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Articles: T Tsubo, T Kudo, A Matsuki, and T Oyama Decreased glucose utilization during prolonged anaesthesia and surgery Can J Anesth 1990; 37: 645-649 [Abstract] [PDF]

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Product of a tissue alkalosis induced by hypocarbia?

Richard G Fiddian-Green   (6 March 2005)

Glucose-K+-insulin and/or omega-3 fatty acid infusions for prolonged anaesthesia/surgery?

Richard G Fiddian-Green   (2 August 2004)

Product of a tissue alkalosis induced by hypocarbia? 6 March 2005
Richard G Fiddian-Green, FRCS, FACS None Send letter to journal: Re: Product of a tissue alkalosis induced by hypocarbia? richardfg{at}hotmail.com Richard G Fiddian-Green	When the peritoneal cavity is opened, the ambient pCO2 and pO2 to which the surface of the bowel and peritoneal cavity are exposed changes suddenly and greatly. The pCO2 falls from some 40 mmHg to almost 0 mmHg, and the pO2 rises from some 40 mmHg to 60 mmHg to over 100 mmHg. Provided perfusion is not compromised the [HCO3-] in the exposed tissues should remain the same as that in the arterial blood superfusing them. The tissue pH and pO2 will, therefore, tend to rise. It is the rise in pH that is of concern. An increase in pH in the gut stimulates anaerobic glycolysis (1) and down regulates oxidative phosphorylation by decreasing the magnitude of the protonmotive force driving it (2). This might well have been the stimulus for the decrease in glucose utilisation and lipid shift seen with prolonged surgery in this study. Should this hypothetical compensatory change fail, the need for nutrient dispatch from the heart should rise and myocardial workload should increase, thereby increasing the likelihoood of adverse myocardial events. If so, the simple solution might be to keep the ambient pCO2 at 40 mmHg possibly by laminar flow with humidified and warmed gases of the appropriate composition. As free radicals may cause uncoupling, any accompanying rise in pO2 might increase the degree of uncoupling present by increasing the yield of free radicals. This is most likely to occur if cytokines have been released, for these convert xanthine dehydrogenase into xanthine oxidase. Whilst uncoupling might increase ATP yield it could, if excessive, precipitate a decrease, unreversed ATP hydrolysis and a precipitous fall in tissue pH. It would seem advisable, therefore, to keep ambient pO2 about 50 mmHg by similar means. This approach would seem preferable to that previously proposed, but does not exclude the possibility that the effects might be additive. 1. Cain SM. pH effects on lactate and excess lactate in relation to O2 deficit in hypoxic dogs. J Appl Physiol. 1977 Jan;42(1):44-9. 2. Gautheron DC. Mitochondrial oxidative phosphorylation and respiratory chain: review. J Inherit Metab Dis. 1984;7 Suppl 1:57-61.
Glucose-K+-insulin and/or omega-3 fatty acid infusions for prolonged anaesthesia/surgery? 2 August 2004
Richard G Fiddian-Green, FRCS, FACS None Send letter to journal: Re: Glucose-K+-insulin and/or omega-3 fatty acid infusions for prolonged anaesthesia/surgery? richardfg{at}hotmail.com Richard G Fiddian-Green	This study has shown that tissue resistance to exogenous insulin and plasma-free fatty acid levels increased during prolonged anaesthesia and surgery even though there was no significant increase in plasma catabolic hormone levels (1). Whilst that does not exclude the possibility of an increased turnover of catabolic hormone the findings indicate a shift in nutrient dependence from glucose to fatty acids. Might this be a physiological adaptation to a progressive increase in tissue dysoxia, that is an increase in dependence upon anaerobic glycolysis for ATP resynthesis? In increasing the ATP yield from each mole nutrient used as substrate in the Krebs cycle the fatty acid shift should have limited the need for increased nutrient delivery imposed by a progressive increase in the degree of dysoxia and hence myocardial workload. This is because in comparison with the 32 moles ATP resynthesised from each mole glucose delivered to tissues 109 moles of ATP are resynthesised from, for example, each mole of palmitic acid delivered. It is currently thought that shifting substrate metabolism from lipids to carbohydrates reduces the deleterious biological and clinical consequences of acute ischaemic events (2). This belief is based upon the demonstration that glucose-insulin-potassium infusion accelerates the recovery of ischaemic myocardium. The beneficial effect might, however, be due to a reduction in myocardial workload induced by in effect increasing nutrient density per unit volume of flowing blood. Giving supplements of omega-3 fatty acids before surgery is also benefical possibly for the same reasons. In patients with chronic heart failure and an implanted defibrillator, however, omega-3 fatty acids are associated with a trend to increased recurrence of ventricular arrhythmias but not mortality (3). Long chain polyunsaturated fatty acids increase mitochondrial membrane permeability to protons and hence uncouple oxidative phosphorylation (4). The effect may be beneficial for, as when thyroxine is administered to a myxoedematous patient, it may be accompanied by an increase in temperature, metabolic rate and oxygen consumption and ATP yield. If excessive, as in the case of thyotoxicosis, uncoupling may be harmful. The harm might be caused by a shift in dependence to ATP resynthesis by anaerobic glycolysis as presumably occurred with prolonged anaesthesia and surgery in this study. Anaerobic glycolysis requires the delivery of 20 times as much glucose to generate 1 mole ATP as that required by oxidative phosphorylation. In effect, therefore, nutrient density per unit of flowing blood is greatly decreased in dysoxia an effect potentially offset by a fatty acid shift. If a fatty acid shift is a physiologocal adaptation to increasing degrees of dysoxia might the increased myocardial workload imposed by prolonged anaesthesia and surgery be averted by infusing omega-3 fatty acids from the induction of anaesthesia? What of the effect of infusing glucose-K+-insulin? Might it be additive? If the increased myocardial workload imposed by prolonged anaesthesia and surgery could be avoided by these and ancillary means perioperative myocardial infarction might be better averted. 1. T Tsubo, T Kudo, A Matsuki, and T Oyama Decreased glucose utilization during prolonged anaesthesia and surgery Can J Anesth 1990; 37: 645-649 2. Berger MM, Mustafa I. Metabolic and nutritional support in acute cardiac failure. Curr Opin Clin Nutr Metab Care. 2003 Mar;6(2):195-201. 3. Cleland JG, Freemantle N, Kaye G, Nasir M, Velavan P, Lalukota K, Mudawi T, Shelton R, Clark AL, Coletta AP. Clinical trials update from the American Heart Association meeting: Omega-3 fatty acids and arrhythmia risk in patients with an implantable defibrillator, ACTIV in CHF, VALIANT, the Hanover autologous bone marrow transplantation study, SPORTIF V, ORBIT and PAD and DEFINITE. Eur J Heart Fail. 2004 Jan;6(1):109-15. 4. Might polyunsaturated fatty acid supplementation in infant formula be harmful? Richard G Fiddian-Green (2 May 2003)Electronic response to: J S Forsyth, P Willatts, C Agostoni, J Bissenden, P Casaer, and G Boehm Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomised controlled trial BMJ 2003; 326: 953