Presentation link: High therapeutic Buprenorphine levels reduce IV Fentanyl respiratory depression

Aim: Examine the effects of sustained buprenorphine (BUP) concentrations on respiratory depression induced by intravenous (IV) fentanyl.
Design: Subjects in this open-label study received pulsed-continuous infusions of placebo (PLC)/fentanyl on Day 1 and BUP/fentanyl on Day 3. BUP infusion targeted plasma concentrations of 1 (n=2), 2 (n=3), or 5ng/mL (n=3). Following BUP or PLC infusion, IV fentanyl boluses of 250, 350, 500, and 700mcg/70kg were administered. Setting: Clinical unit and anesthesia suite in Netherlands.
Participants: Eight opioid-tolerant subjects using >90mg daily oral morphine equivalents.
Measurements: Decrease in minute ventilation (MV), number/duration of apneic events (lasting >20 seconds), need for ventilatory stimulation, and changes in oxygen saturation (SpO2).
Findings: With PLC, abrupt declines in MV were evident following fentanyl boluses. Six of 8 subjects (75%) experienced >1 apneic event requiring verbal ventilatory stimulation to maintain adequate MV. IV fentanyl dose escalation was stopped early after the 2nd (n=2) or 3rd bolus (n=2) in 4 subjects due to prolonged apnea or SpO2 changes. One subject with ~1ng/mL BUP experienced apneic episodes after the 3rd and 4th fentanyl boluses. With BUP, no subjects required verbal ventilatory stimulation, and SpO2 did not drop below 90%. With 1ng/mL BUP, declines in MV were evident following fentanyl boluses; however, subjects with concentrations above 5ng/mL did not have marked changes in MV or repeated apneic events.
Conclusions: These data suggest BUP (especially at concentrations >2 and 5ng/mL) acts as a competitive inhibitor of fentanyl at doses up to 700mcg/70kg, reducing the magnitude of fentanyl-induced respiratory depression.