The pungent smell of ammonia in the air is detectable at concentrations as low as 5 ppm. Hence, significant exposure to ammonia in the air without the patient’s knowledge is rare. Ammonia concentrations of up to 100 ppm in the air is tolerated well for up to several hours.[22] At 1700 ppm, coughing, laryngospasm, and edema of the glottic region start. Concentrations of 2500 to 4500 ppm can be fatal in approx. 30 min and concentrations above 5000 ppm usually produce rapid respiratory arrest. Anhydrous ammonia in concentrations above 10000 ppm is sufficient to evoke skin damage.[23] The US National Institute of Occupational Safety and Health (NIOSH) recommendations state that the maximum permissible time-weighted average (TWA) exposure of anhydrous ammonia for an 8-hour workday of 40 hour-week is 25 ppm.[24]  The short-term exposure limit (STEL) or the concentration at which exposure of longer than 15 minutes is potentially dangerous is 35 ppm. The concentration at which the gas is immediately harmful to life or health (IDLH) is 500 ppm.

There is minimal absorption of ammonia into the systemic circulation if there is short-term (under 120 seconds) inhalational exposure.[25] However, long-term inhalational exposure results in some absorption into the systemic circulation[26] Most of the inhaled ammonia gets dissolved in the mucus of the upper respiratory tract, and 70 to 80% gets excreted in the exhaled air.

Ingested ammonia readily absorbs into the bloodstream, and the liver plays a significant role in its elimination.[27] Quantitative data on the metabolism of exogenous ammonia in humans is not available. However, studies in rats show that the majority of exogenous ammonia converts into glutamate and urea within 30 minutes[28] Orally ingested ammonia is almost completely converted into urea in the liver and excreted via the kidneys as urinary urea, with 25% excreted within the first 6 hours and 72% within three days. However, oral ingestion rarely raised the levels high enough to cause signs of systemic toxicity[29]

There is currently no evidence suggesting that dermal exposure to ammonia results in any form of systemic absorption.

History

Following inhalational injury, the patients generally present with rhinorrhea, scratchy throat, chest tightness, cough, dyspnea, and eye irritation. Since ammonia is a gas with a strong, pungent odor, the onset of symptoms is generally preceded by the patient identifying the smell, and people capable of escaping this environment are not subject to prolonged exposures. Prolonged or severe exposure to the gas results in full-thickness skin burns.

Following ingestion injury, the patients present with oropharyngeal, epigastric, and retrosternal pain. Abdominal pain and similar gastrointestinal symptoms follow if there is perforation of a viscus; this can occur as late as 24 to 72 hours after ingestion. More often than not, there is a preceding history of accidental or suicidal ingestion of ammonia-containing products, commonly, household ammonia-based cleaners. 

Physical Examination

After securing the airway, breathing, and circulation, a brief physical examination should be performed to establish the extent of the exposure. Start by assessing the level of consciousness. Examine the head, ears, eyes, nose, and throat for signs of facial and oral burns, ulcerations, or edema. Examine the respiratory system and evaluate for respiratory rate, oxygen saturation, stridor, drooling, cough, wheezing, rhonchi, and decreased air entry. Completely expose the patient and examine the skin for signs for burns. Special attention to be given to the examination of the eye since ammonia can cause severe damage to the cornea, lens and may even lead to globe perforation. Abdominal examination may be able to delineate epigastric tenderness and peritoneal signs in patients with perforation. Since this can be a late sign, the clinician should repeat the abdominal examination periodically.

There are no reliable laboratory tests that can assess the extent of systemic ammonia toxicity. In patients with preserved liver function, serum ammonia level do not correlate with the extent of external exposure and is of little diagnostic utility.

The following investigations are routine in patients presenting with exposure to ammonia:

• Complete blood count (CBC)
• Blood urea nitrogen (BUN) and creatinine
• Serum lactic acid levels
• Kidney function tests
• Serum electrolytes
• PT, INR
• Blood type and cross-matching
• Urine output monitoring

In patients with suspected respiratory injury,

• Pulse oximetry
• Cardiac monitoring
• Serial blood gases
• Chest radiography
• Pulmonary function tests (PFTs)
• Bronchoscopy in suspected severe acute inhalation
• Ventilation-perfusion (V/Q) scan

In patients with suspected ingestion,

• Abdominal series to rule out perforation following ingestion
• Early endoscopy (within 12 hours) in patients with stridor, drooling, dysphagia or significant oral burns. Endoscopy is a safe procedure in these patients.[30] Please note that the absence of oral burns does not reliably rule out esophageal injury, and hence, early endoscopic evaluation is indicated for a majority of these patients. 

In patients with suspected exposure to the eye,

• Slit-lamp examination with fluorescein staining
• Tonometry
• Conjunctival pH measurement

Since systemic toxicity with external exposure to ammonia is rare, there are no systemic antidotes for the management of ammonia poisoning. Management is largely supportive. Remove the patient from the source and decontaminate the patient. Start by supporting the airway, breathing, and circulation.

After a quick physical examination, assess the need for an advanced airway. Indications for an advanced airway include the following:

• Depressed mental status
• Deep burns in the face or proximal airway
• Hoarseness or stridor
• Severe respiratory distress

Supplement the patient with warm, humidified oxygen. Liberal fluid resuscitation should be avoided as these patients seldom have acute lung injury.

If skin burns are identified during the physical examination, then follow standard burn management. Irrigate the burns with tepid water for at least 15 minutes, followed by frequent irrigation for at least 24 hours. Avoid using any medications or dressing as this will prevent the natural elimination of ammonia by vaporization.

If eye injury is suspected, then irrigate the eye with tepid water for at least 30 minutes or until the conjunctival pH reaches 6.8 to 7.4. Consult ophthalmology early as ammonia exposure can lead to permanent eye damage.

If oral ingestion is suspected, then dilute the ingestion with water or milk. Arrange early gastroenterology consult for endoscopic evaluation. Do not induce emesis as this will incur further injury by the second pass of the toxin. The patient should be kept nil per oral until the completion of an assessment of the need for surgical management. Early surgical management is associated with improved patient outcomes in those patients with an identified impending perforation.[31] In patients who present with dysphagia, a follow-up endoscopy and barium swallow should be performed several weeks later to rule out stricture formation.

The evidence for corticosteroid use in the management of ammonia toxicity is conflicting and hence, should be avoided. Steroids may be beneficial in those patients who are exhibiting signs of airway edema and airway hyperreactivity after exposure to ammonia.

The majority of the patients who present with ammonia exposure can be safely discharged from the emergency department after 6 hours of observation, after ruling out significant injury and if the patient can tolerate oral feed. Some of the indications for hospital admission include persistently symptomatic patients, and those with endoscopically demonstrated burns. Patients with respiratory distress or abnormalities in laboratory values attributable to the ammonia exposure should also be admitted for further evaluation.

Inhalation of high water-soluble high irritative gases presents similar to ammonia inhalation by their predominant effects on the upper airway.[32] Some of these gases include acrolein, ethylene oxide, formaldehyde, hydrogen chloride, and sulfur dioxide. When exposure is severe, the patient presents with symptoms of respiratory distress, and hence, other causes of acute respiratory distress such as status asthmaticus, anaphylaxis, and foreign body aspiration should merit consideration. Ammonia inhalation also results in severe eye irritation. In the absence of a well-defined history of ammonia exposure, acute onset eye pain and irritation should be differentiated from angle-closure glaucoma, impacted foreign body, and corneal abrasions. Ammonia ingestion presents similar to other caustic substance ingestions. Since there is an overlap in their management, differentiation of the specific substance may not be necessary for immediate management.[30] Ammonia exposure on skin presents similar to other chemical and thermal burns caused by sodium hydroxide, potassium hydroxide, and calcium hydroxide.

There were no recorded deaths resulting from exposure to ammonia in the United States in 2017.[15] However, one in every 125 patients suffered from a major adverse event following ammonia exposure. Mild ammonia exposures are largely self-limiting conditions. Absence of symptoms within 24 hours of exposure essentially rules out injury. However, severe or prolonged exposures require hospitalization and may even result in death.[10][33] Clinical observation is that in patients presenting with acute ammonia inhalation, the chest physical examination findings on admission is the best predictor of long term morbidity and mortality.[33][34] In patients presenting with dermal exposure, the extent and depth of burns is the best tool for prognosis. In patients presenting with ingestion, the extent and depth of upper GI burns as visible on endoscopy predict the prognosis and directs subsequent management.[35]

Since ammonia gas erodes the superficial layers of pulmonary epithelium, this predisposes the patient to the development of super-added bacterial or fungal infection. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are also common complications.

Chronic inhalation of mild to moderate levels of ammonia may lead to the development of obstructive airway disease.[36] Severe acute exposure, when it damages the basal layers of the pulmonary epithelium can lead to chronic lung disease and may even necessitate a lung transplant.[37][38]

Following ingestion injury, 83.7% of patients did not develop any long-term complications.[30] Common acute complications include aspiration, altered mental status, and perforation of the viscera. The most likely long-term complication is the development of esophageal stricture.[39][40] Hence, follow-up with serial endoscopy is the recommended approach in these patients.

The agency for toxic substances and disease registry (ATDSR) provides the following recommendations to the general public for avoiding ammonia exposure:

• Ammonia-based household cleaner use requires well-ventilated rooms.
• Avoid storing ammonia-based cleaners in glass bottles as breakage could lead to severe exposure.
• Wear proper clothing and use eye protection while using ammonia-based cleaners.
• Keep ammonia-based cleaners out of reach of children.
• Avoid visiting farming areas where ammonia-based fertilizers are applied, immediately after their application.
• Avoid visiting animal confinement buildings without the use of proper personal protective equipment.

They also recommend that for workers who uses or applies ammonia in farming, always follow proper safety precautions mentioned on the equipment and use personal protective equipment wherever necessary.

The paramedical team and the emergency department plays a major role in the diagnosis and management of these patients. The key to successfully managing ammonia exposure and reducing long-term sequelae is timely interventions. The EMS team can obtain valuable insights into the exposure environment and may provide the first clue to ammonia poisoning. They can initiate decontamination before arriving in the emergency department. The emergency physician, after primary and secondary survey, should initiate early consultation for ophthalmology, gastroenterology, a burn nurse, and plastic surgery depending on the need. Early specialist intervention improves patient outcomes.

Based on the portal of exposure, the patient may need long term follow-up care. Follow-up with a pulmonologist may be necessary for patients with severe acute inhalation, as the development of chronic lung disease is common. Long-term follow-up with a gastroenterologist may be necessary for patients with ingestion to screen for the development of stricture. In patients with intentional or suicidal exposure, Psychiatric consultation may be advisable early in the management of such cases. Nursing will provide inpatient care and monitoring, and evaluate the patient progress on follow-up outpatient visits, and report their findings to the treating physician.

Ammonia toxicity requires an interprofessional team approach, including physicians, specialists (based on exposure type), and specialty-trained nurses all collaborating across disciplines to achieve optimal patient results. [Level V]

Most of the evidence available in ammonia poisoning are case studies, case series, and systematic reviews.