Makindo Medical Notes

⚠️ Safety First: Always be ready to provide ventilatory support if respiratory depression occurs. Have oxygen and flumazenil (benzodiazepine antagonist) available whenever midazolam is administered. Only use under supervision by those trained in airway management and cardiorespiratory resuscitation.

💊 About

Midazolam is a short-acting benzodiazepine used for rapid sedation, anxiolysis, seizure control, and palliative symptom relief. It enhances the effect of the inhibitory neurotransmitter GABA at the GABA_A receptor, increasing chloride influx and causing neuronal hyperpolarisation. Compared with diazepam or lorazepam, midazolam has faster onset and shorter duration, making it ideal for short procedures or when IV access is difficult (e.g., buccal use in seizures). Always 🔗 check the BNF entry here for dose details.

🧠 Mode of Action

• Positive allosteric modulator of the GABA_A receptor in the CNS.
• Enhances the frequency of chloride channel opening → neuronal inhibition.
• Results in anxiolysis, sedation, amnesia, muscle relaxation, and anticonvulsant effects.
• Short acting due to high lipid solubility → rapid CNS penetration and redistribution.

📋 Indications / Typical Doses

• Status epilepticus (especially if IV access not available).
• Procedural sedation and premedication (endoscopy, cardioversion, minor surgery).
• Palliative care — agitation, dyspnoea, or terminal restlessness.
• Adjunct in intensive care for continuous sedation in ventilated patients.

💉 Dose Range (Always check latest BNF or SPC)

🤝 Interactions

• Other CNS depressants: opioids, alcohol, antipsychotics, and antihistamines → additive sedation and respiratory depression.
• CYP3A4 inhibitors (erythromycin, ketoconazole, fluconazole, diltiazem, grapefruit juice) ↑ plasma midazolam → prolonged sedation and apnoea risk.
• CYP3A4 inducers (phenytoin, carbamazepine, rifampicin) ↓ plasma levels → reduced efficacy.

⚠️ Cautions

• Respiratory depression: dose-related and potentiated by other sedatives — always be prepared to support the airway.
• Renal or hepatic impairment: reduced clearance; use smaller doses and monitor sedation depth.
• Elderly and frail: increased sensitivity; start low, go slow.
• Severe COPD or sleep apnoea: risk of hypoventilation even at therapeutic doses.
• Dependence risk: prolonged use (>2 weeks) may cause tolerance and withdrawal if stopped abruptly.

⛔ Contraindications

• Comatose states or severe CNS depression from other causes.
• Severe respiratory failure (unless used for palliation under specialist guidance).
• Hypersensitivity to benzodiazepines.

🩺 Side Effects

• Common: drowsiness, confusion, ataxia, amnesia, hypotension, dry mouth.
• Serious: respiratory depression/apnoea, cardiac arrest (especially with rapid IV injection).
• Allergic: rare anaphylaxis or rash.
• Paradoxical agitation or aggression (rare, esp. in children or elderly).

🧪 Monitoring

• Monitor respiratory rate, O₂ saturation, heart rate, and level of consciousness throughout use.
• Record total dose given and cumulative sedation effect.
• Ensure reversal agent (flumazenil 200 µg IV) and airway adjuncts are immediately available.

🧠 Clinical Pearls

• Midazolam is preferred for pre-hospital and community seizure management — easy to administer buccally and rapid in onset.
• For procedural sedation, always give slowly and titrate; most adverse events occur with rapid IV administration.
• In palliative care, midazolam provides both anxiolysis and respiratory ease (“settling drug”) and is a cornerstone of end-of-life symptom control.
• Unlike diazepam, midazolam has no active metabolites — safer in organ failure, but more potent and shorter-acting.
• Store securely and record administration — a Schedule 3 Controlled Drug under UK law.

📚 References

• BNF: Midazolam
• NICE NG159: COVID-19 and Palliative Care (sedation protocols).
• RCUK: Advanced Life Support – Seizure and Sedation Management Guidelines.
• MHRA Drug Safety Update (2022): Midazolam and risk of prolonged sedation in CYP3A4 inhibitor use.