Alpha 2 agonists for sedation to produce better outcomes from critical illness (A2B trial): protocol for a mixed-methods process evaluation of a randomised controlled trial.

INTRODUCTION: An association between deep sedation and adverse short-term outcomes has been demonstrated although this evidence has been inconsistent. The A2B (alpha-2 agonists for sedation in critical care) sedation trial is designed to determine whether the alpha-2 agonists clonidine and dexmedetomidine, compared with usual care, are clinically and cost-effective. The A2B intervention is a complex intervention conducted in 39 intensive care units (ICUs) in the UK. Multicentre organisational factors, variable cultures, perceptions and practices and the involvement of multiple members of the healthcare team add to the complexity of the A2B trial. From our pretrial contextual exploration it was apparent that routine practices such as type and frequency of pain, agitation and delirium assessment, as well as the common sedative agents used, varied widely across the UK. Anticipated challenges in implementing A2B focused on the impact of usual practice, perceptions of risk, ICU culture, structure and the presence of equipoise. Given this complexity, a process evaluation has been embedded in the A2B trial to uncover factors that could impact successful delivery and explore their impact on intervention delivery and interpretation of outcomes. METHODS AND ANALYSIS: This is a mixed-methods process evaluation guided by the A2B intervention logic model. It includes two phases of data collection conducted during and at the end of trial. Data will be collected using a combination of questionnaires, stakeholder interviews and routinely collected trial data. A framework approach will be used to analyse qualitative data with synthesis of data within and across the phases. The nature of the relationship between delivery of the A2B intervention and the trial primary and secondary outcomes will be explored. ETHICS AND DISSEMINATION: All elements of the A2B trial, including the process evaluation, are approved by Scotland A Research Ethics Committee (Ref. 18/SS/0085). Dissemination will be via publications, presentations and media engagement. TRIAL REGISTRATION NUMBER: NCT03653832.

Early warning scores for sepsis identification and prediction of in-hospital mortality in adults with sepsis: A systematic review and meta-analysis.

AIM: The early warning scores (EWS), quick Sequential Organ Failure Assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) criteria have been proposed as sepsis screening tools. This review aims to summarise and compare the performance of EWS with the qSOFA and SIRS criteria for predicting sepsis diagnosis and in-hospital mortality in patients with sepsis. DESIGN: A systematic review with meta-analysis. REVIEW METHODS: Seven databases were searched from January 1, 2016 until March 10, 2022. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Sensitivity, specificity, likelihood ratios and diagnostic odd ratios were pooled by using the bivariate random effects model. Overall performance was summarised by using the hierarchical summary receiver-operating characteristics curve. This paper adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. RESULTS: Ten studies involving 52,474 subjects were included in the review. For predicting sepsis diagnosis, the pooled sensitivity of EWS (65%, 95% CI: 55, 75) was similar to SIRS ≥2 (70%, 95% CI: 49, 85) and higher than qSOFA ≥2 (37%, 95% CI: 20, 59). The pooled specificity of EWS (77%, 95% CI: 64, 86) was higher than SIRS ≥2 (62%, 95% CI: 41, 80) but lower than qSOFA ≥2 (94%, 95% CI: 86, 98). Results were similar for the secondary outcome of in-hospital mortality. CONCLUSIONS: Although no one scoring system had both high sensitivity and specificity, the EWS had at least equivalent values in most measures of diagnostic accuracy compared with SIRS or qSOFA. IMPLICATIONS FOR THE PROFESSION: Healthcare systems in which EWS is already in place should consider whether there is any clinical benefit in adopting qSOFA or SIRS. NO PATIENT OR PUBLIC CONTRIBUTION: This systematic review did not directly involve patient or public contribution to the manuscript.

Whole blood thiamine, intravenous thiamine supplementation and delirium occurrence in the intensive care unit: retrospective cohort analyses.

BACKGROUND: Thiamine di-phosphate is an essential cofactor in glucose metabolism, glutamate transformation and acetylcholinesterase activity, pathways associated with delirium occurrence. We hypothesised that a deficiency in whole blood thiamine and intravenous thiamine supplementation could impact delirium occurrence. AIM: To establish whether a deficiency in whole blood thiamine and/or intravenous thiamine supplementation within 72 h of intensive care admission is associated with delirium occurrence. METHOD: The first dataset was secondary analysis of a previous study in an intensive care unit in the Netherlands, reported in 2017. The second dataset contained consecutive intensive care admissions 2 years before (period 1: October 2014 to October 2016) and after (period 2: April 2017 to April 2019) routine thiamine supplementation was introduced within 72 h of admission. Delirium was defined as a positive Confusion Assessment Method-Intensive Care Unit score(s) in 24 h. RESULTS: Analysis of the first dataset (n = 57) using logistic regression showed no relationship between delirium and sepsis or whole blood thiamine, but a significant association with age (p = 0.014). In the second dataset (n = 3074), 15.1% received IV thiamine in period 1 and 62.6% during period 2. Hierarchical regression analysis reported reduction in delirium occurrence in the second period; this did not reach statistical significance, OR = 0.81 (95% CI 0.652-1.002); p = 0.052. CONCLUSION: No relationship was detected between whole blood thiamine and delirium occurrence on admission, at 24 and 48 h. It remains unclear whether routine intravenous thiamine supplementation during intensive care admission impacts delirium occurrence. Further prospective randomised clinical trials are needed.