Association of Intraoperative Ventilator Management With Postoperative Oxygenation, Pulmonary Complications, and Mortality.

BACKGROUND: "Lung-protective ventilation" describes a ventilation strategy involving low tidal volumes (VTs) and/or low driving pressure/plateau pressure and has been associated with improved outcomes after mechanical ventilation. We evaluated the association between intraoperative ventilation parameters (including positive end-expiratory pressure [PEEP], driving pressure, and VT) and 3 postoperative outcomes: (1) PaO2/fractional inspired oxygen tension (FIO2), (2) postoperative pulmonary complications, and (3) 30-day mortality. METHODS: We retrospectively analyzed adult patients who underwent major noncardiac surgery and remained intubated postoperatively from 2006 to 2015 at a single US center. Using multivariable regressions, we studied associations between intraoperative ventilator settings and lowest postoperative PaO2/FIO2 while intubated, pulmonary complications identified from discharge diagnoses, and in-hospital 30-day mortality. RESULTS: Among a cohort of 2096 cases, the median PEEP was 5 cm H2O (interquartile range = 4-6), median delivered VT was 520 mL (interquartile range = 460-580), and median driving pressure was 15 cm H2O (13-19). After multivariable adjustment, intraoperative median PEEP (linear regression estimate [B] = -6.04; 95% CI, -8.22 to -3.87; P < .001), median FIO2 (B = -0.30; 95% CI, -0.50 to -0.10; P = .003), and hours with driving pressure >16 cm H2O (B = -5.40; 95% CI, -7.2 to -4.2; P < .001) were associated with decreased postoperative PaO2/FIO2. Higher postoperative PaO2/FIO2 ratios were associated with a decreased risk of pulmonary complications (adjusted odds ratio for each 100 mm Hg = 0.495; 95% CI, 0.331-0.740; P = .001, model C-statistic of 0.852) and mortality (adjusted odds ratio = 0.495; 95% CI, 0.366-0.606; P < .001, model C-statistic of 0.820). Intraoperative time with VT >500 mL was also associated with an increased likelihood of developing a postoperative pulmonary complication (adjusted odds ratio = 1.06/hour; 95% CI, 1.00-1.20; P = .042). CONCLUSIONS: In patients requiring postoperative intubation after noncardiac surgery, increased median FIO2, increased median PEEP, and increased time duration with elevated driving pressure predict lower postoperative PaO2/FIO2. Intraoperative duration of VT >500 mL was independently associated with increased postoperative pulmonary complications. Lower postoperative PaO2/FIO2 ratios were independently associated with pulmonary complications and mortality. Our findings suggest that postoperative PaO2/FIO2 may be a potential target for future prospective trials investigating the impact of specific ventilation strategies for reducing ventilator-induced pulmonary injury.

Posttreatment With the Fatty Acid Amide Hydrolase Inhibitor URB937 Ameliorates One-Lung Ventilation-Induced Lung Injury in a Rabbit Model.

BACKGROUND: One-lung ventilation (OLV)-induced inflammation is a risk factor for acute lung injury that is responsible for 20% of postoperative pulmonary complications after lung resection. Inflammation is an important trigger for acute lung injury. Fatty acid amide hydrolase (FAAH) is the major enzyme that degrades the endocannabinoid arachidonoylethanolamine (AEA), an important regulator of inflammation, and its downstream metabolites such as arachidonic acid (AA) are also involved in inflammation. Importantly, AEA is also found in lung parenchyma. However, it remains unclear whether pharmacological inhibition of FAAH inhibitor using compounds such as URB937 can attenuate OLV-induced lung injury. MATERIALS AND METHODS: New Zealand white rabbits were anesthetized to establish a modified OLV-induced lung injury model. Twenty-four male rabbits were randomly divided into four groups (n = 6): TLV-S (2.5-h two-lung ventilation [TLV] + 1.5 mL/kg saline + 1-h TLV), OLV-S (2.5-h OLV + 1.5 mL/kg saline + 0.5-h OLV + 0.5-h TLV), U-OLV (1.5 mL/kg URB937 + 3.0-h OLV + 0.5-h TLV), and OLV-U (2.5-h OLV + 1.5 mL/kg URB937 + 0.5-h OLV + 0.5-h TLV). Arterial blood gases, lung wet/dry ratio, and lung injury score of the nonventilated lungs were measured. The levels of AEA, AA, prostaglandin I2 (PGI2), thromboxane A2 (TXA2), and leukotriene B4 (LTB4) in the nonventilated lung were also quantified. RESULTS: The arterial oxygenation index (PaO2/FiO2) decreased after 0.5-h OLV in the three OLV groups. The PaO2/FiO2 in the OLV-U group was better than that in the OLV-S and U-OLV groups and was accompanied with reductions in the wet/dry ratio and lung injury scores of the nonventilated lungs. The FAAH inhibitor URB937 administered not before but 2.5 h after OLV attenuated OLV-induced lung injury by increasing AEA levels and reducing the levels of downstream metabolites including AA, PGI2, TXA2, and LTB4. CONCLUSIONS: Posttreatment with the FAAH inhibitor URB937 attenuated OLV-induced lung injury in rabbits and was associated with increased AEA levels and decreased levels of AA and its downstream metabolites.

Esophageal Manometry and Regional Transpulmonary Pressure in Lung Injury.

RATIONALE: Esophageal manometry is the clinically available method to estimate pleural pressure, thus enabling calculation of transpulmonary pressure (Pl). However, many concerns make it uncertain in which lung region esophageal manometry reflects local Pl. OBJECTIVES: To determine the accuracy of esophageal pressure (Pes) and in which regions esophageal manometry reflects pleural pressure (Ppl) and Pl; to assess whether lung stress in nondependent regions can be estimated at end-inspiration from Pl. METHODS: In lung-injured pigs (n = 6) and human cadavers (n = 3), Pes was measured across a range of positive end-expiratory pressure, together with directly measured Ppl in nondependent and dependent pleural regions. All measurements were obtained with minimal nonstressed volumes in the pleural sensors and esophageal balloons. Expiratory and inspiratory Pl was calculated by subtracting local Ppl or Pes from airway pressure; inspiratory Pl was also estimated by subtracting Ppl (calculated from chest wall and respiratory system elastance) from the airway plateau pressure. MEASUREMENTS AND MAIN RESULTS: In pigs and human cadavers, expiratory and inspiratory Pl using Pes closely reflected values in dependent to middle lung (adjacent to the esophagus). Inspiratory Pl estimated from elastance ratio reflected the directly measured nondependent values. CONCLUSIONS: These data support the use of esophageal manometry in acute respiratory distress syndrome. Assuming correct calibration, expiratory Pl derived from Pes reflects Pl in dependent to middle lung, where atelectasis usually predominates; inspiratory Pl estimated from elastance ratio may indicate the highest level of lung stress in nondependent "baby" lung, where it is vulnerable to ventilator-induced lung injury.

A feasibility study into adenosine triphosphate measurement in exhaled breath condensate: a potential bedside method to monitor alveolar deformation.

Recent research suggested an important role for pulmonary extracellular adenosine triphosphate (ATP) in the development of ventilation-induced lung injury. This injury is induced by mechanical deformation of alveolar epithelial cells, which in turn release ATP to the extracellular space. Measuring extracellular ATP in exhaled breath condensate (EBC) may be a non-invasive biomarker for alveolar deformation. Here, we study the feasibility of bedside ATP measurement in EBC. We measured ATP levels in EBC in ten subjects before and after an exercise test, which increases respiratory parameters and alveolar deformation. EBC lactate concentrations were measured as a dilution marker. We found a significant increase in ATP levels in EBC (before 73 RLU [IQR 50-209] versus after 112 RLU [IQR 86-203]; p value 0.047), and the EBC ATP-to-EBC lactate ratio increased as well (p value 0.037). We present evidence that bedside measurement of ATP in EBC is feasible and that ATP levels in EBC increase after exercise. Future research should measure ATP levels in EBC during mechanical ventilation as a potential biomarker for alveolar deformation.

The promises and problems of transpulmonary pressure measurements in acute respiratory distress syndrome.

PURPOSE OF REVIEW: The optimal strategy for assessing and preventing ventilator-induced lung injury in the acute respiratory distress syndrome (ARDS) is controversial. Recent investigative efforts have focused on personalizing ventilator settings to individual respiratory mechanics. This review examines the strengths and weaknesses of using transpulmonary pressure measurements to guide ventilator management in ARDS. RECENT FINDINGS: Recent clinical studies suggest that adjusting ventilator settings based on transpulmonary pressure measurements is feasible, may improve oxygenation, and reduce ventilator-induced lung injury. SUMMARY: The measurement of transpulmonary pressure relies upon esophageal manometry, which requires the acceptance of several assumptions and potential errors. Notably, this includes the ability of localized esophageal pressures to represent global pleural pressure. Recent investigations demonstrated improved oxygenation in ARDS patients when positive end-expiratory pressure was adjusted to target specific end-inspiratory or end-expiratory transpulmonary pressures. However, there are different methods for estimating transpulmonary pressure and different goals for positive end-expiratory pressure titration among recent studies. More research is needed to refine techniques for the estimation and utilization of transpulmonary pressure to guide ventilator settings in ARDS patients.

Extra corporeal membrane oxygenation to facilitate lung protective ventilation and prevent ventilator-induced lung injury in severe Pneumocystis pneumonia with pneumomediastinum: a case report and short literature review.

BACKGROUND: Pulmonary infections caused by Pneumocystis jirovecii in immunocompromised host can be associated with cysts, pneumatoceles and air leaks that can progress to pneumomediastinum and pneumothoraxes. In such cases, it can be challenging to maintain adequate gas exchange by conventional mechanical ventilation and at the same time prevent further ventilator-induced lung injury. We report a young HIV positive male with poorly compliant lungs and pneumomediastinum secondary to severe Pneumocystis infection, rescued with veno-venous extra corporeal membrane oxygenation (V-V ECMO). CASE PRESENTATION: A 26 year old male with no significant past medical history was admitted with fever, cough and shortness of breath. He initially required non-invasive ventilation for respiratory failure. However, his respiratory function progressively deteriorated due to increasing pulmonary infiltrates and development of pneumomediastinum, eventually requiring endotracheal intubation and invasive ventilation. Despite attempts at optimizing gas exchange by ventilatory maneuvers, patients' pulmonary parameters worsened necessitating rescue ECMO therapy. The introduction of V-V ECMO facilitated the use of ultra-protective lung ventilation and prevented progression of pneumomediastinum, maintaining optimal gas exchange. It allowed time for the antibiotics to show effect and pulmonary parenchyma to heal. Further diagnostic workup revealed Pneumocystis jirovecii as the causative organism for pneumonia and serology confirmed Human Immunodeficiency Virus infection. Patient was successfully treated with appropriate antimicrobials and de-cannulated after six days of ECMO support. CONCLUSION: ECMO was an effective salvage therapy in HIV positive patient with an otherwise fatal respiratory failure due to Pneumocystis pneumonia and air leak syndrome.

Cytokines and clinical predictors in distinguishing pulmonary transfusion reactions.

BACKGROUND: Pulmonary transfusion reactions are important complications of blood transfusion, yet differentiating these clinical syndromes is diagnostically challenging. We hypothesized that biologic markers of inflammation could be used in conjunction with clinical predictors to distinguish transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and possible TRALI. STUDY DESIGN AND METHODS: In a nested case-control study performed at the University of California at San Francisco and Mayo Clinic, Rochester, we evaluated clinical data and blood samples drawn before and after transfusion in patients with TRALI (n = 70), possible TRALI (n = 48), TACO (n = 29), and controls (n = 147). Cytokines measured included granulocyte-macrophage-colony-stimulating factor, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-α. Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical predictors and laboratory markers in differentiating TACO, TRALI, and possible TRALI. RESULTS: Before and after transfusion, IL-6 and IL-8 were elevated in patients with TRALI and possible TRALI relative to controls, and IL-10 was elevated in patients with TACO and possible TRALI relative to that of TRALI and controls. For all pulmonary transfusion reactions, the combination of clinical variables and cytokine measurements displayed optimal diagnostic performance, and the model comparing TACO and TRALI correctly classified 92% of cases relative to expert panel diagnoses. CONCLUSIONS: Before transfusion, there is evidence of systemic inflammation in patients who develop TRALI and possible TRALI but not TACO. A predictive model incorporating readily available clinical and cytokine data effectively differentiated transfusion-related respiratory complications such as TRALI and TACO.

Lung Injury After One-Lung Ventilation: A Review of the Pathophysiologic Mechanisms Affecting the Ventilated and the Collapsed Lung.

Lung injury is the leading cause of death after thoracic surgery. Initially recognized after pneumonectomy, it has since been described after any period of 1-lung ventilation (OLV), even in the absence of lung resection. Overhydration and high tidal volumes were thought to be responsible at various points; however, it is now recognized that the pathophysiology is more complex and multifactorial. All causative mechanisms known to trigger ventilator-induced lung injury have been described in the OLV setting. The ventilated lung is exposed to high strain secondary to large, nonphysiologic tidal volumes and loss of the normal functional residual capacity. In addition, the ventilated lung experiences oxidative stress, as well as capillary shear stress because of hyperperfusion. Surgical manipulation and/or resection of the collapsed lung may induce lung injury. Re-expansion of the collapsed lung at the conclusion of OLV invariably induces duration-dependent, ischemia-reperfusion injury. Inflammatory cytokines are released in response to localized injury and may promote local and contralateral lung injury. Protective ventilation and volatile anesthesia lessen the degree of injury; however, increases in biochemical and histologic markers of lung injury appear unavoidable. The endothelial glycocalyx may represent a common pathway for lung injury creation during OLV, because it is damaged by most of the recognized lung injurious mechanisms. Experimental therapies to stabilize the endothelial glycocalyx may afford the ability to reduce lung injury in the future. In the interim, protective ventilation with tidal volumes of 4 to 5 mL/kg predicted body weight, positive end-expiratory pressure of 5 to 10 cm H2O, and routine lung recruitment should be used during OLV in an attempt to minimize harmful lung stress and strain. Additional strategies to reduce lung injury include routine volatile anesthesia and efforts to minimize OLV duration and hyperoxia.

Accuracy of plateau pressure and stress index to identify injurious ventilation in patients with acute respiratory distress syndrome.

BACKGROUND: Guidelines suggest a plateau pressure (PPLAT) of 30 cm H(2)O or less for patients with acute respiratory distress syndrome, but ventilation may still be injurious despite adhering to this guideline. The shape of the curve plotting airway pressure versus time (STRESS INDEX) may identify injurious ventilation. The authors assessed accuracy of PPLAT and STRESS INDEX to identify morphological indexes of injurious ventilation. METHODS: Indexes of lung aeration (computerized tomography) associated with injurious ventilation were used as a "reference standard." Threshold values of PPLAT and STRESS INDEX were determined assessing the receiver-operating characteristics ("training set," N = 30). Accuracy of these values was assessed in a second group of patients ("validation set," N = 20). PPLAT and STRESS INDEX were partitioned between respiratory system (Pplat,Rs and STRESS INDEX,RS) and lung (PPLAT,L and STRESS INDEX,L; esophageal pressure; "physiological set," N = 50). RESULTS: Sensitivity and specificity of PPLAT of greater than 30 cm H(2)O were 0.06 (95% CI, 0.002-0.30) and 1.0 (95% CI, 0.87-1.00). PPLAT of greater than 25 cm H(2)O and a STRESS INDEX of greater than 1.05 best identified morphological markers of injurious ventilation. Sensitivity and specificity of these values were 0.75 (95% CI, 0.35-0.97) and 0.75 (95% CI, 0.43-0.95) for PPLAT greater than 25 cm H(2)O versus 0.88 (95% CI, 0.47-1.00) and 0.50 (95% CI, 0.21-0.79) for STRESS INDEX greater than 1.05. Pplat,Rs did not correlate with PPLAT,L (R(2) = 0.0099); STRESS INDEX,RS and STRESS INDEX,L were correlated (R(2) = 0.762). CONCLUSIONS: The best threshold values for discriminating morphological indexes associated with injurious ventilation were Pplat,Rs greater than 25 cm H(2)O and STRESS INDEX,RS greater than 1.05. Although a substantial discrepancy between Pplat,Rs and PPLAT,L occurs, STRESS INDEX,RS reflects STRESS INDEX,L.

Method development and validation for rat serum fingerprinting with CE-MS: application to ventilator-induced-lung-injury study.

In the search for a noninvasive and reliable rapid screening method to detect biomarkers, a metabolomics fingerprinting approach was developed and applied to rat serum samples using capillary electrophoresis coupled to an electrospray ionization-time of flight-mass spectrometer (CE-TOF-MS). An ultrafiltration method was used for sample pretreatment. To evaluate performance the method was validated with carnitine, choline, ornithine, alanine, acetylcarnitine, betaine, and citrulline, covering the entire electropherogram of pool of rat serum. The linearity for all metabolites was >0.99, with good recovery and precision. Approximately 34 compounds were also confirmed in the pool of rat serum. The method was successfully applied to real serum samples from rats with ventilator-induced lung injury, an experimental rat model for acute lung injury (ALI), giving a total of 1163 molecular features. By use of univariate and multivariate statistics 18 significant compounds were found, of which five were confirmed. The involvement of arginase and nitric oxide synthase has been proved for other lung diseases, meaning the increase of asymmetric dimethyl arginine (ADMA) and ornithine and the decrease of arginine found were in accordance with published literature. Ultimately this fingerprinting approach offers the possibility of identifying biomarkers that could be regularly screened for as part of routine disease control. In this way it might be possible to prevent the development of ALI in patients in critical care units.

Preliminary study of ventilation with 4 ml/kg tidal volume in acute respiratory distress syndrome: feasibility and effects on cyclic recruitment - derecruitment and hyperinflation.

INTRODUCTION: Cyclic recruitment-derecruitment and overdistension contribute to ventilator-induced lung injury. Tidal volume (Vt) may influence both, cyclic recruitment-derecruitment and overdistension. The goal of this study was to determine if decreasing Vt from 6 to 4 ml/kg reduces cyclic recruitment-derecruitment and hyperinflation, and if it is possible to avoid severe hypercapnia. METHODS: Patients with pulmonary acute respiratory distress syndrome (ARDS) were included in a crossover study with two Vt levels: 6 and 4 ml/kg. The protocol had two parts: one bedside and other at the CT room. To avoid severe hypercapnia in the 4 ml/kg arm, we replaced the heat and moisture exchange filter by a heated humidifier, and respiratory rate was increased to keep minute ventilation constant. Data on lung mechanics and gas exchange were taken at baseline and after 30 minutes at each Vt (bedside). Thereafter, a dynamic CT (4 images/sec for 8 sec) was taken at each Vt at a fixed transverse region between the middle and lower third of the lungs. Afterward, CT images were analyzed and cyclic recruitment-derecruitment was determined as non-aerated tissue variation between inspiration and expiration, and hyperinflation as maximal hyperinflated tissue at end-inspiration, expressed as % of lung tissue weight. RESULTS: We analyzed 10 patients. Decreasing Vt from 6 to 4 ml/kg consistently decreased cyclic recruitment-derecruitment from 3.6 (2.5 to 5.7) % to 2.9 (0.9 to 4.7) % (P <0.01) and end-inspiratory hyperinflation from 0.7 (0.3 to 2.2) to 0.6 (0.2 to 1.7) % (P = 0.01). No patient developed severe respiratory acidosis or severe hypercapnia when decreasing Vt to 4 ml/kg (pH 7.29 (7.21 to 7.46); PaCO2 48 (26 to 51) mmHg). CONCLUSIONS: Decreasing Vt from 6 to 4 ml/kg reduces cyclic recruitment-derecruitment and hyperinflation. Severe respiratory acidosis may be effectively prevented by decreasing instrumental dead space and by increasing respiratory rate.

Adverse influence of mixed acidemia on the biocompatibility of continuous veno-venous hemofiltration with respect to the lungs.

Experimental data indicate that hypercapnic adidosis has anti-inflammatory effects. These anti-inflammatory effects may even be a beneficial property in case of low tidal volume ventilation with consecutive hypercapnic acidosis. It is unclear whether these anti-inflammatory effects predominate in critically ill patients who suffer from multiple pro- and anti-inflammatory insults like extracorporeal organ support (pro-inflammatory), metabolic acidosis (pro- and anti-inflammatory), as well as hypoxia (pro-inflammatory). Eighteen pigs were randomized into three groups, mechanically ventilated and connected to a continuous veno-venous hemofiltration (CVVH) as pro-inflammatory insult. A reference group with normal acid-base state obtained normoventilation; a normoxemic acidemia group obtained normoxemic, mixed acidemia due to infusion of lactic and hyperchloremic acid and low tidal volume ventilation, and in a hypoxemic acidemia group the mixed acidemia was paralleled by hypoxemia. Lung histology including pulmonary leukocyte invasion, blood gases, blood cell counts, and hemodynamics were examined. The histological examination of the lungs of acidemic pigs showed a suppressed invasion of leukocytes and thinner alveolar walls compared with normoventilated and with hypoxemic pigs. Enhanced congestion and alveolar red blood cells (RBCs) combined with an increase of the pulmonary artery pressure were observed in acidemic pigs in comparison with the reference group. Normoxemic acidemia reduced the pro-inflammatory reaction to the CVVH and mechanical ventilation in the ventilated lung areas in the form of pulmonary leukocyte invasion. However, this did not result in reduced scores for lung injury. Instead, an increased score for criteria which represent lung injury (congestion and alveolar RBCs) was observed in acidemic pigs.

["The Berlin definition" and clinical significance of high-resolution CT (HRCT) imaging in acute respiratory distress syndrome].

The clinical criteria of acute respiratory distress syndrome (ARDS) defined by the American-European Consensus Conference (AECC) in 1994 was relevant to clinical practice, trials, and researches for two decades. However, a number of issues with the AECC definition have become apparent. The updated and revised criteria of "The Berlin definition", addressing the limitations of the previous AECC definition, were published in 2012. In the first section of this manuscript, the Berlin definition based on data using patients-level meta-analysis of 4188 patients with ARDS, was reviewed. In the second section, the clinical significance and limitation of radiographic imaging, especially, high-resolution CT (HRCT) findings in ARDS were addressed. Although the early exudative phase of ARDS can not be detected even by HRCT, pulmonary fibroproliferation assessed by HRCT in patients with early ARDS predicts increased mortality with an increased susceptibility to multiple organ failure, along with ventilator dependency and its associated outcomes.

[Acute respiratory distress syndrome and pneumonia].

Bacterial and viral pneumonia are the most frequent causes of ARDS. The other infectious risk of developing of ARDS is infections at nonpulmonary sites, and fungal as well as parasites pneumonia. Virtually all patients with ARDS require mechanical ventilation, a major risk factor for the development of VAP.

[Significance of static pressure-volume loop and lung computed tomography for differential diagnostics of parenchymal respiratory insufficiency].

UNLABELLED: Purpose of the study was to determine a significance of static pressure-volume loop and lung computed tomography for differential diagnostics of parenchymal lung failure developing during mechanical ventilation. MATERIALS AND METHODS: 75 patients (42 males and 33 females) with acute lung failure due to parenchymal lung injury during mechanical ventilation were included in to the research. Criteria of including into the research were age over 15, ARDS symptoms absence before respiratory support beginning and modified American-European Consensus Conference ARDS criteria presence during mechanical ventilation (AECC ARDS criteria, 1994--PaO2/FiO2 < 250 mmHg). Lung computed tomography (CT), static compliance and plateau measurement were performed in all patients. Static pressure-volume loop was plotted in 23 patients. RESULTS: diffuse alveolar damage was diagnosed by CT in 24.3% of patients and "wet sponge" symptom in 10.7% of patients. Dorsal atelectasis (77.3%) and ventilator-associated pneumonia (VAP) (82.7%) were diagnosed in most of patients with AECC ARDS criteria. Sensitivity and specificity of PaO2/FiO2 ratio were too low for diagnostics of ARDS (AUROC 0.67) Patients with diffuse alveolar damage had plateau pressure 25 mbar (95% CI 22-32), while patients with local lung injury (VAP or atelectasis) had significantly lower plateau pressure--20 mbar (95% CI 18-22) (p = 0.014). Elevation of plateau pressure over 30 mbar predicted diffuse alveolar damage with specificity of 100%. Lower inflection point values on the static pressure-volume loop was higher in patients with diffuse alveolar damage than in patients with local lung injury--12 mbar (95% CI 7-17) vs. 6 mbar (95% CI 5-10), (p = 0.042, n = 23). Effective (linear) compliance had poor prognostic value for differential diagnostics of acute respiratory failure due to parenchimal lung injury (p = 0.023). CONCLUSION: Lung CT plays leading role in differential diagnostics of parenchymal lung failure developing during mechanical ventilation. In the luck of CT scan elevation of plateau pressure over 30 mbar and values of lower inflection point on the static pressure-volume loop over 12 mbar can predict ARDS.

Host response to mechanical ventilation for viral respiratory tract infection.

Respiratory syncytial virus (RSV) bronchiolitis causes severe respiratory tract infection in infants, frequently necessitating mechanical ventilatory support. However, life-saving, mechanical ventilation aggravates lung inflammation. We set up a model to dissect the host molecular response to mechanical ventilation in RSV infection. Furthermore, the response to induced hypercapnic acidosis, reported to dampen the inflammatory response to mechanical ventilation in non-infectious models, was assessed. BALB/c mice were inoculated with RSV or mock-suspension and ventilated for 5 h on day 5 post inoculation. Mechanical ventilation of infected mice resulted in enhanced cellular influx and increased concentrations of pro-inflammatory cytokines in the bronchoalveolar space. Microarray analysis showed that enhanced inflammation was associated with a molecular signature of a stress response to mechanical ventilation with little effect on the virus-induced innate immune response. Hypercapnic acidosis during mechanical ventilation of infected mice did not change host transcript profiles. We conclude that mechanical ventilation during RSV infection adds a robust but distinct molecular stress response to virus-induced innate immunity activation, emphasising the importance of lung-protective mechanical ventilation strategies. Induced hypercapnic acidosis has no major effect on host transcription profiles during mechanical ventilation for RSV infection, suggesting that this is a safe approach to minimise ventilator-induced lung injury.

Beyond volutrauma in ARDS: the critical role of lung tissue deformation.

Ventilator-induced lung injury (VILI) consists of tissue damage and a biological response resulting from the application of inappropriate mechanical forces to the lung parenchyma. The current paradigm attributes VILI to overstretching due to very high-volume ventilation (volutrauma) and cyclic changes in aeration due to very low-volume ventilation (atelectrauma); however, this model cannot explain some research findings. In the present review, we discuss the relevance of cyclic deformation of lung tissue as the main determinant of VILI. Parenchymal stability resulting from the interplay of respiratory parameters such as tidal volume, positive end-expiratory pressure or respiratory rate can explain the results of different clinical trials and experimental studies that do not fit with the classic volutrauma/atelectrauma model. Focusing on tissue deformation could lead to new bedside monitoring and ventilatory strategies.

A 29-Year-Old Male with a Fatal Case of COVID-19 Acute Respiratory Distress Syndrome (CARDS) and Ventilator-Induced Lung Injury (VILI).

BACKGROUND COVID-19 patients that develop acute respiratory distress syndrome (ARDS) "CARDS" behave differently compared to patients with classic forms of ARDS. Recently 2 CARDS phenotypes have been described, Type L and Type H. Most patients stabilize at the milder form, Type L, while an unknown subset progress to Type H, resembling full-blown ARDS. If uncorrected, phenotypic conversion can induce a rapid downward spiral towards progressive lung injury, vasoplegia, and pulmonary shrinkage, risking ventilator-induced lung injury (VILI) known as the "VILI vortex". No cases of in-hospital phenotypic conversion have been reported, while ventilation strategies in these patients differ from the lung-protective approaches seen in classic ARDS. CASE REPORT A 29-year old male was admitted with COVID-19 pneumonia complicated by severe ARDS, multi-organ failure, cytokine release syndrome, and coagulopathy during his admission. He initially resembled CARDS Type L case, although refractory hypoxemia, fevers, and a high viral burden prompted conversion to Type H within 8 days. Despite ventilation strategies, neuromuscular blockade, inhalation therapy, and vitamin C, he remained asynchronous to the ventilator with volumes and pressures beyond accepted thresholds, eventually developing a fatal tension pneumothorax. CONCLUSIONS Patients that convert to Type H can quickly enter a spiral of hypoxemia, shunting, and dead-space ventilation towards full-blown ARDS. Understanding its nuances is vital to interrupting phenotypic conversion and entry into VILI vortex. Tension pneumothorax represents a poor outcome in patients with CARDS. Further research into monitoring lung dynamics, modifying ventilation strategies, and understanding response to various modes of ventilation in CARDS are required to mitigate these adverse outcomes.

Ventilation, oxidative stress and risk of brain injury in preterm newborn.

Preterm infants have an increased risk of cognitive and behavioral deficits and cerebral palsy compared to term born babies. Especially before 32 weeks of gestation, infants may require respiratory support, but at the same time, ventilation is known to induce oxidative stress, increasing the risk of brain injury. Ventilation may cause brain damage through two pathways: localized cerebral inflammatory response and hemodynamic instability. During ventilation, the most important causes of pro-inflammatory cytokine release are oxygen toxicity, barotrauma and volutrauma. The purpose of this review was to analyze the mechanism of ventilation-induced lung injury (VILI) and the relationship between brain injury and VILI in order to provide the safest possible respiratory support to a premature baby. As gentle ventilation from the delivery room is needed to reduce VILI, it is recommended to start ventilation with 21-30% oxygen, prefer a non-invasive respiratory approach and, if mechanical ventilation is required, prefer low Positive End-Expiratory Pressure and tidal volume.

Ly-6Chigh inflammatory-monocyte recruitment is regulated by p38 MAPK/MCP-1 activation and promotes ventilator-induced lung injury.

Lymphocyte antigen 6Chigh (Ly-6Chigh) inflammatory monocytes, as novel mononuclear cells in the innate immune system, participate in infectious diseases. In this study, we investigated the potential role of these monocytes in ventilator-induced lung injury (VILI) and the possible mechanism involved in their migration to lung tissue. Our results showed that mechanical ventilation with high tidal volume (HTV) increased the accumulation of Ly-6Chigh inflammatory monocytes in lung tissues and that blocking C­C chemokine receptor 2 (CCR2) could significantly reduce Ly-6Chigh inflammatory-monocyte migration and attenuate the degree of inflammation of lung tissues. In addition, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) activity could decrease the secretion of monocyte chemoattractant protein 1 (MCP-1), which in turn decreased the migration of Ly-6Chigh inflammatory monocytes into lung tissue. We also demonstrated that high ventilation caused Ly-6Chigh inflammatory monocytes in the bone marrow to migrate into and aggregate in the lungs, creating inflammation, and that the mechanism was quite different from that of infectious diseases. Ly-6Chigh inflammatory monocytes might play a pro-inflammatory role in VILI, and blocking their infiltration into lung tissue might become a new target for the treatment of this injury.