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Optimal fluid management is critical during mechanical ventilation to mitigate lung damage. Under normovolemia and protective ventilation, pulmonary tensile stress during pressure-support ventilation (PSV) results in comparable lung protection to compressive stress during pressure-controlled ventilation (PCV) in experimental acute lung injury (ALI). It is not yet known whether tensile stress can lead to comparable protection to compressive stress in ALI under a liberal fluid strategy (LF). A conservative fluid strategy (CF) was compared with LF during PSV and PCV on lungs and kidneys in an established model of ALI. Twenty-eight male Wistar rats received endotoxin intratracheally. After 24 h, they were treated with CF (minimum volume of Ringer's lactate to maintain normovolemia and mean arterial pressure ≥70 mmHg) or LF (~4 times higher than CF) combined with PSV or PCV (VT = 6 ml/kg, PEEP = 3 cmH2 O) for 1 h. Nonventilated animals (n = 4) were used for molecular biology analyses. CF-PSV compared with LF-PSV: (1) decreased the diffuse alveolar damage score (10 [7.8-12] vs. 25 [23-31.5], p = 0.006), mainly due to edema in axial and alveolar parenchyma; (2) increased birefringence for occludin and claudin-4 in lung tissue and expression of zonula-occludens-1 and metalloproteinase-9 in lung. LF compared with CF reduced neutrophil gelatinase-associated lipocalin and interleukin-6 expression in the kidneys in PSV and PCV. In conclusion, CF compared with LF combined with PSV yielded less lung epithelial cell damage in the current model of ALI. However, LF compared with CF resulted in less kidney injury markers, regardless of the ventilatory strategy.
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Lesão Pulmonar Aguda , Lesão Pulmonar Aguda/terapia , Animais , Rim , Pulmão , Masculino , Ratos , Ratos Wistar , Respiração Artificial/métodos , Volume de Ventilação PulmonarRESUMO
BACKGROUND: Conflicting data have reported beneficial effects of crystalloids, hyper-oncotic albumin (20%ALB), and iso-oncotic albumin (5%ALB) in critically ill patients. Although hyper-oncotic albumin may minimize lung injury, recent studies have shown that human albumin may lead to kidney damage proportional to albumin concentration. In this context, we compared the effects of Ringer's lactate (RL), 20%ALB, and 5%ALB, all titrated according to similar hemodynamic goals, on pulmonary function, lung and kidney histology, and molecular biology in experimental acute lung injury (ALI). METHODS: Male Wistar rats received Escherichia coli lipopolysaccharide intratracheally (n = 24) to induce ALI. After 24 h, animals were anesthetized and randomly assigned to receive RL, 20%ALB, or 5%ALB (n = 6/group) to maintain hemodynamic stability (distensibility index of inferior vena cava < 25%, mean arterial pressure > 65 mmHg). Rats were then mechanically ventilated for 6 h. Six animals, which received neither ventilation nor fluids (NV), were used for molecular biology analyses. RESULTS: The total fluid volume infused was higher in RL compared to 5%ALB and 20%ALB (median [interquartile range], 10.8[8.2-33.2] vs. 4.8[3.6-7.7] and 4.3[3.9-6.6] mL, respectively; p = 0.02 and p = 0.003). B-line counts on lung ultrasound (p < 0.0001 and p = 0.0002) and serum lactate levels (p = 0.01 and p = 0.01) were higher in RL than 5%ALB and 20%ALB. Diffuse alveolar damage score was lower in 5%ALB (10.5[8.5-12]) and 20%ALB (10.5[8.5-14]) than RL (16.5[12.5-20.5]) (p < 0.05 and p = 0.03, respectively), while acute kidney injury score was lower in 5%ALB (9.5[6.5-10]) than 20%ALB (18[15-28.5], p = 0.0006) and RL (16 [15-19], p = 0.04). In lung tissue, mRNA expression of interleukin (IL)-6 was higher in RL (59.1[10.4-129.3]) than in 5%ALB (27.0[7.8-49.7], p = 0.04) or 20%ALB (3.7[7.8-49.7], p = 0.03), and IL-6 protein levels were higher in RL than 5%ALB and 20%ALB (p = 0.026 and p = 0.021, respectively). In kidney tissue, mRNA expression and protein levels of kidney injury molecule (KIM)-1 were lower in 5%ALB than RL and 20%ALB, while nephronectin expression increased (p = 0.01 and p = 0.01), respectively. CONCLUSIONS: In a rat model of ALI, both iso-oncotic and hyper-oncotic albumin solutions were associated with less lung injury compared to Ringer's lactate. However, hyper-oncotic albumin resulted in greater kidney damage than iso-oncotic albumin. This experimental study is a step towards future clinical designs.
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Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Albuminas/toxicidade , Soluções Cristaloides/toxicidade , Animais , Masculino , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
BACKGROUND: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. METHODS: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naïve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. RESULTS: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naïve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. CONCLUSIONS: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.
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Lesão Pulmonar/etiologia , Macrófagos Alveolares/patologia , Fagócitos/patologia , Acidente Vascular Cerebral/complicações , Animais , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Terapia de Imunossupressão/efeitos adversos , Interleucina-6/análise , Interleucina-6/sangue , Lesão Pulmonar/sangue , Lesão Pulmonar/patologia , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/veterinária , RNA Mensageiro/análise , RNA Mensageiro/sangue , Ratos , Ratos Wistar/imunologia , Ratos Wistar/metabolismo , Estatísticas não Paramétricas , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/fisiopatologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
INTRODUCTION: Robotic-assisted surgery (RAS) has emerged as an alternative minimally invasive surgical option. Despite its growing applicability, the frequent need for pneumoperitoneum and Trendelenburg position could significantly affect respiratory mechanics during RAS. AVATaR is an international multicenter observational study aiming to assess the incidence of postoperative pulmonary complications (PPC), to characterise current practices of mechanical ventilation (MV) and to evaluate a possible association between ventilatory parameters and PPC in patients undergoing RAS. METHODS AND ANALYSIS: AVATaR is an observational study of surgical patients undergoing MV for general anaesthesia for RAS. The primary outcome is the incidence of PPC during the first five postoperative days. Secondary outcomes include practice of MV, effect of surgical positioning on MV, effect of MV on clinical outcome and intraoperative complications. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the Hospital Israelita Albert Einstein. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT02989415; Pre-results.
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Anestesia Geral , Pneumopatias/etiologia , Complicações Pós-Operatórias , Respiração Artificial , Procedimentos Cirúrgicos Robóticos , Humanos , Estudos Multicêntricos como Assunto , Estudos Observacionais como AssuntoRESUMO
Lung ischemia-reperfusion injury remains a major complication after lung transplantation. Variable ventilation (VV) has been shown to improve respiratory function and reduce pulmonary histological damage compared to protective volume-controlled ventilation (VCV) in different models of lung injury induced by endotoxin, surfactant depletion by saline lavage, and hydrochloric acid. However, no study has compared the biological impact of VV vs. VCV in lung ischemia-reperfusion injury, which has a complex pathophysiology different from that of other experimental models. Thirty-six animals were randomly assigned to one of two groups: (1) ischemia-reperfusion (IR), in which the left pulmonary hilum was completely occluded and released after 30 min; and (2) Sham, in which animals underwent the same surgical manipulation but without hilar clamping. Immediately after surgery, the left (IR-injured) and right (contralateral) lungs from 6 animals per group were removed, and served as non-ventilated group (NV) for molecular biology analysis. IR and Sham groups were further randomized to one of two ventilation strategies: VCV (n = 6/group) [tidal volume (VT) = 6 mL/kg, positive end-expiratory pressure (PEEP) = 2 cmH2O, fraction of inspired oxygen (FiO2) = 0.4]; or VV, which was applied on a breath-to-breath basis as a sequence of randomly generated VT values (n = 1200; mean VT = 6 mL/kg), with a 30% coefficient of variation. After 5 min of ventilation and at the end of a 2-h period (Final), respiratory system mechanics and arterial blood gases were measured. At Final, lungs were removed for histological and molecular biology analyses. Respiratory system elastance and alveolar collapse were lower in VCV than VV (mean ± SD, VCV 3.6 ± 1.3 cmH20/ml and 2.0 ± 0.8 cmH20/ml, p = 0.005; median [interquartile range], VCV 20.4% [7.9-33.1] and VV 5.4% [3.1-8.8], p = 0.04, respectively). In left lungs of IR animals, VCV increased the expression of interleukin-6 and intercellular adhesion molecule-1 compared to NV, with no significant differences between VV and NV. Compared to VCV, VV increased the expression of surfactant protein-D, suggesting protection from type II epithelial cell damage. In conclusion, in this experimental lung ischemia-reperfusion model, VV improved respiratory system elastance and reduced lung damage compared to VCV.
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BACKGROUND: Variable ventilation has been shown to improve pulmonary function and reduce lung damage in different models of acute respiratory distress syndrome. Nevertheless, variable ventilation has not been tested during pneumonia. Theoretically, periodic increases in tidal volume (VT) and airway pressures might worsen the impairment of alveolar barrier function usually seen in pneumonia and could increase bacterial translocation into the bloodstream. We investigated the impact of variable ventilation on lung function and histologic damage, as well as markers of lung inflammation, epithelial and endothelial cell damage, and alveolar stress, and bacterial translocation in experimental pneumonia. METHODS: Thirty-two Wistar rats were randomly assigned to receive intratracheal of Pseudomonas aeruginosa (PA) or saline (SAL) (n = 16/group). After 24-h, animals were anesthetized and ventilated for 2 h with either conventional volume-controlled (VCV) or variable volume-controlled ventilation (VV), with mean VT = 6 mL/kg, PEEP = 5cmH2O, and FiO2 = 0.4. During VV, tidal volume varied randomly with a coefficient of variation of 30% and a Gaussian distribution. Additional animals assigned to receive either PA or SAL (n = 8/group) were not ventilated (NV) to serve as controls. RESULTS: In both SAL and PA, VV improved oxygenation and lung elastance compared to VCV. In SAL, VV decreased interleukin (IL)-6 expression compared to VCV (median [interquartile range]: 1.3 [0.3-2.3] vs. 5.3 [3.6-7.0]; p = 0.02) and increased surfactant protein-D expression compared to NV (2.5 [1.9-3.5] vs. 1.2 [0.8-1.2]; p = 0.0005). In PA, compared to VCV, VV reduced perivascular edema (2.5 [2.0-3.75] vs. 6.0 [4.5-6.0]; p < 0.0001), septum neutrophils (2.0 [1.0-4.0] vs. 5.0 [3.3-6.0]; p = 0.0008), necrotizing vasculitis (3.0 [2.0-5.5] vs. 6.0 [6.0-6.0]; p = 0.0003), and ultrastructural lung damage scores (16 [14-17] vs. 24 [14-27], p < 0.0001). Blood colony-forming-unit (CFU) counts were comparable (7 [0-28] vs. 6 [0-26], p = 0.77). Compared to NV, VCV, but not VV, increased expression amphiregulin, IL-6, and cytokine-induced neutrophil chemoattractant (CINC)-1 (2.1 [1.6-2.5] vs. 0.9 [0.7-1.2], p = 0.025; 12.3 [7.9-22.0] vs. 0.8 [0.6-1.9], p = 0.006; and 4.4 [2.9-5.6] vs. 0.9 [0.8-1.4], p = 0.003, respectively). Angiopoietin-2 expression was lower in VV compared to NV animals (0.5 [0.3-0.8] vs. 1.3 [1.0-1.5], p = 0.01). CONCLUSION: In this rat model of pneumonia, VV improved pulmonary function and reduced lung damage as compared to VCV, without increasing bacterial translocation.
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Translocação Bacteriana , Pulmão/fisiopatologia , Pneumonia Bacteriana/terapia , Infecções por Pseudomonas/terapia , Respiração Artificial/métodos , Algoritmos , Animais , Células Endoteliais/patologia , Células Epiteliais/patologia , Inflamação/patologia , Pulmão/ultraestrutura , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/fisiopatologia , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/fisiopatologia , Alvéolos Pulmonares/patologia , Ratos , Ratos Wistar , Testes de Função Respiratória , Volume de Ventilação PulmonarRESUMO
BACKGROUND: The aim of this investigation was to compare ventilation at different levels of positive end-expiratory pressure (PEEP) with regard to clinical important outcomes of intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) at onset of ventilation. METHODS: Meta-analysis of randomized controlled trials (RCTs) comparing a lower level of PEEP with a higher level of PEEP was performed. The primary outcome was in-hospital mortality. RESULTS: Twenty-one RCTs (1393 patients) were eligible. PEEP ranged from 0 to 10 cmH2O and from 5 to 30 cmH2O in the lower PEEP and the higher PEEP arms of included RCTs, respectively. In-hospital mortality was not different between the two PEEP arms in seven RCTs (risk ratio [RR] 0.87; 95% confidence interval [CI] 0.62-1.21; I 2 = 26%, low quality of evidence [QoE]), as was duration of mechanical ventilation in three RCTs (standardized mean difference [SMD] 0.68; 95% CI -0.24 to 1.61; I 2 = 82%, very low QoE). PaO2/FiO2 was higher in the higher PEEP arms in five RCTs (SMD 0.72; 95% CI 0.10-1.35; I 2 = 86%, very low QoE). Development of ARDS and the occurrence of hypoxemia (2 RCTs) were lower in the higher PEEP arms in four RCTs and two RCTs, respectively (RR 0.43; 95% CI 0.21-0.91; I 2 = 56%, low QoE; RR 0.42; 95%-CI 0.19-0.92; I 2 = 19%, low QoE). There was no association between the level of PEEP and any hemodynamic parameter (four RCTs). CONCLUSION: Ventilation with higher levels of PEEP in ICU patients without ARDS at onset of ventilation was not associated with lower in-hospital mortality or shorter duration of ventilation, but with a lower incidence of ARDS and hypoxemia, as well as higher PaO2/FiO2. These findings should be interpreted with caution, as heterogeneity was moderate to high, the QoE was low to very low, and the available studies prevented us from addressing the effects of moderate levels of PEEP.
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BACKGROUND: In patients with emphysema, invasive mechanical ventilation settings should be adjusted to minimize hyperinflation while reducing respiratory effort and providing adequate gas exchange. We evaluated the impact of pressure-controlled ventilation (PCV) and pressure support ventilation (PSV) on pulmonary and diaphragmatic damage, as well as cardiac function, in experimental emphysema. METHODS: Emphysema was induced by intratracheal instillation of porcine pancreatic elastase in Wistar rats, once weekly for 4 weeks. Control animals received saline under the same protocol. Eight weeks after first instillation, control and emphysema rats were randomly assigned to PCV (n = 6/each) or PSV (n = 6/each) under protective tidal volume (6 ml/kg) for 4 h. Non-ventilated control and emphysema animals (n = 6/group) were used to characterize the model and for molecular biology analysis. Cardiorespiratory function, lung histology, diaphragm ultrastructure alterations, extracellular matrix organization, diaphragmatic proteolysis, and biological markers associated with pulmonary inflammation, alveolar stretch, and epithelial and endothelial cell damage were assessed. RESULTS: Emphysema animals exhibited cardiorespiratory changes that resemble human emphysema, such as increased areas of lung hyperinflation, pulmonary amphiregulin expression, and diaphragmatic injury. In emphysema animals, PSV compared to PCV yielded: no changes in gas exchange; decreased mean transpulmonary pressure (Pmean,L), ratio between inspiratory and total time (Ti/Ttot), lung hyperinflation, and amphiregulin expression in lung; increased ratio of pulmonary artery acceleration time to pulmonary artery ejection time, suggesting reduced right ventricular afterload; and increased ultrastructural damage to the diaphragm. Amphiregulin correlated with Pmean,L (r = 0.99, p < 0.0001) and hyperinflation (r = 0.70, p = 0.043), whereas Ti/Ttot correlated with hyperinflation (r = 0.81, p = 0.002) and Pmean,L (r = 0.60, p = 0.04). CONCLUSIONS: In the model of elastase-induced emphysema used herein, PSV reduced lung damage and improved cardiac function when compared to PCV, but worsened diaphragmatic injury.
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BACKGROUND: Protective mechanical ventilation strategies using low tidal volume or high levels of positive end-expiratory pressure (PEEP) improve outcomes for patients who have had surgery. The role of the driving pressure, which is the difference between the plateau pressure and the level of positive end-expiratory pressure is not known. We investigated the association of tidal volume, the level of PEEP, and driving pressure during intraoperative ventilation with the development of postoperative pulmonary complications. METHODS: We did a meta-analysis of individual patient data from randomised controlled trials of protective ventilation during general anesthaesia for surgery published up to July 30, 2015. The main outcome was development of postoperative pulmonary complications (postoperative lung injury, pulmonary infection, or barotrauma). FINDINGS: We included data from 17 randomised controlled trials, including 2250 patients. Multivariate analysis suggested that driving pressure was associated with the development of postoperative pulmonary complications (odds ratio [OR] for one unit increase of driving pressure 1·16, 95% CI 1·13-1·19; p<0·0001), whereas we detected no association for tidal volume (1·05, 0·98-1·13; p=0·179). PEEP did not have a large enough effect in univariate analysis to warrant inclusion in the multivariate analysis. In a mediator analysis, driving pressure was the only significant mediator of the effects of protective ventilation on development of pulmonary complications (p=0·027). In two studies that compared low with high PEEP during low tidal volume ventilation, an increase in the level of PEEP that resulted in an increase in driving pressure was associated with more postoperative pulmonary complications (OR 3·11, 95% CI 1·39-6·96; p=0·006). INTERPRETATION: In patients having surgery, intraoperative high driving pressure and changes in the level of PEEP that result in an increase of driving pressure are associated with more postoperative pulmonary complications. However, a randomised controlled trial comparing ventilation based on driving pressure with usual care is needed to confirm these findings. FUNDING: None.
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Anestesia Geral/efeitos adversos , Pneumopatias/etiologia , Respiração com Pressão Positiva/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Anestesia Geral/métodos , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Volume de Ventilação PulmonarRESUMO
Several respiratory diseases feature increased inflammatory response and catabolic activity, which are associated with glutamine depletion; thus, the benefits of exogenous glutamine administration have been evaluated in clinical trials and models of different respiratory diseases. Recent reviews and meta-analyses have focused on the effects and mechanisms of action of glutamine in a general population of critical care patients or in different models of injury. However, little information is available about the role of glutamine in respiratory diseases. The aim of the present review is to discuss the evidence of glutamine depletion in cystic fibrosis (CF), asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and lung cancer, as well as the results of exogenous glutamine administration in experimental and clinical studies. Exogenous glutamine administration might be beneficial in ARDS, asthma, and during lung cancer treatment, thus representing a potential therapeutic tool in these conditions. Further experimental and large randomized clinical trials focusing on the development and progression of respiratory diseases are necessary to elucidate the effects and possible therapeutic role of glutamine in this setting.
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Asma/tratamento farmacológico , Fibrose Cística/tratamento farmacológico , Glutamina/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Síndrome do Desconforto Respiratório/tratamento farmacológico , Asma/metabolismo , Fibrose Cística/metabolismo , Glutamina/metabolismo , Glutamina/farmacologia , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Síndrome do Desconforto Respiratório/metabolismoRESUMO
Living donor liver donation (LDLD) is an alternative to cadaveric liver donation. We aimed at identifying risk factors and developing a score for prediction of postoperative complications (POCs) after LDLD in donors. This is a retrospective cohort study in 688 donors between June 1995 and February 2014 at Hospital Sírio-Libanês and A.C. Camargo Cancer Center, in São Paulo, Brazil. Primary outcome was POC graded ≥III according to the Clavien-Dindo classification. Left lateral segment (LLS), left lobe (LL), and right lobe resections (RL) were conducted in 492 (71.4%), 109 (15.8%), and 87 (12.6%) donors, respectively. In total, 43 (6.2%) developed POCs, which were more common after RL than LLS and LL (14/87 (16.1%) versus 23/492 (4.5%) and 6/109 (5.5%), resp., p < 0.001). Multivariate analysis showed that RL resection (OR: 2.81, 95% CI: 1.32 to 3.01; p = 0.008), smoking status (OR: 3.2, 95% CI: 1.35 to 7.56; p = 0.012), and blood transfusion (OR: 3.15, 95% CI: 1.45 to 6.84; p = 0.004) were independently associated with POCs. RL resection, intraoperative blood transfusion, and smoking were associated with increased risk for POCs in donors.
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INTRODUCTION: Biphasic positive airway pressure (BIVENT) is a partial support mode that employs pressure-controlled, time-cycled ventilation set at two levels of continuous positive airway pressure with unrestricted spontaneous breathing. BIVENT can modulate inspiratory effort by modifying the frequency of controlled breaths. Nevertheless, the optimal amount of inspiratory effort to improve respiratory function while minimizing ventilator-associated lung injury during partial ventilatory assistance has not been determined. Furthermore, it is unclear whether the effects of partial ventilatory support depend on acute lung injury (ALI) etiology. This study aimed to investigate the impact of spontaneous and time-cycled control breaths during BIVENT on the lung and diaphragm in experimental pulmonary (p) and extrapulmonary (exp) ALI. METHODS: This was a prospective, randomized, controlled experimental study of 60 adult male Wistar rats. Mild ALI was induced by Escherichia coli lipopolysaccharide either intratracheally (ALI(p)) or intraperitoneally (ALI(exp)). After 24 hours, animals were anesthetized and further randomized as follows: (1) pressure-controlled ventilation (PCV) with tidal volume (V(t)) = 6 ml/kg, respiratory rate = 100 breaths/min, PEEP = 5 cmH2O, and inspiratory-to-expiratory ratio (I:E) = 1:2; or (2) BIVENT with three spontaneous and time-cycled control breath modes (100, 75, and 50 breaths/min). BIVENT was set with two levels of CPAP (P(high) = 10 cmH2O and P(low) = 5 cmH2O). Inspiratory time was kept constant (T(high) = 0.3 s). RESULTS: BIVENT was associated with reduced markers of inflammation, apoptosis, fibrogenesis, and epithelial and endothelial cell damage in lung tissue in both ALI models when compared to PCV. The inspiratory effort during spontaneous breaths increased during BIVENT-50 in both ALI models. In ALI(p), alveolar collapse was higher in BIVENT-100 than PCV, but decreased during BIVENT-50, and diaphragmatic injury was lower during BIVENT-50 compared to PCV and BIVENT-100. In ALI(exp), alveolar collapse during BIVENT-100 and BIVENT-75 was comparable to PCV, while decreasing with BIVENT-50, and diaphragmatic injury increased during BIVENT-50. CONCLUSIONS: In mild ALI, BIVENT had a lower biological impact on lung tissue compared to PCV. In contrast, the response of atelectasis and diaphragmatic injury to BIVENT differed according to the rate of spontaneous/controlled breaths and ALI etiology.
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Lesão Pulmonar Aguda/terapia , Ventilação com Pressão Positiva Intermitente/métodos , Pulmão/patologia , Lesão Pulmonar Aguda/etiologia , Animais , Apoptose , Biomarcadores , Brasil , Modelos Animais de Doenças , Endotélio/patologia , Epitélio/patologia , Fibrose , Inalação/fisiologia , Ventilação com Pressão Positiva Intermitente/efeitos adversos , Masculino , Estudos Prospectivos , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Volume de Ventilação Pulmonar/fisiologiaRESUMO
In patients with acute lung injury and acute respiratory distress syndrome, a protective mechanical ventilation strategy characterized by low tidal volumes has been associated with reduced mortality. However, such a strategy may result in alveolar collapse, leading to cyclic opening and closing of atelectatic alveoli and distal airways. Thus, recruitment maneuvers (RMs) have been used to open up collapsed lungs, while adequate positive end-expiratory pressure (PEEP) levels may counteract alveolar derecruitment during low tidal volume ventilation, improving respiratory function and minimizing ventilator-associated lung injury. Nevertheless, considerable uncertainty remains regarding the appropriateness of RMs. The most commonly used RM is conventional sustained inflation, associated with respiratory and cardiovascular side effects, which may be minimized by newly proposed strategies: prolonged or incremental PEEP elevation; pressure-controlled ventilation with fixed PEEP and increased driving pressure; pressure-controlled ventilation applied with escalating PEEP and constant driving pressure; and long and slow increase in pressure. The efficiency of RMs may be affected by different factors, including the nature and extent of lung injury, capability of increasing inspiratory transpulmonary pressures, patient positioning and cardiac preload. Current evidence suggests that RMs can be used before setting PEEP, after ventilator circuit disconnection or as a rescue maneuver to overcome severe hypoxemia; however, their routine use does not seem to be justified at present. The development of new lung recruitment strategies that have fewer hemodynamic and biological effects on the lungs, as well as randomized clinical trials analyzing the impact of RMs on morbidity and mortality of acute lung injury/acute respiratory distress syndrome patients, are warranted.