How does co-administration of propofol and fentanyl affect the minimum alveolar concentration (MAC) of sevoflurane?

MAC Reduction of Sevoflurane with Propofol and Fentanyl Co-Administration

Direct Answer

Co-administration of fentanyl produces a dramatic 61% reduction in sevoflurane MAC at plasma concentrations of 3 ng/ml, with an even greater 83% reduction in MAC-BAR (blockade of adrenergic response), though a ceiling effect occurs beyond 6 ng/ml fentanyl. 1 Propofol is compatible with sevoflurane administration but does not directly reduce MAC requirements in the same manner as opioids. 2

Fentanyl's Effect on Sevoflurane MAC

Dose-Response Relationship

• Fentanyl demonstrates a steep initial MAC reduction: At 3 ng/ml plasma concentration, fentanyl reduces sevoflurane MAC by 61% and MAC-BAR by 83%. 1

• A ceiling effect occurs at higher fentanyl doses: Increasing fentanyl from 3 ng/ml to 6 ng/ml provides only an additional 13% MAC reduction and 9% MAC-BAR reduction, indicating diminishing returns beyond moderate doses. 1

• For tracheal intubation specifically: Fentanyl reduces sevoflurane MAC-TI (minimum alveolar concentration for tracheal intubation) from 3.55% to 2.07% at 1 mcg/kg, to 1.45% at 2 mcg/kg, and to 1.37% at 4 mcg/kg, again demonstrating a ceiling effect between 2-4 mcg/kg. 3

Interaction with Nitrous Oxide

• When 66% nitrous oxide is added: The ceiling effect for fentanyl's MAC reduction disappears, allowing continued dose-dependent reductions in both MAC and MAC-BAR with increasing fentanyl concentrations. 1

• Nitrous oxide alone reduces sevoflurane MAC by approximately 50% in adults and 25% in pediatric patients. 2

Propofol's Role in Sevoflurane Anesthesia

Compatibility Without Direct MAC Reduction

• The FDA label confirms that sevoflurane administration is compatible with propofol and other commonly used intravenous anesthetics, but does not describe propofol as reducing sevoflurane MAC requirements. 2

• Benzodiazepines and opioids are specifically noted to decrease sevoflurane MAC, while propofol is listed separately as a compatible agent without this specific MAC-reducing property. 2

Clinical Applications

• Propofol can be used at the end of sevoflurane anesthesia (1 mg/kg) to reduce emergence agitation in children, with comparable efficacy to fentanyl but with lower incidence of postoperative nausea and vomiting. 4

• The combination of low-dose fentanyl (1.5 mcg/kg) during induction plus propofol (1 mg/kg) at the end of surgery reduces emergence agitation more effectively than either agent alone in pediatric patients. 5

Clinical Algorithm for MAC Management

For Surgical Anesthesia Maintenance

1. Start with baseline sevoflurane MAC (approximately 2% in adults at sea level)

2. If using fentanyl 1-3 mcg/kg: Reduce sevoflurane concentration by approximately 60% (to ~0.8-1.2%) 1

3. If using fentanyl >3 mcg/kg: Do not expect significant additional MAC reduction due to ceiling effect 1

4. If adding 50-66% nitrous oxide: Further reduce sevoflurane requirements by approximately 50% 2

5. Propofol does not require MAC calculation adjustments when used for induction or emergence, as it functions as a compatible co-anesthetic rather than a MAC-reducing agent 2

Important Clinical Pitfalls

Hemodynamic Considerations

• Fentanyl attenuates hemodynamic responses to intubation in a dose-dependent manner even as concomitant sevoflurane concentration decreases, with 4 mcg/kg providing superior suppression of heart rate and blood pressure changes compared to 1-2 mcg/kg. 3

• Sevoflurane produces dose-dependent decreases in blood pressure, and excessive decreases may occur more rapidly than with other volatile anesthetics due to sevoflurane's low blood solubility. 2

Neuromuscular Blockade

• Do not reduce the dose of nondepolarizing muscle relaxants for endotracheal intubation despite sevoflurane's potentiation of neuromuscular blockade, as reduced doses may result in delayed onset or inadequate relaxation. 2

• During maintenance, nondepolarizing muscle relaxant requirements are reduced compared to N2O/opioid anesthesia, and supplemental dosing should be guided by nerve stimulation monitoring. 2

Emergence Management

• For pediatric patients at risk of emergence agitation: Consider administering propofol 1 mg/kg at the end of surgery rather than additional fentanyl to minimize postoperative nausea and vomiting while maintaining comparable agitation reduction. 4