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. Other Sedation agents are preferred in most cases
    2. 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
      2. Titrate: 1 mg increments IV every 3 min (typically up to 5 mg)
  3. Intramuscular
    1. Child: 0.1 to 0.15 mg/kg (up to 10 mg)
    2. Adult: 0.07 mg/kg (up to 10 mg)
  4. Other Dosing
    1. Oral: 0.5 mg/kg/dose
    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 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. Safety

  1. Contraindicated in pregnancy (Category D)
  2. Wait at least 4 hours for Breast Feeding
  3. 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
  4. Reversal: Flumazenil 0.01 mg/kg up to 2 mg over 15 seconds
    1. Do not use if on longterm Benzodiazepines

VII. 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

VIII. 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

IX. 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 10/19/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
MIDAZOLAM HCL 2 MG/2 ML VIAL Generic $0.28 per ml
MIDAZOLAM HCL 2 MG/ML SYRUP Generic $0.75 per ml

Ontology: Midazolam (C0026056)

Definition (NCI_NCI-GLOSS) A drug used to treat anxiety and tension and to relax muscles. It is also being studied in the treatment of nausea and vomiting caused by some cancer treatments. It is a type of benzodiazepine.
Definition (NCI) A short-acting benzodiazepine derivative with an imidazole structure and with anxiolytic, amnestic, hypnotic, anticonvulsant and sedative properties. Midazolam exerts its effect by binding to the benzodiazepine receptor at the gamma-aminobutyric acid (GABA) receptor-chloride ionophore complex in the central nervous system (CNS). This leads to an increase in the opening of chloride channels, membrane hyperpolarization and increases the inhibitory effect of GABA in the CNS. Midazolam may also interfere with the reuptake of GABA, thereby causing accumulation of GABA in the synaptic cleft.
Definition (MSH) A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.
Definition (CSP) 8-chloro-6-(2-fluorophenyl)-1-methyl- 4H- imidazo(1,5a)(1,4)benzodiazepine; short acting benzodiazepine sedative with high liability for abuse; used for preanesthesia sedation (USP lists as an injectable anesthetic).
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D008874
SnomedCT 26800000, 373476007
LNC LP16207-0, MTHU003397
English Midazolam, 4H-Imidazo(1,5-a)(1,4)benzodiazepine, 8-chloro-6-(2-fluorophenyl)-1-methyl-, 8-Chloro-6-(2-fluorophenyl)-1-Methyl- 4H- Imidazo(1,5a)(1,4)Benzodiazepine, midazolam (medication), sedatives midazolam, Midazolam [Chemical/Ingredient], MIDAZOLAM, midazolam, Midazolam (product), Midazolam (substance)
Swedish Midazolam
Czech midazolam
Finnish Midatsolaami
Russian MIDAZOLAM, МИДАЗОЛАМ
Japanese ミダゾラム
Croatian MIDAZOLAM
Polish Midazolam
Spanish midazolam (producto), midazolam (sustancia), midazolam, Midazolam
French Midazolam
German Midazolam
Italian Midazolam
Portuguese Midazolam

Ontology: Versed (C0042553)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D008874
English versed, vers, Versed