DESCRIPTION

Barbiturates are a group of medications used primarily in the treatment of seizure and in some anesthesiology procedures.

FORMS AND USES

• Ultra short-acting barbiturates include methohexital (Brevital), thiamylal (Surital), and thiopental (Pentothal).
• Short-acting preparations include butabarbital (Buticaps, Butisol, Butalan), hexobarbital (Evipal), pentobarbital (Nembutal), and secobarbital (Seconal).
• Long-acting barbiturate preparations include mephobarbital (Mebaral), metharbital (Gemonil), phenobarbital (Arco-Lase, Bellatal belladonna with Phenobarbital Alkaloids, Donnatal, Luminal, Mudrane, Quadrinal, Rexatal, Solfoton), and primidone (Mysoline).
• Veterinary barbiturate products include phenobarbital (Beuthanasia, Euthanasia, Fatal, Lethal, Sleepaway, Succumb) and Secobarbital (Repose).
• Barbiturates can be used to control seizures.
  • Phenobarbital. Adult dose is 60 mg two or three times per day; pediatric dose is 3 to 6 mg/kg/day.
  • Primidone. Adult dose is 250 mg three or four times per day; maintenance dose for children under 8 years of age is 10 to 25 mg/kg/day.
• Barbiturates are also used for sedation.
  • Butabarbital. Adult dose is 15 to 30 mg orally three or four times per day
  • Secobarbital. 100 to 300 mg at bedtime

TOXIC DOSE

• To a naive user, toxicity may begin only slightly above the therapeutic dose.
• Tolerance develops rapidly, and regular abusers may tolerate huge doses.
• Death generally occurs from complications such as aspiration.

PATHOPHYSIOLOGY

• Barbiturates bind to a site that modulates the gamma-aminobutyric acid (GABA) receptor and increases the effects of GABA in the CNS.
• Primidone is metabolized to phenobarbital and phenylethylmalondiamid in the body.
• Phenylethylmalondiamid is biologically active and has effects similar to those of phenobarbital.

EPIDEMIOLOGY

• Poisoning is common.
• Toxic effects following exposure are typically mild to moderate.
• Death occurs rarely, most commonly in mixed ingestions or from complications such as aspiration.

CAUSES

• Toxic ingestion is usually suicidal.
• 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

The elderly may be more sensitive to the sedative effects of barbiturates and have an increased risk of falling.

DRUG DISEASE AND INTERACTIONS

• CNS depression is increased by other depressants.
• Valproic acid and monoamine oxidase inhibitors may increase phenobarbital levels.
• Phenytoin and phenobarbital have variable interactions, either increasing or decreasing the level of one another.

PREGNANCY AND LACTATION

• US FDA Pregnancy Category D. Definite evidence of human fetal risk exists, but benefits in certain situations (e.g., life-threatening situations or serious diseases) may make use of the drug acceptable despite its risks.
• Phenobarbital is teratogenic.
• Barbiturates should be avoided in pregnancy.

Section Outline:

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

DIFFERENTIAL DIAGNOSIS

• Toxicologic causes of mental status depression are numerous, including benzodiazepines, valproic acid, carbamazepine, ethanol, and opiates.
• Nontoxicologic causes include hypoglycemia, hypothermia, intracranial bleed or infection, hyponatremia or other electrolyte disorders, and hypoxia.

SIGNS AND SYMPTOMS

• The primary effect of intoxication is CNS depression.

Vital Signs

Hypotension, hypothermia, and apnea can occur.

HEENT

Nystagmus is common and may occur at therapeutic levels.

Dermatologic

Bullae may occur over pressure areas during coma.

Cardiovascular

• Hypotension is common with intravenous administration.
• Rapid infusion of phenobarbital may result in hypotension due to the propylene glycol diluent.

Pulmonary

Apnea occurs in a doserelated fashion.

Gastrointestinal

Idiosyncratic hepatitis has been reported.

Genitourinary

Massive crystalluria with proteinuria and hematuria has been reported with primidone ingestion.

Musculoskeletal

Rhabdomyolysis and compartment syndrome may occur from external pressure during coma.

Neurologic

• Ataxia, nystagmus, hyporeflexia, and somnolence occur initially and may occur at therapeutic levels.
• As levels of barbiturate increase, stupor and coma develop.

Endocrine

Hypoglycemia has been reported.

PROCEDURES AND LABORATORY TESTS

Essential Tests

Serum phenobarbital level should be checked if phenobarbital or primidone is the suspected toxicant.

Recommended Tests

• Pulse oximetry or arterial blood gases should be monitored to evaluate oxygenation in patients with CNS depression.
• Serum electrolytes, BUN, creatinine, and glucose should be assayed in patients with altered mental status.
• Serum creatine kinase should be checked to assess muscle injury in patients with prolonged coma.
• ECG, serum acetaminophen, and aspirin levels should be performed in an overdose setting to screen for occult ingestion.
• Head CT, lumbar puncture, bacterial cultures, and other tests should be performed in patients with altered mental status of unknown etiology.

Section Outline:

• DIFFERENTIAL DIAGNOSIS
• SIGNS AND SYMPTOMS
  • Vital Signs
  • HEENT
  • Dermatologic
  • Cardiovascular
  • Pulmonary
  • Gastrointestinal
  • Genitourinary
  • Musculoskeletal
  • Neurologic
  • Endocrine
• PROCEDURES AND LABORATORY TESTS
  • Essential Tests
  • Serum phenobarbital level
  • Recommended Tests

• Treatment should focus on airway management, decontamination, and supportive care.
• 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:

• Coma or other severe effects are present.
• Toxic effects are not consistent with barbiturate intoxication.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

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

• Increased somnolence or other severe effects are present.
• Attempted suicide or homicide is possible.
• Patient or caregiver seems unreliable.
• Toxic effects are not consistent with barbiturate intoxication.
• Coingestant, drug interaction, or underlying disease presents an unusual problem.

Admission Considerations

Inpatient management is warranted if patients cannot care for themselves (e.g., ataxia, confusion) or have increasing phenobarbital levels following decontamination.

DECONTAMINATION

Out of Hospital

Emesis should not be induced.

In Hospital

• Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients for large ingestion presenting within 1 hour of ingestion or if serious effects are present.
• One dose of activated charcoal (1-2 g/kg) should be administered if a substantial ingestion has occurred within the previous few hours.

ANTIDOTES

There is no specific antidote for barbiturate poisoning.

ADJUNCTIVE TREATMENT

• Urinary alkalinization using sodium bicarbonate is sometimes employed in cases of phenobarbital intoxication.
• Urinary alkalinization increases phenobarbital clearance, but improved clinical outcomes (shortened duration of coma) have not been demonstrated; alkalinization does not increase clearance of other barbiturates.

Sodium Bicarbonate

• Adult
  • Initial dose of sodium bicarbonate is one to two ampules (44 or 50 mEq per ampule) administered in an intravenous push.
  • This should be followed by two to three ampules of sodium bicarbonate mixed in 1 L of D5W, infused at 200 ml/h.
  • Urinary pH should be monitored hourly; the infusion rate should be increased within clinically reasonable boundaries to produce a urinary pH above 7.5.
• Pediatric
  • Initial dose of sodium bicarbonate is 1 to 2 mEq/kg by intravenous push.
  • This should be followed by one or two ampules of sodium bicarbonate (44 or 50 mEq per ampule) mixed in 1 L D5W, infused at a rate within clinically reasonable boundaries starting at 1.5 to 2.0 times the maintenance rate and adjusted to maintain the urinary pH above 7.5.
• The clinician should consider underlying medical conditions such as congestive heart failure, myocardial ischemia, and renal insufficiency when determining the infusion rate.
• Urinary alkalinization should continue until the patient has demonstrated clinical improvement.
• Supplemental potassium should be administered if the serum level is below 4.0 mEq/L.

Multiple-dose Activated Charcoal

• Phenobarbital clearance is increased by activated charcoal, but has not been shown to alter outcome; it does not increase clearance of other barbiturates.
• A typical treatment regimen is 25 to 50 g (0.5-1.0 g/kg) of activated charcoal orally every 2 to 4 hours.
• A cathartic can be administered with the first dose only.
• Activated charcoal should be discontinued if ileus or obstruction develops, if patient is not passing charcoal stools, or when phenobarbital level (in this instance of phenobarbital ingestion) falls below 45 µg/ml.

Hypotension

Hypotension following barbiturate poisoning should be treated in the standard manner, starting with rapid infusion of 10 to 20 ml/kg of 0.9% saline.

Charcoal Hemoperfusion or Hemodialysis

The clearance of phenobarbital is increased by these procedures, but because of the significant complication rate, these techniques are recommended only for persistent hypotension; in addition, they do not increase clearance of other barbiturates.

Section Outline:

• DIRECTING PATIENT COURSE
  • Admission Considerations
• DECONTAMINATION
  • Out of Hospital
  • In Hospital
• ANTIDOTES
• ADJUNCTIVE TREATMENT
  • Sodium Bicarbonate
  • Multiple-dose Activated Charcoal
  • Hypotension
  • Charcoal Hemoperfusion or Hemodialysis

PATIENT MONITORING

Patient should be monitored continuously for cardiac rhythm, oxygenation, and for complications of coma and aspiration.

EXPECTED COURSE AND PROGNOSIS

• Toxicity develops early; prolonged coma that resolves over several days may follow a large overdose.
• Sequelae of hypoxia, aspiration, and pressure necrosis of the skin and muscle may develop.

DISCHARGE CRITERIA/INSTRUCTIONS

• From the emergency department. Patients with improving symptoms and decreasing barbiturate levels may be discharged following gastrointestinal decontamination, a 4- to 6-hour observation period, and psychiatric evaluation, if needed.
• From the hospital. Patients with decreasing levels and good ambulation may be discharged with therapeutic antiseizure medications, if indicated.

Section Outline:

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

DIAGNOSIS

Failure to evaluate other causes of altered mental status is a common error.

TREATMENT

Failure to provide early aggressive airway management can lead to increased risk of aspiration or respiratory failure.

FOLLOW-UP

Failure to demonstrate decreasing levels and good ambulation prior to discharge may allow a patient to be discharged prematurely.

Section Outline:

• DIAGNOSIS
• TREATMENT
• FOLLOW-UP

Poisoning by sedatives and hypnotics: barbiturates.

See Also: SECTION II, Hypotension chapter; and SECTION III, Activated Charcoal and Sodium Bicarbonate chapters.

RECOMMENDED READING

Poisindex Editorial Staff. Long-acting barbiturates. In: Rumack BR, Sayers NK, Gelman CL, eds. POISINDEX System. Englewood, CO: Micromedex, Inc. (Edition expires November 30, 1997).

Author: Kennon Heard

Reviewer: Katherine M. Hurlbut