Midazolam (Versed)

Anesthesia Implications

Classification: Benzodiazepine (Short Acting), Sedative-Hypnotic, Anticonvulsant
Therapeutic Effects: anxiolysis, amnesia, sedation, hypnosis, antiemetic
Time to Onset: 1-2 minutes IV
Time to Peak: 2 to 3 minutes IV, 30 – 60 minutes PO
Duration: Half life: 1-4 hours

Contraindications

Avoided (but not contraindicated) in the laboring parturient because it will cause the mother to forget the childbirth experience.  There has been some unfounded beliefs that midazolam was the source of defects such as the cleft palate.

Crosses the placenta, which can cause neonatal hypotonia.

Primary Considerations

Rapid onset with short duration

Primary premedication for anxiolysis.

Amnesia may only last 20-30 minutes.

Marked decrease in dosage requirements as the patient increases in age.

Dose-related cardio-depressant impacts include a decreased SVR and blood pressure.  These affects are seen very little in low/premedication doses.

Midazolam has antiemetic effects that outlast the sedation effects.  1-2 mg provided postoperatively in response to PONV had comparable effects to 4 mg of Zofran.

Midazolam, when given in a small dose preoperatively (<= 2mg), does not compromise the rapid recovery of a propofol infusion, but does provide prescribed sedative and amnestic affects.

Sedative synergism occurs when midazolam and opioid analgesics are administered in combination.  The respiratory depressive effects of opioids are also synergistic when used in combination with midazolam. Hypnotic synergism occurs when midazolam and propofol or thiopental are used in combination.

When used for induction and maintenance of anesthesia, midazolam will require substantially more time for return of consciousness when compared to other sedative-hypnotics.

Midazolam produces prolonged periods of postoperative sedation and psychomotor impairment – especially in the elderly.

Raises seizure thresholds, which can prevent or break active seizures.

Does NOT produce a complete burst suppression pattern on the EEG

Redheads require more midazolam and inhalational anesthetics than do blond or dark-haired patients.

Midazolam is on the list of drugs that can precipitate porphyria

Peds: 0.5 to 0.75 mg/kg administered PO 10 to 15 minutes before parental separation.  Intranasal doses (0.2 mg/kg) can be given but may cause some irritation to the nasal mucosa

Cardiac: Midazolam (0.07 to 0.15 mg/kg over 3-5 minutes) followed by ketamine (0.25 to 0.5 mg/kg IV over 1 to 3 minutes), produces excellent sedation, amnesia, and analgesia without significant cardiorespiratory depression.

IV push dose

Premedication: 1-2 mg is the common dosage for adults. 0.02 to 0.04 mg/kg (textbook).
Induction: 0.1 to 0.2 mg/kg IV (after premedication), 0.2-0.4 mg/kg (without premedication)

IV infusion dose

0.25 to 1.0 µg/kg/min is sufficient to sustain hypnosis and sedation when used in combination with volatile anesthetics, opioids, etc

IM dose

Premedication: 0.02 to 0.04 mg/kg

Method of Action

Increases the activity of GABA. The parts of the brain that are responsible for arousal, attention, and memory have a dose-related reduced perfusion when midazolam is administered.

Metabolism

Hepatic. Inactive metabolites (1-hydroxymethylmidazolam)

Elimination

Renal