Remifentanil Infusion Facilitates Early Recovery for Obese Outpatients Undergoing Laparoscopic Cholecystectomy

Despite the well known adverse effects of obesity, it is still the most common nutritional disorder in the United States. Unfortunately, there is a paucity of data supporting the use of one anesthetic technique over another in obese (versus nonobese) patient populations. Prolonged emergence time from general anesthesia in obese patients can be problematic in the ambulatory setting because it can delay the early recovery process. Cork et al. (1) reported that the use of IV anesthetic and analgesic drugs does not guarantee a shorter emergence period in the obese population. Because remifentanil can reduce the required end-tidal concentration of volatile anesthetics by up to 50% (2,3), we hypothesized that the use of a remifentanil infusion during a sevoflurane-based anesthetic would facilitate emergence from anesthesia in obese patients undergoing ambulatory surgery. Methods Thirty ASA physical status II outpatients with a body mass index greater than 30 kg/m2 (4) undergoing elective laparoscopic cholecystectomy procedures were enrolled in this institutional review board approved study after providing written, informed consent. Patients with clinically significant cardiovascular, respiratory, or metabolic diseases, as well as impaired renal or hepatic function, or a history of alcohol or drug abuse were excluded from participating. All patients were premedicated with IV midazolam, 2 mg IV, on arrival in the operating room. Anesthesia was induced with fentanyl, 1 μg/kg IV, followed by propofol, 1.5 mg/kg IV, and rocuronium, 0.6 mg/kg IV, based on lean body weight. After tracheal intubation, anesthesia was maintained with sevoflurane at an initial end-tidal concentration of 0.8% in combination with nitrous oxide (N2O) 65% in oxygen. During the maintenance period, patients were administered either 1) a variable-inspired concentration of sevoflurane, 0.4%–4% (Control group), or 2) a variable-rate infusion of remifentanil, 0.05–0.2 μg · kg−1 · min−1 IV (Remifentanil group) to maintain the mean arterial pressure (MAP) values within 25% of the preanesthetic baseline values, according to a computer-generated randomization scheme. If elevations in heart rate (>100 bpm) or MAP (>25% of the preanesthesia baseline) values persisted despite an inspired sevoflurane concentration of 4% (Control) or a remifentanil infusion rate of 0.2 μg · kg−1 · min−1 (Remifentanil), supplemental “rescue” doses of fentanyl, 50 μg IV, were administered every 3 min until the MAP returned to within 25% of the baseline values. All patients’ lungs were mechanically ventilated to maintain an end-tidal carbon dioxide concentration of 34–40 mm Hg and intermittent bolus doses of rocuronium, 0.15 mg/kg IV, were administered to maintain peak inspiratory pressure values < 30 cm H2O. At the end of surgery, all patients received bupivacaine 0.25% at the portals and ketorolac, 60 mg (30 mg IV and 30 mg intramuscularly), and droperidol, 0.625 mg IV, for analgesic and antiemetic prophylaxis, respectively. On completion of the operation, residual neuromuscular block was reversed with neostigmine, 60 μg/kg IV, and glycopyrrolate, 12 μg/kg IV, and the anesthetic and analgesic drugs were discontinued. Emergence times to awakening (i.e., opening eyes on verbal command) and orientation (i.e., correctly telling date, place, and person) were determined at 1-min intervals after discontinuation of the maintenance anesthetics. Times from discontinuation of anesthesia until the patient was transferred to the postanesthesia care unit (PACU) and was discharged from the PACU were also recorded. Home-readiness criteria was evaluated at 15-min intervals after PACU discharge by using the postanesthesia discharge scoring system (5). Nausea, vomiting, and the need for rescue antiemetics (e.g., metoclopramide, 10 mg IV, ondansetron, 4 mg IV) were assessed by directly questioning the patient at 10-min intervals in the PACU and at 30 min intervals in the Phase II (step-down) unit regarding the presence of emetic symptoms. The requirements for postoperative analgesic medications (e.g., IV fentanyl and oral hydrocodone) were also recorded. A power analysis was performed before the initiation of the study. This analysis suggested that a sample size of 15 patients for each group should be adequate to detect a 30% reduction in the times to awakening with a power of 0.8 (α = 0.05). Two-sample equal-variance t-test was performed for continuous variables and χ2 test with Yates’ correction was performed for discrete variables. Data were expressed as mean ± sd, with P values less than 0.05 considered statistically significant. Results The two treatment groups were similar with respect to demographic characteristics, duration of surgery and anesthesia, baseline and intraoperative MAP and heart rate values, as well as the volume of IV fluids (Table 1). As expected, the average end-tidal concentration of sevoflurane was significantly higher in the Control versus the Remifentanil group (Table 1).Table 1: Demographic Characteristics, Duration of Anesthesia and Surgery, Baseline Hemodynamic Variables, Dosages of Sevoflurane, Remifentanil and Fentanyl, and IV FluidThe times to awakening, extubation, orientation, and transfer to PACU were significantly shorter in the Remifentanil group (Table 2). However, the PACU stay and times to achieve the home-readiness criteria were similar in both study groups. Of the 30 patients studied, 4 patients in the Control group and 2 patients in the Remifentanil group were hospitalized because of surgical complications. There were no statistical differences between the two groups with respect to the incidences of postoperative nausea and vomiting or the requirements for rescue antiemetics and analgesics before hospital discharge or 6 h after the operation if the patient was admitted because of a surgical complication (Table 3).Table 2: Recovery Times After Discontinuation of AnesthesiaTable 3: The Incidences of Postoperative Nausea, Vomiting, and Usage of “Rescue” Analgesics and Antiemetic Drugs Before DischargeDiscussion Remifentanil is a potent opioid with a fast onset and a short duration of action caused by its rapid hydrolysis by tissue esterases. Egan et al. (6) reported that the pharmacokinetics of remifentanil were not significantly different in obese compared with lean patients. In previous outpatient laparoscopy studies, it has been demonstrated that the use of sevoflurane as a maintenance drug had a more favorable recovery profile when compared with desflurane for emetic symptoms (7) and provided a more rapid emergence than propofol (8). In the current study, combining a variable-rate remifentanil infusion (averaging 0.09 μg · kg−1 · min−1) with sevoflurane-N2O anesthesia resulted in a nearly 50% decrease in the end-tidal sevoflurane concentration required for maintaining an adequate depth of anesthesia. The anesthetic-sparing effect of remifentanil contributed to a more rapid emergence after laparoscopic cholysystectomy procedures in these obese patients. The adjunctive use of remifentanil did not increase postoperative side effects, in particular nausea and vomiting. These findings are consistent with a recently published study involving the use of a remifentanil infusion during a desflurane-based anesthetic (3). In this outpatient population, the use of a second dose of propofol at the end of surgery may also be helpful in lowering the incidence of postoperative nausea and vomiting (7). However, the antiemetic effect of propofol appears to be shorter lasting than when droperidol is used for prophylaxis. To minimize the risk of postoperative pain and emetic symptoms after laparoscopic surgery, we recommend administering nonopioid analgesics (e.g., bupivacaine, ketorolac) and prophylactic antiemetics (e.g., droperidol, dexamethasone). In the current study, the more rapid emergence from anesthesia in the Remifentanil group failed to decrease the PACU stay or the discharge time. The recovery policy at the institution where this study was conducted required that all obese outpatients remain in the PACU for a minimum of one hour after general anesthesia. If there was no minimum length of stay requirement in the PACU, it might well have been possible to demonstrate differences in later recovery times. Using this remifentanil-sevoflurane technique, we have subsequently been able to fast-track (i.e., bypass the PACU) some obese outpatients undergoing laparoscopic surgery. In conclusion, remifentanil infusion facilitates a more rapid emergence from a sevoflurane-based anesthetic in obese outpatients undergoing laparoscopic surgery without increasing opioid-related side effects.