eighty patients completed the study (40 in each group). Both groups had similar demographics (Table 1).
Patients in Group P reported significantly less pain than patients in Group S (Fig. 1). The area under the curve was greater in Group S (mean 578.6 cm/min, 95% confidence interval [CI] 471.1–686.1 cm/min) compared with Group P (mean 403 cm/min, 95% CI 319–486.9 cm/min; P = 0.01, Student's t-test). The mean postoperative total morphine consumption in Group P was 3.62 (2.89) mg compared with 4.62 (5.29) mg in Group S (mean difference 1, 95% CI −2.88 to 0.88; P = 0.30) (Fig. 2). There was no difference in the incidence of nausea and vomiting or sedation score at any time points (Table 2).
Although the mean time to discharge in Group P was shorter compared with Group S, this did not achieve statistical significance (mean difference 20.14 min, 95% CI −6.3 to 46.6 min; P = 0.13). There was no difference in the incidence of unanticipated admissions and demand for oral analgesics (Table 3).
This study demonstrated that patients undergoing day-case gynecological surgery anesthetized with propofol had less pain over the immediate postoperative 4-h period than patients anesthetized with sevoflurane. This is consistent with the recent findings of Cheng et al.1 in which propofol-anesthetized patients had less postoperative pain compared with patients anesthetized with volatile anesthetics.
We could not ascertain whether the above finding was attributable to the analgesic properties of propofol or hyperalgesic effects of sevoflurane, although there is evidence in the literature to support both.6–13 There was no difference among the quality of recovery, incidence of nausea and vomiting, sedation, and discharge times between groups. Although there was a difference in the VAS pain scores, we did not find a difference in cumulative morphine consumption between the 2 groups.
We have shown that patients anesthetized with IV propofol anesthesia for gynecological laparoscopic surgery had less pain than patients anesthetized with sevoflurane. Further studies will need to be done to ascertain whether this effect was due to analgesic properties of propofol or hyperalgesic effects of volatile anesthesia.
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