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Introduction

  1. Pharmacology. Pentobarbital is a short-acting barbiturate with anticonvulsant as well as sedative-hypnotic properties. It is used as a third-line drug in the treatment of status epilepticus. It also may reduce intracranial pressure in patients with cerebral edema by inducing vasoconstriction. After intravenous administration of a single dose, the onset of effect occurs within about 1 minute and lasts about 15 minutes. After intramuscular administration, the onset of effect is slower (10-15 minutes). Pentobarbital demonstrates a biphasic elimination pattern; the half-life of the initial phase is 4 hours, and the terminal phase half-life is 35-50 hours. Effects are prolonged after termination of a continuous infusion.
  2. Indications
    1. Status epilepticus unresponsive to conventional anticonvulsant therapy (eg, diazepam, phenytoin, or phenobarbital).
    2. Elevated intracranial pressure, in conjunction with other agents.
    3. Suspected alcohol or sedative-hypnotic drug withdrawal syndrome.
    4. Stimulant-induced agitation and sympathomimetic symptoms refractory to benzodiazepines.
  3. Contraindications
    1. Known sensitivity to the drug.
    2. Manifest or latent porphyria.
  4. Adverse effects
    1. Central nervous system depression, coma, and respiratory arrest may occur, especially with rapid bolus or excessive doses.
    2. Hypotension may result, especially with rapid intravenous infusion (>50 mg/min). This may be caused by the drug itself or the propylene glycol diluent.
    3. Laryngospasm and bronchospasm have been reported after rapid intravenous injection, although the mechanism is unknown.
    4. Parenteral solutions are highly alkaline, and precautions need to be taken to avoid extravasation. Intra-arterial infusions may cause vasospasms and gangrene. Subcutaneous administration may cause necrosis and is not recommended.
    5. Use in pregnancy. FDA Category D (possible fetal risk). Pentobarbital readily crosses the placenta, and chronic use may cause hemorrhagic disease of the newborn (owing to vitamin K deficiency) or neonatal dependency and withdrawal syndrome. However, these potential effects do not preclude its acute, short-term use in a seriously symptomatic patient (Introduction).
  5. Drug or laboratory interactions
    1. Pentobarbital has additive CNS and respiratory depressant effects when used with other sedative-hypnotic agents.
    2. Hepatic enzyme induction may occur within 24-48 hours.
  6. Dosage and method of administration
    1. Intermittent intravenous bolus. Give 100 mg IV slowly over at least 2 minutes; repeat as needed at 2-minute intervals to a maximum dose of 300-500 mg (children: 1-3 mg/kg IV, repeated as needed to a maximum total of 5-6 mg/kg or 150-200 mg).
    2. Intramuscular. Inject 150-200 mg (children: 2-6 mg/kg IM, not to exceed 100 mg) into a large muscle mass (preferably the upper outer quadrant of the gluteus maximus). No more than 5 mL should be administered at an injection site.
    3. Continuous intravenous infusion. Note: Monitor blood pressure and provide airway and ventilatory support as needed.
      1. Low-dose regimen: Administer a loading dose of 5-6 mg/kg IV over 1 hour (not to exceed 50 mg/min; children: 1 mg/kg/min), followed by a maintenance infusion of 0.5-3 mg/kg/h titrated to the desired effect.
      2. For treatment of refractory status epilepticus, give a loading dose of 5-15 mg/kg by IV infusion over 1-2 hours (may give an additional 5-10 mg/kg bolus), followed by a maintenance infusion of 0.5-5 mg/kg/h. If breakthrough seizures occur, administer an additional 5 mg/kg bolus and increase the infusion rate by 0.5-1 mg/kg/h every 12 hours. Note: allow a period of at least 24-48 hours of seizure control before withdrawing the continuous infusion.
      3. For barbiturate coma in severe head trauma with elevated intracranial pressure, give a loading dose of 10 mg/kg IV over 30 minutes, then 5 mg/kg/h for 3 hours, followed by a maintenance infusion of 1-5 mg/kg/h titrated to maintain burst suppression on EEG (burst suppression usually occurs with a serum pentobarbital concentration of 25-40 mg/L).
    4. Oral. For treatment of barbiturate or other sedative-drug withdrawal syndrome, give 200 mg orally, repeated every hour until signs of mild intoxication appear (eg, slurred speech, drowsiness, and nystagmus). Most patients respond to 600 mg or less. Repeat the total initial dose every 6 hours as needed. Phenobarbital is an alternative (see below).