title: Effect of PEEP on phosgene-induced lung edema: pilot study on dogs using protective ventilation strategies.
abstract: Various therapeutic regimes have been proposed for treatment of phosgene-induced acute lung injury (P-ALI). Most of these treatments rely on late-stage supportive measures to maintain the oxygenation of the lung. This exploratory proof-of-concept study on Beagle dogs focused on protective positive end-expiratory pressure (PEEP) ventilation, initiated early at the yet asymptomatic stage after phosgene exposure. Conscious, spontaneously breathing dogs were head-only exposed to a potentially lethal inhalation dose of phosgene (870 ppm × min). Shortly after exposure, the dogs were anesthetized, intubated and then subjected to mechanical ventilation (PEEP; tidal volume (VT)=10-12 mL/kg body weight, 40 breaths/min) at 0, 4, or 12 cm H2O over a post-exposure period of 8h (one dog per setting). For reference, one additional dog received the same dose of phosgene without anesthesia and mechanical ventilation. Time-course changes of hematocrit, leukocytes, and thrombocytes were determined in peripheral blood. At necropsy, changes lung weights, bronchoalveolar lavage, and histology were used to assess the efficacy of treatment. The most salient outcome in the non-ventilated dog was a time-related hemoconcentration and leukocytosis and autopsy findings suggestive of pulmonary congestion and edema. The pulmonary epithelium of the major airways was generally intact; however, in their lumen inflammatory cells, cellular debris and mucus were present. Relative to the dog receiving no intervention, the lung edema was markedly alleviated by PEEP at both 4 and 12 cm H2O but not at 0 cm H2O PEEP. In summary, the time-dependent progression into a life-threatening pulmonary edema can effectively be suppressed by protective, low-pressure PEEP when implemented early enough after exposure to phosgene. However, due to the exploratory nature of this study, the findings may suggest an association between PEEP and protection from pulmonary edema. However, definite conclusions and recommendations cannot be made yet based upon the small sample size and the limited variables examined.
authors.affiliation: Fourth Military Medical University, Department of Toxicology, Xi'an, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Li
authors.affiliation: Bayer HealthCare Pharma, Experimental Toxicology, Wuppertal, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Rosenbruch
authors.affiliation: Bayer HealthCare Pharma, Experimental Toxicology, Wuppertal, Germany. Electronic address: juergen.pauluhn@bayer.com.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Pauluhn
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004285:Dogs; D005260:Female; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010705:Phosgene / Q000633:toxicity*; D010865:Pilot Projects; D018467:Positive-Pressure Respiration, Intrinsic; D011654:Pulmonary Edema / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
chemical_list: D002619:Chemical Warfare Agents; D010705:Phosgene
keywords: Acute lung edema; Pathogenesis; Phosgene; Prognosis; Protective ventilation