Best compliance during a decremental, but not incremental, positive end-expiratory pressure trial is related to open-lung positive end-expiratory pressure: a mathematical model of acute respiratory distress syndrome lungs

A mathematical model of the acute respiratory distress syndrome (ARDS) lung, incorporating simulated gravitational superimposed pressure and alveolar opening and closing pressures, was used to study the mean tidal pressure-volume (PV) slope ("effective compliance") during incremental and decremental positive end-expiratory pressure (PEEP) trials with constant tidal volume (VT) "ventilation." During incremental PEEP, the PEEP giving maximum mean tidal PV slope did not coincide with "open lung PEEP" (minimum PEEP preventing end expiratory collapse of 97.5% of alveoli inflated at end-inspiration), and it varied greatly with varying VT and "lung mechanics." Incremental PEEP with a low VT tests recruitment by the peak pressure, not prevention of collapse by PEEP. During decremental PEEP with a low VT, maximum mean tidal PV slope occurred with PEEP 2-3.5 cm H2O below open-lung PEEP, unless closing pressure was high. High VT, high "specific compliance," and high opening pressures caused slightly greater underestimation of open-lung PEEP. Maximum mean tidal PV slope was always higher (e.g., 93.7 versus 16.69 ml/cm H2O), and the variation in PV slope with PEEP was greater, during decremental PEEP. The maximum PV slope during a decremental PEEP trial with a low VT may be a useful method to determine open-lung PEEP in ARDS, and should be studied clinically.     

The role of CT-scan studies for the diagnosis and therapy of acute respiratory distress syndrome

CT has provided new insights on the pathophysiology of acute respiratory distress syndrome (ARDS), demonstrating that ARDS does not affect the lung parenchyma homogeneously. These findings suggest that lung edema, as assessed by CT scan, should be included in the definition. Lung CT findings may provide a firm rationale for tailoring tidal volume during mechanical ventilation. Ideally, tidal volume should be proportional to the portion of the lung open to ventilation, as assessed by CT scan, rather than to the body weight. CT assessment of lung recruitability seems to be a prerequisite for a rational setting of positive end-expiratory pressure.     

氧合导向最佳呼气末正压对急性呼吸窘迫综合征犬肺局部气体分布和炎症反应的影响

目的 探讨氧合导向最佳呼气末正压(PEEP)对急性呼吸窘迫综合征(ARDS)犬肺组织局部气体分布和炎症反应的影响.方法 静脉注射油酸(油酸组,8只)、肺泡灌洗生理盐水(生理盐水组,8只)复制犬ARDS模型.模型成功后给予氧合导向最佳PEEP进行机械通气,基础状态、模型复制成功及机械通气4 h后均行肺部CT扫描,观察肺局部气体分布.4 h后处死犬,留取肺组织观察病理改变,凝胶迁移率改变电泳(EMSA)测肺组织NF-κB活性,比色法测肺组织髓过氧化物酶(MPO)和丙二醛(MDA)含量,ELISA测肺组织IL-6、IL-10含量.结果 (1)与基础状态比,2组犬模型复制成功后,总肺容积均显著减少,不通气区肺容积明显增加;与模型复制成功时比,2组犬在最佳氧合法确定PEEP水平,CT扫描显示低通气区及不通气区肺容积明显减少,正常通气肺组织增加,但过度膨胀区肺容积也显著增加,以腹侧(非重力依赖区)肺泡过度膨胀明显.与油酸组比,在最佳氧合法确定PEEP水平,生理盐水组过度膨胀区肺容积增多更显著.(2)2组犬肺右下叶腹侧组织损伤评分均明显高于右上叶,肺右下叶背侧组织损伤评分均明显高于右上叶、右下叶腹侧;肺右下叶背侧组织NF-κB活性均明显高于右上叶;肺右下叶背侧、右下叶腹侧组织MPO和MDA含量均明显高于右上叶;肺右下叶背侧组织IL-6、IL-10含量均明显高于右上叶、右下叶腹侧.结论 以氧合导向最佳PEEP致ARDS肺非重力依赖区过度膨胀,加重局部肺损伤.生理盐水组犬肺过度膨胀更显著.     

Respiratory system mechanics in acute respiratory distress syndrome

Respiratory mechanics research is important to the advancement of ARDS management. Twenty-eight years ago, research on the effects of PEEP and VT indicated that the lungs of ARDS patients did not behave in a manner consistent with homogenously distributed lung injury. Both Suter and colleagues] and Katz and colleagues reported that oxygenation continued to improve as PEEP increased (suggesting lung recruitment), even though static Crs decreased and dead-space ventilation increased (suggesting concurrent lung overdistension). This research strongly suggested that without VT reduction, the favorable effects of PEEP on lung recruitment are offset by lung overdistension at end-inspiration. The implications of these studies were not fully appreciated at that time, in part because the concept of ventilator-associated lung injury was in its nascent state. Ten years later. Gattinoni and colleagues compared measurements of static pressure-volume curves with FRC and CT scans of the chest in ARDS. They found that although PEEP recruits collapsed (primarily dorsal) lung segments, it simultaneously causes overdistension of non-dependent, inflated lung regions. Furthermore, the specific compliance of the aerated, residually healthy lung tissue is essentially normal. The main implication of these findings is that traditional mechanical ventilation practice was injecting excessive volumes of gas into functionally small lungs. Therefore, the emblematic low static Crs measured in ARDS reflects not only surface tension phenomena and recruitment of collapsed airspaces but also overdistension of the remaining healthy lung. The studies reviewed in this article support the concept that lung injury in ARDS is heterogeneously distributed, with resulting disparate mechanical stresses, and indicate the additional complexity from alterations in chest wall mechanics. Most of these studies, however, were published before lung-protective ventilation. Therefore, further studies are needed to refine the understanding of the mechanical effects of lung-protective ventilation. Although low-VT ventilation is becoming a standard of care for ARDS patients, many issues remain unresolved; among them are the role of PEEP and recruitment maneuvers in either preventing or promoting lung injury and the effects of respiratory rate and graded VT reduction on mechanical stress in the lungs. The authors believe that advances in mechanical ventilation that may further improve patient outcomes are likely to come from more sophisticated monitoring capabilities (ie, the ability to measure P1 or perhaps Cslice) than from the creation of new modes of ventilatory support.     

Inflammatory pulmonary edema and positive end-expiratory pressure: correlations between imaging and physiologic studies

The anatomic and physiologic response to positive end-expiratory pressure (PEEP) was investigated using computed tomography (CT) in patients with adult respiratory distress syndrome (ARDS). The lesions (densities) in ARDS are distributed inhomogeneously but tend to concentrate in the dependent regions. The estimated lung weight (by CT scan, quantitative analysis, and lung gas volume measured with helium dilution) is, on the average, 200% higher than expected. Changing the body position from supine to prone causes a change in the density distribution in response to gravitational forces. The main effect of PEEP is to clear the densities through alveolar anatomic recruitment. Anatomic recruitment changes the mechanical characteristics of the lung and parallels the improvement in gas exchange. The effects of PEEP on pulmonary arterial pressure appear to be related to anatomic recruitment.     

The value of portable chest roentgenography in adult respiratory distress syndrome. Comparison with computed tomography

In 17 patients with adult respiratory distress syndrome, we used data derived from computed tomographic (CT) scan densitometric analysis to validate the value of portable chest roentgenograms in objectively estimating the amount of pulmonary edema. Chest roentgenograms and CT scans were taken in the same ventilatory conditions (apnea at 10 cm H2O of positive end-expiratory pressure [PEEP]); blood gas samples and hemodynamic parameters were collected at the same time. Roentgenographic analysis was undertaken by independent observers using two standardized scoring systems proposed in the literature. CT scan analysis was performed using the CT number frequency distribution and the gas lung volume (measured by helium dilution technique) to estimate quantitatively the lung density, the lung weight, and the percentage of normally aerated and nonaerated tissue. Knowing the mean CT number of the pulmonary parenchyma in a group of normal subjects, we also inferred the ideal lung weight expected in the study population and computed the excess tissue mass as the difference between actual and ideal lung weight. Both the roentgenographic scoring systems showed direct correlation with the pulmonary impairment as detected by CT scan densitometric analysis (CT number, percentage of nonaerated tissue, lung weight, and excess tissue mass; p less than 0.01) and inverse relation with the percentage of normally aerated tissue (p less than 0.01). We also found a relationship between roentgenographic scores and the impairment in gas exchange as detected by shunt fraction (p less than 0.05). We conclude that standardized reading of portable chest roentgenograms by means of scoring tables is a valuable tool in estimating the amount of pulmonary edema in a patient with adult respiratory distress syndrome.     

Pulmonary and extrapulmonary forms of acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is usually viewed as the functional and morphological expression of a similar underlying lung injury caused by a variety of insults. However, the distinction between ARDS due to a direct (ARDSp) versus an indirect (ARDSexp) lung injury is gaining more attention as a means of better comprehending the pathophysiology of ARDS and for modifying ventilatory management. From the few published studies, we can summarize that: (1) the prevalent damage in early stages of a direct insult is intra-alveolar, whereas in indirect injury it is the interstitial edema. It is possible that the two insults may coexist (i.e., one lung with direct injury (as in pneumonia) and the other with indirect injury, through mediator release from the contralateral pneumonia); (2) the radiological pattern, by chest x-ray or computed tomography (CT), is different in ARDSp (characterized by prominent consolidation) and ARDSexp (characterized by prominent ground-glass opacification); (3) in ARDSp lung elastance is more markedly increased than in ARDSexp, where the main abnormality is the increase in chest wall elastance, due to abnormally high intra-abdominal pressure; (4) positive end-expiratory pressure (PEEP), inspiratory recruitment, and prone position are more effective to improve respiratory mechanics, alveolar recruitment, and gas-exchange in ARDSexp. Further studies are warranted to better define if the distinction between ARDS of different origins can improve clinical management and survival.     

An autopsy case of adult respiratory distress syndrome (ARDS) with peculiar histopathological features modified by a positive end-expiratory pressure (PEEP) therapy

A case is reported of adult respiratory distress syndrome(ARDS) combined with barotrauma due to positive end-expiratory pressure (PEEP) therapy. The patient was a 32-year-old woman with fulminant hepatitis, type B, who died of ARDS 22 days after the onset of the illness. The autopsy revealed extraordinary heavy lungs (left: 923g, right: 985g) with edema in the peripheral part and marked emphysematous changes in the central part near the hili. Histologically, scattered foci of intra-alveolar organization and interstitial fibrosis with hemorrhage were observed, which might have been the result of the proceeding pneumonia. The emphysematous lesion seen in this case was peculiar and not like any type of of ordinary pulmonary emphysema. Judging from the strange, sharply demarcated emphysematous lesion with marked destruction of alveolar structure, and the good preservation of the alveolar structure in the edematous lesion, the emphysematous lesion might be barotrauma which was induced by PEEP therapy on top of pneumonia.     

Pressure-volume curves in acute respiratory distress syndrome: clinical demonstration of the influence of expiratory flow limitation on the initial slope

The presence of an initial segment with a low compliance on the static pressure-volume (PV) curve in patients with acute respiratory distress syndrome (ARDS) indicates that some lung compartments do not initially receive insufflated gas. We tested the hypothesis that an uneven distribution of time constants, producing a "slow compartment," was in part responsible for the change in compliance between the initial and the intermediate segment of the PV curve. In 16 patients with ARDS submitted to mechanical ventilation in volume-controlled mode with a supportive respiratory rate of 15 breaths/minute, we constructed the static PV curve on the first day of respiratory support and determined the intrinsic positive end-expiratory pressure (PEEPi4) during a prolonged end-expiratory pause (4 seconds). We also measured the volume of a "slow compartment" during a prolonged expiration (> 6 seconds), and determined an external PEEP (PEEPe) suppressing PEEPi4. Among the 16 patients studied, 11 exhibited a low inflection point, associated with a "slow compartment" of 172 +/- 83 ml, responsible for a PEEPi4 of 3 +/- 2 cm H2O. Conversely, the five remaining patients had a linear PV curve, associated with a minimal "slow compartment" of 28 +/- 10 ml, responsible for a negligible PEEPi4. We observed that individual slopes of the initial segment of the PV curve were inversely and significantly correlated with the proportion of the "slow compartment" (r = -0.85). We concluded that the shape of the inspiratory PV curve in ARDS might be dependent on the presence of a "slow compartment," and demonstrated that a low external PEEP appeared sufficient to achieve a substantial mechanical improvement in clinical practice.     

死腔分数导向急性呼吸窘迫综合征呼气末正压选择的临床研究

目的 探讨早期急性呼吸窘迫综合征( ARDS)患者采用死腔分数法选择呼气末正压(PEEP)的可行性.方法 选23例机械通气的早期ARDS患者行持续肺膨胀手法充分肺复张,PEEP递减过程中分别采用最小死腔分数法、最大顺应性法、最佳氧合法选择最佳PEEP,观察不同方法选择的PEEP对患者氧合、解剖死腔容积(VD)/潮气容积(VT)、静态肺顺应性(CLst)和功能残气量(FRC)等的影响.结果 最小死腔分数法[(10.1±2.8)cm H2O(1 cm H2O =0.098 kPa)]和最大顺应性法[(11.3±2.5) cmH2O]选择的最佳PEEP间差异无统计学意义(P＞0.05),均明显低于最佳氧合法[(15.0±3.4) cm H2O,P＜0.05].最小死腔分数法选择PEEP机械通气时患者VD/VT(0.53±0.09)较基础状态(0.59±0.09)明显下降,但最大顺应性法和最佳氧合法选择的PEEP机械通气时VD/VT较基础状态未见明显变化.最小死腔分数法选择的PEEP,其氧合指数明显低于最佳氧合法[(288±123) mm Hg(1 mm Hg=0.133 kPa)比(356±119)mm Hg,P＜0.05],与最大顺应性法相比差异无统计学意义(P＞0.05),均高于基础状态.最小死腔分数法选择PEEP机械通气时气道平台压[(24±4) cm H2O]明显低于最大氧合法[(31±9) cm H2O].最佳氧合法选择的PEEP机械通气时的FRC明显高于最小死腔分数法和最大顺应性法.结论 采用最小死腔分数法选择的最佳PEEP,可改善ARDS患者氧合和CLst,减少死腔通气、降低气道平台压,是床边选择最佳PEEP的可行方法.     

急性呼吸窘迫综合征家兔肺不同区域有效血流灌注变化及肺保护性通气对其的影响

目的 通过观察家兔急性呼吸窘迫综合征(ARDS)模型肺不同区域有效血流灌注变化及肺保护性通气对其的影响,探讨ARDS所致严重低氧血症的发生机制。方法 采用静脉注射油酸的方法建立家兔ARDS模型,应用PIM-Ⅱ激光多普勒血流灌注扫描仪观察不同肺通气模式[(大潮气、小潮气 外源性呼气末正压(PEEP)、大潮气 俯卧位、俯卧位 小潮气 PEEP]下肺不同区域(肺上区、肺下区腹侧和肺下区背侧)局部有效血流灌注及动脉血气指标的变化。结果 家兔静脉注射油酸后,(1)肺不同区域氧合指数明显下降,应用肺保护性通气(小潮气 PEEP,俯卧位 小潮气 PEEP)后氧合指数明显改善;(2)肺不同区域局部有效血流灌注均有不同程度的下降,以肺下区背侧最为明显,肺下区腹侧次之,肺上区变化最小,应用肺保护性通气后,小潮气 PEEP对改善肺下区背侧胸膜下肺局部有效血流灌注的效果不如俯卧位 小潮气 PEEP。结论小潮气 PEEP、俯卧位 小潮气 PEEP均可良好改善肺局部有效血流灌注,其中俯卧位 小潮气 PEEP效果尤为明显;右-左分流导致的肺内分流可能是ARDS发生严重进行性低氧血症的主要原因之一。     

基质金属蛋白酶9与急性肺损伤/急性呼吸窘迫综合征

急性呼吸窘迫综合征的本质是弥漫性肺泡毛细血管膜损伤、血管通透性增加所致的通透性肺水肿.基质金属蛋白酶可以降解细胞外基质蛋白,使肺毛细血管通透性增加,引发肺水肿,导致急性肺损伤和(或)急性呼吸窘迫综合征.本文就基质金属蛋白酶9在急性肺损伤/急性呼吸窘迫综合征中的作用及研究进展进行综述.     

Oleic acid vs saline solution lung lavage-induced acute lung injury: effects on lung morphology, pressure-volume relationships, and response to positive end-expiratory pressure

OBJECTIVE: To compare two lung injury models (oleic acid [OA] and saline solution washout [SW]) regarding lung morphology, regional inflation, and recruitment during static pressure-volume (PV) curves, and the effects of positive end-expiratory pressure (PEEP) below and above the lower inflection point (Pflex). METHODS: Fourteen adult pigs underwent OA or SW lung injury. Lung volumes were measured using CT. PV curves were obtained with simultaneous CT scanning at lung apex and base. Fractional inflation and recruitment were compared to data on PEEP above and below Pflex. RESULTS: Severity of lung injury was comparable. At zero PEEP, SW showed an increased amount of edema and poorly aerated lung volume, recruitment during inspiration, and a better oxygenation response with PEEP. Whole-lung PV curves were similar in both models, reflecting changes in alveolar inflation or deflation. On the inspiratory PV limb, recruitment and inflation were on the same line, while there was a substantial difference between deflation and derecruitment on the expiratory limb. PEEP-induced recruitment at lung apex and base was at or above the derecruitment line on the expiratory limb and showed no relationship to the whole-lung expiratory PV curve. CONCLUSIONS: The following conclusions were made: (1) OA and SW models are comparable in mechanics but not in lung injury characteristics; (2) neither inspiratory nor expiratory whole-lung PV curves are useful to select PEEP in order to optimize recruitment; and (3) after recruitment, there is no difference in derecruitment between the models at high PEEP, while more collapse occurs at lower PEEP in the basal sections of SW lungs.     

Adult respiratory distress syndrome profiles by computed tomography

Ten patients with full-blown ARDS, on mechanical ventilation with PEEP underwent lung CT. Seven normal subjects were also studied. Three tomographic levels (apex, hilum, and base) were selected. The most consistent morphologic finding in ARDS was the presence of densities in the dependent regions of the lung. Assuming that the three levels were a representative sample of the whole lung, the lung weight was computed from the mean CT number and lung gas volume. Analysis of the CT number frequency distribution revealed three definite patterns of distribution: type 1, bimodal, with one mode in the normal CT number range; type 2, unimodal narrow distribution, with the mode in the CT range of water; and type 3, unimodal broad distribution in the abnormal CT number range.     

应用肺动态压力-容积曲线低位转折点选择最佳呼气末正压的研究

目的探讨根据动态肺压力-容积曲线低位转折点压力(Pinf)选择急性呼吸窘迫综合征(ARDS)患者最佳呼气末正压(PEEP)的可行性.方法以8例早期ARDS患者为研究对象,测定动态肺压力-容积曲线及Pinfd.采用低流速法测定准静态肺压力-容积曲线,并确定静态肺压力-容积曲线低位转折点压力(Pinfs).调整PEEP水平,观察患者血流动力学、肺机械力学和氧代谢的变化.结果当PEEP从Pinfd-6cmH2O水平增加到Pinfd+6cmH2O时,动脉血氧分压、动脉血氧饱和度、气道平均压和气道峰压均显著增加.与Pinfd+6cmH2O比较,Pinfd-4cmH2O时的动态肺顺应性显著增高.Pinfd+6cmH2O时的心脏指数有降低趋势,Pinfd-4cmH2O时的氧输送有升高趋势.当Pinfd为(12.8±3.2)cmH2O,Pinfs为(11.0±3.2)cmH2O,两者具有正相关性(r=0.99,P《0.05).回归方程为Pinfd=1.66+1.01×Pinfs.结论当ARDS患者行机械通气治疗时,Pinfd-4cmH2O或Pinfs-2cmH2O为最佳PEEP,可获得最大氧输送.     

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.     

Lung recruitment maneuvers in acute respiratory distress syndrome

In the experimental setting, repeated derecruitments of the lungs of ARDS models accentuate lung injury during mechanical ventilation, whereas open lung concept strategies can attenuate the injury. In the clinical setting, recruitment manuevers that use a continuous positive airway pressure of 40 cmH2O for 40 secs improve oxygenation in patients with early ARDS who do not have an impairment in the chest wall. High intermittent positive end-expiratory pressure (PEEP), intermitent sighs, or high-pressure controlled ventilation improves short-term oxygenation in ARDS patients. Both conventional and electrical impedance thoracictomography studies at the clinical setting indicate that high PEEP associated with low levels of pressure control ventilation recruit the collapsed portions of the ARDS lungs and that adequate PEEP levels are necessary to keep the ARDS lungs opened allowing a more homogenous ventilation. High PEEP/low tidal volume ventilation was seen to reduce inflammatory mediators in both bronchoalveolar lavage and plasma, compared to low PEEP/high tidal volume ventilation, after 36 hours of mechanical ventilation in ARDS patients. Recruitment maneuvers that used continuous positive airway pressure levels of 35-40 cmH2O for 40 secs, with PEEP set at 2 cmH2O above the lower inflection point of the pressure-volume curve, and tidal volume < 6 mL/kg were associated with a 28-day intensive care unit survival rate of 62%. This contrasted with a survival rate of only 29% with conventional ventilation (defined as the lowest PEEP for acceptable oxygenation without hemodynamic impairment with a tidal volume of 12 mL/kg), without recruitment manuevers (number needed to treat = 3; p < 0.001). In the near future, thoracic computed tomography associated with high-performance monitoring of regional ventilation may be used at the bedside to determine the optimal mechanical ventilation of the ARDS keeping an opened lung with a homogenous ventilation.     

Therapy for late-phase acute respiratory distress syndrome

Prolonged hypoxemic respiratory failure and evidence of lung organization and fibrosis are features of an ARDS subgroup that is variably identified as "late," "persistent," or "fibroproliferative" ARDS. Early reports suggested that patients with late ARDS had a high mortality unless treated with corticosteroids. A large recent study with improved methodology has demonstrated that despite improvements of pulmonary physiology, corticosteroids do not change mortality of patients who continue to meet ARDS criteria 7 to 28 days after onset of acute lung injury. Additionally, there is no compelling evidence that persistent ARDS confers a higher mortality than that of ALI/ARDS. Observational and interventional studies are needed to increase understanding of the incidence, best management, and outcomes of patients with persistent ARDS.     

Permeability pulmonary edema. Diagnosis and management

The adult respiratory distress syndrome (ARDS) is a common syndrome of diffuse lung injury with high mortality. An underlying mechanism is pulmonary microvascular injury leading to increased permeability, pulmonary edema and impaired gas exchange. Currently ARDS can only be diagnosed as a constellation of symptoms and signs. The development of an accurate clinical marker of pulmonary microvascular injury or a technique to measure pulmonary microvascular permeability may allow earlier and more specific diagnosis. We review ARDS with emphasis on recent work concerning the mechanisms of lung injury, diagnosis, and therapy.     

Volumetric capnography in patients with acute lung injury: effects of positive end-expiratory pressure.

The aim of the study was to analyse the effects of positive end-expiratory pressure (PEEP) on volumetric capnography and respiratory system mechanics in mechanically ventilated patients. Eight normal subjects (control group), nine patients with moderate acute lung injury (ALI group) and eight patients with acute respiratory distress syndrome (ARDS group) were studied. Respiratory system mechanics, alveolar ejection volume as a fraction of tidal volume (VAE/VT), phase III slopes of expired CO2 beyond VAE and Bohr's dead space (VD/VT(Bohr)) at different levels of PEEP were measured. No differences in respiratory system resistances were found between the ALI and ARDS groups. VD/VT(Bohr) and expired CO2 slope beyond VAE were higher in ALI patients (0.52+/-0.01 and 13.9+/-0.7 mmHg x L(-1), respectively) compared with control patients (0.46+/-0.01 and 7.7+/-0.4 mmHg x L(-1), p<0.01, respectively) and in ARDS patients (0.61+/-0.02 and 24.9+/-1.6 mmHg x L(-1), p<0.01, respectively) compared with ALI patients. VAE/VT differed similarly (0.6+/-0.01 in control group, 0.43+/-0.01 in ALI group and 0.31+/-0.01 in ARDS group, p<0.01). PEEP had no effect on VAE/VT, expired CO2 slope beyond VAE and VD/VT(Bohr) in any group. A significant correlation (p<0.01) was found between VAE/VT and expired CO2 slope beyond VAE and lung injury score at zero PEEP. Indices of volumetric capnography are affected by the severity of the lung injury, but are unmodified by the application of positive end-expiratory pressure.