J. Zinserling

Meta-analysis: Ventilation Strategies and Outcomes of the Acute Respiratory Distress Syndrome and Acute Lung Injury

Context Ventilation strategies to protect the lungs of patients with the acute respiratory distress syndrome (ARDS) include low tidal volume, limited airway pressures, and medium to high positive end-expiratory pressure (PEEP), but the adoption of these strategies has been slow in some clinical settings. Contribution This review of randomized trial evidence for low tidal volume and high PEEP ventilation on mortality of patients with ARDS or acute lung injury found that trials were limited in number but showed mortality benefits with lower versus higher tidal volume. High PEEP did not improve mortality in unselected patients but may help patients with life-threatening hypoxemia despite other interventions. Implication Lower tidal volume ventilation strategies should be used for patients with ARDS or acute lung injury. The Editors The acute respiratory distress syndrome (ARDS) is clinically characterized by sudden onset, severe hypoxemia, radiographic evidence of bilateral pulmonary infiltration, and absence of left heart failure (13). Acute lung injury is a subset of ARDS with less severe impairment in oxygenation. Despite apparent improvement in management and outcome of ARDS, the mortality rate in persons with the disease remains high, ranging from 35% to 65% (4). Although mechanical ventilation provides essential life support, it can worsen lung injury (5). Computed tomography images of patients with ARDS show nonhomogeneous distribution of pulmonary aeration. Normally aerated lung regions are relatively small but, when they receive the largest part of tidal volume (Vt) (6, 7), may be exposed to excessive alveolar wall tension and stress because of overdistention (8, 9). Atelectatic lung regions are prone to cyclic recruitment and derecruitment, leading to shear stress in adjacent aerated and nonaerated alveoli (1012). Ventilator-induced lung injury is caused by excessive stress or strain to lung tissues that occurs during mechanical ventilation and aggravates inflammation and diffuse alveolar damage (5, 13). Lung-protective ventilation strategies include ventilation with low Vt and limited airway pressure to reduce ventilator-induced lung injury from overdistention while allowing hypercapnia and medium to high positive end-expiratory pressure (PEEP) to keep alveoli open throughout the ventilator cycle (14). Hypercapnia and acidosis may increase intracranial pressure, induce pulmonary hypertension, depress myocardial contractility, decrease renal blood flow, and release endogenous catecholamines (15). In addition, prevention of cyclic derecruitment with higher PEEP may contribute to overdistention of normally aerated alveoli, counterbalancing the benefits from low Vt and limited airway pressure ventilation cycles (14). The effect of different lung-protective ventilatory strategies in patients with acute lung injury or ARDS has been investigated in randomized, controlled trials (RCTs) testing higher versus lower Vt ventilation at similar PEEP (1619), higher versus lower PEEP strategies during low Vt ventilation (2022), and lower Vt and PEEP titrated greater than the lower inflection point of the individual pressure volume curve versus higher Vt and lower PEEP (23, 24). Results were partially conflicting because of differences in study design and number of enrolled patients. This may explain why most critically ill patients are still ventilated with high Vt at lower or even no PEEP (4, 25). Our objective was to determine whether the different lung-protective ventilatory strategies improve outcome in critically ill adults with acute lung injury or ARDS. Methods Data Sources and Searches We aimed to identify all RCTs assessing the efficacy and outcomes of lower Vt ventilation, higher PEEP application, or a combination of both in adults with acute lung injury or ARDS. The electronic search strategy applied standard filters for identification of RCTs. We searched the Cochrane Central Register of Controlled Trials, MEDLINE (from inception to March 2009), and EMBASE (from inception to March 2009). Our search included the following keywords: acute lung injury, ALI, adult respiratory distress syndrome, ARDS, protective ventilation, lung protective ventilation strategy, pressure-limited ventilation, tidal volume, positive end-expiratory pressure, PEEP, and random. We did not apply language restrictions. In addition to the electronic search, we checked out cross-references from original articles and reviews. Selection of Studies We restricted the analysis to RCTs to guarantee control of selection bias. We did not include study designs containing inadequately adjusted planned co-interventions and quasi-randomized or crossover trials. We considered RCTs that reported mortality as a predefined end point and compared lower versus higher Vt ventilation, lower versus higher PEEP application, or a combination of these strategies in intubated and mechanically ventilated critically ill adults with acute lung injury or ARDS from any cause. Acute lung injury and ARDS had to be defined by the American-European Consensus Conference criteria (26) or by the Lung Injury Severity Score (27). Trials with a low Vt ventilation strategy had to use lower Vt, maximal inspiratory plateau pressure (Pei) of 30 cm H2O or less, or a combination, which resulted in Vt of 8 mL/kg of body weight or less, compared with conventional mechanical ventilation that used Vt ranging between 10 and 15 mL/kg. Regardless of the strategy used to deliver the lower Vt, the 2 study groups had to differ only for Vt and not for other variables associated with a low Vt ventilation strategy. Trials with high PEEP ventilation strategies had to use higher PEEP based on Fio 2PEEP scales, titrating PEEP to greater than the lower inflection point of the individual static or quasi-static pressure volume curve at enrollment or titrating PEEP as high as possible without increasing the maximal Pei to greater than 30 cm H2O compared with conventional mechanical ventilation that used lower PEEP based on fixed Fio 2PEEP scales or lower PEEP at higher Fio 2 to ensure adequate arterial oxygenation. We excluded studies in postoperative patients and those published only in abstract form. We contacted authors to clarify details of trials when necessary. Outcome Measures The primary outcome was mortality, evaluated at hospital discharge. Secondary outcomes included mortality at the end of the planned follow-up, barotrauma, use of rescue therapies owing to life-threatening hypoxemia, ventilator settings, and pulmonary function variables. Barotrauma was defined as any new pneumothorax, pneumomediastinum, subcutaneous emphysema, or pneumatocele after random assignment. Data Extraction and Quality Assessment Two pairs of independent reviewers performed the initial selection by screening titles and abstracts. Citations were selected for further evaluation if the studies they referred to were RCTs of lung-protective ventilatory strategies in critical ill adults or if the title or abstract did not give enough information to make an assessment. For detailed evaluation, we obtained the full text of all possibly relevant studies. Data from each study were extracted independently by the paired reviewers by using a prestandardized data abstraction form. One pair of reviewers was not informed about authors, journal, institutional affiliation, and date of publication. Data extracted from the publications were checked by another reviewer for accuracy. Quality assessment of these studies included use of randomization, reporting of allocation concealment, blinding, adequate selection and description of study population with respect to inclusion and exclusion criteria, similarity of the groups at baseline, use of a predefined treatment protocol, absence of confounders, absence of co-interventions, a priori definition of primary and secondary outcome variables, use of intention-to-treat analysis, extent of follow-up, a priori calculation of sample size, number of patients screened and included in the trial, reports on patients lost to follow-up, and planned or premature termination of the RCT. Two reviewers independently used these criteria to abstract trial quality. We resolved any disagreements by consensus in consultation with a third reviewer if needed. Data Synthesis and Analysis We studied the following comparisons: lower versus higher Vt ventilation using similar PEEP strategies, lower versus higher PEEP level during low Vt ventilation, and the combination of higher Vt and lower PEEP level versus lower Vt and higher PEEP level. Qualitative Analysis We used a narrative summary approach to describe study characteristics and variation in quality indicators among studies and to consider how these factors affect our understanding of the outcomes of the RCTs included in the Cochrane review (28, 29). Quantitative Analysis The meta-analysis was performed according to the Cochrane Collaboration guidelines (30). All statistical analyses were performed with Review Manager, version 4.2 (The Nordic Cochrane Center, Copenhagen, Denmark), the Cochrane Collaborations software for preparing and maintaining Cochrane systematic reviews (30). The pooled effects estimates for binary variables were expressed as odds ratios with 95% CIs, whereas continuous variables were expressed as weighted mean differences with 95% CIs. We tested the difference in estimates of treatment effect between the treatment and control groups for each hypothesis by using a 2-sided z test with statistical significance considered at a P value of less than 0.05. We examined heterogeneity by using the Cochran Q and the I 2 test (31, 32). We predefined heterogeneity as low, moderate, and high, with I 2 statistics greater than 25%, 50%, and 75%, respectively (32). Meta-analysis with a random-effects model was applied with I 2 statistics greater than 25% (33). Otherwise, we performed meta-analysis by using a fixed-effects model. However, the possibil

Determination of functional residual capacity (FRC) by multibreath nitrogen washout in a lung model and in mechanically ventilated patients

Objective: Validation of an open-circuit multibreath nitrogen washout technique (MBNW) for measurement of functional residual capacity (FRC). The accuracy of FRC measurement with and without continuous viscosity correction of mass spectrometer delay time (TD) relative to gas flow signal and the influence of baseline FIO2 was investigated. Design: Laboratory study and measurements in mechanically ventilated patients. Setting: Experimental laboratory and anesthesiological intensive care unit of a university hospital. Patients: 16 postoperative patients with normal pulmonary function (NORM), 8 patients with acute lung injury (ALI) and 6 patients with chronic obstructive pulmonary disease (COPD) were included. Interventions: Change of FIO2 from baseline to 1.0. Measurements and main results: FRC was determined by MBNW using continuous viscosity correction of TD (TDdyn), a constant TD based on the viscosity of a calibration gas mixture (TD0) and a constant TD referring to the mean viscosity between onset and end of MBNW (TDmean). Using TDdyn, the mean deviation between 15 measurements of three different lung model FRCs (FRCmeasured) and absolute volumes (FRCmodel) was 0.2 %. For baseline FIO2 ranging from 0.21 to 0.8, the mean deviation between FRCmeasured and FRCmodel was −0.8 %. However, depending on baseline FIO2, the calculation of FRC using TDmean and TD0 increased the mean deviation between FRCmeasured and FRCmodel to 2–4 % and 8–12 %, respectively. In patients (n = 30) the average repeatability coefficient was 6.0 %. FRC determinations with TDmean and TD0 were 0.8–13.3 % and 4.2–23.9 % (median 2.7 % and 8.7 %) smaller than those calculated with TDdyn.Conclusion: A dynamic viscosity correction of TD improves the accuracy of FRC determinations by MBNW considerably, when gas concentrations are measured in a sidestream. If dynamic TD correction cannot be performed, the use of constant TDmean might be suitable. However, in patient measurements this can cause an FRC underestimation of up to 13 %.

“Proportional assist ventilation” kombiniert mit “automatic tube compensation”

Zusammenfassung“Proportional assist ventilation” (PAV) kombiniert mit “automatic tube compensation” (ATC) stellt ein viel versprechendes Konzept zur Unterstützung einer insuffizienten Spontanatmung dar.Im Gegensatz zur konventionellen druckunterstützten Beatmung (“pressure support ventilation”,PSV) liefert PAV+ATC eine dynamische Druckunterstützung proportional zur Inspirationsbemühung des Patienten und sollte damit den Patienten nicht nur selektiv von der durch eine pathologische Resistance und Elastance des respiratorischen Systems erhöhten Atemarbeit entlasten, sondern auch von der zusätzlichen Arbeit durch den Widerstand des endotrachealen Tubus.Damit erhält der Patient die Möglichkeit durch Modulation des Atemzugvolumens seine Ventilation einem wechselnden Bedarf anzupassen. Dies kann eine bessere Synchronisation von Patient und Beatmungsgerät bedeuten und sollte – verglichen mit PSV – in einem erhöhten Beatmungskomfort resultieren. Da die Unterstützung während PAV als eine Funktion der atemmechanischen Größen des respiratorischen Systems eingestellt wird, deren Bestimmung unter assistierter Spontanatmung bisher aber nicht routinemäßig möglich ist, kann PAV für den Einsatz in der klinischen Routine zurzeit nicht uneingeschränkt empfohlen werden.SummaryThe combination of proportional assist ventilation (PAV) and automatic tube compensation (ATC) is a promising concept for partial ventilatory support. In contrast to conventional pressure support ventilation (PSV), PAV+ATC provides dynamic pressure support depending on the patients initial inspiratory effort.PAV+ATC should selectively unload the respiratory muscles from the additional workload imposed by increased respiratory system resistance and elastance as well as by endotracheal tube resistance.Patients have the ability to modify the tidal volume in response to changes in ventilatory demand, thereby improving patient-ventilator interaction and breathing comfort when compared with PSV.However, since routine measurements of respiratory mechanics during augmented spontaneous breathing are currently unavailable but would be necessary for setting the support level as a function of respiratory system mechanics during PAV, this mode cannot yet be generally recommended for routine clinical use.

Electrical Impedance Tomography for Monitoring of Regional Ventilation in Critically III Patients

Acute lung injury (ALI) is associated with an insult to endothelial and epithelial cells in the lung resulting in release of mediators, increased vascular- and alveolar permeability, interstitial edema formation, alveolar collapse, and thereby arterial hypoxemia [1]–[3]. Although acute respiratory distress syndrome (ARDS) was initially believed to be caused by a diffuse lung injury, computed tomography (CT) of patients with ARDS revealed radiographic densities corresponding to alveolar collapse localized primarily in the dependent lung regions, which correlate with intrapulmonary shunting and account entirely for the observed arterial hypoxemia. Thus, intrapulmonary gas is unhomogeneously distributed during ARDS due to uneven distribution of injury, regional surfactant dysfunction, pulmonary infiltrations and/or alveolar collapse. Positive pressure ventilation, commonly used to improve gas exchange, may further aggravate preexisting lung injury including pneumothorax, alveolar edema, and alveolar rupture [4, 5].

Weight loss of respiratory muscles during mechanical ventilation.

failure. We would like to comment on the documented weight loss of the respiratory muscles. The resting period of 48 h on mechanical ventilation seems relatively short to produce a mass reduction of as much as 20–30% of muscle tissue itself. The question arises, therefore, whether other components of the respiratory muscle samples than muscle tissue itself could have contributed to the weight loss during mechanical ventilaton. If we look at the methodology being used to determine muscle weights, we find that the authors removed the samples before the animals were killed by exsanguination. Therefore, besides muscle tissue, the pieces also contained blood components. Since metabolic demands of respiratory muscles decrease to some extent during rest [2], altered blood flow to the respiratory muscles may have contributed to the different weights of samples in mechanically ventilated and spontaneously breathing animals. Results from our own laboratory support this theory. In our experimental model using pigs with oleic-acid-induced lung injury, we measured diaphragmatic blood flow with colored microspheres. Twelve pigs breathed spontaneously at ambient airway pressure (FIO2 0.35, respiratory rate 47±3/min) (mean±SE) and then were paralyzed and mechanically ventilated (FIO2 0.35, respiratory rate 53±3/min, VT 6.5±0.4 ml/kg, PEEP 5±0 cmH2O, peak inspiratory pressure 15±1 cmH2O). Both spontaneous breathing and mechanical ventilation resulted in hypercapnia (PaCO2 59±4 mmHg and 58±3 mmHg, respectively) at unchanged arterial pH (7.32±0.02 and 7.35±0.03, respectively). Mechanical ventilation significantly improved oxygenation (PaO2/FIO2 269±24 mmHg) as compared to spontaneous breathing (PaO2/FIO2 174±12 mmHg) (P<0.001, students t-test) in these severely injured lungs. Diaphragmatic muscle perfusion was approximately 80% lower during mechanical ventilation (0.10±0.03 ml/g wet tissue weight/min) than during spontaneous breathing (0.50±0.09 ml/g wet tissue weight/min) (P<0.001, students t-test). Thus, the mass reduction during mechanical ventilation found in the study by Capdevila et al. [1] may be at least in part due to the reduced blood flow to the respiratory muscles as compared to the spontaneously breathing rabbits.

Pumpless extracorporeal CO2 removal restores normocapnia and is associated with less regional perfusion in experimental acute lung injury

Lung protective ventilation may lead to hypoventilation with subsequent hypercapnic acidosis (HA). If HA cannot be tolerated or occurs despite increasing respiratory rate or buffering, extracorporeal CO2‐removal using a percutaneous extracorporeal lung assist (pECLA) is an option. We hypothesised that compensation of HA using pECLA impairs regional perfusion. To test this hypothesis we determined organ blood flows in a lung‐injury model with combined hypercapnic and metabolic acidosis.

Vorteile der assistierten Spontanatmung

Summary Spontaneous breathing with Biphasic Positive Airway Pressure (BIPAP) or Airway Pressure Release Ventilation (APRV) caused a reduction in intrapulmonary shunting and dead space ventilation and improvement in arterial oxygenation in patients with acute respiratory distress syndrome. During spontaneous breathing with APRV/BIPAP venous return, cardiac output and oxygen delivery increased while oxygen consumption remained unchanged. In patients early spontaneous breathing with APRV/BIPAP was associated with a better arterial oxygenation than in patients receiving controlled mechanical ventilation for 3 days and were then weaned with APRV/BIPAP. Length of mechanical ventilation, intubation and ICU stay was shorter in patients breathing spontaneously early with APRV/BIPAP. Therefore, early spontaneous breathing with APRV/BIPAP may be of advantage.Zusammenfassung Spontanatmung unter Biphasic Positive Airway Pressure (BIPAP) oder Airway Pressure Release Ventilation (APRV) führt bei Patienten mit akutem Lungenversagen zu einer Reduktion des Blutflusses zu nicht ventilierten Shuntarealen, der Totraumventilation und einer Zunahme des PaO2. Bedingt durch die Spontanatmung nahm der venöse Rückstrom, das Herzzeitvolumen und die Sauerstofftransportkapazität zu, ohne daß der Sauerstoffverbrauch stieg. Bei Patienten, die unter APRV/BIPAP frühzeitig spontan atmeten, war der Gasaustausch signifikant besser als bei den Patienten, die zunächst drei Tage kontrolliert beatmet und anschließend mittels APRV/BIPAP entwöhnt wurden. Die Dauer der maschinellen Beatmung, der Intubation und des Intensivaufenthaltes waren bei Patienten, die frühzeitig unter APRV/BIPAP spontan atmeten, signifikant kürzer. APRV/BIPAP scheint als primäre Unterstützung einer insuffizienten Spontanatmung vorteilhaft zu sein.

Monitoring of Cyclic Opening and Closing of Ventilatory Lung Units Using the Regional Ventilation Delay Index - Preliminary Data

Introduction: Apart from restoring adequate gas exchange, mechanical ventilation should avoid factors that further aggravate lung injury such as cyclic opening and closing of ventilatory units during tidal ventilation. Electrical impedance tomography (EIT) noninvasively measures relative impedance changes in lung tissue during ventilation and is considered a promising monitoring tool to improve ventilatory settings. In order to make complex information from impedance signals interpretable, regional ventilation delay index (RVD) has recently been validated to detect recruitment during a low flow inflation of 1.2 l [4]. To avoid mechanical stress caused by such high tidal inflations, we now modified our RVD method and hypothesized that cyclic opening and closing can be detected with acceptable accuracy during a low flow maneuver with a tidal volume of only 12 ml/kg bw.