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INTRAVENOUS ANESTHESIA

Recovery After Anesthesia with Remifentanil Combined with Propofol, Desflurane, or Sevoflurane for Otorhinolaryngeal Surgery

Department of Anesthesiology, University Hospital, Freiburg, Germany

Address correspondence and reprint requests to Torsten Loop, MD, Department of Anesthesiology, University Hospital, Hugstetterstrasse 55, D-79106 Freiburg, Germany. Address e-mail to torsten{at}ana1.ukl.uni-freiburg.de

Abstract

Because no previous investigation has directly compared the combination of remifentanil (REM) and a hypnotic with that of REM and the newer volatile anesthetics, we studied recovery characteristics and patient satisfaction after the combination of REM with propofol (PRO), desflurane (DES), or sevoflurane (SEVO). One hundred twenty patients were randomly assigned to receive anesthesia with either REM/PRO, REM/DES, REM/SEVO, or thiopental/alfentanil/isoflurane/N₂O (control group) for ear, nose, and throat surgery (n = 30 each). In the REM groups, the dosage of PRO (75 µg · kg^-1 · min^-1), and of DES or SEVO (0.5 minimum alveolar anesthetic concentration) was kept unchanged, and REM was titrated to hemodynamic response. The control group was managed according to standard practice. Early recovery (times to eye opening, extubation, and statement of name and date of birth) was predictably faster and more complete in the REM groups compared with the control group. However, late recovery (times to discharge from postanesthesia care unit and hospital) and overall patient satisfaction were not different among groups. No clinically relevant differences existed among the three REM groups. In conclusion, the combination of REM infusion with small-dose DES, SEVO, or PRO is characterized by predictably rapid, early recovery. However, late recovery and patient satisfaction are comparable to a conventional anesthetic technique.

Implications: Remifentanil anesthesia, combined with small-dose propofol, desflurane, or sevoflurane, enables predictably fast and smooth early recovery after ear, nose, and throat surgery. Despite such faster, early recovery and less need for postoperative analgesic and antiemetic medication, late recovery was comparable among the remifentanil combination groups and the control group.

Predictably rapid emergence from anesthesia and sustained alertness are highly desirable characteristics of any anesthetic technique. The pharmacokinetics of the newly introduced µ-opioid agonist remifentanil (REM) favor prompt emergence from anesthesia (1,2). The pharmacokinetics of the new, inhaled anesthetics desflurane (DES) (3,4) and sevoflurane (SEVO) (4,5) provide similar clinical advantages. When used as hypnotic in small concentrations, DES and SEVO may present an alternative to propofol (PRO). Accordingly, this study was performed to test the hypotheses that (a) a combination of REM with either DES, SEVO, or PRO will provide comparable recovery characteristics, and (b) all REM-based anesthetics will result in faster early and late recovery when compared with a conventional anesthetic technique.

Methods

With approval by the local ethics committee of the University Hospital of Freiburg, and after obtaining informed, written consent, we prospectively studied 120 patients (ASA physical status I–III, ages 16–65 yr) scheduled for elective otorhinolaryngeal surgery. Exclusion criteria included ASA physical status IV, age < 16 or > 65 yr, body weight > 40% above normal, history of alcohol and drug abuse, pregnancy, medication known to affect minimum alveolar anesthetic concentration (MAC), and communication problems. Patients were assigned by block randomization to receive one of four anesthetics combinations (n = 30 each group): REM/PRO, REM/DES, REM/SEVO, or a "conventional" thiopental/alfentanil/isoflurane/N₂O (THIO/ALF/ISO/N₂O) technique, serving as the control group.

No anesthetic premedication was given. Patients randomized to receive REM were given 4 µg/kg IV glycopyrrolate 3–5 min before the induction of anesthesia. Then, 1 µg/kg REM was administered for 30–40 s followed by a continuous infusion of 0.5–1.0 µg · kg^-1 · min^-1 REM. On becoming drowsy, patients of the REM/PRO group received 1 mg/kg of PRO followed by a continuous infusion of 200 µg · kg^-1 · min^-1 PRO. Patients of the REM/DES and REM/SEVO groups were given DES or SEVO via face mask at increasing inspired concentrations of up to a maximum of (age-adjusted) 0.75 MAC. Mivacurium or cisatracurium was administered to facilitate tracheal intubation.

After intubation, PRO, DES, and SEVO were reduced and maintained unchanged throughout the course at 75 µg · kg^-1 · min^-1. At approximately (age-adjusted) 0.5 MAC end-tidal, REM was reduced to 0.3–0.5 µg · kg^-1 · min^-1 and subsequently titrated as required by the hemodynamic response to surgical stimulation.

In the THIO/ALF/ISO/N₂O group, anesthesia was induced by using 5–10 µg/kg IV alfentanil and 3–5 mg/kg of thiopental, followed by vecuronium. After endotracheal intubation, anesthesia was continued with up to (age-adjusted) 1 MAC end-tidal isoflurane, 60% N₂O in O₂, and intermittent bolus doses of 3–5 µg/kg alfentanil. Immediately after intubation, all patients received a suppository of acetaminophen 10–15 mg/kg.

At the start of wound closure, only patients of the REM groups who had surgery involving major soft tissue or bone injury were given an opioid of 0.075–0.1 mg/kg IV piritramide (6). During the last surgical suture, PRO, DES, SEVO, or isoflurane were discontinued. After the final surgical intervention, REM and N₂O were discontinued. Once respiration and response to verbal command were adequate, patients were endotracheally extubated.

We aimed at maintaining intraoperative mean arterial pressure and heart rate within 20% of the preinduction values, primarily by adjusting REM and isoflurane dosages. If this proved inadequate, IV urapidil (for hypertension), metoprolol (for tachycardia), atropine (for bradycardia), or etilefrine (for hypotension) was administered.

Postoperative pain was treated by using incremental IV doses of piritramide 0.05 mg/kg every 10 min until adequate pain relief. At 4 h after the initial acetaminophen application, 1 g of acetaminophen or 100 mg of diclofenac suppositories was administered and repeated every 6–8 h, as indicated.

Postoperative nausea/vomiting was treated by 0.15 mg/kg IV metoclopramide. If nausea did not improve within 10 min, 15 µg/kg IV dehydrobenzperidol was administered and, if necessary, repeated once, after 10 min. Postoperative shivering persisting for longer than 10 min was treated with incremental doses of 0.5 µg/kg up to a total of 2 µg/kg IV clonidine (7). Patients were discharged from the postanesthesia care unit (PACU) directly to the ward, if (a) they had stayed in the PACU for at least 30 min; (b) the modified Aldrete score was 9 (8); and (c) pain and nausea were controlled. Assessment for PACU discharge was made at 15-min intervals. Time of hospital discharge was the surgeon’s decision.

The afternoon before surgery, all patients were instructed in the use of a 10-cm visual analog scale (VAS) for the assessment of pain (0 = no pain, 10 = worst imaginable pain), nausea (0 = no nausea, 10 = worst imaginable nausea), and sleepiness (0 = fully alert, 10 = worst imaginable sleepiness). Scores were assessed the afternoon before surgery (serving as the control), and at 30, 60, 90, and 120 min, and at 4 and 24 h after extubation.

At 48 h after extubation, patient satisfaction with the anesthetic and pain management was assessed, each by VAS (0 = totally unsatisfied, 10 = completely satisfied). Patients were also asked 1) to rate the overall anesthetic experience ("as expected," "worse than expected," or "better than expected"), 2) whether they would or would not have the same anesthetic again, if required, and 3) whether they had any intraoperative recall.

An a priori calculation of study size (9), based on previously reported values for recovery times (10–13) and on ß and values of 0.2 and 0.05, respectively, suggested that 25 patients would be needed in each group to detect a difference in recovery times of 30%. Two-way analysis of variance for repeated measurements with one within-factor (time) and one between-factor (group) followed by the Student-Newman-Keuls test for multiple comparisons were used to analyze VAS data. One-way analysis of variance on ranks followed by Student-Newman-Keuls test for multiple comparisons was used for analysis of data on patient and surgical characteristics, patient satisfaction, recovery times, and drug administrations for each group. Potential univariate correlates of patient satisfaction were identified by linear-regression technique. Then, variables significant at a two-sided P < 0.05 were entered in a multiple linear-regression model. Data involving continuous variables were assessed for distribution, and those not normally distributed are presented as medians and ranges. A P < 0.05 was considered statistically significant.

Results

Patient, anesthetic, and surgical characteristics are summarized in Table 1. Except for the study design-related differences in the use of REM and alfentanil, there were no significant differences among groups.

The vast majority of patients in each group (90% to 97%) received local lidocaine infiltration by the surgeon before incision. A comparable number of patients in each REM group (37% to 47%) received piritramide toward the end of surgery.

Because there were no statistically significant differences in any type of medication within the three REM groups, we pooled the data of the REM groups. We combined piritramide and nonsteroidal antiinflammatory drugs to reflect the need for analgesic medication, combined atropine, etilefrine, metoprolol, and nifedipine to reflect the need for cardiovascular medication, and combined metoclopramide and droperidol to reflect the need for antiemetic medication (Table 3).

When looking at the entire perioperative period, patients of the REM groups required as many interventions as the control group (2.0 vs 2.1 per patient). However, the need for medications in the postoperative period was significantly less (P < 0.05) in the REM groups (1.3 vs 2.0 per patient). This was primarily because of a lesser need for analgesic (0.4 vs 0.6 per patient) and antiemetic (0.2 vs 0.5 per patient) treatment in the early postoperative period. Even when not including the REM/PRO group in the analysis, the entire need for antiemetic treatment in the REM/DES and REM/SEVO groups was less than that in the control group (0.3 vs 0.6 per patient, P < 0.05).

The VAS scores for pain were comparable among groups at all times, and they decreased with time (Figure 1A). During the first 90 min after extubation, VAS scores for nausea were significantly less in the REM/PRO group than in the other groups, and only in this group did they not exceed preoperative control values (Figure 1B). VAS scores for sleepiness were higher in the THIO/ALF/ISO/N₂O control group than in the three REM groups only during the first 60 min after extubation.

View larger version (22K): [in this window] [in a new window]   Figure 1. A, Results are presented as medians and 95% confidence intervals. *P < 0.05 versus preoperative value. P = propofol; D = desflurane; S = sevoflurane; C = control; REM = remifentanil; THIO/ALF/ISO/N2O = thiopental/alfentanil/isoflurane/N2O. B, Results are presented as medians and 95% confidence intervals. *P < 0.05 versus preoperative value. §P < 0.05 versus other groups.

Discussion

Our main findings can be summarized as follows: 1) early recovery from all three REM-based anesthetics was predictably fast and more complete than that from THIO/ALF/ISO/N₂O anesthesia; 2) there was less need for analgesic and antiemetic medication in the early postoperative period in the REM groups; 3) late recovery and patient satisfaction did not differ among the REM groups and the control group; 4) nausea was a multivariate correlate of patient satisfaction; and 5) most differences among the three REM groups were clinically irrelevant, except for slightly earlier fluid intake, ambulation, and less nausea in the early recovery period in the REM/PRO group.

The narrow ranges of early recovery times reflect high predictability. This is particularly remarkable when considering that anesthesia lasted for up to five to six hours. Such early recovery characteristics might provide a safety factor, especially in surgery that involves the upper airway. After REM anesthesia, patients not only recover faster initially, they also stay alert. However, faster early recovery did not translate into faster late recovery as judged by comparable times to discharge from PACU and hospital in all groups.

Because of the rapid offset of action of REM, immediate postoperative pain must be of concern whenever REM-based anesthetics are used. High patient satisfaction with pain management and comparably low pain scores in all four REM groups support the effectiveness of the chosen analgesic approach. Although 53% to 63% of the patients did not prophylactically receive the long-acting opioid piritramide, only 20% to 27% of the patients of the REM groups needed piritramide postoperatively. This emphasizes that prophylactic administration of a long-acting opioid is not necessarily required in each case of REM-based anesthesia. Restricting the indications for the prophylactic use of opioids might help hasten recovery and reduce side effects.

Our results indicate that REM-based anesthetics do not per se increase the incidence of PONV after otorhinolaryngeal surgery. Whereas 30% of patients in the control group required antiemetic therapy, this compares to approximately 20% in the REM/DES and REM/SEVO groups, and to just 3% in the REM/PRO group. The lower incidence of PONV in the REM/PRO group may reflect an intrinsic antiemetic property of propofol (14,15).

The approximately threefold greater requirement for intraoperative cardiovascular medication in the REM groups reflects the higher incidence of hypotension and bradycardia during the induction and the early maintenance phase of anesthesia. The overall postoperative need for pharmacologic intervention per patient was significantly less in the REM groups than in the control group. This difference was entirely because of a lesser requirement for analgesic and antiemetic medication in the first four hours postoperatively. We are unable to provide a satisfactory explanation for this finding.

Despite objective and subjective differences among groups in early recovery characteristics, patient satisfaction was equally high among groups. It is conceivable that the increased attention paid to all patients (required by protocol) influenced their perception of quality of overall perioperative care to an extent that outweighed other factors.

Correlation analysis confirmed that neither the type of anesthesia nor the type of surgery influenced the degree of patient satisfaction. Although univariate correlation analysis suggested that nausea, pain, and sleepiness affect patient satisfaction, only nausea proved to be a multivariate correlate of patient satisfaction. This could explain the tendency toward a higher "better than expected" rating in the REM/PRO group when compared with the other groups (57% vs 33% to 37%).

Very similar infusion rates of REM and PRO have been used in two previous studies involving various types of inpatient and laparoscopic surgery (11,16). Although mean emergence times were comparable to those found in this study, ranges of early recovery times were much larger, despite shorter or comparable duration of anesthesia (11,16). These comparably larger variations (reflecting less predictability) may be caused by premedication with midazolam, an older patient population, and a different handling of REM at the end of surgery (11,16). The reported incidence of nausea (44%) and vomiting (21%) after REM/PRO anesthesia is considerably higher than we observed (16). This may be related to the population studied (i.e., laparoscopic surgery). No further data are available for direct comparison.

In clinical studies, such as this one, choice of a control becomes difficult. There are numerous alternative anesthetic techniques. We chose the THIO/ALF/ISO/N₂O group as our control because this is the technique we routinely use when not using any of the REM-based anesthetics.

The study design did not allow for double-blinded comparison of anesthetic techniques. However, we controlled for the anesthesiologists providing all of the anesthetics (i.e., the two authors), the type of surgery, and the group of surgeons performing the procedures (comparable among groups). Investigator bias in the assessment of recovery status and outcome variables were minimized by recording end points at strictly predetermined time intervals, by having the majority of patients (86%) evaluated postoperatively by trained personnel unaware of the administered anesthetic, and by having all patients complete the questionnaires on satisfaction in the absence of any study or medical personnel.

In conclusion, we have shown that REM-based anesthetics, in combination with small-dose PRO, DES, or SEVO, provide predictably rapid early recovery. However, late recovery and patient satisfaction were not different from a THIO/ALF/ISO/N₂O anesthetic technique.

Acknowledgments

Supported, in part, by the Department of Anesthesiology, University Hospital, Freiburg, Germany. Abbott, Glaxo-Wellcome, and Pharmacia provided study drugs and equipment.

We thank Dr. Albert Benzing for his support with statistical analysis We acknowledge the help of Dr. Thomas Klenzner, Ms. Ursula Gawlowski, Ms. Annette Schelle, and Ms. Christine Fiesel with data acquisition.

Footnotes

Presented, in part, at the 7th Annual Meeting of the European Society of Anaesthesiologists, Barcelona, Spain, April 25–28, 1998.

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