Toxic pulmonary oedema

Regrettably there is, as yet, no known antidote to phosgene poisoning. Consequently treatment is usually directed to the main symptom - toxic pulmonary oedema - the development of which is dose-related [1374]. 

With moderate-large doses (>150 p.p.m. min), toxic pulmonary oedema must be expected doses of 300 p.p.m. min or greater are potentially lethal. X-ray photographs taken two hours after exposure are recommended for early diagnosis. In these cases, large amounts of glucocorticoids should be administered as soon as possible after exposure... 

Clinical manifestation. It includes several syndromes a) pulmotoxic and irritative syndrome - expressed by catarrhal changes on the contact mucosa and respiratory tract, toxic pulmonary oedema b) hemotoxic syndrome - expressed by severe hemolysis of different degrees, in the severe forms - hemolytic shock and anaemia c) hepatal syndrome - characterised by subicterus or icterus, increased liver and bilirubinaemia d) renal syndrome - by oliguria or anuria, pathological deviations in the urine and acute kidney insufficiency. In the extremely severe forms consciousness is disordered. Laboratory blood and urine chemical tests show evidence of phenol metabolites, data for blood damage (increased values of free hemoglobin, reduced number of erythrocytes), positive liver tests etc. 

Respiratory syndrome - strongly expressed with acute dispnea toxic pulmonary oedema ... 

Increased pulmonary toxicity (pulmonary oedema) with the combination of amiodarone and 100% oxygen has been confirmed in mice. ... 

A little later, he vomited, his breathing became shallow and he eventually stopped breathing. CPR was performed but he was pronounced dead 30 min later. Toxicology revealed MDMA (2.6 mg/mL), MDA (0.1 mg/mL), methamphetamine (0.1 mg/mL) and moclobemide. The cause of death was serotonin toxicity, amphetamine toxicity, pulmonary oedema and cerebral oedema. 

TIC include lung-damaging agents (chlorine and phosgene are both used widely in the chemical industry), perfluoroisobutylene (PFIB) and isocyanates. All these compounds can lead to toxic pulmonary oedema at the alveolar level. In addition, there are many respiratory irritant agents which cause effects on the upper airways such as ammonia and hydrogen chloride and agents such as sulphur dioxide and toluene diisocyanate which cause severe bronchoconstriction. 

Mechanisms Underlying the Development of Toxic Pulmonary Oedema and Acute Respiratory Distress Syndrome... 

Fig. 7.2 A field hospital during the First World War. Casualties with toxic pulmonary oedema following a gas attaek outside a field hospital during the First World War. Little could be done for such cases, apart from providing bed rest during the latent period of possible development of pulmonary oedema following the exposure. (Source The National Archive)...

Longer latency production of toxic pulmonary oedema and later acute respiratory distress syndrome with associated type 1 respiratory failure Vesicant agents... 

Also possible toxic pulmonary oedema with type 1 respiratory failure if a dust vector impregnated with mustard agent has been used... 

Proactive to mitigate and pre-empt developing type 1 respiratory failure with the development of toxic pulmonary oedema and acute respiratory distress syndrome during a latent period following exposure. 

Fig. 8.5 Early developing toxic pulmonary oedema. The diffuse opacity in the lung fields is visible only after the effects of developing t3 pe 1 respiratory failure...

This is required to mitigate as much as possible the effects of the toxic agent in producing acute lung injury, toxic pulmonary oedema and possible ARDS (see Chap. 9). 

A typical regime is methylprednisolone 2000 mg IV or IM at 15 min, 6 and 12 h post-exposure. The dose should be repeated every 12 h for 1-5 days until the risk of developing toxic pulmonary oedema has passed. 

At the time of the 1915 attacks and throughout the remainder of the First World War, respiratory life support was unknown, and the management of toxic pulmonary oedema was ineffective (with the exception of the recognition of the importance of resting after a phosgene attack to reduce pulmonary arterial pressure as much as possible). 

The key lesson was the importance of the development of toxic pulmonary oedema from exposure to lung-damaging agents. 

Affected casualties suffered from initial acute airway irritation and inflammatory changes and later from toxic pulmonary oedema. Although the cloud may have contained contaminants and by-products including hydrogen cyanide and oxides of nitrogen, there is little doubt that the main effects were caused by methyl isocyanate which is a known pulmonary oedemagen. Following the release, about 400,000 persons fled the city in a totally uncontrolled evacuation. The evacuation of those who were actually exposed was compounded by a panic evacuation of residents who lived more than 10 km from the release site. 

---