A dose-ranging pilot trial of dexmedetomidine-propofol in children undergoing magnetic resonance imaging

The Takeaway

An anesthetic plan with propofol infusion and single dexmedetomidine provides a safe sedation and didn't significantly extend recovery time.

Study Design

• 79 children aged 1-12, scheduled for MRI
• Single-center, prospective, sequential, dose-ranging trial
• ASA I-III, natural airway, intravenous access prior to sedation
• Propofol-Only cohort received an IV propofol bolus of 2–3 mg/kg followed by a continuous IV infusion of propofol at 250 mcg/kg/min
• Dexmedetomidine cohorts received a 1 mcg/kg bolus of dexmedetomidine followed by a continuous infusion of dexmedetomidine at three different rates
  • 1 mcg/kg/hr (DEX-High)
  • 0.5 mcg/kg/hr (DEX-Low)
  • No infusion (DEX-Bolus)
  • Propofol IV bolus of 2–3 mg/kg given and infusion was initiated at 100 mcg/kg/min, with titration up to 300 mcg/kg/min as needed

Abstract

The optimal sedation/anesthesia technique for magnetic resonance imaging (MRI) scans has not been established. The combination of propofol with dexmedetomidine has been reported, but without systematic dosing data. Our primary aim was to determine the propofol-sparing effect of dexmedetomidine (DEX) when added to propofol for MRI scan sedation/anesthesia utilizing a dose-ranging protocol for four distinct regimens (Propofol-Only, DEX-High, DEX-Low, DEX-Bolus). Our secondary aims were to document adverse events, scan interruptions due to patient movements, and determine recovery time. Seventy-nine patients aged 1-12 years scheduled for MRIs under anesthesia were sequentially enrolled. A 60% reduction in propofol dose required was found in the dexmedetomidine cohorts. There was no difference (p = 0.161) in recovery time between Propofol-Only and DEX-Bolus groups. There were no differences in episodes of hypotension (p = 0.464), bradycardia (p = 0.558), or patient movement (p = 0.273) between the Propofol-Only and dexmedetomidine cohorts. Recovery time was prolonged for DEX-High and DEX-Low groups compared to DEX-Bolus or Propofol-Only. The addition of dexmedetomidine significantly decreased the necessary dose of propofol. Propofol combined with a single bolus of dexmedetomidine (no infusion) provided effective sedation/anesthesia without adverse events or extending recovery time.

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.

Excerpts

Based on our institution’s historical, clinical experience, a 30% reduction in propofol had been observed when patients were administered 0.5–1 mcg/kg bolus of dexmedetomidine.

The utilization of dexmedetomidine led to significant decreases in the propofol dose required to achieve adequate sedation (240.2 mcg/kg/min in Propofol-Only, 100.8 mcg/kg/min in DEX-High, 96.0 mcg/kg/min in DEX-Low, 104.2 mcg/kg/min in DEX-Bolus (p < 0.001)

There was statistical difference between Propofol-Only and the DEX-High and DEX-Low groups for the time to recovery (defined as time of entrance to the PACU to time of patient full responsiveness—Aldrete score > / = 10), but no statistical (p = 0.161) or clinically meaningful difference (7 min) when comparing the Propofol-Only and DEX-Bolus groups

There were no significant differences of hypotension (p = 0.464), bradycardia (p = 0.558), or scan interruptions due to patient movement (p = 0.273) between the Propofol-Only and the Dexmedetomidine cohorts

We propose that our data indicates the use of a single bolus of dexmedetomidine, without adding an infusion, is optimal, since the propofol-sparing effect appeared similar to that found when an infusion was added

One limitation to this study was the premedication of all patients with 0.1 mg/kg IV midazolam. Our findings are similar, but may apply more accurately in institutions where premedication is not standard. Furthermore, an optimal sedative regimen for MRIs should consider potential workflow disturbances due to increased recovery times documented with the introduction of high doses of dexmedetomidine

This data suggests dexmedetomidine alone is often inadequate to supply effective sedation to complete MRI scans without disruptions and supplemental medications are required.

we found that propofol combined with a single bolus of dexmedetomidine with propofol infusion provided effective sedation/anesthesia for MRI scans of average duration without significantly increasing the time to recovery; thus, we believe this regimen warrants further investigation

given our pilot results, we suggest the infusion rate of propofol in the DEX bolus (only) cohort should start at 150 mcg/kg/min and adjusted based on data indicating problems of inadequate or excessive sedation.

Citation

Kim SY, Booth JM, Staffa SJ, Kordun A, Yu J, Cravero JP. A dose-ranging pilot trial of dexmedetomidine-propofol in children undergoing magnetic resonance imaging. J Anesth. 2025 May 11. doi: 10.1007/s00540-025-03511-z. Epub ahead of print. PMID: 40349256.

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