Perioperative glucose control in the diabetic or nondiabetic patient.

Abstract: Patients with diabetes are more likely to undergo surgery than nondiabetics, and maintaining glycemic control in subjects 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 paper reviews the pathophysiology of hyperglycemia during trauma and surgical stress and will provide practical recommendations for the preoperative, intraoperative, and postoperative care of diabetic patients.

Key Words: hyperglycemia, surgery, complications, insulin infusion

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Patients with diabetes are more likely to undergo surgery than are people without diabetes. (1,2) Maintaining glycemic control in subjects with diabetes presents a challenging problem during the perioperative period. Surgery in diabetic patients is associated with longer hospital stay, higher health care resource utilization, and greater perioperative mortality than nondiabetic subjects. (3-6) The higher morbidity and mortality relates in part to the heightened incidence of coronary heart disease, hypertension, renal insufficiency, and increased rates of postoperative complications. (3,6,7) In addition, several observational and interventional studies have indicated that hyperglycemia per se is associated with adverse clinical outcomes in surgical and critically ill patients. (8-12) In this paper, we review the pathophysiology of hyperglycemia during trauma and surgical stress and will provide practical recommendations for the preoperative, intraoperative, and postoperative care of diabetic patients.

Metabolic Consequences of Surgical Stress and Anesthesia

The stress of surgery and anesthesia results in increased secretion of counterregulatory hormones (catecholamines, cortisol, glucagon, and growth hormone) and excessive release of inflammatory cytokines, such as tumor necrosis factor-[alpha], interleukin-6 and interleukin-1[beta]. (13-18) The magnitude of the counterregulatory response relates to the severity of surgery, as well as the type of anesthesia. (5,19) The counter-regulatory response results in a number of alterations in carbohydrate metabolism, including insulin resistance, increased hepatic glucose production, impaired peripheral glucose utilization, and relative insulin deficiency. (20) In the presence of an absolute or relative deficiency of insulin, increased catecholamines and glucagon levels lead to increased gluconeogenesis and glycogenolysis and inhibit glucose utilization in peripheral tissues. (21-23) Epinephrine stimulates glucagon secretion and inhibits insulin release from pancreatic [beta]-cells. (24,25) High cortisol levels increase hepatic glucose production and stimulate protein catabolism and increased circulating amino acid concentration, providing precursors for gluconeogenesis. (22,26) Increased counterregulatory hormones during stress also lead to enhanced lipolysis and increased free fatty acid (FFA) concentration. (27,28) Increased FFA levels produce insulin resistance dose-dependently in diabetic and nondiabetic individuals (29-31) and is an important factor in the development of stress hyperglycemia. Increased FFA levels have been shown to inhibit insulin-stimulated glucose uptake, (30-32) glycogen synthesis, (29) and intracellular signaling cascade function in skeletal muscle. (33)

The type of anesthesia may influence the hyperglycemic response during surgery. General anesthesia has been shown to result in higher blood glucose concentration than local and epidural analgesia. (5,24) Circulating catecholamines, cortisol, and glucagon concentration are higher in patients undergoing general anesthesia. (5,24,34) Volatile anesthetic agents inhibit insulin secretion (35) and increase hepatic glucose production. (36) In contrast, epidural analgesia has a minimal effect on carbohydrate metabolism and levels of counterregulatory hormones are not significantly elevated. (37) It should be noted that the reduced hyperglycemia associated with epidural analgesia is strictly limited to the operative period; afterwards, there is no difference in glycemic control. Several studies have investigated the effect of opioids during general anesthesia on stress response, pain control and glycemic control during the perioperative period. Some studies have reported a reduction in the rate and severity of hyperglycemia with opioid analgesia, (38) but others have not. (39) Interestingly, several clinical and experimental studies have suggested that diabetes or hyperglycemia alters opioid responsiveness. A recent prospective study evaluated the effect of diabetes mellitus on morphine requirements in the postoperative period of subjects undergoing elective total abdominal hysterectomy. (40) Postoperative pain scores were higher in the diabetic group, and they required more morphine for pain control than nondiabetic patients. These findings suggest that the use of opioids during general anesthesia may reduce the rate of hyperglycemia during the perioperative period, but the analgesic effect of morphine is attenuated in diabetes, and larger doses of morphine may be administered to diabetic patients for effective postoperative analgesia. (40)

Blood Glucose and Perioperative Outcome

Increasing evidence suggests that in hospitalized patients with and without diabetes, the presence of hyperglycemia is associated with poor clinical outcomes (8,9,11,41-44) and aggressive glycemic control positively impacts morbidity and mortality. (10,11,43,45-50) We recently reported that one third of patients admitted to general medicine and surgery wards in an urban general hospital had hyperglycemia, defined as an elevated fasting glucose level > 126 mg/dL or 2 or more random blood glucose levels > 200 mg/dL. (8) Of those patients, 26% had a known history of diabetes, and 12% had no history of diabetes before admission. Stress or new hyperglycemia was associated with higher in-hospital mortality rates (16%) compared with those patients with a prior history of diabetes (3%) and subjects with normoglycemia (1.7%).

Pomposelli et al (9) determined the relationship between perioperative glucose control and postoperative infection rates in 100 diabetic patients undergoing elective surgery. The authors found that a single blood glucose level >220 mg/dL on the first postoperative day was a sensitive (87.5%) predictor of postoperative infection. Patients with blood glucose values >220 mg/dL had infection rates that were 2.7 times higher than the rate for patients with lower blood glucose values (31.3% versus 11.5%, respectively). When minor infections were excluded, the relative risk for serious postoperative infection, including sepsis, pneumonia, and wound infections, was 5.7 times higher than those with glucose levels less than 220 mg/dL.

In the United States, approximately 500,000 patients undergo coronary artery bypass grafting (CABG) each year, (51) >20% of whom have diabetes. (52,53) Diabetes is recognized as an independent risk factor in patients undergoing CABG. (45,46,54,56) Perioperative hyperglycemia is associated with a higher risk of deep sternal wound infections and increased mortality, (45,46,54-56) and aggressive glucose control improves outcome in subjects undergoing CABG. (3,8,45,46,48,53-56) In a prospective study of 1,499 consecutive patients undergoing CABG, Furnary et al (54) reported that a conservative perioperative insulin infusion protocol aimed at maintaining blood glucose levels between 150 to 200 mg/dL was associated with a 59% reduction in deep sternal wound infections versus historical controls. In a subsequent report, they found that continuous IV insulin therapy (mean blood glucose: 177 [+ or -] 30 mg/dL) compared with subcutaneous insulin (glucose: 213 [+ or -] 4 mg/dL) resulted in lower mortality, 2.5% versus 5.3%, respectively. (45) In this study, patients with blood glucose levels > 250 mg/dL had a 14.5% mortality, compared with a mortality rate of 0.9% in subjects with blood glucose < 150 mg/dL. (14) A different study assessed the perioperative glucose control and outcome during the first 36 hours following CABG surgery. (55) Compared with patients in the lower quartile (121-206 mg/dL), the risk of infection was increased by 17% for those with blood glucose between 207 to 229 mg/dL, by 78% in subjects with blood glucose between 253 to 352 mg/dL, and by 86% for glucose levels between 230 to 252 mg/dL.

In 2001, Van den Berghe et al (10) reported a prospective study of 1,548 adults randomized to intensive insulin therapy to maintain target blood glucose between 80 to 110 mg/dL (actual mean daily blood glucose = 103 mg/dL) or conventional therapy to maintain target blood glucose between 180 to 200 mg/dL (actual mean daily blood glucose = 153 mg/dL). Two thirds of these patients underwent cardiac surgery and the rest had noncardiac major surgical procedures. Intensive intervention reduced overall in-hospital mortality by 34% in patients with an ICU length of stay of more than 5 days and also reduced requirements for antibiotics, red cell transfusions, kidney dialysis, and prolonged ventilatory support. A further analysis of the cohort (41) reported that for each 20 mg/dL glucose elevation above 100 mg/dL, the risk of ICU mortality was increased by 30%. The rate of hypoglycemia (defined as a blood glucose <40 mg/dL) occurred in 5.1% of the intensively treated patients.

The reasons for poor outcome with high blood glucose levels during the perioperative period remain unclear. Much of the attention has focused on the increased rate of infections and poor wound healing. (57,58) Hyperglycemia is associated with impaired leukocyte function, including decreased phagocytosis, impaired bacterial killing and chemotaxis. (57,59,60) Other effects of hyperglycemia on the immune system include inhibition of polymorphonuclear leukocyte respiratory burst, (61) diminished superoxide generation, inhibition of phospholipase D activity and altered complement function. (60,62) Several prospective and well-designed studies have shown that patients with a postoperative glucose greater than 200 mg/dL have a 17 to 86% increased risk of infection, (55) and that reduction of blood glucose with insulin therapy improves leukocyte function and lowers the risk of local and systemic infections. (10,45,63) Hyperglycemia has also been shown to impair collagen synthesis and to impair wound healing among patients with poorly controlled diabetes. (64,65) In humans and in animal models of diabetes, hyperglycemia has been shown to cause multiple defects in wound healing, including reduced collagen synthesis, reduced wound tensile strength, reduced neovascularization and capillary volume at the site of injury. (64,65) Advanced glycosylation end products accumulate in diabetes and may adversely affect extracellular matrix production, cell function, cytokine production and prevent wound healing. (66)

In addition to the deleterious effects on wound healing, hyperglycemia results in a raised concentration of counter-regulatory hormones and cytokines which lead to increased circulating FFA levels. (67,68) Elevated FFAs have been associated with arrhythmias, increased sympathetic overactivity, elevated blood pressure, a rise in oxidative stress, and endothelial dysfunction. (69-71) They directly activate typical and atypical isoforms of protein kinase C (PKC). (72) Activation of PKC is involved in the regulation of vascular tone and vascular smooth muscle cell growth and may contribute to endothelial dysfunction. At the cellular level, there is evidence that FFAs reduce nitric oxide bioavailability by inhibiting nitric oxide synthase activity and stimulating production of reactive oxygen species (ROS). (73) Reactive oxygen species are associated with activation of extracellular signal-regulated kinase (ERK), transcription factors, phospholipase A2, matrix metalloproteinases, increases in IGF-1 levels and decreases in IGF binding proteins, DNA synthesis, and endothelial function. An acute increase in FFA also causes an inflammatory response, as reflected in an increase in ROS generation and increased NF-[kappa]B binding activity in mononuclear cells. (74) Intensive insulin therapy has been shown to prevent excessive inflammation in critically ill patients. (10,74) Insulin may exert direct anti-inflammatory effects through its suppression of NF-[kappa]B-regulated pathways, including the production of inflammatory cytokines, such as TNF-[alpha], macrophage migration inhibitory factor, and the generation of superoxide. (75-77)

Preoperative Assessment of the Diabetic Patient: Risk Evaluation

The comprehensive operative risk assessment is an important step in the management of the diabetic patient before surgery. (24) The evaluation is oriented to identifying underlying cardiac, pulmonary and renal disease, electrolyte disturbances, presence of macrovascular and microvascular complications, as well as the assessment of antecedent glycemic control.

Adult subjects with diabetes should be considered high-risk for cardiac ischemia. (78) The risk of coronary artery disease is two to four times higher than in the corresponding general population. (79) Asymptomatic diabetic patients have an incidence of acute ischemic events similar to nondiabetic patients with stable coronary artery disease. (80) Diabetics with proven coronary artery disease have poorer long-term outcome after vascular surgery, with an increased probability of cardiac death or myocardial infarction compared with nondiabetics with equivalent disease. (81) In addition, myocardial infarction and ischemia may be silent and frequently unrecognized because of the sympathetic denervation of the heart. (82,83) A low threshold for cardiac testing has been recommended in diabetics, especially those over 50 years of age, with obesity, physical inactivity, hypertension, albuminuria, dyslipidemia, and chronically elevated glucose (>200 mg/dL) and A1C levels (> 7%). (84) The preoperative detection of CAD in diabetic patients is difficult. (85) The standard baseline electrocardiogram has a value of 25% for predicting cardiac events. (86) Asymptomatic diabetic patients with multiple risk factors should be investigated by stress testing if they have a low-functional capacity or if they are to undergo major or vascular surgery. The positive predictive value of all stress tests is modest (20-30%); however, their negative predictive value is excellent (95-100%). (79) Stress tests with dipyridamole-thallium scintigraphy and dobutamine echocardiography are dynamic investigations with better diagnostic accuracy. The American College of Cardiology (ACC) and American Heart Association (AHA) have coauthored guidelines on preoperative cardiac risk assessment. (78,87,88) The ACC/AHA guidelines use major, intermediate, and minor clinical predictors to stratify patients into different cardiac risk categories. Patients with poor functional status or those undergoing high-risk surgery require further risk stratification via cardiac stress testing. High-risk patients with unstable coronary syndromes, patients undergoing major surgery, or when considering coronary revascularization, may merit from preoperative cardiac catheterization by the ACC/AHA guidelines. (78,87,88)

Autonomic neuropathy is a major complication of diabetes, characterized by degeneration of afferent and efferent fibers of the sympathetic and parasympathetic nerves of the heart and peripheral vasculature. (89,90) Cardiac autonomic neuropathy is reported in up to 20 to 40% of diabetic patients with hypertension and appears to be independent of age, duration of diabetes, or the presence of microvascular complications. Cardiac autonomic neuropathy explains the occurrence of silent myocardial ischemia and the impaired cardiovascular response to exercise and stress (24) and may predispose to cardiovascular complications and perioperative hypotension. (91,92) The presence of resting tachycardia, postural hypotension and loss of respiratory heart rate variability should be sought during the examination. (92) Besides cardiac complications, autonomic neuropathy may increase the risk of perioperative complications by decreasing esophageal motility and causing gastroparesis that may lead to vomiting and aspiration of gastric content (93) and by increasing the risk of urinary track infection in the presence of neurogenic bladder.

Renal failure is the most common major complication in the postoperative period and is associated with increased morbidity, mortality, and in-hospital resource utilization. (94,95) The reported incidence of renal dysfunction after cardiac surgery is significantly influenced by the definition used in a given study. The prevalence of renal dysfunction, defined as a postoperative serum creatinine level of [greater than or equal to] 177 [micro]mol/L ([greater than or equal to]2.0 mg/dL) and an increase in serum creatinine level of [greater than or equal to] 62 [micro]mol/L ([greater than or equal to]0.7 mg/dL) from the preoperative level, was observed in 171 (7.7%) of the 2,222 patients undergoing myocardial revascularization. (95) Similarly, a prevalence of postoperative renal dysfunction of 7% has been reported in patients undergoing general surgery. (94) Risk factors for postoperative renal dysfunction include advanced age, type 1 diabetes mellitus, preoperative hyperglycemia, a history of moderate to severe congestive heart failure, a previous coronary artery bypass graft, or preexisting renal disease (as manifested by an elevated serum creatinine level). (95) This risk approximately doubles with one preoperative risk factor and quadruples with two risk factors. Before surgery, a urine analysis is also recommended to rule out urinary tract infection (94) and to determine the amount of proteinuria. The presence of proteinuria is associated with a greater risk of developing acute renal failure in the postoperative period.

Glycemic Goal During the Perioperative Period

Although there are still no proven mechanisms to explain the detrimental effects of hyperglycemia, there are increasing efforts worldwide to improve and maintain appropriate glycemic control during the perioperative period and in critically ill patients. (10,69,96) A recent position statement of the American Association of Clinical Endocrinologists and the American Diabetes Association recommended glycemic targets between 80 to 110 mg/dL for critical patients in the intensive care unit (ICU). For patients with noncritical illness, a preprandial blood glucose less than 110 mg/dL and a random blood glucose level less than 180 mg/dL were recommended. (97) These glucose control parameters applied to surgical patients in the surgical ICU, in particular after CABG procedures. In surgical patients discharged from the ICU to lower acuity units, it was recommended that glucose levels should be maintained as close as possible to normoglycemic levels, either by intensive subcutaneous insulin therapy or by continuation of IV insulin therapy. Recently, several groups have raised concerns about this position statement, including the fact that the AACE position paper was based primarily on findings from a single surgical ICU and the fact that there were no differences on mortality in patients with an ICU length of stay less than 5 days or in patients after vascular surgery. (98) Several large prospective international studies are currently under way that will provide definitive evidence on intensified insulin therapy in critical illness in the ICU.

Intensified glucose control is associated with an increased risk of hypoglycemia. (99,100) Hypoglycemia is commonly encountered in hospitalized patients with altered cognitive status, due to the effects of age, illness, or psychotropic medications. In such patients, the typical symptoms of impending hypoglycemia are not properly perceived. Although most hypoglycemic events are mild and without significant clinical consequences, (10,101) in the cardiac patient, hypoglycemia may result in excess catecholamine release that may aggravate myocardial ischemia or have proarrhythmogenic consequences. (98,102,103) The risk benefit ratio of strict glycemic control in all hospitalized patients must take into account the negative implications of more frequent hypoglycemic events. (10,12,20,96) Continued staff education and the use of frequent blood glucose monitoring facilitate early detection and treatment of hypoglycemic events. (12,20,96)

Approaches to Management

General Principles

Treatment recommendations are generally categorized based on the type of diabetes, nature and extent of the surgical procedure, antecedent pharmacological therapy, and state of metabolic control before surgery. (104) A key factor for success of any regimen requires frequent blood glucose monitoring to allow early detection of any alterations in metabolic control. In general, all patients with type 1 diabetes undergoing minor or major surgical procedures require insulin during the perioperative period (Table 1). In such patients, the stress of surgery may result in the development of diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic syndrome, with negative prognostic consequences. (104-107) Patients with type 2 diabetes undergoing major surgery and coronary revascularization procedures are also candidates for intensive perioperative diabetes management. (23,108,109) Insulin, given either intravenously as a continuous infusion or subcutaneously, is currently the only available agent for effectively controlling glycemia in the hospital. The best method of providing insulin during surgery is debatable. There are a myriad of protocols for the management of this problem, but there are none with clear superiority. Any good regimen should attempt to maintain good glycemic control, avoiding both hyperglycemia and hypoglycemia, should be easy to understand, and should be applicable to different settings (operating room, recovery room, general medicine and surgical wards). Concerns about hypoglycemia due to altered nutrition during the perioperative period is the leading limiting factor in maximizing glycemic control in patients with diabetes. (12,110-112) Fear of hypoglycemia frequently leads to the inappropriate practice of holding a patient's previous outpatient diabetic regimen and initiating "sliding scale" insulin coverage, a practice associated with limited therapeutic success. (113-115) The use of sliding scale should never be the sole regimen in patients with type 1 diabetes or in patients with type 2 diabetes undergoing major surgical procedures.

Patients Treated with Diet Alone

Patients whose diabetes is well controlled by a regimen of diet and physical activity may require no special preoperative intervention for diabetes. (104) Fasting blood glucose should be measured on the morning of surgery, and blood glucose could be controlled with small doses of supplemental short-acting insulin. In contrast, hospitalized patients with poor metabolic control on diet alone (blood glucose >180 mg/dL) should received IV insulin therapy (Table 1).

Patients Treated with Oral Antidiabetic Agents

Of the three primary categories of oral agents--secretagogues, biguanides, and thiazolidinediones--none have been systematically studied during the perioperative period. (12,116) In general, oral agents should be discontinued one day before surgery. Sulfonylureas increase the risk of hypoglycemia; in addition, a longstanding controversy exists regarding the vascular effects of sulfonylureas in patients with cardiac and cerebral ischemia. (117-120) Sulfonylureas inhibit ATP-sensitive potassium channels, resulting in cell membrane deporalization and increased intracellular calcium concentration. (121,122) This mechanism may inhibit ischemic preconditioning and may lead to increased risk of vascular events. (123) Although metformin has a short half-life of approximately 6 hours, it is prudent to temporarily withhold therapy 1 to 2 days before surgery, especially in patients undergoing procedures that increase the risk for renal hypoperfusion, tissue hypoxia, and lactate accumulation. (124,125) Thiazolidinediones increase intravascular volume and may precipitate or worsen congestive heart failure and peripheral edema. (125,126)

In patients with good metabolic control after discontinuation of oral agents, blood glucose could be controlled with small subcutaneous doses (4-10 U) of short-acting insulin (Table 2). Most antidiabetic medications can be restarted once patients start eating, with the exception of metformin, which should be withheld for 48 to 72 hours following surgery or iodinated radiocontrast procedures. Metformin therapy can be restarted after documentation of normal renal function. Patients with poor metabolic control or those scheduled to undergo major surgery should be treated with an IV infusion of insulin and dextrose during the perioperative period.

Type 1 or Type 2 Diabetes Treated with Insulin

Minor Surgery

Most patients receiving insulin before admission can be treated with conventional subcutaneous insulin therapy. If the surgery is to be performed in the morning in a patient treated with intermediate-acting (NPH) insulin, one half of the total morning dose of NPH insulin should be administered. (3,19,23,127) While the patient remains NPO, a 5% dextrose-potassium infusion is infused at a rate of 100 mL/h. The dextrose infusion should be discontinued once oral intake is reinitiated. If needed, blood glucose can be controlled with small doses of supplemental short-acting insulin. In patients treated with basal/bolus insulin combination--glargine and rapid acting insulin analogs (lispro, aspart, glulisine)--the dose of glargine should be continued, but premeal bolus doses should be held until meals are tolerated. Similarly, patients treated with continuous insulin infusion therapy (insulin pumps) should receive their usual basal infusion rate.

Major Surgery

IV infusion of insulin is the standard therapy for the perioperative management of diabetes, especially in type 1 diabetic patients and patients with type 2 diabetes undergoing major procedures. (12,19,100) Several reports have emphasized the advantages of the insulin infusion regimen over subcutaneous delivery. (12,19,100) Insulin-treated patients undergoing major elective surgery should be monitored carefully during the period before admission, aiming for an HbA1c less than 7%. The patient should be admitted the evening before surgery or at least several hours before surgery, especially if glycemic control is suboptimal (hemoglobin [A.sub.1c] >8%). This will allow sufficient time to perform a complete clinical assessment and start insulin infusion before surgery.

Institutions around the world use a variety of insulin infusion algorithms that can be implemented by nursing staff. Recently, several insulin infusion protocols have been reported in the literature. (10,42,45,96) These algorithms facilitate communication between physicians and nurses, achieve correction of hyperglycemia in a timely manner, and provide a method to determine the insulin infusion rate required to maintain blood sugars within a defined target range. (12,101) In most insulin infusion protocols, orders to "titrate drip" are given to achieve a target blood glucose range using an established algorithm or by the application of mathematical rules by nursing staff. (12,101) Two main methods of insulin delivery have been used either combining insulin with glucose and potassium in the same bag (GIK regimen) or giving insulin separately with an infusion pump. The GIK is initiated at a rate of 100 mL/h in a solution of 500 mL of 10% dextrose, 10 mmol of potassium, and 15 U of insulin. Adjustments in the insulin dose are made in 5 U increments according to blood glucose measurements performed at least every 2 hours. (3) Potassium is added to prevent hypokalemia and is monitored at 6-hour intervals. The combined GIK infusion is efficient, safe, and effective but does not permit selective adjustment of insulin delivery without changing the bag. In the United States, separate continuous glucose and insulin infusions are used more frequently than the glucose-potassium-insulin infusion. (10,42,45,96)

A proposed regimen for separate IV insulin infusion for perioperative diabetes management is shown in Table 3. In patients with type 2 diabetes treated with diet or oral antidiabetic agents, we recommend starting continuous insulin infusion when blood glucose levels are > 140 mg/dL; however, patients with type 1 diabetes or with known diabetes treated with insulin can be started on continuous insulin infusion when blood glucose is [greater than or equal to] 70 mg/dL. The initial insulin rate is calculated by dividing the blood glucose level (mg/dL) by 100, then rounding it to nearest 0.5 U (eg, if the initial blood glucose is 260 mg/dL, 260 / 100 = 2.5, start drip at 2.5 U/h). An initial IV insulin bolus is frequently used for patients with significant hyperglycemia (blood glucose > 200 mg/dL). The infusions should be continued postoperatively until oral intake is established, after which the usual diabetes treatment can be resumed.

Adequate glucose should be provided to prevent catabolism, starvation ketosis, and insulin-induced hypoglycemia. The physiologic amount of glucose required to prevent catabolism in the average nondiabetic adult is 120 g/d (or 5 g/h). With preoperative fasting, surgical stress, and ongoing insulin therapy, the caloric requirement in most diabetic patients averages 5 to 10 g/h of glucose. This can be given as 5% or 10% dextrose. An infusion rate of 100 mL/h with 5% dextrose delivers 5 g/h of glucose. If fluid restriction is necessary, the more concentrated 10% dextrose can be used. Fluids containing lactate (ie, Ringer lactate, Hartmann solution) cause exacerbation of hyperglycemia. (3)

Discharge Recommendations

All patients with newly diagnosed diabetes should receive diabetes education, and the outpatient treatment regimen should be discussed before discharge. (30) Arrangements should be made for follow-up with a health care professional who will oversee the patient's diabetes management. The patient or caregiver should receive appropriate instruction on proper dietary therapy, as well as home glucose monitoring techniques. The patient should also be educated on the signs and symptoms of hypoglycemia and hyperglycemia. Finally, patients should be educated on 'sick day' management with a focus on the importance of insulin administration during an illness, blood glucose goals and the use of supplemental short or rapid-acting insulin.

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No man may make another free.
--Zora Neale Hurston

Dawn D. Smiley, MD, and Guillermo E. Umpierrez, MD, FACP, FACE

From the Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, GA.

Reprint requests to Guillermo Umpierrez, MD, FACP, FACE, Associate Professor of Medicine, Emory University School of Medicine, Director, Diabetes and Endocrinology, Grady Health System, 49 Jesse Hill Jr Drive, Atlanta, GA 30303. Email: [e-mail]

Accepted March 1, 2006.

Drs. Smiley and Umpierrez have no disclosures to declare.

RELATED ARTICLE: Key Points

* The comprehensive operative risk assessment is an important step in the management of the diabetic patient before surgery.

* Surgery in diabetic patients is associated with longer hospital stay, higher health care resource utilization, and greater perioperative mortality than in nondiabetic subjects.

* Increasing evidence suggests that in hospitalized medical as well as surgical patients with and without diabetes, the presence of hyperglycemia is associated with poorer clinical outcomes and aggressive glycemic control positively impacts morbidity and mortality.

* Treatment recommendations are generally categorized based on the type of diabetes, nature and extent of the surgical procedure, antecedent pharmacological therapy, and state of metabolic control prior to surgery.

* All patients with diabetes should receive continued diabetes education and the outpatient treatment regimen should be reviewed prior to discharge.

Table 1. Perioperative management of patients with diabetes

I) Minor surgery in DM2 patients not treated with insulin
  * Hold oral agents the day of surgery
  * Patients with "fair" metabolic control (fasting blood glucose < 180
    mg/dL) -- cover with regular insulin or rapid-acting (lispro,
    aspart, glulisine) insulin as needed (see Table 3)
  * Patients with "poor" metabolic control (fasting blood glucose > 180
    mg/dL) -- start continuous insulin infusion.
  * Goals: avoid excessive hyperglycemia (blood glucose >180 mg/dL) and
    hypoglycemia (blood glucose < 80 mg/dL)

II) Minor surgery in DM1 and DM2 patients treated with insulin
  * Hold oral agents (if treated with combination therapy) the day of
    surgery
  * Patients in "fair" metabolic control (fasting blood glucose < 180
    mg/dL):
    - Give half of intermediate-acting insulin (NPH) the morning of the
      surgery
    - While NPO, infuse dextrose 5% saline plus KCl (10-20 mEq/L) at
      100 mL/hour
    - Check blood glucose every 4 to 6 hours while NPO and supplement
      with short-acting insulin (see Table 3)
    - Patient treated with basal (glargine) insulin should receive their
      usual basal insulin dose. Similarly, patients treated with
      continuous insulin infusion therapy (insulin pump) should receive
      their usual basal infusion rate
    - Restart preadmission insulin therapy once food intake is tolerated
  * Patients in "poor' control (fasting blood glucose > 180
    mg/dL) -- start continuous insulin infusion

III) Major surgery in DM1 and DM2 patients treated with insulin
  * Hold oral agents the day of surgery
  * Start continuous insulin infusion prior to surgery and continue
    during perioperative period (Table 3)
  * Goals: Maintain blood glucose < 180 mg/dL during surgery, and blood
    glucose between 80 to 120 mg/dL during the perioperative period in
    the surgical intensive care unit. Start subcutaneous insulin two
    hours prior to discontinuation of insulin infusion. In non-ICU
    settings, avoid excessive hyperglycemia (blood glucose >180 mg/dL)
    and hypoglycemia (blood glucose < 80 mg/dL)

DM1, type 1 diabetes; DM2, type 2 diabetes; NPO, nothing per oral route,
fasting; ICU, intensive care unit.

Table 2. Supplemental sliding scale insulin

  * Type of insulin: regular or rapid-acting insulin (lispro, aspart,
    glulisine) to be given before each meal and at bedtime.
  * Each column represents the number of units of insulin to be added to
    scheduled insulin dose.
    - "Sensitive" column: elderly, cachectic, renal and liver failure,
      and patients with poor oral intake or NPO.
    - "Usual" column: for most patients who are expected to eat all or
      most of their meals.
    - "Insulin Resistant" column: for patients not controlled with
      "usual" column dose, or receiving glucocorticoids, obesity
      (BMI > 30 kg/[m.sup.2]), or patients with diabetes receiving >80
      units/day of insulin.

Blood Glucose  [square]           [square]  [square]
(mg/dL)        Insulin Sensitive  Usual     Insulin Resistant

< 150          0                  0          0
151-180        1                  2          4
181-220        2                  3          4
221-260        3                  4          5
261-300        4                  5          6
301-340        5                  6          7
341-380        6                  7          8
380-420        7                  8          9
> 420          8                  9         10

**Check appropriate column below and cross out other columns

Table 3. Continuous insulin infusion (CII) protocol

I) Initiating continuous insulin infusion (CII):
  * Prepare solution: I unit (U) per l mL of 0.9% normal saline.
  * Start continuous insulin infusion (CII) when blood glucose level >
    140 mg/dL (x 2). Patients with known diabetes treated with insulin
    can start CII when blood glucose [greater than or equal to] 70
    mg/dL.
  * Initial rate: divide blood glucose level (mg/dL) by 100, then round
    to nearest 0.5 U

II) Insulin infusion rate change:
Blood
Glucose (mg/dL) instructions:
> 200      [up arrow] rate by 2 U/h
> 160-200  [up arrow] rate by 1.0 U/h
> 120-160  [up arrow] rate by 0.5 U/h
80-120     No change in rate
60-80      If < 10% lower blood glucose, [down arrow] rate by 1 U/h,
           [check] BG within 30 min
           If > 10% lower blood glucose, [down arrow] rate by 50%,
           [check] BG within 30 min
< 60       Stop infusion (give IV dextrose 12.5 g IV bolus), [check]
           blood glucose within 30 min. When blood glucose > 100 mg/dL,
           restart infusion at 50% of previous rate

III) Patient monitoring:
  * Check capillary blood glucose every hour until it is within goal
    range for 2 hours, and then decrease to every 2 hours.
  * Hourly monitoring may be indicated for critically ill patients even
    if they have stable blood glucose. If a patient is eating, hourly
    blood glucose monitoring is necessary for at least 3 hours after
    eating.
  * Decrease insulin infusion rate by 50% if nutritional therapy (e.g.
    total parenteral nutrition or tube feeds) are discontinued or
    significantly reduced.

IV) Treatment of Hypoglycemia (BG<60 mg/dL)
  * Turn off insulin infusion.
  * Blood glucose level 40-60 mg/dL: give 12.5 g (25 mL) IV bolus of
    dextrose 50% solution. For blood glucose < 40 mg/dL, or if a patient
    is not awake, give 25 g (50 mL) IV bolus of dextrose 50% solution.
  * Recheck BG every 20 minutes, repeat 25 mL of 50% dextrose IV if BG
    <60mg/dL.
  * Restart infusion once BG is >80 mg/dL.

V) Notify the physician:
  * For any blood glucose change greater than 100 mg/dL in one hour.
  * For blood glucose < 40 mg or >360 mg/dL.
  * For hypoglycemia which has not resolved within 20 min of
    administering 50 mL of 50% dextrose.

CII, continuous insulin infusion; BG, blood glucose.
Conversion factors to SI units: serum glucose (mg/dL) x 0.055 mmol/L.