A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults.

BACKGROUND: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).

Intensive care admissions and outcomes associated with short-term exposure to ambient air pollution: a time series analysis.

PURPOSE: Short-term exposure to outdoor air pollution has been positively associated with numerous measures of acute morbidity and mortality, most consistently as excess cardiorespiratory disease associated with fine particulate matter (PM2.5), particularly in vulnerable populations. It is unknown if the critically ill, a vulnerable population with high levels of cardiorespiratory disease, is affected by air pollution. METHODS: We performed a time series analysis of emergency cardiorespiratory, stroke and sepsis intensive care (ICU) admissions for the years 2008-2016, using data from the Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS-APD). Case-crossover analysis was conducted to assess the relationship between air pollution and the frequency and severity of ICU admissions having adjusted for temperature, humidity, public holidays and influenza activity. RESULTS: 46,965 episodes in 87 separate ICUs were analysed. We found no statistically significant associations with admission counts. However, ICU admissions ending in death within 30 days were significantly positively associated with short-term exposure to PM2.5 [RR 1.18, 95% confidence interval (CI) 1.02-1.37, per 10 µg/m3 increase]. This association was more pronounced in those aged 65 and over (RR 1.33, 95% CI 1.11-1.58, per 10 µg/m3). CONCLUSIONS: Increased ICU mortality was associated with higher levels of PM2.5. Larger studies are required to determine if the frequency of ICU admissions is positively associated with short-term exposure to air pollution.

The Australasian Resuscitation in Sepsis Evaluation (ARISE) trial statistical analysis plan.

BACKGROUND: The Australasian Resuscitation in Sepsis Evaluation (ARISE) study is an international, multicentre, randomised, controlled trial designed to evaluate the effectiveness of early goal-directed therapy compared with standard care for patients presenting to the emergency department with severe sepsis. OBJECTIVE: In keeping with current practice, and considering aspects of trial design and reporting specific to non-pharmacological interventions, our plan outlines the principles and methods for analysing and reporting the trial results. The document is prepared before completion of recruitment into the ARISE study, without knowledge of the results of the interim analysis conducted by the data safety and monitoring committee and before completion of the two related international studies. METHODS: Our statistical analysis plan was designed by the ARISE chief investigators, and reviewed and approved by the ARISE steering committee. We reviewed the data collected by the research team as specified in the study protocol and detailed in the study case report form. We describe information related to baseline characteristics, characteristics of delivery of the trial interventions, details of resuscitation, other related therapies and other relevant data with appropriate comparisons between groups. We define the primary, secondary and tertiary outcomes for the study, with description of the planned statistical analyses. RESULTS: We have developed a statistical analysis plan with a trial profile, mock-up tables and figures. We describe a plan for presenting baseline characteristics, microbiological and antibiotic therapy, details of the interventions, processes of care and concomitant therapies and adverse events. We describe the primary, secondary and tertiary outcomes with identification of subgroups to be analysed. CONCLUSION: We have developed a statistical analysis plan for the ARISE study, available in the public domain, before the completion of recruitment into the study. This will minimise analytical bias and conforms to current best practice in conducting clinical trials.

The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis.

OBJECTIVE: To assess whether resuscitation with albumin-containing solutions, compared with other fluids, is associated with lower mortality in patients with sepsis. DATA SOURCES: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases, the metaRegister of Controlled Trials, and the Medical Editors Trial Amnesty Register. STUDY SELECTION: Prospective randomized clinical trials of fluid resuscitation with albumin-containing solutions compared with other fluid resuscitation regimens, which included a population or subgroup of participants with sepsis, were included. DATA EXTRACTION: Assessment of the validity of included studies and data extraction were conducted independently by two authors. DATA SYNTHESIS: For the primary analysis, the effect of albumin-containing solutions on all-cause mortality was assessed by using a fixed-effect meta-analysis. RESULTS: Seventeen studies that randomized 1977 participants were included in the meta-analysis. There were eight studies that included only patients with sepsis and nine where patients with sepsis were a subgroup of the study population. There was no evidence of heterogeneity, I² = 0%. The use of albumin for resuscitation of patients with sepsis was associated with a reduction in mortality with the pooled estimate of the odds ratio of 0.82 (95% confidence limits 0.67-1.0, p = .047). CONCLUSIONS: In this meta-analysis, the use of albumin-containing solutions for the resuscitation of patients with sepsis was associated with lower mortality compared with other fluid resuscitation regimens. Until the results of ongoing randomized controlled trials are known, clinicians should consider the use of albumin-containing solutions for the resuscitation of patients with sepsis.

Corticosteroids to prevent extubation failure: a systematic review and meta-analysis.

PURPOSE: To determine whether corticosteroids reduce the rate of extubation failure in intensive care patients of all age groups. METHODS: Medline, EMBASE, the Cochrane Central Register of Controlled Trials, bibliographies of relevant articles, selected conference abstracts and unpublished trial databases were searched. Randomised clinical trials (RCTs) evaluating corticosteroids for the purpose of preventing extubation failure in mechanically ventilated, critically ill patients of all ages were included. Two authors independently assessed the validity of included studies and extracted data regarding characteristics of the studies and the rates of reintubation and manifestations of laryngeal oedema. RESULTS: Fourteen RCTs including 2,600 participants were included. The mean duration of ventilation prior to attempted extubation ranged from 3 to 21 days. There was a reduction in reintubation with the use of corticosteroids, with a pooled odds ratio (OR) of 0.56 (95% CI; 0.41-0.77, P < 0.0005). The effect of corticosteroids tended to be more pronounced in studies when used at least 12 h prior to attempted extubation (OR 0.41, 95% CI; 0.26-0.64). The results were consistent across neonatal, paediatric and adult populations. There was also a reduction in laryngeal oedema in participants receiving corticosteroids, with a pooled OR of 0.36 (95% CI 0.27-0.49, P < 0.0005). CONCLUSIONS: Corticosteroids reduce laryngeal oedema and importantly reduce the incidence of extubation failure in critically ill patients of all ages.