Management of Phosgene-Induced Acute Lung Injury (ALI) by Personalized Protective PEEP-ECMO: What Can We Learn from Animal Bioassays?

Abstract

Background: Phosgene (carbonyl dichloride) gas is an indispensable chemical intermediate used in numerous industrial processes. Acute lung injury (ALI) caused by accidental inhalation exposure to phosgene is characterized pulmonary edema being phenotypically manifested after an asymptomatic or more precisely phrased “clinical occult” period. Opposite to common clinical practice, protective treatment should be given preference to curative treatment. Treatment initiated already during the asymptomatic phase shortly after exposure requires prognostic endpoints preceding the lung edema for triage and re-triage. Treatment strategies need to be personalized and exposure-dose related. The objective of this post-hoc analysis of published data is to assess prognostic value of ventilation dead-space (Vd/Vt) and extravascular lung water index (EVLWI) to guide treatment by protective PEEP supplemented by venovenous (vv) ECMO. Methods: This paper aims to compare the overarching published framework from systematic toxicological research of phosgene in animal bioassays with the clinical evidence from four accidentally phosgenepoisoned workers admitted to hospital with life-threatening lung edema. Treatment focused on a combination of protective PEEP and ECMO to reverse phosgene-induced deterioration in lung mechanics by personalized mechanical ventilation. Endpoints selected for titration PEEP focused on endpoints indicative of decoupling cardiopulmonary and vascular functions. To better understand any cardiogenic and vascular disturbances, titration endpoints included calculated ventilation dead-space (Vd/Vt), measured extravascular lung water index (EVLWI), arterial blood gases and acid-base status, systemic vascular resistance index (SVRI), and cardiac index (CI). EVLWI and APACHE II criteria guided the course of treatment in adjusting plateau pressure (Pplat), positive end-expiratory pressure (PEEP), and driving pressure (ΔP). Results: Remarkable equivalence of human data and those from controlled inhalation studies with phosgene on rats and dogs was found. The endpoint of choice guiding PEEP ventilation and implementation of ECMO was EVLWI. This maker of lung edema precisely reflects the increased wet lung weights in animals. Conclusions: ECMO-supplemented PEEP not only mitigates hypoxemia at conditions of severe ARDS and it also provides a means to reduce driving and plateau pressures minimizing ventilatorassociated lung injury.