CARBOHYDRATE METABOLISM AND INSULIN RELEASE DURING ETHER AND HALOTHANE ANAESTHESIA

Transcription

1 Brit. J. Anaesth. (1971), 43, 1022 CARBOHYDRATE METABOLISM AND INSULIN RELEASE DURING ETHER AND HALOTHANE ANAESTHESIA BY N. YOSHIMURA, K. KODAMA AND J. YOSHITAKE SUMMARY The effects of diethyl ether and halothane anaesthesia on the arterial blood glucose, redox potential and plasma immunoreactive insulin were investigated in man. During ether anaesthesia the plasma insulin levels increased, while the blood redox potential decreased. During halothane anaesthesia no such changes were found. Metabolic alterations during ether anaesthesia, such as elevation of blood glucose, lactate, pyruvate, and inorganic phosphorus have been described in many articles. It is well known that ether stimulates the release of adrenaline which is a potent inhibitor of insulin secretion. Therefore insulin might play an important role in carbohydrate metabolism during ether anaesthesia. However, there have been few previous reports concerning this problem. This study was primarily concerned with the changes of the plasma insulin levels and of carbohydrate metabolism during ether and halothane anaesthesia. METHODS Twelve male and nine female human subjects were selected from patients who were to undergo a variety of operative procedures, but otherwise were in good health, and ranged in age from 18 to 63 years. None had endocrine disease nor were they receiving hormonal therapy. They were premedicated with atropine sulphate ( mg) intramuscularly 30 minutes before anaesthesia which was induced with nitrous oxide, ether and oxygen, or nitrous oxide, halothane and oxygen, in a semiclosed breathing system. Intubation was achieved with the aid of suxamethonium chloride (0.8 mg/kg). Ether was delivered from a Copper Kettle to produce a 4 per cent mixture in nitrous oxide and oxygen (1:1) to maintain second or third plane surgical anaesthesia; per cent halothane was delivered from a Fluotec vaporizer and mixed with nitrous oxide and oxygen (1:1). Ventilation was controlled with an Engstrom ventilator and small quantities of tubocurarine chloride to maintain a C o2 within normal limits. Only normal saline solution was infused during the study except in two subjects to whom 5 per cent dextrose/water was given intravenously (0.5 g/kg) for an hour following the start of ether anaesthesia. Blood samples were taken through an indwelling needle in the brachial artery before induction of anaesthesia, at 30-minute intervals up to 90 minutes after induction, and usually before the start of surgery. Blood glucose was measured enzymatically with a commercial glucose oxidase preparation (Glucostat, Worthington Biochemical Co., U.S.A.). The redox potential of blood was measured with a platinum electrode K-149 prepared by Radiometer Co., Denmark. More than 10 ml of anaerobically obtained arterial blood was run through a specially made chamber which has a capacity of 5 ml, the last part of blood being sealed within the chamber as shown in figure 1. otential readings were taken at intervals of 1 minute from exactly 1 minute after blood sampling to 15 minutes with an Astrup ph meter. A potential-time curve was prepared which showed a gradual decline as seen in figure 2. Initially the potential-time curve was extrapolated to zero time to obtain the redox potential. However, since the reading obtained by extrapolation does not necessarily represent the in vivo redox potential N. YOSHIMURA,* M.D.; K. KODAMA, M.D.; J. YOSHITAKE, M.D.; Department of Anesthesiology, School of Medicine, Kagoshima University, 8-3 Shiroyama-cho, Kagoshima, Japan. * resent address: Department of Anesthesiology, Jackson Memorial Hospital, Miami, Florida 33136, U.S.A.

2 CARBOHYDRATE METABOLISM AND INSULIN RELEASE 1023 cock KC1 crystal $tirrer cock t.etectrode Saturated KCI solution -Water Jacket Blood - warmed water (38*C) Syri nge FIG. 1 Schematic illustration of the apparatus for measurement of the redox potential of blood using the platinum electrode K-149 prepared by Radiometer Co., Denmark. R- ( ' ' ' I I I I 1 I L FIG. 2 The time course of the normal potential value measured by the electrometric method for a human arterial blood. R-=Redox potential. 15 of blood, the readings at exactly 1 minute after blood sampling were taken as the redox potential of blood, and are reported herein. lasma insulin concentrations were measured in triplicate by a modification of the method of Hales and Randle (1963) using 125 I-labelled insulin and an insulin binding reagent obtained from the Radiochemical Centre, Amersham, England. Blood ph was measured with an Astrup ph meter, and ox, was determined by the Astrup microequilibration technique. RESULTS The collected data are presented in tables I and II. Ether anaesthesia (fig. 3). Concentrations of blood glucose increased significantly during ether anaesthesia. The plasma insulin levels were increased significantly at 60 and 90 minutes after induction of anaesthesia. A significant increase in insulin to glucose ratio (I/G) was observed at 30 minutes after induction, but no further increase occurred thereafter. The blood redox potential decreased significantly at 60 and 90 min after induction of anaesthesia. Haloihane anaesthesia (fig. 3). The changes in carbohydrate metabolism were less than those observed during ether anaesthesia. The plasma insulin level tended to fall, but not significantly, while the level of blood glucose remained almost unchanged. The I/G ratio, therefore, showed a tendency to decrease but not significantly. The blood redox potential remained almost unchanged. Effects of glucose infusion during ether anaesthesia (fig. 4). As shown in table II, the levels of blood glucose, plasma insulin and I/G ratio increased more and the changes of blood redox potential were less than those in ether anaesthesia alone. DISCUSSION It is well known that ether stimulates the endogenous release of adrenaline (Brewster, Bunker and Beecher, 1952). The metabolic changes observed during ether anaesthesia can be ascribed in part to the humoral alterations resulting from ether administration.

3 Blood Glucose Ether anaesthesia Normal Saline. Halothane anaesthesia Normal Saline. lasma Insulin ' (,uu/rnl) 25 InsuUrj- Glucose ( /.) 1 Blood Redox otentb (mv) of< ~~o 3j sb 906" id 5b sir FIG. 3 Effects of ether and halothane anaesthesia on the levels of blood glucose, and plasma insulin, the insulin to glucose ratio, and the blood redox potential in non-diabetic humans. FIG. 4. Effects of glucose infusion on the levels of blood glucose, plasma insulin, insulin to glucose ratio, and blood redox potential in non-^diabetics, a diabetic patient, and in non-diabetic subjects anaesthetized with ether. Blood Glucose ma, /10ml Glucose Infusion Glucose Infusion Glucose Infusion (0.5g7Kg/60min) Non-diabetics Diabetic (Non-diabetics) Conscious Ether anaesthesia lasma Insulin Insulin^ 0r f atio, Blood Redox 3 potential (mv) 2 0 FIG td to > w H CO

4 CARBOHYDRATE METABOLISM AND INSULIN RELEASE 1025 TABLE I Changes in the levels of blood glucose, plasma insulin and insulin/glucose ratio (I/G), and blood redox potential during ether and halothane anaesthesia in man. arameters Ether anaesthesia Glucose (mg/ ml) Insulin (//U/ml) Halothane anaesthesia Glucose (mg/ ml) Insulin (juu/ml) * statistically significant No. of cases compared Before induction 83 ± ± ± ± ± min Time (mean ±SE) <0.01* >0.20** >0.30** with before-induction values. 60min <0.02* <0.05* >0.30** >0.*» ** statistically 90min <0.05* >0.05*» >0.30»* not significant. TABLE II Effects of glucose infusion on the levels of blood glucose, plasma insulin and insulin/glucose ratio (I/G), and blood redox potential during ether anaesthesia. arameters Male, 63 yr., kg Glucose (mg/ ml) Insulin (uu/ml) Male, 35 yr., 55 kg Glucose (mg/ ml) Insulin GuU/ml) Before induction Time 30min tnin min Glucose was administered intravenously at the rate of 0.5 g/kg for an hour following the induction of ether anaesthesia, and thereafter only normal saline solution was infused. orte and colleagues (1966) showed that adrenaline is a potent inhibitor of insulin release in man. According to Takasawa (1970), there is no significant change in blood insulin concentration between 15 and 45 minutes after induction of ether anaesthesia. In this study an elevation of plasma insulin concentration was observed during ether anaesthesia, especially at 60 and 90 minutes after induction. It is unlikely, therefore, that the elevation of blood glucose during ether anaesthesia is due to a decrease of plasma insulin. The objectives of the measurements of blood redox potential were to evaluate the changes in redox state induced by the administration of anaesthetics. In our previous experiments, the changes of redox potential measured in blood varied directly with the ratio of the concentrations of the oxidized and reduced forms of the nicotinamideadenine dinucleotide (NAD/NADH) obtained in the canine liver cells with a slight time lag. A marked decrease of blood redox potential was also observed in the diabetic state, in which I/G ratio was lowered and redox potential was not restored by glucose infusion without insulin (fig. 4, and Yoshimura et al., 1971). In normal conscious subjects the redox potential did not decrease much following glucose infusion, and in subjects anaesthetized with ether, the redox potential was kept near normal and a relatively high I/G ratio was maintained if glucose was given (fig. 4). It may be concluded that ether

5 1026 BRITISH JOURNAL OF ANAESTHESIA anaesthesia is different from the diabetic state in which the I/G ratio was not increased by glucose infusion. ACKNOWLEDGEMENTS We are grateful to Miss R. Honda and Miss T. Sameshima for technical assistance. We would also like to thank Eisai harmacol. Co. for the supply of labelled insulin kit. We also wish to express our appreciation to Dr D. A. Holaday, rofessor of Anesthesiology, University of Miami, for his encouraging advice. art of the data listed in figure 4 has already been published in Jap. J. Anesth., 20, 42. REFERENCES Brewster, W. R. jr., Bunker, J.., and Beecher, H. K. (1952). Metabolic effects of anesthesia. VI: Mechanism of metabolic acidosis and hyperglycemia during ether anesthesia in the dog. Amer. J. hysiol., 171, 37. Hales, C. N., and Randle,. J. (1963). Immunoassay of insulin with antibody precipitate. Biochem. J., 88, 137. orte, D. jr., Graber, A., Kuzuya, T., and Williams, R. H. (1966). The effect of epinephrine on immunoreactive insulin levels in man. J. clin. Invest., 45, 228. Takasawa, T. (1970). Influence of ether anesthesia and surgical stimulation on the levels of blood human growth hormone and insulin concentrations. Jap. J. Anesth., 19, 271. Yoshimura, N., Kodama, K., Nobe, S., Suemori, I., Yoshida, Y., Adachi, H., Yokoyama, I., and Yoshitake, J. (1971). Effects of glucose, xylitol, and dihydroxyacetone on the metabolism and the insulin release in non-diabetic and diabetic human subjects and in dogs subjected to hemorrhagic shock. Jap. J. Anesth., 20, 42. ETUDE DU METABOLISME DES HYDRATES DE CARBONE ET DE LA SECRETION D'INSULINE AU COURS D'ANESTHESIES A L'ETHER ET A L'HALOTHANE SOMMATRE On a etudi chez l'homme, les effets de l'anesth sie a l'ether et a l'halothane sur la glycemie, le potential d'oxydoreduction et l'insuline plasmatique immunoreactive. Au cours de l'anesth^sie a l'ether, les taux d'insuline plasmatique ont augmente, tandis que le potential d'oxydorecluction du sang diminuait. De telles modification n'ont pas 6t observees au cours de l'anesthesie a l'halothane. KOHLENHYDRATSTOFFWECHSEL UND INSULINFREISETZUNG WAHREND ATHER- UND HALOTHAN-NARKOSEN ZUSAMMENFASSUNG Der Einflufi einer Narkose mit Diadiylather und Halothan auf den Glukosespiegel im arteriellen Blut, das' Redoxpotential und das immunreaktive lasmainsulin beim Menschen wurden erforscht. Wahrend der Athernarkose stiegen die lasmainsulinspiegel, wahrend das Blut-Redoxpotential abfiel. Wahrend Halothannarkose wurden keine derartigen Veranderungen gefunden. METABOLISMO DE LOS CARBOHIDRATOS Y LIBERACION DE INSULINA DURANTE LA ANESTESIA OR ETER Y HALOTANO RESUMEN Fueron investigados en el hombre los efectos de eter dietuico y halotano sobre la glucosa de la sangre arterial, potencial redox e insulina inmunorreactiva del plasma. Durante la anestesia por eter aumentaron los niveles de insulina en el plasma mientras que el potencial redox sanguineo disminuyo. No fueron encontrados tales cambios durante la anestesia por halotano. CORRESONDENCE HARMACOLOGY OF SOME DRUGS USED IN LABOUR Sir, I wish to correct a factual error in Dr Burt's excellent review (Brit. J. Anaesth. (1971), 43, 824), because it reflects what I find to be a common misapprehension. It is not true that the Central Midwives Board (CMB) "will permit only pethidine and pentazocine to be used by unsupervised midwives". For good and understandable reasons the Midwives Rules contain no reference to specific drugs (although they do indicate that the apparatus for administering inhalational analgesics must be of an approved type). The choice available in respect both to the drug and dosage to the unsupervised midwife is defined by her Local Health Authority (namely, the Medical Officer of Health) or, in hospital practice, by members of the Consultant medical staff (acting usually through their deputies). It is quite permissible, within the grounds laid down by the Midwives Rules, for an unsupervised midwife to be allowed by her MOH to administer heroin, LSD or whisky if she considers such medication to be appropriate (there would undoubtedly be difficulties in prescribing the latter two for NHS patients!). J. SELWYN CRAWFORD Birmingham