Pentobarbital is a short-acting barbiturate drug that inhibits the neuronal activity. It is used to treat patients with seizures and insomnia. It may cause respiratory paralysis and death if given in high doses or if the patient is not monitored when the drug is given especially after the drug is administered intravenously. It should be avoided with concomitant hypnotics and sedatives.

Indications of Pentobarbital:

• Sedative/ hypnotic/ pre-anesthesia:

  •  It is used for short term treatment of insomnia or as pre-anesthesia.

• Seizures:

  • It is indicated for the management of status epilepticus, cholera, eclampsia, meningitis, tetanus, toxic reactions to strychnine or local anesthetics.

• Off Label Use of Pentobarbital in Adults:

  • Barbiturate coma in severe brain injury patients/elevated intracranial pressure.

Pentobarbital dose in adults:

Note: Adjust dose based on the patient's age, weight, and condition.

Pentobarbital dose in the treatment of Sedative/ hypnotic/ pre-anesthesia:

• 150 to 200 mg intramuscular as a single dose.
• Initial: 100 mg intravenous if needed, may administer additional increments after at least 1 minute, up to a total dose of 200 to 500 mg.

Pentobarbital Dose in Seizures:

Note:

Mechanical ventilation and cardiovascular monitoring required; Titrate the dose until the cessation of electrographic seizures or burst suppression.

• Pentobarbital Neurocritical Care Society recommendations:

  • Loading dose:

    • 5 to 15 mg/kg administered at a rate of ≤50 mg/minute, may give an additional 5 to 10 mg/kg with a continuous infusion.

  • Continuous infusion:

    • 5 to 5 mg/kg/hour.
    • If the patient experiences breakthrough status epilepticus while on continuous infusion, administer an additional 5 mg/kg bolus and increase infusion rate by 0.5 to 1 mg/kg/hour every 12 hours.

Note:

Before withdrawing continuous infusion, electrographic control is recommended for at least 24 to 48 hours, and it should be slowly withdrawn to prevent recurrent status epilepticus.

Barbiturate coma in severe brain injury patients and elevated intracranial pressure (off-label):

• Loading dose:

  • 10 mg/kg intravenous given over 30 minutes (or ≤25 mg/minute), followed by 5 mg/kg every hour for 3 doses, monitor blood pressure and respiratory rate.

• Maintenance infusion:

  • 1 mg/kg/hour initially;
  • The dose may be increased to 2 to 4 mg/kg/hour to maintain burst suppression on EEG.

Pentobarbital dose in children:

Note:

Consider the potential for delayed metabolism or elimination in infants <6 months of age.

Pentobarbital Dose in the Hypnotic:

• Children:

  • 2 to 6 mg/kg intramuscular
  • The maximum dose: 100 mg/dose.
  • Note: Use has generally been replaced by other agents.

Pentobarbital Dose in the Preoperative sedation:

Note:

Use has generally been replaced by other agents.

Infants and Children:

• 2 to 6 mg/kg intramuscular
• The maximum dose is 100 mg/dose.
• 1 to 3 mg/kg intravenous every 10 minutes up to a maximum total dose of 6 mg/kg, not to exceed a total dose of 100 mg.

Pentobarbital Dose in the Procedural sedation:

Note: Use has generally been replaced by other agents.

• Infants and Children:

  • 2 to 6 mg/kg intramuscular.
  • The maximum dose is 100 mg/dose.

• Infants and Children:

  • 1 to 2 mg/kg intravenous initially, additional doses of 1 to 2 mg/kg every 3 to 5 minutes to the desired effect.
  • The usual effective total dose is 1 to 6 mg/kg.
  • The maximum total dose is 100 mg/dose.
  • Note: Patients receiving concurrent barbiturate therapy may require higher total mg/kg doses (up to 9 mg/kg).

• Adolescents:

  • 100 mg

• Oral: Limited data available:

  • Infants:

    • 4 mg/kg/dose per oral, if needed supplemental 2 to 4 mg/kg/dose every 30 minutes.
    • The maximum total dose is 8 mg/kg.

  • Children:

    • <4 years:

      • 3 to 6 mg/kg per oral.
      • The maximum dose is 100 mg/dose.

    • ≥4 years:

      • 1.5 to 3 mg/kg per oral.
      • The maximum dose is 100 mg/dose.

• Rectal: Limited data available:

  • Children:

    • <4 years:

      • 3 to 6 mg/kg;
      • The maximum dose is 100 mg

    • ≥4 years:

      • 5 to 3 mg/kg;
      • The maximum dose is 100 mg

Pentobarbital Dose in the Reduction of elevated ICP:

Note:

Intubation is required. The dose is adjusted according to hemodynamics, ICP, cerebral perfusion pressure, and EEG.

• Low dose:

  • Children and Adolescents:

    • 5 mg/kg intravenous every 4 to 6 hours.

• High-dose pentobarbital coma:

  • Children and Adolescents:

    • Loading dose: 10 mg/kg intravenous over 30 minutes, then 5 mg/kg every hour for 3 hours;
    • The initial maintenance infusion is 1 mg/kg/hour;
    • Adjust the dose to maintain burst suppression on EEG;
    • The maintenance dose range: 1 to 2 mg/kg/hour.

Dose in the Sedation of mechanically ventilated ICU patient (who failed standard therapy):

• Loading dose: 1 mg/kg intravenous followed by 1 mg/kg/hour infusion.
• Additional boluses at a dose equal to hourly rate may be given every 2 hours as needed.
• If ≥4 to 6 boluses are administered within 24 hours, then increase maintenance rate by 1 mg/kg/hour;
• The reported required range: 1 to 6 mg/kg/hour (median: 2 mg/kg/hour).
• Tapering of dose and/or conversion to oral phenobarbital has been reported for therapy ≥5 days.

Note:

Higher loading and initial maintenance doses are known to cause increased chances of adverse effects.

Pentobarbital dose in the treatment of refractory Status epilepticus:

Note:

Mechanical ventilation and cardiovascular monitoring required; titrate the dose to the cessation of electrographic seizures or burst suppression.

• Infants, Children, and Adolescents:

  • Loading dose: 5 mg/kg intravenous;
  • maintenance infusion: 1 mg/kg/hour initially;
  • The dose may be increased up to 3 mg/kg/hour (usual range: 1 to 3 mg/kg/hour);
  • Maintain burst suppression on EEG for 24 to 48 hours (no seizure activity), tapering pentobarbital rate by 0.5 mg/kg every 12 hours has been reported.

• High-dose pentobarbital coma:

  • Infants and Children:

    • Loading dose: 10 to 15 mg/kg  intravenous given slowly over 1 to 2 hours;
    • monitor blood pressure and respiratory rate.
    • Maintenance infusion: Initial: 1 mg/kg/hour;
    • The dose may be increased up to 5 mg/kg/hour (usual range: 0.5 to 5 mg/kg/hour);
    • Maintain burst suppression on EEG;
    • If the patient experiences breakthrough status epilepticus while on continuous infusion, administer an additional 5 mg/kg bolus and increase infusion rate by 0.5 to 1 mg/kg/hour every 12 hours until burst suppression.

Note: Loading doses of 20 to 35 mg/kg (given over 1 to 2 hours) have been utilized in pediatric patients for pentobarbital coma, but these higher loading doses often cause hypotension requiring vasopressor therapy.

Pregnancy Risk Factor D

• If used during pregnancy, barbiturates may cross the placenta. They can be seen in the fetal liver or fetal brain. This could lead to an increase in the incidence of fetal abnormalities.
• If given in the final trimester, it will decrease the frequency of uterine cramps.
• Neonatal neonates can experience withdrawal symptoms such as seizures and hyperirritability if pentobarbital has been given to the mother during the third trimester.
• Pentobarbital can cause respiratory depression in newborns if mothers are given it, especially in premature infants.

Use of pentobarbital while breastfeeding

• Breast milk contains barbiturates.
• Pentobarbital should not be administered to nursing mothers.

Dose adjustment in renal disease:

The manufacturer's labeling does not include any dosage adjustments. Dose reduction is possible.

Notice:Patients on pentobarbital are more likely to experience severe reactions to propylene glycol, especially if their treatment is extended or they are taking greater doses.

Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling. However dose reduction is required.

Side effects of Pentobarbital:                                 

• Cardiovascular:

  • Bradycardia
  • Hypotension
  • Syncope

• Central Nervous System:

  • Abnormality In Thinking
  • Agitation
  • Anxiety
  • Ataxia
  • Central Nervous System Stimulation
  • Confusion
  • Depression
  • Dizziness
  • Drowsiness
  • Hallucination
  • Headache
  • Insomnia
  • Nervousness
  • Nightmares
  • Psychiatric Disturbance

• Dermatologic:

  • Exfoliative Dermatitis
  • Skin Rash

• Gastrointestinal:

  • Constipation
  • Nausea
  • Vomiting

• Hematologic & Oncologic:

  • Megaloblastic Anemia

• Hepatic:

  • Hepatotoxicity

• Hypersensitivity:

  • Angioedema
  • Hypersensitivity Reaction

• Local:

  • Injection Site Reaction

• Neuromuscular & Skeletal:

  • Hyperkinesia
  • Laryngospasm

• Respiratory:

  • Apnea (Especially With Rapid IV Use)
  • Hypoventilation
  • Respiratory Depression

• Miscellaneous:

  • Fever

Contraindications to Pentobarbital:

• Hypersensitivity to barbiturates and any component of the formulation
• Porphyria

Warnings and precautions

• Depression in the CNS:

  • CNS depression can result, which could impair mental or physical abilities. Therefore, it is important to be cautious when operating machinery or driving.

• Respiratory depression

  • Intrachenous pentobarbital may cause respiratory depression so it is important to be careful.
  • Management of seizures and traumatic brain injuries requires intubation.

• Depression

  • You should not use it if you are suffering from depression or suicidal tendencies.

• Hepatic impairment

  • Hepatic impairment requires caution and dose reduction. Avoid it in the case of hepatic impairment.

• Renal impairment

  • Patients with impaired renal function should exercise caution and reduce their doses.

• Substance abuse

  • Pentobarbitol can be addictive and cause dependence in patients who have been abused.

Pentobarbital: Drug Interaction

Monitoring parameters:

• BP
• Renal function tests/BUN
• Serum lactate
• Cardiovascular status
• CNS status
• Osmolal gap
• Respiratory status (for conscious sedation, includes pulse oximetry)
• clinical signs of propylene glycol toxicity (with long term therapy).

Barbiturate coma:

• Monitor oxygenation as well as arterial and central venous pressures to guide fluid and vasoactive therapy for maintenance of blood pressure; temperature

Elevated ICP:

• Monitor ICP, CPP, EEG

How to administer Pentobarbital?

Intramuscular:

• Inject into a large muscular.
• Because of potential tissue irritation, no more than 5mL (250mg) should be injected at one site.

Intravenous

• You can give IV push doses undiluted but the maximum dose should not exceed 50mg/minute
• Because parenteral solutions can be very alkaline, intra-arterial injections should not be used.

Extravasation management

• You should stop the infusion immediately and disconnect it.
• It is important to slowly aspirate the extravasated solution without flushing it.
• It is important to remove the needle and elevate the limb. Warm compresses are recommended.

Mechanism of action of Pentobarbital:

• Barbiturates depress the sensory cortex, decrease motor activity, alter the cerebellar function, and lead to drowsiness or sedation.
• Higher doses of barbiturates have anticonvulsant effects. 
• Higher doses can cause respiratory depression due to its ability to reduce brain metabolism and cerebral bloodflow.

Action in cHildren and Adults Sedation can occur in between 10 and 15 minutes following an intravenous injection, 3 – 5 minutes after intravenous injectables, and 15 – 60 minutes after intravenous injections. Time: For Children and Adults The sedation following an IM injection can last for up to 2 hours. It will also last 15 to 45 minutes after an IV infusion. Protein binding: 45% to 70% Metabolism:Occurs in liver via hydroxylation and glucuronidation. Terminal Half-life elimination: Children: 26 ± 16 hours. Healthy Adults: 22 hours (average) Range: 15 to 50 hours and is dose dependent Excretion: Urine (<1%, as unchanged drug)

International Brands of Pentobarbital:

• Nembutal
• Dormital
• Entobar
• Medinox Mono
• Nembutal
• Pentone
• Praecicalm
• Prodormol
• Sombutol
• Sopental

Pentobarbital Brand Names in Pakistan:

Brands in Pakistan will be updated later.