In patients with acute respiratory distress syndrome (ARDS), lung recruitment maneuvers (LRMs) may prevent ventilator-induced lung injury and improve survival.
To summarize the current evidence in ...support of the use of LRMs in adult patients with ARDS and to inform the recently published American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine clinical practice guideline on mechanical ventilation in ARDS.
We conducted a systematic review and meta-analysis of randomized trials comparing mechanical ventilation strategies with and without LRMs. Eligible trials were identified from among previously published systematic reviews and an updated literature search. Data on 28-day mortality, oxygenation, adverse events, and use of rescue therapy were collected, and results were pooled using random effects models weighted by inverse variance. Strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology.
We screened 430 citations and previous systematic reviews and found six trials eligible for inclusion (n = 1,423 patients in total). The type of LRM varied widely between trials, and five of the trials involved a cointervention with a higher positive end-expiratory pressure (PEEP) ventilation strategy. Risk of bias was deemed high in one trial. In the primary analysis, the only trial without a cointervention showed that LRMs were associated with reduced mortality (one trial; risk ratio RR, 0.62; 95% confidence interval CI, 0.39-0.98; evidence grade = low). Meta-analysis of all six trials also suggested a significant mortality reduction (six trials; RR, 0.81; 95% CI, 0.69-0.95; evidence grade = moderate), and the use of a higher PEEP cointervention did not significantly modify the mortality effect (P = 0.27 for heterogeneity). LRMs were also associated with improved oxygenation after 24 hours (six trials; mean increase, 52 mm Hg; 95% CI, 23-81 mm Hg) and less frequent requirement for rescue therapy (three trials; RR, 0.65; 95% CI, 0.45-0.94). LRMs were not associated with an increased rate of barotrauma (four trials; RR, 0.84; 95% CI, 0.46-1.55). The rate of hemodynamic compromise was not significantly increased with LRMs (three trials; RR, 1.30; 95% CI, 0.92-1.78).
Randomized trials suggest that LRMs in combination with a higher PEEP ventilation strategy reduce mortality, but confidence in this finding is limited. Further trials are required to confirm benefit from LRMs in adults with ARDS.
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 Fi
of 0.50 or greater in 24 intensive care units.
We 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 H
O (n = 653); 568 patients (87%) received PEEP less than 15 cm H
O. Treatment adjuncts were common (n = 440, 66%): neuromuscular blockers (n = 276, 42%), pulmonary vasodilators (n = 118, 18%), prone positioning (n = 67, 10%), extracorporeal life support (n = 29, 4%), and high-frequency oscillatory ventilation (n = 29, 4%). Refractory hypoxemia, defined as Pa
less than 60 mm Hg on Fi
of 1.0, occurred in 138 (21%) patients. At onset of refractory hypoxemia, mean Vt was 7.1 (SD = 2.0) ml/kg (n = 124); 95 patients (77%) received Vt greater than 6 ml/kg. Mean PEEP was 12.1 (SD = 4.4) cm H
O (n = 133); 99 patients (74%) received PEEP less than 15 cm H
O. Among patients with refractory hypoxemia, 91% received treatment adjuncts (126/138), with increased use of neuromuscular blockers (n = 87, 63%), pulmonary vasodilators (n = 57, 41%), and prone positioning (n = 32, 23%).
Patients 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.
Objective To determine clinical and physiological effects of high frequency oscillation compared with conventional ventilation in patients with acute lung injury/acute respiratory distress syndrome ...(ARDS).Design Systematic review and meta-analysis.Data sources Electronic databases to March 2010, conference proceedings, bibliographies, and primary investigators.Study selection Randomised controlled trials of high frequency oscillation compared with conventional ventilation in adults or children with acute lung injury/ARDS.Data selection Three authors independently extracted data on clinical, physiological, and safety outcomes according to a predefined protocol. We contacted investigators of all included studies to clarify methods and obtain additional data. Analyses used random effects models.Results Eight randomised controlled trials (n=419 patients) were included; almost all patients had ARDS. Methodological quality was good. The ratio of partial pressure of oxygen to inspired fraction of oxygen at 24, 48, and 72 hours was 16-24% higher in patients receiving high frequency oscillation. There were no significant differences in oxygenation index because mean airway pressure rose by 22-33% in patients receiving high frequency oscillation (P≤0.01). In patients randomised to high frequency oscillation, mortality was significantly reduced (risk ratio 0.77, 95% confidence interval 0.61 to 0.98, P=0.03; six trials, 365 patients, 160 deaths), and treatment failure (refractory hypoxaemia, hypercapnoea, hypotension, or barotrauma) resulting in discontinuation of assigned therapy was less likely (0.67, 0.46 to 0.99, P=0.04; five trials, 337 patients, 73 events). Other risks were similar. There was substantial heterogeneity between trials for physiological (I2=21-95%) but not clinical (I2=0%) outcomes. Pooled results were based on few events for most clinical outcomes.Conclusion High frequency oscillation might improve survival and is unlikely to cause harm. As ongoing large multicentre trials will not be completed for several years, these data help clinicians who currently use or are considering this technique for patients with ARDS.
Purpose
In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a ...larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock.
Methods
We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60–65 mmHg) versus a higher (75–80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups.
Results
A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95 % CI 7–11). In the lower and higher MAP groups, we observed deviations on 12 versus 8 % of all days on vasopressors (
p
= 0.059). Risks of cardiac arrhythmias (20 versus 36 %,
p
= 0.07) and hospital mortality (30 versus 33 %,
p
= 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60 %,
p
= 0.03) but not in younger patients.
Conclusions
This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy.
CONTEXT Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome. Instituting additional strategies to open collapsed ...lung tissue may further reduce mortality. OBJECTIVE To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original “open-lung approach,” combining low tidal volume, lung recruitment maneuvers,
and high positive-end–expiratory pressure. DESIGN AND SETTING Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia. PATIENTS Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250. INTERVENTIONS The control strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30
cm H2O, and conventional levels of positive end-expiratory pressure (n = 508). The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures (n = 475). MAIN OUTCOME MEASURE All-cause hospital mortality. RESULTS Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment. Tidal volumes remained similar in the 2 groups, and mean positive end-expiratory pressures were 14.6 (SD, 3.4) cm H2O in the experimental group vs 9.8 (SD, 2.7) cm H2O among controls during the first 72
hours (P < .001). All-cause hospital mortality rates were 36.4% and 40.4%, respectively (relative risk RR, 0.90; 95% confidence interval CI, 0.77-1.05; P = .19). Barotrauma rates were 11.2%
and 9.1% (RR, 1.21; 95% CI, 0.83-1.75; P = .33).
The experimental group had lower rates of refractory hypoxemia (4.6%
vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86; P = .01),
death with refractory hypoxemia (4.2% vs 8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previously defined eligible use of rescue therapies (5.1% vs 9.3%; RR, 0.61; 95% CI, 0.38-0.99; P = .045). CONCLUSIONS For patients with acute lung injury and acute respiratory distress syndrome, a multifaceted protocolized ventilation strategy designed to recruit and open the lung resulted in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocolized ventilation strategy. This “open-lung”
strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00182195
Trials investigating use of lower tidal volumes and inspiratory pressures for patients with acute respiratory distress syndrome (ARDS) have shown mixed results.
To compare clinical outcomes of ...mechanical ventilation strategies that limit tidal volumes and inspiratory pressures (LTV) to strategies with tidal volumes of 10 to 15 ml/kg among patients with ARDS.
This is a systematic review and meta-analysis of clinical trials investigating LTV mechanical ventilation strategies. We used random effects models to evaluate the effect of LTV on 28-day mortality, organ failure, ventilator-free days, barotrauma, oxygenation, and ventilation. Our primary analysis excluded trials for which the LTV strategy was combined with the additional strategy of higher positive end-expiratory pressure (PEEP), but these trials were included in a stratified sensitivity analysis. We performed metaregression of tidal volume gradient achieved between intervention and control groups on mortality effect estimates. We used Grading of Recommendations Assessment, Development, and Evaluation methodology to determine the quality of evidence.
Seven randomized trials involving 1,481 patients met eligibility criteria for this review. Mortality was not significantly lower for patients receiving an LTV strategy (33.6%) as compared with control strategies (40.4%) (relative risk RR, 0.87; 95% confidence interval CI, 0.70-1.08; heterogeneity statistic I
= 46%), nor did an LTV strategy significantly decrease barotrauma or ventilator-free days when compared with a lower PEEP strategy. Quality of evidence for clinical outcomes was downgraded for imprecision. Metaregression showed a significant inverse association between larger tidal volume gradient between LTV and control groups and log odds ratios for mortality (β, -0.1587; P = 0.0022). Sensitivity analysis including trials that protocolized an LTV/high PEEP cointervention showed lower mortality associated with LTV (nine trials and 1,629 patients; RR, 0.80; 95% CI, 0.66-0.98; I
= 46%). Compared with trials not using a high PEEP cointervention, trials using a strategy of LTV combined with high PEEP showed a greater mortality benefit (RR, 0.58; 95% CI, 0.41-0.82; P for interaction = 0.05).
The trend toward lower mortality with LTV ventilation in the primary analysis and the significant relationship between the degree of tidal volume reduction and the mortality effect together suggest, but do not prove, that LTV ventilation improves mortality among critically ill adults with ARDS.
Noninvasive positive pressure ventilation (NPPV) provides ventilatory support without the need for an invasive airway approach. Interest has emerged in using NPPV to facilitate earlier removal of an ...endotracheal tube and decrease complications associated with prolonged intubation.
To summarize the evidence comparing NPPV and invasive positive pressure ventilation (IPPV) weaning on clinical outcomes in intubated adults with respiratory failure.
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2008), MEDLINE (January 1966 to April 2008), EMBASE (January 1980 to April 2008), proceedings from four conferences, and personal files; and contacted authors to identify randomized controlled trials comparing NPPV and IPPV weaning.
Randomized and quasi-randomized studies comparing early extubation with immediate application of NPPV to IPPV weaning in intubated adults with respiratory failure.
Two review authors independently assessed trial quality and abstracted data according to prespecified criteria. Sensitivity and subgroup analyses were planned to assess the impact of (i) excluding quasi-randomized trials, and (ii) the etiology of respiratory failure on selected outcomes.
We identified 12 trials of moderate to good quality that involved 530 participants with predominantly chronic obstructive pulmonary disease (COPD). Compared to the IPPV strategy, NPPV significantly decreased mortality (relative risk (RR) 0.55, 95% confidence Interval (CI) 0.38 to 0.79), ventilator associated pneumonia (RR 0.29, 95% CI 0.19 to 0.45), length of stay in an intensive care unit (weighted mean difference (WMD) -6.27 days, 95% CI -8.77 to -3.78) and hospital (WMD -7.19 days, 95% CI -10.80 to -3.58), total duration of ventilation (WVD) -5.64 days (95% CI -9.50 to -1.77) and duration of endotracheal mechanical ventilation (WMD - 7.81 days, 95% CI -11.31 to -4.31). Noninvasive weaning had no effect on weaning failures or the duration of ventilation related to weaning. Excluding a single quasi-randomized trial maintained the significant reduction in mortality and ventilator associated pneumonia. Subgroup analyses suggested that the benefits on mortality and weaning failures were nonsignificantly greater in trials enrolling exclusively COPD patients versus mixed populations.
Summary estimates from 12 small studies of moderate to good quality that included predominantly COPD patients demonstrated a consistent, positive effect on mortality and ventilator associated pneumonia. The net clinical benefits associated with noninvasive weaning remain to be fully elucidated.
Background. Donor interventions, including medications, protocols, and medical devices administered to donors, can enhance transplantable organ quality and quantity and maximize transplantation ...success. However, there is paucity of high-quality evidence about their effectiveness, in part because of ethical, practical, and regulatory challenges, and lack of guidance about conduct of donor intervention randomized controlled trials (RCTs). Methods. With the vision to develop authoritative guidance for conduct of donor intervention RCTs, we convened a workshop of Canadian-United Kingdom experts in organ donation and transplantation ethics, research, and policy to identify stakeholders, explore unique challenges, and develop research agenda to inform future work in this promising field. Results. Donor intervention trials should consider perspectives of broad group of stakeholders including donors, transplant recipients, and their families; researchers in donation and transplantation; research ethics boards; and healthcare providers and administrators involved in donation and transplantation. Unique challenges include (1) research ethics (living versus deceased status of the donor at the time of intervention, intervention versus outcomes assessment in different individuals, harm-benefit analysis in donors versus recipients, consent, and impact on research bystanders); (2) outcome data standardization and linkage; and (3) regulatory and governance considerations. Conclusions. Donor intervention RCTs hold potential to benefit organ transplantation outcomes but face unique research ethics, outcome data, and regulatory challenges. By developing research agenda to address these challenges, our workshop was an important first step toward developing Canada-United Kingdom guidance for donor intervention RCTs that are poised to improve the quality and availability of transplantable organs.
Donation after circulatory death determination frequently involves antemortem heparin administration to mitigate peri-arrest microvascular thrombosis. We systematically reviewed the literature to: ...(1) describe heparin administration practices and (2) explore the effects on transplant outcomes. We searched MEDLINE and EMBASE for studies reporting donation after circulatory death determination heparin practices including use, dosage, and timing (objective 1). To explore associations between antemortem heparin and transplant outcomes (objective 2), we (1) summarized within-study comparisons and (2) used meta-regression analyses to examine associations between proportions of donors that received heparin and transplant outcomes. We assessed risk of bias using the Newcastle Ottawa Scale and applied the GRADE methodology to determine certainty in the evidence. For objective 1, among 55 eligible studies, 48 reported heparin administration to at least some donors (range: 15.8%-100%) at variable doses (up to 1000 units/kg) and times relative to withdrawal of life-sustaining therapy. For objective 2, 7 studies that directly compared liver transplants with and without antemortem heparin reported lower rates of primary nonfunction, hepatic artery thrombosis, graft failure at 5 y, or recipient mortality (low certainty of evidence). In contrast, meta-regression analysis of 32 liver transplant studies detected no associations between the proportion of donors that received heparin and rates of early allograft dysfunction, primary nonfunction, hepatic artery thrombosis, biliary ischemia, graft failure, retransplantation, or patient survival (very low certainty of evidence). In conclusion, antemortem heparin practices vary substantially with an uncertain effect on transplant outcomes. Given the controversies surrounding antemortem heparin, clinical trials may be warranted.
Background
High‐frequency oscillation (HFO) is an alternative to conventional mechanical ventilation that is sometimes used to treat people with acute respiratory distress syndrome, but effects on ...oxygenation, mortality and adverse clinical outcomes are uncertain. This review was originally published in 2004 and was updated in 2013 and again in 2015.
Objectives
To determine the effects of HFO compared to conventional mechanical ventilation on physiological outcomes, clinical outcomes, and mortality when used for the treatment of acute respiratory distress syndrome (ARDS).
Search methods
We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Ovid), MEDLINE (Ovid), EMBASE (Ovid), and ISI, from inception to December 2015. We conducted the original search in 2002. We manually searched reference lists from included studies and review articles; searched conference proceedings of the American Thoracic Society (1994 to 2015), Society of Critical Care Medicine (1994 to 2015), European Society of Intensive Care Medicine (1994 to 2015), and American College of Chest Physicians (1994 to 2015); contacted clinical experts in the field; and searched for unpublished and ongoing trials in clinicaltrials.gov and controlled‐trials.com.
Selection criteria
Randomized controlled trials (RCTs) comparing treatment using HFO with conventional mechanical ventilation for children and adults diagnosed with ARDS.
Data collection and analysis
Three review authors independently extracted data on clinical, physiological, and safety outcomes according to a predefined protocol. We contacted investigators of all included studies to clarify methods and obtain additional data. We used random‐effects models in the analyses.
Main results
We include 10 RCTs (n = 1850); almost all participants had moderate or severe ARDS. For the primary analysis, the risk of bias was low in three studies and unclear in five studies; the overall quality of evidence was very low due to imprecision, inconsistency, indirectness and methodologic limitations. In participants randomized to HFO, there was no significant difference in hospital or 30‐day mortality (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.72 to 1.16; P = 0.46, I² = 66%; 8 trials, 1779 participants, 807 deaths) compared with conventional ventilation. One large multicentre RCT was terminated early because of increased mortality in participants randomized to HFO compared to mechanical ventilation with low tidal volume and high positive end expiratory pressure, with HFO reserved only as a rescue therapy. We found substantial between‐trial statistical heterogeneity (I² = 0% to 66%) for clinical outcomes, including mortality.
Authors' conclusions
The findings of this systematic review suggest that HFO does not reduce hospital and 30‐day mortality due to ARDS; the quality of evidence was very low. Our findings do not support the use of HFO as a first‐line strategy in people undergoing mechanical ventilation for ARDS.
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