ARTICLE REVIEW

The original NICE-SUGAR trial tried to answer the question: Does intensively controlled blood glucose compared to conventionally controlled blood glucose reduce mortality at 90 days in critically ill adults that are expected to be in Intensive Care for 3 days or more? In their 2009 publication, the authors concluded that tighter blood glucose control 4.5 to 6.0mmol/L (compared to a target of less than 10mmol/L) was associated with an increase in mortality at 90 days and an increase in the incidence of significant hypoglycaemia.(1) To date, it is the largest trial (over 6000 patients) which examined the effect of intensive glucose control in the critically ill.

Following on from their original study, the NICE-SUGAR investigators have published (Intensive Care Med June, 2015) the results of a pre-planned subgroup analysis of patients with traumatic brain injuries (TBI).(2)These patients may be at particular risk of adverse outcomes in the context of significant hypoglycaemia.

The intensive control arm targeted a blood glucose range of between 4.5 to 6.0mmol/L whilst the conventional arm targeted blood glucose of less than 10mmol/L. Patients with traumatic brain injuries were identified at the point of randomisation using the following criteria:

• Trauma was the primary reason for hospital admission
• Last non-sedated GCS of 13 or less
• Abnormality on CT scan consistent with acute TBI

Of the 6104 patients from the original cohort, 391 patients were identified as having TBI. 203 (51.9%) were assigned to the intensive arm and 188 (48.1%) were in the conventional arm. Key outcome findings:

• No difference in extended Glasgow outcome score at 2 years
• No difference in mortality at 2 years
• The incidence of moderate and severe hypoglycaemic episodes were significantly greater in the intensive control group

In the original study by Van den Berghe et al., intensive glucose control is associated with lower intracranial pressures and improved functional survival.(3) This new study failed to establish such a benefit. Even though there was an increased incidence of hypoglycaemic episodes, this did not translate to an increase in mortality or morbidity.

Despite some limitations, the strengths of this study include the large number of patients involved (being a sub-group analysis) and a relatively long follow-up time of 2 years.

Take-home message

Targeting moderate glucose control (less than 10mmol/L) is an appropriate strategy for critically ill patients with acute neurological insults, including TBI.

This article review was prepared by ESICM Journal Club member Adrian Wong on behalf of the NEXT Committee.

References

1. Finfer S, et al. Intensive versus conventional glucose control in critically ill patients. The New England Journal of Medicine, 2009. 360(13):1283-1297
2. Finfer S and The NICE SUGAR Study Investigators. Intensive versus Conventional Glucose Control in Critically Ill Patients with Traumatic Brain Injury: Long term follow up of a subgroup of patients from the NICE SUGAR Study. Intensive Care Medicine, June 2015 (IN PRINT)
3. Van den Berghe, G., Schoonheydt, K., Becx, P., Bruyninckx, F., and Wouters, P. J. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology,  2005. 64:1348-1353