Is intravenous (IV) diazepam safe for use in infants?

Safety of Intravenous Diazepam in Infants

Intravenous diazepam should be used with extreme caution in infants due to significant risks of respiratory depression, apnea, and prolonged central nervous system depression, and should only be administered when respiratory support is immediately available.

Risks and Safety Concerns

Diazepam administration in infants carries substantial risks that require careful consideration:

• Respiratory Depression: The FDA drug label explicitly warns that extreme care must be used when administering IV diazepam to patients with limited pulmonary reserve due to the possibility of apnea and/or cardiac arrest 1.

• Prolonged CNS Depression: The FDA label states that "prolonged central nervous system depression has been observed in neonates, apparently due to inability to biotransform diazepam into inactive metabolites" 1.

• Accumulation of Metabolites: Research has shown that accumulation of N-desmethyldiazepam (the main depressive metabolite) occurs in all infants, which must be considered when repeated doses are administered 2.

• Adverse Events: A retrospective study found that 16% of infants receiving benzodiazepines experienced adverse events including seizures, hypotension, and respiratory depression 3.

Administration Guidelines

If diazepam must be used in an infant (such as for status epilepticus where benefits may outweigh risks):

1. Dosing:

   • For status epilepticus: The American Academy of Pediatrics recommends 0.1-0.3 mg/kg IV 4, 5
   • The FDA label specifically states that in pediatric use, "it is recommended that the drug be given slowly over a three-minute period in a dosage not to exceed 0.25 mg/kg" 1

2. Administration Method:

   • IV administration should be done slowly over at least 1 minute for each 5 mg (1 mL) given 1
   • Avoid small veins such as those on the dorsum of the hand or wrist 1
   • Extreme care should be taken to avoid intra-arterial administration or extravasation 1

3. Monitoring Requirements:

   • Continuous respiratory monitoring is essential
   • Resuscitative equipment must be immediately available 1
   • Oxygen saturation should be monitored throughout administration 5

Alternative Routes of Administration

When IV access is not available:

• Rectal Administration: Evidence-based guidelines for management of epilepsy recommend rectal diazepam when IV access is not available 4
• Research has shown rectal administration to be effective in 80% of cases for acute treatment of convulsions in children, with therapeutic concentrations achieved within 5 minutes 2, 6
• Intramuscular administration is not recommended due to erratic absorption 4

Special Considerations

• Neonates (≤30 days): The FDA label states that "efficacy and safety of parenteral diazepam has not been established in the neonate (30 days or less of age)" 1

• Concomitant Medications: When diazepam is used with a narcotic analgesic, the dosage of the narcotic should be reduced by at least one-third and administered in small increments 1

• Continuous Infusion: If continuous infusion is required (rare cases), research suggests doses of at least 1 mg/h (approximately 0.3 mg/kg/h) for full-term infants, with close monitoring of respiration and heart rate 7

In conclusion, while IV diazepam can be used in infants for specific indications like status epilepticus, its use requires extreme caution, appropriate dosing, careful administration techniques, and continuous monitoring due to significant safety concerns.