Determinant Of Ventilator-induced Lung Injury Research Articles

Regional distribution of mechanical strain and macrophage-associated lung inflammation after ventilator-induced lung injury: an experimental study

BackgroundAlveolar macrophages activation to the pro-inflammatory phenotype M1 is pivotal in the pathophysiology of Ventilator-Induced Lung Injury (VILI). Increased lung strain is a known determinant of VILI, but a direct correspondence between regional lung strain and macrophagic activation remains unestablished. [68Ga]Ga-DOTA-TATE is a Positron Emission Tomography (PET) radiopharmaceutical with a high affinity for somatostatin receptor subtype 2 (SSTR2), which is overexpressed by pro-inflammatory-activated macrophages. Aim of the study was to determine, in a porcine model of VILI, whether mechanical strain correlates topographically with distribution of activated macrophages detected by [68Ga]Ga-DOTA-TATE uptake.MethodsSeven anesthetized pigs underwent VILI, while three served as control. Lung CT scans were acquired at incremental tidal volumes, simultaneously recording lung mechanics. [68Ga]Ga-DOTA-TATE was administered, followed by dynamic PET scans. Custom MatLab scripts generated voxel-by-voxel gas volume and strain maps from CT slices at para-diaphragmatic (Para-D) and mid-thoracic (Mid-T) levels. Analysis of regional Voxel-associated Normal Strain (VoStrain) and [68Ga]Ga-DOTA-TATE uptake was performed and a measure of the statistical correlation between these two variables was quantified using the linear mutual information (LMI) method.ResultsCompared to controls, the VILI group exhibited statistically significant higher VoStrain and Standardized Uptake Value Ratios (SUVR) both at Para-D and Mid-T levels. Both VoStrain and SUVR increased along the gravitational axis with an increment described by statistically different regression lines between VILI and healthy controls and reaching the peak in the dependent regions of the lung (for strain in VILI vs. control was at Para-D: 760 ± 210 vs. 449 ± 106; at Mid-T level 497 ± 373 vs. 193 ± 160; for SUVR, in VILI vs. control was at Para-D: 2.2 ± 1.3 vs. 1.3 ± 0.1; at Mid-T level 1.3 ± 1.0 vs. 0.6 ± 0.03). LMI in both Para-D and Mid-T was statistically significantly higher in VILI than in controls.ConclusionsIn this porcine model of VILI, we found a topographical correlation between lung strain and [68Ga]Ga-DOTA-TATE uptake at voxel level, suggesting that mechanical alteration and specific activation of inflammatory cells are strongly linked in VILI. This study represents the first voxel-by-voxel examination of this relationship in a multi-modal imaging analysis.

Mechanical power and normalized mechanical power in pediatric acute respiratory distress syndrome.

Mechanical power (MP) refers to the energy transmitted over time to the respiratory system and serves as a unifying determinant of ventilator-induced lung injury. MP normalization is required to account for developmental changes in children. We sought to examine the relationship between mechanical energy (MEBW), MP normalized to body weight (MPBW), and MP normalized to respiratory compliance (MPCRS) concerning the severity and outcomes of pediatric acute respiratory distress syndrome (pARDS). In this retrospective study, children aged 1 month to 18 years diagnosed with pARDS who underwent pressure-control ventilation for at least 24 h between January 2017 and September 2020 were enrolled. We calculated MP using Becher's equation. Multivariable logistic regression analysis adjusted for age, pediatric organ dysfunction score, and oxygenation index (OI) was performed to determine the independent association of MP and its derivatives 24 h after diagnosing pARDS with 28-day mortality. The association was also studied for 28 ventilator-free days (VFD-28) and the severity of pARDS in terms of OI. Out of 246 admitted with pARDS, 185 were eligible, with an overall mortality of 43.7%. Non-survivors exhibited higher severity of illness, as evidenced by higher values of MP, MPBW, and MEBW. Multivariable logistic regression analysis showed that only MEBW but not MP, MPBW, or MPCRS at 24 h was independently associated with mortality [adjusted OR: 1.072 (1.002-1.147), p = 0.044]. However, after adjusting for the type of pARDS, MEBW was not independently associated with mortality [adjusted OR: 1.061 (0.992-1.136), p = 0.085]. After adjusting for malnutrition, only MP at 24 h was found to be independently associated. Only MPCRS at 1-4 and 24 h but not MP, MPBW, or MEBW at 24 h of diagnosing pARDS was significantly correlated with VFD-28. Normalization of MP is better related to outcomes and severity of pARDS than non-normalized MP. Malnutrition can be a significant confounding factor in resource-limited settings.

Individualized flow-controlled versus conventional pressure-controlled ventilation in on-pump heart surgery (FLOWVENTIN HEARTSURG): study protocol for a randomized controlled trial

BackgroundIn on-pump cardiac surgery, lungs are at high risk of periprocedural organ impairment because of atelectasis formation, ventilator-induced lung injury, and hyperinflammation due to the cardiopulmonary bypass which results in postoperative pulmonary complications in half of this patient population. The new ventilation mode flow-controlled ventilation (FCV) uniquely allows full control of ins- and expiratory airway flows. This approach reduces the mechanical power of invasive ventilation as a possible cause of ventilator-induced lung injury. The scope of FLOWVENTIN HEARTSURG is to compare perioperative individualized FCV with best clinical practice pressure-controlled ventilation (PVC) modes in patients with elective on-pump cardiac surgery procedures. We hypothesize that the postoperative inflammatory response can be reduced by the perioperative application of FCV compared to PCV.MethodsFLOWVENTIN HEARTSURG is a single-center, randomized, parallel-group trial with two intervention arms: perioperative PCV modes (n = 70, PCV group) with an individualized positive end-expiratory pressure (PEEP) and a tidal volume of 6–8 ml/kg predicted bodyweight compared to perioperative FCV (n = 70, FCV group) with an individualized PEEP and driving pressure, resulting in a liberal tidal volume. As the primary study endpoint interleukin 8 plasma level is assessed 6 h after cardiopulmonary bypass as a surrogate biomarker of systemic and pulmonary inflammation. As secondary aims clinically relevant patient outcomes are analyzed, e.g., perioperative lung function regarding oxygenation indices, postoperative pulmonary and extra-pulmonary complications, SIRS-free days as well as ICU and total inpatient stays. As additional sub-studies with an exploratory approach perioperative right ventricular function parameters are assessed by echocardiography and perioperative lung aeration by electrical impedance tomography.DiscussionCurrent paradigms regarding protective low tidal volume ventilation are consciously left in the FCV intervention group in order to reduce mechanical power as a determinant of ventilator-induced lung injury in this high-risk patient population and procedures. This approach will be compared in a randomized controlled trial with current best clinical practice PCV in FLOWVENTIN HEARTSURG.Trial registrationGerman Clinical Trials Register DRKS00018956. Registered on 12 June 2020 (Version 1), last update on 22 August 2022 (Version 4).

New Frontiers in Functional and Molecular Imaging of the Acutely Injured Lung: Pathophysiological Insights and Research Applications.

This review focuses on the advances in the understanding of the pathophysiology of ventilator-induced and acute lung injury that have been afforded by technological development of imaging methods over the last decades. Examples of such advances include the establishment of regional lung mechanical strain as a determinant of ventilator-induced lung injury, the relationship between alveolar recruitment and overdistension, the regional vs. diffuse nature of pulmonary involvement in acute respiratory distress syndrome (ARDS), the identification of the physiological determinants of the response to recruitment interventions, and the pathophysiological significance of metabolic alterations in the acutely injured lung. Taken together, these advances portray multimodality imaging as the next frontier to both advance knowledge of the pathophysiology of these conditions and to tailor treatment to the individual patient’s condition.

Estimation of changes in cyclic lung strain by electrical impedance tomography: Proof-of-concept study.

Cyclic strain may be a determinant of ventilator-induced lung injury. The standard for strain assessment is the computed tomography (CT), which does not allow continuous monitoring and exposes to radiation. Electrical impedance tomography (EIT) is able to monitor changes in regional lung ventilation. In addition, there is a correlation between mechanical deformation of materials and detectable changes in its electrical impedance, making EIT a potential surrogate for cyclic lung strain measured by CT (StrainCT ). To compare the global StrainCT with the change in electrical impedance (ΔZ). Acute respiratory distress syndrome patients under mechanical ventilation (VT 6mL/kg ideal body weight with positive end-expiratory pressure 5 [PEEP 5] and best PEEP according to EIT) underwent whole-lung CT at end-inspiration and end-expiration. Biomechanical analysis was used to construct 3D maps and determine StrainCT at different levels of PEEP. CT and EIT acquisitions were performed simultaneously. Multilevel analysis was employed to determine the causal association between StrainCT and ΔZ. Linear regression models were used to predict the change in lung StrainCT between different PEEP levels based on the change in ΔZ. StrainCT was positively and independently associated with ΔZ at global level (P<.01). Furthermore, the change in StrainCT (between PEEP 5 and Best PEEP) was accurately predicted by the change in ΔZ (R2 0.855, P<.001 at global level) with a high agreement between predicted and measured StrainCT . The change in electrical impedance may provide a noninvasive assessment of global cyclic strain, without radiation at bedside.

Impact of Different Tidal Volume Levels at Low Mechanical Power on Ventilator-Induced Lung Injury in Rats.

Tidal volume (VT) has been considered the main determinant of ventilator-induced lung injury (VILI). Recently, experimental studies have suggested that mechanical power transferred from the ventilator to the lungs is the promoter of VILI. We hypothesized that, as long as mechanical power is kept below a safe threshold, high VT should not be injurious. The present study aimed to investigate the impact of different VT levels and respiratory rates (RR) on lung function, diffuse alveolar damage (DAD), alveolar ultrastructure, and expression of genes related to inflammation [interleukin (IL)-6], alveolar stretch (amphiregulin), epithelial [club cell secretory protein (CC)16] and endothelial [intercellular adhesion molecule (ICAM)-1] cell injury, and extracellular matrix damage [syndecan-1, decorin, and metalloproteinase (MMP)-9] in experimental acute respiratory distress syndrome (ARDS) under low-power mechanical ventilation. Twenty-eight Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 h, 21 animals were randomly assigned to ventilation (2 h) with low mechanical power at three different VT levels (n = 7/group): (1) VT = 6 mL/kg and RR adjusted to normocapnia; (2) VT = 13 mL/kg; and 3) VT = 22 mL/kg. In the second and third groups, RR was adjusted to yield low mechanical power comparable to that of the first group. Mechanical power was calculated as [(Δ/Est,L)/2]× RR (ΔP,L = transpulmonary driving pressure, Est,L = static lung elastance). Seven rats were not mechanically ventilated (NV) and were used for molecular biology analysis. Mechanical power was comparable among groups, while VT gradually increased. ΔP,L and mechanical energy were higher in VT = 22 mL/kg than VT = 6 mL/kg and VT = 13 mL/kg (p < 0.001 for both). Accordingly, DAD score increased in VT = 22 mL/kg compared to VT = 6 mL/kg and VT = 13 mL/kg [23(18.5–24.75) vs. 16(12–17.75) and 16(13.25–18), p < 0.05, respectively]. VT = 22 mL/kg was associated with higher IL-6, amphiregulin, CC16, MMP-9, and syndecan-1 mRNA expression and lower decorin expression than VT = 6 mL/kg. Multiple linear regression analyses indicated that VT was able to predict changes in IL-6 and CC16, whereas ΔP,L predicted pHa, oxygenation, amphiregulin, and syndecan-1 expression. In the model of ARDS used herein, even at low mechanical power, high VT resulted in VILI. VT control seems to be more important than RR control to mitigate VILI.

Does Regional Lung Strain Correlate With Regional Inflammation in Acute Respiratory Distress Syndrome During Nonprotective Ventilation? An Experimental Porcine Study.

It is known that ventilator-induced lung injury causes increased pulmonary inflammation. It has been suggested that one of the underlying mechanisms may be strain. The aim of this study was to investigate whether lung regional strain correlates with regional inflammation in a porcine model of acute respiratory distress syndrome. Retrospective analysis of CT images and positron emission tomography images using [F]fluoro-2-deoxy-D-glucose. University animal research laboratory. Seven piglets subjected to experimental acute respiratory distress syndrome and five ventilated controls. Acute respiratory distress syndrome was induced by repeated lung lavages, followed by 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressures (mean, 4 cm H2O) and high inspiratory pressures (mean plateau pressure, 45 cm H2O). All animals were subsequently studied with CT scans acquired at end-expiration and end-inspiration, to obtain maps of volumetric strain (inspiratory volume - expiratory volume)/expiratory volume, and dynamic positron emission tomography imaging. Strain maps and positron emission tomography images were divided into 10 isogravitational horizontal regions-of-interest, from which spatial correlation was calculated for each animal. The acute respiratory distress syndrome model resulted in a decrease in respiratory system compliance (20.3 ± 3.4 to 14.0 ± 4.9 mL/cm H2O; p < 0.05) and oxygenation (PaO2/FIO2, 489 ± 80 to 92 ± 59; p < 0.05), whereas the control animals did not exhibit changes. In the acute respiratory distress syndrome group, strain maps showed a heterogeneous distribution with a greater concentration in the intermediate gravitational regions, which was similar to the distribution of [F]fluoro-2-deoxy-D-glucose uptake observed in the positron emission tomography images, resulting in a positive spatial correlation between both variables (median R = 0.71 [0.02-0.84]; p < 0.05 in five of seven animals), which was not observed in the control animals. In this porcine acute respiratory distress syndrome model, regional lung strain was spatially correlated with regional inflammation, supporting that strain is a relevant and prominent determinant of ventilator-induced lung injury.

Applying Precision Medicine to Trial Design Using Physiology. Extracorporeal CO2 Removal for Acute Respiratory Distress Syndrome.

In clinical trials of therapies for acute respiratory distress syndrome (ARDS), the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit, based on predicted patient response to treatment (predictive enrichment). In this perspective, we apply the precision medicine paradigm to the emerging use of extracorporeal CO2 removal (ECCO2R) for ultraprotective ventilation in ARDS. ECCO2R enables reductions in tidal volume and driving pressure, key determinants of ventilator-induced lung injury. Using basic physiological concepts, we demonstrate that dead space and static compliance determine the effect of ECCO2R on driving pressure and mechanical power. This framework might enable prediction of individual treatment responses to ECCO2R. Enriching clinical trials by selectively enrolling patients with a significant predicted treatment response can increase treatment effect size and statistical power more efficiently than conventional enrichment strategies that restrict enrollment according to the baseline risk of death. To support this claim, we simulated the predicted effect of ECCO2R on driving pressure and mortality in a preexisting cohort of patients with ARDS. Our computations suggest that restricting enrollment to patients in whom ECCO2R allows driving pressure to be decreased by 5 cm H2O or more can reduce sample size requirement by more than 50% without increasing the total number of patients to be screened. We discuss potential implications for trial design based on this framework.

Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in Experimental Acute Respiratory Distress Syndrome.

Volutrauma and atelectrauma promote ventilator-induced lung injury, but their relative contribution to inflammation in ventilator-induced lung injury is not well established. The aim of this study was to determine the impact of volutrauma and atelectrauma on the distribution of lung inflammation in experimental acute respiratory distress syndrome. Laboratory investigation. University-hospital research facility. Ten pigs (five per group; 34.7-49.9 kg) : Animals were anesthetized and intubated, and saline lung lavage was performed. Lungs were separated with a double-lumen tube. Following lung recruitment and decremental positive end-expiratory pressure trial, animals were randomly assigned to 4 hours of ventilation of the left (ventilator-induced lung injury) lung with tidal volume of approximately 3 mL/kg and 1) high positive end-expiratory pressure set above the level where dynamic compliance increased more than 5% during positive end-expiratory pressure trial (volutrauma); or 2) low positive end-expiratory pressure to achieve driving pressure comparable with volutrauma (atelectrauma). The right (control) lung was kept on continuous positive airway pressure of 20 cm H2O, and CO2 was partially removed extracorporeally. Regional lung aeration, specific [F]fluorodeoxyglucose uptake rate, and perfusion were assessed using computed and positron emission tomography. Volutrauma yielded higher [F]fluorodeoxyglucose uptake rate in the ventilated lung compared with atelectrauma (median [interquartile range], 0.017 [0.014-0.025] vs 0.013 min [0.010-0.014 min]; p < 0.01), mainly in central lung regions. Volutrauma yielded higher [F]fluorodeoxyglucose uptake rate in ventilator-induced lung injury versus control lung (0.017 [0.014-0.025] vs 0.011 min [0.010-0.016 min]; p < 0.05), whereas atelectrauma did not. Volutrauma decreased blood fraction at similar perfusion and increased normally as well as hyperaerated lung compartments and tidal hyperaeration. Atelectrauma yielded higher poorly and nonaerated lung compartments, and tidal recruitment. Driving pressure increased in atelectrauma. In this model of acute respiratory distress syndrome, volutrauma promoted higher lung inflammation than atelectrauma at comparable low tidal volume and lower driving pressure, suggesting that static stress and strain are major determinants of ventilator-induced lung injury.

Bedside assessment of the effects of positive end-expiratory pressure on lung inflation and recruitment by the helium dilution technique and electrical impedance tomography.

Higher positive end-expiratory pressure might induce lung inflation and recruitment, yielding enhanced regional lung protection. We measured positive end-expiratory pressure-related lung volume changes by electrical impedance tomography and by the helium dilution technique. We also used electrical impedance tomography to assess the effects of positive end-expiratory pressure on regional determinants of ventilator-induced lung injury. A prospective randomized crossover study was performed on 20 intubated adult patients: 12 with acute hypoxemic respiratory failure and 8 with acute respiratory distress syndrome. Each patient underwent protective controlled ventilation at lower (7 [7, 8] cmH2O) and higher (12 [12, 13] cmH2O) positive end-expiratory pressures. At the end of each phase, we collected ventilation, helium dilution, and electrical impedance tomography data. Positive end-expiratory pressure-induced changes in lung inflation and recruitment measured by electrical impedance tomography and helium dilution showed close correlations (R (2)=0.78, p<0.001 and R (2)=0.68, p<0.001, respectively) but with relatively variable limits of agreement. At higher positive end-expiratory pressure, recruitment was evident in all lung regions (p<0.01) and heterogeneity of tidal ventilation distribution was reduced by increased tidal volume distending the dependent lung (p<0.001); in the non-dependent lung, on the other hand, compliance decreased (p<0.001) and tidal hyperinflation significantly increased (p<0.001). In the subgroup of ARDS patients (but not in the whole study population) tidal hyperinflation in the dependent lung regions decreased at higher positive end-expiratory pressure (p=0.05), probably indicating higher potential for recruitment. Close correlations exist between bedside assessment of positive end-expiratory pressure-induced changes in lung inflation and recruitment by the helium dilution and electrical impedance tomography techniques. Higher positive end-expiratory pressure exerts mixed effects on the regional determinants of ventilator-induced lung injury; these merit close monitoring.

Optimal ventilation strategy

Premature delivery, is always associated to the failure of respiratory transition and a delayed achievement of an adequate functional residual capacity. For this reason preterm babies (expecially the Extremely Low for Gestational Age -ELGA- infants) frequently need a respiratory support. Non-invasive ventilation (NIV) is widespread used in the management of respiratory distress even in ELGA infants without increasing of neonatal mortality or neurological impairment. The most recent meta-analysis and reviews on NIV approach demonstrated that NIV is a valid alternative to mechanical ventilation (MV) in the management of respiratory failure and resulted in significant reductions in the incidence of Bronchopulmonary dysplasia (BPD) amongst surviving infants [1,2]. Nevertheless, even if non-invasive respiratory support seems to be very efficacious in preterm babies, sometimes ELGA infants require MV. Pressure-limited ventilation is yet the standard mode in neonatal intensive care unit, because the attempts to use traditional volume-controlled ventilation it has been often impractical in very small preterm infants. Moreover pressure-limited ventilation continues to be the primary mode of ventilation in neonates because of its relative simplicity and ability to ventilate effectively despite large ETT leak. The major disadvantage of pressure-limited ventilation is that the tidal volume (VT) varies with changes in lung compliance (e.g after surfactant therapy). The consequences of such rapid improvements in compliance are inadvertent hyperventilation and lung injury from excessively large VT (volutrauma); inadvertent hyperventilation may induce hypocapnia, with high risk of cerebral damage. In literature there are extensive evidence that excessive volume, rather than pressure, is the key determinant of ventilator-induced lung injury (VILI). Inadequate (too small) VT also causes significant problems (atelectrauma): in particular inefficient gas exchange due to increased dead-space to VT ratio. Therefore in the last years volume-targeted ventilation has become an important standard of care in neonatal and pediatric respiratory support too. There are many volume-targeted ventilation modes to be used in neonatal period, but Volume Guarantee (VG) ventilation, it is the most extensively studied volume-targeted ventilation mode in the neonate with respiratory distress. The Cochrane review on volume-targeted ventilation resulted in significant reductions in duration of ventilation, rates of pneumothorax, significant reduction in intraventricular haemorrhage (IVH) and a reduction in the incidence of BPD amongst surviving infants, of borderline statistical significance [3]. The VG ventilation plus adequate PEEP and an open lung strategy [4], seems to be an adequate alternative to High frequency Oscillatory Ventilation (HFOV) in mechanically ventilated infants for RDS.

Ventilator-Induced Lung Injury: Minimizing Its Impact in Patients With or at Risk for ARDSDiscussion

Ventilator-induced lung injury (VILI) results from injury to the blood-gas barrier caused by mechanical ventilation. The determinants of VILI are more complex than originally thought, and include the nature, duration, and intensity of the exposure, as well the pattern of initial insult to the lung. Lung-protective mechanical ventilation founded on these basic principles resulted in improved hospital and long-term mortality. The purpose of this review is to provide a comprehensive assessment of the pathogenesis of VILI and its determinants. We also discuss the best preventive approach in patients with or at risk for ARDS and critically appraise the most recent evidence, expert opinion, and implementation of the acquired knowledge to the bedside.

Short-Term Administration of a High Oxygen Concentration Is Not Injurious in an Ex-Vivo Rabbit Model of Ventilator-Induced Lung Injury

Mechanical ventilation and administration of a high oxygen concentration are simultaneously used in the management of respiratory failure. We conducted this study to evaluate the effect of a high inspired oxygen concentration on ventilator-induced lung injury. Forty sets of isolated/perfused rabbit lungs were randomized for 60 min of pressure-control ventilation at a plateau inspiratory pressure of 25 or 15 cm H(2)O and positive end-expiratory pressure of 3 cm H(2)O while receiving 100% or 21% O(2). The temperature, pH, and partial pressure of CO(2) in the perfusate were maintained the same in all groups (n = 10 for each group). The outcome measures used to assess lung injury included: the change in weight gain and ultrafiltration coefficient, the frequency of vascular failure, the histological lesions and the concentration of tumor necrosis factor-alpha and malondialdehyde in the bronchoalveolar lavage fluid. The two groups ventilated at the higher inspiratory pressure/tidal volume experienced greater weight gain and increases in the ultrafiltration coefficient, more frequently suffered vascular failure, and presented higher composite scores of histological damage than the two groups ventilated at the lower inspiratory pressure/tidal volume. Hyperoxia was not found to further increase any of the monitored markers of lung injury. No difference was noticed among the four experimental groups in the alveolar lavage fluid levels of tumor necrosis factor-alpha or malondialdehyde. These findings suggest that short-term administration of a high oxygen concentration is not a major determinant of ventilator-induced lung injury in this experimental model.

Current ventilatory management of patients with acute lung injury/acute respiratory distress syndrome

The current main objective of mechanical ventilation during acute respiratory distress syndrome (ARDS) is to improve oxygenation while preventing ventilator-induced lung injury (VILI) in order to save a patient’s life. The major determinants of VILI are both hyperinflation of normally aerated lung and repetitive opening and closing of lung units. There are two methods of preventing VILI and, hence, making mechanical ventilation lung protective. The first is to reduce tidal volume to 6 ml/kg predicted body weight and to keep the end-inspiratory airway pressure below 30 cm H2O. This strategy reduced the mortality of patients with ARDS. In a large, multicenter, randomized, controlled trial, patients receiving lower tidal volume (6 ml/kg ideal body weight) had a better chance of survival than those patients receiving a higher tidal volume of 12 ml/kg. Keeping plateau pressure below 30 cm H2O was an associated strategy in this trial. However, it is likely that this value is not a safety threshold in every patient, since overdistension may be present even when plateau pressure is below 30 cm H2O. The second mechanism to prevent VILI is recruiting the nonaerated or poorly aerated lung areas and keeping them recruited. This strategy requires alveolar pressures much larger than 30 cm H2O transiently to overcome the critical opening pressures of the lung. One drawback is hemodynamic impairment. To date, this strategy has not been found to be associated with an improvement of patient outcome.

Volume-targeted Ventilation

After completing this article, readers should be able to: 1. Understand the importance of controlling tidal volume and avoiding hyperventilation/excessive tidal volume. 2. Recognize the importance of optimizing lung inflation and avoiding atelectasis. 3. Delineate the limitations of traditional volume-controlled ventilation in newborns. 4. Describe the various modes of volume-targeted ventilation and their advantages and disadvantages. 5. Describe the key steps in the clinical application of volume guarantee ventilation. Mechanical ventilation has improved to the point where few infants die because of acute respiratory failure. Mortality now is predominantly from other complications of extreme prematurity, such as infection, necrotizing enterocolitis, and intracranial hemorrhage. Consequently, focus has shifted from merely reducing mortality to reducing the incidence of chronic lung disease, which has increased in recent years with improved survival of extremely preterm infants. Although high-frequency ventilation has shown promise, results of clinical trials have been inconsistent, and continued concerns about the hazards of inadvertent hyperventilation have limited its acceptance as first-line therapy in infants who have uncomplicated respiratory distress syndrome (RDS). At the same time, technologically advanced synchronized ventilation has become widely available. The most exciting development in neonatal respiratory support, however, is the advent of volume-targeted modalities of conventional ventilation that, for the first time, allow effective control of delivered tidal volume for neonatal ventilation. Pressure-limited, time-cycled, continuous flow ventilation has been the standard of care in neonatal ventilation for more than 30 years. One of the advantages cited for the preference for pressure-limited over volume-controlled ventilation has been the ability to control the inspiratory pressure directly. Preoccupation with high inspiratory pressure as the chief culprit in lung injury and air leak has been a constant theme in neonatal respiratory support until recently, despite accumulating evidence over more than a decade that volume, rather than pressure, is the critical determinant of ventilator-induced lung injury. Dreyfuss …

Ventilator-induced lung injury.

The clinical relevance of experimental ventilator-induced lung injury has recently received a resounding illustration by the Acute Respiratory Distress Syndrome Network trial that showed a 22% reduction of mortality in patients with acute respiratory disease syndrome when lung mechanical stress was lessened by tidal volume reduction during mechanical ventilation. This clinical confirmation of the concept of ventilator-induced lung injury has also undisputedly substantiated the experimental observation that excessive tidal volume and/or end-inspiratory lung volume is the main determinant of ventilator-induced lung injury. More recently, attention has focused on the roles and implication in the pathogenesis of ventilator-induced lung injury of inflammatory cells and mediators that may be activated and released either in the alveolar space or in the systemic circulation because of the rupture of the alveolar-capillary barrier and on the cellular response to mechanical stress.