Midazolam

Midazolam

Indication

• Midazolam is a benzodiazepine that is used to provide sedation
• It has also been used, after phenobarbital and phenytoin have failed, as an anticonvulsant

Pharmacology

• Midazolam is a water-soluble benzodiazepine
• Midazolam, like other benzodiazepine, interacts with gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, to produce a tranquilizing effect (limbic system), muscle relaxant effect (spinal cord) and hypnotic, sedative, and anticonvulsant effects (cerebral cortex)
• midazolam is almost completely metabolized by the liver
• Hepatic metabolism is predominately by the CYP3A enzyme; erythromycin, for example can significantly inhibit the metabolism of midazolam, resulting in increased serum midazolam concentrations
• the metabolites are eliminated by the kidney; therefore, patients in hepatic or kidney failure will likely require dosage modification
• The sedative effect following IV administration is evident in 3 to 20 minutes; the effectiveness has ranged in length from 2 to 12 hours
• A large variation in the plasma concentration (up to 20x difference) has been reported in infants less than 1 year old. Therefore, some infants may not have adequate serum levels to provide adequate sedation.

Side Effects

• may cause central respiratory depression
• Midazolam associated apnea is dose related and is also dependent on the rate of adminstration
• There are several published (and unpublished) reports of infants who have experienced seizures following an IV bolus of midazolam

Nursing Implications

• ensure infant is on a cardiac respiratory monitor (midazolam may cause central respiratory depression)
• regulary evaluate blood pressure
• monitor O2 saturation with pulse oximetry
• Respiratory depression can intensify with concurrent narcotics (eg. morphine, fentanyl) or drugs that may interfere with the metabolism of midazolam (eg. erythromycin)

• remember that midazolam provides sedation, NOT analgesia.
• do not abruptly stop regularly scheduled midazolam; to avoid withdrawal (that could present as vomiting, diarrhea, decreased responsiveness, tachycardia, tongue thrusting, staring, irritability, agitation, facial grimacing and generalized seizures) the infant should be slowly weaned (10 to 20% per day) from the medication.

Dose

• The conventional route of administration is IV or IM
• IV (slow infusion):
  • 100 mcg/kg (0.1 mg/kg) IV slow infusion over 30 minutes
  • repeat as needed, usually every 2 to 6 hours
  • (the sedative effect is seen within 3 to 20 minutes.)
• Continuous IV Infusion:
  • 0.1 to 2 ug/kg/min (range suggested by most references)
  • infusion rates up to 6 ug/kg/min have been reported
• Rectal
  • 0.3 mg/kg (diluted in NaCl 0.9%) has been used in children to provide pre-operative sedation
  • sedative effect within 20-30 minutes.
  • In 1 study only 36% of children were adequately sedated following 0.3 mg/kg midazolam per rectum; in another study a single dose of midazolam 0.5 mg/kg rectally produced sedation in 97% of children; the onset of action was 15-20 min.
• Intranasal
  • single doses of 0.2 to 0.3 mg/kg have provided sedation in infants and children. (administer approx 1/2 total volume into each nostril)
  • onset of action has been seen within 5 to 15 minutes
• IM
  • a single dose of midazolam, 0.05 to 0.1 mg/kg, has been given to children; time to reach sedation was 15-20 min

Stability

• Midazolam is stable for at least 24 hours at room temperature in saline or dextrose mixtures
• physically campatible with morphine, meperidine and atropine
• Visually compatible during simulated Y-site injection with calcium gluconate, cefazolin, cefotaxime, cimetidine, clindamycin, digoxin, dopamine, fentanyl, gentamicin, methylprednisolone, metronidazole, nitroglycerin, sodium nitroprusside, tobramycin and vancomycin
• Not compatible with ampicillin, ceftazidime, cefuroxime, dexamethasone, dobutamine, furosemide or sodium bicarbonate.