TY - JOUR
T1 - Abrupt deflation after sustained inflation causes lung injury
AU - Katira, Bhushan H.
AU - Engelberts, Doreen
AU - Otulakowski, Gail
AU - Giesinger, Regan E.
AU - Yoshida, Takeshi
AU - Post, Martin
AU - Kuebler, Wolfgang M.
AU - Connelly, Kim A.
AU - Kavanagh, Brian P.
N1 - Funding Information:
Supported by research funds (B.P.K.) from the Canadian Institutes of Health Research. B.P.K. holds the Dr. Geoffrey Barker Chair in Critical Care Research. K.A.C. holds a New Investigator award from the Canadian Institutes of Health Research and an Early Researcher Award from the Ministry of Research and Innovation and Science, Ontario.
Publisher Copyright:
© 2018 by the American Thoracic Society.
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Rationale: Ventilator management in acute respiratory distress syndrome usually focuses on setting parameters, but events occurring at ventilator disconnection are not well understood. Objectives: To determine if abrupt deflation after sustained inflation causes lung injury. Methods: Male Sprague-Dawley rats were ventilated (low VT, 6 ml/kg) and randomized to control (n = 6; positive end-expiratory pressure [PEEP], 3 cm H2O; 100 min) or intervention (n = 6; PEEP, 3-11 cmH2Oover 70 min; abrupt deflation to zero PEEP; ventilation for 30 min). Lung function and injury was assessed, scanning electron microscopy performed, and microvascular leak timed by Evans blue dye (n = 4/group at 0, 2, 5, 10, and 20 min after deflation). Hemodynamic assessment included systemic arterial pressure (n =6), echocardiography (n = 4), and right (n = 6) and left ventricular pressures (n= 6). Measurements and Main Results: Abrupt deflation after sustained inflation (vs. control) caused acute lung dysfunction (compliance 0.48±1.0 vs. 0.82±0.2 m/cm H2O, oxygen saturation as measured by pulse oximetry 67±23.5 vs. 91±4.4%; P,0.05) and injury (wet/dry ratio 6.1±0.6 vs. 4.6±0.4; P,0.01). Vascular leak was absent before deflation and maximal 5-10 minutes thereafter; injury was predominantly endothelial. At deflation, left ventricular preload, systemic blood pressure, and left ventricular end-diastolic pressure increased precipitously in proportion to the degree of injury. Injury caused later right ventricular failure. Sodium nitroprusside prevented the increase in systemic blood pressure and left ventricular end-diastolic pressure associated with deflation, and prevented injury. Injury did not occur with gradual deflation. Conclusions: Abrupt deflation after sustained inflation can cause acute lung injury. It seems to be mediated by acute left ventricular decompensation (caused by increased left ventricular preload and afterload) that elevates pulmonary microvascular pressure; this directly injures the endothelium and causes edema, which is potentiated by the surge in pulmonary perfusion.
AB - Rationale: Ventilator management in acute respiratory distress syndrome usually focuses on setting parameters, but events occurring at ventilator disconnection are not well understood. Objectives: To determine if abrupt deflation after sustained inflation causes lung injury. Methods: Male Sprague-Dawley rats were ventilated (low VT, 6 ml/kg) and randomized to control (n = 6; positive end-expiratory pressure [PEEP], 3 cm H2O; 100 min) or intervention (n = 6; PEEP, 3-11 cmH2Oover 70 min; abrupt deflation to zero PEEP; ventilation for 30 min). Lung function and injury was assessed, scanning electron microscopy performed, and microvascular leak timed by Evans blue dye (n = 4/group at 0, 2, 5, 10, and 20 min after deflation). Hemodynamic assessment included systemic arterial pressure (n =6), echocardiography (n = 4), and right (n = 6) and left ventricular pressures (n= 6). Measurements and Main Results: Abrupt deflation after sustained inflation (vs. control) caused acute lung dysfunction (compliance 0.48±1.0 vs. 0.82±0.2 m/cm H2O, oxygen saturation as measured by pulse oximetry 67±23.5 vs. 91±4.4%; P,0.05) and injury (wet/dry ratio 6.1±0.6 vs. 4.6±0.4; P,0.01). Vascular leak was absent before deflation and maximal 5-10 minutes thereafter; injury was predominantly endothelial. At deflation, left ventricular preload, systemic blood pressure, and left ventricular end-diastolic pressure increased precipitously in proportion to the degree of injury. Injury caused later right ventricular failure. Sodium nitroprusside prevented the increase in systemic blood pressure and left ventricular end-diastolic pressure associated with deflation, and prevented injury. Injury did not occur with gradual deflation. Conclusions: Abrupt deflation after sustained inflation can cause acute lung injury. It seems to be mediated by acute left ventricular decompensation (caused by increased left ventricular preload and afterload) that elevates pulmonary microvascular pressure; this directly injures the endothelium and causes edema, which is potentiated by the surge in pulmonary perfusion.
KW - hemodynamics
KW - lung injury
KW - mechanical ventilation
UR - http://www.scopus.com/inward/record.url?scp=85055819768&partnerID=8YFLogxK
U2 - 10.1164/rccm.201801-0178OC
DO - 10.1164/rccm.201801-0178OC
M3 - Article
C2 - 29902384
AN - SCOPUS:85055819768
SN - 1073-449X
VL - 198
SP - 1165
EP - 1176
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 9
ER -