CHLOROACETIC ACID

Classification | Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

Specific Substances

1) Acide chloroacetique (French)
2) Acide monochloroacetique (French)
3) Acidomonochloroacetico (Italian)
4) Acetic acid, chloro-
5) alpha-Chloroacetic acid
6) Chloracetic acid
7) Chloroacetic acid
8) Chloroacetic acid, liquid
9) Chloroacetic acid, solid
10) Chloroacetic acid, solution
11) Chloroethanoic acid
12) Kyselina chlorotova
13) MCA
14) MKHUK
15) Monochloorazijnzuur (Dutch)
16) Monochloracetic acid
17) Monochloressigsaeure (German)
18) Monochloroacetic acid
19) Monochloroethanoic acid
20) NCI-c 60231
21) STCC 4931416
22) NIOSH/RTECS AF 8575000
23) Molecular Formula: C2-H3-Cl-O2
24) CAS 79-11-8
25) ACETIC ACID, CHLORO- (SOLID)
26) ACIDE CHLORACETIQUE (FRENCH) (SOLID)
27) ACIDE MONOCHLORACETIQUE (FRENCH) (SOLID)
28) ACIDOMONOCHLOROACETICO (ITALIAN) (SOLID)
29) CHLORACETIC ACID (SOLID)
30) CHLOROETHANOIC ACID (SOLID)
31) MCA (SOLID)
32) MONOCHLOORAZIJNZUUR (DUTCH) (SOLID)
33) MONOCHLORACETIC ACID (SOLID)
34) MONOCHLORESSIGSAEURE (GERMAN) (SOLID)
35) MONOCHLOROACETIC ACID (SOLID)
36) MONOCHLOROACETIC ACID SOLUTION (SOLID)
37) MONOCHLOROETHANOIC ACID (SOLID)

1.2.1) MOLECULAR FORMULA
1) C2-H3-Cl-O2
2) ClCH2COOH

Available Forms Sources

1) Chloroacetic acid is produced by chlorination of glacial acetic acid. This takes place in the presence of sulfur, phosphorus, iodine, or acetic anhydride (Lewis, 1993; Budavari, 1996). It may also be produced by trichloroethylene hydrolysis with 90 percent sulfuric acid (Budavari, 1996).

1) Chloroacetic acid is a halogen acid used in the manufacture of dyes and other organic chemicals. It also is used as an herbicide, bacteriostatic substance, and as a preservative (Budavari, 1996; Lewis, 1993).
2) Chloroacetic acid is used as a chemical intermediate in the production of carboxymethylcellulose, ethyl chloroacetate, glycine, synthetic caffeine, sarcosine, thioglycolic acid, EDTA, the herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and 2,4,5-T (2,4,5-trichlorophenoxyacetic acid), and vitamins (ITI, 1988; Lewis, 1993; OHM/TADS , 1996).
3) It is used as a preemergence herbicide and defoliant (Gosselin et al, 1984; EPA, 1985), and also as a treatment for plantar warts in patients.
4) In addition, chloroacetic acid is used as a disinfectant and as a drying agent for curing hay (EPA, 1985).

Overview

Life Support

Clinical Effects

0.2.1)

A) Systemic effects of poisoning may occur following inhalation, dermal, or oral exposure. Exposure to chloroacetic acid vapors may cause eye or mucous membrane irritation.
B) Chloroacetic acid is an irritant and may cause severe burns of exposed eyes, skin, and mucous membranes. Ingestion may cause gastrointestinal irritation, burns, perforation, and subsequent peritonitis. CNS and respiratory depression, hypotension, dysrhythmias, seizures, liver damage, renal failure and pulmonary edema may develop after severe ingestions or exposures.
C) When heated to decomposition, chloroacetic acid emits chlorine gas which may cause respiratory or systemic toxicity.

0.2.4)

A) Conjunctivitis, corneal burns, and nose and throat irritation may occur from direct exposure or chloroacetic acid vapors.

0.2.6)

A) Respiratory tract irritation and centrally-mediated respiratory depression, may occur, and in severe cases, pulmonary edema may be seen.

0.2.7)

A) CNS depression and seizures may occur.

0.2.8)

A) Esophageal and gastrointestinal tract irritation, ulcerations or burns, and in severe cases perforation may develop.

0.2.10)

A) Acute tubular necrosis has been described after severe dermal burns.

0.2.14)

A) Dermal irritation or burns may occur with direct skin contact.

0.2.20)

A) At the time of this review, no reproductive studies were found for chloroacetic acid in humans.
B) In one study, chloroacetic acid was determined to be over 8 times more toxic to embryonic development than it was to adult animals. It was concluded that chloroacetic acid is a high priority item for developmental toxicity tests in pregnant mammals to confirm or refute its apparent unique developmental hazard potential.
C) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
D) No information about possible male reproductive effects was available at the time of this review.

0.2.21)

A) At the time of this review, no studies were found on the potential for carcinogenicity of chloroacetic acid in humans.

Laboratory Monitoring

Treatment Overview

0.4.2)

A) DO NOT INDUCE VOMITING or give bicarbonate to neutralize. Because of the risk of lethal systemic poisoning even after relatively small ingestions of concentrated product, activated charcoal should be administered soon after ingestion. Gastric aspiration may be of benefit soon after ingestion, but carries the risk of complications of perforation or bleeding.
B) MUCOSAL DECONTAMINATION: 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. Patients should not be forced to drink after ingestion of an acid, nor should they be allowed to drink larger volumes since this may induce vomiting, and thereby re-exposure of the injured tissues to the corrosive acid. Dilution may only be helpful if performed in the first seconds to minutes after ingestion.
C) GASTRIC DECONTAMINATION: Ipecac contraindicated. Activated charcoal is not recommended as it may interfere with endoscopy and will not reduce injury to GI mucosa. Consider insertion of a small, flexible nasogastric or orogastric tube to suction gastric contents after recent large ingestion of a strong acid; the risk of further mucosal injury or iatrogenic esophageal perforation must be weighed against potential benefits of removing any remaining acid from the stomach.
D) ENDOSCOPY: Because acid ingestion may cause severe gastric burns with relatively few initial signs and symptoms, endoscopic evaluation is recommended within 24 hours in any patient with a definite history of ingesting a strong acid, even if asymptomatic. If burns are found, follow 10 to 20 days later with a barium swallow.
E) Sucralfate may be useful in relieving symptomatology from acid-induced injury.
F) Observe for symptoms of acute obstruction (pyloric outlet obstruction), at which time parenteral fluids and/or hyperalimentation should be considered. Classically, this occurs at 3 weeks after ingestion.
G) Obtain a follow-up esophagogram and upper GI series about 2 to 4 weeks following ingestion. In severe cases of gastrointestinal necrosis or perforation, surgical consultation should be obtained.
H) PHARMACOLOGIC TREATMENT: The role of corticosteroids is controversial. Consider use in grade 2 burns to the GI tract no more than 48 hours postingestion in patients without active upper gastrointestinal bleeding or evidence of gastroesophageal rupture. Antibiotics are indicated for definite infection or patients with gastroesophageal perforation.
I) If CNS and respiratory depression occur, ensure adequacy of respirations and oxygenation. Endotracheal intubation, supplemental oxygenation, and assisted ventilation may be required.
J) VENTRICULAR DYSRHYTHMIAS/SUMMARY: Institute continuous cardiac monitoring, obtain an ECG, and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders. Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
K) HYPOTENSION: Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine (5 to 20 mcg/kg/min) or norepinephrine (ADULT: begin infusion at 0.5 to 1 mcg/min; CHILD: begin infusion at 0.1 mcg/kg/min); titrate to desired response.
L) SEIZURES: Administer a benzodiazepine; DIAZEPAM (ADULT: 5 to 10 mg IV initially; repeat every 5 to 20 minutes as needed. CHILD: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed) or LORAZEPAM (ADULT: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist. CHILD: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue).

1) Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children greater than 5 years).
2) Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, and hypoxia.

M) RHABDOMYOLYSIS: Administer sufficient 0.9% saline (10 to 15 mL/kg/hour) to maintain urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hr). Monitor input and output, serum electrolytes, CK, and renal function. Diuretics may be necessary to maintain urine output, but should only be considered if urine output is inadequate after volume status is restored. Urinary alkalinization is NOT routinely recommended.
N) Dextrose infusion was effective in preventing hypoglycemia, reducing lactate levels and increasing survival in an animal model of monochloroacetic acid poisoning.

0.4.3)

A) Move victims of inhalation exposure away from the toxic environment and administer 100 percent humidified supplemental oxygen with assisted ventilation if required.
B) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
C) ACUTE LUNG INJURY: Maintain ventilation and oxygenation and evaluate with frequent arterial blood gases and/or pulse oximetry monitoring. Early use of PEEP and mechanical ventilation may be needed.

0.4.4)

A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.

0.4.5)

A) OVERVIEW

1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
2) Treat dermal irritation or burns with standard topical therapy. Patients developing dermal hypersensitivity reactions may require treatment with systemic or topical corticosteroids or antihistamines.

Range Of Toxicity

Clinical Effects

Summary Of Exposure

Heent

3.4.1)

A) Conjunctivitis, corneal burns, and nose and throat irritation may occur from direct exposure or chloroacetic acid vapors.

3.4.3)

A) CONJUNCTIVITIS - Eye irritation may occur following vapor or direct exposure (Grant, 1986).
B) BURNS - Corneal burns may occur if material is splashed directly into the eyes (ITI, 1985).

3.4.5)

A) IRRITATION - Irritation of the mucous membranes of the nose may occur (Sittig, 1985; EPA, 1985).

3.4.6)

A) IRRITATION - Irritation of the mucous membranes of the throat may occur (Sittig, 1985; EPA, 1985).

Cardiovascular

3.5.2)

A) HYPOTENSIVE EPISODE

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Severe hypotension (blood pressure 60 systolic) developed in a 38 year old man 2 hours after sustaining 25 to 30% body surface area burns from splash contact with 80% monochloroacetic acid (Kulling et al, 1992).

B) VENTRICULAR ARRHYTHMIA

1) WITH POISONING/EXPOSURE

a) CASE REPORT - Refractory ventricular tachycardia developed in a 5 year old girl 1.5 hours after ingesting 5 to 6 ml of 80% monochloroacetic acid (Feldhaus et al, 1993; Rogers, 1995).

C) CARDIAC ARREST

1) WITH POISONING/EXPOSURE

a) Nonresponsive cardiac arrest was reported in a 3-year-old child inadvertently exposed to an 80% solution of monochloroacetic acid, which produced second-degree burns on 15% of his total body surface area. The patient died within 12 hours of exposure (Pirson et al, 2003).

3.5.3)

A) ANIMAL STUDIES

1) CARDIOMYOPATHY

a) Dose related cardiomyopathy was reported in F344 rats which were administered monochloroacetic acid by gavage in doses of 0 up to 150 mg/kg daily for 5 days per week for up to 13 weeks. The same effects were not noted in mice. The cause of death in the rats which died during the study was cardiomyopathy (Bryant et al, 1992).

Respiratory

3.6.1)

A) Respiratory tract irritation and centrally-mediated respiratory depression, may occur, and in severe cases, pulmonary edema may be seen.

3.6.2)

A) DISORDER OF RESPIRATORY SYSTEM

1) Respiratory tract irritation may occur, and can progress to pulmonary edema in serious cases (Pirson et al, 2003; Sittig, 1985; EPA, 1985).

B) ACUTE RESPIRATORY INSUFFICIENCY

1) Respiratory depression may occur with severe exposures (Sittig, 1985; Gosselin et al, 1984; EPA, 1985).

C) HEMOPTYSIS

1) Hemoptysis has been reported after inhalation (Kulling et al, 1992).

D) ACUTE LUNG INJURY

1) CASE REPORT - Pulmonary edema was described in a 5-year-old girl who developed refractory ventricular tachycardia 1.5 hours after ingesting 5 to 6 ml of 80% monochloroacetic acid (Feldhaus et al, 1993).

Neurologic

3.7.1)

A) CNS depression and seizures may occur.

3.7.2)

A) CENTRAL NERVOUS SYSTEM DEFICIT

1) CNS depression which may include lethargy and loss of consciousness have been reported after dermal exposure and inhalation (Pirson et al, 2003; Kulling et al, 1992; Sittig, 1985; Gosselin et al, 1984; EPA, 1985) .

B) SEIZURE

1) Generalized seizures have been reported after inhalation and dermal exposure (Gosselin et al, 1984; Kulling et al, 1992).

C) CEREBRAL EDEMA

1) Cerebral edema (Feldhaus et al, 1993) with evidence of herniation (Kulling et al, 1992) has been described in rare cases.
2) CASE REPORT - Cerebral and pulmonary edema were evident on postmortem examination in a 3-year-old male inadvertently exposed to an 80% solution of monochloroacetic acid on his face, neck and chest. Along with second-degree burns on 15% of his total body surface area, inhalation of the vapors was thought to have occurred during exposure (Pirson et al, 2003).

3.7.3)

A) ANIMAL STUDIES

1) NEUROPATHY

a) Studies in mice have found that monochloroacetic acid damages the blood-brain barrier when given at single LD50 and LD80 doses. 10 percent of survivors of these doses also exhibited severe front paw rigidity (Berardi et al, 1987).

Gastrointestinal

3.8.1)

A) Esophageal and gastrointestinal tract irritation, ulcerations or burns, and in severe cases perforation may develop.

3.8.2)

A) GASTRITIS

1) Esophageal or gastrointestinal tract irritation and burns have been reported with oral exposures (EPA, 1985; Feldhaus et al, 1993; Rogers, 1995).

B) PERFORATION OF INTESTINE

1) Severe irritation or burns may result in gastrointestinal bleeding or perforation (EPA, 1985).

C) COLITIS

1) WITH POISONING/EXPOSURE

a) CASE REPORT - A 55-year-old man presented with a 3-day history of vomiting, hematochezia, and oligo-anuria following intentional ingestion of 50 to 75 mL of monochloroacetic acid. A colonoscopy revealed severe hemorrhagic colitis and a biopsy indicated mucosal erosions of the sigmoid and descending colon with submucosal hemorrhage. The patient also developed an acute myocardial infarction as well as features of hemolytic-uremic syndrome characterized by acute renal failure, anemia, and thrombocytopenia. Despite supportive treatment, the patient developed cardiorespiratory arrest and died 5 days post-admission (approximately 8 days post-ingestion) (Nayak et al, 2007).

Hepatic

3.9.2)

A) LIVER ENZYMES ABNORMAL

1) Elevated ALT (654 U/L) and AST (2538 U/L) have been reported after severe dermal burns (Kulling et al, 1992). This patient also developed severe rhabdomyolysis.

B) STEATOSIS OF LIVER

1) Fatty liver was described at autopsy in a 5-year-old girl who developed refractory ventricular tachycardia 1.5 hours after ingesting 5 to 6 ml of 80% monochloroacetic acid (Feldhaus et al, 1993; Rogers, 1995).

3.9.3)

A) ANIMAL STUDIES

1) HEPATIC ENZYMES INCREASED

a) Dose related increases in ALT and AST, as well as increased liver weights, were reported in rats administered monochloroacetic acid by gavage for 13 weeks in doses of 0 up to 150 mg/kg/day. These same effects were not observed in mice (Bryant et al, 1992).

Genitourinary

3.10.1)

A) Acute tubular necrosis has been described after severe dermal burns.

3.10.2)

A) ACUTE RENAL FAILURE SYNDROME

1) WITH POISONING/EXPOSURE

a) Acute renal failure was reported in a 55-year-old man who developed hemolysis after he ingested 50 to 75 mL of monochloroacetic acid. On day 1 of hospital admission (approximately 3 days post-ingestion), the patient's blood urea nitrogen and serum creatinine levels were 310 mg/dL and 9.2 mg/dL, respectively. The patient also developed metabolic acidosis, anemia, thrombocytopenia, hemorrhagic colitis, and myocardial infarction. Despite supportive therapy, including hemodialysis and transfusions of fresh frozen plasma, whole blood, and platelets, the patient developed cardiorespiratory arrest and died 5 days post-admission (approximately 8 days post-ingestion) (Nayak et al, 2007).

2) Acute tubular necrosis has been described after severe dermal burns (Gosselin et al, 1984; Kulling et al, 1992).

3.10.3)

A) ANIMAL STUDIES

1) BUN INCREASED

a) A dose related increase in serum blood urea nitrogen (BUN), as well as increased kidney weights, was noted in F344 rats which were given 0 up to 150 mg/kg/day of monochloroacetic acid by gavage for 5 days/week for up to 13 weeks. These same effects were not noted in mice (Bryant et al, 1992).

Acid-Base

3.11.2)

A) ACIDOSIS

1) WITH POISONING/EXPOSURE

a) Metabolic acidosis has been reported in patients with hypotension, renal failure and seizures (Kulling et al, 1992). Refractory metabolic acidosis was reported following a fatal ingestion of a teaspoonful of wart remover (containing monochloroacetic acid) in a 5-year-old girl (Rogers, 1995). Similar clinical findings were reported in a 3-year-old male inadvertently exposed to an 80% solution of chloroacetic acid, which produced second-degree burns on 15% of his total body surface area. Despite repeated bicarbonate administration, the patient died 12 hours after exposure from a cardiac arrest (Pirson et al, 2003).
b) CASE REPORT - Metabolic acidosis (pH 7.43, PCO2 22 mmHg, PO2 151 mmHg, HCO3 14.5 mEq/L) was reported in a 55-year-old man who intentionally ingested 50 to 75 mL of monochloroacetic acid. The patient also developed hemolytic-uremic syndrome, as evidenced by acute renal failure, anemia, and thrombocytopenia, and an acute myocardial infarction. Despite supportive therapy, the patient died from cardiorespiratory arrest 5 days post-admission (approximately 8 days post-ingestion) (Nayak et al, 2007).

Hematologic

3.13.2)

A) HEMOLYSIS

1) WITH POISONING/EXPOSURE

a) Hemolytic anemia (hemoglobin 6.3 g/dL), thrombocytopenia (35,000/mm), and acute renal failure were reported in a 55-year-old man who intentionally ingested 50 to 75 mL of monochloroacetic acid (Nayak et al, 2007).

Dermatologic

3.14.1)

A) Dermal irritation or burns may occur with direct skin contact.

3.14.2)

A) CHEMICAL BURN

1) Dermal irritation, blisters, or burns may occur with direct skin contact (ITI, 1985; (Sittig, 1985; EPA, 1985; Dancer et al, 1965). Death may occur if more than 3% of the skin is exposed (HSDB , 1991).
2) CASE REPORT - A 3-year-old child was inadvertently exposed to an 80% solution of monochloroacetic acid on his face, neck and chest, which produced second-degree burns on 15% of his total body surface area. Initial symptoms included lethargy, vomiting and loss of consciousness, and laboratory evidence of metabolic acidosis. Despite supportive care, the patient developed shock and died within 12 hours of exposure (Pirson et al, 2003).

Musculoskeletal

3.15.2)

A) RHABDOMYOLYSIS

1) CASE REPORT - Severe rhabdomyolysis, with a peak CPK of 111,120 U/L, developed in a 38 year old man who sustained 25 to 30% body surface area burns from 80% monochloroacetic acid (Kulling et al, 1992).

Reproductive

3.20.1)

3.20.2)

A) ANIMAL STUDIES

1) EMBRYOTOXICITY

a) In one study, chloroacetic acid was determined to be over 8 times more toxic to embryonic development than it was to adult animals (Fu et al, 1990).

1) It was concluded that chloroacetic acid is a high priority item for developmental toxicity tests in pregnant mammals to confirm or refute its apparent unique developmental hazard potential (Fu et al, 1990).

b) Chloroacetic acid given orally to pregnant Long-Evans rats at doses of 0, 17, 35, 70, or 140 mg/kg/day did not affect resorptions or live fetal weight, but it was related to a higher incidence of cardiovascular malformations at the highest dose at which maternal toxicity was manifested (Smith et al, 1990).

3.20.3)

A) LACK OF INFORMATION

1) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.

Carcinogenicity

3.21.1)

A) IARC Carcinogenicity Ratings for CAS79-11-8 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):

1) Not Listed

3.21.2)

A) At the time of this review, no studies were found on the potential for carcinogenicity of chloroacetic acid in humans.

3.21.3)

A) LACK OF INFORMATION

1) At the time of this review, no studies were found on the potential for carcinogenicity of chloroacetic acid in humans.

3.21.4)

A) CARCINOMA

1) Chloroacetic acid was found to be an equivocal tumorigenic agent by RTECS (Registry of Toxic Effects of Chemical Substances) criteria in the mouse with lungs, thorax or respiratory tumors, liver tumors and tumors at the site of application (RTECS , 1991).
2) Orally administered chloroacetic acid was nontumorigenic in mice (HSDB , 1991).

Genotoxicity

Laboratory Monitoring

Monitoring Parameters Levels

4.1.1)

A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
B) If respiratory tract irritation or respiratory depression is evident, monitor arterial blood gases, chest x-ray, and pulmonary function tests.

4.1.2)

A) BLOOD/SERUM CHEMISTRY

1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count and liver and kidney function tests is suggested for patients with significant exposure.

4.1.3)

A) URINALYSIS

1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.

4.1.4)

A) OTHER

1) MONITORING

a) If respiratory tract irritation is present, monitor arterial blood gases and chest x-ray.

2) PULMONARY FUNCTION TESTS

a) If respiratory tract irritation is present, it may be useful to monitor pulmonary function tests.

Radiographic Studies

1) If respiratory tract irritation is present, monitor chest x-ray.

Methods

1) A GC/MS (gas chromatography/mass spectrometry) method has been used for quantitative determination of monochloroacetic acid in blood samples (Rogers, 1995). Routine testing for serum levels of this chemical is not widely available however, and is unlikely to affect management.

Treatment

Life Support

Patient Disposition

6.3.1)

6.3.1.5) OBSERVATION CRITERIA/ORAL

A) Patients symptomatic following exposure should be observed in a controlled setting until all signs and symptoms have fully resolved.

Monitoring

Oral Exposure

6.5.1)

A) GENERAL

1) In ingestion exposures, do not induce emesis because of the danger of causing further caustic injury to the esophagus. Immediate dilution with milk or water may be beneficial. Because of the potential for lethal systemic toxicity even after small ingestions, activated charcoal should be administered.

B) DILUTION

1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The 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).

6.5.2)

A) EMESIS

1) DO NOT INDUCE EMESIS due to the risk of inducing further caustic injury to the GI tract.

B) GASTRIC LAVAGE

1) The possible benefit of early removal of some ingested material by cautious gastric lavage must be weighed against potential complications of perforation or bleeding if significant esophageal or gastrointestinal irritation or burns are present. Simple nasogastric tube suction may be a less invasive method of limiting absorption of toxic liquid substances.

C) INDICATIONS: Consider insertion of a small, flexible nasogastric tube to aspirate gastric contents after large, recent ingestion of caustics. The risk of worsening mucosal injury (including perforation) must be weighed against the potential benefit.
D) PRECAUTIONS:

1) SEIZURE CONTROL: Is mandatory prior to gastric emptying.
2) AIRWAY PROTECTION: Alert patients - place in Trendelenburg and left lateral decubitus position, with suction available. Obtunded or unconscious patients - cuffed endotracheal intubation. COMPLICATIONS:

a) Complications of gastric aspiration may include: aspiration pneumonia, hypoxia, hypercapnia, mechanical injury to the throat, esophagus, or stomach (Vale, 1997). Combative patients may be at greater risk for complications.

E) DILUTION

6.5.3)

A) CONTRAINDICATED TREATMENT

1) DO NOT INDUCE VOMITING due to the risk of causing further caustic injury. Do not give bicarbonate to neutralize, as the addition of a buffer to a strong acid may cause an exothermic reaction and a subsequent rise in temperature which may further injure the GI tract (Maull et al, 1985).

B) IRRIGATION

1) Irrigate the mouth with copious amounts of water or saline. Immediate dilution with small amounts of milk or water may help decontaminate the oral mucosa or dislodge particles of granular acids from the esophageal mucosa.
2) The amount of diluent recommended by the POISINDEX editorial board for caustic alkali ingestion varied, and may be useful in establishing guidelines for acid ingestion. Suggestions ranged from 2 to 12 ounces in adults and 1 to 8 ounces in children. The majority recommended a maximum amount of 8 ounces in adults and 4 ounces in children (Consensus, 1988).
3) Dilution of acid with water has been shown to be ineffective in altering the pH. The dilution of 50 milliliters of 9.5 percent HCl with 800 milliliters of water resulted in a pH change of 0.99 to 1.73 (Maull et al, 1985).

C) ENDOSCOPIC PROCEDURE

1) The following recommendations are extrapolated from experience with ingestions of acids and/or alkaline corrosives.
2) SUMMARY: Obtain consultation concerning endoscopy as soon as possible and perform endoscopy within the first 24 hours when indicated.
3) INDICATIONS: Most studies associating the presence or absence of gastrointestinal burns with signs and symptoms after caustic ingestion have involved primarily alkaline ingestions. Because acid ingestion may cause severe gastric injury with fewer associated initial signs and symptoms, endoscopic evaluation is recommended in any patient with a definite history of ingestion of a strong acid, even if asymptomatic.
4) RISKS: Numerous large case series attest to the relative safety and utility of early endoscopy in the management of caustic ingestion.

a) REFERENCES: Gaudreault et al, 1983; Symbas et al, 1983; Crain et al, 1984; (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; Nuutinen et al, 1994)

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

a) Advancing across the cricopharynx under direct vision
b) Gently advancing with minimal air insufflation
c) Never retroverting or retroflexing the endoscope
d) Using a pediatric flexible endoscope
e) Using extreme caution in advancing beyond burn lesion areas
f) 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).

6) GRADING

a) 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):
b) Grade 0 - Normal examination
c) Grade 1 - Edema and hyperemia of the mucosa; strictures unlikely.
d) Grade 2A - Friability, hemorrhages, erosions, blisters, whitish membranes, exudates and superficial ulcerations; strictures unlikely.
e) Grade 2B - Grade 2A plus deep discreet or circumferential ulceration; strictures may develop.
f) Grade 3A - Multiple ulcerations and small scattered areas of necrosis; strictures are common, complications such as perforation, fistula formation, or gastrointestinal bleeding may occur.
g) 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.

7) FOLLOW UP - If burns are found, follow 10 to 20 days later with barium swallow or esophagram.

D) CORTICOSTEROID

1) The use of steroids for the prevention of strictures after caustic ingestion is controversial. The following recommendations are extrapolated from experience with ingestions of acids and/or alkaline corrosives.
2) CORROSIVE INGESTION/SUMMARY: The use of corticosteroids for the treatment of caustic ingestion is controversial. Most animal studies have involved alkali-induced injury (Haller & Bachman, 1964; Saedi et al, 1973). Most human studies have been retrospective and generally involve more alkali than acid-induced injury and small numbers of patients with documented second or third degree mucosal injury.
3) FIRST DEGREE BURNS: These burns generally heal well and rarely result in stricture formation (Zargar et al, 1989; Howell et al, 1992). Corticosteroids are generally not beneficial in these patients (Howell et al, 1992).
4) SECOND DEGREE BURNS: Some authors recommend corticosteroid treatment to prevent stricture formation in patients with a second degree, deep-partial thickness burn (Howell et al, 1992). However, no well controlled human study has documented efficacy. Corticosteroids are generally not beneficial in patients with a second degree, superficial-partial thickness burn (Caravati, 2004; Howell et al, 1992).
5) THIRD DEGREE BURNS: Some authors have recommended steroids in this group as well (Howell et al, 1992). A high percentage of patients with third degree burns go on to develop strictures with or without corticosteroid therapy and the risk of infection and perforation may be increased by corticosteroid use. Most authors feel that the risk outweighs any potential benefit and routine use is not recommended (Boukthir et al, 2004; Oakes et al, 1982; Pelclova & Navratil, 2005).
6) CONTRAINDICATIONS: Include active gastrointestinal bleeding and evidence of gastric or esophageal perforation. Corticosteroids are thought to be ineffective if initiated more than 48 hours after a burn (Howell, 1987).
7) DOSE: Administer daily oral doses of 0.1 milligram/kilogram of dexamethasone or 1 to 2 milligrams/kilogram of prednisone. Continue therapy for a total of 3 weeks and then taper (Haller et al, 1971; Marshall, 1979). An alternative regimen in children is intravenous prednisolone 2 milligrams/kilogram/day followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks then tapered (Anderson et al, 1990).
8) ANTIBIOTICS: Animal studies suggest that the addition of antibiotics can prevent the infectious complications associated with corticosteroid use in the setting of caustic burns. Antibiotics are recommended if corticosteroids are used or if perforation or infection is suspected. Agents that cover anaerobes and oral flora such as penicillin, ampicillin, or clindamycin are appropriate (Rosenberg et al, 1953).
9) STUDIES

a) ANIMAL

1) Some animal studies have suggested that corticosteroid therapy may reduce the incidence of stricture formation after severe alkaline corrosive injury (Haller & Bachman, 1964; Saedi et al, 1973a).
2) Animals treated with steroids and antibiotics appear to do better than animals treated with steroids alone (Haller & Bachman, 1964).
3) Other studies have shown no evidence of reduced stricture formation in steroid treated animals (Reyes et al, 1974). An increased rate of esophageal perforation related to steroid treatment has been found in animal studies (Knox et al, 1967).

b) HUMAN

1) Most human studies have been retrospective and/or uncontrolled and generally involve small numbers of patients with documented second or third degree mucosal injury. No study has proven a reduced incidence of stricture formation from steroid use in human caustic ingestions (Haller et al, 1971; Hawkins et al, 1980; Yarington & Heatly, 1963; Adam & Brick, 1982).
2) META ANALYSIS

a) Howell et al (1992), analyzed reports concerning 361 patients with corrosive esophageal injury published in the English language literature since 1956 (10 retrospective and 3 prospective studies). No patients with first degree burns developed strictures. Of 228 patients with second or third degree burns treated with corticosteroids and antibiotics, 54 (24%) developed strictures. Of 25 patients with similar burn severity treated without steroids or antibiotics, 13 (52%) developed strictures (Howell et al, 1992).
b) Another meta-analysis of 10 studies found that in patients with second degree esophageal burns from caustics, the overall rate of stricture formation was 14.8% in patients who received corticosteroids compared with 36% in patients who did not receive corticosteroids (LoVecchio et al, 1996).
c) Another study combined results of 10 papers evaluating therapy for corrosive esophageal injury in humans published between January 1991 and June 2004. There were a total of 572 patients, all patients received corticosteroids in 6 studies, in 2 studies no patients received steroids, and in 2 studies, treatment with and without corticosteroids was compared. Of 109 patients with grade 2 esophageal burns who were treated with corticosteroids, 15 (13.8%) developed strictures, compared with 2 of 32 (6.3%) patients with second degree burns who did not receive steroids (Pelclova & Navratil, 2005).

3) Smaller studies have questioned the value of steroids (Ferguson et al, 1989; Anderson et al, 1990), thus they should be used with caution.
4) Ferguson et al (1989) retrospectively compared 10 patients who did not receive antibiotics or steroids with 31 patients who received both antibiotics and steroids in a study of caustic ingestion and found no difference in the incidence of esophageal stricture between the two groups (Ferguson et al, 1989).
5) A randomized, controlled, prospective clinical trial involving 60 children with lye or acid induced esophageal injury did not find an effect of corticosteroids on the incidence of stricture formation (Anderson et al, 1990).

a) These 60 children were among 131 patients who were managed and followed-up for ingestion of caustic material from 1971 through 1988; 88% of them were between 1 and 3 years old (Anderson et al, 1990).
b) All patients underwent rigid esophagoscopy after being randomized to receive either no steroids or a course consisting initially of intravenous prednisolone (2 milligrams/kilogram per day) followed by 2.5 milligrams/kilogram/day of oral prednisone for a total of 3 weeks prior to tapering and discontinuation (Anderson et al, 1990).
c) Six (19%), 15 (48%), and 10 (32%) of those in the treatment group had first, second and third degree esophageal burns, respectively. In contrast, 13 (45%), 5 (17%), and 11 (38%) of the control group had the same levels of injury (Anderson et al, 1990).
d) Ten (32%) of those receiving steroids and 11 (38%) of the control group developed strictures. Four (13%) of those receiving steroids and 7 (24%) of the control group required esophageal replacement. All but 1 of the 21 children who developed strictures had severe circumferential burns on initial esophagoscopy (Anderson et al, 1990).
e) Because of the small numbers of patients in this study, it lacked the power to reliably detect meaningful differences in outcome between the treatment groups (Anderson et al, 1990).

6) ADVERSE EFFECTS

a) The use of corticosteroids in the treatment of caustic ingestion in humans has been associated with gastric perforation (Cleveland et al, 1963) and fatal pulmonary embolism (Aceto et al, 1970).

E) SUCRALFATE

1) Administration of sucralfate, 1 gram dissolved in 30 milliliters of water, four times a day, was used in a 25-year-old man with moderately severe gastric injury after ingestion of hydrochloric acid. No other therapy was given other than antibiotics. Within 48 hours, improvement in symptoms was noted, enabling progression to a liquid diet on the 3rd day.

a) Similar to studies where sucralfate was used in alkali caustic injury, strictures were not prevented, although nearly complete gastric mucosal healing occurred after 2 weeks. The patient received a gastrojejunostomy for pyloric stricture 6 weeks postingestion (Mittal et al, 1989).

2) Sucralfate may be useful in relieving symptomatology from acid-induced injury. Efficacy in accelerating healing or preventing complications has not been proven.

F) INSERTION OF NASOGASTRIC TUBE

1) Penner (1980) argues that following a large ingestion of strong acids, a nasogastric tube should be passed and suction performed in an attempt to remove as much acid as possible prior to cold water dilution which may result in an exothermic reaction (giving off heat) and worsen the burn.
2) Many authorities oppose this procedure fearing esophageal or gastric perforation. Soft nasogastric or orogastric tube should only be passed within 90 minutes following the large ingestion of a strong acid.

G) DIETARY FINDING

1) Depends on degree of damage as assessed by early endoscopy (Dilawari et al, 1984).

1) mild (grade I): may have oral feedings first day
2) moderate (grade II): may have liquids after 48 to 72 hours
3) severe (grade III): jejunostomy tube feedings after 48 to 72 hours

H) BURN

1) If severe burns occur in the mouth then esophageal burns may exist. It is reportedly unusual for acid ingestion to result in esophageal burns. Most burns occur in the pyloric end of the stomach.
2) However, Muhletaler et al (1980) reviewed 39 esophagograms from 27 patients with a proven history of swallowing muriatic acid (27 percent HCl). All esophagograms obtained 11 to 16 days postingestion showed areas of narrowing, submucosal edema, atony, and mucosal ulceration.

a) Twenty-one esophagograms obtained at least 21 days following ingestion showed stricture formation. Edema and esophageal mucosal ulcerations radiologically appeared as blurring or contour irregularities along the esophageal margins.

3) Dilawari (1984) recommends early endoscopy in order to grade severity of injury (mild, moderate, severe) and predict prognosis. All patients with severe burns developed complications such as perforation, stricture, or massive hematemesis. Endoscopy did not contribute to complications. No complications developed in the mild to moderate injury patients.
4) In a prospective study of 41 patients who ingested 50 to 200 milliliters of 20 to 35 percent acid solutions, all were assessed for location, extent, and severity of injury within 36 hours of ingestion by endoscopy or surgery, or at autopsy. Esophageal injury was present in 87.8 percent of the patients, gastric injury in 85.4 percent, and duodenal injury in 34.1 percent.

a) Strictures, perforation, or both developed only in patients with Grade 2b (superficial localized ulceration, friability, blisters, and circumferential ulceration) and Grade 3 (multiple and deep ulcerations and areas of extensive necrosis) burns (Zargar et al, 1989). No complications relating to the endoscopic procedure were reported in this series.

I) OBSTRUCTION

1) Observe patient for symptoms of acute obstruction (pyloric outlet obstruction), at which time parenteral fluids and/or hyperalimentation should be considered. Classically, this occurs at 3 weeks after ingestion.

a) One 3-year-old child developed esophageal stricture 2 years after the acid ingestion in a prospective study of 41 patients. This child had a normal barium study at one year after ingestion (Zargar et al, 1989).

J) FOLLOW-UP VISIT

1) A follow-up esophagram and upper GI series to evaluate for the presence or absence of secondary scarring and/or stricture formation should be obtained about 2 to 4 weeks following ingestion as well as consultation with a gastroenterologist.

K) SURGICAL PROCEDURE

1) In severe cases of gastrointestinal necrosis or perforation, emergent surgical consultation should be obtained. The need for gastric resection or laparotomy in the stable patient is controversial (Chodak & Passaro, 1978; Dilawari et al, 1984a).
2) LAPAROTOMY/LAPAROSCOPY - Early laparotomy or laparoscopy should be considered in patients with endoscopic evidence of severe esophageal or gastric burns after acid ingestion to evaluate for the presence of transmural gastric or esophageal necrosis (Estrera et al, 1986; Meredith et al, 1988; Wu & Lai, 1993). Emergent laparotomy should be strongly considered in any patient with hypotension, altered mental status, or acidemia (Hovarth et al, 1991).

a) STUDY - In a retrospective study of patients with extensive transmural gastroesophageal necrosis after caustic ingestion, all 4 patients treated in the conventional manner (endoscopy, steroids, antibiotics, and repeated evaluation for the occurrence of esophagogastric necrosis and perforation) died, while all 3 patients treated with early laparotomy and immediate esophagogastric resection survived (Estrera et al, 1986).
b) Wu & Lai (1993) reported the results of emergency surgical resection of the alimentary tract in 28 patients who had extensive corrosive injuries due to the ingestion of acids or other caustics. Operative mortality was most frequently associated with sepsis. Non-fatal bleeding, infections, biliary or bronchial fistulas were other noted complications. Morbidity and mortality were related to the severity of the damage and the extent of surgery required.

1) Immediate postoperative management included antibiotics, extensive respiratory care, tracheobronchial toilet, maintenance of fluid, electrolyte and acid-base balance, and jejunostomy feeding or total parenteral nutrition.

L) AIRWAY MANAGEMENT

1) If CNS and respiratory depression occur, ensure adequacy of respirations and oxygenation. Endotracheal intubation, supplemental oxygenation, and assisted ventilation could be required.

M) CONDUCTION DISORDER OF THE HEART

1) VENTRICULAR DYSRHYTHMIAS SUMMARY

a) Obtain an ECG, institute continuous cardiac monitoring and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders (particularly hypokalemia, hypocalcemia, and hypomagnesemia). Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.

2) LIDOCAINE

a) LIDOCAINE/INDICATIONS

1) Ventricular tachycardia or ventricular fibrillation (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010; Vanden Hoek et al, 2010).

b) LIDOCAINE/DOSE

1) ADULT: 1 to 1.5 milligrams/kilogram via intravenous push. For refractory VT/VF an additional bolus of 0.5 to 0.75 milligram/kilogram can be given at 5 to 10 minute intervals to a maximum dose of 3 milligrams/kilogram (Neumar et al, 2010). Only bolus therapy is recommended during cardiac arrest.

a) Once circulation has been restored begin a maintenance infusion of 1 to 4 milligrams per minute. If dysrhythmias recur during infusion repeat 0.5 milligram/kilogram bolus and increase the infusion rate incrementally (maximal infusion rate is 4 milligrams/minute) (Neumar et al, 2010).

2) CHILD: 1 milligram/kilogram initial bolus IV/IO; followed by a continuous infusion of 20 to 50 micrograms/kilogram/minute (de Caen et al, 2015).

c) LIDOCAINE/MAJOR ADVERSE REACTIONS

1) Paresthesias; muscle twitching; confusion; slurred speech; seizures; respiratory depression or arrest; bradycardia; coma. May cause significant AV block or worsen pre-existing block. Prophylactic pacemaker may be required in the face of bifascicular, second degree, or third degree heart block (Prod Info Lidocaine HCl intravenous injection solution, 2006; Neumar et al, 2010).

d) LIDOCAINE/MONITORING PARAMETERS

1) Monitor ECG continuously; plasma concentrations as indicated (Prod Info Lidocaine HCl intravenous injection solution, 2006).

3) AMIODARONE

a) AMIODARONE/INDICATIONS

1) Effective for the control of hemodynamically stable monomorphic ventricular tachycardia. Also recommended for pulseless ventricular tachycardia or ventricular fibrillation in cardiac arrest unresponsive to CPR, defibrillation and vasopressor therapy (Link et al, 2015; Neumar et al, 2010). It should be used with caution when the ingestion involves agents known to cause QTc prolongation, such as fluoroquinolones, macrolide antibiotics or azoles, and when ECG reveals QT prolongation suspected to be secondary to overdose (Prod Info Cordarone(R) oral tablets, 2015).

b) AMIODARONE/ADULT DOSE

1) For ventricular fibrillation or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy give an initial dose of 300 mg IV followed by 1 dose of 150 mg IV. For stable ventricular tachycardias: Infuse 150 milligrams over 10 minutes, and repeat if necessary. Follow by a 1 milligram/minute infusion for 6 hours, then a 0.5 milligram/minute. Maximum total dose over 24 hours is 2.2 grams (Neumar et al, 2010).

c) AMIODARONE/PEDIATRIC DOSE

1) Infuse 5 milligrams/kilogram as a bolus for pulseless ventricular tachycardia or ventricular fibrillation; may repeat twice up to 15 mg/kg. Infuse 5 milligrams/kilogram over 20 to 60 minutes for perfusing tachycardias. Maximum single dose is 300 mg. Routine use with other drugs that prolong the QT interval is NOT recommended (Kleinman et al, 2010).

d) ADVERSE EFFECTS

1) Hypotension and bradycardia are the most common adverse effects (Neumar et al, 2010).

4) PROCAINAMIDE

a) PROCAINAMIDE/INDICATIONS

1) An alternative drug in the treatment of PVCs or recurrent ventricular tachycardia when lidocaine is contraindicated or not effective. It should be avoided when the ingestion involves agents with quinidine-like effects (e.g. tricyclic antidepressants, phenothiazines, chloroquine, antidysrhythmics) and when the ECG reveals QRS widening or QT prolongation suspected to be secondary to overdose(Neumar et al, 2010; Vanden Hoek,TL,et al).

b) PROCAINAMIDE/ADULT LOADING DOSE

1) 20 to 50 milligrams/minute IV until dysrhythmia is suppressed or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%), or a total dose of 17 milligrams/kilogram is given (1.2 grams for a 70 kilogram person) (Neumar et al, 2010).
2) ALTERNATIVE DOSING: 100 mg every 5 minutes until dysrhythmia is controlled, or toxicity develops from procainamide (hypotension develops or the QRS is widened by 50%) or 17 mg/kg have been given (Neumar et al, 2010).
3) MAXIMUM DOSE: 17 milligrams/kilogram (Neumar et al, 2010).

c) PROCAINAMIDE/CONTROLLED INFUSION

1) In conscious patients, procainamide should be administered as a controlled infusion (20 milligrams/minute) because of the risk of QT prolongation and its hypotensive effects (Link et al, 2015)

d) PROCAINAMIDE/ADULT MAINTENANCE DOSE

1) 1 to 4 milligrams/minute via an intravenous infusion (Neumar et al, 2010).

e) PROCAINAMIDE/PEDIATRIC LOADING DOSE

1) 15 milligrams/kilogram IV/Intraosseously over 30 to 60 minutes; discontinue if hypotension develops or the QRS widens by 50% (Kleinman et al, 2010).

f) PROCAINAMIDE/PEDIATRIC MAINTENANCE DOSE

1) Initiate at 20 mcg/kg/minute and increase in 10 mcg/kg/minute increments every 15 to 30 minutes until desired effect is achieved; up to 80 mcg/kg/minute (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).

g) PROCAINAMIDE/PEDIATRIC MAXIMUM DOSE

1) 2 grams/day (Bouhouch et al, 2008; Ratnasamy et al, 2008; Mandapati et al, 2000; Luedtke et al, 1997; Walsh et al, 1997).

h) MONITORING PARAMETERS

1) ECG, blood pressure, and blood concentrations (Prod Info procainamide HCl IV, IM injection solution, 2011). Procainamide can produce hypotension and QT prolongation (Link et al, 2015).

i) AVOID

1) Avoid in patients with QT prolongation and CHF (Neumar et al, 2010).

N) HYPOTENSIVE EPISODE

1) 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.

2) 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).

3) 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).

O) SEIZURE

1) SUMMARY

a) Attempt initial control with a benzodiazepine (eg, diazepam, lorazepam). If seizures persist or recur, administer phenobarbital or propofol.
b) Monitor for respiratory depression, hypotension, and dysrhythmias. Endotracheal intubation should be performed in patients with persistent seizures.
c) Evaluate for hypoxia, electrolyte disturbances, and hypoglycemia (or, if immediate bedside glucose testing is not available, treat with intravenous dextrose).

2) DIAZEPAM

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

3) NO INTRAVENOUS ACCESS

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

4) LORAZEPAM

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

5) PHENOBARBITAL

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

6) OTHER AGENTS

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

1) VALPROATE SODIUM: ADULT DOSE: An initial dose of 20 to 40 mg/kg IV, at a rate of 3 to 6 mg/kg/minute; may give an additional dose of 20 mg/kg 10 minutes after loading infusion. PEDIATRIC DOSE: 1.5 to 3 mg/kg/minute (Brophy et al, 2012).
2) LEVETIRACETAM: ADULT DOSE: 1000 to 3000 mg IV, at a rate of 2 to 5 mg/kg/min IV. PEDIATRIC DOSE: 20 to 60 mg/kg IV (Brophy et al, 2012; Loddenkemper & Goodkin, 2011).
3) LACOSAMIDE: ADULT DOSE: 200 to 400 mg IV; 200 mg IV over 15 minutes (Brophy et al, 2012). PEDIATRIC DOSE: In one study, median starting doses of 1.3 mg/kg/day and maintenance doses of 4.7 mg/kg/day were used in children 8 years and older (Loddenkemper & Goodkin, 2011).
4) TOPIRAMATE: ADULT DOSE: 200 to 400 mg nasogastric/orally OR 300 to 1600 mg/day orally divided in 2 to 4 times daily (Brophy et al, 2012).

P) RHABDOMYOLYSIS

1) SUMMARY: Early aggressive fluid replacement is the mainstay of therapy and may help prevent renal insufficiency. Diuretics such as mannitol or furosemide may be added if necessary to maintain urine output but only after volume status has been restored as hypovolemia will increase renal tubular damage. Urinary alkalinization is NOT routinely recommended.
2) Initial treatment should be directed towards controlling acute metabolic disturbances such as hyperkalemia, hyperthermia, and hypovolemia. Control seizures, agitation, and muscle contractions (Erdman & Dart, 2004).
3) FLUID REPLACEMENT: Early and aggressive fluid replacement is the mainstay of therapy to prevent renal failure. Vigorous fluid replacement with 0.9% saline (10 to 15 mL/kg/hour) is necessary even if there is no evidence of dehydration. Several liters of fluid may be needed within the first 24 hours (Walter & Catenacci, 2008; Camp, 2009; Huerta-Alardin et al, 2005; Criddle, 2003; Polderman, 2004). Hypovolemia, increased insensible losses, and third spacing of fluid commonly increase fluid requirements. Strive to maintain a urine output of at least 1 to 2 mL/kg/hour (or greater than 150 to 300 mL/hour) (Walter & Catenacci, 2008; Camp, 2009; Erdman & Dart, 2004; Criddle, 2003). To maintain a urine output this high, 500 to 1000 mL of fluid per hour may be required (Criddle, 2003). Monitor fluid input and urine output, plus insensible losses. Monitor for evidence of fluid overload and compartment syndrome; monitor serum electrolytes, CK, and renal function tests.
4) DIURETICS: Diuretics (eg, mannitol or furosemide) may be needed to ensure adequate urine output and to prevent acute renal failure when used in combination with aggressive fluid therapy. Loop diuretics increase tubular flow and decrease deposition of myoglobin. These agents should be used only after volume status has been restored, as hypovolemia will increase renal tubular damage. If the patient is maintaining adequate urine output, loop diuretics are not necessary (Vanholder et al, 2000).
5) URINARY ALKALINIZATION: Alkalinization of the urine is not routinely recommended, as it has never been documented to reduce nephrotoxicity, and may cause complications such as hypocalcemia and hypokalemia (Walter & Catenacci, 2008; Huerta-Alardin et al, 2005; Brown et al, 2004; Polderman, 2004). Retrospective studies have failed to demonstrate any clinical benefit from the use of urinary alkalinization (Brown et al, 2004; Polderman, 2004; Homsi et al, 1997).
6) MANNITOL/INDICATIONS

a) Osmotic diuretic used in the management of rhabdomyolysis and myoglobinuria (Zimmerman & Shen, 2013).

7) RHABDOMYOLYSIS/MYOGLOBINURIA

a) ADULT: TEST DOSE: (for patients with marked oliguria or those with inadequate renal function) 0.2 g/kg IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase within 2 to 3 hours. The patient should be reevaluated if there is inadequate response following the second test dose (Prod Info MANNITOL intravenous injection, 2009). TREATMENT DOSE: 50 to 100 g IV as a 15% to 25% solution may be used. The rate should be adjusted to maintain urinary output at 30 to 50 mL/hour (Prod Info mannitol IV injection, urologic irrigation, 2006) OR 300 to 400 mg/kg or up to 100 g IV administered as a single dose (Prod Info MANNITOL intravenous injection, 2009).
b) PEDIATRIC: Dosing has not been established in patients less than 12 years of age(Prod Info Mannitol intravenous injection, 2009). TEST DOSE (for patients with marked oliguria or those with inadequate renal function): 0.2 g/kg or 6 g/m(2) body surface area IV as a 15% to 25% solution infused over 3 to 5 minutes to produce a urine flow of at least 30 to 50 mL/hr; a second test dose may be given if urine flow does not increase; TREATMENT DOSE: 0.25 to 2 g/kg or 60 g/m(2) body surface area IV as a 15% to 20% solution over 2 to 6 hours; do not repeat dose for persistent oliguria (Prod Info MANNITOL intravenous injection, 2009).

8) ADVERSE EFFECTS

a) Fluid and electrolyte imbalance, in particular sodium and potassium; expansion of the extracellular fluid volume leading to pulmonary edema or CHF exacerbations(Prod Info MANNITOL intravenous injection, 2009).

9) PRECAUTION

a) Contraindicated in well-established anuria or impaired renal function not responding to a test dose, pulmonary edema, CHF, severe dehydration; caution in progressive oliguria and azotemia; do not add to whole blood for transfusions(Prod Info Mannitol intravenous injection, 2009); enhanced neuromuscular blockade observed with tubocurarine(Miller et al, 1976).

10) MONITORING PARAMETERS

a) Renal function, urine output, fluid balance, serum potassium, serum sodium, and serum osmolality (Prod Info Mannitol intravenous injection, 2009).

Q) OBSERVATION REGIMES

1) Carefully observe patients with ingestion exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

R) ANURIA

1) If anuria develops, patients may need treatment with hemodialysis.

S) EXPERIMENTAL THERAPY

1) DEXTROSE THERAPY

a) ANIMAL STUDIES

1) In an animal study of severe experimental sodium monochloroacetic acid (SMCA) poisoning, dextrose infusion prevented hypoglycemia, decreased lactate levels and increased survival.

a) Rats (n=63) received 70 mg/kg SMCA subcutaneously (LD99), and then treated with a 10 hour infusion of either saline (n=21), 5% dextrose (n=21), or 10% dextrose (n=21). Saline treated rats developed hypoglycemia; dextrose treated rats did not. Blood lactate levels increased more in the control rats than in either of the dextrose treated groups. In the control group survival was 10% at 10 hours, compared with 57% in the 5% dextrose group, and 78% in the 10% dextrose group. Survival at 14 days was 0 in the control group, 14% in the 5% dextrose group, and 78% in the 10% dextrose group.
b) Based on the inverse relationship between a decrease in glucose and an increase in blood lactate level observed in this study, it was suggested that the target enzyme of MCA inhibition was one that participated in gluconeogenesis or the TCA cycle.
c) In the clinical setting, the authors suggested that a continuous parenteral glucose infusion should be started soon after exposure to MCA as a potentially effective therapy for the prevention of hypoglycemia and metabolic lactic acidosis. The effect of glucose infusion combined with other antidotes remains an area for further study (Shimizu et al, 2002).

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) IRRITATION SYMPTOM

1) Respiratory tract irritation, if severe, can progress to noncardiogenic pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases.
2) There are no controlled studies indicating that early administration of corticosteroids can prevent the development of noncardiogenic pulmonary edema in patients with inhalation exposure to respiratory irritant substances, and long-term use may cause adverse effects (Boysen & Modell, 1989).

a) However, based on anecdotal experience, some clinicians do recommend early administration of corticosteroids (such as methylprednisolone 1 gram intravenously as a single dose) in an attempt to prevent the later development of pulmonary edema.

1) Anecdotal experience with dimethyl sulfate inhalation showed possible benefit of methylprednisolone in the TREATMENT of noncardiogenic pulmonary edema (Ip et al, 1989).

3) Anecdotal experience also indicated that systemic corticosteroids may have possible efficacy in the TREATMENT of drug-induced noncardiogenic pulmonary edema (Zitnik & Cooper, 1990; Stentoft, 1990; Chudnofsky & Otten, 1989) or noncardiogenic pulmonary edema developing after cardiopulmonary bypass (Maggart & Stewart, 1987).
4) It is not clear from the published literature that administration of systemic corticosteroids early following inhalation exposure to respiratory irritant substances can PREVENT the development of noncardiogenic pulmonary edema. The decision to administer or withhold corticosteroids in this setting must currently be made on clinical grounds.

B) 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).

C) AIRWAY MANAGEMENT

1) If CNS or respiratory depression occur, ensure adequacy of respirations and oxygenation. Endotracheal intubation, supplemental oxygenation, and assisted ventilation could be required.

D) OBSERVATION REGIMES

1) Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

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

Eye Exposure

6.8.1)

A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

6.8.2)

A) INJURY OF GLOBE OF EYE

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) MEDICAL FACILITY 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, 1993). 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, 1993). 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, 1993).
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, 1993). 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

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, 1993). 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

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, 1993a).
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, 1993a). 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).

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, 1993a). 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).

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, 1993). 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, 1993).

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

Dermal Exposure

6.9.1)

A) DERMAL DECONTAMINATION

1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. 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) SKIN ABSORPTION

1) Some chemicals can produce systemic poisoning by absorption through intact skin. Carefully observe patients with dermal exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.

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

Enhanced Elimination

1) If anuria develops, patients may need treatment with hemodialysis.

1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Abstracts

Range Of Toxicity

Summary

Minimum Lethal Exposure

1) An estimated probable lethal dose is between 50 and 100 mg/kg for an adult (EPA, 1985).
2) DERMAL - Body surface exposure of up to 5% of an 80% solution of monochloroacetic acid can produce a moderate systemic poisoning; 6% to 10% body surface exposure can produce a severe, potentially lethal poisoning, and 15% or above is considered lethal (Pirson et al, 2003).

1) CASE REPORT - A 3-year-old male died after inadvertent application of an 80% monochloroacetic acid solution over his face, neck and chest, which produced second-degree burns over 15% of his total body surface area. The child died of nonresponsive cardiac arrest 12 hours after exposure despite supportive care (Pirson et al, 2003).
2) CASE REPORT - A 5-year-old girl died despite receiving supportive care after ingesting 5 to 6 mL of an 80% monochloroacetic acid solution (Feldhaus et al, 1993).

1) CASE REPORT - A 55-year-old man developed hemolysis, acute renal failure, hemorrhagic colitis, and an acute myocardial infarction after intentionally ingesting 50 to 75 mL of monochloroacetic acid. Despite aggressive supportive therapy, the patient died approximately 8 days post-ingestion (Nayak et al, 2007).

Maximum Tolerated Exposure

1) Case studies citing particular chloroacetic acid doses were not found in the literature. However, the compound is known to be poisonous by the ingestion, inhalation, and subcutaneous, and intravenous exposure routes. It is a corrosive and a skin, eye, and mucous membrane irritant (Lewis, 1996).

Serum Plasma Blood Concentrations

7.5.2)

A) TOXIC CONCENTRATION LEVELS

1) CASE REPORTS

a) A plasma monochloroacetic acid level was 33 mg/L 4 hours after exposure in a 38-year-old man who died after sustaining 25 to 30% body surface area burns with 80% monochloroacetic acid (Kulling et al, 1992).
b) A post mortem serum monochloroacetic acid level was 100 mg/L in a 5-year-old girl who died after ingesting 5 to 6 ml of an 80% monochloroacetic acid solution (Feldhaus et al, 1993).

Workplace Standards

1) Editor's Note: The listed values are recommendations or guidelines developed by ACGIH(R) to assist in the control of health hazards. They should only be used, interpreted and applied by individuals trained in industrial hygiene. Before applying these values, it is imperative to read the introduction to each section in the current TLVs(R) and BEI(R) Book and become familiar with the constraints and limitations to their use. Always consult the Documentation of the TLVs(R) and BEIs(R) before applying these recommendations and guidelines.

a) Adopted Value

1) Monochloroacetic acid

a) TLV:

1) TLV-TWA: 0.5 ppm
2) TLV-STEL:
3) TLV-Ceiling:

b) Notations and Endnotes:

1) Carcinogenicity Category: A4
2) Codes: IFV, Skin
3) Definitions:

a) A4: Not Classifiable as a Human Carcinogen: Agents which cause concern that they could be carcinogenic for humans but which cannot be assessed conclusively because of a lack of data. In vitro or animal studies do not provide indications of carcinogenicity which are sufficient to classify the agent into one of the other categories.
b) IFV: Inhalable fraction and vapor.
c) Skin: This refers to the potential significant contribution to the overall exposure by the cutaneous route, including mucous membranes and the eyes, either by contact with vapors or, of likely greater significance, by direct skin contact with the substance. It should be noted that although some materials are capable of causing irritation, dermatitis, and sensitization in workers, these properties are not considered relevant when assigning a skin notation. Rather, data from acute dermal studies and repeated dose dermal studies in animals or humans, along with the ability of the chemical to be absorbed, are integrated in the decision-making toward assignment of the skin designation. Use of the skin designation provides an alert that air sampling would not be sufficient by itself in quantifying exposure from the substance and that measures to prevent significant cutaneous absorption may be warranted. Please see "Definitions and Notations" (in TLV booklet) for full definition.

c) TLV Basis - Critical Effect(s): Upper respiratory tract irritation
d) Molecular Weight: 94.5

1) For gases and vapors, to convert the TLV from ppm to mg/m(3):

a) [(TLV in ppm)(gram molecular weight of substance)]/24.45

2) For gases and vapors, to convert the TLV from mg/m(3) to ppm:

a) [(TLV in mg/m(3))(24.45)]/gram molecular weight of substance

e) Additional information:

B) NIOSH REL and IDLH Values for CAS79-11-8 (National Institute for Occupational Safety and Health, 2007):

1) Not Listed

C) Carcinogenicity Ratings for CAS79-11-8 :

1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): A4 ; Listed as: Monochloroacetic acid

2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): Not Listed
4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
5) MAK (DFG, 2002): Not Listed
6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

D) OSHA PEL Values for CAS79-11-8 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):

1) Not Listed

Toxicity Information

7.7.1)

A) Note: All values are from RTECS, 1996 unless otherwise noted.

1) LD50- (ORAL)MOUSE:

a) 255 mg/kg (Budavari, 1996)
b) 165 mg/kg (Lewis, 1996)

2) LD50- (SUBCUTANEOUS)MOUSE:

a) 250 mg/kg

3) LD50- (INTRAPERITONEAL)RAT:

a) 16.6 mg/kg

4) LD50- (ORAL)RAT:

a) 580 mg/kg
b) 76 mg/kg (Budavari, 1996)

5) LD50- (SUBCUTANEOUS)RAT:

a) 5 mg/kg

Pharmacology Toxicology

Toxicologic Mechanism

Physicochemical

Physical Characteristics

Molecular Weight

Other

1) 0.15 mg/m3 (CHRIS , 2002)

Animal Toxicology

References

General Bibliography

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CHLOROACETIC ACID

Classification | Detailed evidence-based information

Therapeutic Toxic Class

Specific Substances

Available Forms Sources

Life Support

Clinical Effects

Laboratory Monitoring

Treatment Overview

Range Of Toxicity

Summary Of Exposure

Heent

Cardiovascular

Respiratory

Neurologic

Gastrointestinal

Hepatic

Genitourinary

Acid-Base

Hematologic

Dermatologic

Musculoskeletal

Reproductive

Carcinogenicity

Genotoxicity

Monitoring Parameters Levels

Radiographic Studies

Methods

Life Support

Patient Disposition

Monitoring

Oral Exposure

Inhalation Exposure

Eye Exposure

Dermal Exposure

Enhanced Elimination

Summary

Minimum Lethal Exposure

Maximum Tolerated Exposure

Serum Plasma Blood Concentrations

Workplace Standards

Toxicity Information

Toxicologic Mechanism

Physical Characteristics

Molecular Weight

Other

General Bibliography