eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Ammonia

Steven Issley, MD, FRCPC, Assistant Professor of Emergency Medicine, Assistant Director of Medical Stimulation Center, Consulting Staff, Department of Emergency Medicine, SUNY-Downstate Medical Center, Kings County Hospital Center
Eddy Lang, MDCM, CCFP (EM), CSPQ, Assistant Professor, Department of Family Medicine, McGill University; Consulting Staff, Department of Emergency Medicine, The Sir Mortimer B Davis-Jewish General Hospital

Updated: Oct 8, 2009

Introduction

Background

At room temperature, ammonia (NH₃) is a highly water-soluble, colorless, irritant gas with a unique pungent odor. Ammonia has a boiling point of -33°C and an ignition temperature of 650°C.

In 1993, anhydrous ammonia was the third most produced chemical by volume in the US. The farming industry uses approximately one third of the ammonia produced in the US as a component of fertilizer and animal feed. Industrial injury most often results from ammonia leaks in fertilizer tanks and hoses and toxic ammonia levels in animal buildings. Swine confinement buildings are particularly notorious for containing toxic levels of ammonia that often exceed threshold limit values. Because ammonia is liberated during combustion of nylon, silk, wood, and melamine, firefighters also are at risk for exposure to this irritant gas.

Before the 1970s, liquid ammonia stored under high pressure was widely used for refrigeration. Although Freon largely has replaced ammonia as a refrigerant, ammonia refrigeration is still used and numerous case reports exist of severe toxicity following unintentional exposure.

Ammonia also is used in the production of explosives, pharmaceuticals, pesticides, textiles, leather, flame-retardants, plastics, pulp and paper, rubber, petroleum products, and cyanide. Furthermore, ammonia is a major component of many common household cleaning and bleaching products (eg, glass cleaners, toilet bowel cleaners, metal polishes, floor strippers, wax removers, smelling salts).

Permissible levels of exposure to toxic gases are defined by time-weighted average (TWA), short-term exposure limit (STEL), and concentration at which toxic gasses are immediately dangerous to life or health (IDLH). The TWA is defined as the concentration for an 8-hour workday of a 40-hour workweek that nearly all workers can be exposed to without adverse effects. Similarly, the STEL is the concentration to which an exposure of longer than 15 minutes is potentially dangerous and may produce immediate or chronic compromise to health. Anhydrous ammonia has a TWA of 25 ppm, an STEL of 35 ppm, and an IDLH of 500 ppm.

Although injury from ammonia most commonly is caused by inhalation, it also may follow ingestion or direct contact with eyes or skin. The clinical presentations of these injuries and their investigation and treatment are discussed in this article; chloramine gas inhalation injury also is discussed.

Pathophysiology

The most common mechanism by which ammonia gas causes damage occurs when anhydrous ammonia (liquid or gas) reacts with tissue water to form the strongly alkaline solution, ammonium hydroxide.

NH₃ + H₂ O Þ NH₄ OH

This reaction is exothermic and capable of causing significant thermal injury.

Ammonium hydroxide can cause severe alkaline chemical burns to skin, eyes, and especially the respiratory system. Mild exposures primarily affect the upper respiratory tract, while more severe exposures tend to affect the entire respiratory system (see Clinical). The gastrointestinal tract also may be affected if ammonia is ingested.

Tissue damage from alkali is caused by liquefaction necrosis and theoretically can penetrate deeper than that caused by an equipotent acid. In the case of ammonium hydroxide, the tissue breakdown liberates water, thus perpetuating the conversion of ammonia to ammonium hydroxide. In the respiratory tract, this results in the destruction of cilia and the mucosal barrier to infection. Furthermore, secretions, sloughed epithelium, cellular debris, edema, and reactive smooth muscle contraction cause significant airway obstruction.

Airway epithelium can regain barrier integrity within 6 hours following exposure if the basal cell layer remains intact. However, damaged epithelium often is replaced by granular tissue, which may be one of the etiologies leading to chronic lung disease following ammonia inhalation injury.

Liquid anhydrous ammonia (-33°C) freezes tissue on contact. To put this in perspective, critical skin damage begins at -4°C and becomes irreversible at -20°C. The degree of tissue injury, however, is proportional to the duration and concentration of exposure.

Similarly, damage to the respiratory system is proportional to depth of inhalation, duration of exposure, concentration, and pH of the gas or liquid.

Ammonia is a product of protein catabolism and is metabolized by the liver. Normal blood ammonia levels range from 10-40 µmol/L. This increases 10% with exposure to 25 ppm but is not considered harmful. Theoretically, patients with liver dysfunction are at increased risk for ammonia toxicity; however, currently no sufficient clinical evidence can confirm this.

Frequency

United States

The 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System reported 2984 single exposures of ammonia. Of these, 94% were unintentional.¹

Similar to previous years, in 2002, US poison control centers reported nearly 6000 cases of toxic ammonia exposure.² Of exposures, 93% were unintentional, and 11% resulted in moderate to severe outcomes. Of note, in cases of household exposure, only 5% were moderate to severe.

Mortality/Morbidity

The 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System reported 2 deaths due to ammonia exposure.¹

Age

According to the 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System, 751 exposures occurred in those younger than 6 years, 339 exposures occurred in those aged 6-19 years, and 1406 exposures occurred in those older than 19 years.¹

Of the 6000 toxic ammonia exposures reported in the American Association of Poison Control Centers' 2002 Annual Report, 70% occurred in adults and 20% occurred in children younger than 6 years.²

• Ingestion of household solutions usually is unintentional and occurs in young children; adult ingestions, however, most often are suicide attempts.
• Inhalation injury is almost always unintentional. Because inhalation exposure generally occurs in an industrial setting, it usually is associated with working adults.

Clinical

History

• Gaseous ammonia effects at various concentrations are as follows:
  • 25 ppm or less - TWA
  • 25-50 ppm - Detectable odor; unlikely to experience adverse effects
  • 50-100 ppm - Mild eye, nose, and throat irritation; may develop tolerance in 1-2 weeks with no adverse effects thereafter
  • 140 ppm - Moderate eye irritation; no long-term sequelae in exposures of less than 2 hours
  • 400 ppm - Moderate throat irritation
  • 500 ppm - IDLH
  • 700 ppm - Immediate eye injury
  • 1000 ppm - Directly caustic to airway
  • 1700 ppm - Laryngospasm
  • 2500 ppm - Fatality (after half-hour exposure)
  • 2500-6500 ppm - Sloughing and necrosis of airway mucosa, chest pain, acute lung injury (ALI), and bronchospasm
  • 5000 ppm - Rapidly fatal exposure
• Inhalation injury
  • Because of its high water solubility, ammonia has a tendency to be absorbed by the water-rich mucosa of the upper respiratory tract. However, unlike most highly water-soluble irritant gases that tend to affect exclusively the upper respiratory tract, ammonia can damage proximally and distally.
  • In 1941, Caplin was the first to classify victims of unintentional ammonia exposure; he described them as mild, moderate, and severe. Patients in the mild group presented with conjunctival and upper respiratory inflammation and pain but showed no signs of respiratory distress.⁴ The moderate group presented similarly but with more exaggerated symptoms. The severe group presented in frank respiratory distress with productive cough, acute lung injury (ALI), and dysphagia.
  • Following a brief ammonia exposure, damage generally is limited to the upper airway mucosa. Brief exposures at very high concentrations, however, can be overwhelming and affect the entire respiratory system. People who are capable of escaping their environment usually are not subject to severe exposures, because they can flee upon detection of ammonia's pungent odor; furthermore, absence of symptoms following inhalational exposure to ammonia essentially rules out significant injury.
  • Pain (oropharyngeal, retrosternal)
  • Dyspnea, hemoptysis - As expected, individuals with reactive airway disease, such as asthmatics, are particularly sensitive to ammonia inhalation.
  • Hoarseness
  • Dysphagia
  • Loss of consciousness
• Farming industry
  • In enclosed animal confinement buildings, ammonia is adsorbed by dust particles that transport it more directly to small airways. Because of this synergistic effect, symptoms have reportedly developed within minutes of entering animal confinement buildings.
  • Symptoms include rhinorrhea, scratchy throat, chest tightness, cough, dyspnea, and eye irritation and usually subside within 24-48 hours.
• Contact - Burns and cold injury
  • Gaseous ammonia combines with water of the skin, eyes, and airways to form ammonium hydroxide. This exothermic reaction results in both heat and chemical burns. Liquid ammonia freezes tissue on contact and may cause full-thickness tissue damage that penetrates deeper than the more conspicuous superficial chemical burns.
  • Concentrations greater than 10,000 ppm are required to cause skin damage. The eyes begin to feel irritated at concentrations of 50-100 ppm; at 700 ppm, immediate eye damage occurs.
• Ingestion
  • Typical household ammonia products (3-10% ammonium hydroxide) have a pH less than 12.5, although the pH of industrial solutions (up to 30% ammonium hydroxide) is often greater than 13. Because caustic alkali burns generally are thought to occur when pH is greater than 12.5, ammonia ingestions in the home usually do not lead to significant damage. However, Klein et al reported 3 cases of oropharyngeal and esophageal injury following intentional ingestion of household solutions with a pH less than 12.⁵
  • Patients present with oropharyngeal, epigastric, and retrosternal pain.
  • Abdominal pain and other gastroenterologic symptoms may occur if ingestion causes viscus perforation (perforation may occur up to 24-72 hours postingestion).
  • Respiratory symptoms may be present if aspiration pneumonia or pneumonitis complicates ingestion.
  • Smelling salts are a less common source of household ammonia ingestion. Often in capsule form, smelling salts, which contain approximately 20% ammonia, release a pungent odor when broken. Smelling salts are found in many first-aid kits as a treatment for syncope; unfortunately, children sometimes bite into them, resulting in minor esophageal burns and mild respiratory symptoms.

Physical

• Inhalation injury
  • Head, ears, eyes, nose, throat (HEENT) - Facial and oral burns and ulcerations
  • Respiration - Tachypnea, oxygen desaturation, stridor, drooling, cough, wheezing, rhonchi, and decreased air entry
  • Central nervous system (CNS) - Loss of consciousness (if exposure is massive)
• Contact - Burns and cold injury
  • Skin - Alkali burns to the skin are yellow, soapy, and soft in texture. When burns are severe, skin turns black and leathery.
  • HEENT - Burns to the eye penetrate particularly deeply and rapidly, leading to destruction of the inner structures within 2-3 minutes; this may progress to globe perforation. Ammonia typically causes more corneal epithelium and lens damage than other alkalis. Intraocular pressure and pH of the anterior chamber rise, resulting in a syndrome similar to acute narrow-angle glaucoma. Other symptoms include iritis, corneal edema, semi-dilated fixed pupil, and eventual cataract formation.
• Ingestion
  • Cardiovascular - With intentional ingestion, hypovolemic shock may occur because of vomiting and third-spacing of intravascular fluid.
  • HEENT - Symptoms include edema of the lips, oropharynx, and upper airway.
  • GI - Patient may experience epigastric tenderness; mediastinitis and peritoneal signs may be present with viscus perforation, which can occur as late as 24-72 hours postingestion.
  • Respiratory -Aspiration pneumonia and pulmonary edema may occur.

Differential Diagnoses

Other Problems to Be Considered

Other toxic inhalations or ingestions
Concomitant trauma
Reactive airway dysfunction syndrome (RADS)

Workup

Laboratory Studies

• Serum acetaminophen level in intentional exposures
• Complete blood count (CBC)
• Electrolytes, blood urea nitrogen (BUN), and creatinine
• Serum lactic acid
• Serial arterial blood gases (ABGs) in cases of significant respiratory distress
  • Metabolic acidosis
  • Respiratory alkalosis
  • Increased alveolar-arterial gradient
• Note that serum ammonia levels are of little value because they do not correlate with clinical condition. However, patients with compromised hepatic function may show increased serum ammonia levels because of less efficient metabolism.

Imaging Studies

• Chest radiography
  • Chest radiographic findings can vary from normal to diffuse micronodular interstitial infiltrates. However, abnormal radiographic findings may take up to 48 hours to develop, even following severe exposure.
  • Other findings to consider are acute lung injury (ALI), acute respiratory distress syndrome (ARDS), secondary bacterial bronchopneumonia, and pneumomediastinum.
• Abdominal series (to rule out perforation following ingestion)

Other Tests

• Cardiac monitor
• Oxygen saturation monitor
• Pulmonary capillary wedge pressure (PCWP) monitoring (in cases of severe ALI or ARDS)
• Pulmonary function tests (PFTs) - Once acute emergency is controlled; useful to gauge severity and monitor progress and recovery
  • Obstructive lung disease (acute and chronic)
  • Restrictive lung disease (chronic)
• Ventilation/perfusion (V/Q) scan - May be useful to gauge severity or progress of disease; unlikely to change acute management
  • Ventilation deficits generally are more pronounced in the larger airways.
  • The ventilation scan also may show abnormal air trapping in the setting of lower airway obstruction.
• Slit-lamp examination with fluorescein staining, tonometry and conjunctival pH (see Physical: HEENT)

Procedures

• Perform bronchoscopy to assess respiratory tract damage following acute inhalation injury (in severe cases).
  • Airway edema, obstruction, and necrosis
  • Epithelial sloughing
  • Laryngitis and tracheitis
  • Diffuse alveolar damage
• Consider endoscopy for significant ingestion exposures (large volume and/or industrial concentrations). Indications are somewhat controversial; obtain a GI consultation if needed. Perform endoscopy on symptomatic patients and patients with intentional exposure within 48 hours following ingestion. The risk of perforation increases if endoscopy is performed more than 72 hours postingestion.
  • Laryngeal and epiglottic edema
  • Friable erythematous esophagus
  • Corrosive injury

Treatment

Prehospital Care

• Immediately remove the patient from the contaminated environment.
• Remove all the patient's clothing.
• Support airway, breathing, and circulation (ABCs) as per advanced cardiac life support (ACLS) and advanced trauma life support (ATLS) guidelines. (ACLS and ATLS guidelines may vary by region, according to training and legal responsibilities of prehospital care providers.)
• If the patient is sufficiently stable, begin copious skin and eye irrigation immediately following exposure. Continue irrigation for at least 20 minutes. Patients then can be covered with a dry, clean dressing and sheet.
• Provide a container for patients with ingestion exposure.

Emergency Department Care

• Decontaminate the patient (if not previously performed) and support ABCs as necessary. Provide warmed humidified oxygen.
• As with all burns, patients with facial or oral lesions are at high risk for developing laryngeal edema. Airway intervention should be aggressive.
• Indications for intubation include severe respiratory distress (hypoxemia, hypercapnia), stridor, hoarseness, deep facial burns, burns identified by bronchoscopy or endoscopy, and depressed mental status.
  • If intubation is necessary, use large size tube to prevent plugging by sloughed mucosa.
  • Some consider procedural sedation preferable to rapid sequence intubation (RSI) because paralysis is risky with a difficult and edematous airway. Furthermore, ventilation cannot be predicted as successful if intubation fails in this context. Positive end respiratory pressure (PEEP) generally is useful (5 cm water minimum).
• Beware of fluid over-resuscitation. Patients may have or may be developing acute lung injury (ALI).
• Follow standard initial burn management. (Discussion is beyond the scope of this article.)
  • Once the patient is adequately stable, irrigate skin with tepid water for at least 15 minutes. Continue frequent regular irrigation for the first 24 hours, in addition to conventional burn management.
  • Debride wounds and dress with 1% silver sulfadiazine (avoid using on face).
  • Administer tetanus prophylaxis.
• Irrigate eye injuries with copious amounts of tepid water for at least 30 minutes or until conjunctival pH is 6.8-7.4; use pH indicator paper to monitor. Examine eye with slit-lamp and fluorescein staining.
  • Perform tonometry to determine if intraocular pressure is elevated.
  • Consult ophthalmology promptly because of risk of perforation and/or permanent eye damage.
• Treat ingestions using the following steps:
  • Rinse mouth and dilute ingestion with approximately 250 mL of water or milk.
  • Do not induce emesis, so as not to reproduce injury with a second pass of toxin.
  • Consult gastroenterology promptly for subsequent endoscopic evaluation (not often performed before 12 hours postingestion).

Consultations

When appropriate, immediately consult an intensivist, medical toxicologist, ophthalmologist (all eye injuries), gastroenterologist, and general and plastic surgeons.

Medication

Management of toxic exposure to ammonia is largely supportive, and medical therapy is directed at hypoxia, bronchospasm, acute lung injury (ALI), hypovolemia, and burns of the skin and eyes.

Antibiotics and corticosteroids are controversial therapies following ammonia inhalation and ingestion exposures.

Although antibiotics and corticosteroids are often used in the acute treatment of patients with inhalation injury, neither has been shown to improve outcome and many believe that corticosteroids may actually increase morbidity. Corticosteroids are recommended to treat bronchospasm in patients with underlying reactive airways disease and acute inhalation injury or for chronic respiratory complications that follow an acute inhalation injury. Patients experiencing signs of airway edema after caustic exposure may benefit from IV administration of dexamethasone (adults: 10 mg; children: 0.6 mg/kg up to 10 mg max).

Use of steroids for the treatment of caustic injuries after caustic ingestion is still very controversial.Intravenous corticosteroids and antibiotics administration can be considered in symptomatic patients following ammonia ingestion with grade IIb (near-circumferential) caustic injuries. Presumably, corticosteroids are administered in order to decrease the incidence and severity of esophageal strictures that occur during healing from significant alkaline injuries. Antibiotics are given because of increased risk of mediastinitis associated with full-thickness esophageal alkaline corrosive burns and steroid use. Although controlled animal studies do support the use of these therapies, no well-controlled human trials have been performed; thus, corticosteroids and antibiotics should be administered in consultation with a GI specialist and surgeon.

If steroids are administered, the recommended dose is 1-2 mg/kg/d of methylprednisolone for 3 weeks followed by gradual tapering. If antibiotics are administered, a broad-spectrum antibiotic (eg, second-generation cephalosporins) is appropriate.

The decision to continue or stop corticosteroid and antibiotic therapy is based on endoscopic findings. Discontinue steroid and antibiotic therapies for patients with no injury or mild mucosal inflammation or ulceration, as they are not at risk for stricture formation. Furthermore, patients with severe transmural burns are at risk for stricture formation, but steroid therapy will not alter their risk. Thus, antibiotic therapy alone is recommended for this group to diminish their risk of mediastinitis. Patients with extensive superficial ulceration or deep discrete or circumferential ulcerations are at risk for stricture formation and may benefit from steroid administration. Consider administering corticosteroids and antibiotics to this group of patients.

Bronchodilators

Bronchodilators selectively stimulate beta 2-adrenergic receptors of the bronchial tree and lungs. Bronchodilation results from relaxation of bronchial smooth muscle, which relieves bronchospasm and reduces airway resistance.

Albuterol, salbutamol (Proventil, Ventolin)

Beta 2-agonist is used for the treatment of bronchospasm. Relaxes bronchial smooth muscle by action on beta 2-receptors with little effect on cardiac muscle contractility.

Dosing

Adult

5 mg/mL of solution for nebulization, mixed as 0.5-1 mL with 2.5 mL of water and nebulized prn

Pediatric

0.2 mg/kg/dose = 0.03 mL/kg/dose (standard solution), prepared as above

Interactions

Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, and sympathomimetic agents; interactions are of relative importance when dealing with life-threatening toxicity

Contraindications

Documented hypersensitivity; tachydysrhythmias

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders

Diuretics

Are sometimes considered for the treatment of acute lung injury (ALI). However, positive end-expiratory pressure (PEEP) may be much more useful than diuretics for optimizing oxygenation because ALI is secondary to alveolar capillary injury, not excess fluid. Nonetheless, a trial of diuretics can be considered in patients with evidence of concomitant fluid overload.

Furosemide (Lasix)

Loop diuretic; inhibits sodium chloride reabsorption in the ascending loop of Henle. Administer IV because this allows for superior potency and a higher peak concentration, despite an increased incidence of adverse effects, particularly ototoxicity (rare).

Dosing

Adult

20 mg IV for patients not regularly using furosemide
40-80 mg IV for patients regularly using furosemide
80-120 mg IV for patients with symptoms refractory to the initial dose at up to 1 h
Higher doses and more rapid redosing for patients in severe distress
If minimal or no response with initial dose, double next dose

Pediatric

Not established

Interactions

Metformin decreases furosemide concentrations;
furosemide interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle relaxing effect of tubocurarine; coadministration with aminoglycosides appears to increase auditory toxicity; hearing loss of varying degrees may occur; may enhance anticoagulant activity of warfarin when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently

Contraindications

Documented hypersensitivity; hepatic coma; anuria; severe electrolyte depletion

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter; may induce prerenal failure

Antibiotics

Although expensive, topical Silvadene has antipseudomonal properties in addition to coverage for most gram-positive organisms.

For eye exposures, antibiotic eye preparations will reduce risk of infection secondary to tissue injury.

Silver sulfadiazine 1% (Silvadene)

Useful in prevention of infections from second- or third-degree burns. Has bactericidal activity against many gram-positive and gram-negative bacteria including yeast.
Wash burn before application to remove previously applied agent.
Not for ophthalmic and facial use.
Other products may be used instead of silver sulfadiazine for partial thickness burns; these include TransCyte, Acticoat, or Biobrane.

Dosing

Adult

Apply using sterile technique to affected areas qd/bid

Pediatric

<2 years: Do not administer (risk of kernicterus)
>2 years: Apply as in adults

Interactions

Effect of proteolytic enzymes is reduced when used concomitantly

Contraindications

Documented hypersensitivity; late pregnancy (risk of kernicterus); facial burns (use Bacitracin instead)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in G-6-PD deficiency and renal insufficiency

Ciprofloxacin (Ciloxan)

Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, S epidermidis, and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis and growth.
Neomycin 5% is described in much of the literature on ammonia-related eye injury; however, newer broad-spectrum antibiotics have fewer adverse effects

Dosing

Adult

1 gtt qid (prophylaxis)

Pediatric

<12 years: Not recommended
>12 years: Administer as in adults

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use may result in overgrowth of nonsusceptible organisms, including fungi

Erythromycin (E-Mycin)

Indicated for infections caused by susceptible strains of microorganisms and for prevention of corneal and conjunctival infections

Dosing

Adult

Apply 1-cm ribbon 4-8 times/d depending on severity of infection

Pediatric

Apply as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, mycobacterial, or fungal infections of eye; patients using steroid combinations after uncomplicated removal of a foreign body from cornea also should avoid using this product

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Do not use topical antibiotics to treat ocular infections that may become systemic; prolonged or repeated antibiotic therapy may result in bacterial or fungal overgrowth of nonsusceptible organisms and may lead to a secondary infection (take appropriate measures if superinfection occurs)

Anticholinergic agents

Induces cycloplegia by blocking the body's parasympathetic (cholinergic) effects in the eye. This is beneficial to prevent ciliary spasm. Should be used in consultation with the ophthalmology service.

Cyclopentolate (AK-Pentolate)

Blocks muscle of ciliary body and sphincter muscle of iris from responding to cholinergic stimulation, thus causing mydriasis and cycloplegia.
Induces mydriasis in 30-60 min and cycloplegia in 25-75 min; these effects last up to 24 hours

Dosing

Adult

1 gtt into affected eye(s) once; may repeat in 24-48 h prn

Pediatric

Administer as in adults

Interactions

Decreases effects of carbachol and cholinesterase inhibitors

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients (eg, elderly patients) in whom increased intraocular pressure may be present; can cause toxic anticholinergic systemic adverse effects (common in children especially infants), but incidence is rare when used sparingly; compressing lacrimal sac by digital pressure for 1-3 min following application may minimize systemic absorption

Homatropine (Isopto Homatropine)

Blocks responses of sphincter muscle of iris and muscle of ciliary body to cholinergic stimulation, producing pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia).
Induces mydriasis in 10-30 min and cycloplegia in 30-90 min; these effects last up to 48 h.

Dosing

Adult

1 gtt into affected eye(s) once; may repeat in 24-48 h prn

Pediatric

1 gtt into affected eye(s) once; may repeat in 24-48 h prn

Interactions

None reported

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients (eg, elderly patients) in whom increased intraocular pressure may be present; toxic anticholinergic systemic adverse effects can occur, but incidence is rare when used sparingly; adverse effects are more common in children, especially infants; compressing lacrimal sac by digital pressure for 1-3 min following instillation minimizes systemic absorption

Tropicamide (Mydriacyl)

Blocks sphincter muscle of iris and muscle of ciliary body from responding to cholinergic stimulation

Dosing

Adult

1 gtt into affected eye(s) once

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients (eg, elderly patients) in whom increased intraocular pressure may be present; toxic anticholinergic systemic adverse effects can occur, but incidence is rare when used sparingly; adverse effects are more common in children, especially infants; compressing lacrimal sac by digital pressure for 1-3 min following instillation minimizes systemic absorption

Corticosteroids

Decrease the formation of fibroblasts on the cornea and may limit intraocular inflammation. However, may potentiate infection. Should be administered only in consultation with the ophthalmology service.

Prednisolone (Pred Forte)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Note that ophthalmologic steroids are controversial; discuss their use with ophthalmology. Also, steroid-antibiotic combination may be useful.

Dosing

Adult

1 gtt q1-6h based on severity of inflammation for 7-10 d

Pediatric

Administer as in adults

Interactions

Effects may decrease in patients taking phenytoin, barbiturates, and rifampin

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hypertension; known to cause cataract formation with chronic use; in prolonged use, withdraw treatment by gradually decreasing frequency of applications to avoid adrenal insufficiency; may increase corneal thinning and melting; risk of globe perforation; discontinue if acute rise in intraocular pressure or ocular infection

Fluorometholone (FML)

Suppresses migration of polymorphonuclear leukocytes and reverses capillary permeability

Dosing

Adult

1 gtt q1-6h based on severity of inflammation for 7-10 d

Pediatric

<2 years: Not established
> 2 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; herpes simplex; keratitis; viral and fungal diseases of the ocular structure

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use my result in elevated intraocular pressure or glaucoma

Rimexolone (Vexol)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Dosing

Adult

1 gtt q1-6h based on severity of inflammation for 7-10 d

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, bacterial ocular infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in corneal or scleral perforation and posterior subcapsular cataracts

Local anesthetics

Used primarily for pain relief. Duration of action is relatively short-lived, limiting usefulness of local anesthetics outside of the hospital or clinic setting.

Proparacaine 0.5% (Alcaine)

Has rapid onset of anesthesia that begins within 13-30 sec after instillation. However, has short duration of action of about 15-20 min.
Least irritating of all topical anesthetics. Prevents initiation and transmission of impulse at nerve cell membrane by stabilizing and decreasing ion permeability.
Onset of action occurs within 20 s of application.
Anesthetic effect may last up to 10-15 min

Dosing

Adult

Instill 1-2 gtt into affected eye; may repeat if desired

Pediatric

Administer as in adults

Interactions

Increases effects of phenylephrine and tropicamide

Contraindications

Documented hypersensitivity; prolonged use

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiac disease or hyperthyroidism and those with abnormal or reduced levels of plasma esterases
Do not use outside the ED because prolonged eye anesthesia can eliminate patient's awareness of mechanical damage to cornea; frequent use of anesthetics may retard healing

Follow-up

Further Inpatient Care

• The majority of patients with unintentional household ammonia exposure will have very mild symptoms and could be discharged safely if asymptomatic and able to tolerate oral intake.
• Admit patients to observation for at least 24 hours if they show significant and persistent signs, symptoms, or abnormalities in laboratory findings attributable to ammonia exposure.
• Admit unstable or potentially unstable patients to the intensive care unit.
• Following ingestion, patients may be discharged if endoscopy results are normal and oral intake is tolerated.
• Intentional ingestions require psychiatric evaluation.

Complications

• Patients can develop chronic respiratory sequelae, particularly with severe ammonia exposures. In a case series by Close et al, exposed patients experienced gradual deterioration of pulmonary function during the first 2-6 months following exposure.⁶ A period of slight improvement was then observed, followed by stabilization of symptoms.
• Long-term effects of ammonia inhalation injury include the following:
  • Cough
  • Hoarseness
  • Obstructive and/or restrictive lung disease
  • Hyper-reactive airway disease and reactive airway dysfunction syndrome (RADS)
  • Impaired gas exchange
  • Residual parenchymal damage
  • Bronchiectasis and bronchiolitis obliterans (following massive exposure)
  • Pulmonary fibrosis
• It is postulated that chronic obstructive disease is secondary to airway lesions more than hyper-reactivity and, therefore, often minimally improved by bronchodilators.

Prognosis

• Most individuals with ammonia inhalation who survive the first 24 hours will recover.
• Patients begin showing improvement within 48-72 hours and may recover fully during this time if exposure was mild.
• For patients with more significant respiratory symptoms, recovery can be expected within several weeks to months.
• Interestingly, Arwood et al found that initial chest x-ray and PaO₂ poorly correlate with outcome and that physical examination on arrival is a more sensitive prognosticating factor.⁷
• Montague and MacNeil, however, note that patients who do not develop chest x-ray findings are less likely to have chronic respiratory sequelae.

Patient Education

• For excellent patient education resources, visit eMedicine's Burns Center. Also, see eMedicine's patient education article Thermal (Heat or Fire) Burns.

Miscellaneous

Special Concerns

• Chloramine gas
  • Chloramines (NH₂ Cl, NHCl₂) are highly water-soluble irritant gases formed when household bleach [(5.25% sodium hypochlorite (NaOCl)] is mixed with 5-10% ammonia solutions (usually cleaning products). Fumes contact moist mucous membranes, reacting with water to produce free ammonia gas (see Inhalation injury), hypochloric acid, and hypochlorous acid. The latter then reacts with water to form hydrochloric acid and nascent oxygen, a strong oxidizing agent with corrosive effects.
  • At low concentration, symptoms include tearing, rhinorrhea, oropharyngeal burning, and cough. Although chloramine gases produce rapid onset of symptoms, these symptoms are mild enough that patients often do not remove themselves promptly from the toxic environment; thus, patients often present after a prolonged exposure time.
  • The physical examination following mild exposure reveals only mild wheezing and decreased air entry or may be entirely unremarkable.
  • Patients with more significant exposure may present with dyspnea, pulmonary edema with secondary hypoxia, nausea, tracheobronchitis, toxic pneumonitis, intrapulmonary shunt, and/or pneumomediastinum. Note that pulmonary edema may ensue within minutes or be delayed for up to 24 hours following exposure.
  • Pulmonary function tests may reveal obstructive, restrictive, or combined patterns, and pulmonary artery occlusive pressure may be less than 17 mm Hg.
• Treat chloramine gas exposure as described under Emergency Department Care.
  • Nebulized sodium bicarbonate (3.75%) has been suggested to be an adjunct to supportive treatment, but little clinical experience with this treatment exists.
  • In Thomas and Storrow's case series of 22 patients with chloramine toxicity, treatment with sodium bicarbonate resulted in no clinical or statistical improvement.

References

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2. Watson WA, Litovitz TL, Rodgers GC. 2002 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2003;21(5):353-421. [Medline].

3. de la Hoz RE, Schlueter DP, Rom WN. Chronic lung disease secondary to ammonia inhalation injury: a report on three cases. Am J Ind Med. 1996;29(2):209-14. [Medline].

4. Caplin M. Ammonia-gas poisoning: 47 cases in a London shelter. Lancet. 1941;2:958-61.

5. Klein J, Olson KR, McKinney HE. Caustic injury from household ammonia. Am J Emerg Med. Jul 1985;3(4):320. [Medline].

6. Close LG, Catlin FI, Cohn AM. Acute and chronic effects of ammonia burns on the respiratory tract. Arch Otolaryngol. Mar 1980;106(3):151-8. [Medline].

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Keywords

anhydrous ammonia, NH₃, liquid ammonia, ammonia exposure, ammonia exposure symptoms, ammonia ingestion, ammonia inhalation, ammonium hydroxide, liquid anhydrous ammonia, toxic ammonia exposure, ammonia toxicity, ammonia poisoning, fertilizer

Contributor Information and Disclosures

Author

Steven Issley, MD, FRCPC, Assistant Professor of Emergency Medicine, Assistant Director of Medical Stimulation Center, Consulting Staff, Department of Emergency Medicine, SUNY-Downstate Medical Center, Kings County Hospital Center
Disclosure: Nothing to disclose.

Coauthor(s)

Eddy Lang, MDCM, CCFP (EM), CSPQ, Assistant Professor, Department of Family Medicine, McGill University; Consulting Staff, Department of Emergency Medicine, The Sir Mortimer B Davis-Jewish General Hospital
Eddy Lang, MDCM, CCFP (EM), CSPQ is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

Medical Editor

Edmond A Hooker II, MD, DrPH, FAAEM, Assistant Professor, Department of Health Services Administration, Xavier University; Associate Clinical Professor, Department of Emergency Medicine, University of Louisville; Assistant Clinical Professor, Department of Emergency Medicine, Wright State University
Edmond A Hooker II, MD, DrPH, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American Public Health Association, Society for Academic Emergency Medicine, and Southern Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

Michael J Burns, MD, Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center
Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

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