Summary
Seven obese and five normal weight patients were studied before, during and after one hour of methoxyflurane-nitrous oxide anaesthesia during peripheral surgical operations and compared with eight patients of normal weight anaesthetized with nitrous oxide-meperidine and d-tubocurare. Estimates were made of renal function, including serum and urinary electrolytes, osmolarity, uric acid, urea and Creatinine. Renal clearances for the latter three substances were also calculated. Serum and urinary inorganic and organic fluoride concentrations were measured, as were renal clearances. This low dose methoxyflurane anaesthesia resulted only in a decrease in uric acid clearance among all the measures, when compared to the meperidine-nitrous oxide controls. The clearance of uric acid remained depressed for longer in the obese patients, but otherwise they did not differ from the normal weight patients. It is possible but not proven that depressed uric acid clearance may be related to the organic fluoride metabolite and an early indicator of methoxyflurane renal toxicity. The previously documented biotransformation of methoxyflurane was seen in this study. A double peak in serum inorganic fluoride was shown in all patients but one. Rather large differences in peak levels of serum inorganic fluoride occurred. The only significant difference between the obese and normal weight patients as far as fluoride metabolism was concerned was a greater variability in the serum inorganic fluoride levels in the obese patients. It would appear that the obese patient metabolizes methoxyflurane in a quantitatively if not qualitatively different fashion than the normal weight patient, perhaps because of fatty infiltration of the liver. Caution is advised in the use of methoxyflurane for more than 90 minutes of low concentration administration in view of the unpredictability of the biotransformation.
Résumé
Douze patients dont sept obèses et cinq normaux, soumis à une chirurgie extraabdominale, ont été étudiés avant, durant et après une heure et demi d’anesthésie à faible concentration de méthoxyflurane et protoxyde d’azote. Une comparaison a été faite avec huit sujets normaux anesthésiés au N2O, mépéridine et d-tubocurare. Les fonctions rénales ont été estimées y compris les électrolytes sériques et urinaires, l’osmolarité, l’acide urique, l’urée et la Créatinine. Les clearances des trois dernières substances ont été mesurées ainsi que les concentrations sériques et urinaires du fluor inorganique et organique et leur clearance.
Parmi toutes les mesures faites, seule la clearance de l’acide urique a diminué avec cette petite concentration de méthoxyflurane par comparaison à celle observée après anesthésie à la mépéridine avec protoxyde d’azote. La clearance de l’acide urique demeure basse plus longtemps chez les obèses. Par ailleurs, ceux-ci ne différent pas des patients normaux. Il est possible, bien que non prouvé, que cette dépression de la clearance d’acide urique soit due à la formation de métabolite du fluor et qu’elle puisse servir comme indice précoce de toxicité rénale du méthoxyflurane.
La biotransformation du méthoxyflurane qui a déjà été documentée, a été retrouvée dans cette étude. Le graphique des modifications du fluor inorganique a montré chez tous les patients, sauf un, une courbe à double crête.
On a constaté des différences relativement prononcées dans les concentrations de pointe du fluor inorganique. En ce qui concerne le métabolisme du fluor, une grande variabilité dans le taux de fluor inorganique sérique chez les obèses était la seule différence observée entre ceux-ci et les patients normaux.
Il semble que le patient obèse metabolise le méthoxyflurane d’une façon quantitativement sinon qualitativement différente du patient normal, peut-être à cause d’une infiltration graisseuse du foie.
On recommande la prudence, même lors de l’usage d’une faible concentration de méthoxyflurane pour une anesthésie de durée supérieure ou égale à 90 minutes, en raison d’un taux de biotransformation dont l’importance est difficile à prévoir.
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Samuelson, P.N., Merin, R.G., Taves, D.R. et al. Toxicity following methoxyflurane anaesthesia. Canad. Anaesth. Soc. J. 23, 465–479 (1976). https://doi.org/10.1007/BF03005975
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DOI: https://doi.org/10.1007/BF03005975