The latest NEJM has an article addressing an issue that I recently posted about, glucose control in the critically ill. This study was in 980 children less than 3 years of age who had undergone cardiac surgery in 2 centers in the US. They were randomized either to tight glucose control, aiming for 4.4 to 6.1 mmol/l, or standard care. Agus MS, Steil GM, Wypij D, Costello JM, Laussen PC, Langer M, Alexander JL, Scoppettuolo LA, Pigula FA, Charpie JR et al: Tight glycemic control versus standard care after pediatric cardiac surgery. N Engl J Med 2012, 367(13):1208-1219.
Standard care meant according to whatever the attending intensivist thought was a good idea, and only 9 of the controls received insulin. Now one feature of this study is that there were not that many controls who were very hyperglycaemic, about 2/3 of each group were above 6.1 at admission to the cardiac ICU, but most controls gradually came down to normal levels pretty quickly even without insulin. Which meant that the groups received the same total glucose infusion, and the same calories. The article is accompanied by an editorial from Brian Kavanagh, Kavanagh BP: Glucose in the icu — evidence, guidelines, and outcomes. New England Journal of Medicine 2012, 367(13):1259-1260. who points out the hazards of writing guidelines, which sometimes turn out to be based on information later shown to be incorrect, as well as reviewing the current status of glucose control in the critically ill child or adult.
So what does this mean for the preterm? It is important to recognize that the mechanisms of hyperglycemia in the preterm are quite different. There is a relative insulin deficiency due to immature processing of proinsulin by the beta cells, and in addition there is a relative insulin resistance, shown by a failure to suppress glucose production during insulin infusion, this insulin resistance is probably due to an immaturity of the GLUT-4 insulin responsive glucose transporter. There is a good short review by Delphine Mitanchez which describes much of the physiology, and another more extensive (in French) by the same author here.
These factors lead to a much higher incidence of hyperglycemia in the extremely preterm, at much lower levels of glucose intake, which lasts much longer. So, as usual, you can’t extrapolate the results from older patients (even though 20% of the patients were less than 30 days old) to small preterm babies.
What the NEJM study also showed was a very low incidence of hypoglycemia in the intervention group, 3%, showing that you can achieve tight control relatively safely, in this study the intervention group had a continuous glucose monitor, but all the insulin dose decisions were based on a bedside glucose meter the results of which were “entered into a proportional–integral–derivative insulin-dosing algorithm on a Microsoft Excel spreadsheet displayed on a dedicated laptop computer at the patient’s bedside.” I have no idea what that means but it sounds high tech; so I am sure that Proportional Integrative Derivative is what we need!