Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Acute kidney injury with combination vancomycin and piperacillin-tazobactam therapy in the ICU: A retrospective cohort study

Vancomycin and piperacillin-tazobactam are commonly used antibiotics. There is increasing evidence to indicate that these therapies in combination predispose patients to acute kidney injury (AKI). However, studies of intensive care unit (ICU) patients with these antibiotics have produced conflicting results.In this single-centre, retrospective cohort study, data was collected on ICU patients prescribed combination vancomycin and piperacillin-tazobactam (VPT) for at least 48 h, compared with patients prescribed vancomycin with either cefepime or meropenem (VMC) for the same time period. Primary outcome was incidence of AKI; secondary outcomes included a desirability of outcome ranking (DOOR) scale, and association between antibiotic duration and kidney injury.A total of 260 patients were included. AKI was observed in 27% of cases overall. Incidence of AKI was higher with VPT compared with VMC on bivariate (relative risk reduction [RRR] 1.9, 95% confidence interval [CI] 0.9-4.1, P = 0.08) and multivariate (RRR 2.2, 95% CI 1.0-4.9, P = 0.05) analyses. Longer duration of antibiotic therapy was associated with increased rates of AKI independent of which antibiotics were prescribed: RRR 4.9, 95% CI 2.1-11.1, P

Nosocomial Infection Rates in Patients Receiving Extracorporeal Membrane Oxygenation Across Australia and New Zealand: An Interim Analysis

Introduction: Extracorporeal membrane oxygenation (ECMO) is a highly invasive method of cardiac and/or pulmonary support used for critically ill patients where less invasive therapies have failed. Nosocomial infection is one of the most frequent and serious complications of ECMO treatment and is reported in up to 64% of patients. It leads to longer periods of mechanical ventilation and ECMO support, as well as longer hospital stays and increased mortality. The mechanisms behind these high infection rates remain unclear. There are limited data on nosocomial infection in these patients in Australia and New Zealand

Nosocomial infection prevalence in patients undergoing extracorporeal membrane oxygenation (ECMO): Protocol for a point prevalence study across Australia and New Zealand

Introduction Extracorporeal membrane oxygenation (ECMO) provides cardiac and/or respiratory support when other therapies fail. Nosocomial infection is reported in up to 64% of patients receiving ECMO and increases morbidity and mortality. These patients are at high risk of infection due, in part, to the multiple invasive devices required in their management, the largest being the cannulae through which ECMO is delivered. Prevalence of nosocomial infection in ECMO patients, including ECMO cannula-related infection, is not well described across Australia and New Zealand. Methods and analysis This is a prospective, observational point prevalence study of 12 months duration conducted at 11 ECMO centres across Australia and New Zealand. Data will be collected for every patient receiving ECMO during 12 predetermined data collection weeks. The primary outcome is the prevalence of laboratory-confirmed bloodstream infection, and suspected or probable nosocomial infections; and the secondary outcomes include describing ECMO cannula dressing and securement practices, and adherence to local dressing and securement guidelines. Data collection will be finalised by March 2019. Ethics and dissemination Relevant ethical and governance approvals have been received. Study results will describe the prevalence of suspected and confirmed nosocomial infection in adult, paediatric and neonatal patients receiving ECMO across Australia and New Zealand. It is expected that the results will be hypothesis generating and lead to interventional trials aimed at reducing the high infection rates seen in this cohort. Results will be published in peer-reviewed journals and presented at relevant conferences. Trial registration number ANZCTRN12618001109291; Pre-results

Additional file 1 of Time in ICU and post-intensive care syndrome: how long is long enough?

Additional file 1. Data used in analysis

The effect of an improved ICU physical environment on outcomes and post-ICU recovery - a protocol

Background: Intensive care medicine continues to improve, with advances in technology and care provision leading to improved patient survival. However, this has not been matched by similar advances in ICU bedspace design. Environmental factors including excessive noise, suboptimal lighting, and lack of natural lights and views can adversely impact staff wellbeing and short- and long-term patient outcomes. The personal, social, and economic costs associated with this are potentially large. The ICU of the Future project was conceived to address these issues. This is a mixed-method project, aiming to improve the ICU bedspace environment and assess impact on patient outcomes. Two innovative and adaptive ICU bedspaces capable of being individualised to patients’ personal and changing needs were co-designed and implemented. The aim of this study is to evaluate the effect of an improved ICU bedspace environment on patient outcomes and operational impact. Methods: This is a prospective multi-component, mixed methods study including a randomised controlled trial. Over a 2-year study period, the two upgraded bedspaces will serve as intervention beds, while the remaining 25 bedspaces in the study ICU function as control beds. Study components encompass (1) an objective environmental assessment; (2) a qualitative investigation of the ICU environment and its impact from the perspective of patients, families, and staff; (3) sleep investigations; (4) circadian rhythm investigations; (5) delirium measurements; (6) assessment of medium-term patient outcomes; and (7) a health economic evaluation. Discussion: Despite growing evidence of the negative impact the ICU environment can have on patient recovery, this is an area of critical care medicine that is understudied and commonly not considered when ICUs are being designed. This study will provide new information on how an improved ICU environment impact holistic patient recovery and outcomes, potentially influencing ICU design worldwide. Trial registration: ACTRN12623000541606. Registered on May 22, 2023. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385845&amp;isReview=true.</p

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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