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(BQ) Part 1 book Reducing mortality in critically ill patients has contents: Tight glycemic control, high frequency oscillatory ventilation, glutamine supplementation in critically ill patients, diaspirin cross linked hemoglobin and blood substitutes, supranormal elevation of systemic oxygen delivery in critically ill patients,... and other contents.
Part II Interventions that Increase Mortality Tight Glycemic Control Cosimo Chelazzi, Zaccaria Ricci, and Stefano Romagnoli 8.1 General Principles: Stress-Induced Hyperglycemia Stress-induced hyperglycemia is common in critically ill and surgical patients, with an incidence of 50 % and 13 %, respectively [1] Critical illness is associated with alterations in homeostasis, i.e., the ability of the organism to keep a physiologic balance [2] When environmental/endogenous stimuli challenge this balance, a shift to a state of “allostasis” occurs, whose target is to reach a new steady state involving all systems, including metabolism During acute critical illness, this response is adaptive, while in prolonged/chronic critical illness is seen as maladaptive [2, 3] Circulating tumor necrosis factor-α (TNF-α), secreted by macrophages in response to infection, passes the hematoencephalic barrier and activates the hypothalamic-pituitary-adrenal axis (HPA) with increased secretion of cortisol, which in turn promotes hepatic glycogenolysis and gluconeogenesis TNF-α inhibits gene transcription for glucose transporter family (GLUT-4), inhibiting intracellular insulin-dependent glucose uptake in adipocytes and myocytes [4] Other metabolic features include decreased levels of insulin-like growth factor-1, reduced peripheral T4-T3 conversion, and suppression of testosterone secretion Endogenous catecholamines increase as well This neurohormonal response progressively drives the metabolism toward hypercatabolism and peripheral insulin resistance in order to preserve energy production in tissues directly involved in acute stress responses, such as white blood cells [2] Hepatic glycogenolysis and C Chelazzi, MD (*) • S Romagnoli Department of Anesthesia and Intensive Care, Oncological Anesthesiology and Intensive Care Unit, Largo Brambilla, 3, Florence, Italy e-mail: cosimochelazzi@gmail.com Z Ricci Pediatric Cardiac Intensive Care Unit, Department of Pediatric Cardiac Surgery, Bambino Gesù Children’s Hospital, Rome, Italy © Springer International Publishing Switzerland 2015 G Landoni et al (eds.), Reducing Mortality in Critically Ill Patients, DOI 10.1007/978-3-319-17515-7_8 63 64 C Chelazzi et al protein breakdown are enhanced in order to promote hepatic gluconeogenesis and synthesis of acute phase proteins, e.g., C-reactive protein and fibrinogen Clinically, a progressive hyperglycemia is observed (“stress hyperglycemia”/“stress diabetes”) whose severity is related to extent and severity of the causing event (see below) In case of prolonged critical illness, insulin resistance, hypercatabolism, and deleterious consequences of acute hyperglycemia become relevant These include: increased susceptibility to infections, mitochondrial dysfunction, persistent inflammation, immune paralysis, anemia, and, possibly, increased mortality [3] 8.2 Clinical Associations of Stress-Induced Hyperglycemia Stress-induced hyperglycemia is associated with worse outcomes in many clinical scenarios, i.e., stroke, traumatic brain injury, myocardial infarction, cardiothoracic surgery, trauma, and burns [5–8] Among 1,826 critically ill patients, those who died had significantly higher glycemia at admission in intensive care unit (ICU) and during their stay [9] Patients with acute myocardial infarction and stroke are particularly susceptible to acute hyperglycemia [5, 7, 8, 10–12] Hyperglycemic trauma patients had increased ICU/hospital length of stay and higher mortality rates, possibly related to increased nosocomial infections and duration of mechanical ventilation (MV) [13] In patients with traumatic brain injury, hyperglycemia at admission was independently related to worse neurological outcomes [14] After coronary artery bypass, the association between hyperglycemia and poor outcome is even stronger, including higher rates of mortality and sternal wound infections, longer ICU length of stay, and increased risk for stroke, myocardial infarction, sepsis, or death [15, 16] Among noncardiac surgical patients, hyperglycemia is associated with higher risk of overall and cardiovascular 30-day mortality This evidence prompted researchers to implement strategies to control hyperglycemia in critically ill patients Although initial results were promising, safety concerns arose about hypoglycemia during continuous insulin infusion The optimal blood glucose target, the ideal method for glucose monitoring, and insulin protocols are still a matter of debate 8.3 Tight Glycemic Control: Main Lines of Evidence In 2001 the Leuven trial, a single-center randomized study, by Van Den Berghe et al., enrolled 1,548 surgical patients to receive intensive insulin therapy (IIT) with continuous intravenous insulin infusion or conventional blood glucose management [17] Targeted blood glucose for IIT patients was 80–110 mg/dL, while for controls was 180–200 mg/dL In all patients, a mix of glucose infusion and parenteral/enteral nutrition was used to reach the caloric intake and prevent hypoglycemia The results of this study were a significant reduction in ICU (−42 %) and in-hospital mortality (−34 %) in the IIT group compared with controls Intensive Tight Glycemic Control 65 insulin therapy was associated with reduced incidence of acute renal failure (−41 %) and blood stream infections (−46 %) Transfusion requirements and incidence of polymyoneuropathy were lower in the IIT group Only % of the enrolled patients were diabetic The incidence of hypoglycemia was significantly higher in the IIT group The strikingly positive results of this study fostered great interest around glycemic control The results were partially reproduced in diabetic patients undergoing coronary artery bypass and treated with IIT to target a blood glucose of 100–150 mg/dL, with a reduction in mortality rate and mediastinitis when compared to historical controls [18] In 2003, Krinsley confirmed better survival rates for patients receiving IIT to target a glycemia of