Jogunčić, Anes

Introduction Sepsis is a global health priority with nearly 50 million cases annually. Cardiovascular dysfunction is common, frequently manifesting as hypotension that persists despite fluid resuscitation. Most affected patients require the use of intravenous (IV) vasoactive agents, typically necessitating intensive care unit (ICU)-level monitoring, invasive interventions and contributing substantially to healthcare costs. Midodrine, an oral alpha-1 agonist approved for orthostatic hypotension, has increasingly been used off-label as a vasopressor-sparing (reducing IV vasopressor use) strategy in sepsis, despite limited and inconsistent evidence. This pragmatic, randomised, open-label trial evaluates the efficacy and safety of midodrine in patients with sepsis-associated hypotension. We hypothesise that, compared with standard care, midodrine administration will reduce the duration of IV vasopressor use. Methods and analysis A total of 308 adult patients with sepsis-associated hypotension will be enrolled (154 per arm). The intervention group will, in addition to standard of care, receive enteral midodrine 10 mg three times daily. Outcomes will be ascertained pragmatically via electronic health record-based data retrieval and adjudicated by research coordinators blinded to treatment assignment. The primary outcome is time alive and off IV vasopressors in the first 28 days (in hours) after randomisation. Secondary outcomes include cumulative vasopressor exposure; use and duration of central venous access; cumulative fluid balance over the first 48 hours and up to 7 days of ICU stay; ICU and hospital length of stay; and ICU-, hospital-, and organ support-free days through day 28. Safety outcomes include adverse events potentially attributable to midodrine during hospitalisation including acute kidney injury. Primary analyses will follow an intention-to-treat framework, including all randomised participants according to their assigned treatment groups. Primary and secondary outcomes will be compared using a van Elteren test stratified by randomisation factors. A predefined secondary Bayesian analysis of the primary outcome will provide complementary estimates of treatment effect. Safety outcomes will be summarised descriptively without formal between-arm hypothesis testing. Ethics and dissemination The Mayo Clinic Institutional Review Board approved this protocol and required written informed consent from all participants (IRB# 24–0 00 121). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT06319248 .

Abstract Background and Aims Acute kidney injury (AKI) is associated with an increased risk of progression to a severe form in every disease and, moreover, is associated with an increased mortality, and so it is also with coronavirus disease 2019 (COVID-19). AKI is a frequent complication in COVID-19 patients admitted to ICU for severe respiratory failure. ICU treatment itself indirectly could cause or exacerbate renal damage, through suboptimal fluid management, drug toxicity, or low human resources. The aims of this study were to assess AKI prevalence, fluid balance and glomerular filtration rate as a predictor of outcome in COVID-19 patients treated in the intensive care unit. Method We retrospectively analysed all adult patients admitted to the ICU at a regional hospital in northern Bavaria, from 1st March to 31st December 2020. Clinical data and laboratory results were retrospectively retrieved from the hospital information system and electronic case files. According to the severity of AKI based on the KDIGO criteria, and laboratory values were followed on the first 7 days on the ICU. In total 320 patients patients were included in the study. Level of significance was set to p<0.05. Results The mean age was 65 ± 19 years, 135 (42%) patients were females, 185 (58%) were males. Median length of ICU stay was 7 (2-13 days) in females, and 8 days (4- to 21 days) in males. At the ICU, 177 patients needed some form of ventilation, from which 109 (needed Invasive mechanical ventilation). During ICU stay, 81 patients have died, with fatality rate of 25%. Patients with AKI (n=48, 15%) at the admission to the ICU, had 2.1 times higher risk of death at the ICU than patients without AKI. There was a statistically significant difference in ICU survival based on a glomerular filtration rate, fluid balance, CRP and leukocyte values, F=1.957, p=0.026; Wilk's Λ=0.724, partial η2 = 0.276 Conclusion Acute kidney injury is common in coronavirus disease 2019, and it is associated with poor clinical outcomes. Even first couple of days at the ICU could point to the outcome, with markers of inflammation, glomerular filtration rate, and fluid balance being most valuable variables.