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1.
Can J Anaesth ; 67(10): 1405-1416, 2020 10.
Article in English | MEDLINE | ID: covidwho-1777848

ABSTRACT

During the coronavirus disease (COVID-19) global pandemic, urgent strategies to alleviate shortages are required. Evaluation of the feasibility, practicality, and value of drug conservation strategies and therapeutic alternatives requires a collaborative approach at the provincial level. The Ontario COVID-19 ICU Drug Task Force was directed to create recommendations suggesting drug conservation strategies and therapeutic alternatives for essential drugs at risk of shortage in the intensive care unit during the COVID-19 pandemic. Recommendations were rapidly developed using a modified Delphi method and evaluated on their ease of implementation, feasibility, and supportive evidence. This article describes the recommendations for drug conservation strategies and therapeutic alternatives for drugs at risk of shortage that are commonly used in the care of critically ill patients. Recommendations are identified as preferred and secondary ones that might be less desirable. Although the impetus for generating this document was the COVID-19 pandemic, recommendations should also be applicable for mitigating drug shortages outside of a pandemic. Proposed provincial strategies for drug conservation and therapeutic alternatives may not all be appropriate for every institution. Local implementation will require consultation from end-users and hospital administrators. Competing equipment shortages and available resources should be considered when evaluating the appropriateness of each strategy.


RéSUMé: Pendant la pandémie mondiale du coronavirus (COVID-19), des stratégies urgentes pour réduire les pénuries sont nécessaires. L'évaluation de la faisabilité, de l'aspect pratique et du mérite des stratégies de préservation des médicaments et des alternatives thérapeutiques nécessite une approche collaborative au niveau provincial. Le Groupe de travail ontarien sur les médicaments à l'USI pendant la COVID-19 a reçu comme mandat d'élaborer des recommandations proposant des stratégies de préservation des médicaments et des alternatives thérapeutiques pour les médicaments essentiels utilisés dans les unités de soins intensifs courant un risque de pénurie pendant la pandémie de COVID-19. Des recommandations ont été rapidement élaborées en utilisant une méthode Delphi modifiée, puis évaluées selon leur facilité de mise en œuvre, leur faisabilité et les données probantes les préconisant. Cet article décrit les recommandations quant aux stratégies de préservation des médicaments et aux alternatives thérapeutiques aux médicaments possiblement à risque de pénurie fréquemment utilisés pour les soins des patients en état critique. Les recommandations sont identifiées comme 'à privilégier' ou 'secondaires' si moins souhaitables. Bien que la pandémie de la COVID-19 ait été l'impulsion incitant la création de ce document, ces recommandations devraient également être applicables pour réduire les pénuries de médicaments en contexte normal. Les stratégies provinciales proposées pour la préservation des médicaments et les alternatives thérapeutiques pourraient ne pas être adaptées pour toutes les institutions. La mise en œuvre locale nécessitera la consultation des utilisateurs et des administrateurs hospitaliers. Il faudrait tenir compte des pénuries de matériel concurrentes et des ressources disponibles lors de l'évaluation de la faisabilité de chaque stratégie.


Subject(s)
Coronavirus Infections/drug therapy , Intensive Care Units , Pharmaceutical Preparations/supply & distribution , Pneumonia, Viral/drug therapy , Advisory Committees , COVID-19 , Critical Illness , Humans , Ontario , Pandemics
2.
BMJ Open ; 12(2): e052893, 2022 02 07.
Article in English | MEDLINE | ID: covidwho-1673433

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has renewed interest in the use of inhaled anaesthetics for sedation of ventilated critically ill patients. Preliminary data show that inhaled anaesthetics reduce lung inflammation, time to extubation and intensive care unit length of stay compared with intravenous sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes is not well described in this setting. Randomised controlled trials are underway to establish if inhaled anaesthetics affect these and other patient and health system outcomes. Our aim is to summarise the known effects of inhaled sedatives on cognitive and psychiatric outcomes. METHODS AND ANALYSIS: In this systematic review, we will use MEDLINE, EMBASE, and PsycINFO to identify studies from 1970 to 2021 that assessed cognitive and psychiatric outcomes in critically ill adult patients sedated with inhaled anaesthetics. We will include case series, observational and cohort studies and randomised controlled trials. We will exclude case studies due to the heterogeneity of reporting in these studies. For randomised controlled trials comparing inhaled to intravenous sedation, we will report cognitive and psychiatric outcomes for both study arms. Studies will be selected based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Data will be extracted using a standardised data extraction tool by two independent reviewers. Studies will be assessed for bias using the Cochrane risk of bias tool for randomised controlled trials, or the Newcastle-Ottawa Scale for cohort and case-control studies. Findings will be reported according to outcome and descriptive statistics will be used to illustrate findings in a narrative fashion. ETHICS AND DISSEMINATION: The systematic review uses published data and therefore does not require ethics approval. Results will be disseminated via publication in peer-reviewed journals and presentation at conferences related to the field. PROSPERO REGISTRATION NUMBER: CRD42021236455.


Subject(s)
Anesthetics , COVID-19 , Adult , Cognition , Critical Illness , Humans , Pandemics , SARS-CoV-2 , Systematic Reviews as Topic
4.
Pharmacotherapy ; 42(1): 58-70, 2022 01.
Article in English | MEDLINE | ID: covidwho-1530208

ABSTRACT

Pregnant and postpartum individuals are known to have an elevated risk of severe COVID-19 compared with their non-pregnant counterparts. Vaccination is the most important intervention to protect these populations from COVID-19-related morbidity and mortality. An added benefit of maternal COVID-19 vaccination is transfer of maternal immunity to newborns and infants, for whom a vaccine is not (yet) approved. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific binding and neutralizing antibodies are present in infant cord blood and breast milk following natural maternal infection and transfer of maternal immunity following COVID-19 vaccination is an area of active research. In this review, we synthesize the available research, discuss knowledge gaps, and outline factors that should be evaluated and reported when studying the transfer of maternal immunity following COVID-19 vaccination. The data reviewed herein suggest that maternal SARS-CoV-2-specific binding antibodies are efficiently transferred via the placenta and breast milk following maternal mRNA COVID-19 vaccination. Moreover, antibodies retain strong neutralizing capacity. Antibody concentrations appear to be at least as high in infant cord blood as in the maternal serum, but lower in breast milk. Breast milk IgA rises rapidly following maternal vaccination, whereas IgG rises later but may persist longer. At least two COVID-19 vaccine doses appear to be required to reach maximal antibody concentrations in cord blood and breast milk. There is no indication that infants consuming breast milk from vaccinated mothers experience serious adverse effects, although follow-up is limited. No clear pattern has emerged regarding changes in milk supply following maternal vaccination. The heterogeneity in important methodological aspects of reviewed studies underscores the need to establish standard best practices related to research on the transfer of maternal COVID-19 vaccine-induced immunity.


Subject(s)
COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Antibodies, Viral/analysis , Antibodies, Viral/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Female , Humans , Infant, Newborn , Milk, Human/immunology , Pregnancy , SARS-CoV-2/immunology
5.
Crit Care Med ; 49(11): 1974-1982, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1475880
6.
Crit Care Med ; 49(10): 1684-1693, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1452742

ABSTRACT

OBJECTIVES: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators. DESIGN: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process. PARTICIPANTS: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process. MEASUREMENTS AND MAIN RESULTS: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization. CONCLUSIONS: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials.


Subject(s)
Hypnotics and Sedatives/pharmacokinetics , Hypnotics and Sedatives/therapeutic use , Congresses as Topic , Consensus , Delphi Technique , District of Columbia , Humans , Hypnotics and Sedatives/pharmacology , Respiration, Artificial/instrumentation , Respiration, Artificial/methods , Time Factors
7.
Chest ; 161(2): 429-447, 2022 02.
Article in English | MEDLINE | ID: covidwho-1401309

ABSTRACT

BACKGROUND: After the publication of a 2014 consensus statement regarding mass critical care during public health emergencies, much has been learned about surge responses and the care of overwhelming numbers of patients during the COVID-19 pandemic. Gaps in prior pandemic planning were identified and require modification in the midst of severe ongoing surges throughout the world. RESEARCH QUESTION: A subcommittee from The Task Force for Mass Critical Care (TFMCC) investigated the most recent COVID-19 publications coupled with TFMCC members anecdotal experience in order to formulate operational strategies to optimize contingency level care, and prevent crisis care circumstances associated with increased mortality. STUDY DESIGN AND METHODS: TFMCC adopted a modified version of established rapid guideline methodologies from the World Health Organization and the Guidelines International Network-McMaster Guideline Development Checklist. With a consensus development process incorporating expert opinion to define important questions and extract evidence, the TFMCC developed relevant pandemic surge suggestions in a structured manner, incorporating peer-reviewed literature, "gray" evidence from lay media sources, and anecdotal experiential evidence. RESULTS: Ten suggestions were identified regarding staffing, load-balancing, communication, and technology. Staffing models are suggested with resilience strategies to support critical care staff. ICU surge strategies and strain indicators are suggested to enhance ICU prioritization tactics to maintain contingency level care and to avoid crisis triage, with early transfer strategies to further load-balance care. We suggest that intensivists and hospitalists be engaged with the incident command structure to ensure two-way communication, situational awareness, and the use of technology to support critical care delivery and families of patients in ICUs. INTERPRETATION: A subcommittee from the TFMCC offers interim evidence-informed operational strategies to assist hospitals and communities to plan for and respond to surge capacity demands resulting from COVID-19.


Subject(s)
Advisory Committees , COVID-19 , Critical Care , Delivery of Health Care/organization & administration , Surge Capacity , Triage , COVID-19/epidemiology , COVID-19/therapy , Critical Care/methods , Critical Care/organization & administration , Evidence-Based Practice/methods , Evidence-Based Practice/organization & administration , Humans , SARS-CoV-2 , Surge Capacity/organization & administration , Surge Capacity/standards , Triage/methods , Triage/standards , United States/epidemiology
8.
Lancet Respir Med ; 9(6): 655-664, 2021 06.
Article in English | MEDLINE | ID: covidwho-1209411

ABSTRACT

The pleiotropic cytokine interleukin-6 (IL-6) has been implicated in the pathogenesis of COVID-19, but uncertainty remains about the potential benefits and harms of targeting IL-6 signalling in patients with the disease. The efficacy and safety of tocilizumab and sarilumab, which block the binding of IL-6 to its receptor, have been tested in adults with COVID-19-related acute respiratory illness in randomised trials, with important differences in trial design, characteristics of included patients, use of co-interventions, and outcome measurement scales. In this Series paper, we review the clinical and methodological heterogeneity of studies of IL-6 receptor antagonists, and consider how this heterogeneity might have influenced reported treatment effects. Timing from clinical presentation to treatment, severity of illness, and concomitant use of corticosteroids are among the factors that might have contributed to apparently inconsistent results. With an understanding of the sources of variability in these trials, available evidence could be applied to guide clinical decision making and to inform the enrichment of future studies.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , COVID-19 , Clinical Trials as Topic , Receptors, Interleukin-6/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/immunology , COVID-19/immunology , COVID-19/therapy , Clinical Trials as Topic/methods , Clinical Trials as Topic/statistics & numerical data , Humans , Patient Selection , Receptors, Interleukin-6/immunology , SARS-CoV-2
9.
Crit Care Med ; 49(3): e219-e234, 2021 03 01.
Article in English | MEDLINE | ID: covidwho-1069322

ABSTRACT

BACKGROUND: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. METHODS: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. RESULTS: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. CONCLUSION: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/therapy , Critical Care , Dexamethasone/therapeutic use , Disease Management , Intensive Care Units , Practice Guidelines as Topic , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Anticoagulants , Evidence-Based Medicine , Hemodynamics , Humans , Hydroxychloroquine , Immunization, Passive , Patient Positioning , Ventilation
10.
Pharmacotherapy ; 40(8): 843-856, 2020 08.
Article in English | MEDLINE | ID: covidwho-602791

ABSTRACT

A hyperinflammatory response to severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, reminiscent of cytokine release syndrome, has been implicated in the pathophysiology of acute respiratory distress syndrome and organ damage in patients with coronavirus disease 2019 (COVID-19). Agents that inhibit components of the pro-inflammatory cascade have garnered interest as potential treatment options with hopes that dampening the proinflammatory process may improve clinical outcomes. Baricitinib is a reversible Janus-associated kinase (JAK)-inhibitor that interrupts the signaling of multiple cytokines implicated in COVID-19 immunopathology. It may also have antiviral effects by targeting host factors that viruses rely for cell entry and by suppressing type I interferon driven angiotensin-converting-enzyme-2 upregulation. However, baricitinib's immunosuppressive effects may be detrimental during acute viral infections by delaying viral clearance and increasing vulnerability to secondary opportunistic infections. The lack of reliable biomarkers to monitor patients' immune status as illness evolves complicates deployment of immunosuppressive drugs like baricitinib. Furthermore, baricitinib carries the risk of increased thromboembolic events, which is concerning given the proclivity towards a hypercoagulable state in patients with COVID-19. In this article, we review available data on baricitinib with an emphasis on immunosuppressive and antiviral pharmacology, pharmacokinetics, safety, and current progress in COVID-19 clinical trials.


Subject(s)
Azetidines/pharmacology , Azetidines/therapeutic use , Coronavirus Infections/complications , Inflammation/drug therapy , Inflammation/etiology , Janus Kinases/antagonists & inhibitors , Pneumonia, Viral/complications , Sulfonamides/pharmacology , Sulfonamides/therapeutic use , Angiotensin-Converting Enzyme 2 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Area Under Curve , Azetidines/administration & dosage , Azetidines/adverse effects , Betacoronavirus , COVID-19 , Clinical Trials as Topic , Cytokines/metabolism , Drug Interactions , Humans , Interferon Type I/biosynthesis , Metabolic Clearance Rate , Pandemics , Peptidyl-Dipeptidase A/biosynthesis , Purines , Pyrazoles , SARS-CoV-2 , Signal Transduction/drug effects , Sulfonamides/administration & dosage , Sulfonamides/adverse effects
11.
Intensive Care Med ; 46(7): 1303-1325, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-574921

ABSTRACT

Given the rapidly changing nature of COVID-19, clinicians and policy makers require urgent review and summary of the literature, and synthesis of evidence-based guidelines to inform practice. The WHO advocates for rapid reviews in these circumstances. The purpose of this rapid guideline is to provide recommendations on the organizational management of intensive care units caring for patients with COVID-19 including: planning a crisis surge response; crisis surge response strategies; triage, supporting families, and staff.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Intensive Care Units/organization & administration , Pandemics , Pneumonia, Viral/therapy , COVID-19 , Coronavirus Infections/epidemiology , Critical Care/standards , Equipment and Supplies, Hospital , Health Care Rationing/standards , Health Workforce , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Intensive Care Units/standards , Personal Protective Equipment , Pneumonia, Viral/epidemiology , Respiration, Artificial/instrumentation , Respiration, Artificial/standards , SARS-CoV-2 , Triage
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