Browsing by Author "Dubo, Sebastian"

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    Acute lung injury secondary to hydrochloric acid instillation induces small airway hyperresponsiveness
    (2021) Basoalto Escobar, Roque Ignacio; Damiani Rebolledo, Luis Felipe; Bachmann Barron, María Consuelo; Fonseca, Marcelo; Barros, Marisol; Soto Muñoz, Dagoberto Igor; Araos, Joaquin; Jalil Contreras, Yorschua Frederick; Dubo, Sebastian; Retamal, Jaime; Bugedo Tarraza, Guillermo Jaime; Henriquez, Mauricio; Bruhn Cruz, Alejandro Rodrigo
    Background: Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure characterized by altered lung mechanics and poor oxygenation. Bronchial hyperresponsiveness has been reported in ARDS survivors and animal models of acute lung injury. Whether this hyperreactivity occurs at the small airways or not is unknown. Objective: To determine ex-vivo small airway reactivity in a rat model of acute lung injury (ALI) by hydrochloric acid (HCl) instillation. Methods: Twelve anesthetized rats were connected to mechanical ventilation for 4-hour, and randomly allocated to either ALI group (HCl intratracheal instillation; n=6) or Sham (intratracheal instillation of 0.9% NaCl; n=6). Oxygenation was assessed by arterial blood gases. After euthanasia, tissue samples from the right lung were harvested for histologic analysis and wet-dry weight ratio assessment. Precision cut lung slice technique (100-200 pm diameter) was applied in the left lung to evaluate ex vivo small airway constriction in response to histamine and carbachol stimulation, using phase-contrast video microscopy. Results: Rats from the ALI group exhibited hypoxemia, worse histologic lung injury, and increased lung wet-dry weight ratio as compared with the sham group. The bronchoconstrictor responsiveness was significantly higher in the ALI group, both for carbachol (maximal contraction of 84.5 +/- 2.5% versus 61.4 +/- 4.2% in the Sham group, P<0.05), and for histamine (maximal contraction of 78.6 +/- 5.3% versus 49.6 +/- 5.3% in the Sham group, P<0.05). Conclusion: In an animal model of acute lung injury secondary to HCL instillation, small airway hyperresponsiveness to carbachol and histamine is present. These results may provide further insight into the pathophysiologi of ARDS.
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    Duration of diaphragmatic inactivity after endotracheal intubation of critically ill patients
    (2021) Sklar, Michael Chaim; Damiani Rebolledo, L. Felipe; Madotto, Fabiana; Jonkman, Annemijn; Rauseo, Michela; Soliman, Ibrahim; Telias, Irene; Dubo, Sebastian; Chen, Lu; Rittayamai, Nuttapol
    Abstract Background In patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity. Methods Prospective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering. Results Seventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0–50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering. Conclusion Low levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity. Trial Registration ClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.
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    Effect of positive end expiratory pressure on lung injury and haemodynamics during experimental acute respiratory distress syndrome treated with extracorporeal membrane oxygenation and near-apnoeic ventilation
    (2021) Araos, Joaquin; Alegría Vargas, Leyla; Garcia, Aline; Cruces, Pablo; Soto Muñoz, Dagoberto Igor; Erranz, Benjamín; Salomon, Tatiana; Medina, Tania; García Valdes, Patricio Hernán; Dubo, Sebastian; Bachmann Barron, María Consuelo; Basoalto Escobar, Roque Ignacio; Valenzuela, Emilio Daniel; Rovegno Echavarría, Maximiliano David; Vera Alarcón, María Magdalena; Retamal Montes, Jaime; Cornejo Rosas, Rodrigo Alfredo; Bugedo Tarraza, Guillermo; Bruhn, Alejandro
    Background: Lung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. Methods: Acute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n¼7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. Results: All pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n¼4) and early death (n¼3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cmH2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. Conclusions: During near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.