ABSTRACT
INTRODUCTION: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk. METHODS AND ANALYSIS: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation. ETHICS AND DISSEMINATION: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309). TRIAL REGISTRATION NUMBER: NCT05148715.
Subject(s)
Calcineurin Inhibitors , Delayed Graft Function , Kidney Transplantation , Tissue Donors , Adult , Female , Humans , Male , Brain Death , Calcineurin Inhibitors/administration & dosage , Calcineurin Inhibitors/therapeutic use , Delayed Graft Function/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Multicenter Studies as Topic , Ontario , Pilot Projects , Quebec , Randomized Controlled Trials as Topic , Tacrolimus/therapeutic use , Tacrolimus/administration & dosageABSTRACT
Despite significant progress in our understanding of the pathophysiology of sepsis and extensive clinical research, there are few proven therapies addressing the underlying immune dysregulation of this life-threatening condition. The aim of this scoping review is to describe the literature evaluating immunotherapy in adult patients with sepsis, emphasizing on methods providing a "personalized immunotherapy" approach, which was defined as the classification of patients into a distinct subgroup or subphenotype, in which a patient's immune profile is used to guide treatment. Subgroups are subsets of sepsis patients, based on any cut-off in a variable. Subphenotypes are subgroups that can be reliably discriminated from other subgroup based on data-driven assessments. Included studies were randomized controlled trials and cohort studies investigating immunomodulatory therapies in adults with sepsis. Studies were identified by searching PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov, from the first paper available until January 29th, 2024. The search resulted in 15,853 studies. Title and abstract screening resulted in 1409 studies (9%), assessed for eligibility; 771 studies were included, of which 282 (37%) were observational and 489 (63%) interventional. Treatment groups included were treatments targeting the innate immune response, the complement system, coagulation and endothelial dysfunction, non-pharmalogical treatment, pleiotropic drugs, immunonutrition, concomitant treatments, Traditional Chinese Medicine, immunostimulatory cytokines and growth factors, intravenous immunoglobulins, mesenchymal stem cells and immune-checkpoint inhibitors. A personalized approach was incorporated in 70 studies (9%). Enrichment was applied using cut-offs in temperature, laboratory, biomarker or genetic variables. Trials often showed conflicting results, possibly due to the lack of patient stratification or the potential influence of severity and timing on immunomodulatory therapy results. When a personalized approach was applied, trends of clinical benefit for several interventions emerged, which hold promise for future clinical trials using personalized immunotherapy.
Subject(s)
Immunotherapy , Precision Medicine , Sepsis , Humans , Precision Medicine/methods , Precision Medicine/trends , Sepsis/therapy , Sepsis/immunology , Sepsis/drug therapy , Immunotherapy/methods , Immunotherapy/trendsABSTRACT
Mortality is a well-established patient-important outcome in critical care studies. In contrast, morbidity is less uniformly reported (given the myriad of critical care illnesses and complications of each) but may have a common end-impact on a patient's functional capacity and health-related quality-of-life (HRQoL). Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences. Hence, as mortality decreases within critical care, it becomes increasingly important to measure intensive care unit (ICU) survivor HRQoL. HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0 (representing death) and 1 (representing full health). They can be combined with survival to calculate quality-adjusted life-years (QALY), which are one of the most widely used methods of combining morbidity and mortality into a composite outcome. Although QALYs have been use for health-technology assessment decision-making, an emerging and novel role would be to inform clinical decision-making for patients, families and healthcare providers about what expected HRQoL may be during and after ICU care. Critical care randomized control trials (RCTs) have not routinely measured or reported HRQoL (until more recently), likely due to incapacity of some patients to participate in patient-reported outcome measures. Further differences in HRQoL measurement tools can lead to non-comparable values. To this end, we propose the validation of a gold-standard HRQoL tool in critical care, specifically the EQ-5D-5L. Both combined health-utility and mortality (disaggregated) and QALYs (aggregated) can be reported, with disaggregation allowing for determination of which components are the main drivers of the QALY outcome. Increased use of HRQoL, health-utility, and QALYs in critical care RCTs has the potential to: (1) Increase the likelihood of finding important effects if they exist; (2) improve research efficiency; and (3) help inform optimal management of critically ill patients allowing for decision-making about their HRQoL, in additional to traditional health-technology assessments.
ABSTRACT
INTRODUCTION: Sepsis, a life-threatening organ dysfunction syndrome occurring in the context of severe infections, remains a major burden on global health with high morbidity and high mortality rates. Despite recent advances in the understanding of its pathophysiology, the treatment of sepsis remains supportive of nature with few interventions specifically designed for treating this complex syndrome. The focus of sepsis trials has increasingly shifted towards targeting excessive inflammation and immunosuppression using immunomodulatory agents. However, it remains uncertain how to identify patients that could benefit from such treatment, whether treatments can be tailored to an individual's immune profile, or at which stage of the disease the intervention should be initiated. In this scoping review, we provide a comprehensive overview of current available literature on immunostimulatory and immunosuppressive therapies against sepsis. METHODS AND ANALYSIS: The aim of this scoping review is to describe and summarise current literature evaluating immunotherapy in adult patients with sepsis. The review will be performed using the framework formulated by Arksey and O'Malley. A comprehensive literature and study collection will be executed by searching PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov to identify clinical trials and cohort studies concerning immunotherapy in adult patients with sepsis. Screening will be performed independently and in duplicate by two reviewers who will also independently extract data into prespecified spreadsheets. We will summarise evidence in tabular format with descriptive statistics. The reported evidence will convey knowledge on the types of immunotherapies studied, and currently being studied, in adult patients with sepsis. ETHICS AND DISSEMINATION: Approval from a medical ethics committee is not required. Once completed, the review will be submitted for publication in a peer-reviewed journal. These results will be of value to clinicians and researchers with an interest in advancing sepsis care.
Subject(s)
Research Design , Sepsis , Adult , Humans , Immunotherapy , Peer Review , Population Groups , Review Literature as Topic , Sepsis/therapyABSTRACT
OBJECTIVES: Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use (24 hr) high-dose tranexamic acid, prompting a reappraisal for tranexamic acid in gastrointestinal bleeding. DATA SOURCES: We conducted a systematic review and meta-analysis of randomized controlled trials comparing tranexamic acid with usual care or placebo in adults with gastrointestinal bleeding. We searched MEDLINE, EMBASE, and CENTRAL (inception to September 2019). DATA SELECTION: Two reviewers independently screened citations, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool in duplicate. The main outcomes were mortality, bleeding, and adverse events. DATA EXTRACTION: Studies were analyzed as high-dose IV tranexamic acid versus all other dosing strategies for tranexamic acid using fixed-effects models. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Five randomized controlled trials evaluated extended-use high-dose IV tranexamic acid, seven evaluating low-dose IV or enteral tranexamic acid. Extended-use high-dose IV tranexamic acid did not reduce mortality (relative risk, 0.98%; 95% CI, 0.88-1.09; I2 = 63%; high certainty) or bleeding (relative risk, 0.92; 95% CI, 0.82-1.04; p = 0.17 and absolute risk differences, -0.7%; 95% CI, -1.5 to 0.3; high certainty) but resulted in a small increase in deep venous thrombosis (relative risk, 2.01; 95% CI, 1.08-3.72; I2 = 0%), pulmonary embolism (relative risk, 1.78; 95% CI, 1.06-3.0; I2 = 0%), and seizure (relative risk, 1.73; 95% CI, 1.03-2.93) with high certainty. Low-dose IV/enteral tranexamic acid did not reduce mortality (relative risk, 0.62; 95% CI, 0.36-1.09; I2 = 0%) but did reduce risk of rebleeding (relative risk, 0.5; 95% CI, 0.33-0.75; I2 = 9%) and need for surgery (relative risk, 0.58; 95% CI, 0.38-0.88; I2 = 11%), with moderate certainty. CONCLUSIONS: Extended-use high-dose IV tranexamic acid does not improve mortality or bleeding outcomes and increases adverse events. Low-dose/enteral tranexamic acid may be effective in reducing hemorrhage; more evidence is required to demonstrate its safety.
Subject(s)
Antifibrinolytic Agents/therapeutic use , Gastrointestinal Hemorrhage/drug therapy , Tranexamic Acid/therapeutic use , Gastrointestinal Hemorrhage/mortality , Humans , Length of Stay/statistics & numerical data , Secondary Prevention/statistics & numerical dataABSTRACT
BACKGROUND: Medical assistance in dying has been available in Canada for 5 years, but it is unclear which practices contribute to high-quality care. We aimed to describe patient and family perspectives of quality of care for medical assistance in dying. METHODS: We conducted a multi-centre, qualitative descriptive study, including face to face or virtual one-hour interviews using a semi-structured guide. We interviewed 21 english-speaking patients found eligible for medical assistance in dying and 17 family members at four sites in Canada, between November 2017 and September 2019. Interviews were de-identified, and analyzed in an iterative process of thematic analysis. RESULTS: We identified 18 themes. Sixteen themes were related to a single step in the process of medical assistance in dying (MAID requests, MAID assessments, preparation for dying, death and aftercare). Two themes (coordination and patient-centred care) were theme consistently across multiple steps in the MAID process. From these themes, alongside participant recommendations, we developed clinical practice suggestions which can guide care. CONCLUSIONS: Patients and families identified process-specific successes and challenges during the process of medical assistance in dying. Most importantly, they identified the need for care coordination and a patient-centred approach as central to high-quality care. More research is required to characterize which aspects of care most influence patient and family satisfaction.
Subject(s)
Suicide, Assisted , Canada , Humans , Medical Assistance , Qualitative Research , Quality of Health CareABSTRACT
SOURCE CITATION: RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet. 2021;397:2049-59. 34000257.
Subject(s)
COVID-19 , Coronavirus Infections , COVID-19/therapy , Humans , Immunization, Passive , SARS-CoV-2 , Treatment Outcome , COVID-19 SerotherapyABSTRACT
CONTEXT: Since Canada decriminalized medical assistance in dying (MAID) in 2015, clinicians and organizations have developed policies and protocols to implement assisted dying in clinical practice. Five years on, there is little consensus as to what constitutes high-quality care in MAID. OBJECTIVES: To describe MAID clinicians' perspectives on quality of care in MAID, including challenges, successes, and clinical practice suggestions. METHODS: We conducted an exploratory, multicenter, and qualitative study at four Canadian centers. Using a semistructured interview guide, we conducted interviews with 20 health care providers. Interviews were transcribed and deidentified before analysis. Adopting a qualitative descriptive approach, we used a thematic analysis to identify primary and secondary themes in the interviews and practice suggestions to improve quality of care to patients who request MAID. RESULTS: We identified three major themes. 1) Improving access and patient experience: clinicians described struggles in ensuring equitable access to MAID and supporting MAID patients and their families. 2) Supporting providers and sustainability: clinicians described managing MAID workload, remuneration, educational needs, and the emotional impact of participating in assisted dying. 3) Institutional support: descriptions of MAID communication tools and training, use of standardized care pathways, interprofessional collaboration, and human resource planning. Clinicians also described suggestions for clinical practice to improve quality of care. CONCLUSION: Canadian health care providers described unique challenges in caring for patients who request MAID, along with practices to improve the quality of care.
Subject(s)
Suicide, Assisted , Canada , Health Personnel , Humans , Medical Assistance , Quality of Health CareABSTRACT
INTRODUCTION: Rates of successful organ donation vary between otherwise comparable intensive care units (ICUs). The ICU staff have a unique perspective into the facilitators and barriers underlying this variation in successful deceased organ donation. RESEARCH QUESTION: What do ICU staff perceive to be the most meaningful facilitators and barriers to deceased organ donation? DESIGN: We designed and conducted a survey of all disciplines working in the ICU to ascertain the perceived facilitators and barriers to donation in an academic tertiary care hospital. Survey reliability was assessed using Cronbach α. Factor analysis was used to assess construct validity and identify potentially redundant survey items. RESULTS: We had responses from 108 ICU staff, including nurses (n = 75), respiratory therapists (n = 14), physicians (n = 12), chaplains (n = 2), as well as social work, pharmacy, physiotherapy, and occupational therapy (n = 1 each). Perceived facilitators included availability of organ donation organization coordinators, explicit institutional support for donation, ICU staff culture toward donation, standardized order sets for donation, presence of ICU staff with donation experience, and bedside nurse presence at discussions about donation. Perceived barriers included ICU staff ruling out potentially suitable donors before consulting a donor coordinator, physician communication skills, low priority for organ donation among operating room staff, limited family understanding of patient prognosis and organ donation, and limited emotional readiness of families to discuss donation. DISCUSSION: Several staff-perceived facilitators and barriers to deceased organ donation were identified in the ICU. Future research could identify strategies to promote these facilitators and overcome barriers.
Subject(s)
Attitude of Health Personnel , Brain Injuries, Traumatic , Communication Barriers , Decision Making , Intensive Care Units , Tissue and Organ Procurement , Humans , Ontario , Surveys and QuestionnairesABSTRACT
PURPOSE: Rates of organ donation vary between otherwise comparable intensive care units (ICUs) suggesting that the process of donation must vary between ICUs. The purpose of this study was to describe the process of organ donation from the perspective of ICU staff, identify important drivers of successful donation, and develop strategies to improve the process of donation. METHODS: We conducted qualitative interviews with 32 ICU staff, including physicians, nurses, and respiratory therapists, using an interview guide developed from previous studies on organ donation. Using a qualitative descriptive approach, we coded interviews using qualitative content analysis. We integrated findings from the interviews in a mixed-methods analysis with previously published data from a document analysis and cross-sectional survey to identify practices that may enhance organ donation in the ICU. RESULTS: Five major themes important to the organ donation process emerged from the interviews: i) staff relationship with organ donation coordinators; ii) standardized processes; iii) ICU staff beliefs; iv) integration of donation and high quality end-of-life care; v) feedback and staff support. In the mixed-methods analysis, we identified 22 actionable practices to enhance the process of organ donation in the ICU. CONCLUSION: Incorporating the perspectives of ICU staff, we were able to identify 22 practice changes that may have a significant cumulative impact on donation outcomes. Future research is required to evaluate whether these findings account for the variability of donation rates between otherwise comparable ICUs.
Subject(s)
Health Personnel/statistics & numerical data , Intensive Care Units , Tissue and Organ Procurement/methods , Adult , Attitude of Health Personnel , Cross-Sectional Studies , Female , Humans , Interviews as Topic , Male , Medical Staff, Hospital/statistics & numerical data , Middle Aged , Nursing Staff, Hospital/statistics & numerical data , Tissue and Organ Procurement/standardsABSTRACT
PURPOSE: To assess the feasibility of a trial evaluating whether hyperoncotic albumin, in addition to diuretics, improves diuresis and facilitates liberation from mechanical ventilation in critically ill adults. MATERIALS AND METHODS: We randomized 46 hemodynamically stable patients with hypoalbuminemia, prescribed diuretics by treating clinicians, to receive 100â¯mL of 25% albumin or 0.9% saline placebo BID, for three days, in blinded fashion. We chose five feasibility measurements: enrolment of 50% of eligible patients, at least one patient/week; administration of study treatment within 2â¯h of diuretics in 85% of patients; completion of study regimen in 80% of patients; and avoidance of open label albumin in 85% of patients. Clinical outcomes included fluid balance, ventilator-free days, and mortality. RESULTS: We randomized 85% of eligible patients. Eighty-four percent received study treatment within 2â¯h of diuretics, 69% received all doses of study treatment. Study treatment was held in the albumin and placebo groups because of no further need for diuresis (4 vs. 1), hypotension (2 v. 4), and albuminâ¯>â¯35 (1 v. 0). Twenty percent of patients received open-label albumin. Clinical outcomes were similar between groups. CONCLUSIONS: The current study design did not demonstrate feasibility, but can inform the design of a definitive trial.
Subject(s)
Albumins/administration & dosage , Critical Illness/therapy , Diuresis/physiology , Diuretics/administration & dosage , Fluid Therapy/methods , Furosemide/administration & dosage , Adult , Aged , Female , Humans , Male , Middle Aged , Pilot ProjectsABSTRACT
OBJECTIVE: To better understand how local policies influence organ donation rates. RESEARCH METHODOLOGY/DESIGN: We conducted a document analysis of our ICU organ donation policies, protocols and order sets. We used a systematic search of our institution's policy library to identify documents related to organ donation. We used Mindnode software to create a publication timeline, basic statistics to describe document characteristics, and qualitative content analysis to extract document themes. SETTING: Documents were retrieved from Hamilton Health Sciences, an academic hospital system with a high volume of organ donation, from database inception to October 2015. FINDINGS: We retrieved 12 active organ donation documents, including six protocols, two policies, two order sets, and two unclassified documents, a majority (75%) after the introduction of donation after circulatory death in 2006. Four major themes emerged: organ donation process, quality of care, patient and family-centred care, and the role of the institution. These themes indicate areas where documented institutional standards may be beneficial. CONCLUSION: Further research is necessary to determine the relationship of local policies, protocols, and order sets to actual organ donation practices, and to identify barriers and facilitators to improving donation rates.
Subject(s)
Intensive Care Units/trends , Organizational Policy , Tissue and Organ Procurement/methods , Humans , Intensive Care Units/organization & administration , Patient-Centered Care/methods , Qualitative Research , Quality of Health Care/organization & administration , Quality of Health Care/standards , Tissue and Organ Procurement/legislation & jurisprudence , Tissue and Organ Procurement/trendsABSTRACT
INTRODUCTION: Medical assistance in dying (MAID), a term encompassing both euthanasia and assisted suicide, was decriminalised in Canada in 2015. Although Bill C-14 legislated eligibility criteria under which patients could receive MAID, it did not provide guidance regarding the technical aspects of providing an assisted death. Therefore, we propose a scoping review to map the characteristics of the existing medical literature describing the medications, settings, participants and outcomes of MAID, in order to identify knowledge gaps and areas for future research. METHODS AND ANALYSIS: We will search electronic databases (MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO), clinical trial registries, conference abstracts, and professional guidelines and recommendations from jurisdictions where MAID is legal, up to June 2017. Eligible report types will include technical summaries, institutional policies, practice surveys, practice guidelines and clinical studies. We will include all descriptions of MAID provision (either euthanasia or assisted suicide) in adults who have provided informed consent for MAID, for any reason, including reports where patients have provided consent to MAID in advance of the development of incapacity (eg, dementia). We will exclude reports in which patients receive involuntary euthanasia (eg, capital punishment). Two independent investigators will screen and select retrieved reports using pilot-tested screening and eligibility forms, and collect data using standardised data collection forms. We will summarise extracted data in tabular format with accompanying descriptive statistics and use narrative format to describe their clinical relevance, identify knowledge gaps and suggest topics for future research. ETHICS AND DISSEMINATION: This scoping review will map the range and scope of the existing literature on the provision of MAID in jurisdictions where the practice has been decriminalised. The review will be disseminated through conference presentations and publication in a peer-reviewed journal. These results will be useful to clinicians, policy makers and researchers involved with MAID.
Subject(s)
Euthanasia, Active/methods , Suicide, Assisted , Canada , Euthanasia, Active/legislation & jurisprudence , Euthanasia, Active, Voluntary/legislation & jurisprudence , Humans , Legislation, Medical , Research Design , Suicide, Assisted/legislation & jurisprudenceABSTRACT
PURPOSE: To identify elements which enable patient and family centred care (PFCC) in the intensive care unit (ICU) and priorities for PFCC research. MATERIALS AND METHODS: We engaged a panel of multidisciplinary stakeholders in a modified Delphi process. Items generated from a literature review and panelist suggestions were rated in 3 successive rounds on a scale from 1 to 7. Median score was used to rate each item's priority, with 5 or more indicating "essential priority," 4 or 5 "moderate priority" and 3 or less "low priority." Interquartile range (IQR) was used to measure consensus, with IQR of 1 indicating "high" consensus, 2 "moderate" consensus, and 3 or greater "low" consensus. RESULTS: Six items were rated essential elements for facilitating PFCC with high consensus (flexible visiting hours, family participation in bedside care, trained family support person, interventions to facilitate continuity of care, staff education to support families, continuity of staff assignments). Three items were rated essential research topics: interventions to facilitate continuity of care following ICU discharge (moderate consensus), family participation in bedside care (low consensus), and decision aids for end of life decision-making (low consensus). CONCLUSIONS: Stakeholders identified clear and distinct priorities for PFCC in clinical care and research, though there was greater consensus for clinical care.
Subject(s)
Critical Care/standards , Family Health/standards , Health Priorities , Patient-Centered Care/standards , Consensus , Critical Care/organization & administration , Decision Making , Delphi Technique , Family , Humans , Intensive Care Units , Patient-Centered Care/organization & administration , ResearchABSTRACT
OBJECTIVE: Constipation is common among critically ill patients and has been associated with adverse patient outcomes. Many ICUs have developed bowel protocols to treat constipation; however, their effect on clinical outcomes remains uncertain. We conducted a systematic review to determine the impact of bowel protocols in critically ill adults. DATA SOURCES: We searched MEDLINE, Embase, CINAHL, CENTRAL, ISRCTN, ClinicalTrials.gov, and conference abstracts until January 2016. STUDY SELECTION: Two authors independently screened titles and abstracts for randomized controlled trials comparing bowel protocols to control (placebo, no protocol, or usual care) in critically ill adults. DATA EXTRACTION: Two authors independently, and in duplicate, extracted study characteristics, outcomes, assessed risk of bias, and appraised the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: We retrieved 4,520 individual articles, and excluded 4,332 articles during title and abstract screening and 181 articles during full-text screening. Four trials, including 534 patients, were eligible for analysis. The use of a bowel protocol was associated with a trend toward a reduction in constipation (risk ratio, 0.50 [95% CI, 0.25-1.01]; p = 0.05; low-quality evidence); no reduction in tolerance of enteral feeds (risk ratio, 0.94 [95% CI, 0.62-1.42]; p = 0.77; low-quality evidence), and no change in the duration of mechanical ventilation (mean difference, 0.01 d [95% CI, -2.67 to 2.69 d]; low-quality evidence). CONCLUSIONS: Large, rigorous, randomized control trials are needed to determine whether bowel protocols impact patient-important outcomes in critically ill adults.
Subject(s)
Clinical Protocols , Constipation/prevention & control , Constipation/therapy , Critical Illness , Intensive Care Units/organization & administration , Humans , Intensive Care Units/standards , Randomized Controlled Trials as TopicABSTRACT
INTRODUCTION: Sepsis is a common and deadly complication of infection. As part of the host response, sympathetic stimulation can result in septic myocardial depression, and metabolic, haematological and immunological dysfunction. Administration of ß-blockers may attenuate this pathophysiological response to infection, but the effects on clinical outcomes are unknown. The objective of this systematic review is to determine the efficacy and safety of ß-blockers in adults with sepsis using data from randomised control trials. METHODS AND ANALYSIS: We will identify randomised control trials comparing treatment with ß-blockers, versus placebo or standard care in adults with sepsis. Data sources will include MEDLINE, EMBASE, CENTRAL, clinical trial registries and conference proceedings. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, risk of bias assessment and evaluation of the quality of the evidence using the GRADE approach. ETHICS AND DISSEMINATION: Our systematic review will evaluate the effects of ß-blockers in adults with sepsis, comprehensively summarising and appraising the available evidence from randomised control trials. The results of this systematic review will help clinicians treating patients with sepsis to understand the potential role of ß-blockade, and inform future research on this topic. Our findings will be disseminated through conference presentation and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42016036933.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Sepsis/drug therapy , Humans , Randomized Controlled Trials as Topic , Research Design , Systematic Reviews as TopicABSTRACT
BACKGROUND: Practicing healthcare professionals and graduates exiting training programs are often ill-equipped to facilitate important discussions about end-of-life care with patients and their families. We conducted a systematic review to evaluate the effectiveness of educational interventions aimed at providing healthcare professionals with training in end-of-life communication skills, compared to usual curriculum. METHODS: We searched MEDLINE, Embase, CINAHL, ERIC and the Cochrane Central Register of Controlled Trials from the date of inception to July 2014 for randomized control trials (RCT) and prospective observational studies of educational training interventions to train healthcare professionals in end-of-life communication skills. To be eligible, interventions had to provide communication skills training related to end-of-life decision making; other interventions (e.g. breaking bad news, providing palliation) were excluded. Our primary outcomes were self-efficacy, knowledge and end-of-life communication scores with standardized patient encounters. Sufficiently similar studies were pooled in a meta-analysis. The quality of evidence was assessed using GRADE. RESULTS: Of 5727 candidate articles, 20 studies (6 RCTs, 14 Observational) were included in this review. Compared to usual teaching, educational interventions to train healthcare professionals in end-of-life communication skills were associated with greater self-efficacy (8 studies, standardized mean difference [SMD] 0.57;95% confidence interval [CI] 0.40-0.75; P < 0.001; very low quality evidence), more knowledge (4 studies, SMD 0.76;95% CI 0.40-1.12; p < 0.001; low quality evidence), and improvements in communication scores (8 studies, SMD 0.69; 95% CI 0.41-0.96; p < 0.001; very low quality evidence). There was insufficient evidence to determine whether these educational interventions affect patient-level outcomes. CONCLUSION: Very low to low quality evidence suggests that end-of-life communication training may improve healthcare professionals' self-efficacy, knowledge, and EoL communication scores compared to usual teaching. Further studies comparing two active educational interventions are recommended with a continued focus on contextually relevant high-level outcomes. TRIAL REGISTRATION: PROSPERO CRD42014012913.
Subject(s)
Communication , Education, Medical , Terminal Care , Humans , Observational Studies as Topic , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: For many patients admitted to the intensive care unit (ICU), preferences for end-of-life care are unknown, and clinicians and substitute decision-makers are required to make decisions about the goals of care on their behalf. We conducted a systematic review to determine the effect of structured communication tools for end-of-life decision-making, compared to usual care, upon the number of documented goals of care discussions, documented code status, and decisions to withdraw life-sustaining treatments, in adult patients admitted to the ICU. METHODS: We searched multiple databases including MEDLINE, Embase, CINAHL, ERIC, and Cochrane from database inception until July 2014. Two reviewers independently screened articles, assessed eligibility, verified data extraction, and assessed risk of bias using the tool described by the Cochrane Collaboration and the Newcastle Ottawa Scale. Pooled estimates of effect (relative risk, standardized mean difference, or mean difference), were calculated where sufficient data existed. GRADE was used to evaluate the overall quality of evidence for each outcome. RESULTS: We screened 5785 abstracts and reviewed the full text of 424 articles, finding 168 eligible articles, including 19 studies in the ICU setting. The use of communication tools increased documentation of goals-of-care discussions (RR 3.47, 95% CI 1.55, 7.75, p = 0.020, very low-quality evidence), but did not have an effect on code status documentation (RR 1.03, 95% CI 0.96, 1.10, p = 0.540, low-quality evidence) or decisions to withdraw or withhold life-sustaining treatments (RR 0.98, 95% CI 0.89, 1.08, p = 0.70, low-quality evidence). The use of such tools was associated with a decrease in multiple measures of health care resource utilization, including duration of mechanical ventilation (MD -1.9 days, 95% CI -3.26, -0.54, p = 0.006, very low-quality evidence), length of ICU stay (MD -1.11 days, 95% CI -2.18, -0.03, p = 0.04, very low-quality evidence), and health care costs (SMD -0.32, 95% CI -0.5, -0.15, p < 0.001, very low-quality evidence). CONCLUSIONS: Structured communication tools may improve documentation of EOL decision making and may result in lower resource use. The supporting evidence is low to very low in quality. Further high-quality randomized studies of simple communication interventions are needed to determine whether structured, rather than ad hoc, approaches to end-of-life decision-making improve patient-level, family-level, and system-level outcomes. TRIAL REGISTRATION: PROSPERO CRD42014012913.