急性呼吸窘迫综合征的随机对照临床研究与实践

随着重症医学的迅速发展,急性呼吸窘迫综合征(ARDS)的临床实践也在不断进步.目前国内外发表了大量关于ARDS的医学论文,其中不乏在循证医学中证据可信度较高的随机对照临床研究(RCT),这必然会进一步推动ARDS的临床实践.     

Albuterol in the treatment of acute respiratory distress syndrome: A meta-analysis of randomized controlled trials

BACKGROUND: This meta-analysis of randomized controlled trials aimed to systematically evaluate the value of albuterol in the treatment of patients with acute respiratory distress syndrome(ARDS).DATA SOURCES: Randomized controlled trials on albuterol treatment of ARDS from its inception to October 2014 were searched systematically. The databases searched included: Pub Med, Ovid EMBASE, Ovid Cochrane, CNKI, WANFANG and VIP. The trials were screened according to the pre-designed inclusion and exclusion criteria. We performed a systematic review and meta-analysis of the randomized controlled trials(RCTs) on albuterol treatment, attempting to improve outcomes, i.e. lowering the 28-day mortality and ventilator-free days.RESULTS: Three RCTs involving 646 patients met the inclusion criteria. There was no significant decrease in the 28-day mortality(risk difference=0.09; P=0.07, P for heterogeneity=0.22, I2=33%). The ventilator-free days and organ failure-free days were significantly lower in the patients who received albuterol(mean difference=–2.20; P0.001, P for heterogeneity=0.49, I2=0% and mean difference=–1.71, P0.001, P for heterogeneity=0.60, I2=0%).CONCLUSIONS: Current evidences indicate that treatment with albuterol in the early course of ARDS was not effective in increasing the survival, but significantly decreasing the ventilator-free days and organ failure-free days. Owing to the limited number of included trails, strong recommendations cannot be made.     

Neuromuscular blocking agents in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials

Introduction

Randomized trials investigating neuromuscular blocking agents in adult acute respiratory distress syndrome (ARDS) have been inconclusive about effects on mortality, which is very high in this population. Uncertainty also exists about the associated risk of ICU-acquired weakness.

Methods

We conducted a systematic review and meta-analysis. We searched the Cochrane (Central) database, MEDLINE, EMBASE, ACP Journal Club, and clinical trial registries for randomized trials investigating survival effects of neuromuscular blocking agents in adults with ARDS. Two independent reviewers abstracted data and assessed methodologic quality. Primary study investigators provided additional unpublished data.

Results

Three trials (431 patients; 20 centers; all from the same research group in France) met inclusion criteria for this review. All trials assessed 48-hour infusions of cisatracurium besylate. Short-term infusion of cisatracurium besylate was associated with lower hospital mortality (RR, 0.72; 95% CI, 0.58 to 0.91; P = 0.005; I² = 0). This finding was robust on sensitivity analyses. Neuromuscular blockade was also associated with lower risk of barotrauma (RR, 0.43; 95% CI, 0.20 to 0.90; P = 0.02; I² = 0), but had no effect on the duration of mechanical ventilation among survivors (MD, 0.25 days; 95% CI, 5.48 to 5.99; P = 0.93; I² = 49%), or the risk of ICU-acquired weakness (RR, 1.08; 95% CI, 0.83 to 1.41; P = 0.57; I² = 0). Primary studies lacked protracted measurements of weakness.

Conclusions

Short-term infusion of cisatracurium besylate reduces hospital mortality and barotrauma and does not appear to increase ICU-acquired weakness for critically ill adults with ARDS.     

Corticosteroid therapy for acute lung injury,acute respiratory distress syndrome,and severe pneumonia: A meta-analysis of randomized controlled trials

Background

Randomized trials investigating the effect of corticosteroids in the treatment of acute lung injury, acute respiratory distress syndrome, and severe pneumonia have had mixed results. We sought to determine whether systemic corticosteroids reduce hospital mortality from these illnesses.

Methods

We conducted a systematic review of published and unpublished randomized trials. We searched MEDLINE, EMBASE, CENTRAL, and CINAHL and reviewed proceedings from relevant society meetings. Two reviewers screened the literature and extracted data independently. For each outcome, we used Grading of Recommendations Assessments, Development and Evaluation (GRADE) criteria to evaluate the quality of the underlying evidence.

Results

We included 12 trials enrolling 966 patients. Pooling across all trials, corticosteroids did not significantly reduce hospital mortality (relative risk, 0.84; 95% confidence interval, 0.66-1.06). In a subgroup analysis by dose of corticosteroid, trials using the equivalent of 2 mg kg⁻¹ d⁻¹ or less of methylprednisolone (9 trials) found lower hospital mortality with corticosteroid therapy (relative risk 0.68; 95% confidence interval, 0.49-0.96). The quality of the evidence underlying the pooled estimate of effect on hospital mortality was low, downgraded for inconsistency and imprecision.

Conclusions

Low-dose corticosteroids administered within 14 days of disease onset may reduce all-cause mortality in patients with acute lung injury, acute respiratory distress syndrome, and severe pneumonia. However, the overall quality of the evidence precludes definitive conclusions regarding the use of corticosteroids in this population.     

Ventilatory management of acute respiratory distress syndrome: a consensus of two

OBJECTIVE: To synthesize the emerging body of experimental, observational, and clinical trial data into a practical guideline for safe and effective ventilatory management of acute respiratory distress syndrome. DATA SOURCES: Relevant, peer-reviewed, scientific literature and personal observations from clinical practice. STUDY SELECTION: Relevant experimental studies and high-impact observational and clinical trials of acute respiratory distress syndrome management. DATA EXTRACTION: Detailed review of information contained in published scientific work. DATA SYNTHESIS: Interactive discussions between the authors that culminated in our consensus view of appropriate management. CONCLUSIONS: Prevention of ventilator-induced lung injury while accomplishing the essential life-supporting roles of mechanical ventilation is a complex undertaking that requires application of principles founded on a broad experimental and clinical database and on the results of well-executed clinical trials. At the bedside, execution of an effective lung-protective ventilation strategy remains an empirical process best guided by integrated physiology and a readiness to revise the management approach depending on the individual's response.     

重症急性胰腺炎并发急性呼吸窘迫综合征的临床分析

目的探讨重症急性胰腺炎（SAP）并发急性呼吸窘迫综合征（ARDS）患者的临床特点及治疗方法。方法SAP患者67例，按是否发生ARDS分为ARDS组和非ARDS组，观察两组患者的呼吸频率、APACHEⅡ评分、Ranson评分、胰腺CT评分、肠蠕动抑制发生率、胰腺感染率及病死率并进行比较。结果ARDS组死亡11例，病死率47．8％。ARDS组入院时呼吸频率、入院时及入院24h APACHEⅡ评分、入院24h Ranson评分、入院时胰腺CT评分、入院24h内肠蠕动抑制发生率以及胰腺感染率和病死率均明显高于非ARDS组（P〈0．05或P〈0．01）。结论SAP患者如入ICU和／或治疗24h后APACHEⅡ评分、Ranson评分、胰腺CT评分仍明显增高，或肠蠕动抑制仍不缓解，同时呼吸频率进行性加快时，要警惕ARDS发生。     

The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Introduction

Prone positioning (PP) has been reported to improve the survival of patients with severe acute respiratory distress syndrome (ARDS). However, it is uncertain whether the beneficial effects of PP are associated with positive end-expiratory pressure (PEEP) levels and long durations of PP. In this meta-analysis, we aimed to evaluate whether the effects of PP on mortality could be affected by PEEP level and PP duration and to identify which patients might benefit the most from PP.

Methods

Publications describing randomized controlled trials (RCTs) in which investigators have compared prone and supine ventilation were retrieved by searching the following electronic databases: PubMed/MEDLINE, the Cochrane Library, the Web of Science and Elsevier Science (inception to May 2013). Two investigators independently selected RCTs and assessed their quality. The data extracted from the RCTs were combined in a cumulative meta-analysis and analyzed using methods recommended by the Cochrane Collaboration.

Results

A total of nine RCTs with an aggregate of 2,242 patients were included. All of the studies received scores of up to three points using the methods recommended by Jadad et al. One trial did not conceal allocation. This meta-analysis revealed that, compared with supine positioning, PP decreased the 28- to 30-day mortality of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS patients ventilated with PEEP ≥10 cmH₂O. Moreover, PP reduced 28- to 30-day mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54 to 0.99; P = 0.04).

Conclusions

PP reduced mortality among patients with severe ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP improved the survival of ARDS patients.     

Thirty years of clinical trials in acute respiratory distress syndrome

OBJECTIVE: To systematically review clinical trials in acute respiratory distress syndrome (ARDS). DATA SOURCES: Computerized bibliographic search of published research and citation review of relevant articles. STUDY SELECTION: All clinical trials of therapies for ARDS were reviewed. Therapies that have been compared in prospective, randomized trials were the focus of this analysis. DATA EXTRACTION: Data on population, interventions, and outcomes were obtained by review. Studies were graded for quality of scientific evidence. MAIN RESULTS: Lung protective ventilator strategy is supported by improved outcome in a single large, prospective trial and a second smaller trial. Other therapies for ARDS, including noninvasive positive pressure ventilation, inverse ratio ventilation, fluid restriction, inhaled nitric oxide, almitrine, prostacyclin, liquid ventilation, surfactant, and immune-modulating therapies, cannot be recommended at this time. Results of small trials using corticosteroids in late ARDS support the need for confirmatory large clinical trials. CONCLUSIONS: Lung protective ventilator strategy is the first therapy found to improve outcome in ARDS. Trials of prone ventilation and fluid restriction in ARDS and corticosteroids in late ARDS support the need for large, prospective, randomized trials.     

Acute respiratory distress syndrome: clinical recognition and preventive management in chiropractic acute care practice

OBJECTIVE: To present clinical information relevant to acute respiratory distress syndrome (ARDS) and its appearance in chiropractic acute care practice. DATA SOURCES: The National Library of Medicine MEDLINE database was used, along with the bibliographies of selected articles and textbooks commonly found in chiropractic college libraries and bookstores. STUDY SELECTION: Clinical studies from the English literature were selected if they pertained to incidence, clinical relevancy, or the association of ARDS with commonly-seen diagnoses in chiropractic neuromusculoskeletal or orthopedic practice. DATA EXTRACTION: All relevant studies identified by the search were evaluated based on information pertinent to chiropractic management of acute care patients. RESULTS: ARDS is a pulmonary distress syndrome with a high mortality rate. Recognizable indications for the possible development of ARDS include chest pain, head injury, and thoracic spine pain with or without trauma. Clinical evaluation, radiographic findings, and laboratory findings are presented to assist practitioners in identifying this disease process of multiple etiology. A study of the basic pathophysiologic processes that occur in the formation of ARDS is presented to help practitioners gain clinical appreciation. Strategies for preventing respiratory distress in chiropractic patients are also presented and include use of the postural position and the clinical maxim of "slow, deep breathing despite pain" to lessen incident rates of subjects at risk. CONCLUSION: Although ARDS may not be prevalent in chiropractic practice, it is important for physicians to be aware of the clinical basics (including its pathophysiology), its medical significance, and the preventive strategies that may be used to minimize its occurrence. This basic understanding will further advance knowledge of this disease complex.     

Meta-analysis of controlled trials of ventilator therapy in acute lung injury and acute respiratory distress syndrome: an alternative perspective

Objective The role of protective ventilation in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is controversial. Evidence was sought from published randomised trials for a consistent treatment effect of protective ventilation and any covariate modification.Design Meta-analysis of protective ventilation trials in ALI/ARDS and meta-regression of covariates on treatment effect (log odds ratio), with respect to 28-day mortality. Heterogeneity impact on the meta-analysis was assessed by the H statistic (substantial impact, >1.5) and graphical analysis. Five trials with a total of 1,202 patients were considered.Measurements and results Average 28-day mortality was 0.40 in the treatment group (protective ventilation, n=605) vs. 0.46 in the control group (control ventilation, n=597). The treatment effect (odds ratio) was: fixed-effects, 0.71 (95% CI 0.56–0.91, p=0.006; heterogeneity, p=0.06) and random effects: 0.80 (95% CI 0.49–1.31, p=0.37). Heterogeneity impact (H statistic=1.50) was adjudged as modest. The treatment effect was significant and (a) favoured protective ventilation for a tidal volume less than 7.7 ml/kg predicted (treatment group) and a mean plateau pressure of 30 cmH₂O or higher (control group) but was not influenced by plateau pressure 21–30 cmH₂O (treatment group) and (b) depended upon plateau pressure difference greater than 5–7 cmH₂O between protective ventilation and standard ventilation.Conclusions Overall treatment effect estimate favoured protective ventilation but did not achieve statistical significance. Protective ventilation depended upon threshold levels of tidal volume, plateau pressure, and plateau pressure difference.Electronic Supplementary Material Electronic supplementary material to this paper can be obtained by using the Springer Link server located at .     

Designing clinical trials in acute lung injury/acute respiratory distress syndrome

PURPOSE OF REVIEW: To review the implications of recent literature for clinical trial design in acute lung injury/acute respiratory distress syndrome (ARDS). RECENT FINDINGS: Refinement of acute lung injury/acute respiratory distress syndrome diagnostic criteria and study enrollment criteria, greater efforts to define usual care appropriately, and balancing of efficacy and effectiveness design principles will be key components of future trials. SUMMARY: Clinical trial design in acute lung injury/acute respiratory distress syndrome faces many challenges. Although we have learned much from past trials, persistent design dilemmas must be addressed for future trials.     

Limitations of clinical trials in acute lung injury and acute respiratory distress syndrome

PURPOSE OF REVIEW: To review the challenges and limitations of randomized clinical trials in acute respiratory distress syndrome, with special emphasis on those pertaining to ventilatory management. RECENT FINDINGS: Superbly executed randomized trials of ventilatory strategy have garnered deserved attention from the critical care community and yet have illustrated the limitations of our current approach to clinical research in this area. Inexact definitions, incomplete mechanistic understanding of complex pathophysiology, inappropriate outcome variables, diverse therapeutic environments, lengthy data acquisition time and ethical constraints on trial design limit the applicability of randomized control trial methodology to acute respiratory distress syndrome and acute lung injury. As yet, clinical practice does not seem to have been greatly impacted by the implications of completed randomized controlled trials per se. Recent issues, both ethical and interpretive, regarding control group participants have raised troubling and theoretically important issues that are yet to be fully resolved. SUMMARY: Without tighter definitions of the condition under treatment, more specific targets for interventions to act upon, stratification that recognizes key interactive elements, and cointerventions based on better mechanistic understanding, randomized controlled trials of new drugs, ventilatory strategy, and other management approaches in acute respiratory distress syndrome are likely to remain a blunt instrument for investigation. As valuable as they are for calling important therapeutic principles to attention and for helping to suggest general guidelines for care, the limitations of randomized controlled trials for treating the individual with acute respiratory distress syndrome must be acknowledged.     

Enteral omega-3 fatty acid supplementation in adult patients with acute respiratory distress syndrome: a systematic review of randomized controlled trials with meta-analysis and trial sequential analysis

Purpose

Controversy remains as to whether enteral supplementation of ω-3 fatty acids (FA) could improve outcomes in patients with acute respiratory distress syndrome (ARDS). Thus, we did a meta-analysis and aimed to investigate the benefit and harm of enteral ω-3 FA supplementation in adult patients with ARDS.

Methods

Databases including PubMed, Embase, the Cochrane Register of Controlled Trials, and Google Scholar were searched to find relevant articles. Randomized controlled trials (RCTs) comparing enteral ω-3 FA supplementation with a control or placebo intervention in adult patients with ARDS were included. The primary outcome was all-cause 28-day mortality. We used the Cochrane Collaboration methodology.

Results

Seven RCTs with 955 adult patients qualified for inclusion, and all the selected trials were considered as at high risk of bias. The use of enteral ω-3 FA did not significantly reduce all-cause 28-day mortality [relative risk (RR), 0.90; 95 % confidence intervals (CI), 0.68–1.18; p = 0.44; I ² = 31 %; random effects]. Trial sequential analysis indicated lack of firm evidence for a 20 % RR reduction in all-cause 28-day mortality. PaO₂/FiO₂ ratio was significantly increased in the ω-3 FA group on day 4 [weighted mean difference (WMD), 45.14; 95 % CI, 16.77–73.51; p = 0.002; I ² = 86 %; random effects] and day 7 (WMD, 33.10; 95 % CI, 1.67–64.52; p = 0.04; I ² = 88 %; random effects). Meta-analysis using a random effects model showed no significant differences in ventilator-free days (VFD) (WMD, 2.47 days; 95 % CI, ?2.85 to 7.79; p = 0.36; I ² = 91 %) or intensive care unit-free days (ICU) (WMD, 2.31 days; 95 % CI, ?2.34 to 6.97; p = 0.33; I ² = 89 %) between the two groups.

Conclusions

Among patients with ARDS, enteral supplementation of ω-3 FA seemed ineffective regarding all-cause 28-day mortality, VFD, and ICU-free days. Routine use of enteral ω-3 FA cannot be recommended based on the available evidence.     

Role of corticosteroids in the management of acute respiratory distress syndrome

BACKGROUND: Evidence exploring the use of corticosteroids for acute respiratory distress syndrome (ARDS) has targeted various stages of disease progression, from preventing ARDS in high-risk patients to halting disease evolution once ARDS has developed. OBJECTIVE: The aim of this review was to evaluate randomized, controlled trials describing the role of corticosteroids in preventing and treating ARDS. METHODS: English-language randomized, controlled trials were identified using MEDLINE via PubMed and EMBASE searches (key terms: acute respiratory distress syndrome, acute lung injury, and corticosteroids; years: 1968-January 2008). RESULTS: A total of 10 trials were found and included in this analysis. Trials describing the role of high-dose corticosteroids compared with controls in preventing ARDS found no benefit, with the range of occurrence of ARDS in at-risk populations from 14% to 64% and absolute increases in mortality from 4% to 31%. Conflicting evidence was found for treating late-phase ARDS with corticosteroids, with 13% hospital mortality among patients receiving corticosteroids versus 63% with controls (P = 0.03) in one small study, but no significant difference was found when evaluating 60-day mortality (corticosteroid group, 29.2% vs control, 28.6%) in another investigation. The use of high-dose corticosteroids for the treatment of early phase ARDS was not associated with significant differences in 45-day mortality (methylprednisolone, 60% vs control, 63%). However, one trial found that methylprednisolone taper for early ARDS was associated with significant improvement in lung function or extubation (69.8% vs 35.7%; P = 0.002), fewer days on mechanical ventilation (median, 5.0 vs 9.5; P = 0.002), higher intensive care unit survival (79.4% vs 57.4%; P = 0.03), but similar rates of hospital survival (methylprednisolone, 76.2% vs control, 57.1%; P = NS). CONCLUSIONS: Data from clinical trials did not support the use of short-course, high-dose corticosteroids for preventing ARDS or for the treatment of early ARDS. Longer-course corticosteroids have not conclusively been associated with improved survival in the treatment of late-phase ARDS but have provided some benefits in other markers of disease severity in this setting and in early phase ARDS. Published trials support the administration of low- to moderate-dose corticosteroids in the treatment of early (<7 days) and late-phase (days 7\2-14) ARDS, but this evidence is controversial.     

Update in ARDS management: recent randomized controlled trials that changed our practice

In the last 7 years, 14 randomized controlled trials in patients with acute respiratory distress syndrome (ARDS) have shown that: Mechanical ventilation with a tidal volume of 6 mL/kg of predicted body weight is better than mechanical ventilation with a tidal volume of 12 mL/kg of predicted body weight. Prone positioning improves oxygenation but poses safety concerns. A high level of positive end-expiratory pressure does not improve survival. High-frequency oscillatory ventilation is in theory the ideal "lung-protective" method, but its benefits have not been proven. No drug therapy has been shown to improve survival in patients with ARDS. Exogenous surfactant may improve oxygenation but has no significant effect on the death rate or length of use of mechanical ventilation. Low-dose inhaled nitric oxide has no substantial impact on the duration of ventilatory support or on the death rate. Partial liquid ventilation may be beneficial in young patients with acute lung injury or ARDS, although further study is needed to confirm this.     

Evidence-based management of acute lung injury and acute respiratory distress syndrome

This report explores the efficacy of existing therapies for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), primarily in terms of clinically important outcomes such as the duration of mechanical ventilation and hospital mortality. Of the 15 therapies reviewed, the strongest evidence suggests that ALI/ARDS should be managed with a low-tidal-volume, pressure-limited approach, with either low or moderately high positive end-expiratory pressure. To date there have been few large, sufficiently powered, randomized controlled clinical trials of ALI/ARDS therapies that addressed patient outcomes. However, there is relatively strong evidence to support conservative fluid management and high-fat, anti-oxidant nutritional formulations. Although most pharmacologic ALI/ARDS therapies have been ineffective, high-dose methylprednisolone is indicated in the subgroups of ALI/ARDS patients who have pneumonia or are at risk of ARDS due to fat embolization.