INTRATHECAL DRUG INFUSIONS RATIONAL USE OF POLYANALGESIA TIMOTHY R. DEER, MD • PRESIDENT AND CEO, THE CENTER FOR PAIN RELIEF, CHARLESTON, WEST VIRGINIA • CLINICAL PROFESSOR OF ANESTHESIOLOGY, WEST VIRGINIA UNIVERSITY • BOARD OF DIRECTORS, INTERNATIONAL NEUROMODULATION SOCIETY • IMMEDIATE PAST CHAIR, AMERICAN SOCIETY OF ANESTHESIOLOGISTS, COMMITTEE ON PAIN MEDICINE • BOARD OF DIRECTORS; AMERICAN ACADEMY OF PAIN MEDICINE AND AMERICAN SOCIETY OF INTERVENTIONAL PAIN PHYSICIANS 2 INS 2009 • SYMPOSIUM ON INTRATHECAL DRUG DELIVERY • DISCLOSURES IN INTRATHECAL DRUG DELIVERY • CONSULTANT: INSET, JOHNSON AND JOHNSON. Intrathecal Pump for Pain ! 1 mg intrathecal morphine = 300 mg oral morphine CONFIDENTIAL Krames ES. J Pain Symptom Manage. 1996 Jun;11(6):333-52 4 Objectives • Review current options for pump infusions • Build on the talks of Dr. Levy and Dr. Abejon • Use a case based approach to discuss the issues • Make conclusions regarding the algorithm of Intrathecal analgesia Clinical Decision Making • Regulatory Approval in your country • Case reports • Lectures and anecdotal information • Retrospective analysis • Double-blind, randomized, prospective studies • Physician innovation with no available evidence • Consensus Statements 2000 Guidelines for Intraspinal Infusion 2007 Polyanalgesic Consensus Guidelines for Management of Pain by Intraspinal Drug Delivery Line 1 Morphine or Hydromorphone or Ziconotide Fentanyl or Clonodine alone OR one of the following 2-drug Line 2 combinations: • Morphine (or Hydromorphone) + Ziconotide • Morphine (or Hydromorphone) + Bupivacaine • Morphine (or Hydromorphone) + Clonidine* 2-drug combinations with Fentanyl plus Ziconotide, Clonidine or Line 3 Bupivacaine OR one of the following 3-drug combinations: • Morphine (or Hydromorphone) + Bupivacaine + Clonidine • Morphine (or Hydromorphone) + Ziconotide + Clonidine • Morphine (or Hydromorphone) + Ziconotide + Bupivacaine Line 4 Sufentanil OR Fentanyl plus any 2 adjunctive agents (Ziconotide, Bupivacaine or Clonidine) Line 5 Ropivacaine, Meperidine, Buprenorphine, Tramadol, Gabapentin CLINICAL APPLICATIONS • THE WAY YOU APPLY THE USE OF POLYANALGESIA SHOULD BE LOGICAL • IT SHOULD BE PATIENT SPECIFIC • FREQUENT RE-EVALUATION IS REQUIRED • A PATENT CATHETER AND WORKING SYSTEM IS CRITICAL FOR A SUCCESFUL TRANSITION IN POLYANALGESIA Catheter Tip Positioning and Location CONFIDENTIAL 13 SYSTEM IS FUNCTIONING ExampleExample ofof cathetercatheter holehole Pump connector pin Implant technique consensus Authored by: statement Dr. Ken Follett Dr. Kim Burchiel Dr. Tim Deer Dr. Du Pen Dr. Joshua Prager Dr. Michael Turner Dr. Robert Coffey CATHETER SAFETY RECOMMENDATIONS Catheter tip Pump anchored with sutures or Paramedian pouch Dural Oblique Entry puncture V-wing anchor Loop of excess Slack in catheter under catheter pump 2-piece connector which also functions as the primary anchor Source: Data on file at Medtronic. THE EASY PATIENT • 72 YEAR OLD WM WITH A PUMP IMPLANT IN 1997 FOR RADICULAR PAIN IN THE LEGS. • GREAT OUTCOMES • PUMP PLACED AT A MORPHINE DOSE AT 0.5 MGS PER DAY WITH 2/10 PAIN AND NO SIDE EFFECTS • 2007 PUMP DOSE AT 16.8 MGS PER DAY WITH A CONCENTRATION OF 40MGS/CC CLINICAL PRESENTATION • RUQ PAIN: DX WITH GALLSTONES • PAIN PERSISTS • LOSS OF SENSATION L5/S1 AND FOOT WEAKNESS • MRI LUMBAR SPINE HNP AT L5/S1 • S/P REOPERATION; • PAIN PERSISTS OVERVIEW • GRANULOMA • AVERAGE TIME TO GRANULOMA: 26 TO 30 MONTHS • MOST COMMON DRUG: MORPHINE • CONCENTRATION: > 40MGS/CC • CATHETER TIP: MORE COMMON IN THE THORACIC SPINE REFERENCE ARTICLES • Management of catheter-tip inflammatory masses: a consensus panel • Hassenbush, et. Al. • Pain Medicine. Volume 3, number 4. 2002 • Incidence of granuloma by MRI analysis in 208 consecutive asymptomatic patients. • Deer • Pain Physician. 2004 GUIDANCE • Management of Intrathecal Catheter-Tip Inflammatory Masses: An Updated 2007 Consensus Statement From An Expert Panel. Neuromodulation. 11(2):77-91, April 2008. • _Deer, Timothy MD *; Krames, Elliot S. MD +; Hassenbusch, Samuel MD, PhD ++; Burton, Allen MD [S]; Caraway, David MD [P]; Dupen, Stuart MD **; Eisenach, James MD ++; Erdek, Michael MD ++++; Grigsby, Eric MD [S][S]; Kim, Phillip MD [P][P]; Levy, Robert MD, PhD ***; McDowell, Gladstone MD +++; Mekhail, Nagy MD ++++++; Panchal, Sunil MD [S][S][S]; Prager, Joshua MD [P][P][P]; Rauck, Richard MD ****; Saulino, Michael MD ++++; Sitzman, Todd MD ++++++++; Staats, Peter MD [S][S][S][S]; Stanton-Hicks, Michael MD [P][P][P][P]; Stearns, Lisa MD *****; Dean Willis, K. MD +++++; Witt, William MD ++++++++++; Follett, Kenneth MDPhD [S][S][S][S][S]; Huntoon, Mark MD [P][P][P][P][P]; Liem, Leong MD ******; Rathmell, James MD ++++++; Wallace, Mark MD ++++++++++++; Buchser, Eric MD [S][S][S][S][S][S]; Cousins, Michael MD [P][P][P][P][P][P]; Ver Donck, Ann MD ******* THE EASY PATIENT • REVISION OF THE CATHETER WAS PERFORMED • NO COMPLICATIONS • TWO DAY ADMISSION • WHAT DRUG DO WE USE NOW? 2007 Polyanalgesic Consensus Guidelines for Management of Pain by Intraspinal Drug Delivery Line 1 Changes ! Added ziconotide to morphine and hydromorphone – Defined starting dose range for Ziconotide as 0.5 mcg/d – 2.4 mcg/d; maximum dose 19.2 mcg/d – Titrate dose slowly to decrease toxicity risk ! Dose and concentration recommendations for morphine and hydromorphone encourage keeping the dose and concentration as low as clinically relevant CASE DECISION LINE TWO • Fentanyl is an option and has not been associated with granuloma • Clonodine and Bupivacaine may be opioid sparing with equianalgesic doses THE CLASSIC CASE • 52 YEAR OLD WITH POST CHEMOTHERAPY INDUCED PERIPHERAL NEUROPATHY • PUMP PLACED IN 2004. EXCELLENT RESULTS FOR FIVE YEARS • DRUG INFUSED: MORPHINE 7.5 MGS PER DAY. • PAIN NOW INCREASING, DEVELOPED PERIPHERAL EDEMA • WHAT ARE THE ISSUES? THE FRUSTRATING CASE • ADD BUPIVACAINE: EDEMA PESISTS DESPITE LOWER MORPHINE DOSE • CHANGE TO HYDROMORPHONE: EDEMA AND NAUSEA • OPIOID WITH CLONODINE IMPROVED PAIN WITH PERSISTENT EDEMA CASE DECISION LINE ONE • Ziconotide was attemped to eliminate the edema • Edema did resolve • No response at 20 ucgs/day • Dizziness, Hallucintions and Depression 2007 Polyanalgesic Consensus Guidelines for Management of Pain by Intraspinal Drug Delivery Line 2 Changes • Added fentanyl as a single agent • Added clonidine as a single agent in neuropathic pain Case Resolution • Patient with good response to clonidine alone starting at 25 ucgs /day and going to 185 ucgs/day • No side effects • No edema REVISIT OTHER OPTIONS PERIPHERAL NERVE STIMULATION 2007 Polyanalgesic Consensus Guidelines for Management of Pain by Intraspinal Drug Delivery Line 3 Changes • Added ziconotide to options for 3-drug combinations of an opioid and 2 adjuvant drugs • Includes fentanyl 2-drug combinations on this line • Cost, drug dosage and concentrations, and admixture compatibility are issues to consider CASE DECISION LINE THREE • THREE DRUG COMBINATIONS CAN BE USEFUL BUT MAY BE LESS DESIRABLE IF A TWO CHAMBER PUMP BECOMES AVAILABLE. • OPTION: OPIOID, LOCAL ANESTHETIC CONOPEPTIDES, ALPHA AGENTS • WATCH COST AND SIDE EFFECTS • COMPOUNDING MUST BE PERFORMED WITH GREAT CARE COMPOUNDING MISHAPS • INTRATHECAL MORPHINE 10MGS/CC • ACTUAL DRUG: LIQUID CODIENE • OUTCOME: 5 CASES OF PARAPLEGIA • INTRATHECAL BUPIVACAINE/FENTANYL • ACTUAL DRUG: TETRACAINE/ METHADONE • DEATH THE END OF LIFE CASE • 56 YO MALE WITH METASTATIC LUNG CANCER TO THE BONE AND THE BRACHIAL PLEXUS • THE ALGORITHM LINE 5 • OPTIONS? Special Considerations • End of Life (estimated 4 week survival) • Midazolam • Ketamine • Tetracaine • Droperidol • Methadone • Droperidol • Odansetron Conclusions • Our scientific knowledge continues to improve in this important area of medicine • Best clinical practice evolves and the need for future revisions of the algorithm will continue • Patient safety and efficacy are the most important considerations for determining the proper algorithm for treatment • In some cases the physician can properly deviate from the algorithm 40.