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Pentobarbital Sodium – An Overview

The pentobarbital-chlorpromazine-alcohol group scale (PCAG) provides a measure of sedation, the amphetamine (A or AMP) scale provides a measure of amphetamine-like effects, the benzedrine group scale (BG) also assesses amphetamine-like effects, the lysergic acid diethylamide (LSD) scale is sensitive to somatic and dysphoric changes, and finally, the morphine-benzedrine group (MBG) is often used to describe euphoria.

Pediatric Sedation and Analgesia

Barbiturates (Thiopental Methohexital, Methohexital and Pentobarbital)

Barbiturates are typically employed to numb children less than 3 years old to conduct diagnostic imaging. They are generally safe, but are not recommended for patients suffering from porphyria. The most serious side effects are respiratory depression with apnea as well as hypotension. Both are more prevalent when barbiturates are administered together with opiates or benzodiazepines.

Thiopental (Pentothal) is a quick-acting barbiturate that has an onset of the action lasting between 30 and 60 seconds when administered intravenously. It takes five to eight minutes when administered in rectally. It can have an effects of 15 minutes when administered intravenously, but up to one hour when it is administered by rectally. Injecting it intravenously with dosages of 20-25 mg/kg, it is usually administered rectally to infants with a dosage of 5-10 mg/kg. Thiopental is known to have the negative effect of reducing intracranial pressure. It is therefore especially beneficial in patients for whom an increase in intracranial pressure can be a problem.

Methohexital (Brevital) is an extremely fast-acting medication that has an onset between 30 and 60 seconds and a time of action that ranges from 5-10 minutes. It’s twice more potent than thiopental and is able to be administered intravenously at a dosage that ranges from 0.5 or 1.0 mg/kg to children who are older than 12 years old. It is not recommended to be given in children who are younger and is not recommended for children with epilepsy of the temporal lobe since it may trigger seizures in this subset. Methohexital is not commonly used in the emergency department due to a single study (Zink 1991) of 102 patients which revealed 22 patients had respiratory depression that required bag-valve mask assistance. Five of the 22 patients had intermittent apnea. When when combined with an analgesic medicine the risk of respiratory depression can be reduced by first administering an medication to reduce pain, and then increasing methohexital dosage to required effects.

Pentobarbital (Nembutal) is a beneficial barbiturate sedative that can be used for more prolonged radiologic procedures like magnetic resonance imaging or scans using positron emission. Its onset of effect that lasts between 3 and 5 mins when administered IV and a period of effect between 30 and 45 minutes. For infants and children older than 6 months old, it is administered intravenously in a dose that ranges from 1 to 3 mg/kg. It is adjusted between 3 and 5 mins to 100 mg or intramuscularly with the dosage of 2-6 mg/kg, with a maximum dose in 100 mg.

Pentobarbital Sodium



Pentobarbital, a sodium salt, has been utilized to treat hypnosis and sedation for the short-term treatment of insomnia. Pentobarbital sodium is also utilized as a premedication for anesthetic procedures. Pentobarbital is approved by FDA for emergency treatment of convulsive events that are acute, e.g., those that are caused by status epilepticus meningitis, eclampsia or cholera, tetanus, as well as allergic reactions to strychnine and local anesthetics. The other indications for pentobarbital include treatment of nonfatal submersion and traumatic/nontraumatic raised intracranial pressure.


Intraperitoneal (IP) injection of pentobarbital can be used in research medicine as an anesthetic for small animals like rat and mouse. Pentobarbital is a key medication for treating seizures triggered by convulsive disorders particularly when they are they are caused by strychnine.

Dosages for Drugs

Short-Acting Barbiturates: Pentobarbital

Pentobarbital is water-soluble. When released into the atmosphere at an estimated vapor pressure of 3x 10-10mmHg (25 degC) It will exist only as particulate phase in the atmosphere. As particulate pentobarbital it is removed from the atmosphere through dry or wet deposition. Pentobarbital isn’t susceptible to photolysis by sunlight since pentobarbital is not a source of any chromophores which absorb light wavelengths that exceed 290 nm. If pentobarbital does get released into soil with a pKa of 7.8 means that it exists as an anion, and is not able to absorb very strongly into soils that contain organic carbon , clays or. Pentobarbital is not likely to break down from soils that are moist on the basis of estimates of Henry’s law constant of 8.4 10-13 atm-cu m mo-1. If it is released into water, pentobarbital isn’t expected to absorb to suspended sediments and substances in water, based on an estimated Koc. The release of water-borne volatiles is not thought to be a major fate-related process, based on the Henry’s law constant estimated. Pentobarbital is estimated to have a bioconcentration factor (BCF) at 11. This suggests that the possibility of bioconcentration in aquatic organisms is very low. Pentobarbital is devoid of functional groups that can hydrolyze easily and hydrolysis isn’t expected to be a major ecological fate process.


The Status Epilepticus and Seizure Clusters

Seizure clusters are also known as acute serial seizures or repetitive seizures are seizures that are tightly grouped, resulting in an increase in the frequency of seizures in comparison to baseline, typically occurring in the range of minutes or a few days. Seizure clusters can include any kind of seizure, and could be different in their severity but, in general, they are completely recovered between seizures. Seizure clusters are more frequent for epilepsy patients who are drug resistant especially those who suffer from epilepsy with no symptoms and extratemporal epilepsy. Patients who have seizure clusters have a higher likelihood to be diagnosed with an history of status epilepticus. Seizure clusters may develop into extended seizures, or even status epilepticus. The progression of seizures can be predicted for patients individually depending on their history of seizures. This can help determine the best course of treatment for seizures that occur in clusters. Small clusters of seizures can be managed with oral doses containing the benzodiazepines. However, more serious clusters, especially those that are that can progress to seizures that last for a long time or have status epilepticus could require alternative methods of treatment. Rectal diazepam was the sole FDA-approved medication for use outside of hospitals by non-medical caregivers (Cereghino and co. 1998) prior to when intranasal Midazolam spray became available in the year of 2019 (Detyniecki and colleagues. 2019). Buccal midazolam is widely in use in Europe and other different countries (Nakken and Lossius and Lossius, 2011,) but hasn’t been recognized by the FDA in the United States. Intranasal diazepam received approval from the US FDA in the year 2020. The effectiveness of intramuscular diazepam given by autoinjectors was confirmed in a controlled, blinded study (Abou-Khalil and co. 2013, 2013) However, it didn’t result in FDA approbation or marketing. Other strategies that were evaluated include buccal diazepam, staccato midazolam.

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Status epilepticus was earlier defined as seizure-related activity that lasts for 30 minutes or recurrent seizures that do not recover between episodes. The 30-minute duration is controversial, because it could delay aggressive treatment, particularly when a prolonged duration is determined in the absence treatment. Evidence from experiments suggests that irreparable neuronal injury can occur within 20-30 minutes of generalized convulsive state epilepticus (GCSE) (Fujikawa 1996; Meldrum and Brierley 1973) So every effort must be taken to stop seizures prior to. The evidence suggests that the bilateral tonic-clonic stage when there is a generalized or focal onset seizures is not more than two minutes (Jenssen and co. 2006a; Theodore et al. 1994) in the event that it develops to become status epilepticus. In the end, it is suggested that aggressive therapy for status epilepticus should begin after five minutes of tonic-clonic stimulation (Lowenstein and. 1999). There is evidence to suggest that FIAS that last more than 10 minutes are likely to develop into status epilepticus (Jenssen and co. 2006a). Based on this information, the ILAE classified epilepticus as a condition “resulting from the inability of the mechanisms that are responsible for the cessation of seizures or the induction of mechanisms that cause abnormally long seizures (after time point t1) and may have lasting effects (after the timepoint at t2)” (Trinka et al. in 2015). The time point t1 of epileptic status was 5 minutes for bilateral seizures that were tonic-clonic, 10-minutes for focal seizures and 10-15 minutes in the absence of seizures.

Anesthesia and Analgesia


Pentobarbital is an oxybarbiturate-based analog of barbituric acids. Pentobarbital may be used as an anesthetic, sedative, and anticonvulsant. The mechanism of action of pentobarbital is similar to propofol and benzodiazepines because GABAA receptors become activated which results in increased GABA binding and the opening of transmembrane chloride channel leading to the hyperpolarization of cells within the nervous system’s central region. Pentobarbital administration causes the effects of dose-dependent hypnosis, sedation muscles relaxation, reduction of sensory cortex as well as the reticular activating mechanism.

Like all GABAA antagonists, pentobarbital displays minimal or no analgesic effects. Pentobarbital causes a dose-dependent respiratory depression that may require assistance with breathing (Peeters and co. 1988). When doses are higher pentobarbital exhibits anticonvulsant as well as hypotensive properties. The cause of hypotension is vasodilation and decreased myocardial contractility and decreased cardiac output. These and other effects on the cardiovascular system depend on the route of administration. They are more likely to be less severe when using IP instead of IV. This is because the blood concentration at its peak is achieved much more slowly than during IV administration. Additionally, the portion of the drug that is absorbed into the portal system is susceptible to destruction within the liver. Hypothermia is a common occurrence and has been observed in Gerbils (Weinandy and Co. 2005). The hypothermia most likely is a result of a decreased vasodilation and metabolism at the basal level. Sedation, as well as respiratory depression may occur when pentobarbital is given alongside tranquilizers, benzodiazepines or alpha2-agonists and opioids propofol, inhalants, and anesthetic agents. Animals who are treated with pentobarbital should receive oxygen-supplementation or monitored by pulse the oximetry. General anesthetic doses can require support for respiratory or endotracheal intubation.

When pentobarbital has been administered an additional source of heat is recommended to be applied to the animal throughout the period of surgery and then continued until full recovery in order to avoid hypothermia. Pentobarbital is given intraperitoneally or intravenously. If used as general anesthetic, it can be administered in an Bolus (Borkowski and colleagues. 1990) or as a CRI. Commercial products usually contain propylene glycol that may cause pain when injected and thrombophlebitis. This is why the intramuscular and subcutaneous methods of injection aren’t advised.

Status Epilepticus


Pentobarbital (or thiopental) can be a complete treatment for SE with refractory. Barbiturates that short-acting are quick however they require intensive care treatment. Doses between 3 and 5 mg/kg, followed by an infusion of 1 to 3 mg/kg/hour are common; certain studies suggest that patients require at minimum 3.5 mg/kg/hour. Effectiveness is measured as the effect on the electroencephalogram, with an attempt to eliminate seizures or aim for a burst suppression or flat record; most reviewers seek a burst suppression pattern. The half-life of pentobarbital ranges from around 20 hours, however it could be extended in higher doses. In this way, prolonged comas after treatment with pentobarbital cannot be attributed to an “burnt out” brain prior to the medication having taken time to disappear. The pentobarbital levels are more effective to determine toxic residuals than in assessing the therapeutic effect.

All SE must be controlled with appropriate doses of pentobarbital. However, hypotension is a common occurrence. Typically it is a matter of volume replacement, and small doses of vasopressors will suffice. Myocardial function and regulation of temperature may be affected. The majority of reports on the use of pentobarbital reveal a very high risk of death that is often attributed to grave underlying illnesses that result in SE that are refractory enough to require pentobarbital. One of the benefits of pentobarbital aside from its constant efficacy when administered in large enough doses, is decrease in cerebral metabolism and blood flow. The infusion is also very easy to regulate. The ideal duration for barbiturate-induced compa hasn’t been defined. The recommendations range from 4 to 72 hours. At least 24 hours could be beneficial. Patients should probably be taking therapeutic doses of two anticonvulsants in addition to pentobarbital withdrawal.


Beta-adrenoceptor antagonists

Pentobarbital enhances clearance and decreases the concentrations in plasma of certain beta-blockers like alprenolol [100-101], resulting in reduction in beta-blockade. In healthy subjects, pentobarbital 100 mg decreased the concentrations in plasma of oral alprenolol at steady state 200 mg/day over a period of 10 days and its metabolite, 4-hydroxyalprenolol with no changes in half-lives.

In eight healthy subjects , pentobarbital 100 mg/day over 10 days decreased the AUC for metoprolol by 32% with significant variation between individuals (2-46 percent).



Pentobarbital is one of the barbiturates that can be capable of deep amnesia, hypnosis, sedation and anticonvulsant action in a dose-dependent way. It is not a natural analgesic with properties. If it is carefully titrated IV the sedation can be felt within 5 minutes, with the duration of 30-40 minutes.


Pentobarbital is an acid derivative of barbituric, is extensively used for anesthesia of nonhuman primates however it triggers significant respiratory and cardiovascular depletion and the effects are in a cumulative manner. The recovery from pentobarbital takes a long time and is often associated with an involuntary exuberance and the occurrence of prolonged ataxia. Pentobarbital is best replaced with other drugs, except for the last resort (nonrecovery) procedures, such as perfusion-fixation, where the effects of the drug on depression are considered not to be important. Thiopental can be a helpful induction agent, however maintaining of anesthesia through continuous infusion or administering multiple doses can result in lengthy recovery times. Therefore, it is best replaced by propofol or alphaxalone.