The Disparate Effects of Epinephrine and Norepinephrine on Hyperglycemia in Cardiovascular Surgery
Hyperglycemia is a metabolic derangement that frequently develops after cardiovascular surgery. The perioperative administration of inotropic and vasoactive agents, such as epinephrine and norepinephrine, are common in the management of cardiac surgery patients and are known to contribute to the development of postoperative hyperglycemia. We hypothesized that hemodynamic support with epinephrine exacerbates postoperative hyperglycemia to a greater degree than does treatment with norepinephrine. This literature review outlines the mechanisms by which epinephrine and norepinephrine alter glucose homeostasis, while highlighting the significant differences in their effects on hepatic glucose mobilization and peripheral glucose utilization. This review suggests that the use of epinephrine exacerbates postoperative hyperglycemia to a greater degree than does norepinephrine.
Abel JJ, Crawford AC. 1897. On the blood-pressure-raising constituent of the suprarenal capsule. Bull Johns Hopkins Hosp 8:151-7.
Antonis A, Clark ML, Hodge RL, Molony M, Pilkington TR. 1967. Receptor mechanisms in the hyperglycaemic response to adrenaline in man. Lancet 1(7500):1135-7.
Bartnik M, Malmberg K, Norhammar A, Tenerz A, Ohrvik J, Rydén L. 2004. Newly detected abnormal glucose tolerance: an important predictor of long-term outcome after myocardial infarction. Eur Heart J 25(22):1990-7.
Bartnik M, Rydén L, Ferrari R, Malmberg K, Pyorala K, Simoons M, et al. 2004. The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe: the Euro Heart Survey on diabetes and the heart. Eur Heart J 25(21):1880-90.
Biggers DW, Myers SR, Neal D, et al. 1989. Role of brain in counterregulation of insulin-induced hypoglycemia in dogs. Diabetes 38(1):7-16.
Connolly CC, Steiner KE, Stevenson RW, et al. 1991. Regulation of glucose metabolism by norepinephrine in conscious dogs. Am J Physiol 261(6 Pt 1):E764-72.
Cryer PE. 1980. Physiology and pathophysiology of the human sympathoadrenal neuroendocrine system. N Engl J Med 303(8):436-44.
Deibert DC, DeFronzo RA. 1980. Epinephrine-induced insulin resistance in man. J Clin Invest 65(3):717-21.
Dufour S, Lebon V, Shulman GI, Petersen KF. 2009. Regulation of net hepatic glycogenolysis and gluconeogenesis by epinephrine in humans. Am J Physiol Endocrinol Metab 297(1):E231-5.
Ebner S, Burnol AF, Ferre P, de Saintaurin MA, Girard J. 1987. Effects of insulin and norepinephrine on glucose transport and metabolism in rat brown adipocytes: potentiation by insulin of norepinephrine-induced glucose oxidation. Eur J Biochem 170(1-2):469-74.
Edwards AV, Silver M. 1972. Comparison of the hyperglycaemic and glycogenolytic responses to catecholamines with those to stimulation of the hepatic sympathetic innervation in the dog. J Physiol 223(2):571-93.
Eigler N, Saccà L, Sherwin RS. 1979. Synergistic interactions of physiologic increments of glucagon, epinephrine, and cortisol in the dog: a model for stress-induced hyperglycemia. J Clin Invest 63(1):114-23.
Furnary AP, Gao G, Grunkemeier GL, et al. 2003. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 125(5):1007-21.
Gerich JE. 1988. Glucose counterregulation and its impact on diabetes mellitus. Diabetes 37(12):1608-17. Lilly Lecture 1988.
Gerstein HC, Miller ME, Ismail-Beigi F, et al. 2014. Effects of intensive glycaemic control on ischaemic heart disease: analysis of data from the randomised, controlled ACCORD trial. Lancet 384(9958):1936-41.
Girish G, Agarwal S, Satsangi DK, Tempe D, Dutta N, Pratap H. 2014. Glycemic control in cardiac surgery: rationale and current evidence. Ann Card Anaesth 17(3):222-8.
Hatmann H, Beckh H, Jungermann K. 1982. Direct control of glycogen metabolism in the perfused rat liver by the sympathetic innervation. Eur J Biochem 123(3):521-6.
Hjemdahl P, Belfrage E, Daleskog M. 1979. Vascular and metabolic effects of circulating epinephrine and norepinephrine: concentration-effect study in dogs. J Clin Invest 64(5):1221-8.
Ito N, Iwaya T, Ikeda K, et al. 2014. Hyperglycemia 3 days after esophageal cancer surgery is associated with an increased risk of postoperative infection. J Gastrointest Surg 18(9):1547-56.
Kvetnansky R, Sabban EL, Palkovits M. 2009. Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiol Rev 89(2):535-606.
Lautt WW. 1983. Afferent and efferent neural roles in liver function. Prog Neurobiol 21(4):323-48.
Marette A, Bukowiecki LJ. 1989. Stimulation of glucose transport by insulin and norepinephrine in isolated rat brown adipocytes. Am J Physiol 257(4 Pt 1):C714-21.
McGuinness OP, Shau V, Benson EM, et al. 1997. Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog. Am J Physiol 273(4 Pt 1) :E674-81.
Mulla I, Schmidt K, Cashy J, et al. 2014. Comparison of glycemic and surgical outcomes after change in glycemic targets in cardiac surgery patients. Diabetes Care 37(11): 2960-5.
Nobin A, Falck B, Ingemansson S, Järhult J, Rosengren E. 1977. Organization and function of the sympathetic innervation. Acta Physiol Scand Suppl 452:103-6.
Oliver G, Schäfer EA. 1895. The physiological effects of extracts of the suprarenal capsules. J Physiol 18(3):230-76
Reddy P, Duggar B, Butterworth J. 2014. Blood glucose management in the patient undergoing cardiac surgery: A review. World J Cardiol 6(11):1209-17.
Rui L. 2014. Energy metabolism in the liver. Compr Physiol 4(1):177-97.
Sacca L, Sherwin R, Felig P. 1978. Effect of sequential infusions of glucagon and epinephrine on glucose turnover in the dog. Am J Physiol 235(3):E287-90.
Sherwin RS, Sacca L. 1984. Effect of epinephrine on glucose metabolism in humans: contribution of the liver. Am J Physiol 247(2 Pt 1):E157-65.
Stevenson RW, Steiner KE, Connolly CC, et al. 1991. Dose-related effects of epinephrine on glucose production in conscious dogs. Am J Physiol 260(3 Pt 1):E363-70.
Takamine J. 1901. The isolation of the active principle of the suprarenal gland. J Physiol 27:29P-30P.
von Euler US. 1946. A specific sympathomimetic ergone in adrenergic nerve fibres (sympathin) and its relations to adrenaline and nor-adrenaline. Acta Physiol Scand 12(1):73-97.
Walaas O, Walaas E. 1950. Effect of epinephrine on rat diaphragm. J Biol Chem 187(2):769-76.
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