Midazolam

Aka: Midazolam, Versed

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II. Indications

  1. Procedural Sedation and Analgesia (PSAA)
    1. Other agents are preferred in most cases (unpredictable)
  2. Rapid Sequence Intubation (induction agent)
    1. Other induction agents are preferred due to the large and unpredictable Midazolam doses required for induction
      1. Rarely given at adequate doses (a typical adult dose for RSI is an astounding 8-10 mg)
    2. Consider where IV Access unavailable or other intubation agents contraindicated
    3. Could be considered in Status Epilepticus (although Thiopental might be preferred)

III. Class

  1. Parenteral short acting Benzodiazepine

IV. Mechanism

  1. Sedative, Anxiolytic, and amnestic effects
  2. Antagonist: Flumazenil

V. Dosing: Procedural Sedation

  1. Indications for Midazolam
    1. Ideal for procedural anxiolysis rather than sedation (e.g. Lumbar Puncture, Nasogastric Tube placement)
    2. Other agents are preferred for moderate Procedural Sedation in most cases
    3. Intranasal Versed in children may allow for imaging, Intravenous Access, Laceration Repair
  2. Intravenous
    1. Age 6 months to 5 years
      1. Initial: 0.05 to 0.1 mg/kg IV
      2. Titrate: Up to 1 mg increments IV every 3 min to max of 0.6 mg/kg
    2. Age 6 to 12 years
      1. Initial: 0.025 to 0.05 mg/kg IV
      2. Titrate: Up to 1 mg increments IV every 3 min to max of 0.4 mg/kg
    3. Adults (and over age 12 years)
      1. Initial: 0.02 mg/kg IV (up to 1 to 2 mg)
      2. Titrate: 1 mg increments IV every 2 to 3 min (typically up to 5 mg in typical adult)
      3. Common procedural anxiolysis dose (e.g. LP, NG placement): 1 to 2 mg IV
  3. Intramuscular
    1. Child: 0.1 to 0.15 mg/kg (up to 5 mg)
    2. Adult: 0.07 mg/kg (up to 5 mg in typical adult, max: 10 mg)
  4. Other Dosing
    1. Oral: 0.5 mg/kg/dose (up to 20 mg) orally
    2. Nasal: 0.2 to 0.5 mg/kg intranasal (1/2 in each nostril) using 5 mg/ml up to 10 mg
    3. Rectal 0.25 to 0.5 mg/kg/dose (up to 20 mg) per Rectum
  5. Commonly used in combination with Fentanyl
    1. When combined with Opioids (e.g. Fentanyl), use lower Midazolam dose
    2. Risk of Deep Sedation with cardiopulmonary depression

VI. Dosing: Status Epilepticus

  1. See Status Epilepticus
  2. Alternative agent when longer acting Benzodiazepines not available or without IV Access (e.g. Ambulance)
    1. Midazolam IM, intranasal or buccal may be more effective and more rapid than Diazepam IV or rectal
    2. Lorazepam and Diazepam are preferred if available for other routes
  3. IV: 0.15 mg/kg up to 4 mg (then infused IV at 1 mcg/kg/min and titrated every 5 min as needed) up to 10 mg
  4. IM: 0.2 mg/kg of the IV formulation up to 10 mg
    1. Weight 13-40 kg: 5 mg IM
    2. Weight >40 kg: 10 mg IM
  5. Rectal: 0.25 to 0.5 mg/kg
    1. May be delivered via tuberculin syringe (without needle) intra-rectally
    2. Commercial preparations are available for home use (Diastat AcuDial at $300 for 2 doses, age >2)
  6. Intranasal
    1. Dose: 0.2 to 0.4 mg/kg up to 10 mg of the IV formulation
    2. Typically given via syringe with MADD atomizer attached (roughly $15)
    3. Commercial preparations are available for home use (Nayzilam at $550 for 2 doses, age>12)
  7. Buccal mucosa: 0.5 mg/kg of the IV formulation

VII. Safety

  1. Pregnancy Category D
  2. Avoid in Lactation
    1. Wait at least 4 hours for Breast Feeding
  3. Schedule IV Controlled Substance
  4. Unpredictable at increased doses (risk of respiratory and cardiovascular depression)
    1. Unreliable sedation for painful procedures
    2. Best delivered in incremental doses (e.g. 1 mg increments)
    3. Exercise extra caution in elderly, debilitated, children, hepatic insufficiency, Dementia
  5. Reversal: Flumazenil 0.01 mg/kg up to 2 mg over 15 seconds
    1. Do not use if on longterm Benzodiazepines

VIII. Pharmacokinetics

  1. General
    1. Duration: 1-4 hours
    2. Half life: 2.5 hours
  2. Oral
    1. Onset: 20 to 30 minutes
    2. Peak: 40 minutes
  3. Intramuscular
    1. Onset: 5 to 7 minutes (up to 10-20 minutes)
    2. Peak: 10 to 15 minutes
    3. Duration: 60-120 minutes
  4. Intravenous
    1. Onset: 2-3 minutes
    2. Peak: 5 to 10 minutes
    3. Duration: 45-60 minutes

IX. Precautions

  1. Monitor closely with respiratory depression
  2. Have Ambubag and Oxygen available when administered
  3. Unpredictable at increased doses (risk of respiratory and cardiovascular depression)
    1. Best delivered in incremental doses (e.g. 1 mg increments)
    2. Risk of Hypotension
  4. Use with caution if risks for respiratory depression
    1. Elderly, debilitated patients or children
    2. Concurrent Narcotic use
    3. Existing CNS depression
    4. Chronic lung disease
    5. Neuromuscular disorder
    6. Apnea history
  5. Risk of Agitation
    1. Elderly
    2. Liver disease

X. Resources

  1. Midazolam Injection (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1abda8b8-48a8-4995-af86-39220d1aa240

XI. References

  1. Miner (2012) APLS Lecture, HCMC, Minneapolis
  2. Hamilton (2012) Tarascon Pharmacopeia, Jones and Bartlett, Burlington
  3. Rispoli (2002) Tarascon Pocket Orthopedics, Loma Linda, p. 115
  4. University Minnesota Childrens - Pediatric Emergency Drug Card
  5. Becker (2012) Anesth Prog 59:28-42 [PubMed]
  6. Brown (2005) Am Fam Physician 71:85-90 [PubMed]
  7. Singh in Blaivas (2012) Emergency Medicine - an International Perspective, p. 199-208

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Cost: Medications

midazolam (on 8/17/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
MIDAZOLAM HCL 2 MG/ML SYRUP Generic $0.65 per ml
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