DESCRIPTION

Bismuth substances include bismuth subsalicylate (the primary form available in commercial products) as well as bismuth subcarbonate, bismuth oxycarbonate, bismuth subgallate, bismuth subnitrate, bismuth subchloride, bismuth triglycollamate, and bismuth sulfide.

FORMS AND USES

• Pharmaceutical preparations containing bismuth subsalicylate include Pepto-Bismol, Corrective Mixture, Infantol Pink, Pabizol with paregoric, and Pept-Aid Soothe.
• Bismuth subsalicylate is used as antibacterial against Helicobacter pylori, as a treatment for dyspepsia and diarrhea, and as a topical application for skin lesions.
• Typical dosages
  • Bismuth subcitrate. 240 mg twice daily or 120 mg four times daily for 4 to 8 weeks (ulcer therapy).
  • Bismuth subgallate. 0.6 to 2 g for gastrointestinal disturbances.
  • Bismuth subsalicylate. 500 mg up to total 4 g/day for diarrhea therapy.

TOXIC DOSE

Toxicity from a single ingestion is unusual. It commonly develops from chronic exposure, particularly injections of bismuth.

PATHOPHYSIOLOGY

• Most medicinal bismuth products contain insoluble trivalent salts.
• Classification of bismuth compounds
  • Group 1. Water-insoluble compounds, minimally absorbed, nontoxic (e.g., bismuth subcarbonate, bismuth subnitrate, bismuth subsalicylate).
  • Group 2. Lipophilic compounds can produce hepatotoxicity and neurotoxicity (e.g., bismuth subgallate).
  • Group 3. Absorbed and can lead to renal damage; includes water-soluble organic compounds (e.g., bismuth triglycollamate).
  • Group 4. Minimal absorption, nontoxic, water-soluble compounds that hydrolyze to produce insoluble bismuth compounds (e.g., bismuth subchloride, bismuth sulfide).
• Excretion. Insoluble forms of bismuth are retained in the kidneys, bones, and gastric wall; slow elimination occurs by the kidneys. Soluble forms are quickly eliminated in urine and saliva.

EPIDEMIOLOGY

• Poisoning is uncommon.
• Toxic effects following exposure are typically mild, with death rarely occurring.

CAUSES

• Most common cause of poisoning is 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

• Absorption of oral preparations increases in settings of altered intestinal mucosal integrity (e.g., Crohn's disease).
• Renal toxicity has occurred most frequently in patients with immature kidneys (particularly in children less than 3 years of age).

PREGNANCY AND LACTATION

• Bismuth subsalicylate. 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.
• Insoluble bismuth salts accumulate in the placenta; however, children born of mothers with bismuth encephalopathy appear normal at birth.

Section Outline:

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

DIFFERENTIAL DIAGNOSIS

Nontoxicologic causes of salivation, bluish discoloration of gums, loss of teeth, ulcerative stomatitis, and encephalopathy may include lead poisoning and mercury poisoning.

SIGNS AND SYMPTOMS

• Large or repeated exposures may produce increased salivation as an early effect, followed by encephalopathy and renal injury.

HEENT

Increased salivation, pyorrhea and ulcerative stomatitis may develop. A bluish line develops along gums due to bismuth deposition in fibrous tissues.

Dermatologic

A maculopapular rash ("erythema of the ninth day") may occur.

Cardiovascular

Myocardial injury has been reported after chronic exposure, although it rarely occurs.

Gastrointestinal

Nausea, vomiting, and diarrhea may occur in acute or chronic exposure.

Hepatic

Jaundice and fatty changes may develop in the liver with chronic exposure.

Renal

Proteinuria and microscopic hematuria occur early in the course of chronic exposure, whereas Fanconi syndrome, renal failure, and anuria may occur later.

Hematologic

Intestinal bacteria may reduce bismuth subnitrate to nitrate, which can cause methemoglobinemia and nitrate poisoning.

Musculoskeletal

Osteoarthropathy, osteoporosis, and osteomalacia may develop.

Neurologic

• Anorexia, headaches, malaise, confusion, tremors, and encephalopathy may occur.
• Encephalopathy may develop with chronic ingestion, starting with prodrome of malaise and lasting from weeks to months.
• Rapid deterioration may occur over 24 to 48 hours, including signs of confusion, dysarthria, gait disturbance, pseudotremor, and myoclonic jerks.

PROCEDURES AND LABORATORY TESTS

Essential Tests

• Results of liver function tests will be elevated if there is liver injury.
• Serum electrolytes, BUN, and creatinine levels are used to assess kidney injury.

Recommended Tests

• Salicylate levels are measured to check for salicylate toxicity.
• Bismuth levels are available from reference laboratories. Serum or blood bismuth levels less than 5 µg/dl are rarely toxic. However, levels do not correlate well with toxicity.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Gastrointestinal
  • Hepatic
  • Renal
  • Hematologic
  • Musculoskeletal
  • Neurologic
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Recommended Tests

• Treatment should be focused on termination of bismuth exposure.
• Treatment is primarily supportive once bismuth has been absorbed and deposited in the bones and other organs.
• 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:

• Severe or persistent effects develop.
• Toxic effects are not consistent with bismuth 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.
• Toxic effects develop.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted if the patient exhibits altered mental status, renal dysfunction, or clinically significant effects.

DECONTAMINATION

Out of Hospital

Ipecac should be administered to induce emesis within 1 hour of an acute ingestion for the alert pediatric or adult patient if health-care evaluation will be delayed.

In Hospital

• Ipecac should be administered to induce emesis within 1 hour of acute ingestion for the alert patient who is too small to have effective gastric lavage.
• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion.
• 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.

ANTIDOTES

d-Penicillamine

• Adult dose
  • 15 to 40 mg/kg/day orally, maximum 250 to 500 mg four times daily
• Pediatric dose
  • 20 to 30 mg/kg/day, once or twice daily

Dimercaprol

The dose for adult or pediatric patients is 3 mg/kg within 8 to 12 hours of bismuth ingestion.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
  • d-Penicillamine
  • Dimercaprol

PATIENT MONITORING

Specific monitoring is not necessary in uncomplicated cases.

EXPECTED COURSE AND PROGNOSIS

• Recovery is expected if encephalopathy and renal failure do not develop.
• Encephalopathy may take several weeks to resolve or may not improve.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Patients may be discharged when clinical effects have stabilized and decontamination has been completed, and after psychiatric evaluation, if needed.
• From the hospital. Patients may be discharged after toxic effects resolve or stabilize and after psychiatric evaluation, if needed.

PATIENT EDUCATION

Use of bismuth subsalicylate preparations should be avoided in children under 16 years of age due to salicylate component.

Section Outline:

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

Failure to consider bismuth exposure

FOLLOW-UP

• Bismuth subsalicylate-containing compounds can increase the risk of Reye syndrome in children due to salicylate.
• Avoid use of bismuth subsalicylate-containing compounds if using oral anticoagulants, probenecid, methotrexate, or other forms of salicylate.

Toxic effects of specified metals (bismuth).

See Also: SECTION II, British Anti-Lewisite and d-penicillamine chapters.

RECOMMENDED READINGS

Gryboski JD, Gotoff SP. Bismuth nephrotoxicity. N Engl J Med 1961;265:1289-1291.

Mendelowitz PC, Hoffman RS, Weber S. Bismuth absorption and myoclonic encephalopathy during bismuth subsalicylate therapy. Ann Intern Med 1990;112:140-141.

Pickering LK, Feldman S, Ericsson CD, Cleary TG. Absorption of salicylate and bismuth from bismuth subsalicylate-containing compound (Pepto-Bismol). J Pediatr 1981;99:654-656.

Author: Kathleen Graham

Reviewer: Luke Yip