Effect of PEEP on phosgene-induced lung edema: Pilot study on dogs using protective ventilation strategies

Li, Wenli; Martin, Rachel W.; Pauluhn, Jürgen

doi:10.1016/j.etp.2014.10.003

Cited by 19 publications

(13 citation statements)

References 40 publications

(40 reference statements)

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“…Secondary changes in cardiovascular control and hemodynamics add another dimension of complexity. These conclusions from small‐animal models were further substantiated in exploratory proof‐of‐concept studies in dogs [17] and pigs [22] with protective positive PEEP ventilation. This mode of ventilation strategy was demonstrated to improve survival in patients with ARDS [31, 120, 121], especially when begun early after the initiating encounter.…”

Section: Inhalation Studies—larger Animalsmentioning

confidence: 83%

“…Details of the head‐only chamber used for dog inhalation studies have been published elsewhere [17,20]. This mode of exposure to phosgene differed from those of other authors using larger animals.…”

Section: Inhalation Methods—larger Animalsmentioning

confidence: 99%

“…Microscopy confirmed reduced hemorrhage, neutrophilic infiltration, and intra‐alveolar edema. Thus, the time‐dependent progression into life‐threatening pulmonary edema can be effectively suppressed by protective, low‐pressure PEEP when implemented sufficiently early after exposure to phosgene [17]. Anesthetized pigs were instrumented and exposed to phosgene (concentration × time (Cxt), 2350 mg × min/m 3 or 573 ppm × min) and then ventilated with intermittent PEEP (V T = 10 mL/kg; PEEP 3 cm H 2 O; 20 breaths/min; FiO 2 : 0.24), monitored for 6 h after exposure, and then randomized into treatment groups: V T at 8 or 6 mL/kg; PEEP 8 cm H 2 O; 20 or 25 breaths/min; FiO 2 : 0.4.…”

Section: Inhalation Studies—larger Animalsmentioning

confidence: 99%

“…Therapeutic approaches have traditionally been based on hypothetical pathways elucidated through in vivo research on rodents. Putative mechanisms of phosgene‐induced ALI range from direct interaction and deterioration of lung surfactants and associated changes in lung mechanics [16,17] to free radical attacks on neuronal, endothelial and epithelial cells, resulting in tissue destruction and mediator release [18,19]. Canine, ovine, and porcine models have been used when studying the cardiopulmonary and hematological effects of methods used in humans.…”

Section: Introductionmentioning

confidence: 99%

“…This review discusses the most salient findings from toxicological and pharmacological research on rats and dogs over a period of one decade [17, 20, 37, 38, 41–50]. The objective of this project was not only to develop inhalation exposure systems to expose rats and dogs to phosgene under highly controlled conditions and similar modes of exposure [20, 33, 37, 38, 49, 51] but also to study the early physiological events involved in phosgene‐induced ALI, including options for causal and preventive treatment strategies.…”

Section: Introductionmentioning

confidence: 99%

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Phosgene‐induced acute lung injury (ALI): differences from chlorine‐induced ALI and attempts to translate toxicology to clinical medicine

Pauluhn

2017

Clinical & Translational Med

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BackgroundPhosgene (carbonyl dichloride) gas is an indispensable chemical inter‐mediate used in numerous industrial processes. There is no clear consensus as to its time‐ and inhaled‐dose‐dependent etiopathologies and associated preventive or therapeutic treatment strategies. MethodsCardiopulmonary function was examined in rats exposed by inhalation to the alveolar irritant phosgene or to the airway irritant chlorine during and following exposure. Terminal measurements focused on hematology, protein extravasation in bronchoalveolar lavage (BAL), and increased lung weight. Noninvasive diagnostic and prognostic endpoints in exhaled breath (carbon dioxide and nitric oxide) were used to detect the clinically occult stage of pulmonary edema. ResultsThe first event observed in rats following high but sublethal acute exposure to phosgene was the stimulation of alveolar nociceptive vagal receptors. This afferent stimulation resulted in dramatic changes in cardiopulmonary functions, ventilation: perfusion imbalances, and progressive pulmonary edema and phospholipoproteinosis. Hematology revealed hemoconcentration to be an early marker of pulmonary edema and fibrin as a discriminating endpoint that was positive for the airway irritant chlorine and negative for the alveolar irritant phosgene. ConclusionsThe application of each gas produced typical ALI/ARDS (acute lung injury/acute respiratory distress syndrome) characteristics. Phosgene‐induced ALI showed evidence of persistent apnea periods, bradycardia, and shifts of vascular fluid from the peripheral to the pulmonary circulation. Carbon dioxide in expired gas was suggestive of increased ventilation dead space and appeared to be a harbinger of progressively developing lung edema. Treatment with the iNOS inhibitor aminoguanidine aerosol by inhalation reduced the severity of phosgene‐induced ALI when applied at low dose‐rates. Symptomatic treatment regimens were considered inferior to causal modes of treatment.

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Section: Inhalation Studies—larger Animalsmentioning

confidence: 83%

Section: Inhalation Methods—larger Animalsmentioning

confidence: 99%

Section: Inhalation Studies—larger Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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