Perioperative Glycemic Control

Transcription

1 Perioperative Glycemic Control Essay Submitted by: Moshira Sayed Mohamed M.B., B.Ch In fulfillment of the M.Sc. degree in Anesthesia Supervised by: Prof. Dr. Hanan Mahmoud Kamal Professor of Anesthesiology Faculty of Medicine, Cairo University Prof. Dr. Hanan Farouk Khafagy Ass. Professor of Anesthesiology Theodor Bilharz Research Institute Dr. Amira Refaie Hassan Lecturer of Anesthesiology Faculty of Medicine, Cairo University Faculty of Medicine Cairo University 2012

2 ABSTRACT Patients with diabetes are more likely to undergo surgery than nondiabetics, and maintaining glycemic control in persons with diabetes can be challenging during the perioperative period. Surgery in diabetic patients is associated with longer hospital stay, higher health care resource utilization, and greater perioperative mortality. In addition, several observational and interventional studies have indicated that hyperglycemia is associated with adverse clinical outcomes in surgical and critically ill patients. This review will provide practical recommendations for the preoperative, intraoperative, and postoperative care of diabetic patients. Key Words: hyperglycemia, hypoglycemia, surgery, complications, insulin.

3 ACKNOWLEDGEMENT First and foremost thanks to Allah, the most beneficial and merciful I am heartily thankful to Prof. Dr. Hanan Mahmoud Kamal, Professor of Anesthesiology, Faculty of Medicine, Cairo University, for her effective guidance, valuable suggestions and meticulous cooperation. I would like to express my deepest gratitude to Prof. Dr. Hanan Farouk Khafagy, Assistant Professor of Anesthesiology, Theodor Bilharz Research Institute for her continuous guidance and unlimited support, valuable instructions and for her great effort in supervision of this work I am extremely grateful to Dr. Amira Refaie Hassan, Lecturer of Anesthesiology, Faculty of Medicine, Cairo University, for giving me much of her time, advice and efforts. My profound appreciation and deep thanks to Dr. Mohamed Ahmed Maher, Lecturer of Anesthesiology, Theodor Bilharz Research Institute, for his continuous help and encouragement, he was so helpful, caring and supportive all through. I would like to thank all the staff members and colleagues of the Anesthesiology Department, Theodor Bilharz Research Institute, for their faithful advices and kind help. It is difficult to fulfill the right and to express my feelings towards My Family & Friends for their deep and close support and reassurance with endless patience. Moshira Sayed 2012

4 TABLE of CONTENTS INTRODUCTION Chapter 1: PHYSIOLOGY of GLYCEMIC CONTROL.. I. Glucose Transport.. II. Glucose Homeostasis. Chapter 2: DIABETES MELLITUS I. Epidemiology II. Classification and Diagnosis III. Clinical Presentations of Diabetes IV. Treatment of Diabetes. V. Measuring Metabolic Control of Diabetes VI. Diabetic Metabolic Emergencies VII. Complications of Diabetes Chapter 3: MODULATORS of HYPERGLYCEMIA in the PERIOPERATIVER PERIOD I. Neuroendocrinal Stress Response II. Insulin resistance. III. Effect of Perioperative Management on Glycemic State Chapter4: HYPERGLYCEMIA and PERIOPERATIVE OUTCOMES I. Pathophysiology of Hyperglycemia II. Potential Causes of Hyperglycemia in the Diabetic and NonDiabetic. III. Effects of Hyperglycemia.. IV. Benefits of Controlling Hyperglycemia V. Glycemic Goal during the Perioperative Period

5 Table of Contents Chapter 5: HYPOGLYCEMIA I. Definition.. II. Pathophysiology of Hypoglycemia III. Clinical Picture of Hypoglycemia IV. Causes of Hypoglycemia... V. Hypoglycemia and Clinical Perioperative Applications Chapter 6: PRACTICAL MANAGEMENT of PERIOPERATIVE HYPERGLYCEMIA I. Perioperative Management. II. Intraoperative Management.. III. Postoperative Management.. ENGLISH SUMMARY.. REFERENCES... ARABIC SUMMARY

6 List of Tables Table Table (1): Potassium therapy in DKA. Table (2): Feasibility of day case surgery in diabetics. Table (3): Classification of surgical procedures. Table (4): Sliding scale insulin. Page

7 List of Figures Figure Figure (1): The organs involved in glucose metabolism. Figure (2): Glucose tolerance curve. Page 6 14 Figure (3): Schematic presentation of the progression of insulin resistance. Figure (4): Representation of insulin dose response curve. Figure (5): The relationship between acute illness and hyperglycemia

8 List of Abbreviations ACTH: Adrenocrtico-trophic hormone. ADA: American Diabetes Association. AIDS: Acquired immune deficiency syndrome. ATP: Adenosine tri-phosphate. BG: Blood glucose. BIS: Bi spectral index. BMI: Body mass index. BP: Blood pressure. CBF: Cerebral blood flow. CNS: Central nervous system. CO 2: Carbon di-oxide. D: Day. DKA: Diabetic ketoacidosis. Dl: Deci liter. DM: Diabetes mellitus. ESR: Erythrocyte sedimentation rate. FBG: Fasting blood glucose. FDA: Food and Drug Adminstiration. FFA: Free fatty acid. FPG: Fasting plasma glucose. GABA: Gamma amino butyric acid. GDM: Gestational diabetes mellitus.

9 List of Abbreviations GH: Growth hormone. GIK: Glucose insulin and potassium. GLP-1: Glucagon like peptide. GLUT: Glucose transporter from 1-12 and H + myoinositol. Gm: gram. H + : Hydrogen ion. Hb: Hemoglobin. HBA1c: Glycosylated hemoglobin. HCO 3 : Bicarbonate. HNF: Hepatocyte nuclear factor. Hr: Hour. ICU: Intensive care unit. IFG: Impaired fasting glucose. I-G: Insulin glucose. IGC: Intensive glycemic control. IGF: Insulin like growth factor. IGT: Impaired glucose tolerance. IIT: Intensive insulin therapy. IL: Interlukin. IR: Insulin receptor. IV: Intravenous. K: Potassium. KATP: ATP sensitive potassium channels.

10 List of Abbreviations KCL: Potassium chloride. Kg: Kilo gram. L: Liter. meq: Millie equivalent. Mg: milligram. Min: Minute. Mmol: mill mole. MODY: Maturity onset diabetes of the young. Mol: mole. NPH: Neutral protamine hagedorn. NPO: Nothing per mouth. OGTT: Oral glucose tolerance test. PKC: Protein kinase-c. SNS: Sympathetic nervous system. SSI: Sliding scale insulin. TEE: Trans-esophageal echocardiography. TGC: Tight glycemic control. TNF: Tumor necrosis factor. U: Unit. μg: Micro gram. μu: Micro unit.

11 Introduction Development of hyperglycemia after major surgery is very common even in patients with no history of diabetes mellitus, and is modulated by many factors. These factors include perioperative metabolic state, intraoperative management of the patient, and neuroendocrine stress response to surgery. 1 Acute insulin resistance which is a state of decreased biological effect to any given concentration of insulin, develops perioperatively and contributes significantly to hyperglycemia. 2 When it occurs acutely, the pancreas in some individuals may not be able to respond with appropriate hyperinsulinemia, and the result is hyperglycemia. This condition is affected by age, genetic predisposition, ethnicity, physical activity, and body weight. Insulin resistance increases by poor perioperative caloric intake and negative nitrogen balance and is mediated by proinflammatory molecules, free fatty acids, and counter-regulatory hormones. 3 During surgical or traumatic injury, peripheral resistance to the action of insulin may be profound at the level of the prime controllers of glucose (adipose tissue, liver, heart, and skeletal system). 4, 5 Since diabetic patients require more surgeries and receive critical care more frequently than their non-diabetic counterparts, preemptive identification and anticipation of diabetic complications and co-morbidities, along with an optimized treatment plan, is the foundation for the proper intensive care of this growing population. 6 Diabetics are classified as Type I which results from β cell destruction and usually leads to absolute insulin deficiency and Type II which results from progressive insulin secretory defect on the background of insulin resistance. 7 Another types of diabetes can result due to genetic defects, malfunction of the exocrine pancreas, other endocrinopathies, certain medications, and gestation. 1 1

12 Introduction The majority of investigations uses the term hyperglycemia very loosely and uses varying thresholds for initiating treatment. The current guidelines of the American college of endocrinology and the American diabetes association (ADA) stated that individuals with fasting plasma glucose (FPG): mg/dl are considered as pre-diabetic. Whereas those with FPG level 126 mg/dl have diabetes mellitus. 7 Hyperglycemia is associated with poor outcomes in critically ill and postsurgical patients due to its deleterious effects on the vascular, hemodynamic, and immune systems especially when glucose level greater than 250 mg/dl. It is associated with abnormalities in leukocyte function, including: granulocyte adherence, impaired phagocytosis, delayed chemotaxsis and decreased bactericidal capacity. These leukocyte abnormalities are the cause of postoperative infection and improve with tight glycemic control (TGC) (target serum glucose <110 mg/dl). 8 Initial studies demonstrated improved outcomes in critically ill, postsurgical patients who received intensive glycemic control (IGC). These results were quickly extrapolated to other clinical areas, and IGC was eagerly recommended in the perioperative period. However, recent prospective trials have not been able to show the benefit of IGC; neither an appropriate therapeutic glycemic target nor the true efficacy of perioperative glycemic control has been fully determined. IGC increases the risk of hypoglycemia significantly in critically ill patients with attendant risks of transient or, in rare cases, permanent complications. Clearly, intensive insulin administration and the need to monitor the patient come at a cost of time and money. 1 2

13 Introduction Low glucose levels initiate a compensatory stress response and a typical set of symptoms. However, in the perioperative period and during critical illness, the signs of hypoglycemia may be masked, the compensatory response may be blunted, and the affected patients may be incapable of communicating the symptoms. The ischemic brain reverts to anaerobic metabolism and lactate production as a source of energy. Decreasing glucose levels rapidly and acutely may decrease the lactate supply to the ischemic brain and potentially exacerbate brain injury. 9 Moreover; unrecognized hypoglycemia can have deleterious 10, 11 consequences and has been associated with increased mortality. 3

14 CHAPTER: 1 PHYSIOLOGY of GLYCEMIC CONTROL

15 Physiology of Glycemic Control Glucose represents the final product of carbohydrate metabolism and is considered the main source of energy production for the majority of mammalian cell types. For instance, the amount of free energy liberated by oxidation of one mole of glucose is 686,000 calories. It is particularly vital for the brain where it is essentially the sole substrate for energy metabolism. 12 I. Glucose Transport: Glucose must be transported through the cell membrane into the cellular cytoplasm before it can be utilized by the cells. Glucose cannot diffuse through pores of the cell membrane because the maximum molecular weight of the particles that can pass is about 100 g/mol while glucose has molecular weight 180 g/mol. Glucose enters the cell by 1 of 2 methods: facilitated diffusion or active transport. 13 Facilitated diffusion is the mechanism by which glucose pass to the interior of the cells with a reasonable degree of freedom. After penetrating through the lipid matrix of the cell membrane, there are large numbers of glucose carrier protein molecules called glucose transporters (GLUTs) (GLUT-1 to -12, H+/myoinositol transporter) that can bind with glucose. In this bound form, the glucose can be transported by the carrier from one side of the membrane to the other side and then released. Therefore, if the concentration of glucose is greater on one side of the membrane than on the other side, more glucose will be transported from the high-concentration area to the low-concentration area than in the opposite direction. 14 4

16 Physiology of glycemic control Although insulin is an important hormone involved in glucose homeostasis, not all cells is insulin dependent for glucose transport. Insulin dependent cells include skeletal and cardiac muscle, adipose tissue where GLUT-4 predominates, and the liver, whose glucose uptake is primarily regulated by GLUT-2. Glucose transport into muscle and adipose tissue via a pool of GLUT-4 membrane proteins that move rapidly to the cell surface upon activation of the insulin receptor (IR) is the rate-limiting step in insulin mediated glucose disposal. 15 Hence, any condition that reduces the amount of insulin secretion or decreases the cellular sensitivity to insulin s action, or both, will result in hyperglycemia. In contrast, insulinindependent glucose transport is most notable in the pancreas, brain, and immune and endothelial cells. 16 Active transport of glucose occurs in certain special epithelial cells that are specifically adapted for this function such as the gastrointestinal membrane or through the epithelium of the renal tubules. The glucose is transported by the mechanism of active sodium-glucose co-transport, in which active transport of sodium provides energy for absorbing glucose against a concentration difference. 17 II. Glucose Homeostasis: In the normal person the blood glucose (BG) concentration is very narrowly controlled, usually in a range between 80 and 90 mg/dl of blood in the fasting person each morning before breakfast. This concentration increases to 120 to 140 mg/dl during the first hr or so following a meal, but the feedback systems for control of BG return the glucose concentration very rapidly back to the control level, usually within two hrs after the last absorption of carbohydrates. Conversely, in starvation the gluconeogensis function of the liver provides the glucose that is required to maintain the fasting blood glucose level (FBG). 18 5

17 Physiology of glycemic control The mechanism for achieving the high degree of control is done by (Figure 1): 1-The liver and its role in blood glucose buffer system 2-Insluin 3-Glucagon 4-Hypothalamus 18 Fig1: The organs involved in glucose metabolism The liver and its role in blood glucose buffer system: After meal, BG level rises to a very high concentration and the rate of insulin secretion also increase, as much as two third of the glucose absorbed from the gut is almost immediately stored in the liver in the form of glycogen. Then, during the succeeding hours, when both the BG concentration and the rate of 6

18 Physiology of glycemic control insulin secretion fall, the liver releases glucose back into the blood. Thus, the liver decreases the variations in BG concentration to about three fold. In patients with severe liver disease; it becomes almost impossible to maintain a narrow range of BG concentration. 19 The mechanism underlying the autoregulation of hepatic glucose production appears to depend on the status of hepatic glycogen stores. Under hyperglycemic conditions in which the hepatic glycogen store is large, hepatic glucose output is inhibited secondary to a decrease in the glycogenolytic rate, or by enhanced glucose cycling. Under conditions in which the glycogen stores are depleted as following a prolonged fast, hepatic gluconeogensis is enhanced by autoregulation, perhaps secondary to increase the uptake of gluconeogenic substrates. 18 Glucokinase is the enzyme responsible for glucose phosphorylation and is important to capture glucose into the cells. It plays a key role in the autoregulation of hepatic glucose production because it controls the final common pathway for the release of glucose into the circulation. Patients with type II diabetes display an impaired inhibition of endogenous glucose production in response to exogenous glucose. This defect has been attributed to the failure of hyperglycemia to increase the influx through glucokinase. It is possible that similar alterations in glucokinase activity play a role in the pathogenesis of stress hyperglycemia Insulin: A. Insulin Secretion and Its Regulation : The basal rate of insulin secretion is 0.4 to 0.7 U/hr, increasing rapidly by 4- to 5-fold after ingestion of food. The half-life of insulin in the blood is approximately 5 to 6 min, although its cellular activity upon binding to the IR is substantially longer. Increased levels of glucose in the plasma trigger the release of 7

19 Physiology of glycemic control insulin from β-cells in the pancreatic islets of Langerhans. 21 The secretion of insulin is not exclusively governed by the plasma glucose level but also modulated by other pancreatic hormone (glucagon) and intestinal hormones collectively known as incretins: e.g. glucagon-like peptide-1(glp-1). Other intestinal hormones such as cholecystokinin and gastrin promote islet cell neogenesis and may indirectly influence glucose homeostasis. 22 GLP-1 is a potent hormone secreted by the L-cells of the intestines and discrete populations of neurons. Traditionally, the gut hormone is thought to regulate glucose homeostasis via directly acting on the β-cells to stimulate insulin secretion and its biosynthesis, decrease glucagon secretion, and promote pancreatic β-cell growth. GLP-1 s action centrally has been associated with the control of food intake. It was found that central nervous system (CNS) GLP-1 signaling is involved in regulating peripheral insulin secretion and partitioning of glucose disposal, which collectively increases hepatic glycogen storage in preparation for the next fasting state. 23 B.Metabolic Effects of Insulin: 1) Promotion of glucose uptake in insulin-sensitive cells by translocation of a specific glucose transporter (GLUT-4) to the cell membrane. 24 2) Promotion of glycogen synthesis, the chief storage form of intracellular glucose. 24 3) Physiologically, insulin reduces circulating glucose concentrations by increasing the uptake of glucose into peripheral tissues, especially skeletal muscle. In the liver, insulin activates glucokinase and decreases endogenous (primarily hepatic) glucose production by reducing gluconeogenesis and glycogenolysis. 24 8

20 Physiology of glycemic control C. Non metabolic Effects of Insulin: 1) Insulin has an anti inflammatory action through suppression of several proinflammatory transcription factors (nuclear factor- K B, early growth response-1, and activating protein-1) and decreases the expression of endotoxin-mediated inflammatory mediators; interleukin [IL]-1β, IL-6, macrophage migration inhibitor factor, and tumor necrosis factor [TNF]-α. 25 2) Insulin acts as an inhibitor of platelet aggregation and a selective vasodilator through augmentation of nitric oxide production in both platelets and the endothelium. 25 3) Insulin has antioxidant, antithrombotic, and antifibrinolytic properties as it decreases expression of tissue factor, plasminogen activator inhibitor-1, reactive oxygen species, intracellular adhesion molecule-1, and monocyte chemotactic protein-1 generation. 26 4) Antiapoptotic properties of insulin have also been well described Glucagon: Glucagon is an anti insulin hormone which is secreted by alpha cells of the islets of Langerhans of the pancreas when BG concentration falls and has several functions that are opposed to those of insulin. The most important of these functions is to increase BG concentration. 27 A. Effects of glucagon: The major effects of glucagon on glucose metabolism are glycogenolysis and increased gluconeogenesis in the liver. Both of these effects greatly enhance the availability of glucose to the other organs of the body. Most other effects of 9