Versed


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midazolam

(mid-ay-zoe-lam) ,

Versed

(trade name)

Classification

Therapeutic: antianxiety agents
Pharmacologic: benzodiazepines
Pregnancy Category: D

Indications

Oral: Preprocedural sedation and anxiolysis in pediatric patients. Intramuscular: Intravenous: Preoperative sedation/anxiolysis/amnesia. Intravenous: Provides sedation/anxiolysis/amnesia during therapeutic, diagnostic, or radiographic procedures (conscious sedation):
  • Aids in the induction of anesthesia and as part of balanced anesthesia,
  • As a continuous infusion, provides sedation of mechanically ventilated patients during anesthesia or in a critical care setting,
  • Status epilepticus.

Action

Acts at many levels of the CNS to produce generalized CNS depression.
Effects may be mediated by GABA, an inhibitory neurotransmitter.

Therapeutic effects

Short-term sedation.
Postoperative amnesia.

Pharmacokinetics

Absorption: Rapidly absorbed following oral and nasal administration; undergoes substantial intestinal and first-pass hepatic metabolism. Well absorbed following IM administration; IV administration results in complete bioavailability.
Distribution: Crosses the blood-brain barrier and placenta; excreted in breast milk.
Protein Binding: 97%.
Metabolism and Excretion: Almost exclusively metabolized by the liver, resulting in conversion to hydroxymidazolam, an active metabolite, and 2 other inactive metabolites (metabolized by cytochrome P450 3A4 enzyme system); metabolites are excreted in urine.
Half-life: Preterm neonates: 2.6–17.7 hr; Neonates: 4–12 hr; Children: 3–7 hr; Adults: 2–6 hr (increased in renal impairment, HF, or cirrhosis).

Time/action profile (sedation)

ROUTEONSETPEAKDURATION
IN5 min10 min30–60 min
IM15 min30–60 min2–6 hr
IV1.5–5 minrapid2–6 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Cross-sensitivity with other benzodiazepines may occur;Shock;Comatose patients or those with pre-existing CNS depression;Uncontrolled severe pain;Acute angle-closure glaucoma; Obstetric: Benzodiazepine drugs may ↑ risk of congenital malformations; use in the last weeks of pregnancy has caused CNS depression in the neonate; Lactation: Lactation; Pediatric: Products containing benzyl alcohol should not be used in neonates.
Use Cautiously in: Pulmonary disease;HF;Renal impairment;Severe hepatic impairment;Obese pediatric patients (calculate dose on the basis of ideal body weight); Pediatric: Rapid injection in neonates has caused severe hypotension and seizures, especially when used with fentanyl; Geriatric: Older patients (especially >70 yr) are more susceptible to cardiorespiratory depressant effects; dosage ↓ required.

Adverse Reactions/Side Effects

Central nervous system

  • agitation
  • drowsiness
  • excess sedation
  • headache

Ear, Eye, Nose, Throat

  • blurred vision

Respiratory

  • apnea (life-threatening)
  • laryngospasm (life-threatening)
  • respiratory depression (life-threatening)
  • bronchospasm
  • coughing

Cardiovascular

  • cardiac arrest (life-threatening)
  • arrhythmias

Gastrointestinal

  • hiccups
  • nausea
  • vomiting

Dermatologic

  • rashes

Local

  • phlebitis at IV site (most frequent)
  • pain at IM site

Interactions

Drug-Drug interaction

↑ CNS depression with alcohol, antihistamines, opioid analgesics, and other sedative/hypnotics (↓ midazolam dose by 30–50% if used concurrently).↑ risk of hypotension with antihypertensives, opioid analgesics, acute ingestion of alcohol, or nitrates.Midazolam is metabolized by the cytochrome P450 3A4 enzyme system; drugs that induce or inhibit this system may be expected to alter the effects of midazolam.Carbamazepine, phenytoin, rifampin, rifabutin, and phenobarbital ↓ levels.Erythromycin, cimetidine, ranitidine, diltiazem, verapamil, fluconazole, itraconazole, and ketoconazole ↓ metabolism and may ↑ risk of toxicity.Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.Long-term use of St. John's wort may significantly ↓ levels.Grapefruit juice ↓ metabolism and may ↑ risk of toxicity.

Route/Dosage

Dose must be individualized, taking caution to reduce dose in geriatric patients and in those who are already sedatedPreoperative Sedation/Anxiolysis/Amnesia
Oral (Children 6 mo–16 yr) 0.25–0.5 mg/kg, may require up to 1 mg/kg (dose should not exceed 20 mg); patients with cardiac/respiratory compromise or concurrent CNS depressants—0.25 mg/kg.
Intramuscular (Adults Otherwise Healthy and <60 yr) 0.07–0.08 mg/kg 1 hr before surgery (usual dose 5 mg).
Intramuscular (Adults ≥60 yr, Debilitated or Chronically Ill) 0.02–0.03 mg/kg 1 hr before surgery (usual dose 1–3 mg).
Intramuscular (Children) 0.1–0.15 mg/kg up to 0.5 mg/kg 30–60 min prior to procedure; not to exceed 10 mg/dose.
Conscious Sedation for Short Procedures
Intravenous (Adults and Children Otherwise Healthy >12 yr and <60 yr) 1–2.5 mg initially; dosage may be ↑ further as needed. Total doses >5 mg are rarely needed (↓ dose by 50% if other CNS depressants are used). Maintenance doses of 25% of the dose required for initial sedation may be given as necessary.
Intravenous (Children 6–12 yr) 0.025–0.05 mg/kg initially, then titrate dose carefully, may need up to 0.4 mg/kg total, maximum dose 10 mg.
Intravenous (Children 6 mo–5 yr) 0.05 mg/kg initially, then titrate dose carefully, may need up to 0.6 mg/kg total, maximum dose 6 mg.
Intravenous (Geriatric Patients ≥60 yr, Debilitated or Chronically Ill) 1–1.5 mg initially; dose may be ↑ further as needed. Total doses >3.5 m g are rarely needed (↓ dose by 30% if other CNS depressants are used). Maintenance doses of 25% of the dose required for initial sedation may be given as necessary.
Intranasal (Children) 0.2–0.3 mg/kg, may repeat in 5–15 min.
Status Epilepticus
Intravenous (Children >2 mo) 0.15 mg/kg load followed by a continuous infusion of 1 mcg/kg/min. Titrate dose upward q 5 min until seizure controlled, range: 1–18 mcg/kg/min.

Induction of Anesthesia (Adjunct)

May give additional dose of 25% of initial dose if needed
Intravenous (Adults Otherwise Healthy and <55 yr) 300–350 mcg/kg initially (up to 600 mcg/kg total). If patient is premedicated, initial dose should be further ↓.
Intravenous (Geriatric Patients >55 yr) 150–300 mcg/kg as initial dose. If patient is premedicated, initial dose should be further ↓.
Intravenous (Adults —Debilitated) 150–250 mcg/kg initial dose. If patient is premedicated, initial dose should be further ↓.

Sedation in Critical Care Settings

Intravenous (Adults) 0.01–0.05 mg/kg (0.5–4 mg in most adults) initially if a loading dose is required; may repeat q 10–15 min until desired effect is obtained; may be followed by infusion at 0.02–0.1 mg/kg/hr (1–7 mg/hr in most adults).
Intravenous (Children) Intubated patients only—0.05–0.2 mg/kg initially as a loading dose; follow with infusion at 0.06–0.12 mg/kg/hr (1–2 mcg/kg/min), titrate to effect, range: 0.4–6 mcg/kg/min.
Intravenous (Neonates >32 wk) Intubated patients only—0.06 mg/kg/hr (1 mcg/kg/min).
Intravenous (Neonates <32 wk) Intubated patients only—0.03 mg/kg/hr (0.5 mcg/kg/min).

Availability (generic available)

Injection: 1 mg/mL, 5 mg/mL
Syrupcherry flavor: 2 mg/mL

Nursing implications

Nursing assessment

  • Assess level of sedation and level of consciousness throughout and for 2–6 hr following administration.
  • Monitor BP, pulse, and respiration continuously during IV administration. Oxygen and resuscitative equipment should be immediately available.
  • If overdose occurs, monitor pulse, respiration, and BP continuously. Maintain patent airway and assist ventilation as needed. If hypotension occurs, treatment includes IV fluids, repositioning, and vasopressors.
    • The effects of midazolam can be reversed with flumazenil (Romazicon).

Potential Nursing Diagnoses

Ineffective breathing pattern (Adverse Reactions)
Risk for injury (Side Effects)

Implementation

  • high alert: Accidental overdose of oral midazolam syrup in children has resulted in serious harm or death. Do not accept orders prescribed by volume (5 mL or 1 tsp); instead, request dose be expressed in milligrams. Have second practitioner independently check original order and dose calculations. Midazolam syrup should only be administered by health care professionals authorized to administer conscious sedation.
  • Oral: To use the Press-in Bottle Adaptor (PIBA), remove the cap and push bottle adaptor into neck of bottle. Close bottle tightly with cap. Solution is a clear red to purplish-red cherry-flavored syrup. Then remove cap and insert tip of oral dispenser in bottle adaptor. Push the plunger completely down toward tip of oral dispenser and insert firmly into bottle adaptor. Turn entire unit (bottle and oral dispenser) upside down. Pull plunger out slowly until desired amount of medication is withdrawn into oral dispenser. Turn entire unit right side up and slowly remove oral dispenser from the bottle. Tip of dispenser may be covered with tip of cap until time of use. Close bottle with cap after each use.
    • Dispense directly into mouth. Do not mix with any liquid prior to dispensing.
  • Intranasal: Administer using a 1 mL needleless syringe into the nares over 15 sec. Using the 5 mg/mL injection, administer half dose into each nare.
  • Intramuscular: Administer IM doses deep into muscle mass, maximum concentration 1 mg/mL.
  • Intravenous Administration
  • pH: 2.9–3.7.
  • Diluent: Administer undiluted or diluted with D5W or 0.9% NaCl.Concentration: Undiluted: 1 mg/mL or 5 mg/mL. Diluted: 0.03–3 mg/mL.
  • Rate: Administer slowly over at least 2–5 min. Titrate dose to patient response. Rapid injection, especially in neonates, has caused severe hypotension.
  • Continuous Infusion: Diluent: Dilute with 0.9% NaCl or D5WConcentration: 0.5–1 mg/mL.
  • Rate: Based on patient's weight (see Route/Dosage section). Titrate to desired level of sedation. Assess sedation at regular intervals and adjust rate up or down by 25–50% as needed. Dose should also be decreased by 10–25% every few hours to find minimum effective infusion rate, which prevents accumulation of midazolam and provides more rapid recovery upon termination.
  • Y-Site Compatibility: alemtuzumab, alfentanil, amikacin, amiodarone, anidulafungin, argatroban, atracurium, atropine, aztreonam, benztropine, bivalirudin, bleomycin, buprenorphine, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefotaxime, cefoxitin, ceftaroline, ceftriaxone, ciprofloxacin, cisatracurium, cisplatin, cyanocobalamin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexmedetomidine, digoxin, diltiazem, diphenhydramine, docetaxel, dopamine, doripenem, doxacurium, doxarubicin hydrochloride, doxycycline, enalaprilat, epinephrine, epirubicin, eptifibatide, erythromycin lactobionate, esmolol, etomidate, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, folic acid, gemcitabine, gentamicin, glycopyrrolate, granisetron, heparin, hydromorphone, idarubicin, ifosfamide, irinotecan, isoproterenol, labetalol, levofloxacin, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, metaraminol, methadone, methoxamine, methyldopate, metoclopramide, metoprolol, metronidazole, milrinone, mitoxantrone, morphine, multivitamins, mycophenolate, nalbuphine, naloxone, nesiritide, nicardipine, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxacillin, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pancuronium, papaverine, pemetrexed, penicillin G potassium, pentamidine, pentazocine, phentolamine, phenylephrine, phytonadione, potassium chloride, procainamide, promethazine, propranolol, protamine, pyridoxime, quinupristin/dalfopristin, ranitidine, remifentanil, rifampin, rocuronium, streptokinase, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiotepa, tigecycline, tirofiban, tobramycin, tolazoline, trimetaphan, vancomycin, vasopressin, vecuronium, verapamil, vincristine, vinorelbine, voriconazole, zoledronic acid
  • Y-Site Incompatibility: acyclovir, aminocaproic acid, aminophylline, amphotericin B cholesteryl, amphotericin B colloidal, amphotericin B lipid complex, amphotericin B liposome, ampicillin, ampicillin/sulbactam, ascorbic acid, azathioprine, cefepime, ceftazidime, cefuroxime, chloramphenicol, dantrolene, dexamethasone sodium phosphate, diazepam, diazoxide, epoetin alfa, ertapenem, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, indomethacin, ketorolac, methotrexate, micafungin, omeprazole, pantoprazole, pentobarbital, phenobarbital, phenytoin, piperacillin/tazobactam, potassium acetate, prochlorperazine, sodium bicarbonate, thiopental, trimethoprim/sulfamethoxazole

Patient/Family Teaching

  • Inform patient that this medication will decrease mental recall of the procedure.
  • May cause drowsiness or dizziness. Advise patient to request assistance prior to ambulation and transfer and to avoid driving or other activities requiring alertness for 24 hr following administration.
  • Instruct patient to inform health care professional prior to administration if pregnancy is suspected.
  • Advise patient to avoid alcohol or other CNS depressants for 24 hr following administration of midazolam.

Evaluation/Desired Outcomes

  • Sedation during and amnesia following surgical, diagnostic, and radiologic procedures.
  • Sedation and amnesia for mechanically ventilated patients in a critical care setting.

Versed

(vûr-sĕd′)
A preparation of the drug midazolam hydrochloride; formerly a trademark.

Versed

a trademark for a parenteral central nervous system depressant (midazolam hydrochloride).

Versed®

Midazolam Pharmacology A preoperative sedative
References in classic literature ?
He had caught the words "expectant method," and rang chimes on this and other learned phrases to accompany the assurance that Lydgate "knew a thing or two more than the rest of the doctors--was far better versed in the secrets of his profession than the majority of his compeers.
Never," she insisted, and a light that shone in her eyes as she said it would have meant much to a man better versed in the ways of women than was Norman of Torn.
But if he could use his teeth and hands to advantage, he found one even better versed in the school of savage warfare to which he had reverted, for Tarzan of the Apes closed with him, and they fell to the floor tearing and rending at one another like two bull apes; while the primitive priestess stood flattened against the wall, watching with wide, fear-fascinated eyes the growing, snapping beasts at her feet.
He was versed in every form of duplicity, and yet he felt that in the presence of this young aristocrat, who was smiling upon him so delightfully, he was little more than a babe in wisdom, an amateur pure and simple.
Van Baerle was sufficiently versed in the history of his country to know that the celebrated Grotius was confined in that castle after the death of Barneveldt; and that the States, in their generosity to the illustrious publicist, jurist, historian, poet, and divine, had granted to him for his daily maintenance the sum of twenty-four stivers.
She was certainly not a woman versed in the ways of man and in the ways of handling man.
With all his sagacity, Rabourdin was better versed in matters of administration than in parliamentary optics, and he was far indeed from imagining how his confidence would be received; he little thought that the great work that filled his mind would seem to the minister nothing more than a theory, and that a man who held the position of a statesman would confound his reform with the schemes of political and self-interested talkers.
These coats-of-arms could be read, where a scroll would be meaningless, and the bowman, like most men of his age, was well versed in the common symbols of heraldry.