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Total liquid ventilation efficacy in an ovine model of severe meconium aspiration syndrome

Avoine, Olivier MSc; Bossé, Dominick MSc; Beaudry, Benoit MSc; Beaulieu, Alexandre MSc; Albadine, Roula MD; Praud, Jean-Paul MD, PhD; Robert, Raymond PhD; Micheau, Philippe PhD; Walti, Hervé MD

doi: 10.1097/CCM.0b013e31820ead1a
Laboratory Investigations

Objective: To test the hypothesis that total liquid ventilation enables a more effective and better tolerated lavage than a bronchoalveolar lavage performed with diluted surfactant in a newborn ovine model of severe acute meconium aspiration syndrome.

Design: Prospective, randomized, interventional study.

Setting: Animal research laboratory at the Faculté de médecine et des sciences de la santé de l'université de Sherbrooke, Sherbrooke, Canada.

Subjects: Twenty-three newborn lambs, <4 days, 2.5–4.0 kg in weight.

Interventions: Animals were intubated, anesthetized, and paralyzed. Catheters were placed in the femoral artery and jugular vein. Severe meconium aspiration syndrome was obtained by instillation of a 25% dilution of human meconium in saline (1 mL/kg × 2). Lambs were then randomized in 12 total liquid ventilation-bronchoalveolar lavage (minute ventilation of 160 mL/kg/min with perfluorodecalin) vs. 11 bronchoalveolar lavage performed with diluted surfactant (conventional ventilation + 30 mL/kg in two aliquots bronchoalveolar lavage with 5 mg/mL BLES surfactant). Surviving lambs were ventilated for a total of 4 hrs and euthanized.

Measurements and Main Results: Arterial blood gases, systemic and pulmonary hemodynamic parameters using the thermodilution method, percentage of recovered meconium, and lung histologic scores. Total liquid ventilation bronchoalveolar lavage enabled a significantly higher Pao2 throughout the experiment. Paco2, pH, and hemodynamic parameters were comparable for both groups except for an increase in mean pulmonary arterial pressure during total liquid ventilation. Total liquid ventilation bronchoalveolar lavage allowed for 43 ± 14% of the instilled meconium to be removed vs. 28 ± 10% for bronchoalveolar lavage performed with diluted surfactant (p = .022). Lung histologic analysis showed no difference between total scores.

Conclusions: Total liquid ventilation bronchoalveolar lavage is well tolerated and more effective in terms of meconium washout and gas exchange than bronchoalveolar lavage performed with diluted surfactant in this experimental model of severe meconium aspiration syndrome. These positive results open the way to further experiments in our ovine model, ultimately aiming at a clinical trial with total liquid ventilation bronchoalveolar lavage to treat severe meconium aspiration syndrome.

From the Departments of Pediatrics and Department of Physiology and Biophysics (OA, DB, J-PP, HW), Mechanical Engineering (BB, AB, RR, PM), and Pathology (RA), Université de Sherbrooke, Sherbrooke, Canada.

This work was supported in part by The Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada; La Fondation des Étoiles; L'Équipe de Recherche Périnatale sur les Ovins de l'université de Sherbrooke; and Le Fonds québécois de la recherche sur la nature et les technologies.

Drs. Praud, Micheau, and Walti are members of the FRSQ-funded Centre de recherche clinique Étienne-Le Bel. Dr. Praud received a grant from the Canadian Institutes of Health Research. Drs. Praud, Robert, and Walti filed a patent on November 29, 2002 (Canadian Patent Application, 2,413,041), a European patent was delivered on January 17, 2007 (1, 424, 090), and a U.S. patent was delivered on June 1, 2010 (7,726,311). The invention is a medical apparatus used to perform total liquid ventilations with a liquid vector biologically inert and appropriate to the gaseous exchanges. The remaining authors have not disclosed any potential conflicts of interest.

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© 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins