Nonconvulsive Status Epilepticus

Nonconvulsive status epilepticus is prolonged or repeated electrographic seizure activity with altered awareness or behaviour but without prominent convulsive motor signs. The diagnosis rests on EEG.

Epidemiology. It accounts for a large part of status epilepticus in intensive care. About one in ten comatose patients who undergo EEG shows nonconvulsive seizures, with higher rates after convulsive status and in sepsis, brain injury and cardiac arrest. It is frequently missed.

Causes and associations.

• Prior convulsive status that has become subtle.
• Acute brain injury (stroke, haemorrhage, head injury, anoxia), encephalitis and sepsis.
• Epilepsy with antiseizure medicine withdrawal and benzodiazepine withdrawal.
• Drugs lowering seizure threshold: beta lactams in renal failure, carbapenems, cefepime, theophylline, tramadol and bupropion.
• Metabolic disorders and, in older adults, de novo absence status in late life.

Classification. Absence status, focal status with impaired awareness, comatose status after convulsive status, and status in critically ill patients with coma or fluctuating consciousness.

Pathophysiology. Sustained synchronous cortical discharge occurs without propagation to cause convulsions. Injury risk rises with duration in structural disease and critical illness. Absence status is generally benign for neurones, while focal and comatose forms may be harmful.

Presentation is confusion, reduced responsiveness, fluctuating consciousness, staring, speech arrest, automatisms, perseveration, behaviour change, psychosis like states or unexplained coma. Subtle eyelid or facial twitching, nystagmus or minimal myoclonus may be present. Unexplained alteration of consciousness, especially after convulsions, in sepsis, after brain injury or in older adults, warrants EEG.

Red flags.

• Failure to wake within 20 to 30 minutes after convulsions stop.
• Unexplained coma in intensive care.
• New cognitive change after cefepime, carbapenem, theophylline or tramadol exposure, or after withdrawal of a benzodiazepine or antiseizure medicine.

EEG is required, ideally continuous for at least 24 hours, and for 48 hours in comatose patients because many seizures appear after 24 hours. Criteria are epileptiform discharges over 2.5 Hz, or discharges of 2.5 Hz or less with evolution in frequency, amplitude or location, or EEG and clinical improvement after an intravenous antiseizure drug.

A benzodiazepine challenge (lorazepam 1 to 2 mg IV in aliquots every 2 to 5 minutes, up to 0.1 mg/kg in total, with EEG and clinical review) supports the diagnosis but a negative response does not exclude it, and clinical improvement without EEG improvement is not diagnostic.

Also check glucose, electrolytes, calcium, creatinine, liver tests, ammonia, toxicology, drug levels and infection markers, and do MRI brain.

Differential diagnosis.

• Toxic and metabolic encephalopathy with triphasic waves, which may respond clinically to benzodiazepines.
• Delirium, psychosis and the postictal state.
• Hypoglycaemia, encephalitis, hepatic encephalopathy and uraemia.
• Transient global amnesia and psychogenic states.

Stabilise airway, breathing and circulation. Check glucose and give dextrose 25 g IV (adults) if under 3.0 mmol/L. Remove precipitants, such as stopping cefepime or carbapenems or adjusting them to renal function.

Focal status with impaired awareness, and comatose forms. Give a first line benzodiazepine and then a second line drug.

• Lorazepam 0.1 mg/kg IV (maximum 4 mg a dose), repeated once after 5 to 10 minutes. Monitor respiration and blood pressure.
• Levetiracetam 60 mg/kg IV over 10 minutes (maximum 4500 mg), maintenance adjusted to eGFR: 500 to 1000 mg every 12 hours for eGFR 50 to 79, 250 to 750 mg every 12 hours for 30 to 49, and 250 to 500 mg every 12 hours under 30.
• Valproate 40 mg/kg IV over 10 minutes (maximum 3000 mg). Avoid in liver disease, mitochondrial disease and pregnancy.
• Fosphenytoin 20 mg PE/kg IV at up to 150 mg PE/min (maximum 1500 mg PE) with ECG monitoring.
• Lacosamide 200 to 400 mg IV is an option. Monitor the PR interval and avoid in second or third degree heart block.

Absence status. Lorazepam 1 to 2 mg IV (repeat to a total of 0.1 mg/kg) or diazepam 5 to 10 mg IV, then valproate 40 mg/kg IV (maximum 3000 mg) or levetiracetam 60 mg/kg IV (maximum 4500 mg). Avoid carbamazepine, phenytoin, vigabatrin and tiagabine, which can worsen absence status.

Intensity of treatment. In critically ill comatose patients, escalate to an anaesthetic infusion only when seizures persist and the likely benefit outweighs the harm, because aggressive treatment may worsen outcome in frail or very ill patients. When used, give midazolam 0.2 mg/kg IV bolus then 0.05 to 2 mg/kg/h, or propofol 1 to 2 mg/kg IV bolus then 2 to 5 mg/kg/h (under 48 hours for any rate over 5 mg/kg/h), with continuous EEG.

Monitoring. Continuous EEG, level of consciousness, sedation, glucose, electrolytes, and renal and liver function.

Referral and escalation. Refer to neurology for EEG interpretation. Escalate to intensive care when consciousness is falling, the airway is threatened or an anaesthetic infusion is needed.

Special groups. In older adults, use lower doses and expect more sedation. In renal impairment, adjust levetiracetam and avoid precipitating beta lactams. In pregnancy, avoid valproate.