Barbiturates status epilepticus

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

Diazepam (Valium, Diastat) [C-IVj [Anxiolytic, Skeletal Muscle Relaxant, Anticonvulsant, Sedative/Hypnotic/ Benzodiazepine] Uses Anxiety, EtOH withdrawal, muscle spasm, status epilepticus, panic disorders, amnesia, preprocedure sedation Action Benzodiazepine Dose Adults. Status epilepticus 5-10 mg IV/IM Anxiety 2-5 mg IM/IV Preprocedure 5-10 mg IV just prior to procedure Peds. Status epilepticus 0.5-2 mg IV/IM Sedation 0.2-0.5 mg/kg IV (onset w/in 5IV and 30 min IM duration about 1 h IV and IM) Caution [D, / -] Contra Coma, CNS depression, resp d es-sion, NAG, severe uncontrolled pain, PRG Disp Tabs 2, 5, 10 mg soln 1, 5 mg/mL inj 5 mg/mL rectal gel 2.5, 5, 10, 20 mg/mL SE Sedation, amnesia, bradycardia, i BP, rash, X resp rate Interactions T Effects W/ antihistamines, azole antifungals, BBs, CNS depressants, cimetidine, ciprofloxin, disulfiram, INH, OCP, omeprazole, phenytoin, valproic acid, verapamil, EtOH, kava kava, valman T effects OF digoxin, diuretics X effects w/ barbiturates, carbamazepine. 

Refractory status epilepticus that has failed to respond to one of these treatments, and has continued for more than 20-30 min, requires urgent action. The accepted strategy is to paralyze and ventilate the patient and administer an antiepileptic drug in sufficient dosage to suppress EEG evidence of seizure activity. The barbiturate anaesthetic thiopental (thiopentone), the benzodiazepine midazolam, and the anaesthetic propofol have all been used. What little comparative evidence there is remains inconclusive. Such treatment can only be carried out with facilities for artificial ventilation and intensive care, and effects can only be monitored by EEG recording. 

Onset of unconsciousness is rapid but it is associated with a high incidence of excitatory effects, comparable to methohexitone, but these can be reduced by prior administration of an opioid. Analogous to the barbiturates, etomidate decreases CMR02, CBF and ICP but the haemodynamic stability of the drug will maintain CPP. Its well-known inhibition of adrenocortical function limits its clinical usefulness for long-term control of elevated ICP. While etomidate can produce convulsion-like EEC potentials in the absence of apparent convulsions, it has been used to terminate status epilepticus. 

Two prominent aspects of benzodiazepines limit their usefulness. The first is their pronounced sedative effect, which is unfortunate both in the treatment of status epilepticus and in chronic therapy. Children may manifest a paradoxical hyperactivity, as with barbiturates. The second problem is tolerance, in which seizures may respond initially but recur within a few months. The remarkable antiseizure potency of these compounds often cannot be realized because of these limiting factors. 

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. 

Barbiturates may also be used to treat a life-threatening seizure condition called Status Epilepticus. Most epileptic seizures last for several seconds and then resolve on their own, but occasionally a patient will continue seizing for several minutes or even hours. This can be very dangerous because the seizure may cause serious damage to the patient s muscles and internal organs. Patients with this condition must be admitted to a hospital, and injectable medicines must be used to try to stop the seizure. The first drugs that are tried are benzodiazepines and some newer anti-epileptic medications, but if these fail to break the seizure, barbiturates like pentobarbital or secobarbital are used. 

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

If the decision is made to attempt AED withdrawal, this should be done gradually. This may be particularly true for patients with profound developmental disabilities. Some patients will have a recurrence of seizures as the AEDs are withdrawn. Sudden withdrawal is associated with the precipitation of status epilepticus. Withdrawal seizures are of particular concern for agents such as benzodiazepines and barbiturates. Seizure relapse has been reported to be more common if the AEDs are withdrawn over 1 to 3 months than over 6 months. 

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. 

Because it markedly lowers cerebral metabolism, thiopental has been used as a protectant against cerebral ischemia. At least one human study suggests that thiopental may be efficacious in ameliorating ischemic damage in the perioperative setting. Thiopental also reduces intraocular pressure. Perhaps due to their CNS depressant activity, barbiturates are effective anticonvulsants thiopental in particular is effective in the treatment of status epilepticus. 

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). 

Most reports in the clinical literature recommend stopping the convulsion within 1 hour, using drastic measures, such as hypothermia and barbiturate coma, if necessary.108 The mortality of status epilep-ticus (usually defined as a convulsion lasting 60 min, or a series of convulsions lasting 60 min without consciousness intervening) is said to be 6% to 30%. Moreover, twice that number of victims acquire irreversible neurological deficits as a result of status epilepticus.108 (In a study of children, permanent deficits were found to occur in 34%.109) These data emphasize the need for an effective anticonvulsant. 

Orlowski JP, Erenberg G, Lueders H, Cruse RP. Hypothermia and barbiturate coma for refractory status epilepticus. Crit Care Med. 1984 12 367-372. 

I. Pharmacology. Pentobarbital is a short-acting barbiturate with anticonvulsant as well as sedative-hypnotic properties. It is used as a third-line drug in the treatment of status epilepticus. It may also reduce intracranial pressure in patients with cerebral edema by inducing vasoconstriction. After intravenous administration of a single dose, the onset of effect occurs within about 1 minute and lasts about 15 minutes. Pentobarbital demonstrates a biphasic elimination pattern the half-life of the initial phase is 4 hours, and the terminal phase half-life is 35-50 hours. Effects are prolonged after termination of a continuous infusion. 

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