A fasting glucose level below 100 mgd L

• A fasting glucose level below 100 mg/d. L is considered normal. • Individuals with documented fasting glucose levels above 126 mg/d. L are considered diabetics and those with levels between 100 and 125 mg/d. L are considered prediabetics • DM is the most commonly occurring endocrine disease found in surgical patients. Although the most serious complications of DM are related to its character as a chronic disease, it can cause difficulties in the short-term management of acute illness. • Occasionally, DM remains clinically inapparent until exacerbated by the stress of trauma or surgery • The principles of the treatment of DM will be easier to understand if we review the physiology of glucose metabolism and the stress response and then consider some of the specific pathologic entities that comprise the clinical picture of DM.

• Classification: • DM is primarily a disease of glucose metabolism; however, it has numerous manifestations and has a range of endocrinologic effects. Despite a variety of etiologic factors, its hallmark is a deficiency, either absolute or relative, in the amount of insulin effect to the tissues. • Type I (formerly called insulin-dependent diabetes mellitus) accounts for 5 to 10% of all DM cases and is distinguished from type II (formerly called non–insulindependent diabetes mellitus), which accounts for the remaining 90 to 95% of all DM cases.

• The patient with type I DM typically experiences the onset of disease early in life(juvenile-onset diabetes). • the patient with type I DM is not obese • had an abrupt onset of the disease • has very low levels of circulating insulin • Disease in these patients cannot be controlled with diet or oral hypoglycemic agents; rather, it mandates treatment with insulin as there is an absolute deficiency of insulin. • It is difficult to maintain an optimal glucose level in patients with type I DM; they are more likely to become ketotic and are likely to sustain the end-organ complications of diabetes if they live long enough

• Patients with type II DM(adult-onset diabetes)typically experience a gradual onset of the disease later in life. because of the obesity epidemic, adolescents and teenagers are presenting more frequently with this disorder. • are often obese • have resistance to the effects of insulin • have normal or even elevated levels of insulin • In milder forms, this version of diabetes can often be treated with diet, lifestyle modifications, and oral hypoglycemic agents. • • • Because these patients are relatively resistant to ketosis, their disease may be clinically inapparent until exacerbated by the stress of surgery or intercurrent illness. This classification of DM is only a generalization. The milder type II form can occur in young people, and many older adults can acquire a severe and brittle form of type I.

• Secondary DM can be a result of a disease that damages the pancreas and thus impairs insulin secretion. Pancreatic surgery, chronic pancreatitis, cystic fibrosis, and hemochromatosis can damage the pancreas and impair insulin secretion sufficiently to produce clinical DM. • Glucagonoma • Pheochromocytoma • acromegaly • Cushing disease or steroid therapy • Gestational diabetes is a common medical problem of pregnancy and may presage future type II DM.

• Physiology • Insulin has multiple and complex interactions with lipid, protein, and glucose metabolism. It also has many nonmetabolic functions. • Insulin is a small protein produced by the ß cells of the islets of Langerhans in the pancreas. The basal rate of insulin secretion is about 1 U/hr, which can increase by five- to tenfold after ingestion of food. Normal production in the adult human is approximately 40 to 50 U/day. • Insulin is metabolized in the liver and kidney. In patients with hepatic dysfunction, the loss of gluconeogenesis and a prolongation of insulin effect increase the risk of hypoglycemia. in patients with renal disease, the action of insulin is prolonged and they are more prone to hypoglycemia. Exogenous insulin should be administered judiciously in diabetic patients with renal disease.

• Glucose and amino acids directly stimulate insulin release. • vagal stimulation, increases insulin release, as do ß-adrenergic stimulation and a-adrenergic blockade. • Nitric oxide stimulates insulin secretion. • Potassium depletion decreases insulin secretion. • The most fundamental action of insulin is to stimulate increased cellular uptake of glucose in skeletal muscle cells, adipose tissue, and cardiac cells. • The brain, liver, and immune cells are exceptions, as insulin does not affect glucose transport. Hence, the diabetic patient has hyperglycemia because of inadequate cellular uptake of glucose • Along with glucose, potassium enters the cells under the influence of insulin • Other important metabolic functions of insulin include the stimulation of glycogen formation, as well as the suppression of gluconeogenesis and lipolysis. The patient with insulin deficiency has low glycogen stores and active gluconeogenesis. This implies that in the diabetic patient with a deficiency of glycogen, protein must be broken down to make glucose.

• During stress, elevations in the circulating levels of cortisol, glucagon, catecholamines, and growth hormone all act to cause hyperglycemia. In addition, glucagon and adrenergic stimulation exert a suppressive effect on insulin release. Furthermore, inflammatory mediators released during stress enhance the release of the counterregulatory hormones and directly affect the intracellular signaling pathways of insulin, culminating in significant insulin resistance. • mild hyperglycemia may occur in the stressed patient who does not have DM. • In the diabetic patient, stress makes the hyperglycemia more difficult to control. • In a patient with minimal or subclinical DM before the stressful episode, the hyperglycemia may become difficult to manage during the stress-related event.

• Treatment: • Patients with type I DM require insulin to survive. • The risk of microvascular complications can be decreased if tight glycemic control is maintained near normal levels of blood glucose. Patients may be on a range of doses of short-, intermediate-, and longacting insulin, with doses given one to six times per day, depending on the desire for tight control. • Patients with type II DM initially may be treated with diet control and exercise. If this fails to control glucose levels or the diabetes worsens, therapy with an oral agent is indicated. • Sulfonylureas (glyburide, glipizide, glimepiride) • glinides (repaglinide, nateglinide) enhance ß-cell insulin secretion. Metformin is a biguanide that decreases hepatic glucose output and enhances the sensitivity of both hepatic and peripheral tissues to insulin

• Anesthetic Management • Successful management of the diabetic patient depends as much, if not more, on the proper management of the chronic • complications of the disease as on acute glycemic management. • Preoperative • A thorough preoperative search must be done for end-organ complications of DM. In addition to a thorough history and physical examination, a recent ECG, blood urea nitrogen, potassium, creatinine, glucose, and urinalysis are essential. • Atherosclerosis develops earlier and is more widespread in diabetic patients compared with nondiabetic patients. Manifestations include coronary artery disease, peripheral vascular disease, cerebrovascular disease, and renovascular disease. The incidence of postoperative myocardial infarction is increased in diabetic patients, and the complication rate is higher.

• Silent myocardial ischemia and infarction occur more commonly in diabetic patients, perhaps because of sensory neuropathy of the visceral afferents to the heart. DM may be associated with a cardiomyopathy in the face of angiographically normal coronary arteries, possibly with diffuse disease in arteries too small to be visualized. • Preoperative hyperglycemia, as documented by increased hemoglobin A 1 c, has been associated with poor perioperative outcomes in a variety of clinical situations

• Laryngoscopy can be difficult in up to 40% of juvenile • • patients with DM presenting for renal transplantation. This may be because of diabetic stiff joint syndrome, a frequent complication of type I DM leading to decreased mobility of the atlantooccipital joint. The “prayer sign, ” an inability to approximate the palmar surfaces of the interphalangeal joints, is associated with stiff joint syndrome and may predict difficult laryngoscopy. Diabetic nephropathy eventually occurs in up to 40 to 50% of patients with DM. Albuminuria usually precedes a steady decline in renal function. Diabetic patients with autonomic neuropathy are at increased risk for intraoperative hypotension and perioperative cardiorespiratory arrest. There may be an exaggerated pressor response to tracheal intubation.

• Autonomic function may be tested by measuring the beat-to-beat variation in heart rate during breathing, heart rate response to a Valsalva maneuver, and orthostatic changes in diastolic blood pressure and heart rate. • Autonomic neuropathy predisposes to intraoperative hypothermia. • Diabetic patients may have delayed gastric emptying as a result of diabetic autonomic neuropathy, and therefore an increased risk of pulmonary aspiration of gastric contents.

• Metoclopramide may be useful in emptying the stomach of solid food. • oral hypoglycemics have been held before surgery because of fear of hypoglycemia in the fasted patient. With modern shorteracting agents, this may be unnecessary because the risk is much reduced. • It is desirable to discontinue metformin preoperatively because it has been associated with severe lactic acidosis during episodes of hypotension, poor perfusion, or hypoxia. • Unless the patient has a surgical emergency, patients with diabetic ketoacidosis or hyperosmolar coma should receive intensive medical management before coming to the operating room

• Intraoperative: • The details of the anesthetic plan depend intimately on the endorgan complications. • Invasive monitoring may be indicated • , awake intubation may be necessary if a difficult intubation is predicted, fluid management and drug choices may depend on renal function • pulmonary aspiration must be considered if there is gastroparesis. • Blood glucose levels should be measured before and after surgery. • Hourly measurements are reasonable in high-risk patients. • The standard glucose dosage for an adult patient is 5 to 10 g/hr (100 to 200 m. L of 5% dextrose solution hourly) • Routine administration of glucose-containing intravenous fluids is not recommended.

Monitoring of the patient who arrives in the operating room with significant metabolic impairment, such as diabetic ketoacidosis, is similar to management in the medical intensive care unit, including hourly determinations of blood glucose, arterial p. H, electrolytes, and fluid balance. Frequent reassessments, with medical consultation as needed, guide the use of fluids, electrolytes, especially potassium, insulin, phosphate, and glucose • Another area of patient monitoring that is extremely important in the diabetic patient is positioning on the operating table. • Injuries to the limbs or nerves are more likely in the patient who arrives in the operating room already compromised by diabetic peripheral vascular disease or neuropathy. The peripheral nerves may already be partly ischemic and therefore particularly vulnerable to pressure or stretch injuries •

• Glycemic Goals: • Insulin secretion can be decreased by the direct effects of anesthetics, while significant insulin resistance develops postoperatively. • The degree of insulin resistance is directly related to surgical trauma. • Intraoperative and postoperative hyperglycemia is predicable in patients who present for cardiac and high-risk noncardiac surgery and/or have poor glycemic control preoperatively Hyperglycemia significantly impairs chemotaxis, phagocytosis, generation of reactive oxygen species, and intracellular killing of bacteria. • Acute hyperglycemia has also been shown to lead to poor outcomes in the setting of myocardial infarction and stroke. • • Hyperglycemia is associated with poor perioperative outcomes.

• In summary, association between perioperative hyperglycemia and poor outcomes is strong • Although hyperglycemia develops frequently in patients who undergo cardiac or high-risk noncardiac surgery • Many endocrinologic societies recommend maintaining glycemic levels to <110 mg/d. L in the ICU patients and <150 mg/d. L in diabetic patients undergoing cardiac surgery • Until the results of current trials are available it seems prudent to maintain glucose levels <180 mg/d. L, especially in the perioperative period.

• Management of Perioperative Hyperglycemia: Many factors influence the glucose levels in the perioperative period. Endogenous insulin secretion exogenous insulin administration insulin resistance endogenous glucose production exogenous glucose administration and overall glucose consumption

• Insulin resistance can be modified • by the stress of surgery and the inflammatory state • diet and physical activity. • Postoperative ambulation and physical activity can alter glucose consumption acutely. • Insulin can be administered in many different ways. The simplest route is to administer it subcutaneously. Few studies have adopted this route and they have not been very successful in maintaining tight or timely control. In the perioperative setting, the state of peripheral perfusion is extremely variable and peripheral vasoconstriction is common. • Most study protocols that have demonstrated desirable glycemic control in the acute care setting have used continuous intravenous insulin infusion combined with intravenous bolus injections. Targeted glucose levels can be achieved effectively using these dynamic scale protocols combined with frequent blood glucose determinations.

• wholeblood glucose values and plasma glucose values are different, and the same is true for arterial and venous blood. • Therefore, a real possibility exists of overdosing or underdosing a patient with insulin. • Hence, aberrant glucose values should be confirmed by central laboratory measurements, and practitioners should be aware of the performance of these point-of-care devices used in their institutions.

• Type I Diabetes • Type I diabetics require insulin or they will rapidly develop ketoacidosis and its complications. • This treatment can be given by administering one half to two thirds of the patient's usual intermediate-acting insulin subcutaneously on the morning of surgery. • In addition to this basal insulin, a regular insulin sliding scale (RISS) can be added and titrated to blood glucose measurement. • Alternatively, an insulin infusion of 1 to 2 U/hr can meet basal metabolic needs and be adjusted to maintain blood glucose at the desired level. • With either method, a slow glucose infusion (dextrose 5% in water at 75 to 100 m. L/hr) will prevent hypoglycemia while the patient is fasting.

• Type II Diabetes • Sulfonyl-ureas should be held while the patient is NPO (nothing per mouth) to decrease the risk of hypoglycemia and because they interfere with the cardioprotective effect of ischemic preconditioning. Metformin probably should also be held, especially if there is a risk of decreased renal function perioperatively because of a risk of lactic acidosis. Thiazolidinediones can be continued because they do not predispose to hypoglycemia • For type II patients taking oral agents alone, RISS can be added to control blood glucose levels. Patients receiving chronic insulin can be treated similarly to the type I patient by giving one-half the usual NPH (neutral protamine Hagedorn) dose the morning of surgery, supplemented by a RISS, or an insulin infusion titrated to blood glucose.

• Emergencies • Patients may present with metabolic instability, Stress trauma and infection may all lead to increased insulin requirements and insulin resistance.

• Diabetic Ketoacidosis • If the diabetic patient has insufficient insulin effect to block the mobilization and metabolism of free fatty acids, the metabolic byproducts acetoacetate and ß-hydroxybutyrate accumulate. • These ketone bodies are organic acids and cause a metabolic acidosis with an increased unmeasured anion gap. Clinically, the patient often presents because of intercurrent illness trauma untoward cessation of insulin therapy. Although hyperglycemia is almost always present, the degree of hyperglycemia does not correlate with the severity of the acidosis. Blood sugar levels are often in the 300 to 500 mg/d. L range. The patient is always dehydrated because of the combination of the hyperglycemia-induced osmotic diuresis and the nausea and vomiting typical of this syndrome.

• Because leukocytosis, abdominal pain, GI ileus, and mildly elevated amylase levels are all common in ketoacidosis, an occasional patient is misdiagnosed as having an intra-abdominal surgical problem. • Treatment of diabetic ketoacidosis includes insulin administration and fluid and electrolyte replacement • An intravenous bolus of 10 to 20 U of insulin achieves rapid maximal effect. • Further insulin can be administered by intravenous infusion or intermittent bolus every 30 to 60 minutes. When blood glucose levels decrease below 250 mg/d. L, glucose should be added to the intravenous fluid while insulin therapy continues. • Fluid requirements can be marked; 1 to 2 L of isotonic fluid, should be given over 1 to 2 hours

• • Further deficits can be replaced more gradually. Potassium replacement is a key concern in patients with diabetic ketoacidosis. Because of the diuresis, the total-body potassium stores are reduced. However, acidosis by itself causes a shift of potassium ions out of the cell. Thus, the serum potassium concentration may be normal or even slightly elevated while the patient is acidotic. As soon as the metabolic acidosis is corrected, the potassium ions shift back into the cells. Therefore, early and vigorous potassium replacement is required in these patients, with the exception of those patients in renal failure. Hypophosphatemia also occurs with the correction of the acidosis and, if severe, may cause impairment of ventilation, resulting from skeletal muscle weakness in the vulnerable patient. Instead of diabetic ketoacidosis, the diabetic patient with a metabolic acidosis may have lactic acidosis, which results from poor tissue perfusion or sepsis. It is diagnosed by the presence of an increased serum lactate concentration without an elevated ketone concentration

• Table 49 -11 Management of Diabetic Ketoacidosis • Regular insulin, 10 U IV bolus, followed by an insulin infusion nominally at (blood glucose/150) U/hr • Isotonic IV fluids as guided by vital signs and urine output; anticipate 4– 10 L deficit • When urine output is >0. 5 m. L/kg/hr, give potassium chloride, 10– 40 m. Eq/hr (with continuous ECG monitoring when the rate is >10 m. Eq/hr) • When serum glucose decreased to 250 mg/d. L, add dextrose 5% at 100 m. L/hr Consider sodium bicarbonate to correct p. H <6. 9

• Hypoglycemia is the clinical occurrence most feared in the management of diabetic patients. • The precise level at which symptomatic hypoglycemia occurs is variable. The normal, fasted patient may have blood sugar levels lower than 50 mg/d. L without symptoms. • However, the diabetic patient who has a chronically elevated blood sugar level may be symptomatic at levels significantly above this glucose concentration. • Hypoglycemia is almost impossible to diagnose clinically in the unconscious patient. • In the awake patient, hypoglycemia often produces central nervous system changes ranging from light-headedness to coma with seizures. • with hypoglycemia, there is a reflex catecholamine release that produces overt sympathetic hyperactivity causing tachycardia, lacrimation, diaphoresis, and hypertension

• In the anesthetized patient, these signs of sympathetic hyperactivity can be easily misinterpreted as inadequate or “light” anesthesia. • Furthermore, in patients being treated with ßadrenergic blocking agents or in patients with advanced diabetic autonomic neuropathy, the sympathetic hyperactivity of hypoglycemia may be obscured. • Thus, the clinical diagnosis of hypoglycemia in the surgical patient may be difficult to make, and only a high degree of suspicion and frequent blood glucose checks can prevent this complication. • Treatment is with 25 g of intravenous dextrose • Or juice if the patient is alert. • Hypoglycemia is more likely to occur in the diabetic surgical patient if insulin or sulfonylureas are given without supplemental glucose. With renal insufficiency, the action of insulin and oral hypoglycemic agents is prolonged