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Benzodiazepine — Short-Acting Sedative Pregnancy: Avoid in first trimester (cleft palate reports — limited human data); single perioperative dose in third trimester acceptable; neonatal respiratory depression and withdrawal if prolonged use; discuss risk with patient

Midazolam (Surgical — Anxiolysis/Sedation)

Brand names: Hypnovel, Buccolam (buccal)

Adult dose

Dose: Pre-operative anxiolysis: 1–2 mg IV or 7.5 mg oral (1 hour pre-surgery); Procedural sedation: 1–2.5 mg IV titrated (over 2 min); Induction supplement: 0.05–0.1 mg/kg IV; ICU sedation: 0.02–0.1 mg/kg/hour IV infusion
Route: IV / IM / Oral / Buccal
Frequency: Single pre-op dose; or titrated IV for procedure; or continuous infusion
Max: 5 mg IV for procedural sedation (elderly: max 3.5 mg); 0.1 mg/kg/hour ICU infusion
Water-soluble at acidic pH in vial; lipophilic at body pH — rapid CNS penetration. Shortest-acting benzodiazepine. Anterograde amnesia is a key clinical advantage for pre-operative and procedural use. Reversible with flumazenil. MUST have resuscitation equipment available for IV use.

Paediatric dose

Dose: 0.5 mg/kg
Route: Oral/nasal/buccal (pre-op); IV 0.1 mg/kg titrated
Frequency: Single pre-op dose
Max: 20 mg oral pre-med; 6 mg IV titrated
Paediatric pre-operative anxiolysis: midazolam 0.5 mg/kg oral (max 20 mg) or 0.2–0.3 mg/kg nasal 15–20 min before induction. Buccal midazolam (Buccolam) for acute seizures: age-based dosing 2.5–10 mg buccal.

Dose adjustments

Renal

No dose adjustment for single dose. Prolonged infusion in renal failure: active metabolite (1-hydroxymidazolam glucuronide) accumulates — reduce rate and consider alternative.

Hepatic

Significant reduction required in hepatic impairment — prolonged sedation. Reduce infusion rate by 50% in moderate-severe hepatic failure.

Paediatric weight-based calculator

Paediatric pre-operative anxiolysis: midazolam 0.5 mg/kg oral (max 20 mg) or 0.2–0.3 mg/kg nasal 15–20 min before induction. Buccal midazolam (Buccolam) for acute seizures: age-based dosing 2.5–10 mg buccal.

Clinical pearls

  • Pre-operative oral midazolam in children: 0.5 mg/kg oral (max 20 mg) given 15–30 min before induction reduces separation anxiety and emergence agitation — produces acceptable sedation without airway compromise in most children; MHRA note: monitor for respiratory depression even with oral pre-med
  • Midazolam + fentanyl for procedural sedation: extremely effective for endoscopy, cardioversion, joint aspiration; MUST use minimum effective doses; have flumazenil and naloxone immediately available; continuous SpO2 monitoring mandatory
  • ICU prolonged infusion: tolerance develops rapidly (24–48 hours); cumulative effect in hepatic/renal failure leads to prolonged sedation after infusion discontinuation ('ICU psychosis' and delayed extubation); consider switching to propofol for shorter-duration sedation in ventilated patients

Contraindications

  • Myasthenia gravis
  • Severe hepatic impairment (relative — prolonged effect)
  • Acute narrow-angle glaucoma
  • Alcohol intoxication with CNS depression

Side effects

  • Respiratory depression (particularly with opioids — MHRA warning)
  • Apnoea (rapid IV injection or high dose)
  • Hypotension (vasodilation — in hypovolaemic patients)
  • Paradoxical disinhibition (in elderly, children, personality disorders)
  • Anterograde amnesia (therapeutic and side effect)
  • Cumulative sedation (infusions — tolerance and prolonged effect)

Interactions

  • Opioids (MHRA 2016 + 2020 warning: profound respiratory depression and death — fentanyl, morphine, oxycodone; reduce both doses if combined)
  • CYP3A4 inhibitors (fluconazole, ketoconazole, erythromycin — increase midazolam levels dramatically)
  • CYP3A4 inducers (rifampicin, phenytoin — dramatically reduce midazolam — loss of sedation)

Monitoring

  • Continuous SpO2 and respiratory rate during IV administration
  • BP (hypotension particularly in hypovolaemia)
  • Level of consciousness (RAMSAY or RASS score in ICU)
  • Arousal after procedure (recover in monitored environment until GCS returns to baseline)

Reference: BNFc; BNF 90; MHRA Drug Safety Update 2016 (opioid + benzo); RCoA Regional Anaesthesia Guidelines; NICE NG180 (Sedation in Adults); BNFc; MHRA SPC Hypnovel. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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