Accidental inhalation injury of phosgene gas leading to acute respiratory distress syndrome.

Irritant gas exposure may lead to significant respiratory distress as is seen in the present case of 25 year old male worker who suffered accidental phosgene inhalation. He remained asymptomatic for six hours but later landed up in Acute Respiratory Distress Syndrome in the hospital and required ventilatory support. No investigative feature is diagnostic of the nature of irritant gas. Similarly there is no antidote available to the phosgene. Only timely administered supportive management may lead to successful outcome.

INTRODUCTION

Inhalation injury is a common occupational hazard and may be because of smoke or chemical substances (fumes). Chemical inhalation is sometimes cause of severe respiratory distress and may even lead to Acute Respiratory Distress Syndrome (ARDS). Phosgene (carbonyl chloride; chemical formula COCl2) has been widely used as a chemical warfare agent in the past, particularly in World War. Its exposure can occurs to the persons working in the manufacturing industries of aniline dyes, polycarbonate resins, coal tar, pesticides, isocyanides, polyurethane, and pharmaceuticals. Phosgene inhalation poses significant risk to workers who may be accidently exposed and may be life threatening; as is illustrated by the following case report.

CASE REPORT

A 25 year old nonsmoker and non alcohalic male laborer suffered inhalation injury to phosgene gas after accidental leakage while working in a pesticide manufacturing factory. Immediately after exposure he experienced lacrimation, nausea, and dry cough with burning sensation in his mouth and throat. After six hours of exposure he developed breathlessness. The patient did not complain of chest pain, hemoptysis orthopnoea or Paroxysmal Nocturnal Dyspnoea. Initially he was admitted to the nearby hospital and managed conservatively. However within 24 hrs his condition worsened and he developed severe respiratory distress thus he was referred to our hospital, a tertiary care referral center for respiratory and intensive care. At the time of admission he was conscious and oriented to time place and person. He was febrile having temperature of 100 F, tachycardia of 130/min and tachyopnea of 36/min. using accessory muscle of respiration. His SpO2 was 80% without oxygen. On chest auscultation bilateral coarse crepitations were present. His cardiovascular and abdominal examination did not reveal any abnormality. His laboratory investigation revealed total leukocyte count 24000/cmm, with majority of polymorphs. His biochemical, renal and hepatic parameters were within normal limits. His X-ray chest was suggestive of bilateral hilar fluffy shadow characteristic batwing appearance [Figure 1]. He was given high flow oxygen therapy with face mask. After 30 minutes arterial blood gas analysis showed acidemia and hypoxia. Noninvasive ventilation was tried but within an hour shifted to invasive ventilatory support. Antibiotic therapy in the form of third generation cephalosporin was started prophylacticaly along with supportive therapy. He remained hemodynamic stable throughout ICU stay. His Endotracheal aspirate culture was sent immediately after intubation and after 48 hours of ventilatory support. Both the culture reports were sterile. He gradually improved with treatment and was successfully weaned off from ventilator on 6th day of ICU stay. He was shifted to general ward on 8th day and was discharged from the hospital on 10th day. He regularly came in follow up every week and recovered completely after 6 weeks.

Figure 1

X-ray chest showing bilateral fluffy shadow involving both hilar region

DISCUSSION

This Patient presented to us as case of inhalation injury after accidental leakage of irritant gas from pesticide factory. We could identify the toxic gas as phosgene only after consultation with the pesticide factory management. Phosgene is a chemical irritant, and with the advent of new technology, uses of better protective measure and discovery of newer agents its use being stopped as war gas. Now a day's Phosgene exposure can occurs during the manufacture of aniline dyes, polycarbonate resins, coal tar, pesticides, isocyanides, polyurethane and pharmaceuticals. Few case reports of occupational phosgene exposure in workers of these industries have been seen.[12] Phosgene is a highly toxic gas and exposure may have a fatal outcome.[3] An inhalation of more than 3 ppm concentration of the gas is considered highly toxic. Respiratory symptoms may be delayed by a latent period of several hours as is seen in our patient. Symptom may range from mild irritation of upper airways and dry cough to adult respiratory distress syndrome depending upon the concentration and duration of exposure.[4] Diagnosis of phosgene exposure may be straight forward in workers presenting from such industrial plants where there is a recognized risk. In other situations, a high index of suspicion is required. Suspicion should be aroused in presence of characteristic history of a peculiar musty smelling gas. However there is no specific reliable diagnostic test for the confirmation and despite several studies, no parameters in the latent period allow an accurate assessment of the degree of exposure.[5]

The pathogenesis of phosgene poisoning is not clearly understood as no human studies are available. Only animal studies have given some overview of the pathogenesis and histological changes occurring after the exposure. These studies have shown that within an hour of the exposure pulmonary edema, inflammatory and interstitial changes takes place in the terminal bronchial areas. Early changes are characterized by the leakage of the edema fluid, fibrin and erythrocyte from the pulmonary vasculature into the alveolar space and interstitial tissue. These changes progress further up to 8 to 48 hrs. After 48 hrs the organization of the fibrin and epithelial regeneration starts, characterized by decrease in the edema fluid and inflammatory cells showing transition from pulmonary injury to the repair.[6]

Treatment is primarily supportive as there is no known antidote for phosgene. Any patient with a history and symptoms that suggest the possibility of phosgene exposure should be kept under observation for at least 24 hrs All severe cases benefit from close monitoring and oxygen therapy if oxygen saturation is below 90%. Role of corticosteroid both in nebulised as well as injectable form has been studied in various animal models and human cases. None of the form has shown advantage in the outcome of the patient.[7] Few studies were conducted with use of N-acetyl cystiene, aminophylline, ibuprofen, pentoxyphylline and isoproterenol in animal models. They have shown that these agent are helpful in decreasing the development of pulmonary edema and inflammatory cascade but, human experiment are lacking.[8-10] Our patient did not received either corticosteroid or any of these agents. Though role of antibiotics in treatment is not understood and raised leukocyte count may be simple protective response of the bone marrow to the insult. Antibiotic therapy was given to the patient to prevent chances of secondary bacterial infection. Our patient responded with positive pressure ventilation and extubated within a week.

However it took him around 45 days to recover to normal. The complete recovery after phosgene exposure may take a long time, and most patients continue to complain of exertional dyspnoea for several months after exposure.