Manage

There are 10 essentials to know when prescribing opioids:

1. Opioids are the medication of choice for both pain and dyspnea in advanced disease.
2. Pain and dyspnea are strong drivers of the respiratory system. Opioids, using recommended starting doses and titrating appropriately, do not cause respiratory depression, even in cardiopulmonary disease.
3. Persistent symptoms require regular dosing, i.e. short-acting opioid q4 hours.
4. Not all opioids are the same, and inter-individual analgesia/side effects vary widely.
5. Always order breakthrough with regular dosing: 10% of total daily opioid dose q1h Recalculate breakthrough dose when regular dose is changed.
6. If 3 or more breakthroughs used in the last 24 hours, increase the regular dose.
7. Titrate dose to the best symptom control with the fewest side effects.
8. When you prescribe an opioid, prescribe a laxative.
9. If side effects are intolerable, consider rotating opioid.
10. Educate patient/family about control of symptoms and opioid safety.

Opioid Equianalgesic Table – if other opioids available

Calculating breakthrough dose

Review + calc new dose

Switching to sustained release (SR) if available

Opioid rotation

Oral to parenteral

Sedation

Nausea

Constipation

Opioid-induced neurotoxicity

Pruritis

Respiratory depression secondary to opioids

Adjuvants

Total Pain

• Pain has physical, psychological, spiritual, social, iatrogenic components
• Consider total pain when you cannot find source of pain, multiple medications trials not effective, pain resolving but distress still high
• Is anxiety or depression complicating the pain? If so treating the anxiety or depression will help the pain.
• Listen, validate the feelings of patients, correct any misunderstandings/myths about the disease or prognosis.
• Encourage discussion between patient and family about issues that are worrying the patient

Antidepressants

• see section on depression management

Benzodiazepines

• in frail older adults: levomepromazine/methotrimeprazine is better than benzodiazepine
• for moderate to severe ongoing anxiety: diazepam 2.5-10mg bid qid
• for acute short-acting anxiety/panic (temporary use until antidepressant onsets): lorazepam 0.5-2mg bid-qid prn

• recommend supportive psychological and spiritual counseling
• discussing and providing information about disease-progression and the dying process may relieve specific anxieties
• avoid anxiety triggers

Exclude systemic causes that could be contributing: NSAIDS (stop), Vitamin K deficiency due to liver failure (Vitamin K 5-10mg s.c. or p.o. if available).

Visible vessel: clamp and ligate or cauterize.

Multiple sites of vascular bed:

1. Vaginal: insert foley catheter into bladder, with speculum in – add acetone soaked gauze dressing until cavity full.
2. Pressure dressings:
   1. Vagina: acetone-soaked dressings and place Foley catheter in bladder.
   2. Nasopharynx: insert Foley catheter (lubricated with lidocaine gel) into nasopharynx and inflate balloon (5ml for child, 10ml for adult), gently pull forward until held in posterior nasopharynx, pack anterior nasal cavity. Remove after 48 hours.
   3. Bladder: continuous saline irrigation, 1% alum in saline irrigation, formalin 2-4% irrigation (painful).
   4. Rectum: Moh’s paste (see below) just to the bleeding site, cover with petroleum jelly and gauze (painful), formalin instillation (painful).
3. Topical hemostatic agents:
   1. Tranexamic acid: 500mg tab dissolved in saline, soaked in gauze and applied with pressure.
   2. Moh’s paste: zinc chloride (50 g), distilled water (25 mL), zinc starch (19 g), and glycerol (15 mL). Preserved at room temperature for 1 year. Painful – must give s.c. morphine before applying to area.
   3. epinephrine 1:1000: apply to site with gauze and pressure.
4. Rectum: Moh’s paste (see below) just to the bleeding site, cover with petroleum jelly and gauze (painful), formalin instillation (painful), sulcrafate enema: 2g in 20ml suspension bid for 10 days – radiation induced bleeding.

Systemic measures: (also used for intractable localized or localized that is not amenable to local measures).

Tranexamic acid: 1.5gm stat then 500-1000 tid. Discontinue 1 week after bleeding stopped or reduce to 500mg tid.

Radiotherapy: helpful for refractory localized bleeding and bleeding in a hollow organ (not radiation caused bleeding)

Rare but distressing for patient, family and staff.

Major arterial erosion – manifests as surface hemorrhage, hemoptysis, hematemesis, rectal bleed.

Identify patients at risk: ulcerating mass in neck, recurrent smaller bleeds from lung, gut, coagulation problems.

If no radiation therapy possible to prevent massive bleed, then prepare for possibility.

• Keep dark (black, brown, dark green or blue) towels at bedside.
• Sedation for patient drawn up and available for use – lorazepam 1-2mg i.v., s.c., i.m. or midazolam 5-10mg i.v., s.c., i.m.. Will keep for up to 30 days if kept in dark envelope or container.
• Turn patient on side if hematemesis or hemoptysis occurring. Administer sedation. Repeat dose in 10 min if bleeding ongoing and patient not sedated.
• Apply pressure to surface bleed with dark towels.

If bleeding risk high warn family and prepare them to act. Unless patient asks, consider discussing only with family.

Needs a combination of medications:

• Antiemetics: haloperidol +/- metoclopramide (not in proximal obstructions) see Manage nausea.
• Analgesics: opioid regular +prn for constant pain – see Manage pain/Opioids.
• Antispasmodic only if severe cramps: hyoscine butylbromide 10-20mg s.c. tid-qid.
• Corticosteroids: dexamethasone 8-16mg s.c. once daily in AM trial for 5-7 days – stop if no improvement in obstruction.
• Anti-secretory agents: ranitidine 100mg s.c. bid (as good as octreotide but much cheaper).

• IV fluids as needed.
• NG can be used temporarily until nausea controlled by medications.
• Venting gastrostomy tube if nausea and vomiting persist.

Review and stop anticholinergics and benzodiazepines (unless alcohol withdrawal).

Non-agitated delirium

Agitated delirium

• Limit activities and noise around patient.
• Use natural light to orient patient to day/night time.
• Familiar/calm people with the patient.
• Avoid physical restraints.

Osmotic laxative

• PEG 3350 17-34g in juice daily if available.
• Lactulose 15-30ml daily or bid if available.

Stimulant

• Senna 1-3 tabs daily to bid.
• Bisacodyl 10-30mg tablets once daily.

Suppository

• Bisacodyl 10mg suppository once daily.

Softeners

• Docusate not supported by evidence.

Enemas

• Mineral oil

Encourage:

• regular bowel routine
• privacy
• activity if possible
• oral fluids

• Helpful with neuropathic pain, insomnia, appetite.
• Helpful in those that have anxiety and depression.

SSRI

• for depression without co-existing pain.
• citalopram 10-40mg/day. Start low and titrate up every two weeks.

TCA

• not recommended in frail older adults.
• Amitriptyline 25-150mg once daily. Start low and titrate up every two weeks.

• Listening to patient, validating feelings and educated about disease and dispelling myths and fears about disease or dying.

If diarrhea severe use oral rehydration solution to maintain adequate hydration. Loperamide 2-4mg as needed, up to 16mg/day.

Codeine 10mg tid or morphine 2.5-5mg for more severe diarrhea.

Manage opioid side effects

• Common side effect with starting/increasing dose; should clear within 48-72 hours.
• If drowsiness persists and pain is controlled, reduce opioid.
• If drowsiness persists and pain is not controlled, rotate opioid.
• If unable to reduce or rotate opioid, consider stimulant.

Methylphenidate if available

• 5-10mg p.o./s.c. in the a.m. and noon.
• frail older adult: 2.5-5mg p.o. in a.m. and noon.

There are 10 essentials to know when prescribing opioids:

1. Opioids are the medication of choice for both pain and dyspnea in advanced disease.
2. Pain and dyspnea are strong drivers of the respiratory system. Opioids, using recommended starting doses and titrating appropriately, do not cause respiratory depression, even in cardiopulmonary disease.
3. Persistent symptoms require regular dosing, i.e. short-acting opioid q4 hours.
4. Not all opioids are the same, and inter-individual analgesia/side effects vary widely.
5. Always order breakthrough with regular dosing: 10% of total daily opioid dose q1h Recalculate breakthrough dose when regular dose is changed.
6. If 3 or more breakthroughs used in the last 24 hours, increase the regular dose.
7. Titrate dose to the best symptom control with the fewest side effects.
8. When you prescribe an opioid, prescribe a laxative.
9. If side effects are intolerable, consider rotating opioid.
10. Educate patient/family about control of symptoms and opioid safety.

Opioid Equianalgesic Table – if other opioids available

Morphine to fentanyl

Fentanyl has no active metabolites so well tolerated in renal failure

Starting p.o. dose based on patient being opioid naive: patient has NOT had 5 days of continuous opioid exposure (i.e. short-acting q4hr p.o./s.c.; long-acting q12hr; transdermal)

Morphine conversion factor: see Opioid Equianalgesic Table

Methadone: need to know how to use. Also used for substance dependence.

Calculating breakthrough dose

Review + calc new dose

Switching to sustained release (SR) if available

Opioid rotation

Oral to parenteral

Sedation

Nausea

Constipation

Opioid-induced neurotoxicity

Pruritis

Respiratory depression secondary to opioids

Levomepromazine/Methotrimeprazine

• 5-10mg p.o./s.c. tid
• frail older adults: 2.5-5mg p.o./s.c. tid

Benzodiazepines

• no evidence that they reduce dyspnea.
• may cause delirium in frail older adults.

Oxygen

• little evidence that it relieves dyspnea even in hypoxic patients.

Furosemide

• if heart failure is cause of dyspnea, give furosemide 40-80mg p.o. or s.c. daily.

Anti-anxiety

• if strong anxiety component, consider anxiolytics or antidepressants.

Fanning the patient

• stimulates trigeminal V2 branch and reduces dyspnea.
• direct gentle breeze across face.

Calm presence

• a calm provider is essential.
• family distress can exacerbate dyspnea.
• meditation/relaxation/prayer may help.

Position

• 45-60 degrees upright, arms away from sides supported by pillows.

• Normal saline + KCL (10mEq/l) at a rate of 2-3 liters/24 hrs
• Furosemide not helpful
• Monitor K⁺, Na⁺, Cr, Ca⁺² and fluid status until Ca⁺² normal

• Pamidronate I.V. 60-90mg in 250-500ml normal saline over 2-3 hrs very effective but may be expensive
• Clodrinate 1500mg in 250-500ml normal saline over 2-3 hrs I.V. or 6-8hrs s.c. but not very effective
• If severe renal impairment (eGFR<30) rehydrate before giving above medications
• Steroids useful in hematological cancers only

Appetite stimulants

• Usually not effective in patients with advanced disease.

Corticosteroids

• Dexamethasone 4mg p.o./s.c. in a.m. daily may help temporarily.
• Prednisolone 5mg tablet in a.m. daily.

Treat early satiety with metoclopramide or domperidone.

• Treat reversible causes.
• Eating is for pleasure only in advanced illness.
• Suggest eating small amounts of favourite foods that are tolerated.

Two main roads to death:

Usual (up to 90%)

• Lethargic → obtunded → comatose → death

Difficult (don’t allow to happen!)

• Restless → confused → delirious →myoclonus → seizures → comatose → death

Managing symptoms in last hours

Natural process of dying

• Shift the focus of care to family and caregivers.
• Make the space and time for cultural and religious rites.
• If you know the patient, take some time yourself to review what has happened and say goodbye.

Clinical issues that commonly arise in the last hours of living include the management of feeding and hydration, changes in consciousness, delirium, pain, breathlessness, and secretions.

In anticipation of the event, inform the family and other professionals about what to do and what to expect.

Care provided during those last hours and days can have profound effects, not just on the patient, but on all who participate.

At the very end of life, there is no second chance to get it right.

During the last hours of their lives, most patients require continuous skilled care.

The environment must allow family and friends access to their loved one around the clock.

Advance preparation of family is essential.

Everyone must be aware of the patient’s health status, knowledgeable about the potential time course, signs, and symptoms of the dying process, and their potential management.

Help families to understand that what they see may be very different from the patient’s experience.

If they are left unprepared and unsupported, family members may live with frustration, worry, fear, or guilt that they did something wrong or caused the patient’s death.

Although it is possible to give families or professional caregivers a general idea of how long the patient might live, always advise them about the inherent unpredictability of the moment of death.

Changes During the Dying Process

Neurologic dysfunction, including:

Fatigue and weakness

Cutaneous ischemia

Decreasing appetite and food intake

Decreasing fluid intake and dehydration

Mucosal and conjunctival care

Communication with the unconscious patient

Terminal delirium

Respiratory dysfunction

Loss of ability to swallow

Pain

Encourage those who need to touch, hold, and even kiss the person’s body as they feel most comfortable (while maintaining universal body fluid precautions).

When letting people know about the death, follow the guidelines for communicating bad news.

Try to avoid breaking unexpected news by telephone, as communicating in person provides much greater opportunity for assessment and support.

If additional visitors arrive, spend a few moments to prepare them for what they are likely to see.

For many, moving the body is a major confrontation with the reality of the death.

Some family members will wish to witness the removal.

Others will find it very difficult and will prefer to be elsewhere.

Telephone Notification

May be a sign of opioid neurotoxicity.

If combined with other symptoms of opioid neurotoxicity (sedation, confusion, hallucinations, agitation) rotate opioid if possible.

See Manage pain Opioid Calculations

If patient in last hours to days of life manage myoclonus with midazolam 1-5mg s.c. q1hr prn or lorazepam 0.5-2mg q6-8hrs prn.

If another opioid not available consider reducing dose of opioid and adding: adjuvant medication such as dexamethasone for all types of pain, and dyspneaneuropathic adjuvant for neuropathic pain e.g. amitriptyline or mirtazapine, NSAID for bone pain

Immediate therapy:

• lorazepam 1-2mg i.v., s.c., i.m. q10 min until stopped
• midazolam 5-10mg i.v., s.c., i.m. q10 minutes until stopped
• diazepam 5-10mg i.v., s.c., i.m. q10 minutes until stopped

Status epilepticus: if seizure persists after 3 doses of above add Phenobarbital 100mg sc.

Prevention of further seizures if medications available: Phenytoin 300mg q2 hrs X 3 doses to load.

Maintenance dose 300-400mg once daily depending on response and side effects.

For severe renal function reduce dose by 50%.

Blood levels just before next dose 5 days after initiation or dosage change.

Beware medication interactions

Metoclopramide

• 10-20mg p.o./s.c. qid
• in severe renal failure: 5mg p.o./s.c. qid

Haloperidol

• 1-2 mg p.o./s.c. bid-tid
• frail older adults: 0.5-1mg p.o./s.c. bid

Dexamethasone

• 4-8mg p.o./s.c. once daily in a.m.

Levomepromazine/Methotrimeprazine

• 2.5-5mg p.o./s.c. bid-tid

Ondansetron

• 4-8mg p.o., s.c., I.V. q 8hrs

Dimenhydrinate

• 25-50mg p.o./s.c. tid to qid

Nabilone

• 0.5-2mg bid

Suggested medications for types of nausea

• suggest small meals and small volumes of liquids
• cool foods have less odor – less nausea
• treat constipation
• inhaling isopropyl alcohol from a soaked cloth or gauze pad reduces nausea rapidly and gives relief until medication starts to work

• Keep head elevated.
• Manage dyspnea.
• Dexamethasone 12-16mg daily I.V., s.c., p.o. for emergency treatment. Lower dose for less emergent treatment.
• Radiotherapy, chemotherapy, anticoagulation for clots as appropriate and available.

Start by determining if the cause is reversible:

• pain or dyspnea
• insomnia
• anemia
• hypothyroidism
• medication side-effects
• distress: depression/anxiety

For insomnia:
Levomepromazine/Methotrimeprazine

• 2.5-10mg p.o./s.c. HS

Zopiclone

• 3.75-15mg p.o. HS

Trazadone

• 12.5-50mg p.o. HS

• Encourage exercise, if possible.
• Pace level of activity: prioritize activities so energy is available for most meaningful ones, and limit visitors.
• Transfuse if anemic (but do not repeat if there’s no benefit).

May be constant or incident with dressing change or movement.

Systemic opioids may not control pain adequately.

Opioid receptors present on open wounds and fungating tumors.

Methadone powder 100mg in 10g of inert wound powder (1% concentration).

Use 2.5g of mix per 15cm² (3inch²) of surface area (approx.).

Apply as last step prior to dressing.

Shake on wound or tumor – completely cover open tissue with a thick layer of powder.

Ensure undermined tissue surface is covered with mix.

If pain relieved, patient drowsy – reduce systemic opioid.

May use morphine in hydrophilic gel at 1% concentration if methadone unavailable.

For dressing change pain: see Incident pain.

Irrigate wound with warm saline, removes necrotic tissue and bacteria causing smell.

Local debridement by soaking necrotic areas with saline-filled gauze and gently wiping.

Bleeding risk high with cutting tissue in malignant wound.

Metronidazole tablets crushed and sprinkled over the wound (after the topical opioid).

Odor controlled with tray of cat litter or charcoal under patient’s bed.

If smell ongoing, metronidazole 500mg p.o. bid can be tried. Not as effective as topical.