What is the best approach to manage an active seizure in an emergency room (ER) patient with a suspected overdose, considering their airway, breathing, and circulation (ABCs) and potential need for medication such as benzodiazepines (e.g. lorazepam) or antiepileptic drugs (e.g. levetiracetam)?

Managing Active Seizures in Overdose Patients

Immediately administer IV lorazepam 4 mg at 2 mg/min while simultaneously securing the airway and assessing for reversible causes—benzodiazepines are the definitive first-line treatment with 65% efficacy in terminating seizures, regardless of the overdose etiology. 1, 2

Immediate Stabilization (0-5 Minutes)

Airway and breathing take absolute priority before any pharmacologic intervention. Overdose patients progress to cardiac arrest through loss of airway patency and respiratory failure, not primary cardiac pathology. 1, 3

Critical First Actions:

• Position the patient to protect the airway—turn to side if possible, do not restrain or place anything in the mouth 2
• Establish IV access and prepare for bag-mask ventilation with oxygen immediately available 1, 2
• Check fingerstick glucose immediately—hypoglycemia is a rapidly reversible cause that must be corrected simultaneously 2
• Administer IV lorazepam 4 mg at 2 mg/min (can repeat once after 5 minutes if seizure continues) 1, 2

Key pitfall: Lorazepam is superior to diazepam (65% vs 56% success rate) and has longer duration of action than other benzodiazepines, making it the preferred agent. 2 If lorazepam is unavailable, use IV diazepam or IM midazolam 10 mg as alternatives. 2

Simultaneous Evaluation for Reversible Causes:

While administering benzodiazepines, immediately assess for: 1, 2

• Hypoglycemia (check fingerstick glucose)
• Hyponatremia (obtain basic metabolic panel)
• Hypoxia (pulse oximetry, supplemental oxygen)
• Drug toxicity (obtain history of ingestion—particularly tricyclic antidepressants, sympathomimetics, anticholinergics)
• Withdrawal syndromes (alcohol, benzodiazepines)

Critical consideration in overdose patients: Do not administer flumazenil to reverse benzodiazepine overdose if the patient is seizing, as flumazenil can precipitate refractory seizures and remove benzodiazepine-mediated seizure suppression, particularly dangerous in mixed overdoses with cyclic antidepressants. 1

Second-Line Treatment (5-20 Minutes)

If seizures continue after two doses of lorazepam (total 8 mg), immediately escalate to one of the following second-line agents—do not delay. 1, 2

Recommended Second-Line Agents (Choose One):

Valproate is the preferred second-line agent with superior safety profile: 2

• Dose: 20-30 mg/kg IV over 5-20 minutes (typically 1500-2500 mg for average adult)
• Efficacy: 88% seizure control
• Hypotension risk: 0% (significantly safer than phenytoin)
• Advantage: No cardiac monitoring required, minimal cardiovascular effects

Levetiracetam is an excellent alternative: 1, 2, 4

• Dose: 30 mg/kg IV over 5 minutes (maximum 2500-3000 mg)
• Efficacy: 68-73% seizure control
• Advantage: Minimal adverse effects, no hypotension risk, no cardiac monitoring required
• Particularly useful in: Elderly patients, those with cardiovascular instability

Fosphenytoin (traditional agent): 1, 2

• Dose: 20 mg PE/kg IV at maximum rate of 50 mg/min
• Efficacy: 84% seizure control
• Hypotension risk: 12%
• Requires: Continuous ECG and blood pressure monitoring
• Disadvantage: Slower administration, cardiovascular toxicity

Phenobarbital: 1, 2

• Dose: 20 mg/kg IV over 10 minutes
• Efficacy: 58.2% as initial second-line agent
• Major concern: Higher risk of respiratory depression and hypotension
• Use cautiously in: Overdose patients already at risk for respiratory compromise

Critical decision point: Valproate appears superior to phenytoin in head-to-head trials (88% vs 84% efficacy, 0% vs 12% hypotension risk) while maintaining similar efficacy, making it the preferred second-line agent in hemodynamically unstable overdose patients. 2

Refractory Status Epilepticus (20+ Minutes)

If seizures persist despite benzodiazepines and one second-line agent, this defines refractory status epilepticus—initiate continuous EEG monitoring and prepare for anesthetic agents. 1, 2

Third-Line Anesthetic Agents:

Midazolam infusion (first-choice anesthetic): 2

• Loading dose: 0.15-0.20 mg/kg IV bolus
• Infusion: 1 mg/kg/min continuous infusion, titrate up by 1 mg/kg/min every 15 minutes to maximum 5 mg/kg/min
• Efficacy: 80% overall success rate
• Hypotension risk: 30% (significantly lower than pentobarbital)
• Advantage: Better hemodynamic profile than barbiturates

Propofol: 2

• Loading dose: 2 mg/kg bolus
• Infusion: 3-7 mg/kg/hour
• Efficacy: 73% seizure control
• Hypotension risk: 42%
• Advantage: Shorter ventilation time (4 days vs 14 days with pentobarbital)
• Requires: Mechanical ventilation, continuous blood pressure monitoring

Pentobarbital (most effective but highest risk): 2

• Loading dose: 13 mg/kg bolus
• Infusion: 2-3 mg/kg/hour
• Efficacy: 92% seizure control (highest of all agents)
• Hypotension risk: 77% requiring vasopressors
• Disadvantage: Prolonged mechanical ventilation (mean 14 days), severe hypotension

All anesthetic agents require: 2

• Mechanical ventilation and respiratory support
• Continuous EEG monitoring to guide titration
• Continuous blood pressure monitoring
• Vasopressor support readily available

Special Considerations in Overdose Patients

Respiratory Management:

Overdose patients have compounded respiratory depression risk from both the ingested substance and seizure medications. 1, 5

• Have airway equipment immediately available before administering any benzodiazepine
• Prepare for bag-mask ventilation and intubation
• Monitor oxygen saturation continuously
• Be prepared to provide mechanical ventilation regardless of medication route

Mixed Overdoses:

Benzodiazepine overdose should not preclude timely naloxone administration when opioid co-ingestion is suspected—this is particularly critical given opioid-adulterated illicit drugs. 1 Administer naloxone 0.4-2 mg IV/IM/IN while maintaining ventilation if opioid toxicity is suspected. 3

Avoid These Critical Errors:

• Never use neuromuscular blockers alone (e.g., rocuronium)—they only mask motor manifestations while allowing continued electrical seizure activity and brain injury 2
• Never skip to third-line agents (pentobarbital, propofol) until benzodiazepines and a second-line agent have been tried 2
• Never use flumazenil in seizing patients or those with suspected cyclic antidepressant co-ingestion—it precipitates refractory seizures and dysrhythmias 1, 5

Monitoring Requirements:

• Continuous vital sign monitoring, particularly respiratory status and blood pressure 2
• Continuous EEG monitoring once refractory status epilepticus is reached 2
• Monitor for at least 30 minutes after last benzodiazepine dose for delayed respiratory depression 2
• Continue monitoring until risk of recurrent toxicity is low, as naloxone and benzodiazepine antagonist effects may be shorter than the ingested substance 3