What are the guidelines for using lorazepam (Ativan) in pediatric patients?

Lorazepam Use in Pediatric Patients

Lorazepam is most commonly used in pediatric patients for acute agitation and status epilepticus, with weight-based dosing of 0.05-0.1 mg/kg (maximum 4 mg per dose) via IV/IM routes, though it is NOT FDA-approved for status epilepticus in children and carries significant risks including respiratory depression and paradoxical excitation in younger patients. 1, 2, 3

Primary Indications and Dosing

Acute Agitation/Behavioral Emergencies

• Lorazepam is the most commonly used benzodiazepine for acute pediatric agitation, with advantages including no extrapyramidal symptoms, low addiction potential, and high therapeutic index 1
• Standard dosing: 0.05-0.1 mg/kg PO/IM/IV for children (prepubertal ages 6-12 years) 1
• Adolescent dosing: 0.5-1 mg, may repeat every 30-60 minutes 1
• Combination therapy: Often combined with haloperidol or risperidone in older adolescents (>16 years) for enhanced effect, and can be administered in the same syringe with butyrophenones 1

Status Epilepticus (Off-Label Use)

• Critical caveat: The FDA has NOT established safety and effectiveness of lorazepam for status epilepticus in pediatric patients, and a randomized trial of 273 children failed to demonstrate superiority over diazepam 3
• Despite lack of FDA approval, the American Academy of Pediatrics recommends 0.05-0.1 mg/kg IV (maximum 4 mg per dose) for status epilepticus, repeatable every 10-15 minutes 2
• Alternative IM dosing: 0.2 mg/kg (maximum 6 mg per dose) when IV access unavailable 2
• Time course: IV onset 5-10 minutes, peak 15-30 minutes, duration 2 hours; IM onset 15 minutes, peak 1 hour, duration 6-8 hours 1
• Important limitation: Lorazepam is rapidly redistributed and seizures often recur within 15-20 minutes, necessitating long-acting anticonvulsant coverage with phenytoin (18 mg/kg IV) or fosphenytoin (20 mg phenytoin equivalents/kg) 2

Critical Safety Concerns

Respiratory Depression

• Respiratory support must be immediately available regardless of route, with continuous oxygen saturation monitoring 2, 4
• Increased risk of apnea when combined with other sedatives, particularly in neonates and young children 1, 2
• Assisted ventilation was required in 18% of pediatric patients treated with lorazepam for status epilepticus in clinical trials 3

Paradoxical Excitation

• Occurs in 10-30% of children under 8 years of age, characterized by tremors, agitation, euphoria, logorrhea, and brief visual hallucinations 3
• Paradoxical behavioral disinhibition from benzodiazepines is especially common in younger children and those with developmental disabilities 1

Benzyl Alcohol Toxicity

• Lorazepam injection contains benzyl alcohol as a preservative, which has been associated with "gasping syndrome" in neonates at doses >99 mg/kg/day 3
• Symptoms include: CNS depression, metabolic acidosis, gasping respirations, seizures, intracranial hemorrhage, cardiovascular collapse 3
• Premature and low-birth-weight infants are at highest risk and practitioners should consider cumulative benzyl alcohol load from all sources 3

Neonatal Considerations

• Phenobarbital is preferred first-line for neonatal seizures (10 mg/kg IV), not lorazepam 4
• If lorazepam is used in neonates: Maintain unobstructed airway, monitor vital signs continuously, have artificial ventilation equipment immediately available 4
• Research suggests lorazepam may be effective for refractory neonatal seizures at 0.05 mg/kg IV (up to 0.15 mg/kg total), though this remains off-label 5

Contraindications and Precautions

• Absolutely contraindicated for intoxication 1
• Use with extreme caution in patients with respiratory compromise 1
• Never give oral lorazepam to a patient who just had a seizure due to aspiration risk in the postictal period 2
• Avoid flumazenil to reverse sedation in seizure patients, as it will precipitate seizure recurrence 2

Drug Interactions

• Oral contraceptives: Decrease lorazepam half-life by 55% and increase clearance 3.7-fold; may need to increase lorazepam dose by 50% 3
• Probenecid: Prolongs lorazepam half-life by 130% and decreases clearance by 45%; reduce lorazepam dose by 50% when coadministered 3

Pharmacokinetics in Children

• Systemic clearance in children: 1.3 ± 0.4 ml/min/kg, somewhat higher than adults (1.0 ± 0.4 ml/min/kg) 6
• Terminal half-life: 10.5 ± 2.9 hours in children 6
• Tachyphylaxis occurs with repeated dosing; lorazepam becomes progressively less effective when sequential doses are required 7

Post-Administration Monitoring

• Continue monitoring for seizure recurrence for at least 2 hours after initial lorazepam administration 2
• Monitor for: Respiratory depression, hypotension, sedation (67% of patients in trials), paradoxical excitation 1, 3
• Return to baseline mental status averages 2 hours longer with lorazepam compared to diazepam 3

Alternative Routes (Non-Intravenous)

• Buccal/intranasal routes show similar efficacy to IV administration but avoid delays in establishing IV access 8
• Intranasal lorazepam appears as effective as IV lorazepam (RR 0.96,95% CI 0.82-1.13) 8
• Rectal administration has erratic absorption and is not recommended as first-line 2