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Insulin therapy in the intensive care unit 

Insulin therapy in the intensive care unit
Insulin therapy in the intensive care unit

Greet Van den Berghe

, Yoo-Mee Vanwijngaerden

, and Dieter Mesotten

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date: 19 May 2022

Critical illness triggers an acute stress response, of which the inflammatory reaction has always been in the forefront of clinical interest. Nevertheless, the changes in metabolism during acute critical illness have also been well characterized for a long time. Increased metabolic rate and release of large quantities of glucose, fatty acids, and amino acids from the body’s stores result in hyperglycaemia, hyperlipidaemia, and increased protein turnover. Until recently, these metabolic changes have been deemed adaptive or even beneficial, and metabolic intervention studies have been limited. Metabolism needs to redirect energy supply to vital organs, such as the brain and the blood cells, which rely mainly on glucose as their source of energy. The mobilization of amino acids for example supports healing of wounded tissues and synthesis of acute phase proteins in the liver. Although the acute metabolic changes may have beneficial connotations, it is also well established that a prolonged stress response triggers a sustained and irreversible catabolic state, with excessive breakdown of lean body mass, which may hamper recovery (1).

Until recently, blood glucose control has not been a major focus for the intensive care physician. Only in patients with known diabetes mellitus were blood glucose levels more regularly measured, and even then without a widely accepted treatment policy. Nevertheless, patients without established diabetes mellitus develop hyperglycaemia too. The practice of ‘permissive hyperglycaemia’, tolerating blood glucose levels up to 12 mmol/l (215 mg/dl) in fed critically ill patients, was considered standard care. Blood glucose concentrations of 9–11 mmol/l (160–200 mg/dl) were recommended to maximize cellular glucose uptake while avoiding hyperosmolarity, osmotic diuresis, and fluid shifts. In addition, moderate hyperglycaemia was often viewed as a buffer against hypoglycaemia-induced brain damage. Consequently, intravenous insulin infusions, and certainly clear-cut blood glucose targets, were rarely used.

Nevertheless, hyperglycaemia is clearly associated with adverse outcome. Large observational studies in critically ill patients and patients with a myocardial infarction reveal a J-shaped relationship between blood glucose level and the risk of mortality. In all those studies, the lowest risk of death is when admission or mean circulating glucose levels are between 5 and 8 mmol/l (90 and 140 mg/dl). Remarkably, in patients with established diabetes mellitus prior to intensive care admission, the relationship between hyperglycaemia and mortality is significantly blunted and shifted to the right (Fig. As these associations are derived from observational studies, hyperglycaemia could still either reflect an adaptive, beneficial response (‘just a marker of severity of illness’), or could actively induce complications, as in diabetes mellitus, and hereby contribute to adverse outcomes (‘cause of disease’). In order to show a causal relationship between hyperglycaemia and mortality risk, randomized controlled trials that target and achieve different blood glucose levels had to be done.

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