Chlorine Gas Toxicity

Etiology

Chlorine gas can be used as a disinfecting agent at swimming pools, or it could form by mixing household agents. The combination of bleach (sodium hypochlorite) with acid produces chlorine gas, a heavy green-yellow gas with a strong odor. Chlorine gas has also been used as an industrial solvent and has other industrial uses such as the production of bulk materials, bleached paper products, plastics such as PVC, and solvents. Chlorine gas is also used to make dyes, textiles, paint, and even medications.

Chlorine gas is pressurized and cooled for easy storage in liquid form.  When released, the liquid form of chlorine quickly turns into yellow-green colored gas with an irritating odor. Since chlorine is heavier than air, it accumulates in low-lying areas.

Chlorine gas has been used as an agent of war as recently as 2007 in Iraq.

Epidemiology

In 2016, the American Association of Poison Control Centers reported over 6300 exposures to chlorine, making it the most common inhalational irritant in the United States. About 35% of exposures to chlorine gas were attributed to the mixing of household acid with hypochlorite.[2]

In addition to household exposure, there have been multiple episodes of incidents involving chlorine gas release. One of the worst was a 2007 collision of a railroad tanker carrying chlorine with another train causing rupture of the tank and release of 90 tons of chlorine gas into the surrounding area. Exposure to chlorine gas at the site of the accident resulted in 9 fatalities and 520 visits to local emergency departments in Graniteville, South Carolina.[3]

Chlorine gas is also the most frequent cause of major toxic release incidents internationally. Because of its widespread industrial use, chlorine gas has substantial potential for accidental release.

Besides household and industrial accidental exposures, chlorine gas has also been used as an agent of war. Germany used chlorine gas in World War I as a chemical weapon. More recently, in 2007, insurgents in Iraq executed multiple attacks by outfitting chlorine tankers with explosives and detonating them in multiple locations, causing hundreds of civilian casualties.

Pathophysiology

Chlorine was thought to cause direct tissue damage by generating free oxygen species. However, more recent studies show that cellular injury may result from the oxidation of functional groups in cell components from the reaction of chlorine gas with tissue water. This reaction forms hypochlorous and hydrochloric acid along with free oxygen radicals.

Hypochlorous and hydrochloric acid cause most of the toxic effects attributed to chlorine gas. These acids are produced by the reaction of chlorine (Cl2) with water.[4]

• Cl2+ H2O <--> HCl + HOCl <--> 2HCl + O-

Mild exposure may cause mucosal membrane irritation.  More severe exposure will induce edema of both the upper airway and the lung parenchyma. Large acute exposure can induce wheezing, cough, and dyspnea. Acute lung injury and/or adult respiratory distress syndrome (ARDS) can also be seen in some severe cases. Chlorine gas is primarily reactive only at a local level, thus absorbed systemic effects are not commonly observed.[5][6]

Acids formed by the reaction of chlorine gas with water can react with the conjunctival mucous membrane, and although rare due to buffering by the tear film, can cause burns and corneal abrasions. These acid burns are generally superficial, only affecting the epithelial and basement membrane.

Toxicokinetics

Experimental studies using a low concentration of chlorine gas show that the upper airway absorbs the vast majority of inhaled chlorine. The lower respiratory tract absorbs only 5% of chlorine gas. Animal models suggest that chlorine gas absorbed in the lower respiratory tract causes much greater toxicity than similar amounts in the upper airway. Thus, the upper airway functions as a protective scrubber to the exposure of chlorine gas.

When exposed to low concentration chlorine gas (up to 2 ppm), mucous membrane irritation results. Higher concentration exposures between 9 ppm and 50 ppm may lead to chemical pneumonitis and bronchiolitis obliterans.  In animal models, exposure to 200 ppm leads to extensive bronchial constriction. Exposure to levels of 800 ppm proves lethal to half of all exposed animals, while concentrations of 2000 ppm lead to immediate respiratory arrest.[4]

History and Physical

Symptoms of chlorine gas exposure are usually varied depending on the type of exposure. For acute exposure at low levels (less than 5 ppm), patients can have lacrimation, nose and throat irritation, and excess salivation. Acute exposure at high levels causes dyspnea, violent cough, nausea, vomiting, lightheadedness, headache, chest pain, abdominal discomfort, and corneal burns, in addition to the same symptoms of low-level acute exposure. Chronic exposure to chlorine gas can lead to chest pain, cough, sore throat, and hemoptysis.

On physical exam, clinicians can discover respiratory findings such as tachypnea, cyanosis, wheezing, intercostal retractions, decreased breath sounds, rales, nasal flaring, stridor, hemorrhage of the respiratory tract, and rhinorrhea. Non-respiratory findings may include tachycardia, lacrimation, and salivation.[4]

Evaluation

Most patients should have pulse oximetry performed if possible. Mass casualty exposures may require triage of resources to those with more obvious symptoms. Acutely exposed patients with significant symptoms frequently will require a chest radiograph to determine the degree of lower respiratory tract involvement. Those with pronounced systemic symptoms (vomiting, altered mental status, acidosis, among others) will require laboratory evaluation which may include serum electrolytes, BUN and creatinine levels, arterial blood gas analysis, and electrocardiography.  After stabilization, pulmonary function testing, ventilation-perfusion testing, and laryngoscopy/bronchoscopy are occasionally used to determine the extent of the injury.

Treatment / Management

Treatment of chlorine gas exposure is mostly supportive. Removal of the individual from the contaminated environment is the first step of management. Clinicians will assess the patient’s airway, breathing, and circulation and provide humidified oxygen as necessary. Severe exposures may require endotracheal intubation.  In cases of non-cardiogenic pulmonary edema, positive end-expiratory pressure (PEEP), fluid restriction, and diuretics can be used. Bronchospasm is treated with beta-agonists such as albuterol. The management of ocular exposure requires irrigation with copious water or saline. 

If irritation continues, clinicians should evaluate for corneal abrasion. Nebulized, 4% sodium bicarbonate may prove helpful as an adjunct treatment of chlorine gas exposure, although experience with this treatment is limited. Research has not yet proven any benefit to corticosteroids nor the administration of systemic nitrites as a treatment for chlorine gas exposure.[7](B3)

Differential Diagnosis

Most exposures to chlorine gas will present with a clear history of exposure obtained either from the patient themselves or first responders arriving from the scene. From prior exposures at chlorinated swimming pools, most patients will recognize the distinct odor of chlorine gas. Rarely a patient in respiratory distress and altered mental status may be found after the complete dispersal of chlorine gas, making the history unclear. Salivation, lacrimation, rhinorrhea, and bronchospasm can occur in cholinergic toxicity as well as chlorine gas exposure.

Prognosis

Chlorine gas exposure usually has a good prognosis, with most exposed individuals recovering without significant residual deficits. Pulmonary edema appears to be the most common cause of morbidity for moderate-to-severe exposures. This usually occurs within 2 to 4 hours of exposure to moderate chlorine concentration (25 to 50 ppm) or 30 to 60 minutes of severe exposure (greater than 50 ppm). Resolution of pulmonary abnormalities usually ensues a week to a month after exposure. Smokers and patients with asthma are likely to have persistent obstructive pulmonary defects.[8]

Studies on the long-term adverse effects from acute chlorine exposure are inconclusive, with some studies showing decreased vital capacity, diffusing capacity, and total lung capacity and others showing no consistent pattern of pulmonary function deficits.[7][9]

Complications

Sloughing of the pulmonary mucosa can occur within 3 to 5 days in severe exposures leading to chemical pneumonitis that can often be complicated by secondary bacterial invasion and infection. Smoking and pre-existing respiratory conditions such as asthma and chronic obstructive pulmonary disease appear to increase the risk of long-term complications such as pulmonary fibrosis.[10]