Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU.

BACKGROUND: Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 .).

A single-centre, prospective cohort study of COVID-19 patients admitted to ICU for mechanical ventilatory support.

BACKGROUND: Mortality rates in COVID-19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may not be generalizable due to differences in demographics, healthcare organization and surge capacity. We present a cohort of mechanically ventilated COVID-19 patients from a resource-rich, publicly financed healthcare system. METHODS: Prospective study from a tertiary hospital. Consecutive SARS-CoV-2 positive adult patients admitted to the ICU for mechanical ventilation from 10 March 2020 to 04 May 2020 were included. Triage and treatment were protocolized. High-dose dalteparin was adjusted by D-dimer. Demographics, treatments and high-resolution physiological variables were collected. Outcomes were 30-day and hospital mortality. Data are medians (quartiles). RESULTS: Of the 1484 persons in the hospital catchment area testing positive for SARS-CoV-2, 201 (13.5%) were hospitalized. Thirty-eight (19%) patients were mechanically ventilated, of whom five (13%) died. Of the 163 patients treated with supplemental oxygen, eight (5%) died. In ventilated patients (75% males, age 61 (53-70) years), severe, moderate and mild ARDS was present in 25%, 70% and 5%. Tidal volume ≤8 mL/kg ideal bodyweight was achieved in 34 (94%) patients. Proning and neuromuscular blockers were used in 19 (54%) and 20 (61%) patients. Duration of ventilation was 12 days (8-23). D-dimer peaked at 3.8 mg/L (2.1-5.3), and maximum dalteparin dose was 15 000 IU/24 h (10 000-15 000). Despite organizational changes, a high degree of adherence to treatment protocols was achieved. CONCLUSION: In a prospective cohort study of mechanically ventilated COVID-19 patients treated in a resource-rich, publicly financed healthcare system, mortality was considerably lower than previously reported in retrospective studies.

Transfusion requirements in septic shock (TRISS) trial - comparing the effects and safety of liberal versus restrictive red blood cell transfusion in septic shock patients in the ICU: protocol for a randomised controlled trial.

BACKGROUND: Transfusion of red blood cells (RBC) is recommended in septic shock and the majority of these patients receive RBC transfusion in the intensive care unit (ICU). However, benefit and harm of RBCs have not been established in this group of high-risk patients. METHODS/DESIGN: The Transfusion Requirements in Septic Shock (TRISS) trial is a multicenter trial with assessor-blinded outcome assessment, randomising 1,000 patients with septic shock in 30 Scandinavian ICUs to receive transfusion with pre-storage leuko-depleted RBC suspended in saline-adenine-glucose and mannitol (SAGM) at haemoglobin level (Hb) of 7 g/dl or 9 g/dl, stratified by the presence of haematological malignancy and centre. The primary outcome measure is 90-day mortality. Secondary outcome measures are organ failure, ischaemic events, severe adverse reactions (SARs: anaphylactic reaction, acute haemolytic reaction and transfusion-related circulatory overload, and acute lung injury) and mortality at 28 days, 6 months and 1 year.The sample size will enable us to detect a 9% absolute difference in 90-day mortality assuming a 45% event rate with a type 1 error rate of 5% and power of 80%. An interim analysis will be performed after 500 patients, and the Data Monitoring and Safety Committee will recommend the trial be stopped if a group difference in 90-day mortality with P ≤0.001 is present at this point. DISCUSSION: The TRISS trial may bridge the gap between clinical practice and the lack of efficacy and safety data on RBC transfusion in septic shock patients. The effect of restrictive versus liberal RBC transfusion strategy on mortality, organ failure, ischaemic events and SARs will be evaluated.