MAC Reduction with Propofol and Fentanyl Co-Administration
Yes, administering propofol and fentanyl with sevoflurane significantly reduces the MAC value of sevoflurane, with fentanyl producing the most dramatic effect—up to 61% MAC reduction at plasma concentrations of 3 ng/mL, and an additional 83% reduction in MAC-BAR (blockade of adrenergic response). 1
Fentanyl's Effect on Sevoflurane MAC
Fentanyl produces a steep, dose-dependent reduction in sevoflurane MAC with a ceiling effect:
- At 3 ng/mL plasma concentration: 61% reduction in MAC and 83% reduction in MAC-BAR 1
- At 6 ng/mL plasma concentration: Only an additional 13% MAC reduction and 9% MAC-BAR reduction beyond the 3 ng/mL level, demonstrating a clear ceiling effect 1
- For tracheal intubation (MAC-TI): Fentanyl 1 mcg/kg reduces sevoflurane MAC-TI from 3.55% to 2.07%; 2 mcg/kg reduces it to 1.45%; and 4 mcg/kg reduces it to 1.37%, with no significant difference between 2 and 4 mcg/kg doses 2
The ceiling effect is critical: Beyond 3-6 ng/mL fentanyl, you gain minimal additional MAC reduction, so escalating fentanyl doses provides diminishing returns 1
Nitrous Oxide Interaction
When N₂O (66%) is added to the sevoflurane-fentanyl combination:
- The ceiling effect observed with fentanyl alone disappears 1
- MAC and MAC-BAR continue to decrease with increasing fentanyl concentrations without plateau 1
- N₂O itself reduces sevoflurane MAC by approximately 50% in adults and 25% in pediatric patients 3
Propofol's Effect on Sevoflurane MAC
Propofol co-administration with sevoflurane:
- When used as a continuous infusion (100 mcg/kg/min) with fentanyl, propofol maintains stable lumbar CSF pressure, unlike sevoflurane alone which increases CSF pressure by 2±2 mmHg at both 0.5 and 1.0 MAC 4
- The FDA label confirms sevoflurane administration is compatible with propofol and other commonly used intravenous anesthetics 3
- A comparative study found sevoflurane and propofol (both with fentanyl) produced overall similar inflammatory responses 5
Clinical Implications for MAC Dosing
When combining these agents, expect the following MAC reductions:
- Fentanyl alone: Maximum 61% MAC reduction at therapeutic plasma levels (3 ng/mL) 1
- With N₂O added: Further MAC reduction of approximately 50% in adults 3
- Propofol infusion: Provides stable anesthetic depth when combined with sevoflurane and fentanyl, though specific MAC reduction percentages are not quantified in the available evidence 4
Important Caveats
Neuromuscular blockade considerations:
- Sevoflurane potentiates nondepolarizing muscle relaxants (vecuronium, pancuronium, atracurium) similarly to isoflurane 3
- For endotracheal intubation, do not reduce the dose of nondepolarizing muscle relaxants despite reduced sevoflurane MAC 3
- During maintenance, required doses of muscle relaxants will be reduced compared to N₂O/opioid anesthesia; use nerve stimulation to guide supplemental dosing 3
Hemodynamic monitoring:
- Sevoflurane produces dose-dependent decreases in blood pressure, and these changes occur more rapidly than with other volatile anesthetics due to sevoflurane's low blood solubility 3
- Fentanyl attenuates hemodynamic responses to intubation in a dose-dependent manner, even as concomitant sevoflurane concentration decreases 2
- When combining sevoflurane with calcium antagonists, marked hypotension may occur; blood pressure should be closely monitored 3
Practical dosing strategy:
- Start with fentanyl 2-3 mcg/kg to achieve near-maximal MAC reduction (approximately 60%) 1, 2
- Avoid exceeding fentanyl 4 mcg/kg as this provides minimal additional benefit due to the ceiling effect 1, 2
- If using N₂O, you can achieve further MAC reduction beyond the fentanyl ceiling 1
- Titrate sevoflurane concentration downward by approximately 40-60% when using therapeutic fentanyl doses 1