Isoflurane and Sevoflurane Induce Severe Hepatic Insulin Resistance in a Canine Model

Abstract

IntroductionAnesthesia induces insulin resistance, which may contribute to elevated blood glucose and adverse post-operative outcomes in critically ill patients, and impair glycemic control in surgical patients with diabetes. However, little is known about the mechanisms by which anesthesia impairs insulin sensitivity. Here we investigate the effects of anesthesia on insulin sensitivity in metabolic tissues.MethodsHyperinsulinemic-euglycemic clamps were performed in 32 lean (control diet; n = 16 conscious versus n = 16 anesthetized) and 24 fat-fed (6 weeks fat-feeding; n = 16 conscious versus n = 8 anesthetized) adult male mongrel dogs in conjunction with tracer methodology to differentiate hepatic versus peripheral insulin sensitivity. Propofol was administered as an intravenous bolus (3mg/kg) to initiate anesthesia, which was then maintained with inhaled sevoflurane or isoflurane (2–3%) for the duration of the procedure.ResultsAnesthesia reduced peripheral insulin sensitivity by approximately 50% in both lean and fat-fed animals as compared to conscious animals, and insulin action at the liver was almost completely suppressed during anesthesia such that hepatic insulin sensitivity was decreased by 75.5% and; 116.2% in lean and fat-fed groups, respectively.ConclusionInhaled anesthesia induces severe hepatic insulin resistance in a canine model. Countermeasures that preserve hepatic insulin sensitivity may represent a therapeutic target that could improve surgical outcomes in both diabetic and healthy patients.

Effects of anesthesia on renal function and metabolism in rats assessed by hyperpolarized MRI

“…Sevoflurane is an inhalation anesthetic with low blood solubility, which makes the anesthesia procedure with a particularly fast induction and recovery, even after long procedures . Sevoflurane has been linked to increased blood glucose and decreased insulin sensitivity, and has been proposed to induce toxicity in the developing brain with prolonged procedures …”

“…19 Sevoflurane has been linked to increased blood glucose and decreased insulin sensitivity, and has been proposed to induce toxicity in the developing brain with prolonged procedures. 20,21 Inactin is an easily intraperitoneally administered anesthetic used primarily in rodents. It is effective for many hours without any supplement.…”

Immediate effect of transmucosal application of corn syrup or 50% dextrose solution on blood glucose concentrations in healthy dogs

“…Evaluation of the effect of buccal mucosal absorption without a degree of ingestion presents a challenge as sedation and anesthesia have known effects on glucose metabolism and, as previously discussed, volumes required to reach the empiric 0.5–1 g/kg dose would not be acceptable for administration in a clinically obtunded or unconscious animal. The high viscosity of the corn syrup made it more amenable to mucosal application (compared with the 50% dextrose solution and water).…”

Sevoflurane Impairs Insulin Secretion and Tissue‐Specific Glucose Uptake In Vivo

“…Sevoflurane, a commonly used anaesthetic , impairs glucose tolerance after IV glucose tolerance test (IVGTT) and intraperitoneal glucose tolerance test (IPGTT) in rodents . This may involve impaired insulin secretion from the pancreas , and reduced pharmacodynamics effects of insulin manifested as hepatic insulin resistance. Thus, in a canine model, sevoflurane anaesthesia suppressed insulin‐mediated glucose disposal by 20% compared to conscious dogs during a hyperinsulinaemic clamp .…”

“…This may involve impaired insulin secretion from the pancreas , and reduced pharmacodynamics effects of insulin manifested as hepatic insulin resistance. Thus, in a canine model, sevoflurane anaesthesia suppressed insulin‐mediated glucose disposal by 20% compared to conscious dogs during a hyperinsulinaemic clamp . Less is known about the effects of anaesthesia on tissues important for glucose disposal.…”