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. Other patients requiring sedation
    1. Alcohol Withdrawal
    2. Peri-procedure sedation
    3. Neurocritical care patients
    4. Tachycardic patients on Vasopressors

III. Contraindications

  1. Severe Bradycardia
  2. Hemodynamically unstable (significant Hypotension)

IV. 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

V. 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)

VI. Pharmacokinetics

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

VII. Dosing: General

  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: 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]

X. 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. 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. 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

XI. 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

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Related Studies

Ontology: Dexmedetomidine (C0113293)

Definition (MSH) A imidazole derivative that is an agonist of ADRENERGIC ALPHA-2 RECEPTORS. It is closely-related to MEDETOMIDINE, which is the racemic form of this compound.
Definition (NCI) An imidazole derivate and active d-isomer of medetomidine with analgesic, anxiolytic and sedative properties. Dexmedetomidine selectively binds to presynaptic alpha-2 adrenoceptors located in the brain, thereby inhibiting the release of norepinephrine from synaptic vesicles. This leads to an inhibition of postsynaptic activation of adrenoceptors, which inhibit sympathetic activity, thereby leading to sedation and anxiolysis. The analgesic effect of this agent is mediated by binding to alpha-2 adrenoceptors in the spinal cord.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D020927
SnomedCT 438079000, 437750002
English (+)-4-((S)-alpha,2,3-Trimethylbenzyl)imidazole, 1H-Imidazole, 4-(1-(2,3-dimethylphenyl)ethyl)-, (R)-, Dexmedetomidine (substance), Dexmedetomidine (product), Dexmedetomidine, Dexmedetomidine [Chemical/Ingredient], DEXMEDETOMIDINE, dexmedetomidine
Swedish Dexmedetomidin
Czech dexmedetomidin
Finnish Deksmedetomidiini
Russian DEKSMEDETOMIDIN, ДЕКСМЕДЕТОМИДИН
Japanese プレセデックス, デキサメデトミジン, デキスメデトミジン, デクスメデトミジン塩酸塩, デクスメデトミジン, 塩酸デクスメデトミジン, D-メデトミジン
Spanish dexmedetomidina, Dexmedetomidina, Dexmedetomidina (sustancia), dexmedetomidina (producto)
Polish Deksmedetomidyna
French Dexmédétomidine
German Dexmedetomidin
Italian Dexmedetomidina
Portuguese Dexmedetomidina
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Precedex (C0876757)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D020927
English Hospira Brand of Dexmedetomidine Hydrochloride, Precedex, precedex
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: Dexdomitor (C2732176)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
English Dexdomitor
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Pharmacology

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