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Dexmedetomidine

Rachel Sloan Cancilla, MD

Northside Anesthesiology Consultants

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Overview

  • Selective alpha 2 adrenergic agonist
  • Greater affinity for alpha 2 compared to alpha 1 receptors (1620:1), similar to clonidine but 8 times more selective for alpha 2
  • Inhibition of norephinephrine
  • Routes of administration: IV, IM, IN, PO, subcutaneous, buccal, rectal
  • Anesthetic, sedative, anxiolytic, sympatholytic, analgesic properties
  • Benefits: reduce emergence delirium, decrease opioid requirements (acts on receptors in dorsal horn and locus coerulus), decrease postoperative nausea and shivering, possible neuroprotective effects in neonates, minimal respiratory depression

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Adverse Effects

  • Hypotension
  • Bradycardia
  • Hypertension
  • Tachycardia
  • Constipation
  • Nausea
  • Respiratory Depression
  • Agitation
  • Rare: afib, hypokalemia, hyper-/hypo-glycemia, hypocalcemia, hypomagnesia, acute renal failure, ARDS, pleural effusion, anxiety, fever, anemia

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Adverse Effects

  • Beware using in patients with heart block, bradycardia, or severe ventricular dysfunction
  • Hypotension, bradycardia, sinus arrest secondary to rapid IV administration (Tx: stop infusion, pressors)
  • Caution in patients with diabetes and elderly due to possible CV affects
  • Caution in patients of younger age (infants) or congenital heart disease
  • Transient hypertension: during loading dose secondary to peripheral vasoconstriction (Tx: slow infusion)
  • Tachyphylaxis possible with infusions > 24 hours
  • Withdrawal (hypertension, tachycardia, agitation) possible after rapid discontinuation after infusion lasting > 24 hours
  • Dose reduction recommended in patients with hepatic impairment
  • Pregnancy Risk Factor C

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Pharmacokinetics

  • Metabolism: hepatic (CYP2A6); decrease dose in patients with hepatic impairment
  • 94% protein bound
  • Excretion: urine
  • Elimination half life: 2 hours

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Dosing

  • Adult sedation: loading dose 0.5 - 1 mcg/kg over 10 – 20 min followed by infusion 0.2 – 1.0 mcg/kg/hr
  • Pediatric sedation: loading dose 0.5 – 1.0 mcg/kg over 10 min followed by infusion 0.2 – 0.7 mcg/kg/hr
  • Pediatric premedication: 1 -2 mcg/kg IN 30-60 min prior to procedure
  • Pediatric T&A: 0.3 – 0.5 mcg/kg given over 20 – 30 min
  • Dosage forms: 4 mcg/mL; 100 mcg/ mL

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Precedex and Airway Reflexes

  • “Comparison of the Effects of Dexmedetomidine Versus Fentanyl on Airway Reflexes and Hemodynamic Responses to Tracheal Extubation During Rhinoplasty: A Double-Blind, Randomized, Controlled Study” By Recep Aksu et al
  • 40, ASA 1 and 2 patients undergoing elective rhinoplasty randomized into 2 groups
  • 5 min prior to extubation, patients given 0.5mcg/kg dexmedetomidine OR fentanyl 1mcg/kg over 5 min
  • Extubation quality evaluated using scale: 1 = no coughing; 2 = minimal coughing (1-2 times); 3 = moderate coughing (3-4 times); 4 = severe coughing (5-10 times) and straining; 5 = poor extubation, coughing > 10 times,

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Precedex and Airway Reflexes

  • No cough significantly higher in patient group receiving dexmedetomidine (85%) compared to fentanyl (30%)
  • No severe coughing or laryngospasm in group receiving dexmedetomidine
  • No significant differences in SpO2, postoperative sedation scores, extubation/awakening times between the groups
  • Conclusion: dexmedetomidine 0.5mcg/kg IV prior to extubation was more effective than fentanyl at attenuating airway reflexes to extubation

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Precedex and Awake FOI

  • “A Comparative Study of Midazolam Alone or in Combination with Dexmedetomidine or Clonidine for Awake Fiberoptic Intubation” by N Bano et al.
  • Prospective double-blind randomized study
  • 60 patients ASA 1 and 2 ages 18-60 with anticipated difficult airway for elective surgery
  • Each patient received same airway topicalization with 4% lido neb and 10% lidocaine spray to tongue and oropharynx

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Precedex and Awake FOI

  • Each group received midazolam 0.04 mg/kg IV prior to infusion of study drug
  • Group M: loading dose of midazolam 0.05 mg/kg over 10 min followed by maintenance infusion at 0.05 mg/kg/h
  • Group D: loading dose of dexmedetomidine 1 mcg/kg over 10 min followed by maintenance infusion of 0.5 mcg/kg/h
  • Group C: loading dose of clonidine 2 mcg/kg over 10 min followed by maintenance infusion of 2 mcg/kg/h

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Precedex and Awake FOI

  • Intubation Score: Vocal cord movement (1: Open 2: moving 3: closing 4: closed) + Coughing (1: none 2: <2 cough 3: 3-5 cough 4: >5 cough) + Limb Movements (1: none 2: slight 3: moderate 4: severe)
  • Comfort Score for FOI: 1: no reaction 2: small grimace 3: heavy grimace 4: verbal objection 5: movement of head or hands
  • Tolerance After Intubation: 1: Cooperative 2: minimal resistance 3: severe resistance

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Precedex and Awake FOI

  • Mean time to RSS > 2 significantly higher in Group M (6.87 + 0.91 min) compared to Group D (5.53 + 0.74 min) and C (6.13 + 0.83 min)
  • Mean time to intubation least in Group D (4.53 + 0.91) compared to Group M (6.40 + 0.50 min) and M (5.5.53 + 0.74 min)
  • Intubation Score, Comfort score, and Tolerance Score significantly greater in Group M compared to Groups D and C
  • MAP and HR significantly higher in Group M compared to Groups D and C
  • Desaturation in Group C significant compared to Groups D and M
  • No bradycardia, hypotension, or transient hypertension in any group

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Precedex and Awake FOI

  • Conclusion: Patients receiving dexmedetomidine and clonidine were calmer, more cooperative, with more hemodynamic stability than patients receiving midazolam alone during awake fiberoptic intubation. Dexmedetomidine maintained spontaneous respirations better than clonidine when each drug was combined with other sedatives (midazolam)

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Precedex and Extubation

  • “Alleviating Stress Response to Tracheal Extubation in Neurosurgical Patients: A Comparative Study of Two Infusion Doses of Dexmedetomidine” by A Luthra et al
  • Concern for emergence from intracranial surgery: airway irritation, tachycardia and HTN (potentially leading to increased ICP, brain edema, hematoma)
  • 90 patients ASA 1-2 for intracranial surgeries
  • 3 groups: Group D0.2: 0.2 mcg/kg/h; Group D0.4 0.4 mcg/kg/h; Group P (placebo) 0.9% NS
  • Group D0.2 and D0.4 groups received dexmedetomidine loading dose 0.5 mcg/kg over 10 min after dural closure followed by infusion (0.2 or 0.4 mcg/kg/hr) until extubation
  • Objectives: Hemodynamic changes (HR, MAP), airway reflexes (cough), emergence time, time to extubation

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Precedex and Extubation

  • Cough: Group D0.4 100% no cough; Group D0.2 80% no cough and 20% mild cough; Group P 33.3% mild cough, 40% moderate cough, 3.3% severe cough
  • Emergence: Group D0.4 was 11.4 + 4.1 min; group D0.2 was 8.2 + 2.6 min; Group P was 9.9 + 2.7 min; only 1 patient in Group D0.4 was deeply sedated; Group D0.4 had statistically but not clinically significant increase in emergence time
  • Hemodynamics: Group P 73.3% had HTN and tachycardia on emergence and 23.3% had emergence HTN only; : Group D0.4 3.3% had HTN and tachycardia on emergence, 3.3% had emergence HTN only; group D0.2 had 1 patient with hypotension

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Precedex and Extubation

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Precedex and Extubation

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Precedex and Extubation

  • Conclusion: Dexmedetomidine suppresses hemodynamic responses and airway reflexes to extubation without delaying emergence

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Precedex and Emergence Delirium

  • “Effect of Single-Dose Dexmedetomidine on Intraoperative Hemodynamics and Postoperative Recovery during Pediatric Adenotonsillectomy” by K Sharma et al.
  • Prospective, randomized, placebo-controlled study
  • 60 patients; ASA 1 and 2 children ages 5-10 having elective adenotonsillectomy
  • Group D received 1 mcg/kg IV infusion over 10 min of dexmedetomidine prior to induction
  • Group C received saline infusion over 10 min prior to induction
  • Both groups received 0.5 mg/kg midazolam preop and 1 mg/kg tramadol IV post extubation

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Precedex and Emergence Delirium

  • Pediatric Agitation Emergence Delirium Scale

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  • Score > 12 have 100% sensitivity and 94.5% specificity for diagnosis of Emergence Delirium
  • Emergence Delirium rates reported between 2 – 80% (incidence more likely 20-30%)

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Precedex and Emergence Delirium

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  • Visual Analog Scale (VAS)

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  • Ramsay Sedation Scale (RSS)

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Precedex and Emergence Delirium

  • PAED scores: Group C (13.84 + 1.39) vs Group D (9.37 + 1.33)
  • All patients in Group C had PAED score > 12 vs 6.67% patients in Group D
  • No significant difference in VAS scores
  • RSS: Higher in Group D (2.62 + 0.49) vs Group C (1.6 + 0.5)
  • No patients had RSS > 3
  • No episodes of bradycardia or hypotension
  • Longer time to extubation in Group D (7.70 + 1.62) vs Group C (5.23 + 1.91)

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Precedex and Emergence Delirium

  • Conclusion: Dexmedetomidine 1 mcg/kg given over 10 min to children having adenotonsillectomy resulted in significant decrease in postoperative emergence delirium without causing excessive sedation

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Precedex and Pediatric Anxiety

  • “The Comparison of Dexmedetomidine and Midazolam Premedication on Postoperative Anxiety in Children for Hernia Repair Surgery: A randomized controlled trial” by Du Z et al.
  • Double-blind, randomized controlled trial
  • 90 patients, ages 6 to 11, ASA 1 and 2 having elective hernia repair
  • IV inserted preoperatively in all patients
  • Group M: 20 min prior to OR, IV infusion of midazolam (0.08 mg/kg) over 10 min
  • Group D: 20 min prior to OR, IV infusion of dexmedetomidine (0.5mcg/kg) over 10 min

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Precedex and Pediatric Anxiety

  • Preoperative and postoperative anxiety assessed using modified Yale Preoperative Anxiety Scale
    • Assesses 5 items: activity, emotional expressitivity, state of arousal, vocalization, and use of parents
    • Scores: 23.5-30 indicates no or mild anxiety; scores >30 indicate severe anxiety
    • Anxiety assessed during preoperative interview, 5 min after meds, prior to rolling to OR, 2 and 4 hours postoperatively
  • Pain assessed using visual analogue scale

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Precedex and Pediatric Anxiety

  • Group D had increased anxiety 5 minutes after administration but decreased anxiety prior to OR
  • Group D had significantly lower anxiety postoperatively than Group D preoperatively, and Group M postoperatively (both at 2 and 4 hours)
  • Group D had lower pain scores compared to Group M at 2 and 4 hours and 1 day postoperatively
  • No difference in pain at one week and one month postoperatively between the two groups

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Precedex and Pediatric Anxiety

  • Precedex has onset time of 10-15 min which may explain increase in anxiety after 5 min
  • Precedex has half life of 2-3 hours explaining lower postoperative anxiety
  • Conclusion: Precedex can help lower postoperative anxiety in children compared to midazolam

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Precedex and Analgesia

  • “Dexmedetomidine infusion as an analgesic adjuvant during laparoscopic cholecystectomy: a randomized controlled study” by Kateryna Bielka et al
  • Randomized, parallel-group, placebo-controlled study
  • 60 adult patients, ASA 1 and 2, undergoing laparoscopic cholecystectomy

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Precedex and Analgesia

  • Group C: placebo, normal saline infusion from induction of anesthesia to extubation
  • Group D: 0.5 mcg/kg/hr dexmedetomidine from induction of anesthesia to extubation

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Precedex and Analgesia

  • Group D:
    • longer time to first use of rescue analgesia (180 min in Group D vs 80 min in Group C, p = 0.001)
    • decrease in postoperative morphine consumption (median 5 mg/24 h for Group D vs 15 mg/24 h for Group C, p = 0.001)
    • lower intraoperative fentanyl consumption (p = 0.001)
    • Shorter time from end of surgery to extubation (10 min in Group D vs 20 min in Group C, p = 0.001)
    • Decreased incidence of persistent post-surgical pain

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Precedex and Spine Surgery

  • “Effect of a low-dose dexmedetomidine infusion on intraoperative hemodynamics, anesthetic requirement and recovery profile in patients undergoing lumbar spine surgery” by Sandeep Kundra et al
  • Randomized double blinded study, 60 patients undergoing elective laminectomy at one or two levels
  • Group A: dexmedetomidine infusion 0.3mcg/kg/hr
  • Group B: saline infusion

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Precedex and Spine Surgery

  • Mean HR not significantly different between groups
  • MAP significantly lower in Group A but only for first 30 minutes
  • Intraoperative blood loss lower in Group A (263.5 + 58.7 mL) compared to Group B (347.7 + 72.9 mL)
  • Mean Etsevo significantly lower in Group A compared to Group B
  • Mean emergence time, mean tracheal extubation time, mean recovery times significantly shorter in Group A compared to Group B
  • Opioid requirement not significantly different between groups
  • Bradycardia and hypotension similar between groups

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Conclusions

  • Use of precedex may be advantageous for use
    • Attenuating airway reflexes upon extubation
    • Providing hemodynamic stability upon extubation
    • Making patients calm and cooperative with minimal respiratory depression during procedures including awake fiberoptic intubation
    • Decrease in postoperative pediatric emergence delirium and anxiety
    • Decrease in anesthetic requirement

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References

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  • Aksu R, Akin A, Biçer C, Esmaoğlu A, Tosun Z, Boyaci A. Comparison of the effects of dexmedetomidine versus fentanyl on airway reflexes and hemodynamic responses to tracheal extubation during rhinoplasty: A double-blind, randomized, controlled study. Curr Ther Res Clin Exp. 2009;70(3):209–220. doi:10.1016/j.curtheres.2009.06.003
  • Bano N, Singh P, Singh D, Prabhakar T. A Comparative Study of Midazolam Alone or in Combination with Dexmedetomidine or Clonidine for Awake Fiberoptic Intubation. Anesth Essays Res. 2019;13(3):539–546. doi:10.4103/aer.AER_64_19
  • Du Z, Zhang XY, Qu SQ, et al. The comparison of dexmedetomidine and midazolam premedication on postoperative anxiety in children for hernia repair surgery: A randomized controlled trial. Paediatr Anaesth. 2019;29(8):843–849. doi:10.1111/pan.13667

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References

  • Kundra S, Taneja S, Choudhary AK, Katyal S, Garg I, Roy R. Effect of a low-dose dexmedetomidine infusion on intraoperative hemodynamics, anesthetic requirements and recovery profile in patients undergoing lumbar spine surgery. J Anaesthesiol Clin Pharmacol. 2019;35(2):248–253. doi:10.4103/joacp.JOACP_338_18
  • Luthra A, Prabhakar H, Rath GP. Alleviating Stress Response to Tracheal Extubation in Neurosurgical Patients: A Comparative Study of Two Infusion Doses of Dexmedetomidine. J Neurosci Rural Pract. 2017;8(Suppl 1):S49–S56. doi:10.4103/jnrp.jnrp_91_17
  • Sharma K, Kumar M, Gandhi R. Effect of Single-Dose Dexmedetomidine on Intraoperative Hemodynamics and Postoperative Recovery during Pediatric Adenotonsillectomy. Anesth Essays Res. 2019;13(1):63–67. doi:10.4103/aer.AER_178_18