Intraspinal analgesia for Cancer Pain

Intraspinal analgesia for Cancer Pain Ri 錢穎群 劉耀臨 Indications  The 4th step in managing pain of malignant origin  Unsuccessful treatment with sequential strong systemic opioid drug trials despite escalating doses  Treatment with systemic opioids with effective pain relief but with unacceptable side effects Advantages  Lower dose than systemic use (1/10 rule for morphine)  Longer analgesic effect  Fewer opioid side effects Adverse effects and Complications  Same as systemic opioids but less severe  Tolerance Best Practice & Research Clinical Anaesthesiology Vol.16, NO.4, pp.651-665, 2002 Catheter placement  Percutaneous: simple, cheap, risk of infection, high failure rate  Tunnelled: more helpful, providing months of effective analgesia  Implantable programmable infusion pump: expensive, continuous infusion, good daily activity, good quality of life (for long-term analgesia, >3 months) Implantable intrathecal pump  A multicenter, prospective clinical study  Numeric Analog Scale↓  opioid use↓  Opioid side effect index↓  “breakthrough” pain The Journal of Pain, Vol 4, No 8 (October), 2003: pp 441-447 Intrathecal vs Epidural Best Practice & Research Clinical Anaesthesiology Vol.16, NO.4, pp.651-665, 2002 Continuous infusion vs intermittent bolus Best Practice & Research Clinical Anaesthesiology Vol.16, NO.4, pp.651-665, 2002  single-shot epidural or intrathecal opioids may serve as an indicator to the future success of continuous infusions or patientcontrolled analgesia using opioids.  Adequate relief of pain with trial spinal oipoids is mandatory before proceeding to more permanent procedures for long-term treatment. Opioid agents       Morphine Hydromorphone Fentanyl Meperidine Methadone The exact dose comparison for different opioids for intraspinal use is not available Non-opioid agents  sodium channel antagonist: bupivacaine, ropivacaine  α2 agonist: clonidine  N-type voltage-gated calcium-channel antagonist: Ziconotide  NMDA receptor antagonist: Ketamine  GABA agonist, adenosine agonist, cholinesterase inhibitor Bupivacaine, Ropivacaine      Local anesthetics Combination with opioids Synergistic effect No significant side effect Ropivacaine is more selective for sensory versus motor nerves between the sensory and motor blockade Clonidine  Approved by FDA for epidural analgesia  Action on α2-adrenergic receptors in superficial dorsal horn region of the spinal cord  Combination with opioids  Side effects: hypotension, bradycardia, sedation Zinconotide  Adventage: no development of tolerance like opioids after prolonged use  Intrathecal delivery provided clinically and statisticlly analgesia in patients with pain from cancer and AIDS  Side effects: confusion, dizziness, urinary retention, constipation, nystagmus, ataxia, convulsion JAMA. 2003;291:63-70 Others     Baclofen Midazolam Adenosine neostigmine  The efficacy of intraspinally administered agents need to be studied in different type of cancer pain syndrome. Case 1         60y/o male C.C.: face swelling, right flank pain First admitted on 4/21 Right supraclavicular lymph node biopsy: adenocarcinoma Diagnosis: NSCLC, stage IV SVC syndrome s/p stenting on 4/23 Discharged on 4/30 Admitted again on 5/21 due to abdominal pain  Acute pancreatitis with abdominal pain on 5/18, recurred on 6/17 (pancreatic metastasis)  T12~L1 right paraspinal mass, right adrenal mass were noted on CT  Chemotherapy of weekly Gemzar was started on 6/11  Palliative radiotherapy to the RUL mass was performed on 6/18 Pain profile  Right flank pain since 4/13  4/21住院workup，接受biopsy, 放stent  4/30出院，出院止痛處方： durogesic(2.5mg/patch) q3d codeine (15mg) 1# po q6h naposine (250mg)1# po TID  5/18出現abdominal pain，來到ER，診斷為 pancreatitis  5/21再度住院，止痛處方： durogesic (2.5mg/patch) q3d codeine (30) 1# po q6h demerol ½ amp IV q6h prn when pain  5/31 morphine sol. (0.1%) 10 ml po q6h  6/3 照會麻醉科做epidural analgesia  6/11 PCEA  6/15 Intrathecal analgesia (morphine 0.5mg/5ml + marcaine 2.5mg, q12h) Discussion         The cause of right flank pain？ Oral morphine Titration？ Durogesic的使用？ Demerol及codeine的使用？ Adjuvant的使用？ 考慮使用spinal analgesia的理由 更頻繁的疼痛控制評估？ implantable pump？ Case 2  75 year-old woman  Chief Complaint: Progressive abdominal distension, poor appetite and weight loss in recent one month  Pain tomography: left flank pain, left lower extremity pain, abd pain  Lt RCC s/p radical nephrectomy, splenectomy, and distal pancreatectomy in 1997-08, s/p C/T  RCC recurrence with iliacus muscle and iliac bone involvement s/p re-op since 2001-09  Osteoporosis with T12 to L3 compression fracture  Chronic renal insufficiency Pain Control  ~04-21: NSAID (Naposin)  04-21: Temgesic 1# SL q2h prn shift to: Depain X 1# HS PO Paramol 1# PO prn Morphine (0.1%) 5cc q6h PO  04-30: RT  06-08: epidural analgesia  06-15: intrathecal analgesia  06-19: hold IT morphine Discussion     The cause of pain on injection? Another way to relieve her pain? Intractable intractable cancer pain? Timing of consultation with anesthesiologist? Encapsulation  Symptoms: – Pain on injection – Increasing need for analgesics  Sign: Pain 1992;49(3):369–371 – Inability to aspirate CSF from the catheter – Increased serum levels of morphine and increased levels of M-3-G in the CSF Pain 103 (2003) 217–220 Palliative Radiation therapy (1)  Biological basis of analgesia following radiation is not fully understood  75 to 100 percent of patients with diffuse metastatic bone pain respond to hemibody radiation  Pain relief within 24 hours  Nausea, diarrhea, bone marrow depression, fatal radiation pneumonitis Clin Orthop 1995 Mar;(312):105-19 Palliative Radiation therapy (2)  Tumor type and treatment regimen may not predict the response to radiotherapy  RCC of the kidney, non-small cell carcinomas of the lung.  Vertebral body collapse and spinal instability are 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 opioid peptides and catecholamines  Patients responding to intrathecal morphine  Significant reductions in complementary opioid intake Pain 87 (2000) 19-32 Transdermal fentanyl  Effective alternative to oral morphine  Best reserved for patients whose opioid requirements are stable  less constipation than morphine (Megens et al, 1998) British Journal of Cancer (2001) 84(5), 587–593 Thanks for your attention!!