Intraspinal analgesia for CaIntraspinal analgesia for Cancer Painncer Pain

Ri Ri 錢穎群 劉耀臨錢穎群 劉耀臨

IndicationsIndications

The The 4th step4th step in managing pain of malignant in managing pain of malignant originorigin

Unsuccessful treatmentUnsuccessful treatment with sequential stro with sequential strong systemic opioid drug trials despite escalang systemic opioid drug trials despite escalating doses ting doses

Treatment with systemic opioids with effectivTreatment with systemic opioids with effective pain relief but with e pain relief but with unacceptable side effecunacceptable side effectsts

AdvantagesAdvantages

Lower dose than systemic use (1/10 rule for Lower dose than systemic use (1/10 rule for morphine)morphine)

Longer analgesic effectLonger analgesic effect Fewer opioid side effectsFewer opioid side effects

Adverse effects and ComplicationsAdverse effects and Complications

Same as systemic opiSame as systemic opioids but less severeoids but less severe

ToleranceTolerance

Best Practice & Research Clinical Anaesthesiology Vol.16, NO.4, pp.651-665, 2002

Catheter placementCatheter placement

PercutaneousPercutaneous: simple, cheap, risk of infectio: simple, cheap, risk of infection, high failure raten, high failure rate

TunnelledTunnelled: more helpful, providing months of : more helpful, providing months of effective analgesiaeffective analgesia

Implantable programmable infusion pumpImplantable programmable infusion pump: e: expensive, continuous infusion, good daily acxpensive, continuous infusion, good daily activity, good quality of life (for long-term analgtivity, good quality of life (for long-term analgesia, >3 months)esia, >3 months)

Implantable intrathecal pumpImplantable intrathecal pump

A multicenter, prospective cliA multicenter, prospective clinical studynical study

Numeric Analog Scale↓Numeric Analog Scale↓ opioid use↓opioid use↓ Opioid side effect index↓Opioid side effect index↓ ““breakthrough” painbreakthrough” pain

The Journal of Pain, Vol 4, No 8 (October), 2003: pp 441-447

Intrathecal vs EpiduralIntrathecal vs Epidural

Best Practice & Research Clinical Anaesthesiology Vol.16, NO.4, pp.651-665, 2002

Continuous infusion vs intermittent bolusContinuous infusion vs intermittent bolus

Best Practice & Research Clinical Anaesthesiology Vol.16, NO.4, pp.651-665, 2002

single-shot epidural or intrathecal opioids msingle-shot epidural or intrathecal opioids may serve as an indicator to the future succesay serve as an indicator to the future success of continuous infusions or patient-controlles of continuous infusions or patient-controlled analgesia using opioids.d analgesia using opioids.

Adequate relief of pain with trial spinal oipoiAdequate relief of pain with trial spinal oipoids is mandatory before proceeding to more ds is mandatory before proceeding to more permanent procedures for long-term treatmepermanent procedures for long-term treatment.nt.

Opioid agentsOpioid agents

MorphineMorphine HydromorphoneHydromorphone FentanylFentanyl MeperidineMeperidine MethadoneMethadone The exact dose comparison for different opiThe exact dose comparison for different opi

oids for intraspinal use is not availableoids for intraspinal use is not available

Non-opioid agentsNon-opioid agents

sodium channel antagonist: bupivacaine, rosodium channel antagonist: bupivacaine, ropivacainepivacaine

αα2 agonist: clonidine2 agonist: clonidine N-type voltage-gated calcium-channel antaN-type voltage-gated calcium-channel anta

gonist: Ziconotidegonist: Ziconotide NMDA receptor antagonist: KetamineNMDA receptor antagonist: Ketamine GABA agonist, adenosine agonist, cholinestGABA agonist, adenosine agonist, cholinest

erase inhibitorerase inhibitor

Bupivacaine, RopivacaineBupivacaine, Ropivacaine

Local anestheticsLocal anesthetics Combination with opioidsCombination with opioids Synergistic effectSynergistic effect No significant side effectNo significant side effect Ropivacaine is more selective for sensory vRopivacaine is more selective for sensory v

ersus motor nerves between the sensory anersus motor nerves between the sensory and motor blockaded motor blockade

ClonidineClonidine

Approved by FDA for epidural analgesiaApproved by FDA for epidural analgesia Action on α2-adrenergic receptors in superfiAction on α2-adrenergic receptors in superfi

cial dorsal horn region of the spinal cordcial dorsal horn region of the spinal cord Combination with opioidsCombination with opioids Side effects: hypotension, bradycardia, sedaSide effects: hypotension, bradycardia, seda

tiontion

ZinconotideZinconotide

Adventage: no development of tolerance like Adventage: no development of tolerance like opioids after prolonged useopioids after prolonged use

Intrathecal delivery provided clinically and stIntrathecal delivery provided clinically and statisticlly analgesia in patients with pain from atisticlly analgesia in patients with pain from cancer and AIDScancer and AIDS

Side effects: confusion, dizziness, urinary reSide effects: confusion, dizziness, urinary retention, constipation, nystagmus, ataxia, contention, constipation, nystagmus, ataxia, convulsionvulsion

JAMA. 2003;291:63-70

OthersOthers

BaclofenBaclofen MidazolamMidazolam AdenosineAdenosine neostigmineneostigmine

The efficacy of intraspinally administered agThe efficacy of intraspinally administered agents need to be studied in different type of cents need to be studied in different type of cancer pain syndrome.ancer pain syndrome.

Case 1Case 1

60y/o male60y/o male C.C.: face swelling, C.C.: face swelling, right flank painright flank pain First admitted on 4/21First admitted on 4/21 Right supraclavicular lymph node biopsy: adenocaRight supraclavicular lymph node biopsy: adenoca

rcinomarcinoma Diagnosis: Diagnosis: NSCLC, stage IVNSCLC, stage IV SVC syndromeSVC syndrome s/p stenting on 4/23 s/p stenting on 4/23 Discharged on 4/30Discharged on 4/30 Admitted again on 5/21 due to abdominal painAdmitted again on 5/21 due to abdominal pain

Acute pancreatitisAcute pancreatitis with abdominal pain on 5/18, re with abdominal pain on 5/18, recurred on 6/17 (pancreatic metastasis)curred on 6/17 (pancreatic metastasis)

T12~L1 right paraspinal mass, right adrenal mass T12~L1 right paraspinal mass, right adrenal mass were noted on CTwere noted on CT

Chemotherapy of weekly Gemzar was started on 6Chemotherapy of weekly Gemzar was started on 6/11/11

Palliative radiotherapy to the RUL mass was perforPalliative radiotherapy to the RUL mass was performed on 6/18 med on 6/18

Pain profilePain profile

Right flank pain since 4/13Right flank pain since 4/13 4/214/21住院住院 workupworkup ，接受，接受 biopsy, biopsy, 放放 stentstent 4/304/30出院，出院止痛處方：出院，出院止痛處方： durogesic(2.5mg/patch) q3ddurogesic(2.5mg/patch) q3d codeine (15mg) 1# po q6hcodeine (15mg) 1# po q6h naposine (250mg)1# po TIDnaposine (250mg)1# po TID 5/185/18出現出現 abdominal painabdominal pain ，來到，來到 ERER，診斷為，診斷為 panpan

creatitiscreatitis

5/215/21再度住院，止痛處方：再度住院，止痛處方： durogesic (2.5mg/patch) q3ddurogesic (2.5mg/patch) q3d codeine (30) 1# po q6hcodeine (30) 1# po q6h demerol ½ amp IV q6h prn when paindemerol ½ amp IV q6h prn when pain 5/31 morphine sol. (0.1%) 10 ml po q6h5/31 morphine sol. (0.1%) 10 ml po q6h 6/3 6/3 照會麻醉科做照會麻醉科做 epidural analgesiaepidural analgesia 6/11 PCEA6/11 PCEA 6/15 Intrathecal analgesia (morphine 0.5mg/5ml + 6/15 Intrathecal analgesia (morphine 0.5mg/5ml +

marcaine 2.5mg, q12h)marcaine 2.5mg, q12h)

DiscussionDiscussion

The cause of right flank painThe cause of right flank pain ？？ Oral morphine TitrationOral morphine Titration ？？ DurogesicDurogesic的使用？的使用？ DemerolDemerol 及及 codeinecodeine 的使用？的使用？ AdjuvantAdjuvant 的使用？的使用？ 考慮使用考慮使用 spinal analgesiaspinal analgesia 的理由的理由 更頻繁的疼痛控制評估？更頻繁的疼痛控制評估？ implantable pumpimplantable pump？？

Case 2Case 2

75 year-old woman75 year-old woman Chief Complaint: Progressive abdominal distChief Complaint: Progressive abdominal dist

ension, poor appetite and weight loss in recension, poor appetite and weight loss in recent one monthent one month

Pain tomography: left flank pain, left lower ePain tomography: left flank pain, left lower extremity pain, abd painxtremity pain, abd pain

Lt RCC s/p radical nephrectomy, splenectoLt RCC s/p radical nephrectomy, splenectomy, and distal pancreatectomy in 1997-08, smy, and distal pancreatectomy in 1997-08, s/p C/T/p C/T

RCC recurrence with iliacus muscle and iliaRCC recurrence with iliacus muscle and iliac bone involvement s/p re-op since 2001-09c bone involvement s/p re-op since 2001-09

Osteoporosis with T12 to L3 compression frOsteoporosis with T12 to L3 compression fracture acture

Chronic renal insufficiencyChronic renal insufficiency

Pain ControlPain Control

~04-21: NSAID (Naposin)~04-21: NSAID (Naposin) 04-21: Temgesic 1# SL q2h prn04-21: Temgesic 1# SL q2h prn shift to: Depain X 1# HS POshift to: Depain X 1# HS PO Paramol 1# PO prn Paramol 1# PO prn Morphine (0.1%) 5cc q6h POMorphine (0.1%) 5cc q6h PO 04-30: 04-30: RTRT 06-08: epidural analgesia06-08: epidural analgesia 06-15: intrathecal analgesia06-15: intrathecal analgesia 06-19: hold IT morphine06-19: hold IT morphine

DiscussionDiscussion

The cause of pain on The cause of pain on injectioninjection?? Another way to Another way to relieverelieve her pain? her pain? Intractable intractable cancer pain?Intractable intractable cancer pain? Timing of consultation with anesthesiologist?Timing of consultation with anesthesiologist?

EncapsulationEncapsulation

Symptoms: – Pain on injection– Increasing need for analgesics

Sign:– Inability to aspirate CSF from the catheter– Increased serum levels of morphine and increas

ed levels of M-3-G in the CSF

Pain 1992;49(3):369–371

Pain 103 (2003) 217–220

Palliative Radiation therapy (1)Palliative Radiation therapy (1)

Biological basis of analgesia following radiatiBiological basis of analgesia following radiation is not fully understoodon is not fully understood

75 to 100 percent of patients with diffuse me75 to 100 percent of patients with diffuse metastatic bone pain respond to hemibody raditastatic bone pain respond to hemibody radiation ation

Pain relief within 24 hoursPain relief within 24 hours Nausea, diarrhea, bone marrow depression, Nausea, diarrhea, bone marrow depression,

fatal radiation pneumonitisfatal radiation pneumonitis

Clin Orthop 1995 Mar;(312):105-19

Palliative Radiation therapy (2)Palliative Radiation therapy (2)

Tumor type and treatment regimen may not Tumor type and treatment regimen may not predict the response to radiotherapypredict the response to radiotherapy

RCC of the kidney, non-small cell RCC of the kidney, non-small cell carcinomas of the lungcarcinomas of the lung..

Vertebral body collapse and spinal instability Vertebral body collapse and spinal instability are best treated with surgical fixationare best treated with surgical fixation

Radiother Oncol 1989 Feb;14(2):95-101

Chromaffin Cell Allografts into the CSF

Chromaffin cells in the medullary portion of

the adrenal glands Producing and releasing high levels of opioi

d peptides and catecholamines Patients responding to intrathecal morphine Significant reductions in complementary opi

oid intake

Pain 87 (2000) 19-32

Transdermal fentanyl

Effective alternative to oral morphine Best reserved for patients whose opioid req

uirements are stable less constipation than morphine (Megens et al, 1998)

British Journal of Cancer (2001) 84(5), 587–593

Thanks for your attention!!Thanks for your attention!!