Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults in the intensive care unit with suspected hypoxic ischaemic encephalopathy following a cardiac arrest (Mega-ROX HIE).

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with hypoxic ischaemic encephalopathy (HIE) following a cardiac arrest who are receiving invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: To summarise the protocol and statistical analysis plan for the Mega-ROX HIE trial. Design setting and participants: Mega-ROX HIE is an international randomised clinical trial that will be conducted within an overarching 40,000-participant registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We expect to enrol approximately 4000 participants with suspected HIE following a cardiac arrest who are receiving invasive mechanical ventilation in the ICU. Main outcome measures: The primary outcome is in-hospital all-cause mortality up to 90 days from the date of randomisation. Secondary outcomes include duration of survival, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and the proportion of participants discharged home. Results and conclusions: Mega-ROX HIE will compare the effect of conservative vs. liberal oxygen therapy regimens on day-90 in-hospital mortality in adults in the ICU with suspected HIE following a cardiac arrest. The protocol and planned analyses are reported here to mitigate analysis bias. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN 12620000391976).

Interventions for improving critical care in low- and middle-income countries: a systematic review.

PURPOSE: To systematically review the typology, impact, quality of evidence, barriers, and facilitators to implementation of Quality Improvement (QI) interventions for adult critical care in low- and middle-income countries (LMICs). METHODS: MEDLINE, EMBASE, Cochrane Library and ClinicalTrials.gov were searched on 1st September 2022. The studies were included if they described the implementation of QI interventions for adult critical care in LMICs, available as full text, in English and published after 2000. The risks of bias were assessed using the ROB 2.0/ROBINS-I tools. Intervention strategies were categorised according to a Knowledge Translation framework. Interventions' effectiveness were synthesised by vote counting and assessed with a binomial test. Barriers and facilitators to implementation were narratively synthesised using the Consolidated Framework for Implementation Research. RESULTS: 78 studies were included. Risk of bias was high. The most common intervention strategies were Education, Audit & Feedback (A&F) and Protocols/Guidelines/Bundles/Checklists (PGBC). Two multifaceted strategies improved both process and outcome measures: Education and A&F (p = 0.008); and PGBC with Education and A&F (p = 0.001, p < 0.001). Facilitators to implementation were stakeholder engagement, organisational readiness for implementation, and adaptability of interventions. Barriers were lack of resources and incompatibility with clinical workflows. CONCLUSIONS: The evidence for QI in critical care in LMICs is sparse and at high risk of bias but suggests that multifaceted interventions are most effective. Co-designing interventions with and engaging stakeholders, communicating relative advantages, employing local champions and adapting to feedback can improve implementation. Hybrid study designs, process evaluations and adherence to reporting guidelines would improve the evidence base.

Prevalence of frailty and association with patient centered outcomes: A prospective registry-embedded cohort study from India.

PURPOSE: We aimed to study the prevalence of frailty, evaluate risk factors, and understand impact on outcomes in India. METHODS: This was a prospective registry-embedded cohort study across 7 intensive care units (ICUs) and included adult patients anticipated to stay for at least 48 h. Primary exposure was frailty, as defined by a score ≥ 5 on the Clinical Frailty Scale and primary outcome was ICU mortality. Secondary outcomes included in-hospital mortality and resource utilization. We used generalized linear models to evaluate risk factors and model association between frailty and outcomes. RESULTS: 838 patients were included, with median (IQR) age 57 (42,68) yrs.; 64.8% were male. Prevalence of frailty was 19.8%. Charlson comorbidity index (OR:1.73 (95%CI:1.39,2.15)), Subjective Global Assessment categories mild/moderate malnourishment (OR:1.90 (95%CI:1.29, 2.80)) and severe malnourishment (OR:4.76 (95% CI:2.10,10.77)) were associated with frailty. Frailty was associated with higher odds of ICU mortality (adjusted OR:2.04 (95% CI:1.25,3.33)), hospital mortality (adjusted OR:2.36 (95%CI:1.45,3.84)), development of stage2/3 AKI (unadjusted OR:2.35 (95%CI:1.60, 3.43)), receipt of non-invasive ventilation (unadjusted OR:2.68 (95%CI:1.77, 4.03)), receipt of vasopressors (unadjusted OR:1.47 (95%CI:1.04, 2.07)), and receipt of kidney replacement therapy (unadjusted OR:3.15 (95%CI:1.90, 5.17)). CONCLUSIONS: Frailty is common among critically ill patients in India and is associated with worse outcomes. STUDY REGISTRATION: CTRI/2021/02/031503.