Effect of patient-ventilator asynchrony on lung and diaphragmatic injury in experimental acute respiratory distress syndrome in a porcine model.

BACKGROUND: Patient-ventilator asynchrony during mechanical ventilation may exacerbate lung and diaphragm injury in spontaneously breathing subjects. We investigated whether subject-ventilator asynchrony increases lung or diaphragmatic injury in a porcine model of acute respiratory distress syndrome (ARDS). METHODS: ARDS was induced in adult female pigs by lung lavage and injurious ventilation before mechanical ventilation by pressure assist-control for 12 h. Mechanically ventilated pigs were randomised to breathe spontaneously with or without induced subject-ventilator asynchrony or neuromuscular block (n=7 per group). Subject-ventilator asynchrony was produced by ineffective, auto-, or double-triggering of spontaneous breaths. The primary outcome was mean alveolar septal thickness (where thickening of the alveolar wall indicates worse lung injury). Secondary outcomes included distribution of ventilation (electrical impedance tomography), lung morphometric analysis, inflammatory biomarkers (gene expression), lung wet-to-dry weight ratio, and diaphragmatic muscle fibre thickness. RESULTS: Subject-ventilator asynchrony (median [interquartile range] 28.8% [10.4] asynchronous breaths of total breaths; n=7) did not increase mean alveolar septal thickness compared with synchronous spontaneous breathing (asynchronous breaths 1.0% [1.6] of total breaths; n=7). There was no difference in mean alveolar septal thickness throughout upper and lower lung lobes between pigs randomised to subject-ventilator asynchrony vs synchronous spontaneous breathing (87.3-92.2 µm after subject-ventilator asynchrony, compared with 84.1-95.0 µm in synchronised spontaneous breathing;). There were also no differences between groups in wet-to-dry weight ratio, diaphragmatic muscle fibre thickness, atelectasis, lung aeration, or mRNA expression levels for inflammatory cytokines pivotal in ARDS pathogenesis. CONCLUSIONS: Subject-ventilator asynchrony during spontaneous breathing did not exacerbate lung injury and dysfunction in experimental porcine ARDS.

Predictive ability of viscoelastic testing using ClotPro® for short-term outcome in patients with severe Covid-19 ARDS with or without ECMO therapy: a retrospective study.

BACKGROUND: SARS-CoV-2 infections are suspected to trigger the coagulation system through various pathways leading to a high incidence of thromboembolic complications, hypercoagulation and impaired fibrinolytic capacity were previously identified as potentially mechanisms. A reliable diagnostic tool for detecting both is still under discussion. This retrospective study is aimed to examine the prognostic relevance of early viscoelastic testing compared to conventional laboratory tests in COVID-19 patients with acute respiratory distress syndrome (ARDS). METHODS: All mechanically ventilated patients with COVID-19 related ARDS treated in our intensive care unit (ICU) between January and March 2021 were included in this study. Viscoelastic testing (VET) was performed using the ClotPro® system after admission to our ICU. Prevalence of thromboembolic events was observed by standardized screening for venous and pulmonary thromboembolism using complete compression ultrasound and thoracic computed tomography pulmonary angiography at ICU admission, respectively. We examined associations between the severity of ARDS at admission to our ICU, in-hospital mortality and the incidence of thromboembolic events comparing conventional laboratory analysis and VET. ECMO related coagulopathy was investigated in a subgroup analysis. The data were analyzed using the Mann-Whitney U test. RESULTS: Of 55 patients enrolled in this study, 22 patients required treatment with ECMO. Thromboembolic complications occurred in 51% of all patients. Overall hospital mortality was 55%. In patients with thromboembolic complications, signs of reduced fibrinolytic capacity could be detected in the TPA assay with prolonged lysis time, median 460 s (IQR 350-560) vs 359 s (IQR 287-521, p = 0.073). Patients with moderate to severe ARDS at admission to our ICU showed increased maximum clot firmness as a sign of hypercoagulation in the EX-test (70 vs 67 mm, p < 0.05), FIB-test (35 vs 24 mm, p < 0.05) and TPA-test (52 vs 36 mm, p < 0.05) as well as higher values of inflammatory markers (CRP, PCT and IL6). ECMO patients suffered more frequently from bleeding complications (32% vs 15%). CONCLUSION: Although, the predictive value for thromboembolic complications or mortality seems limited, point-of-care viscoelastic coagulation testing might be useful in detecting hypercoagulable states and impaired fibrinolysis in critically ill COVID-19 ARDS patients and could be helpful in identifying patients with a potentially very severe course of the disease.

Changes in lung aeration and respiratory function after open abdominal surgery: A quantitative magnetic resonance imaging study.

BACKGROUND: Atelectasis is one of the most common respiratory complications in patients undergoing open abdominal surgery. Peripheral oxygen saturation (SpO2 ) and forced vital capacity (FVC) are bedside indicators of postoperative respiratory dysfunction. The aim of this study was to describe the changes in lung aeration, using quantitative analysis of magnetic resonance imaging (MRI) and the diagnostic accuracy of SpO2 and FVC to detect postoperative atelectasis. METHODS: Post-hoc analysis of a randomized trial conducted at a University Hospital in Dresden, Germany. Patients undergoing pre- and postoperative lung MRI were included. MRI signal intensity was analyzed quantitatively to define poorly and nonaerated lung compartments. Postoperative atelectasis was defined as nonaerated lung volume above 2% of the total lung volume in the respective MRI investigation. RESULTS: This study included 45 patients, 27 with and 18 patients without postoperative atelectasis. Patients with atelectasis had higher body mass index (p = .024), had more preoperative poorly aerated lung volume (p = .049), a lower preoperative SpO2 (p = .009), and a lower preoperative FVC (p = .029). The amount of atelectasis correlated with preoperative SpO2 (Spearman's ρ = -.51, p < .001) and postoperative SpO2 (ρ = -.60, p < .001), and with preoperative FVC (ρ = -.29, p = .047) and postoperative FVC (ρ = -.40, p = .006). A postoperative SpO2 ≤ 94% had 74% sensitivity and 78% specificity to detect atelectasis, while postoperative FVC ≤ 50% had 56% sensitivity and 100% specificity to detect atelectasis. CONCLUSION: SpO2 and FVC correlated with the amount of postoperative non-aerated lung volume, showing acceptable diagnostic accuracy in bedside detection of postoperative atelectasis.

Comparative effects of neurally adjusted ventilatory assist and variable pressure support on lung and diaphragmatic function in a model of acute respiratory distress syndrome: A randomised animal study.

BACKGROUND: Variable assisted mechanical ventilation has been shown to improve lung function and reduce lung injury. However, differences between extrinsic and intrinsic variability are unknown. OBJECTIVE: To investigate the effects of neurally adjusted ventilatory assist (NAVA, intrinsic variability), variable pressure support ventilation (Noisy PSV, extrinsic variability) and conventional pressure-controlled ventilation (PCV) on lung and diaphragmatic function and damage in experimental acute respiratory distress syndrome (ARDS). DESIGN: Randomised controlled animal study. SETTING: University Hospital Research Facility. SUBJECTS: A total of 24 juvenile female pigs. INTERVENTIONS: ARDS was induced by repetitive lung lavage and injurious ventilation. Animals were randomly assigned to 24 h of either: 1) NAVA, 2) Noisy PSV or 3) PCV (n=8 per group). Mechanical ventilation settings followed the ARDS Network recommendations. MEASUREMENTS: The primary outcome was histological lung damage. Secondary outcomes were respiratory variables and patterns, subject-ventilator asynchrony (SVA), pulmonary and diaphragmatic biomarkers, as well as diaphragmatic muscle atrophy and myosin isotypes. RESULTS: Global alveolar damage did not differ between groups, but NAVA resulted in less interstitial oedema in dorsal lung regions than Noisy PSV. Gas exchange and SVA incidence did not differ between groups. Compared with Noisy PSV, NAVA generated higher coefficients of variation of tidal volume and respiratory rate. During NAVA, only 40.4% of breaths were triggered by the electrical diaphragm signal. The IL-8 concentration in lung tissue was lower after NAVA compared with PCV and Noisy PSV, whereas Noisy PSV yielded lower type III procollagen mRNA expression than NAVA and PCV. Diaphragmatic muscle fibre diameters were smaller after PCV compared with assisted modes, whereas expression of myosin isotypes did not differ between groups. CONCLUSION: Noisy PSV and NAVA did not reduce global lung injury compared with PCV but affected different biomarkers and attenuated diaphragmatic atrophy. NAVA increased the respiratory variability; however, NAVA yielded a similar SVA incidence as Noisy PSV. TRIAL REGISTRATION: This trial was registered and approved by the Landesdirektion Dresden, Germany (AZ 24-9168.11-1/2012-2).

Effects of variable versus nonvariable controlled mechanical ventilation on pulmonary inflammation in experimental acute respiratory distress syndrome in pigs.

BACKGROUND: Mechanical ventilation with variable tidal volumes (VT) may improve lung function and reduce ventilator-induced lung injury in experimental acute respiratory distress syndrome (ARDS). However, previous investigations were limited to less than 6 h, and control groups did not follow clinical standards. We hypothesised that 24 h of mechanical ventilation with variable VT reduces pulmonary inflammation (as reflected by neutrophil infiltration), compared with standard protective, nonvariable ventilation. METHODS: Experimental ARDS was induced in 14 anaesthetised pigs with saline lung lavage followed by injurious mechanical ventilation. Pigs (n=7 per group) were randomly assigned to using variable VT or nonvariable VT modes of mechanical ventilation for 24 h. In both groups, ventilator settings including positive end-expiratory pressure and oxygen inspiratory fraction were adjusted according to the ARDS Network protocol. Pulmonary inflammation (primary endpoint) and perfusion were assessed by positron emission tomography using 2-deoxy-2-[18F]fluoro-d-glucose and 68Gallium (68Ga)-labelled microspheres, respectively. Gas exchange, respiratory mechanics, and haemodynamics were quantified. Lung aeration was determined using CT. RESULTS: The specific global uptake rate of 18F-FDG increased to a similar extent regardless of mode of mechanical ventilation (median uptake for variable VT=0.016 min-1 [inter-quartile range, 0.012-0.029] compared with median uptake for nonvariable VT=0.037 min-1 [0.008-0.053]; P=0.406). Gas exchange, respiratory mechanics, haemodynamics, and lung aeration and perfusion were similar in both variable and nonvariable VT ventilatory modes. CONCLUSION: In a porcine model of ARDS, 24 h of mechanical ventilation with variable VT did not attenuate pulmonary inflammation compared with standard protective mechanical ventilation with nonvariable VT.

Association between pre-operative biological phenotypes and postoperative pulmonary complications: An unbiased cluster analysis.

BACKGROUND: Biological phenotypes have been identified within several heterogeneous pulmonary diseases, with potential therapeutic consequences. OBJECTIVE: To assess whether distinct biological phenotypes exist within surgical patients, and whether development of postoperative pulmonary complications (PPCs) and subsequent dependence of intra-operative positive end-expiratory pressure (PEEP) differ between such phenotypes. SETTING: Operating rooms of six hospitals in Europe and USA. DESIGN: Secondary analysis of the 'PROtective Ventilation with HIgh or LOw PEEP' trial. PATIENTS: Adult patients scheduled for abdominal surgery who are at risk of PPCs. INTERVENTIONS: Measurement of pre-operative concentrations of seven plasma biomarkers associated with inflammation and lung injury. MAIN OUTCOME MEASURES: We applied unbiased cluster analysis to identify biological phenotypes. We then compared the proportion of patients developing PPCs within each phenotype, and associations between intra-operative PEEP levels and development of PPCs among phenotypes. RESULTS: In total, 242 patients were included. Unbiased cluster analysis clustered the patients within two biological phenotypes. Patients with phenotype 1 had lower plasma concentrations of TNF-α (3.8 [2.4 to 5.9] vs. 10.2 [8.0 to 12.1] pg ml; P < 0.001), IL-6 (2.3 [1.5 to 4.0] vs. 4.0 [2.9 to 6.5] pg ml; P < 0.001) and IL-8 (4.7 [3.1 to 8.1] vs. 8.1 [6.0 to 13.9] pg ml; P < 0.001). Phenotype 2 patients had the highest incidence of PPC (69.8 vs. 34.2% in type 1; P < 0.001). There was no interaction between phenotype and PEEP level for the development of PPCs (43.2% in high PEEP vs. 25.6% in low PEEP in phenotype 1, and 73.6% in high PEEP and 65.7% in low PEEP in phenotype 2; P for interaction = 0.503). CONCLUSION: Patients at risk of PPCs and undergoing open abdominal surgery can be clustered based on pre-operative plasma biomarker concentrations. The two identified phenotypes have different incidences of PPCs. Biologic phenotyping could be useful in future randomised controlled trials of intra-operative ventilation. TRIAL REGISTRATION: The PROtective Ventilation with HIgh or LOw PEEP trial, including the substudy from which data were used for the present analysis, was registered at ClinicalTrials.gov (NCT01441791).

Kinetics of plasma biomarkers of inflammation and lung injury in surgical patients with or without postoperative pulmonary complications.

BACKGROUND: Postoperative pulmonary complications (PPCs) are common after major abdominal surgery. The kinetics of plasma biomarkers could improve identification of patients developing PPCs, but the kinetics may depend on intraoperative ventilator settings. OBJECTIVE: To test whether the kinetics of plasma biomarkers are capable of identifying patients who will develop PPCs, and whether the kinetics depend on the intraoperative level of positive end-expiratory pressure (PEEP). DESIGN: A preplanned substudy of a randomised controlled trial. SETTING: Operation room of five centres. PATIENTS: Two hundred and forty-two adult patients scheduled for abdominal surgery at risk of developing PPCs. INTERVENTIONS: High (12 cmH2O) versus low (≤2 cmH2O) levels of PEEP. MAIN OUTCOME MEASURES: Individual PPCs were combined as a composite endpoint. Plasma samples were collected before surgery, directly after surgery and on the fifth postoperative day. The levels of the following were measured: tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8, the soluble form of the Receptor for Advanced Glycation End-products (sRAGE), Surfactant Protein (SP)-D, Clara Cell protein (CC)-16 and Krebs von den Lungen 6 (KL6). RESULTS: Blood sampling was complete in 242 patients: 120 patients in the high PEEP group and 122 patients in the low PEEP group. Increases in plasma levels of TNF- IL-6, IL-8 and CC-16, and a decrease in plasma levels of SP-D were greater in patients who developed PPCs; however, the area under the receiver operating characteristic curve was low for all biomarkers. CC-16 was the only biomarker whose level increased more in patients who had received high levels of PEEP. CONCLUSION: In patients undergoing abdominal surgery and at risk of developing PPCs, plasma levels of biomarkers for inflammation or lung injury showed distinct kinetics with development of PPCs, but none of the biomarkers showed sufficient prognostic value. The use of high levels of PEEP was associated with increased levels of CC-16, suggesting lung overdistension. TRIAL REGISTRATION: The PROVHILO trial, including this substudy, was registered at clinicaltrials.gov (NCT01441791).

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

OBJECTIVE: 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. DESIGN: Laboratory investigation. SETTING: University-hospital research facility. SUBJECTS: Ten pigs (five per group; 34.7-49.9 kg) INTERVENTIONS: : 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Effects of ultraprotective ventilation, extracorporeal carbon dioxide removal, and spontaneous breathing on lung morphofunction and inflammation in experimental severe acute respiratory distress syndrome.

BACKGROUND: To investigate the role of ultraprotective mechanical ventilation (UP-MV) and extracorporeal carbon dioxide removal with and without spontaneous breathing (SB) to improve respiratory function and lung protection in experimental severe acute respiratory distress syndrome. METHODS: Severe acute respiratory distress syndrome was induced by saline lung lavage and mechanical ventilation (MV) with higher tidal volume (VT) in 28 anesthetized pigs (32.8 to 52.5 kg). Animals (n = 7 per group) were randomly assigned to 6 h of MV (airway pressure release ventilation) with: (1) conventional P-MV with VT ≈6 ml/kg (P-MVcontr); (2) UP-MV with VT ≈3 ml/kg (UP-MVcontr); (3) UP-MV with VT ≈3 ml/kg and SB (UP-MVspont); and (4) UP-MV with VT ≈3 ml/kg and pressure supported SB (UP-MVPS). In UP-MV groups, extracorporeal carbon dioxide removal was used. RESULTS: The authors found that: (1) UP-MVcontr reduced diffuse alveolar damage score in dorsal lung zones (median[interquartile]) (12.0 [7.0 to 16.8] vs. 22.5 [13.8 to 40.8]), but worsened oxygenation and intrapulmonary shunt, compared to P-MVcontr; (2) UP-MVspont and UP-MVPS improved oxygenation and intrapulmonary shunt, and redistributed ventilation towards dorsal areas, as compared to UP-MVcontr; (3) compared to P-MVcontr, UP-MVcontr and UP-MVspont, UP-MVPS yielded higher levels of tumor necrosis factor-α (6.9 [6.5 to 10.1] vs. 2.8 [2.2 to 3.0], 3.6 [3.0 to 4.7] and 4.0 [2.8 to 4.4] pg/mg, respectively) and interleukin-8 (216.8 [113.5 to 343.5] vs. 59.8 [45.3 to 66.7], 37.6 [18.8 to 52.0], and 59.5 [36.1 to 79.7] pg/mg, respectively) in dorsal lung zones. CONCLUSIONS: In this model of severe acute respiratory distress syndrome, MV with VT ≈3 ml/kg and extracorporeal carbon dioxide removal without SB slightly reduced lung histologic damage, but not inflammation, as compared to MV with VT = 4 to 6 ml/kg. During UP-MV, pressure supported SB increased lung inflammation.

Intraoperative protective mechanical ventilation for prevention of postoperative pulmonary complications: a comprehensive review of the role of tidal volume, positive end-expiratory pressure, and lung recruitment maneuvers.

Postoperative pulmonary complications are associated with increased morbidity, length of hospital stay, and mortality after major surgery. Intraoperative lung-protective mechanical ventilation has the potential to reduce the incidence of postoperative pulmonary complications. This review discusses the relevant literature on definition and methods to predict the occurrence of postoperative pulmonary complication, the pathophysiology of ventilator-induced lung injury with emphasis on the noninjured lung, and protective ventilation strategies, including the respective roles of tidal volumes, positive end-expiratory pressure, and recruitment maneuvers. The authors propose an algorithm for protective intraoperative mechanical ventilation based on evidence from recent randomized controlled trials.

Modulation of stress versus time product during mechanical ventilation influences inflammation as well as alveolar epithelial and endothelial response in rats.

BACKGROUND: Mechanical ventilation can lead to lung biotrauma when mechanical stress exceeds safety thresholds. The authors investigated whether the duration of mechanical stress, that is, the impact of a stress versus time product (STP), influences biotrauma. The authors hypothesized that higher STP levels are associated with increased inflammation and with alveolar epithelial and endothelial cell injury. METHODS: In 46 rats, Escherichia coli lipopolysaccharide (acute lung inflammation) or saline (control) was administered intratracheally. Both groups were protectively ventilated with inspiratory-to-expiratory ratios 1:2, 1:1, or 2:1 (n = 12 each), corresponding to low, middle, and high STP levels (STPlow, STPmid, and STPhigh, respectively). The remaining 10 animals were not mechanically ventilated. RESULTS: In animals with mild acute lung inflammation, but not in controls: (1) messenger RNA expression of interleukin-6 was higher in STPhigh (28.1 ± 13.6; mean ± SD) and STPlow (28.9 ± 16.0) versus STPmid (7.4 ± 7.5) (P < 0.05); (2) expression of the receptor for advanced glycation end-products was increased in STPhigh (3.6 ± 1.6) versus STPlow (2.3 ± 1.1) (P < 0.05); (3) alveolar edema was decreased in STPmid (0 [0 to 0]; median, Q1 to Q3) compared with STPhigh (0.8 [0.6 to 1]) (P < 0.05); and (4) expressions of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 were higher in STPlow (3.0 ± 1.8) versus STPhigh (1.2 ± 0.5) and STPmid (1.4 ± 0.7) (P < 0.05), respectively. CONCLUSIONS: In the mild acute lung inflammation model used herein, mechanical ventilation with inspiratory-to-expiratory of 1:1 (STPmid) minimized lung damage, whereas STPhigh increased the gene expression of biological markers associated with inflammation and alveolar epithelial cell injury and STPlow increased markers of endothelial cell damage.

[Intraoperative protective ventilation reduces postoperative pulmonary complications - PRO]. / Protektive Beatmung reduziert postoperative pulmonale Komplikationen - Pro.

Postoperative pulmonary complications add to higher mortality and morbidity. This risk could be lowered with intraoperative protective ventilation, especially with low tidal volumes. The application of PEEP and the use of recruitment maneuvers can enhance the lung function during surgery, but can also cause haemodynamic instability. In patients with open abdominal surgery and no lung damage or obesity, PEEP and recruitment maneuvers have no protective effect against postoperative pulmonary complications. It is still unclear, wether the use of intraoperative PEEP in other patient groups and during different surgery procedures is relevant for lung protection.

Higher levels of spontaneous breathing reduce lung injury in experimental moderate acute respiratory distress syndrome.

OBJECTIVES: To assess the effects of different levels of spontaneous breathing during biphasic positive airway pressure/airway pressure release ventilation on lung function and injury in an experimental model of moderate acute respiratory distress syndrome. DESIGN: Multiple-arm randomized experimental study. SETTING: University hospital research facility. SUBJECTS: Thirty-six juvenile pigs. INTERVENTIONS: Pigs were anesthetized, intubated, and mechanically ventilated. Moderate acute respiratory distress syndrome was induced by repetitive saline lung lavage. Biphasic positive airway pressure/airway pressure release ventilation was conducted using the airway pressure release ventilation mode with an inspiratory/expiratory ratio of 1:1. Animals were randomly assigned to one of four levels of spontaneous breath in total minute ventilation (n = 9 per group, 6 hr each): 1) biphasic positive airway pressure/airway pressure release ventilation, 0%; 2) biphasic positive airway pressure/airway pressure release ventilation, > 0-30%; 3) biphasic positive airway pressure/airway pressure release ventilation, > 30-60%, and 4) biphasic positive airway pressure/airway pressure release ventilation, > 60%. MEASUREMENTS AND MAIN RESULTS: The inspiratory effort measured by the esophageal pressure time product increased proportionally to the amount of spontaneous breath and was accompanied by improvements in oxygenation and respiratory system elastance. Compared with biphasic positive airway pressure/airway pressure release ventilation of 0%, biphasic positive airway pressure/airway pressure release ventilation more than 60% resulted in lowest venous admixture, as well as peak and mean airway and transpulmonary pressures, redistributed ventilation to dependent lung regions, reduced the cumulative diffuse alveolar damage score across lungs (median [interquartile range], 11 [3-40] vs 18 [2-69]; p < 0.05), and decreased the level of tumor necrosis factor-α in ventral lung tissue (median [interquartile range], 17.7 pg/mg [8.4-19.8] vs 34.5 pg/mg [29.9-42.7]; p < 0.05). Biphasic positive airway pressure/airway pressure release ventilation more than 0-30% and more than 30-60% showed a less consistent pattern of improvement in lung function, inflammation, and damage compared with biphasic positive airway pressure/airway pressure release ventilation more than 60%. CONCLUSIONS: In this model of moderate acute respiratory distress syndrome in pigs, biphasic positive airway pressure/airway pressure release ventilation with levels of spontaneous breath higher than usually seen in clinical practice, that is, more than 30% of total minute ventilation, reduced lung injury with improved respiratory function, as compared with protective controlled mechanical ventilation.

Higher levels of spontaneous breathing induce lung recruitment and reduce global stress/strain in experimental lung injury.

BACKGROUND: Spontaneous breathing (SB) in the early phase of the acute respiratory distress syndrome is controversial. Biphasic positive airway pressure/airway pressure release ventilation (BIPAP/APRV) is commonly used, but the level of SB necessary to maximize potential beneficial effects is unknown. METHODS: Experimental acute respiratory distress syndrome was induced by saline lung lavage in anesthetized and mechanically ventilated pigs (n = 12). By using a Latin square and crossover design, animals were ventilated with BIPAP/APRV at four different levels of SB in total minute ventilation (60 min each): (1) 0% (BIPAP/APRV0%); (2) greater than 0 to 30% (BIPAP/APRV>0-30%); (3) greater than 30 to 60% (BIPAP/APRV>30-60%); and (4) greater than 60% (BIPAP/APRV>60%). Gas exchange, hemodynamics, and respiratory variables were measured. Lung aeration was assessed by high-resolution computed tomography. The distribution of perfusion was marked with Ga-labeled microspheres and evaluated by positron emission tomography. RESULTS: The authors found that higher levels of SB during BIPAP/APRV (1) improved oxygenation; (2) decreased mean transpulmonary pressure (stress) despite increased inspiratory effort; (3) reduced nonaerated lung tissue, with minimal changes in the distribution of perfusion, resulting in decreased low aeration/perfusion zones; and (4) decreased global strain (mean ± SD) (BIPAP/APRV0%: 1.39 ± 0.08; BIPAP/APRV0-30%: 1.33 ± 0.03; BIPAP/APRV30-60%: 1.27 ± 0.06; BIPAP/APRV>60%: 1.25 ± 0.04, P < 0.05 all vs. BIPAP/APRV0%, and BIPAP/APRV>60% vs. BIPAP/APRV0-30%). CONCLUSIONS: In a saline lung lavage model of experimental acute respiratory distress syndrome in pigs, levels of SB during BIPAP/APRV higher than currently recommended for clinical practice, that is, 10 to 30%, improve oxygenation by increasing aeration in dependent lung zones without relevant redistribution of perfusion. In presence of lung recruitment, higher levels of SB reduce global stress and strain despite an increase in inspiratory effort.

Spontaneous breathing in mild and moderate versus severe acute respiratory distress syndrome.

PURPOSE OF REVIEW: This review summarizes the most recent clinical and experimental data on the impact of spontaneous breathing in acute respiratory distress syndrome (ARDS). RECENT FINDINGS: Spontaneous breathing during assisted as well as nonassisted modes of mechanical ventilation improves lung function and reduces lung damage in mild and moderate ARDS. New modes of assisted mechanical ventilation with improved patient ventilator interaction and enhanced variability of the respiratory pattern offer additional benefit on lung function and damage. However, data supporting an outcome benefit of spontaneous breathing in ARDS, even in its mild and moderate forms, are missing. In contrast, controlled mechanical ventilation with muscle paralysis in the first 48 h of severe ARDS has been shown to improve survival, as compared with placebo. Currently, it is unclear whether ventilator settings, rather than the severity of lung injury, determine the potential of spontaneous breathing for benefit or harm. SUMMARY: Clinical and experimental studies show that controlled mechanical ventilation with muscle paralysis in the early phase of severe ARDS reduces lung injury and even mortality. At present, spontaneous breathing should be avoided in the early phase of severe ARDS, but considered in mild-to-moderate ARDS.

A new adaptive controller for volume-controlled mechanical ventilation in small animals.

BACKGROUND: This study aimed to develop and evaluate an adaptive control system for volume-controlled ventilation (VCV) in small animals to guarantee accurate delivery of tidal volume (VT) in the presence of changes in lung mechanics. METHODS: The adaptive control system to control the Harvard Inspira ventilator was designed and evaluated on a custom-made physical model during step changes of resistance and elastance of the respiratory system assessing difference in minute ventilation (ΔMVc) during convergence cycles (NC). The controller was then evaluated during conventional and variable volume VCV in rats with acute respiratory distress syndrome (ARDS) induced by intratracheal HCl (six animals/group), where the difference between desired and applied VT (dVT,d), its root-mean square error (RMSE) and relative deviation from target minute ventilation (ΔMV) were determined. RESULTS: The controller showed fast convergence NC < 20 cycles with an acceptable ΔMVC < 10% in simulations and nearly abolished dVT,d (VCV: 0.23 ± 0.1 mL to 0.0 ± 0.0 mL, P < .001 and vVCV: 0.05 ± 0.8 mL to 0.0 ± 0.0 mL, P < .001), significantly reduced RMSE (VCV: 0.23 ± 0.1 to 0.04 ± 0.01 mL, P < .001 and vVCV: 0.13 ± 0.04 to 0.08 ± 0.02 mL, P < .001) and ΔMV (VCV: 11.6 ± 4.2 to 0.04 ± 0.15%, P < .001 and vVCV: -3 ± 3.8 to -0.35 ± 1.3 %, P < .001) in animal experiments. In VCV the improvement was more pronounced, due to reduced respiratory system elastance in this group (VCV: 5.6 cmH2O mL(-1) versus vVCV: 3.8 cmH2O mL(-1), P < .001). CONCLUSIONS: The new adaptive controller ensured accurate delivery of VT in VCV and proved valuable for mechanical ventilation of small animals especially in ARDS research.

[Ventilation concepts under extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome (ARDS)]. / Beatmungskonzepte unter extrakorporaler Membranoxygenierung bei akutem Lungenversagen.

Extracorporeal membrane oxygenation (ECMO) is often the last resort for escalation of treatment in patients with severe acute respiratory distress syndrome (ARDS). The success of treatment is mainly determined by patient-specific factors, such as age, comorbidities, duration and invasiveness of the pre-existing ventilation treatment as well as the expertise of the treating ECMO center. In particular, the adjustment of mechanical ventilation during ongoing ECMO treatment remains controversial. Although a reduction of invasiveness of mechanical ventilation seems to be reasonable due to physiological considerations, no improvement in outcome has been demonstrated so far for the use of ultraprotective ventilation regimens.

Nucleated red blood cells as a prognostic marker for mortality in patients with SARS-CoV-2-induced ARDS: an observational study.

BACKGROUND: The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with poor outcome. Evidence regarding the predictive value of NRBCs in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) remains elusive. The aim of this study was to evaluate the predictive validity of NRBCs in these patients. METHODS: Daily NRBC values of adult patients with SARS-CoV-2-induced ARDS were assessed and their predictive validity for mortality was statistically evaluated. A cut-off level based on the patient's maximum NRBC value during ICU stay was calculated and further specified according to Youden's method. Based on this cut-off value, further analyses such as logistic regression models and survival were performed. RESULTS: 413 critically ill patients with SARS-CoV-2-induced ARDS were analyzed. Patients who did not survive had significantly higher NRBC values during their ICU stay compared to patients who survived (1090/µl [310; 3883] vs. 140/µl [20; 500]; p < 0.0001). Patients with severe ARDS (n = 374) had significantly higher NRBC values during ICU stay compared to patients with moderate ARDS (n = 38) (490/µl [120; 1890] vs. 30/µl [10; 476]; p < 0.0001). A cut-off level of NRBC ≥ 500/µl was found to best stratify risk and was associated with a longer duration of ICU stay (12 [8; 18] vs. 18 [13; 27] days; p < 0.0001) and longer duration of mechanical ventilation (10 [6; 16] vs. 17 [12; 26] days; p < 0.0001). Logistic regression analysis with multivariate adjustment showed NRBCs ≥ 500/µl to be an independent risk factor of mortality (odds ratio (OR) 4.72; 95% confidence interval (CI) 2.95-7.62, p < 0.0001). Patients with NRBC values below the threshold of 500/µl had a significant survival advantage over those above the threshold (median survival 32 [95% CI 8.7-43.3] vs. 21 days [95% CI 18.2-23.8], log-rank test, p < 0.05). Patients who once reached the NRBC threshold of ≥ 500/µl during their ICU stay had a significantly increased long-term mortality (median survival 489 days, log-rank test, p = 0.0029, hazard ratio (HR) 3.2, 95% CI 1.2-8.5). CONCLUSIONS: NRBCs predict mortality in critically ill patients with SARS-CoV-2-induced ARDS with high prognostic power. Further studies are required to confirm the clinical impact of NRBCs to eventually enhance decision making.

Effects of intravascular volume replacement on lung and kidney function and damage in nonseptic experimental lung injury.

BACKGROUND: Intravascular volume replacement is often required in the presence of increased pulmonary capillary leakage, for example in patients with volutrauma with major hemorrhage. In the present study, the effects of Ringer's acetate (RA), gelatin-polysuccinate (GEL), and a modern hydroxyethyl starch (HES, 6% 130/0.42) on lung and kidney function and damage were compared in a two-hit model of acute lung injury. The authors hypothesized that GEL and HES, compared to RA: (1) reduced lung histological damage, (2) impaired kidney morphology and function. METHODS: Acute lung injury was induced in 30 anesthetized pigs by tidal volumes approximately 40 ml/kg, after saline lung lavage. Protective ventilation was initiated and approximately≈25% of estimated blood volume was drawn. Animals were randomly assigned to receive RA, GEL, or HES (n = 10/group) aimed at approximately 90% of intrathoracic blood volume before blood drainage. RESULTS: Fluid volumes were higher with RA (2,250 ± 764 ml) than GEL (704 ± 159 ml) and HES (837 ± 82 ml) (P < 0.05). Compared to RA, HES reduced diffuse alveolar damage overall, and GEL in nondependent zones only. GEL and HES yielded lower wet-to-dry ratios compared to RA (6.5 ± 0.5 and 6.5 ± 0.6 vs. 7.9 ± 0.9, respectively, P < 0.05). HES and RA resulted in less kidney damage than GEL, but kidney function did not differ significantly among groups. Compared to GEL, HES yielded lower lung elastance (55 ± 12 vs. 45 ± 13 cm H2O/l, P < 0.05) and intra-abdominal pressure (15 ± 5 vs. 11 ± 4 cm 14;H2O, P < 0.05). CONCLUSIONS: In this model of acute lung injury, intravascular volume expansion after major hemorrhage with HES yielded less lung damage than RA and less kidney damage than GEL.