Influence of Fractional Inspired Oxygen Tension on Lung Perfusion Distribution, Regional Ventilation, and Lung Volume during Mechanical Ventilation of Supine Healthy Swine.

BACKGROUND: Lower fractional inspired oxygen tension (Fio2) during general anesthesia can reduce lung atelectasis. The objectives are to evaluate the effect of two Fio2 (0.4 and 1) during low positive end-expiratory pressure (PEEP) ventilation over lung perfusion distribution, volume, and regional ventilation. These variables were evaluated at two PEEP levels and unilateral lung atelectasis. METHODS: In this exploratory study, 10 healthy female piglets (32.3 ± 3.4 kg) underwent mechanical ventilation in two atelectasis models: (1) bilateral gravitational atelectasis (n = 6), induced by changes in PEEP and Fio2 in three combinations: high PEEP with low Fio2 (Fio2 = 0.4), zero PEEP (PEEP0) with low Fio2 (Fio2 = 0.4), and PEEP0 with high Fio2 (Fio2 = 1); and (2) unilateral atelectasis (n = 6), induced by left bronchial occlusion, with the left lung aerated (Fio2 = 0.21) and low aerated (Fio2 = 1; n = 5 for this step). Measurements were conducted after 10 min in each step, encompassing assessment of respiratory mechanics, oxygenation, and hemodynamics; lung ventilation and perfusion by electrical impedance tomography; and lung aeration and perfusion by computed tomography. RESULTS: During bilateral gravitational atelectasis, PEEP reduction increased atelectasis in dorsal regions, decreased respiratory compliance, and distributed lung ventilation to ventral regions with a parallel shift of perfusion to the same areas. With PEEP0, there were no differences between low and high Fio2 in respiratory compliance (23.9 ± 6.5 ml/cm H2O vs. 21.9 ± 5.0; P = 0.441), regional ventilation, and regional perfusion, despite higher lung collapse (18.6 ± 7.6% vs. 32.7 ± 14.5%; P = 0.045) with high Fio2. During unilateral lung atelectasis, the deaerated lung had a lower shunt (19.3 ± 3.6% vs. 25.3 ± 5.5%; P = 0.045) and lower computed tomography perfusion to the left lung (8.8 ± 1.8% vs. 23.8 ± 7.1%; P = 0.007). CONCLUSIONS: PEEP0 with low Fio2, compared with high Fio2, did not produce significant changes in respiratory system compliance, regional lung ventilation, and perfusion despite significantly lower lung collapse. After left bronchial occlusion, the shrinkage of the parenchyma with Fio2 = 1 enhanced hypoxic pulmonary vasoconstriction, reducing intrapulmonary shunt and perfusion of the nonventilated areas.

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in Acute Respiratory Distress Syndrome with Class III Obesity. A Clinical Trial.

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension.Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6).Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7-10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and [Formula: see text]/[Formula: see text] matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13-4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2-0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15-6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the [Formula: see text]/[Formula: see text] ratio.Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure.Clinical trial registered with www.clinicaltrials.gov (NCT02503241).

Driving pressure and long-term outcomes in moderate/severe acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) patients may present impaired in lung function and structure after hospital discharge that may be related to mechanical ventilation strategy. The aim of this study was to evaluate the association between functional and structural lung impairment, N-terminal-peptide type III procollagen (NT-PCP-III) and driving pressure during protective mechanical ventilation. It was a secondary analysis of data from randomized controlled trial that included patients with moderate/severe ARDS with at least one follow-up visit performed. We obtained serial measurements of plasma NT-PCP-III levels. Whole-lung computed tomography analysis and pulmonary function test were performed at 1 and 6 months of follow-up. A health-related quality of life survey after 6 months was also performed. RESULTS: Thirty-three patients were enrolled, and 21 patients survived after 6 months. In extubation day an association between driving pressure and NT-PCP-III was observed. At 1 and 6 months forced vital capacity (FVC) was negatively correlated to driving pressure (p < 0.01). At 6 months driving pressure was associated with lower FVC independently on tidal volume, plateau pressure and baseline static respiratory compliance after adjustments (r2 = 0.51, p = 0.02). There was a significant correlation between driving pressure and lung densities and nonaerated/poorly aerated lung volume after 6 months. Driving pressure was also related to general health domain of SF-36 at 6 months. CONCLUSION: Even in patients ventilated with protective tidal volume, higher driving pressure is associated with worse long-term pulmonary function and structure.

Quantitative Dual-Energy Computed Tomography Predicts Regional Perfusion Heterogeneity in a Model of Acute Lung Injury.

OBJECTIVE: The aims of this study were to investigate the ability of contrast-enhanced dual-energy computed tomography (DECT) for assessing regional perfusion in a model of acute lung injury, using dynamic first-pass perfusion CT (DynCT) as the criterion standard and to evaluate if changes in lung perfusion caused by prone ventilation are similarly demonstrated by DECT and DynCT. METHODS: This was an institutional review board-approved study, compliant with guidelines for humane care of laboratory animals. A ventilator-induced lung injury protocol was applied to 6 landrace pigs. Perfused blood volume (PBV) and pulmonary blood flow (PBF) were respectively quantified by DECT and DynCT, in supine and prone positions. The lungs were segmented in equally sized regions of interest, namely, dorsal, middle, and ventral. Perfused blood volume and PBF values were normalized by lung density. Regional air fraction (AF) was assessed by triple-material decomposition DECT. Per-animal correlation between PBV and PBF was assessed with Pearson R. Regional differences in PBV, PBF, and AF were evaluated with 1-way analysis of variance and post hoc linear trend analysis (α = 5%). RESULTS: Mean correlation coefficient between PBV and PBF was 0.70 (range, 0.55-0.98). Higher PBV and PBF values were observed in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were -10.24 mL/100 g per zone for PBV (P < 0.001) and -223.0 mL/100 g per minute per zone for PBF (P < 0.001). Prone ventilation also revealed higher PBV and PBF in dorsal versus ventral regions. Dorsal-to-ventral linear trend slopes were -16.16 mL/100 g per zone for PBV (P < 0.001) and -108.2 mL/100 g per minute per zone for PBF (P < 0.001). By contrast, AF was lower in dorsal versus ventral regions in supine position, with dorsal-to-ventral linear trend slope of +5.77%/zone (P < 0.05). Prone ventilation was associated with homogenization of AF distribution among different regions (P = 0.74). CONCLUSIONS: Dual-energy computed tomography PBV is correlated with DynCT-PBF in a model of acute lung injury, and able to demonstrate regional differences in pulmonary perfusion. Perfusion was higher in the dorsal regions, irrespectively to decubitus, with more homogeneous lung aeration in prone position.

High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious.

RATIONALE: In acute respiratory distress syndrome (ARDS), atelectatic solid-like lung tissue impairs transmission of negative swings in pleural pressure (Ppl) that result from diaphragmatic contraction. The localization of more negative Ppl proportionally increases dependent lung stretch by drawing gas either from other lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator. Lowering the level of spontaneous effort and/or converting solid-like to fluid-like lung might render spontaneous effort noninjurious. OBJECTIVES: To determine whether spontaneous effort increases dependent lung injury, and whether such injury would be reduced by recruiting atelectatic solid-like lung with positive end-expiratory pressure (PEEP). METHODS: Established models of severe ARDS (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon manometry), and stretch (electrical impedance tomography; pig) were measured. Respiratory drive was evaluated in 11 patients with ARDS. MEASUREMENTS AND MAIN RESULTS: Although injury during muscle paralysis was predominantly in nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory effort increased injury (indicated by positron emission tomography and histology) in dependent lung. Stronger effort (vs. muscle paralysis) caused local overstretch and greater tidal recruitment in dependent lung, where more negative Ppl was localized and greater stretch was generated. In contrast, high PEEP minimized lung injury by more uniformly distributing negative Ppl, and lowering the magnitude of spontaneous effort (i.e., deflection in esophageal pressure observed in rabbits, pigs, and patients). CONCLUSIONS: Strong effort increased dependent lung injury, where higher local lung stress and stretch was generated; effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may offset need for paralysis.

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.

Physiologic effects of alveolar recruitment and inspiratory pauses during moderately-high-frequency ventilation delivered by a conventional ventilator in a severe lung injury model.

BACKGROUND AND AIMS: To investigate whether performing alveolar recruitment or adding inspiratory pauses could promote physiologic benefits (VT) during moderately-high-frequency positive pressure ventilation (MHFPPV) delivered by a conventional ventilator in a porcine model of severe acute respiratory distress syndrome (ARDS). METHODS: Prospective experimental laboratory study with eight pigs. Induction of acute lung injury with sequential pulmonary lavages and injurious ventilation was initially performed. Then, animals were ventilated on a conventional mechanical ventilator with a respiratory rate (RR) = 60 breaths/minute and PEEP titrated according to ARDS Network table. The first two steps consisted of a randomized order of inspiratory pauses of 10 and 30% of inspiratory time. In final step, we removed the inspiratory pause and titrated PEEP, after lung recruitment, with the aid of electrical impedance tomography. At each step, PaCO2 was allowed to stabilize between 57-63 mmHg for 30 minutes. RESULTS: The step with RR of 60 after lung recruitment had the highest PEEP when compared with all other steps (17 [16,19] vs 14 [10, 17]cmH2O), but had lower driving pressures (13 [13,11] vs 16 [14, 17]cmH2O), higher P/F ratios (212 [191,243] vs 141 [105, 184] mmHg), lower shunt (23 [20, 23] vs 32 [27, 49]%), lower dead space ventilation (10 [0, 15] vs 30 [20, 37]%), and a more homogeneous alveolar ventilation distribution. There were no detrimental effects in terms of lung mechanics, hemodynamics, or gas exchange. Neither the addition of inspiratory pauses or the alveolar recruitment maneuver followed by decremental PEEP titration resulted in further reductions in VT. CONCLUSIONS: During MHFPPV set with RR of 60 bpm delivered by a conventional ventilator in severe ARDS swine model, neither the inspiratory pauses or PEEP titration after recruitment maneuver allowed reduction of VT significantly, however the last strategy decreased driving pressures and improved both shunt and dead space.

Transpulmonary Pressure Describes Lung Morphology During Decremental Positive End-Expiratory Pressure Trials in Obesity.

OBJECTIVES: Atelectasis develops in critically ill obese patients when undergoing mechanical ventilation due to increased pleural pressure. The current study aimed to determine the relationship between transpulmonary pressure, lung mechanics, and lung morphology and to quantify the benefits of a decremental positive end-expiratory pressure trial preceded by a recruitment maneuver. DESIGN: Prospective, crossover, nonrandomized interventional study. SETTING: Medical and Surgical Intensive Care Units at Massachusetts General Hospital (Boston, MA) and University Animal Research Laboratory (São Paulo, Brazil). PATIENTS/SUBJECTS: Critically ill obese patients with acute respiratory failure and anesthetized swine. INTERVENTIONS: Clinical data from 16 mechanically ventilated critically ill obese patients were analyzed. An animal model of obesity with reversible atelectasis was developed by placing fluid filled bags on the abdomen to describe changes of lung mechanics, lung morphology, and pulmonary hemodynamics in 10 swine. MEASUREMENTS AND MAIN RESULTS: In obese patients (body mass index, 48 ± 11 kg/m), 21.7 ± 3.7 cm H2O of positive end-expiratory pressure resulted in the lowest elastance of the respiratory system (18.6 ± 6.1 cm H2O/L) after a recruitment maneuver and decremental positive end-expiratory pressure and corresponded to a positive (2.1 ± 2.2 cm H2O) end-expiratory transpulmonary pressure. Ventilation at lowest elastance positive end-expiratory pressure preceded by a recruitment maneuver restored end-expiratory lung volume (30.4 ± 9.1 mL/kg ideal body weight) and oxygenation (273.4 ± 72.1 mm Hg). In the swine model, lung collapse and intratidal recruitment/derecruitment occurred when the positive end-expiratory transpulmonary pressure decreased below 2-4 cm H2O. After the development of atelectasis, a decremental positive end-expiratory pressure trial preceded by lung recruitment identified the positive end-expiratory pressure level (17.4 ± 2.1 cm H2O) needed to restore poorly and nonaerated lung tissue, reestablishing lung elastance and oxygenation while avoiding increased pulmonary vascular resistance. CONCLUSIONS: In obesity, low-to-negative values of transpulmonary pressure predict lung collapse and intratidal recruitment/derecruitment. A decremental positive end-expiratory pressure trial preceded by a recruitment maneuver reverses atelectasis, improves lung mechanics, distribution of ventilation and oxygenation, and does not increase pulmonary vascular resistance.

Volume-controlled Ventilation Does Not Prevent Injurious Inflation during Spontaneous Effort.

RATIONALE: Spontaneous breathing during mechanical ventilation increases transpulmonary pressure and Vt, and worsens lung injury. Intuitively, controlling Vt and transpulmonary pressure might limit injury caused by added spontaneous effort. OBJECTIVES: To test the hypothesis that, during spontaneous effort in injured lungs, limitation of Vt and transpulmonary pressure by volume-controlled ventilation results in less injurious patterns of inflation. METHODS: Dynamic computed tomography was used to determine patterns of regional inflation in rabbits with injured lungs during volume-controlled or pressure-controlled ventilation. Transpulmonary pressure was estimated by using esophageal balloon manometry [Pl(es)] with and without spontaneous effort. Local dependent lung stress was estimated as the swing (inspiratory change) in transpulmonary pressure measured by intrapleural manometry in dependent lung and was compared with the swing in Pl(es). Electrical impedance tomography was performed to evaluate the inflation pattern in a larger animal (pig) and in a patient with acute respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing in injured lungs increased Pl(es) during pressure-controlled (but not volume-controlled) ventilation, but the pattern of dependent lung inflation was the same in both modes. In volume-controlled ventilation, spontaneous effort caused greater inflation and tidal recruitment of dorsal regions (greater than twofold) compared with during muscle paralysis, despite the same Vt and Pl(es). This was caused by higher local dependent lung stress (measured by intrapleural manometry). In injured lungs, esophageal manometry underestimated local dependent pleural pressure changes during spontaneous effort. CONCLUSIONS: Limitation of Vt and Pl(es) by volume-controlled ventilation could not eliminate harm caused by spontaneous breathing unless the level of spontaneous effort was lowered and local dependent lung stress was reduced.

Spontaneous Effort During Mechanical Ventilation: Maximal Injury With Less Positive End-Expiratory Pressure.

OBJECTIVES: We recently described how spontaneous effort during mechanical ventilation can cause "pendelluft," that is, displacement of gas from nondependent (more recruited) lung to dependent (less recruited) lung during early inspiration. Such transfer depends on the coexistence of more recruited (source) liquid-like lung regions together with less recruited (target) solid-like lung regions. Pendelluft may improve gas exchange, but because of tidal recruitment, it may also contribute to injury. We hypothesize that higher positive end-expiratory pressure levels decrease the propensity to pendelluft and that with lower positive end-expiratory pressure levels, pendelluft is associated with improved gas exchange but increased tidal recruitment. DESIGN: Crossover design. SETTING: University animal research laboratory. SUBJECTS: Anesthetized landrace pigs. INTERVENTIONS: Surfactant depletion was achieved by saline lavage in anesthetized pigs, and ventilator-induced lung injury was produced by ventilation with high tidal volume and low positive end-expiratory pressure. Ventilation was continued in each of four conditions: positive end-expiratory pressure (low or optimized positive end-expiratory pressure after recruitment) and spontaneous breathing (present or absent). Tidal recruitment was assessed using dynamic CT and regional ventilation/perfusion using electric impedance tomography. Esophageal pressure was measured using an esophageal balloon manometer. MEASUREMENTS AND RESULTS: Among the four conditions, spontaneous breathing at low positive end-expiratory pressure not only caused the largest degree of pendelluft, which was associated with improved ventilation/perfusion matching and oxygenation, but also generated the greatest tidal recruitment. At low positive end-expiratory pressure, paralysis worsened oxygenation but reduced tidal recruitment. Optimized positive end-expiratory pressure decreased the magnitude of spontaneous efforts (measured by esophageal pressure) despite using less sedation, from -5.6 ± 1.3 to -2.0 ± 0.7 cm H2O, while concomitantly reducing pendelluft and tidal recruitment. No pendelluft was observed in the absence of spontaneous effort. CONCLUSIONS: Spontaneous effort at low positive end-expiratory pressure improved oxygenation but promoted tidal recruitment associated with pendelluft. Optimized positive end-expiratory pressure (set after lung recruitment) may reverse the harmful effects of spontaneous breathing by reducing inspiratory effort, pendelluft, and tidal recruitment.

Moderately high frequency ventilation with a conventional ventilator allows reduction of tidal volume without increasing mean airway pressure.

BACKGROUND: The aim of this study was to explore if positive-pressure ventilation delivered by a conventional ICU ventilator at a moderately high frequency (HFPPV) allows a safe reduction of tidal volume (V T) below 6 mL/kg in a porcine model of severe acute respiratory distress syndrome (ARDS) and at a lower mean airway pressure than high-frequency oscillatory ventilation (HFOV). METHODS: This is a prospective study. In eight pigs (median weight 34 [29,36] kg), ARDS was induced by pulmonary lavage and injurious ventilation. The animals were ventilated with a randomized sequence of respiratory rates: 30, 60, 90, 120, 150, followed by HFOV at 5 Hz. At each step, V T was adjusted to allow partial pressure of arterial carbon dioxide (PaCO2) to stabilize between 57 and 63 mmHg. Data are shown as median [P25th,P75th]. RESULTS: After lung injury, the PaO2/FiO2 (P/F) ratio was 92 [63,118] mmHg, pulmonary shunt 26 [17,31]%, and static compliance 11 [8,14] mL/cmH2O. Positive end-expiratory pressure (PEEP) was 14 [10,17] cmH2O. At 30 breaths/min, V T was higher than 6 (7.5 [6.8,10.2]) mL/kg, but at all higher frequencies, V T could be reduced and PaCO2 maintained, leading to reductions in plateau pressures and driving pressures. For frequencies of 60 to 150/min, V T progressively fell from 5.2 [5.1,5.9] to 3.8 [3.7,4.2] mL/kg (p < 0.001). There were no detrimental effects in terms of lung mechanics, auto-PEEP generation, hemodynamics, or gas exchange. Mean airway pressure was maintained constant and was increased only during HFOV. CONCLUSIONS: During protective mechanical ventilation, HFPPV delivered by a conventional ventilator in a severe ARDS swine model safely allows further tidal volume reductions. This strategy also allowed decreasing airway pressures while maintaining stable PaCO2 levels.

Validação de um modelo suíno da síndrome do desconforto respiratório agudo (SDRA) grave e persistente / Validation of severe and persistent acute respiratory distress syndrome (ARDS) porcine model

A Sindrome do Desconforto Respiratório Agudo (SDRA) apresenta alta taxa de mortalidade em UTI. Sua principal característica é alteração da permeabilidade da membrana alvéolo capilar, com liberação de agentes inflamatórios, disfunção de surfactantes e da aeração pulmonar, queda da complacência e dos níveis de oxigenação. Frequentemente evolui com necessidade de suporte ventilatório. Vários modelos experimentais foram propostos na tentativa de reproduzir as mesmas característica da SDRA encontradas em pacientes, porém com pouco sucesso. Tem sido difícil reproduzir modelos estáveis, e por períodos prolongados. Assim, o nosso objetivo foi validar um novo modelo de SDRA, submetido a um período de observação e estabilização de 40 horas de ventilação mecânica protetora, testando a reprodutibilidade das principais características da apresentação clínica da SDRA. Realizamos o estudo em suínos, divididos em 3 grupos : SHAM (não submetido a Lesão), LESÃO (submetido a lavagem total pulmonar e ventilação lesiva por 3 horas) e VMP40 (submetido a Lesão e 40hs de ventilação protetora segundo a estratégia ARDSNET). Observamos que os níveis de PaO2 e complacência tiveram queda significativa após a lesão mantendo esta queda ao final de 40 horas. Os níveis de citocinas IL1, IL8 e IL6 tiveram um aumento significativa logo após a lesão, mantendo aumento significativo de IL1 e IL8 nas 40 horas de observação. Os níveis de polimorfonuclear no bal também tiveram um aumento significante, mantido nas 40 horas. Uma significativa alteração da permeabilidade alveolo-capilar foi demonstrada pelo aumento de proteínas no lavado broncoalveolar, aumento da água extravascular pulmonar, e aumento da relação peso seco/úmido que foram persistentes após 40hs da estratégia protetora ARDSnet. A lesão histológica foi evindenciada pela presença de todos os componentes clássicos: membrana hialina, hemorragia alveolar, infiltrado inflamatório e edema alveolar, também mantidos por 40hs. Conclusão: O...

The Acute Respiratory Distress Syndrome (ARDS) has high mortality in the ICU. Its main features comprise the disruption of the alveolo-capillary membrane with permeability alterations, release of inflammatory agents, and physiological dysfunctions like surfactant function degradation, loss of compliance and reduced PaO2 levels demanding ventilatory support. Several experimental models were developed in an attempt to simulate the same characteristics of ARDS in patients, but could not reproduce the complex, florid characteristics or the persistent damage for long periods. This study aimed to validate a new ARDS model in our laboratory, submited to an stabilization/observation period of 40 hours period of protective mechanical ventilation (according to the protective ARDSnet strategy), during which we tested the persistence of the main physiopathological characteristics of ARDS. We conducted the study in pigs divided into 3 groups : SHAM (not injured), INJURY (total lung lavage and injurious mechanical ventilation for 3hs) and MVP40 (injury protective mechanical ventilation for aditional 40hs-ARDSNET strategy). Respiratory-system compliance and PaO2 significantly decreased after injury, with a persistent drop till the end of 40hs. The levels of IL1, IL6 and IL8 cytokines presented a significant increase immediately after injury, with persistent levels of IL1 and IL8 after 40hs. Polymorphonuclear cells in the BAL were also increased after injury, with persistent levels after 40 hours. Gross alterations in the alveolo-capillary permeability were demonstrated by increased levels of proteins in the bronchoalveolar lavage, increased extravascular lung water and an increased wet/dry lung-weight ratio that remained elevated after 40hs of protective strategy. Histological injury was confirmed by visualization of hyaline membranes, frequent alveolar hemorrhage, alveolar edema and massive inflammatory infiltration. Conclusion: The proposed model reproduced the clinical...

Spontaneous effort causes occult pendelluft during mechanical ventilation.

RATIONALE: In normal lungs, local changes in pleural pressure (P(pl)) are generalized over the whole pleural surface. However, in a patient with injured lungs, we observed (using electrical impedance tomography) a pendelluft phenomenon (movement of air within the lung from nondependent to dependent regions without change in tidal volume) that was caused by spontaneous breathing during mechanical ventilation. OBJECTIVES: To test the hypotheses that in injured lungs negative P(pl) generated by diaphragm contraction has localized effects (in dependent regions) that are not uniformly transmitted, and that such localized changes in P(pl) cause pendelluft. METHODS: We used electrical impedance tomography and dynamic computed tomography (CT) to analyze regional inflation in anesthetized pigs with lung injury. Changes in local P(pl) were measured in nondependent versus dependent regions using intrabronchial balloon catheters. The airway pressure needed to achieve comparable dependent lung inflation during paralysis versus spontaneous breathing was estimated. MEASUREMENTS AND MAIN RESULTS: In all animals, spontaneous breathing caused pendelluft during early inflation, which was associated with more negative local P(pl) in dependent regions versus nondependent regions (-13.0 ± 4.0 vs. -6.4 ± 3.8 cm H2O; P < 0.05). Dynamic CT confirmed pendelluft, which occurred despite limitation of tidal volume to less than 6 ml/kg. Comparable inflation of dependent lung during paralysis required almost threefold greater driving pressure (and tidal volume) versus spontaneous breathing (28.0 ± 0.5 vs. 10.3 ± 0.6 cm H2O, P < 0.01; 14.8 ± 4.6 vs. 5.8 ± 1.6 ml/kg, P < 0.05). CONCLUSIONS: Spontaneous breathing effort during mechanical ventilation causes unsuspected overstretch of dependent lung during early inflation (associated with reciprocal deflation of nondependent lung). Even when not increasing tidal volume, strong spontaneous effort may potentially enhance lung damage.

Cell therapy for fibrotic interstitial pulmonary disease: experimental study.

Parte superior do formulário Digite um texto ou endereço de um site ou traduza um documento. The aim of this study is to evaluate the histological changes in lung parenchyma of pigs affected by interstitial lung disease induced after the infusion of bone marrow mononuclear cells (BMMCs). Ten female swines were submitted to pulmonary fibrosis induced by a single dose of intratracheal bleomicine sulfate. Animals were arranged into two groups: Group 1: induced-disease control and Group 2: cell therapy using BMMCs. Both groups were clinically evaluated for 180 days. High-resolution computed tomography (HRCT) was performed at 90 and 180 days. BMMC sampling was performed in cell therapy group at 90 days. Euthanasia was performed, and samples were collected for histology and immunohistochemistry. The 90-days HRCT demonstrated typical interstitial lesions in pulmonary parenchyma similarly to human disease. The 180-days HRCT in Group 1 demonstrated advanced stages of the disease when compared with Group 2. Immunohistochemistry analysis suggests the presence of pre-existent vessels and neoformed vessels as well as predominant young cells in the injured parenchyma of Group 2. Immunohistochemistry analysis suggests that cell therapy would promote a reconstructive response. Histology and HRCT analysis suggest a positive application of swine as a model for a bleomicine inducing of fibrotic interstitial pulmonary disease.

Effects of different mechanical ventilation strategies on the mucociliary system.

OBJECTIVE: To evaluate the effects of different mechanical ventilation (MV) strategies on the mucociliary system. DESIGN AND SETTING: Experimental study. SUBJECTS: Twenty-seven male New Zealand rabbits. INTERVENTIONS: After anesthesia, animals were tracheotomized and ventilated with standard ventilation [tidal volume (Vt) 8 ml/kg, positive end expiratory pressure (PEEP) 5 cmH(2)O, flow 3 L/min, FiO(2) 0.4] for 30 min. Next, animals were randomized into three groups and ventilated for 3 h with low volume (LV): Vt 8 ml/kg, PEEP 5 cmH(2)O, flow 3 L/min (n = 6); high volume (HV): Vt 16 ml/kg, PEEP 5 cmH(2)O, flow 5 L/min (n = 7); or high pressure (HP): Ppeak 30 cmH(2)O, PEEP 12 cmH(2)O (n = 8). Six animals (controls) were ventilated for 10 min with standard ventilation. Vital signals, blood lactate, and respiratory system mechanics were verified. Tracheal tissue was collected before and after MV. MEASUREMENTS: Lung and tracheal tissue sections were stained to analyze inflammation and mucosubstances by the point-counting method. Electron microscopy verified tracheal cell ultrastructure. In situ tracheal ciliary beating frequency (CBF), determined using a videoscopic technique, and tracheal mucociliary transport (TMCT), assessed by stereoscopic microscope, were evaluated before and after MV. RESULTS: Respiratory compliance decreased in the HP group. The HV and HP groups showed higher lactate levels after MV. Macroscopy showed areas of atelectasis and congestion on HV and HP lungs. Lung inflammatory infiltrate increased in all ventilated groups. Compared to the control, ventilated animals also showed a reduction of total and acid mucus on tracheal epithelium. Under electron microscopy, injury was observed in the ciliated cells of the HP group. CBF decreased significantly after MV only in the HP group. TMCT did not change significantly in the ventilated groups. CONCLUSIONS: Different MV strategies induce not only distal lung alterations but also morphological and physiological tracheal alterations leading to mucociliary system dysfunction.

Real-time detection of pneumothorax using electrical impedance tomography.

OBJECTIVES: Pneumothorax is a frequent complication during mechanical ventilation. Electrical impedance tomography (EIT) is a noninvasive tool that allows real-time imaging of regional ventilation. The purpose of this study was to 1) identify characteristic changes in the EIT signals associated with pneumothoraces; 2) develop and fine-tune an algorithm for their automatic detection; and 3) prospectively evaluate this algorithm for its sensitivity and specificity in detecting pneumothoraces in real time. DESIGN: Prospective controlled laboratory animal investigation. SETTING: Experimental Pulmonology Laboratory of the University of São Paulo. SUBJECTS: Thirty-nine anesthetized mechanically ventilated supine pigs (31.0 +/- 3.2 kg, mean +/- SD). INTERVENTIONS: In a first group of 18 animals monitored by EIT, we either injected progressive amounts of air (from 20 to 500 mL) through chest tubes or applied large positive end-expiratory pressure (PEEP) increments to simulate extreme lung overdistension. This first data set was used to calibrate an EIT-based pneumothorax detection algorithm. Subsequently, we evaluated the real-time performance of the detection algorithm in 21 additional animals (with normal or preinjured lungs), submitted to multiple ventilatory interventions or traumatic punctures of the lung. MEASUREMENTS AND MAIN RESULTS: Primary EIT relative images were acquired online (50 images/sec) and processed according to a few imaging-analysis routines running automatically and in parallel. Pneumothoraces as small as 20 mL could be detected with a sensitivity of 100% and specificity 95% and could be easily distinguished from parenchymal overdistension induced by PEEP or recruiting maneuvers. Their location was correctly identified in all cases, with a total delay of only three respiratory cycles. CONCLUSIONS: We created an EIT-based algorithm capable of detecting early signs of pneumothoraces in high-risk situations, which also identifies its location. It requires that the pneumothorax occurs or enlarges at least minimally during the monitoring period. Such detection was operator-free and in quasi real-time, opening opportunities for improving patient safety during mechanical ventilation.

Abordagem clínica e laboratorial do bócio uninodular sólido: vantagens da determinaçäo da calcitonina sérica por métodos distintos no rastreamento do carcinoma medular de tireóide, forma esporádica / Clinical and laboratorial approach of solid uninodular goiter: advantage of serum calcitonin determination by different methods in medullar thyroid carcinoma screening, sporadic form

A apresentação clínica mais freqüente da forma esporádica do carcinoma medular da tireóide (CMT) é o bócio uninodular sólido (BUS), apresentação esta semelhante aos demais tumores que afetam a glândula. O estabelecimento da freqüência de CMT em BUS apresenta implicações importantes não só diagnósticas, como também terapêuticas, visto a abordagem cirúrgica do CMT diferir de outros tumores tireoideanos. Para investigar a prevalência de CMT em BUS, dosamos calcitonina (CT) sérica, marcador bioquímico do CMT, por métodos distintos (RIA e IRMA) em 60 casos (55 mulheres; com idades entre 22 e 75 anos). A análise citológica obtida através de punção biópsia (PAAF) revelou 100 por cento de especificidade e 67 por cento de sensibilidade na detecção de carcinoma de tireóide. Considerando-se o grau de suspeita clínica para neoplasia tireoideana e os achados anatomopatológicos, houve 60 por cento de correlação positiva. CMT foi diagnosticado através da elevação da CT sérica em um dos 59 casos (1,69 por cento) e confirmado posteriormente pela PAAF e anatomopatológico. A incidência de CMT entre os casos de neoplasias tireoideanas nesta amostra foi de 12,5 por cento (1/8). Concluímos que a dosagem rotineira da CT sérica em casos com BUS não só complementa o estudo desta doença, como auxilia fortemente no diagnóstico do CMT. Tanto o IRMA como o RIA mostraram-se métodos úteis no rastreamento do CMT. Entretanto, o RIA pode provavelmente detectar ainda mais precocemente a elevação de formas não monoméricas da molécula de CT, as quais nos casos de CMT são usualmente mais abundantes que as formas monoméricas.