Emergency Seizure Medicines

Emergency seizure medicines stop prolonged seizures and prevent brain injury. Status epilepticus is a seizure lasting 5 minutes or more, or repeated seizures without recovery. Treatment follows a time sequence: first-line benzodiazepine, second-line anticonvulsant, then anaesthesia. Treat the cause at the same time (hypoglycaemia, infection, eclampsia, drug toxicity, withdrawal).

Classification. Benzodiazepines (lorazepam, midazolam, diazepam); second-line anticonvulsants (levetiracetam, phenytoin, fosphenytoin, valproate, phenobarbital); anaesthetic agents (propofol, midazolam infusion, thiopental); specific agents (magnesium, pyridoxine, glucose).

Mechanism. Benzodiazepines and barbiturates enhance GABA-A inhibition. Phenytoin and valproate block sodium channels. Levetiracetam acts on synaptic vesicle protein SV2A. Magnesium blocks NMDA receptors.

Pharmacokinetics. Lorazepam acts within 5 minutes and lasts 12 to 24 hours. Midazolam intramuscular acts in 5 to 10 minutes. Diazepam redistributes quickly, so seizures can return. Phenytoin needs a slow infusion.

Practical points.

• Time the seizure and give the first drug at 5 minutes.
• Do not give second doses of benzodiazepines more than once, because breathing suppression builds.
• Give fosphenytoin (20 mg phenytoin equivalents/kg) when available, since it causes less vein injury.
• Phenytoin is ineffective in alcohol withdrawal and drug-induced seizures.
• Avoid valproate in women of childbearing age, in liver disease or mitochondrial disease unless no alternative.

• First-line. Benzodiazepine, with intramuscular midazolam or buccal midazolam where there is no intravenous access.
• Alternative. Rectal diazepam; intravenous diazepam if lorazepam is unavailable.
• Specialist. Anaesthetic infusions, ketamine, refractory status regimens, ketogenic diet, pyridoxine in infants.
• Emergency. All seizures lasting 5 minutes or more, repeated seizures, eclampsia.

Selection. Levetiracetam, valproate and phenytoin have similar efficacy in established status; choose by availability, comorbidity and pregnancy. Use magnesium for eclampsia.

Contraindications. Phenytoin: heart block, bradycardia. Valproate: liver disease, mitochondrial disorders, pregnancy. Benzodiazepines: severe respiratory depression without airway support. Phenobarbital: porphyria.

Serious adverse effects.

• Respiratory depression and hypotension (benzodiazepines, phenobarbital, propofol).
• Phenytoin: arrhythmia and hypotension with fast infusion, tissue necrosis (purple glove syndrome).
• Valproate: liver failure, hyperammonaemia, pancreatitis, teratogenicity.
• Levetiracetam: irritability, behaviour change, rarely rash.

Major interactions. Phenytoin induces CYP enzymes (warfarin, contraceptives, antiretrovirals); valproate raises lamotrigine levels; enzyme inducers shorten midazolam and benzodiazepine effects; carbapenems lower valproate levels.

Common prescribing errors.

• Delaying the first drug.
• Underdosing the benzodiazepine.
• Giving phenytoin too fast or diluting it in glucose.
• Missing hypoglycaemia, alcohol or eclampsia as the cause.
• Not planning for the airway.

Special groups.

• Pregnancy: magnesium for eclampsia; levetiracetam acceptable; avoid valproate; lorazepam or midazolam for acute seizures.
• Breastfeeding: acute use acceptable; monitor the infant.
• Children: weight-based doses; buccal or intramuscular midazolam first; phenobarbital in neonates.
• Older adults: lower phenytoin infusion rates, higher risk of breathing depression.
• Kidney: reduce levetiracetam dose; phenytoin free levels rise in low albumin.
• Liver: avoid valproate; reduce doses.
• East Africa: diazepam, phenobarbital and phenytoin are the most widely available, and intravenous levetiracetam and lorazepam are often absent; cerebral malaria, meningitis and neurocysticercosis are common causes of seizures, so check glucose and treat infection promptly.

Monitoring. Airway, oxygen saturation, blood pressure, ECG with phenytoin, glucose, sodium, calcium, magnesium, renal and liver tests; EEG if consciousness does not return.

Referral and escalation. Seizure over 30 minutes, need for intubation, unknown cause, pregnancy-related seizure, or suspected infection of the brain.

Comparison with alternative classes. Benzodiazepines work fastest and stop most seizures when given early. Second-line drugs prevent recurrence. Anaesthesia is reserved for refractory cases.