Can phenobarbital be administered intravenously (IV)?

Can Phenobarbital Be Given Intravenously?

Yes, phenobarbital can and should be administered intravenously for specific indications including status epilepticus, acute seizures, and when oral administration is impossible or impractical. 1

Approved Indications for IV Phenobarbital

IV phenobarbital is FDA-approved for:

• Status epilepticus and acute convulsive episodes (including those associated with eclampsia, cerebral hemorrhage, meningitis, tetanus, and toxic reactions) 1
• Emergency seizure control when rapid therapeutic levels are needed 1
• Sedation when oral routes are not feasible (unconscious patients, resistant patients, or when prompt action is required) 1
• Preoperative sedation 1

Dosing Guidelines

Adults

• Status epilepticus/acute convulsions: 20-320 mg IV, may repeat in 6 hours as necessary 1
• Loading dose for status epilepticus: 15-20 mg/kg over 10-15 minutes 2
• Maximum infusion rate: Do not exceed 60 mg/min 1

Pediatrics

• Status epilepticus: 15-20 mg/kg over 10-15 minutes IV 2, 1
• Anticonvulsant maintenance: 4-6 mg/kg/day for 7-10 days to achieve blood levels of 10-15 mcg/mL 1
• Preoperative sedation: 1-3 mg/kg IM or IV 1

Neonates

• Loading dose: 15-20 mg/kg IV, which produces blood levels of approximately 20 mcg/mL shortly after administration 1, 3
• Maintenance: 3-4 mg/kg/day (not to exceed 5 mg/kg/day to avoid accumulation) 3

Clinical Evidence for IV Use

Phenobarbital is equally efficacious to other first-line agents for status epilepticus. The VA Cooperative Study demonstrated that phenobarbital was equally effective as lorazepam, phenytoin, and phenytoin plus diazepam in managing status epilepticus 2. More recent evidence from China showed IV phenobarbital achieved 81.1% success rate in generalized convulsive status epilepticus, significantly higher than valproate's 44.4% 4.

WHO guidelines recommend IV phenobarbital as second-line therapy. When IV access is available and seizures continue after benzodiazepines, IV phenobarbital or phenytoin should be administered for sustained control 2. The Annals of Emergency Medicine guidelines also recommend phenobarbital as one of several acceptable agents for refractory status epilepticus 2.

Critical Safety Considerations

Administration Technique

• Use large veins only (avoid dorsum of hand or wrist) to minimize thrombosis risk 1
• Avoid varicose veins due to retarded circulation 1
• Never inject intraarterially - this can cause gangrene requiring amputation 1
• Careful aspiration technique is mandatory to avoid inadvertent arterial injection 1

Monitoring Requirements

Continuous monitoring is essential during IV administration:

• Blood pressure, respiration, and cardiac function must be maintained 1
• Vital signs must be recorded 1
• Equipment for resuscitation and artificial ventilation must be available 1
• Oxygen saturation monitoring is required 2

Major Adverse Effects

Respiratory depression and hypotension are the primary concerns:

• Phenobarbital causes profound respiratory depression and hypotension through vasodilatatory and cardiodepressant effects 2
• In the Chinese study, 5.4% of patients required ventilation and 5.4% developed serious hypotension 4
• Risk increases when combined with other sedative agents, particularly benzodiazepines 2

Timing Considerations

Phenobarbital requires 15 minutes or more to reach peak brain concentrations after IV administration. 1 This delayed onset means:

• Continuous injection until seizures stop can cause brain concentrations to exceed therapeutic needs 1
• Use minimal amounts required and wait for anticonvulsant effect before administering second dose 1
• The combination of barbiturate-induced depression plus postictal depression can be dangerous once seizures are controlled 1

Special Populations

Renal/Hepatic Impairment

Dosage must be reduced in patients with impaired renal function or hepatic disease 1

Elderly/Debilitated

Dosage should be reduced as these patients are more sensitive to barbiturates 1

Obesity

Dosing should be calculated using total body weight, with a loading dose of approximately 19.5 mg/kg TBW 5

Therapeutic Drug Monitoring

• Therapeutic anticonvulsant level: 10-25 mcg/mL 1
• Toxic concentrations: >50 mg/L may induce coma; >80 mg/L may be fatal 6
• Neonatal therapeutic range: 15-30 mcg/mL 3

Common Pitfalls to Avoid

1. Do not inject too rapidly - exceeding 60 mg/min in adults increases risk of cardiorespiratory depression 1
2. Do not use subcutaneous route - this is contraindicated 1
3. Do not use intramuscular diazepam as alternative - erratic absorption makes it unreliable 2
4. Do not continue injecting until seizures stop - this leads to excessive brain concentrations and severe depression 1
5. Do not use prophylactically in all seizure patients - prophylactic phenobarbital increased mortality in Kenyan children with cerebral malaria, particularly when combined with multiple diazepam doses 2