Saturday, March 31, 2012

Getting Acquainted with Dexmedetomidine

The Gist:  Dexmedetomidine is an alpha-2 agonist used for ICU sedation, procedural sedation, and awake endotracheal intubation.  Give a loading dose of 1 mcg/kg over 10 minutes and then set up a drip of about 0.6 mcg/kg/hr.  This should result in a sedated patient with somewhat preserved airway reflexes but may result in some hypotension and bradycardia.  This pharmaceutical may be too labor intensive for some EDs but may play a growing role in sedation and awake intubation in some patient populations and supplies of other agents wane.

Our favorite induction drugs for rapid sequence intubation (RSI), induction, and procedural sedation seem to continuously be in short supply.   A propofol shortage stunned the United States a couple of years ago (MJ must have had some mad connections to get his hands on this) and currently the meager etomidate supplies in many EDs and ORs are carefully guarded.  These shortages, often spawned by few generic drug manufacturers, have necessitated the use of other induction/anesthetic agents.  Etomidate has three manufacturers, one went out of business, one is small, and the other is frequently "shut down" by the FDA.  Therefore, I suppose it's time to seriously consider other drugs.  Conversations regarding alternatives have included ketamine (NMDA antagonist with little respiratory depression but potential emergence reactions and hemodynamic instability), thiopental, midazolam, and dexmedetomidine.  Thus, I decided it was time to get to know some of the other agents.

Fittingly, the March 21, 2012 edition of  JAMA also featured an article comparing ICU sedation with dexmedetomidine versus propofol or midazolam in a randomized, double-blind non-inferiority trial.  The authors reported that dexmedetomidine was non-inferior to the other two drugs and might have some benefit with regard to achieving the desired level of sedation and reduced duration of mechanical ventilation.  Additionally, there appeared to be a trend towards reduced rates of delirium in the dexmedetomidine arms of the study (1).

  • Centrally acting alpha-2 receptor agonist akin to clonidine
    • Increased firing of inhibitory neurons in CNS
    • Analgesia provided through decreased substance P production in dorsal horn of spinal cord (2)
  • 100 mcg/mL vial to be diluted with normal saline to 4 mcg/mL (3)
  • Half-life = 6 minutes (2)
Dose - involves a loading dose followed by maintenance infusion:
  • Procedural Sedation
    • Loading dose: 1mcg/kg over 10 minutes
    • Maintenance: 0.2-1 mcg/kg/hr (titrated to effect, generally about 0.6 mcg/kg/hr)
  • Intubation (awake)
    • Loading dose: 1mcg/kg over 10 minutes 
    • Then, 0.7 mcg/kg/hr until ETT is in place  (4, 5)
  • ICU sedation
    • Maintenance 0.2-1.4 mcg/kg/hr
  • No specific renal/hepatic dosing adjustments noted but caution in hepatic insufficiency
  • Hypotension (not the drug of choice in the shocky or septic patients)
  • Bradycardia (apparently patients with diabetes are a little more prone to these effects)
  • Cost - this drug is expensive
    • Wholesale = $55.00 per 200 mcg vial (3)
  • Potentially cumbersome to prepare and administer in the ED, requiring monitoring and titration to achieve appropriate sedation
  • Probably not good in the acutely agitated/psychotic patient
    • A study published in December 2011 demonstrated an overwhelming amount of adverse effects and resource utilization in thirteen patients with psychotic-like behavior in the ED (6).  
  • Can mitigate increased intraocular pressure so may have a role in traumatic hyphema/open globe injury (although more due to the decreased rates of emesis in the latter) (2)
  • Has some historical use in pre-medication for RSI to blunt the increased sympathetic activity associated with endotracheal intubation
  • Preserves respiratory reflexes more than propofol
  • Provides some analgesia
  • Potentially good for long-term sedation as it leaves patients
  • May be available when standard agents are not on hand
Disclaimer:  I have absolutely no firsthand experience with this pharmaceutical...yet.
1. Jakob S, Ruokonen E, Grounds R, et al.  Dexmedetomidine vs Midazolam or Propofol for Sedation During Prolonged Mehcanical Ventilation.  JAMA 2012; 307 (11). 
3.  Buck, M.  Dexmedetomidine for Sedation in the Pediatric Incentive Care Setting.  Pediatr Pharm. 2006;12(1)
4.  Unger, R. J., & Gallagher, C. J. Dexmedetomidine sedation for awake fiberoptic intubation. Seminars in Anesthesia Perioperative Medicine and Pain : 25 (2), 65-70. Elsevier.
5.  Weingert, S.  Awake Intubation. Accessed on 31 March 2012.
6.  Calver LIsbister GK. "Dexmedetomidine in the emergency department: assessing safety and effectiveness in difficult-to-sedate acute behavioural disturbance"   Emerg Med J. 2011 Dec 8. 

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