Anesthetic agents

  • Per-Olof Jarnberg

Renal function impairment remains a common event in connection with anesthesia and surgery. Severe perioperative renal dysfunction (SCr > 6 mg/dL, CrCl ≤ 15 ml/min) accounts for one half of all patients requiring acute dialysis [1] and is associated with a mortality in excess of 50% [2]. Mild to moderate renal function impairment is surprisingly common after surgery. In a group of 278 patients undergoing non-emergency general, vascular, or gynecological surgery, 65 of the patients developed an increase in serum creatinine levels ≥ 20% within the first six postoperative days [3]. Thirty-two patients had increases that were sustained for more than 48 hours. For half of these patients, creatinine clearance had not returned to baseline levels by the time of discharge.

In most cases, the periope rative changes in renal function are not due to the anesthetic agent itself, although some volatile anesthetics have nephrotoxic potential due to direct toxicity of their metabolites. Instead, postoperative renal failure is more commonly multifactorial. Risk factors include: 1) preexisting renal or cardiac disease, 2) the type of surgical procedure, 3) occur rence of rhabdomyolysis or hemolysis, 4) adverse hemodynamic events, 5) inappropriate fluid management, and 6) concurrent administration of potentially nephrotoxic substances such as radiographic contrast agents, aminoglycoside antibiotics, and cyclosporine. Such risk factors usually play a more important role than the anesthetic agent in the development of postoperative renal dysfunction [4].


Anesthetic Agent Volatile Anesthetic Fluoride Level Sevoflurane Anesthesia Inorganic Fluoride 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kasiske BL, Kjellstrand CM. Perioperative management of patients with chronic renal failure and postoperative acute renal failure. Urol Clin North Am 1983;10(1):35-50.PubMedGoogle Scholar
  2. 2.
    Metnitz PG, Krenn CG, Steltzer H, Lang T, Ploder J, Lenz K, et al. Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients. Crit Care Med 2002;30(9):2051-8.PubMedGoogle Scholar
  3. 3.
    Charlson ME, MacKenzie CR, Gold JP, Shires GT. Postoperative changes in serum creatinine. When do they occur and how much is important? Ann Surg 1989;209(3):328-33.PubMedGoogle Scholar
  4. 4.
    Coggins C, Fang LS-T. Acute renal failure associated with antibiotics, anesthetic agents, and radiographic contrats agents. In: Brenner BM, Lazarus, JM, editor. Acute Renal Failure: Churchill Livingstone; 1988. p. 295-352.Google Scholar
  5. 5.
    Pringle H MR, Pringle S. Clinical effects of ether anaesthesia on renal activity. Brit Med J 1905;2:542-545.Google Scholar
  6. 6.
    Blackmore WP EK, Wiegand OF, Lipsey R. Renal and cardiovascular effects of halothane. Anesthesiology 1960;27:793-803.Google Scholar
  7. 7.
    Mazze RI, Cousins MJ, Barr GA. Renal effects and metabolism of isoflurane in man. Anesthesiology 1974;40(6):536-42.PubMedGoogle Scholar
  8. 8.
    Cousins MJ, Greenstein LR, Hitt BA, Mazze RI. Metabolism and renal effects of enflurane in man. Anesthesiology 1976;44(1):44- 53.PubMedGoogle Scholar
  9. 9.
    Jarnberg PO, Ekstrand J, Irestedt L, Santesson J. Renal function and fluoride formation and excretion during enflurane anaesthesia. Acta Anaesthesiol Scand 1979;23(5):444-52.PubMedGoogle Scholar
  10. 10.
    Deutsch S, Goldberg M, Stephen GW, Wu WH. Effects of halothane anesthesia on renal function in normal man. Anesthesiology 1966;27(6):793-804.PubMedGoogle Scholar
  11. 11.
    Bastron RD, Pyne JL, Inagaki M. Halothane-induced renal vasodilation. Anesthesiology 1979;50(2):126-31.PubMedGoogle Scholar
  12. 12.
    Priano LL. Effect of halothane on renal hemodynamics during normovolemia and acute hemorrhagic hypovolemia. Anesthesiol- ogy 1985;63(4):357-63.Google Scholar
  13. 13.
    Gelman S, Fowler KC, Smith LR. Regional blood flow during isoflurane and halothane anesthesia. Anesth Analg 1984;63(6):557- 65.PubMedGoogle Scholar
  14. 14.
    Jarnberg PO, Marrone, B, Priano, LL. Enflurane preserves renal blood flow. Anesthesiology 1990;73:A572.Google Scholar
  15. 15.
    Hysing ES, Chelly JE, Doursout MF, Merin RG. Comparative effects of halothane, enflurane, and isoflurane at equihypotensive doses on cardiac performance and coronary and renal blood flows in chronically instrumented dogs. Anesthesiology 1992;76(6):979- 84.PubMedGoogle Scholar
  16. 16.
    Lessard MR, Trepanier CA. Renal function and hemodynamics during prolonged isoflurane-induced hypotension in humans. Anesthesiology 1991;74(5):860-5.PubMedGoogle Scholar
  17. 17.
    Cho KW KS, Koh GY, Seul KH, Kim HJ, Song HS. Renalm and renin effects of sodium thiopental in rabbits. Ren Physiol 1987;10:261- 271.PubMedGoogle Scholar
  18. 18.
    Bidwai AV, Stanley TH, Bloomer HA, Blatnick RA. Effects of anesthetic doses of morphine on renal function in the dog. Anesth Analg 1975;54(3):357-60.PubMedGoogle Scholar
  19. 19.
    Hunter JM, Jones RS, Utting JE. Effect of anaesthesia with nitrous oxide in oxygen and fentanyl on renal function in the artificially ventilated dog. Br J Anaesth 1980;52(3):343-8.PubMedGoogle Scholar
  20. 20.
    Priano LL. Effects of high-dose fentanyl on renal haemodynamics in conscious dogs. Can Anaesth Soc J 1983;30(1):10-8.PubMedGoogle Scholar
  21. 21.
    Jarnberg PO, Leyden P, Woods L. Renal blood flow is maintained during propofol anesthesia in dogs. Anesthesiology 1992;77: A655.Google Scholar
  22. 22.
    Baratz RA, Philbin DM, Patterson RW. Plasma antidiuretic hormone and urinary output during continuous positive-pressure breathing in dogs. Anesthesiology 1971;34(6):510-3.PubMedGoogle Scholar
  23. 23.
    Hall SV, Johnson EE, Hedley-Whyte J. Renal hemodynamics and function with continuous positive-pressure ventilation in dogs. Anesthesiology 1974;41(5):452-61.PubMedGoogle Scholar
  24. 24.
    Jarnberg PO, de Villota ED, Eklund J, Granberg PO. Effects of positive end-expiratory pressure on renal function. Acta Anaesthesiol Scand 1978;22(5):508-14.PubMedGoogle Scholar
  25. 25.
    Kharasch ED, Yeo KT, Kenny MA, Buffington CW. Atrial natriuretic factor may mediate the renal effects of PEEP ventilation. Anes- thesiology 1988;69(6):862-9.Google Scholar
  26. 26.
    Andrivet P, Adnot S, Brun-Buisson C, Chabrier PE, Darmon JY, Braquet P, et al. Involvement of ANF in the acute antidiuresis during PEEP ventilation. J Appl Physiol 1988;65(5):1967-74.PubMedGoogle Scholar
  27. 27.
    Van Dyke R CM, Poznak AV. Metabolism of volatile anesthetics: 1. Conversion in vivo of several anesthetics to 14 CO2 and chloride. Biochem Pharmacol 1964;13:1239-1248.Google Scholar
  28. 28.
    Subcommittee on the National Halothane Study of the Committee on Anesthesia. National Academy of Sciences-National Re- search Council. Summary of the national halothane study: possible association halothane anesthesia and postoperative necrosis. JAMA 1966;197:775-83.Google Scholar
  29. 29.
    Mazze RI, Trudell JR, Cousins MJ. Methoxyflurane metabolism and renal dysfunction: clinical correlation in man. Anesthesiology 1971;35(3):247-52.PubMedGoogle Scholar
  30. 30.
    Thummel KE, Kharasch ED, Podoll T, Kunze K. Human liver microsomal enflurane defluorination catalyzed by cytochrome P-450 2E1. Drug Metab Dispos 1993;21(2):350-7.PubMedGoogle Scholar
  31. 31.
    Pacifici GM, Viani A, Franchi M, Gervasi PG, Longo V, Di Simplicio P, et al. Profile of drug-metabolizing enzymes in the cortex and medulla of the human kidney. Pharmacology 1989;39(5):299-308.PubMedGoogle Scholar
  32. 32.
    Nebert DW, Adesnik M, Coon MJ, Estabrook RW, Gonzalez FJ, Guengerich FP, et al. The P450 gene superfamily: recommended nomenclature. DNA 1987;6(1):1-11.PubMedGoogle Scholar
  33. 33.
    Waxman DJ. Interactions of hepatic cytochromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression. Biochem Pharmacol 1988;37(1):71-84.PubMedGoogle Scholar
  34. 34.
    Conney AH. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev 1967;19(3):317-66.PubMedGoogle Scholar
  35. 35.
    Pantuck EJ, Pantuck CB, Conney AH. Effect of streptozotocin-induced diabetes in the rat on the metabolism of fluorinated volatile anesthetics. Anesthesiology 1987;66(1):24-8.PubMedGoogle Scholar
  36. 36.
    Rehder K, Forbes J, Alter H, Hessler O, Stier A. Halothane biotransformation in man: a quantitative study. Anesthesiology 1967;28(4):711-5.PubMedGoogle Scholar
  37. 37.
    Cohen EN, Trudell JR, Edmunds HN, Watson E. Urinary metabolites of halothane in man. Anesthesiology 1975;43(4):392-401.PubMedGoogle Scholar
  38. 38.
    Lind RC, Gandolfi AJ, Sipes IG, Brown BR, Jr., Waters SJ. Oxygen concentrations required for reductive defluorination of halothane by rat hepatic microsomes. Anesth Analg 1986;65(8):835-9.PubMedGoogle Scholar
  39. 39.
    Wood CL, Gandolfi AJ, Van Dyke RA. Lipid binding of a halothane metabolite. Relationship to lipid peroxidation in vitro. Drug Metab Dispos 1976;4(4):305-13.PubMedGoogle Scholar
  40. 40.
    Trudell JR, Bosterling B, Trevor AJ. Reductive metabolism of halothane by human and rabbit cytochrome P-450. Binding of 1- chloro-2,2,2-trifluoroethyl radical to phospholipids. Mol Pharmacol 1982;21(3):710-7.PubMedGoogle Scholar
  41. 41.
    Van Dyke RA, Gandolf AJ. Anaerobic release of fluoride from halothane. Relationship to the binding of halothane metabolites to hepatic cellular constituents. Drug Metab Dispos 1976;4(1):40-4.PubMedGoogle Scholar
  42. 42.
    Chase RE, Holaday DA, Fiserova-Bergerova V, Saidman LJ, Mack FE. The biotransformation of ethrane in man. Anesthesiology 1971;35(3):262-7.PubMedGoogle Scholar
  43. 43.
    Burke TR, Jr., Branchflower RV, Lees DE, Pohl LR. Mechanism of defluorination of enflurane. Identification of an organic metabolite in rat and man. Drug Metab Dispos 1981;9(1):19-24.PubMedGoogle Scholar
  44. 44.
    Maduska AL. Serum inorganic fluoride levels in patients receiving enflurane anesthesia. Anesth Analg 1974;53(3):351-3.PubMedGoogle Scholar
  45. 45.
    Mazze RI, Calverley RK, Smith NT. Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers. Anesthesiology 1977;46(4):265-71.PubMedGoogle Scholar
  46. 46.
    Rice SA, Fish KJ. Anesthetic metabolism and renal function in obese and nonobese Fischer 344 rats following enflurane or iso- flurane anesthesia. Anesthesiology 1986;65(1):28-34.PubMedGoogle Scholar
  47. 47.
    Dooley JR, Mazze RI, Rice SA, Borel JD. Is enflurane defluorination inducible in man? Anesthesiology 1979;50(3):213-7.PubMedGoogle Scholar
  48. 48.
    Mazze RI, Woodruff RE, Heerdt ME. Isoniazid-induced enflurane defluorination in humans. Anesthesiology 1982;57(1):5-8.PubMedGoogle Scholar
  49. 49.
    Loehning RW, Mazze RI. Possible nephrotoxicity from enflurane in a patient with severe renal disease. Anesthesiology 1974;40(2):203-5.PubMedGoogle Scholar
  50. 50.
    Eichhorn JH, Hedley-Whyte J, Steinman TI, Kaufmann JM, Laasbert LH. Renal failure following enflurane anesthesia. Anesthesiology 1976;45(5):557-60.PubMedGoogle Scholar
  51. 51.
    Holaday DA, Fiserova-Bergerova V, Latto IP, Zumbiel MA. Resistance of isoflurane to biotransformation in man. Anesthesiology 1975;43(3):325-32.PubMedGoogle Scholar
  52. 52.
    Mazze RI, Hitt BA, Cousins MJ. Effect of enzyme induction with phenobarbital on the in vivo and in vitro defluorination of isoflu- rane and methoxyflurane. J Pharmacol Exp Ther 1974;190(3):523-9.PubMedGoogle Scholar
  53. 53.
    Rice SA, Talcott RE. Effects of isoniazid treatment on selected hepatic mixed-function oxidases. Drug Metab Dispos 1979;7(5):260- 2.PubMedGoogle Scholar
  54. 54.
    Holaday DA, Smith FR. Clinical characteristics and biotransformation of sevoflurane in healthy human volunteers. Anesthesiology 1981;54(2):100-6.PubMedGoogle Scholar
  55. 55.
    Fujii K, Morio, M, Kikuchi,. Pharmacokinetic study in excretion of inorganic fluoride, a metabolite of sevoflurane. Hiroshima J Med Sci 1987;36:89-94.PubMedGoogle Scholar
  56. 56.
    Kobayashi Y, Ochiai R, Takeda J, Sekiguchi H, Fukushima K. Serum and urinary inorganic fluoride concentrations after prolonged inhalation of sevoflurane in humans. Anesth Analg 1992;74(5):753-7.PubMedGoogle Scholar
  57. 57.
    Frink EJ, Jr., Malan TP, Jr., Isner RJ, Brown EA, Morgan SE, Brown BR, Jr. Renal concentrating function with prolonged sevoflurane or enflurane anesthesia in volunteers. Anesthesiology 1994;80(5):1019-25.PubMedGoogle Scholar
  58. 58.
    Cook TL, Beppu WJ, Hitt BA, Kosek JC, Mazze RI. A comparison of renal effects and metabolism of sevoflurane and methoxyflurane in enzyme-induced rats. Anesth Analg 1975;54(6):829-35.PubMedGoogle Scholar
  59. 59.
    Nishiyama T, Hirasaki A. Effects of sevoflurane anaesthesia on renal function--duration of administration and area under the curve and rate of decrease of serum inorganic fluoride. Eur J Anaesthesiol 1995;12(5):477-82.PubMedGoogle Scholar
  60. 60.
    Frink EJ, Jr., Malan TP, Jr., Brown EA, Morgan S, Brown BR, Jr. Plasma inorganic fluoride levels with sevoflurane anesthesia in morbidly obese and nonobese patients. Anesth Analg 1993;76(6):1333-7.PubMedGoogle Scholar
  61. 61.
    Higuchi H, Arimura S, Sumikura H, Satoh T, Kanno M. Urine concentrating ability after prolonged sevoflurane anaesthesia. Br J Anaesth 1994;73(2):239-40.PubMedGoogle Scholar
  62. 62.
    Conzen PF, Nuscheler M, Melotte A, Verhaegen M, Leupolt T, Van Aken H, et al. Renal function and serum fluoride concentrations in patients with stable renal insufficiency after anesthesia with sevoflurane or enflurane. Anesth Analg 1995;81(3):569-75.PubMedGoogle Scholar
  63. 63.
    Tsukamoto N, Hirabayashi Y, Shimizu R, Mitsuhata H. The effects of sevoflurane and isoflurane anesthesia on renal tubular function in patients with moderately impaired renal function. Anesth Analg 1996;82(5):909-13.PubMedGoogle Scholar
  64. 64.
    Hanaki C, Fujii K, Morio M, Tashima T. Decomposition of sevoflurane by sodalime. Hiroshima J Med Sci 1987;36(1):61-7.PubMedGoogle Scholar
  65. 65.
    Fang ZX, Eger EI, 2nd. 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(3):564-8.PubMedGoogle Scholar
  66. 66.
    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(6):667-9.PubMedGoogle Scholar
  67. 67.
    Gonsowski CT, Laster MJ, Eger EI, 2nd, Ferrell LD, Kerschmann RL. Toxicity of compound A in rats. Effect of a 3-hour administra- tion. Anesthesiology 1994;80(3):556-65.PubMedGoogle Scholar
  68. 68.
    Keller KA, Callan C, Prokocimer P, Delgado-Herrera L, Friedman MB, Hoffman GM, et al. Inhalation toxicity study of a haloalkene degradant of sevoflurane, Compound A (PIFE), in Sprague-Dawley rats. Anesthesiology 1995;83(6):1220-32.PubMedGoogle Scholar
  69. 69.
    Morio M, Fujii K, Satoh N, Imai M, Kawakami U, Mizuno T, et al. Reaction of sevoflurane and its degradation products with soda lime. Toxicity of the byproducts. Anesthesiology 1992;77(6):1155-64.PubMedGoogle Scholar
  70. 70.
    Kharasch ED, Thorning D, Garton K, Hankins DC, Kilty CG. Role of renal cysteine conjugate beta-lyase in the mechanism of com- pound A nephrotoxicity in rats. Anesthesiology 1997;86(1):160-71.PubMedGoogle Scholar
  71. 71.
    Goldberg ME, Cantillo J, Gratz I, Deal E, Vekeman D, McDougall R, et al. Dose of compound A, not sevoflurane, determines changes in the biochemical markers of renal injury in healthy volunteers. Anesth Analg 1999;88(2):437-45.PubMedGoogle Scholar
  72. 72.
    Higuchi H, Sumita S, Wada H, Ura T, Ikemoto T, Nakai T, et al. Effects of sevoflurane and isoflurane on renal function and on pos- sible markers of nephrotoxicity. Anesthesiology 1998;89(2):307-22.PubMedGoogle Scholar
  73. 73.
    Eger EI, 2nd, Koblin DD, Bowland T, Ionescu P, Laster MJ, Fang Z, et al. Nephrotoxicity of sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg 1997;84(1):160-8.PubMedGoogle Scholar
  74. 74.
    Eger EI, 2nd, Gong D, Koblin DD, Bowland T, Ionescu P, Laster MJ, et al. Dose-related biochemical markers of renal injury after sevoflurane versus desflurane anesthesia in volunteers. Anesth Analg 1997;85(5):1154-63.PubMedGoogle Scholar
  75. 75.
    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(6):1231-7.PubMedGoogle Scholar
  76. 76.
    Kharasch ED, Frink EJ, Jr., Zager R, Bowdle TA, Artru A, Nogami WM. Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity. Anesthesiology 1997;86(6):1238-53.PubMedGoogle Scholar
  77. 77.
    Ebert TJ, Messana LD, Uhrich TD, Staacke TS. Absence of renal and hepatic toxicity after four hours of 1.25 minimum alveolar anesthetic concentration sevoflurane anesthesia in volunteers. Anesth Analg 1998;86(3):662-7.PubMedGoogle Scholar
  78. 78.
    Forster H, Dudziak R. [Causes for the reaction between dry soda lime and halogenated inhalation anesthetics]. Anaesthesist 1997;46(12):1054-63.PubMedGoogle Scholar
  79. 79.
    Forster H, Warnken UH, Asskali F. [Various reactions of sevoflurane with the individual components of soda lime]. Anaesthesist 1997;46(12):1071-5.PubMedGoogle Scholar
  80. 80.
    Neumann MA, Laster MJ, Weiskopf RB, Gong DH, Dudziak R, Forster H, et al. The elimination of sodium and potassium hydroxides from desiccated soda lime diminishes degradation of desflurane to carbon monoxide and sevoflurane to compound A but does not compromise carbon dioxide absorption. Anesth Analg 1999;89(3):768-73.PubMedGoogle Scholar
  81. 81.
    Murray JM, Renfrew CW, Bedi A, McCrystal CB, Jones DS, Fee JP. Amsorb: a new carbon dioxide absorbent for use in anesthetic breathing systems. Anesthesiology 1999;91(5):1342-8.PubMedGoogle Scholar
  82. 81a.
    Keijzer C, Perez, RSGM, De Lange, JJ. Compound A and carbon monoxide production from sevoflurane and seven different types of carbon dioxide absorbent in a patient model Acta Anaesth Scand 2007;51(1):31-37.Google Scholar
  83. 82.
    Koblin DD, Eger EI, 2nd, Johnson BH, Konopka K, Waskell L. I-653 resists degradation in rats. Anesth Analg 1988;67(6):534-8.PubMedGoogle Scholar
  84. 83.
    Eger EI, 3rd. Stability of I-653 in soda lime. Anesth Analg 1987;66(10):983-5.PubMedGoogle Scholar
  85. 84.
    Eger EI, 2nd, Johnson BH, Strum DP, Ferrell LD. Studies of the toxicity of I-653, halothane, and isoflurane in enzyme-induced, hypoxic rats. Anesth Analg 1987;66(12):1227-9.PubMedGoogle Scholar
  86. 85.
    Eger EI, 2nd, Johnson BH, Ferrell LD. Comparison of the toxicity of I-653 and isoflurane in rats: a test of the effect of repeated anesthesia and use of dry soda lime. Anesth Analg 1987;66(12):1230-3.PubMedGoogle Scholar
  87. 86.
    Jones RM, Koblin DD, Cashman JN, Eger EI, 2nd, Johnson BH, Damask MC. Biotransformation and hepato-renal function in vol- unteers after exposure to desflurane (I-653). Br J Anaesth 1990;64(4):482-7.PubMedGoogle Scholar
  88. 87.
    Koblin DD, Weiskopf RB, Holmes MA, Konopka K, Rampil IJ, Eger EI, 2nd, et al. Metabolism of I-653 and isoflurane in swine. Anesth Analg 1989;68(2):147-9.PubMedGoogle Scholar
  89. 88.
    Sutton TS, Koblin DD, Gruenke LD, Weiskopf RB, Rampil IJ, Waskell L, et al. Fluoride metabolites after prolonged exposure of volunteers and patients to desflurane. Anesth Analg 1991;73(2):180-5.PubMedGoogle Scholar
  90. 89.
    Artusio JF, Jr., Van Poznak A, Hunt RE, Tiers RM, Alexander M. A clinical evaluation of methoxyflurane in man. Anesthesiology 1960;21:512-7.PubMedGoogle Scholar
  91. 90.
    Haynes RJ. Agents affecting calcification. In: Gilman AF RT, Nies AS, Taylor P, editor. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 8th ed: Pergamon Press; 1990. p. 1518-1522.Google Scholar
  92. 91.
    Roman RJ, Carter JR, North WC, Kauker ML. Renal tubular site of action of fluoride in Fischer 344 rats. Anesthesiology 1977;46(4):260- 4.PubMedGoogle Scholar
  93. 92.
    Cittanova ML, Lelongt B, Verpont MC, Geniteau-Legendre M, Wahbe F, Prie D, et al. Fluoride ion toxicity in human kidney collect- ing duct cells. Anesthesiology 1996;84(2):428-35.PubMedGoogle Scholar
  94. 93.
    Crandell WB, Pappas SG, Macdonald A. Nephrotoxicity associated with methoxyflurane anesthesia. Anesthesiology 1966;27(5):591- 607.PubMedGoogle Scholar
  95. 94.
    Mazze RI, Shue GL, Jackson SH. Renal dysfunction associated with methoxyflurane anesthesia. A randomized, prospective clinical evaluation. Jama 1971;216(2):278-88.PubMedGoogle Scholar
  96. 95.
    Holaday DA, Rudofsky S, Treuhaft PS. The metabolic degradation of methoxyflurane in man. Anesthesiology 1970;33(6):589- 93.PubMedGoogle Scholar
  97. 96.
    Cousins MJ, Mazze RI. Methoxyflurane nephrotoxicity. A study of dose response in man. Jama 1973;225(13):1611-6.PubMedGoogle Scholar
  98. 97.
    Cousins MJ, Mazze RI, Kosek JC, Hitt BA, Love FV. The etiology of methoxyflurane nephrotoxicity. J Pharmacol Exp Ther 1974;190(3):530-41.PubMedGoogle Scholar
  99. 98.
    Frascino JA. Effect of inorganic fluoride on the renal concentrating mechanism. Possible nephrotoxicity in man. J Lab Clin Med 1972;79(2):192-203.PubMedGoogle Scholar
  100. 99.
    Kharasch ED, Hankins DC, Thummel KE. Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity. Anesthesiology 1995;82(3):689-99.PubMedGoogle Scholar
  101. 100.
    Brown BR, Jr. Shibboleths and jigsaw puzzles. The fluoride nephrotoxicity enigma. Anesthesiology 1995;82(3):607-8.PubMedCrossRefGoogle Scholar
  102. 101.
    Mazze RI, Jamison R. Renal effects of sevoflurane. Anesthesiology 1995;83(3):443-5.PubMedGoogle Scholar
  103. 102.
    Kharasch ED, Schroeder JL, Liggitt HD, Park SB, Whittington D, Sheffels P. New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 1): Identification of the nephrotoxic metabolic pathway. Anesthesiology 2006;105(4):726-36.PubMedGoogle Scholar
  104. 103.
    Kharasch ED, Schroeder JL, Liggitt HD, Ensign D, Whittington D. New insights into the mechanism of methoxyflurane neph- rotoxicity and implications for anesthetic development (part 2): Identification of nephrotoxic metabolites. Anesthesiology 2006;105(4):737-45.PubMedGoogle Scholar
  105. 104.
    Selinsky BS, Perlman ME, London RE. In vivo nuclear magnetic resonance studies of hepatic methoxyflurane metabolism. II. A reevaluation of hepatic metabolic pathways. Mol Pharmacol 1988;33(5):567-73.PubMedGoogle Scholar
  106. 105.
    Chen PS, Jr., Gardner DE, Hodge HC, O’Brien JA, Smith FA. Renal clearance of fluoride. Proc Soc Exp Biol Med 1956;92(4):879- 83.PubMedGoogle Scholar
  107. 106.
    Carlson CH, Armstrong WD, Singer L. Distribution and excretion of radiofluoride in the human. Proc Soc Exp Biol Med 1960;104:235- 9.PubMedGoogle Scholar
  108. 107.
    Hosking DJ, Chamberlain MJ. Studies in man with 18 F. Clin Sci 1972;42(2):153-61.PubMedGoogle Scholar
  109. 108.
    Ekstrand J, Ehrnebo M, Boreus LO. Fluoride bioavailability after intravenous and oral administration: importance of renal clear- ance and urine flow. Clin Pharmacol Ther 1978;23(3):329-37.PubMedGoogle Scholar
  110. 109.
    Whitford GM, Pashley DH, Stringer GI. Fluoride renal clearance: a pH-dependent event. Am J Physiol 1976;230(2):527-32.PubMedGoogle Scholar
  111. 110.
    Ekstrand J, Ehrnebo M, Whitford GM, Jarnberg PO. Fluoride pharmacokinetics during acid-base balance changes in man. Eur J Clin Pharmacol 1980;18(2):189-94.PubMedCrossRefGoogle Scholar
  112. 111.
    Jarnberg PO, Ekstrand J, Irestedt L. Renal fluoride excretion and plasma fluoride levels during and after enflurane anesthesia are dependent on urinary pH. Anesthesiology 1981;54(1):48-52.PubMedGoogle Scholar
  113. 112.
    Barzel US, Jowsey J. The effects of chronic acid and alkali administration on bone turnover in adult rats. Clin Sci 1969;36(3):517- 24.PubMedGoogle Scholar
  114. 113.
    Leake RD, Trygstad CW. Glomerular filtration rate during the period of adaptation to extrauterine life. Pediatr Res 1977;11(9 Pt 1):959-62.PubMedGoogle Scholar
  115. 114.
    Jose PA, Fildes RD, Gomez RA, Chevalier RL, Robillard JE. Neonatal renal function and physiology. Curr Opin Pediatr 1994;6(2):172- 7.PubMedGoogle Scholar
  116. 115.
    Fisher DM, Robinson S, Brett CM, Perin G, Gregory GA. Comparison of enflurane, halothane, and isoflurane for diagnostic and therapeutic procedures in children with malignancies. Anesthesiology 1985;63(6):647-50.PubMedGoogle Scholar
  117. 116.
    Lerman J, Sikich N, Kleinman S, Yentis S. The pharmacology of sevoflurane in infants and children. Anesthesiology 1994;80(4):814- 24.PubMedGoogle Scholar
  118. 117.
    Frink EJ, Jr., Green WB, Jr., Brown EA, Malcomson M, Hammond LC, Valencia FG, et al. Compound A concentrations during sevo- flurane anesthesia in children. Anesthesiology 1996;84(3):566-71.PubMedGoogle Scholar
  119. 118.
    Bedford RF, Ives HE. The renal safety of sevoflurane. Anesth Analg 2000;90(3):505-8.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Per-Olof Jarnberg
    • 1
  1. 1.Department of Anesthesiology and Peri-Operative MedicinePortlandUSA

Personalised recommendations