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Influence of neurally adjusted ventilatory assist and positive end-expiratory pressure on breathing pattern in rabbits with acute lung injury*

Allo, Jean-Christophe MD; Beck, Jennifer C. PhD; Brander, Lukas MD; Brunet, Fabrice MD; Slutsky, Arthur S. MD; Sinderby, Christer A. PhD

doi: 10.1097/01.CCM.0000242520.50665.9F
Laboratory Investigations

Objective: To evaluate the influence of neurally adjusted ventilatory assist (NAVA) and positive end-expiratory pressure (PEEP) on the control of breathing in rabbits with acute lung injury.

Design: Prospective animal study.

Setting: Experimental laboratory in a university hospital.

Subjects: Male White New Zealand rabbits (n = 18).

Intervention: Spontaneously breathing rabbits with hydrochloric acid-induced lung injury were ventilated with NAVA and underwent changes in NAVA gain and PEEP (six nonvagotomized and five vagotomized). Seven other nonvagotomized rabbits underwent 4 hrs of ventilation with hourly titration of PEEP, Fio2, and NAVA gain.

Measurements and Main Results: We studied diaphragm electrical activity, respiratory pressures, and breathing pattern. After lung injury, 0 cm H2O of PEEP resulted in high tonic and no discernible phasic diaphragm electrical activity in the nonvagotomized rabbits; stepwise increases in PEEP (up to 11.7 ± 2.6 cm H2O) reduced tonic but increased phasic diaphragm electrical activity. Increasing the NAVA gain reduced phasic diaphragm electrical activity to almost half and abolished esophageal pressure swings. Tidal volume remained at 4–5 mL/kg, and respiratory rate did not change. In the vagotomized group, lung injury did not induce tonic activity, and phasic activity and tidal volume were several times higher than in the nonvagotomized rabbits. Four hours of breathing with NAVA restored breathing pattern and neural and mechanical breathing efforts to pre-lung injury levels.

Conclusions: Acute lung injury can cause a vagally mediated atypical diaphragm activation pattern in spontaneously breathing rabbits. Modulation of PEEP facilitates development of phasic diaphragm electrical activity, whereupon implementation of NAVA can efficiently maintain unloading of the respiratory muscles without delivering excessive tidal volume in rabbits with intact vagal function.

From the Service d'Acceuil et de Traitement des Urgences, Hôpital Cochin, Paris, France (JCA); Sunnybrook and Women's College Health Sciences Centre, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (JCB); and the Department of Critical Care Medicine, St. Michael's Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada (LB, FB, ASS, CAS).

The work was performed at Department of Critical Care Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.

Drs. Beck and Sinderby have made inventions related to neural control of mechanical ventilation that are patented. The license for these patents belongs to Maquet Critical Care. Future commercial uses of this technology may provide financial benefit to Drs. Beck and Sinderby through royalties. Drs. Beck and Sinderby each own 50% of Neurovent Research Inc. Neurovent Research is a research and development company that builds the equipment and catheters for research studies. Neurovent Research has a consulting agreement with Maquet Critical Care. Dr. Slutsky consults for companies that make ventilators, specifically, Maquet Critical Care and Hamilton Medical, and is compensated for these consultations. The remaining authors have not disclosed any potential conflicts of interest.

Dr. Allo was supported, in part, by the St. Michael Hospitals' Pitts Foundation, Toronto, Ontario, Canada; Dr. Beck was supported, in part, by National Institutes of Health grant 1 R21 HD45047-01; Dr. Brander holds postdoctoral fellowships from the Swiss Foundation for Fellowships in Medicine and Biology (SSMBS) provided by Novartis AG and from the Division of Respirology at the University of Toronto provided by Merck-Frosst.

© 2006 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins