Precedex: A New Alternative for Pediatric Sedation

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Precedex A New Alternative for Pediatric
Sedation?

• Michelle Alletag, M.D.
• PL-2, Dept. of Pediatrics
• UT Southwestern Medical Center at Dallas

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Abstract

• Precedex (Dexmedetomidine) is a relatively new
  sedation/analgesic agent. While not yet approved
  for pediatric patients, it is rapidly gaining
  favor in the Pediatric intensive care setting.
  This review is the result of a general search for
  information regarding Precedex, including safety
  and potential efficacy. The study reviewed was
  ineffective in proving safety or efficacy when
  compared with standard regimens of
  benzodiazepines and opioids, and points to the
  need for more research prior to further use.

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Clinical Background Pt. A

• A 4 y.o. girl with a hx. of multiple long-term
  intubations 2/2 her presenting illness, and then
  complications from a bone marrow transplant.
• Significant hx. of sedation difficulties,
  hypertension, and tachycardia.
• Precedex (Dexmedetomidine) added as a secondary
  agent to current sedation/analgesia regimen.
• Pt. had rapid and persistent decrease in HR
  (within one hour)
• No significant improvement in sedation
• Precedex discontinued after two days

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Clinical Background Pt. B

• 2 month old healthy male infant with RSV
  bronchiolitis, intubated for apnea in ER and
  placed on Precedex upon admission to the PICU
  (extubation anticipated within 24-48 hrs).
• Within 12 hours of Precedex initiation, developed
  acute episode of bradycardia requiring CPR
• Bradycardia not attributable to apneic or
  desaturation episode
• Precedex discontinued
• No further episodes of bradycardia

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Question

• Is Precedex a safe and viable alternative to
  standard benzodiazepines for sedation of
  intubated pediatric patients?

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Search Strategy

• OVID Search for
• 1 Precedex limited to pharmacokinetics, side
  effects, and mechanism of action
• 2 Randomized controlled trials comparing
  Precedex with standard forms of sedation
  (Fentanyl/Versed)

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The Result

• Tobias JD, Berkenbosch JW. Sedation During
  Mechanical Ventilation in Infants and Children
  Dexmedetomidine versus Midazolam. Southern
  Medical Journal 2004 97(5) 451-455.
• A prospective, randomized trial to compare the
  efficacy of midazolam versus dexmedetomidine for
  sedation during mechanical ventilation of infants
  and children.

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First, What Is Precedex?

• Dexmedetomidine HCl
• a selective, centrally-acting alpha-2 blocker
• has sedative, anxiolytic, and analgesic effects
• Inhibits sympathetics
• activates parasympathetics
• Rapid distribution (6 minutes) and half-life (2
  hours)
• Similar to Clonidine (but 800x more specific for
  alpha-2) and Etomidate.
• FDA-approved for short-term (lt24 hours) sedation
  in adults

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Is a benzodiazepine alternative even
necessary?

• Benzodiazepine/Opioid Withdrawal is Common
• Short-term (inadequate sedation)
• Long-term (need for methadone/valium can hold up
  discharge)
• Midazolam can lead to oversedation and thus
  short-term delays in extubation

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Problems with Precedex

• Known to cause significant hypotension and
  bradycardia
• average 20-point drop in both systolic and
  diastolic blood pressure in adults
• Limited/anecdotal experience only in
  infants/children

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The Study

• A prospective, randomized controlled trial
  comparing Precedex and Versed efficacy in
  ventilated children for a 24-hour period only
• 3 Groups of 10 Patients
• Versed Control Group (0.22mg/kg/h)
• Precedex 0.25mcg/kg/h
• Precedex 0.5mcg/kg/h
• Level of Sedation assessed based on 3 sedation
  scales
• Tobias et al. Southern Medical Journal 2004
  97(5) 451-455

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Sedation Indices

• Measured Sedation Indices
• Ramsay Scale (Scale of 1-6 1 being agitated, 6
  most sedated)
• PICU Sedation Scale (Scale of 1-4)
• Tracheal Suctioning Score (Scale of 1-6)
• Bispectral Index Monitor
• EEG evaluation of state of alertness
• Number of prn Morphine boluses required to
  maintain adequate sedation
• Tobias et al. Southern Medical Journal 2004
  97(5) 451-455

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Results

• No significant differences between all three
  groups in average score of the sedation scales
• Ramsey Score of 1 (indicating inadequate
  sedation) assigned at least once in
• 60 of patients in Midazolam group
• 40 of patients in the Dexmedetomidine
  0.25mcg/kg/h
• 20 of patients in the Dexmedetomidine
  0.5mcg/kg/h
• 83 of patients in either Dexmedetomidine group
  who were assigned a Ramsey score of 1 were lt12
  months of age
• Tobias et al. Southern Medical Journal 2004
  97(5) 451-455

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Results cont.

• Decrease in number of Morphine boluses given in
  both Precedex groups
• Statistically insignificant in Midazolam v.
  Dexmedetomidine at 0.25mcg/kg/h
• P 0.02 for Midaz v. Dexmedetomadine at
  0.5mcg/kg/h
• No significant difference in blood pressures
  among the three groups
• Significant decrease in heart rates in both
  Dexmedetomidine groups
• Decrease was statistically significant despite
  one infant being removed from study secondary to
  profound bradycardia)
• Tobias et al. Southern Medical Journal 2004
  97(5) 451-455

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Strengths of the Study

• Evaluated both the sedation effects and the
  cardiovascular side effects of the two
  medications
• Randomized and double-blinded to eliminate bias
• Used multiple scores and criteria to evaluate
  sedation

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Weaknesses

• Very small cohort (low power). No specific
  hypothesis. Removed a patient from results data
  due to an adverse effect.
• No age exclusion
• average age was equivalent at 34 months, but
  with a very broad range
• No exclusion criteria
• Postoperative patients may have very different
  sedation/analgesic needs from patients with
  respiratory failure or shock.
• Drugs for the study provided by Abbott
  Pharmaceuticals.

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Conclusions

• Cannot conclude that Precedex is a safe or
  effective alternative to Versed.
• Side effects concerning enough that further
  studies are indicated prior to routine use.
• Precedex could be an appropriate agent for a
  select group of PICU patients, but more
  experience is needed.

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Conclusions Who is a candidate for Precedex?

• Patients likely to be ventilated for lt24 hours
• Age gt 1 year (unless further studies can show a
  better safety profile for infants)
• Stable baseline cardiovascular status
• No underlying liver disease (hepatically
  metabolized)
• Post-op heart patients may benefit from the
  negative chronotropic effects and short half-life

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Further Research Potential

• A randomized controlled trial using a much larger
  cohort
• A study that includes infants only (Case Reports
  of adverse effects are mostly in kids 12 mos. or
  younger)
• A randomized controlled trial evaluating time to
  extubation in dexmedetomidine v. midazolam (since
  we really only have anecdotal evidence)

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References

• Tobias JD, Berkenbosch JW. Sedation During
  Mechanical Ventilation in Infants and Children
  Dexmedetomidine versus Midazolam. Southern
  Medical Journal 2004 97(5) 451-455.
• Tobias JD, Berkenbosch JW. Initial Experience
  with Dexmedetomidine in Paediatric-Aged Patients.
  Paediatric Anesthesia 2002 12 171-175.
• Tobias JD, Berkenbosch JW. Additional Experience
  with Dexmedetomidine in Pediatric Patients.
  Southern Medical Journal 2003 96 871-875.
• Petroz Guy C, et. al. A Phase I, Two-Center
  Study of the Pharmacokinetics and
  Pharmacodynamics of Dexmedetomidine in Children.
  Anesthesiology 2006 105(6) 1098-1110.
• Tobias Joseph D. Dexmedetomidine Applications
  in Pediatric Critical Care and Pediatric
  Anesthesiology. Pediatric Critical Care Medicine
  2007 8(2) 1-17.