GLUCOSE TOLERANCE DURING ANAESTHESIA AND SURGERY. COMPARISON OF GENERAL AND EXTRADURAL ANAESTHESIA

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1 Br.J. Anaesth. (19),, 49 GLUCOSE TOLERANCE DURING ANAESTHESIA AND SURGERY. COMPARISON OF GENERAL AND EXTRADURAL ANAESTHESIA A. HOUGHTON, J. B. HlCKEY, S. A. ROSS AND J. DUPRE SUMMARY The effects of general and extradural anaesthesia on glucose tolerance and plasma cortisol concentration in the surgical patient were assessed. Normal glucose tolerance and insulin release were observed under extradural anaesthesia, whereas general anaesthesia produced decreases in both glucose tolerance and insulin release. The plasma cortisol concentration was increased in both groups. These results indicate possible nutritional advantages in conducting surgery under extradural anaesthesia. General anaesthesia and surgery induce a state of glucose intolerance and insulin suppression (Allison, Tomlin and Chamberlain, 199). Moreover, extradural blockade can modify the hyperglycaemia associated with abdominal surgery (Bromage, Shibata and Willoughby, 191); however, in this and similar studies (Keating, 19; Cullingford, 19; Oyama and Matsuki, 19), glucose tolerance was not assessed during the regional blockade. The present study was undertaken to measure the degree of "surgical stress" present in each patient by comparing the glucose tolerance test (g.t.t.), insulin response and cortisol concentrations before operation with an exactly similar profile obtained during operation. Since the above-mentioned studies on glucose concentrations during regional blockade did not control certain factors which affect glucose metabolism, a standard operative stress was chosen and, as detailed below, these factors were eliminated. PATIENTS AND METHODS Following a full explanation, informed consent was obtained from 12 Caucasian patients who were otherwise healthy and who were undergoing either general (g.a.) or extradural anaesthesia (six in each group) for hysterectomy (one vaginal hysterectomy in each group). All patients underwent comparable, lower abdominal surgery so that direct stimulation of the liver A. HOUGHTON,* M.B., CH.B., D.OBST.R.C.O.G., F.F.A.R.C.S. \ J. B. HlCKEY, M.A., B.M., B.CH., F.F.A.R.C.S.; S. A. ROSS, M.R.A.C.P.; J. DUPRE, F.R.C.P.; Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada. Correspondence to A. Houghton, Department of Anaesthesia, Ninewells Hospital and Medical School, Dundee DD2 1UB. -912// and pancreas, key organs in glucose metabolism, was minimized. Normal saline was the only fluid infused (at the rate of ml h" 1, beginning on arrival in the anaesthetic room). Blood (which contains dextrose) was not required by any patient. No vasopressors were given. The patients undergoing extradural blockade did not receive adrenaline or supplementary general anaesthesia. Splanchnic blockade was assumed to accompany the sensory blockade (at least to the 4th thoracic dermatome as measured by pinprick). General anaesthesia was induced with thiopentone 2-3 mg and maintained with nitrous oxide in oxygen. Supplements of pethidine and pancuronium bromide were administered as required. The patient's lungs were ventilated via a Bain circuit with fresh gas flows set at ml kg- 1 min" 1 (Bain and Spoerel, 19). Extradural anaesthesia was induced with a high lumbar injection of an appropriate volume of plain bupivacaine.% to achieve bilateral sensory loss to the 4th thoracic dermatome. These patients were conscious throughout surgery and breathed air with oxygen enrichment. After an overnight fast a standard (Samols and Marks, 19) 2-g i.v. glucose tolerance test (g.t.t.) was performed twice on each patient; on the day before operation (control g.t.t.) and again during surgery the following morning, at approximately the same hour. Before each g.t.t. (control and operative) two basal blood samples were obtained. On the day of operation these were taken before and after the induction of anaesthesia. Control and operative g.t.t. were compared in terms of (a) the K value or slope of the logarithmic plot of the plasma glucose concentration from 2 to min of the g.t.t. (Samols and Marks, 19) and (b) the insulin response to the Macmillan Journals Ltd 19

2 49 BRITISH JOURNAL OF ANAESTHESIA TABLE I. Fasting glucose and glucose disposal rate (K value) after glucose load Fasting plasma glucose (mmol litre" 1 ) K value Group Patient Age (yr) O (pre) O (post) O General anaesthesia * 1.f.3*.*.2*.* **.13 Extradural anaesthesia t l.iof.1* 1.f f t.9t C = control, preoperative; O = operative day; pre = preinduction; post = diabetic; **P<.1. postinduction; * diabetic range; borderline injected glucose, expressed as the area under the incremental insulin curve from to min of the g.t.t. All blood samples were taken from an antecubital vein and analysed in triplicate for plasma concentrations of glucose and immunoreactive insulin (i.r.i.). Plasma cortisol estimations, employing the method of Murphy and Pattee (194), were performed also on aliquots of the second basal, 3- and -min samples. A Beckman glucose analyser was used to measure the plasma glucose concentration and radioimmunoassay was utilized to measure plasma i.r.i. (storage of the latter samples at 2 C for less than 1 month). Results were analysed using Student's paired t test. RESULTS Glucose tolerance test (table I) Fasting concentrations of glucose (mmol litre" 1 )* were similar on both days (g.a. means 4.4, 4.4; extradural means 9,.) and the induction of anaesthesia produced little change (pre- and postinduction means: g.a., 4.4 and 4.4; extradural,. and.). The K value or glucose disposal rate was decreased significantly (P<.1) in every *1 mmol litre" 1 = 1 mg/1 ml. patient in the g.a. group but was decreased only slightly in two patients in the extradural group, being increased in the other four patients (fig. 1). MEAN K VALUE (»SEM) 1.-, i.o N.S. FIG. 1. glucose disposal rate (K value) and SEM after glucose load.

3 GLUCOSE TOLERANCE DURING ANAESTHESIA 49 Insulin concentrations and response (table II) Values for fasting insulin (JXU. ml" 1 ) were similar on both days (g.a. mean.,.3; extradural means 1., 13) and the induction of anaesthesia produced little change (pre- and post-induction means: g.a..3,.3; extradural 13, 12.3). The insulin response ((ui. h" 1 ) was inhibited during g.a. in three of four patients (mean preoperative value 143, intraoperative 92). Moderate augmentation of insulin release was seen in all the patients undergoing extradural anaesthesia (mean preoperative 1439, intraoperative 11). plasma cortisol (ug df 1 ) (±SEM) I Plasma cortisol concentration (fig. 2) Cortisol concentrations were not affected during eight control g.t.t. General anaesthesia did not increase the plasma cortisol concentration but surgery did (P<.2). Extradural anaesthesia in awake patients did increase the plasma cortisol concentrations (P<.2) and these values were maintained during surgery. The mean heart rates (beat min^1) and systolic arterial pressures (mm Hg) at the mid-point of the operative g.t.t s were: g.a. group, 92 and 13 respectively; extradural group, and 9 respectively. DISCUSSION This study has shown that extradural anaesthesia, in contrast to general anaesthesia, preserved glucose tolerance with an augmented insulin release. 3 Time of g.t.t. (min) I FIG. 2. plasma cortisol and SEM, fasting and after glucose load. = day before operation, B = basal, n = (two g.a. only);» = g.a. group, B = post-induction, n = ; O = extradural group, B = post-induction, n =. *P<.2. A combination of afferent and splanchnic blockade induced by high extradural anaesthesia during surgery is likely to have a major influence on glucose metabolism. Stress hyperglycaemia involves three splanchnic mechanisms. "Liver glucose output is TABLE II. Fasting insulin (i.r.i.) and insulin response (incremental area) after glucose load Fasting i.r.i. (ixu. ml- 1 ) Insulin response Group Patient C O (pre) O (post) C O General anaesthesia Extradural anaesthesia C = control, preoperative; O = operative day; pre = preinduction; post = postinduction; sample-series from patients,, 11, 12 were lost.

4 49 BRITISH JOURNAL OF ANAESTHESIA increased through the hepatic innervation, increased catecholamine release, and the pancreatic innervation which inhibits insulin and releases glucagon" (Bloom, 19). Infused glucose increases the insulin/ glucagon ratio, promoting glucose uptake (Unger, Muller and Faloona, 191). Therefore, splanchnic efferent activity both increases glucose production and inhibits glucose uptake. The glucose tolerance curve thus indirectly measures splanchnic activity. Insulin (an anabolic hormone) is not suppressed in the stressed patient during extradural anaesthesia, but this effect is but one aspect of the total hormonalmetabolic response to extradural blockade. Afferent blockade of painful operative stimuli may have prevented sympathetic arousal in our patients, but potential central arousal from anxiety cannot be excluded, although our conscious patients were outwardly calm. The finding, during general anaesthesia, of normal plasma cortisol concentrations which increased during surgery, confirms other studies (Clarke, Johnston and Sheridan, 19). High cortisol concentrations were noted in the awake patients who underwent extradural block and are analogous to the increases observed after operation with good extradural analgesia (Lush et al., 192). These large concentrations support our "central arousal" hypothesis. Since high values were seen during surgery in both our groups, it is unlikely that acute, physiological increases in plasma cortisol concentration contribute to the glucose intolerance of surgery. Changes in human growth hormone may have contributed to our observations on glucose tolerance, since the hormone is unaffected during spinal anaesthesia and surgery (Oyama and Matsuki, 19), yet increases during neuroleptanaesthesia (Oyama and Takiguchi, 19). Unknown variables, possibly contributing to the observed differences, include hepatic blood flow and vagal tone (Woods and Porte, 194). During surgery, extradural blockade permits more normal utilization of infused glucose. This preservation of glucose metabolism may assist nutrition in the patient undergoing surgery. Although none of the patients was known to suffer from diabetes, four in the extradural group had small K values before operation (table I). Therefore, it may be an advantage to conduct surgery in the diabetic patient under extradural anaesthesia in order to facilitate glucose utilization. However, further study of these responses is indicated. ACKNOWLEDGEMENTS We wish to thank the gynaecologists of the Royal Victoria Hospital, Montreal, for permission to study their patients. We also are indebted to our colleagues in the Royal Victoria and Ninewells Hospitals for their kind assistance. REFERENCES Allison, S. P., Tomlin, P. J., and Chamberlain, M. J. (199). Some effects of anaesthesia and surgery on carbohydrate and fat metabolism. Br. J. Anaesth., 41,. Bain, J. A., and Spoerel, W. E. (19). Prediction of arterial carbon dioxide tension during controlled ventilation with a modified Mapleson D system. Can. Anaesth. Soc. J., 22, 34. Bloom, S. R. (19). Glucagon. Br. J. Hosp. Med., 13, 1. Bromage, P. R., Shibata, H. R., and Willoughby, H. W. (191). Influence of prolonged epidural blockade on blood sugar and cortisol responses to operations upon the upper part of the abdomen and the thorax. Surg. Gynecol. Obstet., 132, 11. Clarke, R. S. J., Johnston, H., and Sheridan, B. (19). The influence of anaesthesia and surgery on plasma cortisol, insulin and free fatty acids. Br. J. Anaesth., 42, 29. Cullingford, D. W. J. (19). The blood-sugar response to anaesthesia and surgery in Southern Indians. Br. J. Anaesth., 3, 43. Keating, V. (19). Carbohydrate metabolism; the effects of surgery in a tropical population. Anaesthesia, 13, 434. Lush, D., Thorpe, J. N., Richardson, J., and Bowen, D. J. (192). The effect of epidural analgesia on the adrenocortical response to surgery. Br.J. Anaesth., 44, 119. Murphy, B. E., and Pattee, C. J. (194). Determination of plasma corticoids by competitive protein binding analysis using gel filtration. J. Clin. Endocrinol., 24, 149. Oyama, T., and Matsuki, A. (19). Effects of spinal anaesthesia and surgery on carbohydrate and fat metabolism in man. Br. J. Anaesth., 42, 23. Takiguchi, M. (19). Effects of neuroleptanaesthesia on plasma levels of growth hormone and insulin. Br. J. Anaesth., 42, 11. Samols, E., and Marks, V. (19). Interpretation of the intravenous glucose test. Lancet, 1, 42. Unger, R. H., Muller, W. A., and Faloona, G. R.(191). Insulin/glucagon ratio. Trans. Assoc. Am. Physicians, 4, 122. Woods, S. C, and Porte, D. (194). Neural control of the endocrine pancreas. Physiol. Rev., 4, 9. TOLERANCE AU GLUCOSE PENDANT L'ANES- THESIE ET L'INTERVENTION CHIRURGICALE. COMPARAISON DES ANESTHESIES GENERALE ET EXTRADURALE RESUME On a evalue les effets des anesthesies generate et extradurale sur la tolerance au glucose et les concentrations de cortisol dans le plasma sur des malades chirurgicaux. On a observe, sous anesthesie extradurale, une tolerance normale au glucose et un degagement normal d'insuline, alors que

5 GLUCOSE TOLERANCE DURING ANAESTHESIA l'anesthesie generate a produit une diminution de la tolerance au glucose et du degagement d'insuline. La concentration de cortisol dans le plasma a augmente dans les deux groupes. Ces resultats laissent penser qu'il existe peut-etre des avantages nutritifs a proceder a des interventions chirurgicales sous anesthesie extradurale. GLUKOSE-TOLERANZ WAHREND NARKOSE UND CHIRURGISCHER EINGRIFFE. VERGLEICH ZWISCHEN ALLGEMEINER UND EXTRADURALER ANASTHESIE ZUSAMMENFASSUNG Die Wirkungen allgemeiner und extraduraler Narkose auf Glukose-Toleranz und Plasma-Cortisolkonzentrationen bei chirurgischen Patienten wurden beurteilt. Normale Glukose- Toleranz und Insulin-Freigabe wurden unter extraduraler Narkose beobachtet, wahrend allgemeine Narkose zu Abstiegen sowohl bei Glukose-Toleranz als auch bei Insulin- Freigabe fuhrte. Die Cortisolkonzentrationen im Plasma wurden in beiden Gruppen erhoht. Diese Resultate zeigen mogliche ernahrungsmassige Vorteile bei der Durchfuhrung von Operationen unter extraduraler Narkose. 499 TOLERANCIA DE GLUCOSA DURANTE ANESTESIA Y CIRUGlA COMPARACIN ENTRE LA ANESTESIA GENERAL Y LA EXTRADURAL SUMARIO Se evaluaron los efectos ejercidos por la anestesia general y la extradural sobre la tolerancia de glucosa y la concentracion de plasma de cortisol en el paciente sometido a cirugia. Se observo una tolerancia de glucosa y liberacion de insulina normales bajo anestesia extradural, mientras que la ane anestesia general produjo disminuciones tanto en la tolerancia de glucosa como en la liberacion de insulina. La concentracion de plasma de cortisol fue aumentada en ambos grupos. Los resultados indican posibles ventajas nutritivas en la conduction de cirugia bajo anestesia extradural. 4