RESUMO

Alveolar macrophages (AM) and monocytes (MO) are myeloid cells that play a substantial role in the development and establishment of the innate and adaptive immune response. These cells are crucial for host defense against various pathogens, but their role in malaria is poorly understood. Here, we characterize the dynamics of AMs and recruited leukocytes subpopulations in the airways during experimental Plasmodium berghei NK65-NY (PbNK65). We show that PbNK65 infection induces an increased pulmonary vascular permeability that provides Ly6Clow MOs, neutrophils (NEU), CD4+ and CD8+ lymphocytes in the airways. This inflammatory environment resulted in an increase in the population and alteration of the activation state of the AMs. Taken together, the data presented provide new insights into airway inflammation associated with pulmonary malaria.

RESUMO

Pulmonary contusion (PC), defined as damage to the lung parenchyma with edema and hemorrhage, has classically been associated with acceleration-deceleration injuries. It is a frequent pathology in clinical practice. However, its clinical presentation and imaging findings are nonspecific. Patients with this entity can present with findings that can range from mild dyspnea to life-threatening respiratory failure and hemodynamic instability. We present the case of a 61-year-old man, a former smoker, who presented to the emergency department after suffering blunt chest trauma. On admission, he complained of only mild shortness of breath, and his vital signs were typical. Initial imaging identified asymmetric pulmonary infiltrates and mediastinal lymphadenopathy; this was suspicious for additional pathology in addition to PC. After an exhaustive evaluation, a neoplastic or infectious disease process was ruled out. Even though the patient presented with a clinical deterioration of respiratory function compatible with secondary acute respiratory distress syndrome, there was a complete recovery after supportive measures and supplemental oxygen. In conclusion, the nonspecific clinical and imaging findings in patients with pulmonary contusion warrant a complete evaluation of these cases. An early diagnosis is essential to establish adequate support and monitoring to prevent possible complications that could worsen the patient's prognosis.

Assuntos

Contusões , Lesão Pulmonar , Ferimentos não Penetrantes , Humanos , Masculino , Pessoa de Meia-Idade , Contusões/diagnóstico por imagem , Lesão Pulmonar/diagnóstico por imagem , Lesão Pulmonar/etiologia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico por imagem , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Pulmão/diagnóstico por imagem , Dispneia/etiologia

RESUMO

BACKGROUND: PEEP is a cornerstone treatment for children with pediatric ARDS. Unfortunately, its titration is often performed solely by evaluating oxygen saturation, which can lead to inadequate PEEP level settings and consequent adverse effects. This study aimed to assess the impact of increasing PEEP on hemodynamics, respiratory system mechanics, and oxygenation in children with ARDS. METHODS: Children receiving mechanical ventilation and on pressure-controlled volume-guaranteed mode were prospectively assessed for inclusion. PEEP was sequentially changed to 5, 12, 10, 8 cm H2O, and again to 5 cm H2O. After 10 min at each PEEP level, hemodynamic, ventilatory, and oxygenation variables were collected. RESULTS: A total of 31 subjects were included, with median age and weight of 6 months and 6.3 kg, respectively. The main reasons for pediatric ICU admission were respiratory failure caused by acute viral bronchiolitis (45%) and community-acquired pneumonia (32%). Most subjects had mild or moderate ARDS (45% and 42%, respectively), with a median (interquartile range) oxygenation index of 8.4 (5.8-12.7). Oxygen saturation improved significantly when PEEP was increased. However, although no significant changes in blood pressure were observed, the median cardiac index at PEEP of 12 cm H2O was significantly lower than that observed at any other PEEP level (P = .001). Fourteen participants (45%) experienced a reduction in cardiac index of > 10% when PEEP was increased to 12 cm H2O. Also, the estimated oxygen delivery was significantly lower, at 12 cm H2O PEEP. Finally, respiratory system compliance significantly reduced when PEEP was increased. At a PEEP of 12 cm H2O, static compliance had a median reduction of 25% in relation to the initial assessment (PEEP of 5 cm H2O). CONCLUSIONS: Although it may improve arterial oxygen saturation, inappropriately high PEEP levels may reduce cardiac output, oxygen delivery, and respiratory system compliance in pediatric subjects with ARDS with low potential for lung recruitability.

RESUMO

Acute lung injury (ALI) is a significant clinical challenge associated with high morbidity and mortality. Worldwide, it affects approximately 200.000 individuals annually, with a staggering 40 % mortality rate in hospitalized cases and persistent complications in out-of-hospital cases. This review focuses on the key immunological pathways underlying bacterial ALI and the exploration of mouse models as tools for its induction. These models serve as indispensable platforms for unraveling the inflammatory cascades and biological responses inherent to ALI, while also facilitating the evaluation of novel therapeutic agents. However, their utility is not without challenges, mainly due to the stringent biosafety protocols required by the diverse bacterial virulence profiles. Simple and reproducible models of pulmonary bacterial infection are currently available, including intratracheal, intranasal, pleural and, intraperitoneal approaches. These models use endotoxins such as commercially available lipopolysaccharide (LPS) or live pathogens such as Pseudomonas aeruginosa, Mycobacterium tuberculosis, and Streptococcus pneumoniae, all of which are implicated in the pathogenesis of ALI. Combining murine models of bacterial lung infection with in-depth studies of the underlying immunological mechanisms is a cornerstone in advancing the therapeutic landscape for acute bacterial lung injury.

Assuntos

Lesão Pulmonar Aguda , Modelos Animais de Doenças , Animais , Lesão Pulmonar Aguda/microbiologia , Camundongos , Humanos , Índice de Gravidade de Doença

RESUMO

BACKGROUND: Adjusting trunk inclination from a semi-recumbent position to a supine-flat position or vice versa in patients with respiratory failure significantly affects numerous aspects of respiratory physiology including respiratory mechanics, oxygenation, end-expiratory lung volume, and ventilatory efficiency. Despite these observed effects, the current clinical evidence regarding this positioning manoeuvre is limited. This study undertakes a scoping review of patients with respiratory failure undergoing mechanical ventilation to assess the effect of trunk inclination on physiological lung parameters. METHODS: The PubMed, Cochrane, and Scopus databases were systematically searched from 2003 to 2023. INTERVENTIONS: Changes in trunk inclination. MEASUREMENTS: Four domains were evaluated in this study: 1) respiratory mechanics, 2) ventilation distribution, 3) oxygenation, and 4) ventilatory efficiency. RESULTS: After searching the three databases and removing duplicates, 220 studies were screened. Of these, 37 were assessed in detail, and 13 were included in the final analysis, comprising 274 patients. All selected studies were experimental, and assessed respiratory mechanics, ventilation distribution, oxygenation, and ventilatory efficiency, primarily within 60 min post postural change. CONCLUSION: In patients with acute respiratory failure, transitioning from a supine to a semi-recumbent position leads to decreased respiratory system compliance and increased airway driving pressure. Additionally, C-ARDS patients experienced an improvement in ventilatory efficiency, which resulted in lower PaCO2 levels. Improvements in oxygenation were observed in a few patients and only in those who exhibited an increase in EELV upon moving to a semi-recumbent position. Therefore, the trunk inclination angle must be accurately reported in patients with respiratory failure under mechanical ventilation.

Assuntos

Insuficiência Respiratória , Humanos , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Respiração Artificial/métodos , Mecânica Respiratória/fisiologia , Postura/fisiologia , Posicionamento do Paciente/métodos , Tronco/fisiopatologia , Tronco/fisiologia

RESUMO

BACKGROUND: Protective ventilation seems crucial during early Acute Respiratory Distress Syndrome (ARDS), but the optimal duration of lung protection remains undefined. High driving pressures (ΔP) and excessive patient ventilatory drive may hinder lung recovery, resulting in self-inflicted lung injury. The hidden nature of the ΔP generated by patient effort complicates the situation further. Our study aimed to assess the feasibility of an extended lung protection strategy that includes a stepwise protocol to control the patient ventilatory drive, assessing its impact on lung recovery. METHODS: We conducted a single-center randomized study on patients with moderate/severe COVID-19-ARDS with low respiratory system compliance (CRS < 0.6 (mL/Kg)/cmH2O). The intervention group received a ventilation strategy guided by Electrical Impedance Tomography aimed at minimizing ΔP and patient ventilatory drive. The control group received the ARDSNet low-PEEP strategy. The primary outcome was the modified lung injury score (mLIS), a composite measure that integrated daily measurements of CRS, along with oxygen requirements, oxygenation, and X-rays up to day 28. The mLIS score was also hierarchically adjusted for survival and extubation rates. RESULTS: The study ended prematurely after three consecutive months without patient enrollment, attributed to the pandemic subsiding. The intention-to-treat analysis included 76 patients, with 37 randomized to the intervention group. The average mLIS score up to 28 days was not different between groups (P = 0.95, primary outcome). However, the intervention group showed a faster improvement in the mLIS (1.4 vs. 7.2 days to reach 63% of maximum improvement; P < 0.001), driven by oxygenation and sustained improvement of X-ray (P = 0.001). The intervention group demonstrated a sustained increase in CRS up to day 28 (P = 0.009) and also experienced a shorter time from randomization to room-air breathing (P = 0.02). Survival at 28 days and time until liberation from the ventilator were not different between groups. CONCLUSIONS: The implementation of an individualized PEEP strategy alongside extended lung protection appears viable. Promising secondary outcomes suggested a faster lung recovery, endorsing further examination of this strategy in a larger trial. Clinical trial registration This trial was registered with ClinicalTrials.gov (number NCT04497454) on August 04, 2020.

RESUMO

OBJECTIVES: During the Coronavirus disease (COVID-19) pandemic, clinicians recommended awake-prone positioning (APP) to avoid the worst outcomes. The objectives of this study were to investigate if APP reduces intubation, death rates, and hospital length of stay (HLOS) in acute COVID-19. METHODS: We performed a retrospective cohort with non-mechanically ventilated patients hospitalized in a reference center in Manaus, Brazil, 2020. Participants were stratified into APP and awake-not-prone positioning (ANPP) groups. Also, we conducted a systematic review and performed a meta-analysis to understand if this intervention had different outcomes in resource-limited settings (PROSPERO CRD42023422452). RESULTS: A total of 115 participants were allocated into the groups. There was no statistical difference between both groups regarding time to intubation (HR: 0.861; 95CI: 0.474-1.1562; p=0.622) and time to death (HR: 1.666; 95CI: 0.939-2.951; p=0.081). APP was not significantly associated with reduced HLOS. A total of 86 articles were included in the systematic review, of which 76 (88,3%) show similar findings after APP. Also, low/middle, and high-income countries were similar regarding such outcomes. CONCLUSION: APP in COVID-19 does not present clinical improvement that affects mortality, intubation rate and HLOS. The lack of a prone position protocol, obtained through a controlled study, is necessary. After 3 years, APP benefits are still inconclusive.

Assuntos

COVID-19 , Posicionamento do Paciente , Humanos , COVID-19/mortalidade , COVID-19/terapia , Decúbito Ventral , Estudos Retrospectivos , Posicionamento do Paciente/métodos , Masculino , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Feminino , Idoso , Vigília , Brasil/epidemiologia , Intubação Intratraqueal/estatística & dados numéricos , SARS-CoV-2 , Resultado do Tratamento , Respiração Artificial

RESUMO

We report the feasibility of a combined approach of very low low tidal volume (VT) and mild therapeutic hypothermia (MTH) to decrease the ventilatory load in a severe COVID-19-related acute respiratory distress syndrome (ARDS) cohort. Inclusion criteria was patients ≥18-years-old, severe COVID-19-related ARDS, driving pressure ∆P >15 cmH2O despite low-VT strategy, and extracorporeal therapies not available. MTH was induced with a surface cooling device aiming at 34°C. MTH was maintained for 72 h, followed by rewarming of 1°C per day. Data were shown in median (interquartile range, 25%-75%). Mixed effects analysis and Dunnett's test were used for comparisons. Seven patients were reported. Ventilatory load decreased during the first 24 h, minute ventilation (VE) decreased from 173 (170-192) to 152 (137-170) mL/kg/min (P = 0.007), and mechanical power (MP) decreased from 37 (31-40) to 29 (26-34) J/min (P = 0.03). At the end of the MTH period, the VT, P, and plateau pressure remained consistently close to 3.9 mL/kg predicted body weight, 12 and 26 cmH2O, respectively. A combined strategy of MTH and ultraprotective mechanical ventilation (MV) decreased VE and MP in severe COVID-19-related ARDS. The decreasing of ventilatory load may allow maintaining MV within safety thresholds.

RESUMO

OBJECTIVE: To determine the relative effectiveness of Helmet-CPAP (H_CPAP) with respect to high-flow nasal cannula oxygen therapy (HFNO) in avoiding greater need for intubation or mortality in a medium complexity hospital in Chile during the year 2021. DESIGN: Cohort analytical study, single center. SETTING: Units other than intensive care units. PATIENTS: Records of adults with mild to moderate hypoxemia due to coronavirus type 2. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Need for intubation or mortality. RESULTS: 159 patients were included in the study, with a ratio by support of 2:10 (H_CPAP:HFNO). The 46.5% were women, with no significant differences by sex according to support (p = 0.99, Fisher test). The APACHE II score, for HFNO, had a median of 10.5, 3.5 units higher than H_CPAP (p < 0.01, Wilcoxon rank sum). The risk of intubation in HFNO was 42.1% and in H_CPAP 3.8%, with a significant risk reduction of 91% (95% CI: 36.9%-98.7%; p < 0.01). APACHE II does not modify or confound the support and intubation relationship (p > 0.2, binomial regression); however, it does confound the support and mortality relationship (p = 0.82, RR homogeneity test). Despite a 79.1% reduction in mortality risk with H_CPAP, this reduction was not statistically significant (p = 0.11, binomial regression). CONCLUSIONS: The use of Helmet CPAP, when compared to HFNO, was an effective therapeutic ventilatory support strategy to reduce the risk of intubation in patients with mild to moderate hypoxemia caused by coronavirus type 2 in inpatient units other than intensive care. The limitations associated with the difference in size, age and severity between the arms could generate bias.

Assuntos

COVID-19 , Pressão Positiva Contínua nas Vias Aéreas , Hipóxia , Oxigenoterapia , Humanos , Masculino , Feminino , COVID-19/terapia , COVID-19/complicações , COVID-19/mortalidade , Pessoa de Meia-Idade , Hipóxia/terapia , Hipóxia/etiologia , Pressão Positiva Contínua nas Vias Aéreas/métodos , Idoso , Oxigenoterapia/métodos , Intubação Intratraqueal , Dispositivos de Proteção da Cabeça , Resultado do Tratamento , APACHE , Índice de Gravidade de Doença , Adulto , Mortalidade Hospitalar , Estudos de Coortes , Chile/epidemiologia

RESUMO

INTRODUCTION AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, causing the current pandemic of acute respiratory disease known as COVID-19. Liver injury due to COVID-19 is defined as any liver injury occurring during the course of the disease and treatment of patients with COVID-19, with or without liver disease. The incidence of elevated liver transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ranges from 2.5 to 76.3%. The aim of the present study was to describe the hepatic biochemical abnormalities, after a SARS-CoV-2-positive polymerase chain reaction (PCR) test, and the mortality rate in critically ill patients. MATERIALS AND METHODS: A retrospective study was conducted that included 70 patients seen at a private hospital in Mexico City, within the time frame of February-December 2021. Median patient age was 44.5 years (range: 37-57.2) and 43 (61.4%) of the patients were men. Liver function tests were performed on the patients at hospital admission. RESULTS: Gamma glutamyl transferase (GGT) levels were elevated (p = 0.032), as were those of AST (p = 0.011) and ALT (p = 0.021). The patients were stratified into age groups: 18-35, 36-50, and > 50 years of age. The 18 to 35-year-olds had the highest liver enzyme levels and transaminase levels were higher, the younger the patient. Due to the low mortality rate (one patient whose death did not coincide with a hepatic cause), the multivariate analysis showed an R2 association of 0.689, explained by AST, GGT, and C-reactive protein levels. CONCLUSIONS: Despite the increase in transaminases in our study population during the course of COVID-19, there was no increase in mortality. Nevertheless, hospitalized patient progression should be continuously followed.

RESUMO

ABSTRACT Objective: To evaluate the association between driving pressure and tidal volume based on predicted body weight and mortality in a cohort of patients with acute respiratory distress syndrome caused by COVID-19. Methods: This was a prospective, observational study that included patients with acute respiratory distress syndrome due to COVID-19 admitted to two intensive care units. We performed multivariable analyses to determine whether driving pressure and tidal volume/kg predicted body weight on the first day of mechanical ventilation, as independent variables, are associated with hospital mortality. Results: We included 231 patients. The mean age was 64 (53 - 74) years, and the mean Simplified Acute and Physiology Score 3 score was 45 (39 - 54). The hospital mortality rate was 51.9%. Driving pressure was independently associated with hospital mortality (odds ratio 1.21, 95%CI 1.04 - 1.41 for each cm H2O increase in driving pressure, p = 0.01). Based on a double stratification analysis, we found that for the same level of tidal volume/kg predicted body weight, the risk of hospital death increased with increasing driving pressure. However, changes in tidal volume/kg predicted body weight were not associated with mortality when they did not lead to an increase in driving pressure. Conclusion: In patients with acute respiratory distress syndrome caused by COVID-19, exposure to higher driving pressure, as opposed to higher tidal volume/kg predicted body weight, is associated with greater mortality. These results suggest that driving pressure might be a primary target for lung-protective mechanical ventilation in these patients.

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RESUMO Objetivo: Avaliar a associação entre driving pressure e volume corrente ajustado pelo peso predito com a mortalidade em uma coorte de pacientes com síndrome do desconforto respiratório agudo por COVID-19. Métodos: Estudo prospectivo e observacional que incluiu pacientes com síndrome do desconforto respiratório agudo por COVID-19 admitidos em duas unidades de terapia intensiva. Foi realizada análise multivariada para determinar se a driving pressure e o volume corrente/kg de peso predito, aferidos no primeiro dia de ventilação mecânica, associavam-se de forma independente com a mortalidade hospitalar. Resultados: Foram incluídos 231 pacientes. A mediana de idade foi de 64 (53 - 74) anos, e a mediana do Simplified Acute and Physiology Score 3 foi de 45 (39 - 54). A mortalidade hospitalar foi de 51,9%. A driving pressure se associou de forma independente com a mortalidade hospitalar (razão de chance de 1,21; IC95% de 1,04 - 1,41 para cada cm H2O de aumento da driving pressure, p = 0,01). Com base na análise de dupla estratificação, encontrou-se que, para o mesmo nível de volume corrente/kg de peso predito, o risco de mortalidade hospitalar aumentava com o incremento da driving pressure. No entanto, mudanças no volume corrente/kg de peso predito não se associaram com a mortalidade quando não resultavam em aumento da driving pressure. Conclusão: Em pacientes com síndrome do desconforto respiratório agudo por COVID-19, exposição a maior driving pressure, ao contrário da exposição a maior volume corrente/kg de peso predito, associou-se com maior mortalidade hospitalar. Os resultados sugerem que a driving pressure poderia ser o alvo primário para a condução da ventilação mecânica protetora nesses pacientes.

RESUMO

Introducción: la pandemia de COVID-19 produjo una alta mortalidad en el mundo. Sin embargo, las presentaciones más críticas de la enfermedad han sido poco caracterizadas en nuestra región. Objetivo: estudiar la presentación clínica, evolución y mortalidad en pacientes ingresados en la unidad de medicina intensiva de un centro COVID-19 de referencia. Pacientes y método: estudio clínico, prospectivo, observacional de SARS-CoV-2 durante las primeras etapas de la pandemia en Uruguay. Se definió mortalidad en unidad de cuidados intensivos (UCI) como desenlace primario. Resultados: en 274 pacientes, la edad mediana fue de 65 años (IQR 54-73), el sexo masculino representó el 57% y el índice de Charlson tuvo una mediana de 3 (IQR 2-5). La mortalidad en UCI fue 59,9%. Las principales causas de muerte fueron: hipoxemia refractaria, disfunción orgánica múltiple y shock refractario. La edad (Odds Ratio (OR) = 1,06; IC de 95% 1,03 - 1,09), ocupación de camas (OR = 1,04, IC 95%: 1,02 - 1,07), sexo masculino (OR = 2,14, IC 95%: 0,93 - 5,06), ventilación mecánica invasiva (OR = 51,7, IC 95%: 16,5 - 208,6), coinfección al ingreso (OR = 2,34, IC 95%: 0,88 - 6,77) y enfermedad renal crónica previa (OR = 13,1, IC 95%: 2,29 - 129,2) fueron predictores independientes de mortalidad. La primera ola de la pandemia se produjo por la circulación de las variantes P.6 y P.1 del coronavirus, en una población con muy bajo porcentaje de vacunación (8%). Conclusiones: estos resultados en pacientes críticos aportan una descripción detallada del impacto de la pandemia por SARS-CoV-2 en un centro de referencia y constituyen una base para enfrentar futuros eventos epidémicos.

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Introduction: COVID-19 has caused high mortality worldwide. However, the most critical presentations of the disease have been poorly characterized in our region. Objective: to study the clinical presentation, progression, and mortality in patients admitted to the Intensive Care Unit (ICU) of a COVID-19 Reference Center. Patients and methods: clinical, prospective, observational study of SARS-CoV-2 during the early stages of the pandemic in Uruguay. ICU mortality was defined as the primary outcome. Results: in 274 patients, the median age was 65 years (IQR 54-73), male gender accounted for 57%, and the Charlson Index was 3 (IQR 2-5). ICU mortality was 59.9%. The main causes of death were refractory hypoxemia, multiple organ dysfunction, and refractory shock. Age (Odds Ratio (OR) = 1.06; 95% CI 1.03 - 1.09), bed occupancy (OR= 1.04, 95% CI: 1.02 -1.07), male gender (OR= 2.14, 95% CI 0.93 - 5.06), invasive mechanical ventilation (OR= 51.7, 95% CI 16.5 - 208.6), coinfection at admission (OR= 2.34, 95% CI 0.88 - 6.77), and pre-existing chronic kidney disease (OR= 13.1, 95% CI 2.29 - 129.2) were independent predictors of mortality. The first wave of the pandemic was driven by the circulation of the P.6 and P.1 variants of the coronavirus in a population with a very low vaccination percentage (8%). Conclusions: these results in critical patients provide a detailed description of the impact of the SARS-CoV-2 pandemic in a reference center and serve as a foundation for addressing future epidemic events.

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Introdução: a COVID-19 causou alta morbimortalidade em todo o mundo, embora as formas graves da doença tenham sido pouco caracterizadas nos países da América Latina. Objetivos: analisar o quadro clínico, a evolução e a mortalidade em pacientes com COVID-19 atendidos em uma unidade de terapia intensiva (UTI) em um Centro de Referência. Métodos: Estudo clínico, prospectivo e observacional de pacientes com SARS-CoV-2 durante a primeira onda da pandemia no Uruguai. A mortalidade na UTI foi o resultado primário. Resultados: oram estudados 274 pacientes, com uma mediada de idade de 65 anos (IQR 54-73), sendo a maioria do sexo masculino (57%). O índice de Charlson foi de 3 (IQR 2-5). A mortalidade geral na UTI foi de 59,9%. As principais causas de morte foram hipoxemia refratária, disfunção orgânica múltipla e choque refratário. A idade (Odds Ratio (OR) = 1,06; IC 95% 1,03-1,09), ocupação de leitos (OR = 1,04; IC 95%: 1,02-1,07), sexo masculino (OR = 2,14; IC 95%: 0,93-5,06), ventilação mecânica invasiva (OR = 51,7; IC 95%: 16,5-208,6), coinfecção na admissão (OR = 2,34; IC 95%: 0,88-6,77) e doença renal crônica pré-existente (OR = 13,1; IC 95%: 2,29-129,2) foram preditores independentes de mortalidade. A primeira onda da pandemia foi impulsionada pela circulação das variantes P.6 e P.1 do SARS-CoV-2 em uma população com uma taxa de vacinação muito baixa (8%). Conclusões: esses resultados em pacientes críticos fornecem uma descrição detalhada do impacto da pandemia SARS-CoV-2 em um Centro de Referência e constituem uma base para o enfrentamento de futuros eventos epidêmicos.

Assuntos

Estado Terminal , Cuidados Críticos , SARS-CoV-2 , COVID-19 , Respiração Artificial , Síndrome do Desconforto Respiratório do Recém-Nascido , Estudos Prospectivos , Estudo Observacional , Estudo Clínico

RESUMO

BACKGROUND: Internal redistribution of gas, referred to as pendelluft, is a new potential mechanism of effort-dependent lung injury. Neurally-adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV +) follow the patient's respiratory effort and improve synchrony compared with pressure support ventilation (PSV). Whether these modes could prevent the development of pendelluft compared with PSV is unknown. We aimed to compare pendelluft magnitude during PAV + and NAVA versus PSV in patients with resolving acute respiratory distress syndrome (ARDS). METHODS: Patients received either NAVA, PAV + , or PSV in a crossover trial for 20-min using comparable assistance levels after controlled ventilation (> 72 h). We assessed pendelluft (the percentage of lost volume from the non-dependent lung region displaced to the dependent region during inspiration), drive (as the delta esophageal swing of the first 100 ms [ΔPes 100 ms]) and inspiratory effort (as the esophageal pressure-time product per minute [PTPmin]). We performed repeated measures analysis with post-hoc tests and mixed-effects models. RESULTS: Twenty patients mechanically ventilated for 9 [5-14] days were monitored. Despite matching for a similar tidal volume, respiratory drive and inspiratory effort were slightly higher with NAVA and PAV + compared with PSV (ΔPes 100 ms of -2.8 [-3.8--1.9] cm H2O, -3.6 [-3.9--2.4] cm H2O and -2.1 [-2.5--1.1] cm H2O, respectively, p < 0.001 for both comparisons; PTPmin of 155 [118-209] cm H2O s/min, 197 [145-269] cm H2O s/min, and 134 [93-169] cm H2O s/min, respectively, p < 0.001 for both comparisons). Pendelluft magnitude was higher in NAVA (12 ± 7%) and PAV + (13 ± 7%) compared with PSV (8 ± 6%), p < 0.001. Pendelluft magnitude was strongly associated with respiratory drive (ß = -2.771, p-value < 0.001) and inspiratory effort (ß = 0.026, p < 0.001), independent of the ventilatory mode. A higher magnitude of pendelluft in proportional modes compared with PSV existed after adjusting for PTPmin (ß = 2.606, p = 0.010 for NAVA, and ß = 3.360, p = 0.004 for PAV +), and only for PAV + when adjusted for respiratory drive (ß = 2.643, p = 0.009 for PAV +). CONCLUSIONS: Pendelluft magnitude is associated with respiratory drive and inspiratory effort. Proportional modes do not prevent its occurrence in resolving ARDS compared with PSV.

RESUMO

ABSTRACT Objective: To assess the effect of atelectasis during mechanical ventilation on the periatelectatic and normal lung regions in a model of atelectasis in rats with acute lung injury induced by lipopolysaccharide. Methods: Twenty-four rats were randomized into the following four groups, each with 6 animals: the Saline-Control Group, Lipopolysaccharide Control Group, Saline-Atelectasis Group, and Lipopolysaccharide Atelectasis Group. Acute lung injury was induced by intraperitoneal injection of lipopolysaccharide. After 24 hours, atelectasis was induced by bronchial blocking. The animals underwent mechanical ventilation for two hours with protective parameters, and respiratory mechanics were monitored during this period. Thereafter, histologic analyses of two regions of interest, periatelectatic areas and the normally-aerated lung contralateral to the atelectatic areas, were performed. Results: The lung injury score was significantly higher in the Lipopolysaccharide Control Group (0.41 ± 0.13) than in the Saline Control Group (0.15 ± 0.51), p < 0.05. Periatelectatic regions showed higher lung injury scores than normally-aerated regions in both the Saline-Atelectasis (0.44 ± 0.06 x 0.27 ± 0.74 p < 0.05) and Lipopolysaccharide Atelectasis (0.56 ± 0.09 x 0.35 ± 0.04 p < 0.05) Groups. The lung injury score in the periatelectatic regions was higher in the Lipopolysaccharide Atelectasis Group (0.56 ± 0.09) than in the periatelectatic region of the Saline-Atelectasis Group (0.44 ± 0.06), p < 0.05. Conclusion: Atelectasis may cause injury to the surrounding tissue after a period of mechanical ventilation with protective parameters. Its effect was more significant in previously injured lungs.

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RESUMO Objetivo: Avaliar o efeito da atelectasia durante a ventilação mecânica nas regiões periatelectáticas e pulmonares normais em um modelo de atelectasia em ratos com lesão pulmonar aguda induzida por lipopolissacarídeo. Métodos: Foram distribuídos aleatoriamente 24 ratos em quatro grupos, cada um com 6 animais: Grupo Salina-Controle, Grupo Lipopolissacarídeo-Controle, Grupo Salina-Atelectasia e Grupo Lipopolissacarídeo-Atelectasia. A lesão pulmonar aguda foi induzida por injeção intraperitoneal de lipopolissacarídeo. Após 24 horas, a atelectasia foi induzida por bloqueio brônquico. Os animais foram submetidos à ventilação mecânica por 2 horas com parâmetros ventilatórios protetores, e a mecânica respiratória foi monitorada durante esse período. Em seguida, foram realizadas análises histológicas de duas regiões de interesse: as áreas periatelectásicas e o pulmão normalmente aerado contralateral às áreas atelectásicas. Resultados: O escore de lesão pulmonar foi significativamente maior no Grupo Controle-Lipopolissacarídeo (0,41 ± 0,13) do que no Grupo Controle-Solução Salina (0,15 ± 0,51), com p < 0,05. As regiões periatelectásicas apresentaram escores maiores de lesão pulmonar do que as regiões normalmente aeradas nos Grupos Atelectasia-Solução Salina (0,44 ± 0,06 versus 0,27 ± 0,74, p < 0,05) e Atelectasia-Lipopolissacarídeo (0,56 ± 0,09 versus 0,35 ± 0,04, p < 0,05). O escore de lesão pulmonar nas regiões periatelectásicas foi maior no Grupo Atelectasia-Lipopolissacarídeo (0,56 ± 0,09) do que na região periatelectásica do Grupo Atelectasia-Solução Salina (0,44 ± 0,06), p < 0,05. Conclusão: A atelectasia pode causar lesão no tecido circundante após um período de ventilação mecânica com parâmetros ventilatórios protetores. Seu efeito foi mais significativo em pulmões previamente lesionados.

RESUMO

INTRODUCCIÓN: La mortalidad por pacientes por COVID-19 grave que desarrollaban neumonía grave y síndrome de dificultad respiratoria agudo (SDRA) grave ha sido significativa a pesar del tratamiento oportuno. Es importante determinar predictores tempranos de enfermedad que nos ayuden a estratificar aquellos pacientes con mayor riesgo de fallecer. Se pretende estudiar el comportamiento del puntaje APP (APPS) como predictor de ello, basados en algunos reportes de uso y utilidad en el SDRA. no COVID-19. OBJETIVO: Determinar si el APPS es útil como predictor de mortalidad en SDRA. por COVID-19 grave. PACIENTES Y MÉTODO: Se realizó un estudio tipo cohorte retrospectivo, incluyendo pacientes de la Unidad de Cuidados Intensivos (UCI), con SDRA. por COVID-19 grave, que ingresaron a la UCI del Hospital Regional Docente de Trujillo (HRDT) en el período abril 2020- abril 2021. Se evalúo la utilidad del APPS como predictor de mortalidad em dicha población. RESULTADOS: El APPS demostró ser un factor asociado a mortalidad en pacientes con SDRA. y COVID-19 grave (RPa 1,34; IC 95% 1,16 a 1,56; p < 0,001). Además, encontramos que, al realizar un modelo de predicción ajustado por edad, sexo, SOFA, APPS, shock, Indice de Charlson (ICh), se comportan como factores asociados a mortalidad el APPS, el sexo masculino (RPa: 1,48; IC 95% 1,09 a 2,049; p < 0,05) y el ICh (RPa: 1,11; IC 95% 1,02 a 1,21; p < 0,05). CONCLUSIÓN: El APPS, el sexo masculino y el ICh son predictores de mortalidad en SDRA. por COVID-19 grave.

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BACKGROUND: Mortality in patients with severe COVID-19 who developed severe pneumonia and severe Acute Respiratory Distress Syndrome (ARDS) has been significant despite timely treatment. It is important to determine early predictors of disease that help us to stratify those patients with a higher risk of death. It is intended to study the behavior of the APPS score as a predictor of this, based on some reports of use and usefulness in non-COVID-19 ARDS. AIM: To determine if the APP score is useful as a predictor of mortality in ARDS due to severe COVID-19. METHOD: A retrospective cohort study was carried out, including patients from the Intensive Care Unit (ICU) with ARDS due to severe COVID-19 who were admitted to the ICU of the Trujillo Regional Teaching Hospital (HRDT) in the period March 2020 to March 2021. The usefulness of the APP score as a predictor of mortality in mentioned population was evaluated. RESULTS: The APP score proved to be a factor associated with mortality in patients with ARDS and severe COVID-19 (APR 1.34; 95% CI 1.16 to 1.56; p < 0.001). We also found that when performing a prediction model adjusted for age, sex, SOFA, APP score, shock and Charlson Index (ICh) we found that the APP score, male sex (APR: 1.48; 95% CI 1.09 to 2.049; p < 0.05) and the ICh behave as factors associated with mortality (RPa: 1.11; 95% CI 1.02 to 1.21; p < 0.05). CONCLUSION: The APP score, male sex, and ICh are predictors of mortality in ARDS due to severe COVID-19.

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , COVID-19/complicações , Análise Multivariada , Valor Preditivo dos Testes , Estudos Retrospectivos , Curva ROC , Mortalidade Hospitalar , COVID-19/mortalidade , Unidades de Terapia Intensiva

RESUMO

BACKGROUND: In the acute distress respiratory syndrome (ARDS), specific lung regions can be exposed to excessive strain due to heterogeneous disease, gravity-dependent lung collapse and injurious mechanical ventilation. Computed tomography (CT) is the gold standard for regional strain assessment. An alternative tool could be the electrical impedance tomography (EIT). We aimed to determine whether EIT-based methods can predict the dynamic relative regional strain (DRRS) between two levels of end-expiratory pressure (PEEP) in gravity-non-dependent and dependent lung regions. METHODS: Fourteen ARDS patients underwent CT and EIT acquisitions (at end-inspiratory and end-expiratory) at two levels of PEEP: a low-PEEP based on ARDS-net strategy and a high-PEEP titrated according to EIT. Three EIT-based methods for DRRS were compared to relative CT-based strain: (1) the change of the ratio between EIT ventilation and end-expiratory lung impedance in arbitrary units ([ΔZAU low-PEEP/EELIAU low-PEEP]/[ΔZAU high-PEEP/EELIAU high-PEEP]), (2) the change of ΔZ/EELI ratio calibrated to mL ([ΔZml low-PEEP/EELIml low-PEEP]/[ΔZml high-PEEP/EELIml high-PEEP]) using CT data, and (3) the relative change of ∆ZAU (∆ZAU low-PEEP/∆ZAU high-PEEP). We performed linear regressions analysis and calculated bias and limits of agreement to assess the performance of DRRS by EIT in comparison with CT. RESULTS: The DRRS assessed by (ΔZml low-PEEP/EELIml low-PEEP)/(ΔZml high-PEEP/EELIml high-PEEP) and ∆ZAU low-PEEP/∆ZAU high-PEEP showed good relationship and agreement with the CT method (R2 of 0.9050 and 0.8679, respectively, in non-dependent region; R2 of 0.8373 and 0.6588, respectively, in dependent region; biases ranging from - 0.11 to 0.51 and limits of agreement ranging from - 0.73 to 1.16 for both methods and lung regions). Conversely, DRRS based on EELIAU ([ΔZAU low-PEEP/EELIAU low-PEEP]/[ΔZAU high-PEEP/EELIAU high-PEEP]) exhibited a weak negative relationship and poor agreement with the CT method for both non-dependent and dependent regions (R2 ~ 0.3; bias of 3.11 and 2.08, and limits of agreement of - 2.13 to 8.34 and from - 1.49 to 5.64, respectively). CONCLUSION: Changes in DRRS during a PEEP trial in ARDS patients could be monitored using EIT, based on changes in ΔZmL/EELIml and ∆ZAU. The relative change ∆ZAU offers the advantage of not requiring CT data for calibration.

Assuntos

Respiração com Pressão Positiva , Síndrome do Desconforto Respiratório , Humanos , Impedância Elétrica , Respiração com Pressão Positiva/métodos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Tomografia/métodos

RESUMO

Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory illness primarily associated with microvascular endothelial changes, particularly in the lungs. However, the role of the pulmonary epithelium in HCPS pathogenesis remains unclear. This study explores the potential of soluble Receptors for Advanced Glycation End-products (sRAGE) as a biomarker for assessing pulmonary epithelial damage in severe HCPS, challenging the prevailing view that endothelial dysfunction is the sole driver of this syndrome. We conducted a cross-sectional study on critically ill HCPS patients, categorizing them into mild HCPS, severe HCPS, and negative control groups. Plasma sRAGE levels were measured, revealing significant differences between the severe HCPS group and controls. Our findings suggest that sRAGE holds promise as an indicator of pulmonary epithelial injury in HCPS and may aid in tracking disease progression and guiding therapeutic strategies. This study brings clarity on the importance of investigating the pulmonary epithelium's role in HCPS pathogenesis, offering potential avenues for enhanced diagnostic precision and support in this critical public health concern.

Assuntos

Doenças Transmissíveis , Infecções por Hantavirus , Síndrome Pulmonar por Hantavirus , Lesão Pulmonar , Orthohantavírus , Humanos , Receptor para Produtos Finais de Glicação Avançada , Endotélio Vascular , Estudos Transversais , Pulmão/patologia , Biomarcadores , Lesão Pulmonar/patologia , Síndrome Pulmonar por Hantavirus/diagnóstico

RESUMO

COVID-19, a disease caused by the SARS-CoV-2 virus, poses significant threats to the respiratory system and other vital organs. Long non-coding RNAs have emerged as influential epigenetic regulators and promising biomarkers in respiratory ailments. The objective of this study was to identify candidate lncRNAs in SARS-CoV-2-positive individuals compared to SARS-CoV-2-negative individuals and investigate their potential association with ARDS-CoV-2 (acute respiratory distress syndrome). Employing qRT-PCR, we meticulously examined the expression profiles of a panel comprising 84 inflammation-related lncRNAs in individuals presenting upper respiratory infection symptoms, categorizing them into those testing negative or positive for SARS-CoV-2. Notably, first-phase PSD individuals exhibited significantly elevated levels of AC000120.7 and SENP3-EIF4A1. In addition, we measured the expression of two lncRNAs, AC000120.7 and SENP3-EIF4A1, in patients with ARDS unrelated to SARS-CoV-2 (n = 5) and patients with ARDS induced by SARS-CoV-2 (ARDS-CoV-2, n = 10), and interestingly, expression was also higher among patients with ARDS. Intriguingly, our interaction pathway analysis unveiled potential interactions between lncRNA AC000120.7, various microRNAs, and genes associated with inflammation. This study found higher expression levels of lncRNAs AC000120.7 and SENP3-EIF4A1 in the context of infection-positive COVID-19, particularly within the complex landscape of ARDS.

RESUMO

OBJECTIVES: First, to investigate whether the severity of acute respiratory distress syndrome (ARDS) influences ventilator-induced lung injury (VILI) risk in ventilated patients with similar mechanical power of respiratory system (MPRS). Second, to determine whether, under these circumstances, there is a relationship between transpulmonary mechanical power (MPTp) normalized to the aerated lung (specific lung mechanical power or SLMP) and VILI risk, and third, to determine whether normalizing MPRS to compliance of respiratory system (CRS) can replace SLMP to bedside. DESIGN: Prospective cohort study. SETTING: The study was conducted in a tertiary academic ICU. PATIENTS: The study included 18 patients with ARDS. INTERVENTIONS: Ventilatory settings were adjusted to achieve a similar MPRS. MEASUREMENTS AND MAIN RESULTS: Mechanical power was normalized to CRS (specific mechanical power or SMP = MPRS/CRS), and SLMP was calculated as the ratio between MPTp and end-expiratory lung volume (SLMP = MPTp/EELV). The strain was defined as the ratio between tidal volume and EELV (strain = Vt/EELV), stress as transpulmonary pressure at the end of inspiration, and atelectrauma as the difference between expiration and inspiration in the nonaerated lung. Although patients had been ventilated with similar MPRS = 23.75 (23-24) J/min and MPTp = 11.6 (10.8-12.8) J/min, SLMP increased linearly with the fall in Pao2/Fio2 (R = -0.83, p = 0.0001). MPRS only correlated positively with VILI-associated mechanisms when normalized to aerated lung size: correlations between SLMP and stress (R = 0.9, R2 = 0.84, p = 0.00004), strain (R = 0.97, R2 = 0.94, p < 0.00001) and atelectrauma (R = 0.82, R2 = 0.70, p = 0.00002), and correlations between SMP and stress (R = 0.86, R2 = 0.75, p = 0.00001), strain (R = 0.68, R2 = 0.47, p = 0.001) and atelectrauma (R = 0.67, R2 = 0.46, p = 0.002). CONCLUSIONS: The results suggest that normalizing mechanical power to lung-aerated size or CRS may correlate positively with stress, strain, and atelectrauma.

RESUMO

BACKGROUND: Trunk inclination from semirecumbent head-upright to supine-flat positioning reduces driving pressure and increases respiratory system compliance in patients with acute respiratory distress syndrome (ARDS). These effects are associated with an improved ventilatory ratio and reduction in the partial pressure of carbon dioxide (PaCO2). However, these physiological effects have not been completely studied, and their mechanisms have not yet been elucidated. Therefore, this study aimed to evaluate the effects of a change in trunk inclination from semirecumbent (45°) to supine-flat (10°) on physiological dead space and ventilation distribution in different lung regions. RESULTS: Twenty-two ARDS patients on pressure-controlled ventilation underwent three 60-min steps in which trunk inclination was changed from 45° (baseline) to 10° (intervention) and back to 45° (control) in the last step. Tunk inclination from a semirecumbent (45°) to a supine-flat (10°) position resulted in a higher tidal volume [371 (± 76) vs. 433 (± 84) mL (P < 0.001)] and respiratory system compliance [34 (± 10) to 41 (± 12) mL/cmH2O (P < 0.001)]. The CO2 exhaled per minute improved from 191 mL/min (± 34) to 227 mL/min (± 38) (P < 0.001). Accordingly, Bohr's dead space ratio decreased from 0.49 (± 0.07) to 0.41 (± 0.06) (p < 0.001), and PaCO2 decreased from 43 (± 5) to 36 (± 4) mmHg (p < 0.001). In addition, the impedance ratio, which divides the ventilation activity of the ventral region by the dorsal region ventilation activity in tidal images, dropped from 1.27 (0.83-1.78) to 0.86 (0.51-1.33) (p < 0.001). These results, calculated from functional EIT images, indicated further ventilation activity in the dorsal lung regions. These effects rapidly reversed once the patient was repositioned at 45°. CONCLUSIONS: A change in trunk inclination from a semirecumbent (45 degrees) to a supine-flat position (10 degrees) improved Bohr's dead space ratio and reduced PaCO2 in patients with ARDS. This effect is associated with an increase in tidal volume and respiratory system compliance, along with further favourable impedance ventilation distribution toward the dorsal lung regions. This study highlights the importance of considering trunk inclination as a modifiable determinant of physiological parameters. The angle of trunk inclination is essential information that must be reported in ARDS patients.