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1.
BMC Anesthesiol ; 21(1): 9, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419396

RESUMO

BACKGROUND: Pneumonia induced by 2019 Coronavirus (COVID-19) is characterized by hypoxemic respiratory failure that may present with a broad spectrum of clinical phenotypes. At the beginning, patients may have normal lung compliance and be responsive to noninvasive ventilatory support, such as CPAP. However, the transition to more severe respiratory failure - Severe Acute Respiratory Syndrome (SARS-CoV-2), necessitating invasive ventilation is often abrupt and characterized by a severe V/Q mismatch that require cycles of prone positioning. The aim of this case is to report the effect on gas exchange, respiratory mechanics and hemodynamics of tripod (or orthopneic sitting position) used as an alternative to prone position in a patient with mild SARS-CoV-2 pneumonia ventilated with helmet CPAP. CASE PRESENTATION: A 77-year-old awake and collaborating male patient with mild SARS-CoV-2 pneumonia and ventilated with Helmet CPAP, showed sudden worsening of gas exchange without dyspnea. After an unsuccessful attempt of prone positioning, we alternated three-hours cycles of semi-recumbent and tripod position, still keeping him in CPAP. Arterial blood gases (PaO2/FiO2, PaO2, SaO2, PaCO2 and A/a gradient), respiratory (VE, VT, RR) and hemodynamic parameters (HR, MAP) were collected in the supine and tripod position. Cycles of tripod position were continued for 3 days. The patient had a clinically important improvement in arterial blood gases and respiratory parameters, with stable hemodynamic and was successfully weaned and discharged to ward 10 days after pneumonia onset. CONCLUSIONS: Tripod position during Helmet CPAP can be applied safely in patients with mild SARS-CoV-2 pneumonia, with improvement of oxygenation and V/Q matching, thus reducing the need for intubation.


Assuntos
/diagnóstico por imagem , Pressão Positiva Contínua nas Vias Aéreas/métodos , Posicionamento do Paciente/métodos , Mecânica Respiratória/fisiologia , Idoso , Humanos , Masculino , Resultado do Tratamento
2.
PLoS One ; 15(12): e0244963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33378363

RESUMO

The COVID-19 pandemic disrupted the world in 2020 by spreading at unprecedented rates and causing tens of thousands of fatalities within a few months. The number of deaths dramatically increased in regions where the number of patients in need of hospital care exceeded the availability of care. Many COVID-19 patients experience Acute Respiratory Distress Syndrome (ARDS), a condition that can be treated with mechanical ventilation. In response to the need for mechanical ventilators, designed and tested an emergency ventilator (EV) that can control a patient's peak inspiratory pressure (PIP) and breathing rate, while keeping a positive end expiratory pressure (PEEP). This article describes the rapid design, prototyping, and testing of the EV. The development process was enabled by rapid design iterations using additive manufacturing (AM). In the initial design phase, iterations between design, AM, and testing enabled a working prototype within one week. The designs of the 16 different components of the ventilator were locked by additively manufacturing and testing a total of 283 parts having parametrically varied dimensions. In the second stage, AM was used to produce 75 functional prototypes to support engineering evaluation and animal testing. The devices were tested over more than two million cycles. We also developed an electronic monitoring system and with automatic alarm to provide for safe operation, along with training materials and user guides. The final designs are available online under a free license. The designs have been transferred to more than 70 organizations in 15 countries. This project demonstrates the potential for ultra-fast product design, engineering, and testing of medical devices needed for COVID-19 emergency response.


Assuntos
/terapia , Desenho de Equipamento/métodos , Respiração Artificial/instrumentação , Ventiladores Mecânicos/efeitos adversos , Animais , Humanos , Respiração Artificial/métodos , Mecânica Respiratória/fisiologia , Taxa Respiratória/fisiologia , Suínos
3.
PLoS One ; 15(10): e0237643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33064729

RESUMO

We previously reported that maternal cigarette smoke (CS) exposure resulted in impairment of central chemoreception and induced mitochondrial dysfunction in offspring parafacial respiratory group (pFRG), the kernel for mammalian central chemoreception. We also found that hydrogen sulfide (H2S) could attenuate maternal CS exposure-induced impairment of central chemoreception in the rat offspring in vivo. Mitochondrial ATP sensitive potassium (mitoKATP) channel has been reported to play a significant role in mitochondrial functions and protect against apoptosis in neurons. Thus, we hypothesize here that mitoKATP channel plays a role in the protective effects of H2S on neonatal central chemoreception in maternal CS-exposed rats. Our findings revealed that pretreatment with NaHS (donor of H2S, 22.4mM) reversed the central chemosensitivity decreased by maternal CS exposure, and also inhibited cell apoptosis in offspring pFRG, however, 5-HD (blocker of mitoKATP channels, 19mM) attenuated the protective effects of NaHS. In addition, NaHS declined pro-apoptotic proteins related to mitochondrial pathway apoptosis in CS rat offspring pFRG, such as Bax, Cytochrome C, caspase9 and caspase3. NaHS or 5-HD alone had no significant effect on above indexes. These results suggest that mitoKATP channels play an important role in the protective effect of H2S against impairment of central chemoreception via anti-apoptosis in pFRG of rat offspring exposed to maternal CS.


Assuntos
Células Quimiorreceptoras/efeitos dos fármacos , Fumar Cigarros/efeitos adversos , Sulfeto de Hidrogênio/metabolismo , Exposição Materna/efeitos adversos , Canais de Potássio/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Células Quimiorreceptoras/patologia , Células Quimiorreceptoras/fisiologia , Feminino , Bulbo/efeitos dos fármacos , Bulbo/patologia , Bulbo/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Mecânica Respiratória/efeitos dos fármacos , Mecânica Respiratória/fisiologia , Sulfetos/metabolismo , Sulfetos/farmacologia
5.
Anesthesiology ; 133(5): 1106-1117, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32898217

RESUMO

BACKGROUND: A lung rest strategy is recommended during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome (ARDS). However, spontaneous breathing modes are frequently used in this context. The impact of this approach may depend on the intensity of breathing efforts. The authors aimed to determine whether a low spontaneous breathing effort strategy increases lung injury, compared to a controlled near-apneic ventilation, in a porcine severe ARDS model assisted by extracorporeal membrane oxygenation. METHODS: Twelve female pigs were subjected to lung injury by repeated lavages, followed by 2-h injurious ventilation. Thereafter, animals were connected to venovenous extracorporeal membrane oxygenation and during the first 3 h, ventilated with near-apneic ventilation (positive end-expiratory pressure, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5/min). Then, animals were allocated into (1) near-apneic ventilation, which continued with the previous ventilatory settings; and (2) spontaneous breathing: neuromuscular blockers were stopped, sweep gas flow was decreased until regaining spontaneous efforts, and ventilation was switched to pressure support mode (pressure support, 10 cm H2O; positive end-expiratory pressure, 10 cm H2O). In both groups, sweep gas flow was adjusted to keep Paco2 between 30 and 50 mmHg. Respiratory and hemodynamic as well as electric impedance tomography data were collected. After 24 h, animals were euthanized and lungs extracted for histologic tissue analysis. RESULTS: Compared to near-apneic group, the spontaneous breathing group exhibited a higher respiratory rate (52 ± 17 vs. 5 ± 0 breaths/min; mean difference, 47; 95% CI, 34 to 59; P < 0.001), but similar tidal volume (2.3 ± 0.8 vs. 2.8 ± 0.4 ml/kg; mean difference, 0.6; 95% CI, -0.4 to 1.4; P = 0.983). Extracorporeal membrane oxygenation settings and gas exchange were similar between groups. Dorsal ventilation was higher in the spontaneous breathing group. No differences were observed regarding histologic lung injury. CONCLUSIONS: In an animal model of severe ARDS supported with extracorporeal membrane oxygenation, spontaneous breathing characterized by low-intensity efforts, high respiratory rates, and very low tidal volumes did not result in increased lung injury compared to controlled near-apneic ventilation.


Assuntos
Modelos Animais de Doenças , Oxigenação por Membrana Extracorpórea/métodos , /terapia , Mecânica Respiratória/fisiologia , Índice de Gravidade de Doença , Animais , Feminino , Suínos
6.
PLoS One ; 15(9): e0238402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915810

RESUMO

Infants are at risk for potentially life-threatening postoperative apnea (POA). We developed an Automated Unsupervised Respiratory Event Analysis (AUREA) to classify breathing patterns obtained with dual belt respiratory inductance plethysmography and a reference using Expectation Maximization (EM). This work describes AUREA and evaluates its performance. AUREA computes six metrics and inputs them into a series of four binary k-means classifiers. Breathing patterns were characterized by normalized variance, nonperiodic power, instantaneous frequency and phase. Signals were classified sample by sample into one of 5 patterns: pause (PAU), movement (MVT), synchronous (SYB) and asynchronous (ASB) breathing, and unknown (UNK). MVT and UNK were combined as UNKNOWN. Twenty-one preprocessed records obtained from infants at risk for POA were analyzed. Performance was evaluated with a confusion matrix, overall accuracy, and pattern specific precision, recall, and F-score. Segments of identical patterns were evaluated for fragmentation and pattern matching with the EM reference. PAU exhibited very low normalized variance. MVT had high normalized nonperiodic power and low frequency. SYB and ASB had a median frequency of respectively, 0.76Hz and 0.71Hz, and a mode for phase of 4o and 100o. Overall accuracy was 0.80. AUREA confused patterns most often with UNKNOWN (25.5%). The pattern specific F-score was highest for SYB (0.88) and lowest for PAU (0.60). PAU had high precision (0.78) and low recall (0.49). Fragmentation was evident in pattern events <2s. In 75% of the EM pattern events >2s, 50% of the samples classified by AUREA had identical patterns. Frequency and phase for SYB and ASB were consistent with published values for synchronous and asynchronous breathing in infants. The low normalized variance in PAU, was consistent with published scoring rules for pediatric apnea. These findings support the use of AUREA to classify breathing patterns and warrant a future evaluation of clinically relevant respiratory events.


Assuntos
Pletismografia/estatística & dados numéricos , Mecânica Respiratória/fisiologia , Aprendizado de Máquina não Supervisionado , Apneia/diagnóstico , Apneia/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Pletismografia/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Processamento de Sinais Assistido por Computador
7.
Medicine (Baltimore) ; 99(34): e21778, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846806

RESUMO

BACKGROUND: There are some clinical reports on dysphagia in patients with chronic obstructive pulmonary disease (COPD); however, its pathophysiology remains largely unknown.Changes in respiratory function occur in patients with COPD causing a decrease in tidal volume and an increase in respiratory rate (tachypnea). In addition, it leads to lack of coordination between respiration and swallowing.A new treatment called nasal high flow (NHF) has been introduced for patients with COPD, replacing the traditional non-invasive ventilation (NIV) procedure. The NHF therapy involves inhalation of high flow of humidified air, which reduces respiratory effort in patients with COPD. Furthermore, NHF therapy facilitates swallowing of saliva even during respiratory management. A recent clinical study reported that high-flow nasal cannula oxygen therapy for 6 weeks improved the health-related quality of life and reduced hypercapnia in patients with stable COPD. Taken together, NHF therapy is gaining attention in the clinical management of patients with COPD.Therefore, in this study, we aim to examine the efficacy of NHF therapy on the coordination between breathing and swallowing of saliva during daytime nap in patients with COPD. METHODS/DESIGN: This open-label, investigator-initiated, single center study will evaluate the efficacy of NHF therapy on the coordination between breathing and swallowing of saliva during the daytime nap in COPD patients with forced expiratory volume in 1 second (FEV1%) of <70% during treatment at the Nagasaki University Hospital Respiratory Rehabilitation Center. Evaluations will be performed during the 90 to 180 minute "daytime nap" in the measurement room of the hospital. The primary endpoint will be the rate of appearance of the expiratory phase after swallowing of saliva and the frequency of swallowing during the measurement period. DISCUSSION: The purpose of this study is to obtain evidence regarding the utility of NHF as a potential therapeutic device for COPD patients to prevent aspiration of saliva during the sleep stage of daytime nap. The utility will be assessed by comparing the decrease in incidence rates of the expiratory phase after swallowing of saliva in the NHF device group and the control group, wherein this device was not used.


Assuntos
Deglutição/fisiologia , Ventilação não Invasiva/métodos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Mecânica Respiratória/fisiologia , Cânula , Humanos , Ventilação não Invasiva/efeitos adversos , Projetos de Pesquisa , Saliva
8.
Crit Care ; 24(1): 529, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859264

RESUMO

BACKGROUND: Whether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes. METHODS: Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmH2O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO2/FiO2, FiO2, PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study. RESULTS: Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th-75th percentiles] PaO2/FiO2 in the two groups was 119 mmHg [101-142] and 116 mmHg [87-154]. Average compliance (41 ml/cmH2O [32-52] vs. 36 ml/cmH2O [27-42], p = 0.045) and ventilatory ratio (2.1 [1.7-2.3] vs. 1.6 [1.4-2.1], p = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO2/FiO2 was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO2/FiO2 in both cohorts, but more remarkably in COVID-19 patients (p = 0.005). Recruitability was not different between cohorts (p = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP. CONCLUSIONS: Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small.


Assuntos
Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , /fisiopatologia , Idoso , Betacoronavirus , Infecções por Coronavirus/terapia , Feminino , Humanos , Unidades de Terapia Intensiva , Itália , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Respiração com Pressão Positiva , Testes de Função Respiratória , Mecânica Respiratória/fisiologia
9.
Anesthesiology ; 133(4): 867-878, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32701573

RESUMO

BACKGROUND: Complete airway closure during expiration may underestimate alveolar pressure. It has been reported in cases of acute respiratory distress syndrome (ARDS), as well as in morbidly obese patients with healthy lungs. The authors hypothesized that complete airway closure was highly prevalent in obese ARDS and influenced the calculation of respiratory mechanics. METHODS: In a post hoc pooled analysis of two cohorts, ARDS patients were classified according to body mass index (BMI) terciles. Low-flow inflation pressure-volume curve and partitioned respiratory mechanics using esophageal manometry were recorded. The authors' primary aim was to compare the prevalence of complete airway closure according to BMI terciles. Secondary aims were to compare (1) respiratory system mechanics considering or not considering complete airway closure in their calculation, and (2) and partitioned respiratory mechanics according to BMI. RESULTS: Among the 51 patients analyzed, BMI was less than 30 kg/m2 in 18, from 30 to less than 40 in 16, and greater than or equal to 40 in 17. Prevalence of complete airway closure was 41% overall (95% CI, 28 to 55; 21 of 51 patients), and was lower in the lowest (22% [3 to 41]; 4 of 18 patients) than in the highest BMI tercile (65% [42 to 87]; 11 of 17 patients). Driving pressure and elastances of the respiratory system and of the lung were higher when complete airway closure was not taken into account in their calculation. End-expiratory esophageal pressure (ρ = 0.69 [95% CI, 0.48 to 0.82]; P < 0.001), but not chest wall elastance, was associated with BMI, whereas elastance of the lung was negatively correlated with BMI (ρ = -0.27 [95% CI, -0.56 to -0.10]; P = 0.014). CONCLUSIONS: Prevalence of complete airway closure was high in ARDS and should be taken into account when calculating respiratory mechanics, especially in the most morbidly obese patients.


Assuntos
Obstrução das Vias Respiratórias/epidemiologia , Obstrução das Vias Respiratórias/fisiopatologia , Índice de Massa Corporal , /fisiopatologia , Mecânica Respiratória/fisiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/fisiopatologia , Respiração com Pressão Positiva/métodos , Prevalência , Estudos Prospectivos , Testes de Função Respiratória/métodos , Estudos Retrospectivos
10.
Anesthesiology ; 133(4): 750-763, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32675698

RESUMO

BACKGROUND: Body habitus, pneumoperitoneum, and Trendelenburg positioning may each independently impair lung mechanics during robotic laparoscopic surgery. This study hypothesized that increasing body mass index is associated with more mechanical strain and alveolar collapse, and these impairments are exacerbated by pneumoperitoneum and Trendelenburg positioning. METHODS: This cross-sectional study measured respiratory flow, airway pressures, and esophageal pressures in 91 subjects with body mass index ranging from 18.3 to 60.6 kg/m2. Pulmonary mechanics were quantified at four stages: (1) supine and level after intubation, (2) with pneumoperitoneum, (3) in Trendelenburg docked with the surgical robot, and (4) level without pneumoperitoneum. Subjects were stratified into five body mass index categories (less than 25, 25 to 29.9, 30 to 34.9, 35 to 39.9, and 40 or higher), and respiratory mechanics were compared over surgical stages using generalized estimating equations. The optimal positive end-expiratory pressure settings needed to achieve positive end-expiratory transpulmonary pressures were calculated. RESULTS: At baseline, transpulmonary driving pressures increased in each body mass index category (1.9 ± 0.5 cm H2O; mean difference ± SD; P < 0.006), and subjects with a body mass index of 40 or higher had decreased mean end-expiratory transpulmonary pressures compared with those with body mass index of less than 25 (-7.5 ± 6.3 vs. -1.3 ± 3.4 cm H2O; P < 0.001). Pneumoperitoneum and Trendelenburg each further elevated transpulmonary driving pressures (2.8 ± 0.7 and 4.7 ± 1.0 cm H2O, respectively; P < 0.001) and depressed end-expiratory transpulmonary pressures (-3.4 ± 1.3 and -4.5 ± 1.5 cm H2O, respectively; P < 0.001) compared with baseline. Optimal positive end-expiratory pressure was greater than set positive end-expiratory pressure in 79% of subjects at baseline, 88% with pneumoperitoneum, 95% in Trendelenburg, and ranged from 0 to 36.6 cm H2O depending on body mass index and surgical stage. CONCLUSIONS: Increasing body mass index induces significant alterations in lung mechanics during robotic laparoscopic surgery, but there is a wide range in the degree of impairment. Positive end-expiratory pressure settings may need individualization based on body mass index and surgical conditions.


Assuntos
Índice de Massa Corporal , Laparoscopia/métodos , Respiração com Pressão Positiva/métodos , Mecânica Respiratória/fisiologia , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Volume de Ventilação Pulmonar/fisiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/etiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle
11.
Br J Anaesth ; 125(3): 383-392, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32682559

RESUMO

BACKGROUND: Higher intraoperative driving pressures (ΔP) are associated with increased postoperative pulmonary complications (PPC). We hypothesised that dynamic adjustment of PEEP throughout abdominal surgery reduces ΔP, maintains positive end-expiratory transpulmonary pressures (Ptp_ee) and increases respiratory system static compliance (Crs) with PEEP levels that are variable between and within patients. METHODS: In a prospective multicentre pilot study, adults at moderate/high risk for PPC undergoing elective abdominal surgery were randomised to one of three ventilation protocols: (1) PEEP≤2 cm H2O, compared with periodic recruitment manoeuvres followed by individualised PEEP to either optimise respiratory system compliance (PEEPmaxCrs) or maintain positive end-expiratory transpulmonary pressure (PEEPPtp_ee). The composite primary outcome included intraoperative ΔP, Ptp_ee, Crs, and PEEP values (median (interquartile range) and coefficients of variation [CVPEEP]). RESULTS: Thirty-seven patients (48.6% female; age range: 47-73 yr) were assigned to control (PEEP≤2 cm H2O; n=13), PEEPmaxCrs (n=16), or PEEPPtp_ee (n=8) groups. The PEEPPtp_ee intervention could not be delivered in two patients. Subjects assigned to PEEPmaxCrs had lower ΔP (median8 cm H2O [7-10]), compared with the control group (12 cm H2O [10-15]; P=0.006). PEEPmaxCrs was also associated with higher Ptp_ee (2.0 cm H2O [-0.7 to 4.5] vs controls: -8.3 cm H2O [-13.0 to -4.0]; P≤0.001) and higher Crs (47.7 ml cm H2O [43.2-68.8] vs controls: 39.0 ml cm H2O [32.9-43.4]; P=0.009). Individualised PEEP (PEEPmaxCrs and PEEPPtp_ee combined) varied widely (median: 10 cm H2O [8-15]; CVPEEP=0.24 [0.14-0.35]), both between, and within, subjects throughout surgery. CONCLUSIONS: This pilot study suggests that individualised PEEP management strategies applied during abdominal surgery reduce driving pressure, maintain positive Ptp_ee and increase static compliance. The wide range of PEEP observed suggests that an individualised approach is required to optimise respiratory mechanics during abdominal surgery. CLINICAL TRIAL REGISTRATION: NCT02671721.


Assuntos
Abdome/cirurgia , Cuidados Intraoperatórios/métodos , Respiração com Pressão Positiva/métodos , Complicações Pós-Operatórias/prevenção & controle , Mecânica Respiratória/fisiologia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
14.
Am J Physiol Lung Cell Mol Physiol ; 319(3): L562-L575, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32579393

RESUMO

The poorly understood tolerance toward high tidal volume (VT) ventilation observed in critically ill children and age-equivalent animal models may be explained by surfactant homeostasis. The aim of our prospective animal study was to test whether high VT with adequate positive end-expiratory pressure (PEEP) is associated with surfactant de novo synthesis and secretion, leading to improved lung function, and whether extreme mechanical ventilation affects intracellular lamellar body formation and exocytosis. Rats (14 days old) were allocated to five groups: nonventilated controls, PEEP 5 cmH2O with VT of 8, 16, and 24 mL/kg, and PEEP 1 cmH2O with VT 24 mL/kg. Following 6 h of ventilation, lung function, surfactant proteins and phospholipids, and lamellar bodies were assessed by forced oscillation technique, quantitative real-time polymerase chain reaction, mass spectrometry, immunohistochemistry, and transmission electron microscopy. High VT (24 mL/kg) with PEEP of 5 cmH2O improved respiratory system mechanics and was not associated with lung injury, elevated surfactant protein expression, or surfactant phospholipid content. Extreme ventilation with VT 24 mL/kg and PEEP 1 cmH2O produced a mild inflammatory response and correlated with higher surfactant phospholipid concentrations in bronchoalveolar lavage fluid without affecting lamellar body count and morphology. Elevated phospholipid concentrations in the potentially most injurious strategy (VT 24 mL/kg, PEEP 1 cmH2O) need further evaluation and might reflect accumulation of biophysically inactive small aggregates. In conclusion, our data confirm the resilience of infant rats toward high VT-induced lung injury and challenge the relevance of surfactant synthesis, storage, and secretion as protective factors.


Assuntos
Lesão Pulmonar/metabolismo , Lesão Pulmonar/fisiopatologia , Surfactantes Pulmonares/metabolismo , Volume de Ventilação Pulmonar/fisiologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Pulmão/metabolismo , Pulmão/fisiopatologia , Ratos , Mecânica Respiratória/fisiologia , Tensoativos/metabolismo
15.
Lancet Respir Med ; 8(8): 765-774, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32569585

RESUMO

BACKGROUND: The COVID-19 pandemic is challenging advanced health systems, which are dealing with an overwhelming number of patients in need of intensive care for respiratory failure, often requiring intubation. Prone positioning in intubated patients is known to reduce mortality in moderate-to-severe acute respiratory distress syndrome. We aimed to investigate feasibility and effect on gas exchange of prone positioning in awake, non-intubated patients with COVID-19-related pneumonia. METHODS: In this prospective, feasibility, cohort study, patients aged 18-75 years with a confirmed diagnosis of COVID-19-related pneumonia receiving supplemental oxygen or non-invasive continuous positive airway pressure were recruited from San Gerardo Hospital, Monza, Italy. We collected baseline data on demographics, anthropometrics, arterial blood gas, and ventilation parameters. After baseline data collection, patients were helped into the prone position, which was maintained for a minimum duration of 3 h. Clinical data were re-collected 10 min after prone positioning and 1 h after returning to the supine position. The main study outcome was the variation in oxygenation (partial pressure of oxygen [PaO2]/fractional concentration of oxygen in inspired air [FiO2]) between baseline and resupination, as an index of pulmonary recruitment. This study is registered on ClinicalTrials.gov, NCT04365959, and is now complete. FINDINGS: Between March 20 and April 9, 2020, we enrolled 56 patients, of whom 44 (79%) were male; the mean age was 57·4 years (SD 7·4) and the mean BMI was 27·5 kg/m2 (3·7). Prone positioning was feasible (ie, maintained for at least 3 h) in 47 patients (83·9% [95% CI 71·7 to 92·4]). Oxygenation substantially improved from supine to prone positioning (PaO2/FiO2 ratio 180·5 mm Hg [SD 76·6] in supine position vs 285·5 mm Hg [112·9] in prone position; p<0·0001). After resupination, improved oxygenation was maintained in 23 patients (50·0% [95% CI 34·9-65·1]; ie, responders); however, this improvement was on average not significant compared with before prone positioning (PaO2/FiO2 ratio 192·9 mm Hg [100·9] 1 h after resupination; p=0·29). Patients who maintained increased oxygenation had increased levels of inflammatory markers (C-reactive protein: 12·7 mg/L [SD 6·9] in responders vs 8·4 mg/L [6·2] in non-responders; and platelets: 241·1 × 103/µL [101·9] vs 319·8 × 103/µL [120·6]) and shorter time between admission to hospital and prone positioning (2·7 days [SD 2·1] in responders vs 4·6 days [3·7] in non-responders) than did those for whom improved oxygenation was not maintained. 13 (28%) of 46 patients were eventually intubated, seven (30%) of 23 responders and six (26%) of 23 non-responders (p=0·74). Five patients died during follow-up due to underlying disease, unrelated to study procedure. INTERPRETATION: Prone positioning was feasible and effective in rapidly ameliorating blood oxygenation in awake patients with COVID-19-related pneumonia requiring oxygen supplementation. The effect was maintained after resupination in half of the patients. Further studies are warranted to ascertain the potential benefit of this technique in improving final respiratory and global outcomes. FUNDING: University of Milan-Bicocca.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Decúbito Ventral , Troca Gasosa Pulmonar/fisiologia , /fisiopatologia , Adolescente , Adulto , Idoso , Infecções por Coronavirus/terapia , Cuidados Críticos/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Estudos Prospectivos , /virologia , Mecânica Respiratória/fisiologia , Adulto Jovem
16.
Life Sci ; 257: 117994, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32569780

RESUMO

Sleep-disordered breathing is characterized by disruptions of normal breathing patterns during sleep. Obesity is closely related to hypoventilation or apnea and becomes a primary risk factor for sleep-disordered breathing. Leptin, a peptide secreted by adipose tissue, has been implicated in central control of breathing. Activation of the retrotrapezoid nucleus (RTN) neurons, a critical central respiratory chemoreceptor candidate, potentiates a central drive to breathing. Here, we ask whether the disordered leptin signaling in the RTN is responsible for obesity-related hypoventilation. In a diet induced obesity (DIO) mouse model, the hypercapnic ventilatory response (HCVR) was assessed and the cellular leptin signaling in the RTN was examined. Our main findings demonstrate that DIO mice exhibit overweight, hypercapnia, high levels of serum and cerebrospinal leptin. During exposure to room air, DIO mice manifest basal hypoventilation with a rapid and shallow breathing pattern. Exposure to CO2 elicits the impaired HCVR in DIO mice. In addition, both the number of CO2-activated neurons and expression of TASK-2 channels in the RTN are dramatically reduced in DIO mice. Moreover, there is leptin signaling disorder in RTN neurons in DIO mice, including a significant decrease in leptin-activated RTN neurons, downregulation of phosphorylated STAT3 and upregulation of SOCS3. Altogether, we suggest that the disordered leptin/STAT3/SOCS3 signaling pathway in the RTN plays a role in obesity-related hypoventilation.


Assuntos
Células Quimiorreceptoras/metabolismo , Leptina/metabolismo , Obesidade/metabolismo , Animais , Dióxido de Carbono/metabolismo , Células Quimiorreceptoras/fisiologia , Hipercapnia/metabolismo , Leptina/fisiologia , Masculino , Bulbo/metabolismo , Bulbo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Obesidade/fisiopatologia , Respiração , Mecânica Respiratória/fisiologia , Transdução de Sinais , Sono/fisiologia
17.
J Sports Sci ; 38(20): 2321-2328, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32573345

RESUMO

Studies on running biomechanics and energetics are usually conducted on a treadmill. To ensure that locomotion on a treadmill is comparable to locomotion overground, participants need to be expert in the use of the device. This study aimed to identify the number and duration of sessions needed to obtain stable measurements for spatiotemporal and metabolic parameters in unexperienced treadmill runners. Fourteen male recreational runners performed three 15-min treadmill running trials in different days at a submaximal speed. Spatiotemporal and metabolic parameters were registered at minutes: 5, 10, 15 and their within-trial and between-trial changes were analysed using a two-way repeated measures ANOVA and Bonferroni post-hoc test. Within-trial differences were found in step frequency (decreased over time), Step Length and Contact Time (increased), reaching stability at different time points. Ventilator parameters increased, reaching stability after 5-10 min, while heart rate increased progressively over time. The only between-trial differences were an increase in step length and a decrease in step frequency at min 1, between trials 1 and 3. In conclusion, at least three running trials of 15 min are required to familiarize with the device. The last 5 min of the third trial can be regarded as stable measurements.


Assuntos
Teste de Esforço/psicologia , Aprendizagem , Corrida/psicologia , Adulto , Fenômenos Biomecânicos , Habituação Psicofisiológica , Frequência Cardíaca/fisiologia , Humanos , Masculino , Consumo de Oxigênio/fisiologia , Prática Psicológica , Mecânica Respiratória/fisiologia , Corrida/fisiologia , Fatores de Tempo
18.
Int J Sports Med ; 41(9): 582-588, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32353882

RESUMO

Acute prolonged endurance running has been shown to alter muscle-specific circulating microRNA (miRNA) levels. Here, eighteen participants completed an 8 km run. We assessed the levels of hsa-miR-1-3p, -133a-3p, -133b, and -206 and their correlation with conventional biomarkers following exercise. Compared to before exercise (Pre), 8 km run significantly increased the lactate level immediately after exercise (0 h). Myoglobin (Mb) level increased at 0 h while creatine kinase (CK) level increased 24 h after exercise (24 h). The levels of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin I (cTnI) were all elevated at 24 h and within the normal physiological range; The levels of hsa-miR-1-3p, -133a-3p, -133b significantly increased at 0 h but only hsa-miR-133a-3p still elevated at 24 h. Only hsa-miR-206 level decreased at 24 h; Additionally, the changes of hsa-miR-1-3p and hsa-miR-133a-3p were correlated with Mb at 24 h. These findings suggest that muscle-specific miRNA elevation in plasma is likely physiological and that these miRNA may be used as potential biomarkers for load monitoring in individuals.


Assuntos
MicroRNA Circulante/sangue , Músculo Esquelético/metabolismo , Resistência Física/fisiologia , Corrida/fisiologia , Adaptação Fisiológica , Biomarcadores/sangue , Frequência Cardíaca/fisiologia , Humanos , Ácido Láctico/sangue , Masculino , Músculo Esquelético/lesões , Consumo de Oxigênio/fisiologia , Condicionamento Físico Humano/fisiologia , Mecânica Respiratória/fisiologia , Corrida/lesões , Adulto Jovem
20.
PLoS One ; 15(5): e0232450, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32433692

RESUMO

Many insects show discontinuous respiration with three phases, open, closed, and fluttering, in which the spiracles open and close rapidly. The relative durations of the three phases and the rate of fluttering during the flutter phase vary for individual insects depending on developmental stage and activity, vary between insects of the same species, and vary even more between different species. We studied how the rate of oxygen uptake during the flutter phase depends on the rate of fluttering. Using a mathematical model of oxygen diffusion in the insect tracheal system, we derive a formula for oxygen uptake during the flutter phase and how it depends on the length of the tracheal system, percentage of time open during the flutter phase, and the flutter rate. Surprisingly, our results show that an insect can have its spiracles closed a high percentage of time during the flutter phase and yet receive almost as much oxygen as if the spiracles were always open, provided the spiracles open and close rapidly. We investigate the respiratory gain due to fluttering for four specific insects. Our formula shows that respiratory gain increases with body size and with increased rate of fluttering. Therefore, insects can regulate their rate of oxygen uptake by varying the rate of fluttering while keeping the spiracles closed during a large fraction of the time during the flutter phase. We also use a mathematical model to show that water loss is approximately proportional to the percentage of time the spiracles are open. Thus, insects can achieve both high oxygen intake and low water loss by keeping the spiracles closed most of the time and fluttering while open, thereby decoupling the challenge of preventing water loss from the challenge of obtaining adequate oxygen uptake.


Assuntos
Insetos/fisiologia , Modelos Biológicos , Oxigênio/fisiologia , Estruturas Animais/anatomia & histologia , Estruturas Animais/fisiologia , Animais , Água Corporal/metabolismo , Himenópteros/fisiologia , Insetos/anatomia & histologia , Lepidópteros/fisiologia , Conceitos Matemáticos , Respiração , Mecânica Respiratória/fisiologia , Traqueia/anatomia & histologia , Traqueia/fisiologia
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