Protective Ventilation Strategies in the Management of Phosgene-Induced Acute Lung Injury

Abstract

Phosgene is a chemical widely used in the plastics industry and has been used in warfare. It produces a life-threatening pulmonary edema within hours of exposure, to which no specific antidote exists. This study aims to examine the pathophysiological changes seen with low tidal volume ventilation (protective ventilation (PV)) strategies compared to conventional ventilation (CV), in a model of phosgene-induced acute lung injury. Anesthetized pigs were instrumented and exposed to phosgene (concentration x time (Ct), 2,350 mg x min x m(-3)) and then ventilated with intermittent positive pressure ventilation (tidal volume (TV) = 10 ml x kg(-1); positive end expiratory pressure, 3 cm H2O; frequency, 20 breaths x min(-1); fractional concentration of inspired oxygen, 0.24), monitored for 6 hours after exposure, and then randomized into treatment groups: CV, PV (A) or (B) (TV, 8 or 6 ml x kg(-1); positive end expiratory pressure, 8 cm H2O; frequency, 20 or 25 breaths x min(-1); fractional concentration of inspired oxygen, 0.4). Pathophysiological parameters were measured for up to 24 hours. The results show that PV resulted in improved oxygenation, decreased shunt fraction, and mortality, with all animals surviving to 24 hours compared to only three of the CV animals. Microscopy confirmed reduced hemorrhage, neutrophilic infiltration, and intra-alveolar edema.

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

“…Unsurprisingly, anti-inflammatory mitigation principles (dexamethasone and salicylate alone and in combination; Liu et al, 2013;Luo et al, 2014) were inefficacious. Supportive evidence of a cardiogenic etiopathology seems to be that non-invasive, early protective mechanical ventilation proved to be beneficial in this explorative dog model as well as in pigs using a longer postexposure ventilation period as used as in this study (Brown et al, 2002;Parkhouse et al, 2007). Further research is warranted to investigate the outcome over an extended post-phosgene exposure time-period up to 24 h. With increased post-exposure period any increasing circulatory instability may require a well-balanced, ideally conservative, fluid resuscitation.…”

“…Non-invasive, continuous positive airway pressure ventilation (CPAP) is an accepted, readily available mode of treatment in acute cardiogenic pulmonary edema. Increasing evidence suggests that CPAP-like ventilation has efficacy in experimental models and patients to mitigate even severe potentially lethal lung edema, if implemented early enough (Colmenero-Ruiz et al, 1997;Dueck et al, 1977;Grainge and Rice, 2010;Lorraine et al, 2000;Nieman et al, 2013;Parkhouse et al, 2007;Ruiz-Bailén et al, 1999;Roy et al, 2012; http://dx.doi.org/10. 1016/j.etp.2014.10.003 0940-2993/© 2014 Published by Elsevier GmbH.…”

The injured lung: clinical issues and experimental models

“…The protective ventilation strategy significantly improved survival, arterial blood oxygenation and pathology at 24 h [7]. Oxygen supplementation also significantly improved survival and arterial blood oxygenation at 24 h even when given at low flow (40% versus 80%) and delayed onset (started 12 h postexposure) [24].…”

“…Briefly, initial exposure is followed by an asymptomatic period that varies in duration with dose (6-12 h); this is followed by non-cardiogenic pulmonary oedema leading to respiratory failure and death. A number of similarities exist between the injury produced by CG exposure and that reported in patients with ALI or ARDS [6,7]. Other agents employed during WW1 included sulphur mustard (HD), which was first used at Ypres in 1917.…”

Phosgene Exposure: A Case of Accidental Industrial Exposure

“…ARDSNet-recommended ventilation strategies have shown improvement in 24 h of survival in one large pig model [24]. Oxygen therapy has been widely advocated since World War I; however, early high-dose oxygen could be potentially harmful through the production of reactive oxygen species.…”