A 76 year old man with no comorbidities was admitted to the intensive care unit following an oesophagectomy. During routine blood sugar monitoring, his blood glucose was found to be just over 10 for two consecutive readings so he was commenced on a variable rate insulin infusion. Six hours later, despite hourly monitoring, he had a blood sugar of 3.6. The insulin infusion was stopped and his blood sugar rose back to normal levels. He suffered no apparent ill effects from his hypoglycaemic episode.

What is the rationale behind current glycaemic control on the intensive care unit?

Helen Vollmer

Until 2008 the majority of intensive care units in the United Kingdom were using intensive insulin therapy to maintain tight glycaemic control.(1) This was following the landmark study by Van den Berghe et al published in 2001, which found that intensive insulin therapy maintaining blood glucose levels at or below 6.1mmol/l in predominantly cardiac surgical patients conferred a reduction in bloodstream infections, renal failure, blood transfusions, critical-illness polyneuropathy, ventilated days and mortality.(2) This was reinforced by a further study, by the same author, demonstrating a survival benefit in medical critically ill patients who stayed in the intensive care unit for greater than 3 days. Interestingly for those patients staying less than 3 days, the mortality was greater in those who received intensive insulin therapy.(3)

Research published in 2008-9, including a trial by The Normoglycaemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study committee, challenged the earlier studies by finding that intensive glucose control increased mortality among adults in intensive care as opposed to those patients treated with a conventional approach of maintaining blood glucose levels less than 10mmol/l. Other studies (VISEP and Glucontrol) were terminated early due to the higher incidence of hypoglycaemia in the intensive insulin therapy groups. There has been a corresponding shift in UK intensive care units (as in this unit) to a conventional glycaemic control protocol with a target blood glucose of 10mmol/l or less, in line with the results of these studies.(1)

The deleterious effect of hypoglycaemia is well known. Hypoglycaemia in intensive care patients is defined on a biological threshold without account of neurological signs, which is different to the definition in diabetic patients which emphasises the clinical features. Critically ill patients are often unable to describe clinical symptoms due to a spontaneous or sedation-induced reduction in consciousness. This inability to detect early warning signs increased the risk of severe hypoglycaemia.

Hyperglycaemia in the non-diabetic critically ill is due to insulin resistance and is part of the physiological stress response. It has been found to increase morbidity and mortality in non-cardiac surgical patients. A blood glucose level >11.1mmol/l also strongly correlates with higher APACHE II scores, organ dysfunction and a higher risk of infections.(5) Peri-operative hyperglycaemia is associated with surgical site infections which have implications for mortality, morbidity and healthcare economics. A Cochrane review found no evidence to support strict glycaemic control over a conventional strategy when looking at perioperative insulin therapy in reducing surgical site infections.(6)

However, it is difficult to ascertain whether a transient post-operative hyperglycaemia has the same effects as persisting hyperglycaemia in a long stay criticall ill surgical patient. Glycaemic control in cardiac and neurosurgical patients has been demonstrated to confer benefit but there is a paucity of studies in the literature on general surgical patients. General surgical patients are still a heterogeneous group encompassing elective gastro-intestinal and non-intestinal surgery as well as emergency patients with conditions such as faecal peritonitis. The above studies do not make the distinction between different groups of surgical patients. It is possible that other hospitals use a separate surgical high dependency facility to monitor the elective cases post-operatively and that patients such as described in this case are not admitted to their intensive care units and therefore not part of the data collected for these trials.

The use of protocols for glycaemic control is recommended(7) and are in widespread use(1). Standardisation of intravenous insulin therapy across a mixed medical/surgical intensive care unit has been shown to reduce the incidence of hypoglycaemia by four-fold as well as improve efficiency in terms of time taken to achieve target range for blood glucose and length of time blood glucose is maintained in the target range.(8) This study used an intensive insulin protocol with a target range of 4.5-6.1mmol/l, so the benefits of a protocol may be less marked if using a conventional target of<10mmol/l.

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References:

1) Paddle J, Eve R, Sharpe K. Changing practice with changing research: results of two UK national surveys of intensive insulin therapy in intensive care patients. Anaesthesia 2011; 66:92-96
2) Van den Berghe G, Wouters P, Weekers F et al. Intensive insulin therapy in critically ill patients. New England Journal of Medicine 2001; 345(19):1359-1367
3) Van den Berghe G, Wilmer A, Hermans G et al. Intensive insulin therapy in the medical ICU. New England Journal of Medicine 2006; 354(5):449-461
4) The NICE-SUGAR Investigators. Intensive v conventional glucose control in critically ill patients. New England Journal of Medicine 2009; 360(13):1283-1297
5) Christiansen C, Toft P, Jorgensen H et al. Hyperglycaemia and mortality in critically ill patients. Intensive Care Medicine 2004; 30:1685-1688
6) Kao L, Meeks D, Moyer V, Lally K. Peri-operative glycaemic control regimens for preventing surgical site infections in adults. Cochrane Database of Systematic Reviews 2009; 3(CD006806):1361-6137
7) Ichai C, Preiser J-C. International recommendations for glucose control in adult non-diabetic critically ill patients. Critical Care 2010; 14:R166
8) Kanji S, Singh A, Tierney M et al. Standardisation of intravenous insulin therapy improves the efficiency and safety of blood glucose control in critically ill adults. Intensive Care Medicine 2004; 30:804-810