Cancer Pain II Severe acute pain despite high dose opioid therapy Treatment of nausea and vomiting Neuropathic cancer pain

Case report 1 - Mr. Johnson – Rectum-CA 64 years old 2 previous operations Anterior rectal resection Post-OP colostomy Currently receiving radiation therapy because of bone metastasis Current medication: 300 mg morphine Ibuprofen as needed Antiemetic: ondansetron 8 mg Laxative: bisacodyl 5 – 15 mg

Case report 2 - Mr. Johnson – Rectum-CA Severe pain in the sacral region (region of radiation therapy) after the 6th irradiation Pain rating: 9-10 (NRS) Stabbing, pressive pain, „excruciating“ Selfmedication:Ibuprofen 800 mg with no effect

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Case report 3 - Mr. Johnson – Rectum-CA Patient experienced adequate pain relief after titration application of 40mg morphine i.v. and 40mg dexamethasone pain rating: 3-6 (NRS) Patient came to the clinic the following morning for CT-diagnostics Because of severe pain even after 20 mg morphine i.v., patient still could not lie on his back on the CT table

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Case report 4 - Mr. Johnson – Rectum-CA They performed the diagnostic procedure after turning the patient Pain was due to edema caused by radiation therapy With a therapy of 300 mg morphine, 200 mg diclofenac and 450 mg pregabalin, patient experienced satisfactory pain reduction for several weeks Pain rating: 2-5 (NRS) 6 months later: Increasing fatigue with this therapy

Case report 5 - Mr. Johnson – Rectum-CA Results of laboratory diagnostics: Blood Urea Nitrogen (BUN) 84 mg/dl Creatinine from 0.9 to 2.6 mg/dl Liver enzymes normal

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Treatment of patients with opioid tolerance Opioid rotation or Combination with antihyperalgesic agents NMDA receptor antagonist S-Ketamine 0.5 - 2 mg/kg /d Sodium channel blocker Lidocaine 0.5 – 1 mg/kg /h Intrathecal analgesic administration Anghelescu DL, Oakes LL: Ketamine use for reduction of opioid tolerance in a 5-year-old girl with end-stage abdominal neuroblastoma. J Pain Symptom Manage. 2005 Jul;30(1):1-3. Mercadante et.al.:Long-term ketamine subcutaneous continuous infusion in neuropathic cancer pain. J Pain Symptom Manage. 1995 Oct;10(7):564-8. Koppert W, Weigand M, Neumann F, Sittl R,: Perioperative intravenous lidocaine has preventive effects on post- operative pain and morphine consumption after major abdominal surgery. Anesth Analg. 2004 Apr;98(4):1050-5,.

Nausea and vomiting in cancer patients Basics Case reports

Incidence in subjects with advanced cancer: Nausea and vomiting Incidence in subjects with advanced cancer: 40-70% of patients Grond S et al. Journal of Pain and Symptom Management, 1994; 9: 372-82

Nausea and vomiting – important questions How often do nausea and vomiting occur? Is the vomiting accompanied by nausea? Does the nausea remain after a vomiting episode? Is there a temporal connection between the vomiting and food intake? Are you currently receiving chemotherapy or radiation? Which medicinal products are you currently receiving?

Nausea and vomiting Evaluation in subjects with intractable vomiting Abdominal and rectal examination Signs of cranial pressure Lab values (creatinine, calcium, carbamazepine and digoxin levels) Radiological diagnostics

Causes of nausea and vomiting Chemotherapy, radiotherapy, opioids Gastrointestinal stenosis Metabolic imbalance Increased intracranial pressure Pain, anxiety

Nausea and vomiting – control zones Control zone I before enteral toxin absorption Control zone III Central: Circumventricular organs including Taste Smell Balance Hearing Vision Facial senses Area postrema Control zone II before enteral toxin absorption Nausea and vomiting – control zones Chemoreceptors Mechanoreceptors Polymodal receptors Nociceptors Gastro- intestinal tract Control zone III after toxin absorption Best-perfused organs Periphery

Nausea and vomiting – regions and receptors Antiemetic center AEZ Psyche µ VZ Enk H1 Achm + + - - + µ CB1 CTZ VC + + + H1 Achm D2 5HT3 D2 GI 5HT3 5HT4 Vagal afferent pathways Medicines, toxins, metabolites via bloodstream Chemo- and mechano- receptors From: Oxford Textbook of Palliative Medicine p. 490

Receptor profile of the main antiemetics Dopamine receptor (D2) Acetylcholine receptor Histamine receptor (H1) Serotonin receptor (5-HT3) Neurokinin receptor (NK1) Metoclopramide ++++ Ant + Ag + Ant ++ Ant Haloperidol ++++ Ant (+?) Ant + Ant Ondansetron ++++ Ant Dimenhydrinate +-++ Ant ++ Ant ++++ Ant Scopolamine + Ant ++++ Ant + Ant Levomepromazine ++ Ant ++ Ant ++++ Ant Aprepitant ++++ Ant

Case report 44-year-old patient Diagnosis: ovarian cancer Underwent radiochemotherapy and surgical removal of tumour. Chemotherapy: Tamoxifen 20mg BID until 3 days previously Current situation: Pain management with ibuprofen 600 mg TID and morphine 120 mg p.o. daily Lab: Ca and urea within normal limits Developed heavy nausea and vomiting since switching to the strong opioid morphine

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Nausea and vomiting – opioid related Benzodiazepine Haloperidol Dimenhydrinate / Metoclopramide Consider switching to a different opioid

Radiology dedicted mechanical obstruction surgery not possible. Case report 64-year-old patient Diagnosis: advanced colorectal carcinoma Patient received radiochemotherapy Current situation: Adjuvant chemotherapy with 5FU once weekly Pain management with metamizole 3 g daily and tramadol 600 mg daily. Progressive recurrent vomiting for the past week. Vomiting continued after metoclopramide was administered, plus additional colicky pain. Radiology dedicted mechanical obstruction surgery not possible.

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Nausea and vomiting – due to mechanical stenosis Octreotide Dexamethasone - Ondansetron Haloperidol - Dimenhydrinate - Butylscopolamine Surgery, stomach tube, PEG

Case report 16-year-old female patient Diagnosis: Ewing‘s sarcoma Treatment to date: Preoperative chemotherapy Current situation: Nausea and vomiting after the first three blocks despite cortisone and ondansetron

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Nausea and vomiting – chemotherapy induced Low dose Benzodiazepine Aprepitant Ondansetron - Dexamethasone Patient-friendly environment, relaxation, acupuncture

Acupuncture, “psychotherapy” and hypnosis Dupuis et.al :Options for the prevention and management of acute chemotherapy-induced nausea and vomiting in children. Paediatr Drugs. 2003;5(9):597-613. Review.

Corticoids – dexamethasone (Fortecortin®) Action: Antiemetic mechanism of action unknown (possibly detumescence of the brain tissue irritated by antineoplastics / inhibition of prostaglandin synthesis) multiple kinds of action, especially interaction with intercellular structurs Indication: Chemotherapy malignant bowel obstruction Elevated intracranial pressure (at higher doses than for chemotherapy)

Summary Anamnesis and detailed pain diagnosis is a prerequisite for an individual mechanism-oriented tumor pain therapy Detect and treat neuropathic pain components Use Opioids / MOR-NRI in consideration of side effects and interactions Treat breakthrough pain adequately Tumor pain therapy is an interdisciplinary and multiprofessional task! If necessary use invasive methods.

Cancer pain is sometimes difficult to treat but do not give up – sometimes an invasive procedure is the solution