Onset of Action: Remifentanil vs Fentanyl vs Sufentanil
Remifentanil has the fastest onset of action among these three opioids, with peak effect occurring within 1-3 minutes, followed by sufentanil, and then fentanyl. 1, 2
Pharmacokinetic Comparison
Remifentanil - Fastest Onset
- Remifentanil achieves peak effect within less than 5 minutes, with maximum effect occurring within 15 minutes 3
- The rapid onset is attributed to its low pKa (less than physiological pH), allowing it to circulate primarily in the non-ionized form, which quickly penetrates the blood-brain barrier and rapidly equilibrates across the plasma/effect site interface 2
- Context-sensitive half-time remains consistently short at 3.2 minutes, even after prolonged infusions exceeding 8 hours 2
- Blood concentrations change within 5-10 minutes with infusion rate adjustments: every 0.1 mcg/kg/min change produces a corresponding 2.5 ng/mL change in blood concentration 1
Sufentanil - Intermediate Onset
- Sufentanil has a faster onset of action than fentanyl due to its greater lipophilicity and mu-receptor binding capacity 4
- Produces more rapid onset and better initial quality of analgesia compared to morphine, buprenorphine, or hydromorphone when administered epidurally 5
- Has shorter distribution and elimination half-lives compared to fentanyl 5
Fentanyl - Slowest Onset
- Fentanyl has the slowest onset among the three agents 6
- Depends on hepatic biotransformation and renal excretion, with potential for accumulation in organ dysfunction 7
- Alfentanil (a fentanyl derivative) has quicker onset than fentanyl itself, but this comparison focuses on the three agents specified 8
Clinical Implications
Titration Advantages
- Remifentanil allows the easiest titration with maintenance infusion rates of 0.05-0.3 mcg/kg/min 7
- The rapid onset and offset enable precise control of analgesia depth during procedures 2
- In intubated patients, a more rapid increase to steady state (within 3-5 minutes) can be achieved with a 1.0 mcg/kg bolus combined with infusion rate increase 1
Critical Disadvantage of Remifentanil
- Despite its rapid onset advantage, remifentanil requires mandatory transition analgesia planning: longer-acting opioids (such as morphine) must be administered 20 minutes before anticipated end of surgery, or regional anesthesia must be established 7
- The quick dissipation of analgesic effect following discontinuation represents a significant clinical disadvantage unless minimal postoperative pain is anticipated 2
Practical Considerations
- Remifentanil's rapid onset makes it ideal for procedures requiring quick analgesia titration and rapid recovery 2
- Sufentanil offers a balance between rapid onset and longer duration compared to remifentanil 4
- Fentanyl provides simpler bolus dosing but slower onset, making it less suitable when immediate effect is required 7
- All three agents require careful monitoring for respiratory depression, with remifentanil showing particularly pronounced vagomimetic properties in small children, elderly, and hypovolemic patients 8