Palliative care is listed by the World Health Organization (WHO) as one of the four major priorities in oncology management. It is defined as “the active and comprehensive medical care of patients who have failed to respond to treatment, and the control of pain, other symptoms, psychological, spiritual and social problems, with the aim of achieving the best quality of life for patients and their families”. Pain in advanced malignancy puts patients in extreme physical and mental pain, and is the primary reason for patients to request euthanasia, which is also an important topic in modern medicine. According to the information published by WHO, about 80% of advanced cancer patients suffer from pain, and 30% of them have unbearable severe pain. Therefore, the palliative treatment for patients with advanced malignant tumor is mainly to control pain. Xie Guanglun, Department of Pain, Henan Cancer Hospital
I. Treatment of Pain Causes Radiotherapy and chemotherapy are good methods with specific analgesic effect, but radiotherapy or chemotherapy should not be decided simply for the treatment of pain, but should seek a balance between pain relief and adverse reactions, and it is appropriate to adopt them under the premise of obvious benefit to patients. Surgical procedures can relieve pain caused by intestinal obstruction, unstable skeletal structures and nerve compression, but the favorable aspects and risks of surgery and the estimated duration of benefit must be properly evaluated. Treatment of complications Such as timely detection and control of infection, timely calcium supplementation for patients with bone metastases, etc. Drug pain treatment Three steps of pain treatment ① First step – non-opioid drugs: Patients with mild cancer pain can generally tolerate it and can live and sleep normally without disturbance should use non-opioid painkillers. The most commonly used ones are non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs include: aspirin, diclofenac, nimesulide, celecoxib, etc. They are effective for pain arising from bone metastatic cancer pain, mechanical traction of the periosteum by the tumor, pressure on soft tissues such as muscle or subcutaneous, or pressure on the pleura/peritoneum. Adverse effects, including platelet dysfunction, gastrointestinal ulcer, renal damage, etc., should be well known when applied. The occurrence of adverse reactions is closely related to the dose, therefore, for patients who need long-term pain treatment, the adverse reactions, capping effect and restrictive dose of NSAIDs should be fully considered. Do not increase the dose blindly, and enter the second step in time if the pain relief is not satisfactory. The second step–weak opioids: when non-opioid drugs do not provide satisfactory pain relief, sleep is disturbed, and appetite is reduced, weak opioid analgesics should be used. Such drugs include codeine, oxycodone, etc. The principle of gradual transition to the second step should be adopted, that is, while giving NSAIDs, weak opioid analgesics should be given gradually. (3) The third step – strong opioid drugs; strong opioid analgesics are used for moderate to severe cancer pain with poor response to non-opioid and weak opioid drugs. Most patients are satisfied with the pain relief after using these drugs, but they are prone to drug dependence and drug resistance, and the effect of repeated drug use gradually decreases, and the dose needs to be increased continuously to maintain the pain relief effect. The efficacy of strong opioid analgesics varies greatly among individuals and is usually started with a small dose and increased to an appropriate dose according to clinical experience. The analgesic effect of opioids does not have a ceiling effect, and as the dose increases, the analgesic effect is enhanced. Immediate release morphine dosage: 5 to 200mg, taken orally every 4 hours. Generally start from 5mg, individual can start from 1Omg or more. If the patient has good pain relief and drowsiness after the first oral dose, the dose can be reduced for the second time, and vice versa, the dose can be increased or the interval between doses can be shortened for the second time. Morphine controlled-release tablets may be administered orally every 12 hours.
Fentanyl extended-release transdermal patch (Doregis) is applied to the skin and stored first in the epidermis and gradually reaches the whole body through circulation. The fullest effect appears 8 to 16 hours after patching, and the effective concentration can generally be maintained for 72 hours. After 15 days of continuous application, 96.8% of patients can achieve more than moderate remission. Its clinical effect is satisfactory, and the adverse effects are light, and patients have better alertness and sleep quality. Precautions for the clinical application of strong opioids; ① timely application, use the full dose, and often adjust the dose according to the condition; ② increase the single drug dose when the pain increases, rather than increasing the number of doses; ③ those who receive immediate release morphine treatment can double the dose at bedtime to prevent waking up from pain; ④ controlled release tablets should not be crushed for application; ⑤ the intensity of pain and the process of dose adjustment should be recorded; ⑥ pay attention to the prevention and treatment of adverse drug reactions. Adjuvant drugs in three-step treatment Adjuvant drugs can be used to treat the all-round pain of cancer pain patients. These drugs are not painkillers per se, but can be used as an adjunct to treat certain kinds of cancer pain or adverse reactions. ① Corticosteroids; they can reduce inflammatory edema of tissues around cancer lesions, thus reducing cancer pain. When combined with NSAIDs, attention should be paid to the superposition of adverse reactions. ②Anti-convulsants: effective for pain caused by tearing pain, burning pain and chemotherapy drug spillover due to nerve injury. Commonly used are carbamazepine and gabapentin. ③Antidepressants; can enhance the analgesic effect of morphine, or have a direct analgesic effect. It can improve mood, promote sleep, and is more effective for neuropathic pain. The initial dose of amitriptyline is 25mg at bedtime, which can be gradually increased every 3 days, with a maximum daily limit of 150mg. ④NMDA receptor antagonist: inhibits central excitation, improves morphine efficacy, and is also effective for refractory neuropathic pain. ⑤α2-adrenoceptor agonists: Colistin can be administered orally or via epidural route, and is especially effective for neuropathic pain.
General principles of drug treatment for cancer pain ① Oral principle: oral administration does not require the help of others and is more convenient, safe and economical. If patients have difficulty in swallowing, severe vomiting or gastrointestinal obstruction, fentanyl transdermal patch or other rectal suppositories can be used, etc. Continuous subcutaneous infusion of drug delivery by infusion pump is chosen only when necessary. ②Step principle: the standardized pain management principle of the three steps should be strictly implemented like the routine of radiotherapy, chemotherapy and surgery. ③On-time principle: pain medication should be given regularly at planned intervals rather than waiting for patients to request it. The next dose should be given before the effect of the previous dose wears off, so as to ensure continuous pain relief. Sudden severe pain can be temporarily given as needed. ④The principle of individualization: the dosage of analgesics varies from person to person, and the effective analgesic dose varies greatly from patient to patient. For each individual, the dosage should be selected to meet the individual’s needs. The appropriate analgesic dose should ensure that the analgesic effect can be maintained for more than 4 hours without obvious adverse effects. The dose of strong opioids may be increased without limit. (5) Detailed principles: The physician must examine in detail and identify whether the pain is caused by the tumor itself, or by other treatments, or by comorbidities, or other pain unrelated to the cancer. In addition, it is important to identify localized pain and involvement pain, whether the pain is peripheral or plexus and spinal cord involvement, and what aggravates the pain and relieves it. This is the basis for choosing reasonable pain relief measures. III. Non-pharmacological treatment Psychological treatment Late stage cancer patients have negative psychology, pessimism and disappointment, depression, sense of abandonment and loss, therefore, it is necessary to strengthen psychological treatment and care to reassure them, make them face the reality and cherish their limited life. Social needs are also part of the needs of the terminally ill, such as unfulfilled wishes, financial problems in treating the disease, and matters after their own death, etc. For these needs, the patient should be given a satisfactory and practical answer as much as possible. Physical therapy Massage, heat, acupuncture, and ultrasound are all helpful in aiding pain relief. Han’s Acupoint Nerve Stimulator (HANS) activates the body’s endogenous opioid system, releasing three morphine-like substances (endorphin, enkephalin, and prednisolone) to replace the function of exogenous morphine and exert a systemic analgesic effect. In addition, stimulation of the thick nerve fibers at the site of pain can also produce local analgesic effects. Nerve block therapy Some cancer pain patients still have severe pain after strict application of the three-step drug treatment program, or they cannot fully accept the three-step program due to the contraindication of drugs, etc., which is called intractable cancer pain. Nerve block therapy provides an excellent route to control intractable cancer pain. Epidural or subarachnoid administration of opioids Spinal administration of small doses of opioids has the advantage of preserving sensory, motor, and sympathetic function, and this method can be performed on an outpatient basis. Spinal opioid therapy is done to evaluate effectiveness prior to insertion of a permanent catheter. Afterwards, the catheter is placed and bridged to the patient’s self-contained or slow-release pump, and morphine and other drugs are injected into the guide tube, which can achieve satisfactory and rapid analgesia. The key to the technique is the subcutaneous fixation of the catheter to the side of the body, with a heparin cap attached to the outer end of the catheter for its administration and to avoid infection. Patients and families can quickly learn its use and administer it themselves, without hindering the patient’s movement. These nerve blocks are best performed under the guidance of imaging equipment. (1) Peripheral nerve destructive block: If the cancer pain is limited and drug treatment is not effective, blocking peripheral nerves with different concentrations of phenol, ethanol or adriamycin solution or destroying nerves with radiofrequency can often achieve satisfactory results. (2) Epidural nerve destruction block: compared with peripheral nerve block, epidural block can block both somatic and autonomic nerves, and the blocking range is larger and more effective; compared with subarachnoid block, it can avoid meningeal irritation and spinal cord or spinal nerve injury, but its effect is not as good as subarachnoid block. (3) Subarachnoid nerve destruction block: This method is effective in controlling cancer pain, and most of the reported pain relief time is 2 weeks to 3 months, and a few patients can last for 4-12 months. (4) Destructive block of the celiac plexus: It can provide good relief of epigastric pain and back involvement pain caused by malignant tumors of intestinal origin. This method is most commonly used for pancreatic cancer, and complete pain relief can be obtained in 60% to 85% of patients; it is also effective for tumor-based pain in the distal esophagus, stomach, liver, bile duct, small intestine, proximal colon, adrenal gland and kidney. ⑤ In addition, sympathetic ganglion destructive blocks and pituitary destructive blocks are available.
The control of pain in advanced malignancy is a problem of the whole society, and patients should be given back the right to be pain-free as if they were vulnerable. In our country, many patients with advanced pain from malignant tumors have not been able to receive adequate pain relief treatment. We clinicians should be obliged to improve our knowledge and related skills so that patients with malignant tumors can finish the last part of their lives with dignity and respect.