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This Manual has been designed for use in the NICU at London Health Sciences Centre (LHSC), London, Ontario, Canada, and represents clinical practice at this institution. The information contained within the Manual may not be applicable to other centres. If users of this Manual are not familiar with a drug, it is recommended that the official monograph be consulted before it is prescribed and administered. Any user of this information is advised that the contributors, Editor and LHSC are not responsible for any errors or omissions, and / or any consequences arising from the use of the information in this Manual.

LORAZEPAM

Indication

  • 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.

Pharmacology

  • 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

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)

Precautions

  • 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

Dose

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

Supplied

  • 4 mg/mL, 1 mL ampoule (keep refrigerated)

    SHOULD BE DILUTED BEFORE USE

    The procedure is as follows

    1. Two labels will come from Pharmacy. These will be afixed to a zip-lock plastic bag.
      1. Computer label:

        Baby Smith NICU 18Nov93
        Lorazepam 4mg/mL ampoule
        0.2 mg IV q6h prn
      2. Additional label that provides directions for dilution:

        NAME Baby Smith NICU

        ADD 0.25 mL OF LORAZEPAM 4 mg/mL

        TO
        9.75 mL OF DILUENT (D5W)
        TO PRODUCE A FINAL CONCENTRATION OF
        1 mg/10mL = 0.1 mg/mL = 100 mcg/mL

        DOSE = 200 mcg (0.2 mg)
                   = 2 mL OF 100 mcg/mL SOLN

        IV Q 6 H (PRN)

    2. Empty 10 mL vials with the following label will also be supplied for the nurse to make the dilution:

      LORAZEPAM *100 MCG/mL*
      * NOTE STRENGTH*

      EXPIRES 24H AFTER PREPN
      PREPARED:_____@_____HRS
      REFRIGERATE

References

  1. McEvoy G K (ed): AHFS Drug Information, American Society of Hospital Pharmacists, 1991.
  2. The Pharmacological Basis of Therapeutics, Gilman AG, Goodman LS Rall TW and Murad F (eds), 7th Edition, MacMillan, 1985
  3. Krogh CME et al (ed): Compendium of Pharmaceuticals and Specialties, Canadian Pharmaceutical Association, 1992.
  4. Cronin CMG: Neurotoxicity of lorazepam in a premature infant (letter) Pediatrics 1992; 89:1129-30
  5. 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.
  6. Roddy SM, McBride MC and Torres CF: Treatment of neonatal seizures with lorazepam (abstract), Ann Neurol 1987; 22: 412.
  7. Rieter PO and Stiles AD: Lorazepam toxicity in a premature infant, The Annals of Pharmacotherapy 1993; 27: 727-729.
  8. Wong AH, Lee DSC and Knoppert DC: Seizure activity following intravenous administration of lorazepam in very low birth weight infants (unpublished).
  9. 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.
  10. 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.



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