TY - JOUR
T1 - Dynamic positive end-expiratory pressure strategies using time and pressure recruitment at birth reduce early expression of lung injury in preterm lambs
AU - Tingay, David G.
AU - Pereira-Fantini, Prue M.
AU - Miedema, Martijn
AU - McCall, Karen E.
AU - Perkins, Elizabeth J.
AU - Dowse, Georgie
AU - Schinckel, Nicholas
AU - Sourial, Magdy
AU - Davis, Peter G.
N1 - Funding Information: This study is supported by a National Health and Medical Research Council Project Grant (Grant ID 1009287) and the Victorian Government Operational Infrastructure Support Program (Melbourne, Australia). D.G.T. was supported by a National Health and Medical Research Council Clinical Career Development Fellowship (Grant ID 1053889). P.G.D. is supported by a National Health and Medical Research Council Program Grant (Grant ID 606789). P.G.D. is supported by a National Health and Medical Research Council Practitioner Fellowship (Grant ID 556600). Chiesi Farmaceutici S.p.A. (Parma, Italy) provided the Curosurf used in this study as part of an unrestricted grant to D.G.T. at the Murdoch Children’s Research Institute. Swisstom AG (Landquart, Switzerland) manufactured EIT belts custom-built for lambs for this study. All EIT hardware was purchased by Murdoch Children’s Research Institute. Funding Information: The authors thank Regina Oakley for assistance in lamb management and preparation of some of the gas exchange and lung mechanics data, and Sarah White and Rebecca Sutton for assistance in the preparation of the ewes. This study is supported by a National Health and Medical Research Council Project Grant (Grant ID 1009287) and the Victorian Government Operational Infrastructure Support Program (Melbourne, Australia). D.G.T. was supported by a National Health and Medical Research Council Clinical Career Development Fellowship (Grant ID 1053889). P.G.D. is supported by a National Health and Medical Research Council Program Grant (Grant ID 606789). P.G.D. is supported by a National Health and Medical Research Council Practitioner Fellowship (Grant ID 556600). Chiesi Farmaceutici S.p.A. (Parma, Italy) provided the Curosurf used in this study as part of an unrestricted grant to D.G.T. at the Murdoch Children’s Research Institute. Swisstom AG (Landquart, Switzerland) manufactured EIT belts custom-built for lambs for this study. All EIT hardware was purchased by Murdoch Children’s Research Institute. Funding Information: D.G.T. has previously received grant funding from Chiesi Farmaceutici unrelated to this study. None of the other authors has any conflicts of interest, financial or otherwise, to disclose. Publisher Copyright: Copyright © 2022 the American Physiological Society.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Positive end-expiratory pressure (PEEP) is critical to the preterm lung at birth, but the optimal PEEP level remains uncertain. The objective of this study was to determine the effect of maximum PEEP levels at birth on the physiological and injury response in preterm lambs. Steroid-exposed preterm lambs (124-127 days gestation; n = 65) were randomly assigned from birth to either 1) positive pressure ventilation (PPV) at 8 cmH2O PEEP or 3-min dynamic stepwise PEEP strategy (DynPEEP), with either 2) 20 cmH2O maximum PEEP (10 PEEP second steps) or 3) 14 cmH2O maximum PEEP (20-s steps), all followed by standardized PPV for 90 min. Lung mechanics, gas exchange, regional ventilation and aeration (electrical impedance tomography), and histological and molecular measures of lung injury were compared between groups. Dynamic compliance was greatest using a maximum 20 cmH2O (DynPEEP). There were no differences in gas exchange, end-expiratory volume, and ventilator requirements. Regional ventilation became more uniform with time following all PEEP strategies. For all groups, gene expression of markers of early lung injury was greater in the gravity nondependent lung, and inversely related to the magnitude of PEEP, being lowest in the 20 cmH2O DynPEEP group overall. PEEP levels had no impact on lung injury in the dependent lung. Transient high maximum PEEP levels using dynamic PEEP strategies may confer more lung protection at birth.
AB - Positive end-expiratory pressure (PEEP) is critical to the preterm lung at birth, but the optimal PEEP level remains uncertain. The objective of this study was to determine the effect of maximum PEEP levels at birth on the physiological and injury response in preterm lambs. Steroid-exposed preterm lambs (124-127 days gestation; n = 65) were randomly assigned from birth to either 1) positive pressure ventilation (PPV) at 8 cmH2O PEEP or 3-min dynamic stepwise PEEP strategy (DynPEEP), with either 2) 20 cmH2O maximum PEEP (10 PEEP second steps) or 3) 14 cmH2O maximum PEEP (20-s steps), all followed by standardized PPV for 90 min. Lung mechanics, gas exchange, regional ventilation and aeration (electrical impedance tomography), and histological and molecular measures of lung injury were compared between groups. Dynamic compliance was greatest using a maximum 20 cmH2O (DynPEEP). There were no differences in gas exchange, end-expiratory volume, and ventilator requirements. Regional ventilation became more uniform with time following all PEEP strategies. For all groups, gene expression of markers of early lung injury was greater in the gravity nondependent lung, and inversely related to the magnitude of PEEP, being lowest in the 20 cmH2O DynPEEP group overall. PEEP levels had no impact on lung injury in the dependent lung. Transient high maximum PEEP levels using dynamic PEEP strategies may confer more lung protection at birth.
KW - lung injury
KW - positive end-expiratory pressure
KW - preterm infant
KW - resuscitation
UR - http://www.scopus.com/inward/record.url?scp=85139572315&partnerID=8YFLogxK
U2 - https://doi.org/10.1152/ajplung.00047.2022
DO - https://doi.org/10.1152/ajplung.00047.2022
M3 - Article
C2 - 35997273
SN - 1040-0605
VL - 323
SP - L464-L472
JO - American journal of physiology. Lung cellular and molecular physiology
JF - American journal of physiology. Lung cellular and molecular physiology
IS - 4
ER -