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.
We randomized 46 hemodynamically stable patients with hypoalbuminemia, prescribed diuretics by treating clinicians, to receive 100 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 2 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.
We randomized 85% of eligible patients. Eighty-four percent received study treatment within 2 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 albumin > 35 (1 v. 0). Twenty percent of patients received open-label albumin. Clinical outcomes were similar between groups.
The current study design did not demonstrate feasibility, but can inform the design of a definitive trial.
•Hyperoncotic albumin increases colloid osmotic pressure, making it an attractive adjunct to diuretics in critically ill patients•This pilot randomized trial tested the feasibility of a definitive study to assess the impact of hyperoncotic albumin in addition to diuretics•The pilot study did not demonstrate feasibility, though it identified challenges which could be addressed prior to a future trial•Patients assigned to albumin had greater increases in colloid osmotic pressure and serum albumin•Physiologic outcomes were similar between the two groups; the study was underpowered to address clinical outcomes
OBJECTIVES:While early mobilization is safe and enhances functional recovery in critically ill adults, rehabilitation practices in critically ill children are not well characterized. The objective of ...this study was to evaluate the knowledge, perceptions, and stated practices of early mobilization among physicians and physiotherapists practicing in Canadian pediatric critical care units.
DESIGN AND MEASUREMENTS:A self-administered survey was mailed to 102 physicians and 35 physiotherapists. Survey domains included barriers to early mobilization, the timing, nature and thresholds for rehabilitation, and staffing workload. We assessed for associations using chi-square tests.
MAIN RESULTS:The overall response rate was 64.2% (88 of 137), representing 59.8% (61 of 102) physicians and 77.1% (27 of 35) physiotherapists, respectively. Key institutional barriers to early mobilization included a lack of practice guidelines (75.4% physician, 48.1% physiotherapist respondents; p = 0.01) and the need for physician orders prior to initiating physiotherapy (26.2% physician vs 55.6% physiotherapist, p = 0.008). Only 3.4% of respondents reported having local guidelines for early mobilization. Conflicting perceptions regarding the clinical thresholds for early mobilization and the safety of early mobilization were the most commonly reported patient-level barriers. Increasing illness severity was associated with decreased clinician comfort with early mobilization. Respiratory physiotherapy and passive range of motion were the most frequently applied rehabilitation interventions (77.8%), while pregait physiotherapy and ambulation were only sometimes or infrequently (70.4%) used. The type and extent of physiotherapy varied depending on the time of day and week.
CONCLUSIONS:There are numerous perceived institutional, patient- and provider-level barriers to early mobilization in Canadian pediatric critical care units, and diverse opinions on the appropriateness of early mobilization. Limited awareness of existing literature and the lack of practice guidelines on early mobilization are not surprising in light of the paucity of pediatric-specific evidence. These results strongly support the need for further research, evaluating the feasibility, safety, and efficacy of early mobilization in critically ill children.
ObjectivesThis review investigates the impact of corticosteroids on donation rates and transplant outcomes in light of findings from randomised controlled trials (RCTs) and to highlight the sources ...of uncertainty in this unresolved donor management issue.Data sourcesWe searched electronic databases, trial registries and conference proceedings for RCTs evaluating corticosteroid therapy in neurologically deceased donors.Study selection and data extractionIndependent reviewers assessed eligibility, evaluated risk of bias and abstracted data, including donor haemodynamic data, number of organs recovered and transplant outcomes. Where possible, we pooled results. For each outcome, we assessed the overall quality of evidence using The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.Data synthesisEleven RCTs with different corticosteroid regimens were included. Most trials assessed a once-daily infusion of methylprednisolone. Aside from one study showing improved liver graft function, no individual study or pooled analysis showed benefit of corticosteroids for any outcome: vasopressor use (three trials; relative risk (RR) 0.96; 95% CI 0.89 to 1.05), multiple organs recovered (two trials; RR 0.82; 95% CI 0.61 to 1.11), acute graft rejection (three trials; RR 0.91; 95% CI 0.60 to 1.39) or graft dysfunction (eight trials; RR 1.01; 95% CI 0.83 to 1.24). Two trials investigated adverse effects and found similar rates between groups. Quality of evidence was moderate or low for all outcomes.ConclusionCurrent clinical trials are limited in numbers and size to identify benefits or harms of corticosteroid therapy for deceased organ donors. In the face of these results, administering or withholding steroids both appear reasonable courses of action.
By minimizing tidal lung strain and maintaining alveolar recruitment, high-frequency oscillatory ventilation (HFOV) may protect against ventilator-induced lung injury.
To summarize the current ...evidence in support of the use of HFOV in adult patients with acute respiratory distress syndrome.
We conducted a systematic review and meta-analysis of randomized trials comparing mortality rates with the use of HFOV versus conventional mechanical ventilation for adult patients with acute respiratory distress syndrome. Eligible trials were identified from previously published systematic reviews and an updated literature search. Data on 28-day mortality, oxygenation, adverse events, and use of rescue therapies were collected; effects were pooled using random effects models weighted by inverse variance. Strength of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology.
Six trials were eligible for inclusion (total n = 1,715 patients). Four trials mandated lung-protective ventilation in the control group and one trial applied a higher positive end-expiratory pressure (PEEP) ventilation strategy in the control group. None of the trials were judged to be at high risk of bias, though all were unblinded. In trials that did not systematically employ any cointerventions with HFOV and that targeted low tidal volumes in the patients randomized to conventional ventilation (primary analysis), HFOV had no significant effect on mortality (three trials; risk ratio RR, 1.14; 95% confidence interval CI, 0.88 to 1.48; evidence grade = high). Pooled analysis of all six trials also did not suggest a significant mortality reduction (RR, 0.94; 95% CI, 0.71 to 1.24; evidence grade = low). The single trial that employed a conventional ventilation strategy with both lower tidal volumes and higher PEEP as control reported higher mortality in patients receiving HFOV (RR, 1.41; 95% CI, 1.12 to 1.79). HFOV was not associated with improved oxygenation after 24 hours (five trials; mean increase of 10 mm Hg; 95% CI, -16 to 37 mm Hg). Rates of barotrauma were not different between HFOV and conventional ventilation, although significant benefit or harm could not be excluded (RR, 1.15; 95% CI, 0.61 to 2.17).
Published randomized trials suggest that HFOV is not associated with a mortality benefit, and may even be harmful in comparison to ventilation with low tidal volumes and higher levels of PEEP.
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.
Objective Loss to follow-up (LTFU) can be a major difficulty for any clinical research study. The objective of this systematic review was to assess the extent of LTFU and its potential effect in ...studies of adult trauma patients with blunt thoracic aortic injuries (BTAIs). Methods Studies comparing management of BTAIs were systematically reviewed. Duplicate independent review was used for study selection, data abstraction, and critical appraisals. Results Thirty-six studies were included for synthesis, of which 94.1% applied a retrospective cohort design to prospective institutional databases. The mean LTFU at 1 year was 26.5% ± 31.6% for endovascular repair and 20.6% ± 34.2% for open repair groups. Not having a surgical/interventional specialist as a first or senior author was associated with a 39.7% higher LTFU at 1 year ( P = .002). Studies with a higher risk of bias, later publication year, or North American origin were associated with a significantly higher risk for LTFU at 1 year ( P ≤ .001). Nearly half of included studies assessed in-hospital outcomes exclusively. Only 38.2% explicitly reported LTFU data. Eight studies explicitly described the method of dealing with LTFU: eight used survival analysis and one used a national Social Security Death Index. Sensitivity analyses using plausible worst-case LTFU scenarios resulted in 14% to 17% of studies changing direction of effect. Conclusions There is significant LTFU in trauma studies comparing operative methods for BTAIs. LTFU is generally handled and reported suboptimally, and sensitivity analyses suggest that study results are sensitive to differential LTFU. This has implications for the evidence-based choice of the operative method. Some protective factors that may aid in reducing LTFU were identified, one of which was involvement of a surgical or interventional specialist as a key author.
BACKGROUND:The authors investigated the methodological validity of plastic surgery randomized controlled trials that compared surgical interventions.
METHODS:An electronic search identified ...randomized controlled trials published between 2000 and 2013. Reviewers, independently and in duplicate, assessed manuscripts and performed data extraction. Methodological safeguards (randomization, allocation concealment, blinding, and incomplete outcome data) were examined using the Cochrane risk of bias tool. Regression analysis was used to identify trial characteristics associated with risk of bias.
RESULTS:Of 1664 potentially eligible studies, 173 randomized controlled trials were included. Proper randomization and allocation concealment methods were described in 61 of 173 (35 percent) and 21 of 173 (12 percent), respectively. Outcome assessors were blinded in 58 of 173 (34 percent) trials, and patients were blinded in 45 of 173 (26 percent). Follow-up rates were high, with 99 of 173 (57 percent) randomized controlled trials appearing to have complete follow-up. An intention-to-treat analysis was used in 19 of 173 (11 percent) trials. One-third (58 of 173, 34 percent) did not state their primary outcomes. The most common type of primary outcome used was a symptom/quality of life, class III, outcome (73 of 173, 42 percent). Multinomial regression demonstrated trials reporting an a priori sample size as more likely to have a low risk of bias (p = 0.001).
CONCLUSIONS:This article highlights methodological safeguards that plastic surgeons should consider when interpreting results of a surgical randomized controlled trial. Allocation concealment, outcome assessor blinding, and patient blinding were identified as areas of concern. Valid and reliable outcome measures are being used in plastic surgery. This analysis provides strong rationale for continued focus on the performance and reporting of clinical trials within our specialty.
We sought to examine changes in acute respiratory distress syndrome (ARDS) management over a 12-year period of two successive randomized trials.
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.
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).
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.
•Evolution of ARDS management was studied in two successive trials over 12 years.•Over this time, tidal volume index and plateau pressures decreased; PEEP increased.•Use of volume-controlled ventilation reduced; use of other modes remained static.•Use of corticosteroids and neuromuscular blockade increased.•Inhaled nitric oxide and high frequency oscillatory ventilation use increased.
Purpose
Canadian donor management practices have not been reported. Our aim was to inform clinicians and other stakeholders about the range of current practices.
Methods
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.
Results
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.
Conclusion
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.
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