Therapeutic Toxic Class

A)

Specific Substances

A)

1) Alkyl (C8-C18) dimethyl benzyl ammonium
2) chloride (USP)
3) Zephiran chloride(R)
4) CAS 8001-54-5

1) Diisobutyl phenoxy ethoxy ethyl dimethyl
2) benzyl ammonium chloride
3) Hyamine 1622(R)
4) CAS 121-54-0

1) Cetyl dimethyl benzyl ammonium chloride
2) Benzyl hexadecyl dimethyl ammonium chloride
3) Hexadecyldimethyl benzyl ammonium chloride
4) CAS 122-18-9

1) Ceepryn chloride(R)
2) 1-Hexadecyl pyridinium chloride
3) CPC
4) CAS 123-03-5

1) Benzyl dimethyl stearyl ammonium chloride
2) Stearyl dimethyl benzyl ammonium chloride
3) CAS 122-19-0

1) Hexadecyl trimethyl ammonium bromide
2) Cetyl trimethyl ammonium bromide
3) Cetrimide(R)
4) CAS 57-09-0

1) EPTMAC
2) Oxiranemethanamimium
3) N,N,N-trimethyl chloride
4) 2,3 epoxypropyl trimethyl ammonium chloride.

1) CATIONIC SURFACTANT
2) CATIONIC WETTING AGENT
3) CATIONIC DETERGENTS
4) DETERGENT (CATIONIC)
5) QUATERNARY AMMONIUM COMPOUNDS
6) QUATERNARY PYRIDIUM GERMICIDES
7) QAC

Available Forms Sources

A)

1) BENZALKONIUM CHLORIDE

TRADE NAME	CONCENTRATION
generic concentrates	17-17.5%
Benza(R)	1:750(0.13%)
Germicin(R)	50%
Zephiran(R)	1:750(0.13%)
Zephiran concentrate	17%

2) CETYLPYRIDINIUM CHLORIDE

a) Troches or lozenges: 1 to 2.5 mg
b) Mouthwash: 0.05 to 0.5%

Life Support

A)

Clinical Effects

0.2.1)

A) USES: Detergents are used for cleaning and decontamination.
B) TOXICOLOGY: The primary effects of these products are mucosal and tissue irritation. They act by disrupting lipid bilayers. The risk of toxicity is related to concentration; severe injury is rare unless the concentration is more than 7.5%.
C) EPIDEMIOLOGY: Exposures to household products are common, but generally result in only minor irritation. Exposure to concentrated products (more than 7.5%) is rare, but can cause corrosive injury. Mortality and serious morbidity are rare.
D) WITH POISONING/EXPOSURE

1) MILD TO MODERATE TOXICITY: Irritation of the oral mucosa, eyes, or skin may develop depending on the route of exposure. Vomiting, diarrhea, and abdominal pain may occur after ingestion.
2) SEVERE TOXICITY: Ingestion of concentrated solutions may produce burns of the mouth, pharynx, and esophagus. Hemorrhagic gastrointestinal (GI) tract necrosis and peritonitis may develop rarely. Bronchospasm, aspiration pneumonitis, hypoxemia, and acute lung injury are rare complications. CNS depression progressing to coma and shock are rare complications in patients with severe ingestion or corrosive GI injury. Hemolysis has occurred following unintentional IV administration and epidural irrigation of cetrimonium bromide. Methemoglobinemia has been reported following peritoneal irrigation of cetrimonium bromide. Eye exposure may cause effects ranging from mild discomfort to very serious corneal damage. Dermal necrosis can develop after exposure to concentrated formulations.

0.2.4)

A) Eye exposure may cause effects ranging from mild discomfort (0.1% solutions) to very serious corneal damage (10% solutions). Ototoxicity has been reported in experimental animals when such agents were instilled into the inner ear; instillation of dilute solutions into ears with intact tympanic membranes is not predicted to be irritating. Mild to severe caustic burns of the lips, tongue, mouth, and throat have been reported following ingestion.

0.2.5)

A) Hypotension and cardiac arrest have rarely been reported.

0.2.6)

A) Respiratory muscle paralysis as been reported after parenteral administration of cetrimonium bromide. Acute lung injury and hypoxemia have been reported after aspiration. Occupational asthma can develop with repeated exposure.

0.2.7)

A) CNS depression progressing to coma, and respiratory muscle paralysis has been reported after parenteral administration of cetrimonium bromide.

0.2.8)

A) Vomiting, diarrhea, and abdominal pain may occur. Ingestion of concentrated solutions may produce burns of the mouth, pharynx, and esophagus. Hemorrhagic GI tract necrosis and peritonitis have been reported.

0.2.9)

A) Hepatic necrosis and elevated serum hepatic aminotransferases have been reported.

0.2.10)

A) WITH POISONING/EXPOSURE

1) Renal failure has been reported with delayed presentation following a large volume ingestion of a benzethonium-containing wound disinfectant.

0.2.11)

A) Metabolic acidosis has been reported.

0.2.13)

A) Hemolysis has occurred following epidural irrigation and unintentional IV administration with cetrimonium bromide. Methemoglobinemia was reported following peritoneal irrigation with cetrimonium bromide.

0.2.14)

A) Dermal necrosis has been reported following application of 12% to 17.5% solutions and powder of cetrimonium bromide. A patch test with a 2% solution also produced necrosis. A number of these agents have caused irritant or allergic contact dermatitis.

0.2.20)

A) In a postnatal mouse screening test, Benzethonium Chloride caused excessive maternal mortality, a decreased reproductive index, decreased percent pup survival, and decreased birth weights.
B) Cetyltrimethylammonium Bromide increased the number of dead implantations in pregnant mice. The number of malformed fetuses was dose-dependent, and abnormalities observed included cleft palate and minor skeletal defects.

Laboratory Monitoring

A)

B)

C)

D)

E)

Treatment Overview

0.4.2)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) The vast majority of exposures require only supportive care. The mouth should be rinsed and a small amount of water or milk given to patients with minor ingestions.

B) MANAGEMENT OF SEVERE TOXICITY

1) Evaluate for evidence of caustic injury to the gastrointestinal (GI) mucosa. Endoscopy should be performed within 12 hours in any patient with deliberate ingestion of a high concentration, or patients with stridor, pain with swallowing, or persistent vomiting. Administer intravenous fluids for hypotension and evaluate for GI bleeding. Maintain adequate ventilation and oxygenation; endotracheal intubation may be necessary in patients with upper airway edema or aspiration.

C) DECONTAMINATION

1) PREHOSPITAL: Emesis is not recommended because of possible corrosive effects. Dilute with small amounts of milk or water.
2) HOSPITAL: Dilute orally with small amounts of water or milk. Activated charcoal is not effective.

D) ANTIDOTE

1) None

E) ENHANCED ELIMINATION

1) There is no role for these procedures as systemic absorption is not the cause of toxicity.

F) PATIENT DISPOSITION

1) HOME CRITERIA: Unintentional "taste" of dilute solutions in patients with no symptoms or only minor irritation can be observed in the home.
2) OBSERVATION CRITERIA: Patients with deliberate ingestions, more than mild symptoms, and all acute ingestions of quaternary ammonium compounds should be evaluated and managed in a healthcare facility.
3) ADMISSION CRITERIA: Severe respiratory tract injury, severe GI symptoms, corneal burns.
4) CONSULT CRITERIA: If corrosive GI injury is suspected, consult a gastroenterologist for endoscopy. Consult an ophthalmologist for any patient with corneal burns. Consult a medical toxicologist or poison center for any patient with significant toxicity.

G) DIFFERENTIAL DIAGNOSIS

1) Includes other agents with corrosive effects (eg, acids, alkali).

0.4.3)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) The vast majority of exposures require only supportive care.

B) MANAGEMENT OF SEVERE TOXICITY

1) Administer oxygen. Treat bronchospasm with inhaled beta agonists. Evaluate for evidence of aspiration or upper airway edema. Endotracheal intubation may be necessary.

C) DECONTAMINATION

1) Move patient from the toxic environment to fresh air. Administer oxygen. Monitor for respiratory distress.

D) AIRWAY MANAGEMENT

1) Maintain an open airway and perform orotracheal intubation in patients with respiratory distress, aspiration, or upper airway edema or burns.

0.4.4)

A) MANAGEMENT OF MILD TO MODERATE TOXICITY

1) The vast majority of exposures require only supportive care. Exposed eyes should be irrigated with copious amounts of water.

B) MANAGEMENT OF SEVERE TOXICITY

1) Exposed eyes should be irrigated with copious amounts of water for at least 30 minutes. The pH of the cul-de-sac should be tested after irrigation and a slit lamp exam performed. Ophthalmologic consultation should be obtained in patients with corneal burns.

0.4.5)

A) OVERVIEW

1) MANAGEMENT OF MILD TO MODERATE TOXICITY

a) The vast majority of exposures require only supportive care. Exposed skin should be irrigated with copious amounts of water.

2) MANAGEMENT OF SEVERE TOXICITY

a) Irrigate the exposed area with copious amounts of water and remove contaminated clothing and jewelry.

Range Of Toxicity

A)

Clinical Effects

Respiratory

3.6.1)

A) Respiratory muscle paralysis as been reported after parenteral administration of cetrimonium bromide. Acute lung injury and hypoxemia have been reported after aspiration. Occupational asthma can develop with repeated exposure.

3.6.2)

A) PARALYSIS

1) WITH POISONING/EXPOSURE

a) Paralysis of the respiratory muscles has occurred after intravenous injection and epidural application of cetrimide (Klouche et al, 1994; Gode et al, 1975).

B) ACUTE LUNG INJURY

1) WITH POISONING/EXPOSURE

a) Acute lung injury may occur (Adelson & Sunshine, 1952). Pulmonary edema was described in 1 of 5 infants unintentionally fed a dilute antiseptic solution of chlorhexidine 0.05% and cetrimide 1% (Mucklow, 1988).
b) CASE SERIES/PEDIATRIC: In a series of 9 infants who were inadvertently given quaternary ammonium nasally, all developed inflammation and edema of the nasal mucosa, erosive pharyngitis, and caustic esophageal injury (confirmed by endoscopy). All demonstrated hypersalivation, bradypnea and gastrointestinal pain. Six developed cough, 5 developed vomiting, 1 developed bradycardia, and 1 developed keratitis. Six required endotracheal intubation for respiratory failure, and 4 patients developed acute lung injury. One patient each developed sequelae of nasal membrane damage and pulmonary segmental atelectasias (Nisse et al, 2002).

C) BRONCHOSPASM

1) WITH POISONING/EXPOSURE

a) Occupational asthma has been reported from exposure to benzalkonium chloride (Purohit et al, 2000; Innocenti, 1978).

D) ASPIRATION PNEUMONIA

1) WITH POISONING/EXPOSURE

a) ELDERLY: Three elderly patients with dementia ingested quaternary ammonium compound disinfectants and developed massive aspiration (thought to be secondary to caustic detergent aspiration) and pneumonia. Effects included gastrointestinal injury (ie, burns and necroses), as well as severe dyspnea and stridor and respiratory failure in 1 case. Two of the 3 patients died within several days of exposure due to increasing respiratory insufficiency (Hahn et al, 2000).

E) TOXIC PNEUMONITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT/PEDIATRIC: A 2-day-old full-term neonate was inadvertently given 2 teaspoonfuls of antiseptic solution (container was similar to sterile water bottle) containing 10% benzalkonium chloride and immediately began to cry and have difficulty breathing. Initial symptoms included inspiratory and expiratory stridor and bilateral rhonchi. Respiratory acidosis (pH 7.13, PaCO2 72.1 mmHg, PaO2 58.7), along with edematous epiglottis and vocal cords were present requiring intubation and mechanical ventilation. On day 3, chest x-ray showed bilateral patchy infiltrates and reticular shadowing suggestive of chemical pneumonitis. Hospital course also included gastrointestinal hemorrhage that resolved within 2 days. The patient gradually improved and steroids were tapered. The infant recovered completely and was discharged on day 33 (Okan et al, 2007).

F) HYPOXEMIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Hypoxemia was described in a 70-year-old woman who ingested 40 mL of a concentrated benzalkonium chloride solution (van Berkel & de Wolff, 1988).

3.6.3)

A) ANIMAL STUDIES

1) DYSPNEA

a) CETYLPYRIDINIUM CHLORIDE: Experimental animals exposed by inhalation experienced reversible weight loss, nasal discharge, dyspnea, chromodacryorrhea, and eye irritation (Lin et al, 1991).

2) IRRITATION

a) Benzalkonium chloride may be classified to class I acute inhalation toxicity. A study, performed on female Wistar rats, showed a strong inflammatory and irritant activity on the lungs after inhalation, and stimulated dynamic patterns of IL-6 and IgE production and protein infiltration from blood vessels to bronchoalveolar lavage fluid (Swiercz et al, 2008).

Neurologic

3.7.1)

A) CNS depression progressing to coma, and respiratory muscle paralysis has been reported after parenteral administration of cetrimonium bromide.

3.7.2)

A) CENTRAL NERVOUS SYSTEM DEFICIT

1) WITH POISONING/EXPOSURE

a) Parenteral administration of Cetrimonium bromide may result in severe CNS depression and paralysis of respiratory and skeletal muscles (Klouche et al, 1994; Gode et al, 1975).

Gastrointestinal

3.8.1)

A) Vomiting, diarrhea, and abdominal pain may occur. Ingestion of concentrated solutions may produce burns of the mouth, pharynx, and esophagus. Hemorrhagic GI tract necrosis and peritonitis have been reported.

3.8.2)

A) VOMITING

1) WITH POISONING/EXPOSURE

a) Gastrointestinal irritation may result in nausea, vomiting, abdominal pain, dysphagia, and rarely hematemesis (Chan, 1994).

B) GASTROINTESTINAL AND DIGESTIVE INJURY

1) WITH POISONING/EXPOSURE

a) Focal hemorrhagic necrosis of the gastrointestinal tract may occur following ingestion of concentrated solutions. Children with esophageal burns may drool, as it is painful to swallow.
b) Concentrated (10% to 15%) cationic detergents, usually commercial or hospital germicides, are remarkably caustic and may produce burns of the mouth and esophagus. There is only 1 report involving lesser concentrations. In this case, a 7.5% solution did not result in burns (Tiess & Nagel, 1967). It is unknown at what concentration corrosive effects may be expected not to occur.
c) ELDERLY ADULTS: Five elderly patients with senile dementia ingested a 10% solution of benzalkonium chloride. Four developed burning oral pain and sialorrhea. The fifth patient developed erythema of the lips and mouth after ingesting less than 50 mL of the solution and vomited and collapsed shortly afterwards. Level of consciousness gradually decreased and she died 3 hours after ingestion. Autopsy revealed marked corrosive injury to the GI tract (Hitosugi et al, 1998).

1) In a similar study, 2 of 3 elderly patients with dementia developed serious gastrointestinal injury (ie, severe necroses and caustic burns) after ingesting quaternary ammonium compound (ie, benzalkonium chloride {15% and 20% solutions ingested}, and a 2% solution of didecyldimethylammonium chloride {amount unknown}) disinfectants. Two patients died within 3 days of exposure from complications of aspiration (Hahn et al, 2000).

d) INFANTS: In a series of 9 infants who were inadvertently given quaternary ammonium nasally, all developed inflammation and edema of the nasal mucosa, erosive pharyngitis, and caustic esophageal injury (confirmed by endoscopy). All demonstrated hypersalivation, bradypnea, and gastrointestinal pain. Six developed cough, 5 developed vomiting, 1 developed bradycardia, and 1 developed keratitis. Six required endotracheal intubation for respiratory failure, and 4 patients developed acute lung injury. One patient each developed sequelae of nasal membrane damage and pulmonary segmental atelectasias (Nisse et al, 2002).

1) CASE REPORT: A 2-day-old full-term neonate was inadvertently given 2 teaspoonfuls of antiseptic solution (container was similar to sterile water bottle) containing 10% benzalkonium chloride and immediately began to cry and have difficulty breathing. Initial symptoms included respiratory insufficiency requiring intubation and mechanical ventilation. On day 6, the patient developed an upper gastrointestinal hemorrhage. An abdominal x-ray was normal and ultrasound showed thickening of the gastric mucosa and multiple bright echogenic focuses. Following supportive care, the bleeding stopped in 2 days and enteral feeds were restarted. The infant recovered completely and was discharged on day 33 (Okan et al, 2007).

C) PERITONITIS

1) WITH POISONING/EXPOSURE

a) Injection of hydatid cysts with 5% cetrimonium bromide, followed by peritoneal irrigation with a 0.5% solution has resulted in chemical peritonitis, adhesions, and obstruction (Gilchrist, 1979).

D) DIARRHEA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Profuse diarrhea and dehydration were reported in a woman who ingested 40 mL of a 33.3% benzalkonium chloride solution (van Berkel & de Wolff, 1988).

Hepatic

3.9.1)

A) Hepatic necrosis and elevated serum hepatic aminotransferases have been reported.

3.9.2)

A) HEPATIC NECROSIS

1) WITH POISONING/EXPOSURE

a) Hepatic necrosis has been a finding in fatal cases (Tiess & Nagel, 1967).

B) LIVER ENZYMES ABNORMAL

1) WITH POISONING/EXPOSURE

a) Elevated serum hepatic aminotransferases were noted after an overdose of benzalkonium chloride (van Berkel & de Wolff, 1988).
b) Pharmaceutical industry workers exposed to CETYLPYRIDINIUM CHLORIDE and a number of other substances had increased serum hepatic transaminase levels (Tomei et al, 1995).

Genitourinary

3.10.1)

A) WITH POISONING/EXPOSURE

1) Renal failure has been reported with delayed presentation following a large volume ingestion of a benzethonium-containing wound disinfectant.

3.10.2)

A) ACUTE RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 23-year-old man, who ingested 150 mL of Makiron(R) in a suicide attempt, presented with severe hepatopathy, pneumonia, and acute renal failure 30 hours postingestion. Upon admission, components of Makiron(R), including naphazoline (1.4 mcg/mL), chlorpheniramine (0.81 mcg/mL), dibucaine (3.2 mcg/mL) and benzethonium (5.5 mcg/mL), were detected in the patient's plasma. The hepatopathy and pneumonia resolved several days later; however, the patient required continuation of dialysis 3 times per week for 17 days due to persistence of anuria (Hanji et al, 2008).

Acid-Base

3.11.1)

A) Metabolic acidosis has been reported.

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT/BENZALKONIUM CHLORIDE: Metabolic acidosis and hypotension were reported following ingestion of benzalkonium chloride (van Berkel & de Wolff, 1988).
b) CASE REPORT/CETRIMONIUM BROMIDE: Peritoneal irrigation with more than a liter of cetrimonium bromide 1% solution resulted in metabolic acidosis, hypotension, hypochloremia, hyperkalemia, and an increased anion gap in a 44-year-old man undergoing surgical excision of hydatid cysts (Momblano et al, 1984).

Hematologic

3.13.1)

A) Hemolysis has occurred following epidural irrigation and unintentional IV administration with cetrimonium bromide. Methemoglobinemia was reported following peritoneal irrigation with cetrimonium bromide.

3.13.2)

A) HEMOLYSIS

1) WITH POISONING/EXPOSURE

a) CETRIMONIUM BROMIDE: Hemolysis was reported following irrigation of an epidural hydatid cyst in a 29-year-old man using 1% cetrimide, and unintentional IV infusion of 5 mL of 5% cetrimide in a 6-month-old infant (Klouche et al, 1994; Gode et al, 1975).

B) METHEMOGLOBINEMIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT: Liberal irrigation of a hydatid cyst during surgical excision with a 0.1% solution of cetrimide produced a methemoglobin level of 38.7% in a 45-year-old woman (Baraka et al, 1980).

C) HEMATOLOGY FINDING

1) WITH POISONING/EXPOSURE

a) Cationic detergents have damaged human lymphocytes in vitro (Hrabak et al, 1982).

Dermatologic

3.14.1)

A) Dermal necrosis has been reported following application of 12% to 17.5% solutions and powder of cetrimonium bromide. A patch test with a 2% solution also produced necrosis. A number of these agents have caused irritant or allergic contact dermatitis.

3.14.2)

A) SKIN NECROSIS

1) WITH POISONING/EXPOSURE

a) Dermal necrosis has been reported following application of 12% to 17.5% solutions and powder of cetrimonium bromide. Occlusion appears to have been a factor in many of these cases (Mercer, 1983; Inman, 1982; August, 1975). A patch test with a 2% solution also produced necrosis (August, 1975).
b) BENZALKONIUM CHLORIDE/CASE REPORT: A 33-year-old woman developed oral necrotic lesions 5 days following unintentional injection of benzalkonium chloride into the oral mucosa instead of the intended local anesthetic during a dental procedure. The patient also experienced paresthesia of the vestibular mucosa and the lower lip. Despite chlorhexidine mouth gargles over the next 10 days, the lesions had not improved, necessitating surgical intervention with debridement and gingival sulcoplasty. Healing was uneventful and the paresthesia completely resolved within 3 months (Kilic et al, 2011).

B) DERMATITIS

1) WITH POISONING/EXPOSURE

a) Many cationic detergents can cause irritant or allergic contact dermatitis, even with fume/vapor exposure (Chowdhury & Statham, 2002)Wong & Watson, 2001; (Kanerva et al, 2000; Park et al, 2000; Mowad, 1998; Dejobert et al, 1997; Corazza & Virgili, 1993; Cusano & Luciano, 1993; Klein et al, 1991; Mathias, 1984).
b) BENZALKONIUM CHLORIDE: A 0.1% solution produced skin reactions in 24% of patients after a 48 hour patch test, and severe pustular and/or bullous reactions were caused by concentrations of 0.5% or greater in 80% of patients (Wahlberg et al, 1985). It is thought that benzalkonium chloride should be regarded as a weak allergen and more likely to produce a cutaneous irritant reaction (Uter et al, 2008; Basketter et al, 2004; Fuchs et al, 1993). The antiseptic bath emollient Oilatum(R) Plus contains a relatively high concentration of 6% benzalkonium chloride. There have been multiple case reports of irritant dermatitis with superficial desquamation and rapid improvement after avoidance of exposure to the antiseptic solution (Hann et al, 2007; Saw & Hindmarsh, 2005; Storer et al, 2004; Loo, 2003).
c) BHETA (Bis-hydroxyethyl-tallow amine) is an antistatic agent used on plastic boxes that caused dermatitis in 48% of employees who contacted it (Bennett et al, 1988).
d) EPTMAC: Allergic contact dermatitis was seen in workers exposed to the cationic surfactant 2,3-epoxypropyl trimethyl ammonium chloride. The material appears to be a strong sensitizer (Estlander et al, 1986). In a large case series in Helsinki, Finland, from 1974 to 1990, approximately 50% of patients (n=3731) developed an occupational skin disease. Approximately 8% of those patients had an occupational skin disease caused by epoxy compounds, including 2,3-epoxypropyl trimethyl ammonium chloride. Allergic contact dermatitis, irritant contact dermatitis, and contact urticaria were among the skin manifestations (Jolanki, 1991).
e) GLYCIDYL TRIMETHYL AMMONIUM CHLORIDE: Contact dermatitis developed in factory workers handling glycidyl trimethyl ammonium chloride after 1 to 3 months of exposure (Estlander et al, 1986).
f) QUATERNIUM 15 (Dowicil 200): There have been frequent cases of occupational allergic contact dermatitis reported due to exposure to this agent (Tosti et al, 1990).

C) SKIN ULCER

1) WITH POISONING/EXPOSURE

a) BENZALKONIUM CHLORIDE: There are numerous reports of corrosive burns secondary to skin contact with benzalkonium chloride in concentrations of 10% or greater. There is only one report involving lesser concentrations. In this case, a 7.5% solution did not cause burns (Tiess & Nagel, 1967). It is unknown at what concentration corrosive effects may be predicted not to occur.
b) METHYL BENZETHONIUM CHLORIDE was suspected to cause irritant contact dermatitis in a 31-year-old patient exposed via an ointment (Maibach & Mathias, 1985).
c) In normal human epidermal keratinocytes, cationic detergents were more cytotoxic than other detergents (Ikarashi et al, 1993).

3.14.3)

A) ANIMAL STUDIES

1) CETYLPYRIDINIUM CHLORIDE/STEARYL PHENYL ETHYLDIMETHYLAMMONIUM TOSYLATE were extremely irritating to the skin (either abraded or intact) in rabbits (Lin & Hemming, 1996).

Immunologic

3.19.2)

A) HYPERSENSITIVITY REACTION

1) WITH POISONING/EXPOSURE

a) CASE REPORT: A 58-year-old woman with a history of allergic rhinitis, sinusitis, and reactive airway disease developed a hypersensitivity reaction during a preoperative Proventil nebulization treatment. She became dizzy and flushed with a cough. A similar reaction was seen when rechallenged with a topical anesthetic/decongestant. The common factor in both instances was benzalkonium chloride (BC), and an ID skin-test with 0.001% BC solution gave a positive response (facial flushing with edema, severe cough and throat fullness). Avoidance of products containing BC significantly reduced the patient's reactive airway disease (Ponder & Wray, 1993).

Reproductive

3.20.1)

A) In a postnatal mouse screening test, Benzethonium Chloride caused excessive maternal mortality, a decreased reproductive index, decreased percent pup survival, and decreased birth weights.
B) Cetyltrimethylammonium Bromide increased the number of dead implantations in pregnant mice. The number of malformed fetuses was dose-dependent, and abnormalities observed included cleft palate and minor skeletal defects.

3.20.3)

A) ANIMALS

1) In a postnatal mouse screening test, Benzethonium Chloride caused excessive maternal mortality, a decreased reproductive index, decreased percent pup survival, and decreased birth weights (Anon, 1987).
2) Cetyltrimethylammonium Bromide increased the number of dead implantations in pregnant mice. The number of malformed fetuses was dose-dependent, and abnormalities observed included cleft palate and minor skeletal defects (Isomaa & Ekman, 1975).

Summary Of Exposure

A)

B)

C)

D)

1) MILD TO MODERATE TOXICITY: Irritation of the oral mucosa, eyes, or skin may develop depending on the route of exposure. Vomiting, diarrhea, and abdominal pain may occur after ingestion.
2) SEVERE TOXICITY: Ingestion of concentrated solutions may produce burns of the mouth, pharynx, and esophagus. Hemorrhagic gastrointestinal (GI) tract necrosis and peritonitis may develop rarely. Bronchospasm, aspiration pneumonitis, hypoxemia, and acute lung injury are rare complications. CNS depression progressing to coma and shock are rare complications in patients with severe ingestion or corrosive GI injury. Hemolysis has occurred following unintentional IV administration and epidural irrigation of cetrimonium bromide. Methemoglobinemia has been reported following peritoneal irrigation of cetrimonium bromide. Eye exposure may cause effects ranging from mild discomfort to very serious corneal damage. Dermal necrosis can develop after exposure to concentrated formulations.

Heent

3.4.1)

A) Eye exposure may cause effects ranging from mild discomfort (0.1% solutions) to very serious corneal damage (10% solutions). Ototoxicity has been reported in experimental animals when such agents were instilled into the inner ear; instillation of dilute solutions into ears with intact tympanic membranes is not predicted to be irritating. Mild to severe caustic burns of the lips, tongue, mouth, and throat have been reported following ingestion.

3.4.2)

A) WITH POISONING/EXPOSURE

1) BENZALKONIUM CHLORIDE: A 33-year-old woman developed swelling of the lower lip, chin, and neck immediately after unintentional injection of benzalkonium chloride into the oral mucosa instead of the intended local anesthetic during a dental procedure. The patient also experienced dyspnea and briefly lost consciousness. The swelling continued to increase for 4 days, then gradually resolved over the next 10 days following administration of corticosteroids and antihistamines (Kilic et al, 2011).

3.4.3)

A) BENZALKONIUM CHLORIDE: A drop of 0.1% solution to the human eye caused mild discomfort that subsided in 2 to 3 hours. Superficial desquamation of conjunctival epithelium usually resolves within 24 hours (Swan, 1944).

1) CASE REPORT: Inadvertent use of Mycocide NS (containing <1% benzalkonium chloride) antimicrobial solution in the eye 6 weeks following corneal transplant resulted in immediate burning and tearing. Examination revealed mucoid drainage and a large bulbar conjunctival epithelial staining defect. The ocular surface healed 4 days later with appropriate treatment (Steinemann & Brown, 1998).
2) CASE REPORT: Inadvertent soaking of a soft contact lens in a solution containing benzalkonium chloride (Dacriose(R)) resulted in corneal injury, epithelial damage, and decreased visual acuity which resolved within 3 weeks (Gasset, 1977).
3) CASE SERIES: Inadvertent use of a 0.01% solution of benzalkonium chloride intraocularly during cataract surgery caused pain, blurred vision, photophobia, glare, diurnal changes in visual acuity. Physical findings included corneal epithelial edema, stromal edema Descemet's membrane folds, and opacification of the posterior capsule. Best corrected visual acuity ranged from 6/9 to counting fingers (Eleftheriadis et al, 2002; Liu et al, 2001).
4) CASE REPORT: A 60-year-old man with a history of glaucoma presented with ocular irritation and severe bilateral conjunctival inflammation after beginning therapy with prescriptive eyedrops. Conjunctival biopsy demonstrated noncaseating granulomatous inflammation with the substantia propria. With stepwise discontinuation of each of his prescription eyedrops, his condition improved and finally resolved. It was hypothesized that the cause was a benzalkonium chloride-containing preservative found in all of his eyedrops (Kahana et al, 2007).

B) CETRIMONIUM BROMIDE: Severe eye injury has been described after exposure to a 15% solution (Dewey & Malone, 1968).
C) CETYLPYRIDINIUM CHLORIDE: Serious corneal injury may occur (Lin & Hemming, 1996; Grant, 1986; Green et al, 1985). Ophthalmic exposure to xerographic toners containing up to 2% CPC resulted in minor external ocular irritation only (Green et al, 1985).
D) ANIMAL STUDIES

1) SUMMARY: Eye exposure may result in effects ranging from mild discomfort to severe corneal damage, depending on the agent and the concentration. Cationic surfactants were more irritating than other surfactants when instilled into rabbit eyes (North-Root et al, 1982). The differences in irritant potential between various cationic detergents is probably related to their solubility (lipid versus water) and the degree of cationic character (Lin & Hemming, 1996).
2) BENZALKONIUM CHLORIDE: A drop or 2 of 10% solution can cause severe corneal damage, resulting in opacity and vascularization. Application of 10% solutions to monkey's eyes produced edema and corneal opacity that cleared by 18 days, with residual corneal hyperplasia (Grant, 1986).
3) CETYLPYRIDINIUM CHLORIDE: Animals exposed to 0.05 to 0.29 mg/L developed corneal epithelial hyalinization, and acute corneal and iris inflammation (Lin et al, 1991).
4) Significant irritation or injury have been observed in rabbit eyes following exposure to 0.1% to 1% solutions of the following compounds (Grant, 1986):

1) Benzethonium chloride
2) Decyltrimethyl ammonium bromide
3) Dodecyltrimethyl ammonium bromide
4) Hexadecyldimethyl ethyl ammonium bromide
5) Tetradecyltrimethyl ammonium bromide

3.4.5)

A) NASAL MUCOSAL INJURY: In a series of 9 infants who were inadvertently given quaternary ammonium nasally, all developed inflammation and edema of the nasal mucosa, erosive pharyngitis, and caustic esophageal injury (confirmed by endoscopy). All demonstrated hypersalivation, bradypnea, and gastrointestinal pain. Six developed cough, 5 developed vomiting, 1 developed bradycardia, and 1 developed keratitis. Six patients required endotracheal intubation for respiratory failure and 4 patients developed acute lung injury. One patient each developed sequelae of nasal membrane damage and pulmonary segmental atelectasias (Nisse et al, 2002).
B) CILIARY INJURY: Chronic use of benzalkonium chloride decreases ciliary movement and reduces mucociliary transport (Bernstein, 2000).
C) RHINITIS: Many nasal decongestant sprays contain benzalkonium chloride as a preservative. Repeated use of nasal decongestants for symptomatic relief of allergic rhinitis often results in rhinitis medicamentosa (RM). This condition involving "rebound swelling" and additional congestion may be partly due to benzalkonium chloride-induced nasal mucosal swelling (Graf, 1999; Graf et al, 1999).

1) Scadding (2000) presented data suggesting benzalkonium chloride (BKC) found in glucocorticoid nasal sprays (fluticasone) does not cause significant mucosal damage. Also, a study of glucocorticoid nasal spray (fluticasone) containing BKC versus placebo + BKC use in patients with chronic rhinosinusitis showed no difference in infective exacerbations. In fact, no patients in either group developed an infective exacerbation, and the author speculates these results would not be feasible if BKC was interfering with mucociliary clearance as Graf suggested (Scadding, 2000).

D) ANIMAL STUDIES

1) Cetylpyridinium chloride caused nasal irritation and discharge in exposed rats (Lin et al, 1991).

3.4.6)

A) SUMMARY: Depending on the agent and concentration, mild to severe caustic burns of the lips, tongue, mouth, and throat have been reported.
B) BURNS: Sporadic cases of burns of the tongue, mouth soreness, and a chalk-like taste were reported following use of a lozenge containing domiphen bromide (Anon, 1982).

1) CASE REPORT/PEDIATRIC: Caustic burns of the lips, mouth, and tongue occurred in 5 previously healthy newborn breastfed infants within minutes of being accidentally fed a dilute antiseptic solution of chlorhexidine 0.05% and cetrimide 1% (Mucklow, 1988).
2) PHARYNGEAL DESTRUCTION developed after ingestion of cetrimonium bromide (Mathieu-Nolf et al, 1985a).

Cardiovascular

3.5.1)

A) Hypotension and cardiac arrest have rarely been reported.

3.5.2)

A) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) Hypotension has been described following overdose (van Berkel & de Wolff, 1988; Tiess & Nagel, 1967).

B) CARDIAC ARREST

1) WITH POISONING/EXPOSURE

a) CETRIMONIUM BROMIDE: Cardiac arrest was associated with ingestion of 100 mg of cetrimonium bromide (Mathieu-Nolf et al, 1985a) and inadvertent IV administration of cetrimonium bromide in a 6-month-old infant (Gode et al, 1975).

Genotoxicity

A)

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) Most exposures do not require specific testing.
B) Obtain a CBC and monitor serum electrolytes and renal function in patients with concern for gastrointestinal (GI) burns.
C) Obtain a chest radiograph in patients with respiratory symptoms.
D) Obtain an upright chest radiograph if GI perforation is suspected, although a normal radiograph does not exclude perforation.
E) Endoscopy should be performed within 12 hours in patients in whom GI burns are a concern; deliberate ingestion of high concentration products can result in stridor, persistent vomiting, drooling, abdominal pain, or an inability to swallow.

4.1.2)

A) Obtain a CBC and monitor serum electrolytes and renal function in patients with concern for gastrointestinal (GI) burns.

4.1.4)

A) OTHER

1) ENDOSCOPY

a) Endoscopy should be performed within 12 hours in patients in whom GI burns are a concern; deliberate ingestion of high concentration products can result in stridor, persistent vomiting, drooling, abdominal pain, or an inability to swallow.

Radiographic Studies

A)

1) CETRIMONIUM BROMIDE: Household products containing cetrimonium bromide were found to be radiopaque in in vitro studies by Woolf et al (1993). This may be valuable to clinicians when dealing with large ingestions of unknown household cleaners or detergents (Woolf et al, 1993).

B)

1) Obtain a chest radiograph in patients with respiratory symptoms.
2) Obtain an upright chest radiograph if GI perforation is suspected, although a normal radiograph does not exclude perforation.

Treatment

Life Support

A)

Patient Disposition

6.3.1)

6.3.1.1) ADMISSION CRITERIA/ORAL

A) Severe respiratory tract injury, severe GI symptoms, corneal burns.

6.3.1.2) HOME CRITERIA/ORAL

A) Unintentional "taste" of dilute solutions in patients with no symptoms or only minor irritation can be observed in the home.

6.3.1.3) CONSULT CRITERIA/ORAL

A) If corrosive GI injury is suspected, consult a gastroenterologist for endoscopy. Consult an ophthalmologist for any patient with corneal burns. Consult a medical toxicologist or poison center for any patient with significant toxicity.

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients with deliberate ingestions, more than mild symptoms, and all acute ingestions of quaternary ammonium compounds should be evaluated and managed in a healthcare facility.

Monitoring

A)

B)

C)

D)

E)

Oral Exposure

6.5.1)

A) PREHOSPITAL: Emesis is not recommended because of possible corrosive effects. Dilute with small amounts of water or milk. Move patient from the toxic environment to fresh air. Administer oxygen. Monitor for respiratory distress.

6.5.2)

A) DILUTION

1) If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. The exact ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
2) USE OF DILUENTS IS CONTROVERSIAL: While experimental models have suggested that immediate dilution may lessen caustic injury (Homan et al, 1993; Homan et al, 1994; Homan et al, 1995), this has not been adequately studied in humans.
3) DILUENT TYPE: Use any readily available nontoxic, cool liquid. Both milk and water have been shown to be effective in experimental studies of caustic ingestion (Maull et al, 1985; Rumack & Burrington, 1977; Homan et al, 1995; Homan et al, 1994; Homan et al, 1993).
4) ADVERSE EFFECTS: Potential adverse effects include vomiting and airway compromise (Caravati, 2004).
5) CONTRAINDICATIONS: Do NOT attempt dilution in patients with respiratory distress, altered mental status, severe abdominal pain, nausea or vomiting, or patients who are unable to swallow or protect their airway. Diluents should not be force fed to any patient who refuses to swallow (Rao & Hoffman, 2002).

6.5.3)

A) MONITORING OF PATIENT

1) Most exposures do not require specific testing.
2) Obtain a CBC and monitor serum electrolytes and renal function in patients with concern for gastrointestinal (GI) burns.
3) Obtain a chest radiograph in patients with respiratory symptoms.
4) Obtain an upright chest radiograph if GI perforation is suspected, although a normal radiograph does not exclude perforation.
5) Endoscopy should be performed within 12 hours in patients in whom GI burns are a concern; deliberate ingestion of high concentration products can result in stridor, persistent vomiting, drooling, abdominal pain, or an inability to swallow.

B) BURN

1) ENDOSCOPY

a) SUMMARY: Obtain consultation concerning endoscopy as soon as possible, and perform endoscopy within the first 24 hours when indicated.
b) INDICATIONS: Endoscopy should be performed in adults with a history of deliberate ingestion, adults with any signs or symptoms attributable to inadvertent ingestion, and in children with stridor, vomiting, or drooling after unintentional ingestion (Crain et al, 1984). Endoscopy should also be performed in children with dysphagia or refusal to swallow, significant oral burns, or abdominal pain after unintentional ingestion (Gaudreault et al, 1983; Nuutinen et al, 1994). Children and adults who are asymptomatic after accidental ingestion do not require endoscopy (Gupta et al, 2001; Lamireau et al, 2001; Gorman et al, 1992).
c) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.

1) REFERENCES: (Dogan et al, 2006; Symbas et al, 1983; Crain et al, 1984a; Gaudreault et al, 1983a; Schild, 1985; Moazam et al, 1987; Sugawa & Lucas, 1989; Previtera et al, 1990; Zargar et al, 1991; Vergauwen et al, 1991; Gorman et al, 1992)

d) The risk of perforation during endoscopy is minimized by (Zargar et al, 1991):

1) Advancing across the cricopharynx under direct vision
2) Gently advancing with minimal air insufflation
3) Never retroverting or retroflexing the endoscope
4) Using a pediatric flexible endoscope
5) Using extreme caution in advancing beyond burn lesion areas
6) Most authors recommend endoscopy within the first 24 hours of injury, not advancing the endoscope beyond areas of severe esophageal burns, and avoiding endoscopy during the subacute phase of healing when tissue slough increases the risk of perforation (5 to 15 days after ingestion) (Zargar et al, 1991).

e) GRADING

1) Several scales for grading caustic injury exist. The likelihood of complications such as strictures, obstruction, bleeding, and perforation is related to the severity of the initial burn (Zargar et al, 1991):
2) Grade 0 - Normal examination
3) Grade 1 - Edema and hyperemia of the mucosa; strictures unlikely.
4) Grade 2A - Friability, hemorrhages, erosions, blisters, whitish membranes, exudates and superficial ulcerations; strictures unlikely.
5) Grade 2B - Grade 2A plus deep discreet or circumferential ulceration; strictures may develop.
6) Grade 3A - Multiple ulcerations and small scattered areas of necrosis; strictures are common, complications such as perforation, fistula formation or gastrointestinal bleeding may occur.
7) Grade 3B - Extensive necrosis through visceral wall; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding are more likely than with 3A.

f) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.
g) SCINTIGRAPHY - Scans utilizing radioisotope labelled sucralfate (technetium 99m) were performed in 22 patients with caustic ingestion and compared with endoscopy for the detection of esophageal burns. Two patients had minimal residual isotope activity on scanning but normal endoscopy and two patients had normal activity on scan but very mild erythema on endoscopy. Overall the radiolabeled sucralfate scan had a sensitivity of 100%, specificity of 81%, positive predictive value of 84% and negative predictive value of 100% for detecting clinically significant burns in this population (Millar et al, 2001). This may represent an alternative to endoscopy, particularly in young children, as no sedation is required for this procedure. Further study is required.
h) MINIPROBE ULTRASONOGRAPHY - was performed in 11 patients with corrosive ingestion . Findings were categorized as grade 0 (distinct muscular layers without thickening, grade I (distinct muscular layers with thickening), grade II (obscured muscular layers with indistinct margins) and grade III (muscular layers that could not be differentiated). Findings were further categorized as to whether the worst appearing image involved part of the circumference (type a) or the whole circumference (type b). Strictures did not develop in patients with grade 0 (5 patients) or grade I (4 patients) lesions. Transient stricture formation developed in the only patient with grade IIa lesions, and stricture requiring repeated dilatation developed in the only patient with grade IIIb lesions (Kamijo et al, 2004).

C) HYPOTENSIVE EPISODE

1) Hypotension and shock, usually from GI hemorrhage, should be initially treated with fluids and blood products.
2) SUMMARY

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

3) DOPAMINE

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

4) NOREPINEPHRINE

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).

D) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

Inhalation Exposure

6.7.1)

A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

6.7.2)

A) ACUTE LUNG INJURY

1) ONSET: Onset of acute lung injury after toxic exposure may be delayed up to 24 to 72 hours after exposure in some cases.
2) NON-PHARMACOLOGIC TREATMENT: The treatment of acute lung injury is primarily supportive (Cataletto, 2012). Maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases and/or pulse oximetry. If a high FIO2 is required to maintain adequate oxygenation, mechanical ventilation and positive-end-expiratory pressure (PEEP) may be required; ventilation with small tidal volumes (6 mL/kg) is preferred if ARDS develops (Haas, 2011; Stolbach & Hoffman, 2011).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

3) FLUIDS: Crystalloid solutions must be administered judiciously. Pulmonary artery monitoring may help. In general the pulmonary artery wedge pressure should be kept relatively low while still maintaining adequate cardiac output, blood pressure and urine output (Stolbach & Hoffman, 2011).
4) ANTIBIOTICS: Indicated only when there is evidence of infection (Artigas et al, 1998).
5) EXPERIMENTAL THERAPY: Partial liquid ventilation has shown promise in preliminary studies (Kollef & Schuster, 1995).
6) CALFACTANT: In a multicenter, randomized, blinded trial, endotracheal instillation of 2 doses of 80 mL/m(2) calfactant (35 mg/mL of phospholipid suspension in saline) in infants, children, and adolescents with acute lung injury resulted in acute improvement in oxygenation and lower mortality; however, no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was noted. Adverse effects (transient hypoxia and hypotension) were more frequent in calfactant patients, but these effects were mild and did not require withdrawal from the study (Wilson et al, 2005).
7) However, in a multicenter, randomized, controlled, and masked trial, endotracheal instillation of up to 3 doses of calfactant (30 mg) in adults only with acute lung injury/ARDS due to direct lung injury was not associated with improved oxygenation and longer term benefits compared to the placebo group. It was also associated with significant increases in hypoxia and hypotension (Willson et al, 2015).

B) CONTACT DERMATITIS

1) Allergic contact dermatitis can occur with airborne exposure (Corazza & Virgili, 1993).

C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

6.8.1)

A) Exposed eyes should be irrigated with copious amounts of water for at least 30 minutes. An examination should be performed in patients with persistent pain or visual changes and in those exposed to high concentration solutions. Ophthalmologic consultation should be obtained in patients with corneal burns. Following an alkali ocular burn, free alkali appears to be regenerated via slow dissociation of cation from combination with corneal proteins in sufficient amount to keep the pH above normal during 15 or 20 minutes of irrigation. Thus, it is paramount to continue irrigation for at least 30 minutes (Grant & Schuman, 1993).

6.8.2)

A) CORNEAL BURN

1) EVALUATION

a) ASSESSMENT CAUSTIC EYE BURNS: It may take 48 to 72 hours after the burn to assess correctly the degree of ocular damage (Brodovsky et al, 2000).
b) The 1965 Roper-Hall classification uses the size of the corneal epithelial defect, the degree of corneal opacification and extent of limbal ischemia to evaluate the extent of the chemical ocular injury (Brodovsky et al, 2000; Singh et al, 2013):

1) GRADE 1 (prognosis good): Corneal epithelial damage; no limbal ischemia.
2) GRADE 2 (prognosis good): Cornea hazy; iris details visible, ischemia less than one-third of limbus.
3) GRADE 3 (prognosis guarded): Total loss of corneal epithelium; stromal haze obscures iris details; ischemia of one-third to one-half of limbus.
4) GRADE 4 (prognosis poor): Cornea opaque; iris and pupil obscured, ischemia affects more than one-half of limbus.

c) A newer classification (Dua) is based on clock hour limbal involvement as well as a percentage of bulbar conjunctival involvement (Singh et al, 2013):

1) GRADE 1 (prognosis very good): 0 clock hour of limbal involvement and 0% conjunctival involvement.
2) GRADE 2 (prognosis good): Less than 3 clock hour of limbal involvement and less than 30% conjunctival involvement.
3) GRADE 3 (prognosis good): Greater than 3 and up to 6 clock hour of limbal involvement and greater than 30% to 50% conjunctival involvement.
4) GRADE 4 (prognosis good to guarded): Greater than 6 and up to 9 clock hour of limbal involvement and greater than 50% to 75% conjunctival involvement.
5) GRADE 5 (prognosis guarded to poor): Greater than 9 and less than 12 clock hour of limbal involvement and greater than 75% and less than 100% conjunctival involvement.
6) GRADE 6 (very poor): Total limbus (12 clock hour) involved and 100% conjunctival involvement.

2) IRRIGATION

a) Begin irrigation immediately with copious amounts of water or sterile 0.9% saline, which ever is more rapidly available. Lactated Ringer's solution may also be effective. Once irrigation has begun, instill a drop of local anesthetic (eg, 0.5% proparacaine) for comfort; switching from water to slightly warmed sterile saline may also improve patient comfort (Singh et al, 2013; Spector & Fernandez, 2008; Ernst et al, 1998; Grant & Schuman, 1993a). In one study, isotonic saline, lactated Ringer's solution, normal saline with bicarbonate, and balanced saline plus (BSS Plus) were compared and no difference in normalization of pH were found; however, BSS Plus was better tolerated and more comfortable (Fish & Davidson, 2010).

1) Continue irrigation for at least an hour or until the superior and inferior cul-de-sacs have returned to neutrality (check pH every 30 minutes), pH of 7.0 to 8.0, and remain so for 30 minutes after irrigation is discontinued (Spector & Fernandez, 2008; Brodovsky et al, 2000a). After severe alkaline burns, the pH of the conjunctival sac may only return to a pH of 8 or 8.5 even after extensive irrigation (Grant & Schuman, 1993a). Irrigating volumes up to 20 L or more have been used to neutralize the pH (Singh et al, 2013; Fish & Davidson, 2010). Immediate and prolonged irrigation is associated with improved visual acuity, shorter hospital stay and fewer surgical interventions (Kuckelkorn et al, 1995; Saari et al, 1984).
2) Search the conjunctival sac for solid particles and remove them while continuing irrigation (Grant & Schuman, 1993a).
3) For significant alkaline or concentrated acid burns with evidence of eye injury irrigation should be continued for at least 2 to 3 hours, potentially as long as 24 to 48 hours if pH not normalized, in an attempt to normalize the pH of the anterior chamber (Smilkstein & Fraunfelder, 2002). Emergent ophthalmologic consultation is needed in these cases (Spector & Fernandez, 2008).

3) MINOR INJURY

a) SUMMARY

1) If ocular damage is minor, artificial tears/lubricants, topical cycloplegics, and antibiotics may be all that are needed.

b) ARTIFICIAL TEARS

1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

c) TOPICAL CYCLOPLEGIC

1) Use to guard against development of posterior synechiae and ciliary spasm (Brodovsky et al, 2000b; Grant & Schuman, 1993a). Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

d) TOPICAL ANTIBIOTICS

1) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993a). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008).

e) PAIN CONTROL

1) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993a). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).

4) SEVERE INJURY

a) SUMMARY

1) If the damage is minor, the above may be all that is needed. For grade 3 or 4 injuries, one or more of the following may be used, only with ophthalmologic consultation: acetazolamide, topical timolol, topical steroids, citrate, ascorbate, EDTA, cysteine, NAC, penicillamine, tetracycline, or soft contact lenses.

b) ARTIFICIAL TEARS

1) To promote re-epithelization, preservative-free artificial tears/lubricants (eg, hyaluronic acid hourly) may be used (Fish & Davidson, 2010; Tuft & Shortt, 2009).

c) PAIN CONTROL

1) If pain control is required, oral or parenteral NSAIDs or narcotics are preferred to topical ocular anesthetics, which may cause local corneal epithelial damage if used repeatedly (Spector & Fernandez, 2008; Grant & Schuman, 1993a). However, topical 0.5% proparacaine has been recommended (Spector & Fernandez, 2008).

d) CARBONIC ANHYDRASE INHIBITOR

1) Acetazolamide (250 mg orally 4 times daily) may be given to control increased intraocular pressure (Singh et al, 2013; Tuft & Shortt, 2009; Spector & Fernandez, 2008).

e) TOPICAL STEROIDS

1) DOSE: Dexamethasone 0.1% ointment 4 times daily to reduce inflammation. If persistent epithelial defect is present, discontinue dexamethasone by day 14 to reduce the risk of stromal melt (Tuft & Shortt, 2009). Other sources suggest that corticosteroids should be stopped if the epithelium has not covered surface defects by 5 to 7 days (Grant & Schuman, 1993b).
2) Topical prednisolone 0.5% has also been used. A further increase in corneoscleral melt may occur if topical steroids are used alone. In one study, topical prednisolone 0.5% was used in combination with topical ascorbate 10%; no increase in corneoscleral melt was observed when topical steroids were used until re-epithelization (Singh et al, 2013; Fish & Davidson, 2010).
3) In one retrospective study, fluorometholone 1% drops were administered every 2 hours initially, then decreased to four times daily when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete (Brodovsky et al, 2000a).

a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000a).

f) ASCORBATE

1) Oral or topical ascorbate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
2) DOSE: Ascorbate 10% 4 times daily topically or 1 g orally (2 g/day) (Singh et al, 2013; Tuft & Shortt, 2009).
3) Ascorbate is needed for the formation of collagen and the concentration of ascorbate in the anterior chamber is decreased when the ciliary body is damaged by alkali burns (Tuft & Shortt, 2009; Grant & Schuman, 1993b). In one retrospective study, ascorbate drops (10%) were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received 500 mg of oral ascorbate 4 times daily, until discharge from the hospital (Brodovsky et al, 2000a).

a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000a).

g) CITRATE

1) Topical citrate may be used to promote epithelial healing and reduce the risk of stromal necrosis (Fish & Davidson, 2010).
2) DOSE: Potassium citrate 10% 4 times daily topically (Tuft & Shortt, 2009).
3) Citrate chelates calcium, and thereby interferes with the harmful effects of neutrophil accumulation, such as release of proteolytic enzymes and superoxide free radicals, phagocytosis and ulceration (Grant & Schuman, 1993b). In one retrospective study, 10% citrate drops were administered every 2 hours, then decreased to 4 times a day when there was evidence of progressive corneal reepithelialization and lessened inflammation, and discontinued when corneal reepithelialization was complete. These patients also received a urinary alkalinizer containing 720 mg of citric acid anhydrous and 630 mg of sodium citrate anhydrous 3 times daily, until discharge from the hospital (Brodovsky et al, 2000a).

a) STUDY: The combination of intensive topical corticosteroids, topical citrate and ascorbate, and oral citrate and ascorbate was associated with improved best corrected visual acuity and a trend towards more rapid corneal reepithelialization in Grade 3 alkali burns in one retrospective study (Brodovsky et al, 2000a).

h) COLLAGENASE INHIBITORS

1) Inhibitors of collagenase can inhibit collagenolytic activity, prevent stromal ulceration, and promote wound healing. Several effective agents, such as cysteine, n-acetylcysteine, sodium ethylenediamine tetra acetic acid (EDTA), calcium EDTA, penicillamine, and citrate, have been recommended (Singh et al, 2013; Tuft & Shortt, 2009; Perry et al, 1993; Seedor et al, 1987).
2) TETRACYCLINE: Has been found to have an anticollagenolytic effect. Systemic tetracycline 50 mg/kg/day reduced the incidence of alkali-induced corneal ulcerations in rabbits (Seedor et al, 1987).
3) DOXYCYCLINE: Decreased epithelial defects and collagenase activity in a rabbit model of alkali burns to the eye (Perry et al, 1993). DOSE: 100 mg twice daily (Tuft & Shortt, 2009).

i) ANTIBIOTICS

1) An antibiotic ophthalmic ointment or drops should be used for as long as epithelial defects persist (Brodovsky et al, 2000b; Grant & Schuman, 1993a). Topical erythromycin or tetracycline ointment may be used (Spector & Fernandez, 2008). In patients with severe burns, a topical fluoroquinolone antibiotic drop 4 times daily may also be used (Tuft & Shortt, 2009). A topical fourth generation fluoroquinolone has been recommended as an antimicrobial prophylaxis in patients with large epithelial defect (Fish & Davidson, 2010).

j) TOPICAL CYCLOPLEGIC

1) Cyclopentolate 0.5% or 1% eye drops may be administered 4 times daily to control pain (Tuft & Shortt, 2009; Spector & Fernandez, 2008).

k) SOFT CONTACT LENSES

1) A bandage contact lens (eg, silicone hydrogel) may make the patient more comfortable and protect the surface (Fish & Davidson, 2010; Tuft & Shortt, 2009). Hydrophilic high oxygen permeability lenses are preferred (Singh et al, 2013). Soft lenses with intermediate water content and inherent rigidity may facilitate reepithelialization. The use of 0.5 normal sodium chloride drops hourly and artificial tears or lubricant eyedrops instilled 4 times a day may help maintain adequate hydration and lens mobility.

5) SURGICAL THERAPY

a) SURGICAL THERAPY CAUSTIC EYE INJURY

1) Early insertion of methylmethacrylate ring or suturing saran wrap over palpebral and cul-de-sac conjunctiva may prevent fibrinosis adhesions and reduce fibrotic contracture of conjunctiva, but the advantage of such treatments is not clear.
2) Limbal stem cell transplantation has been used successfully in both the acute stage of injury and the chronically scarred healing phase in patients with persistent epithelial defects after chemical burns (Azuara-Blanco et al, 1999; Morgan & Murray, 1996; Ronk et al, 1994).
3) In some patients, amniotic membrane transplantation (AMT) has been successful in improving corneal healing and visual acuity in patients with persistent epithelial defects after chemical burns. It can restore the conjunctival surface and decrease limbal stromal inflammation (Fish & Davidson, 2010; Sridhar et al, 2000; Su & Lin, 2000; Meller et al, 2000; Azuara-Blanco et al, 1999).
4) Control glaucoma. Remove any cataracts formed (Fish & Davidson, 2010; Tuft & Shortt, 2009).
5) In patients with severe injury, tenonplasty can be performed to promote epithelialization and prevent melting (Tuft & Shortt, 2009).
6) A keratoprosthesis placement has also been indicated in severe cases (Fish & Davidson, 2010). Penetrating keratoplasty is usually delayed as long as possible as results appear to be better with a greater lag time between injury and keratoplasty (Grant & Schuman, 1993a).

B) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

6.9.1)

A) Remove contaminated clothing and jewelry and irrigate exposed areas with copious amounts of water. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

6.9.2)

A) IRRITATION SYMPTOM

1) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

B) BURN

1) APPLICATION

a) These recommendations apply to patients with MINOR chemical burns (FIRST DEGREE; SECOND DEGREE: less than 15% body surface area in adults; less than 10% body surface area in children; THIRD DEGREE: less than 2% body surface area). Consultation with a clinician experienced in burn therapy or a burn unit should be obtained if larger area or more severe burns are present. Neutralizing agents should NOT be used.

2) DEBRIDEMENT

a) After initial flushing with large volumes of water to remove any residual chemical material, clean wounds with a mild disinfectant soap and water.
b) DEVITALIZED SKIN: Loose, nonviable tissue should be removed by gentle cleansing with surgical soap or formal skin debridement (Moylan, 1980; Haynes, 1981). Intravenous analgesia may be required (Roberts, 1988).
c) BLISTERS: Removal and debridement of closed blisters is controversial. Current consensus is that intact blisters prevent pain and dehydration, promote healing, and allow motion; therefore, blisters should be left intact until they rupture spontaneously or healing is well underway, unless they are extremely large or inhibit motion (Roberts, 1988; Carvajal & Stewart, 1987).

3) TREATMENT

a) TOPICAL ANTIBIOTICS: Prophylactic topical antibiotic therapy with silver sulfadiazine is recommended for all burns except superficial partial thickness (first-degree) burns (Roberts, 1988). For first-degree burns bacitracin may be used, but effectiveness is not documented (Roberts, 1988).
b) SYSTEMIC ANTIBIOTICS: Systemic antibiotics are generally not indicated unless infection is present or the burn involves the hands, feet, or perineum.
c) WOUND DRESSING:

1) Depending on the site and area, the burn may be treated open (face, ears, or perineum) or covered with sterile nonstick porous gauze. The gauze dressing should be fluffy and thick enough to absorb all drainage.
2) Alternatively, a petrolatum fine-mesh gauze dressing may be used alone on partial-thickness burns.

d) DRESSING CHANGES:

1) Daily dressing changes are indicated if a burn cream is used; changes every 3 to 4 days are adequate with a dry dressing.
2) If dressing changes are to be done at home, the patient or caregiver should be instructed in proper techniques and given sufficient dressings and other necessary supplies.

e) Analgesics such as acetaminophen with codeine may be used for pain relief if needed.

4) TETANUS PROPHYLAXIS

a) The patient's tetanus immunization status should be determined. Tetanus toxoid 0.5 milliliter intramuscularly or other indicated tetanus prophylaxis should be administered if required.

C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Enhanced Elimination

A)

1) There is no role for these procedures as systemic absorption is not the cause of toxicity.

Abstracts

Case Reports

A)

1) A 70-year-old woman who ingested 40 mL of a 33.3% (200 mg/kg) aqueous benzalkonium chloride solution was admitted 7 hours postingestion with confusion, stupor, dehydration, profuse diarrhea, and bullae covering the palate.

a) Esophagoscopy revealed gastric, hypopharynx, and esophageal mucosal lesions. Hypotension and metabolic acidosis were described 10 hours postingestion.
b) The patient regained full consciousness in a week. Mucosal lesions had healed except for small granulated and erosive areas in the esophagus by 18 days (van Berkel & de Wolff, 1988).

Range Of Toxicity

Summary

A)

Minimum Lethal Exposure

A)

B)

1) QUATERNIUM 28 AND 29

a) Unintentional ingestion of about 1 ounce of a 10% solution of Hyamine 2389, which had been diluted to a 7.5% solution in a mixed alcoholic beverage resulted in death in a 45-year-old woman within 25 minutes of ingestion. The total amount of methyldodecylbenzyl trimethyl ammonium chloride ingested was approximately 2.25 grams. At autopsy, pulmonary edema was found but gastrointestinal corrosion was absent (Adelson & Sunshine, 1952).

2) BENZALKONIUM CHLORIDE

a) SUMMARY: Benzalkonium-chloride (a quaternary ammonium compound) can produce rapid toxic effects (ie, caustic burns and respiratory depression) following minimal ingestions; doses of about 100 mg/kg are thought to be potentially life-threatening (Hahn et al, 2000).
b) Ingestion of a 15% to 17.4% preparations in amounts of 100 to 400 mg/kg of benzalkonium chloride produced death in 4 cases. Severe gastrointestinal and esophageal necrosis were present on autopsy, with pulmonary and cerebral edema (Tiess & Nagel, 1967).

1) Two elderly patients with dementia ingested 15% to 20% benzalkonium chloride disinfectant products and both developed severe necroses and caustic burns of the gastrointestinal tract. Four days after exposure, one of the patients died from massive aspiration and respiratory insufficiency after ingesting 25 mL of a disinfectant containing 20% benzalkonium chloride (Hahn et al, 2000).

c) Parenteral administration of 5 to 15 mg/kg of a 10% solution has resulted in death in 5 cases (Tiess & Nagel, 1967).
d) Rectal administration of 700 mg/kg of a 15% solution caused death in one case (Tiess & Nagel, 1967).

3) DIDECYLDIMETHYLAMMONIUM CHLORIDE

a) An elderly patient with dementia ingested an unknown amount of disinfectant containing 2% didecyldimethylammonium chloride, and developed rapid symptoms of aspiration pneumonia, and died from respiratory failure within 3 days of exposure (Hahn et al, 2000).

4) CETYLPYRIDINUM CHLORIDE

a) INHALATION

1) ANIMALS: The LC50 in rats is 0.09 mg/liter (Lin et al, 1991).

Maximum Tolerated Exposure

A)

1) Esophageal burns are possible with ingestion of just a few mL of concentrated solution.
2) Corrosive effects have been seen with ingestion of 10% or more concentrated solutions (Tiess & Nagel, 1967; van Berkel & de Wolff, 1988).

B)

1) CETYLPYRIDINIUM CHLORIDE

a) The minimum concentration that produced skin irritation to abraded rabbit skin was 0.4%. The minimum amount to produce conjunctival irritation was 0.03%. A 1% solution instilled into the bladder produced marked inflammation and edema (Warren et al, 1942).

2) CETRIMONIUM BROMIDE

a) A shampoo containing 12% cetrimonium bromide produced a burn with blister and bullae formation following a spill on the chest of a 20-month-old boy (Inman, 1982).
b) A 27-year-old man ingested 500 mL of Cetavlon(R) (100 mg of Cetrimonium Bromide) which resulted in upper airway destruction, coma, and cardiac arrest. He was successfully resuscitated and discharged 14 days after the exposure (Mathieu-Nolf et al, 1985).

3) FABRIC SOFTENERS

a) Generally contain cationic detergents with two long chain alkyl groups and are considered much less toxic than those with a single such group.

4) BENZALKONIUM CHLORIDE

a) Ingestion of 40 mL of 33.3% solution (200 mg/kg) resulted in esophageal and gastric burns and CNS depression (van Berkel & de Wolff, 1988).
b) Skin exposure to concentrations of 0.5% or greater produced severe pustular and bullous lesions (Wahlberg et al, 1985).

Toxicity Information

7.7.1)

A) LD50- (ORAL)RAT:

1) 400 mg/kg
2) 445 mg/kg

B) LD50- (ORAL)RAT:

1) 420 mg/kg

C) LD50- (INTRAPERITONEAL)RAT:

1) 6 mg/kg

D) LD50- (ORAL)RAT:

1) 200 mg/kg

E) LD50- (SUBCUTANEOUS)RAT:

1) 250 mg/kg

F) LD50- (ORAL)MOUSE:

1) 725 mg/kg

G) LD50- (ORAL)RAT:

1) 91 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

A)

B)

C)

Physicochemical

Animal Toxicology

Clinical Effects

11.1.3)

A) Clinical signs include oral or pharyngeal hyperemia, oral ulceration, ptyalism (salivation), emesis, muscle weakness and fasciculations, eyelid ptosis, CNS and respiratory depression, seizures, and hematemesis (Coulson et al, 1961; (Grier, 1967).
B) DIFFERENTIAL DIAGNOSIS - Signs can mimic those of organophosphorus compound poisoning.
C) DERMAL EXPOSURE - Chemical burns were reported following use of an undiluted 17 percent solution of benzalkonium chloride as an electrical conductant during normal EKG monitoring in cats and dogs (Bilbrey et al, 1989).

11.1.6)

A) Dermal exposure, especially of feet, can result in marked erythema, inflammation, contact dermatitis, and systemic signs (Trapani et al, 1982).
B) Chemical burns were reported following use of an undiluted 17 percent solution of benzalkonium chloride as an electrical conductant during normal EKG monitoring in cats and dogs (Bilbrey et al, 1989).

Treatment

11.2.1)

A) GENERAL TREATMENT

1) SUMMARY

a) Begin treatment immediately.
b) Keep animal warm and do not handle unnecessarily.
c) Remove the patient and other animals from the source of contamination or remove dietary sources.

2) Treatment should always be done on the advice and with the consultation of a veterinarian.
3) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
4) ASPCA ANIMAL POISON CONTROL CENTER

a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.

5) SMALL ANIMALS: Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only.
6) In the case of a poisoning involving large animals, consult a veterinary poison control center.

11.2.2)

A) GENERAL

1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.

11.2.4)

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) ORAL EXPOSURE -

1) Emesis is only indicated when the detergent ingested is NOT CAUSTIC and when the time since ingestion is one hour or less. If in doubt about the caustic nature of the detergent preparation ingested (dependent on the concentration), DO NOT induce emesis. Corrosive effects have been seen with 10 percent or greater concentrated products (Tiess & Nagel, 1967; van Berkel & de Wolff, 1988).
2) The danger of attempting gastric lavage following ingestion of a caustic solution likewise probably outweighs its benefit.
3) These products are well adsorbed to activated charcoal, and rapid administration of charcoal is the primary decontamination technique recommended.

b) DILUTION -

1) Give a slurry of powdered milk (50 to 100 milliliters), gelatin, milk, or egg white per os.

c) EMESIS AND LAVAGE -

1) CAUTION: Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
2) HORSES OR CATTLE: DO NOT attempt to induce emesis in ruminants (cattle) or equids (horses).
3) DOGS AND CATS

a) IPECAC: If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
b) APOMORPHINE: Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.

1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.

4) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.

a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.

d) ACTIVATED CHARCOAL/CATHARTIC -

1) ACTIVATED CHARCOAL: Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
2) CATHARTIC: Administer a dose of a saline or sorbitol cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.

e) OCULAR DECONTAMINATION -

1) Rinse eyes with copious amounts of tepid water for 15 minutes. If irritation, pain, or photophobia persist, see your veterinarian.

f) INHALATION DECONTAMINATION -

1) Move patient to fresh air. Monitor patient for respiratory distress. Emergency airway support and supplemental oxygen with assisted ventilation may be needed. If a cough or difficulty in breathing develops, evaluate for respiratory tract irritation or bronchitis.

g) DERMAL DECONTAMINATION -

1) Wash exposed animals with soap and water. If possible, shave or clip long hair to facilitate thorough cleaning. All handlers should wear gloves and protect themselves from exposure.
2) Some chemicals can produce systemic toxicosis via absorption through the intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs and treat as necessary.

11.2.5)

A) GENERAL TREATMENT

1) VITAL FUNCTIONS -

a) Treat symptomatically; no antidote or specific treatment exists (Coppock et al, 1988).
b) A patient that has been decontaminated should be admitted for at least 24 hours.

2) SUPPORT RESPIRATORY FUNCTION -

a) Monitor patient for respiratory depression and provide supportive care.

3) SEIZURES -

a) SEIZURES/LARGE ANIMALS: May be controlled with diazepam.

1) HORSES/DIAZEPAM: Neonates: 0.05 to 0.4 milligrams/kilogram; Adults: 25 to 50 milligrams. Give slowly intravenously to effect; repeat in 30 minutes if necessary.
2) CATTLE, SHEEP AND SWINE/DIAZEPAM: 0.5 to 1.5 milligrams/kilogram intravenously to effect.

b) SEIZURES/DOGS & CATS:

1) DIAZEPAM: 0.5 to 2 milligrams/kilogram intravenous bolus; may repeat dose every ten minutes for four total doses. Give slowly over 1 to 2 minutes to effect.
2) PHENOBARBITAL: 5 to 30 milligrams/kilogram over 5 to 10 minutes intravenously to effect.
3) REFRACTORY SEIZURES: Consider anaesthesia or heavy sedation. Administer pentobarbital to DOGS & CATS at a dose of 3 to 15 milligrams/kilogram intravenously slowly to effect. May need to repeat in 4 to 8 hours. Be sure to protect the airway.

4) GASTROINTESTINAL TRACT IRRITATION -

a) Observe patients with ingestion carefully for esophageal or laryngeal burns; if burns are present, consider esophagoscopy to determine their extent.
b) SUCRALFATE: For relief of gastric irritation or ulceration, administer sucralfate as follows: DOGS: (body weight less than 20 kilograms) 500 milligrams three to four times daily; (weight greater than 20 kilograms) one gram three to four times daily.

1) Give sucralfate one hour before feeding and wait two hours prior to cimetidine dosing.

c) CIMETIDINE:

1) DOGS: 5 to 10 milligrams/kilogram per os, intravenously, or intramuscularly every 6 to 8 hours
2) CATS: 2.5 to 5 milligrams/kilogram per os, intravenously, or intramuscularly every 8 to 12 hours

5) FOLLOW-UP -

a) Instruct the owner to return for a follow up appointment at which physical examination and appropriate laboratory tests will be repeated.

Continuing Care

11.4.1)

11.4.1.2) DECONTAMINATION/TREATMENT

A) GENERAL TREATMENT

1) SUMMARY

a) Begin treatment immediately.
b) Keep animal warm and do not handle unnecessarily.
c) Remove the patient and other animals from the source of contamination or remove dietary sources.

2) Treatment should always be done on the advice and with the consultation of a veterinarian.
3) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
4) ASPCA ANIMAL POISON CONTROL CENTER

a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.

5) SMALL ANIMALS: Due to lack of reports of large animal intoxication with this substance, the following sections address small animals (dogs and cats) only.
6) In the case of a poisoning involving large animals, consult a veterinary poison control center.

11.4.2)

11.4.2.2) GASTRIC DECONTAMINATION

A) GASTRIC DECONTAMINATION

1) GENERAL TREATMENT

a) ORAL EXPOSURE -

1) Emesis is only indicated when the detergent ingested is NOT CAUSTIC and when the time since ingestion is one hour or less. If in doubt about the caustic nature of the detergent preparation ingested (dependent on the concentration), DO NOT induce emesis. Corrosive effects have been seen with 10 percent or greater concentrated products (Tiess & Nagel, 1967; van Berkel & de Wolff, 1988).
2) The danger of attempting gastric lavage following ingestion of a caustic solution likewise probably outweighs its benefit.
3) These products are well adsorbed to activated charcoal, and rapid administration of charcoal is the primary decontamination technique recommended.

b) DILUTION -

1) Give a slurry of powdered milk (50 to 100 milliliters), gelatin, milk, or egg white per os.

c) EMESIS AND LAVAGE -

1) CAUTION: Carefully examine patients with chemical exposure before inducing emesis. If signs of oral, pharyngeal, or esophageal irritation, a depressed gag reflex, or central nervous system excitation or depression are present, EMESIS SHOULD NOT BE INDUCED.
2) HORSES OR CATTLE: DO NOT attempt to induce emesis in ruminants (cattle) or equids (horses).
3) DOGS AND CATS

a) IPECAC: If within 2 hours of exposure: induce emesis with 1 to 2 milliliters/kilogram syrup of ipecac per os.
b) APOMORPHINE: Dogs may vomit more readily with 1 tablet (6 milligrams) apomorphine diluted in 3 to 5 milliliters water and instilled into the conjunctival sac or per os.

1) Dogs may also be given apomorphine intravenously at 40 micrograms/kilogram, although this route may not be as effective.

4) LAVAGE: In the absence of a gag reflex or if vomiting cannot be induced, place a cuffed endotracheal tube and begin gastric lavage.

a) Pass large bore stomach tube and instill 5 to 10 milliliters/kilogram water or lavage solution, then aspirate. Repeat 10 times.

d) ACTIVATED CHARCOAL/CATHARTIC -

1) ACTIVATED CHARCOAL: Administer activated charcoal. Dose: 2 grams/kilogram per os or via stomach tube. Avoid aspiration by proper restraint, careful technique, and if necessary tracheal intubation.
2) CATHARTIC: Administer a dose of a saline or sorbitol cathartic such as magnesium or sodium sulfate (sodium sulfate dose is 1 gram/kilogram). If access to these agents is limited, give 5 to 15 milliliters magnesium oxide (Milk of Magnesia) per os for dilution.

e) OCULAR DECONTAMINATION -

1) Rinse eyes with copious amounts of tepid water for 15 minutes. If irritation, pain, or photophobia persist, see your veterinarian.

f) INHALATION DECONTAMINATION -

1) Move patient to fresh air. Monitor patient for respiratory distress. Emergency airway support and supplemental oxygen with assisted ventilation may be needed. If a cough or difficulty in breathing develops, evaluate for respiratory tract irritation or bronchitis.

g) DERMAL DECONTAMINATION -

1) Wash exposed animals with soap and water. If possible, shave or clip long hair to facilitate thorough cleaning. All handlers should wear gloves and protect themselves from exposure.
2) Some chemicals can produce systemic toxicosis via absorption through the intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs and treat as necessary.

References

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FeedBack

DETERGENTS-CATIONIC

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Dermatologic

Immunologic

Reproductive

Summary Of Exposure

Heent

Cardiovascular

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Case Reports

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Toxicity Information

Toxicologic Mechanism

Clinical Effects

Treatment

Continuing Care

General Bibliography