复旦大学上海医学院肿瘤学系

1. Fudan University Shanghai Cancer Center 《Basic Clinical Oncology-Symoptom Management and Palliative Care》 Pain Fudan University Cancer Center Cheng Wen-Wu 复旦大学上海医学院肿瘤学系

2. Who am I? • Cheng Wen-Wu • Director of palliative care department, Shanghai cancer hospital, Fudan university. • Traditional Chinese Medicine (Shanghai) and palliative care (MD Anderson cancer center, Texas)

3. Overview of pain • major symptoms in cancer patients: either early or advanced stage • global common problem: 30% to 50% of new cancer patients ; advanced patients reach 70% to 90%.

4. Definition of pain • "an unpleasant sensory and emotional experience associated with actual or potential tissue injury or described in terms of such damage." • “injury” and “suffering or distress”

5. “Pain is whatever the experience the person says it is, existing whenever patient says it does” • The patient's chief complaint should be believed.

6. Impact of pain • The interaction of pain with concurrent symptoms such as anorexia, nausea, constipation, delirium, dyspnea, depression, anxiety and insomnia, and so on. • The patients and their families might think that the intensification of pain is a harbinger of impending death.

7. Causes of pain • Tumor: ① tumor compression and invasion to adjacent organs, tissue, nerves, bones or blood vessels or metastasis.② inflammation caused by tumor-induced mediators (e.g, interleukin, bradykinin) and so on. • Treatment-related: ① Postsurgical pain syndrome (eg, thoracotomy, mastectomy, amputation surgery, surgical scars and nerve damage).② Postchemotherapy pain (eg, polyneuropathy, osseous necrosis, thrombophlebitis and mucositis).③ Postradiation pain (eg, local damage, neural fibrosis, medullary lesions, bone necrosis and mucositis).

8. Cancer-related pain: the pain is caused by some symptoms such as constipation, pressure sores and muscle spasm. • Non-physiological pain: ① Spiritual pain.② Psychological trauma. • Non-cancer pain: non-cancer-related pain (eg, myofascial, musculoskeletal problems). • There are two or more causes of pain in most of advanced cancer patients.

9. Type of pain • Duration:acute(transient) and chronic (more than 3 months) pain, • Pathophysiological mechanisms and characteristics:nociceptive and neuropathic pain.

10. Assessment of pain • What should we assess? • clinical manifestations and psychological problems. • Why should we assess? “diagnosis” and “treatment”. • Any else be added? Sociological and psychological factors.

11. Multi-faceted assessment of cancer pain • ① etiology (tumor, tumor-related treatment, and tumor-related diseases); • ② severity; • ③ alcohol and drug addiction ; • ④ psychological distress (somatization); • ⑤ cognitive function; • ⑥ pain mechanism (neuropathic, non-neuropathic); • ⑦ pain characteristics (continuous, incidental); • ⑧exacerbating and relieving factors; • ⑨impact the activities of patient’s daily life, sleep, mood and other affects; • ⑩ other pain-related symptoms.

12. Pain intensity and efficacy evaluation • Numeric Rating Scale (NRS) tool for pain: the pain intensity is scaled as 0 to 10, 0 to 10 figures represent varying degrees of pain: 0 being no pain and 10 being worst severe pain; the patients are asked to say one number which represents their degree of pain at present time. The scale which also can be divided into three sections, namely: mild pain (including the number equal to or below 3), moderate pain (4-6), and severe pain (7-10). • If the pain intensity can gradually reduced through treatment, and can be controlled in 3 or below 3, that is, the efficacy is significant, and pain control is reasonable.

13. Flowsheet of the clinical assessment of pain • Believe the patient’s complaint of pain. • Take a careful history of the pain complaint to place it temporally in the patient’s cancer history. • Assess the characteristics of each pain, including its site, its pattern of referral, and its aggravating and relieving factors. • Clarify the temporal aspects of pain: acute, subacute, chronic, episodic, intermittent, breakthrough, or incident. • Evaluate the response to previous and current analgesic therapies. • Evaluate the psychological state of the patient. • Ask if the patient has a past history of alcohol or drug dependence. • Perform a careful medical and neurologic examination. • Design the diagnostic and therapeutic approach to suit the individual. • Reassess the patient’s response to pain therapy. • Discuss advance directives with the patient and family. • 0 to 10 scale for pain intensity is very useful.

14. Three-step analgesic ladder treatment • Why should we use this guideline? • Three-step analgesic ladder regimen of the WHO is a widely accepted pharmacological therapy for cancer pain around the world. As long as we follow the basic principle, most of the pain will be controlled effectively. • And what elite is in it?......

15. Mild pain: non-opioid analgesics (nonsteroidal, anti-inflammatory drugs NSAIDs) ± adjuvant drugs; • Moderate pain: weak opioids (codeine, tramadol) ± non-opioid analgesics ± adjuvant drug; • Severe pain: strong opioids (morphine, hydromorphone, fentanyl, methadone, oxycodone) ± Non-opioid analgesics ± adjuvant drugs

16. Basic principles • ① Administration according to the ladder: from weak to strong, step by step. • ② Regular administration: titration. • ③ Oral medication: no injury. • ④ Personalized Medicine: unique. • ⑤ Pay attention to specific details: details and side effects.

17. Common analgesic drugs weak: codenie, tramadol Narcotic analgesics short half-life: morphine, pethidine, hydrocodone strong long half-life: methadone, levorphanol Non-narcotic analgesics: NSAIDs, antidepressants, antispam, antiepileptic, steroids, benzodiazepine, psychotropic, bisphoshonates, anticonvulsants, phenothiazine, local analgesics.

18. Mode of administration • Oral • Rectal • Transdermal • Mucosal • Injection • Perineural • Patient self-control

19. Route of administration • “Adult cancer pain” of the National Comprehensive Cancer Network (NCCN) is a good tool details the procedure. • Escalate (titrate), ongoing, rotate.

20. Side effects of narcotic analgesics and treatment • Side effects is normal. • Pre-treatment and hydration. • Lower dose for organ dysfuction.

21. Caution:sedation, confusion and delirium, nausea and vomiting, constipation, pruritus, retention, and respiratory depression are the most side effects encountered in the clinical use of opioids. When evaluating for opiods-related side effects, clinician should distinguish whether the side effects are due to the opioids, other drugs, or the disease progression.

22. Tolerance and dependency issues of narcotic analgesics • We should understand the basic principles of narcotic analgesics and distinguish different concepts of drug tolerance, physical dependenceand psychological dependence (addiction), even pseudo-addiction.

23. ① Drug tolerance of narcotic analgesics: dose with disease. • ② Physical dependence: long time use, suddenly reduce, withdrawal. • ③ Psychological dependence (addiction): obsessive-compulsive disorder. • ④ Pseudo-addiction: dose inadequate, can be revised.

24. Nonpharmacological Treatment • Besides medication therapy for pain, stimulation and ablation, never blocks, physical therapy, psychological and behavioral approaches, and acupuncture technique are some else in pain relief. • With advanced disease, when active anticancer therapy is no longer effective, it is common for patients and families to request that if nothing else can be done that at least their pain should be adequately managed.

25. Summary of pain treatment • Three-step analgesic ladder regimen of the WHO is a useful guideline for pain relief. That is, for patients with mild pain, mainly choose non-opioid analgesics ± adjuvant drugs; for patients with moderate pain, mainly choose weak opioids ± non-opioid analgesics ± adjuvant drug; for patients with severe pain, choose strong opioids ± Non-opioid analgesics ± adjuvant drugs. At all levels, certain NSAIDs and adjuvant drugs may be used for specific indications. The use of analgesics increases from weak to strong step by step. Unless the patient presenting is in severe pain, a strong opioid should be treated immediately.

26. The basic rule for pharmacotherapy is to maximize pain relief and minimize side effects. So, administration by three-step analgesic ladder, regular administration, oral or non-trauma medication, personalized medication, detail management, and familiar with the drugs are beneficial content of the rule. • Common analgesic drugs can be simply divided into non-narcotic analgesics and narcotic analgesic drugs.

27. Oral, rectal, transdermal, mucosal, injecting, perineural, and patient self-control administration are the clinical administration for varies patients. Every path has its advantage and disadvantage for right person. • NCCN provides a detail guideline for pain management in clinic.

28. Opioids may cause some side effects, pr-treatment can prevent the morbidity. The appropriate symptomatic treatment is given for the present symptoms. • Using reasonably the appropriate narcotic analgesics and its dose, the drug tolerance, physical dependence, addiction, pseudo-addiction can be avoided.

29. Besides medication therapy for pain, stimulation and ablation, never blocks, physical therapy, psychological and behavioral approaches, and acupuncture technique are the complimentary therapy for pain relief. • There is no “golden standard” for patient to make all pain smooth away rapidly; the methods which can be suitable for patient, and let he/she feels comfortable, it is just so-called good pain management.

30. Fudan University Shanghai Cancer Center Recommended Readings: WHO three-step analgesic ladder; NCCN adult cancer pain. If you have any question, please contact me. Teacher’s name：Cheng Wen-Wu Department of palliative care, Shanghai Cancer Hospital email:cwwxxm@sina.com Thank you! 复旦大学上海医学院肿瘤学系