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Pronunciation
(pen toe BAR bi tal)
Generic Available (U.S.)
No
Index Terms
Controlled Substance
C-II
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Sedative/hypnotic; refractory status epilepticus
Use: Unlabeled
Barbiturate coma in patients with severe brain injury (eg, hemorrhagic stroke, traumatic brain injury) and increased intracranial pressure
Pregnancy Risk Factor
D
Pregnancy Considerations
Barbiturates can be detected in the placenta, fetal liver and fetal brain. Fetal and maternal blood concentrations may be similar following parenteral administration. An increased incidence of fetal abnormalities may occur following maternal use. When used during the third trimester of pregnancy, withdrawal symptoms may occur in the neonate including seizures and hyperirritability; symptoms may be delayed up to 14 days. Use during labor does not impair uterine activity; however, respiratory depression may occur in the newborn; resuscitation equipment should be available, especially for premature infants.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Small amounts of barbiturates are found in breast milk.
Contraindications
Hypersensitivity to barbiturates or any component of the formulation; porphyria
Warnings/Precautions
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension: May cause hypotension particularly when administered intravenously; use with caution in hemodynamically unstable patients (hypotension or shock). High doses used to induce pentobarbital coma cause hypotension requiring vasopressor therapy.
• Respiratory depression: May cause respiratory depression particularly when administered intravenously; use with caution in patients with respiratory disease. Intubation is typically required prior to treatment for status epilepticus or traumatic brain injury.
Disease-related concerns:
• Depression: Use with caution in patients with depression or suicidal tendencies.
• Hepatic impairment: Use with caution in patients with hepatic impairment; reduce dose as appropriate. Do not use in patients with hepatic coma.
• Renal impairment: Use with caution in patients with renal impairment; reduce dose as appropriate.
• Substance abuse: Use with caution in patients with a history of drug abuse; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
Concurrent drug therapy issues:
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
Special populations:
• Debilitated patients: Use with caution in patients who are debilitated.
• Elderly: Use with caution in the elderly; closely monitor elderly or debilitated patients for impaired cognitive or motor performance. May be inappropriate in this age group due to increased risk for adverse effects and high addiction potential.
Dosage form specific issues:
• Alkaline solution: Solution for injection is highly alkaline and extravasation may cause local tissue damage.
• Propylene glycol toxicity: Intravenous solution may contain propylene glycol (PG). One case report has described a patient who developed lactic acidosis possibly secondary to PG accumulation following a continuous infusion of pentobarbital (Miller, 2008). Consider monitoring for signs of PG toxicity (eg, lactic acidosis, acute renal failure, osmol gap) in patients who require a continuous infusion of pentobarbital.
Other warnings/precautions:
• Acute pain: Do not administer to patients in acute pain; may heighten/worsen sense of pain.
• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Adverse Reactions
Frequency not defined.
Cardiovascular: Bradycardia, hypotension, syncope
Central nervous system: Abnormal thinking, agitation, anxiety, ataxia, CNS excitation, confusion, depression, dizziness, drowsiness, fever, hallucinations, headache, hyperkinesia, insomnia, nervousness, nightmares, psychiatric disturbances, somnolence
Dermatologic: Angioedema, exfoliative dermatitis, rash
Gastrointestinal: Constipation, nausea, vomiting
Hematologic: Megaloblastic anemia
Hepatic: Hepatotoxicity
Local: Injection site reactions
Respiratory: Apnea (especially with rapid I.V. use), hypoventilation, laryngospasm, respiratory depression
Miscellaneous: Gangrene with inadvertent intra-arterial injection, hypersensitivity reactions
Metabolism/Transport Effects
Induces CYP2A6 (strong), CYP3A4 (strong)
Drug Interactions
Acetaminophen: Barbiturates may increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double aripiprazole dose when initiating concomitant therapy with a CYP3A4 inducer (e.g., carbamazepine). Monitor response and adjust aripiprazole dose as clinically indicated. If CYP3A4 inducer is discontinued, reduce aripiprazole dose to 10-15 mg/day. Risk D: Consider therapy modification
Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. Risk X: Avoid combination
Beta-Blockers: Barbiturates may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. Risk C: Monitor therapy
Boceprevir: CYP3A4 Inducers (Strong) may decrease the serum concentration of Boceprevir. Management: Avoid strong CYP3A4 inducers with boceprevir when possible, and closely monitor response to boceprevir if such a combination cannot be avoided. Carbamazepine, phenytoin, phenobarbital, rifampin, and St. John's wort are considered contraindicated. Risk D: Consider therapy modification
Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Risk X: Avoid combination
Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor therapy
Calcium Channel Blockers: Barbiturates may increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Exceptions: Clevidipine. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of Anticonvulsants (Barbiturate). Specifically, osteomalacia and rickets. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
Chloramphenicol: May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol. Risk D: Consider therapy modification
Clarithromycin: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Contraceptives (Estrogens): Barbiturates may diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of a non-hormonal contraceptive is recommended. Risk D: Consider therapy modification
Contraceptives (Progestins): Barbiturates may diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: Consider therapy modification
Corticosteroids (Systemic): Barbiturates may decrease the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Risk X: Avoid combination
CycloSPORINE: Barbiturates may increase the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Barbiturates may increase the metabolism of CycloSPORINE (Systemic). Risk D: Consider therapy modification
CYP2A6 Substrates: CYP2A6 Inducers (Strong) may increase the metabolism of CYP2A6 Substrates. Risk C: Monitor therapy
CYP3A4 Substrates: CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Risk D: Consider therapy modification
Disopyramide: Barbiturates may increase the metabolism of Disopyramide. Risk C: Monitor therapy
Divalproex: May decrease the metabolism of Barbiturates. Barbiturates may decrease the serum concentration of Divalproex. Risk C: Monitor therapy
Doxycycline: Barbiturates may decrease the serum concentration of Doxycycline. Risk D: Consider therapy modification
Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Risk X: Avoid combination
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Etoposide: Barbiturates may decrease the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: Barbiturates may decrease the serum concentration of Etoposide Phosphate. Barbiturates may increase the metabolism, via CYP isoenzymes, of etoposide phosphate. Risk C: Monitor therapy
Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers, but if strong CYP3A4 inducers cannot be avoided, consider gradually (in 5 mg increments) increasing the everolimus dose from 10 mg/day to 20 mg/day (adult doses). Risk X: Avoid combination
Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane prescribing information recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity and/or inadequate clinical response. Risk D: Consider therapy modification
Felbamate: May increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Felbamate. Management: Monitor for elevated barbiturate concentrations/toxicity if felbamate is initiated/dose increased, or reduced concentrations/effects if felbamate is discontinued/dose decreased. Refer to phenobarbital dosing guidelines for patients receiving that agent. Risk C: Monitor therapy
Fosphenytoin: Barbiturates may enhance the CNS depressant effect of Fosphenytoin. Fosphenytoin may increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse drug reactions, consider increasing gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers. Carefully monitor clinical response and development of adverse reactions. Risk D: Consider therapy modification
Griseofulvin: Barbiturates may decrease the serum concentration of Griseofulvin. Risk C: Monitor therapy
GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Consider increasing the guanfacine dose (within the labeled dosage range) when such a combination is used. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m2 to 60 mg/m2 (given as a 4-hour infusion), as tolerated, should be considered. Risk D: Consider therapy modification
Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Ketorolac (Nasal): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Ketorolac (Systemic): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
LamoTRIgine: Barbiturates may decrease the serum concentration of LamoTRIgine. Management: See lamotrigine prescribing information for specific age-dependent dosing guidelines regarding concurrent use with a barbiturate, as well as for adjusting lamotrigine dosing if concurrent barbiturate therapy is discontinued. Risk D: Consider therapy modification
Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk X: Avoid combination
Linagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Linagliptin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Risk X: Avoid combination
Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with Clcr less than 30 mL/min. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Meperidine: Barbiturates may enhance the CNS depressant effect of Meperidine. Barbiturates may increase serum concentrations of the active metabolite(s) of Meperidine. Risk C: Monitor therapy
Methadone: Barbiturates may decrease the serum concentration of Methadone. Risk C: Monitor therapy
Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Risk X: Avoid combination
Pazopanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pazopanib. Risk X: Avoid combination
Phenytoin: May enhance the CNS depressant effect of Barbiturates. Phenytoin may increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Phenytoin. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Management: Avoid concomitant use of praziquantel with strong CYP3A4 inducers. Discontinue rifampin 4 weeks prior to initiation of praziquantel therapy. Rifampin may be resumed the day following praziquantel completion. Risk X: Avoid combination
Primidone: May enhance the adverse/toxic effect of Barbiturates. Primidone is converted to phenobarbital, and thus becomes additive with existing barbiturate therapy. Risk C: Monitor therapy
Propafenone: Barbiturates may decrease the serum concentration of Propafenone. Risk C: Monitor therapy
Pyridoxine: May increase the metabolism of Barbiturates. Apparent in high pyridoxine doses (eg, 200 mg/day) Risk C: Monitor therapy
QuiNIDine: Barbiturates may enhance the hepatotoxic effect of QuiNIDine. Barbiturates may decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Barbiturates. Risk C: Monitor therapy
Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. Risk X: Avoid combination
Roflumilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining strong CYP3A4 inducers with roflumilast. The Canadian product monograph makes no such recommendation but notes that such agents may reduce roflumilast therapeutic effects. Risk X: Avoid combination
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Risk X: Avoid combination
SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing sunitinib dose and monitor clinical response and toxicity closely. Risk D: Consider therapy modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider therapy modification
Teniposide: Barbiturates may decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Risk D: Consider therapy modification
Theophylline Derivatives: Barbiturates may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Thiazide Diuretics: Barbiturates may enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor. Risk X: Avoid combination
Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed. Risk X: Avoid combination
Toremifene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. Risk X: Avoid combination
Tricyclic Antidepressants: Barbiturates may increase the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Risk C: Monitor therapy
Valproic Acid: May decrease the metabolism of Barbiturates. Barbiturates may decrease the serum concentration of Valproic Acid. Risk C: Monitor therapy
Vandetanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Risk X: Avoid combination
Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Barbiturates may increase the metabolism of Vitamin K Antagonists. Risk D: Consider therapy modification
Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Storage
Store at controlled room temperature of 15°C to 30°C (68°F to 77°F); protect from freezing and avoid excessive heat. When mixed with an acidic solution, precipitate may form. Use only clear solution.
Compatibility
Stable in D5LR, D51/4NS, D51/2NS, D5NS, D10W, LR, 1/2NS; variable stability (consult detailed reference) in D5W, NS.
Y-site administration: Compatible: Acyclovir, insulin (regular), linezolid, propofol. Incompatible: Amphotericin B cholesteryl sulfate complex, fenoldopam.
Compatibility in syringe: Compatible: Aminophylline, ephedrine, hyaluronidase, hydromorphone, neostigmine, scopolamine, sodium bicarbonate, thiopental. Incompatible: Butorphanol, chlorpromazine, cimetidine, dimenhydrinate, diphenhydramine, droperidol, fentanyl, glycopyrrolate, hydroxyzine, meperidine, midazolam, nalbuphine, pentazocine, prochlorperazine edisylate, promethazine, ranitidine. Variable (consult detailed reference): Atropine, morphine.
Mechanism of Action
Barbiturate with sedative, hypnotic, and anticonvulsant properties. Barbiturates depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, and hypnosis. In high doses, barbiturates exhibit anticonvulsant activity; barbiturates produce dose-dependent respiratory depression; reduce brain metabolism and cerebral blood flow in order to decrease intracranial pressure
Pharmacodynamics/Kinetics
Onset of action: I.M.: 10-15 minutes (Krauss, 2006); I.V.: Almost immediate, within 3-5 minutes (Krauss, 2006)
Duration: I.V.: Variable
Distribution: Vd: Children: 0.8 L/kg (Schaible, 1982); Adults: 1 L/kg (Ehrnebo, 1974)
Protein binding: 45% to 70%
Metabolism: Hepatic via hydroxylation and glucuronidation (Wermeling, 1985)
Half-life elimination: Terminal: Children: 26 ± 16 hours (Schaible, 1982); Adults: Healthy: 22 hours (average; Ehrnebo, 1974); (range: 15-50 hours; dose dependent)
Excretion: Urine
Dosage
Note: Adjust dose based on patients age, weight, and condition.
Children:
Hypnotic/sedative:
I.M.: 2-6 mg/kg; maximum: 100 mg/dose
I.V.: 1-6 mg/kg titrated in 1-2 mg/kg increments every 3-5 minutes to desired effect (Krauss, 2006)
Refractory status epilepticus: I.V.: Note: Intubation required; adjust dose based on hemodynamics, seizure activity, and EEG. Various regimens available (Abend, 2008; Hanhan, 2001; Holmes, 1999; Kim, 2001):
Loading dose: 5-15 mg/kg given slowly over 1 hour; maintenance infusion: 0.5-5 mg/kg/hour to maintain burst suppression; continue for 12-48 hours of no seizure activity; may taper infusion rate by 0.5 mg/kg/hour every 12 hours
Adults:
Hypnotic/sedative:
I.M.: 150-200 mg
I.V.: Initial: 100 mg; decrease dose for elderly or debilitated patients. If needed, may administer additional increments after at least 1 minute, up to a total dose of 200-500 mg
Barbiturate coma in severe brain injury patients/elevated intracranial pressure (unlabeled use; Bratton, 2007): I.V.: Loading dose: 10 mg/kg 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: Initial: 1 mg/kg/hour; may increase to 2-4 mg/kg/hour; maintain burst suppression on EEG.
Refractory status epilepticus: I.V.: Note: Intubation required; adjust dose based on hemodynamics, seizure activity, and EEG. Various regimens available (Abou Khaled, 2008; Millikan, 2009; Mirski, 2008; Yaffe, 1993):
Loading dose: 10-15 mg/kg (5-10 mg/kg in patients with pre-existing hypotension) administer slowly over 1 hour; initial maintenance infusion: 0.5-1 mg/kg/hour; adjust to maintain burst suppression pattern on EEG; maintenance infusion dose range: 0.5-10 mg/kg/hour
Note: During active seizure activity when increasing maintenance infusion rate, some experts suggest administration of an additional 5 mg/kg bolus given the long half-life of pentobarbital.
Elderly: Not recommended for use in the elderly; decrease dose if use becomes necessary
Dosing adjustment in renal impairment: Reduce dosage in patients with renal dysfunction
Dosing adjustment in hepatic impairment: Reduce dosage in patients with liver dysfunction
Administration: I.M.
Pentobarbital may be administered by deep I.M.; inject into a large muscle. No more than 5 mL (250 mg) should be injected at any one site because of possible tissue irritation.
Administration: I.V.
Pentobarbital must be administered by slow I.V. injection. Do not exceed 50 mg/minute; I.V. push doses may be given undiluted. Parenteral solutions are highly alkaline; avoid extravasation; avoid intra-arterial injection.
Administration: I.V. Detail
pH: 9.5
Monitoring Parameters
Respiratory status (for conscious sedation, includes pulse oximetry), cardiovascular status, CNS status; cardiac monitor and blood pressure monitor required; temperature with high doses (eg, barbiturate coma)
Elevated ICP: Monitor ICP, CPP, EEG
Reference Range
Therapeutic:
Sedation: 1-5 mcg/mL (SI: 4-22 micromole/L)
Coma or intracranial pressure therapy: Target: 30-40 mcg/mL (SI: 132-176 micromole/L) (Bratton, 2007)
Potentially toxic: >10 mcg/mL (SI: >44 micromole/L); dependent on reason for use and patient condition
Patient Education
Patient instructions and information are determined by patient condition and therapeutic purpose.
Geriatric Considerations
Not recommended for use in the elderly; decrease dose if use becomes necessary.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: During induction of barbiturate coma for refractory status epilepticus or traumatic brain injury, patients require intubation as well as arterial and central venous monitoring to guide fluid and vasoactive therapy for maintenance of blood pressure. High-dose pentobarbital generally produces poikilothermia. High doses of barbiturates are potentially immunosuppressive.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Nursing: Physical Assessment/Monitoring
Keep patient under observation. Monitor cardio/respiratory status and institute patient safety precautions.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as sodium:
Nembutal®: 50 mg/mL (20 mL, 50 mL) [contains ethanol 10%, propylene glycol 40%]
References
Abend NS and Dlugos DJ, "Treatment of Refractory Status Epilepticus: Literature Review and a Proposed Protocol," Pediatr Neurol, 2008, 38(6):377-90.
Abou Khaled KJ, Hirsch LJ, “Updates in the Management of Seizures and Status Epilepticus in Critically Ill Patients,” Neurol Clin, 2008, 26(2):385-408, viii.
Brain Trauma Foundation, American Association of Neurological Surgeons, Joint Section on Neurotrauma and Critical Care, “Use of Barbiturates in the Control of Intracranial Hypertension,” J Neurotrauma, 2000, 17(6-7):527-30.
Bratton SL, Chestnut RM, Ghajar J, et al, “Guidelines for the Management of Severe Traumatic Brain Injury. XI. Anesthetics, Analgesics, and Sedatives,” J Neurotrauma, 2007, (24 Suppl 1):71-6.
Ehrnebo M, “Pharmacokinetics and Distribution Properties Of Pentobarbital in Humans Following Oral and Intravenous Administration,”J Pharm Sci, 1974, 63(7):1114-8.
Eisenberg HM, Frankowski RF, Contant CF, et al, “High-Dose Barbiturate Control of Elevated Intracranial Pressure in Patients With Severe Head Injury,” J Neurosurg, 1988, 69(1):15-23.
Fick DM, Cooper JW, Wade WE, et al, “Updating the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults: Results of a U.S. Consensus Panel of Experts,” Arch Intern Med, 2003, 163(22):2716-24.
Fischer JH and Raineri DL, “Pentobarbital Anesthesia for Status Epilepticus,” Clin Pharm, 1987, 6(8):601-2.
Hanhan UA, Fiallos MR, and Orlowski JP, “Status Epilepticus,” Pediatr Clin North Am, 2001, 48(3):683-94.
Holmes GL and Riviello JJ Jr, "Midazolam and Pentobarbital for Refractory Status Epilepticus," Pediatr Neurol, 1999, 20(4):259-64.
Hubbard AM, Markowitz RI, Kimmel B, et al, “Sedation for Pediatric Patients Undergoing CT and MRI,” J Comput Assist Tomogr, 1992, 16(1):3-6.
Kim SJ, Lee DY, and Kim JS, "Neurologic Outcomes of Pediatric Epileptic Patients With Pentobarbital Coma," Pediatr Neurol, 2001, 25(3):217-20.
Krauss B and Green SM, “Procedural Sedation and Analgesia in Children,” Lancet, 2006, 367(9512):766-80.
Manno EM, “New Management Strategies in the Treatment of Status Epilepticus,” Mayo Clin Proc, 2003, 78(4):508-18.
Meierkord H, Boon P, Engelsen B, et al, “EFNS Guideline on the Management of Status Epilepticus,” Eur J Neurol, 2006, 13(5):445-50.
Miller MA, Forni A, and Yogaratnam D, “Propylene Glycol-Induced Lactic Acidosis in a Patient Receiving Continuous Infusion Pentobarbital,” Ann Pharmacother, 2008, 42(10):1502-6.
Millikan D, Rice B, and Silbergleit R, “Emergency Treatment of Status Epilepticus: Current Thinking,” Emerg Med Clin North Am, 2009, 27(1):101-13, ix.
Mirski MA and Varelas PN, “Seizures and Status Epilepticus in the Critically Ill,”Crit Care Clin, 2008, 24(1):115-47
Pereira JK, Burrows PE, Richards HM, et al, “Comparison of Sedation Regimens for Pediatric Outpatient CT,” Pediatr Radiol, 1993, 23(5):341-4.
Schaible DH, Cupit GC, Swedlow DB, et al, “High-Dose Pentobarbital Pharmacokinetics in Hypothermic Brain-Injured Children,” J Pediatr, 1982, 100(4):655-60.
Wermeling D, Record K, Bell R, et al, “Hemodialysis Clearance of Pentobarbital During Continuous Infusion,” Ther Drug Monit, 1985, 7(4):485-7.
Yaffe K and Lowenstein DH, “Prognostic Factors of Pentobarbital Therapy for Refractory Generalized Status Epilepticus,” Neurology, 1993, 43(5):895-900.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
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