Approach
The principles of managing patients with newly diagnosed hyperglycemia or diabetes remain the same as those for patients with well-known and established diabetes. However, additional factors must be considered. Insulin resistance and insulin secretion can be affected by many factors in patients admitted to the hospital. In addition, most inpatients have unreliable oral intake, frequent procedures requiring changes in nutrition, and new drug schedules. Patients taking oral drugs as outpatients may be unable to continue these drugs in the hospital due to fluctuating renal function or procedures requiring intravenous contrast (metformin), heart failure exacerbations (thiazolidinediones), or inability to have oral intake before surgery.
Distinguishing between type 1 diabetes mellitus, type 2 diabetes mellitus, and new-onset hyperglycemia can help establish a clear plan for glycemic control during hospital admission. Patients with newly discovered hyperglycemia have been shown to have a significantly higher in-hospital mortality than patients who have a history of diabetes or people with normoglycemia.[8] Vigilance is needed for detecting ketoacidosis in patients with type 1 diabetes. See Diabetic ketoacidosis
In both the critical and noncritical care venues, glycemic control should be individualized to the patient's status and to the resources available to the hospital system.[1][20] Both hyperglycemia and hypoglycemia are associated with higher mortality, independent of known history of diabetes.[3][11]
Management strategy and goals remain similar in medical and surgical patients, but hypoglycemia is a more frequently encountered problem in medical patients, and outcomes are worse in this group; therefore, avoidance of hypoglycemia is essential.[15]
Goals of glycemic control
With the recognition that hyperglycemia is not simply a result of stress or illness, but a condition that requires treatment in its own right, multiple trials have been undertaken to better elucidate the goals of glycemic control for critically ill patients; the conclusions from this research have varied from advising tight glucose control in the intensive care unit (ICU) to suggesting there is no mortality benefit of intensive insulin therapy and that a higher mortality may even be associated with tight glycemic control.[21][22][23]
The American Diabetes Association (ADA) recommends the glycemic goals for most critically ill individuals with hyperglycemia to be 140-180 mg/dL [(7.8-10.0 mmol/L]), with more stringent goals (110-140 mg/dL [6.1-7.8 mmol/L]) for selected critically ill individuals as long as this can be attained without significant hypoglycemia.[1]
The Canadian Diabetes Association recommends target glucose levels between 106 and 180 mg/dL (6.0 to 10.0 mmol/L) for most critically ill hospitalized patients.[2]
Uncontrolled hyperglycemia; surgery; or critical illness
Insulin is considered the preferred form of treatment for inpatients. Intravenous insulin infusion is the preferred method of delivering insulin in critically ill patients.[20] In patients with type 1 diabetes, withholding insulin may lead to ketoacidosis. Infusion of dextrose for nutrition, along with intravenous insulin administration, is essential.
In patients who are not critically ill but have uncontrolled hyperglycemia, or are to undergo surgery, treatment often involves starting subcutaneous insulin and stopping oral drugs. Subcutaneous insulin doses can then be adjusted as needed.
Several randomized trials have shown that a basal-bolus insulin regimen is more effective in controlling hyperglycemia than sliding scale insulin alone in noncritically ill patients admitted to the hospital.[24][25] The Endocrine Society recommends that adults with diabetes treated with diet or noninsulin medications who experience hyperglycemia >140 mg/dL (>7.8 mmol/L) may begin initial therapy with correctional insulin or scheduled insulin to maintain glucose targets in the range of 100-180 mg/dL (5.6 to 10.0 mmol/L). This target of 100-180 mg/dL (5.6 to 10.0 mmol/L) is also the same for adults with insulin-treated diabetes prior to admission who are hospitalized for noncritical illness.[4] The ADA recommends that, for noncritically ill individuals, insulin therapy should be started or intensified to treat persist hyperglycemia if blood glucose readings are ≥180 mg/dL (≥10.0 mmol/L) on two separate occasions within 24 hours.[1] The ADA also advises that either basal insulin or basal plus bolus correctional insulin may be used in noncritically ill hospitalized patients with poor oral intake or those who are taking nothing by mouth. Note that sliding scale insulin alone is strongly discouraged in the inpatient setting.[1]
Other considerations include:
For patients who were on insulin at home, their home doses can be added up to give their total daily insulin dose.
For subcutaneous insulin, basal insulin can either be long-acting (glargine, detemir, degludec) or intermediate-acting (NPH). Second-generation basal insulins, such as insulin glargine (300 units/mL) and insulin degludec (100 units/mL and 200 units/mL), have lower peak-to-trough ratios, have longer duration of action than the first-generation basal insulins, and provide less glycemic variability. Patients who use these preparations can be continued on these while in the hospital.[26][27]
For regimens using long-acting insulin, one half of the total daily dose is given as long-acting insulin and one half as rapid-acting insulin. Long-acting insulin should be given once or twice daily. Rapid-acting insulin should be given in divided doses before each meal.[24]
For regimens using intermediate-acting insulin, two-thirds of the total daily dose is given in the morning (further divided into two-thirds NPH insulin and one third fast-acting insulin), and one third in the evening (further divided into half fast-acting with the evening meal and half NPH with the evening meal or preferably at bedtime).
One study suggests that basal insulin plus sliding scale insulin is an option for patients with type 2 diabetes. In 375 patients with type 2 diabetes randomized to receive basal insulin (glargine) plus sliding scale insulin (glulisine), basal insulin (glargine) and scheduled mealtime plus correction sliding scale insulin (glulisine), or sliding scale insulin alone (regular insulin), the two regimens - basal plus sliding scale, and basal plus scheduled mealtime plus sliding scale - achieved the same glycemic control, and performed better than sliding scale alone.[28]
One randomized controlled trial comparing basal-bolus insulin with or without supplemental short-acting insulin at bedtime to correct bedtime hyperglycemia in patients with type 2 diabetes found no improvement in mean fasting glucoses with the use of the bedtime supplement. Therefore, correction of bedtime hyperglycemia with fast-acting insulin is not recommended for inpatients with type 2 diabetes.[29]
The authors of this topic do not recommend the use of sliding scales alone in the majority of clinical circumstances. However, sliding scales may be used on occasion for 24 hours to determine the insulin requirements in some patients. Additionally, sliding scales alone can be considered for patients hospitalized with noncritical illness and no history of diabetes with only mild hyperglycemia >140 mg/dL but <180 mg/dL.[4]
Essentially, the principles of glucose management in patients with newly detected hyperglycemia remain the same as those for patients with established diabetes. Avoiding hypo- and hyperglycemia is particularly important, as in some settings this has been associated with worse outcomes.[30]
For patients receiving insulin infusions in the ICU, established computerized protocols that recommend predetermined changes in infusion rates are increasing in popularity.[1] They facilitate nursing processes, improve efficiency, and have been shown to reduce glucose variance.[31] In addition, coadministration of basal insulin analog may facilitate the transition from intravenous to subcutaneous insulin.[1] Use of the real-time continuous glucose monitor (CGM) has been shown to lower the incidence of hypoglycemia but increases nursing workload.[32] Others have commented on the "migration" of the outpatient glucose meter to the ICU owing to its ease of use and speediness. However, results from a central laboratory are obviously more accurate than those from a handheld device. Perhaps if intensive insulin therapy and tight glycemic control are to remain the standard of care, improving the accuracy of the bedside glucose measurement will help to avoid hypoglycemia.[33] The ADA recommends bedside blood glucose monitoring every 30 minutes to 2 hours for patients receiving intravenous insulin.[1]
The AACE guidelines recommend intravenous insulin for all critically ill patients with hyperglycemia above target.[3][11] A variety of protocols have been published and, although there are extremely few head-to-head comparisons, the end results are similar in all.[1][3][11][21][34][35] Yale Insulin Infusion Protocol Opens in new window
Surgery:
Patients admitted for minor elective surgery who take oral antidiabetic drugs may continue their oral drug if the procedure is short and the patient is expected to eat later the same day.
For longer, more complicated procedures, oral drugs are usually discontinued in favor of starting basal-bolus insulin given subcutaneously starting the day of surgery.
While there are little data to inform the timing of discontinuation of glucagon-like peptide-1 (GLP-1) receptor agonists prior to surgery, the American Society of Anesthesiologists (ASA) recommends considering discontinuation of weekly GLP-1 receptor agonists 1 week before elective surgery due to the risk of pulmonary aspiration of gastric contents.[36] For patients on daily dosing, the advice from the ASA is to consider holding GLP-1 agonists on the day of elective surgery. There is ongoing debate as to whether these recommendations are reasonable.[37]
For patients using insulin before hospitalization, the dose of intermediate-acting insulin is reduced by 30% to 50% the day of surgery. True basal insulins such as glargine or detemir can usually be given at or close to their routine dose. Rapid-acting insulins are held while the patient is not eating.
Long and complicated surgical procedures require intravenous insulin infusion for glucose control and there are a number of algorithms available. In converting stable post-surgical patients from intravenous insulin to subcutaneous basal-bolus regimens, the total daily intravenous dose can be reduced by 20%. Fifty percent of that total is then administered as long-acting insulin once or twice daily, with the other 50% divided into two or three premeal injections.
Supportive care:
Hypoglycemia must be avoided.[20] In all patients, adequate nutrition and fluid replacement should be ensured. Total parenteral nutrition may be required in patients who are not eating. In patients with type 1 diabetes, a dextrose-containing intravenous fluid is appropriate, along with insulin administration.
Electrolytes should be monitored and corrected as required. Potassium should be added to intravenous fluids according to local floor protocols to prevent and treat hypokalemia.
Discharge:
Measurement of HbA1c is valuable in determining the plan at discharge. A high HbA1c indicates poor preexisting control and suggests need for increased or modified antidiabetic therapy (e.g., starting insulin or maximizing oral agents).[3][8]
A wide range of therapy is available for long-term diabetes management. Some patients may need to continue taking insulin at home until complete recovery allows a transition to other drugs.[20]
Patients without known diabetes also need follow-up blood sugar levels, possible tests for diagnosis, and possible continued treatment.
Well-controlled pre-existing diabetes: stable non-critical illness
Insulin is considered the preferred form of treatment for most inpatients. Oral drugs may be used carefully in selected patients whose blood sugars are well controlled and who are eating normally, if there are no contraindications and it can be assured that the patient's feeding status will not be switched to nil by mouth. Metformin use should be closely monitored given its contraindications (renal impairment, acute heart failure, contrast studies), though will probably need to be discontinued. Thiazolidinediones are not recommended in those patients with fluid retention as part of their presenting condition. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have been associated with diabetic ketoacidosis, including euglycemic diabetic ketoacidosis, and it is recommended to stop them upon admission, and 3 days prior to scheduled surgery.[38] However, the use of SGLT2 inhibitors in the hospital setting remains a subject of investigation with specific patients appearing to benefit from their addition.[39] The ADA recommends that patients with type 2 diabetes hospitalized with heart failure be started or continued on an SGLT2 inhibitor after recovery from acute illness if no contraindications are present.[1]
Drugs with hypoglycemic effects may be difficult to dose appropriately with changes in a patient's feeding status.
Type 1 diabetes
Patients admitted to the hospital who have well-controlled blood glucose levels can continue taking their usual insulin regimen if meal consumption remains similar to home intake. The ADA recommends that an insulin schedule with basal and correction components is necessary for all hospitalized people with type 1 diabetes, even when taking nothing by mouth, with the addition of prandial insulin when eating.[1] A reduction of the mealtime insulin doses can be made depending on food consumption.
Type 2 diabetes
There is no strong evidence to suggest whether patients with type 2 diabetes should continue taking oral antidiabetic drugs if they can as inpatients. Most inpatients would be switched to basal-bolus insulin regimen. However, physicians could consider allowing well-controlled, normoglycemic patients who are eating to continue on their oral antidiabetic drugs if there are no contraindications and if it can be assured that the patient's feeding status will not be switched to nil by mouth.
Several randomized trials show that patients with mild to moderate hyperglycemia can be managed with dipeptidyl dipeptidase-4 inhibitors with or without long-acting basal insulin.[40][41][42]
Hypoglycemia
Patients at increased risk of hypoglycemia include those with reduced nutritional intake, malnutrition, renal or hepatic impairment, heart failure, malignancy, infection, sepsis, older age, and cognitive impairment.[1][3][11]
Compared with sliding scale insulin, basal-bolus insulin is more frequently associated with hypoglycemia.[15][20] Insulin can induce hypoglycemia leading to neuroglycopenia. Hypoglycemia is associated with adverse outcomes, especially in ICU patients. Sedation or beta-blockers may mask symptoms of neuroglycopenia, and counter-regulatory responses may be impaired. Changes in corticosteroid dosing, reduced dextrose or parenteral nutrition given intravenously, or altered oral nutritional intake may also result in hypoglycemia. Oral drugs that are insulin secretagogues (sulfonylureas or meglitinides) may also potentially precipitate hypoglycemia.
The ADA and the AACE recommend reassessing the insulin regimen when the patient's blood glucose is <100 mg/dL (<5.6 mmol/L), and modifying the regimen when the glucose is <70 mg/dL (<3.9 mmol/L).[1][3][11]
Hypoglycemia should be avoided by regular monitoring of blood glucose and changes in therapy as needed; for example, reducing an insulin infusion rate promptly. Oral glucose or orange juice may be given for mild hypoglycemia in patients taking orally. For severe or refractory hypoglycemia, or in patients unable to take orally, 50% dextrose should be given intravenously and the blood glucose monitored closely for the next hour. Some clinicians prefer to use a 10% or 20% glucose (dextrose) solution to reduce the risk of post-treatment hyperglycemia or extravasation injury.[43] Alternatively, glucagon can be given intramuscularly. Newer glucagon formulations are available in some countries; see Emerging treatments.
Children
In a randomized trial on pediatric patients undergoing cardiac surgery, tight glycemic control with blood glucose targets of 80-110 mg/dL (4.4 to 6.1 mmol/L) did not significantly change the infection rate, mortality, length of stay, or measures of organ failure, compared with standard care.[44] In a trial of critically ill pediatric patients (cardiac surgery patients excluded) with hyperglycemia, patients in the tight glycemic control group (blood glucose targets of 80-110 mg/dL [4.4 to 6.1 mmol/L]) had higher rates of healthcare-associated infections and significantly higher rates of severe hypoglycemia compared with those in the higher blood glucose targets (150-180 mg/dL [8.3 to 10.0 mmol/L]) group. No significant differences in mortality, measures of organ failure, or the number of ventilator-free days compared with standard care were observed. The trial was stopped early as critically ill children had no evidence of benefit from tight glycemic control, but were at risk of possible harm.[45] Where available, a pediatric endocrinologist should be consulted when managing hospitalized children with diabetes, particularly if critically ill.
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