Dexmedetomidine

Aka: Dexmedetomidine, Precedex, Dexdor, Dexdomitor

1. 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. Other patients requiring sedation
      1. Alcohol Withdrawal
      2. Peri-procedure sedation
      3. Neurocritical care patients
      4. Tachycardic patients on Vasopressors
2. Contraindications
   1. Severe Bradycardia
   2. Hemodynamically unstable (significant Hypotension)
3. Mechanism
   1. Selective central alpha-2-Adrenergic Agonist (similar to Clonidine) with Sedative properties
      1. Lacks the peripheral effects on vascular resistance of Clonidine
      2. However, sedation effect is maintained
   2. Brainstem G-Protein activation inhibits Norepinephrine release
      1. Decreases sympathetic tone and Peripheral Vascular Resistance
4. Advantages
   1. Keeps a patient sleepy but awakenable and will respond to questions
   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)
5. Pharmacokinetics
   1. Onset: 10 minutes
   2. Duration: 1-2 hours
   3. Renal and hepatic metabolism
6. Dosing: General Sedation
   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
7. 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
8. Dosing: Intranasal for Procedural Sedation
   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]
9. Dosing: Sublingual for Agitation (Schizophrenia, Bipolar Disorder)
   1. 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
   2. 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
10. Adverse Effects
    1. Severe Bradycardia
       1. If Heart Rate drops below minimum threshold, stop infusion for 30 min, and restart at 1/2 prior rate
       2. Risk of sinus and AV Node slowing in pediatric patients
    2. Hypotension
       1. Transient Hypertension may occur with rapid infusion or bolus
       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
11. References
    1. Swaminathan and Weingart in Herbert (2019) EM:Rap 19(6): 14
    2. Fisher and Fisher (2018) Crit Dec Emerg Med 32(1): 24
    3. Kay (2015) Crit Dec Emerg Med 29(8): 11-17