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Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation.
Am J Respir Crit Care Med. 2019 03 01; 199(5):603-612.AJ

Abstract

RATIONALE

There is wide variability in mechanical ventilation settings during extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome. Although lung rest is recommended to prevent further injury, there is no evidence to support it.

OBJECTIVES

To determine whether near-apneic ventilation decreases lung injury in a pig model of acute respiratory distress syndrome supported with ECMO.

METHODS

Pigs (26-36 kg; n = 24) were anesthetized and connected to mechanical ventilation. In 18 animals lung injury was induced by a double-hit consisting of repeated saline lavages followed by 2 hours of injurious ventilation. Then, animals were connected to high-flow venovenous ECMO, and randomized into three groups: 1) nonprotective (positive end-expiratory pressure [PEEP], 5 cm H2O; Vt, 10 ml/kg; respiratory rate, 20 bpm), 2) conventional-protective (PEEP, 10 cm H2O; Vt, 6 ml/kg; respiratory rate, 20 bpm), and 3) near-apneic (PEEP, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5 bpm). Six other pigs were used as sham. All groups were maintained during the 24-hour study period.

MEASUREMENTS AND MAIN RESULTS

Minute ventilation and mechanical power were lower in the near-apneic group, but no differences were observed in oxygenation or compliance. Lung histology revealed less injury in the near-apneic group. Extensive immunohistochemical staining for myofibroblasts and procollagen III was observed in the nonprotective group, with the near-apneic group exhibiting the least alterations. Near-apneic group showed significantly less matrix metalloproteinase-2 and -9 activity. Histologic lung injury and fibroproliferation scores were positively correlated with driving pressure and mechanical power.

CONCLUSIONS

In an acute respiratory distress syndrome model supported with ECMO, near-apneic ventilation decreased histologic lung injury and matrix metalloproteinase activity, and prevented the expression of myofibroblast markers.

Authors+Show Affiliations

1 Departamento de Medicina Intensiva.1 Departamento de Medicina Intensiva.2 Escuela de Kinesiología, and.3 Center of Acute Respiratory Critical Illness, Santiago, Chile. 4 Centro de Investigación de Medicina Veterinaria, Escuela de Medicina Veterinaria, Facultad de Ecología y Recursos Naturales, Universidad Andrés Bello, Santiago, Chile.1 Departamento de Medicina Intensiva.5 Centro de Medicina Regenerativa, Facultad de Medicina Clínica Alemana-Universidad del Desarrollo, Santiago, Chile.1 Departamento de Medicina Intensiva.6 Unidad de Pacientes Críticos Pediátrica, Clínica Alemana, Santiago, Chile.7 Escuela de Enfermería, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile.1 Departamento de Medicina Intensiva.8 Departamento de Enfermedades Respiratorias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.8 Departamento de Enfermedades Respiratorias, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.9 Departamento de Anatomía Patológica, Instituto Nacional del Tórax, Santiago, Chile.1 Departamento de Medicina Intensiva. 10 Escuela de Kinesiología, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso, Chile; and.1 Departamento de Medicina Intensiva. 3 Center of Acute Respiratory Critical Illness, Santiago, Chile.3 Center of Acute Respiratory Critical Illness, Santiago, Chile. 11 Unidad de Pacientes Críticos, Departamento de Medicina, Hospital Clínico Universidad de Chile, Santiago, Chile.1 Departamento de Medicina Intensiva. 3 Center of Acute Respiratory Critical Illness, Santiago, Chile.1 Departamento de Medicina Intensiva. 3 Center of Acute Respiratory Critical Illness, Santiago, Chile.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30216736

Citation

Araos, Joaquin, et al. "Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model With Extracorporeal Membrane Oxygenation." American Journal of Respiratory and Critical Care Medicine, vol. 199, no. 5, 2019, pp. 603-612.
Araos J, Alegria L, Garcia P, et al. Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation. Am J Respir Crit Care Med. 2019;199(5):603-612.
Araos, J., Alegria, L., Garcia, P., Cruces, P., Soto, D., Erranz, B., Amthauer, M., Salomon, T., Medina, T., Rodriguez, F., Ayala, P., Borzone, G. R., Meneses, M., Damiani, F., Retamal, J., Cornejo, R., Bugedo, G., & Bruhn, A. (2019). Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation. American Journal of Respiratory and Critical Care Medicine, 199(5), 603-612. https://doi.org/10.1164/rccm.201805-0869OC
Araos J, et al. Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model With Extracorporeal Membrane Oxygenation. Am J Respir Crit Care Med. 2019 03 1;199(5):603-612. PubMed PMID: 30216736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation. AU - Araos,Joaquin, AU - Alegria,Leyla, AU - Garcia,Patricio, AU - Cruces,Pablo, AU - Soto,Dagoberto, AU - Erranz,Benjamín, AU - Amthauer,Macarena, AU - Salomon,Tatiana, AU - Medina,Tania, AU - Rodriguez,Felipe, AU - Ayala,Pedro, AU - Borzone,Gisella R, AU - Meneses,Manuel, AU - Damiani,Felipe, AU - Retamal,Jaime, AU - Cornejo,Rodrigo, AU - Bugedo,Guillermo, AU - Bruhn,Alejandro, PY - 2018/9/15/pubmed PY - 2020/1/7/medline PY - 2018/9/15/entrez KW - acute respiratory distress syndrome KW - extracorporeal membrane oxygenation KW - mechanical ventilation KW - myofibroblast KW - ventilator-induced lung injury SP - 603 EP - 612 JF - American journal of respiratory and critical care medicine JO - Am J Respir Crit Care Med VL - 199 IS - 5 N2 - RATIONALE: There is wide variability in mechanical ventilation settings during extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome. Although lung rest is recommended to prevent further injury, there is no evidence to support it. OBJECTIVES: To determine whether near-apneic ventilation decreases lung injury in a pig model of acute respiratory distress syndrome supported with ECMO. METHODS: Pigs (26-36 kg; n = 24) were anesthetized and connected to mechanical ventilation. In 18 animals lung injury was induced by a double-hit consisting of repeated saline lavages followed by 2 hours of injurious ventilation. Then, animals were connected to high-flow venovenous ECMO, and randomized into three groups: 1) nonprotective (positive end-expiratory pressure [PEEP], 5 cm H2O; Vt, 10 ml/kg; respiratory rate, 20 bpm), 2) conventional-protective (PEEP, 10 cm H2O; Vt, 6 ml/kg; respiratory rate, 20 bpm), and 3) near-apneic (PEEP, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5 bpm). Six other pigs were used as sham. All groups were maintained during the 24-hour study period. MEASUREMENTS AND MAIN RESULTS: Minute ventilation and mechanical power were lower in the near-apneic group, but no differences were observed in oxygenation or compliance. Lung histology revealed less injury in the near-apneic group. Extensive immunohistochemical staining for myofibroblasts and procollagen III was observed in the nonprotective group, with the near-apneic group exhibiting the least alterations. Near-apneic group showed significantly less matrix metalloproteinase-2 and -9 activity. Histologic lung injury and fibroproliferation scores were positively correlated with driving pressure and mechanical power. CONCLUSIONS: In an acute respiratory distress syndrome model supported with ECMO, near-apneic ventilation decreased histologic lung injury and matrix metalloproteinase activity, and prevented the expression of myofibroblast markers. SN - 1535-4970 UR - https://www.unboundmedicine.com/medline/citation/30216736/Near_Apneic_Ventilation_Decreases_Lung_Injury_and_Fibroproliferation_in_an_Acute_Respiratory_Distress_Syndrome_Model_with_Extracorporeal_Membrane_Oxygenation_ DB - PRIME DP - Unbound Medicine ER -