Diabetes mellitus is characterized by impairment of carbohydrate metabolism caused by an absolute or relative deficiency of insulin or of insulin respon-siveness, which leads to hyperglycemia and glycos-uria. The diagnosis is based on an elevated fasting plasma glucose greater than 126 mg/dL or glycated hemoglobin (HbA1c) of 6.5% or greater. Values are sometimes reported for blood glucose, which runs 12–15% lower than plasma glucose. Even when test-ing whole blood, newer glucose meters calculate and display plasma glucose.
Diabetes is classified in multiple ways (Table 34–2). Type 1 (insulin-requiring due to endogenous insulin deficiency) and type 2 (insulin-resistant) diabetes are the most common and well
known. Diabetic ketoacidosis (DKA) is associated with type 1 diabetes mellitus, but rarely individuals with DKA appear phenotypically to have type 2 dia-betes mellitus. Long-term complications of diabetes include retinopathy, kidney disease, hypertension, coronary artery disease, peripheral and cerebral vascular disease, and peripheral and autonomic neuropathies.
There are three life-threatening acute compli-cations of diabetes and its treatment—DKA, hyper-osmolar nonketotic coma, and hypoglycemia—in addition to other acute medical problems (such as sepsis) in which the presence of diabetes makes treatment more difficult. Decreased insulin activ-ity allows the catabolism of free fatty acids into ketone bodies (acetoacetate and β-hydroxybutyrate), some of which are weak acids . Accumulation of these organic acids results in DKA, an anion-gap metabolic acidosis. DKA can easily be distinguished from lactic acidosis, with which it can coexist; lactic acidosis is identified by elevated plasma lactate (>6 mmol/L) and the absence of urine and plasma ketones (although they can occur concurrently and starvation ketosis may occur with lactic acidosis). Alcoholic ketoacidosis can follow heavy alcohol consumption (binge drinking) in a nondiabetic patient and may include a normal or slightly elevated blood glucose level. Such patients may also have a disproportionate increase in β-hydroxybutyrate compared with acetoacetate, incontrast to those with DKA.
Infection is a common precipitating cause of DKA in a known diabetic patient, and DKA may be the reason that a previously undiagnosed person with type 1 diabetes presents for medical treatment. Clinical manifestations of DKA include tachypnea (respiratory compensation for the metabolic aci-dosis), abdominal pain, nausea and vomiting, and changes in sensorium. The treatment of DKA should include correcting the often substantial hypovole-mia, the hyperglycemia, and the total body potas-sium deficit. This is typically accomplished with a continuous infusion of isotonic fluids and potassium and an insulin infusion.
The goal for decreasing blood glucose in keto-acidosis should be 75–100 mg/dL/h or 10%/h. Therapy generally begins with an intravenous insu-lin infusion at 0.1 units/kg/h. DKA patients may be resistant to insulin, and the insulin infusion rate may need to be increased if glucose concentrations do not decrease. As glucose moves intracellularly, so does potassium. Although this can quickly lead to a critical level of hypokalemia if not corrected, overaggressive potassium replacement can lead to an equally life-threatening hyperkalemia. Potassium and blood glucose should be monitored frequently during treatment of DKA.
Several liters of 0.9% saline (1–2 L the first hour, followed by 200–500 mL/h) may be required to cor-rect dehydration in adult patients. When plasma glucose decreases to 250 mg/dL, an infusion of D5W should be added to the insulin infusion to decrease the possibility of hypoglycemia and to provide a con-tinuous source of glucose (with the infused insulin) for eventual normalization of intracellular metabo-lism. Patients may benefit from precise monitoring of urinary output during initial treatment of DKA.
Bicarbonate is rarely needed to correct severe acidosis (pH < 7.1) as the acidosis corrects with volume expansion and with normalization of the plasma glucose concentration.
Ketoacidosis is not a feature of hyperosmolarnonketotic coma possibly because enough insu-lin is available to prevent ketone body formation. Instead, a hyperglycemia-induced diuresis leads to dehydration and hyperosmolality. Severe dehydra-tion may eventually lead to kidney failure, lactic acidosis, and a predisposition to form intravascular thromboses. Hyperosmolality (frequently exceed-ing 360 mOsm/L) induces dehydration of neurons, causing changes in mental status and seizures. Severe hyperglycemia causes a factitious hypona-tremia: each 100 mg/dL increase in plasma glucose lowers plasma sodium concentration by 1.6 mEq/L. Treatment includes fluid resuscitation with normal saline, relatively small doses of insulin, and potas-sium supplementation.
Hypoglycemia in the diabetic patient is the result of an absolute or relative excess of insulin relative to carbohydrate intake and exercise. Furthermore, dia-betic patients are incompletely able to counter hypo-glycemia despite secreting glucagon or epinephrine (counterregulatory failure). The dependence of the brain on glucose as an energy source makes it the organ most susceptible to episodes of hypoglycemia. If hypoglycemia is not treated, mental status changescan progress from anxiety, lightheadedness, or con-fusion to convulsions and coma. Systemic manifes-tations of hypoglycemia result from catecholamine discharge and include diaphoresis, tachycardia, and nervousness. Most of the signs and symptoms of hypoglycemia will be masked by general anesthe-sia. Although the lower boundary of normal plasma glucose levels is ill-defined, medically important hypoglycemia is present when plasma glucose is less than 50 mg/dL. The treatment of hypoglycemia in anesthetized or critically ill patients consists of intra-venous administration of 50% glucose (each milli-liter of 50% glucose will raise the blood glucose of a 70-kg patient by approximately 2 mg/dL). Awake patients can be treated orally with fluids containing glucose or sucrose.
Abnormally elevated hemoglobin A1c concentrations identify patients who have maintained poor control of blood glucose over time. These patients may be at greater risk for perioperative hyperglycemia, peri-operative complications, and adverse outcomes. The perioperative morbidity of diabetic patients is related to their preexisting end-organ damage. Unfortunately, one third to one half of patients with type 2 diabetes mellitus may be unaware of their condition.
A preoperative chest radiograph in a diabetic patient is more likely to uncover cardiac enlargement, pulmonary vascular congestion, or pleural effusion, but is not routinely indicated. Diabetic patients also have an increased incidence of ST-segment and T-wave-segment abnormalities on preoperative elec-trocardiograms (ECGs). Myocardial ischemia or old infarction may be evident on an ECG despite a nega-tive history. Diabetic patients with hypertension have a 50% likelihood of coexisting diabetic autonomicneuropathy (Table 34–3). Reflex dysfunction ofthe autonomic nervous system may be increased by old age, diabetes of longer than 10 years’ duration, coronary artery disease, or β- adrenergic blockade.
Diabetic autonomic neuropathy may limit the patient’s ability to compensate (with tachycar-dia and increased peripheral resistance) for intravas-cular volume changes and may predispose the patient
to cardiovascular instability (eg, postinduction hypotension) and even sudden cardiac death. The incidence of perioperative cardiovascular instability appears increased by the concomitant use of angio-tensin-converting enzyme inhibitors or angiotensin receptor blockers. Autonomic dysfunction contrib-utes to delayed gastric emptying (diabetic gastropare-sis). Premedication with a nonparticulate antacid and metoclopramide is often used in an obese diabetic patient with signs of cardiac autonomic dysfunction. However, autonomic dysfunction can affect the gas-trointestinal tract without any signs of cardiac involvement.
Diabetic renal dysfunction is manifested first by proteinuria and later by elevated serum creatinine. By these criteria, most patients with type 1 diabetes have evidence of kidney disease by 30 years of age. Because of an increased incidence of infections related to a compromised immune system, strict attention to aseptic technique, important for all patients, is espe-cially important in those with diabetes.
Chronic hyperglycemia can lead to glycosyl-ation of tissue proteins and limited mobility of joints.
Temporomandibular joint and cervical spine mobility should be assessed preoperatively indiabetic patients to reduce the likelihood of unan-ticipated difficult intubations. Difficult intubation has been reported in as many as 30% of persons with type 1 diabetes.
The goal of intraoperative blood glucose manage-ment is to avoid hypoglycemia while maintaining blood glucose below 180 mg/dL. Attempting to maintain strict euglycemia is imprudent; “loose” blood glucose control (>180 mg/dL) also carries risk. The exact range over which blood glucose should be maintained in critical illness has been the subject of several much-discussed clinical trials. Hyperglycemia has been associated with hyperosmo-larity, infection, poor wound healing, and increased mortality. Severe hyperglycemia may worsen neu-rological outcome following an episode of cerebral ischemia and may compromise outcome following cardiac surgery or after an acute myocardial infarc-tion. Unless severe hyperglycemia is treated aggres-sively in type 1 diabetic patients, metabolic control may be lost, particularly in association with major surgery or critical illness. Maintaining blood glucose control (<180 mg/dL) in patients undergoing car-diopulmonary bypass decreases infectious compli-cations. A benefit of true “tight” control (<150 mg/ dL) during surgery or critical illness has not yet been demonstrated convincingly and in some studies has been associated with worse outcome than “looser” control (<180 mg/dL).
Lack of consensus regarding the appropriate target for blood glucose has not prevented periop-erative glucose management from becoming yet another indicator of so-called “quality” anesthetic care. Consequently, anesthesia staff should carefully review their current practices to ensure that their glucose management protocols are in line with insti-tutional expectations.
Control of blood glucose in pregnant diabetic patients improves fetal outcome. Nonetheless, as noted earlier, the brain’s dependence on glucose as an energy supply makes it essential that hypoglyce-mia be avoided.
Th ere are several common perioperative management regimens for insulin-dependent dia-betic patients. In the most time-honored (but not terribly effective) approach, the patient receives a fraction—usually half—of the total morning insu-lin dose in the form of intermediate-acting insulin (Table 34–4). To decrease the risk of hypoglycemia, insulin is administered after intravenous access has been established and the morning blood glucose level is checked. For example, a patient who nor-mally takes 30 units of NPH (neutral protamine
Hagedorn; intermediate-acting) insulin and 10 units of regular or Lispro (short-acting) insulin or insulin analogue each morning and whose blood glucose is at least 150 mg/dL would receive 15 units (half the normal 30-unit morning dose) of NPH subcu-taneously before surgery along with an infusion of 5% dextrose solution (1.5 mL/kg/h). Absorption of subcutaneous or intramuscular insulin depends on tissue blood flow, however, and can be unpredict-able during surgery. Dedication of a small-gauge intravenous line for the dextrose infusion prevents interference with other intraoperative fluids and drugs. Supplemental dextrose can be administered if the patient becomes hypoglycemic (<100 mg/dL). However, intraoperative hyperglycemia (>150–180 mg/dL) is treated with intravenous regular insulin according to a sliding scale. One unit of regular insu-lin given to an adult usually lowers plasma glucose by 25–30 mg/dL. It must be stressed that these doses are approximations and do not apply to patients in catabolic states (eg, sepsis, hyperthermia).
An alternative method is to administer regu-lar insulin as a continuous infusion. The advantage of this technique is more precise control of insulin delivery than can be achieved with a subcutaneous or intramuscular injection of NPH insulin, partic-ularly in conditions associated with poor skin and muscle perfusion. Regular insulin can be added to normal saline in a concentration of 1 unit/mL andthe infusion begun at 0.1 unit/kg/h. As blood glu-cose fluctuates, the regular insulin infusion can be adjusted up or down as required. The dose required may be approximated by the following formula:
A general target for the intraoperative mainte-nance of blood glucose is less than 180 mg/dL. The tighter control afforded by a continuous intravenous technique may be preferable in patients with type 1 diabetes.
When administering an intravenous insu-lin infusion to surgical patients, adding some (eg, 20 mEq) KCl to each liter of fluid may be useful, as insulin causes an intracellular potassium shift. Because individual insulin needs can vary dramati-cally, any formula should be considered as only a crude guideline.
If the patient is taking an oral hypoglycemic agent preoperatively rather than insulin, the drug canbe continued until the day of surgery. However, sulfonylureas and metformin have long half-lives and many clinicians will discontinue them 24–48 h before surgery. They can be started postop-eratively when the patient resumes oral intake. Metformin is restarted if renal and hepatic function remain adequate. The effects of oral hypoglycemic drugs with a short duration of action can be prolonged in the presence of kidney failure. Many patients main-tained on oral antidiabetic agents will require insulin treatment during the intraoperative and postoperative periods. The stress of surgery causes elevations in counterregulatory hormones (eg, catecholamines, glucocorticoids, growth hormone) and inflammatory mediators such as tumor necrosis factor and interleu-kins. Each of these contributes to stress hyperglyce-mia, which increases insulin requirements. In general, type 2 diabetic patients tolerate minor, brief surgical procedures without any exogenous insulin. However, many ostensibly “nondiabetic” patients show pro-nounced hyperglycemia during critical illness and require a period of insulin therapy.
The key to any management regimen is to monitor plasma glucose levels frequently. Patients receiving insulin infusions intraoperatively may need to have their glucose measured hourly. Those with type 2 diabetes vary in their ability to produce and respond to endogenous insulin, and measure-ment every 2 or 3 h may be sufficient. Likewise, insulin requirements vary with the extensiveness of the surgical procedure. Bedside glucose meters are capable of determining the glucose concen-tration in a drop of blood obtained from a finger stick (or withdrawn from a central or arterial line) within a minute. These devices measure the color conversion of a glucose oxidase–impregnated strip. Their accuracy depends, to a large extent, on adherence to the device’s specific testing proto-col. Monitoring urine glucose is of value only for detecting glycosuria.
Patients who take NPH or other protamine-containing insulin preparations have an increased risk of allergic reactions to protamine sulfate— including anaphylactoid reactions and death. Unfortunately, operations that require the use of heparin and subsequent reversal with protamine (eg, cardiopulmonary bypass) are more common in diabetic patients. The usefulness of a small prot-amine test dose of 1–5 mg over 5–10 min prior to the full reversal dose is unclear, although this is recom-mended by some clinicians.
Patients who use subcutaneous insulin infu-sion pumps for management of type 1 diabetes usually can leave the pump programmed to deliver “basal” amounts of regular insulin (or insulin glargine). This is the amount of insulin required during fasting. Such patients can safely undergo short outpatient surgery with the pump on the basal setting. If more extensive inpatient proce-dures are required, these patients will normally be managed with intravenous insulin infusions as described earlier.
Close monitoring of blood glucose must continue postoperatively. There is considerable patient-to-patient variation in onset and duration of action of insulin preparations ( Table 34–5). For example, the onset of action of subcutaneous regular insulin is less than 1 h, but in rare patients its duration of action may continue for 6 h. NPH insulin typically has an onset of action within 2 h, but the action can last longer than 24 h. Another reason for close
monitoring is the progression of stress hyperglyce-mia in the recovery period.