What is the recommended method of administration for lorazepam (Ativan) in neonates?

Lorazepam Administration in Neonates

Recommended Route of Administration

Intravenous (IV) administration is the preferred and recommended route for lorazepam in neonates, particularly for seizure management, though intramuscular (IM) administration may be used when IV access is unavailable. 1

IV Administration Protocol

Preparation and Dilution

• Lorazepam injection must be diluted with an equal volume of compatible solution immediately prior to IV use 1
• Compatible diluents include: Sterile Water for Injection, Sodium Chloride Injection, or 5% Dextrose Injection 1
• Mix thoroughly by gently inverting the container repeatedly until homogenous—do not shake vigorously as this causes air entrapment 1

Rate of Administration

• The rate of IV injection should not exceed 2 mg per minute 1
• The drug may be injected directly into a vein or into the tubing of an existing IV infusion 1

Dosing for Neonatal Seizures

• For refractory neonatal seizures (after phenobarbital failure), administer 0.05 mg/kg IV, which may be repeated up to a total dose of 0.15 mg/kg if necessary 2
• Clinical response typically occurs within 3 minutes of administration 2

IM Administration (Alternative Route)

• IM lorazepam is not preferred because therapeutic levels are not reached as quickly as with IV administration 1
• However, when IV access is unavailable, IM route may prove useful 1
• When given IM, inject undiluted deep into the muscle mass 1

Critical Safety Considerations in Neonates

Pharmacokinetic Alterations

• Neonates have dramatically altered lorazepam pharmacokinetics: total clearance is reduced by 80%, terminal half-life is prolonged 3-fold, and volume of distribution is decreased by 40% compared to adults 1
• Lorazepam metabolism depends on glucuronidation, an enzymatic process that is severely depressed in premature infants, leading to drug accumulation and toxicity 3
• Neonates conjugate lorazepam slowly to the inactive glucuronide, which is then excreted in urine where it remains detectable for over 7 days 4

Toxicity Risk in Preterm Infants

• Premature infants are at particularly high risk for lorazepam toxicity due to immature glucuronidation pathways 3
• Toxic accumulation can manifest as extreme hypotonia, unresponsiveness, and prolonged sedation lasting days after discontinuation 3
• Cord plasma concentrations exceeding 45 mcg/L are associated with three-quarters of infants requiring ventilation at birth 4

Respiratory Monitoring Requirements

• Maintain an unobstructed airway, monitor vital signs continuously, and have artificial ventilation equipment immediately available 1
• Be prepared to provide respiratory support, as there is increased risk of apnea when combined with other sedative agents 5
• Monitor oxygen saturation continuously 5

Clinical Context: Status Epilepticus Management

First-Line Treatment

• Phenobarbital is the preferred first-line anticonvulsant for neonatal seizures 5, 6
• Neonatal phenobarbital dosing: 10 mg/kg IV (compared to 20 mg/kg in children) 5
• Neonates have increased risk of phenytoin toxicity due to decreased protein binding; phenobarbital is preferred over phenytoin 5

Second-Line Treatment with Lorazepam

• Lorazepam should be reserved for seizures refractory to phenobarbital (after 40 mg/kg total dose) 2
• Six of seven neonates in one study responded with complete cessation of seizures within 3 minutes of lorazepam administration 2
• No patients developed apnea or hypotension during or immediately after lorazepam infusion in this cohort 2

Common Pitfalls to Avoid

• Do not use lorazepam as first-line therapy for neonatal seizures—phenobarbital remains the drug of choice 5, 6
• Never administer undiluted lorazepam IV—always dilute with equal volume of compatible solution 1
• Do not exceed 2 mg/minute infusion rate to minimize cardiovascular effects 1
• Avoid prolonged or repeated dosing in premature infants due to severe risk of accumulation and toxicity 3
• Do not assume adult or pediatric dosing applies—neonates require specific dose adjustments due to dramatically altered pharmacokinetics 1
• Inspect solution visually for particulate matter and discoloration before administration; do not use if discolored or contains precipitate 1

Special Populations

Preterm vs. Term Neonates

• Intravenous lorazepam use before 37 weeks gestation should be restricted to hospitals with neonatal intensive care facilities 4
• Preterm babies have higher incidence of low Apgar scores, need for ventilation, hypothermia, and poor suckling compared to term infants 4
• Full-term neonates generally tolerate lorazepam better, with complications limited primarily to slight delay in establishing feeding 4