1. Intrathecal Narcotics for Post- operative Analgesia Kristopher R Davignon, MD Dept of Anessthesia Grand Rounds March 2007

2. Intrathecal Narcotics Opioids were know to the ancient Sumerians as of 4000 B.C. 1971 Opioid receptor discovered 1973 Receptors found in the brain 1976 Receptors found in the spinal cord 1979 Early reports of intrathecal opioids producing analgesia

3. Intrathecal Narcotics Thoracic and Upper Abdominal Procedures Elective Total Hip Arthroplasty 350,000 Procedures per year in the US + 5 min to consent + 15 min for procedure

4. Overview and Goals Anatomy, Physiology & Pharmacology Complications Evidence Based Practice Dose-Response Future Directions

5. Anatomy, Physiology & Pharmacology

6. Drug disposition depends primarily on lipid solubility Any drug rapidly redistributes opioid is detectable in the cisterna magna within 30 min of lumbar intrathecal administration

7. Anatomy, Physiology & Pharmacology Opiods Morphine Meperidine Hydromorphone Sufentanil & Fentanyl Methadone Non Opiods Clonidine Neostigmine Adenosine Epinephrine Ketorolac Midazolam Preservative

8. Anatomy, Physiology & Pharmacology Lipophilic opioids Rapidly traverse the dura; sequestered in epidural fat (and enter systemic circulation) Rapidly penetrate the spinal cord and bind receptors and nonspecific sites

9. Anatomy, Physiology & Pharmacology Hydrophilic opiods Limited binding to epidural fat and nonspecific receptors Slower transfer to systemic circulation Higher CSF concentrations accounting for rostral spread

10. Anatomy, Physiology & Pharmacology

11. “Complications” Pruritus Mechanism unclear – likely opiod receptor mediated (not histamine) Incidence 30-100% Rx: Antihistamines, 5-HT 3 antagonist, opiod antagonists (or agonist-antagonists), propofol

12. “Complications” Urinary Retention Not dose dependent Can last 14-16 hours Most frequent with Morphine 35 % incidence Mechanism related to sacral parasympathetic outflow inhibition Allows increase in maximal bladder capacity

13. “Complications” Nausea and Vomiting Incidence 30 % Most profound with Morphine Likely due to cephalad migration of drug to area postrema

14. “Complications” Respiratory Depression Incidence is dose dependent Very Rare 0.09% to 0.4% Likely no more clinically relevant than for IV narcotics Monitoring for 18-24 hours when using lipophilic opiods

15. “Complications” PDPH Age, Gender, History of PDPH, Obesity Multiple dural puncture, Needle size, Needle design

17. “Complications” PDPH Rx: hydration Caffeine Sumatriptan ACTH EBP

18. “Complications” Neuropraxia/Paralysis Epidural hematoma Epidural abcess

19. Evidence Based Practice What types of surgery is amenable to intrathecal narcotics? What doses should we use? What outcomes can we affect?

20. Types of Surgery Thoracic Including Cardiac Intra-abdominal Including C/S, AAA, Open Cholecystectomy Lower Extremity Including THA & TKA

21. Narcotic Only (worst) Narcotic + LA (best) LA Only

23. “the Dose” 1) Optimal dose depends on the surgical procedure 2) Incidence of side effects increases in proportion to dose (especially with doses > 300 ųg)

24. “the Dose”

25. Dosing for THA Use lowest dose possible! Studies have used doses as low as 0.025 mg Older studies used doses as high as 0.5mg Ideal dose seems to be 0.1 mg Lower doses don’t provide good analgesia Higher doses plagued with pruritis

26. Dosing for THA

28. Affecting Outcomes

29. Do Improved Pain Scores Matter?

31. Future Directions Anticoagulants Use of stents and anti-platelet agents Aggressive DVT prophlaxis Absence of laboratory evidence of these agents Sustained release neuraxial narcotic Depodur

32. Future Directions Depodur (morphine sulfate extended release liposome injection)

33. Future Directions

34. Better Pain Scores for 48 hours Studied in Hip Arthroplasty, Cesarean Section, Lower Abdominal Surgery No significant difference in side effects from IV narcotic

35. Conclusions Pain management in the in-patient setting is becoming a priority for adminstrative organizations A majority of in-patient pain management is post-operative Neuraxial narcotics consistently reduce patient’s VAS