The Takeaway

A 1 mcg/kg bolus of Dexmedetomidine reduced the propofol and remifentanil requirements during anesthesia maintenance in children when administered as a postinduction bolus.

Study Design

• Randomized, double-blind, controlled trial
• 67 Children, ASA Status I or II, aged 2-10 years undergoing elective dental surgery
• Exclusion Criteria: inhalational induction requirement, neurological or CV conditions (including HTN), had received preoperative sedatives or anxiolytics (e.g., benzodiazepines), weight <5th percentile or >95th percentile for age, or had hypersensitivity to dexmedetomidine or any other study medication
• Arms: placebo, dexmedetomidine boluses of 0.25 mcg/kg, 0.5 mcg/kg, and 1 mcg/kg
• Primary outcome: time-averaged changes in mean infusion rates of propofol and remifentanil vs placebo
• Secondary outcomes: sedation scores, pain scores, total fentanyl doses given in recovery, and time to discharge from PACU

Physiology Refresh

Precedex is a highly selective alpha-2 adrenergic receptor agonist that works primarily through the following mechanisms:

Primary Mechanism: Alpha-2 Adrenergic Receptor Activation

Dexmedetomidine binds with high selectivity to alpha-2 receptors (particularly the alpha-2A subtype) with an alpha-2 selectivity ratio of approximately 1600:1. This is significantly higher than clonidine, another alpha-2 agonist.

Central Nervous System Effects

1. Locus Coeruleus: The primary site of action is the locus coeruleus in the brainstem, where dexmedetomidine inhibits norepinephrine release by presynaptic activation of alpha-2 receptors.
2. Sedation: Unlike traditional sedatives (benzodiazepines, propofol), dexmedetomidine produces a unique "arousable sedation" resembling natural sleep. Patients can be easily awakened and remain cooperative even during sedation.
3. Anxiolysis: Reduces anxiety without significant respiratory depression.

Analgesic Effects

Dexmedetomidine produces analgesia through:

• Inhibition of substance P release in the dorsal horn of the spinal cord
• Activation of alpha-2 receptors in the spinal cord
• Modulation of descending noradrenergic pathways

The analgesic effect is moderate but can significantly reduce opioid requirements.

Sympatholytic Effects

1. Hemodynamic effects: Produces a biphasic cardiovascular response:
   • Initial transient hypertension (due to peripheral alpha-2B receptor activation)
   • Followed by hypotension and bradycardia (due to central sympatholytic effects)
2. Reduces plasma catecholamine levels by up to 90%

Other Physiological Effects

1. Minimal respiratory depression: Unlike opioids and other sedatives, dexmedetomidine preserves respiratory drive even at higher doses.
2. Anti-shivering properties: Useful for hypothermia management and post-anesthetic shivering.
3. Neuroprotective potential: May reduce ischemic injury through several mechanisms including modulation of apoptosis.
4. Organ-protective effects: Some evidence suggests protective effects on heart, kidney, and brain tissue, likely through anti-inflammatory and anti-oxidant properties.

Abstract

Background: Dexmedetomidine, an α₂-adrenergic agonist, reduces propofol and remifentanil requirements when used as an adjunct to total intravenous anesthesia in adults, but studies in a pediatric population are sparse. This study investigates the magnitude of dose-sparing effects of a postinduction dexmedetomidine bolus on propofol and remifentanil requirements during pediatric surgery.

Methods: In this randomized, double-blind, controlled trial, children aged 2-10 years undergoing elective dental surgery were assigned to one of four groups: placebo, 0.25 mcg/kg dexmedetomidine, 0.5 mcg/kg dexmedetomidine, and 1 mcg/kg dexmedetomidine. Maintenance with fixed-ratio propofol and remifentanil total intravenous anesthesia followed a bispectral index (BIS)-guided algorithm designed to maintain a stable depth of anesthesia. The primary outcomes were time-averaged maintenance infusion rates of propofol and remifentanil. Secondary outcomes in the postanesthetic care unit included sedation scores, pain scores, and time to discharge.

Results: Data from 67 patients were available for analysis. The median [interquartile range] propofol infusion rate was lower in the 1 mcg/kg dexmedetomidine group (180 [164-185] mcg/kg/min) versus placebo (200 [178-220] mcg/kg/min): percent change -10.0%; 95% CI -2.4 to -19.8; p = 0.013. The remifentanil infusion rate was also lower in the 1 mcg/kg dexmedetomidine group (0.089 [0.080, 0.095] mcg/kg/min) versus placebo (0.103 [0.095, 0.106] mcg/kg/min): percent change, -13.7%; 95% CI -5.47 to -21.0; p = .022. However, neither propofol nor remifentanil infusion rates were significantly different in the 0.25 or 0.5 mcg/kg dexmedetomidine groups. In the postanesthesia care unit, there were no differences in pain or sedation scores, and time to discharge was not significantly prolonged in any dexmedetomidine group.

Conclusion: Dexmedetomidine 1 mcg/kg reduced the propofol and remifentanil requirements during maintenance of anesthesia in children when administered as a postinduction bolus.

Excerpts

The intraoperative effect of dexmedetomidine in lowering anesthetic requirements in total intravenous anesthesia (TIVA) has been well demonstrated in adults

Although the safety of TIVA in children has been established, the increased dose requirements for propofol, compared to adults, can be associated with respiratory and cardiovascular complications during pediatric anesthesia. Additionally, minimizing anesthesia exposure may be an important consideration given concerns around associations with neurodevelopmental sequelae

The primary outcome measures were time-averaged changes in mean infusion rates of propofol and remifentanil compared to the placebo group. Secondary outcome measures were sedation scores after discontinuing the propofol-remifentanil infusion, pain scores and total fentanyl doses given in the postanesthetic care unit (PACU), and time to discharge from PACU.

The administration of 1 μg/kg of dexmedetomidine (DEX-1) resulted in lower propofol (−10.0%) and remifentanil (−13.7%) requirements, whereas the 0.25 μg/kg (DEX-0.25) and 0.50 μg/kg (DEX-0.5) doses did not decrease the propofol or remifentanil infusions rates significantly.

While our present trial demonstrates an anesthetic-sparing effect on propofol-remifentanil TIVA, the dose reduction was less than the hypothesized 30%

It may have particular utility in two clinical scenarios: Short but stimulating procedures such as dental surgery and adenotonsillectomy where a reduced propofol dose facilitates more rapid recovery of adequate spontaneous respiration and emergence from anesthesia, and for the many pediatric procedures amenable to a TIVA technique with spontaneous respiration via nasal cannulae.

Propofol has a narrow therapeutic index for the margin between loss of consciousness and apnea or hypopnea. Reducing the dose required to achieve a given depth of anesthesia by coadministering dexmedetomidine may increase the safety margin of this technique, which warrants further investigation.

Citation

Lee VCL, Ridgway R, West NC, Görges M, Whyte SD. Anesthetic-sparing effect of dexmedetomidine during total intravenous anesthesia for children undergoing dental surgery: A randomized controlled trial. Paediatr Anaesth. 2024 Dec;34(12):1213-1222. doi: 10.1111/pan.14987. Epub 2024 Aug 28. PMID: 39193655.

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