From the Guidelines
The combination of bupivacaine, fentanyl, and adrenaline produces spinal cord analgesia through complementary mechanisms that enhance pain relief while minimizing side effects. Bupivacaine, a long-acting local anesthetic, blocks sodium channels in nerve fibers, preventing the generation and transmission of pain signals, with a minimum local analgesic dose of 1.99 mg for labor analgesia, as reported by Stocks et al. 1. Fentanyl, an opioid, binds to mu-opioid receptors in the dorsal horn of the spinal cord, inhibiting the release of excitatory neurotransmitters involved in pain transmission, with studies suggesting that at least 15 µg is required to achieve reliable analgesia when combined with 2.5 mg bupivacaine 1. Adrenaline (epinephrine) causes local vasoconstriction, which slows the vascular absorption of the other drugs, prolonging their duration of action and keeping them concentrated at the site of administration.
Key Mechanisms
- Bupivacaine blocks sodium channels in nerve fibers
- Fentanyl binds to mu-opioid receptors in the spinal cord
- Adrenaline causes local vasoconstriction, prolonging drug action
Typical Dosing
- Bupivacaine: 1.75 mg with 15 µg fentanyl for reliable analgesia in labor, as found by Whitty et al. 1
- Fentanyl: at least 15 µg required for reliable analgesia when combined with 2.5 mg bupivacaine
- Adrenaline: small doses, typically 0.1-0.2mg, to minimize side effects while desirably prolonging the action of bupivacaine and fentanyl. This combination provides more effective pain control than any single agent alone, with reduced side effects due to the lower doses of each component, as supported by the study by Wong et al. 1.
From the Research
Mechanism of Spinal Cord Analgesia
The combination of bupivacaine, fentanyl, and adrenaline causes spinal cord analgesia through several mechanisms:
- Bupivacaine, a local anesthetic, blocks nerve conduction by inhibiting sodium channels, thereby reducing pain transmission 2, 3, 4, 5, 6.
- Fentanyl, an opioid, binds to opioid receptors in the spinal cord, activating descending pain inhibitory pathways and reducing pain transmission 2, 3, 4, 5.
- Adrenaline (epinephrine) enhances the analgesic effects of bupivacaine and fentanyl by reducing blood flow to the spinal cord, which decreases the clearance of these drugs and prolongs their effects 4, 5, 6.
- The combination of these drugs may also have a synergistic effect, enhancing the analgesic efficacy of each individual component 2, 4, 5.
Effects on Pain Relief
Studies have shown that the combination of bupivacaine, fentanyl, and adrenaline provides effective pain relief in various clinical settings:
- In patients undergoing cesarean section, the addition of fentanyl to intrathecal bupivacaine increased the duration of analgesia and provided hemodynamic stability 2.
- In patients undergoing lower limb surgery, the combination of bupivacaine and fentanyl provided effective postoperative pain relief with minimal side effects 3.
- In patients undergoing major upper abdominal surgery, the addition of fentanyl to a thoracic epidural infusion of bupivacaine and adrenaline improved pain relief and reduced the need for rescue analgesia 4.
- The combination of bupivacaine, fentanyl, and adrenaline also provided effective pain relief in patients undergoing elective caesarean section, with reduced need for intraoperative analgesic supplements 5.
Optimal Concentration of Adrenaline
The optimal concentration of adrenaline in a thoracic epidural analgesic infusion of bupivacaine and fentanyl has been studied:
- A dose-finding study found that the minimally effective concentration of adrenaline to maintain relief of dynamic pain is approximately 1.5 microg/ml 6.
- The study also found that reducing the concentration of adrenaline below 1.5 microg/ml resulted in increased pain intensity and decreased sensory blockade 6.