A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome

RATIONALE: Ventilation in the prone position for about 7 h/d in patients with acute respiratory distress syndrome (ARDS), acute lung injury, or acute respiratory failure does not decrease mortality. Whether it is beneficial to administer prone ventilation early, and for longer periods of time, is unknown. METHODS: We enrolled 136 patients within 48 h of tracheal intubation for severe ARDS, 60 randomized to supine and 76 to prone ventilation. Guidelines were established for ventilator settings and weaning. The prone group was targeted to receive continuous prone ventilation treatment for 20 h/d. RESULTS: The intensive care unit mortality was 58% (35/60) in the patients ventilated supine and 43% (33/76) in the patients ventilated prone (p = 0.12). The latter had a higher simplified acute physiology score II at inclusion. Multivariate analysis showed that simplified acute physiology score II at inclusion (odds ratio [OR], 1.07; p < 0.001), number of days elapsed between ARDS diagnosis and inclusion (OR, 2.83; p < 0.001), and randomization to supine position (OR, 2.53; p = 0.03) were independent risk factors for mortality. A total of 718 turning procedures were done, and prone position was applied for a mean of 17 h/d for a mean of 10 d. A total of 28 complications were reported, and most were rapidly reversible. CONCLUSION: Prone ventilation is feasible and safe, and may reduce mortality in patients with severe ARDS when it is initiated early and applied for most of the day.     

急性肺损伤/急性呼吸窘迫综合征患者侧卧位通气与俯卧位通气的对比观察

目的　评价侧卧位通气和俯卧位通气对急性肺损伤 /急性呼吸窘迫综合征 (ALI/ARDS)患者的临床疗效 ,并对两种通气方法进行对比观察。方法　以 2 0 0 2年 3月为分界线 ,将 2 4例患者分为两组分别施行侧卧位通气 (2 0 0 2年 4月后 13例 )和俯卧位通气 (2 0 0 2年 3月前 11例 ) ,监测体位改变前、后的呼吸循环指标并分别进行比较。结果　体位改变 1h后 ,两组患者动脉血氧分压(PaO2 )均升高 ,侧卧位组由 (10 3± 12 )mmHg(1mmHg =0 .133kPa)上升到 (12 6± 13)mmHg,差异有显著性 (P <0 0 1) ;俯卧位组由 (87± 19)mmHg上升到 (119± 15 )mmHg(P <0 0 1)。以PaO2 升高 10mmHg为治疗有效标准 ,治疗有效率侧卧位组 6 1 5 % ,俯卧位组 6 3 6 % ,两组比较差异无显著性 (P >0 0 5 )。结论　作为ALI/ARDS的辅助治疗手段 ,侧卧位通气与俯卧位通气的治疗有效率接近 ,但侧卧位实施更容易 ,护理更方便 ,值得临床进一步探讨。     

Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome.

In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS.     

New modalities of mechanical ventilation: high-frequency oscillatory ventilation and airway pressure release ventilation

Management of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) is largely supportive, with the use of mechanical ventilation being a central feature. Recent advances in the understanding of ALI/ARDS and mechanical ventilation have revealed that lung-protective ventilation strategies may attenuate ventilator-associated lung injury and improve patient morbidity/mortality. High-frequency oscillatory ventilation and airway pressure release ventilation are two novel alternative modes of ventilation that theoretically fulfill the principles of lung protection and may offer an advantage over conventional ventilation for ALI/ARDS.     

Pediatric acute lung injury: prospective evaluation of risk factors associated with mortality

RATIONALE: The 1994 American European Consensus Committee definitions of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) have not been applied systematically in the pediatric population. OBJECTIVES: The purpose of this study was to evaluate prospectively the epidemiology and clinical risk factors associated with death and prolonged mechanical ventilation in all pediatric patients admitted to two large, pediatric intensive care units with ALI/ARDS using Consensus criteria. METHODS: All pediatric patients meeting Consensus Committee definitions for ALI were prospectively identified and included in a relational database. MEASUREMENTS AND MAIN RESULTS: There were 328 admissions for ALI/ARDS with a mortality of 22%. Multivariate logistic regression analyses revealed (1) the initial severity of oxygenation defect, as measured by the Pa(O2)/FI(O2) ratio; (2) the presence of nonpulmonary and non-central nervous system (CNS) organ dysfunction; and (3) the presence of CNS dysfunction were independently associated with mortality and prolonged mechanical ventilation. A substantial fraction of patients (28%) did not require mechanical ventilation at the onset of ALI; 46% of these patients eventually required intubation for worsening ALI. CONCLUSIONS: Mortality in pediatric ALI/ARDS is high and several risk factors have major prognostic value. In contrast to ALI/ARDS in adults, the initial severity of arterial hypoxemia in children correlates well with mortality. A significant fraction of patients with pediatric ALI/ARDS can be identified before endotracheal intubation is required. These patients provide a valuable group in whom new therapies can be tested.     

Mortality rates for patients with acute lung injury/ARDS have decreased over time

BACKGROUND: Over the last decade, several studies have suggested that survival rates for patients with acute lung injury (ALI) or ARDS may have improved. We performed a systematic analysis of the ALI/ARDS literature to document possible trends in mortality between 1994 and 2006. METHODS: We used the Medline database to select studies with the key words "acute lung injury," "ARDS," "acute respiratory failure," and "mechanical ventilation." All studies that reported mortality rates for patients with ALI/ARDS defined according to the criteria of the American European Consensus Conference were selected. We excluded studies with < 30 patients and studies limited to specific subgroups of ARDS patients such as sepsis, trauma, burns, or transfusion-related ARDS. RESULTS: Seventy-two studies were included in the analysis. There was a wide variation in mortality rates among the studies (15 to 72%). The overall pooled mortality rate for all studies was 43% (95% confidence interval, 40 to 46%). Metaregression analysis suggested a significant decrease in overall mortality rates of approximately 1.1%/yr over the period analyzed (1994 to 2006). The mortality reduction was also observed for hospital but not for ICU or 28-day mortality rates. CONCLUSIONS: In this literature review, the data are consistent with a reduction in mortality rates in general populations of patients with ALI/ARDS over the last 10 years.     

High-frequency ventilation for acute lung injury and ARDS

In patients with acute lung injury (ALI) and ARDS, conventional mechanical ventilation (CV) may cause additional lung injury from overdistention of the lung during inspiration, repeated opening and closing of small bronchioles and alveoli, or from excessive stress at the margins between aerated and atelectatic lung regions. Increasing evidence suggests that smaller tidal volumes (VTs) and higher end-expiratory lung volumes (EELVs) may be protective from these forms of ventilator-associated lung injury and may improve outcomes from ALI/ARDS. High-frequency ventilation (HFV)-based ventilatory strategies offer two potential advantages over CV for pateints with ALI/ARDS. First, HFV uses very small VTs, allowing higher EELVs with less overdistention than is possible with CV. Second, despite the small VTs, high respiratory rates during HFV allow the maintenance of normal or near-normal PaCO(2) levels. In this review, the use of HFV as a lung protective strategy for patients with ALI/ARDS is discussed.     

The efficacy and safety of prone positioning in adults patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Background

Prone positioning for acute respiratory distress syndrome (ARDS) has no impact on mortality despite significant improvements in oxygenation. However, a recent trial demonstrated reduced mortality rates in the prone position for severe ARDS. We evaluated effects of prone position duration and protective lung strategies on mortality rates in ARDS.

Methods

We extensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) reporting on prone positioning during acute respiratory failure in adults for inclusion in our meta-analysis.

Results

Eight trials met our inclusion criteria, Totals of 1,099 and 1,042 patients were randomized to the prone and supine ventilation positions. The mortality rates associated with the prone and supine positions were 41% and 47% [risk ratio (RR), 0.90; 95% confidence interval (CI), 0.82-0.98, P=0.02], but the heterogeneity was moderate (P=0.01, I²=61%). In a subgroup analysis, the mortality rates for lung protective ventilation (RR 0.73, 95% CI, 0.62-0.86, P=0.0002) and duration of prone positioning >12 h (RR 0.75, 95% CI, 0.65-0.87, P<0.0001) were reduced in the prone position. Prone positioning was not associated with an increased incidence of cardiac events (RR 1.01, 95% CI, 0.87-1.17) or ventilator associated pneumonia (RR 0.88, 95% CI, 0.71-1.09), but it was associated with an increased incidence of pressure sores (RR 1.23, 95% CI, 1.07-1.41) and endotracheal dislocation (RR 1.33, 95% CI, 1.02-1.74).

Conclusions

Prone positioning tends to reduce the mortality rates in ARDS patients, especially when used in conjunction with a lung protective strategy and longer prone position durations. Prone positioning for ARDS patients should be prioritized over other invasive procedures because related life-threatening complications are rare. However, further additional randomized controlled design to study are required for confirm benefit of prone position in ARDS.     

The role of cytokines during the pathogenesis of ventilator-associated and ventilator-induced lung injury

Mortality rates from acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) range from 30 to 65%. Although mechanical ventilation (MV) may delay mortality in critically ill patients with ALI/ARDS, it may also cause a lung injury that further promotes and perpetuates ALI/ARDS and multiorgan dysfunction syndrome (MODS). Recent studies have demonstrated that lung protective strategies of MV, as compared with the injurious strategy of conventional MV (CMV) can reduce absolute mortality rates during ALI/ARDS. The protective strategies limit tidal volumes and peak/plateau pressures while maximizing positive end-expiratory pressure. The injury to the lung by CMV is characterized histologically by edema, leukocyte extravasation, and endothelial and epithelial damage. Both human and animal studies suggest that alveolar cell deformation from CMV leads to the release of cytokines/chemokines which orchestrate the extravasation, activation, and recruitment of leukocytes, causing ventilator-associated lung injury (VALI) and ventilator-induced lung injury (VILI). Moreover, VALI/VILI can perpetuate the chronic inflammatory response during ALI/ARDS and MODS. This article explores the role of cytokines/chemokines during the pathogenesis of VALI/VILI.     

Prone positioning in patients with acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure that is characterized by marked hypoxemia, bilateral infiltrates on chest radiograph, and no clinical evidence of left ventricular failure. Mechanical ventilation with positive end-expiratory pressure (PEEP) is a cornerstone therapy for ARDS patients. Because the fundamental aim of supportive treatment is to improve arterial oxygenation, several alternatives to mechanical ventilation with PEEP have been used. One of these alternative therapies is prone positioning, which has been used safely to improve oxygenation in many patients with ARDS. Despite encouraging results, however, the use of prone positioning is not widely accepted as an adjunct to therapy in hypoxemic patients because, aside from temporarily improving gas exchange, it does not seem to affect the outcome of these patients. This article reviews the rationale for using prone positioning in ARDS patients who require intubation and mechanical ventilation.     

Prone positioning in acute respiratory distress syndrome

The ultimate efficacy of prone positioning in ARDS is difficult to evaluate because of heterogeneous study populations, the variances in the duration of the prone position, and the small sample sizes used in most studies. Prone positioning offers an easy, readily available treatment option for refractory hypoxemia. Although there is a rationale supporting the hypothesis that prone ventilation could reduce the mortality of ARDS patients, currently there are insufficient clinical data to support this hypothesis.     

机械通气在急性呼吸窘迫综合征中的应用进展

在治疗急性呼吸窘迫综合征的各种手段中,呼吸机机械通气是至关重要的.各种机械通气方式及参数的设置对于改善患者预后极为重要.从现有的研究资料来看,小潮气量机械通气(<6 ml/kg预计体质量,并使平台压小于30 cm H_2O)能减少死亡率,是急性呼吸窘迫综合征治疗的标准疗法.而个体化的呼气末正压通气也是一个有前途的值得研究的方向.其他一些方法例如俯卧位通气、肺复张等不能作为常规的一线治疗,而只能作为严重情况下低氧血症的挽救治疗.另外本文也就机械通气在2009年甲型H1N1流感所致急性呼吸窘迫综合征的治疗方面做了简单综述.     

Statins for the prevention and treatment of acute lung injury and acute respiratory distress syndrome: A systematic review and meta‐analysis

The purpose of this meta‐analysis was to assess whether statins could reduce the morbidity of acute lung injury and acute respiratory distress syndrome (ALI/ARDS) in high‐risk patients and improve the clinical outcomes of patients with ALI/ARDS. Studies were obtained from PubMed, Medline, Embase and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) and cohort studies, which reported morbidity, mortality, ventilator‐free days, length of stay in intensive care unit and hospital or oxygenation index, were included in our meta‐analysis. Risk ratio (RR) and weighted mean difference (WMD) were calculated using fixed or random effect model. A total of 13 studies covering 12 145 patients were included. Both the only RCT (P = 0.10) and cohort studies (RR, 1.02; 95% CI, 0.67 to 1.55; P = 0.94) showed that statin therapy did not lower the morbidity of ALI/ARDS in high‐risk patients. The mortality of ALI/ARDS patients was less likely to be improved by statins (RCT, RR, 1.00; 95% CI, 0.84 to 1.20; P = 0.97; cohort studies, RR, 1.04; 95% CI, 0.85 to 1.27; P = 0.72). Moreover, no significant difference was observed in ventilator‐free days, length of stay in intensive care unit as well as hospital and oxygenation index. This meta‐analysis suggests that statins neither provide benefit for lowering the morbidity of ALI/ARDS in high‐risk patients nor improve the clinical outcomes of ALI/ARDS patients. Hence, it may not be appropriate to advocate statin use for the prevention and treatment of ALI/ARDS.     

Respiratory failure

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common causes of hypoxemic respiratory failure. Multiple etiologies lead to direct and indirect pulmonary injury that progresses through an acute exudative phase, fibroproliferative phase, and recovery phase. Inflammatory mechanisms are thought to play a predominant role in the pathophysiology of ALI/ARDS. Mechanical ventilation with a lower tidal volume and an inspiratory plateau pressure of < or = 30 cm H2O is one intervention that has demonstrated a reduction in mortality. A clinical trial to determine the role of restrictive versus liberal fluid management is underway. Inhaled nitric oxide has been used to improve oxygenation but has not resulted in any outcome benefit. Glucocorticoids may be beneficial in the fibroproliferative phase of lung injury by suppressing chronic inflammation. Rigorous clinical trials of new and established interventions are required to determine optimum therapy and reduce mortality in ALI/ARDS.     

The effects of early and repeated prone positioning in pediatric patients with acute lung injury

STUDY OBJECTIVE: To describe the physiologic changes and to evaluate the safety of placing pediatric patients with acute lung injury (ALI) prone for 20 h/d during the acute phase of their illness. DESIGN: Single-center prospective case series. SETTING: Tertiary-level pediatric ICU. PATIENTS: Consecutive patients with bilateral pulmonary parenchymal disease requiring intubation and mechanical ventilation with a PaO(2)/fraction of inspired oxygen (FIO(2)) ratio /= 20 mm Hg in PaO(2)/FIO(2) ratio or a decrease of >/= 10% in oxygenation index when shifted from a supine to a prone position during the study period. During the 107 patient-days and 214 positioning cycles, no critical incidents occurred. Furthermore, no patient experienced a persistent decrease in oxygen saturation as measured by pulse oximetry (SpO(2)) of > 10% from values obtained when in the supine position, failed to keep their SpO(2) at > 85%, or experienced an increased respiratory rate of > 40 breaths/min when prone. Using the COMFORT score, patients were objectively rated to be equally comfortable in both the supine and prone positions. Patients also were able to resume spontaneous ventilation and to progress toward endotracheal extubation while in the prone position. Iatrogenic injury associated with prolonged prone positioning included stage II pressure ulcers in six patients (24%). CONCLUSIONS: The pediatric patients in this series demonstrated improvements in oxygenation without serious iatrogenic injury after prone positioning. This study provides a foundation for a prospective randomized study investigating the effect of early and repeated prone positioning on clinical outcomes in pediatric patients with ALI.     

气道压力释放通气联合俯卧位通气对中重度急性呼吸窘迫综合征患者呼吸功能及预后有改善作用

目的：分析气道压力释放通气（APRV）联合俯卧位通气对中重度急性呼吸窘迫综合征（ARDS）患者呼吸功能及预后的改善作用。方法：回顾性分析56例中重度ARDS患者临床病历资料，均采用APRV联合俯卧位通气治疗。记录患者治疗前和治疗12、24、48、72h后的动脉血氧分压（PaO2）、二氧化碳分压（PaCO2）、气道平均压(Pmean）、气道峰压(Ppeak)、肺动态顺应性（Cydn)、氧合指数(PaO2/FiO2)、肺泡动脉氧分压差(PA2DO2)的改变；统计患者的28d病死率、机械通气时间、入住ICU住院时间及不良事件的发生情况。结果：随着治疗时间的增加，PaCO2、Pmean、Ppeak、P2-aDO2水平整体呈下降趋势，而PaO2、Cydn、PaO2/FiO2水平呈升高趋势（P均＜0.05）；治疗72h后，患者PaO2、Ppeak、Cydn、PA-aDO2、PaO2/FiO2水平趋于稳定状态。患者28d病死率为25.00%，机械通气时间（9.87±2.01）d，重症肺炎与脓毒症患者病死率较高；入住ICU时间（11.36±3.65）d，不良反应发生率为8.93%。结论：APRV联合俯卧位通气治疗重度ARDS效果较明显，可改善患者通气状态及氧合指数，有效避免肺损伤，对改善患者预后有效。     

Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark, and Iceland. The ARF Study Group.

To determine the incidence and 90-d mortality of acute respiratory failure (ARF), acute lung injury (ALI), and the acute respiratory distress syndrome (ARDS), we carried out an 8-wk prospective cohort study in Sweden, Denmark, and Iceland. All intensive care unit (ICU) admissions (n = 13,346) >/= 15 yr of age were assessed between October 6th and November 30th, 1997 in 132 of 150 ICUs with resources to treat patients with intubation and mechanical ventilation (I + MV) >/= 24 h. ARF was defined as I + MV >/= 24 h. ALI and ARDS were defined using criteria recommended by the American-European Consensus Conference on ARDS. Calculation to correct the incidence for unidentified subjects from nonparticipating ICUs was made. No correction for in- or out-migration from the study area was possible. The population in the three countries >/= 15 yr of age was 11.74 million. One thousand two hundred thirty-one ARF patients were included, 287 ALI and 221 ARDS patients were identified. The incidences were for ARF 77.6, for ALI 17.9, and for ARDS 13.5 patients per 100,000/yr. Ninety-day mortality was 41.0% for ARF, including ALI and ARDS patients, 42.2% for ALI not fulfilling ARDS criteria, and 41.2% for ARDS.     

Mechanical ventilation in ARDS: a state-of-the-art review

Mechanical ventilation is an essential component of the care of patients with ARDS, and a large number of randomized controlled clinical trials have now been conducted evaluating the efficacy and safety of various methods of mechanical ventilation for the treatment of ARDS. Low tidal volume ventilation (相似文献   

Partial liquid ventilation for acute respiratory distress syndrome

PLV represents an intriguing alternative paradigm in the approach to the patient with ALI. Within the past decade, substantial information has become available regarding this technique. Clearly, PLV is feasible in patients with ALI and ARDS, and it appears to be safe with respect to short-term effects on hemodynamics and lung physiology, as well as long-term toxicity (although further research in this area is warranted). Although PLV has not yet been proven to be superior to traditional mechanical ventilation for patients with ALI or ARDS, PLV possesses an intriguing combination of physical, physiologic, and biologic effects: "Liquid PEEP" effect--e.g., more effective recruitment of dependent lung zones than achieved by gas ventilation Anti-inflammatory effects Lavage of alveolar debris Mitigation of ventilator-induced lung injury Direct anti-inflammatory effects--e.g., decreased macrophage release of proinflammatory cytokines, etc. Prevention of nosocomial pneumonia Combination with other modalities--e.g., exogenous surfactant replacement, inhaled NO, prone position Enhanced delivery of drugs or gene vectors into the lung. The results of ongoing and future clinical trials will be necessary to establish whether PLV improves clinical outcomes in patients with ALI or ARDS, or specific subgroups of such patients. Significant work also remains to be done to define the optimum dose level of PLV and the most appropriate ventilatory strategies.     

控制性肺膨胀在不同病因急性肺损伤中的临床观察

目的:观察控制性肺膨胀(SI)对肺部疾患、肺外疾患引起的急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS)患者的疗效。方法:60例ALI/ARDS患者按病因不同分为两组,每组30例。A组:肺部疾患导致ALI/ARDS(primarily from pulmonary diseases,ARDSp)。B组:肺外疾患导致ALI/ARDS(primarily from extra-pulmo-nary diseases,ARDSexp)。均在常规治疗基础上予呼吸机辅助呼吸,实行肺保护性通气,如指氧饱和度(SpO2)低于90%,予控制性肺膨胀治疗,于治疗前后监测气道平台压(Pplat)、吸入峰压(Ppeak)、平均气道压(Pmean)、呼吸系统顺应性(Crs)、气道阻力(R)、心率(HR)、中心静脉压(CVP)、平均动脉压(MAP)及动脉血气分析。结果:B组PaO2、SpO2的改善均明显优于A组(P<0.05)。结论:肺外源性的ALI/ARDS对SI的反应优于肺内源性的ALI/ARDS。