Early Allograft Function in Renal Transplant Recipients: Is it Affected by Volatile Anesthetics? M. Yildirima, H.F. Kucuka, T. Demira, S. Yakupoglub, A. Yavuzc, and E. Aric,* a Department of Transplantation, Kartal Research and Training Hospital, Istanbul, Turkey; bDepartment of Anesthesia, Kartal Research and Training Hospital, Istanbul, Turkey; and cDepartment of Nephrology, Kartal Research and Training Hospital, Istanbul, Turkey
ABSTRACT Background. Different inhalational anesthetics have various hemodynamic effects, either on the global circulation or on renal perfusion. The purpose of the current retrospective, single-center study was to evaluate allograft function of renal transplant recipients after transplantation surgery under either sevoflurane or isoflurane anesthesia. Methods. From January 2004 through February 2014, a total of 240 patients undergoing renal transplantation were retrospectively enrolled in this study. The recipients were categorized into a sevoflurane or isoflurane group based on the type of volatile anesthetic used. The evaluated outcomes were serum urea and creatinine values and volume of diuresis at day 14 after transplantation. Results. There were no differences between the 2 anesthesia groups regarding age, gender, duration and etiology of end-stage renal disease, duration and type of dialysis regimen, and source of transplantation (living or cadaveric). Length of hospitalization was higher in the sevoflurane group when compared with the isoflurane group (21.64 11.55 days vs 17.35 8.06 days; P ¼ .033). Similarly, the sevoflurane group had more postoperative complications then the isoflurane group. Although serum creatinine levels were similar between the 2 groups, the serum level of urea was higher (89.56 47.60 mg/dL vs 76.85 65.42 mg/dL; P ¼ .038) and the volume of diuresis was lower (3718.00 2558.94 mL/24 hours vs 4991.25 2861.90 mL/24 hours; P ¼ .042) in the sevoflurane group when compared with the isoflurane group. Conclusion. Our data seem to suggest a potential role of isoflurane for improving allograft function and reducing complications more safely than sevoflurane as a volatile anesthetic in patients undergoing renal transplantation.
R
ENAL transplantation is the best option for patients with end-stage renal disease (ESRD) because of its association with better quality of life, better cost/benefit ratio, and, possibly, longer survival [1]. Volatile anesthetics have been frequently used for general anesthesia for renal transplantation [2]. The typical volatile anesthetics commonly used are sevoflurane and isoflurane [3,4]. Sevoflurane has the potential to adversely affect the kidney function because an inorganic fluoride ion from the defluorination of sevoflurane and compound A from reaction with carbon dioxide absorbent are associated with nephrotoxicity [5,6]. On the other hand, isoflurane is not known to undergo degradation to nephrotoxic difluorovinyl products.
Although any nephrotoxic effect of sevoflurane in humans has not yet been proven, this issue is still subject to debate due to literature related to sevofluraneinduced nephrotoxicity [5e9]. The aim of the present study was to investigate the allograft function of renal transplant recipients after transplantation surgery under either sevoflurane or isoflurane anesthesia.
*Address correspondence to Assoc. Prof. Elif Ari, Department of Nephrology, Kartal Research and Training Hospital, Semsi Denizer Street, 34890 Kartal/Istanbul, Turkey. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.04.048
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1352
Transplantation Proceedings, 47, 1352e1355 (2015)
VOLATILE ANESTHETICS
METHODS Study Population From January 2004 through February 2014, a total of 240 patients undergoing renal transplantation under sevoflurane or isoflurane anesthesia were retrospectively enrolled in the current study. Patients undergoing perioperative transfusion or reoperation were excluded.
Anesthesia Protocol All patients were administered general anesthesia via tracheal intubation with artificial mechanical ventilation. The technique included an endovenous induction (thiopental or propofol), fentanyl, a muscle relaxant (atracurium or cisatracurium), and a halogenated agent (sevoflurane or isoflurane), which was vaporized in a mixture of oxygen and air. We used a Siemens Servo 900D ventilator with a circular anesthesia system where the carbon dioxide absorbent was soda lime. We divided the patients into 2 groups according to the inhalational anesthetic: a sevoflurane group (n ¼ 116), and an isoflurane group (n ¼ 124).
Data Collection Medical records and laboratory data were reviewed. Patient characteristics including age, gender, body mass index, and medical history including duration and etiology of ESRD, duration and type of dialysis regimen, and source of transplantation (living or cadaveric) were recorded. Intraoperative data, which included surgical and anesthetic times, administered fluids, intraoperative blood loss, urine output, were recorded. Duration of hospitalization, type of postoperative complications, and urine output were assessed as postoperative data. Laboratory data which included hemoglobin, hematocrit, platelet count, albumin, liver function tests, renal function tests, were also recorded. We collected all these variables from the patients preoperatively, on the first postoperative day, and on the 14th postoperative day.
Statistical Analysis Continous data were presented as mean standard deviation (SD) and analyzed using the independent Student t test or MannWhitney U test. Categorical data were presented as percentages and analyzed using the chi-square test or Fisher exact test. Twotailed P values .05 12.53 14.42 12.56 6.68 13.48 4.76 >.05 8.21 4.60 58/66 101/23
8.89 5.06 >.05 49/67 92/24
41 32 8 27 16
40 21 3 34 18
97 18 9
84 24 8
Although there were no significant differences in intraoperative laboratory measurements, postoperative complications were higher in the sevoflurane group when compared with the isoflurane group. Acute cellular and humoral rejection rates, pulmonary complications such as pneumonia and pleural effusion, deep venous thrombosis, perirenal hematoma, and lymphocele frequencies were similar between the 2 groups (Table 3). But, fever (P ¼ .040), urinary tract infection (P ¼ .048), and acute tubular necrosis (P ¼ .044) frequencies were higher in the sevoflurane group when compared with the isoflurane group (Table 3). Renal functional parameters in the study groups are reported in Table 4. Although serum creatinine levels did not differ between the groups (P > .05), serum urea of the sevoflurane group was higher (P ¼ .038) as well as urine output was lower (P ¼ .042) when compared with the isoflurane group at day 14 in the postoperative period. DISCUSSION
RESULTS
Clinical and demographic characteristics of the sevoflurane and isoflurane patient groups are given in Table 1. There were no significant differences in age, gender, duration and etiology of ESRD, duration and type of dialysis regimen, and source of transplantation (living or cadaveric) among groups. Table 2 shows the intraoperative data of both groups. Operation time did not differ between the groups. Although there were no significant differences in intraoperative central venous pressure measurements and serum concentrations of hemoglobin and albumin, length of hospitalization of the sevoflurane group was significantly higher than that of the isoflurane group (P ¼ .033).
The present retrospective study demonstrated for the first time that a volatile anesthetic isoflurane might be superior Table 2. Intraoperative and Postoperative Clinical Data of the Study Population According to the Anesthesia Type Isoflurane Group (n ¼ 124)
Sevoflurane Group (n ¼ 116)
P
Operation time (min) 217.14 37.45 241.22 71.08 >.05 Length of hospital stay (d) 17.35 8.06 21.64 11.55 .033 Intraoperative central 8.75 4.16 9.10 3.54 >.05 venous pressure (mm Hg) Intraoperative hemoglobin 10.88 1.67 10.35 1.42 >.05 concentration (g/dL) Intraoperative albumin 3.76 0.48 3.82 0.44 >.05 concentration (g/dL)
1354
YILDIRIM, KUCUK, DEMIR ET AL
Table 3. Postoperative Complications of the Study Population According to the Anesthesia Type Postoperative Complications
Isoflurane Group (n ¼ 124)
Sevoflurane Group (n ¼ 116)
P
Fever Urinary tract infection Pneumonia Acute cellular rejection Acute humoral rejection Acute tubular necrosis Pleural effusion Deep venous thrombosis Perirenal hematoma Lymphocele
18.20% 14.93% 3.71% 2.46% 1.89% 19.50% 3.94% 1.80% 11.42% 4.45%
24.86% 17.99% 3.18% 2.78% 1.67% 24.95% 2.97% 1.67% 10.78% 4.49%
.040 .048 >.05 >.05 >.05 .044 >.05 >.05 >.05 >.05
to another volatile anestethic sevoflurane in renal transplantation operations. We demonstrated for the first time that isoflurane might improve allograft function as well as reduce metabolic complications when compared with sevoflurane at the early postoperative period in renal transplant recipients. All currently used volatile anesthetics are degraded by the strong bases in carbon dioxide absorbents to by-products that are potentially toxic. Isoflurane is degraded by desiccated absorbents to carbon monoxide, which can significantly elevate carboxyhemoglobin concentrations. Sevoflurane is degraded to difluorovinyl products, which are nephrotoxic in rats [10]. According to our results, isoflurane is superior in preserving allograft functions in renal transplant recipients at the early postoperative period. The patients in the isoflurane group had lower serum urea and higher urine output when compared with sevoflurane at postoperative day 14. Our results are particularly different from the current literature. Teixeira et al reported that sevoflurane or isoflurane had no influence on the outcome of allograft function in renal transplantation [11]. Conzen et al demonstrated that sevoflurane or isoflurane does not alter renal function in chronic kidney disease [4]. On the contrary, Lee et al showed that the decrease of blood urea nitrogen (BUN) at 72 hours after surgery was less prominent in patients with sevoflurane than with isoflurane [12]. We also found that length of hospitalization was higher in the sevoflurane group than the isoflurane group. Although the operation time did not differ between the 2 groups, metabolic complications were higher with sevoflurane. Fever, urinary tract infection, and acute tubular necrosis were
Table 4. Early Graft Functions of the Study Population According to the Anesthesia Type Postoperative d 14
Volume of diuresis (mL/24 h) Urea (mg/dL) Creatinine (mg/dL)
Isoflurane Group (n ¼ 124)
Sevoflurane Group (n ¼ 116)
4991.25 2861.90 3718.00 2558.94
P
higher with sevoflurane. We interpreted that these complications induced the prolongation of hospital stay. We also demonstrated that metabolic complications were not derived from intraoperative hemodynamic variations. Intraoperative central venous pressure measurements showed that intraoperative hemodynamic stabilization did not differ between the study groups. Furthermore, intraoperative hemoglobin and albumin concentrations of the study groups (Table 2) demonstrated that anemia and/or hypoalbuminemia were not the reasons for early allograft toxicity. It is well known that sevoflurane has many advantages such as pleasant odor, no pungency, and bronchodilating effect [13]. However, the concern about the nephrotoxicity of sevoflurane exists still [9]. The issues of nephrotoxicity related to sevoflurane are based not only on its fluoride metabolite but also compound A [13,14]. Previous investigations of sevoflurane metabolism demonstrated that a fluoride ion concentration >50 mmol/L could be observed when sevoflurane was used during operations. Although this 50 mmol/L concentration is the toxic threshold associated with nephrotoxicity, renal toxicity was not reported with sevoflurane [5,15]. Compound A (fluoromethyl-2-2difluoro-1-(trifluoromethyl) vinyl ether) is the other concerning metabolite associated with the use of sevoflurane. Compound A is formed during the interaction of sevoflurane with carbon dioxide absorbents, and it has been shown to be a dose-dependent nephrotoxin in rats [6]. Exposure to compound A is known to cause dosedependent albuminuria, glucosuria, or enzymuria [16]. We did not study serum concentrations of fluoride ion or compound A, but it can be speculated that these metabolites could be the reason(s) for early allograft toxicity. This is the first demonstration that isoflurane can be used more safely than sevoflurane in renal transplantations. The results of the present study seem to suggest that isoflurane may have benefits in allograft function at the early postoperative period. Therefore, it is likely that the observed benefit of isoflurane could mainly be exerted through less nephrotoxic effects on renal tubular cells compared with sevoflurane. Due to the retrospective design of the study, the results should be interpreted with caution and causal relationship can not be suggested. It would be interesting to assess the allograft functions and complications in a long-term followup study and analyze the possible relationship with the choice of volatile anesthetics of renal transplant recipients. In conclusion, present data show that isoflurane can be used more safely than sevoflurane in transplantations. Further prospective, randomized, controlled studies are needed to determine the possible beneficial effects of isoflurane on allograft functions and metabolic complications among renal transplant recipients.
.042
REFERENCES 76.85 65.42 1.24 0.89
89.56 47.60 1.38 0.74
.038 >.05
[1] Ojo AO, Hanson JA, Meier-Kriesche H, et al. Survival in recipients of marginal cadaveric donor kidneys compared with other
VOLATILE ANESTHETICS recipients and wait-listed transplant candidates. J Am Soc Nephrol 2001;12(3):589e97. [2] Campagna JA, Miller KW, Forman SA. Mechanisms of actions of inhaled anesthetics. N Engl J Med 2003;348(21):2110e24. [3] Baxter PJ, Garton K, Kharasch ED. Mechanistic aspects of carbon monoxide formation from volatile anesthetics. Anesthesiology 1998;89(4):929e41. [4] Conzen PF, Kharasch ED, Czerner SF, et al. Low-flow sevoflurane compared with low-flow isoflurane anesthesia in patients with stable renal insufficiency. Anesthesiology 2002;97(3):578e84. [5] 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(5):753e7. [6] 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(6):1220e32. [7] Goldberg ME, Cantillo J, Larijani GE, et al. Sevoflurane versus isoflurane for maintenance of anesthesia: are serum inorganic fluoride ion concentrations of concern? Anesth Analg 1996;82(6):1268e72. [8] Ebert TJ, Arain SR. Renal responses to low-flow desflurane, sevoflurane, and propofol in patients. Anesthesiology 2000;93(6): 1401e6.
1355 [9] Mazze RI. The safety of sevoflurane in humans. Anesthesiology 1992;77(6):1062e3. [10] Gonsowski CT, Laster MJ, Eger 2nd EI, et al. Toxicity of compound A in rats. Effect of a 3-hour administration. Anesthesiology 1994;80(3):556e65. [11] Teixeira S, Costa G, Costa F, et al. Sevoflurane versus isoflurane: does it matter in renal transplantation? Transplant Proc 2007;39(8):2486e8. [12] Lee HC, Kim D, Ahn W, et al. Comparison of the renal safety between carbon dioxide absorbent products under sevoflurane anesthesia: a pilot study. Korean J Anesthesiol 2012;63(1): 11e7. [13] Young CJ, Apfelbaum JL. Inhalational anesthetics: desflurane and sevoflurane. J Clin Anesth 1995;7(7):564e77. [14] 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(4):775e81. [15] Frink Jr EJ, Malan TP, Atlas M, et al. Clinical comparison of sevoflurane and isoflurane in healthy patients. Anesth Analg 1992;74(2):241e5. [16] Bedford RF, Ives HE. The renal safety of sevoflurane. Anesth Analg 2000;90(3):505e8.
ABSTRACT Background. Different inhalational anesthetics have various hemodynamic effects, either on the global circulation or on renal perfusion. The purpose of the current retrospective, single-center study was to evaluate allograft function of renal transplant recipients after transplantation surgery under either sevoflurane or isoflurane anesthesia. Methods. From January 2004 through February 2014, a total of 240 patients undergoing renal transplantation were retrospectively enrolled in this study. The recipients were categorized into a sevoflurane or isoflurane group based on the type of volatile anesthetic used. The evaluated outcomes were serum urea and creatinine values and volume of diuresis at day 14 after transplantation. Results. There were no differences between the 2 anesthesia groups regarding age, gender, duration and etiology of end-stage renal disease, duration and type of dialysis regimen, and source of transplantation (living or cadaveric). Length of hospitalization was higher in the sevoflurane group when compared with the isoflurane group (21.64 11.55 days vs 17.35 8.06 days; P ¼ .033). Similarly, the sevoflurane group had more postoperative complications then the isoflurane group. Although serum creatinine levels were similar between the 2 groups, the serum level of urea was higher (89.56 47.60 mg/dL vs 76.85 65.42 mg/dL; P ¼ .038) and the volume of diuresis was lower (3718.00 2558.94 mL/24 hours vs 4991.25 2861.90 mL/24 hours; P ¼ .042) in the sevoflurane group when compared with the isoflurane group. Conclusion. Our data seem to suggest a potential role of isoflurane for improving allograft function and reducing complications more safely than sevoflurane as a volatile anesthetic in patients undergoing renal transplantation.
R
ENAL transplantation is the best option for patients with end-stage renal disease (ESRD) because of its association with better quality of life, better cost/benefit ratio, and, possibly, longer survival [1]. Volatile anesthetics have been frequently used for general anesthesia for renal transplantation [2]. The typical volatile anesthetics commonly used are sevoflurane and isoflurane [3,4]. Sevoflurane has the potential to adversely affect the kidney function because an inorganic fluoride ion from the defluorination of sevoflurane and compound A from reaction with carbon dioxide absorbent are associated with nephrotoxicity [5,6]. On the other hand, isoflurane is not known to undergo degradation to nephrotoxic difluorovinyl products.
Although any nephrotoxic effect of sevoflurane in humans has not yet been proven, this issue is still subject to debate due to literature related to sevofluraneinduced nephrotoxicity [5e9]. The aim of the present study was to investigate the allograft function of renal transplant recipients after transplantation surgery under either sevoflurane or isoflurane anesthesia.
*Address correspondence to Assoc. Prof. Elif Ari, Department of Nephrology, Kartal Research and Training Hospital, Semsi Denizer Street, 34890 Kartal/Istanbul, Turkey. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2015.04.048
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1352
Transplantation Proceedings, 47, 1352e1355 (2015)
VOLATILE ANESTHETICS
METHODS Study Population From January 2004 through February 2014, a total of 240 patients undergoing renal transplantation under sevoflurane or isoflurane anesthesia were retrospectively enrolled in the current study. Patients undergoing perioperative transfusion or reoperation were excluded.
Anesthesia Protocol All patients were administered general anesthesia via tracheal intubation with artificial mechanical ventilation. The technique included an endovenous induction (thiopental or propofol), fentanyl, a muscle relaxant (atracurium or cisatracurium), and a halogenated agent (sevoflurane or isoflurane), which was vaporized in a mixture of oxygen and air. We used a Siemens Servo 900D ventilator with a circular anesthesia system where the carbon dioxide absorbent was soda lime. We divided the patients into 2 groups according to the inhalational anesthetic: a sevoflurane group (n ¼ 116), and an isoflurane group (n ¼ 124).
Data Collection Medical records and laboratory data were reviewed. Patient characteristics including age, gender, body mass index, and medical history including duration and etiology of ESRD, duration and type of dialysis regimen, and source of transplantation (living or cadaveric) were recorded. Intraoperative data, which included surgical and anesthetic times, administered fluids, intraoperative blood loss, urine output, were recorded. Duration of hospitalization, type of postoperative complications, and urine output were assessed as postoperative data. Laboratory data which included hemoglobin, hematocrit, platelet count, albumin, liver function tests, renal function tests, were also recorded. We collected all these variables from the patients preoperatively, on the first postoperative day, and on the 14th postoperative day.
Statistical Analysis Continous data were presented as mean standard deviation (SD) and analyzed using the independent Student t test or MannWhitney U test. Categorical data were presented as percentages and analyzed using the chi-square test or Fisher exact test. Twotailed P values .05 12.53 14.42 12.56 6.68 13.48 4.76 >.05 8.21 4.60 58/66 101/23
8.89 5.06 >.05 49/67 92/24
41 32 8 27 16
40 21 3 34 18
97 18 9
84 24 8
Although there were no significant differences in intraoperative laboratory measurements, postoperative complications were higher in the sevoflurane group when compared with the isoflurane group. Acute cellular and humoral rejection rates, pulmonary complications such as pneumonia and pleural effusion, deep venous thrombosis, perirenal hematoma, and lymphocele frequencies were similar between the 2 groups (Table 3). But, fever (P ¼ .040), urinary tract infection (P ¼ .048), and acute tubular necrosis (P ¼ .044) frequencies were higher in the sevoflurane group when compared with the isoflurane group (Table 3). Renal functional parameters in the study groups are reported in Table 4. Although serum creatinine levels did not differ between the groups (P > .05), serum urea of the sevoflurane group was higher (P ¼ .038) as well as urine output was lower (P ¼ .042) when compared with the isoflurane group at day 14 in the postoperative period. DISCUSSION
RESULTS
Clinical and demographic characteristics of the sevoflurane and isoflurane patient groups are given in Table 1. There were no significant differences in age, gender, duration and etiology of ESRD, duration and type of dialysis regimen, and source of transplantation (living or cadaveric) among groups. Table 2 shows the intraoperative data of both groups. Operation time did not differ between the groups. Although there were no significant differences in intraoperative central venous pressure measurements and serum concentrations of hemoglobin and albumin, length of hospitalization of the sevoflurane group was significantly higher than that of the isoflurane group (P ¼ .033).
The present retrospective study demonstrated for the first time that a volatile anesthetic isoflurane might be superior Table 2. Intraoperative and Postoperative Clinical Data of the Study Population According to the Anesthesia Type Isoflurane Group (n ¼ 124)
Sevoflurane Group (n ¼ 116)
P
Operation time (min) 217.14 37.45 241.22 71.08 >.05 Length of hospital stay (d) 17.35 8.06 21.64 11.55 .033 Intraoperative central 8.75 4.16 9.10 3.54 >.05 venous pressure (mm Hg) Intraoperative hemoglobin 10.88 1.67 10.35 1.42 >.05 concentration (g/dL) Intraoperative albumin 3.76 0.48 3.82 0.44 >.05 concentration (g/dL)
1354
YILDIRIM, KUCUK, DEMIR ET AL
Table 3. Postoperative Complications of the Study Population According to the Anesthesia Type Postoperative Complications
Isoflurane Group (n ¼ 124)
Sevoflurane Group (n ¼ 116)
P
Fever Urinary tract infection Pneumonia Acute cellular rejection Acute humoral rejection Acute tubular necrosis Pleural effusion Deep venous thrombosis Perirenal hematoma Lymphocele
18.20% 14.93% 3.71% 2.46% 1.89% 19.50% 3.94% 1.80% 11.42% 4.45%
24.86% 17.99% 3.18% 2.78% 1.67% 24.95% 2.97% 1.67% 10.78% 4.49%
.040 .048 >.05 >.05 >.05 .044 >.05 >.05 >.05 >.05
to another volatile anestethic sevoflurane in renal transplantation operations. We demonstrated for the first time that isoflurane might improve allograft function as well as reduce metabolic complications when compared with sevoflurane at the early postoperative period in renal transplant recipients. All currently used volatile anesthetics are degraded by the strong bases in carbon dioxide absorbents to by-products that are potentially toxic. Isoflurane is degraded by desiccated absorbents to carbon monoxide, which can significantly elevate carboxyhemoglobin concentrations. Sevoflurane is degraded to difluorovinyl products, which are nephrotoxic in rats [10]. According to our results, isoflurane is superior in preserving allograft functions in renal transplant recipients at the early postoperative period. The patients in the isoflurane group had lower serum urea and higher urine output when compared with sevoflurane at postoperative day 14. Our results are particularly different from the current literature. Teixeira et al reported that sevoflurane or isoflurane had no influence on the outcome of allograft function in renal transplantation [11]. Conzen et al demonstrated that sevoflurane or isoflurane does not alter renal function in chronic kidney disease [4]. On the contrary, Lee et al showed that the decrease of blood urea nitrogen (BUN) at 72 hours after surgery was less prominent in patients with sevoflurane than with isoflurane [12]. We also found that length of hospitalization was higher in the sevoflurane group than the isoflurane group. Although the operation time did not differ between the 2 groups, metabolic complications were higher with sevoflurane. Fever, urinary tract infection, and acute tubular necrosis were
Table 4. Early Graft Functions of the Study Population According to the Anesthesia Type Postoperative d 14
Volume of diuresis (mL/24 h) Urea (mg/dL) Creatinine (mg/dL)
Isoflurane Group (n ¼ 124)
Sevoflurane Group (n ¼ 116)
4991.25 2861.90 3718.00 2558.94
P
higher with sevoflurane. We interpreted that these complications induced the prolongation of hospital stay. We also demonstrated that metabolic complications were not derived from intraoperative hemodynamic variations. Intraoperative central venous pressure measurements showed that intraoperative hemodynamic stabilization did not differ between the study groups. Furthermore, intraoperative hemoglobin and albumin concentrations of the study groups (Table 2) demonstrated that anemia and/or hypoalbuminemia were not the reasons for early allograft toxicity. It is well known that sevoflurane has many advantages such as pleasant odor, no pungency, and bronchodilating effect [13]. However, the concern about the nephrotoxicity of sevoflurane exists still [9]. The issues of nephrotoxicity related to sevoflurane are based not only on its fluoride metabolite but also compound A [13,14]. Previous investigations of sevoflurane metabolism demonstrated that a fluoride ion concentration >50 mmol/L could be observed when sevoflurane was used during operations. Although this 50 mmol/L concentration is the toxic threshold associated with nephrotoxicity, renal toxicity was not reported with sevoflurane [5,15]. Compound A (fluoromethyl-2-2difluoro-1-(trifluoromethyl) vinyl ether) is the other concerning metabolite associated with the use of sevoflurane. Compound A is formed during the interaction of sevoflurane with carbon dioxide absorbents, and it has been shown to be a dose-dependent nephrotoxin in rats [6]. Exposure to compound A is known to cause dosedependent albuminuria, glucosuria, or enzymuria [16]. We did not study serum concentrations of fluoride ion or compound A, but it can be speculated that these metabolites could be the reason(s) for early allograft toxicity. This is the first demonstration that isoflurane can be used more safely than sevoflurane in renal transplantations. The results of the present study seem to suggest that isoflurane may have benefits in allograft function at the early postoperative period. Therefore, it is likely that the observed benefit of isoflurane could mainly be exerted through less nephrotoxic effects on renal tubular cells compared with sevoflurane. Due to the retrospective design of the study, the results should be interpreted with caution and causal relationship can not be suggested. It would be interesting to assess the allograft functions and complications in a long-term followup study and analyze the possible relationship with the choice of volatile anesthetics of renal transplant recipients. In conclusion, present data show that isoflurane can be used more safely than sevoflurane in transplantations. Further prospective, randomized, controlled studies are needed to determine the possible beneficial effects of isoflurane on allograft functions and metabolic complications among renal transplant recipients.
.042
REFERENCES 76.85 65.42 1.24 0.89
89.56 47.60 1.38 0.74
.038 >.05
[1] Ojo AO, Hanson JA, Meier-Kriesche H, et al. Survival in recipients of marginal cadaveric donor kidneys compared with other
VOLATILE ANESTHETICS recipients and wait-listed transplant candidates. J Am Soc Nephrol 2001;12(3):589e97. [2] Campagna JA, Miller KW, Forman SA. Mechanisms of actions of inhaled anesthetics. N Engl J Med 2003;348(21):2110e24. [3] Baxter PJ, Garton K, Kharasch ED. Mechanistic aspects of carbon monoxide formation from volatile anesthetics. Anesthesiology 1998;89(4):929e41. [4] Conzen PF, Kharasch ED, Czerner SF, et al. Low-flow sevoflurane compared with low-flow isoflurane anesthesia in patients with stable renal insufficiency. Anesthesiology 2002;97(3):578e84. [5] 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(5):753e7. [6] 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(6):1220e32. [7] Goldberg ME, Cantillo J, Larijani GE, et al. Sevoflurane versus isoflurane for maintenance of anesthesia: are serum inorganic fluoride ion concentrations of concern? Anesth Analg 1996;82(6):1268e72. [8] Ebert TJ, Arain SR. Renal responses to low-flow desflurane, sevoflurane, and propofol in patients. Anesthesiology 2000;93(6): 1401e6.
1355 [9] Mazze RI. The safety of sevoflurane in humans. Anesthesiology 1992;77(6):1062e3. [10] Gonsowski CT, Laster MJ, Eger 2nd EI, et al. Toxicity of compound A in rats. Effect of a 3-hour administration. Anesthesiology 1994;80(3):556e65. [11] Teixeira S, Costa G, Costa F, et al. Sevoflurane versus isoflurane: does it matter in renal transplantation? Transplant Proc 2007;39(8):2486e8. [12] Lee HC, Kim D, Ahn W, et al. Comparison of the renal safety between carbon dioxide absorbent products under sevoflurane anesthesia: a pilot study. Korean J Anesthesiol 2012;63(1): 11e7. [13] Young CJ, Apfelbaum JL. Inhalational anesthetics: desflurane and sevoflurane. J Clin Anesth 1995;7(7):564e77. [14] 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(4):775e81. [15] Frink Jr EJ, Malan TP, Atlas M, et al. Clinical comparison of sevoflurane and isoflurane in healthy patients. Anesth Analg 1992;74(2):241e5. [16] Bedford RF, Ives HE. The renal safety of sevoflurane. Anesth Analg 2000;90(3):505e8.
