midazolam hydrochloride

midazolam hydrochloride

(mid ay' zoh lam)

Pregnancy Category D

Controlled Substance C-IV

Drug classes

Benzodiazepine (short-acting)

CNS depressant

Therapeutic actions

Exact mechanisms of action not understood; acts mainly at the limbic system and reticular formation; potentiates the effects of GABA, an inhibitory neurotransmitter;anxiolytic and amnesia effects occur at doses below those needed to cause sedation, ataxia; has little effect on cortical function.

Indications

·        IV or IM: Sedation, anxiolysis, and amnesia prior to diagnostic, therapeutic, or endoscopic procedures or surgery

·        Induction of general anesthesia

·        Continuous sedation of intubated and mechanically ventilated patients as a component of anesthesia or during treatment in the critical care setting

·        Unlabeled uses: Treatment of epileptic seizure or refractory status epilepticus

Contraindications and cautions

·        Contraindicated with hypersensitivity to benzodiazepines; psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication; pregnancy (cleft lip or palate, inguinal hernia, cardiac defects, microcephaly, pyloric stenosis have been reported when used in first trimester; neonatal withdrawal syndrome reported in infants); neonates.

·        Use cautiously in elderly or debilitated patients; with impaired liver or kidney function, lactation.

Available forms

Injection—5 mg/mL, 1 mg/mL

Dosages

WARNING: Midazolam should only be administered by a person trained in general anesthesia and with equipment for maintaining airway and resuscitation on hand. Administer IV with continuous monitoring of respiratory and CV function. Individualize dosage; use lower dosage in the elderly and debilitated patients. Adjust dosage according to use of other premedication.

ADULTS

·        Preoperative sedation, anxiety, amnesia:
< 60 yr: 70–80 mcg/kg IM 1 hr before surgery (usual dose, 5 mg).
> 60 yr or debilitated: 20–50 mcg/kg IM 1 hr before surgery (usual dose, 1–3 mg).

·        Conscious sedation for short procedures:
< 60 yr: 1–1.5 mg IV initially, maintenance dose of 25% of initial dose.
> 60 yr: 1–2.5 mg IV initially, maintenance dose of 25% initial dose.

·        Induction of anesthesia:
< 55 yr: 300–350 mcg/kg IV (up to a total of 600 mcg/kg).
> 55 yr: 150–300 mcg/kg IV as initial dose.

·        Debilitated adults: 150–250 mcg/kg IV as initial dose.

·        Sedation in critical care areas: 10–50 mcg/kg (0.5–4 mg usual dose) as a loading dose; may repeat q 10–15 min until desired effect is seen; continuous infusion of 20–100 mcg/kg/hr to sustain effect.

PEDIATRIC PATIENTS

·        Preoperative sedation, anxiety, amnesia:
6 mo-16 yr: 0.01-0.15 mg/kg IM; do not exceed 10 mg/dose.

·        Conscious sedation for short procedures, > 12 yr: 1–1.5 mg IV initially, maintenance dose of 25% of initial dose.

·        Conscious sedation for short procedures prior to anesthesia:
6 mo–5 yr: 50–100 mcg/kg IV. Do not exceed 6 mg total dose.
6–12 yr: 25–50 mcg/kg IV initially. Up to 400 mcg/kg may be used; do not exceed 10 mg/dose.

·        Sedation in critical care areas for intubated patients only: 50–200 mcg/kg IV as a loading dose, then continuous infusion of 60–120 mcg/kg/hr.

Neonates > 32 wks' gestation: 60 mcg/kg/hr IV.

Neonates < 32 wks' gestation: 30 mcg/kg/hr IV.

IV facts

Preparation: Do not mix with other solutions; do not mix in plastic bags or tubing; may be used undiluted or diluted in D₅W, 0.9% normal saline, or lactated Ringers.

Infusion: Inject slowly into large vein over 2 min, monitoring patient response.

Incompatibilities: Do not mix with any other drugs.

Y-site incompatibilities: Albumin, ampicillin, ceftazidime, cefuroxime, clonidine, dexamethasone, foscarnet, furosemide, hydrocortisone, methotrexate, nafcillin,omeprazole, sodium bicarbonate.

Pharmacokinetics

Route	Onset	Peak	Duration
IM	15 min	30 min	2–6 hr
IV	3–5 min	< 30 min	2–6 hr

Metabolism: Hepatic metabolism; T_1/2: 1.8–6.8 hr

Distribution: Crosses placenta; enters breast milk

Excretion: Urine

Adverse effects

·        CNS: Transient, mild drowsiness (initially); sedation, depression, lethargy, apathy, fatigue, light-headedness, disorientation, restlessness, confusion, crying, delirium, headache, slurred speech, dysarthria, stupor, rigidity, tremor, dystonia, vertigo, euphoria, nervousness, difficulty in concentration, vivid dreams, psychomotor retardation, extrapyramidal symptoms; mild paradoxical excitatory reactions (during first 2 wk of treatment), visual and auditory disturbances,diplopia, nystagmus, depressed hearing, nasal congestion

·        CV: Bradycardia, tachycardia, CV collapse, hypertension, hypotension, palpitations, edema

·        Dermatologic: Urticaria, pruritus, skin rash, dermatitis

·        GI: Constipation, diarrhea, dry mouth, salivation, nausea, anorexia, vomiting, difficulty in swallowing, gastric disorders, elevations of blood enzymes: LDH, alkaline phosphatase, AST, ALT, hepatic dysfunction, jaundice

·        GU: Incontinence, urinary retention, changes in libido, menstrual irregularities

·        Hematologic: Decreased Hct, blood dyscrasias

·        Other: Phlebitis and thrombosis at IV injection sites, hiccups, fever, diaphoresis, paresthesias, muscular disturbances, gynecomastia; pain, burning, and redness after IM injection

·        Dependence: Drug dependence with withdrawal syndrome when drug is discontinued (more common with abrupt discontinuation of higher dosage used for longer than 4 mo)

Interactions

Drug-drug

·        Risk of increased CNS depression if combined with alcohol, antihistamines, opioids, other sedatives; decrease midazolam dose by up to 50% if any of these combinations are used

·        Decreased effectiveness if given with carbamazepine, phenytoin, rifampin, rifabutin, phenobarbital; monitor patient response carefully

Drug-food

·        Decreased metabolism and increased effects of midazolam with grapefruit juice; avoid this combination

Nursing considerations

Assessment

·        History: Hypersensitivity to benzodiazepines; psychoses, acute narrow-angle glaucoma, shock, coma, acute alcoholic intoxication with depression of vital signs; elderly or debilitated patients; impaired liver or kidney function; pregnancy, lactation

·        Physical: Weight; skin color, lesions; orientation, affect, reflexes, sensory nerve function, ophthalmologic examination; P, BP; respiratory rate, adventitious sounds; bowel sounds, normal output, liver evaluation; normal output; LFTs, renal function tests, CBC

Interventions

·        WARNING: Do not administer intra-arterially, which may produce arteriospasm or gangrene.

·        Do not use small veins (dorsum of hand or wrist) for IV injection.

·        Administer IM injections deep into muscle.

·        Monitor IV injection site for extravasation.

·        Arrange to reduce dose of midazolam if patient is also being given opioid analgesics; reduce dosage by at least 50% and monitor patient closely.

·        Monitor level of consciousness before, during, and for at least 2–6 hr after administration of midazolam.

·        Carefully monitor P, BP, and respirations carefully during administration.

·        WARNING: Keep resuscitative facilities readily available; have flumazenil available as antidote if overdose should occur.

·        Keep patients in bed for 3 hr; do not permit ambulatory patients to operate a vehicle following an injection.

·        Arrange to monitor liver and kidney function and CBC at intervals during long-term therapy.

·        Establish safety precautions if CNS changes occur (use side rails, accompany ambulating patient).

·        Provide comfort measures and reassurance for patients receiving diazepam for tetanus.

·        Arrange to taper dosage gradually after long-term therapy.

·        Provide patient with written information regarding recovery and follow-up care. Midazolam is a potent amnesiac and memory may be altered.

Teaching points

·        This drug will help you to relax and will make you go to sleep; this drug is a potent amnesiac and you will not remember what has happened to you.

·        Avoid using alcohol or sleep-inducing or over-the-counter drugs before receiving this drug. If you feel that you need one of these preparations, consult your health care provider.

·        You may experience these side effects: Drowsiness, dizziness (these may become less pronounced after a few days; avoid driving a car or engaging in other dangerous activities if these occur); GI upset; dreams, difficulty concentrating, fatigue, nervousness, crying (it may help to know that these are effects of the drug; consult your health care provider if these become bothersome).

·        Report severe dizziness, weakness, drowsiness that persists, rash or skin lesions, visual or hearing disturbances, difficulty voiding.

Adverse effects in Italic are most common; those in Bold are life-threatening.