Hyperglycaemia and mortality in critically ill patients. A prospective study.

OBJECTIVE: To describe hyperglycaemia as a possible marker of morbidity and mortality in critically ill medical and surgical patients admitted to a multidisciplinary ICU. DESIGN: Prospective cohort study. SETTING: A 13-bed non-cardiac multidisciplinary ICU in a university hospital. PATIENTS AND PARTICIPANTS: Adult patients consecutively admitted to the ICU in a 6-month period. Patients with fewer than 2 days' stay in the ICU and patients with known diabetes were excluded. MEASUREMENTS AND RESULTS: At admission a registration form was filled in including demographic data, first and second day APACHE II scores, infections and daily maximum blood glucose level. In surgical patients, high maximum blood glucose level during the stay in ICU was correlated with increased mortality, morbidity and frequency of infection. In medical patients, we found a non-significant trend towards a correlation between hyperglycaemia and morbidity and mortality, respectively. CONCLUSIONS: High blood glucose level during the stay in ICU was a marker of increased morbidity and mortality in critically ill surgical patients. In medical patients the same trend was found, but non-significant. The population of patients in the present study are heterogeneous and the results from surgical critically ill patients should not be generalised to medical patients.

Acute hyperinsulinemia restrains endotoxin-induced systemic inflammatory response: an experimental study in a porcine model.

BACKGROUND: Intensive insulin therapy in critically ill patients reduces morbidity and mortality. The current study elucidates whether acute hyperinsulinemia per se could attenuate the systemic cytokine response and improve neutrophil function during endotoxin (lipopolysaccharide)-induced systemic inflammation in a porcine model. METHODS: Pigs were anesthetized, mechanically ventilated, randomized into four groups, and followed for 570 min: group 1 (anesthesia solely, n = 10), group 2 (hyperinsulinemic euglycemic clamp [HEC], n = 9), group 3 (lipopolysaccharide, n = 10), group 4 (lipopolysaccharide-HEC, n = 9). Groups 3 and 4 were given a 180-min infusion of lipopolysaccharide (total, 10 microg/kg). Groups 2 and 4 were clamped (p-glucose: 5 mM/l, insulin 0.6 mU.kg(-1).min(-1)) throughout the study period. Changes in pulmonary and hemodynamic function, circulating cytokines, free fatty acids, glucagon, and neutrophil chemotaxis were monitored. RESULTS: Tumor necrosis factor alpha and interleukin 6 were significantly reduced in the lipopolysaccharide-HEC group compared with the lipopolysaccharide group (both P = 0.04). In the lipopolysaccharide-HEC group, the glucagon response was diminished compared with the lipopolysaccharide group (P < 0.05). Serum free fatty acid concentrations were decreased in animals exposed to HEC. Animals receiving lipopolysaccharide showed an increase in pulmonary pressure (P < 0.001), but otherwise, there were no major changes in pulmonary or hemodynamic function. Neutrophil function was impaired after lipopolysaccharide administration. CONCLUSION: Hyperinsulinemia concomitant with normoglycemia reduces plasma concentrations of tumor necrosis factor alpha and the catabolic hormone glucagon in lipopolysaccharide-induced systemic inflammation in pigs. The finding strongly supports the role of insulin as an antiinflammatory hormone. Whether the effect to some extent operates via a reduced free fatty acid concentration is unsettled.

The roles of insulin and hyperglycemia in sepsis pathogenesis.

Hyperglycemia is a risk marker of morbidity and mortality in acute critical illness, and insulin therapy seems to be beneficial in this patient group. Whether this is true for a population of sepsis patients, as such, has not been investigated in clinical trials, but evidence from in vitro studies and experimental sepsis suggests that this may be the case. The endocrinology of septic patients is characterized by a shift in the balance between insulin and its counter-regulatory hormones favoring the latter. This leads to prominent metabolic derangements composed of high release and low use of glucose, amino acids, and free fatty acids (FFA), resulting in increased blood levels of these substrates. Circulating, proinflammatory mediators further enhance this state of global catabolism. Increased levels of glucose and FFA have distinct effects on inflammatory signaling leading to additional release of proinflammatory mediators and endothelial and neutrophil dysfunction. Insulin has the inherent capability to counteract the metabolic changes observed in septic patients. Concomitantly, insulin therapy may act as a modulator of inflammatory pathways inhibiting the unspecific, inflammatory activation caused by metabolic substrates. Given these properties, insulin could conceivably be serving a dual purpose for the benefit of septic patients.

[The systematic inflammatory response after major trauma]. / Det systemisk inflammatoriske respons ved akutte traumer.

Few investigations have elucidated the acute inflammatory response after accidental trauma before the patients were anesthetized and treated with analgetics and intravenous fluid. The cellular immunological response seems to be characterized by an initial activation followed by suppression. In major tissue trauma, the granulocytes are the major effector cells. Activated granulocytes are redistributed from the peripheral blood into the tissues, where release of proteolytic enzymes and oxygen-free radicals participate in the development of systemic inflammation and organ dysfunction. The antigen presentation capacity of monocytes and the cytotoxicity of NK-cells are reduced following major trauma. High concentrations of proinflammatory and antiinflammatory cytokines can be measured locally in the injured tissue. In uncomplicated cases, elevated cytokine concentrations are measured in the blood for a few days, whereas a sustained high cytokine production seems to correlate with organ dysfunction and mortality.