What is the management for a patient with lorazepam (Ativan) toxicity?

Management of Lorazepam Toxicity

Lorazepam toxicity requires immediate supportive care with airway management as the priority, followed by consideration of flumazenil administration in select cases without contraindications, and continuous monitoring for at least 2 hours after intervention due to risk of resedation.

Clinical Presentation of Lorazepam Toxicity

Lorazepam overdose typically manifests with:

• Mild cases: Drowsiness, mental confusion, paradoxical reactions, dysarthria, and lethargy 1
• Severe cases: Ataxia, hypotonia, hypotension, cardiovascular depression, respiratory depression, hypnotic state, coma, and potentially death 1
• Metabolic complications: Propylene glycol toxicity (from IV formulation) presenting as anion gap metabolic acidosis, hyperosmolality, and hyperlactatemia 2, 3

Management Algorithm

Step 1: Initial Assessment and Stabilization

• Secure airway, breathing, and circulation

  • Ensure patent airway and provide supplemental oxygen if needed 4
  • Monitor vital signs continuously 4
  • Establish IV access 4

• Avoid inducing emesis due to risk of aspiration 1

• Consider gastric lavage only if performed soon after ingestion or in symptomatic patients 1

• Administer activated charcoal to limit drug absorption if appropriate 1

Step 2: Specific Interventions

• For hypotension: Administer norepinephrine bitartrate injection 1

• For respiratory depression: Provide ventilatory support as needed 5

• Consider flumazenil administration in hospital settings for pure benzodiazepine overdose:

  • Adult dosing: Initial dose of 0.2 mg IV over 30 seconds, with additional doses of 0.3 mg IV if no response after 30 seconds (maximum cumulative dose: 3 mg) 4
  • Pediatric dosing: 0.01 mg/kg (up to 0.2 mg) IV over 15 seconds 4

Step 3: Monitoring and Continued Care

• Monitor for at least 2 hours after the last dose of flumazenil due to risk of resedation 4

• Check for propylene glycol toxicity in patients receiving IV lorazepam:

  • Monitor anion gap, osmolal gap, serum lactate, and renal function 2, 3
  • Consider discontinuing IV lorazepam if toxicity develops 2

• Hemodialysis consideration: Lorazepam is poorly dialyzable, but its inactive metabolite (lorazepam glucuronide) may be highly dialyzable 1

Important Contraindications and Precautions

Flumazenil Contraindications

Avoid flumazenil in patients with:

• Known seizure disorders
• Chronic benzodiazepine use (risk of precipitating withdrawal)
• Suspected mixed overdoses
• ECG abnormalities suggesting tricyclic antidepressant toxicity
• Recent neuromuscular blocking agent administration 4

Special Considerations

• Mixed overdoses: For suspected opioid co-ingestion, administer naloxone before flumazenil 4

• Propylene glycol toxicity risk factors:

  • High-dose IV lorazepam (>10 mg/hr)
  • Prolonged administration (>48 hours)
  • Renal dysfunction 2, 3, 6

• Pediatric and premature infant concerns: Neonates and premature infants are at higher risk of toxicity due to immature glucuronidation pathways 7

Pitfalls to Avoid

1. Administering flumazenil to chronic benzodiazepine users - may precipitate seizures and withdrawal syndrome 4

2. Overlooking propylene glycol toxicity - monitor for unexplained anion gap, metabolic acidosis, and hyperosmolality in patients receiving high-dose IV lorazepam 2, 3

3. Failing to monitor after flumazenil administration - resedation can occur due to flumazenil's short half-life (0.7-1.3 hours) compared to lorazepam's longer duration of action 4

4. Neglecting renal function - patients with renal impairment are at higher risk for propylene glycol accumulation and toxicity 6

5. Underestimating the severity of mixed overdoses - always consider potential co-ingestions that may complicate management 4, 1