Risk factors for hyperglycemia
Diabetes mellitus.
Medications including exogenous glucocorticoids, vasopressors, lithium, and beta‐blockers.
Inflammatory conditions including sepsis.
Overfeeding, intravenous dextrose, commonly used parenteral nutrition.
Dialysis solutions, antibiotic solutions.
Insufficient insulin.
Volume depletion can cause hyperglycemia.
Bed rest.
Prevention of hyperglycemia
In order to potentially reduce the adverse effects of hyperglycemia, it has to be recognized early with the necessary management implemented immediately. However, other than early detection and management, there is no evidence of any means of preventing hyperglycemia prior to its occurrence.
Diagnosis
Differential diagnosis of hyperglycemia in the ICU
| Differential diagnosis | Features |
| Diabetes mellitus | Elevated hemoglobin A1c, weight loss, polyuria, polydipsia |
| Hormonal disorders such as Cushing's disease or acromegaly | Elevated cortisol/growth hormone, weight gain, Cushingoid features |
| Drug such as steroids, sympathomimetic drugs | History of medication use |
Typical presentation
Critically ill patients with hyperglycemia present differently compared with otherwise healthy diabetic patients. In a critically ill patient, polyuria, polydipsia, and other common symptoms of hyperglycemia may not be present. Patients may present with acute kidney injury and decreased urine output. Due to the severity of illness, including delirium and mechanical ventilation, patients may not be able to communicate their symptoms. Moreover, given the acuity of glucose change, the physical exam may be equivocal and therefore routine blood tests are essential for diagnosis.
Clinical diagnosis
History
Symptoms depend on both glucose level and duration of hyperglycemia:
Cardiovascular: myocardial injury, electrolyte imbalances causing arrhythmia.
Constitutional: lethargy.
Gastrointestinal: nausea, vomiting.
Neurologic: mental status changes, encephalopathy, seizures, chorea, and other involuntary movements.
Renal: polyuria, acute kidney injury.
Physical examination
Depending on the cause of hyperglycemia, some physical exam findings may be present. In stress‐induced hyperglycemia, however, arguably the commonest cause in the critically ill patient, the physical exam may not be very revealing.
Physical exam findings may include acanthosis nigricans in diabetes mellitus and Cushingoid features in Cushing’s disease.
Laboratory diagnosis
Blood gas analyzers are considered accurate, making them the ideal test in the critical care unit. Blood gas analysis requires arterial blood draws, and monitoring via an arterial line would be preferred to provide adequate glucose control. Despite being invasive, it is the consensus recommendation for glucose monitoring of severely ill patients.
Non‐invasive point‐of‐care (POC) glucose testing devices utilizing fingerstick or tiny amounts of blood obtained via an indwelling vascular line are the most widely used tests for hyperglycemia. These provide rapid results in critically ill patients where glucose fluctuations are unpredictable. POC testing, however, is inaccurate, sometimes differing by as much as 20% from reference values.
Continuous glucose monitoring systems of the glucose in the interstitial space every 10 seconds is a promising test providing an average glucose value every 5 minutes.
The glucose trend may be more useful than the absolute glucose value when using less accurate blood glucose monitors such as POC and continuous interstitial glucose monitors.
Stress‐related hyperglycemia in the ICU is acute and therefore would not usually cause an elevation in hemoglobin A1c, making this a method to potentially differentiate between stress‐induced hyperglycemia and long‐standing diabetes.
Potential pitfalls/common errors made regarding diagnosis of disease
The diagnosis of diabetes mellitus in the ICU is commonly missed given the incidence of hyperglycemia due to secondary causes. One study showed that 26% of diabetic patients were undiagnosed during their admission to the ICU. These patients had a higher likelihood of requiring an insulin infusion, higher average blood glucose, an increased percentage of hyperglycemia and hypoglycemia (i.e. higher glycemic variability), and increased mortality. These findings suggest that a high suspicion of diabetes in order to anticipate insulin requirement might be beneficial.
Due to glycemic variability in the critically ill patient, routine monitoring, sometimes continuous, is recommended. A patient who is normoglycemic on admission may not remain so throughout their ICU stay and may even require an insulin infusion at some point depending on the degree of hyperglycemia. Therefore routine glucose measurements are recommended during critical illness with strict guidelines on initiation of insulin therapy.
Treatment
Much controversy surrounds the idea of what constitutes ideal blood glucose targets in the critically ill patient. Multiple trials have yielded contradictory results. Initially, stringent glucose level control was advocated; however this recommendation was challenged because of the recognition that hyperglycemia was the body's way of adapting to stress. In the early 2000s, the Leuven surgical trial concluded that intensive glucose control decreased mortality. Despite the faults of this trial, it created a movement for strict glucose goals of around 120 mg/dL.
However, the subsequent NICE‐SUGAR trial, targeting a glucose level less than 180 mg/dL, showed decreased mortality and less hypoglycemia compared with intensive glucose control. Despite the contradicting evidence, the consensus at this time is to target a glucose level of 140–180 mg/dL.
There is no universally accepted insulin regimen for glycemic control in critically ill patients. However, to avoid prolonged hypoglycemia, which may be harmful, insulin infusions and intermittent short‐acting insulin are typically used until the patient is stable enough to be transitioned to subcutaneous
