0
September 24, 1973, Vol 225, No. 13 >
ARTICLE | September 24, 1973

Methoxyflurane Nephrotoxicity: Title and subTitle BreakA Study of Dose Response in Man FREE

Michael J. Cousins, MB; Richard I. Mazze, MD
[+] Author Affiliations

Reprint requests to Department of Anesthesia, Stanford University School of Medicine, Stanford University Service, Veterans Administration Hospital, Palo Alto, CA 94304 (Dr. Cousins).


JAMA. 1973;225(13):1611-1616. doi:10.1001/jama.1973.03220410023005
Text Size: A A A
Published online
Article
References

Dose-related abnormalities in renal function occurred in ten of 18 patients following administration of methoxyflurane (Penthrane) with the usual anesthetic adjuvants. Eight control patients anesthetized with halothane (Fluothane) showed no abnormalities in renal function.

Subclinical toxicity occurred following methoxyflurane at minimum alveolar concentration (MAC) for 2.5 to 3 hours, that is 2.5 to 3 MAC hours (serum inorganic fluoride, >50 micromols/liter), while clinical toxicity was present in all patients at dosages greater than five MAC hours (serum inorganic fluoride, >90 micromols/liter). Superimposed on the dose-response relationship were other factors that probably increased nephrotoxicity. These were as follows: individual variations in metabolism of methoxyflurane; increased sensitivity to the nephrotoxic effects of inorganic fluoride; presence of enzyme induction; and interaction of methoxyflurane with other nephrotoxic drugs.

The use of methoxyflurane in clinical anesthesia should be restricted to situations where it offers specific advantages and where dosages less than 2.5 MAC hours can be attained.

REFERENCES

1 +
Mazze RI, Shue GL, Jackson SH:  Renal dysfunction associated with methoxyflurane anesthesia: A randomized, prospective clinical evaluation . JAMA 216:278-288, 1971;.
2 +
Mazze RI, Trudell JR, Cousins MJ:  Methoxyflurane metabolism and renal dysfunction: Clinical correlation in man . Anesthesiology 35:247-252, 1971;.
3 +
Cousins MJ, Nishimura TG, Mazze RI:  Renal effects of low-dose methoxyflurane with cardiopulmonary bypass . Anesthesiology 36:286-292, 1972;.
4 +
Mazze RI, Cousins MJ, Kosek JC:  Dose-related methoxyflurane nephrotoxicity in rats: A biochemical and pathological correlation . Anesthesiology 36:571-587, 1972;.
5 +
Mazze RI, Cousins MJ, Kosek JC:  Strain differences in metabolism and susceptibility to the nephrotoxic effects of methoxyflurane in rats . J Pharmacol Exp Ther 184:481-488, 1973;.
6 +
Kosek JC, Mazze RI, Cousins MJ:  The morphology and pathogenesis of nephrotoxicity following methoxyflurane (Penthrane) anesthesia: An experimental model in rats . Lab Invest 27:575-580, 1972;.
7 +
 Methoxyflurane Nephrotoxicity. Committee on Anesthesia, National Academy of Science, National Research Council . JAMA 217:958-959, 1971;.
8 +
Saidman LJ, et al:  Minimum alveolar concentrations of methoxyflurane, halothane, ether and cyclopropane in man: Correlation with theories of anesthesia . Anesthesiology 28:994-1002, 1967;.
9 +
Hayes MA, Goldenberg IS:  Renal effects of anesthesia and operation mediated by endocrines . Anesthesiology 24:487-499, 1963;.
10 +
Crandell WB, Pappas SG, Macdonald A:  Nephrotoxicity associated with methoxyflurane anesthesia . Anesthesiology 27:591-607, 1966;.
11 +
Aprahamian HA, et al:  The influence of general anesthetics on water and solute excretion in man . Ann of Surg 150:122-130, 1959;.
12 +
Mazze RI, Cousins MJ:  Combined nephrotoxicity of gentamicin and methoxyflurane anesthesia in man . Br J Anaesth 45:394-398, 1973;.
13 +
Barr GA, et al:  An animal model for combined methoxyflurane and gentamicin nephrotoxicity . Br J Anaesth 45:306-312, 1973;.
14 +
Kuzucu EY:  Methoxyflurane, tetracycline, and renal failure . JAMA 211:1162-1164, 1970;.
15 +
Hollenberg NK, et al:  Irreversible acute oliguric renal failure: A complication of methoxyflurane anesthesia . N Engl J Med 286:877-879, 1972;.
16 +
Panner BJ, et al:  Toxicity following methoxyflurane anesthesia: I. Clinical and pathological observations in two fatal cases . JAMA 214:86-90, 1970;.
17 +
Wiseman A:  Effect of inorganic fluoride on enzymes , in Smith FA (ed): Handbook of Experimental Pharmacology , vol 20, Pharmacology of Fluorides, part (2) . New York, Springer-Verlag, 1970;, pp 48-93.
18 +
Whitford GM, Taves DR:  Fluoride-induced diuresis: Renal tissue solute concentrations, functional, hemodynamic, and histological correlates in the rat . Anesthesiology , to be published.
19 +
Halpren BA, Kempson RL, Coplon NA:  Interstitial fibrosis and chronic renal failure following methoxyflurane anesthesia . JAMA 223:1239-1242, 1973;.
20 +
Lowe HJ: Dose-regulated Penthrane (methoxyflurane) anesthesia . North Chicago, Abbott Laboratories, 1972;.

Figures

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Mazze RI, Shue GL, Jackson SH:  Renal dysfunction associated with methoxyflurane anesthesia: A randomized, prospective clinical evaluation . JAMA 216:278-288, 1971;.
2 +
Mazze RI, Trudell JR, Cousins MJ:  Methoxyflurane metabolism and renal dysfunction: Clinical correlation in man . Anesthesiology 35:247-252, 1971;.
3 +
Cousins MJ, Nishimura TG, Mazze RI:  Renal effects of low-dose methoxyflurane with cardiopulmonary bypass . Anesthesiology 36:286-292, 1972;.
4 +
Mazze RI, Cousins MJ, Kosek JC:  Dose-related methoxyflurane nephrotoxicity in rats: A biochemical and pathological correlation . Anesthesiology 36:571-587, 1972;.
5 +
Mazze RI, Cousins MJ, Kosek JC:  Strain differences in metabolism and susceptibility to the nephrotoxic effects of methoxyflurane in rats . J Pharmacol Exp Ther 184:481-488, 1973;.
6 +
Kosek JC, Mazze RI, Cousins MJ:  The morphology and pathogenesis of nephrotoxicity following methoxyflurane (Penthrane) anesthesia: An experimental model in rats . Lab Invest 27:575-580, 1972;.
7 +
 Methoxyflurane Nephrotoxicity. Committee on Anesthesia, National Academy of Science, National Research Council . JAMA 217:958-959, 1971;.
8 +
Saidman LJ, et al:  Minimum alveolar concentrations of methoxyflurane, halothane, ether and cyclopropane in man: Correlation with theories of anesthesia . Anesthesiology 28:994-1002, 1967;.
9 +
Hayes MA, Goldenberg IS:  Renal effects of anesthesia and operation mediated by endocrines . Anesthesiology 24:487-499, 1963;.
10 +
Crandell WB, Pappas SG, Macdonald A:  Nephrotoxicity associated with methoxyflurane anesthesia . Anesthesiology 27:591-607, 1966;.
11 +
Aprahamian HA, et al:  The influence of general anesthetics on water and solute excretion in man . Ann of Surg 150:122-130, 1959;.
12 +
Mazze RI, Cousins MJ:  Combined nephrotoxicity of gentamicin and methoxyflurane anesthesia in man . Br J Anaesth 45:394-398, 1973;.
13 +
Barr GA, et al:  An animal model for combined methoxyflurane and gentamicin nephrotoxicity . Br J Anaesth 45:306-312, 1973;.
14 +
Kuzucu EY:  Methoxyflurane, tetracycline, and renal failure . JAMA 211:1162-1164, 1970;.
15 +
Hollenberg NK, et al:  Irreversible acute oliguric renal failure: A complication of methoxyflurane anesthesia . N Engl J Med 286:877-879, 1972;.
16 +
Panner BJ, et al:  Toxicity following methoxyflurane anesthesia: I. Clinical and pathological observations in two fatal cases . JAMA 214:86-90, 1970;.
17 +
Wiseman A:  Effect of inorganic fluoride on enzymes , in Smith FA (ed): Handbook of Experimental Pharmacology , vol 20, Pharmacology of Fluorides, part (2) . New York, Springer-Verlag, 1970;, pp 48-93.
18 +
Whitford GM, Taves DR:  Fluoride-induced diuresis: Renal tissue solute concentrations, functional, hemodynamic, and histological correlates in the rat . Anesthesiology , to be published.
19 +
Halpren BA, Kempson RL, Coplon NA:  Interstitial fibrosis and chronic renal failure following methoxyflurane anesthesia . JAMA 223:1239-1242, 1973;.
20 +
Lowe HJ: Dose-regulated Penthrane (methoxyflurane) anesthesia . North Chicago, Abbott Laboratories, 1972;.

Letters

Submit a Letter
CME Course for:


You need to register in order to view this quiz.


To understand the clinical management of acute heart failure syndromes.
Accreditation Information The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
To view and print your certificate and access a summary of your CME courses go to My CME.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Compression-Only CPR: Pushing the Science Forward
Cone
AAM 2010;304:1493-1495.
All you need to read in the other general journals
BMJ 2010;341:c5893-c1494.
Submit a Response

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

© 2012 American Medical Association. All Rights Reserved.
Powered bySilverchair Information Systems