Rational use of opioids in anesthesiology


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Rational use of opioids in anesthesiology

  1. 1. Rational Use of Opioids in Anesthesiology Yury Khelemsky, MD Assistant Professor Anesthesiology and Pain Medicine The Mount Sinai Medical Center
  2. 2. MOA <ul><li>Opiate–receptor activation inhibits the presynaptic release and postsynaptic response to excitatory neurotransmitters (eg, acetylcholine, substance P) from nociceptive neurons. The cellular mechanism for this neuromodulation may involve alterations in potassium and calcium ion conductance. </li></ul>
  3. 3. Why use opioids <ul><li>Block stress response (catecholamine, cortisol, ADH) better than VA – ultimate effect on outcome? </li></ul><ul><li>Balanced anesthesia (reduce dose of other anesthetic agents – propofol, VA, paralytics) </li></ul><ul><li>Postoperative analgesia </li></ul>
  4. 4. Issues with Opioids <ul><li>Histamine release: morphine and meperidine. Hypotension/bronchospasm </li></ul><ul><li>Urinary retention: reversed by methylnaltrexone </li></ul><ul><li>Decreased GI motility: may have “full stomach” even with adequate NPO </li></ul><ul><li>Sphincter of Oddi spasm: clinical significance? </li></ul><ul><li>N/V: much less when used with propofol TIVA, give prophylaxis </li></ul><ul><li>Synergistic increase in sedation/resp. depression when used with other anesthetics (i.e. benzos) </li></ul>
  5. 5. How opioids effect Ventilation
  6. 6. A and C, Reduction of the concentration of sevoflurane by increasing concentrations of fentanyl at which 50% or 95% of patients did not move at skin incision (MAC or MAC 95 , respectively). B and D, Reduction of the concentration of sevoflurane by increasing concentrations of fentanyl at which 50% or 95% of patients did not show sympathetic responses (an increase in heart rate or mean arterial pressure >15%) at skin incision (MAC-BAR or MAC-BAR 95 , respectively).
  7. 7. Morphine <ul><li>Effect on MAC: decreases MAC in a dose dependent manner with a ceiling of about 65% MAC reduction </li></ul><ul><li>Even with severe Respiratory Depression (decrease response of medulary center to CO2) pts are arousable and will breathe on command. </li></ul><ul><li>Muscle Rigidity and Myoclonus – rate of administration or high dose </li></ul><ul><li>Histamine release usually with higher doses (1mg/kg) </li></ul><ul><li>Morphine-6-Glucuronide is a more potent, metabolite with similar duration of action. May accumulate in renal failure. </li></ul>
  8. 8. Meperidine (Demerol) <ul><li>Should only be used for postoperative shivering 12.5-50mg effective </li></ul><ul><li>Normeperidine is an active metabolite accumulation of which may cause seizure </li></ul><ul><li>Avoid in patients taking MAOI </li></ul><ul><li>Has local anesthetic and vagolytic (atropine-like) action </li></ul>
  9. 9. Fentanyl <ul><li>50-100x as potent as morphine. So 10mg of morphine IV is equianalgesic to about 100-200mcg of fentanyl. </li></ul><ul><li>3mcg/kg bolus about 30 minutes prior to incision reduced MAC by 50%. 1.5mcg/kg reduced MAC-BAR (SNS response) by 60-70%. </li></ul><ul><li>Reduces requirement of propofol for TIVA in a similar proportion (Barash p. 477) </li></ul><ul><li>Used as a sole agent 50-100mcg/kg. Exceptionally hemodynamic stability. Awareness… </li></ul><ul><li>Chest wall rigidity at higher doses, but may see even with 7mcg/kg. May sometimes be laryngospasm. </li></ul><ul><li>1-5mcg/kg at least 3 min before laryngoscopy may blunt (not ablate) response. </li></ul>
  10. 10. Hydromorphone (Dilaudid) <ul><li>4-5x as potent as morphine. 10mg morphine IV is equianalgesic to 2-2.5mg dilaudid. </li></ul><ul><li>Rapid onset, longer analgesia than fentanyl. </li></ul><ul><li>Excellent SC bioavailability </li></ul><ul><li>Less hydrophilic than morphine, but less lipophilic than fentanyl – great for epidural infusions. </li></ul>
  11. 11. Methadone <ul><li>About 1-2x as potent as morphine. But conversion changes based on duration of use and dosage </li></ul><ul><li>Increases QTc (prolongation >500msec associated with Torsades) </li></ul><ul><li>Racemic mixture of L-methadone: mu agonist and D-Methadone: NMDA antagonist (like ketamine) </li></ul><ul><li>Analgesic effect lasts for 6-8h, but prevention of opioid withdrawal for much longer (this is why only need QD dosing in methadone maintenance) </li></ul><ul><li>Lots of literature, but everyone talks about “that” paper </li></ul>
  12. 12. That paper <ul><li>Intraoperative Methadone Improves Postoperative Pain Control in Patients Undergoing Complex Spine Surgery </li></ul><ul><li>Antje Gottschalk , MD †, Marcel E. Durieux , MD, PhD and Edward C. Nemergut , MD </li></ul><ul><li>BACKGROUND: Patients undergoing complex spine surgery frequently experience severe pain in the postoperative period. The combined opiate receptor agonist/ N -methyl-d-aspartate receptor antagonist methadone may be an optimal drug for these patients given the probable involvement of N -methyl-d-aspartate systems in the mechanism of opioid tolerance and hyperalgesia. </li></ul><ul><li>METHODS: Twenty-nine patients undergoing multilevel thoracolumbar spine surgery with instrumentation and fusio n were enrolled in this prospective study and randomized to receive either methadone (0.2 mg/kg ) before surgical incision or a continuous sufentanil infusion of 0.25 μg/kg/h after a load of 0.75 μg/kg . Postoperative analgesia was provided using IV opioids by patient-controlled analgesia. Patients were assessed with respect to pain scores (visual analog scale from 0 to 10), cumulative opioid requirement, and side effects at 24, 48, and 72 hours after surgery. </li></ul><ul><li>RESULTS: Demographic data, duration, and type of surgery were comparable between the groups. Methadone reduced postoperative opioid requirement by approximately 50% at 48 hours (sufentanil versus methadone group, median [25%/75% interquartile range]: 63 mg [27.3/86.1] vs 25 mg [16.5/31.5] morphine equivalents, P = 0.023; and 72 hours: 34 mg [19.9/91.5] vs 15 mg [8.8/27.8] morphine equivalents, P = 0.024) after surgery. In addition, pain scores were lower by approximately 50% in the methadone group at 48 hours after surgery (sufentanil versus methadone group [mean ± SD] 4.8 ± 2.4 vs 2.8 ± 2.0, P = 0.026). The incidence of side effects was comparable in both groups. </li></ul><ul><li>CONCLUSION: Perioperative treatment with a single bolus of methadone improves postoperative pain control for patients undergoing complex spine surgery. </li></ul><ul><li>Anesth Analg. 2011 Jan;112(1):218-23. </li></ul>
  13. 13. Remifentanyl <ul><li>Approximately 1-2x more potent than fentanyl </li></ul><ul><li>Large bolus dosing leads to hypotension/brady </li></ul><ul><li>Can decrease MAC by up to 91% </li></ul><ul><li>Hyperalgesia – may be minimized with ketamine or lidocaine </li></ul><ul><li>Must give longer acting medication for posto pain </li></ul><ul><li>Context sensitive half life of about 4 minutes. </li></ul>
  14. 14. Opioid Comparison Opioid Onset (min) Peak (min) Duration (h) Elim T1/2 (h) Protein binding (%) IV equianalgesic dose to morphine 10mg IV (mg) Fentanyl <1 5 0.5-1 3.7 85 0.1 Methadone 15 15 4 8-59 90 5-10 Morphine 5 20 4 1.5 M6G-3 30 Hydromorphone 10 20 4 2.6 8-20 1.5 Sufentanyl <1 <5 0.5 18min 92 0.01 Remifentanyl <1 <1 5-10 4 70 0.05-0.1
  15. 15. Onset of Opioids
  16. 16. Context Sensitive Half-Life
  17. 17. Relative Potency Only about 50% cross-tolerance ( incomplete cross tolerance ) between opioids – if one is not effective or produces side-effects, try another.
  18. 18. Bottom Line <ul><li>Administer balanced anesthesia </li></ul><ul><li>Avoid morphine in asthma and renal insufficiency </li></ul><ul><li>Our usual doses of fentanyl are short acting. Titrate longer acting drugs for post-operative analgesia </li></ul>