IDD Best Practices

1. NANS 16th Annual Meeting Las Vegas 2012 IDD Best Practices Kathy Clagg RN ONC The Center for Pain Relief Tristate Huntington, WV Gail McGlothlen APRN MS CNS Napa Pain Institute Napa, CA

2. Introduction • In early 2006, Medtronic received an increase in the rate of spontaneous reports of patient death within 3 days of implant and initiation of intrathecal drug therapy. • From 1998-2007 a total of 88 patients died within 3 days of pump implant, refill, replacement, reprogramming, dose change or catheter revision. • An investigation identified multiple factors which contributed to the adverse events; device malfunction was not the cause of these adverse events. • Problem: Patients receiving IT morphine for non-cancer pain experience a higher mortality rate. • Significance: Most deaths were preventable. • Action: Identify & mitigate contributing factors that resulted in patient deaths to improve the safety of IT morphine. (Coffey et al., 2009)

3. IDD Best Practices PanelFebruary 2011 • Brian Bruel, MD Houston, TX • Eric Buchser, MD Morges, Switzerland • David Caraway, MD Huntington WV • Michael Cousins, MD Sydney, Australia • Timothy Deer, MD Charleston WV • Marilyn Jacobs, PhD, PsyD Los Angeles, CA • Robert Levy, MD, PhD Chicago, IL • Gail McGlothlen, APRN-BC CNS Napa, CA • Joshua Prager, MD, MS Los Angeles, CA • Richard Rauck, MD Winston Salem, NC • Peter Staats, MD Shrewsbury, NJ • Lisa Stearns, MD Scottsdale, AZ

4. Goal: Improve Clinical Practice Objectives: • Identify Key IDD Safety Issues along the Clinical Care Continuum • Review IDD Best Practices Panel Recommendations • Discuss Strategies to Integrate Recommendations into Clinical Practice

5. IDD Steps MRI Studies: abstinence syndrome and other issues Patient selection Pump Implantation Therapy management Starting IT Meds Trialing Pump Refills Pump replacement or restart Diagnosis of inadequate analgesia Catheter Revision or failure Dosing and medication adjustments Issues • Psychosocial • Co-morbidities • Obesity/ sleep • apnea • Appropriate • diagnosis • Systemic • medications • Respiratory depression • Local • infection • IT dose equivalence • Downward • titration of • systemic • opioid • Patient • monitoring • Trialing • procedures • Respiratory • depression • Local • infection • Potential drug-drug interactions with anesthesia • Pump and catheter placement • Pump programming • Respiratory • depression • Drug withdrawal • Catheter • dislodgement or • fracture • Inflammatory • mass detection • and prevention • Inflammatory • mass • complications • Respiratory • depression • Drug • withdrawal • Pump complications • Pocket fills • Current systemic • meds • IT dose equivalence • and conversion • Respiratory • depression • Respiratory arrest • Ziconotide SE’s • Hypothalamic • pituitary axis • suppression • Respiratory • depression • Drug-drug • interactions • Catheter dislodgement • or fracture Prager, J.

6. Identify Key IDD Safety Issues along the Clinical Care Continuum • Inadequate Monitoring • Dosing Errors • Synergism with Concomitant Systemic Drugs • Reservoir Refills and Pocket Fills

7. IDD Trialing: Inadequate Monitoring and Dosing Decisions • Recommendations: • Patients considered for IDD should have a trial • Single-Shot trials not considered Best Practice • Observed in a monitored environment during the course of the trial • Integration: • Co-morbidities should be well controlled prior to the trial: coag status • Review the patient’s daily morphine equivalent with the physician • Patients with OSA should bring their equipment to the trial • Appropriate monitoring • Patients with cancer pain may forego a trial prior to implant

8. Pump Implant: Inadequate Monitoring, Dosing, Concentration Errors & Infection • Recommendations: • Pumps must be implanted and managed by Physicians trained and skilled in IDD therapy with working knowledge of: • Pump mechanics • Pharmacotherapy • Pump programming • Overnight observation for initiation of opioids or baclofen • Start low and go slow • Opioid conversion tables not appropriate for determining dose • Clinicians must practice vigilance and well-established aseptic tech to prevent SSI

9. Pump Implant: Inadequate Monitoring, Dosing, Concentration Errors & Infection • Integration • Pre-op • R/O infection: check urine & CBC, toenails and skin folds • Review CDC guidelines for the prevention of SSI • Stabilize coag status • If anti-coagulated check with hematologist • Review ASRA guidelines for the anti-coagulated patient • Communicate with Physician patient’s daily morphine equiv • Consider drug concentration that allows for low dosing • Post-op • Overnight observation • Sterile dressing change (CDC, 1999)

10. Initiating IT Meds • ITMS: Respiratory Depression/Arrest Ziconotide: Confusion/Dizziness • Recommendations: • Overnight observation • Physician personally oversees initial programming • Start low and go slow for both opioids & ziconotide • Start ziconotide at 0.5mcg/d and titrate q 1-2 weeks • Opioid conversion tables inappropriate for IT opioids • Eliminate systemic opioids if possible or reduce by 50% • Caution with any CNS acting drugs • Titrate doses cautiously & monitor for efficacy and side effects

11. Initiating IT Meds ITMS: Respiratory Depression/ArrestZiconotide: Confusion/dizziness • Integration: • Patient and Family Teaching • Signs and symptoms of overmedication, including sleepiness and confusion • Importance of reporting all medications to provider at each visit • Keeping all appts for F/U and pump reservoir refills • Alert radiologist to pump when undergoing MRI • No alcohol is the only safe alcohol with IT and systemic opioids • Titrating doses in F/U • PTM dosing total approximately 20-30% of daily IT opioid dose • Be absolutely sure of all programming • Minimize synergistic drugs

12. Change in Device Status: Respiratory Depression • Recommendations • Overnight observation for all patients with: • New intrathecal device • Replacement of pump or pump pocket revision requiring discontinuation/re-initiation of therapy • Catheter failure requiring discontinuation/re-initiation of therapy • Replacement of pump with baclofen-filled reservoir for withdrawal or overdose • Pumps should be replaced at or before the 6mos ERI • Not necessary to replace a functioning catheter

13. Change in Device Status: Respiratory Depression • Integration • For prolonged therapy interruption restart infusion at lower dose • Converting from Ziconotide to ITMS should require overnight observation: • Refill/reprogramming that accounts for the old drug in the pump tubing and external catheter • Time of drug onset • Perform meticulous reprogramming • Monitor pump status with each refill noting ERI and start preparations for pump replacement before 6mos • Consider catheter evaluation and granuloma screening prior to scheduled pump replacement

14. Programming: Respiratory Depression as a Result of Programming Errors • Recommendations: • Expertise in pump construction, functioning, and precise programming. • Meticulous programming and dosage calculations • Initial programming (time of implant) • Timing of onset of drug effect is delayed if no priming bolus programmed • Delayed respiratory depression can occur at 18-24 hrs after initiation of therapy • Physician personally oversees initial programming • Changing drug concentrations • Awareness that inner pump tubing is inaccessible • Accounting for pump and catheter volumes filled with old concentration • Calculate and program bridge boluses accurately

15. Programming: Respiratory Depression as a Result of Programming Errors • Integration: • Read technical manual. Request training from your local rep. Understand and practice the math! • For technical questions, call manufacturer’s tech line. • While programming a pump, keep the environment as distraction free as possible. Do not rush. Check, double-check and triple-check your math and programming! • With concentration changes, use minimum programmable flow rate to determine lowest dose • Review the programming printout before allowing the patient to leave.

16. Patient Status Changes: Respiratory Depression from Medication Synergism or Health Status Change • Recommendations: • Patients and family members should report to managing physician or provider: • Addition of CNS depressants because this class can alter a stable patient’s response to IT therapies • New co-morbidities as these may change drug requirements • Any change in neurologic status including new somnolence or dementia

17. Patient Status Changes: Respiratory Depression from Medication Synergism or Health Status Change • Integration • Evaluate for any cognitive changes • Review medication list every visit • Poly-pharmacy: evaluate for drugs that compete with same metabolic pathways or potentiate CNS depression • Ask if there have been any changes in their health since last visit • Ask about all OTC drugs especially aspirin containing compounds • Ask about alcohol use • Consider UDT /State prescription monitoring programs to verify medication compliance & safety

18. Inadequate Analgesia: Respiratory Depression/Drug Withdrawal due to Catheter Mal-position, Fracture or Inflammatory Mass • Recommendations: • Catheter tip placed in the Lumbar thecal sac below conus • PA/Lat XR, catheval via sideport for performance of myelogram • All patients should be routinely monitored for prodromal clinical s/s of inflammatory mass • ITMS use the lowest dose possible for the longest time possible • Avoid highly concentrated solutions • All patients with IDD need to alert the radiologist when undergoing an MRI and follow manufacturer’s recommendations

19. Inadequate Analgesia: Respiratory Depression, Drug Withdrawal due to Catheter Mal-position, Fracture or Inflammatory Mass • Integration: Think • Programming error- check the most recent printout • Catheter mal-position or fracture-order catheter eval • Granuloma-screening protocol including focused neuro exam • Anticipate urgent catheter revision for patients on ITB • Instruct patients to have their pump read following MRI to assure “motor stall recovery occurred” • Missed refill appointment

20. Pump Refills: Respiratory Depression or Acute Withdrawals due to Pocket Fill In May 1996-Sept 2010 Medtronic received 351 reports related to pocket fills: • 8 patient deaths • 270 were serious or life-threatening • 58 required no medical intervention • 15 events severity unknown

21. Pump Refills: Respiratory Depression or Acute Withdrawals due to Pocket Fill • 1992 MS SeromaWu & Patt • 2000 HyCl SQ/extrav. Frye & Vance • 2004 Hy Needle dislodg. Coyne et al. • 2011 Medtronic Medical Device Letter • 2011 ClUnkJohnson et al. • 2012 Cl Uneventful(2) Perruchoud et al.Bent needle(1) • 2012 Cl Septum damage Perruchoud et al.

22. Pump Refills: Respiratory Depression or Acute Withdrawals due to Pocket Fill • Recommendations: • Review S/S overdose, underdose & withdrawal with family • Observe for 30 mins after pump refill • Suspected or Known pocket fillrapidly assess patient • Confusion • Sedation • Respiratory depression which may require narcan/airway management • Hypo-Hypertension • Re-access reservoir port and aspirate contents • Determine pocket fill volume by comparing reservoir contents with initial injectate volume

23. Pump Refills: Respiratory Depression or Acute Withdrawals due to Pocket Fill • Integration: Minimizing Risk for Adverse Outcome from a Pocket Fill • Identify patients at risk • Place the patient in an optimal position • Always have the refill needle perpendicular to the surface of the pump • Always reposition the refill needle when in doubt • Instruct the patient to report any unusual sensation • Check for passive injectate with PFNS • Monitor patients post-refill for 30 mins • Have a plan should a pocket fill occur

24. Pump Refills: Respiratory Depression or Acute Withdrawals due to Pocket Fill • 4 case reports using ultrasound to locate reservoir refill access port (Yang et al., 2012; Shankar, 2009; Hurdle, 2007; Greher, 2005) • 1 preclinical feasibility study that evaluated real-time ultrasound-guided pump reservoir refill in cadavers • Ability to identify pump versus pocket fill • Results: predictive values equivocal • Easy to master, inverted pump distinctly different appearance (Gofeld & McQueen, 2011)

25. Pump Refills: Respiratory Depression or Acute Withdrawals due to Pocket Fill reservoir access port pump surface pump surface (Greher, Eichenberger & Gustorff, 2005) (Napa Pain Institute, 2012)

26. Pump Refills: Respiratory Depression or Acute Withdrawals due to Pocket Fill • Integration: Minimizing Injury from Pocket Fill • Signs/Symptoms of Pocket Fill: • Sleepy/confused/respiratory depression • Hypertension/hemodynamic instability/confusion • Call for help & initiate emergency plan • Diagnosis: • Aspirate the reservoir contents and compare with the volume of injectate • Discrepancy indicates a pocket or partial pocket fill and volume/dose • Treatment: • Be prepared to administer narcan, provide airway management & hemodynamic monitoring • Transfer patient to appropriate monitored setting and supportive care

27. Pump Refills: Respiratory Depression or Acute Withdrawals due to Pocket Fill • Opioids • Respiratory depression • Clonidine • Hypertension • Baclofen • Sedation/muscle weakness/seizure • Ziconotide • Sedation/cardiovascular instability • Bupivacaine • Dizziness/tinnitus/seizure/respiratory depression (Johnson, Visser & Goucke, 2011)

28. IDD Best Practices: Respiratory Depression is the Key Safety Issue • Deaths from overdose can be prevented • Patient safety and therapy outcomes can be optimized through: • Start Low and Go Slow Dosing • Precise Device Programming/Accurate Reservoir Refilling • Overnight Observation for Device Status Changes • Vigilance in Monitoring for Changes in Patient Status

29. References Coffey, R., Owens, M., Broste, S., Dubois, M., Ferrante, F., Schultz, D., Stearns, L. & Turner, M. (2009). Mortality associated with implantation and management of intrathecal opioid drug infusion systems to treat noncancer pain. Anesthesiology, Vol. 111, No. 4, 881-891. Coffey, R., Owens, M., Broste, S., Dubois, M., Ferrante, F., Schultz, D., Stearns, L. & Turner, M. (2010). Medical practice perspective: Identification and mitigation of risk factors for mortality associated with intrathecal opioids for non-cancer pain. Pain Medicine, 11, 1001-1009. Coyne, P., Hansen, L., Laird, J., Buster, P. & Smith, T. (2004). Massive hydromorphone dose delivered subcutaneously instead of intrathecally; Guidelines for prevention and management of opioid, local anesthetic, and clonidine overdose. Journal of Pain and Symptom Management vol 28; 273-276. Deer, T. (2010). A critical time for practice change in the pain treatment continuum: We need to reconsider the role of pumps in the patient care algorithm. Pain Medicine, 11, 987-989. Frye, C. & Vance, M. (2000). Hypertensive crisis and myocardial infarction following massive clonidine overdose. Annals of Pharmacotherapy 34: 611-615. Greher, M., Eichenberger, U. & Gustorff, B. (2005). Sonographic localization of an implanted infusion pump injection port: Another useful application of ultrasound in pain medicine. Anesthesiology 102: 243. Gofeld, M. & McQueen, C. (2011). Ultrasound-guided intrathecal pump access and prevention of the pocket fill. Pain Medicine 12: 607-611. Hurdle, M. Locketz, A. & Smith, J. (2007). A technique for ultrasound-guided intrathecal drug dellivery system refills. American Journal of Physical Medicine and Rehabilitation vol. 86, no. 3: 250-251. Johnson, M. Visser, E. & Goucke, C. (2011). Massive clonidine overdose during refill of an implanted drug delivery device for intrathecal analgesia: A review of inadvertent soft-tissue injection during implantable drug delivery device refills and its management. Pain Meicine 12: 1032-1040 Medtronic. (2011). Medical device correction, important clinical information about pocket fills synchromed ®II and synchromed EL implantable drug pumps. Perruchoud, C., Bovy, M., Durrer, A., Rosato, M., Rutschmann, B., Mustaki, J. & Buchser, E. (2012). Severe hypertension following accidental clonidine overdose during the refilling of an implanted intrathecal drug delivery system. Neuromodulation 15 (1):31-4. Perrchoud, C., Bovy, M., Rutschmann, Be., Durrer, A. & Buchser, E. (2012). Silicone septum leakage at the origin of a drug overdose in a patient implanted with an intrathecal pump. NeuromodulationOct 25. doi: 10.1111/j. ahead of print. Rathmell, J. & Miller, M. (2009). Death after initiation of intrathecal drug therapy for chronic pain. Anesthesiology, Vol 111, No. 4, 706-708. Shankar, H. (2009). Ultrasound-guided localization of difficult-to-access refill port of the intrathecal pump reservoir. Neuromodulation 12: 215-218. Wu, C. & Patt, R. (1992). Accidental overdose of systemic morphine during intended refill of intrathecal infusion device. Anesthesia & Analgesia Vol. 75: 130-132. Yang, T., Wang, J., Chiu, J., Lai, C., chan, R. & Lee, S. (2012). Ultrasound-guided refilling of an intrathecalbaclofen pump-a case report. Childs Nervous system . Ahead of print.