Pentobarbital sodium is a short-acting barbiturate that has sedative-hypnotic properties and anticonvulsant activities at anesthetic doses.1
Pentobarbital sodium is used to control status epilepticus or acute seizure episodes resulting from other causes (e.g., meningitis, poisons, eclampsia, tetanus, or cholera).1
Status epilepticus is a medical emergency that must be treated promptly to reduce substantial morbidity and mortality.2, 3 Guidelines from the Neurocritical Care Society and the American Epilepsy Society recommend that status epilepticus be treated rapidly with sequential therapies until seizures are controlled.2, 3 Benzodiazepines (e.g., IV lorazepam, IM midazolam, IV diazepam) are the drugs of choice for initial emergent treatment (within the first 5 to 20 minutes of therapy) of status epilepticus.2, 3 If seizures continue, a second-line agent should be administered.2, 3 The American Epilepsy Society states that reasonable second-line options include fosphenytoin, valproic acid, and levetiracetam; there is no clear eveidence that any of these options is better than the others.3 IV phenobarbital is a reasonable second-therapy alternative.3 For the treatment of refractory status epilepticus, options may include repeat doses of second-line therapies or anesthetic doses of thiopental, midazolam, pentobarbital, or propofol.2, 3
Pentobarbital sodium is FDA-labeled for use as a sedative or preanesthetic medication; however, it has fallen out of favor for this use, in part due to the unpredictable response and prolonged recovery time associated with its use in children.1, 95, 96, 97, 98
Pentobarbital sodium is FDA-labeled for use as a hypnotic for the short-term treatment of insomnia; however, barbiturates appear to lose their efficacy for sleep induction and maintenance after 2 weeks of treatment, and the significant adverse effects and overdose potential associated with barbiturates has curtailed their use in this setting.1, 99 Other agents are currently preferred for the treatment of insomnia.99, 100
Elevated Intracranial Pressure
Pentobarbital has been used parenterally in high doses to manage increased intracranial pressure† associated with head trauma.4, 5 Although one randomized controlled trial found that adding high-dose pentobarbital to conventional treatment reduced intracranial pressure compared with conventional treatment alone,4 barbiturate therapy has not been associated with improvements in morbidity or mortality in this setting.5 Barbiturates have also been associated with clinically significant hypotension in some patients with head injury.5 Results of one study indicate that mannitol may be more effective than pentobarbital for controlling elevated intracranial pressure.5
Guidelines on the management of severe traumatic brain injury recommend treating intracranial pressures >22 mm Hg in adults and >20 mm Hg in pediatric patients; higher intracranial pressures have been associated with worse outcomes, including increased mortality.6, 7, 8, 9 First-line interventions for increased intracranial pressure in adults with severe traumatic brain injury include additional analgesia/sedation and cerebrospinal fluid (CSF) drainage.9 If these are insufficient, second-line interventions may include hyperosmolar therapy (e.g., mannitol, hypertonic saline) and neuromuscular paralysis.9 If intracranial pressure remains uncontrolled despite these interventions, high-dose barbiturate or propofol therapy should be considered.6, 9 Similar interventions are used in pediatric patients with severe traumatic brain injury and elevated intracranial pressure; in pediatric patients who are refractory to first-tier treatments (i.e., CSF drainage, hyperosmolar therapy, additional analgesia/sedation, neuromuscular blockade), options for second-tier therapy include barbiturate infusions, moderate hypothermia, hyperventilation, and higher levels of hyperosmolar therapy.7, 8
Dispensing and Administration Precautions
Pentobarbital sodium may be administered by deep IM or slow IV injection.1 The drug also has been administered as a continuous IV infusion† in the treatment of refractory status epilepticus; administration by continuous IV infusion requires assisted ventilation and cardiovascular monitoring..2 IV administration of pentobarbital should usually be reserved for acute treatment, when other routes of administration are not feasible or immediate onset is necessary.1
Because parenteral pentobarbital solution is highly alkaline, extreme caution should be taken to avoid perivascular extravasation or accidental intra-arterial injection of the drug.1 Extravascular injection of pentobarbital can cause local tissue damage and subsequent necrosis, while intra-arterial injection can lead to transient pain, or in severe cases, gangrene of the limb.1 If complaints of limb pain occur in patients receiving pentobarbital injection, the injection should be stopped.1
Pentobarbital sodium injection should be stored at 20-25°C (excursions permitted from 15-30°C); freezing and exposure of the injection to extreme heat should be avoided.1 The drug should not be used if there is discoloration or precipitation.1
Pentobarbital sodium injection is usually administered in a concentration of 50 mg/mL as a slow IV injection (not to exceed 50 mg/minute).1 Fractional doses should be administered to allow adequate time to distribute into the CNS.1 A time interval of at least 1 minute is required to determine the full effect of an IV dose of the drug.1
Following IV administration, the onset of action of pentobarbital is almost immediate, although maximal CNS depression may not occur until after 15 minutes.1
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 |
Administer by deep IM injection into a large muscle.1 Do not exceed a volume of 5 mL at any one site due to possible tissue irritation.1
Dosage of pentobarbital sodium must be individualized for each patient, taking into consideration the patient's age, weight, and condition.1 Dosage of pentobarbital sodium is expressed in terms of the sodium salt.1
No average IV dosage of pentobarbital sodium is available.1 The manufacturer states that a commonly used initial IV dose for a 70-kg adult is 100 mg.1 A time interval of at least 1 minute is required to determine the full effect of an IV dose of the drug.1 If necessary, additional small doses may be administered up to a total of 200-500 mg for adults.1
When IV pentobarbital sodium is given for the treatment of refractory seizures in mechanically ventilated patients receiving cardiovascular monitoring, some experts recommend an initial dose of 5-15 mg/kg administered no faster than 50 mg/minute; an additional 5-10 mg/kg dose may be administered if necessary.2 The recommended dosage for a continuous infusion is 0.5-5 mg/kg per hour; additional 5 mg/kg bolus doses may be administered for breakthrough seizures.2 The continuous infusion may be increased by 0.5-1 mg/kg/hour every 12 hours, titrated to EEG findings.2
When the drug is administered in the management of seizure states, the dosage of pentobarbital should be kept to a minimum to avoid compounding the CNS and respiratory depression which may follow seizures.1 The IV injection must be made slowly, and adequate time should be allowed for the drug to distribute into the CNS.1
The usual IM hypnotic dosage of pentobarbital sodium for adults is 150-200 mg as a single dose.1
No average IV dosage of pentobarbital sodium is available.1 A frequently used initial IV dosage for a 70-kg adult is 100 mg.1 A time interval of at least 1 minute is required to determine the full effect of an IV dose of the drug.1 If necessary, additional small doses may be administered up to a total of 200-500 mg for adults.1
When used for the short-term treatment of insomnia, the drug should not be administered for periods >2 weeks.1 To prevent rebound in REM sleep, withdrawal of a single therapeutic dose over 5 or 6 days has been recommended when barbiturates are discontinued following prolonged use.1
No average IV dosage of pentobarbital sodium is available.1 A frequently used initial IV dosage for a 70-kg adult is 100 mg.1 A time interval of at least 1 minute is required to determine the full effect of an IV dose of the drug.1 If necessary, additional small doses may be administered up to a total of 200-500 mg for adults.1
No average IV dosage of pentobarbital sodium is available.1 A frequently used initial IV dose for a 70-kg adult is 100 mg with additional small doses administered if necessary up to a total of 200-500 mg.1 A proportional dosage reduction is recommended for pediatric patients.1 A time interval of at least 1 minute is required to determine the full effect of an IV dose of the drug.1
When IV pentobarbital is given for the treatment of refractory status epileptius in mechanically ventilated patients receiving cardiovascular monitoring, some experts recommend an initial dose of 5-15 mg/kg administered no faster than 50 mg/minute; an additional 5-10 mg/kg dose may be administered if necessary.2 The recommended dosage for a continuous infusion is 0.5-5 mg/kg per hour; additional 5 mg/kg bolus doses may be administered for breakthrough seizures.2 The continuous infusion may be increased by 0.5-1 mg/kg per hour every 12 hours, titrated to EEG findings.2
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.1 The injection must be made slowly, and adequate time should be allowed for the drug to distribute into the CNS.1
The usual IM hypnotic dosage for children is 2-6 mg/kg (not to exceed 100 mg).1
No average IV dosage of pentobarbital sodium is available.1 A frequently used initial IV dose for a 70-kg adult is 100 mg with additional small doses administered if necessary up to a total of 200-500 mg.1 A proportional dosage reduction is recommended for pediatric patients.1 A time interval of at least 1 minute is required to determine the full effect of an IV dose of the drug.1
When used for the short-term treatment of insomnia, the drug should not be administered for periods >2 weeks.1 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.1
No average IV dosage of pentobarbital is available.1 A frequently used initial IV dose for a 70-kg adult is 100 mg with additional small doses administered if necessary up to a total of 200-500 mg.1 A proportional dosage reduction is recommended for pediatric patients.1 A time interval of at least 1 minute is required to determine the full effect of an IV dose of the drug.1
The manufacturer recommends using caution and reducing the initial dosage of pentobarbital sodium in patients with hepatic impairment.1 Pentobarbital should be avoided in patients demonstrating premonitory signs of hepatic coma.1
The manufacturer recommends reducing the dosage of pentobarbital sodium in patients with renal impairment.1
Because geriatric patients may be more sensitive to barbiturates, the manufacturer recommends reducing the dosage of pentobarbital sodium.1
In general, dosage selection for geriatric patients should be undertaken with caution and started at the lower end of the dosage range, taking into account the greater frequency of reduced hepatic, renal, or cardiac function and of concomitant diseases or drug therapy.1
The manufacturer recommends reducing the dosage of pentobarbital sodium in debilitated patients.1
Prolonged use of barbiturates such as pentobarbital can cause tolerance, psychological dependence, and physical dependence.1 Daily administration of doses exceeding 400 mg of pentobarbital sodium for approximately 90 days is likely to cause some physical dependence, while daily doses of 600-800 mg for at least 35 days is likely to cause withdrawal seizures.1 As tolerance to a barbiturate develops, the amount of drug needed to maintain intoxication increases.1 Abrupt discontinuation after chronic use in a dependent patient can result in withdrawal.1 Symptoms of withdrawal can include delirium, convulsions, and potentially death.1
Treatment of barbiturate dependence requires cautious and gradual drug withdrawal over an extended period of time.1 One withdrawal method recommends substitution of 30 mg of phenobarbital administered orally for every 100-200 mg dose of the barbiturate that the patient was receiving, administered in 3 or 4 divided doses (not to exceed 600 mg daily).1 If the patient experiences withdrawal symptoms on the first day of this regimen, a loading dose of 100-200 mg of phenobarbital may be administered IM, in addition to the oral regimen.1 After stabilization on phenobarbital, the total daily dose of phenobarbital is decreased by 30 mg per day.1 Alternatively, patients may be initiated on withdrawal treatment at the regular dosage level, and their daily dosage decreased by 10% if tolerated.1
Infants physically dependent on barbiturates may be administered 3-10 mg/kg per day of phenobarbital.1 Upon cessation of withdrawal symptoms (e.g., hyperactivity, sleep disturbances, tremors, hyperreflexia), the dosage of phenobarbital may be gradually decreased and completely withdrawn over a 2-week period.1
Administer pentobarbital with caution, if at all, to patients who are mentally depressed, have suicidal tendencies, or a history of drug abuse.1
Rapid IV administration of pentobarbital can result in respiratory depression, apnea, laryngospasm, or vasodilation with blood pressure reductions.1 Rate of IV injection should not exceed 50 mg/minute.1 Patients should be carefully observed during administration and equipment for resuscitation and artifical ventilation should be available.1
Patients with Acute or Chronic Pain
Although the use of barbiturates for sedation in postoperative surgical patients and as an adjunct to chemotherapy is well established, caution should be undertaken when barbiturates such as pentobarbital are administered in patients with acute or chronic pain because of the risk of paradoxical excitation.1 Additionally, administration of barbiturates such as pentobarbital in patients with acute or chronic pain may mask important pain symptoms.1
Fetal/Neonatal Morbidity and Mortality
Barbiturates such as pentobarbital can cause fetal harm when administered during pregnancy.1 Retrospective, case-controlled studies indicate an association between maternal ingestion of barbiturates and a higher than expected incidence of fetal abnormalities.1 Following oral or parenteral administration, barbiturates readily cross the placenta and are distributed into the placenta, fetal liver, and fetal brain to the greatest extent.1 Measured plasma concentrations in the fetus approach that of the mother's following parenteral administration of barbiturates.1
Withdrawal symptoms can occur in infants born to mothers exposed to barbiturates during the last trimester of pregnancy.1
If pentobarbital is administered during pregnancy, or the patient becomes pregnant while receiving the drug, the patient should be informed of the potential fetal hazard.1
Concurrent use of other CNS depressants may potentiate CNS depression.1
Animal data indicate that use of anesthetic and sedation drugs, including pentobarbital sodium, that block N-methyl-d-aspartic acid (NMDA) receptors and/or potentiate γ-aminobutyric acid (GABA) activity leads to increased neuronal apoptosis in the developing brain and results in long-term cognitive deficits when administered for >3 hours.1 Although the clinical importance of these findings have not been fully elucidated, the window of vulnerability to these neurodevelopmental changes is thought to correlate with exposure during the third trimester of pregnancy through the first year of life in humans, but may extend to approximately 3 years of age.1
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, 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).1
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; no specific general anesthetic or sedation drug has been shown to be safer than any other such drug.1 When procedures requiring the use of general anesthetics or sedation drugs are considered for young children or pregnant women, clinicians should take into consideration the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.1
Based on animal data, repeated or prolonged use of general anesthetics and sedatives, including pentobarbital sodium, during the third trimester of pregnancy may result in adverse neurodevelopmental effects in the fetus.1 The clinical importance 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.1
Infants with long-term exposure to barbiturates in utero may exhibit an immediate or delayed onset of withdrawal symptoms (e.g., seizures, hyperirritability) up to 14 days after birth.1
If pentobarbital is administered during pregnancy, or the patient becomes pregnant while receiving the drug, the patient should be informed of the potential fetal hazard.1
Because barbiturates such as pentobarbital are excreted into the milk in small amounts, caution should be exerted when barbiturates are administered to nursing women.1
Females and Males of Reproductive Potential
Barbiturates such as phenobarbital increase the metabolism of estrogenic and proestrogenic hormones, resulting in potential reduced efficacy of hormonal oral contraceptives.1
In patients receiving oral hormonal contraceptives with pentobarbital pretreatment or concomitant therapy, an alternative contraceptive method should be used.1
Animal data indicate that use of anesthetic and sedation drugs, including pentobarbital, that block NMDA receptors and/or potentiate GABA activity leads to increased neuronal apoptosis in the developing brain and results in long-term cognitive deficits when administered for >3 hours.1 Although the clinical importance of these findings have not been fully elucidated, the window of vulnerability to these neurodevelopmental changes is thought to correlate with exposure during the third trimester of pregnancy through the first year of life in humans, but may extend to approximately 3 years of age.1
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, although there are substantial limitations to this data.1
Anesthetic and sedation drugs are an essential component of care for children who require surgery or other procedures that cannot be delayed; no specific general anesthetic or sedation drug has been shown to be safer than any other such drug.1 When procedures requiring the use of general anesthetics or sedation drugs are considered for young children, clinicians should take into consideration the benefits, risks (including potential risk of adverse neurodevelopmental effects), and appropriate timing and duration of the procedure.1
Clinical studies of pentobarbital did not include a sufficient number of patients ≥65 years of age to assess differences compared to younger adults.1 Other reported clinical experiences with pentobarbital have also not identified differences in response between geriatric and younger adult patients.1
Geriatric patients may be more sensitive to barbiturate therapy, and may frequently react to barbiturates with excitement, confusion, or depression.1
Debilitated patients may be more sensitive to barbiturate therapy, and may frequently react to barbiturates with excitement, confusion, or depression.1
Pentobarbital must be administered with caution in patients with hepatic impairment.1 Avoid use of the drug in patients with premonitory signs of hepatic coma.1
The pharmacokinetics of pentobarbital have not been studied in patients with renal impairment.1
The most common adverse effect reported in up to 3% of patients receiving pentobarbital is somnolence.1 Other less common adverse effects reported in <1% of patients receiving pentobarbital include agitation, confusion, hyperkinesia, ataxia, CNS depression, nightmares, nervousness, psychiatric disturbance, hallucinations, insomnia, anxiety, dizziness, thinking abnormalities, hypoventilation, apnea, bradycardia, hypotension, syncope, nausea and vomiting, constipation, headache, injection site reactions, hypersensitivity reactions (angioedema, skin rash, exfoliative dermatitis), fever, liver damage, and megaloblastic anemia (following chronic use).1
Pentobarbital is metabolized by, and induces hepatic microsomal enzymes.1 Although most reported drug interaction experience has involved the use of phenobarbital, these interactions are applicable to other barbiturates such as pentobarbital.1
Barbiturates have been shown to induce hepatic microsomal enzymes, resulting in increased metabolism and decreased anticoagulant response of oral anticoagulants (e.g., warfarin).1 Patients who are stable on an anticoagulant regimen may require dosage adjustments of the anticoagulant when pentobarbital is added or withdrawn.1
Concomitant use of barbiturates with phenytoin may increase the metabolism of phenytoin or have no effect.1 Because of this variable response, plasma levels of phenytoin and the barbiturate should be monitored frequently when the drugs are used concomitantly.1
Valproic acid reduces barbiturate metabolism; therefore, plasma levels of the barbiturate should be monitored and dosage adjusted appropriately when used concomitantly with valproic acid.1
Concomitant use of other CNS depressants (e.g., other sedatives or hypnotics, antihistamines, tranquilizers, or alcohol) can produce additive CNS depressant effects when used with pentobarbital.1
Barbiturates enhance the metabolism of exogenously administered corticosteroids through the induction of hepatic microsomal enzymes.1 Patients who are stable on corticosteroid therapy may require dosage adjustments of the corticosteroid when barbiturate therapy is added or withdrawn.1
Monoamine Oxidase (MAO) Inhibitors
Concomitant use of MAO inhibitors prolongs the effect of barbiturates due to impaired metabolism.1
Pretreatment with or concomitant administration of phenobarbital increases the metabolism of estradiol, which can reduce the efficacy of oral hormonal contraceptives and result in pregnancy.1 In patients receiving hormonal (estrogen or progestin-containing) oral contraceptives during phenobarbital therapy, an alternative contraceptive method is recommended.1
Likely because of the induction of hepatic microsomal enzymes, concomitant use of phenobarbital shortens the elimination half-life of doxycycline for as long as 2 weeks after discontinuation of the barbiturate.1 If doxycycline is used concomitantly with doxycycline, the clinical response to doxycycline should be monitored closely.1
Phenobarbital interferes with the oral absorption of griseofulvin, resulting in reduced plasma concentrations of the drug.1 Although the clinical importance of these findings has not been established, the manufacturer states to avoid the concomitant administration of phenobarbital and griseofulvin.1
Pentobarbital, a barbiturate, is a nonselective CNS depressant that is primarily used as a sedative hypnotic, and at subhypnotic doses, as an anticonvulsant.1 At high enough therapeutic dosages, barbiturates induce anesthesia and exhibit anticonvulsant activity.1 At lower dosages not sufficient to induce anesthesia, barbiturates have little analgesic activity, and instead may increase reactions to painful stimuli.1 The CNS effects of pentobarbital are related to the blockage of N-methyl-d-aspartic acid (NMDA) receptors and/or potentiation of γ-aminobutyric acid (GABA) activity.1 Barbiturates can produce varying levels of CNS mood alteration, including excitation to mild sedation, hypnosis, and deep coma.1 Barbiturate activity includes depression of the sensory cortex, decreased motor activity, and altered cerebellar function, which produce drowsiness, sedation, and hypnosis.1 Barbiturates also cause respiratory depression, which is dose dependent.1 At large hypnotic dosages, the respiratory depression produced by barbiturates is similar to the slight decrease in blood pressure and heart rate experienced during physiologic sleep.1
Although pentobarbital has been used for the short term treatment of insomnia, barbiturate-induced sleep differs from physiological sleep.1 Barbiturates such as pentobarbital reduce the amount of time spent in the rapid eye movement (REM) phase of sleep or dreaming, and the amount of time spent in stages III and IV sleep.1
The onset of action of pentobarbital occurs within 1 minute following IV administration.1 The duration of action of barbiturates, related to rate of redistribution throughout the body, is highly variable and can vary in the same patient.1 Maximal CNS depression may not occur until 15 minutes or more after IV administration.1
Plasma pentobarbital concentrations in the therapeutic range of 0.5-3 mcg/mL generally produce sedation and calm, and plasma concentrations of 10-15 mcg/mL produce significant respiratory depression and coma; plasma concentrations of >15 mcg/mL are potentially lethal.1
Pentobarbital is rapidly distributed into all tissues and fluids with high concentrations in the brain, liver, and kidneys.1 The drug crosses the placenta and distributes into milk.1 Pentobarbital is metabolized primarily by hepatic microsomal enzymes.1 Metabolites of pentobarbital are primarily excreted into the urine, and less commonly into the feces.1 The amount of unchanged pentobarbital that is excreted into the urine is considered negligible.1 Inactive metabolites undergo excretion as conjugates of glucuronic acid.1 The elimination half-life of pentobarbital ranges from 15-50 hours and is dose dependent.1
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* | PENTobarbital Sodium Solution | |
Nembutal® Sodium Solution (C-II) | Hikma |
* 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.
1. Hikma Pharmaceuticals (dba Leucadia Pharmaceuticals). Pentobarbital sodium injection prescribing information. Carlsbad, CA; 2019 Dec.
2. Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, Laroche SM, Riviello JJ Jr, Shutter L, Sperling MR, Treiman DM, Vespa PM; Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012 Aug;17(1):3-23.
3. Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, Bare M, Bleck T, Dodson WE, Garrity L, Jagoda A, Lowenstein D, Pellock J, Riviello J, Sloan E, Treiman DM. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016 Jan-Feb;16(1):48-61.
4. Eisenberg HM, Frankowski RF, Contant CF, Marshall LF, Walker MD. High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg. 1988 Jul;69(1):15-23.
5. Roberts I, Sydenham E. Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD000033.
6. Carney N, Totten AM, O'Reilly C, Ullman JS, Hawryluk GW, Bell MJ, Bratton SL, Chesnut R, Harris OA, Kissoon N, Rubiano AM, Shutter L, Tasker RC, Vavilala MS, Wilberger J, Wright DW, Ghajar J. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2017 Jan 1;80(1):6-15.
7. Kochanek PM, Tasker RC, Carney N, Totten AM, Adelson PD, Selden NR, Davis-O'Reilly C, Hart EL, Bell MJ, Bratton SL, Grant GA, Kissoon N, Reuter-Rice KE, Vavilala MS, Wainwright MS. Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines, Executive Summary. Neurosurgery. 2019 Jun 1;84(6):1169-1178.
8. Kochanek PM, Tasker RC, Bell MJ, Adelson PD, Carney N, Vavilala MS, Selden NR, Bratton SL, Grant GA, Kissoon N, Reuter-Rice KE, Wainwright MS. Management of Pediatric Severe Traumatic Brain Injury: 2019 Consensus and Guidelines-Based Algorithm for First and Second Tier Therapies. Pediatr Crit Care Med. 2019 Mar;20(3):269-279.
9. Alam HB, Vercruysse G, Martin M, Brown CVR, Brasel K, Moore EE, Sava J, Ciesla D, Inaba K; Western Trauma Association Critical Decisions in Trauma Committee. Western Trauma Association critical decisions in trauma: Management of intracranial hypertension in patients with severe traumatic brain injuries. J Trauma Acute Care Surg. 2020 Feb;88(2):345-351.
95. Practice Guidelines for Moderate Procedural Sedation and Analgesia 2018: A Report by the American Society of Anesthesiologists Task Force on Moderate Procedural Sedation and Analgesia, the American Association of Oral and Maxillofacial Surgeons, American College of Radiology, American Dental Association, American Society of Dentist Anesthesiologists, and Society of Interventional Radiology. Anesthesiology. 2018 Mar;128(3):437-479.
96. Coté CJ, Wilson S; AMERICAN ACADEMY OF PEDIATRICS; AMERICAN ACADEMY OF PEDIATRIC DENTISTRY. Guidelines for Monitoring and Management of Pediatric Patients Before, During, and After Sedation for Diagnostic and Therapeutic Procedures. Pediatrics. 2019 Jun;143(6):e20191000.
97. Kienstra AJ, Ward MA, Sasan F, Hunter J, Morriss MC, Macias CG. Etomidate versus pentobarbital for sedation of children for head and neck CT imaging. Pediatr Emerg Care. 2004 Aug;20(8):499-506.
98. Pershad J, Wan J, Anghelescu DL. Comparison of propofol with pentobarbital/midazolam/fentanyl sedation for magnetic resonance imaging of the brain in children. Pediatrics. 2007 Sep;120(3):e629-36.
99. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017 Feb 15;13(2):307-349.
100. Department of Veterans Affairs (VA) and Department of Defense (DoD). VA/DoD Clinical Practice Guideline for the Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea, 2025. [Web]
249. ASHP. Standardize 4 Safety: pediatric continuous infusion standard. Updated 2025 Mar. From ASHP website. Updates may be available at ASHP website. [Web]
555. Institute for Safe Medication Practices (ISMP). ISMP List of Confused Drug Names. ISMP; 2024.