01Basic Opioid Pharmacology
Analgesia is produced by μ (mu) opioid receptor agonism: - In the brain (periaqueductal gray matter) - In the spinal cord (substantia gelatinosa)
Side-effect profile is consistent across the class: - Sedation, respiratory depression - Chest-wall rigidity (rapid bolus of potent fentanyl/sufentanil/remifentanil) - Bradycardia, hypotension (especially with other anesthetics) - Pruritus, nausea, ileus, urinary retention - Miosis (useful to assess patients under GA) - Reduce MAC of volatile anesthetics.
Opioids alone are hemodynamically stable; in combination with volatiles or propofol they ↓ CO/SV/BP.
02Opioid Receptor Subtypes
| Receptor | Clinical effect | Agonists |
|---|---|---|
| μ (mu) | Supraspinal analgesia (μ1), respiratory depression (μ2), physical dependence, muscle rigidity | Morphine, fentanyl, met-enkephalin, β-endorphin |
| κ (kappa) | Sedation, spinal analgesia | Nalbuphine, butorphanol, dynorphin, oxycodone |
| δ (delta) | Analgesia, behavioral, epileptogenic | Leu-enkephalin, β-endorphin |
| σ (sigma) | Dysphoria, hallucinations | Pentazocine, ketamine |
03Opioid Comparison
| Drug | Equianalgesic IV | Peak | Duration (single bolus) | Infusion? |
|---|---|---|---|---|
| Fentanyl | 50 mcg | 3–5 min | 30–60 min | Use with caution* |
| Alfentanil | 150–250 mcg | 1–2 min | 5–10 min | Uncommon |
| Sufentanil | 5 mcg | 3–5 min | 20–45 min | OR |
| Remifentanil | 50 mcg | 3–5 min | 5–10 min | OR |
| Morphine | 5 mg | 10–20 min | 4–5 h | ICU/comfort |
| Hydromorphone | 0.75 mg | 5–15 min | 2–4 h | ICU |
| Meperidine | 37.5 mg | 5–15 min | 2–4 h | No |
| Methadone | 2.5 mg | 10 min | 24 h | No |
*Fentanyl infusion: long context-sensitive half-time — predict prolonged duration after stopping.
04Fentanyl
- Synthetic phenylpiperidine; 75–125× more potent than morphine.
- Easy to titrate — rapid onset and short duration after a single bolus.
- Frequently used to blunt sympathetic response to laryngoscopy / LMA placement.
- Context-sensitive half-time grows dramatically with infusion — cut dose in half every 2 hours and expect a prolonged tail.
- No histamine release; no active metabolites.
05Hydromorphone
- 5–7× more potent than morphine.
- Longer duration of action (2–4 h) → workhorse for postoperative analgesia and PCA.
- Titrate to effect near end of case for smooth wakeup — peak effect can take ~15 min.
- Metabolite (hydromorphone-3-glucuronide) has no analgesic activity but can cause neuroexcitation in renal failure.
- No histamine release.
- Preferred over morphine in renal failure.
06Remifentanil
- Esterase-metabolized (plasma esterases) → context-INSENSITIVE half-time (~5–10 min regardless of duration).
- Infusion: start 0.05–0.1 mcg/kg/min, titrate as needed (rarely > 0.3 mcg/kg/min).
- Useful when intense intraoperative stimulation but minimal post-op pain expected, OR when paralysis is contraindicated (neuromonitoring).
- Bradycardia is common — have glycopyrrolate or atropine ready for bolus dosing.
- Sudden cessation → acute opioid tolerance (within minutes). Treatable with more opioid.
- Long, high-dose infusions (> 0.15 mcg/kg/min) → opioid-induced hyperalgesia. Less responsive to additional opioid.
- Always have a longer-acting opioid on board before stopping the infusion.
- Dosing units: mcg/kg/MIN (not /hr — don't confuse with sufentanil dosing).
07Sufentanil
- 5–10× more potent than fentanyl.
- High-dose cardiac induction provides exceptional hemodynamic stability.
- Infusion dosing mcg/kg/HOUR (not /min — common error).
- Useful neuraxially (intrathecal/epidural).
08Morphine
- Natural opioid; histamine release → hypotension, urticaria.
- Active metabolite morphine-6-glucuronide is renally cleared → accumulates in renal failure with prolonged sedation/respiratory depression.
- Intrathecal morphine (Duramorph): excellent post-op analgesia up to 24 h. Monitor for delayed respiratory depression.
09Strategies for Opioid Use
- Standard GETA: use fentanyl to blunt sympathetic response to laryngoscopy; transition to longer-acting hydromorphone before incision; titrate near end of case based on RR.
- Short ambulatory cases: smaller doses of fentanyl ± local infiltration.
- Painful surgery, smooth wakeup needed: load with hydromorphone early; use remifentanil infusion for moment-to-moment titration; assess RR on wean.
- OSA / opioid-sparing: multimodal (acetaminophen, NSAID, regional, ketamine infusion, dexmedetomidine).
- Anticipate respiratory depression in PACU when redosing after a case.