(NEJM 2008;358(2):125) Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis Background The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. Methods In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/), or modified Ringer’s lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points. Results The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [ mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [ mmol per liter], P ). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, 40 mg per deciliter [ mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (% vs. %, P ), as was the rate of serious adverse events (% vs. %, P=). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer’s lactate. Conclusions The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. ( number, NCT00135473  .)
Every hour of delay can increase mortality by %, and time to antibiotic initiation has been shown to be the strongest predictor of patient outcome ! 19,20 In a Canadian study involving patients with meningitis, a delay of antibiotics by 6 hours increased mortality 8 fold. 21 Factors involved in antibiotic selection include assessment of the likely source, host/patient factors, and local antibiotic resistance patterns (consulting the local antibiogram is essential). Gram-positive infections account for over 50% of cases, with gram-negative accounting for approximately 35%. The important aspect is covering for suspected organisms. If the patient is unresponsive, evaluate the antibiotic regimen and ensure you have adequate coverage. Broadening antibiotics early is better than too narrow of coverage. 21,22
The process of infection by bacteria or fungi may result in systemic signs and symptoms that are variously described. Approximately 70% of septic shock cases were once traceable to gram-negative bacteria that produce endotoxins , however, with the emergence of MRSA and the increased use of arterial and venous catheters, gram-positive bacteria are implicated approximately as commonly as bacilli . In rough order of increasing severity these are, bacteremia or fungemia; sepsis, severe sepsis or sepsis syndrome; septic shock, refractory septic shock, multiple organ dysfunction syndrome, and death.