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International audience; BACKGROUND Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).

Purpose We sought to examine changes in acute respiratory distress syndrome (ARDS) management over a 12-year period of two successive randomized trials. Methods Analyses included baseline data, from eligible patients, prior to influence of trial protocols, and daily study data, from randomized patients, of variables not determined by trial protocols. Mixed linear regressions examined changes in practice year-on-year. Results A total of 2376 patients met the inclusion criteria. Over the 12-year period, baseline tidal volume index decreased (9.0 to 7.0 ml/kg, p < 0.001), plateau pressures decreased (30.8 to 29.0 cmH2O, p < 0.05), and baseline positive end-expiratory pressures increased (10.8 to 13.2 cmH2O, p < 0.001). Volume-controlled ventilation declined from 29.4 to 14.0% (p < 0.01). Use of corticosteroids increased (baseline: 7.7 to 30.3%; on study: 32.6 to 61.2%; both p < 0.001), as did neuromuscular blockade (baseline: 12.3 to 24.5%; on study: 55.5 to 70.0%; both p < 0.01). Inhaled nitric oxide use increased (24.9 to 65.8%, p < 0.05). We observed no significant change in prone positioning (16.2 to 18.9%, p = 0.70). Conclusions Clear trends were apparent in tidal volume, airway pressures, ventilator modes, adjuncts and rescue therapies. With the exception of prone positioning, and outside the context of rescue therapy, these trends appear consistent with the evolving literature on ARDS management.

To categorize, quantify and interpret findings documented in feedback letters of monitoring or auditing visits for an investigator-initiated, peer-review funded multicenter randomized trial testing probiotics for critically ill patients.In 37 Canadian centers, monitoring and auditing visits were performed by 3 trained individuals; findings were reported in feedback letters. At trial termination, we performed duplicate content analysis on letters, categorizing observations first into unique findings, followed by 10 pre-determined trial quality management domains. We further classified each observation into a) missing operational records, b) errors in process, and potential threats to c) data integrity, d) patient privacy or e) safety.Across 37 monitoring or auditing visits, 75 unique findings were categorized into 10 domains. Most frequently, observations were in domains of training documentation (180/566 [32%]) and the informed consent process (133/566 [23%]). Most observations were missing operational records (438/566 [77%]) rather than errors in process (128/566 [23%]). Of 75 findings, 13 (62/566 observations [11%]) posed a potential threat to data integrity, 1 (1/566 observation [0.18%]) to patient privacy, and 9 (49/566 observations [8.7%]) to patient safety.Monitoring and auditing findings predominantly concerned missing documentation with minimal threats to data integrity, patient privacy or safety.PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial): NCT02462590.

Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices. This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces. Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34–35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces. These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials. Trial registration: www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.

Background Critical care research coordinators implement study protocols in intensive care units, yet little is known about their experiences. Objective To identify the responsibilities, stressors, motivators, and job satisfaction of critical care research coordinators in Canada. Methods Responses to a self-administered survey were collected in order to identify and understand factors that motivate and stress research coordinators and enhance their job satisfaction. Items were generated in 5 domains (demographics, job responsibilities, stressors, motivators, and satisfaction). Face validity pretesting was conducted and clinical sensibility was evaluated. Items were rated on 5-point Likert scales. Descriptive analyses were used to report results. Results The response rate was 78% (66 of 85). Most critical care research coordinators (71%) were employed full time; they were engaged in 9 studies (7 academic, 2 industry); and 49% were nurses. Of 30 work responsibilities, the most frequently cited were submitting ethics applications (89%), performing data entry (89%), and attending meetings (87%). Highest-rated stressors were unrealistic workload and weekend/holiday screening; highest-rated motivators were a positive work environment and team spirit. Overall, 26% were “very satisfied” and 53% were “satisfied” with their jobs. Conclusions Critical care research coordinators in Canada indicate that, despite significant work responsibilities, they are satisfied with their jobs thanks to positive work environments and team spirit.

Objectives It is unknown whether more frequent screening of invasively ventilated patients, identifies patients earlier for a spontaneous breathing trial, and shortens the duration of ventilation. We assessed the feasibility of conducting a large trial to evaluate screening frequency in critically ill adults in the North American context. Design We conducted two contemporaneous, multicenter, pilot, randomized controlled trials (the LibeRation from MEchanicaL VEntilAtion and ScrEening Frequency [RELEASE] and Screening Elderly PatieNts For InclusiOn in a Weaning [SENIOR] trials) to address concerns regarding the potential for higher enrollment, fewer adverse events, and better outcomes in younger patients. Setting Ten and 11 ICUs in Canada, respectively. Patients Parallel trials of younger (RELEASE Interventions Each trial compared once daily screening to "at least twice daily" screening led by respiratory therapists. Measurements and main results In both trials, we evaluated recruitment (aim: 1-2 patients/month/ICU) and consent rates, reasons for trial exclusion, protocol adherence (target: ≥ 80%), crossovers (aim: ≤ 10%), and the effect of the alternative screening frequencies on adverse events and clinical outcomes. We included 155 patients (53 patients [23 once daily, 30 at least twice daily] in RELEASE and 102 patients [54 once daily, 48 at least twice daily] in SENIOR). Between trials, we found similar recruitment rates (1.32 and 1.26 patients/month/ICU) and reasons for trial exclusion, high consent and protocol adherence rates (> 92%), infrequent crossovers, and few adverse events. Although underpowered, at least twice daily screening was associated with a nonsignificantly faster time to successful extubation and more successful extubations but significantly increased use of noninvasive ventilation in both trials combined. Conclusions Similar recruitment and consent rates, few adverse events, and comparable outcomes in younger and older patients support conduct of a single large trial in North American ICUs assessing the net clinical benefits associated with more frequent screening.

Background Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality. Methods We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing. Results We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range [IQR] 2–4) and 6 days (stool; IQR 4.25–6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = − 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045). Conclusions The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients. Trial registration ClinicalTrials.gov ID NCT01782755. Registered February 4 2013. Electronic supplementary material The online version of this article (10.1186/s12931-018-0950-5) contains supplementary material, which is available to authorized users.

Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices.This prospective observational cohort study enrolled consecutive, newly consented organ donors from August 1 2015 to July 31 2018 at 27 academic and five community adult intensive care units in British Columbia, Alberta, Ontario, and Quebec. Research staff prospectively recorded donor management data. Provincial organ donation organizations verified the organs donated. We formally compared practices across provinces.Over a median collection period of eight months, 622 potential donors were classified at baseline as having neurologic determination of death (NDD donors; n = 403) or circulatory death (DCD donors; n = 219). Among NDD donors, 85.6% underwent apnea testing (rarely with carbon dioxide insufflation), 33.2% underwent ancillary testing, and subsequent therapeutic hypothermia (34-35°C) was rare. Neurologic determination of death donors were more hemodynamically unstable with most having received vasopressin and norepinephrine infusions, with a large majority having received high-dose corticosteroids and intravenous thyroxine. Among DCD donors, 61.6% received corticosteroids, and 8.9% received thyroxine. Most donors did not receive lung-protective ventilation strategies. Invasive procedures after donation consent included bronchoscopy (71.7%), cardiac catheterization (NDD donors only; 21.3%), and blood transfusions (19.3%). Physicians ordered intravenous antemortem heparin for 94.8% of DCD donors. The cohort donated 1,629 organs resulting in 1,532 transplants. Case selection, death determinations, and hormone, nutrition and heparin practices all varied across provinces.These study findings highlight areas for knowledge translation and further clinical research. Interprovincial discrepancies will likely pose unique challenges to national randomized trials.www.clinicaltrials.gov (NCT03114436); registered 10 April, 2017.RéSUMé: OBJECTIF: Les pratiques canadiennes de prise en charge des donneurs n’ont pas été rapportées. Notre objectif était d’informer les cliniciens et autres parties intéressées quant à l’éventail des pratiques actuelles. MéTHODE: Cette étude de cohorte observationnelle et prospective a recruté des donneurs d’organes consécutifs ayant récemment consenti au don entre le 1

Improving the medical care of deceased organ donors to increase transplant rates and improve allograft function requires an understanding of the current epidemiology and clinical practices of deceased donation within intensive care units (ICUs). Herein, we report the results of our investigation into the feasibility of a multicentre prospective cohort study addressing the afformentioned issues. We conducted a 12-month prospective observational cohort study in six ICUs and one coronary care unit in Hamilton, Canada. We included consecutive children and adults following consent for deceased organ donation (including neurologic determination of death [NDD] or donation after circulatory death [DCD]). Intensive care unit research staff recorded donor management data from hospital records, extending from one day prior to the consent for organ donation up to the time of organ retrieval. The provincial Organ Donation Organization (ODO) supplemented these data and, additionally, provided data on corresponding organ recipients. We identified, evaluated, and measured three potential obstacles to the feasibility of a national cohort study: obtaining authorization to implement the study with a waiver of research consent, accessibility of transplant recipient data, and the time required to complete very detailed case report forms (CRFs), with valuable lessons learned for implementation in future projects. The local Research Ethics Board and the ODO Privacy Office both authorized the recording of donor and recipient study data with a waiver of research consent. Sixty-seven consecutive consented donors were included (31 NDD and 36 DCD donors); 50 of them provided 144 organs for transplantation to 141 recipients. We identified the age and sex of the recipients as well as the location and date of transplant for all organ recipients in Ontario; however, we obtained no recipient data for six organs transported outside of Ontario. Intensive care unit research staff estimated that future CRF completion will require five to seven hours per patient. The Hamilton-DONATE pilot study supports the feasibility of a larger cohort study to describe the epidemiology and clinical practices related to deceased donor care in Canada. wwwclinicaltrials.gov (NCT02902783). Registered 16 September 2016.

Clinicians' current practice patterns in the management of acute respiratory distress syndrome (ARDS) and refractory hypoxemia are not well described.To describe mechanical ventilation strategies and treatment adjuncts for adults with ARDS, including refractory hypoxemia.This was a prospective cohort study (March 2014-February 2015) of mechanically ventilated adults with moderate-to-severe ARDS requiring an FiWe enrolled 664 patients: 222 (33%) with moderate and 442 (67%) with severe ARDS. On Study Day 1, mean Vt was 7.5 (SD = 2.1) ml/kg predicted body weight (n = 625); 80% (n = 501) received Vt greater than 6 ml/kg. Mean positive end-expiratory pressure (PEEP) was 10.5 (3.7) cm HPatients with moderate-to-severe ARDS receive treatment adjuncts frequently, especially with refractory hypoxemia. Paradoxically, therapies with less evidence supporting their use (e.g., pulmonary vasodilators) were over-used, whereas those with more evidence (e.g., prone positioning, neuromuscular blockade) were under-used. Patients received higher Vts and lower PEEP than would be suggested by the evidence.

Patients eligible for randomized controlled trials may not be enrolled for various reasons. Nonenrollment may affect study generalizability and lengthen the time required for trial completion.To describe characteristics and outcomes of eligible nonenrolled (ENE) patients in a multicenter trial of mechanical ventilation strategies.Within the OSCILLATE trial of high-frequency oscillation (HFO) versus conventional ventilation (CV) in adults with adult respiratory distress syndrome, and with approval from research ethics boards, we collected a minimal dataset on patients who satisfied eligibility criteria but were not enrolled. We categorized ENE patients as ENE-HFO and ENE-CV based on receipt of HFO at any time. We used multivariable logistic regression to assess the association between ENE status and mortality.A total of 548 patients were randomized, and 546 were ENE. The most common reasons for ENE were no consent (42%), physician refusal (24%), missed randomization window (15%), and current HFO use (14%). Compared with randomized patients in respective arms of the trial, ENE-HFO patients were younger and had worse lung injury, whereas ENE-CV patients had lower illness severity. ENE status was independently associated with mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.06-1.84; P = 0.02), with no significant interaction with ventilation treatment group.Nonenrollment was common, with approximately one ENE patient for every randomized patient. Our study suggests that enrollment in trials of mechanical ventilation may be associated with improved outcomes compared with standard care and highlights the need for prospective tracking and transparent reporting of ENE patients as part of trial management.

Background Platelet transfusions are commonly used to treat critically ill patients with thrombocytopenia. Whether platelet transfusions are associated with a reduction in the risk of major bleeding is unknown. Patients/Methods Observational cohort study nested in a previous multicenter, randomized thromboprophylaxis trial in the intensive care unit (ICU). The objective was to evaluate the association between platelet transfusions and adjudicated major bleeding events. Platelet transfusion episodes were reviewed for timing of administration, product type, and dose. Major bleeding with and without platelet transfusions was adjusted for severity of thrombocytopenia, use of anti‐platelet agents, surgery and other covariates. Secondary outcomes were thrombosis, death in ICU and platelet count increment. Results Among 2,256 patients, 71 (3.1%) received 190 platelet transfusions. Of those, 121 (63.7%) were administered to 54 non‐bleeding, thrombocytopenic patients. Adjusted rates of major bleeding were not statistically different with or without the administration of platelet transfusions (hazard ratio for transfused patients 0.85; 95% confidence interval, 0.42‐1.72). We did not find a significant association between platelet transfusion use and thrombosis or death in ICU in adjusted analyses. Thrombocytopenia, anemia, major or minor bleeding and use of anticoagulants were associated with platelet transfusion administration. The median post‐transfusion platelet count increment was 20×109/L at 3.5 hours post‐transfusion. Conclusions Rates of major bleeding were not different for patients who did and did not receive platelet transfusions. Inferences were limited by the small number of transfused patients. Clinical trials are needed to better investigate the potential hemostatic benefit and potential harms of platelet transfusions for this high‐risk population.

Objectives High-frequency oscillation is used for adults with acute lung injury/acute respiratory distress syndrome. Given the uncertain benefits, our objective was to describe contemporary patient selection, high-frequency oscillation utilization, and outcomes. Design Utilization review. Setting Ten academic centers (Ontario, Canada; January 1, 2005-January 31, 2007). Patients We included 190 consecutive adults treated with high-frequency oscillation and retrospectively abstracted data on patient demographics, gas exchange, hemodynamics, settings during conventional ventilation and high-frequency oscillation, adjunctive therapies, and outcomes. We used logistic regression to explore associations with oxygenation response and hemodynamic and ventilatory complications (2 hrs after high-frequency oscillation initiation) and mortality. Continuous data are reported as mean (sd) or median (quartile 1, quartile 3). Interventions None. Measurements and main results Patients (60.0% male; mean age, 52; sd 17) had predominantly acute lung injury/acute respiratory distress syndrome (89.8%) and were severely ill (mean Acute Physiology and Chronic Health Evaluation II score, 28; sd, 9) and hypoxemic (mean Pao2/Fio2, 80; sd, 42). High-frequency oscillation was started a median of 2 (1, 8) days after intubation and continued for a median of 3 (2, 7) days. During high-frequency oscillation, adjunctive treatments (neuromuscular blockade, 75.6%; recruitment maneuvers, 49.5%; nitric oxide, 34.0%; steroids, 63.1%) and new barotrauma or chest tube placement (23.5%) were common. Ten patients (5.3%) had technical complications; five required a new ventilator. Reasons for stopping high-frequency oscillation included death or withdrawal of life support (39.1%), significant improvement in respiratory failure (37.6%), and inadequate improvement (23.3%). One hundred and twenty-eight of 189 patients died in hospital. Most (62.5%) had a positive oxygenation response after 2 hrs of high-frequency oscillation (mean absolute increase in PaO₂/FiO₂, 22 [SD, 54]; 95% confidence interval of mean 14-31). A minority had lower PaO₂/FiO₂ (32.5%) or a hemodynamic (27.5%) or ventilatory (30.5%) complication. Older age, Acute Physiology and Chronic Health Evaluation II score, and Paco2 before high-frequency oscillation were independently associated with mortality. Conclusions Most patients treated with high-frequency oscillation have acute respiratory distress syndrome and severe hypoxemia that modestly improves 2 hrs after high-frequency oscillation application. However, oxygenation worsens in some patients, complications are common, and mortality is high.

IntroductionResearch on the management of deceased organ donors aims to improve the number and quality of transplants and recipient outcomes. In Canada, this research is challenged by regionalisation of donation services within provinces and the geographical, clinical and administrative separation of donation from transplantation services. This study aims to build a national platform for future clinical trials in donor management. Objectives are to engage collaborators at donation hospitals and organ donation organisations (ODOs) across Canada, describe current practices, evaluate the effectiveness of donation-specific interventions and assess the feasibility of future clinical trials.Methods and analysisThis ongoing prospective observational study of the medical management of deceased organ donors will enrol more than 650 consented potential donors from adult intensive care units at 33 hospital sites across Canada, each participating for 12 months. ODOs ensure enrolment of consecutive eligible participants. Research staff record detailed data about participants, therapies, organ assessments, death declaration procedures and adverse clinical exposures from the time of donation consent to organ recovery. ODOs provide reasons that organs are declined, dates and places of transplantation, and recipient age and sex.Descriptive analyses will summarise current practices. Effectiveness analyses will examine donation-specific interventions with respect to the number of transplants, using multilevel regression models to account for clustering by donor, hospitals and ODOs. Feasibility analyses will focus on acceptance of the research consent model; participation of academic and community hospitals as well as ODOs; and accessibility of recipient data.Ethics and disseminationThis study uses a waiver of research consent. Hospitals will receive reports on local practices benchmarked to (1) national practices and (2) national donor management guidelines. We will report findings to donation and transplant collaborators (ie, clinicians, researchers, ODOs) and publish in peer-reviewed journals.Trial registration numberNCT03114436.

Objective: Enrollment of individual patients into more than one study has been poorly evaluated. The objective of this study was to describe the characteristics of patients, researchers and centers involved in coenrollment, studies precluding coenrollment, and the prevalence, patterns, predictors, and outcomes of coenrollment in a randomized clinical trial. Design, Setting, Methods: We conducted an observational study nested within the OSCILLation for Acute Respiratory Distress Syndrome Treated Early Trial, which compared high-frequency oscillatory ventilation to conventional ventilation. We collected patient, center, and study data on coenrollment in randomized patients. Multilevel regression examined factors independently associated with coenrollment, considering clustering within centers. We examined the effect of coenrollment on safety and the trial outcome. Interventions None. Measurements and Main Results: Overall, 127 of 548 randomized patients (23.2%) were coenrolled in 25 unique studies. Coenrollment was reported in 17 of 39 centers (43.6%). Patients were most commonly coenrolled in one additional randomized clinical trial (76; 59.8%). Coenrollment was less likely in older patients (odds ratio, 0.87; 95% CI, 0.76–0.997), and in ICUs with greater than 26 beds (odds ratio, 0.56; 95% CI, 0.34–0.94), and more likely by investigators with more than 11 years of experience (odds ratio, 1.73; 95% CI, 1.06–2.82), by research coordinators with more than 8 years of experience (odds ratio, 1.87; 95% CI, 1.11–3.18) and in Canada (odds ratio, 4.66; 95% CI, 1.43–15.15). Serious adverse events were similar between coenrolled high-frequency oscillatory ventilation and control patients. Coenrollment did not modify the treatment effect of high-frequency oscillatory ventilation on hospital mortality. Conclusions: Coenrollment occurred in 23% of patients, commonly in younger patients, in smaller centers with more research infrastructure, and in Canada. Coenrollment did not influence patient safety or trial results.

We identified 16 randomized controlled trials (RCTs) of methods for weaning patients from mechanical ventilation, 8 of which were trials of discontinuation assessment strategies, 5 of which were trials of stepwise reduction in mechanical ventilatory support, and 3 of which were trials comparing alternative ventilation modes for weaning periods lasting < 48 h. We found that different thresholds for deciding when a patient is ready for a trial of spontaneous breathing, different criteria for a successful trial, and different thresholds for extubation may overwhelm the impact of alternative ventilation strategies. Nevertheless, the results of these studies suggest the possibility that multiple daily T-piece weaning or pressure support may be superior to synchronized intermittent mandatory ventilation. Other RCTs suggest that early extubation with the back-up institution of noninvasive positive-pressure ventilation as needed may be a useful strategy in selected patients.

Automated weaning has not been compared with a paper-based weaning protocol in North America.We conducted a pilot randomized trial comparing automated weaning with protocolized weaning in critically ill adults to evaluate clinician compliance and acceptance of the weaning and sedation protocols, recruitment, and impact on outcomes.From August 2007 to October 2009, we enrolled critically ill adults requiring more than 24 hours of mechanical ventilation and at least partial reversal of the condition precipitating respiratory failure at nine Canadian intensive care units. We randomized patients who tolerated at least 30 minutes of pressure support and either failed or were not yet ready to undergo a spontaneous breathing trial to automated or protocolized weaning. Both groups used pressure support, included spontaneous breathing trials, used a common positive end-expiratory pressure-FI(O(2)) chart, sedation protocol, and criteria for extubation, reintubation, and noninvasive ventilation.We recruited 92 patients (49 automated, 43 protocolized) over 26 months. Adherence to assigned weaning protocols and extreme sedation scale scores fell within prespecified thresholds. Combined physician-respiratory therapist and nurse acceptance scores of the study weaning and sedation protocols, respectively, were not significantly different. Automated weaning patients had significantly shorter median times to first successful spontaneous breathing trial (1.0 vs. 4.0 d; P0.0001), extubation (3.0 vs. 4.0 d; P = 0.02), and successful extubation (4.0 vs. 5.0 d; P = 0.01), and underwent fewer tracheostomies and episodes of protracted ventilation.Compared with a standardized protocol, automated weaning was associated with promising outcomes that warrant further investigation. Minor protocol modifications may increase compliance, facilitate recruitment, and enhance feasibility. Clinical trial registered with www.controlled-trials.com (ISRCTN43760151).

Over the past two decades, the use of noninvasive positive-pressure ventilation and noninvasive continuous positive airway pressure by mask has increased substantially for acutely ill patients. Initial case series and uncontrolled cohort studies that suggested benefit in selected patients[1][1]–[

Ventilator-associated pneumonia (VAP) is an important patient safety issue in critically ill patients.To develop an evidence-based guideline for the prevention of VAP.MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews.The authors systematically searched for relevant randomized, controlled trials and systematic reviews that involved mechanically ventilated adults and were published before 1 April 2003.Physical, positional, and pharmacologic interventions that may influence the development of VAP were considered. Independently and in duplicate, the authors scored the validity of trials; the effect size and confidence intervals; the homogeneity of results; and safety, feasibility, and economic issues.Recommended: The orotracheal route of intubation, changes of ventilator circuits only for each new patient and if the circuits are soiled, use of closed endotracheal suction systems that are changed for each new patient and as clinically indicated, heat and moisture exchangers in the absence of contraindications, weekly changes of heat and moisture exchangers, and semi-recumbent positioning in the absence of contraindications. Consider subglottic secretion drainage and kinetic beds. Not recommended: Sucralfate to prevent VAP in patients at high risk for gastrointestinal bleeding and topical antibiotics to prevent VAP. Because of insufficient or conflicting evidence, no recommendations were made about systematically searching for maxillary sinusitis, chest physiotherapy, the timing of tracheostomy, prone positioning, prophylactic intravenous antibiotics, or intravenous plus topical antibiotics.No formal economic analysis was performed, and patient perspectives were not considered.If effectively implemented, this guideline may decrease the morbidity, mortality, and costs of VAP in mechanically ventilated patients.

We identified 10 randomized trials that compared alternative management approaches to patient care during and following cardiovascular surgery. One overall strategy involved a modification of anesthesia, in particular, a reduction in the dosage of fentanyl and benzodiazepine or the substitution of fentanyl for propofol (five randomized controlled trials [RCTs]). Pooled results show a shorter duration of ventilation (7 h) and a shorter duration of hospital stay (approximately 1 day) associated with lower anesthetic doses. The second strategy involved early vs late extubation once patients were admitted to the ICU (five RCTs). Pooled results show a shorter duration of ventilation (13 h) and a shorter duration of ICU stay (half a day) associated with early extubation. An additional 8 nonrandomized trials had findings that were consistent with the 10 RCTs. Reintubation, complications, and mortality rates were too low to draw conclusions about these outcomes. Overall, these studies indicate that anesthetic, sedation, and early-extubation strategies in selected cardiac surgery patients are associated with a shorter duration of mechanical ventilation and shorter lengths of ICU and hospital stays.

Over the past 5 years, several interventions have been shown in randomized clinical trials (RCTs) to reduce mortality in patients with ARDS. The current use of these interventions in clinical practice, along with those of unproven benefit, is unknown.

Background Previous trials suggesting that high-frequency oscillatory ventilation (HFOV) reduced mortality among adults with the acute respiratory distress syndrome (ARDS) were limited by the use of outdated comparator ventilation strategies and small sample sizes. Methods In a multicenter, randomized, controlled trial conducted at 39 intensive care units in five countries, we randomly assigned adults with new-onset, moderate-to-severe ARDS to HFOV targeting lung recruitment or to a control ventilation strategy targeting lung recruitment with the use of low tidal volumes and high positive end-expiratory pressure. The primary outcome was the rate of in-hospital death from any cause. Results On the recommendation of the data monitoring committee, we stopped the trial after 548 of a planned 1200 patients had undergone randomization. The two study groups were well matched at baseline. The HFOV group underwent HFOV for a median of 3 days (interquartile range, 2 to 8); in addition, 34 of 273 patients (12%) in the control group received HFOV for refractory hypoxemia. In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P = 0.005). This finding was independent of baseline abnormalities in oxygenation or respiratory compliance. Patients in the HFOV group received higher doses of midazolam than did patients in the control group (199 mg per day [interquartile range, 100 to 382] vs. 141 mg per day [interquartile range, 68 to 240], P