Fluid Resuscitation in Sepsis: Reexamining the Paradigm

Sepsis results in widespread inflammatory responses altering homeostasis. Associated circulatory abnormalities (peripheral vasodilation, intravascular volume depletion, increased cellular metabolism, and myocardial depression) lead to an imbalance between oxygen delivery and demand, triggering end organ injury and failure. Fluid resuscitation is a key part of treatment, but there is little agreement on choice, amount, and end points for fluid resuscitation. Over the past few years, the safety of some fluid preparations has been questioned. Our paper highlights current concerns, reviews the science behind current practices, and aims to clarify some of the controversies surrounding fluid resuscitation in sepsis

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 48hrs. 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. <br/

Implementation of recommendations on the use of corticosteroids in severe COVID-19

Importance Research diversity and representativeness are paramount in building trust, generating valid biomedical knowledge, and possibly in implementing clinical guidelines. Objectives To compare variations over time and across World Health Organization (WHO) geographic regions of corticosteroid use for treatment of severe COVID-19; secondary objectives were to evaluate the association between the timing of publication of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (June 2020) and the WHO guidelines for corticosteroids (September 2020) and the temporal trends observed in corticosteroid use by region and to describe the geographic distribution of the recruitment in clinical trials that informed the WHO recommendation. Design, Setting, and Participants This prospective cohort study of 434 851 patients was conducted between January 31, 2020, and September 2, 2022, in 63 countries worldwide. The data were collected under the auspices of the International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC)–WHO Clinical Characterisation Protocol for Severe Emerging Infections. Analyses were restricted to patients hospitalized for severe COVID-19 (a subset of the ISARIC data set). Exposure Corticosteroid use as reported to the ISARIC-WHO Clinical Characterisation Protocol for Severe Emerging Infections. Main Outcomes and Measures Number and percentage of patients hospitalized with severe COVID-19 who received corticosteroids by time period and by WHO geographic region. Results Among 434 851 patients with confirmed severe or critical COVID-19 for whom receipt of corticosteroids could be ascertained (median [IQR] age, 61.0 [48.0-74.0] years; 53.0% male), 174 307 (40.1%) received corticosteroids during the study period. Of the participants in clinical trials that informed the guideline, 91.6% were recruited from the United Kingdom. In all regions, corticosteroid use for severe COVID-19 increased, but this increase corresponded to the timing of the RECOVERY trial (time-interruption coefficient 1.0 [95% CI, 0.9-1.2]) and WHO guideline (time-interruption coefficient 1.9 [95% CI, 1.7-2.0]) publications only in Europe. At the end of the study period, corticosteroid use for treatment of severe COVID-19 was highest in the Americas (5421 of 6095 [88.9%]; 95% CI, 87.7-90.2) and lowest in Africa (31 588 of 185 191 [17.1%]; 95% CI, 16.8-17.3). Conclusions and Relevance The results of this cohort study showed that implementation of the guidelines for use of corticosteroids in the treatment of severe COVID-19 varied geographically. Uptake of corticosteroid treatment was lower in regions with limited clinical trial involvement. Improving research diversity and representativeness may facilitate timely knowledge uptake and guideline implementation

Performance evaluation of a multinational data platform for critical care in Asia

Background: The value of medical registries strongly depends on the quality of the data collected. This must be objectively measured before large clinical databases can be promoted for observational research, quality improvement, and clinical trials. We aimed to evaluate the quality of a multinational intensive care unit (ICU) network of registries of critically ill patients established in seven Asian low- and middle-income countries (LMICs). Methods: The Critical Care Asia federated registry platform enables ICUs to collect clinical, outcome and process data for aggregate and unit-level analysis. The evaluation used the standardised criteria of the Directory of Clinical Databases (DoCDat) and a framework for data quality assurance in medical registries. Six reviewers assessed structure, coverage, reliability and validity of the ICU registry data. Case mix and process measures on patient episodes from June to December 2020 were analysed. Results: Data on 20,507 consecutive patient episodes from 97 ICUs in Afghanistan, Bangladesh, India, Malaysia, Nepal, Pakistan and Vietnam were included. The quality level achieved according to the ten prespecified DoCDat criteria was high (average score 3.4 out of 4) as was the structural and organizational performance -- comparable to ICU registries in high-income countries. Identified strengths were types of variables included, reliability of coding, data completeness and validation. Potential improvements included extension of national coverage, optimization of recruitment completeness validation in all centers and the use of interobserver reliability checks. Conclusions: The Critical Care Asia platform evaluates well using standardised frameworks for data quality and equally to registries in resource-rich settings

Protocol and statistical analysis plan for the mega randomised registry trial comparing conservative vs. liberal oxygenation targets in adults with sepsis in the intensive care unit (Mega-ROX Sepsis)

Background: The effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis receiving unplanned invasive mechanical ventilation in the intensive care unit (ICU) is uncertain. Objective: The objective of this study was to summarise the protocol and statistical analysis plan for the Mega-ROX Sepsis trial. Design, setting, and participants: The Mega-ROX Sepsis trial is an international randomised clinical trial that will be conducted within an overarching 40,000-patient registry-embedded clinical trial comparing conservative and liberal ICU oxygen therapy regimens. We anticipate that between 10,000 and 13,000 patients with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU will be enrolled in this trial. 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 patients discharged home. Results and conclusions: Mega-ROX Sepsis will compare the effect of conservative vs. liberal oxygen therapy on 90-day in-hospital mortality in adults with sepsis who are receiving unplanned invasive mechanical ventilation in the ICU. The protocol and a prespecified approach to analyses are reported here to mitigate analysis bias

Understanding patient and family experiences of critical care in Bangladesh and India: What are the priority actions to promote person-centred care?

Patients’ experiences in the intensive care unit (ICU) can enhance or impair their subsequent recovery. Improving patient and family experiences on the ICU is an important part of providing high quality care. There is little evidence to guide how to do this in a South Asian critical care context. This study addresses this gap by exploring the experiences of critically ill patients and their families in ICUs in Bangladesh and India. We elicit suggestions for improvements from patients, families and staff and highlight examples of practices that support person-centred care. This multi-site hospital ethnography was carried out in five ICUs in government hospitals in Bangladesh and India, selected using purposive sampling. Qualitative data were collected using non-participant observation and semi-structured interviews and analysed using reflexive thematic analysis. A total of 108 interviews were conducted with patients, families, and ICU staff. Over 1000 hours of observation were carried out across the five study sites. We identified important mediators of patient and family experience that span many different aspects of care. Factors that promote person-centred care include access to ICU for families, support for family involvement in care delivery, clear communication with patients and families, good symptom management for patients, support for rehabilitation, and measures to address the physical, environmental and financial needs of the family. This study has generated a list of recommendations that can be used by policy makers and practitioners who wish to implement person-centred principles in the ICU

Mixed methods study protocol for combining stakeholder-led rapid evaluation with near real-time continuous registry data to facilitate evaluations of quality of care in intensive care units [version 1; peer review: awaiting peer review]

BACKGROUND: Improved access to healthcare in low- and middle-income countries (LMICs) has not equated to improved health outcomes. Absence or unsustained quality of care is partly to blame. Improving outcomes in intensive care units (ICUs) requires delivery of complex interventions by multiple specialties working in concert, and the simultaneous prevention of avoidable harms associated with the illness and the treatment interventions. Therefore, successful design and implementation of improvement interventions requires understanding of the behavioural, organisational, and external factors that determine care delivery and the likelihood of achieving sustained improvement. We aim to identify care processes that contribute to suboptimal clinical outcomes in ICUs located in LMICs and to establish barriers and enablers for improving the care processes. METHODS: Using rapid evaluation methods, we will use four data collection methods: 1) registry embedded indicators to assess quality of care processes and their associated outcomes; 2) process mapping to provide a preliminary framework to understand gaps between current and desired care practices; 3) structured observations of processes of interest identified from the process mapping and; 4) focus group discussions with stakeholders to identify barriers and enablers influencing the gap between current and desired care practices. We will also collect self-assessments of readiness for quality improvement. Data collection and analysis will be performed in parallel and through an iterative process across eight countries: Kenya, India, Malaysia, Nepal, Pakistan, South Africa, Uganda and Vietnam. CONCLUSIONS: The results of our study will provide essential information on where and how care processes can be improved to facilitate better quality of care to critically ill patients in LMICs; thus, reduce preventable mortality and morbidity in ICUs. Furthermore, understanding the rapid evaluation methods that will be used for this study will allow other researchers and healthcare professionals to carry out similar research in ICUs and other health services

Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study

Background: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, There is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. Methods: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. Findings: Among 1 642 632 non-COVID-19 admissions, There was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. Interpretation: Increased ICU mortality occurred among non-COVID- 19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles

Worldwide clinical intensive care registries response to the pandemic : An international survey

Funding Information: Dr. Kumar is partially supported by Wellcome Trust grant (WT-215522) for his role as National Coordinator, IRIS. Funding Information: Dr. Martin Sigurdsson is supported by Landspitali Science Fund for COVID19 related projects. Funding Information: Drs. Salluh and Soares are supported in part by individual research grants from CNPq and FAPERJ.Peer reviewe

Global outbreak research: harmony not hegemony

No abstract available