1. Slow IV push
   50 to 150 micrograms/kg as a slow push over 5 minutes. Can be repeated Q2-4H as required.
   Give lower dose if opiates being administered simultaneously.
2. Continuous intravenous infusion
   10-60 micrograms/kg/hour. Dosage can be increased if necessary.

Indications

1. Sedation/anaesthesia.
2. Anticonvulsant (3^rd or 4^th line).

Contraindications and Precautions

1. Known hypersensitivity to midazolam.
2. Shock.
3. Caution in preterm infants, especially extreme immaturity.
4. Caution in neonates with hepatic or renal impairment.
5. Caution when concurrent use with opiates, particularly fentanyl.
6. Caution when concurrent use with other anticonvulsants.

Interactions

1. Concurrent administration with erythromycin promotes accumulation.
2. May alter the depth of and prolong the recovery from concurrent neuromuscular blockade.
3. Xanthines may decrease the anaesthetic/sedative effect of benzodiazepines. Care needs to be taken with adding or withdrawing caffeine or aminophylline.

Clinical Pharmacology

Midazolam, an imidazobenzodiazepine, has anxiolytic, sedative, muscle relaxant and anticonvulsant actions. Facilitates the action in the brain of gamma aminobutyric acid, a naturally occurring neurotransmitter. Absorption 30% with oral and 50% with nasal administration. Rapid and extensive distribution. Highly protein bound. Hepatic metabolism to active and inactive derivatives, impaired by poor hepatic perfusion . Very slow elimination via the kidneys. Elimination half-life variable (6-7 hours in infants close to term, longer in less mature infants), with the major metabolite (1-hydroxymidazolam) having an even shorter half-life. Rapid onset of action (<3 minutes) and peak sedative action <20 minutes after IV administration. Anticonvulsant action may be more rapid. The IV preparation has a pH of 3.

Possible Adverse Effects

1. Hypotension and reduced cardiac output, particularly when used in combination with fentanyl.
2. Respiratory depression and apnoea.
3. Hypotonia.
4. Seizures or seizure-like activity may be seen following rapid bolus administration and in patients with underlying CNS disorders.
5. Cerebral blood flow velocities are reported to decrease transiently in preterm infants receiving midazolam boluses, possibly reflecting the reduction in blood pressure.
6. Nasal administration in children and adults has been reported to produce a burning sensation.

Special Considerations

1. Lower doses of midazolam should be considered in neonates with reduced cardiac output.
2. Development of tolerance and a requirement for higher doses may occur with prolonged use.
3. Prolonged use may result in neonatal abstinence syndrome.
4. Recent systematic review has suggested that routine use of midazolam for sedation in ventilated infants is associated with an increased incidence of adverse neurological outcomes. ⁹
5. Management of midazolam overdose and/or toxicity: stop midazolam, supportive therapy (ventilation, volume expansion etc.), consider use of specific antagonist flumazenil (very limited experience in the neonate).