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Lung Stress and Strain during Mechanical Ventilation for Acute Respiratory Distress Syndrome

RATIONALE Lung injury caused by a ventilator results from nonphysiologic lung stress (transpulmonary pressure) and strain (inflated volume to functional residual capacity ratio). OBJECTIVES To determine whether plateau pressure and tidal volume are adequate surrogates for stress and strain, and to quantify the stress to strain relationship in patients and control subjects. METHODS Nineteen postsurgical healthy patients (group 1), 11 patients with medical diseases (group 2), 26 patients with acute lung injury (group 3), and 24 patients with acute respiratory distress syndrome (group 4) underwent a positive end-expiratory pressure (PEEP) trial (5 and 15 cm H2O) with 6, 8, 10, and 12 ml/kg tidal volume. MEASUREMENTS AND MAIN RESULTS Plateau airway pressure, lung and chest wall elastances, and lung stress and strain significantly increased from groups 1 to 4 and with increasing PEEP and tidal volume. Within each group, a given applied airway pressure produced largely variable stress due to the variability of the lung elastance to respiratory system elastance ratio (range, 0.33-0.95). Analogously, for the same applied tidal volume, the strain variability within subgroups was remarkable, due to the functional residual capacity variability. Therefore, low or high tidal volume, such as 6 and 12 ml/kg, respectively, could produce similar stress and strain in a remarkable fraction of patients in each subgroup. In contrast, the stress to strain ratio-that is, specific lung elastance-was similar throughout the subgroups (13.4 +/- 3.4, 12.6 +/- 3.0, 14.4 +/- 3.6, and 13.5 +/- 4.1 cm H2O for groups 1 through 4, respectively; P = 0.58) and did not change with PEEP and tidal volume. CONCLUSIONS Plateau pressure and tidal volume are inadequate surrogates for lung stress and strain. Clinical trial registered with www.clinicaltrials.gov (NCT 00143468).

Albumin Replacement in Patients with Severe Sepsis or Septic Shock

BACKGROUND Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. METHODS In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. RESULTS During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. CONCLUSIONS In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).

Lung Opening and Closing during Ventilation of Acute Respiratory Distress Syndrome

RATIONALE The effects of high positive end-expiratory pressure (PEEP) strictly depend on lung recruitability, which varies widely during acute respiratory distress syndrome (ARDS). Unfortunately, increasing PEEP may lead to opposing effects on two main factors potentially worsening the lung injury, that is, alveolar strain and intratidal opening and closing, being detrimental (increasing the former) or beneficial (decreasing the latter). OBJECTIVES To investigate how lung recruitability influences alveolar strain and intratidal opening and closing after the application of high PEEP. METHODS We analyzed data from a database of 68 patients with acute lung injury or ARDS who underwent whole-lung computed tomography at 5, 15, and 45 cm H(2)O airway pressure. MEASUREMENTS AND MAIN RESULTS End-inspiratory nonaerated lung tissue was estimated from computed tomography pressure-volume curves. Alveolar strain and opening and closing lung tissue were computed at 5 and 15 cm H(2)O PEEP. In patients with a higher percentage of potentially recruitable lung, the increase in PEEP markedly reduced opening and closing lung tissue (P < 0.001), whereas no differences were observed in patients with a lower percentage of potentially recruitable lung. In contrast, alveolar strain similarly increased in the two groups (P = 0.89). Opening and closing lung tissue was distributed mainly in the dependent and hilar lung regions, and it appeared to be an independent risk factor for death (odds ratio, 1.10 for each 10-g increase). CONCLUSIONS In ARDS, especially in patients with higher lung recruitability, the beneficial impact of reducing intratidal alveolar opening and closing by increasing PEEP prevails over the effects of increasing alveolar strain.

Decrease in PaCO2 with prone position is predictive of improved outcome in acute respiratory distress syndrome.

ObjectiveTo determine whether gas exchange improvement in response to the prone position is associated with an improved outcome in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). DesignRetrospective analysis of patients in the pronation arm of a controlled randomized trial on prone positioning and patients enrolled in a previous pilot study of the prone position. SettingTwenty-eight Italian and two Swiss intensive care units. PatientsWe studied 225 patients meeting the criteria for ALI or ARDS. InterventionsPatients were in prone position for 10 days for 6 hrs/day if they met ALI/ARDS criteria when assessed each morning. Respiratory variables were recorded before and after 6 hrs of pronation with unchanged ventilatory settings. Measurements and Main ResultsWe measured arterial blood gas alterations to the first pronation and the 28-day mortality rate. The independent risk factors for death in the general population were the Pao2/Fio2 ratio (odds ratio, 0.992; confidence interval, 0.986–0.998), the minute ventilation/Paco2 ratio (odds ratio, 1.003; confidence interval, 1.000–1.006), and the concentration of plasma creatinine (odds ratio, 1.385; confidence interval, 1.116–1.720). Pao2 responders (defined as the patients who increased their Pao2/Fio2 by ≥20 mm Hg, 150 patients, mean increase of 100.6 ± 61.6 mm Hg [13.4 ± 8.2 kPa]) had an outcome similar to the nonresponders (59 patients, mean decrease −6.3 ± 23.7 mm Hg [−0.8 ± 3.2 kPa]; mortality rate 44% and 46%, respectively; relative risk, 1.04; confidence interval, 0.74–1.45, p = .65). The Paco2 responders (defined as patients whose Paco2 decreased by ≥1 mm Hg, 94 patients, mean decrease −6.0 ± 6 mm Hg [−0.8 ± 0.8 kPa]) had an improved survival when compared with nonresponders (115 patients, mean increase 6 ± 6 mm Hg [0.8 ± 0.8 kPa]; mortality rate 35.1% and 52.2%, respectively; relative risk, 1.48; confidence interval, 1.07–2.05, p = .01). ConclusionALI/ARDS patients who respond to prone positioning with reduction of their Paco2 show an increased survival at 28 days. Improved efficiency of alveolar ventilation (decreased physiologic deadspace ratio) is an important marker of patients who will survive acute respiratory failure.

Ventilator-induced lung injury: the anatomical and physiological framework.

Since its introduction into the management of the acute respiratory distress syndrome, mechanical ventilation has been so strongly interwoven with its side effects that it came to be considered as invariably dangerous. Over the decades, attention has shifted from gross barotrauma to volutrauma and, more recently, to atelectrauma and biotrauma. In this article, we describe the anatomical and physiologic framework in which ventilator-induced lung injury may occur. We address the concept of lung stress/strain as applied to the whole lung or specific pulmonary regions. We challenge some common beliefs, such as separately studying the dangerous effects of different tidal volumes (end inspiration) and end-expiratory positive pressures. Based on available data, we suggest that stress at rupture is only rarely reached and that high tidal volume induces ventilator-induced lung injury by augmenting the pressure heterogeneity at the interface between open and constantly closed units. We believe that ventilator-induced lung injury occurs only when a given threshold is exceeded; below this limit, mechanical ventilation is likely to be safe.

Positive end-expiratory pressure.

Purpose of review In the last 2 years, several reports have dealt with recruitment/positive end-expiratory pressure (PEEP) selection. Most of them confirm previous results and few add new information. Recent findings It has been definitely confirmed that opening pressures are different throughout the acute respiratory distress syndrome lung parenchyma, ranging from 5–10 up to 30–40 cmH2O. The highest opening pressures are required to open the most dependent lung regions. It has been found that in 2 s, most of the recruitable lung regions may be open when a proper pressure is applied. The best way to assess recruitment is computed tomography scanning, whereas lung mechanics are a reasonable bedside surrogate. Impedance tomography has been increasingly tested, whereas gas exchange is the less reliable indicator of recruitment. A large outcome study showed that higher PEEP might provide survival benefit in a subgroup of more severe patients as compared with lower PEEP. To set PEEP in each individual patient, the use of the expiratory limb of the pressure–volume curve has been suggested. Setting PEEP according to transpulmonary pressure has a robust physiological background, although it requires confirmatory study. Summary Indiscriminate application of recruitment maneuver in unselected acute respiratory distress syndrome population does not provide benefits. However, in the most severe patients, recruitment maneuver has to be considered and higher PEEP applied. To individualize PEEP, the expiratory phase has to be considered, and the esophageal pressure measurement to compute the transpulmonary pressure should be progressively introduced in clinical practice.

Refining Ventilatory Treatment for Acute Lung Injury and Acute Respiratory Distress Syndrome

ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) IS the clinical manifestation of inflammatory lung edema originating from a variety of insults. Since its first description 40 years ago, the mainstays of management have been institution of mechanical ventilation to ventilate the incompliant lungs, inspired oxygen for hypoxemia, and when hypoxemia is severe, the addition of positive end-expiratory pressure (PEEP) to increase end-expiration lung volume, which facilitates O2 gas exchange. Early on, physicians recognized that the high intrathoracic pressures of mechanical ventilation caused parenchymal stress or rupture, known as barotrauma. However, it took several years to identify the local injury resulting from intratidal opening and closing of parts of the lung (atelectrauma) and the inflammatory reaction of the lung to nonphysiological stress (biotrauma). Subsequently computed tomographic scanning showed that the lung fraction open to gas exchange in ARDS is small, equivalent in size to that of a young child (baby lung model). This observation provided the anatomical basis for the concept of volutrauma, focused on the excessive strain within the baby lung induced by tidal ventilation. Taken together, these multiple potentially damaging factors are now called ventilatorinduced lung injury (VILI). In the last decade, prevention of VILI through gentle lung treatment, by adjusting either tidal volume or PEEP, has become the major goal of mechanical ventilatory support not just for ARDS but for the broader population of patients with acute lung injury (ALI). With regard to tidal volume, this line of reasoning and research was most conclusively supported by the National Heart, Lung, and Blood Institute ARDS Network trial demonstrating an improvement in survival for patients with ALI or ARDS who were ventilated with low tidal volumes (6 mL/kg of predicted body weight) compared with those ventilated with higher tidal volumes (12 mL/kg of predicted body weight). Although many argued that the tidal volume in the control group might have been higher than existing practice, the tidal volume in the interventional group marked a stark departure from usual care and has resulted in a dramatic change in the approach to tidal volume setting for ALI and ARDS. The optimal PEEP strategy, however, has remained unresolved. Evidence from animal studies suggested that higher PEEP (in the range of 10-15 cm H2O) could prevent VILI. Thus, many clinicians were surprised when the first large randomized clinical trial comparing higher levels of PEEP with lower levels of PEEP in patients with ALI and ARDS, the National Heart, Lung, and Blood Institute’s ARDS Network Assessment of Low Tidal Volume and Elevated EndExpiratory Lung Volume to Obviate Lung Injury (ALVEOLI) study, was stopped for futility. In this issue of the JAMA, 2 new large international randomized trials examining the effects of PEEP on outcome in patients with ALI and ARDS are presented. In the Lung Open Ventilation (LOV) trial, the level of PEEP administered, either lower or higher, was selected according to an oxygenation scale conceptually similar to the one used in the previous ALVEOLI study. In the Expiratory Pressure (Express) trial, PEEP selection was based on a more subtle and refined approach, using bedside assessment of lung mechanics instead of gas exchange. This method identified a minimal distention strategy (lower level of PEEP) and an increased recruitment strategy (higher level of PEEP). Despite the different criteria used for PEEP selection, the PEEP levels tested were similar in the 2 studies. In the LOV study, mean PEEP levels on day 1 were 15.6 cm H2O and 10.1 cm H2O, and the subsequent hospital mortality rates were 36.4% and 40.4%. In the Express study, mean PEEP levels on day 1 were 15.8 cm H2O and 8.4 cm H2O, and the

Continuous positive airway pressure delivered with a "helmet": effects on carbon dioxide rebreathing.

Objective:The “helmet” has been used as a novel interface to deliver noninvasive ventilation without applying direct pressure on the face. However, due to its large volume, the helmet may predispose to Co2 rebreathing. We hypothesized that breathing with the helmet is similar to breathing in a semiclosed environment, and therefore the Pco2 inside the helmet is primarily a function of the subject’s Co2 production and the flow of fresh gas through the helmet. Design:Human volunteer study. Setting:Laboratory in a university teaching hospital. Subjects:Eight healthy volunteers. Interventions:We delivered continuous positive airway pressure (CPAP) with the helmet under a variety of ventilatory conditions in a lung model and in volunteers. Measurements and Main Results:Gas flow and Co2 concentration at the airway were measured continuously. End-tidal Pco2, Co2 production, and ventilatory variables were subsequently computed. We found that a) when CPAP was delivered with a ventilator, the inspired Co2 of the volunteers was high (12.4 ± 3.2 torr [1.7 ± 0.4 kPa]); b) when CPAP was delivered with a continuous high flow system, inspired Co2 of the volunteers was low (2.5 ± 1.2 torr [0.3 ± 0.2 kPa]); and c) the inspired Co2 calculated mathematically for a semiclosed system model of Co2 rebreathing was highly correlated with the values measured in a lung model (r2 = .97, slope = 0.92, intercept = −1.17, p < .001) and in the volunteers (r2 = .94, slope = 0.96, intercept = 0.90, p < .001). Conclusions:a) The helmet predisposes to Co2 rebreathing and should not be used to deliver CPAP with a ventilator; b) continuous high flow minimizes Co2 rebreathing during CPAP with the helmet; and c) minute ventilation and Pco2 should be monitored during CPAP with the helmet.

Bedside selection of positive end-expiratory pressure in mild, moderate, and severe acute respiratory distress syndrome.

Objective:Positive end-expiratory pressure exerts its effects keeping open at end-expiration previously collapsed areas of the lung; consequently, higher positive end-expiratory pressure should be limited to patients with high recruitability. We aimed to determine which bedside method would provide positive end-expiratory pressure better related to lung recruitability. Design:Prospective study performed between 2008 and 2011. Setting:Two university hospitals (Italy and Germany). Patients:Fifty-one patients with acute respiratory distress syndrome. Interventions:Whole lung CT scans were taken in static conditions at 5 and 45 cm H2O during an end-expiratory/end-inspiratory pause to measure lung recruitability. To select individual positive end-expiratory pressure, we applied bedside methods based on lung mechanics (ExPress, stress index), esophageal pressure, and oxygenation (higher positive end-expiratory pressure table of lung open ventilation study). Measurements and Main Results:Patients were classified in mild, moderate and severe acute respiratory distress syndrome. Positive end-expiratory pressure levels selected by the ExPress, stress index, and absolute esophageal pressures methods were unrelated with lung recruitability, whereas positive end-expiratory pressure levels selected by the lung open ventilation method showed a weak relationship with lung recruitability (r2 = 0.29; p < 0.0001). When patients were classified according to the acute respiratory distress syndrome Berlin definition, the lung open ventilation method was the only one which gave lower positive end-expiratory pressure levels in mild and moderate acute respiratory distress syndrome compared with severe acute respiratory distress syndrome (8 ± 2 and 11 ± 3 cm H2O vs 15 ± 3 cm H2O; p < 0.05), whereas ExPress, stress index, and esophageal pressure methods gave similar positive end-expiratory pressure values in mild, moderate, and severe acute respiratory distress syndrome. The positive end-expiratory pressure selected by the different methods were unrelated to each other with the exception of the two methods based on lung mechanics (ExPress and stress index). Conclusions:Bedside positive end-expiratory pressure selection methods based on lung mechanics or absolute esophageal pressures provide positive end-expiratory pressure levels unrelated to lung recruitability and similar in mild, moderate, and severe acute respiratory distress syndrome, whereas the oxygenation-based method provided positive end-expiratory pressure levels related with lung recruitability progressively increasing from mild to moderate and severe acute respiratory distress syndrome.

Stress and strain within the lung.

Purpose of reviewTo describe the physiological meaning and the clinical application of the lung stress and strain concepts. Recent findingsThe end-inspiratory plateau pressure and ratio of tidal volume/ideal body weight are inadequate surrogates for the end-inspiratory stress (equal to the transpulmonary pressure) and the end-inspiratory strain (change in lung volume relative to the resting volume). For a given plateau pressure or tidal volume/ideal body weight, stress and strain may vary largely due to the variability of chest wall elastance and the resting lung volume. The injurious limits of stress and strain in healthy lungs are reached when stress and strain reach the total lung capacity. This occurs when the resting lung volume (the baby lung in case of acute respiratory distress syndrome) is increased by two-fold to three-fold. As these limits are rarely reached in clinical practice and damage has been reported with stress and strain well below this upper limit, this implies the presence in the lung parenchyma of regions which act as stress raisers or pressure multipliers. These are primarily linked to the inhomogeneous distribution of local stress and strain. SummaryEnd-inspiratory stress and strain, as well as the lung inhomogeneity and the stress raisers, must be taken in account when setting mechanical ventilation.