title: Reduction in adverse effects of mechanical ventilation in rabbits with acute respiratory failure by treatment with extracorporeal CO2 removal and a large fluid volume of diluted surfactant.
abstract: The long-term outcome of infants with severe respiratory distress syndrome can be improved by optimizing surfactant therapy and minimizing the risk for pulmonary barovolutrauma and oxygen toxicity. The authors hypothesized that this may be achieved with low frequency ventilation and extracorporeal CO2 removal (LFV-ECCO2R), in combination with intratracheal instillation of a large fluid volume with diluted surfactant. Lung lavaged rabbits were initially ventilated with continuous positive pressure ventilation. The rabbits were randomized to treatment with LFV-ECCO2R and surfactant (experimental group), or surfactant only (control group). In the experimental group, the rabbits were treated with a large volume (16 ml/kg) of diluted surfactant (6.25 mg/ml) at a dose of 100 mg/kg body weight. After surfactant therapy, the FiO2 100% was gradually decreased. During 4 hours, the extracorporeal bloodflow was adjusted to maintain the PaCO2 between 4.0-6.0 kPa. Thereafter, the rabbits were allowed to breathe spontaneously with 2.5 cm H2O continuous positive airway pressure ventilation (CPAP) and 40% oxygen. In the control group, the rabbits received the same surfactant therapy. During the study period, the rabbits remained ventilated with an inspiratory oxygen concentration (FiO2) of 100% for 4 hours. The ventilator flow was adjusted to maintain the PaCO2 between 4.0 and 6.0 kPa. Thereafter, positive-end expiratory pressure was decreased to 2.5 cm H2O and FiO2 was gradually decreased to 40%. In the experimental group, FiO2 was decreased to 40% in a stepwise fashion whereby the PaO2 could be maintained easily within the normal range. Extracorporeal flow rates during perfusion ranged from 20-35 ml/kg/min and were sufficient to keep the PaCO2 and pH within normal limits. After 4 hours, the rabbits could breathe spontaneously with CPAP and 40% oxygen, while normal blood gas values were maintained. All rabbits survived the experiment. In the control group, all rabbits experienced severe hypoxemia, despite FiO2 of 100% oxygen and, during the course of weaning, all rabbits died because of hypoxia. In conclusion, the present study demonstrated that barovolutrauma due to mechanical ventilation, and oxygen toxicity due to high FiO2, can be minimized in an animal model of acute respiratory failure by the combination of LFV-ECCO2R and surfactant therapy.
authors.affiliation: Department of Pediatrics, University Hospital Groningen, The Netherlands.
authors.forename: F B
authors.initials: FB
authors.lastname: Plötz
authors.forename: P H
authors.initials: PH
authors.lastname: Mook
authors.forename: N J
authors.initials: NJ
authors.lastname: Jansen
authors.forename: S B
authors.initials: SB
authors.lastname: Oetomo
authors.forename: C R
authors.initials: CR
authors.lastname: Wildevuur
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000097:blood* / Q000302:isolation & purification*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005112:Extracorporeal Circulation / Q000379:methods*; D005440:Fluid Therapy; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000209:etiology / Q000628:therapy; D007231:Infant, Newborn; D055370:Lung Injury; D010100:Oxygen / Q000097:blood; D010865:Pilot Projects; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D011817:Rabbits; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods*; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy; D012131:Respiratory Insufficiency / Q000097:blood / Q000628:therapy*
chemical_list: D011663:Pulmonary Surfactants; D002245:Carbon Dioxide; D010100:Oxygen