MIDAZOLAM HYDROCHLORIDE

MIDAZOLAM HYDROCHLORIDE
(mid'az-zoe-lam)
Classifications: benzodiazepine anxiolytic; sedative-hypnotic;
Therapeutic: antianxiety; sedative-hypnotic

Prototype: Lorazepam
Pregnancy Category: D
Controlled Substance: Schedule IV

Availability

2 mg/mL syrup; 1 mg/mL, 5 mg/mL injection

Action

Short-acting parenteral benzodiazepine that intensifies activity of gamma-aminobenzoic acid (GABA), a major inhibitory neurotransmitter of the brain, by interfering with its reuptake and promoting its accumulation at neuronal synapses. This calms the patient, relaxes skeletal muscles, and in high doses produces sleep.

Therapeutic Effect

Has CNS depressant with muscle relaxant, sedative-hypnotic, anticonvulsant, and amnestic properties.

Uses

Sedation before general anesthesia, induction of general anesthesia; to impair memory of perioperative events (anterograde amnesia); for conscious sedation prior to short diagnostic and endoscopic procedures; and as the hypnotic supplement to nitrous oxide and oxygen (balanced anesthesia) for short surgical procedures.

Contraindications

Intolerance to benzodiazepines; acute narrow-angle glaucoma; shock, coma; acute alcohol intoxication; intraarterial injection; status asthmaticus; pregnancy (category D), obstetric delivery, lactation.

Cautious Use

Patient with COPD; chronic kidney failure; cardiac disease; pulmonary insufficiency; dementia; electrolyte imbalance; neuromuscular disease; Parkinson's disease; psychosis; CHF; older adults; bipolar disorder.

Route & Dosage

Conscious Sedation
Adult: IM 0.07–0.08 mg/kg 30–60 min before procedure IV 1–2.5 mg, may repeat in 2 min prn; Intubated Patients, 0.05–0.2 mg/kg/h by continuous infusion
Child: IM 0.08 mg/kg x 1 dose PR 0.3 mg/kg x 1 dose; Intubated Patients, 2 mcg/kg/min by continuous infusion, may increase by 1 mcg/kg/min q30 min until light sleep is induced
Neonate: IV 0.5–1 mcg/kg/min

IV Induction for General Anesthesia
Adult: IV Premedicated, 0.15–0.25 mg/kg over 20–30 sec, allow 2 min for effect IV Non premedicated, 0.3–0.35 mg/kg over 20–30 sec, allow 2 min for effect
Child: IV 0.15 mg/kg followed by 0.05 mg/kg q2min times 1–3 doses

Status Epilepticus
Child: IV Loading Dose >2 mo, 0.15 mg/kg IV Maintenance Dose 1 mcg/kg/min infusion, may titrate upward as needed q5min

Preoperative Sedation
Child: PO <5 y, 0.5 mg/kg; >5 y, 0.4–0.5 mg/kg

Administration

Intramuscular
  • Inject IM drug deep into a large muscle mass.
Intravenous

PREPARE: Direct: Dilute in D5W or NS to a concentration of 0.25 mg/mL (e.g., 1 mg in 4 mL or 5 mg in 20 mL).  IV Infusion: Add 5 mL of the 5 mg/mL concentration to 45 mL of D5W or NS to yield 0.5 mg/mL.  

ADMINISTER: Direct for Conscious Sedation: Give over ≥2 min.  Direct for Induction of Anesthesia: Give over 20–30 sec.  Direct for Neonate: DO NOT give bolus dose; give over at least 2 min.  IV Infusion: Give at a rate based on weight.  

INCOMPATIBILITIES Solution/additive: Lactated Ringer's, pentobarbital, perphenazine, prochlorperazine. Y-site: Albumin, amoxicillin, amoxicillin/clavulanate, amphotericin B cholesteryl complex, ampicillin, bumetanide, butorphanol, ceftazidime, cefuroxime, clonidine, dexamethasone, foscarnet, fosphenytoin, furosemide, hydrocortisone, imipenem/cilastatin, methotrexate, nafcillin, omeprazole, sodium bicarbonate, thiopental, TPN, trimethoprim/sulfamethoxazole.

  • Store at 15°–30° C (59°–86° F), therapeutic activity is retained for 2 y from date of manufacture.

Adverse Effects (≥1%)

CNS: Retrograde amnesia, headache, euphoria, drowsiness, excessive sedation, confusion. CV: Hypotension. Special Senses: Blurred vision, diplopia, nystagmus, pinpoint pupils. GI: Nausea, vomiting. Respiratory: Coughing, laryngospasm (rare), respiratory arrest. Skin: Hives, swelling, burning, pain, induration at injection site, tachypnea. Body as a Whole: Hiccups, chills, weakness.

Interactions

Drug: Alcohol, cns depressants, anticonvulsants potentiate CNS depression; cimetidine increases midazolam plasma levels, increasing its toxicity; may decrease antiparkinsonism effects of levodopa; may increase phenytoin levels; smoking decreases sedative and antianxiety effects. Food: Grapefruit juice (>1 qt/d) may increase risk of myopathy and rhabdomyolysis. Herbal: Kava, valerian may potentiate sedation. Echinacea, St. John's wort may reduce efficacy.

Pharmacokinetics

Onset: 1–5 min IV; 5–15 min IM, 20–30 min PO. Peak: 20–60 min. Duration: <2 h IV; 1–6 h IM. Distribution: Crosses blood–brain barrier and placenta. Metabolism: In liver (CYP3A4). Elimination: In urine. Half-Life: 1–4 h.

Nursing Implications

Assessment & Drug Effects

  • Inspect insertion site for redness, pain, swelling, and other signs of extravasation during IV infusion.
  • Monitor closely for indications of impending respiratory arrest. Resuscitative drugs and equipment should be immediately available.
  • Monitor for hypotension, especially if the patient is premedicated with a narcotic agonist analgesic.
  • Monitor vital signs for entire recovery period. In obese patient, half-life is prolonged during IV infusion; therefore, duration of effects is prolonged (i.e., amnesia, postoperative recovery).
  • Be aware that overdose symptoms include somnolence, confusion, sedation, diminished reflexes, coma, and untoward effects on vital signs.

Patient & Family Education

  • Do not drive or engage in potentially hazardous activities until response to drug is known. You may feel drowsy, weak, or tired for 1–2 d after drug has been given.
  • Be prepared for amnesia to prevent an upsetting postoperative period.
  • Review written instructions to assure future understanding and compliance. Patient teaching during amnestic period may not be remembered. Even if dose is small and depth of amnesia is unclear, relearn information.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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