Hydroxyethyl starch (HES) is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis.

Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization. A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621.)

For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival. Randomized controlled open-label trial. Nine multidisciplinary intensive care units across Denmark. A total of 1,200 critically ill patients were included after meeting the following eligibility requirements: expected intensive care unit stay of ≥ 24 hrs, nonpregnant, judged to not be harmed by blood sampling, bilirubin <40 mg/dL, and triglycerides <1000 mg/dL (not suspensive). : Patients were randomized either to the "standard-of-care-only arm," receiving treatment according to the current international guidelines and blinded to procalcitonin levels, or to the "procalcitonin arm," in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements. The primary end point was death from any cause at day 28; this occurred for 31.5% (190 of 604) patients in the procalcitonin arm and for 32.0% (191 of 596) patients in the standard-of-care-only arm (absolute risk reduction, 0.6%; 95% confidence interval [CI] -4.7% to 5.9%). Length of stay in the intensive care unit was increased by one day (p = .004) in the procalcitonin arm, the rate of mechanical ventilation per day in the intensive care unit increased 4.9% (95% CI, 3.0-6.7%), and the relative risk of days with estimated glomerular filtration rate <60 mL/min/1.73 m was 1.21 (95% CI, 1.15-1.27). Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit. The procalcitonin strategy like the one used in this trial cannot be recommended.

Objectives To evaluate the long term effects of perioperative β blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. Design Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. Setting University anaesthesia and surgical centres and one coordinating centre. Participants 921 patients aged > 39 scheduled for major non-cardiac surgery. Interventions 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days. Main outcome measures The composite primary outcome measure was time to all cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. Secondary outcome measures were time to all cause mortality, cardiac mortality, and non-fatal cardiac morbidity. Results Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462 patients in the metoprolol group (21%) and 93 of 459 patients in the placebo group (20%) (hazard ratio 1.06, 0.80 to 1.41) during a median follow-up of 18 months (range 6-30). All cause mortality was 16% (74/462) in the metoprolol group and 16% (72/459) in the placebo group (1.03, 0.74 to 1.42). The difference in risk for the proportion of patients with serious adverse events was 2.4% (− 0.8% to 5.6%). Conclusions Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes. Confidence intervals, however, were wide, and the issue needs reassessment. Trial registration Current Controlled Trials ISRCTN58485613 [controlled-trials.com.