The global burden of critical care and decreasing sepsis mortality

The mortality of sepsis may be decreasing and, because there are more survivors, it is increasingly important to understand the epidemiology, pathogenesis, genetics, prevention, and treatment of the impaired long-term outcomes of sepsis. Recent insights on the clearance of bacterial products during sepsis suggest new strategies for early intervention. Immune suppression/immune reprogramming to decrease later secondary infections is a novel strategy now in clinical trials. The Protocolized Care for the Early Septic Shock (ProCESS), Australasian Resuscitation in Sepsis Evaluation (ARISE) and ProMISe randomized controlled trials (RCTs) of early goal-directed therapy (EGDT) usual care found no differences between groups in mortality. versus Fluid therapies may not require full-on EGDT, but rather emphasize the importance of early recognition and resuscitation of sepsis. The Albumin Italian Outcome Sepsis (ALBIOS) RCT did not find a difference between albumin (titrated to serum albumin >30 g/L) and crystalloid in severe sepsis. However, in a subgroup analysis, mortality was lower in the albumin group in patients who had septic shock. Therapeutic use of albumin may be beneficial in septic shock, but requires further evaluation in RCTs. A recent RCT of conservative liberal transfusion strategies (70 90 g/L, respectively) found no versus versus difference in mortality in septic shock. The transfusion threshold in septic shock is now 70–90 g/L. Although there was no difference in mortality between a usual or a high target mean arterial pressure (MAP) for septic shock resuscitation, a higher MAP target may be beneficial in patients who have pre-existing hypertension, because higher MAP may decrease the incidence of acute kidney injury (AKI) and need for renal replacement therapy (RRT). Nutrition practice can continue with enteral nutrition started on days 2–3 (i.e., early but there is no indication for very early parenteral nutrition). Acute respiratory distress syndrome (ARDS) is the commonest complication of sepsis. Two recent RCTs of simvastatin and rosuvastatin in ARDS were not positive. Early statins at appropriate doses and plasma levels deserve a trial in sepsis. In future, perhaps three changes could improve the chances of having positive trials in sepsis: the use of biomarkers to stratify patients; adaptive trial design to enhance dose selection and reject compounds that are unlikely to be suitable at Phase 2; and the use of composite organ dysfunction as the primary outcome. 1,2