Individualising blood glucose control in ICU patients: evidence and practical implementations.

Many intensive care unit patients develop hyperglycaemia, and this is associated with an increased risk of adverse outcomes. Landmark randomised controlled trials (RCTs) suggest the impact of lowering blood glucose to the healthy, age-adjusted fasting range, hereafter called tight glucose control, depends on the accuracy of the glucose control protocol and the nutritional strategy. In the context of early parenteral nutrition, a condition that induces severe, iatrogenic hyperglycaemia, tight glucose control significantly reduced morbidity and mortality compared to tolerating severe hyperglycaemia. In the absence of early parenteral nutrition, hyperglycaemia was less severe; tight glucose control, applied with a computerised protocol that avoided severe hypoglycaemia, did not impact mortality nor the duration of ICU dependency as primary endpoint in a large multicentre RCT, but was associated with a less pronounced benefit on selected morbidity outcomes. Conversely, tight glucose control, using a protocol that considerably increased the risk of severe hypoglycaemic events, concomitantly increased mortality; nevertheless, the cause of excess mortality in this trial remains unproven and other mechanisms may have contributed as well. Altogether, evidence suggests that severe and iatrogenic hyperglycaemia and hypoglycaemia should both be avoided. From a pathophysiologic point of view, tight glucose control may be superior in selected settings if it can be applied with a validated protocol that avoids severe hypoglycaemia. In the absence of such a protocol, the increased risk of severe hypoglycaemia may offset any benefit of preventing hyperglycaemia, and tolerating intermediate blood glucose targets is likely the default setting. In the paper, we suggest specific blood glucose targets that differ according to the clinical context. Future research should aim at strategies that further optimise the quality of blood glucose control and study whether these improve patient-centred outcomes, and investigate whether specific patient populations benefit from individualised targets.