Source: FDA, National Drug Code (US) Revision Year: 2022
Sevoflurane is an inhalational anesthetic agent for use in induction and maintenance of general anesthesia. Minimum alveolar concentration (MAC) of sevoflurane in oxygen for a 40-year-old adult is 2.1%. The MAC of sevoflurane decreases with age (see DOSAGE AND ADMINISTRATION for details).
Because of the low solubility of sevoflurane in blood (blood/gas partition coefficient @ 37°C = 0.63-0.69), a minimal amount of sevoflurane is required to be dissolved in the blood before the alveolar partial pressure is in equilibrium with the arterial partial pressure. Therefore, there is a rapid rate of increase in the alveolar (end-tidal) concentration (FA) toward the inspired concentration (FI) during induction.
In a study in which seven healthy male volunteers were administered 70% N2O/30%O2 for 30 minutes followed by 1.0% sevoflurane and 0.6% isoflurane for another 30 minutes the FA/FI ratio was greater for sevoflurane than isoflurane at all time points. The time for the concentration in the alveoli to reach 50% of the inspired concentration was 4-8 minutes for isoflurane and approximately 1 minute for sevoflurane.
FA/FI data from this study were compared with FA/FI data of other halogenated anesthetic agents from another study. When all data were normalized to isoflurane, the uptake and distribution of sevoflurane was shown to be faster than isoflurane and halothane, but slower than desflurane. The results are depicted in Figure 3.
The low solubility of sevoflurane facilitates rapid elimination via the lungs. The rate of elimination is quantified as the rate of change of the alveolar (end-tidal) concentration following termination of anesthesia (FA), relative to the last alveolar concentration (FaO) measured immediately before discontinuance of the anesthetic. In the healthy volunteer study described above, rate of elimination of sevoflurane was similar compared with desflurane, but faster compared with either halothane or isoflurane. These results are depicted in Figure 4.
Figure 3. Ratio of Concentration of Anesthetic in Alveolar Gas to Inspired Gas:
Figure 4. Concentration of Anesthetic in Alveolar Gas Following Termination of Anesthesia:
The effects of sevoflurane on the displacement of drugs from serum and tissue proteins have not been investigated. Other fluorinated volatile anesthetics have been shown to displace drugs from serum and tissue proteins in vitro. The clinical significance of this is unknown. Clinical studies have shown no untoward effects when sevoflurane is administered to patients taking drugs that are highly bound and have a small volume of distribution (e.g., phenytoin).
Sevoflurane is metabolized by cytochrome P450 2E1, to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. Once formed HFIP is rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite. No other metabolic pathways for sevoflurane have been identified. In vivo metabolism studies suggest that approximately 5% of the sevoflurane dose may be metabolized.
Cytochrome P450 2E1 is the principal isoform identified for sevoflurane metabolism and this may be induced by chronic exposure to isoniazid and ethanol. This is similar to the metabolism of isoflurane and enflurane and is distinct from that of methoxyflurane which is metabolized via a variety of cytochrome P450 isoforms. The metabolism of sevoflurane is not inducible by barbiturates. As shown in Figure 5, inorganic fluoride concentrations peak within 2 hours of the end of sevoflurane anesthesia and return to baseline concentrations within 48 hours post-anesthesia in the majority of cases (67%). The rapid and extensive pulmonary elimination of sevoflurane minimizes the amount of anesthetic available for metabolism.
Figure 5. Serum Inorganic Fluoride Concentrations for Sevoflurane and Other Volatile Anesthetics
Legend:
Pre-Anesth. = Pre-anesthesia
Up to 3.5% of the sevoflurane dose appears in the urine as inorganic fluoride. Studies on fluoride indicate that up to 50% of fluoride clearance is nonrenal (via fluoride being taken up into bone).
Fluoride ion concentrations are influenced by the duration of anesthesia, the concentration of sevoflurane administered, and the composition of the anesthetic gas mixture. In studies where anesthesia was maintained purely with sevoflurane for periods ranging from 1 to 6 hours, peak fluoride concentrations ranged between 12 µM and 90 µM. As shown in Figure 6, peak concentrations occur within 2 hours of the end of anesthesia and are less than 25 µM (475 ng/mL) for the majority of the population after 10 hours. The half-life is in the range of 15-23 hours.
It has been reported that following administration of methoxyflurane, serum inorganic fluoride concentrations > 50 µM were correlated with the development of vasopressin-resistant, polyuric, renal failure. In clinical studies with sevoflurane, there were no reports of toxicity associated with elevated fluoride ion levels.
Figure 6. Fluoride Ion Concentrations Following Administration of Sevoflurane (mean MAC = 1.27, mean duration = 2.06 hr) Mean Fluoride Ion Concentrations (n=48):
Fluoride concentrations have been measured after single, extended, and repeat exposure to sevoflurane in normal surgical and special patient populations, and pharmacokinetic parameters were determined.
Compared with healthy individuals, the fluoride ion half-life was prolonged in patients with renal impairment, but not in the elderly. A study in 8 patients with hepatic impairment suggests a slight prolongation of the half-life. The mean half-life in patients with renal impairment averaged approximately 33 hours (range 21-61 hours) as compared to a mean of approximately 21 hours (range 10-48 hours) in normal healthy individuals. The mean half-life in the elderly (greater than 65 years) approximated 24 hours (range 18-72 hours). The mean half-life in individuals with hepatic impairment was 23 hours (range 16-47 hours). Mean maximal fluoride values (Cmax) determined in individual studies of special populations are displayed below.
Table 1. Fluoride Ion Estimates in Special Populations Following Administration of Sevoflurane:
| n | Age (yr) | Duration (hr) | Dose (MAC·hr) | Cmax (µM) | |
|---|---|---|---|---|---|
| PEDIATRIC PATIENTS | |||||
| Anesthetic | |||||
| Sevoflurane-O2 | 76 | 0-11 | 0.8 | 1.1 | 12.6 |
| Sevoflurane-O2 | 40 | 1-11 | 2.2 | 3.0 | 16.0 |
| Sevoflurane/N2O | 25 | 5-13 | 1.9 | 2.4 | 21.3 |
| Sevoflurane/N2O | 42 | 0-18 | 2.4 | 2.2 | 18.4 |
| Sevoflurane/N2O | 40 | 1-11 | 2.0 | 2.6 | 15.5 |
| ELDERLY | 33 | 65-93 | 2.6 | 1.4 | 25.6 |
| RENAL | 21 | 29-83 | 2.5 | 1.0 | 26.1 |
| HEPATIC | 8 | 42-79 | 3.6 | 2.2 | 30.6 |
| OBESE | 35 | 24-73 | 3.0 | 1.7 | 38.0 |
n = number of patients studied.
Changes in the depth of sevoflurane anesthesia rapidly follow changes in the inspired concentration.
In the sevoflurane clinical program, the following recovery variables were evaluated:
1. Time to events measured from the end of study drug:
2. Recovery of cognitive function and motor coordination was evaluated based on:
3. Other recovery times were:
Some of these variables are summarized as follows:
Table 2. Induction and Recovery Variables for Evaluable Pediatric Patients in Two Comparative Studies: Sevoflurane versus Halothane:
| Time to End-Point (min) | Sevoflurane Mean ± SEM | Halothane Mean ± SEM |
|---|---|---|
| Induction | 2.0 ± 0.2 (n=294) | 2.7 ± 0.2 (n=252) |
| Emergence | 11.3 ± 0.7 (n=293) | 15.8 ± 0.8 (n=252) |
| Response to command | 13.7 ± 1.0 (n=271) | 19.3 ± 1.1 (n=230) |
| First analgesia | 52.2 ± 8.5 (n=216) | 67.6 ± 10.6 (n=150) |
| Eligible for recovery discharge | 76.5 ± 2.0 (n=292) | 81.1 ± 1.9 (n=246) |
n = number of patients with recording of events.
Table 3. Recovery Variables for Evaluable Adult Patients in Two Comparative Studies: Sevoflurane versus Isoflurane:
| Time to Parameter: (min) | Sevoflurane Mean ± SEM | Isoflurane Mean ± SEM |
|---|---|---|
| Emergence | 7.7 ± 0.3 (n=395) | 9.1 ± 0.3 (n=348) |
| Response to command | 8.1 ± 0.3 (n=395) | 9.7 ± 0.3 (n=345) |
| First analgesia | 42.7 ± 3.0 (n=269) | 52.9 ± 4.2 (n=228) |
| Eligible for recovery discharge | 87.6 ± 5.3 (n=244) | 79.1 ± 5.2 (n=252) |
n = number of patients with recording of recovery events.
Table 4. Meta-Analyses for Induction and Emergence Variables for Evaluable Adult Patients in Comparative Studies: Sevoflurane versus Propofol:
| Parameter | No. of Studies | Sevoflurane Mean ± SEM | Propofol Mean ± SEM |
|---|---|---|---|
| Mean maintenance anesthesia exposure | 3 | 1.0 MAC·hr. ± 0.8 (n=259) | 7.2 mg/kg/hr ± 2.6 (n=258) |
| Time to induction: (min) | 1 | 3.1 ± 0.18* (n=93) | 2.2 ± 0.18** (n=93) |
| Time to emergence: (min) | 3 | 8.6 ± 0.57 (n=255) | 11.0 ± 0.57 (n=260) |
| Time to respond to command: (min) | 3 | 9.9 ± 0.60 (n=257) | 12.1 ± 0.60 (n=260) |
| Time to first analgesia: (min) | 3 | 43.8 ± 3.79 (n=177) | 57.9 ± 3.68 (n=179) |
| Time to eligibility for recovery discharge: (min) | 3 | 116.0 ± 4.15 (n=257) | 115.6 ± 3.98 (n=261) |
* Propofol induction of one sevoflurane group = mean of 178.8 mg ± 72.5 SD (n=165)
** Propofol induction of all propofol groups = mean of 170.2 mg ± 60.6 SD (n=245)
n = number of patients with recording of events.
Sevoflurane was studied in 14 healthy volunteers (18-35 years old) comparing sevoflurane-O2 (Sevo/O2) to sevoflurane-N2O/O2 (Sevo/N2O/O2) during 7 hours of anesthesia. During controlled ventilation, hemodynamic parameters measured are shown in Figures 7-10:
Figure 7. Heart Rate:
Figure 8. Mean Arterial Pressure
Figure 9. Systemic Vascular Resistance
Figure 10. Cardiac Index
Sevoflurane is a dose-related cardiac depressant. Sevoflurane does not produce increases in heart rate at doses less than 2 MAC.
A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane versus isoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg with both sevoflurane and isoflurane. Consequently, the interaction of sevoflurane with epinephrine appears to be equal to that seen with isoflurane.
RYR1 and CACNA1S are polymorphic genes, and multiple pathogenic variants have been associated with malignant hyperthermia susceptibility (MHS) in patients receiving volatile anesthetic agents, including sevoflurane. Case reports as well as ex-vivo studies have identified multiple variants in RYR1 and CACNA1S associated with MHS. Variant pathogenicity should be assessed based on prior clinical experience, functional studies, prevalence information, or other evidence (see CONTRAINDICATIONS, WARNINGS – Malignant Hyperthermia).
Studies on carcinogenesis have not been performed for either sevoflurane or Compound A.
No mutagenic effect of sevoflurane was noted in the Ames test, mouse micronucleus test, mouse lymphoma mutagenicity assay, human lymphocyte culture assay, mammalian cell transformation assay, 32P DNA adduct assay, and no chromosomal aberrations were induced in cultured mammalian cells.
Similarly, no mutagenic effect of Compound A was noted in the Ames test, the Chinese hamster chromosomal aberration assay and the in vivo mouse micronucleus assay. However, positive responses were observed in the human lymphocyte chromosome aberration assay. These responses were seen only at high concentrations and in the absence of metabolic activation (human S-9).
In a study in which male rats were treated with sevoflurane (0.22%, 0.66%, 1.1%, or 2.2% equals 0.1, 0.3, 0.5, or 1.0 MAC) three hours per day every other day starting 64 days prior to mating and female rats were treated with the same dosing regimen 14 days prior to mating until Gestation Day 7, there was no clear impact on male or female fertility.
Published studies in animals demonstrate that the use of anesthetic agents during the period of rapid brain growth or synaptogenesis results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester through the first several months of life, but may extend out to approximately 3 years of age in humans.
In primates, exposure to 3 hours of an anesthetic regimen that produced a light surgical plane of anesthesia did not increase neuronal cell loss; however, treatment regimens of 5 hours or longer increased neuronal cell loss. Data in rodents and in primates suggest that the neuronal and oligodendrocyte cell losses are associated with subtle but prolonged cognitive deficits in learning and memory. The clinical significance of these nonclinical findings is not known, and healthcare providers should balance the benefits of appropriate anesthesia in pregnant women, neonates and young children who require procedures against the potential risks suggested by the nonclinical data (see WARNINGS – Pediatric Neurotoxicity, PRECAUTIONS – Pregnancy, PRECAUTIONS – Pediatric Use).
Sevoflurane was administered to a total of 3185 patients. The types of patients are summarized as follows:
Table 5. Patients Receiving Sevoflurane in Clinical Studies:
| Type of Patients | Number | Studied |
|---|---|---|
| ADULT | 2223 | |
| Cesarean Delivery | 29 | |
| Cardiovascular and patients at risk of myocardial ischemia | 246 | |
| Neurosurgical | 22 | |
| Hepatic impairment | 8 | |
| Renal impairment | 35 | |
| PEDIATRIC | 962 |
Clinical experience with these patients is described below.
The efficacy of sevoflurane in comparison to isoflurane, enflurane, and propofol was investigated in 3 outpatient and 25 inpatient studies involving 3591 adult patients. Sevoflurane was found to be comparable to isoflurane, enflurane, and propofol for the maintenance of anesthesia in adult patients. Patients administered sevoflurane showed shorter times (statistically significant) to some recovery events (extubation, response to command, and orientation) than patients who received isoflurane or propofol.
Sevoflurane has a nonpungent odor and does not cause respiratory irritability. Sevoflurane is suitable for mask induction in adults. In 196 patients, mask induction was smooth and rapid, with complications occurring with the following frequencies: cough, 6%; breathholding, 6%; agitation, 6%; laryngospasm, 5%.
Sevoflurane was compared to isoflurane and propofol for maintenance of anesthesia supplemented with N2O in two studies involving 786 adult (18-84 years of age) ASA Class I, II, or III patients. Shorter times to emergence and response to commands (statistically significant) were observed with sevoflurane compared to isoflurane and propofol.
Table 6. Recovery Parameters in Two Outpatient Surgery Studies: Least Squares Mean ± SEM:
| Sevoflurane/N2O | Isoflurane/N2O | Sevoflurane/N2O | Propofol/N2O | |
|---|---|---|---|---|
| Mean Maintenance | 0.64 ± 0.03 | 0.66 ± 0.03 | 0.8 ± 0.5 | 7.3 ± 2.3 |
| Anesthesia | MAC·hr. | MAC·hr. | MAC·hr. | mg/kg/hr. |
| Exposure ± SD | (n=245) | (n=249) | (n=166) | (n=166) |
| Time to Emergence (min) | 8.2 ± 0.4 (n=246) | 9.3 ± 0.3 (n=251) | 8.3 ± 0.7 (n=137) | 10.4 ± 0.7 (n=142) |
| Time to Respond to Commands (min) | 8.5 ± 0.4 (n=246) | 9.8 ± 0.4 (n=248) | 9.1 ± 0.7 (n=139) | 11.5 ± 0.7 (n=143) |
| Time to First Analgesia (min) | 45.9 ± 4.7 (n=160) | 59.1 ± 6.0 (n=252) | 46.1 ± 5.4 (n=83) | 60.0 ± 4.7 (n=88) |
| Time to Eligibility for Discharge from Recovery Area (min) | 87.6 ± 5.3 (n=244) | 79.1 ± 5.2 (n=252) | 103.1 ± 3.8 (n=139) | 105.1 ± 3.7 (n=143) |
n = number of patients with recording of recovery events.
Sevoflurane was compared to isoflurane and propofol for maintenance of anesthesia supplemented with N2O in two multicenter studies involving 741 adult ASA Class I, II or III (18-92 years of age) patients. Shorter times to emergence, command response, and first post-anesthesia analgesia (statistically significant) were observed with sevoflurane compared to isoflurane and propofol.
Table 7. Recovery Parameters in Two Inpatient Surgery Studies: Least Squares Mean ± SEM:
| Sevoflurane/N2O | Isoflurane/N2O | Sevoflurane/N2O | Propofol/N2O | |
|---|---|---|---|---|
| Mean Maintenance | 1.27 MAC·hr. | 1.58 MAC·hr. | 1.43 MAC·hr. | 7.0 mg/kg/hr |
| Anesthesia | ± 0.05 | ± 0.06 | ± 0.94 | ± 2.9 |
| Exposure ± SD | (n=271) | (n=282) | (n=93) | (n=92) |
| Time to Emergence (min) | 11.0 ± 0.6 (n=270) | 16.4 ± 0.6 (n=281) | 8.8 ± 1.2 (n=92) | 13.2 ± 1.2 (n=92) |
| Time to Respond to Commands (min) | 12.8 ± 0.7 (n=270) | 18.4 ± 0.7 (n=281) | 11.0 ± 1.20 (n=92) | 14.4 ± 1.21 (n=91) |
| Time to First Analgesia (min) | 46.1 ± 3.0 (n=233) | 55.4 ± 3.2 (n=242) | 37.8 ± 3.3 (n=82) | 49.2 ± 3.3 (n=79) |
| Time to Eligibility for Discharge from Recovery Area (min) | 139.2 ± 15.6 (n=268) | 165.9 ± 16.3 (n=282) | 148.4 ± 8.9 (n=92) | 141.4 ± 8.9 (n=92) |
n = number of patients with recording of recovery events.
The concentration of sevoflurane required for maintenance of general anesthesia is age-dependent (see DOSAGE AND ADMINISTRATION). Sevoflurane or halothane was used to anesthetize 1620 pediatric patients aged 1 day to 18 years, and ASA physical status I or II (948 sevoflurane, 672 halothane). In one study involving 90 infants and children, there were no clinically significant decreases in heart rate compared to awake values at 1 MAC. Systolic blood pressure decreased 15%-20% in comparison to awake values following administration of 1 MAC sevoflurane; however, clinically significant hypotension requiring immediate intervention did not occur. Overall incidences of bradycardia [more than 20 beats/min lower than normal (80 beats/min)] in comparative studies was 3% for sevoflurane and 7% for halothane. Patients who received sevoflurane had slightly faster emergence times (12 vs. 19 minutes), and a higher incidence of post-anesthesia agitation (14% vs. 10%).
Sevoflurane (n=91) was compared to halothane (n=89) in a single-center study for elective repair or palliation of congenital heart disease. The patients ranged in age from 9 days to 11.8 years with an ASA physical status of II, III, and IV (18%, 68%, and 13% respectively). No significant differences were demonstrated between treatment groups with respect to the primary outcome measures: cardiovascular decompensation and severe arterial desaturation. Adverse event data was limited to the study outcome variables collected during surgery and before institution of cardiopulmonary bypass.
Sevoflurane has a nonpungent odor and is suitable for mask induction in pediatric patients. In controlled pediatric studies in which mask induction was performed, the incidence of induction events is shown below (see ADVERSE REACTIONS).
Table 8. Incidence of Pediatric Induction Events:
| Sevoflurane (n=836) | Halothane (n=660) | |
|---|---|---|
| Agitation | 14% | 11% |
| Cough | 6% | 10% |
| Breathholding | 5% | 6% |
| Secretions | 3% | 3% |
| Laryngospasm | 2% | 2% |
| Bronchospasm | <1% | 0% |
n = number of patients.
Sevoflurane (n=518) was compared to halothane (n=382) for the maintenance of anesthesia in pediatric outpatients. All patients received N2O and many received fentanyl, midazolam, bupivacaine, or lidocaine. The time to eligibility for discharge from post-anesthesia care units was similar between agents (see CLINICAL PHARMACOLOGY, ADVERSE REACTIONS).
Sevoflurane was compared to isoflurane as an adjunct with opioids in a multicenter study of 273 patients undergoing CABG surgery. Anesthesia was induced with midazolam (0.1-0.3 mg/kg); vecuronium (0.1-0.2 mg/kg), and fentanyl (5-15 mcg/kg). Both isoflurane and sevoflurane were administered at loss of consciousness in doses of 1.0 MAC and titrated until the beginning of cardiopulmonary bypass to a maximum of 2.0 MAC. The total dose of fentanyl did not exceed 25 mcg/kg. The average MAC dose was 0.49 for sevoflurane and 0.53 for isoflurane. There were no significant differences in hemodynamics, cardioactive drug use, or ischemia incidence between the two groups. Outcome was also equivalent. In this small multicenter study, sevoflurane appears to be as effective and as safe as isoflurane for supplementation of opioid anesthesia for coronary bypass grafting.
Sevoflurane-N2O was compared to isoflurane-N2O for maintenance of anesthesia in a multicenter study in 214 patients, age 40-87 years who were at mild-to-moderate risk for myocardial ischemia and were undergoing elective non-cardiac surgery. Forty-six percent (46%) of the operations were cardiovascular, with the remainder evenly divided between gastrointestinal and musculoskeletal and small numbers of other surgical procedures. The average duration of surgery was less than 2 hours. Anesthesia induction usually was performed with thiopental (2-5 mg/kg) and fentanyl (1-5 mcg/kg). Vecuronium (0.1-0.2 mg/kg) was also administered to facilitate intubation, muscle relaxation or immobility during surgery. The average MAC dose was 0.49 for both anesthetics. There was no significant difference between the anesthetic regimens for intraoperative hemodynamics, cardioactive drug use, or ischemic incidents, although only 83 patients in the sevoflurane group and 85 patients in the isoflurane group were successfully monitored for ischemia. The outcome was also equivalent in terms of adverse events, death, and postoperative myocardial infarction. Within the limits of this small multicenter study in patients at mild-to-moderate risk for myocardial ischemia, sevoflurane was a satisfactory equivalent to isoflurane in providing supplemental inhalation anesthesia to intravenous drugs.
Sevoflurane (n=29) was compared to isoflurane (n=27) in ASA Class I or II patients for the maintenance of anesthesia during cesarean section. Newborn evaluations and recovery events were recorded. With both anesthetics, Apgar scores averaged 8 and 9 at 1 and 5 minutes, respectively.
Use of sevoflurane as part of general anesthesia for elective cesarean section produced no untoward effects in mother or neonate. Sevoflurane and isoflurane demonstrated equivalent recovery characteristics. There was no difference between sevoflurane and isoflurane with regard to the effect on the newborn, as assessed by Apgar Score and Neurological and Adaptive Capacity Score (average = 29.5). The safety of sevoflurane in labor and vaginal delivery has not been evaluated.
Three studies compared sevoflurane to isoflurane for maintenance of anesthesia during neurosurgical procedures. In a study of 20 patients, there was no difference between sevoflurane and isoflurane with regard to recovery from anesthesia. In 2 studies, a total of 22 patients with intracranial pressure (ICP) monitors received either sevoflurane or isoflurane. There was no difference between sevoflurane and isoflurane with regard to ICP response to inhalation of 0.5, 1.0, and 1.5 MAC inspired concentrations of volatile agent during N2O-O2-fentanyl anesthesia. During progressive hyperventilation from PaCO2 = 40 to PaCO2 = 30, ICP response to hypocarbia was preserved with sevoflurane at both 0.5 and 1.0 MAC concentrations. In patients at risk for elevations of ICP, sevoflurane should be administered cautiously in conjunction with ICP-reducing maneuvers such as hyperventilation.
A multicenter study (2 sites) compared the safety of sevoflurane and isoflurane in 16 patients with mild-to-moderate hepatic impairment utilizing the lidocaine MEGX assay for assessment of hepatocellular function. All patients received intravenous propofol (1-3 mg/kg) or thiopental (2-7 mg/kg) for induction and succinylcholine, vecuronium, or atracurium for intubation. Sevoflurane or isoflurane was administered in either 100% O2 or up to 70% N2O/O2. Neither drug adversely affected hepatic function. No serum inorganic fluoride level exceeded 45 µM/L, but sevoflurane patients had prolonged terminal disposition of fluoride, as evidenced by longer inorganic fluoride half-life than patients with normal hepatic function (23 hours vs. 10-48 hours).
Sevoflurane was evaluated in renally impaired patients with baseline serum creatinine >1.5 mg/dL. Fourteen patients who received sevoflurane were compared with 12 patients who received isoflurane. In another study, 21 patients who received sevoflurane were compared with 20 patients who received enflurane. Creatinine levels increased in 7% of patients who received sevoflurane, 8% of patients who received isoflurane, and 10% of patients who received enflurane. Because of the small number of patients with renal insufficiency (baseline serum creatinine greater than 1.5 mg/dL) studied, the safety of sevoflurane administration in this group has not yet been fully established. Therefore, sevoflurane should be used with caution in patients with renal insufficiency (see WARNINGS).
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