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Intrathecal Narcotics for Postoperative Analgesia Kristopher R Davignon, MD Dept of Anessthesia Grand Rounds March 2007 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 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 Overview and Goals • Anatomy, Physiology & Pharmacology • Complications • Evidence Based Practice • Dose-Response • Future Directions Anatomy, Physiology & Pharmacology Anatomy, Physiology & Pharmacology • 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 Anatomy, Physiology & Pharmacology • Opiods • • • • • • Non Opiods Morphine Meperidine Hydromorphone Sufentanil & Fentanyl Methadone Preservative • • • • • • Clonidine Neostigmine Adenosine Epinephrine Ketorolac Midazolam 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 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 Anatomy, Physiology & Pharmacology “Complications” • Pruritus • Mechanism unclear – likely opiod receptor mediated (not histamine) • Incidence 30-100% • Rx: Antihistamines, 5-HT3 antagonist, opiod antagonists (or agonist-antagonists), propofol “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 “Complications” • Nausea and Vomiting • Incidence 30 % • Most profound with Morphine • Likely due to cephalad migration of drug to area postrema “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 “Complications” • PDPH • Age, Gender, History of PDPH, Obesity • Multiple dural puncture, Needle size, Needle design “Complications” • PDPH • Rx: • • • • • hydration Caffeine Sumatriptan ACTH EBP “Complications” • Neuropraxia/Paralysis • Epidural hematoma • Epidural abcess Evidence Based Practice • What types of surgery is amenable to intrathecal narcotics? • What doses should we use? • What outcomes can we affect? Types of Surgery • Thoracic • Including Cardiac • Intra-abdominal • Including C/S, AAA, Open Cholecystectomy • Lower Extremity • Including THA & TKA • Narcotic Only (worst) • Narcotic + LA (best) • LA Only “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) “the Dose” 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 Dosing for THA Dosing for THA Affecting Outcomes Do Improved Pain Scores Matter? 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 Future Directions •Depodur (morphine sulfate extended release liposome injection) DepoFoam™ Encapsulation DepoFoam™ Particle (diameter: 15 microns) Reference: SkyePharma Website. DepoFoam™ overview. Please see full Prescribing Information. 6 Drug-filled Chamber Future Directions DepoFoam™: Appearance of Formulation Settled Particles • Vials of DepoDur™ should be gently inverted to resuspend the particles immediately prior to withdrawal from the vial. Aggressive agitation should be avoided. • Vials shown are for demonstration purposes only. Actual DepoDur™ vials are amber in color and the liquid inside is not easily visible. Please see full Prescribing Information. 7 Resuspended Particles Future Directions • Better Pain Scores for 48 hours • Studied in Hip Arthroplasty, Cesarean Section, Lower Abdominal Surgery • No significant difference in side effects from IV narcotic 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