Pentobarbital sodium is a barbiturate hypnotic.
Pentobarbital sodium is used principally as a hypnotic in the short-term treatment of insomnia for periods up to 2 weeks in duration; barbiturates appear to lose their efficacy for sleep induction and maintenance after this period of time. Pentobarbital sodium also is used preoperatively to relieve anxiety and provide sedation and has been used for routine sedation.
Pentobarbital sodium may be used IV or IM to control status epilepticus or acute seizure episodes resulting from meningitis, poisons, eclampsia, alcohol withdrawal, tetanus, or chorea. Pentobarbital sodium may also be used parenterally or rectally to provide basal hypnosis for general, spinal, or regional anesthesia, or to facilitate intubation procedures. Pentobarbital sodium has also been used parenterally to control acute episodes of agitated behavior in psychoses, but has little value in long-term management of psychoses.
Pentobarbital may also be used to withdraw barbiturates or nonbarbiturate hypnotics in patients who are physically dependent on these drugs.
Pentobarbital has been used parenterally in high doses to induce coma in the management of cerebral ischemia† and increased intracranial pressure† associated with head trauma, stroke, Reye's syndrome, cardiac arrest, asphyxiation, or drowning and to ameliorate or prevent the sequelae that are associated with cerebral ischemia during neurosurgical procedures† that require long periods of cerebral hypoxia. The drug has reportedly reduced cerebral blood flow and subsequently reduced cerebral edema and/or intracranial pressure. Based on limited published data, pentobarbital appears more likely to be effective in patients younger than 35 years of age and in those with closed head injuries associated with intracranial hypertension than in those older than 35 years of age and/or with focal or global cerebral ischemia. Further well-controlled studies are needed to determine the safety and efficacy of pentobarbital in the management of cerebral ischemia.
Pentobarbital sodium may be administered by deep IM or slow IV injection. IV administration of pentobarbital sodium should usually be reserved for inducing anesthesia or emergency treatment of acute seizure episodes or acute episodes of agitated behavior in psychoses. The drug also has been administered orally and rectally, but oral formulations of pentobarbital or pentobarbital sodium and suppositories of pentobarbital sodium no longer are commercially available in the US.
After IM administration of large hypnotic doses, the patient should be observed closely for 20-30 minutes to assure that narcosis will not be excessive. No more than 250 mg or 5 mL of a solution of pentobarbital sodium should be injected IM at any one site.
Pentobarbital sodium injection is usually administered in a concentration of 50 mg/mL. The rate of IV injection should not exceed 50 mg/minute. During slow IV injection of the drug, vital signs should be monitored; blood pressure, respiration, and cardiac function should be maintained; and equipment for resuscitation and artificial ventilation should be readily available.
Standardized concentrations for pentobarbital have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. 249Multidisciplinary expert panels were convened to determine recommended standard concentrations. 249Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. 249 For additional information on S4S (including updates that may be available), see [Web].249
Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
Pediatric patients (<50 kg) | 8 mg/mL 50 mg/mL | mg/kg/hour |
Dosage of pentobarbital sodium must be individualized for each patient. Dosage should be reduced in geriatric or debilitated patients and in patients with impaired hepatic function. Following chronic administration, the drug should be withdrawn slowly to avoid the possibility of precipitating withdrawal symptoms if the patient is physically dependent on the drug.
For the treatment of insomnia, the drug should not be administered for periods exceeding 2 weeks. To prevent rebound in rapid eye movement (REM) sleep, withdrawal of a single therapeutic dose over 5 or 6 days has been recommended when barbiturates are discontinued following prolonged use.
The IM hypnotic dose of pentobarbital sodium for adults is 150-200 mg. The IM hypnotic dose for children is 2-6 mg/kg or 125 mg/m2, with a maximum dose of 100 mg.
When pentobarbital sodium is used as a preanesthetic medication, adults are usually given 150-200 mg IM. As a preanesthetic medication in children, pentobarbital sodium is usually given in an approximate dose of 5 mg/kg.
IV dosage of pentobarbital sodium is mainly determined by the patient's reaction to the slow administration of the drug. A frequently used initial IV dose for a 70-kg adult is 100 mg. The initial dose should be proportionately reduced for debilitated or pediatric patients; children are often given 50 mg initially. A time interval of at least 1 minute is required to determine the full effect of an IV dose of the drug. If necessary, additional small doses may be administered up to a total of 200-500 mg for adults. When the drug is administered in the management of seizure states, IV dosage should be kept to a minimum to avoid compounding the CNS and respiratory depression which may follow seizures. The injection must be made slowly, and adequate time should be allowed for the drug to distribute into the CNS. For specific procedures, techniques of administration, and dosages for basal anesthesia, specialized references should be consulted.
When pentobarbital is used to withdraw barbiturates or nonbarbiturate hypnotics in physically dependent patients, a stabilizing dose is established (usually pentobarbital is administered at 6-hour intervals) which is then reduced by no more than 100 mg per day. If withdrawal symptoms reappear, the dosage should be maintained or slightly increased until such symptoms disappear. Severely dependent patients can usually be withdrawn from barbiturates in 14-21 days.
Pentobarbital shares the toxic potentials of the barbiturates, and the usual precautions of barbiturate administration should be observed. (See Cautions in the Barbiturates General Statement 28:24.04.)
IV administered pentobarbital sodium may cause respiratory depression, apnea, laryngospasm, bronchospasm, or hypotension, particularly if the drug is administered too rapidly. When administered IV, the drug must be administered slowly, and personnel and equipment should be readily available for administration of artificial respiration.
FDA warns that repeated or prolonged use of general anesthetics and sedation drugs, including pentobarbital sodium, in children younger than 3 years of age or during the third trimester of pregnancy may affect brain development.750,753 Animal studies in multiple species, including nonhuman primates, have demonstrated that use for longer than 3 hours of anesthetic and sedation drugs that block N -methyl-d-aspartic acid (NMDA) receptors and/or potentiate γ-aminobutyric acid (GABA) activity leads to widespread neuronal and oligodendrocyte cell loss and alterations in synaptic morphology and neurogenesis in the brain, resulting in long-term deficits in cognition and behavior.750,751,752,753 Across animal species, vulnerability to these neurodevelopmental changes occurs during the period of rapid brain growth or synaptogenesis; this period is thought to correlate with the third trimester of pregnancy through the first year of life in humans, but may extend to approximately 3 years of age.750 The clinical relevance of these animal findings to humans is not known.750
While some published evidence suggests that similar deficits in cognition and behavior may occur in children following repeated or prolonged exposure to anesthesia early in life, other studies have found no association between pediatric anesthesia exposure and long-term adverse neurodevelopmental outcomes.750,752 Most studies to date have had substantial limitations, and it is not clear whether the adverse neurodevelopmental outcomes observed in children were related to the drug or to other factors (e.g., surgery, underlying illness).750 There is some clinical evidence that a single, relatively brief exposure to general anesthesia in generally healthy children is unlikely to cause clinically detectable deficits in global cognitive function or serious behavioral disorders;750,751,752 however, further research is needed to fully characterize the effects of exposure to general anesthetics in early life, particularly for prolonged or repeated exposures and in more vulnerable populations (e.g., less healthy children).750 For further information, see Cautions: Pediatric Precautions, in the Barbiturates General Statement 28:24.04.
Anesthetic and sedation drugs are an essential component of care for children and pregnant women who require surgery or other procedures that cannot be delayed;750,753 no specific general anesthetic or sedation drug has been shown to be less likely to cause neurocognitive deficits than any other such drug.750 Pending further accumulation of data in humans from well-designed studies, decisions regarding the timing of elective procedures requiring anesthesia should take into consideration both the benefits of the procedure and the potential risks.750 When procedures requiring the use of general anesthetics or sedation drugs are considered for young children or pregnant women, clinicians should discuss with the patient, parent, or caregiver the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.750,753 FDA states that procedures that are considered medically necessary should not be delayed or avoided.750,753
Based on animal data, repeated or prolonged use of general anesthetics and sedation drugs, including pentobarbital sodium, during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus.750,753 The clinical relevance of these animal findings to humans is not known; the potential risk of adverse neurodevelopmental effects should be considered and discussed with pregnant women undergoing procedures requiring general anesthetics and sedation drugs.750 (See Cautions: Pediatric Precautions.)
Pentobarbital shares the actions of the sedative-hypnotic barbiturates.
Nearly all of an oral or rectal dose of pentobarbital is absorbed from the GI tract. (Rectal and oral preparations of the drug no longer are commercially available in the US.) Following oral administration of pentobarbital, peak plasma concentrations are usually reached in 30-60 minutes. Plasma pentobarbital concentrations of 1-5 mcg/mL generally produce sedation, and plasma concentrations of 5-15 mcg/mL produce sleep in most patients; however, plasma concentrations of greater than 10 mcg/mL may produce deep coma, and those in excess of 30 mcg/mL are potentially lethal.
When pentobarbital is administered orally or rectally, the onset of action occurs within 15-60 minutes. The onset of action is within 1 minute following IV administration and within 10-25 minutes following IM administration. Like secobarbital, pentobarbital probably has a duration of hypnotic effect of 1-4 hours following oral or rectal administration and about 15 minutes following IV administration.
Approximately 35-45% of pentobarbital is bound to plasma proteins.
Plasma concentrations of pentobarbital decline in a biphasic manner with a half-life of about 4 hours for the first phase and 35-50 hours for the second phase.
Pentobarbital is metabolized by the liver chiefly by penultimate oxidation of the 1-methylbutyl substituent to a secondary alcohol, 5-ethyl-5-(3'-hydroxy-1'-methylbutyl) barbituric acid (hydroxypentobarbital) which is an inactive metabolite. Approximately 40-50% of an oral hypnotic dose of pentobarbital is excreted in urine as hydroxypentobarbital. The 1-methylbutyl substituent of pentobarbital can also be oxidized to form pentobarbital carboxylic acid, and small quantities of this metabolite have been found in urine. Less than 1% of an oral hypnotic dose of the drug is excreted in urine unchanged. Glucuronide conjugates of alcohols along with further oxidation products not yet identified may account for the remainder of the dose. Increasing the urinary flow enhances excretion of pentobarbital only slightly, and alkalinization of the urine produces no clinically important increase in excretion of the drug.
Pentobarbital is a barbiturate.
Pentobarbital sodium injection should be stored at room temperature; freezing and exposure of the injection to extreme heat should be avoided. Brief exposure to temperatures up to 40°C will not adversely affect the injection. Aqueous solutions of pentobarbital sodium are not stable, and solutions for injection should not be used if they contain a precipitate. The drug is more stable in propylene glycol, and this vehicle is used as a solvent in commercially available injections. Solutions of pentobarbital sodium should not be added to acidic solutions because precipitation of pentobarbital may occur.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Pentobarbital sodium is subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection | 50 mg/mL* | Nembutal® Sodium Solution ( C-II ) |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
249. ASHP. Standardize 4 Safety: pediatric continuous infusion standard. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]
750. US Food and Drug Administration. Drug safety communication: FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women. Silver Spring, MD; 2016 Dec 14. From FDA website. [Web]
751. Davidson AJ, Disma N, de Graaff JC et al. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet . 2016; 387:239-50. [PubMed 26507180]
752. Sun LS, Li G, Miller TL et al. Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood. JAMA . 2016; 315:2312-20. [PubMed 27272582]
753. US Food and Drug Administration. Drug safety communication: FDA approves labeling changes for use of general anesthetic and sedation drugs in young children. Silver Spring, MD; 2017 Apr 27. From FDA website. [Web]