Objective Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. Methods The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575–590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit? (2) Should we monitor preload and fluid responsiveness in shock? (3) How and when should we monitor stroke volume or cardiac output in shock? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock? Four types of statements were used: definition, recommendation, best practice and statement of fact. Results Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. Conclusions This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock.

Early resuscitation is a key factor to limit progression to multiple organ dysfunction and death in patients with septic shock.^1,2 Shock is characterized by increased serum lactate levels and signs of tissue hypoperfusion including abnormal peripheral perfusion.²

Rationale: It is unknown whether lactate monitoring aimed to decrease levels during initial treatment in critically ill patients improves outcome. Objectives: To assess the effect of lactate monitoring and resuscitation directed at decreasing lactate levels in intensive care unit (ICU) patients admitted with a lactate level of greater than or equal to 3.0 mEq/L. Methods: Patients were randomly allocated to two groups. In the lactate group, treatment was guided by lactate levels with the objective to decrease lactate by 20% or more per 2 hours for the initial 8 hours of ICU stay. In the control group, the treatment team had no knowledge of lactate levels (except for the admission value) during this period. The primary outcome measure was hospital mortality. Measurements and Main Results: The lactate group received more fluids and vasodilators. However, there were no significant differences in lactate levels between the groups. In the intention-to-treat population (348 patients), hospital mortality in the control group was 43.5% (77/177) compared with 33.9% (58/171) in the lactate group (P = 0.067). When adjusted for predefined risk factors, hospital mortality was lower in the lactate group (hazard ratio, 0.61; 95% confidence interval, 0.43–0.87; P = 0.006). In the lactate group, Sequential Organ Failure Assessment scores were lower between 9 and 72 hours, inotropes could be stopped earlier, and patients could be weaned from mechanical ventilation and discharged from the ICU earlier. Conclusions: In patients with hyperlactatemia on ICU admission, lactate-guided therapy significantly reduced hospital mortality when adjusting for predefined risk factors. As this was consistent with important secondary endpoints, this study suggests that initial lactate monitoring has clinical benefit. Clinical trial registered with www.clinicaltrials.gov (NCT00270673).

To assess the safety and efficacy of the nitric oxide synthase inhibitor 546C88 in patients with septic shock. The predefined primary efficacy objective was survival at day 28. Multiple-center, randomized, two-stage, double-blind, placebo-controlled, safety and efficacy study. A total of 124 intensive care units in Europe, North America, South America, South Africa, and Australasia. A total of 797 patients with septic shock diagnosed for <24 hrs. Patients with septic shock were allocated to receive 546C88 or placebo (5% dextrose) for up to 7 days (stage 1) or 14 days (stage 2) in addition to conventional therapy. Study drug was initiated at 0.05 mL.kg(-1).hr(-1) (2.5 mg.kg(-1).hr(-1) 546C88) and titrated up to a maximum rate of 0.4 mL.kg(-1).hr(-1) to maintain mean arterial pressure between 70 and 90 mm Hg while attempting to withdraw concurrent vasopressors. Hemodynamic variables, organ function data, microbiological data, concomitant therapy, and adverse event data were recorded at baseline, throughout treatment, and at follow-up. The primary end point was day-28 survival. The trial was stopped early after review by the independent data safety monitoring board. Day-28 mortality was 59% (259/439) in the 546C88 group and 49% (174/358) in the placebo group (p <.001). The overall incidence of adverse events was similar in both groups, although a higher proportion of the events was considered possibly attributable to study drug in the 546C88 group. Most of the events accounting for the disparity between the groups were associated with the cardiovascular system (e.g., decreased cardiac output, pulmonary hypertension, systemic arterial hypertension, heart failure). The causes of death in the study were consistent with those expected in patients with septic shock, although there was a higher proportion of cardiovascular deaths and a lower incidence of deaths caused by multiple organ failure in the 546C88 group. In this study, the nonselective nitric oxide synthase inhibitor 546C88 increased mortality in patients with septic shock.