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The Use of Pentobarbital Sodium

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 Pentobarbital)

Barbiturates are used to relax children younger than three years old for diagnostic imaging. They are fairly safe, however they are not advised for those suffering from porphyria. Most serious adverse effects include respiratory depression with apnea as well as hypotension. Both occur more frequently when barbiturates used together with opiates or benzodiazepines.

Thiopental (Pentothal) is a quick-acting barbiturate, with an onset the action lasting between 30 and 60 seconds when it is administered intravenously, and five to eight minutes when administered in rectally. It can have an 15 minutes of effect when administered intravenously, but up to one hour when it is administered by rectally. When administered intravenously, at dosages of 20-25 mg/kg, it is usually administered rectally to infants in a dose of 5-10 mg/kg. Thiopental is known to have the benefit of reducing the pressure in the intracranial artery; it is thus particularly beneficial for patients for whom an increase in intracranial pressure is an issue.

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Methohexital (Brevital) can be described as an extremely-short-acting drug with an onset between 30 and 60 seconds and a time of effects that ranges from 5-10 minutes. It’s twice as powerful as thiopental, and is able to be administered intravenously at a dosage in the range of 0.5 up to 1.0 mg/kg to children who are older than 12 years old. It should not be used to children younger than 12 years old and is not recommended for children with epilepsy of the temporal lobe as it could trigger seizures in this subset. Methohexital isn’t used often in the emergency department due to a single research (Zink 1991) of 102 patients which revealed 22 patients had respiratory depression that required bag-valve mask assistance. Five of the patients suffered from an acute apnea. When coupled with an analgesic drug the risk of respiratory depression can be reduced by administering the drug to ease pain and then increasing methohexital dosage to required effectiveness.

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 of between 3 and 5 minutes when administered intravenously and a period of effect of 30 to 45 mins. In infants and children younger than 6 months old, it is administered intravenously in a dose between 1 and 3 mg/kg. It is gradually increased between 3 and 5 minutes until the maximum dose of 100 mg or intramuscularly with the dosage of 2-6 mg/kg, with a maximum dose that is 100 milligrams.

Pentobarbital Sodium



Pentobarbital sodium salt is used to treat hypnosis and sedation for the short-term treatment of insomnia. Pentobarbital sodium is also employed as a premedication during anesthetic procedures. Pentobarbital is approved by the FDA for emergency treatment of convulsive events that are acute, e.g., those that are caused by status epilepticus meningitis, eclampsia or cholera 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 the field of experimental medicine to act as an anesthetic for small animals like rats and mouse. Pentobarbital is a powerful medication for treating seizures triggered by convulsive disorders which are often they are caused by strychnine.

Dosages for Drugs

Short-Acting Barbiturates: Pentobarbital

Pentobarbital is water-soluble. If it is released into the air with an estimated vapor pressure of 3x 10-10mmHg (25 degC) It will exist only as particulate phase in the atmosphere. As particulate pentobarbital it will be eliminated from the air by either dry or wet deposition. Pentobarbital isn’t susceptible to photolysis by sunlight since pentobarbital is not a source of the chromophores that absorb light wavelengths that exceed 290 nm. If pentobarbital does get released into soil and has a pKa value of 7.8 means that it is present as an anion that is not able to absorb very strongly into soils that contain clay or organic carbon. Pentobarbital is not likely to break down from soils that are moist on the basis of the estimated Henry’s law constant of 8.4 10-13 atm-cu-m mo-1. When released into water pentobarbital isn’t expected to absorb to suspended sediments and substances in water, based on an estimated Koc. Volatilization of water isn’t likely to be a significant fate-related process, based on Henry’s law constant estimates. Pentobarbital is estimated to have a bioconcentration factor (BCF) that is 11. This suggests the potential for bioconcentration within aquatic organisms is very low. Pentobarbital does not contain functional groups that are able to hydrolyze and hydrolysis isn’t expected to be a significant 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 frequency of seizures as compared to the baseline, generally occurring in the range of minutes to a few days. Seizure clusters can include any kind of seizure, and could be different in their severity however, by definition, they are completely recovered between seizures. Seizure clusters are most common in epilepsy patients who have drug resistance and, in particular, those who have epilepsy with no symptoms and extratemporal epilepsy. Seizure clusters in patients have a higher likelihood to be diagnosed with an epileptic history. Seizure clusters may be a precursor to long-lasting seizures, or even to status epilepticus. This progression could be anticipated for patients individually according to their history of seizures. This could determine the best course of treatment for seizures that occur in clusters. The milder clusters can be treated with oral doses containing the benzodiazepines. However, more serious clusters, especially those that are which can lead to seizures that last for a long time or have status epilepticus might require different methods of treatment. Rectal diazepam is the only FDA-approved medication for use outside of hospitals by non-medical caregivers (Cereghino and co. 1998) prior to when intranasal Midazolam spray received approval in the year 2019 (Detyniecki and colleagues. 2019,). Buccal midazolam is widely in use in Europe as well as in a variety of different countries (Nakken and Lossius in 2011) however, it has not been accepted for use in the United States. Intranasal diazepam has been approved by US FDA in the year 2020. The effectiveness of intramuscular diazepam administered by autoinjectors was proven in a blinded controlled study (Abou-Khalil and co. 2013, 2013) However, it didn’t result in FDA acceptance or marketing. Other strategies that were evaluated include buccal diazepam as well as staccato midazolam.

Status epilepticus was earlier defined as seizure-related activity that lasts for 30 minutes or recurrent seizures with no recovery between episodes. The duration of 30 minutes has been the subject of debate because it could delay aggressive treatment, particularly when a prolonged duration is anticipated in the absence of treatment. Evidence from experiments suggests that irreparable neuronal injury can occur after 20-30 mins of generalized convulsive state epilepticus (GCSE) (Fujikawa et al., 1996; Meldrum and Brierley 1973) Therefore, every effort must be taken to stop seizures prior to. The evidence suggests that the tonic-clonic period bilaterally of generalized or focal seizures lasts no longer than two minutes (Jenssen and colleagues. 2006a; Theodore et al. 1994) however, it can develop to become status epilepticus. This is why it is recommended that a vigorous treatment for status epilepticus should begin after five minutes of tonic-clonic activities (Lowenstein and. 1999). There is evidence to suggest that FIAS that last more than 10 minutes are likely to become status epilepticus (Jenssen and co. 2006a). Based on this data, 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 timing point 2)” (Trinka et al. (2015)). The time point t1 of epileptic status was 5 minutes for bilateral tonic-clonic seizures. 10-15 minutes in the case of focal seizures and 10-15 minutes in the absence of seizures.

Anesthesia and Analgesia


Pentobarbital is an oxybarbiturate-based analog to barbituric acid. 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 get activated which results in increased GABA binding and the opening of transmembrane chloride channels , leading to the hyperpolarization of cells within the nervous system’s central region. The administration of pentobarbital causes an effect that is dose-dependent, including hypnosis as well as muscle relaxation and stimulation of sensory cortex as well as the reticular activating mechanism.

Like other GABAA agonists, pentobarbital exhibits very little or no analgesic effect. Pentobarbital induces a dose-dependent depression of the respiratory system that could require respiratory assistance (Peeters and co. 1988). When doses are higher pentobarbital has anticonvulsant and hypotensive properties. The cause of hypotension is vasodilation and decreased myocardial contractility and a decrease in cardiac output. The effects of these and other cardiovascular conditions depend on the method of administration. They tend to be less noticeable when using IP instead of IV. This is because the blood concentration at its peak is achieved slower than when 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 most likely cause of hypothermia is result of a decreased vasodilation and basal metabolism. Sedation, as well as respiratory depression could occur if pentobarbital given alongside tranquilizers, benzodiazepines and alpha2-agonists and opioids propofol and inhalant anesthetic agents. Animals who are treated with pentobarbital should be provided with oxygen supplemental or monitored using pulse oxygen oximetry. General anesthetic doses can require respiratory support or intubation.

When pentobarbital has been administered an additional source of heat must be applied to animal during the time of the surgery and then continued until full recovery in order to avoid hypothermia. Pentobarbital is given intraperitoneally or intravenously. In the case of 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. Therefore, the intramuscular and subcutaneous methods of injection aren’t advised.

Status Epilepticus


Pentobarbital (or thiopental) can be a complete treatment for SE with refractory. Short-acting barbiturates can be absorbed quickly however, they need intensive treatment. The dose range that range from 3 to 5 mg/kg, followed by an infusion of 1 to 3 mg/kg/hour are common; there are studies that 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 pentobarbital therapy cannot be attributed to the “burnt out” brain prior to the medication having taken time to disappear. The pentobarbital levels are more effective in determining the residual toxicity of a drug than in assessing the therapeutic effect.

All SE must be controlled with appropriate doses of pentobarbital. However, hypotension is a common occurrence. Typically the volume replacement method and low doses of vasopressors 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 serious underlying conditions that cause SE resistant enough to warrant pentobarbital. One of the benefits of pentobarbital apart from its enduring efficacy when administered in large doses, is the decrease in cerebral metabolism as well as blood flow. It is also simple to alter. The ideal duration for barbiturate-induced compa hasn’t been determined. The recommendations range from 4 to 72 hours. A minimum of 24 hours could be beneficial. Patients are likely to be taking therapeutic doses of two anticonvulsants in addition to pentobarbital withdrawal.


Beta-adrenoceptor antagonists

Pentobarbital improves the clearance and lowers the plasma concentrations of certain beta-blockers, including alprenolol [100-101], resulting in reduction in beta-blockade. In six healthy individuals, pentobarbital 100 mg decreased the concentrations in plasma of oral alprenolol at steady state 200 mg/day for 10 consecutive days and its metabolite, 4-hydroxyalprenolol without affecting half-lives.

In eight healthy individuals, pentobarbital 100 mg/day for 10 consecutive days decreased the AUC for metoprolol100 mg by 32 percent with significant variation between individuals (2-46 percent).



Pentobarbital can be described as a barbiturate that can be capable of causing profound 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 it is sedative within 5 minutes and has the duration of 30-40 minutes.


Pentobarbital is the barbituric acid derivative is widely used to treat anesthesia of nonhuman primates however, it can cause 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 excessive excitement in the involuntary state and ataxia for a long time. Pentobarbital is more effective replaced by other drugs, except for the final (nonrecovery) procedures like perfusion-fixation, where the depressant effects of this medication are not considered to be significant. Thiopental can be a helpful induction agent, however maintaining of anesthesia through continuous infusion or administering multiple doses can result in long recovery times and it should be replaced with propofol or alphaxalone.