Status epilepticus phenobarbital

Occasionally, status epilepticus (an emergency situation characterized by continual seizure activity with no interruptions) can occur. Diazepam (Valium) is most often the initial drug prescribed for this condition. However, because the effects of diazepam last less than 1 hour, a longer-lasting anticonvulsant, such as phenytoin or phenobarbital, also must be given to control the seizure activity. 

The Working Group on Status Epilepticus recommends that phenobar-bital be given after a BZ plus phenytoin has failed. Most practitioners agree that phenobarbital is the long-acting anticonvulsant of choice in patients with hypersensitivity to the hydantoins or in those with cardiac conduction abnormalities. 

Barbiturates Phenobarbital- (PB) Status epilepticus Epilepsy, all forms Tonic-clonic 40 to 60 Liver 25% eliminated unchanged in urine... 

Seizures. Simple isolated seizures may require only observation and supportive care. Repetitive seizures or status epilepticus require therapy. Give IV diazepam or lorazepam followed by fosphenytoin and/or phenobarbital. Pancuronium may also be considered. 

Phenobarbital is still used for the management of partial seizures, generalized tonic-clonic seizures and for the control of status epilepticus. However because of its low therapeutic index and the possibility of dependence, phenobarbital has largely been displaced by other anticonvulsants. For newborns phenobarbital is often the drug of first choice. If given together with sodium valproate the metabolism of phenobarbital may be inhibited while in combination with carbamazepine the serum concentrations of carbamazepine will be reduced due to enzyme induction by phenobarbital. 

Phenobarbital Enhances phasic GABAa receptor responses reduces excitatory synaptic responses Nearly complete absorption not significantly bound to plasma proteins peak concentrations in Vi to 4 h no active metabolites tjy2 varies from 75 to 125 h Generalized tonic-clonic seizures, partial seizures, myoclonic seizures, generalized seizures, neonatal seizures, status epilepticus Toxicity Sedation, cognitive issues, ataxia, hyperactivity Interactions Valproate, carbamazepine, felbamate, phenytoin, cyclosporine, felodipine, lamotrigine, nifedipine, nimodipine, steroids, theophylline, verapamil, others... 

When utilized as sedative hypnotics, barbiturates are administered orally. They are rapidly and completely absorbed by this route with nearly 100% bioavailability and an onset of action ranging from 10 to 60 min.3 Sodium salts are more rapidly absorbed than free acids. Intramuscular injections of sodium salts should be made deep into the muscle to prevent pain and tissue damage. Some barbiturates are also administered rectally barbiturates utilized for the induction and maintenance of anesthesia (thiopental) or for treating status epilepticus (phenobarbital) are administered intravenously. 

In a multicenter, randomized, double-blind comparison of diazepam (0.15 mg/kg followed by phenytoin 18 mg/kg), lorazepam (0.1 mg/kg), phenobarbital (15 mg/kg), and phenytoin (18 mg/kg) in 518 patients with generalized convulsive status epilepticus, lorazepam was more effective than phenytoin and at least as effective as phenobarbital or diazepam plus phenytoin (1). Drug-related adverse effects did not differ significantly among the treatments and included hypoventilation (up to 17%), hypotension (up to 59%), and cardiac rhythm disturbances (up to 9%). 

A 20-month-old girl developed status epilepticus after ingesting camphor and required ventilation. She was treated with intravenous diazepam and phenobarbital and nasogastric-activated charcoal and made a complete neurological recovery (3). 

Seizures are present in 30% of patients with star fruit intoxication [17], and most patients have convulsive [6, 8,10,11,13,14,17,18,19] or non-convulsive [16] status epilepticus. The mortality rate of patients with seizures occurring after star fruit intoxication (severe intoxication) is significantly higher than of patients without seizures [13, 17]. Phenytoin, midazolam, diazepam and phenobarbital seem to have little or no effect on the control of persistent seizures provoked by star fruit toxicity. However, significant clinical improvement of seizure was demonstrated in one patient after the use of profofol [20]. 

Barbiturates (Phenobarbital, mephobarbital, primidone) Treat grand mal and acute episodes or status epilepticus, meningitis, toxic rations, and eclampsia... 

Additional studies carried out in animal models of temporal lobe epilepsy (TLE) further support the use of selective ABCBl inhibitors to reverse drug resistance in RE. Thus, tariquidar potentiates the effect of phenytoin and countervails resistance to phenobarbital in a rat model of TLE. Furthermore, cyclosporin A helps reverse resistance to phenytoin in a rat model of AED-resistant status epilepticus. Finally, verapamil counteracts resistance to oxacarbazepine in rats with pilocarpine-induced seizures [42]. 

Crawford TO, Mitchell WG, Fishman LS, Snodgrass SR. Very-high-dose phenobarbital for refractory status epilepticus in children. Neurology 1988 38 1035-1040. 

Mirski MA,Wilhams MA, Hanlet DF. Prolonged pentobarbital and phenobarbital coma for refractory generalized status epilepticus. Crit Care Med 1995 23 400-404. 

Phenobarbital has selective antiseizure activity at low doses and has a long half-life suitable for maintenance treatment in seizure disorders (for characteristics of barbiturates, see sedative-hypnotics). Clonazepam is usually a backup drug in absence and myoclonic seizures it causes marked sedation at anticonvulsant doses. IV lorazepam and diazepam are both used in status epilepticus. 

Status epilepticus Lorazepam, diazepam, phenytoin, or fosphenytoin Phenobarbital (long term)... 

ABSORPTION, FATE, AND EXCRETION For sedative-hypnotic use, the barbiturates usually are administered orally (Table 16-3) absorption is rapid and nearly complete. The onset of action varies from 10-60 minutes, depending on the agent and the formulation, and is delayed by the presence of food in the stomach. When necessary, intramuscular injections of solutions of the sodium salts should be placed deeply into large muscles to avoid the pain and possible necrosis that can result at more superficial sites. The intravenous route usually is reserved for the management of status epilepticus (phenobarbital sodium) or for the induction and/or maintenance of general anesthesia (e.g., thiopental or methohexital). 

A. Pentobarbital is used for the management of status epilepticus that is unresponsive to conventional anticonvulsant therapy (eg, diazepam, phenytoin, or phenobarbital). If the use of pentobarbital for seizure control is considered, consultation with a neurologist is recommended. 

A. Control of tonic-clonic seizures and status epilepticus, generally as a seconder third-line agent after diazepam or phenytoln have been tried. Note For treatment of dmg-Induced seizures, especially seizures caused by theophylline, phenobarbital Is often tried before phenytoln. 

A. Control of generalized tonic-clonic seizures or status epilepticus. However, benzodiazepines (see p 415) and phenobarbital (p 486) are generally more effective for treating drug-induced seizures. 

Prasad, A, Williamson, JM, Bertram, EH (2002) Phenobarbital and MK-801, but not phenytoin, improve the long-term outcome of status epilepticus. Ann Neurol, 51 175-181. 

Malamiri RA, Ghaempanah M, Khosroshahi N, Nikkhah A, Bavarian B, Ashrafi MR. Efficacy and safety of intravenous sodium valproate versus phenobarbital in controlling convulsive status epilepticus and acute prolonged convulsive seizures in children a randomised trial. Eur J Paediatr Neurol September 2012 16(5) 536-41. 

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