| JOURNAL HOME | CME HOME | THIS MONTH | PAST ISSUES | ETOC | COLLECTIONS |
| AUTHORS | REVIEWERS | EDITORIAL BOARD | FEEDBACK | RSS | HELP |
 
|
|
|
||
|
|
© 2000 International Anesthesia Research Society
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
We assessed the effects of prolonged low-flow sevoflurane anesthesia on renal and hepatic functions by comparing high-flow sevoflurane with low-flow isoflurane anesthesia. Thirty patients scheduled for surgery of
10 h in duration randomly received either low-flow (1 L/min) sevoflurane anesthesia (n = 10), high-flow (6–10 L/min) sevoflurane anesthesia (n = 10), or low-flow (1 L/min) isoflurane anesthesia (n = 10). We measured the circuit concentrations of Compound A and serum fluoride. Renal function was assessed by blood urea nitrogen, serum creatinine, creatinine clearance, and urinary excretion of glucose, albumin, protein, and N-acetyl-ß-D-glucosaminidase. The hepatic function was assessed by serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, and total bilirubin. Compound A exposure was 277 ± 120 (135–478) ppm-h (mean ± SD [range]) in the low-flow sevoflurane anesthesia. The maximum concentration of serum fluoride was 53.6 ± 5.3 (43.4–59.3) µmol/L for the low-flow sevoflurane anesthesia, 47.1 ± 21.2 (21.4–82.3) µmol/L for the high-flow sevoflurane anesthesia, and 7.4 ± 3.2 (3.2–14.0) µmol/L for the low-flow isoflurane anesthesia. Blood urea nitrogen and serum creatinine were within the normal range, and creatinine clearance did not decrease throughout the study period in any group. Urinary excretion of glucose, albumin, protein, and N-acetyl-ß-D-glucosaminidase increased after anesthesia in all groups, but no significant differences were seen among the three groups at any time point after anesthesia. Lactate dehydrogenase and alkaline phosphatase on postanesthesia Day 1 were higher in the high-flow sevoflurane group than in the low-flow sevoflurane group. However, there were no significant differences in any other hepatic function tests among the groups. We conclude that prolonged low-flow sevoflurane anesthesia has the same effect on renal and hepatic functions as high-flow sevoflurane and low-flow isoflurane anesthesia.
Implications: During low-flow sevoflurane anesthesia, intake of Compound A reached 277 ± 120 ppm-h, but the effect on the kidney and the liver was the same in high-flow sevoflurane and low-flow isoflurane anesthesia.
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Sevoflurane is partly degraded by carbon dioxide absorbents to fluoromethyl-2,2-difluoro-1-(trifluoro- methyl) ether (Compound A) (1,2). Compound A is a dose-dependent nephrotoxin in rats, with a threshold for microscopic renal injury of 150 to 300 ppm-h (3–7). The concentration of Compound A in the anesthesia circuit increases as the fresh gas-flow rate decreases (8,9); thus, patients who are anesthetized with low-flow sevoflurane inhale more Compound A. Therefore, the use of sevoflurane is safe when it is delivered at high fresh gas-flow rates, but the effect of low-flow sevoflurane anesthesia on the kidney remains to be clarified in humans. The Food and Drug Administration places no restrictions on sevoflurane anesthesia at fresh gas-flow rates of >2 L/min, but does not recommend the use of low-flow sevoflurane anesthesia at rates <1 L/min or the use of sevoflurane up to 2 minimum alveolar anesthetic concentration (MAC) h at 1 L/min. This is partly because there is insufficient clinical data on low-flow sevoflurane anesthesia of <1 L/min, and that the nephrotoxic threshold of Compound A in humans is uncertain.
Eger et al. (10) observed transient albuminuria, glucosuria, and an increase in urinary 
glutathione-S-transferase (GST) in volunteers anesthetized with 3% sevoflurane with a fresh gas-flow rate of 2 L/min for 8 h. Eger et al. (11) also reported that when volunteers were given sevoflurane for 2 and 4 h in the same experimental setting, renal injury markers did not increase in 2-h sevoflurane anesthesia, but slight albuminuria and increased urinary GST were seen in 4-h sevoflurane anesthesia. Therefore, Eger et al. suggested that the threshold for renal injury in humans is between 80 and 168 ppm-h of Compound A. In contrast, Ebert et al. (12,13) reported that with the same setting, neither 4-h nor 8-h sevoflurane administration caused any significant effects on renal function.
To address the recent controversy of whether Compound A causes renal injury, we compared low-flow sevoflurane anesthesia (1 L/min) with high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia in patients who were undergoing prolonged surgery. Postanesthetic renal function was assessed by both possible biomarkers to Compound A and conventional markers (7,14). We also applied the conventional hepatic tests to assess the possible hepatotoxicity of Compound A.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
This study was approved by our institution’s Committee on Human Research, and informed consent was obtained from each patient individually. The study group consisted of 30 patients of ASA physical status I or II with tumors of the head and neck who were scheduled to undergo tumor resection, and for whom prolonged surgery of
10 h duration was planned. Patients whose medical history, physical examination, or laboratory tests showed evidence of abnormal hepatic or renal function were excluded from the study. Patients who received an enzyme inducer such as phenobarbital before anesthesia and chemotherapy for cancer before or up to 5 days after anesthesia were also excluded. Patients were selected randomly to receive sevoflurane anesthesia at a fresh gas-flow rate of 1 L/min (low-flow sevoflurane group; n = 10), or 6–10 L/min (high-flow sevoflurane group; n = 10), or isoflurane anesthesia at a fresh gas-flow rate of 1 L/min (low-flow isoflurane group; n = 10). Fresh Baralyme® (Allied Healthcare Products, Inc., St. Louis, MO) was placed into the canister in the low-flow sevoflurane and low-flow isoflurane groups immediately before the anesthesia. Instead of carbon dioxide absorbent, glass balls were placed into the canister in the high-flow sevoflurane group. The anesthetic machine used was Modulus® CD Anesthesia System (Ohmeda, Madison, WI).
The patients were premedicated with 50 mg of hydroxyzine and 0.5 mg of atropine IM 45 min before the induction of anesthesia. Anesthesia was induced by using 2 to 2.5 mg/kg propofol and 0.15 to 0.2 mg/kg vecuronium IV. After tracheal intubation, the fresh gas-flow rate was set to 1 L/min in the low-flow sevoflurane and low-flow isoflurane groups, and to 6–10 L/min in the high-flow sevoflurane group. In the high-flow sevoflurane group, the fresh gas-flow rate was adjusted so that rebreathing did not occur (inspired CO2 concentration = 0). The ratio of oxygen to nitrous oxide flow rates was adjusted to maintain the oxygen concentration in the inspiratory limb at >30%. The anesthetic concentration was adjusted to maintain systolic blood pressure within ±20% of baseline. Hypertensive responses that were not controlled with sevoflurane or isoflurane were treated with an IV bolus of 50 to 100 µg fentanyl. Ventilation was controlled with a tidal volume of 10 to 12 mL/kg, with the ventilatory rate adjusted to maintain a PaCO2 of 30 to 40 mm Hg. Postoperative antibiotics were restricted to 2 g/d of cefotiam hydrochloride up to 3 days after anesthesia.
During anesthesia, the end-tidal CO2 concentration and inspired and end-tidal anesthetic concentrations, were monitored by mass spectrometry (Medical Gas Analyzer 1100; Perkin-Elmer, Pomona, CA). The mass spectrometer was calibrated against known concentrations of sevoflurane and isoflurane that were verified by calibration with a gas chromatograph (model GC-9A; Shimadzu, Kyoto, Japan).
In the low-flow sevoflurane group, the concentration of Compound A in the inspiratory limb of the circle system was measured by using a gas chromatograph (model GC-9A; Shimadzu) equipped with a gas sampler (model MGS-5; Shimadzu). Samples were drawn from the circuit at 0.5, 1, 2 h and subsequently every 2 h during anesthesia and at the end of anesthesia into a gas-tight syringe. A glass column with a length of 5 m and an internal diameter of 3 mm packed with 20% dioctyl phthalate on a Chromosorb WAW® (Technolab SC Corp., Osaka, Japan) 80:100 mesh was maintained at 100°C. The injection port was maintained at 140°C. A carrier stream of nitrogen flowing at 50 mL/min was delivered through the column to a hydrogen flame ionization detector.
The radial artery was cannulated to permit blood samples to be obtained for plasma fluoride (F-) analysis during and after anesthesia. Plasma F- analysis was performed before anesthesia, at 5-h intervals during anesthesia and at 0, 1, 2, 3, 24, 48, and 72 h after termination of anesthesia by using an ion-selective electrode (Orion Research, Cambridge, MA) calibrated with a standard solution of sodium fluoride.
Blood samples were obtained before, and on Days 1, 2, 3, and 5 after, anesthesia for measurement of blood urea nitrogen (BUN), serum creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and total bilirubin. Twenty-four-hour urine samples were collected before anesthesia, for each 24-h period from 0 to 72 h and 5 days after anesthesia for measurement of creatinine, glucose, albumin, protein, and N-acetyl-ß-D-glucosaminidase (NAG). NAG activity was expressed relative to creatinine.
Measured values were expressed as mean ± SD (range). The MAC hour exposure was calculated from the percent anesthetic concentration and the duration of exposure. MAC values of 1.71% and 1.15% were used for sevoflurane and isoflurane, respectively. The area under the Compound A concentration curve (Compound A AUC) was calculated as the product of inspired Compound A concentration and duration of exposure using the rhomboid rule. An intergroup comparison of patient characteristics, anesthesia time, MAC hour, and maximum serum F- concentration was performed using one-way analysis variance with Fisher’s protected least significant difference. Inter- and intragroup comparisons of laboratory data were performed using two-way repeated measures analysis of variance. A P value < 0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
There were no significant differences in height, body weight, anesthesia time, or MAC hour exposure among the study groups (Table 1). The patients in the low-flow isoflurane group were younger than those in the other two groups (Table 1).
|
In the low-flow sevoflurane group, the individual maximum concentration of Compound A was 28.5 ± 7.9 (18.8–42.3) ppm. The concentration of Compound A measured reached 26.6 ± 8.6 ppm at 2 h after the initiation of anesthesia and tended to decrease thereafter (Figure 1). The average Compound A AUC in the low-flow sevoflurane group was 277 ± 120 (135–478) ppm-h.
|
The maximum concentration of serum inorganic fluoride was 53.6 ± 5.3 (43.4–59.3) µmol/L for the low-flow sevoflurane group, 47.1 ± 21.2 (21.4–82.3) µmol/L for the high-flow sevoflurane group, and 7.4 ± 3.2 (3.2–14.0) µmol/L for the low-flow isoflurane group. Eight patients in the low-flow sevoflurane group and four patients in the high-flow sevoflurane group had plasma F- concentrations of >50 µmol/L. The concentration in the low-flow isoflurane group was significant less than those in the low- and high-flow sevoflurane groups, but there were no significant differences between the low- and high-flow sevoflurane groups (Table 1).
There were no significant differences in BUN and serum creatinine among the groups (Table 2). No patients in any of the three groups had BUN or serum creatinine concentration values in excess of the upper limit of the normal range (BUN, 22 mg/dL; serum creatinine, 1.3 mg/dL). Creatinine clearance did not decrease after anesthesia in any group, and there were no significant differences among the groups (Table 2).
|
Renal effects of the three groups were also measured by urinary excretion of glucose, albumin, protein, and NAG. The values of these renal tests increased after anesthesia in all groups, and there were no significant differences among the groups (Table 3, Figure 2). There was no significant correlation between these increased (individual maximal) values and the Compound A AUC (Figure 3).
|
|
|
Hepatic effects of anesthesia were measured by serum AST, ALT, LDH, ALP, and total bilirubin. AST and ALT increased after anesthesia. Abnormal AST and ALT values were seen in all groups, but there was no significant difference among the groups (Table 4). No positive correlation could be found between AST and ALT or Compound A AUC (Figure 4). LDH increased on postanesthesia Day 5 in the high-flow sevoflurane and the low-flow isoflurane groups, but did not increase in the low-flow sevoflurane group. ALP did not increase after anesthesia in all groups. LDH and ALP on postanesthesia Day 1 were higher in the high-flow sevoflurane group than in the low-flow sevoflurane group. However, there were no significant differences between the groups in LDH and ALP at any other time point (Table 4). Total bilirubin increased after anesthesia, but there were no significant differences among the groups (Table 4). Abnormal increases in total bilirubin of >2 mg/dL were observed in one patient of the low-flow sevoflurane group and three patients of the low-flow isoflurane group.
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The threshold of Compound A for renal injury in rats ranges from 50 to 144 ppm when they are exposed for three hours (3,6), which is equivalent to a dose of 150 to 342 ppm-h. The primary injury is necrosis of the proximal tubule cells (14). The most possible biomarkers for this injury in rats are proteinuria, glucosuria, and enzymuria (
GST) (7,14). Compound A nephrotoxicity is dose-dependent, and thus, longer exposure to Compound A causes further renal injury, and consequently, an increase in BUN and serum creatinine (14).
Eger et al. (10) reported that volunteers who were given 3% sevoflurane at a fresh gas-flow rate of 2 L/min for eight hours showed transient albuminuria, glucosuria, and an increase in urinary GST. In the same setting, Eger et al. (11) found a small amount of albuminuria and increased GST after four hours of administration of sevoflurane but no injury after two hours. Based on the findings of these two studies, Eger et al. concluded that Compound A nephrotoxicity is dose-dependent in humans as in rats, and that the nephrotoxic threshold of Compound A is between 80 and 168 ppm-h, similar to that of rats. In contrast, Ebert et al. (12,13) reported that using the same setting, neither four- nor eight-hour sevoflurane anesthesia altered renal function. Clinical studies have found either that low-flow sevoflurane anesthesia did not influence renal function or that transient albuminuria and glucosuria occurred (15–17).
The amount of exposure to Compound A during low-flow sevoflurane anesthesia for a relatively short period of two to three hours does not affect the kidney. However, there is no agreement about whether the kidney is altered when the amount of exposure to Compound A increases with prolonged anesthesia. In a previous study (18), we evaluated the safety of prolonged sevoflurane anesthesia in 50 surgical patients and found that low-flow sevoflurane anesthesia exceeding 10 hours had a similar effect on kidney and liver to that of isoflurane anesthesia. In that study, however, we used BUN and serum creatinine to assess renal injury but did not use the most possible biomarkers for the nephrotoxicity of Compound A. Although BUN and serum creatinine are routinely used to assess renal injury in clinical practice, some think that proteinuria, glucosuria, and enzymuria (GST) are better biomarkers for Compound A when assessing Compound A nephrotoxicity. We used glucosuria, albuminuria, proteinuria and NAG as possible biomarkers, and BUN and serum creatinine to assess renal injury.
Our results demonstrated that BUN and serum creatinine did not increase after low-flow sevoflurane anesthesia, which is consistent with previous results from studies using volunteers or clinical studies (10–13,15–18), and thus no abnormality in the standard biomarkers was seen for low-flow sevoflurane anesthesia. With regard to the possible biomarkers, urinary glucose, albumin, protein, and NAG were increased after low-flow sevoflurane anesthesia. However, these increases were observed in high-flow sevoflurane and low-flow isoflurane anesthesia with no significant difference among the three groups, and were not related to the amount of inhaled Compound A. These increases might be attributed to the effect of the use of drugs other than the anesthetics. Therefore, although the possible markers increased after low-flow sevoflurane anesthesia, they do not appear to be associated with Compound A.
In studies of Compound A toxicity, much attention has been given to the kidney, but Eger et al. (10) suggested that Compound A might also be hepatotoxic as shown by transient increases in ALT. Our study demonstrated that the hepatic function values increased on Day 5 after low-flow sevoflurane anesthesia, but these increases were not significantly different as compared with high-flow sevoflurane and low-flow isoflurane anesthesia, and were not correlated with the amount of inhaled Compound A. Therefore, prolonged low-flow sevoflurane anesthesia is not likely to cause hepatotoxicity. This view was supported by previous studies (12,18,19).
We tried to determine whether inhalation of large amounts of Compound A compromises kidney and liver function. To achieve a large exposure to Compound A, patients must inhale large concentrations of Compound A for a long period of time. Because Compound A concentrations correlate to sevoflurane concentrations (9,20–22), administration of a large sevoflurane concentration creates a large exposure to Compound A. We did not use this approach to maintain cardiovascular stability by giving nitrous oxide concomitantly and fentanyl when necessary. Furthermore, the carbon dioxide absorbent we used, Baralyme, produces large concentrations of Compound A in the circuit.
Methoxyflurane nephrotoxicity is probably caused by plasma fluoride concentrations in excess of 50 µmol/L (23). In 12 patients who received either low- or high-flow sevoflurane anesthesia, the maximal fluoride concentration exceeded 50 µmol/L. However, because of sevoflurane’s rapid elimination, the area under the plasma fluoride concentration curve is smaller during sevoflurane versus methoxyflurane anesthesia (24–26). Furthermore, the intrarenal metabolism of methoxyflurane may result in impaired renal concentrating ability, whereas the relative lack of intrarenal metabolism of sevoflurane and, therefore, lack of intrarenal fluoride, probably provides a greater safety margin for sevoflurane (27,28). Consistent with this theory, several reports and our study document normal renal concentrating ability after exposure to 8–9.5 hours of sevoflurane (10,25,29).
In conclusion, we assessed the effect of prolonged low-flow sevoflurane anesthesia on the kidney and liver using conventional and possible biomarkers. During low-flow sevoflurane anesthesia, intake of Compound A reached 277 ± 120 ppm-h, but the effect on the kidney and the liver was the same in high-flow sevoflurane and low-flow isoflurane anesthesia. Specific toxicity on the kidney and liver was not observed in the surgical patients.
|
Footnotes |
|---|
Presented in part at the annual meeting of the American Society of Anesthesiologists, Dallas, TX, October 1999.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
-
Wallin RF, Regan BM, Napoli MD, Stern IJ. Sevoflurane: a new inhalational anesthetic agent. Anesth Analg 1975; 54: 758–65.
[Abstract/Free Full Text] - Morio M, Fujii K, Satoh N, et al. Reaction of sevoflurane and its degradation products with soda lime: toxicity of the byproducts. Anesthesiology 1992; 77: 1155–64.[Web of Science][Medline]
- Gonsowski CT, Laster MJ, Eger EI II, et al. Toxicity of compound A in rats: effect of a 3-hour administration. Anesthesiology 1994; 80: 556–65.[Web of Science][Medline]
- Gonsowski CT, Laster MJ, Eger EI II, et al. Toxicity of compound A in rats: effect of increasing duration of administration. Anesthesiology 1994; 80: 566–73.[Web of Science][Medline]
- Kandel L, Laster MJ, Eger EI II, et al. Nephrotoxicity in rats undergoing a one-hour exposure to compound A. Anesth Analg 1995; 81: 559–63.[Abstract]
- Keller KA, Callan C, Prokocimer P, et al. Inhalation toxicity study of a haloalkene degradant of sevoflurane, compound A (PIFE), in Sprague-Dawley rats. Anesthesiology 1995; 83: 1220–32.[Web of Science][Medline]
- Kharasch ED, Hoffman GM, Thorning D, et al. Role of renal cysteine conjugate ß-lyase pathway in inhaled compound A nephrotoxicity in rats. Anesthesiology 1998; 88: 1624–33.[Web of Science][Medline]
-
Bito H, Ikeda K. Effect of total flow rate on the concentration of degradation products generated by reaction between sevoflurane and soda lime. Br J Anaesth 1995; 74: 667–9.
[Abstract/Free Full Text] - Fang ZX, Eger EI II. Factors affecting the concentration of compound A resulting from the degradation of sevoflurane by soda lime and Baralyme® in a standard anesthetic circuit. Anesth Analg 1995; 81: 564–8.[Abstract]
- Eger EI II, Koblin DD, Bowland T, et al. Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg 1997; 84: 160–8.[Abstract]
- Eger EI II, Gong D, Koblin DD, et al. Dose-related biochemical markers of renal injury after sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg 1997; 85: 1154–63.[Abstract]
- Ebert TJ, Frink EJ, Kharasch ED. Absence of biochemical evidence for renal and hepatic dysfunction after 8 hours of 1.25 minimum alveolar concentration sevoflurane anesthesia in volunteers. Anesthesiology 1998; 88: 601–10.[Web of Science][Medline]
- Ebert TJ, Messana LD, Uhrich TD, et al. Absence of renal and hepatic toxicity after four hours of 1.25 minimum alveolar anesthetic concentration sevoflurane anesthesia in volunteers. Anesth Analg 1998; 86: 662–7.[Abstract]
- Kharasch ED, Thorning D, Garton K, et al. Role of renal cysteine conjugate ß-lyase in the mechanism of compound A nephrotoxicity in rats. Anesthesiology 1997; 86: 160–71.[Web of Science][Medline]
- Bito H, Ikeuchi Y, Ikeda K. Effects of low-flow sevoflurane anesthesia on renal function: comparison with high-flow sevoflurane anesthesia and low-flow isoflurane anesthesia. Anesthesiology 1997; 86: 1231–7.[Web of Science][Medline]
- Kharasch ED, Frink EJ Jr, Zager R, et al. Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity. Anesthesiology 1997; 86: 1238–53.[Web of Science][Medline]
- Higuchi H, Sumita S, Wada H, et al. Effects of sevoflurane and isoflurane on renal function and possible markers of nephrotoxicity. Anesthesiology 1998; 89: 307–22.[Web of Science][Medline]
- Bito H, Ikeda K. Renal and hepatic function in surgical patients after low-flow sevoflurane or isoflurane anesthesia. Anesth Analg 1996; 82: 173–6.[Abstract]
-
Bito H, Ikeda K. Plasma inorganic fluoride and intracircuit degradation product concentrations in long-duration, low-flow sevoflurane anesthesia. Anesth Analg 1994; 79: 946–51.
[Abstract/Free Full Text] - Bito H, Ikeda K. Long-duration, low-flow sevoflurane anesthesia using two carbon dioxide absorbents: quantification of degradation products in the circuit. Anesthesiology 1994; 81: 340–5.[Web of Science][Medline]
- Munday IT, Ward PM, Foden ND, et al. Sevoflurane degradation by soda lime in a circle breathing system. Anaesthesia 1996; 51: 622–6.[Web of Science][Medline]
- Fang ZX, Kandel L, Laster MJ, et al. Factors affecting production of compound A from the interaction of sevoflurane with Baralyme and soda lime. Anesth Analg 1996; 82: 775–81.[Abstract]
-
Cousins MJ, Mazze RI. Methoxyflurane nephrotoxicity: a study of dose response in man. JAMA 1973; 225: 1611–6.
[Abstract/Free Full Text] -
Kobayashi Y, Ochiai R, Takeda J, et al. Serum and urinary inorganic fluoride concentrations after prolonged inhalation of sevoflurane in humans. Anesth Analg 1992; 74: 753–7.
[Abstract/Free Full Text] - Frink EJ Jr, Malan TP, Isner J, et al. Renal concentrating function with prolonged sevoflurane or enflurane anesthesia in volunteers. Anesthesiology 1994; 80: 1019–25.[Web of Science][Medline]
- Frink EJ Jr, Ghantous H, Malan TP, et al. Plasma inorganic fluoride with sevoflurane anesthesia: correlation with indices of hepatic and renal function. Anesth Analg 1992; 74: 231–5.[Web of Science][Medline]
- Brown BR Jr. Shibboleths and jigsaw puzzles: the fluoride nephrotoxicity enigma. Anesthesiology 1995; 82: 607–8.[Web of Science][Medline]
- Kharasch ED, Hankins DC, Thummel KE. Human kidney methoxyflurane and sevoflurane metabolism. Anesthesiology 1995; 82: 689–99.[Web of Science][Medline]
- Munday IT, Stoddart PA, Jones RM, et al. Serum fluoride concentration and urine osmolality after enflurane and sevoflurane anesthesia in male volunteers. Anesth Analg 1995; 81: 353–9.[Abstract]
This article has been cited by other articles:
|
|
 |
|
  H. Ture, A. Mercan, O. Koner, B. Aykac, and U. Ture The Effects of Propofol Infusion on Hepatic and Pancreatic Function and Acid-Base Status in Children Undergoing Craniotomy and Receiving Phenytoin Anesth. Analg., August 1, 2009; 109(2): 366 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Robards and S. J. Brull The Anesthetic Implications of Crigler-Najjar Syndrome Anesth. Analg., February 1, 2007; 104(2): 435 - 436. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Stachnik Inhaled anesthetic agents Am. J. Health Syst. Pharm., April 1, 2006; 63(7): 623 - 634. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Kharasch, J. L. Schroeder, T. Bammler, R. Beyer, and S. Srinouanprachanh Gene Expression Profiling of Nephrotoxicity from the Sevoflurane Degradation Product Fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl Ether ("Compound A") in Rats Toxicol. Sci., April 1, 2006; 90(2): 419 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Reich, A. S. Everding, M. Bulla, O. A. Brinkmann, and H. Van Aken Hepatitis After Sevoflurane Exposure in an Infant Suffering from Primary Hyperoxaluria Type 1 Anesth. Analg., August 1, 2004; 99(2): 370 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Kharasch, E. J. Frink Jr., A. Artru, P. Michalowski, G. A. Rooke, and W. Nogami Long-Duration Low-Flow Sevoflurane and Isoflurane Effects on Postoperative Renal and Hepatic Function Anesth. Analg., December 1, 2001; 93(6): 1511 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Laisalmi, A.-M. Teppo, A.-M. Koivusalo, E. Honkanen, P. Valta, and L. Lindgren The Effect of Ketorolac and Sevoflurane Anesthesia on Renal Glomerular and Tubular Function Anesth. Analg., November 1, 2001; 93(5): 1210 - 1213. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
