DESCRIPTION

Benzocaine is a local anesthetic.

FORMS AND USES

• U.S. FDA-labeled indications for use include numerous indications involving mild to moderate localized pain or irritation.
• Benzocaine can be found in topical ointments, creams, gels, solutions, aerosols, and sprays.
• Formulations in which benzocaine is present include Tympagesic, Auralgan, Oragel, Benzodent, Orabase, Merocaine, Tyrozets, Americaine, Applicaine, BanSmoke, Burneze, Chigger-Tox, Dent's Toothache preparations, Dentispray, Dermoplast, Detane, Diet Ayds, Hurricaine, Lanacane, Numzident, Orajel, Orabase, SensoGARD, Slim Mint, Spec-T, Subcutin N, Teething Syrup, Topicaine, Trocaine, Unguentine, Vicks Children's Chloraseptic, Aerocaine, Aerotherm, Aezodent, Aidex, Allergen, Anbesol, Animine, Anocaine, Antibiotic Cold Sore Ointment, Antipyrine and Benzocaine Otic Solution, Anusept, Appedrine, and Auralgicin.
• Benzocaine is sometimes added to street drugs as an adulterant.

TOXIC DOSE

Ingestion of just 1 to 2 ml of 7.5% benzocaine gel can produce toxicity in infants.

PATHOPHYSIOLOGY

• Benzocaine is a local anesthetic that is metabolized to aniline and then further metabolized to phenylhydroxylamine and nitrobenzene.
• These potent agents (phenylhydroxylamine and nitrobenzene) are capable of oxidizing hemoglobin to methemoglobin, which results in methemoglobinemia.
  • Methemoglobin is hemoglobin in the Fe³⁺ (oxidized) state instead of normal Fe²⁺ state.
  • It is continuously produced in cells and reduced back to Fe²⁺ by the enzyme NADH (nicotinamide adenine dinucleotide, reduced form) methemoglobin reductase.

EPIDEMIOLOGY

• Poisoning is common due to the large number of over-the-counter products.
• Toxic effects following exposure are typically mild, and death occurs rarely.

CAUSES

• Toxicity usually occurs as a result of therapeutic misadventure.
• Child neglect or abuse should be considered if the patient is less than 1 year of age, suicide attempt if the patient is over 6 years of age.

RISK FACTORS

• Infants under the age of four months have greater susceptibility due to reduced NADH methemoglobin reductase activity.
• Topical use is not recommended in children less than 2 years of age.

PREGNANCY AND LACTATION

US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.

Section Outline:

• DESCRIPTION
• FORMS AND USES
• TOXIC DOSE
• PATHOPHYSIOLOGY
• EPIDEMIOLOGY
• CAUSES
• RISK FACTORS
• PREGNANCY AND LACTATION

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of methemoglobinemia include the use or ingestion of dapsone, nitrites, nitrates, chloroquine, primaquine, sulfonamide, aniline dyes, naphthalene, chlorates, phenacetin, mafenide acetate, phenazopyridine, resorcinol, aminobenzenes, and acetanilid.
• Nontoxicologic causes of methemoglobinemia primarily involve deficiency of NADH methemoglobin reductase.

SIGNS AND SYMPTOMS

• Toxic effects are caused by cellular hypoxia induced by decreased oxygen delivery to cells.

Vital Signs

Tachycardia, hypotension, and tachypnea are rare unless hemolysis or methemoglobinemia develop.

HEENT

Prolonged mucous membrane contact can result in irritation.

Dermatologic

• Cyanosis may develop due to methemoglobinemia.
• Rash is common with topical use.

Cardiovascular

Tachycardia and hypotension can result from methemoglobinemia.

Pulmonary

Dyspnea due to methemoglobin-induced hypoxia.

Gastrointestinal

Nausea and vomiting are common.

Hematologic

• Most cases of methemoglobinemia involve overdose.
• Idiosyncratic reactions have been reported following therapeutic doses.

Fluids and Electrolytes

Lactic acidosis due to relative hypoxia induced by methemoglobin.

Neurologic

• Altered mental status due to methemoglobin-induced hypoxia.
• Seizures occur in severe toxicity.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Methemoglobin level. Normal is less than 3%.
• If methemoglobin level is unavailable, a drop of the patient's blood can be placed upon a white sheet and compared with that of a normal control; blood with methemoglobinemia has a characteristic chocolate brown color.

Recommended Tests

• Arterial blood gases should be measured in symptomatic patients using a cooximeter because calculated oxygen saturations may be inaccurate in the presence of methemoglobin.
• Serum glucose-6-phosphate dehydrogenase (G-6-PD) determination should be made to determine etiology in patients with methemoglobinemia.
• Serum electrolytes, BUN, and creatinine can be used to assess for elevated anion gap acidosis.

Not Recommended Tests

Benzocaine in either plasma or urine can confirm exposure but qualitative levels are not clinically useful.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Hematologic
  • Fluids and Electrolytes
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests
  • Not Recommended Tests

• Treatment initially should focus on decontamination, supportive respiratory care, and administration of methylene blue, if indicated.
• Administration of 100% oxygen is critical in symptomatic patients.
• Dose and time of exposure should be determined for all substances involved.

DIRECTING PATIENT COURSE

The health-care professional should call the poison control center when:

• Cyanosis, acidosis, respiratory distress, or other severe effects are present.
• Toxic effects are not consistent with benzocaine poisoning.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

The patient should be referred to a health-care facility when:

• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted if the patient is symptomatic, exhibits an elevated methemoglobin level, or requires treatment with methylene blue.

DECONTAMINATION

Out of Hospital

• Emesis should be avoided due to potentially rapid onset of seizures and CNS depression.
• Exposed skin areas should be washed to limit further absorption.

In Hospital

• Ipecac-induced emesis is not recommended.
• Nasogastric aspiration using a nasogastric tube within the first 30 to 60 minutes following a large ingestion may be beneficial; however, because benzocaine is rapidly absorbed, gastric aspiration is useful only soon after ingestion.
• If there is concern of a coingestant, then gastric lavage with a large-bore orogastric tube may be indicated.
• One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.
• Exposed skin areas should be washed to limit further absorption.

ANTIDOTES

Methylene blue is used to reverse methemoglobinemia.

• Indications. The decision to treat methemoglobinemia is based primarily on the patient's clinical condition; any evidence of CNS or cardiac hypoxia (anxiety, confusion, hypotension, chest pain, etc.) indicates a need for treatment.
• Contraindications. Methylene blue is relatively contraindicated when patient has known NADH methemoglobin reductase deficiency or G-6-PD deficiency.
• Method of administration. 1 to 2 mg/kg should be given intravenously over 5 minutes.
  • Clinical improvement should be apparent shortly after administration.
  • Methemoglobin level should be repeated 30 minutes later.
  • If the level remains elevated and the patient is still symptomatic, a repeat dose of 1 to 2 mg/kg intravenously over 5 minutes can be given.
• Potential adverse effects
  • Hemolysis can occur in patients with G-6-PD deficiency.
  • A paradoxical worsening of methemoglobinemia can occur with extremely large doses (unlikely with cumulative dose of less than 7 mg/kg).

ADJUNCTIVE TREATMENT

Exchange transfusion has been used rarely when life-threatening methemoglobinemia is refractory to methylene blue therapy or patient has severe G-6-PD deficiency.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT

PATIENT MONITORING

• Patient should be placed on continuous cardiac and hemodynamic monitoring.
• Serial methemoglobin levels should be checked until normal is approached and level does not recur after last dose of methylene blue.

EXPECTED COURSE AND PROGNOSIS

• Nearly all patients recover quickly if treatment is initiated before hypoxic injury occurs.
• Patients with hypoxic injury or G-6-PD deficiency may have prolonged course.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency room. Asymptomatic patients with a normal or decreasing methemoglobin level can be discharged after decontamination, a 4- to 6-hour period of observation, and psychiatric evaluation, if needed.
• From the hospital. Patient may be discharged when symptoms resolve and methemoglobin level is normal.

PATIENT EDUCATION

• Patient should return if fatigue, dyspnea, lightheadedness, shortness of breath, or cyanosis develop or recur.
• Patients with G-6-PD deficiency should be warned to avoid preparations containing benzocaine.

Section Outline:

• PATIENT MONITORING
• EXPECTED COURSE AND PROGNOSIS
• DISCHARGE CRITERIA/INSTRUCTIONS
• PATIENT EDUCATION

DIAGNOSIS

• The pO₂ on the arterial blood gases reflects the partial pressure of oxygen dissolved in the blood and may be normal despite significant methemoglobinemia.
• A normal oxygen saturation by pulse oximetry does not rule out methemoglobinemia.
• Sulfhemoglobinemia produces effects indistinguishable from methemoglobinemia and should be suspected when methemoglobinemia fails to respond to methylene blue treatment.

TREATMENT

Methemoglobinemia may be recurrent despite treatment, especially in the face of continued gastrointestinal or dermal absorption of benzocaine.

Section Outline:

• DIAGNOSIS
• TREATMENT

Poisoning by other central nervous system depressants and anesthetics: surface (topical) and infiltration anesthetics.

See Also: SECTION II, Methemoglobinemia chapter; and SECTION III, Methylene Blue chapter.

RECOMMENDED READING

POISINDEX Editorial Staff. Benzocaine. In: Rumack BH, Hess AJ, Gelman CR, eds. POISINDEX system. Englewood, CO: Micromedex, Inc. (edition expires August 31, 1997).

Price D. Methemoglobinemia. In: Goldfrank LR, et al., eds. Goldfrank's toxicologic emergencies. 6th ed. Norwalk, CT: Appleton & Lange, 1998.

Author: Edwin K. Kuffner

Reviewer: Luke Yip