This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at ...https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .
Polymicrobial sepsis is associated with worse patient outcomes than monomicrobial sepsis. Routinely used culture-dependent microbiological diagnostic techniques have low sensitivity, often leading to ...missed identification of all causative organisms. To overcome these limitations, culture-independent methods incorporating advanced molecular technologies have recently been explored. However, contamination, assay inhibition and interference from host DNA are issues that must be addressed before these methods can be relied on for routine clinical use. While the host component of the complex sepsis host-pathogen interplay is well described, less is known about the pathogen's role, including pathogen-pathogen interactions in polymicrobial sepsis. This review highlights the clinical significance of polymicrobial sepsis and addresses how promising alternative molecular microbiology methods can be improved to detect polymicrobial infections. It also discusses how the application of shotgun metagenomics can be used to uncover pathogen/pathogen interactions in polymicrobial sepsis cases and their potential role in the clinical course of this condition.
There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant ...therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled "a randomized embedded multifactorial adaptive platform." The design has five key features:
) randomization, allowing robust causal inference;
) embedding of study procedures into routine care processes, facilitating enrollment, trial efficiency, and generalizability;
) a multifactorial statistical model comparing multiple interventions across multiple patient subgroups;
) response-adaptive randomization with preferential assignment to those interventions that appear most favorable; and
) a platform structured to permit continuous, potentially perpetual enrollment beyond the evaluation of the initial treatments. The trial randomizes patients to multiple interventions within four treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens. The trial generates estimates of superiority, inferiority, and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection. The trial will also compare ventilatory and oxygenation strategies, and has capacity to address additional questions rapidly during pandemic respiratory infections. As of January 2020, REMAP-CAP (Randomized Embedded Multifactorial Adaptive Platform for Community-acquired Pneumonia) was approved and enrolling patients in 52 intensive care units in 13 countries on 3 continents. In February, it transitioned into pandemic mode with several design adaptations for coronavirus disease 2019. Lessons learned from the design and conduct of this trial should aid in dissemination of similar platform initiatives in other disease areas.Clinical trial registered with www.clinicaltrials.gov (NCT02735707).
The purpose of late phase clinical trials is to generate evidence of sufficient validity and generalisability to be translated into practice and policy to improve health outcomes. It is therefore ...crucial that the chosen endpoints are meaningful to the clinicians, patients and policymakers that are the end-users of evidence generated by these trials. The choice of endpoints may be improved by understanding their characteristics and properties. This narrative review describes the evolution, range and relative strengths and weaknesses of endpoints used in late phase trials. It is intended to serve as a reference to assist those designing trials when choosing primary endpoint(s), and for the end-users charged with interpreting these trials to inform practice and policy.
In The Lancet,1 Pipat Thongnoi and colleagues report a case of severe respiratory failure secondary to influenza A infection in a young woman who was 33 weeks pregnant with triplets, which sadly ...resulted in the death of the mother and all three infants.
Reducing unnecessary routine diagnostic testing has been identified as a strategy to curb wasteful healthcare. However, the safety and efficacy of targeted diagnostic testing strategies are ...uncertain. The aim of this study was to systematically review interventions designed to reduce pathology and chest radiograph testing in patients admitted to the intensive care unit (ICU). A predetermined protocol and search strategy included OVID MEDLINE, OVID EMBASE and the Cochrane Central Register of Controlled Trials from inception until 20 November 2019. Eligible publications included interventional studies of patients admitted to an ICU. There were no language restrictions. The primary outcomes were in-hospital mortality and test reduction. Key secondary outcomes included ICU mortality, length of stay, costs and adverse events. This systematic review analysed 26 studies (with more than 44,00 patients) reporting an intervention to reduce one or more diagnostic tests. No studies were at low risk of bias. In-hospital mortality, reported in seven studies, was not significantly different in the post-implementation group (829 of 9815 patients, 8.4%) compared with the preintervention group (1007 of 9848 patients, 10.2%), (relative risk 0.89, 95% confidence intervals 0.79 to 1.01, P1/40.06, I2 39%). Of the 18 studies reporting a difference in testing rates, all reported a decrease associated with targeted testing (range 6%-72%), with 14 (82%) studies reporting >20% reduction in one or more tests. Studies of ICU targeted test interventions are generally of low quality. The majority report substantial decreases in testing without evidence of a significant difference in hospital mortality.
It remains unclear as to whether mechanical valves have a role in pulmonary valve replacement. A systematic review and meta-analysis was performed to answer this question. Nineteen observational ...studies, including 299 pediatric and adult patients with a mean follow-up of 73 months, were analyzed. Nonstructural valve deterioration and valve thrombosis occurred in 1.5% and 2.2% of patients, respectively. Surgical reintervention was required in 0.9% of cases and thrombolysis was required in 0.5%. Mechanical valves in the pulmonary position are associated with a low incidence of valve deterioration and thrombosis, as well as freedom from reoperation and thrombolysis.
Background
Frailty and delirium are prevalent among older adults admitted to the intensive care unit (ICU) and associated with adverse outcomes; however, their relationships have not been extensively ...explored. This study examined the association between frailty and mortality and length of hospital stay (LOS) in ICU patients, and whether the associations are mediated or modified by an episode of delirium.
Methods
Retrospective analysis of data from the Australian New Zealand Intensive Care Society Adult Patient Database. A total of 149,320 patients aged 65 years or older admitted to 203 participating ICUs between 1 January 2017 and 31 December 2020 who had data for frailty and delirium were included in the analysis.
Results
A total of 41,719 (27.9%) older ICU patients were frail on admission, and 9,179 patients (6.1%) developed delirium during ICU admission. Frail patients had significantly higher odds of in-hospital mortality (OR: 2.15, 95% CI 2.05–2.25), episodes of delirium (OR: 1.86, 95% CI 1.77–1.95), and longer LOS (log-transformed mean difference (MD): 0.24, 95% CI 0.23–0.25). Acute delirium was associated with 32% increased odds of in-hospital mortality (OR: 1.32, 95% CI 1.23–1.43) and longer LOS (MD: 0.54, 95% CI 0.50–0.54). The odds ratios (95% CI) for in-hospital mortality were 1.37 (1.23–1.52), 2.14 (2.04–2.24) and 2.77 (2.51–3.05) for non-frail who developed delirium, frail without delirium, and frail and developed delirium during ICU admission, respectively. There was very small but statistically significant effect of frailty on in-hospital mortality (
b
for indirect effect: 0.00037,
P
< 0.001) and LOS (
b
for indirect effect: 0.019,
P
< 0.001) mediated through delirium.
Conclusion
Both frailty and delirium independently increase the risk of in-hospital mortality and LOS. Acute delirium is more common in frail patients; however, it does not mediate or modify a clinically meaningful amount of the association between frailty and in-hospital mortality and LOS.
Background
The human gastrointestinal tract harbours a complex multi-kingdom community known as the microbiome.
Dysbiosis
refers to its disruption and is reportedly extreme in acute critical illness ...yet its clinical implications are unresolved. The review systematically evaluates the association between gut dysbiosis and clinical outcomes of patients early in critical illness.
Methods
Following PRISMA guidelines, a prospectively registered search was undertaken of MEDLINE and Cochrane databases for observational studies undertaking metagenomic sequencing of the lower gastrointestinal tract of critically ill adults and children within 72 h of admission. Eligible studies reported an alpha diversity metric and one or more of the primary outcome, in-hospital mortality, or secondary clinical outcomes. After aggregate data were requested, meta-analysis was performed for four studies with in-hospital mortality stratified to high or low Shannon index.
Results
The search identified 26 studies for systematic review and 4 had suitable data for meta-analysis. No effect of alpha diversity was seen on in-hospital mortality after binary transformation of Shannon index (odds ratio 0.52, CI 0.12–4.98,
I
2
= 0.64) however certainty of evidence is low. Pathogen dominance and commensal depletion were each more frequently associated with in-hospital mortality, adverse clinical and ecological sequelae, particularly overabundance of
Enterococcus
.
Conclusions
There is a paucity of large, rigorous observational studies in this population. Globally, alpha diversity was dynamically reduced in early ICU admission in adults and children and was not associated with in-hospital mortality. The abundance of taxa such as
Enterococcus
spp. appears to offer greater predictive capacity for important clinical and ecological outcomes.
Objective: To describe the characteristics and outcomes of patients admitted to regional and rural intensive care units (ICUs).
Design, setting and participants: Retrospective database review using ...the Australian and New Zealand Intensive Care Society Adult Patient Database for admissions between January 2009 and June 2019. Characteristics and outcomes of patients admitted to regional and rural ICUs were compared with metropolitan and tertiary ICUs.
Main outcome measures: Primary outcome was hospital mortality. Secondary outcomes included patient characteristics, ICU mortality, ICU and hospital length of stay, need for mechanical ventilation and need for interhospital transfer.
Results: Over the sampling period, admissions to regional/ rural ICUs averaged nearly 19 000 episodes per annum and comprised 20% of critical care admissions in Australia. Unadjusted mortality was lower, a result that persisted after adjustment for a range of confounders (odds ratio, 0.73; 95% CI, 0.67-0.80; P < 0.01). Admissions are more likely to be emergencies, and patients are more likely to live in areas of relative disadvantage and to require interhospital transfer, but are less likely to require mechanical ventilation.
Conclusions: Although illness severity is lower for patients admitted to regional/rural ICUs, hospital mortality after adjustment for a range of confounders is lower. Compared with tertiary ICUs, emergency admissions are more likely, which may have implications for surge capacity during pandemic illness, while mechanical ventilation is less frequently required. Regional/rural ICUs provide care to a substantial proportion of critically ill patients and have a crucial role in the support of regional Australians.
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