- lorazepam is used in adult as a sedative agent and also as an anticonvulsant. It has also been used in neonates for these indications. However, there is very little literature which has been published in this area.
- lorazepam is a benzodiazepine and shares the actions (ie. anxiolytic, sedative, hypnotic skeletal muscle relaxant and anticonvulsant) of this group of drugs
- the CNS sedative/hypnotic effects of benzodiazepines are thought to be medicated by the inhibitory neurotransmitter, gamma-aminobutyric acid
- disinhibition is possible and can produce paradoxical CNS stimulation
- lorazepam is metabolized in the liver, the majority of the drug is connected to the glucuronide derivative; less than 1% of a dose is eliminated unchanged via the kidneys
- 10 neonates (39.6 weeks gestational age, 3260g) received a single lorazepam dose of 0.05 to 0.1 mg/kg (50 to 100 mcg/kg) IV to control seizures that were unresponsive to phenobarbital and/or phenytoin(124), the mean half life was 40.2 h, significantly greater than that reported in children (10.5 h) and adults (12.9 h); all seizure activity was stopped within 5 min in all 10 neonates, without any observable side effects
- the most frequent side effects are those which are an extension of its CNS depressant effects (excessive sleepiness, drowsiness)
- other possible side effects include respiratory depression, partial airway obstruction, skin rash, vomiting and pain and erythema at the injection site
- paradoxical effects, manifested as irritability and excitability, have occurred with benzodiazepines
- symptoms of serious overdosage may include ataxia, hypotonic and hypotension
- at least 4 cases of neonatal seizures following the IV administration of lorazepam have been reported in the literature(80,121); we also have experience of 2 neonatal seizures following the IV administration of lorazepam(122)
- lorazepam should be diluted before use. It must NOT be injected intraarterially (can result in arteriospasm), special care should be taken to ensure that extravasation does not occur
- respiratory depression and hypotension, 2 possible side effects, are believed to be primarily due to the high propylene glycol content (80%) which is present in the undiluted concentration (4mg/mL). To avoid this, the drug should be administered over several minutes. The 4 mg/mL concentration also contains polyethylene glycol 18% and benzyl alcohol 2%. At SJHC we recommend that lorazepam 4 mg/mL be diluted with D5W to produce a 1 mg/mL concentration.
- the possibility of seizures following the IV administration of lorazepam should be borne in mind
- taper lorazepam over 2 to 4 days if therapy is extended
FOR SEIZURE CONTROL WHICH IS REFRACTORY TO CONVENTIONAL ANTICONVULSANT THERAPY (ie. PHENOBARBITAL, PHENYTOIN)
- the use of lorazepam for the above indication has been reported in 1 paper (7 infants).(81) A single dose of 0.05mg/kg (50mcg/kg) was given IV over 2 to 5 minutes
- in another report, 13 neonates (25 to 43 weeks) who had been previously treated with phenobarbital and/or phenytoin, received lorazepam 0.04 to 0.1 mg/kg; seven received a single dose, 6 infants received 2 or more doses.(82)
FOR SEDATION OF THE MECHANICAL VENTILATED NEONATE
- single IV doses of 0.1 to 0.43 mg/kg of lorazepam were given from 2 to 13 times within 24h to 15 neonates who were inadequately sedated with phenobarbital; these infants received lorazepam for up to 15 consecutive days without any lorazepam-associated toxicity or withdrawal symptoms.(123)
- our limited experience at SJHC suggests that an initial dose of 0.05 to 0.1 mg/kg (50 to 100 mcg/kg) IV Q6H may be adequate
- give slow IV push
- McEvoy G K (ed): AHFS Drug Information, American Society of Hospital Pharmacists, 1991.
- The Pharmacological Basis of Therapeutics, Gilman AG, Goodman LS Rall TW and Murad F (eds), 7th Edition, MacMillan, 1985
- Krogh CME et al (ed): Compendium of Pharmaceuticals and Specialties, Canadian Pharmaceutical Association, 1992.
- Cronin CMG: Neurotoxicity of lorazepam in a premature infant (letter) Pediatrics 1992; 89:1129-30
- Deshmukh A, Wittert W, Schnitzler E et al: Lorazepam in the treatment of refractory neonatal seizures, American Journal of Diseases in Children 1986; 14: 1042-1044.
- Roddy SM, McBride MC and Torres CF: Treatment of neonatal seizures with lorazepam (abstract), Ann Neurol 1987; 22: 412.
- Rieter PO and Stiles AD: Lorazepam toxicity in a premature infant, The Annals of Pharmacotherapy 1993; 27: 727-729.
- Wong AH, Lee DSC and Knoppert DC: Seizure activity following intravenous administration of lorazepam in very low birth weight infants (unpublished).
- Maloley PA, Gal P, Mize R et al: lorazepam dosing in neonates - application of objective sedation scores, DICP The Annals of Pharmacotherapy 1990; 24:326-327.
- McDermott CA, Kowalczyk AL, Schnitzler ER et al: Pharmacokinetics of lorazepam in critically ill neonates with seizures, The Journal of Pediatrics 1992; 120:479-483.