Perioperative management of blood glucose in adults with diabetes mellitus

INTRODUCTION — Diabetes mellitus is a common chronic disorder, affecting approximately 10 percent of the United States population [1]. Patients with diabetes have an increased incidence of cardiovascular disease, peripheral artery disease, and neuropathy, and these, combined with the frequent microvascular complications of the disease, often translate into more surgical interventions.

Careful assessment of patients with diabetes prior to surgery is required because of their complexity and high risk of coronary heart disease, which may be relatively asymptomatic compared with the nondiabetic population. Diabetes mellitus is also associated with increased risk of perioperative infection and postoperative cardiovascular morbidity and mortality [2,3].

One key aspect of the perioperative management is diabetes care. The complex interplay of being nil per os (NPO) preoperatively, the operative procedure, anesthesia, and additional postoperative factors such as sepsis, disrupted meal schedules and altered nutritional intake, hyperalimentation, and emesis can lead to labile blood glucose levels. A rational approach to diabetes mellitus care allows the clinician to anticipate alterations in glucose and improve glycemic management perioperatively [4].

This review will discuss the preoperative evaluation of patients with diabetes, general glycemic goals, and management of blood glucose in the perioperative period. The special circumstances of glucocorticoid therapy and hyperalimentation are also reviewed. More details regarding glucose management in hospitalized patients in general are found separately. (See "Management of diabetes mellitus in hospitalized patients" and "Glycemic control in critically ill adult and pediatric patients".)

EFFECT OF SURGERY ON GLYCEMIA — Surgery and general anesthesia cause a neuroendocrine stress response with release of counterregulatory hormones, such as epinephrine, glucagon, cortisol, and growth hormone, and of inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-alpha. These neurohormonal changes result in metabolic abnormalities including insulin resistance, decreased peripheral glucose utilization, impaired insulin secretion, increased lipolysis, and protein catabolism, leading to hyperglycemia and even ketosis in some cases [5-14].

The magnitude of counterregulatory hormone release varies per individual and is influenced by the type of anesthesia (general anesthesia is associated with larger metabolic abnormalities as compared with epidural anesthesia), the extent of the surgery (cardiovascular bypass surgery resulting in significantly higher insulin resistance), and additional postoperative factors such as sepsis, hyperalimentation, and glucocorticoid use. The hyperglycemic response to these factors may be attenuated by diminished caloric intake during and immediately after surgery, making the final glycemic balance difficult to predict.

PREOPERATIVE EVALUATION AND PLANNING

Clinical evaluation — The preoperative evaluation of any patient, including those with diabetes mellitus, focuses on cardiopulmonary risk assessment and mitigation of risk. Coronary heart disease is much more common in individuals with diabetes than in the general population, and in addition, patients with diabetes have an increased risk of silent ischemia [15,16]. Therefore, assessment of cardiac risk is essential in patients with diabetes [3]. Other associated conditions, such as hypertension, obesity, chronic kidney disease, cerebrovascular disease, and autonomic neuropathy, need to be assessed prior to surgery as these conditions may complicate anesthesia and postoperative care. (See "Anesthesia for patients with diabetes mellitus", section on 'Preanesthesia evaluation'.)

All patients require a careful history and physical examination, with further evaluation required in certain individuals. Key elements of the initial assessment include the following:

●Determination of the type of diabetes:

•Patients with type 2 diabetes are insulin resistant and may be managed with diet, oral agents, and/or injectable agents, including insulin.

•Patients with type 1 diabetes are insulin deficient and must be managed with insulin. They are at much higher risk of diabetic ketoacidosis and must have basal insulin supplied at all times.

●Evaluation for the presence of long-term complications of diabetes mellitus, including retinopathy, nephropathy, neuropathy, autonomic neuropathy, coronary heart disease, peripheral vascular disease, and hypertension.

●Assessment of preoperative diabetes management, including frequency of monitoring, average blood glucose levels, glycated hemoglobin (A1C) levels, and range of blood glucose levels including prior hypoglycemia.

●Assessment of history of hypoglycemia, including frequency, timing, awareness, and severity.

●Detailed history of diabetes therapy, especially medications that can cause hypoglycemia, including insulin (focusing on type, dose, and timing), sulfonylureas, and meglitinides.

●Other pharmacologic therapy, including type of medication, dosing, and specific timing.

●Characteristics of surgery, including when the patient must stop eating prior to surgery, type of surgery (major or minor), timing of the operative procedure, duration of the procedure, planned use of perioperative steroids, and whether insulin infusion devices (insulin pumps), if used, can safely be continued intraoperatively.

●Type of anesthetic, including epidural or regional versus general anesthesia (epidural or regional anesthesia has minimal effects on glucose metabolism and insulin resistance) [17].

Laboratory — Basic investigation should include a baseline:

●Electrocardiogram (ECG)

●Serum creatinine

●A1C if not measured in previous three months

●Blood glucose

ECG abnormalities, such as abnormal Q waves suggestive of previous myocardial infarction, and chronic kidney disease are risk factors for major postoperative cardiac events. Further investigations including noninvasive cardiac testing should be considered on an individual basis. (See "Evaluation of cardiac risk prior to noncardiac surgery".)

A1C levels will provide information on chronic glycemia, and this is an important element in determining adequacy of current glycemic management, especially insulin dosing, in insulin-requiring patients. There is some suggestion that elevated A1C levels predict a higher rate of postoperative adverse events, including infections, myocardial infarction, and mortality [18-23]. As an example, in a prospective study of 3089 patients (1240 with and 1849 without a diagnosis of diabetes) undergoing elective coronary artery bypass grafting who had A1C measured as part of routine preoperative laboratory testing, higher A1C, but not the diagnosis of diabetes, was associated with an increased incidence of death, myocardial infarction, and deep sternal wound infection. When analyzed across the whole study population, there were significant increases per unit rise in A1C in mortality (odds ratio [OR] 1.4), myocardial infarction (OR 1.55), and deep sternal wound infection (OR 1.38) after adjustment for multiple covariates [20]. Further threshold analyses showed an increased risk of death (OR 4.41) and deep sternal wound infection (OR 5.29) for patients with A1C values above 8.6 and 7.8 percent (70.5 and 61.7 mmol/mol), respectively. A1C thresholds for delaying elective surgery are reviewed elsewhere. (See "Anesthesia for patients with diabetes mellitus", section on 'Level of blood glucose control'.)

It is uncertain whether past chronic glycemia, reflected by A1C, is the risk factor for adverse events or whether A1C is a surrogate for poor perioperative glucose management. In a retrospective analysis of electronic medical records, elevated perioperative glucose (>200 mg/dL [>11 mmol/L]), but not A1C, was associated with increased 30-day mortality [24]. Preoperative glucose levels can additionally help to stratify risk for postoperative wound infections [25,26]. Elevated preoperative glucose levels (>200 mg/dL [>11 mmol/L]) were associated with deep wound infections in a case control study (OR 10.2, 95% CI 2.4-43) [25].

Care coordination — A coordinated care plan should be established among providers involved in the patient's perioperative management. Patients with diabetes are at elevated risk of adverse outcomes in the perioperative setting, and key contributors to this elevated risk include inadequate communication among providers and insufficient planning specifically for diabetes-related care [27]. A plan for glucose management and monitoring should be determined in advance of surgery, as should the specific, respective roles of the surgical and consultative teams in the patient's perioperative care [28]. In addition, changes to any of the following should be communicated to all providers prior to implementation:

●Nutritional plan

●Administration of dextrose-containing fluids

●Renal replacement therapy, including scheduled dialysis sessions and the dextrose content of the dialysate used for peritoneal dialysis

●Glucocorticoid therapy

●Diabetes medical therapy

GOALS OF GLYCEMIC MANAGEMENT

General goals — The goals of perioperative diabetes management include:

●Maintenance of fluid and electrolyte balance

●Avoidance of hypoglycemia – Hypoglycemia is a potentially life-threatening complication of poor perioperative metabolic management. Severe hypoglycemia (ie, serum glucose concentration <40 mg/dL [2.2 mmol/L]), even for short periods of time, can induce arrhythmias, other cardiac events, or transient cognitive deficits. Hypoglycemia and subsequent neuroglucopenia can be difficult to detect in sedated or anesthetized patients. (See 'Avoidance of hypoglycemia' below.)

●Avoidance of marked hyperglycemia – Hyperglycemia can cause volume and electrolyte disturbances mediated by osmotic diuresis and may also result in caloric and protein loss in under-insulinized patients, which can, in turn, adversely affect wound healing. In addition, observational studies show an association between perioperative hyperglycemia in patients with diabetes and an increased risk of postoperative infection [29,30]. (See 'Glucose management' below and "Susceptibility to infections in persons with diabetes mellitus", section on 'Risk of infection'.)

●Prevention of ketoacidosis/hyperosmolar states – Patients with type 1 diabetes mellitus are insulin deficient and are prone to developing ketosis and acidosis. A potential mistake is to manage these patients like type 2 diabetes patients who are not ketosis prone (eg, holding long-acting insulin if the glucose level is in the normal range), with the consequent risk of ketoacidosis. Similarly, failure to provide pre-meal, rapid-acting insulin for persons with type 1 diabetes will result in unacceptable post-meal glucose excursions. Patients with type 2 diabetes are susceptible to developing hyperosmolar hyperglycemic state (also known as nonketotic hyperosmolar state) associated with severe volume depletion and neurologic complications, and they may develop ketoacidosis in the setting of extreme stress. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis".)

Glycemic targets — Beyond avoidance of marked hyperglycemia and hypoglycemia, optimal perioperative glucose targets have not been rigorously established. Although there are varying opinions on what the target blood glucose should be, there is little evidence to support specific targets. Given the risk of hypoglycemia (especially in unmonitored settings), in our practice, we aim to keep glucose readings between 110 and 180 mg/dL (6.1 to 10 mmol/L). However, a less stringent glucose target may be considered depending on patient comorbidities, prognosis, and risk for hypoglycemia, or when close glucose monitoring may not be available. The risk of hypoglycemia can be reduced by frequent glucose monitoring and carefully designed management protocols. (See "Management of diabetes mellitus in hospitalized patients", section on 'Glycemic targets' and "Glycemic control in critically ill adult and pediatric patients".)

The American Diabetes Association (ADA) has endorsed a target glucose range for the perioperative period of 80 to 180 mg/dL (4.4 to 10 mmol/L) [31]. Other diabetes guideline bodies recommend glycemic targets of between 90 and 180 mg/dL (5 to 10 mmol/L) for noncritically ill hospitalized patients [32,33].

In a meta-analysis of 20 randomized trials (2670 patients with diabetes) comparing intensive (<120 or <160 mg/dL [<6.7 or <8.3 mmol/L] for most trials) versus conventional (variable) glycemic targets in the perioperative period, intensive glycemic management perioperatively did not lead to significant reductions in infectious complications, length of hospital stay, or all-cause mortality, but did increase risk of hypoglycemia [34]. Intensive glycemic management slightly reduced the rate of cardiovascular events, but the quality of evidence was low. Among the trials, intensive management achieved a mean reduction in blood glucose level of 13 to 91 mg/dL (0.72 to 5.0 mmol/L) compared with conventional management.

Avoidance of hypoglycemia — Avoiding hypoglycemia during anesthesia and in the postoperative phase is important because hypoglycemic symptoms are virtually impossible for the sedated patient to sense and, similarly, its signs are difficult for health care providers to detect. The goals in the perioperative setting are to preoperatively identify patients at highest risk for hypoglycemia, appropriately adjust diabetes treatment preoperatively to prevent its occurrence, and monitor for any episodes of hypoglycemia by measuring glucose levels to ensure prompt treatment.

●Who is at risk? – Patients at high risk for perioperative hypoglycemia include patients with type 1 diabetes, particularly individuals with longer duration of diabetes, history of frequent or severe hypoglycemia, poor nutritional status, low body mass index (BMI), or impaired awareness of hypoglycemia [35-37]. Hypoglycemia may also affect patients with type 2 diabetes who use insulin or take a sulfonylurea or a meglitinide.

●Preoperative diabetes medication adjustment – (See 'Preoperative medication instructions' below.)

●Administration of dextrose-containing fluids – For all patients receiving intravenous (IV) insulin therapy or those on other insulin regimens who are nil per os (NPO) for a procedure, administration of dextrose-containing fluids can help reduce the risk of hypoglycemia. (See 'Type 1 or insulin-treated type 2 diabetes' below and 'Long and complex procedures' below.)

●Monitoring – In the perioperative setting, hypoglycemia can be detected through monitoring of blood glucose levels, which are typically checked every one to two hours during surgery (for patients treated with insulin or insulin secretagogues). (See "Anesthesia for patients with diabetes mellitus", section on 'Monitoring blood glucose'.)

After recovery from anesthesia or sedation, hypoglycemia may be suspected based upon patient-reported symptoms, including tremor, palpitations, anxiety, sweating, hunger, and paresthesias. All of these symptoms may be reduced in patients recovering from anesthesia and surgery. The hypoglycemic thresholds at which these symptoms occur are quite variable. In patients with diabetes, these symptoms of hypoglycemia may occur at glucose levels of <70 mg/dL (3.9 mmol/L). Hypoglycemia can also cause cognitive dysfunction, which may occur at plasma glucose concentrations below 60 mg/dL (3.3 mmol/L) and will further impair patients' ability to recognize and report hypoglycemia to their caretakers. More severe neurologic symptoms, including obtundation, seizures, and coma, occur with progressive hypoglycemia. The glycemic thresholds for these responses may shift to higher plasma glucose concentrations in patients with chronic hyperglycemia and to lower plasma glucose concentrations in patients with repeated episodes of hypoglycemia, such as may be associated with intensive therapy of diabetes. (See "Hypoglycemia in adults without diabetes mellitus: Clinical manifestations, causes, and diagnosis", section on 'Clinical manifestations'.)

●Management – In patients with diabetes, hypoglycemia is defined as all episodes of an abnormally low plasma glucose concentration (with or without symptoms) that expose the individual to potential harm. Although the cutoff value has been debated, clinicians should become concerned about the possibility of hypoglycemia in a perioperative patient at a glucose level ≤70 mg/dL (3.9 mmol/L). (See "Hypoglycemia in adults without diabetes mellitus: Clinical manifestations, causes, and diagnosis", section on 'Diagnostic evaluation'.)

Depending upon the blood glucose level, management options include:

•Increasing frequency of blood glucose surveillance, as needed

•Decreasing the rate of an insulin infusion or subsequent dose of subcutaneous insulin

•Administering oral carbohydrate if the clinical setting allows oral intake

•Administering IV dextrose

For a sedated, anesthetized patient with a blood glucose of <70 mg/dL, we typically administer IV dextrose (25 g) and repeat blood glucose measurements in 5 to 10 minutes. After acute treatment, continued infusion of dextrose or an increase in the infusion rate may be necessary.

In the awake patient with a normal swallowing mechanism and gag reflex, symptomatic hypoglycemia is typically treated with at least 15 g of carbohydrates (glucose tablet, sweetened fruit juice). In patients unable to take anything by mouth, hypoglycemia can be treated by giving 25 to 50 cc of 50% IV dextrose (12.5 to 25 grams). The treatment of hypoglycemia is reviewed in more detail elsewhere. (See "Hypoglycemia in adults with diabetes mellitus", section on 'Reversing hypoglycemia'.)

GLUCOSE MANAGEMENT — Several strategies exist to maintain target range glucose levels perioperatively, but there is no consensus as to the optimal approach [36,38-40]. Most protocols for insulin administration are formulated based on a combination of expert opinion and physician preference. The strategies described below, while sensible, have not been proven to optimally reduce outcomes of morbidity, mortality, and hospital length of stay. The role of insulin infusions has not been clarified, but these strategies are often expensive, labor intensive, and even impossible at some hospitals. Ultimately, even well-coordinated plans for diabetic management are dynamic, being influenced by predictable and sometimes unpredictable events. Decisions of which regimens to utilize and when to use them will depend upon individual patients, hospital settings and resources, and the clinician's own judgment.

Ideally, all patients with diabetes mellitus should have their surgery as early as possible in the morning to minimize the disruption of their management routine while being nil per os (NPO).

Preoperative medication instructions — Diabetes medications should be adjusted preoperatively to prevent hypoglycemia or excessive hyperglycemia while fasting in preparation for surgery.

Oral agent or noninsulin injectable medication — Patients with type 2 diabetes who take oral hypoglycemic drugs and/or injectable glucagon-like peptide 1 (GLP-1) receptor agonists (eg, exenatide, liraglutide, semaglutide, dulaglutide, and lixisenatide) or dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (eg, tirzepatide) are advised as follows:

●Sodium-glucose cotransporter 2 (SGLT2) inhibitors – SGLT2 inhibitors (eg, empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, bexagliflozin) should be stopped three to four days before surgery [31,41,42]. These agents increase the risk of urinary tract infections and hypovolemia. There have also been reports of postoperative euglycemic diabetic ketoacidosis in patients with type 2 diabetes taking SGLT2 inhibitors [43,44]. Euglycemic diabetic ketoacidosis may be under-recognized in the postoperative period, given its atypical presentation, and closer monitoring of ketones is required in this setting [45]. (See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Adverse effects'.)

●Other oral agents, GLP-1 receptor agonists, or dual GLP-1 and GIP receptor agonists – Daily GLP-1 receptor agonists (eg, liraglutide) and oral diabetes medications other than SGLT2 inhibitors should be withheld starting on the morning of scheduled surgery. We typically ask patients to withhold once-weekly GLP-1-based therapies for a week prior to surgery [46]. These medications are withheld for the following reasons:

•Metformin is contraindicated in conditions that increase the risk of renal hypoperfusion, lactate accumulation, and tissue hypoxia.

•Sulfonylureas and meglitinides can cause hypoglycemia.

•Thiazolidinediones may worsen fluid retention and peripheral edema and could precipitate congestive heart failure.

•Dipeptidyl peptidase 4 (DPP-4) inhibitors, GLP-1 receptor agonists, and dual GLP-1 and GIP receptor agonists could alter gastrointestinal motility and potentially increase the risk of pulmonary aspiration of gastric contents during deep sedation and general anesthesia [47]. (See "Anesthesia for patients with diabetes mellitus", section on 'Medication regimen' and "Rapid sequence induction and intubation (RSII) for anesthesia", section on 'Patients taking GLP-1 receptor agonists'.)

Since DPP-4 inhibitors are generally considered not to increase the risk of hypoglycemia, some experts continue DPP-4 inhibitors on the day of surgery [39,40].

Insulin injection — Patients with type 1 diabetes and some insulin-treated patients with type 2 diabetes are insulin deficient. They are at risk of diabetic ketoacidosis and must have basal insulin supplied at all times. Basal insulin dosing generally accounts for approximately one-half of an individual's total daily insulin dose. It is necessary to prevent ketoacidosis and limit protein loss during reduced caloric intake and perioperative stress. Therefore, basal insulin must be given to insulin-deficient patients even in the absence of oral intake [48]. Some patients may require a reduction in their usual dose of basal insulin on the morning of surgery.

The adjustment of insulin doses and regimens in the transition from usual outpatient care to inpatient and perioperative care is highly individual. The major changes in eating, activity levels and the superimposed perioperative stress, potential use of glucocorticoids, intravenous (IV) fluids with dextrose, and numerous other factors may disrupt glucose management and affect the specific choice of insulin regimens and dosing. These factors require an individualized approach to insulin management in hospitalized patients. The approach that follows provides a guideline for adjustment but cannot substitute for careful evaluation of these factors for each patient in selecting dosing perioperatively.

●Basal insulin only (type 2 diabetes)

•Once-daily dosing – Patients with type 2 diabetes who take only once-daily basal insulin (eg, NPH, glargine, detemir, degludec) may continue basal insulin without any change to their usual regimen, as long as the basal insulin dose has been adjusted appropriately as an outpatient and results in safe morning glucose levels. In patients whose basal insulin dose is calculated to keep the blood glucose in normal or low-normal ranges, or when there is history of low glucose measures as an outpatient, we often reduce the dose by 10 to 25 percent to lower the risk of perioperative hypoglycemia. (If patients need to eat to treat hypoglycemia on the morning of surgery, the surgery may need to be rescheduled for another day.) If the patient takes insulin once daily in the evening, the dose typically is reduced by 10 to 25 percent on the night prior to surgery.

In a retrospective study comparing different dose reductions of basal insulin, reducing the regularly scheduled, once-daily, evening basal insulin dose by 25 percent on the night before surgery was associated with a higher proportion of achieved target glucose level on the day of surgery [49].

•Twice-daily dosing – Patients with type 2 diabetes who take twice-daily basal insulin may also be able to continue their usual regimen, as long as the basal dose has been correctly calculated. If there is concern about preoperative hypoglycemia, we reduce both doses (morning and prior evening) by 10 to 25 percent.

●Basal and prandial insulin – For patients (with type 1 or type 2 diabetes) who take two types of insulin (basal and prandial), we advise as follows:

•Omit any prandial insulin (regular, lispro, aspart, glulisine) after fasting begins, typically on the morning of surgery.

•If basal insulin (eg, NPH, glargine, detemir, degludec) is given once daily in the morning, advise the patient to give between one-half to two-thirds of their usual total morning insulin dose (prandial plus basal insulin) as basal insulin to prevent ketosis during the procedure.

•If basal insulin is given once daily in the evening, reduce the dose of basal insulin on the evening prior to surgery by 10 to 25 percent (unless morning glucose levels are generally high, in which case, the full dose can be given).

•If basal insulin is given two or more times per day, reduce the prior evening dose by 10 to 25 percent as noted above (unless morning glucose levels are generally high, in which case, the full dose can be given) and give between one-third to one-half of the total morning dose (prandial plus basal insulin) as basal insulin on the morning of surgery.

●Pre-mixed insulin – Fixed-ratio, pre-mixed insulins are used by some patients with type 2 diabetes for convenience. In this setting, the dose on the evening prior to surgery should be reduced by approximately 20 percent and the dose on the morning of surgery by 50 percent [40]. However, if the morning blood glucose is <120 mg/dL, the morning dose should be held.

We almost never prescribe pre-mixed insulins for the treatment of type 1 diabetes (see "General principles of insulin therapy in diabetes mellitus", section on 'Pre-mixed insulins'). For the rare patient with type 1 diabetes using a pre-mixed insulin preparation, the prior evening dose should not be changed, and the morning of surgery dose can be reduced by 20 percent. If the morning blood glucose is low, the patient may need to use a basal insulin preparation (rather than a pre-mixed preparation). Patients with type 1 diabetes must have some basal insulin supplied at all times, even when not eating.

Continuous subcutaneous insulin infusion (insulin pump) — Patients using an insulin pump may continue with their usual basal infusion rate, assuming that the catheter and pump can remain safely in place during the procedure and that the patient will be awake and alert postoperatively to resume self-management. If the patient prefers to discontinue the pump at home (or if it must be discontinued due to patient or surgical conditions), they should administer basal insulin (according to their programmed insulin settings) two to three hours prior to discontinuation of the pump.

Intraoperative

Type 2 diabetes treated with diet alone — For short procedures, patients with type 2 diabetes managed by diet alone may not require any therapy perioperatively. Blood glucose levels should be checked preoperatively and soon after the surgery. IV solutions do not require dextrose if insulin is not given.

For long surgeries (more than two hours) or surgeries associated with expected high glucose levels (eg, coronary artery bypass grafting, organ transplants with steroid use), intraoperative glucose testing every one to two hours should be performed either by laboratory or point-of-care testing (capillary "fingerstick" using a blood glucose meter). Fingerstick glucose levels are less reliable in patients who are critically ill, on vasopressor agents, or hypotensive, and venous or arterial blood and laboratory testing should be used in these cases [50]. (See "Anesthesia for patients with diabetes mellitus", section on 'Monitoring blood glucose'.)

Supplemental short-acting (eg, regular) or rapid-acting (eg, lispro, aspart, or glulisine) insulin (table 1) may be given as correction insulin (subcutaneously) in patients whose glucose levels rise over the desired target (table 2). In this setting, it is typically administered every four to six hours. (See 'Correction insulin' below.)

Type 2 diabetes treated with oral hypoglycemic agents/noninsulin injectables — Most patients who are meeting glycemic targets (A1C <7 percent [53 mmol/mol]) on oral and/or noninsulin injectable agents (eg, GLP-1 receptor agonists) will not need insulin for short surgical procedures. Blood glucose should be monitored every two hours, either by laboratory or a blood glucose meter. In patients who are critically ill, on vasopressor agents, or hypotensive, venous or arterial blood and laboratory testing should be used instead of fingerstick samples with a blood glucose meter. (See "Anesthesia for patients with diabetes mellitus", section on 'Monitoring blood glucose'.)

For patients who develop hyperglycemia, supplemental short-acting or rapid-acting insulin (table 1) may be administered subcutaneously (typically every four to six hours), based on measured glucose levels (table 2). Correction insulin is administered until the patient is eating and either can resume oral agents or a basal-bolus insulin regimen. Most diabetes medications can be restarted after surgery when patients resume eating, with the exception of metformin, which should be delayed in patients with suspected renal hypoperfusion until documentation of adequate renal function. (See 'Correction insulin' below and 'Postoperative' below.)

Type 1 or insulin-treated type 2 diabetes

Short procedures — Generally, patients who use insulin can continue with subcutaneous insulin (table 1) perioperatively (rather than an insulin infusion) for procedures that are not long and complex (eg, less than two hours) [13,51-57].

●Start dextrose-containing IV solution (D5 [5% dextrose] with either water or with one-half isotonic saline) at a rate of 75 to 125 cc/hour to provide 3.75 to 6.25 g glucose/hour to avoid the metabolic changes of starvation [52-57].

●Check blood sugars either by fingerstick or with a laboratory method every hour, and more frequently if blood glucose is <100 mg/dL (5.5 mmol/L) or if the rate of fall is rapid. Fingerstick glucose levels are less reliable in patients who are critically ill, are on vasopressor agents, or are hypotensive, and venous or arterial blood and laboratory testing should be used in these cases.

●For patients who develop hyperglycemia, supplemental short-acting or rapid-acting insulin may be administered subcutaneously, based on frequently measured glucose levels (table 2). (See 'Correction insulin' below.)

Long and complex procedures

IV insulin infusion — Intravenous (IV) insulin infusion is usually required for long and complex procedures (eg, coronary artery bypass graft, renal transplant, or prolonged neurosurgical operations). There are numerous IV insulin infusion algorithms published in the literature, with insulin and glucose solutions being infused separately or as a combined glucose-insulin-potassium (GIK) solution [48,52-61]. We prefer separate insulin and glucose IV solutions, rather than a GIK infusion. Generally, insulin infusions should be started early in the morning prior to surgery to allow time to achieve stable glycemia. (See "Interactive diabetes case 12: Perioperative management of a 67-year-old patient with type 2 diabetes who undergoes coronary artery bypass surgery".)

Studies comparing subcutaneous insulin administration versus IV infusion have found a marked increase in variability of the glucose concentration when using the subcutaneous route [48,58]. The variability in plasma glucose levels with subcutaneous insulin regimens has been attributed, in part, to varying degrees of insulin absorption in the setting of vasoconstriction and hypoperfusion and hypothermia.

The safety of IV insulin infusion in highly monitored settings has been demonstrated by many studies [48,52-61]. In addition, insulin infusions are more readily titrated because the half-life of IV insulin is short (ie, 5 to 10 minutes), allowing for rapid, reliable changes in insulin delivery and more precise glucose management.

IV insulin regimens require:

●Close monitoring of blood glucose – Glucose checks should be, at minimum, every one to two hours (even shorter intervals may be required if blood glucose levels are <100 mg/dL [5.5 mmol/L] or if the rate of fall is rapid, suggesting hypoglycemia could develop quickly).

●Intraoperative glucose testing performed either by laboratory or point-of-care testing. Fingerstick glucose levels are less reliable in patients who are critically ill, are hypotensive, or are on vasopressor agents, and venous or arterial blood and laboratory testing should be used in these cases.

●Electrolyte monitoring of potassium and bicarbonate.

●Insulin infusion protocols whenever possible.

●Monitoring and interpretation of laboratory values and infusion protocols by trained staff.

An important note is that insulin infusions should not be stopped altogether, even if hypoglycemia is present, without some basal insulin for patients with type 1 diabetes to prevent ketosis. In cases of hypoglycemia, insulin infusions may be reduced and the glucose infusion increased to maintain glucose targets.

Separate insulin and glucose IV solutions — We prefer separate insulin and glucose intravenous (IV) solutions. With this regimen, dextrose is administered at approximately 5 to 10 g of glucose/hour, and a separate insulin infusion is given using short-acting insulin. Many type 1 diabetes patients require an infusion at a rate of 1 to 2 units/hour, while more insulin-resistant type 2 diabetes patients can require higher insulin rates.

A commonly followed algorithm calculates the initial rate by dividing the blood glucose level (in mg/dL) by 100 and then rounding the result in units/hour (eg, glucose of 210 mg/dL divided by 100 = 2.1 units/hour) [56]. Based on capillary glucose levels, the insulin infusion will be adjusted as needed to achieve the individualized glucose target (eg, glucose 120 to 160 mg/dL, increase by 0.5 units/hour; 160 to 200 mg/dL, increase by 1 unit/hour; >200 mg/dL, increase by 2 units/hour). In case of hypoglycemia, the insulin infusion can be decreased to 0.5 units/hour and the glucose infusion rate increased to maintain glucose targets.

The rate of insulin infusion should be titrated depending on the procedure and the degree of insulin resistance. For coronary artery bypass procedures, the insulin requirements may increase up to 10-fold, especially after recovery from the hypothermic period, necessitating an increase in the initial insulin rate by three to five times [62].

This regimen is flexible and does not require changes of entire solution bags like the GIK infusion.

Glucose-insulin-potassium infusion — The GIK drip is a single-solution infusion that includes 500 mL of 10% dextrose, 10 mmol of potassium chloride, and 15 units of short-acting insulin [63]. The solution is infused at an initial rate of 100 mL/hour. The solution can be altered depending on the blood glucose by adding or subtracting 5 units of insulin. Potassium is added to prevent hypokalemia and is monitored at six-hour intervals.

This regimen is safe because the insulin and glucose are given together, but it is more cumbersome and may require frequent changes of IV solution.

Postoperative — Blood glucose should continue to be monitored at least every two hours postoperatively until the patient is awake and alert.

●Patients treated with IV insulin infusion – If an insulin infusion has been used, it should be continued postoperatively in patients who do not resume eating. Continue to monitor plasma glucose every one to two hours. Once it seems likely that solid food will be tolerated, the patient can be transitioned to a subcutaneous regimen, and then the insulin infusion can be discontinued. Because of the short half-life of IV regular insulin, the first dose of subcutaneous insulin must be given before discontinuation of the IV insulin infusion. If intermediate or long-acting insulin is used, it should be given two to three hours prior to discontinuation, whereas short- or rapid-acting insulin should be given one to two hours prior to stopping the infusion. (See "Interactive diabetes case 12: Perioperative management of a 67-year-old patient with type 2 diabetes who undergoes coronary artery bypass surgery".)

●Patients treated with subcutaneous insulin – For patients with short procedures who were treated with subcutaneous insulin in the preoperative and intraoperative phases and who have not resumed eating, continue subcutaneous insulin along with IV dextrose (usually 5 g of glucose/hour = 100 mL/hour of 5% dextrose in water or in one-half isotonic saline solution) to prevent hypoglycemia and reduce stress related proteolysis and catabolic changes.

Once the patient is able to tolerate food, a subcutaneous basal-bolus insulin regimen can be restarted. For patients with type 2 diabetes who are hospitalized after their procedure, oral intake is almost always reduced in the hospital compared with the outpatient setting. In type 2 diabetes, insulin requirements are sensitive to reduced intake, and therefore, it may be necessary to reduce the typical outpatient dose of basal insulin (often by >25 percent) to prevent hypoglycemia. (See "Management of diabetes mellitus in hospitalized patients", section on 'Patients treated with insulin' and "Management of diabetes mellitus in hospitalized patients", section on 'Patients with type 1 diabetes'.)

●When to resume oral agents and/or GLP-1 receptor agonists – For patients with type 2 diabetes previously treated with oral agents, GLP-1 receptor agonists, or dual GLP-1 and GIP receptor agonists, the preoperative diabetes treatment regimen may be reinstated once the patient is eating well. However, there are a few caveats for certain oral hypoglycemic agents.

•Metformin should not be restarted in patients with impaired kidney function considered unsafe for metformin use (usually eGFR <30 mL/min/1.73 m²), significant hepatic impairment, or congestive heart failure. (See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Contraindications'.)

•Sulfonylureas stimulate insulin secretion and may cause hypoglycemia; they should be started only after eating has been well established. A step-up approach can be used for patients on high-dose sulfonylureas, starting at low doses and adjusting them until the usual dose is reached. (See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Precautions'.)

•DPP-4 agents may be restarted in the postoperative period when the patient is eating, as the risk of hypoglycemia is low [64,65]. (See "Dipeptidyl peptidase 4 (DPP-4) inhibitors for the treatment of type 2 diabetes mellitus".)

•GLP-1 receptor agonists and dual GLP-1 and GIP receptor agonists should not be restarted until post-anesthesia nausea and/or vomiting (if present) has resolved and the patient is eating normally. (See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Gastrointestinal'.)

•SGLT2 inhibitors should not be restarted in the inpatient setting due to risk of dehydration, volume contraction, genitourinary tract infections, and euglycemic diabetic ketoacidosis. For patients having day surgery, they can be restarted when the patient is eating and drinking normally. (See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Adverse effects'.)

•Thiazolidinediones should not be used if patients develop congestive heart failure or problematic fluid retention, or if there are any liver function abnormalities. (See "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Contraindications'.)

More details regarding the management of diabetes in hospitalized patients are found separately. (See "Management of diabetes mellitus in hospitalized patients".)

Correction insulin

●Indications – Varying doses of short-acting or rapid-acting insulin may be used to supplement usual pre-meal short-acting or rapid-acting insulin in patients on prescheduled basal and prandial insulin (basal-bolus insulin) regimens to correct pre-meal glucose excursions (table 2). In this setting, the additional insulin is referred to as "correction insulin." It may also be administered in patients with type 2 diabetes treated with basal insulin alone, either before meals or every six hours in patients who are NPO.

Correction insulin alone may be used short term, as initial insulin therapy or as a dose-finding strategy, in patients with type 2 diabetes previously treated at home with diet or an oral agent who will not be eating regularly during hospitalization. In this setting, it is typically administered every six hours as regular or rapid-acting insulin, until the patient is eating and either can resume oral agents or a basal-bolus regimen is initiated.

In randomized trials comparing sliding-scale regular insulin with a basal-bolus insulin regimen (glargine once daily and glulisine before meals) or a basal plus regimen (glargine once daily with corrective doses of glulisine before meals) in patients with oral agent-treated type 2 diabetes admitted to the hospital for general elective or emergency surgery, patients randomly assigned to sliding-scale regular insulin alone had significantly higher mean glucose concentrations (eg, 172 versus 145 mg/dL [9.6 versus 8.0 mmol/L]) and a significantly higher frequency of the composite outcome (24.3 versus 8.6 percent), which included wound infection, pneumonia, bacteremia, respiratory failure, and acute renal failure [66,67]. Among the individual components of the composite outcome, higher frequency of wound infections (10.3 versus 2.9 percent) was the only outcome that reached borderline statistical significance. (See "Management of diabetes mellitus in hospitalized patients", section on 'Patients treated with insulin'.)

●Contraindications – When used as sole methods of insulin delivery, sliding scales of correction insulin can be problematic since they delay administration of insulin until hyperglycemia is present and frequently cause wide fluctuations in the serum glucose as they only react to past glucose concentrations. Correction insulin alone should not be used as the sole treatment for patients with type 1 diabetes, in whom ketosis can occur before significant hyperglycemia is present, or for insulin-treated type 2 diabetes.

●Dosing – Corrective insulin typically is given when glucose levels are >150 mg/dL (8.3 mmol/L), and the amount of insulin depends upon the degree of insulin sensitivity of the patient, caloric intake, and the glycemic target (table 3) (see 'Glycemic targets' above). Older, lean, type 1 diabetes patients or individuals with kidney or liver failure are usually considered to be "insulin sensitive," while obesity or treatment with glucocorticoids are usually associated with an insulin-resistant state. Smaller doses of insulin are given at bedtime to avoid nocturnal hypoglycemia. Many different regimens have been used, with no studies demonstrating the superiority of one over the others. Since there is a large patient-to-patient variability in terms of insulin sensitivity and response to clinical changes, the absolute dose choice is empirical and, most importantly, frequent (daily) adjustments based on glucose levels need to be made. (See "Management of diabetes mellitus in hospitalized patients", section on 'Correction insulin'.)

SPECIAL CONSIDERATIONS

Glucocorticoid therapy — Glucocorticoids are used for the treatment of many disorders and are often given as an anti-emetic, or in "stress" doses perioperatively if adrenal insufficiency is suspected, in the setting of shock, and sometimes when intraoperative radiologic procedures use radio-opaque dye. Glucocorticoids can worsen preexisting diabetes mellitus and may precipitate steroid-induced hyperglycemia in patients without preexisting diabetes. Studies examining treatment strategies are lacking, and the recommendations presented are based primarily on simplicity of execution.

●Blood glucose ≤200 mg/dL (11 mmol/L) – Any of the oral hypoglycemic medications can be used in patients with a constant dose of steroids and minimal elevation in blood glucose (≤200 mg/dL [11 mmol/L]).

●Blood glucose >200 mg/dL (11 mmol/L) – Insulin is necessary when glucose levels are elevated (>200 mg/dL) and for patients who are started on large doses of steroids or who have their dose increased significantly. For morning prednisone-treated patients, a morning dose of intermediate-acting insulin (eg, NPH), which has the same temporal profile of glucose lowering as prednisone's glucose-raising profile, can be used to achieve acceptable glycemia. The additional benefit of using NPH in this setting rather than a long-acting insulin (eg, glargine, degludec) is that it is easier to titrate when the steroid dose is frequently changed.

Twice-daily NPH with short-acting insulin given in a subcutaneous sliding scale every six hours may be needed to achieve glucose targets in patients using longer-acting steroids or patients on steroids dosed twice daily. For patients who receive steroids long term, the daily NPH dose can be adjusted by adding up the correction doses of short-acting insulin administered on the day prior, and then by adding approximately 50 percent of the total daily correction dose to the total NPH dose.

While there are no guidelines for specific insulin regimens in patients on oral or intravenous (IV) steroids, considerations should be given to the specific steroids used and their doses, as the magnitude and timing of the hyperglycemic response depends on the type and dose of glucocorticoids. As an example, in one randomized trial of 185 patients with and without diabetes undergoing noncardiac surgery, there was little hyperglycemic response with low, anti-emetic dose dexamethasone (4 to 8 mg IV) in patients with diabetes, and only a slightly greater response in persons without diabetes [68]. However, higher doses of dexamethasone (1 mg/kg) or methylprednisolone (15 to 30 mg/kg) were associated with large increases in glucose levels in patients having cardiac surgery [69]. (See "The management of the surgical patient taking glucocorticoids" and "Major side effects of systemic glucocorticoids".)

Morning prednisone increases glucose levels for 6 to 10 hours, with values coming down during the late afternoon and night, while longer-acting steroids or twice-daily dosing will require more prolonged insulin coverage.

A two- to threefold increase in the total daily insulin dose is frequently needed in patients on high-dose steroid therapy. For such patients, a variable-rate insulin and glucose infusion may be appropriate, especially with variable dosing of glucocorticoids.

Hyperalimentation — Total parenteral nutrition (TPN) and nasogastric enteral feeds are commonly used in patients who are malnourished or severely ill. (See "Management of diabetes mellitus in hospitalized patients", section on 'Patients receiving enteral or parenteral feedings'.)

●Parenteral nutrition – TPN will often increase the serum blood glucose and necessitate large doses of insulin to achieve glycemic targets in patients with diabetes. (See "Nutrition support in critically ill patients: Parenteral nutrition" and "Overview of perioperative nutrition support".)

Some investigators recommend using a variable-rate insulin infusion when the patient is first started on TPN [70]. Once the patient is on a stable infusion rate of TPN, add 80 to 100 percent of the total insulin requirement directly to the TPN solution bag. As an example, if the patient requires 20 units of insulin per 24 hours, add 16 to 20 units of short-acting insulin in the TPN solution that is administered continuously over 24 hours. A subcutaneous insulin sliding scale using short-acting insulin may be used initially to identify the 24-hour insulin requirement if insulin infusion is not feasible, and should be converted to a twice-daily, intermediate-acting insulin if the TPN solution and rate are stable. TPN orders should always include an order to substitute dextrose infusion and recalibrate insulin dosing if the TPN is interrupted for more than an hour.

●Enteral nutrition – For nasogastric feeds administered continuously over 24 hours, either a variable-rate IV insulin infusion or twice-daily intermediate-acting insulin plus sliding-scale short-acting insulin every four to six hours may be administered. Changes in insulin regimen must precede any changes in nasogastric feeding regimens (ie, changes from 24-hour infusion to three times a day bolus feeds). As with TPN, interruption of continuous enteral feeding for more than an hour will require IV dextrose to prevent hypoglycemia and recalibration of insulin dosing. Thus, good communication between the surgeon, dietitian, and the person managing diabetes care is important.

Emergency procedures — When emergency surgery is required in a patient with diabetes whose glucose levels are very high (for example, greater than 250 mg/dL [13.9 mmol/L]) or low enough to threaten hypoglycemia (<100 mg/dL [5.5 mmol/L]), blood glucose levels should be monitored with fingerstick or whole venous blood methods at least every hour and more frequently for blood glucose levels <70 mg/dL (3.9 mmol/L).

●Many patients with type 1 diabetes and very elevated glucose levels may be managed most conveniently with an IV insulin infusion through a reliable IV access.

●For patients with type 2 diabetes and elevated blood glucose levels (>250 mg/dL [13.9 mmol/L]) who require emergency surgery, we treat with an IV insulin infusion or subcutaneous insulin. For long procedures, an insulin infusion is preferred. If the patient had been using a long-acting basal insulin (eg, glargine, degludec) once daily or a continuous infusion of short-acting or rapid-acting insulin (insulin pump), it should be continued along with the IV insulin infusion or additional corrective subcutaneous insulin.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diabetes mellitus in adults".)

SUMMARY AND RECOMMENDATIONS

●Preoperative evaluation – All patients require a careful preoperative history and physical examination, with further evaluation required in certain individuals. Basic laboratory investigation should include a baseline electrocardiogram (ECG), assessment of renal function (serum creatinine), glycated hemoglobin (A1C) if not measured in previous four to six weeks, and blood glucose. Associated conditions, such as coronary heart disease, hypertension, obesity, chronic kidney disease, cerebrovascular disease, and autonomic neuropathy, need to be assessed prior to surgery as these conditions may complicate anesthesia and postoperative care. (See 'Preoperative evaluation and planning' above and "Anesthesia for patients with diabetes mellitus".)

●Goals of glycemic management – The goals of perioperative diabetes management include avoidance of hypoglycemia, prevention of ketoacidosis, maintenance of fluid and electrolyte balance, and avoidance of marked hyperglycemia. (See 'General goals' above.)

•Glycemic targets – There are few studies evaluating the optimal intraoperative blood glucose level for patients with diabetes. During surgical procedures and in the postoperative phase, we aim to keep the glucose readings between 110 and 180 mg/dL (6.1 to 10 mmol/L). Glycemic targets must take into account the individual patient's situation and whether these goals can be safely achieved within each individual hospital system. (See 'Glycemic targets' above.)

•Timing of surgery – Ideally, all patients with diabetes mellitus should have their surgery prior to 9 AM to minimize the disruption of their management routine while being nil per os (NPO). (See 'Glucose management' above.)

●Preoperative medication instructions

•Oral agent or noninsulin injectable medications – Patients with type 2 diabetes who take sodium-glucose cotransporter 2 (SGLT2) inhibitors (eg, empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, bexagliflozin) should discontinue them three to four days before surgery. Daily glucagon-like peptide 1 (GLP-1) receptor agonists (eg, liraglutide) and oral diabetes medications other than SGLT2 inhibitors should be withheld starting on the morning of scheduled surgery. We typically ask patients to withhold once-weekly GLP-1-based therapies for a week prior to surgery. (See 'Preoperative medication instructions' above and "Anesthesia for patients with diabetes mellitus", section on 'Medication regimen'.)

•Insulin injection – Patients with type 1 diabetes and some insulin-treated patients with type 2 diabetes are insulin deficient. They are at much higher risk of diabetic ketoacidosis and must have some basal insulin supplied at all times, even when not eating. Prandial insulin (regular, lispro, aspart, glulisine) should be stopped when caloric intake is discontinued in preparation for surgery. (See 'Insulin injection' above.)

●Intraoperative glucose management

•Type 2 diabetes treated with diet – For short procedures, patients with type 2 diabetes managed by diet alone may not require any therapy perioperatively. Blood glucose levels should be checked preoperatively and soon after the surgery. For long surgeries (more than two hours) or surgeries associated with expected high glucose levels (eg, coronary artery bypass grafting, organ transplants with steroid use), intraoperative glucose testing every one to two hours should be performed either by laboratory or point-of-care testing (capillary "fingerstick" using a blood glucose meter). Supplemental short-acting (eg, regular) or rapid-acting (eg, lispro, aspart, or glulisine) insulin (table 1) may be given subcutaneously (typically every four to six hours) to patients whose glucose levels rise over the desired target (table 2). (See 'Type 2 diabetes treated with diet alone' above and 'Correction insulin' above.)

•Type 2 diabetes treated with oral agent and/or noninsulin injectable medication – For patients with type 2 diabetes managed with oral agents and/or noninsulin injectables (eg, GLP-1 receptor agonists), blood glucose should be monitored every two hours, either by laboratory or point-of-care testing (capillary "fingerstick" using a blood glucose meter). For patients who develop hyperglycemia, supplemental short-acting or rapid-acting insulin (table 1) may be administered subcutaneously (typically every four to six hours), based on measured glucose levels (table 2). (See 'Type 2 diabetes treated with oral hypoglycemic agents/noninsulin injectables' above and 'Correction insulin' above.)

•Type 1 or insulin-treated type 2 diabetes – Generally, patients who use insulin can continue with subcutaneous insulin perioperatively at a reduced dose (rather than an insulin infusion) for procedures that are not long and complex (eg, no more than one or two missed meals). However, IV insulin infusion is usually required for long and complex procedures (eg, coronary artery bypass graft, renal transplant, or prolonged neurosurgical operations). (See 'Type 1 or insulin-treated type 2 diabetes' above.)

●Postoperative glucose management – If an insulin infusion has been used, it should be continued postoperatively in patients who do not resume eating. Continue to monitor glucoses every one to two hours. Once it seems likely that solid food will be tolerated, the patient can be switched to subcutaneous insulin, and then the insulin infusion can be discontinued. For most patients with type 2 diabetes, the preoperative diabetes treatment regimen (oral agents, noninsulin injectables, oral agents plus insulin, or basal-bolus insulin) may be reinstated once the patient is eating well. However, there are a few caveats for certain oral hypoglycemic agents. (See 'Postoperative' above.)