on 21-Nov-2021 (Sun)

On the one hand, the stress of the acute illness tends to raise blood glucose concentrations. On the other hand, the anorexia that often accompanies illness or the need for fasting before procedures tend to do the opposite. Because the net effect of these countervailing forces is not easily predictable in a given patient, the target blood glucose concentration should generally be higher than when the patient is stable.

In general, the goals are to:

● Avoid hypoglycemia

● Avoid severe hyperglycemia, volume depletion, and electrolyte losses

● Ensure adequate nutrition

● Assess patient educational needs and address informational deficiencies

● Ensure appropriate glucose management upon discharge until patient can be seen by the clinician managing his or her diabetes as an outpatient

Hypoglycemia should be avoided if at all possible. Measures to reduce the risk of hypoglycemia include:

● Adequate reduction in antihyperglycemic therapy when caloric intake is stopped or reduced.

● Avoidance of standard "sliding scale" of insulin without consideration of the patient's specific circumstances.

● Avoidance of overly aggressive attempts to provide "tight" glycemic management intraoperatively [3] or with intensive insulin therapy in critically ill patients [4].

Although relatively brief and mild hypoglycemia does not usually have clinically significant sequelae, hospitalized patients are particularly vulnerable to severe, prolonged hypoglycemia since they may be unable to sense or respond to the early warning signs and symptoms of low blood glucose.

Hypoglycemia (ie, serum glucose concentration <70 mg/dL [3.9 mmol/L]) can be harmful due to the effects of counterregulatory hormones, especially catecholamines, which may possibly induce arrhythmias and other cardiac events. This is especially true in older adults and those with preexisting ischemic heart disease.

If the blood glucose falls to or below 54 mg/dL (3.0 mmol/L, termed "clinically significant hypoglycemia"), cognitive deficits may also ensue, which can lead to falls or aspiration. In a retrospective cohort study of over 2500 patients with diabetes hospitalized in the general wards, inpatient mortality was significantly higher for patients with at least one hypoglycemic (≤50 mg/dL [2.8 mmol/L]) episode [ 5].

Serious hyperglycemia should be avoided (see 'Prevention and treatment of hyperglycemia' below). Hyperglycemia can cause volume and electrolyte disturbances mediated by osmotic diuresis and may also result in caloric and protein loss in under-insulinized patients.

Whether or not hyperglycemia imposes an independent risk for infection is a controversial issue. It is a longstanding clinical observation that patients with diabetes are more susceptible to infection [6]. Furthermore, immune and neutrophil function are impaired during marked hyperglycemia.

For most noncritically ill hospitalized patients with diabetes, we suggest a preprandial blood glucose target <140 mg/dL (7.8 mmol/L) with all random glucose values <180 mg/dL (10 mmol/L).

In general, all glucose levels should be kept below the 180 mg/dL (10.0 mmol/L) range to avoid further escalations, which may be associated with dehydration, glycosuria, and caloric loss, and to reduce the risk of infection and, although rare, of developing ketoacidosis

A reasonable glycemic goal to avoid hypoglycemia is to achieve fasting blood glucose concentrations no lower than 90 to 100 mg/dL (5.0 to 5.6 mmol/L); this will usually provide a reasonable "cushion" in case the concentration falls further as the patient's illness improves.

For the majority of critically ill patients, we agree with ADA recommendations for a blood glucose target of 140 to 180 mg/dL (7.8 to 10.0 mmol/L) [10]. Achieving this goal will usually require an insulin infusion, which should be initiated for persistent hyperglycemia ≥180 mg/dL (10.0 mmol/L). The data supporting these glycemic goals are presented separately.

Treatment of hyperglycemia in hospitalized patients depends upon the type of diabetes, the patient's current blood glucose concentrations, prior treatment, the clinically assessed severity of illness, and the expected caloric intake during the acute episode (algorithm 1 and algorithm 2) [1,11-13].

In the absence of controlled clinical trials or even observational data regarding how best to manage the inpatient with diabetes, the management approach outlined below is based primarily upon clinical expertise.

Importantly, in patients with diabetes (or hyperglycemia) who are eating, the blood glucose monitoring should occur just before the meal. In those who are receiving nothing by mouth, or receiving continuous tube feeds or total parenteral nutrition, the blood glucose monitoring should occur at regular, fixed intervals, usually every six hours.

Although most patients will have type 2 diabetes, many will require insulin therapy, if only temporarily, during inpatient admissions. In such patients, insulin may be given subcutaneously with an intermediate-acting insulin, such as neutral protamine hagedorn (human NPH), or a long-acting (basal) insulin analog, such as glargine, detemir, or degludec combined with a pre-meal rapid-acting insulin analog (lispro, aspart, glulisine) in patients who are eating regular meals (ie, a "basal-bolus" regimen) (algorithm 1 and algorithm 2).

In the usual patient with type 2 diabetes managed with oral agents or injectable glucagon-like peptide 1 (GLP-1) receptor agonists, and whose glucose management is good on admission, the temporary use of a sliding scale is reasonable for just one to two days as the trajectory of the patient's glycemic management becomes apparent (see 'Correction insulin' below). However, after this period of time, a decision should be made about a more physiological glucose management strategy for the remainder of the hospitalization (algorithm 1 and algorithm 2).

This was illustrated in an observational study of 171 patients with diabetes who were admitted to a university hospital, 130 of whom (76 percent) were placed on a sliding-scale insulin regimen [14]. Sliding-scale insulin regimens when administered alone were associated with a threefold higher risk of hyperglycemic episodes as compared with no therapy (relative risk [RR] 2.85 for "aggressive" scales, beginning at blood glucose 150 mg/dL [8.3 mmol/L] and 3.25 for "conservative" scales, beginning at blood glucose 200 mg/dL [11.1 mmol/L; p<0.05]). Thus, in this observational study, the use of sliding-scale insulin alone provided no benefit.

Varying doses of rapid-acting insulin can be added to usual pre-meal rapid-acting insulin in patients on basal-bolus regimens to correct pre-meal glucose excursions. In this setting, the additional insulin is referred to as "correction insulin" (algorithm 1 and algorithm 2). It is added to planned mealtime doses to correct for pre-meal hyperglycemia. The dose of correction insulin should be individualized based upon relevant patient characteristics, such as previous level of glucose management, previous insulin requirements, and, if possible, the carbohydrate content of meals. When administered prior to meals, the type of correction insulin (eg, short acting or rapid acting) should be the same as the usual pre-meal insulin.

However, some practitioners institute intravenous insulin therapy (human regular insulin in solution) in certain circumstances, such as those with marked hyperglycemia (blood glucose >300 to 350 mg/dL [>16.7 to 19.4 mmol/L]) or in type 1 diabetes, especially those undergoing long and difficult surgery or those who will be expected to have significantly curtailed oral nutritional intake for several days postoperatively. There are little data showing that intravenous insulin is superior to subcutaneous insulin.

In addition, the safe implementation of insulin infusion protocols requires frequent monitoring of blood glucose, which is not typically available on a general medical ward. Practical considerations including skill and availability of the nursing staff may impact the choice of delivery; complex intravenous regimens may be dangerous where nurses are short staffed or inexperienced

Several published insulin infusion protocols appear to be both safe and effective, with low rates of hypoglycemia, although most have been validated only in the ICU setting, where the nurse-to-patient ratio is higher than on the general medical and surgical wards [13,15,16].

In the course of giving an intravenous regular insulin infusion, we recommend starting with approximately half the patient's usual total daily insulin dose, divided into hourly increments until the trend of blood glucose values is known, and then adjusting the dose accordingly. A reasonable regimen usually involves a continuous insulin infusion at a rate of 1 to 5 units of regular insulin per hour; within this range, the dose of insulin is increased or decreased according to the patient's usual insulin dose.

In patients who are not eating, concomitant glucose infusion is necessary to provide some calories, reduce protein loss, and decrease the risk of hypoglycemia; separate infusions allow for more flexible control.

When the patient receiving intravenous insulin is more stable and the intercurrent event has passed, the prior insulin regimen can be resumed, assuming that it was effective in achieving glycemic goals. Because of the short half-life of intravenous regular insulin, the first dose of subcutaneous insulin must be given before discontinuation of the intravenous 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.

For a patient with reasonable glycemic management (A1C ≤8 percent) at home with diet or an oral agent, correction insulin alone (varying doses of short- or rapid-acting insulin) is a reasonable initial treatment strategy (see 'Correction insulin' above).

If the patient is unable to eat normally, oral agents (or injectable GLP-1 receptor agonists) should be discontinued. In patients who are eating and who do not have contraindications to their oral agent, oral agents (or injectable GLP-1 receptor agonists) may be cautiously continued

However, if contraindications develop or if blood glucoses are persistently elevated (>180 mg/dL [10.0 mmol/L]), these drugs should be discontinued and a more formal and comprehensive insulin regimen prescribed (algorithm 1 and algorithm 2). Therapy should be returned to the patient's previous regimen (assuming that it had been effective) as soon as possible after the acute episode, usually as soon as the patient has resumed eating his or her usual diet.

However, if the patient is eating and fingerstick glucose levels are consistently elevated (≥180 mg/dL [10.0 mmol/L]), a basal-bolus insulin regimen should be initiated. Insulin requirements can be estimated based upon a patient's body weight (algorithm 1). Alternatively, requirements can be based upon the total number of units of correction insulin administered over the course of a hospital day. Approximately 50 percent of the total daily dose can be given as basal insulin, and the remaining approximately 50 percent can be given in equally divided doses prior to meals (one-third prior to each meal).