Dexmedetomidine

Aka: Dexmedetomidine, Precedex, Dexdor, Dexdomitor

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II. Indications

  1. Post-Intubation Sedation and Analgesia
    1. Use other agents (e.g. Propofol) in the first hour after intubation (delayed effect with Dexmedetomidine)
    2. Short-term sedation and weaning (<24 hours up to 4-5 days) in ICU patients on Mechanical Ventilation
    3. Tachyphylaxis occurs with use >24 hours and esp. >4-5 days
  2. Noninvasive Positive Pressure Ventilation or NIPPV (e.g. BIPAP)
    1. Dexmedetomidine may help patients tolerate the NIPPV mask
  3. Agitation in Schizophrenia or Bipolar Disorder
    1. FDA approved sublingual form in 2022 (see dosing below)
  4. Alcohol Withdrawal
    1. Adjunct for Agitation, when combined with Benzodiazepines and Barbiturates
  5. Other patients requiring sedation
    1. Peri-procedure sedation
    2. Neurocritical care patients
    3. Tachycardic patients on Vasopressors

III. Contraindications

  1. Severe Bradycardia
  2. Hemodynamically unstable (significant Hypotension)
  3. Heart Block

IV. Mechanism

  1. Selective central alpha-2-Adrenergic Agonist (similar to Clonidine) with Sedative properties
    1. Decreases CNS Norepinephrine release resulting in Sedative effects
    2. Lacks the peripheral effects on vascular resistance of Clonidine
    3. However, sedation effect is maintained
  2. Brainstem G-Protein activation inhibits Norepinephrine release
    1. Decreases sympathetic tone and Peripheral Vascular Resistance

V. Advantages

  1. Keeps a patient sleepy but awakenable and will respond to questions (without the perceptual disturbance seen with Ketamine)
  2. Patients maintain their airway and respiratory drive (ideal for Mechanical Ventilation weaning)
  3. Generic (previously very expensive as a trade name drug)
  4. Opioid sparing (offers sedation and Analgesic properties)

VI. Pharmacokinetics

  1. Onset: 10 minutes
  2. Duration: 1-2 hours
  3. Renal and hepatic metabolism

VII. Dosing: General Sedation (ICU <24 hours)

  1. Load
    1. Option 1: Infuse 1 mcg/kg in adults (0.5 to 1 mcg/kg in children) over 10 minutes OR
      1. Precaution: Bolus may result in Bradycardia and Hypotension
    2. Option 2: Start high dose infusion 1 to 1.4 mcg/kg/hour without bolus
      1. Decrease infusion rate in the first 30-60 minutes to maintenance infusion
  2. Infusion: 0.2 to 0.7 mcg/kg/hour in adults (0.2 to 0.5 mcg in children)
    1. Titrate to desired level of sedation, modifying dose every 30 min to 0.2 to 1.5 mcg/kg/hour
    2. Decrease dosing in hepatic dysfunction and the elderly
  3. Reduce dose in over age 65 years or renal/hepatic Impairment

VIII. Dosing: Post-Intubation Sedation

  1. Another Sedative (e.g. Propofol or Ketamine) should be used initially to maintain initial sedation
  2. Start Dexmedetomidine at 0.5 mcg/kg/h infusion
  3. Increase Dexmedetomidine by 0.1 mcg/kg/h as needed up to 1.5 mcg/kg/h

IX. Dosing: Procedural Sedation

  1. May be used in combination with Ketamine
  2. Onset of activity is delayed 5 minutes or more
  3. Intramuscular
    1. Dose: 2 mcg/kg (range 0.5 to 4 mcg/kg)
  4. Intranasal
    1. Dose: 2-3 mcg/kg
    2. Onset in 13-25 minutes and duration for 85 minutes (longer in adults)
    3. Intranasal use rarely causes Bradycardia or Syncope
    4. Oriby (2019) Anesth Pain Med 9(1): e85227 +PMID:30881910 [PubMed]

X. Dosing: Sublingual for Agitation (Schizophrenia, Bipolar Disorder)

  1. Unlikely to be effective as single agent in moderate to severe Agitation
    1. Consider as adjunct to other measures
  2. Mild to moderate Agitation
    1. Initial: 120 mcg sublingual or buccal
    2. Repeated: 60 mcg SL every 2 hours prn for up to 2 doses
    3. Maximum: 240 mcg in 24 hours
  3. Severe Agitation
    1. Initial: 180 mcg sublingual or buccal
    2. Repeated: 90 mcg SL every 2 hours prn for up to 2 doses
    3. Maximum: 360 mcg in 24 hours

XI. Safety

  1. Pregnancy Category C
  2. Unknown Safety in Lactation

XII. Adverse Effects

  1. Severe Bradycardia
    1. Higher risk with high dose Dexmedetomidine
    2. If Heart Rate drops below minimum threshold, stop infusion for 30 min, and restart at 1/2 prior rate
    3. Risk of sinus and AV Node slowing in pediatric patients
  2. Hypotension
    1. Transient Hypertension may occur with rapid infusion or bolus, especially at higher doses
    2. Low dose Epinephrine infusion may be used to counter Dexmedetomidine Bradycardia and Hypotension
    3. Orthostatic Hypotension may occur (sublingual Dexmedetomidine)
  3. Dry Mouth
  4. Potent Diuretic
  5. Tachyphylaxis
    1. Risk of tolerance (within 4-5 days of starting Dexmedetomidine, as early as 24 hours in some patients)
    2. Results in less sedation and risk of withdrawal
    3. Transition to Clonidine if Dexmedetomidine tolerance develops

XIII. Resources

  1. Dexmedetomidine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8fb7886c-7762-4b72-989b-0fe8e963b4b8

XIV. References

  1. Shoenberger, Swaminathan and Strayer in Swadron (2022) EM:Rap 22(11): 21-2
  2. Swaminathan and Weingart in Herbert (2019) EM:Rap 19(6): 14
  3. Fisher and Fisher (2018) Crit Dec Emerg Med 32(1): 24
  4. Kay (2015) Crit Dec Emerg Med 29(8): 11-17

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