Midazolam

Midazolam - is a water-soluble benzodiazepine with a short duration of action (elimination half-life 1–4 hours). However, prolonged coma has been reported in some critically ill patients usually after prolonged infusions. Midazolam is metabolised to the metabolite a-hydroxy midazolam, which is rapidly conjugated. Accumulation of midazolam after prolonged sedation has been observed in critically ill patients. In renal failure the glucuronide may also accumulate, causing narcosis.

Uses
Sedation
Anxiolysis

Contraindications
As an analgesic
Airway obstruction

Administration
• IV bolus: 2.5–5mg PRN
• IV infusion: 0.5–6 mg/h

Administer neat or diluted in glucose 5% or sodium chloride 0.9% Titrate dose to level of sedation required. Stop or reduce infusion each day until patient awakes, when it is restarted. Failure to assess daily will result in delayed awakening when infusion is finally stopped.
Time to end effects after infusion: 30 min to 2 hours (but see below).

How not to use midazolam
The use of flumazenil after prolonged use may produce confusion, toxic psychosis, convulsions, or a condition resembling delirium
tremens.

Adverse effects
Residual and prolonged sedation
Respiratory depression and apnoea
Hypotension

Cautions
Enhanced and prolonged sedative effect results from interaction with:
• opioid analgesics
• antidepressants
• antihistamines
• a-blockers
• anti-psychotics

Enhanced effect in the elderly and in patients with hypovolaemia, vasoconstriction or hypothermia.

Midazolam is metabolised by the hepatic microsomal enzyme system (cytochrome P450s). Induction of the P450 enzyme system by another drug can gradually increase the rate of metabolism of midazolam, resulting in lower plasma concentrations and a reduced effect.Conversely inhibition of the metabolism of midazolam results in a higher plasma concentration and an increased effect. Examples of enzyme inducers and inhibitors are listed on There is now available a specific antagonist, flumazenil.

Organ failure
CNS: sedative effects increased
Cardiac: exaggerated hypotension
Respiratory: respiratory depression
Hepatic: enhanced and prolonged sedative effect. Can precipitate coma
Renal: increased cerebral sensitivity

Renal replacement therapy
No further dose modification is required during renal replacement therapy; though accumulation of active metabolite will occur in renal failure so care is required to avoid prolonged sedation upon cessation of midazolam.