Intrathecal Drug Delivery

Intrathecal Drug Delivery Bruce D. Nicholson, MD

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Learning Objectives Review indications for intrathecal therapy Discuss rational and technique for intrathecal therapy Describe the risks and benefit of therapy

Pain Definitions  The IASP defines pain as “an unpleasant sensory and emotional experience associated with actual or perceived tissue damage or described in terms of such damage”1  Pain can be classified according to primary etiology2 – Nociceptive – Neuropathic – Mixed neuropathic and nociceptive

 All types of pain can also be classified by duration3 – Acute: less than 6 weeks – Sub-acute: between 6 weeks and 3 months – Chronic: lasting > 3-6 months

1 Merskey H,

Bogduk N, eds. Classification of Chronic Pain, 2nd Ed. IASP Press Seattle, 1994 2 Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003; pg 361-374 3 Koes BW, et al. Br Med J. 2006;332:1430-1434

Pain  Unpleasant sensory or emotional experience  2 types of pain: acute and chronic  Chronic: – Nociceptive

• Somatic • Visceral

– Neuropathic

• Central • Peripheral

– Mixed Pain

• Many patients have a combination of both because disease or trauma has damaged both nerve cells and other tissues

Nociceptive Pain Somatic pain arises from bone and joint, muscle, skin, and connective tissue • Aching or throbbing • Localized

Visceral pain arises from visceral organs such as GI tract and pancreas • Tumor involvement • Obstructive

Neuropathic Pain Abnormal processing of sensory input by the peripheral or central nervous system Centrally generated pain Peripherally generated pain

Definition of Chronic Pain Frequent or constant pain that does not respond to the usual treatments Unlike acute pain, which gets better and goes away in a short time, chronic pain persists for at least several months

Indications for Neurostimulation and Intrathecal Drug Delivery Therapy

Cole AJ. In Low Back Pain Handbook, 2nd ed. 2003; pg 362. Refer to full prescribing information for Medtronic Neurostimulation Systems and Synchromed速 II and Isomed速 Drug Infusion Systems

Benefits of IDD therapy Pain relief for patients who have not received adequate relief with conventional therapies Reduce or eliminate oral opiate usage Improve functional status

Chronic Pain Treatment Continuum Advanced Pain Therapies

Second-Tier Pain Therapies First-Tier Pain Therapies

Diagnosis NSAIDs TENS Psychological Therapy Nerve Blocks Physical Therapy OTC Pain Medications

Opioids Neurolysis Thermal Procedures

Neurostimulation Implantable Drug Pumps Surgical Intervention Neuroablation

Intrathecal (“IT”) pain therapy involves the infusion of pain medication directly into the subarachnoid IT space

Intrathecal Drug Delivery (IDD) Therapy  IDD therapy involves the delivery of pain medicine in the intrathecal space  The pump is connected to a thin, flexible catheter; both are implanted under the skin  Smaller doses of medication are needed for effective pain relief because drug is delivered directly to the pain receptors

Intrathecal Drug Infusion System Indications  FDA approved therapies for intrathecal infusion  Chronic intrathecal infusion of preservative-free morphine sulfate sterile solution in the treatment of chronic intractable pain  Chronic intrathecal infusion of preservative-free ziconotide sterile solution for the management of severe chronic pain  Also indicated for chronic intrathecal infusion of baclofen intrathecal injection for severe spasticity Lioresal® is a registered trademark of Novartis Pharmaceuticals, Inc.

Intrathecal Infusion Drugs Morphine* Baclofen* Ziconotide* Hydromorphone Fentanyl Bupivacaine Clonidine *FDA for intrathecal infusion

Approximate Equivalent Daily Doses of Morphine Route of Administration

Relative Potency (mg)*

Oral

300

Intravenous

100

Epidural

20

Intrathecal

1

*

Relative approximations based on clinical observations Lamer TJ: Mayo Clin Proc. May 1994;69(5):473-80.

Check List for Patient Selection  Failure of oral/transdermal opiate use or undesirable side effects  More conservative therapies have failed  An observable pathology exists that is concordant with the pain complaint  Further surgical intervention is not indicated  No serious untreated drug habituation exists  Psychological evaluation and clearance for implantation has been obtained

Patient Selection Patients with refractory nociceptive –Failed back syndrome –Multiple trauma –Compression fractures –End stage osteoarthritis –Cancer

Patient Selection (cont’d) Patients with refractory neuropathic pain –CRPS type 1 and 2 –Failed back syndrome –Peripheral neuropathy –Cancer

Patient Selection (cont’d) Patients with refractory cancer pain –Bone metastasis –Nerve infiltration –Intolerance to oral opiates –Estimated 6 months or greater life expectancy

Painful Patterns

IDD Trial Purpose of trial is to assess efficacy and tolerability of intrathecal opiates Successful outcome is at least a 50% reduction in baseline pain during trial Minimal side-effect profile

IDD Trial (cont’d)  Pre trial evaluation for weaning of oral opiates  3-5 trial period  Placement of intrathecal spinal catheter  Trialing methods – Single intrathecal opiate injection – Continuous intrathecal micro-infusion

 Daily evaluation of therapeutic response – Pain reduction – Side effect issues

IDD Implantation An incision is made over the spine for insertion of the catheter A pocket is formed under the skin to hold the IDD pump The catheter is tunneled under the skin and connected to the IDD pump, incisions are closed, and the procedure is complete

Intrathecal Infusion Therapy

Infusion Pump

Intrathecal Catheter

Implant Procedure for IDD

Potential Benefits of IDD Therapy  Pain relief for patients who have not received adequate relief with conventional therapies  Reduction in adverse effects from oral opioids such as nausea, vomiting, sedation, and constipation  Decreased or elimination of oral analgesics  Increased ability to perform activities of daily living  Patient control within physician-set limits  May be effective for patients who do not experience relief from neurostimulation therapy Lamer TJ: Mayo Clin Proc. May 1994;69(5):473-80; Paice JA, et al: J Pain Symptom Manage.1996;11(2):71-80.

Intrathecal Therapy Patient Profiles Intractable Back Pain  82 y.o female 20 year hx progressive severe low back pain VAS 3/10 at rest and 10/10 when standing for 5 minutes or longer  Not a surgical candidate  Oral opiates not effective, does not tolerate dose escalation  Post implant able to ambulate up to 30 minutes

Pain Diagram

Intrathecal Infusion Therapy Diffuse Intractable Pain

 54 y.o male diffuse musculoskeletal and peripheral neuropathic pain  VAS 8/10 taking oxycodone 80mg TID and oxycodone-IR 15-30mg QID  Post implant completely self weaned from oral opiates  Recently fractured coccyx while sky diving

Pain Diagram

The state of medicine is worse than that of total ignorance. Could we divest ourselves of everything we suppose we know in it, we should start from a higher ground and with fairer prospects Thomas Jefferson 1799