Effect of intensive insulin therapy on coagulation and fibrinolysis of respiratory critically ill patients

Most intensive care deaths beyond the first few days of critical illness are attributable to nonresolving multiple organ failure (MOF), either due to or coinciding with sepsis. One of the mechanisms that is thought to contribute to the pathogenesis of MOF is microvascular thrombosis. Recently, we reported improved survival and prevention of MOF of critically ill patients with the use of intensive insulin therapy to maintain normoglycemia for at least several days [1, 2]. We hypothesize that intensive insulin therapy also prevents severe coagulation abnormalities, thereby contributing to less organ failure and better survival.

We studied a subgroup of long-stay critically ill patients with a respiratory disease upon ICU admission, who had been enrolled in a randomized controlled trial evaluating the impact of intensive insulin therapy in medical ICU patients [2]. Plasma samples were analyzed for a panel of coagulation markers (prothrombin time, activated partial thromboplastin time, fibrinogen and D-dimer levels) that were used to assign points towards the International Society of Thrombosis and Haemostasis overt disseminate intravascular coagulation (DIC) score. Circulating plasma thrombin–antithrombin complexes and plasminogen inhibitor type 1 levels were also determined. As markers of inflammation, we measured circulating serum levels of several cytokines and CRP.

Mortality of intensive insulin-treated patients was lower than of conventionally treated patients for all classes of upon-admission DIC score, except for those patients with a DIC score of 6 or higher. There was no effect of insulin therapy on any of the fibrinolytic, coagulation or inflammatory parameters tested. The accuracy of the DIC score to predict mortality in this patient sample was only moderate and comparable with that of CRP and the SOFA score. Also, circulating plasminogen inhibitor type 1 or thrombin–antithrombin complexes levels did not correlate well with mortality or DIC score.

These findings indicate that the coagulation system did not play a key role in mediating the survival benefit of intensive insulin therapy.