Midazolam HCl

A to Z Drug Facts

 Action Depresses all levels of CNS, including limbic and reticular formation, probably through increased action of GABA, which is major inhibitory neurotransmitter in brain.

 Indications Preoperative sedative; conscious sedation prior to diagnostic, therapeutic or endoscopic procedures; induction of general anesthesia; supplement to nitrous oxide and oxygen for short surgical procedures; infusion for sedation of intubated and mechanically ventilated patients as a component of anesthesia or during treatment in critical care setting. Unlabeled use(s): Treatment of epileptic seizures; alternative for the termination of refractory status epilepticus.

 Contraindications Hypersensitivity to benzodiazepines; uncontrolled pain; existing CNS depression; shock; acute narrow-angle glaucoma; acute alcohol intoxication; coma.

 Route/Dosage

Preoperative Sedative

ADULTS: IM 0.07–0.08 mg/kg approximately 1 hr before surgery.

Conscious Sedation

ADULTS: IV 1–2.5 mg as 1 mg/ml dilution over 2 min. Increase by small increments to total dose of £ 5 mg at no less than 2 min intervals; use less if patient is premedicated with other CNS depressants. CHILDREN: IM 0.1–0.15mg/kg. Doses up to 0.5 mg/kg have been used for more anxious patients. Total dose usually does not exceed 10 mg. CHILDREN 6 < MONTHS: IV Titrate in small increments to clinical effect and monitor carefully. CHILDREN 6 MONTHS-5 YR: 0.05 to 0.1 mg/kg. Total dose up to 0.6 mg/kg may be necessary. Do not exceed 6 mg. 6–12 YR: 0.025 to 0.05 mg/kg. Total dose up to 0.4 mg/kg. Do not exceed 10 mg. 12–16 yr: Dose as adults.

Induction of General Anesthesia

UNPREMEDICATED ADULT PATIENTS: IV 0.3–0.35 mg/kg as 1 mg/ml dilution over 20–30 sec, allowing 2 min for effect; may use increments of approximately 25% of initial dose. PREMEDICATED ADULT PATIENTS: IV 0.15–0.35 mg/kg over 20–30 sec.

Continuous Infusion

ADULTS: Loading dose: .01–0.05 mg/kg given slowly over several minutes. May be repeated at 10–15 minute intervals until adequate sedation is achieved. Maintenance: .02–0.1 mg/kg/hr (1 to 7 mg/hr). PEDIATRIC (NON-NEONATAL): IV 0.05–0.2 mg/kg over at least 2 to 3 minutes in patients whose trachea is intubated. Loading dose may be followed by continuous IV infusion at 0.06–0.12 mg/kg/hr (1 to 2 mcg/kgl/min). Increase or decrease » 25% of the initial infusion rate or subsequent infusion rate. INTUBATED PRETERM AND TERM NEONATES < 32 WEEKS: 0.03 mg/kg/hr (0.5 mcg/kg/min). > 32 WEEKS: 0.06 mg/kg/hr (1 mcg/kg/min).

Maintenance of anesthesia IV Increments of » 25% of induction dose in response to signs of lightening of anesthesia and repeat as necessary.

 Interactions

Anesthetics, inhalation: Inhalation anesthetics may need to be reduced if midazolam is used as an induction agent. IV administration decreases minimum alveolar concentration of halothane required for general anesthesia. Azole antifungal agents: Serum concentration of certain benzodiazepines may be increased and prolonged, producing enhanced CNS depression and prolonged effects. Barbiturates, alcohol, other CNS depressants: May prolong effect and increase risk of underventilation or apnea. Cimetidine: May increase midazolam levels. Droperidol, narcotics, secobarbital: May accentuate hypnotic effect of midazolam. INCOMPATIBILITIES: Dimenhydrinate, pentobarbital, perphenazine, prochlorperazine, ranitidine. Ethanol: Increased CNS effects with acute ethanol ingestion. Fluvoxamine: educed clearance, prolonged half-life and increased serum concentrations of certain benzodiazepines may occur. Sedation or ataxia may be increased. Indinavir: Possibly severe sedation and respiratory depression. Oral contraceptives: Coadministration may result in prolongation of benzodiazepine half-life. Propofol: harmacologic effects of propofol may be increased. Rifamycins: harmacokinetic parameters of benzodiazepines may be altered. Ritonavir: Possibly severe sedation and respiratory depression. Theophyllines: Sedative effects of benzodiazepines may be antagonized. Thiopental: Moderate reduction in induction dosage requirements has been noted following use of IM midazolam for premedication. Valproic acid: harmacokinetic parameters of benzodiazepines may be increased. Liver metabolism may be decreased. Verapamil: Effects of certain benzodiazepines may be increased, producing increased CNS depression and prolonged effects.

 Lab Test Interferences None well documented.

 Adverse Reactions

CV: Bigeminy; hypotension; PVCs; tachycardia; cardiac arrest; vasovagal episode; bradycardia; nodal rhythm. RESP: Respiratory depression or arrest; decreased tidal volume, decreased respiratory rate; apnea, coughing; laryngospasm; bronchospasm; dyspnea; hyperventilation; heezing; shallow respirations; airway obstruction; tachypnea. CNS: Headache; oversedation; retrograde amnesia; euphoria or dysphoria; confusion; rgumentativeness; anxiety; emergence delirium and dreaming; nightmares; tonic/clonic movements; tremor; athetoid movements; ataxia; dizziness; slurred speech; aresthesia; weakness; loss of balance; drowsiness; nervousness; agitation; estlessness; prolonged emergence from anesthesia; insomnia; dysphonia. EENT: Vision disturbances; nystagmus; pinpoint pupils; cyclic eyelid movements; locked ears; blurred vision; diplopia; difficulty focusing; loss of balance. GI: Nausea; vomiting; acid taste; excessive salivation; retching. DERM: Hives; hive-like elevation at injection site; swelling or feeling of burning; warmth or coldness at injection site; rash; pruritus. OTHER: Pain, tenderness and induration at injection site; yawning; chills; ethargy; weakness; toothache; faint feeling; hematoma. Children: Desaturation; apnea; hypotension; paradoxical reactions; hiccough; seizure-like activity; nystagmus.

 Precautions

Pregnancy: Category D. Labor and delivery: Drug not recommended because of transplacental transfer. Lactation: Midazolam is excreted in breast milk. Exercise caution when administering to a nursing mother. Children: As a group, pediatric patients generally require higher dosages of midazolam (mg/kg) than do adults. Younger (< 6 years old) pediatric patients may require higher dosages (mg/kg) than older pediatric patients and may require closer monitoring. In obese pediatric patients, calculate the dose based on ideal body weight. Elderly or debilitated patients: May need to decrease dosage. Titration should be more gradual. Special risk patients: High-risk surgical patients require lower doses. Patients with COPD are unusually sensitive to respiratory depressant effects. In renal or heart failure patients, give less frequently. Exercise care when administering to patients with uncompensated acute illness (eg, severe fluid or electrolyte disturbances). Serious cardiorespiratory events: Have occurred, including respiratory depression, airway obstruction, desaturation, permanent neurologic injury, apnea, respiratory arrest or cardiac arrest, sometimes resulting in death. Improper dosing: Reactions such as agitation, involuntary movements, hyperactivity and combativeness have been reported. Neonates: Rapid injection has been associated with severe hypotension. Seizures have been reported in neonates following rapid IV administration. Ophthalmic: Moderate lowering of IOP following induction with midazolam. Intra-arterial injection: Unknown. Renal function impairment: Patients with renal impairment may have longer elimination half-life for midazolam, which may result in slower recovery. Intracranial pressure/circulatory side effects: Does not protect against the increase in intracranial pressure or circulatory effects associated with endotracheal intubation under light general anesthesia. Hazardous tasks: No patient should operate hazardous machinery or a motor vehicle until the side effects of the drug have subsided or until the day after anesthesia and surgery, whichever is longer.

 Administration/Storage

• For IM administration, inject deeply in large muscle mass.
• Prior to intravenous administration, ensure availability of resuscitative equipment.
• For IV administration, titrate slowly to achieve desired effect (initiation of slurred speech).
• Do not use IV loading dose in neonates; the infusion may be run more rapidly for the first several hours to establish therapeutic plasma levels.
• Frequently reassess the rate of infusion, particularly after the first 24 hours, so as to administer the lowest dose and reduce the potential for drug accumulation.
• Give no more than 2.5 mg over at least 2 min; wait additional 2 min to fully evaluate the sedative effect.
• Continuously monitor patients for hypoventilation or apnea.
• Do not administer IV medication as rapid or bolus dose. Excessive or rapid IV dosing may result in respiratory arrest.
• Avoid intra-arterial injection.
• Avoid extravasation.
• May mix midazolam in same syringe as morphine, meperidine, atropine or scopolamine.
• Midazolam is compatible with Sodium Chloride for Injection, D5W, Ringer's Lactate Solution for 24 hr.
• Store at room temperature.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note history of glaucoma, hypersensitivity to benzodiazepines and existing CNS depression.
• Continuously monitor patient for hypoventilation or apnea.
• Assist with ambulation after procedure until drowsiness resolves.
• Because serious life-threatening cardiorespiratory events have been reported, make provision for monitoring, detection and correction of these reactions for every patient regardless of health status.

 Patient/Family Education

• Inform patient and family pre-operatively about possibility of temporary postoperative amnesia.
• Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness until drowsiness has subsided or until day after administration, whichever is longer.
• Advise patient to avoid alcohol and other CNS depressants for 24 hr following administration.
• The patient should inform her physician if she is pregnant, planning to become pregnant or is breastfeeding.
• Patients receiving continuous infusion in critical care settings over an extended period of time may experience symptoms of withdrawal following abrupt discontinuation.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts