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

2. 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

3. 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

4. Discussion ?
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5. Others

7. 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

8. Discussion ?
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9. Others

11. 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

12. 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

13. Discussion ?
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14. Others

16. Treatment of patients with opioid tolerance
Opioid rotation or
Combination with antihyperalgesic agents
NMDA receptor antagonist S-Ketamine 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 Jul;30(1):1-3.
Mercadante et.al.:Long-term ketamine subcutaneous continuous infusion in neuropathic cancer pain. J Pain Symptom Manage 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 Apr;98(4):1050-5,.

18. Nausea and vomiting in cancer patients
Basics
Case reports

19. 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:

20. 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?

21. 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

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

23. 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

24. Nausea and vomiting – regions and receptors
Antiemetic
center
AEZ
Psyche VZ
Enk H1
Achm + + - - +
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

25. 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

26. 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

27. Discussion ?
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28. Others

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

31. 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.

32. Discussion ?
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33. Others

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

36. 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

37. Discussion ?
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38. Others

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

41. 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): Review.

42. 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)

43. 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.

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