The Comparative Effects of Sevoflurane Versus Propofol in the Induction and Maintenance of Anesthesia in Adult Patients

The Comparative Effects of Sevoflurane Versus Propofol in the Induction and Maintenance of Anesthesia in Adult Patients W. Scott Jell&h, MD, PhD*, Cynthia A. Lien, MDt, H. Jerrel Fontenot, MD, PhDS, and Richard Hall, MD, FRCPC, FCCP§

*Department of Anesthesiology, Loyola University Medical Center, Maywood, Illinois; tDepartment of Anesthesiology, The New York Hospital, Cornell Medical Center, New York, New York; SDepartment of Anesthesiology, University Hospital of Arkansas, Little Rock, Arkansas; and SDepartments of Anesthesiology and Pharmacology and of Surgery, Dalhousie University, Victoria General Hospital, Halifax, Nova Scotia, Canada

A randomized, prospective study was performed at four institutions to compare anesthetic induction, maintenance, and recovery characteristics between sevoflurane- and propofol-based anesthesia in 186 ASA physical status I and II patients undergoing elective surgical procedures of l-3 h. Group 1 (n = 93) patients received sevoflurane-nitrous oxide for both induction and maintenance of anesthesia while Group 2 (n = 93) received propofol-nitrous oxide anesthesia. Induction of anesthesia and tracheal intubation times were significantly shorter with propofol (2.2 % 0.2 min, 5.1 ? 0.3 min, respectively) than with sevoflurane (3.1 ? 0.2 min, 7.2 + 0.3 min, respectively). Emergence times after sevoflurane (8.8 ? 1.2 min) were significantly shorter than with propofol(13.2 t 1.2 min). Overall frequency of complication-free induction, maintenance, and emergence did not differ between the two anesthetic

groups. However, side effects involving airway excitement were more prevalent during mask induction with sevoflurane as compared to propofol. Patients in the sevoflurane group were oriented and required postoperative analgesia much earlier than those who received propofol. Both groups were hemodynamically stable throughout the study period. The incidence of postoperative nausea, vomiting, and pain-discomfort scores were similar between the two groups. Urinary specific gravity decreased in the sevoflurane-treated group while serum creatinine and urinary pH were unchanged from preoperative values in both groups. Sevoflurane compared favorably with propofol when used for anesthesia for elective procedures of l-3 h duration.

(Anesth Analg 1996;82:479-85)

I nhaled volatile anesthetics are widely used for maintenance of general anesthesia because of their ease of administration and predictable intraopera-

tive and recovery characteristics. Since the introduc- tion of propofol in the late 198Os, intravenous anesthesia is also now commonly used. The kinetics of propofol allow for rapid induction of anesthesia, ad- equate maintenance, and rapid recovery of consciousness (1,2). Studies comparing propofol with inhaled anesthetics generally have found propofol to be superior in both recovery characteristics (times to orientation, command response, eye opening) and

This work was supported in part by a grant from Abbott Labo- ratories.

Presented in part at the 1994 Annual Meeting of the American Society of Anesthesiologists, San Francisco, CA.

Accepted for publication November 9,1995. Address correspondence and reprint requests to W. Scott Jellish,

MD, PhD, Department of Anesthesiology, Loyola University Med- ical Center, 2160 S. First Ave., Maywood, Illinois.

diminished negative postoperative outcomes (nausea, vomiting, depression) (3-5). Sevoflurane, a new inhaled anesthetic, has a low blood solubility which provides for both rapid induction and recovery times (6). The nonpungent odor of the drug makes it agree- able for most patients, especially during an inhaled induction of anesthesia.

This study was designed to compare the induction, maintenance, emergence, and safety characteristics of sevoflurane anesthesia with those of propofol in patients undergoing elective surgical procedures lasting up to three hours.

Methods

After approval by the institutional review boards of the four participating study centers, 186 ASA physical status I and II patients provided informed, written consent and were admitted to the study. All were older than 18 yr and were undergoing elective surgical

01996 by the International Anesthesia Research Society 0003~2999/96/$5.00 Anesth Analg 1996;82:479-85 479

480 JELLISH ET AL. COMPARISON OF SEVOFLURANE WITH PROPOFOL

ANESTH ANALG 1996;82:479-85

procedures expected to last for up to 3 h. Patients were excluded from the study if they had a history of neu- rologic disease, malignant hyperthermia, preexisting renal insufficiency, had general anesthesia within the last 2 wk, had a positive pregnancy test, or were breast feeding at the time of surgery.

Separate randomizations were performed at each study center in randomly allocated equal blocks of two, four, and six patients. Group 1 (n = 93) received sevoflurane as their primary anesthetic while Group 2 (n = 93) received a propofol-based anesthetic. Patients were not randomized until l-2 h prior to the surgery when sealed randomized envelopes were opened to reveal the treatment assignment for each patient. En- rollment occurred simultaneously at all centers from March 10 to October 28, 1993. Preoperative medica- tions were administered at the discretion of the anesthesiologist and included metoclopramide 10 mg in- travenously (IV), ranitidine 50 mg IV, and midazolam 1-2 mg IV, given shortly before induction of anesthesia. Standard monitoring was used. Patients received fentany12 pg/kg IV 2 min prior to induction of anesthesia. In most instances, after loss of eyelash reflex, vecuronium 0.1 mg/kg IV was given prior to tracheal intubation. After denitrogenation, Group 1 patients had anesthesia induced by mask with sevoflurane starting at 0.5% and incrementally increased to 3.5%- 4.0% inhaled concentration with 67% N,O in oxygen at a total gas flow of 6 L. Group 2 patients received propofol1.5-2.0 mg/kg IV for induction of anesthesia. Maintenance anesthesia consisted of the primary anesthetic, along with 67% N,O in oxygen at a total gas flow of 3 L, titrated to maintain hemodynamic variables within 15% of preinduction levels. If the depth of anesthesia was considered inadequate (indicated by movement, swallowing, tearing, sweating, tachycardia, or mean arterial pressure [MAP] increases > 15% of that obtained 1 min prior to induction [preinduction]), vital signs were recorded and the level of primary anesthetic was increased. If the patient did not respond to increases in the level of primary anesthetic, additional doses of fentanyl up to l-3 pg . kg-’ . h-i were permitted.

Demographic data including age, weight, height, and duration of surgery were recorded for each patient. In addition to the standard anesthetic record, an independent observer recorded MAP and heart rate (HR) at baseline (prestudy), preinduction, every minute from induction to incision, every minute for 5 min after incision, and every 15 min thereafter until the anesthetic was discontinued. These values were also measured after admission to the postanesthesia care unit and every 10 min thereafter until discharge from the postanesthesia care unit. The number of hy- potensive episodes (MAP decrease of greater than 15% of preinduction values) and the administration of

sympathomimetic drugs were also recorded. Intraop- erative time intervals recorded included induction (start of anesthetic until loss of eye lash reflex), endo- tracheal intubation (start of anesthetic until intubation), extubation (end of anesthetic until extubation), command response (end of anesthetic until the patient squeezed the independent observer’s hand on command and demonstrated purposeful movement), and orientation (end of anesthetic until the patient stated his or her name, date of birth, and age).

Successful induction and emergence from anesthesia were defined as the absence of any common side effects (coughing, breath holding, excitement, laryngospasm, excessive secretions, shivering, or any other untoward event) during that time period. The presur- gical period was defined as the start of study drug administration to the start of the surgical procedure, i.e., skin incision, and the emergence period was from the end of anesthesia to orientation. Successful maintenance of anesthesia was defined as the absence of any study drug-related adverse hemodynamic events (hypertension [MAP > 15% above preinduction values], hypotension [MAP > 15% below preinduction values], premature ventricular contractions, and bradycardia or tachycardia judged subjectively to be significant for the patient by the anesthesiologist).

At the completion of surgery, neuromuscular blockade was assessed for residual paralysis and, if found, was antagonized with neostigmine 70 pg/kg and glycopyrrolate 15 pg/kg IV. Thereafter, administration of the anesthetic was discontinued and patients breathed 100% 0,. To reproducibly assess emergence time, the patient was asked in a normal tone of voice by an independent observer to open his or her eyes. This was repeated every minute until an appropriate response was obtained. Then when clinically appropriate, tracheal extubation was performed. The patient’s were then asked to squeeze the hand of the observer every minute after tracheal extubation until a positive response was again noted.

In the postoperative period the patient was moni- tored for approximately 2 h by the independent observer. Levels of consciousness were assessed and recorded every 5 min until all of the following discharge criteria were met: vital signs stable for 0.5 h; the patient was conversant, cooperative, alert, and oriented to time and place; and the patient had no intractable side effects. Once these criteria were met, the respon- sible anesthesiologist at each institution discharged the patient. Additional recovery variables recorded from the time the anesthetic was terminated included time to first postoperative analgesia and the time until eligible for discharge. During the recovery period, scores for the Objective Pain-Discomfort Scale were recorded upon admission to the postanesthesia care unit and every 10 min thereafter up to 120 min. The


JELLISH ET AL. 481 COMPARISON OF SEVOFLURANE WITH PROPOFOL

Pain-Discomfort Scale was based on a total score between 0 and 10 where 0 = best and 10 = worst. The total score was the sum of five subsections which evaluated blood pressure (hypo- or hypertension), crying, movement, agitation, and verbal evaluation. Each subsection was scored between 0 and 2. If patients required analgesia, morphine was administered and recorded. Meperidine was also used for analgesia or, if necessary, to control shivering. The incidence of postoperative vomiting was recorded while the sever- ity of nausea was assessed using a loo-mm visual analog scale system. The number and dose of antiemetics administered (usually after the first episode of vomiting/retching or complaints of severe nausea> was also recorded.

Pre- and postoperative renal function was assessed from blood obtained to measure serum creatinine and urinary samples for pH and specific gravity.

Age, weight, and height were compared between the two study groups using one-way analysis of vari- ance (ANOVA). Efficacy of the two anesthetic tech- niques was analyzed by comparing induction, intubation, extubation, emergence, command response, and orientation times along with times to first requirement for postsurgical analgesia and time eligible for discharge from recovery by two-way ANOVA with study center, treatment, and the interaction between study center and treatment as covariates. Urinary pH, specific gravity, serum creatinine, HR, and MAP were compared at specified times between the two study groups using one-way ANOVA. Incidences of nausea and vomiting were analyzed by Fisher’s exact test. Comparisons were made of the Objective Pain- Discomfort Scale scores between groups by totaling the score at each evaluation time point and perform- ing a nonparametric one-way analysis (Kruskal- Wallis) test for significance. All values shown are rep- resented as mean + SEM with statistical significance determined at P < 0.05.

Results

Patient characteristics and surgical duration did not differ between groups (Table 1). Thirty-nine percent (72/186) of all patients studied were ASA class I. Shorter times for induction of anesthesia and tracheal intubation were observed for the propofol group as compared to the sevoflurane group. The overall frequency of induction side effects between groups did not differ (Table 2). The sevoflurane group, however, had a much larger clustering of airway excitatory side effects as compared to the propofol group. Surgical and anesthetic durations were similar between groups (Table 3). The incidence of intraoperative hypotension, use of sympathomi- metics and other less common complications during maintenance of anesthesia did not differ (Table 3).

Table 1. Patient Characteristics, Use of Preoperative Antiemetics, and Surgical Subsets

Sex (M/F) Age Height (cm) Weight (kg) Metoclopramide Ranitidine Midazolam Surgery type

Musculoskeletal Intraabdominal Genitourinary Other

Sevoflurane

40/53 44 2 13

169 + 11 75 + 20

36/93 (39%) 40/93 (43%) 25/93 (27%)

32% 20% 25% 23%

Propofol

37/56 42 + 14

167 + 12 76 + 18

35/93 (38%) 37/93 (40%) 26/93 (28%)

34% 31% 16% 19%

Values are means t- SEM. No significant differences between anesthetics were noted for any vari-

able.

Table 2. Anesthetic Induction Times and Side Effects

Sevoflurane Propofol (n = 93) (n = 93)

Time to induction (min) 3.1 ? 0.2 2.2 ? 0.2* Time to tracheal intubation (min) 7.2 ? 0.3 5.1 ? 0.3* Complication-free induction 72/93 (77%) 74/93 (80%) Induction side effects

Breath holding 3 (3%) 0 (0%) Cough 1 (1%) 0 (0%) Excitement 8 (9%) 0 (0%) Laryngospasm 2 (2%) 0 (0%) Other” 13 (14%) 19 (20%)

Values are means t sBra a Hypotension, hypertension, bradycardia, hypoxia, hyperthermia, hypo-

thermia, injection site pain. *P < 0.05.

The requirements for fentanyl administration were similar between the groups (Table 3). Extubation time, response to command time and time to orientation were significantly shorter for the sevoflurane group (Table 4). Patients in the sevoflurane group required administration of postoperative analgesia earlier than those in the propofol group (Table 4). No significant differences were noted in the type and incidence of administration of postoperative analgesics, emergence complications, and time eligible for discharge from recovery between the two groups (Table 4). The most common adverse experiences after surgery were those associated with the digestive system. Sevoflurane and propofol patients experienced a similar frequency of vomiting and nausea (Table 4). The number of patients requiring antiemetics postoperatively did not differ between groups (56/93 vs 53/93 for sevoflurane and propofol, respectively). The incidence of nausea and vomiting was also determined in patients who received anticholinesterases (Table 4) and no difference was detected. No differences were observed

482 JELLISH ET AL. ANESTH ANALG COMPARISON OF SEVOFLURANE WITH PROPOFOL 1996;82:479-85

Table 3. Intraoperative Time Intervals, Hemodynamic Stability, and Complications

Surgical duration (min)

Anesthetic duration (min)

Fentanyl (2 pg/kg) Neostigmine Glycopyrrolate” Sympathomimeticsb

Complication-free maintenance

Complications Hypotension Bradycardia Shivering Hypertension Increased salivation Tachycardia Ventricular

extrasystoles

Sevoflurane

104 + 6

132 + 7

78/93 (83%) 71/93 (76%) 68/93 (73%) 13/93 (15%) 82/93 (88%)

11/93 (12%) 3 (3%) 0 (0%) 1 (1%) 0 (0%) 1 (1%) 1 (1%)

Propofol

108 + 6

134 + 7

87/93 (94%) 73/93 (78%) 72/93 (77%) 19/93 (21%) 80/93 (86%)

6/93 (6%) 2 (2%) 1 (1%) 4 (4%) 1 (1%) 0 (0%) 0 (0%)

Values are means 2 SEM. No differences between groups were detected. a Patients received &opine during administration of neostigmine. b Includes treatment for adverse hemodynamics and as part of surgical

preparation for hemostasis.

between the two treatment groups with respect to mean total scores on the Objective Pain-Discomfort Scale. The mean scores ranged from a high of 1.7 t 0.1 vs 1.4 + 0.1 for sevoflurane and propofol, respectively, at 20 min after recovery room admission, to a low of 0.6 2 0.1 vs 0.5 -+ 0.1 for sevoflurane and propofol, respectively, at 120 min after recovery room admission. The number of patients who received either postoperative morphine or meperidine was similar between the two groups.

Prestudy HR and MAP were not significantly different between groups (Table 5). Significant, but clinically unimportant, changes were noted in HR and MAP in the propofol group at induction compared to values obtained 1 min prior to anesthesia. These changes were not seen in the sevoflurane group (Table 5). On admission to the postanesthesia care unit the HR was increased from that observed at the 1-min prior to induction of anesthesia value in both groups, whereas the MAP was relatively unchanged. At discharge from the postanesthesia care unit, HR values were similar to the prestudy and 1-min prior to induction of anesthesia values in both groups while MAP was significantly decreased in the sevoflurane group. At the 24-h postanesthesia interval, HR was increased from prestudy values in both groups, while MAP was decreased (Table 5). Comparisons between groups re- vealed a significant reduction in MAP at induction of anesthesia in the propofol group and a larger increase in HR after admission to the postanesthesia care unit in patients receiving sevoflurane (Table 5).

Table 4. Emergence Times, Recovery Events, and Emergence Complications

Sevoflurane Propofol

Time required for Extubation (min) 921 Command 11 -c 1

response (min) Orientation (min) 15 ? 2

Complication-free 60/93 (65%) Emergence

Emergence complications

Breath holding 1 (1%) Cough 12 (13%) Excitement 5 (5%) Excess salivation 2 (2%) Shivering 4 (4%) Other@ 7 (8%)

Recovery First postoperative 38 ? 3

analgesia (min) Morphine 71/93 (76%) Meperidine 42/93 (45%) Eligible for 148 -c 9

discharge (min) Somnolence 16/93 (17%) Nausea 41/93 (44%) Vomiting 18/93 (19%) Received anticholinesterase

Nausea 34/71 (48%) Vomiting 13/71 (18%)

No anticholinesterase Nausea 7/22 (31%) Vomiting 5/22 (23%)

13 + 1 14 -c 1

20 2 2 61/93 (66%)

2 (2%) 16 (17%)

5 (5%) 6 (7%) 8 (9%) 7 (8%)

49 + 3*

75/93 (80%) 39/93 (42%)

141 5 9

16/93 (17%) 37/93 (40%) 18/93 (19%)

31/73 (43%) 14/73 (19%)

6/20 (30%) 4/20 (20%)

Values are mean k sEM. a Includes drowsiness, hyperthermia, hypotension, tachycardia, bradycar-

dia, hypertension, dizziness, hypoxia, and apnea. *P < 0.05.

No significant intergroup differences were noted between baseline serum creatinine, urinary pH, or specific gravity (Table 6). Serum creatinine values increased from baseline in 7% of patients in the propofol group and only 1% of patients receiving sevoflurane. However, the overall mean change from baseline was not significant for either group. In addition, no difference was observed in either group for mean changes from baseline to first postanesthesia assessment for urinary pH (Table 6). Within the sevoflurane group, however, a significant mean decrease from baseline was observed for specific gravity (Table 6). No differences were noted between the groups when comparing change from baseline values for either serum creatinine, urinary pH, or specific gravity (Table 6).

Discussion

This study demonstrates that sevoflurane anesthesia compares favorably with propofol in both ease of induction and recovery after surgical procedures lasting


JELLISH ET AL. 483 COMPARISON OF SEVOFLURANE WITH I’ROPOFOL

Table 5. Hemodynamic Variables; Summary of Changes from Baseline in All Treated Patients

Variable/ Sevofhxane Propofol

evaluation time n Mean + SEM II Mean 5 SEM

Heart rate Prestudy 1 min prior to

anesthesia Induction Admit RR D/C RR Postanesthesia

24 h MAP

Prestudy 1 min prior to

anesthesia Induction Admit RR” D/C RR” Postanesthesia

24 h

93 77 + 1 90 79 2 2

90 79 -c 2 86 92 88 + 2** 92 92 77 + 1 92 a5 81 -t 1” 86

93 91 + 1.0 93 91 + 1 90 95 + 1* 92 92 -c 2

90 93 2 2 83 90 + 2+t 77 97 k 2* 80 94 k 2 84 88 t 1** 83 90.0 t 1 85 87 + 1*$ 86 89 -c 1*

93 92

75 + 1 74 2 2

76 -c 2* 79 2 2*+* 75 + 2 81 _c 1*$

Values are mean + SEM. Change in n observed at different time points due to exclusion of data

collected-at times other than specified. _ RR = recovery room; D/C = discharge. * P < 0.05 versus urestudv. t P < 0.05 versus ‘sevofluiane at same time. $ P < 0.05 versus 1 min prior to anesthesia.

up to three hours. Induction side effects occurred with equal frequency. However, airway excitement was more prevalent with sevoflurane than propofol. Although the time required for an inhaled induction and intubation was longer with sevoflurane anesthesia compared to IV induction with propofol, recovery from anesthesia (extubation and command response) was shorter after sevoflurane. In addition, the sevoflurane-treated group required postoperative analgesia earlier than the propofol-treated group.

The time required for induction of anesthesia with sevoflurane was longer than the 109 seconds found by Smith et al. (7). This difference reflects the method of anesthetic induction. We incrementally increased sevoflurane concentrations over the course of anesthetic induction until control of ventilation was obtained while Smith et al.‘s group started induction of anesthesia using 5% sevoflurane and maintained this concentration until anesthetic induction was complete. Recovery times seen here compared well with the seven-minute times noted by Wiesner et al. (8) but are double those of Smith et al. (7). All recovery times noted in this study are within the range of five to nine minutes previously reported (9,lO). The recovery times after propofol administration seen here are similar to those reported by Doze et al. (11) but are double those of others (3,4) and probably reflect methodologic differences concerning opioid administration (none administered), time of anesthetic discontinuation, and

the titration of anesthetic to hemodynamic effect. In one study (3) the primary anesthetic was stopped five minutes before the end of the procedure, whereas our study design only allowed for the discontinuation of primary anesthetic at the end of surgery.

Since both groups received similar amounts of perioperative opioids, the earlier requirement for postoperative analgesia in the sevoflurane group was not due to a larger opioid use intraoperatively in the propofol group. The shorter time for requesting postoperative analgesics in the sevoflurane group probably reflects its rapid recovery profile and lack of tissue solubility and accumulation. It has been speculated (12) but not substantiated (13) that propofol may have some analgesic effects. After long infusions, propofol’s terminal elimination half-life is increased which is thought to occur from drug accumulation in poorly perfused peripheral tissue compartments (14). This might produce a delayed recovery from propofol anesthesia. In addition, some patients have been reported to have small secondary increases in propofol blood concentrations during the early postoperative period which may reflect return of propofol from stor- age sites to the blood (15). Although of no apparent clinical significance, this small increase in propofol levels might be enough to reduce the need for imme- diate analgesia.

Propofol has an antiemetic effect, particularly after operations documented to produce nausea and vomiting (16). It is somewhat surprising that both groups had similar and high incidences of emesis. Many factors influence postoperative nausea and vomiting. Young age, obesity, and diabetes have all been linked to postoperative emesis (17). These factors were ne- gated by the fact that our study population had few diabetics, had similar average ages, were in good physical health, and of similar body habitus. Addi- tional factors that could influence nausea and vomiting include type and site of surgery (17). No large differences were noted in the types of surgery done between study groups. Orthopedic procedures pre- dominated along with intraabdominal procedures especially cholecystectomy. Female gender is associated with three times the incidence of postoperative emesis (18). Our study groups, however, had approximately equal ratios of male to female patients. Reversal of neuromuscular blockade by neostigmine may influence the incidence of postoperative emesis (19). We compared patients who received neostigmine with those who did not and found no significant difference in the incidence of nausea and vomiting between groups (Table 4). Finally, patients in both study groups received perioperative analgesics with equal frequency. Possibly the improved incidence in postoperative nausea and vomiting with propofol, as compared to inhaled anesthetics, is lost

484 JELLISH ET AL. ANESTH ANALG COMPARISON OF SEVOFLURANE WITH I’ROI’OFOL 1996;82:479-85

Table 6. Analysis of Changes from Baseline to Postanesthesia Determinations of Renal Function

Variable

Creatinine (mmol/L)

Urine pH

Specific gravity

Treatment group Baseline

Sevoflurane 83.22 2 1.98 Propofol 78.12 ? 1.78 Sevoflurane 6.05 2 0.11 Propofol 5.94 + 0.10 Sevoflurane 1.018 + 0.001 Propofol 1.017 2 0.001

Postanesthesia

85.79 -c 3.73 78.83 ? 2.03 6.25 -c 0.11 6.13 5 0.13

1.015 t 0.001* 1.016 + 0.001

Values are mean 2 SEM. No sienifkant differences were found between groups. * P < 0.05 versus baseline.

when opioids are added (11). It is also possible that sevoflurane has less emetic potential compared to other inhaled anesthetics because it is less pungent and has a short emergence time which may be associated with less depression of cognitive function in the postoperative period. The nausea and vomiting data from this study can be criticized, however, because control over some of the confounding variables known to affect these symptoms was not strictly maintained.

The group that received propofol for induction of anesthesia had increased HR and decreased MAP when compared to the sevoflurane group. This is not surprising, considering the now well documented effect of an induction dose of propofol in producing a 15%-30% decrease in MAP, especially when administered with an opioid analgesic (20). The incidence of bradycardia and hypotension during maintenance of anesthesia was not appreciably different between the groups. These results are similar to other studies which show both sevoflurane (7,8) and propofol (3,4) to be anesthetics which maintain MAP and HR close to preinduction values, especially in healthy ASA physical status I and II individuals. All patients had a significant increase in HR from initial values on admission to the postanesthesia care unit. This increase was higher in patients treated with sevoflurane which may be a reflection of the more rapid emergence seen with the drug. These patients may have been more awake and oriented than their counterparts receiving propofol as reflected by the fact that the sevoflurane- treated group required postoperative analgesia sooner than those who received propofol. The clinical impor- tance of these hemodynamic differences are minimal, with both groups demonstrating marked stability throughout the study period.

Sevoflurane undergoes biotransformation and degradation at a rate of approximately 3.3% +- 1.7% of total uptake (21). Although this is not its main elimination pathway, a byproduct of this metabolism is the produc- tion of inorganic and organic fluoride. While fluoride- related nephrotoxicity has not been observed in clinical assessments of sevoflurane in Japan (22) and North America (23), there are still questions concerning sevoflurane biotransformation and degradation rates

that result in higher fluoride levels than seen after anesthesia with isoflurane, halothane, and desflurane (21). Fluoride levels in excess of 50 pmol/L have been shown to reduce renal concentrating ability (24). Although inorganic fluoride was not determined in the present study, fluoride levels after one to one and one-half hours of sevoflurane exposure are reported to reach 19-26 pmol/L (7,21). This is well below the threshold considered harmful (24). In this study of similar duration, no outward clinical signs of renal toxicity were noted in the sevoflurane group compared to preoperative evalua- tions. However, subtle changes would not have been detected by our methods of assessing renal function. A small but significant decrease in specific gravity, an in- direct method of measuring renal concentrating ability, was noted from baseline after sevoflurane exposure. Al- though this change was small, it was not observed in the group that received propofol. No attempt was made to control other factors known to affect renal function and the implications of this is unclear. However, it is possible that the metabolism of sevoflurane during anesthesia with approximate fresh gas flows of 3 L produced a small change in renal concentrating ability.

In conclusion, we have demonstrated that sevoflurane compares favorably with propofol for both ease of induction and emergence from anesthesia. Postop- eratively, both groups had an equal incidence of nausea and vomiting. Sevoflurane had a quicker immedi- ate emergence as compared to propofol, but no differences were noted in eligible time to discharge or ambulation. Sevoflurane may be a useful alternative to propofol in providing anesthesia where rapid emergence and recovery of cognitive function are desired.

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The Comparative Effects of Sevoflurane Versus Propofol in the Induction and Maintenance of Anesthesia in Adult Patients