Understanding Pentobarbital Sodium: A Comprehensive Guide to Its Uses, Dosages, and Side Effects

Understanding Pentobarbital Sodium is a powerful drug that has been used for a variety of medical purposes since the 1930s. It is a barbiturate, meaning it depresses the central nervous system and induces sedation, making it useful for anesthesia, sleep disorders, and even euthanasia. But like any powerful drug, pentobarbital sodium can be dangerous when used improperly.

Key Indications

Pentobarbital is approved for:

• Sedation/Hypnosis: Short-term treatment of insomnia or pre-anesthesia.
• Seizures: Management of status epilepticus, eclampsia, tetanus, and toxic reactions (e.g., strychnine poisoning).
• Off-Label Uses: Barbiturate coma for severe brain injury or elevated intracranial pressure (ICP).

What is Pentobarbital Sodium?

Pentobarbital sodium is a white, crystalline powder that is usually administered as an injection. It belongs to the class of drugs known as barbiturates, which were first introduced in the early 1900s and quickly gained popularity as sedatives and anesthetics.

Today, pentobarbital sodium is most commonly used as a short-acting sedative or anesthetic, although it can also be used to treat sleep disorders or as part of a euthanasia protocol.

Uses of Pentobarbital Sodium

Sedation and Anesthesia

One of the most common uses of pentobarbital sodium is as a sedative or an anesthetic. It is often used in hospital settings to help patients relax before surgery or other medical procedures. In low doses, it can also be used to treat insomnia or other sleep disorders.

Euthanasia

Pentobarbital sodium is also used as part of a euthanasia protocol for animals and humans. In these cases, the drug is administered at a much higher dose than for sedation or anesthesia, causing rapid and painless death.

Seizure Management

In some cases, pentobarbital sodium can be used to manage seizures in patients who have not responded to other treatments. This is typically reserved for severe cases, as the drug can have serious side effects.

Dosages of Pentobarbital Sodium

Note: Doses vary by indication, age, and clinical context. Always adjust for renal/hepatic impairment.

For sedation or anesthesia, the typical dosage is between 100-300 milligrams, depending on the patient’s weight and other factors. For euthanasia, the dosage is much higher, usually between 1-5 grams.

It’s important to note that pentobarbital sodium is a powerful drug that can be dangerous when used improperly. Only trained medical professionals should administer the drug, and patients should be closely monitored for signs of adverse reactions.

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 the infusion rate by 0.5 to 1 mg/kg/hour every 12 hours.

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 a 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 the hourly rate may be given every 2 hours as needed.
• If ≥4 to 6 boluses are administered within 24 hours, then increase the 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 the 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.
• 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 Sodium

As with any medication, pentobarbital sodium can cause side effects. Some of the most common side effects include:

• Drowsiness
• Dizziness
• Headache
• Nausea and vomiting
• Confusion
• Respiratory depression

In rare cases, pentobarbital sodium can also cause more serious side effects, such as:

• Allergic reactions
• Seizures
• Coma
• Cardiac arrest

Patients who are taking pentobarbital sodium should be closely monitored for any signs of adverse reactions, and medical attention should be sought immediately if any serious side effects occur.

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

  • Intravenous 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

Risk Factor C (Monitor therapy)
Alcohol (Ethyl)	CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl).
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Beta-Blockers	Barbiturates may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol.
Blood Pressure Lowering Agents	The hypotensive effects of blood pressure-lowering medications may be strengthened by barbiturates.
Brexanolone	Brexanolone’s CNS-depressing effects may be amplified by other CNS depressants.
Brimonidine (Topical)	CNS depressants may have an enhanced CNS depressant impact.
Bromopride	CNS depressants may have an enhanced CNS depressant impact.
Calcium Channel Blockers	Calcium Channel Blockers’ metabolism may be accelerated by barbiturates. Management: Keep an eye out for any diminished therapeutic effects of barbiturate medication when concurrently using calcium channel blockers. There may need to be dose modifications with calcium channel blockers. The concomitant use of phenobarbital and nimodipine is not recommended. Clevidipine is an exception.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
Dimethindene (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Doxylamine	May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Felbamate	May raise the level of barbiturates in the blood. Barbiturates may lower the level of felbamate in the serum. Management: If felbamate is started or the dose is increased, keep an eye out for increased barbiturate concentrations and toxicity or lowered concentrations and effects. For patients using phenobarbital, consult the recommended dosage schedule.
Griseofulvin	Barbiturates may lower the level of griseofulvin in the blood.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Lofexidine	May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirtazapine	CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
Multivitamins/Minerals (with ADEK, Folate, Iron)	May lower the level of barbiturates in the blood.
Nabilone	CNS depressants may have an enhanced CNS depressant impact.
Piribedil	Piribedil’s CNS-depressing effects may be enhanced by other CNS depressants.
Pramipexole	The sedative effects of pramipexole might be enhanced by CNS depressants.
Primidone	May intensify the hazardous or harmful effects of barbiturates. Primidone is metabolised to phenobarbital, making it a barbiturate treatment addition.
Propacetamol	Barbiturates may speed up Propacetamol’s metabolism. This could both reduce the intended effects of propacetamol and raise the danger of liver damage.
Pyridoxine	Barbiturates’ metabolism could be accelerated. It is possible that high pyridoxine doses (200 mg/day, for example) will speed up the metabolism of barbiturates.
ROPINIRole	The sedative effects of CNS depressants may increase those of ROPINIRole.
Rotigotine	Rotigotine’s sedative effects may be boosted by CNS depressants.
Rufinamide	CNS depressants’ harmful or toxic effects could be increased.
Selective Serotonin Reuptake Inhibitors	Selective serotonin reuptake inhibitors may have a worsened or more hazardous effect when taken with CNS depressants. Particularly, there may be an increased risk of psychomotor impairment.
Tetrahydrocannabinol	CNS depressants may have an enhanced CNS depressant impact.
Tetrahydrocannabinol and Cannabidiol	CNS depressants may have an enhanced CNS depressant impact.
Theophylline Derivatives	Barbiturates may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline.
Thiazide and Thiazide-Like Diuretics	Barbiturates may enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Valproate Products	May increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Valproate Products.
Risk Factor D (Consider therapy modification)
Blonanserin:	NS Depressants may enhance the CNS depressant effect of Blonanserin.
Buprenorphine	CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants and avoid such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.
Chloramphenicol (Systemic)	May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol (Systemic).
Chlormethiazole	May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used.
CycloSPORINE (Systemic)	Barbiturates may increase the metabolism of CycloSPORINE (Systemic).
Doxycycline	Barbiturates may lower the level of Doxycycline in the blood.
Droperidol	CNS depressants may have an enhanced CNS depressant impact. Consider lowering the dosage of droperidol or other CNS drugs (such as opioids or barbiturates) when they are used concurrently. In separate drug interaction monographs, exceptions to this monograph are covered in more detail.
Estrogen Derivatives (Contraceptive)	Estrogen derivatives’ therapeutic effects may be lessened by barbiturates (Contraceptive). Failure with contraception is possible. Use of a non-hormonal contraception is advised for management.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
HydrOXYzine	May enhance the CNS depressant effect of Barbiturates. Management: Consider a decrease in the barbiturate dose, as appropriate, when used together with hydroxyzine. With concurrent use, monitor patients closely for excessive response to the combination.
LamoTRIgine	Barbiturates may lower the level of LamoTRIgine in the blood. Management: For precise age-dependent dosing instructions on the use of a barbiturate in conjunction with another substance, as well as information on how to alter lamotrigine dosage if concurrent barbiturate therapy is stopped, refer to the prescribing information for lamotrigine.
Mefloquine	May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of other CNS Depressants. Management: Reduce the adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after a clinically effective methotrimeprazine dose is established.
Opioid Agonists	CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Progestins (Contraceptive)	Barbiturates may diminish the therapeutic effect of Progestins (Contraceptive). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
Suvorexant	CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug.
Teniposide	Teniposide’s serum levels may drop if you use barbiturates. Management: Because of the possibility of decreasing teniposide concentrations, consider alternatives to combined treatment with barbiturates and teniposide. If the combination must be used, keep a watchful eye on the teniposide response.
Tricyclic Antidepressants	Tricyclic Antidepressants’ metabolism may be accelerated by barbiturates. Barbiturates may speed up the metabolism of substances that block vitamin K. Management: Pay closer attention to INR. After a barbiturate is started or given at a higher dose, it may be necessary to raise the dosage of an anticoagulant.
Vitamin K Antagonists (eg, warfarin)	Following barbiturate withdrawal or dose reduction, anticoagulant dose reductions may be required.
Zolpidem	The CNS-depressant action of zolpidem may be enhanced by CNS depressants. Men with additional CNS depressants should lower their sublingual zolpidem dose to 1.75 mg under the Intermezzo brand. Such a dose change is not advised.
Risk Factor X (Avoid combination)
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Benznidazole	May enhance the adverse/toxic effect of Products Containing Propylene Glycol.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Hemin	Barbiturates may diminish the therapeutic effect of Hemin.
Methoxyflurane	Barbiturates may intensify Methoxyflurane’s nephrotoxic effects. Barbiturates may speed up methoxyflurane’s metabolism.
MetroNIDAZOLE (Systemic)	The negative or hazardous effects of products containing propylene glycol may be increased. There could be a reaction like disulfiram.
Mianserin	May intensify barbiturates’ CNS depressive effects. Barbiturates’ therapeutic effects may be lessened by minaserin. Barbiturates may lower the Mianserin serum levels.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Somatostatin Acetate	May enhance the adverse/toxic effect of Barbiturates.
Thalidomide	The CNS-depressant effect of thalidomide may be enhanced by CNS depressants.
Ulipristal	Barbiturates may lower Ulipristal’s serum levels.

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, and EEG

How to administer Pentobarbital?

Intramuscular:

• Inject into a large muscle.
• 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.e
• 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, affect cerebellar function, and lead to drowsiness or sedation.
• Higher doses of barbiturates have anticonvulsant effects.
• Higher doses can cause respiratory depression due to their ability to reduce brain metabolism and cerebral blood flow.

Action in Children and Adults Sedation can occur in between 10 and 15 minutes following an intravenous injection, 3 – 5 minutes after intravenous injection, and 15 – 60 minutes after intravenous injection. 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 the 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.t Excretion: Urine (<1%, as unchanged drug)

International Brands of Pentobarbital:

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

Conclusion

Pentobarbital sodium is a powerful drug that has been used for a variety of medical purposes for decades. It can be an effective sedative or anesthetic when used properly, and it has also been used