This guideline presents strategies for the assessment and management of cancer pain, and symptoms associated with advanced disease, in patients  19 years of age. Part 2 is divided into seven sections, providing recommendations for evidence-based symptom management with algorithms to facilitate quick access to the information required. Hyperlinked notes in the algorithm refer back to more detailed information within each symptom section.#
- Constipation: Guideline  Medication Table -   There are many etiologies (e.g., reduced food/fluid/mobility and adverse effects of medications). 2. Exclude impaction when a patient presents already constipated. Abdominal x-ray can be useful when physical examination is inconclusive. 3. Minimize/avoid rectal interventions (enemas, suppositories, manual evacuation), except in crisis management. Note that rectal interventions are contraindicated when there is potential for serious infection (neutropenia) or bleeding (thrombocytopenia), or when there is rectal/anal disease. 4. When risk factors are ongoing, as they are in most cancer patients, suggest laxatives regularly versus prn. Adjust dose individually. Laxatives are most effective when taken via escalating dose according to response, termed "bowel protocol". 5. Sennosides (e.g., Senokot) are the first choice of laxative for prevention and treatment. Patients with irritable bowel syndrome may experience painful cramps with stimulant laxatives and often prefer osmotic laxatives such as lactulose or polyethylene glycol (PEG). There is weak evidence that lactulose and sennosides are equally effective; 1 however lactulose can taste unpleasant and cause bloating. 6. If rectal measures are required, generally a stimulant suppository is tried first, then an enema as the next option. 7. The BC Palliative Care Drug Plan covers laxatives written on a prescription for eligible patients. 8. For patients with opioid-induced constipation, after a trial of first-line recommended stimulant laxatives and osmotic laxatives, methylnaltrexone (or nalaxegol) may be helpful. Cancer, GI malignancy, GI ulcer, Ogilvie's syndrome and concomitant use of certain medications (e.g., NSAIDs, steroids and bevacizumab) may increase the risk of GI perforation in patients receiving methylnaltrexone.  9. A bowel protocol and patient handouts on constipation are available at: / networks/family-practice-oncology-network/guidelines-protocols. Guidelines & Protocols Advisory Committee 2. Patients are at high risk of suicide and have an increased desire for hastened death. 3 3. A useful depression screening question is, "Have you been depressed most of the time for the past two weeks?" 4 4. A diagnosis of depression in the terminally ill may be made when at least two weeks of depressed mood is accompanied by symptoms of hopelessness, helplessness, worthlessness, guilt, lack of reactivity, or suicidal ideation.
- DSM-IV criteria for depression are not very helpful because vegetative symptoms like anorexia, weight loss, fatigue, insomnia, and impaired concentration may accompany end stage progressive illness.
- Risk factors for depression include:
- personal or family history of depression;
- social isolation, concurrent illnesses (e.g., COPD, CHF);
- alcohol or substance abuse; - poorly controlled pain;
- advanced stage of illness;
- certain cancers (head and neck, pancreas, primary or metastatic brain cancers); - chemotherapy agents (vincristine, vinblastine, asparagines, intrathecal methotrexate, interferon, interleukin); - corticosteroids (especially after withdrawal); and - abrupt onset of menopause (e.g., withdrawal of hormone replacement therapy, use of tamoxifen).
- Non-pharmacological treatments are the mainstay of treatment for the symptom of depression without a diagnosis of primary affective disorder. 2. Treatment of pain and other reversible physical symptoms should occur before initiating antidepressant medication. 3. If a diagnosis of primary affective disorder is uncertain in a depressed patient, consider psychiatric referral and a trial of antidepressant medication (refer to Appendix A: Medications Used in Palliative Care for Depression). Consider drug interactions, adverse side effect profiles, and beneficial side effects when choosing an antidepressant. 4. In the terminally ill, start with half the usual recommended starting dose of antidepressant. 5 5. First line therapy is with a selective serotonin reuptake inhibitor (SSRI), 2 selective serotonin norepinephrine reuptake inhibitor (SSNRI), or noradrenergic and specific serotonergic antidepressant (NaSSA).
- Tricyclic antidepressants (especially nortryptiline and desipramine) can be considered due to their co-analgesic benefit for neuropathic pain (refer to Appendix A -Medications Used in Palliative Care for Depression). Avoid with constipation, urinary retention, dry mouth, orthostatic hypotension, or cardiac conduction delays. 7. When anticipated survival time is short, consider psychostimulants due to their more immediate onset of effect, 2 but avoid them in the presence of agitation, confusion, insomnia, anxiety, paranoia, or cardiac comorbidity. 8. If life expectancy is 1-3 months, start a psychostimulant and an antidepressant together and then withdraw the stimulant while titrating the antidepressant upwards.

# Hyperlinks indicate additional information available in guideline sections above: A = Assessment M = Management
Depression screening question "Have you been depressed most of the time for the past two weeks?"

# Depression (A4) Vegetative symptoms
Due to progressive life-limiting illness (A5)

# Key Recommendations
- Use opioids first line for pharmacological management of dyspnea for patients with incurable cancer.
- Use of opioids in the non-cancer population for breathlessness, especially those with chronic obstructive pulmonary disease (COPD), needs extreme caution and probable consultation with a Palliative Care Physician.
Dyspnea is breathing discomfort that varies in intensity but may not be associated with hypoxemia, tachypnea, or orthopnea. It occurs in up to 80% of patients with advanced cancer. 1
Investigations and imaging should be guided by stage, prognosis, and whether results will change management.
- Ask the patient to describe dyspnea severity using a 1-10 scale.
- Identify underlying cause(s) and treat as appropriate. 2 3. History and physical exam lead to accurate diagnosis in two-thirds of cases. 3 4. Investigations: CBC/diff, electrolytes, creatinine, oximetry +/-ABGs and pulmonary function, ECG, BNP when indicated. 5. Imaging: Chest x-ray and CT scan chest, when indicated.
- Proven therapy includes opioids for relief of dyspnea. For non-cancer patients with breathlessness, especially those with COPD, use of opioids requires extreme caution and consultation with a Palliative Care Physician should be considered. 4 2. Oxygen is only beneficial for relief of hypoxemia. 5 3. Adequate control of dyspnea relieves suffering and improves a patient's quality of life. 6 4. Treat reversible causes where possible and desirable, according to goals of care. 5. Always utilize non-pharmacological treatment: education and comfort measures.

# } Pharmacological Treatment
Opioids, +/-benzodiazepines or neuroleptics, +/-steroids.

# Drug Comments

# Opioids (drugs of first choice)
- If opioid naive, start with morphine 2.5-5 mg PO (SC dose is half the PO dose) q4h or equianalgesic dose of hydromorphone or oxycodone. - Breakthrough should be half of the q4h dose ordered q1h prn.
- If opioid tolerant, increase current dose by 25-50%.
- When initiating, start an antiemetic (metoclopramide) and bowel protocol.
- Therapeutic doses used to treat dyspnea do not decrease oxygen saturation or cause differences in respiratory rate or CO 2 levels. 3 - Nebulized forms have NOT been shown to be superior to oral opioids and are not recommended. 7
- Prescribe prn for anxiety and respiratory "panic attacks".
- Lorazepam 0.5-2 mg SL q2-4h prn.
- Consider SC midazolam in rare cases.
- Methotrimeprazine 2.5-5 mg PO/SC q8h, then titrate to effect.
- Dexamethasone 8-24 mg PO/SC/IV qam depending on severity and cause of dyspnea. - Particularly for bronchial obstruction, lymphangitic, carcinomatosis, and SVC syndrome; also for bronchospasm, radiation pneumonitis and idiopathic interstitial pulmonary fibrosis.

# Supplemental Oxygen
- Indicated only for hypoxia (insufficient evidence of benefit otherwise). 6

# Pharmacological Treatments
Dyspnea screen (0-10 scale)

# Non-pharmacological Treatments

# Yes No
Tailor dose to each patient; those who are elderly, cachectic, debilitated or with renal or hepatic dysfunction may require reduced dosages; consult most current product monograph for this information: / databasdon/index-eng.php

# Key Recommendations
- Select anti-nausea medication based on the etiology of the nausea and vomiting.
- Nausea and vomiting are common, but can be controlled with antiemetics.
- Identify and discontinue medications that may be the cause.
- Further assessment may include lab tests and imaging to investigate (e.g., GI tract disturbance, electrolyte/calcium imbalance, intracranial disease, and sepsis). 4. Good symptom control may require rehydration, which can be carried out in the home, hospice, or residential care facility using hypodermoclysis, a simple, safe and effective technique that avoids venous access (refer to Appendix A -Hypodermoclysis Protocol).
- Non-pharmacological: modifications to diet (e.g., small bland meals) and environment (e.g., control smells and noise), relaxation and good oral hygiene, and acupressure (for chemotherapy-induced acute nausea, but not for delayed symptoms). 2. Pharmacological: match treatment to cause (e.g., if opioid-induced, metoclopramide (sometimes IV or SC initially) and domperidone are most effective). Most drugs are covered by the BC Palliative Care Drug Plan, except olanzapine and ondansetron (refer to Appendix B -Medications Used in Palliative Care for Nausea and Vomiting). 3. Consider pre-emptive use of anti-nauseates in opioid-naive patients. Hypodermoclysis is a simple, safe and effective technique for subcutaneously administering fluids to a patient who requires hydration. It avoids the need for venous access in patients who, at the end of life, often have very poor veins. In the home/ hospice/residential care facility settings, it can be carried out without the need for fully IV credentialed nursing staff. Refer to the local Home and Community Care office (refer Associated Document: Resource Guide for Practitioners) for when and how to refer.

# Nausea and Vomiting Management Algorithm
There are two critical considerations regarding initiating hypodermoclysis in palliative patients:
- Objectives and timelines must be clear and agreed upon by the family and caregivers.
- Will adding fluids to a patient whose organ function is failing precipitate cardiac failure and/or cause or worsen lung secretions?
- A 23-25 gauge butterfly needle is inserted under the skin at a 30-45 degree angle. Ask patients which site is preferred of the following choices:
- For ambulatory patients, consider using chest (subclavicular area), back (infrascapular area) and upper abdominal wall (avoiding waist). o For bed-bound patients, use medial or lateral thighs or upper abdomen. o Avoid previously irradiated skin, anterior or lateral thigh if edema is present, abdomen if ascites is present, breast tissue, lateral placement near the shoulder, arms, and perineum/groin. - The fluids used are commonly normal saline (0.9%), normal saline/dextrose (2/3-1/3) and Ringer's Lactate. Dextrose cannot be used as a hypodermoclysis solution. - The infusion rate can be up to 75 ml/hr. Solutions are infused by gravity, i.e., a pump is usually not necessary.
- Some patients may only require 1 litre 3-4 times per week, rather than daily administration. A smaller volume (

# Key Recommendations
- Follow opioid management principles.
- Utilize adjuvant medication for pain-specific management.

# Assessment } Signs and Symptoms
Use the OPQRSTUV mnemonic to assess pain:
- Continuous pain requires continuous analgesia; prescribe regular dose versus prn.
- Start with regular short-acting opioids and titrate to effective dose over a few days before switching to slow release opioids.
- Once pain control is achieved, long-acting (q12h oral or q3days transdermal) agents are preferred to regular short-acting oral preparations for better compliance and sleep. - Always provide appropriate breakthrough doses of opioid medication, ~10% of total daily dose dosed q1h prn.
- Incident pain (e.g., provoked by activity) may require up to 20% of the total daily dose, given prior to the precipitating activity.
- Use appropriate adjuvant analgesics at any step (e.g., NSAIDs, corticosteroids).
- Record patient medications consistently.

# Patient is at extreme risk of respiratory depression
Buprenorphine transdermal patch f a Fentanyl is primarily (75%) cleared as inactive metabolites by the kidney and methadone is cleared hepatically. b Morphine is the least preferred in renal failure because of renally cleared active metabolites. c Meperidine (Demerol) should not be used for the treatment of chronic pain. d In 2018, Health Canada removed the requirement for an exemption to the federal restriction on methadone prescribing. The College of Physicians and Surgeons of British Columbia has released appropriate guidance on prescribing methadone, a Methadone for Analgesia Guidelines, and a new Prescribing Methadone practice standard. Physicians are expected to acquire the relevant education and training to prescribe methadone for analgesia. This can be demonstrated through completion of the Canadian Virtual Hospice Methadone for Pain course (methadone4pain.ca) and/or by reading the Methadone for Analgesia guideline. e When changing from oral route to buccal or rectal route, use 1:1 dosing with the oral 10mg/ml concentrated solution, and modify if needed depending on effect. If larger doses are required, a more concentrated solution may be compounded, up to a maximum of 40mg/ml.  Island Health hospital pharmacy will concentrate to 50mg/ ml. f Not covered by BC Pharmacare.

# Opioid Switching ("rotation")
- Switch to another opioid when inadequate analgesia is obtained despite dose-limiting adverse effects (AEs). This allows for clearance of opioid metabolites and possibly more effective opioid receptor agonist profile from the new drug. - Switch to an equianalgesic dose of the second opioid, bearing in mind that published ratios are only a guide and that reassessment and dose modification are required. - When switching because of AEs (e.g., delirium or generalized hyperalgesia), determine the equianalgesic dose and reduce this dose by 25%. Observe closely, allowing for onset of the new and wearing-off of the previous drug. - Refer to Appendix A -Equianalgesic Conversion for Morphine. A, B, C

# Fentanyl Transdermal Patch Equianalgesic Conversion
- Assess whether symptom is fatigue or weakness (generalized or localized). 2. Distinguish fatigue from depression. 3. Look for reversible causes of fatigue or weakness (refer to Fraser Health, Hospice Palliative Care Symptom Guidelines, Fatigue, available at www.fraserhealth.ca/media/11FHSymptomGuidelinesFatigue.pdf).
- After treating reversible causes and providing non-pharmacological treatment recommendations, consider pharmacological treatment (refer to Appendix A: Medications Used in Palliative Care for Fatigue), if consistent with patient's goals of care.

# Addressing Adverse Effects from Opioids
If the AE is not managed symptomatically and persists for more than one week, switch to another opioid.

# Adverse Effect Intervention Constipation
- Stepwise escalation of regular oral stimulant or osmotic laxative on opioid initiation.

# The principles of the Guidelines and Protocols Advisory Committee are to:
- encourage appropriate responses to common medical situations - recommend actions that are sufficient and efficient, neither excessive nor deficient - permit exceptions when justified by clinical circumstances