Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS).

INTRODUCTION: Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock. METHODS AND ANALYSIS: This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of fulfilling septic shock definition according to Sepsis-3 consensus conference. Using Doppler ultrasound, physicians will interrogate the IVC, HV, PV and IRV 6-12 hours after randomisation. Study investigators will provide web-based educational sessions to ultrasound operators and adjudicate image acquisition and interpretation. The primary outcome will be RRT or death within 28 days of septic shock. We will assess the hazard of RRT or death as a function of venous congestion using a Cox proportional hazards model. Sub-distribution HRs will describe the hazard of RRT given the competing risk of death. ETHICS AND DISSEMINATION: We obtained ethics approval for the AS-2 RCT, including this observational substudy, from local ethics boards at all participating sites. We will report the findings of this study through open-access publication, presentation at international conferences, a coordinated dissemination strategy by investigators through social media, and an open-access workshop series in multiple languages. TRIAL REGISTRATION NUMBER: NCT05057611.

Effect of Body Mass Index on Clinical Events After Acute Coronary Syndromes.

The association between body mass index (BMI) and major clinical events after acute coronary syndrome (ACS) remains controversial. We investigated the impact of BMI on major clinical events after ACS in a large individual patient data meta-analysis. Data on 81,553 patients from 45 different countries with ACS enrolled in 8 large randomized clinical trials were included, followed up for a median of 171 days. The mean age was 63.4 ± 11.7, 70% were male, and the mean BMI was 27.3 ± 4.7 kg/m2. Compared with upper-normal-weight participants (BMI 21.75 to 24.9 kg/m2, reference category), underweight participants (<18.5 kg/m2) had an increased risk of death (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.10 to 1.66, p = 0.004). Both overweight subcategories, BMI 25 to 27.5 kg/m2 (HR 0.81, 95% CI 0.75 to 0.89, p <0.001) and BMI 27.5 to 29.9 kg/m2 (HR 0.84, 95% CI 0.76 to 0.92, p <0.001), and type I obesity (30 to 34.9, HR 0.81, 95% CI 0.73 to 0.89, p <0.001) had a significantly lower mortality. Type II and III obesities were not significantly associated with mortality. Mortality was lowest at a BMI of 30.9 kg/m2. Compared with normal-weight patients, overweight and obese categories were related with a significantly lower risk of bleeding and refractory ischemia. Overweight patients had a lower risk of myocardial infarction, heart failure hospitalizations, and heart failure-related deaths. There were no associations between BMI and revascularization rates or stroke. In conclusion, underweight and normal-weight patients were associated with an increased mortality risk, bleeding, ischemia, and heart failure compared with those with higher BMI after ACS.