Case Western Reserve University School of Medicine

University Hospitals Case Medical CenterCleveland, Ohio

Intrathecal Hydromorphone and Intrathecal Hydromorphone and Bupivacaine Combination Therapy Bupivacaine Combination Therapy for Failed Back Surgery Syndromefor Failed Back Surgery Syndrome

Michael Hanes, M.D., I. Elias Veizi, M.D., Ph.D., Connie Wang, Salim Hayek, M.D., Ph.D.

Division of Pain MedicineDepartment of Anesthesiology

Animation by: George Williams, MD

Intrathecal Drug Delivery• Failed back surgery syndrome

(FBSS)– Most common non-cancer indication for

IDDS– Localized pain– Mixed pain = neuropathic + nociceptive

• Hydromorphone and bupivacaine = PACC 2nd line therapy

1. Raphael, JH. et al (2002) BMC Musculoskeletal Dis 3(17).2. Deer, TR. et al (2010) Neuromodulation Sep 15(5)13(3): 436-466.

Animation by: George Williams, MD

Line 1

Morphine

Hydromorphone Ziconotide Fentanyl

Line 2

Morphine +

bupivacaine

Ziconotide + opioid

Hydromorphone +

bupivacaine

Fentanyl + bupivacaine

Line 3

Opioid (morphine, hydromorphone, or fentanyl) + clonidine Sufentanil

Line 4

Opioid + clonidine + bupivacaine Sufentanil + bupivacaine OR clonidine

Line 5 Sufentanil + bupivacaine + clonidine

2012 Polyanalgesic Algorithm for Intrathecal Therapies in Nociceptive PainLine 1: Morphine and ziconotide are approved by the US Food and Drug Administration for IT therapy and are recommended as first-line therapy for nociceptive pain. Hydromorphone is recommended on the basis of widespread clinical use and apparent safety. Fentanyl has been upgraded to first-line use by the consensus conference.Line 2: Bupivacaine in combination with morphine, hydromorphone, or fentanyl is recommended. Alternatively, the combination of ziconotide and an opioid drug can be employed.Line 3: Recommendations include clonidine plus an opioid (ie, morphine, hydromorphone, or fentanyl) or sufentanil monotherapy.Line 4: The triple combination of an opioid, clonidine, and bupivacaine is recommended. An alternate recommendation is sufentanil in combination with either bupivacaine or clonidine.Line 5: The triple combination of sufentanil, bupivacaine, and clonidine is suggested.

Deer TR et al., Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel. Neuromodulation. 2012 Sep;15(5):436-466

Animation by: George Williams, MD

Line 1 Morphine Ziconotide Morphine +

Bupivacaine

Line 2

Hydromorphone

Hydromorphone + bupivacaine or

Hydromorphone + clonidine

Morphine + clonidine

Line 3 Clonidine Ziconotide +

opioid FentanylFentanyl +

bupivacaine or Fentanyl +

clonidineLine 4

Opioid + clonidine + bupivacaine Bupivacaine + clonidine

Line 5 Baclofen2012 Polyanalgesic Algorithm for Intrathecal Therapies in Neuropathic painLine 1: Morphine and ziconotide are approved by the US Food and Drug Administration for IT therapy and are recommended as first-line therapy for neuropathic pain. The combination of morphine and bupivacaine is recommended for neuropathic pain on the basis of clinical use and apparent safety. Line 2: Hydromorphone, alone or in combination with bupivacaine or clonidine is recommended. Alternatively, the combination of morphine and clonidine may be used. Line 3: Third-line recommendations for neuropathic pain include clonidine, ziconotide plus an opioid, and fentanyl alone or in combination with bupivacaine or clonidine.Line 4: The combination of bupivacaine and clonidine (with or without an opioid drug) is recommended. Line 5: Baclofen is recommended on the basis of safety, although reports of efficacy are limited.

Deer TR et al., Polyanalgesic Consensus Conference 2012: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel. Neuromodulation. 2012 Sep;15(5):436-466

Animation by: George Williams, MD

Bernards CM. Curr Opin in Anaesth 2004, 17:441–447

Bupivacaine Diffusion

Veizi IE, et al. (2011) Pain Medicine 12:1481-89.

Animation by: George Williams, MD

Study Objective

• Purpose: Examine the efficacy of IT coadministration of hydromorphone and bupivacaine from the outset of IT therapy and up to 24 months after implantation of IDDS.

Animation by: George Williams, MD

Study Population• Retrospective review

– 38 FBSS patients– 2007 – 2011– Followed for up to 2 years

Age, years Mean (SEM) 65 (2.1)Gender, no. (%) of patients Male Female

18 (47.3)20 (52.6)

Baseline NRS pain score Mean (SEM) 8 (0.3)Oral opioid dose at time of implant (mg/day) Mean (SEM) 53.6 (9.9)

Animation by: George Williams, MD

Intrathecal Pump Implantation• Stepwise

multidisciplinary treatment approach.

• 24-48 hr in-patient trial with continuous IT infusion– Hydromorphone ~10

mcg/ml + bupivacaine 0.625 mg/ml

– 0.2 ml/hr – >50% pain relief

• Implantation– Hydromorphone +

bupivacaine– Titrated for pain relief

and AE• Personal therapy

manager (PTM)– Set to deliver

hydromorphone + bupivacaine (0.5-1.2 mg) per bolus

Intrathecal Hydromorphone Daily Dose on Initiation of IDDS (mcg/day) Mean (SEM)

113.8 (18.2)

Intrathecal Bupivacaine Daily Dose on Initiation of IDDS (mg/day) Mean (SEM)

5.7 (0.1)

Animation by: George Williams, MD

ResultsPain Intensity Oral Opioid Consumption

Data presented as mean (line) ± SEM (whiskers)* Denotes significant difference from time 0.

Animation by: George Williams, MD

Intrathecal Dose Escalation

• Hydromorphone r2 = 0.9939• Bupivacaine r2 = 0.3371

Animation by: George Williams, MD

Intrathecal Hydromorphone Dose Escalation

• r2 = 0.7202• Slope = 13.93

Veizi IE, et al. (2011) Pain Medicine 12:1481-89.

• r2 = 0.969• Slope (O+B) =

14.58

Animation by: George Williams, MD

Conclusion

• IT hydromorphone and bupivacaine effective for FBSS.– Improved pain intensity– Reduction in oral opioid consumption– Decreased IT opioid dose escalation

Animation by: George Williams, MD

THANK YOU!