The principles of palliative symptom management:
- Symptoms can be affected by psychosocial, spiritual and existential distress: assessment of the whole person (body, mind, spirit) contributes to good symptom management
- A person cannot come to terms with their illness and the future if they have ongoing uncontrolled symptoms
- Medication and non-medication therapies are equally important
- Frequent reassessment and adjustment of therapy is essential to achieving best symptom control
- Communication can be therapeutic: follow the talk tips and suggestions as part of the management
Pain
Opioids are the medications of choice for moderate to severe pain in advanced disease. Adjuvants and other therapies should always be considered.
Always consider total pain.
Essential opioid principles
There are 10 essentials to know when prescribing opioids:
- Opioids are the medication of choice for both pain and dyspnea in advanced disease.
- 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.
- Persistent symptoms require regular dosing, i.e. short-acting opioid q4 hours.
- Not all opioids are the same, and inter-individual analgesia/side effects vary widely.
- Always order breakthrough with regular dosing: 10% of total daily opioid dose q1h Recalculate breakthrough dose when regular dose is changed.
- If 3 or more breakthroughs used in the last 24 hours, increase the regular dose.
- Titrate dose to the best symptom control with the fewest side effects.
- When you prescribe an opioid, prescribe a laxative.
- If side effects are intolerable, consider rotating opioid.
- Educate patient/family about control of symptoms and opioid safety.
Talk tip: “Controlling pain helps you to have better quality of life, and may even help you live longer.”
Talk tip: “Morphine medication can always be increased if you have more pain. It does not lose effectiveness over time.”
Talk tip: “Our goal is to prevent pain, so take the medication as directed even if you don’t have pain at that time.”
Opioid Equianalgesic Table – if other opioids available
Name | PO Dose |
---|---|
Codeine | 60mg |
Tramadol | 50mg |
Morphine | 10mg |
Hydromorphone | 2mg |
Oxycodone | 7.5mg |
Fentanyl – see note below |
Good choice in frail elders and patients with renal failure – BUT – use upper conversion range.Patients with normal renal function and non-elders use lower conversion range.Breakthrough dose
Calculate breakthrough dose based on morphine equivalents of the patch. Lowest dose patch = 12mcg/hr
Opioid dosing
Opioid | Starting PO Dose | Oral/ SC Dose | Starting PO Dose Frail, Older/CRF | Active Metabolites |
---|---|---|---|---|
Codeine (300-400mg max dose/day) | 30-60mg q4hr | 2 tabs/ n/a | 30mg q4hr | +++ |
Tramadol (400-600mg max dose/day) | 50-100 mg q4-6hrs | n/a | 50mg q4-6hrs | ++ |
Morphine | 5-10 mg q4h | 10mg/5mg | 2.5-5mg q4hr | +++ |
Hydromorphone | 1-2mg q4h | 2mg/1mg | .5-1mg q4h | ++ |
Oxycodone | 5-10mg q4h | 7.5mg/ n/a | 2.5-5mg q4h | 0 |
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
Opioid Calculations
Calculating breakthrough dose
Example
Morphine 50mg q4hr total daily dose 50×6=300mg. 300/10=30mg q1hrprn
Review + calc new dose
Example
Morphine 20mg q4hr, with 4 breakthroughs of 10mg q1h Total daily opioid dose (20×6) + (4×10) = 160mg
New dosing
160/6 = 25mg q4hr with breakthrough of 15mg q1hrprn
Switching to sustained release (SR) if available
Total daily dose
Add total regular dose + breakthroughs (if used) Total daily dose /2
Opioid SR q12 hours
Note about younger patients
They metabolize rapidly and may require q8hr dosing.
Opioid rotation
Total daily dose X morphine conversion factor = total daily morphine equivalents.
Total daily new opioid dose
Daily morphine equivalents/conversion factor to new opioid: reduce 25-50% in case of tolerance to previous opioid. Divide by dosing interval.
Morphine conversion factor
- morphine 10mg
- codeine 60mg
- tramadol 50mg
- hydromorphone 2mg
- oxycodone 7.5mg
Example
Oxycodone 10mg tab q4hr = 60mg of oxycodone/day = 80mg morphine equivalents per day = 60mg morphine per day (reduced for cross tolerance) = 10 mg morphine p.o. q4hr, morphine 5mg q1hrprn for breakthrough.
Oral to parenteral
Add up regular oral doses + breakthroughs (if used).
Total daily oral dose/2 = total parenteral dose. Divide by 6 to get q4hr dose
Example
Morphine SR 120mg p.o. q12h x 2 = 240mg total daily morphine dose p.o. = 120mg total parenteral morphine dose = 20mg s.c. q4h regular, morphine 12mg s.c. q1hrprn for breakthrough.
Opioid side effects
Sedation
Tolerance develops in 2-5 days. If not, rotate opioid if available. If symptom controlled, reduce dose.
Talk tip: “You may be drowsy for the first two days, but it should clear after that.”
Nausea
Nausea is common in the first week.
Metoclopramide
- 10mg p.o./s.c. qid
Haloperidol
- 0.05mg p.o./s.c. bid-tid
If on codeine and have nausea rotate to morphine. Stay on antiemetic if nausea persists after a week on morphine.
Constipation
Constipation always occurs with opioid use. Use stimulant laxative (senna) +/- osmotic laxative (PEG, lactulose).
Opioid-induced neurotoxicity
Spectrum of neurotoxicity symptoms from reduced LOC, myoclonus, hallucinations, delirium, and rarely to seizures. Rotate opioid if possible, consider hydration, treat concurrent infection if present.
Pruritis
Note: not a sign of allergy. Antihistamines may help if it persists beyond a week.
Respiratory depression secondary to opioids
Differential diagnosis: sedation from medications (benzodiazepines or neuroleptics), hypoglycemia, head trauma, exhaustion, actively dying.
Treatment
Mild – moderate: reduce/review dosing of all sedating medications.
Severe: Risk of severe pain, aspiration and opioid withdrawal with full dose naloxone. Dilute dose naloxone: dilute 1ml (0.4mg/ml) naloxone in 9ml saline, slow IV push (0.5-1ml q2min) Goal of naloxone is to improve ventilation. Partial reversal of respiratory disturbance by naloxone does not confirm opioid as the primary cause particularly if problems develop during stable opioid dosing.
Adjuvants
- Paracetamol/acetaminophen Mild to moderate pain only
- 100-500mg tablets or 500mg suppositories
- Maximum daily dose of 3-4g
Corticosteroids
- metastatic bone and visceral pain
- raised ICP
- neuropathic pain where nerve compression occurring
- dexamethasone 8-16mg p.o./s.c. daily in am, if effective at 48 hours reduce to lowest effective dose
Neuropathic pain
(includes pain secondary to ischemia)
- corticosteroids
- antidepressants: amitriptyline, mirtazapine,
- anticonvulsants: gabapentin 300-400mg q6hrs – start low and titrate up (max dose 3600mg/day) carbamazepine 100-200mg – start low and titrate up (max dose 1200mg/day, very poorly tolerated in frail older adults)
Metastatic bone pain
- corticosteroids
- NSAIDS: ibuprofen 200-400mg q6hrs (max dose 2400mg/day), diclofenac 25-50mg q8hrs (max dose 150-200mg/day or diclofenac 50-75mg injectable q8-12hrs
- bisphosphonates useful in widespread disease: pamidronate IV 90mg in 250ml of D5W over 2 hrs q 4 weeks. Avoid if severe renal failure
- radiotherapy if available
Visceral pain
- corticosteroids
- colicky pain: butylbromide 10-20mg p.o./s.c. tid-qid
Other therapies
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
Anxiety
Anxiety: Spectrum from response to a crisis → adjustment disorder → major anxiety disorder. Ensure anxiety not secondary to poor symptom control, especially pain or dyspnea.
Delirium can present with anxiety-like symptoms.
Medications
Antidepressants
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
Other therapies
- recommend supportive psychological and spiritual counseling
- discussing and providing information about disease-progression and the dying process may relieve specific anxieties
- avoid anxiety triggers
Ascites
Common in malignancy but also occurs in cirrhosis, CHF and tuberculosis.
Pharmacologic
Diuretics helpful in ascites due to portal hypertension (cirrhosis, CHF).
Spironolactone 50-100mg p.o. daily and furosemide 20-40mg p.o. daily. Increase as tolerated, continue depending on positive effect. Follow serum Na and K.
In malignancy – peritoneal disease, lymphatic obstruction, +/- liver mets – diuretics not helpful.
Paracentesis
In advanced malignancy, CHF and cirrhosis: paracentesis for symptomatic relief.
If tense abdomen (large ascites) safe to proceed without ultrasound.
Patient semi-recumbent with empty bladder.
Sterile technique. Prepare skin with antiseptic. Lidocaine to freeze entry site and tract to peritoneum.
Use Z technique to prevent leakage after procedure.
Use 14-16 gauge syringe with long needle attached to IV extension tube.
Gravity drain as much as possible in malignancy (5-6 liters) For other causes drain to comfort, monitor vitals to avoid excess fluid shift.
Consider tunneled catheter if fluid rapidly re-accumulates.
Bleeding
Localized bleeding: ulcerated wound, fungating tumor
Generalized: from platelet dysfunction, thrombocytopenia or coagulation disorder.
Localized bleeding
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:
- Vaginal: insert foley catheter into bladder, with speculum in – add acetone soaked gauze dressing until cavity full.
- Pressure dressings:
- Vagina: acetone-soaked dressings and place Foley catheter in bladder.
- 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.
- Bladder: continuous saline irrigation, 1% alum in saline irrigation, formalin 2-4% irrigation (painful).
- Rectum: Moh’s paste (see below) just to the bleeding site, cover with petroleum jelly and gauze (painful), formalin instillation (painful).
- Topical hemostatic agents:
- Tranexamic acid: 500mg tab dissolved in saline, soaked in gauze and applied with pressure.
- 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.
- epinephrine 1:1000: apply to site with gauze and pressure.
- 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.
Generalized 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)
Massive 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.
Bowel Obstruction
Medical Management: indicated in patients with multiple sites of obstruction, peritoneal carcinomatosis, advanced disease, poor performance status, inoperable, unstentable.
Surgery: indicated in patients with good performance status, slowly progressive cancer and survival estimated at >6 months.
Stents: Indicated in patients with good performance status, survival estimated >1 month, colonic obstruction 2cm above anal margin or duodenal obstruction proximal to ligament of Treitz.
Medications
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).
Other Therapies
- IV fluids as needed.
- NG can be used temporarily until nausea controlled by medications.
- Venting gastrostomy tube if nausea and vomiting persist.
Confusion/delirium
Principle: Always manage symptoms of delirium as well as consider reversible causes. If life expectancy is less than a few days, managing symptoms only may be appropriate.
Reversible causes
H=hypovolemia, hypoglycemia, hypercalcemia
I=infection
M=medications
B=bladder outlet obstruction/retention
O=oxygen deficiency
P=pain
Medications
Review and stop anticholinergics and benzodiazepines (unless alcohol withdrawal).
Non-agitated delirium
Haloperidol
- 2-5mg p.o./s.c. q8-12hrs + breakthrough does q1hr.
- frail older adult: 0.5-2mg p.o./s.c. q12hrs + breakthrough dose q1hr.
Levomepromazine/Methotrimeprazine
- 5-50mg p.o./s.c. at hs depending on need for sedation to sleep.
- frail older adult: 2.5-25mg p.o./s.c. at hs.
- if available quetiapine less likely to cause tardive dyskinesia in Parkinson’s Disease patients.
Talk tip: To family: “Delirium is common in people with serious illness. We always try to reduce the distress and if possible reverse the delirium.”
If close to end-of-life, may not be able to reverse, but always treat symptoms.
Agitated delirium
Severe delirium/agitation is an emergency.
Midazolam
- 5-10mg s.c. q20 mins to settle.
- Frail older adults: 1.25-5mg s.c. q20 mins to settle.
- For agitated terminal delirium: midazolam infusion 2.5mg-10mg per hour by continuous infusion pump. Bolus of 2.5-5mg q15 minutes prn for breakthrough agitation. Titrate infusion to have patient looking like peaceful sleeping.
Levomepromazine/Methotrimeprazine
- 5-10mg – 25mg s.c. q6hrso./s.c. + q1hr breakthrough dose.
- frail older adult: 2.5-5mg q6hrso./s.c. + q1hr breakthrough dose.
Talk tip: To family “Delirium is common in people with serious illness. We always manage the symptoms of agitation and distress and if possible, reverse the delirium.”
If close to end-of-life, may not be able to reverse, but always treat symptoms.
Other therapies
- 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.
Constipation
Common with opioids and reduced activity in advanced illness. Prevent constipation from opioids by daily use of laxative. Many local remedies will work well (papaya, kiwi, figs, ripe banana, olive oil, coconut oil) and should be tried before any medications.
Medications
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
Other therapies
Encourage:
- regular bowel routine
- privacy
- activity if possible
- oral fluids
Cough
Constant cough can cause headache, insomnia, vomiting and exhaustion.
Exclude potentially reversible causes of cough – infection/aspiration, GE reflux, obstruction/compression of bronchus, heart failure, COPD exacerbation, medications.
Non-pharmacologic: saline via nebulizer reduces dryness and irritation of airways.
Pharmacologic: Opioids are best treatment. No opioid better than another. If on regular opioid increase dose by 20-25%. If not on opioid initiate as for dyspnea.
Depression
Depression: spectrum from response to a crisis → adjustment disorder → major depressive disorder. Under-recognized and under-treated.
Good screening tool for all ages with advanced disease is geriatric depression scale.
Medications
(atypical)
- 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.
Other therapies
- Listening to patient, validating feelings and educated about disease and dispelling myths and fears about disease or dying.
Diarrhea
For HIV patient follow WHO HIV guidelines for treatment of persistent diarrhea.
In other palliative diseases, most common causes are: other bacterial or parasitic infections constipation with overflow diarrhea, C difficile infection due to antibiotic use, medications including laxatives, post-surgical changes.
Medications
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.
Other therapies
Drowsiness
Drowsiness: inability to hold conversation, read or concentrate because of sleepiness. Patient may or may not have co-existent tiredness.
Manage drowsiness because it may reduce quality of life.
Medications
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.
Talk tip: When prescribing any opioid, warn patient to expect drowsiness in the first 2-3 days.
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.
Dyspnea – shortness of breath
Opioids are the medications of choice for dyspnea in advanced disease.
Adjuvants and other therapies should always be considered.
Essential opioid principles
There are 10 essentials to know when prescribing opioids:
- Opioids are the medication of choice for both pain and dyspnea in advanced disease.
- 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.
- Persistent symptoms require regular dosing, i.e. short-acting opioid q4 hours.
- Not all opioids are the same, and inter-individual analgesia/side effects vary widely.
- Always order breakthrough with regular dosing: 10% of total daily opioid dose q1h Recalculate breakthrough dose when regular dose is changed.
- If 3 or more breakthroughs used in the last 24 hours, increase the regular dose.
- Titrate dose to the best symptom control with the fewest side effects.
- When you prescribe an opioid, prescribe a laxative.
- If side effects are intolerable, consider rotating opioid.
- Educate patient/family about control of symptoms and opioid safety.
Talk tip: “Controlling shortness of breath helps you to have better quality of life, and may even help you live longer.”
Talk tip: “Morphine medication can always be increased if you have more shortness of breath. It does not lose effectiveness over time.”
Talk tip: “Our goal is to prevent shortness of breath, so take the medication as directed even if you are not short of breath at that time.”
Opioid Equianalgesic Table – if other opioids available
Name | PO Dose |
---|---|
Codeine | 60mg |
Tramadol | 50mg |
Morphine | 10mg |
Hydromorphone | 2mg |
Oxycodone | 7.5mg |
Fentanyl – see note below |
Morphine to fentanyl
Fentanyl 25mcg/hr patch = 60-134mg morphine/day orally.
Good choice in frail elders and patients with renal failure – BUT – use upper conversion range.
Patients with normal renal function and non-elders use lower conversion range.
Breakthrough dose
Calculate breakthrough dose based on morphine equivalents of the patch. Lowest dose patch = 12mcg/hr
Opioid dosing
Opiod | Starting PO Dose | Oral/ SC Dose | Starting PO Dose Frail, Older/CRF | Active Metabolites |
---|---|---|---|---|
Codeine (300-400mg max dose/day) | 30-60mg q4hr | 2 tabs/ n/a | 30mg q4hr | +++ |
Tramadol (400-600mg max dose/day) | 50-100 mg q4-6hrs | n/a | 50mg q4-6hrs | ++ |
Morphine | 5-10 mg q4h | 10mg/5mg | 2.5-5mg q4hr | +++ |
Hydromorphone | 1-2mg q4h | 2mg/1mg | .5-1mg q4h | ++ |
Oxycodone | 5-10mg q4h | 7.5mg/ n/a | 2.5-5mg q4h | 0 |
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.
Opioid Calculations
Calculating breakthrough dose
Example
Morphine 50mg q4hr total daily dose 50×6=300mg. 300/10=30mg q1hr prn
Review + calc new dose
Divide this by dosing intervals.
This is new regular dose.
Recalculate breakthrough dose.
Example
Morphine 20mg q4hr, with 4 breakthroughs of 10mg q1h
Total daily opioid dose (20×6) + (4×10) = 160mg
New dosing 160/6 = 25mg q4hr with breakthrough of 15mg q1hr prn
Switching to sustained release (SR) if available
Total daily dose
Add total regular dose + breakthroughs (if used)
Total daily dose /2
Opioid SR q12hours
Note about younger patients
They metabolize rapidly and may require q8hr dosing.
Opioid rotation
Total daily dose X morphine conversion factor = total daily morphine equivalents.
Total daily new opioid dose
Daily morphine equivalents/conversion factor to new opioid: reduce 25-50% in case of tolerance to previous opioid.
Divide by dosing interval.
Morphine conversion factor
- morphine 10mg
- codeine 60mg
- tramadol 50mg
- hydromorphone 2mg
- oxycodone 7.5mg
Example
Oxycodone 10mg tab q4hr = 60mg of oxycodone/day = 80mg morphine equivalents per day = 60mg morphine per day (reduced for cross tolerance) = 10 mg morphine p.o. q4hr, morphine 5mg q1hr prn for breakthrough.
Oral to parenteral
Add up regular oral doses + breakthroughs (if used).
Total daily oral dose/2 = total parenteral dose.
Divide by 6 to get q4hr dose
Example
Morphine SR 120mg p.o. q12hx2 = 240mg total daily morphine dose p.o. = 120mg total parenteral morphine dose = 20mg s.c. q4h regular, morphine 12mg s.c. q1hr prn for breakthrough.
Opioid side effects
Sedation
If not, rotate opioid if available.
If symptom controlled, reduce dose.
Talk tip: “You may be drowsy for the first two days, but it should clear after that.”
Nausea
Nausea is common in the first week.
Metoclopramide
- 10mgo./s.c. qid
Haloperidol
- 5mg bid-tid
If on codeine and have nausea rotate to morphine.
Stay on antiemetic if nausea persists after a week on morphine.
Constipation
Constipation always occurs with opioid use.
Use stimulant laxative (senna) +/- osmotic laxative (PEG, lactulose).
Opioid-induced neurotoxicity
Spectrum of neurotoxicity symptoms from reduced LOC, myoclonus, hallucinations, delirium, and rarely to seizures.
Rotate opioid if possible, consider hydration, treat concurrent infection if present.
Pruritis
Note: Not a sign of allergy. Antihistamines may help if it persists beyond a week.
Respiratory depression secondary to opioids
Respiratory depression due to opioids = increased pCO2 + decreased pO2 + low respiratory rate.
Assess O2 saturation if possible, respiratory rate and signs of hypoventilation.
Differential diagnosis: sedation from medications (benzodiazepines or neuroleptics), hypoglycemia, head trauma, exhaustion, actively dying.
Treatment
Mild – moderate: reduce/review dosing of all sedating medications.
Severe: Risk of severe pain, aspiration and opioid withdrawal with full dose naloxone.
Dilute dose naloxone: dilute 1ml (0.4mg/ml) naloxone in 9ml saline, slow IV push (0.5-1ml q2min)
Goal of naloxone is to improve ventilation.
Partial reversal of respiratory disturbance by naloxone does not confirm opioid as the primary cause particularly if problems develop during stable opioid dosing.
Adjuvants
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.
Other therapies
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.
Talk tip: “Many people are fearful of dying when they feel short of breath. Do you feel like this?”
Patient will benefit from a plan for severe dyspnea episodes and discussion that they will not die gasping for breath as dyspnea can be managed.
Severe dyspnea in advanced illness is an emergency and needs treatment with opioids.
Hiccup/Singultus
Repeated involuntary contraction of diaphragm and respiratory muscles.
Most common causes are GI related: diaphragmatic irritation due to gastric distention, hepatomegaly, ascites, abscess, infection.
Identify underlying cause and correct if possible.
Pharmacologic
Metoclopramide 10-20mg p.o./s.c./i.v. q6hrs
Simethicone 80-160mg p.o. tid-qid
Baclofen 5-10mg p.o. tid
Chlorpromazine 12.5-50mg p.o. tid prn – can be very sedating. Use only if severe and persistent.
Midazolam 1-5mg s.c. prn if severe and persistent.
Hypercalcemia
Management depends on stage of disease, age (younger>older benefit from treatment), patient preference
IV Rehydration
- 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
Medications
- 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
Itch/Pruritis
Not all itch mediated by histamine. Central nervous system component involved in kidney and liver failure pruritis.
Treatment
- Treat dry skin
- Lidocaine 2-10% ointment/lotion used for localized itch. Toxicity possible if used over large areas
- Camphor 0.5% Menthol 0.5% in ointment base PRN
- Paroxetine 10-20mg p.o. daily (works in 24-48 hours, sedation)
- Mirtazapine 7.5-30mg p.o. daily (weight gain, sedation possible)
Lack of appetite/anorexia
Start by determining if lack of appetite is reversible: check for constipation, nausea, poor oral hygiene, thrush.
If due to cachexia from disease see the talk tips at the bottom of the page.
Medications
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.
Other therapies
- Treat reversible causes.
- Eating is for pleasure only in advanced illness.
- Suggest eating small amounts of favourite foods that are tolerated.
Talk tip: If the patient has cachexia, emphasize to patient/family that patient is declining because of disease not because they are not eating.
Focus on hunger and thirst needs, not hydration and nutrition.
If appropriate, review natural process of dying and that it’s natural to not want to eat and drink.
Last days and hours, death and afterwards
Symptoms to expect in last hours
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
- Use opioids to manage dyspnea and any pain.
- Provide frequent mouth care.
- If using IV fluids stop as may increase pulmonary congestion. If removal of fluids signals abandonment to family reduce fluid to 50ml/hour.
Discomfort, pain, dyspnea:
- For patient who has not received opioid in past 3 days: Morphine 2.5-5mg s.c. q1hrprn.
- For patient who has received opioid in past 3 days: Continue the same order if it is morphine. Rotate opioid to morphine s.c. if currently oral (see Opioid calculations).
Confusion and/or agitation:
- Levomepromazine/Methotrimeprazine 2.5-5mg s.c. q4hrs prn.
Upper airway secretions:
- Change position of patient.
- Hyoscine butylbromide 10-20mg s.c. bid-qid prn.
- Scopolamine 0.2mg s.c. q3hrs prn if available.
Fever:
- Acetaminophen 650mg per rectum q4hrs prn.
Terminal delirium:
- Do not allow the patient to remain agitated. See manage Confusion/delirium: Medications – Agitated delirium.
Natural process of dying
Supporting and managing the family
- Review patient status for symptoms that aren’t controlled.
- Gather information about family perception of patient’s comfort.
- Review goals of care and irreversibility of unfolding events, particularly if taking longer than family expects.
- Ask family how they’re doing, and watch for signs of intense anxiety or distress.
Continuous Palliative Sedation Therapy
- Use of continuous sedation to reduce the patient’s level of awareness of their symptoms.
- Refractory and intolerable suffering in the last 1-2 weeks of life.
- Aim of sedation is to relieve the suffering, does not hasten death.
- Usually for agitated delirium, refractory dyspnea or pain.
- Midazolam 1-10mg s.c./hr depending on level of sedation required.
- Levomepromazine 2.5-25mg s.c. q4-6hrs depending on level of sedation required.
At time of death
- 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.
Talk tip: Ask the family, “How were his/her final moments?” “How are you feeling?” “Do you have any questions?”
After death
Talk tip: This might be the family’s first experience with a death. Validate that what they are seeing is a natural part of the dying process.
The Last Hours of Living: Practical Advice for Clinicians
Full Medscape article with references can be found at Medscape.
Introduction
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.
Preparing for the Last Hours of Life
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.
Physiologic Changes and Symptom Management
Changes During the Dying Process
Fatigue, weakness, Cutaneous ischemia
- Erythema over bony prominences
- Skin breakdown, wounds
Decreasing appetite/ food intake, wasting
Decreasing fluid intake, dehydration
- Aspiration
- Peripheral edema due to hypoalbuminemia
Cardiac dysfunction, renal failure
- Tachycardia
- Hypertension followed by hypotension
- Peripheral and central cyanosis Mottling of the skin (livedo reticularis)
Neurologic dysfunction, including:
Decreasing level of consciousness, Decreasing ability to communicate
Terminal delirium
- Early signs of cognitive failure (e.g., day-night reversal)
- Agitation, restlessness
- Purposeless, repetitious movements
- Moaning, groaning
Respiratory dysfunction
Loss of ability to swallow
Loss of sphincter control
Pain
- Facial grimacing
- Tension in forehead, between eyebrows
Loss of ability to close eyes
- Eyelids not closed
- Whites of eyes showing (with or without pupils visible)
Fatigue and weakness
Patients who are too fatigued to move and have joint position fatigue may require passive movement of their joints every 1 to 2 hours.
Cutaneous ischemia
As the patient approaches death, the need for turning lessens as the risk for skin breakdown becomes less important.
Intermittent massage before and after turning, particularly to areas of contact, can both be comforting and reduce the risk for skin breakdown by improving circulation and shifting edema.
Avoid massaging areas of non-blanching erythema or actual skin breakdown.
Decreasing appetite and food intake
Most dying patients lose their appetite.
Unfortunately, families and professional caregivers may interpret cessation of eating as “giving in” or “starving to death.”
Studies demonstrate that parenteral or enteral feeding of patients near death neither improves symptom control nor lengthens life.
Anorexia may be helpful as the resulting ketosis can lead to a sense of well-being and diminish discomfort.
Clinicians can help families understand that loss of appetite is expected at this stage.
Remind them that the patient is not hungry, that food either is not appealing or may be nauseating, that the patient would likely eat if he or she could, that the patient’s body is unable to absorb and use nutrients, and that clenching of teeth may be the only way for the patient to express his/her desire not to eat.
Above all, help them to find alternative ways to nurture the patient so that they can continue to participate and feel valued during the dying process.
Decreasing fluid intake and dehydration
This may heighten onlookers’ distress as they worry that the dehydrated patient will suffer, particularly if he or she becomes thirsty.
Most experts feel that dehydration in the last hours of living does not cause distress and may stimulate endorphin release that promotes the patient’s sense of well-being.
Patients with peripheral edema or ascites have excess body water and salt and are not dehydrated.
Excess parenteral fluids can lead to fluid overload with consequent peripheral or pulmonary edema, worsened breathlessness, cough, and orotracheobronchial secretions, particularly if there is significant hypoalbuminemia.
Mucosal and conjunctival care
Coat the lips and anterior nasal mucosa hourly with a thin layer of petroleum jelly to reduce evaporation.
If eyelids are not closed, moisten conjunctiva with an ophthalmic lubricating gel or physiologic saline solution frequently to avoid painful dry eyes.
Communication with the unconscious patient
Although we do not know what unconscious patients can hear, extrapolation from data from the operating room and “near death” experiences suggests that at times their awareness may be greater than their ability to respond.
It is prudent to assume that the unconscious patient hears everything.
Advise families and professional caregivers to talk to the patient as if he or she were conscious.
Terminal delirium
It presents as confusion, restlessness, and/or agitation, with or without day-night reversal.
To the family who do not understand it, agitated terminal delirium can be very distressing.
When moaning, groaning, and grimacing accompany the agitation and restlessness, these symptoms are frequently misinterpreted as physical pain.
However, it is a myth that uncontrollable pain suddenly develops during the last hours of life when it has not previously been a problem.
A trial of opioids may be beneficial in the unconscious patient who is difficult to assess.
If the trial of opioids does not relieve agitation or makes the delirium worse or precipitates myoclonic jerks, pursue alternative therapies directed at suppressing the symptoms associated with delirium.
Respiratory dysfunction
Many fear that the comatose patient will experience a sense of suffocation.
Knowledge that the unresponsive patient may not be experiencing breathlessness or “suffocating,” and will not benefit from oxygen (which may prolong the dying process) can be very comforting.
Low doses of opioids and methotrimeprazine are appropriate to manage any perception of breathlessness.
If the patient is already on opioids the dose can be increased.
Loss of ability to swallow
Weakness and decreased neurologic function frequently combine to impair the patient’s ability to swallow.
Buildup of saliva and oropharyngeal secretions may lead to gurgling, crackling, or rattling sounds with each breath.
Once the patient is unable to swallow, cease oral intake.
Muscarinic receptor blockers (anticholinergics) are commonly used agents to control respiratory secretions when death is imminent.
They only prevent formation of new secretions so evidence suggests that the earlier treatment is initiated, the better it works.
If excessive fluid accumulates in the back of the throat and upper airways, it can be cleared by repositioning the patient.
Suctioning is frequently ineffective, as fluids are beyond the reach of the catheter, and may only stimulate an otherwise peaceful patient and distress family members who are watching.
Pain
Although difficult to assess, continuous pain in the semiconscious or obtunded patient may be associated with grimacing and continuous facial tension, particularly across the forehead and between the eyebrows.
The possibility of pain must also be considered when physiologic signs occur, such as transitory tachycardia that may signal distress.
Do not confuse pain with the restlessness, agitation, moaning, and groaning that accompany terminal delirium.
If the diagnosis is unclear, a trial of a higher dose of opioid may be necessary to judge whether pain is driving the observed behaviors.
When Death Occurs
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).
Notifying Others of the Death
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
In some cases, you may choose to tell someone by telephone that the patient’s condition has “changed,” and wait for them to come to the bedside to tell the news.
Factors to consider in weighing whether to break the news over the telephone include:
- whether death was expected,
- what the anticipated emotional reaction of the person may be,
- whether the person is alone,
- whether the person is able to understand,
- how far away the person is,
- the availability of transportation for the person, and
- the time of day (or night).
Inevitably, there are times when notification of death by telephone is unavoidable.
Use the same plan as you would for breaking bad news. See Communication section.
Myoclonus & Seizures
Myoclonus
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
Seizures/convulsions
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
Nausea
Multiple causes of nausea in advanced disease. Consider regular antiemetic if using 2 or more prns per day.
May need >1 antiemetic to control.
Medications
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
Malignant bowel obstruction: haloperidol, dexamethasone +/- metoclopramide (not in proximal obstruction)
Constipation: treat the constipation! Motion/positional: dimenhydrinate
Anxiety, fear, anticipatory nausea: levomepromazine/methotrimeprazine, nabilone, lorazepam in younger patients
Raised intracranial pressure: dexamethasone
Chemotherapy, radiotherapy-induced, dexamethasone ondansetron if available
Other therapies
- 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
Spasticity
Disruption of descending inhibitory modulation of motor neurons producing hyperexcitability.
Spinal cord injury, traumatic brain injury, cerebral palsy, stroke, ALS, MS are major causes.
Spasticity causes pain, reduced mobility, muscle spasms and contracture.
Treatment should be based on patient goals – relieve pain, improve mobility, reduce spasms at night, etc…
Non-pharmacologic
Manual therapy – stretching, massage, heat etc… splinting, aids to mobility.
Pharmacologic
Diazepam 2.5-5mg p.o.at bedtime to start. Very long half life.
If daytime therapy needed, titrate very slowly to 60mg p.o. daily in divided doses.
Baclofen 5-10mg p.o.tid, titrate very slowly to 100mg p.o. daily in divided doses.
Do not stop baclofen suddenly – severe withdrawal symptoms.
Spinal Cord Compression (SCC)
Most common malignancies: multiple myeloma, lymphoma, lung, breast, prostate, renal.
Be vigilant for SCC – cancer patient with new onset limb weakness, or loss of bladder/bowel control or back pain (worse with coughing, moving, neck flexion) consider SCC.
Prognosis for paralysis depends on stage of neurological damage at diagnosis – emergency action can save mobility.
Neuro exam to detect loss of sensation or motor.
Whole spine MRI or CT myelogram is imaging of choice.
Plain X-rays only detect bone destruction – many false negatives.
Management
While awaiting imaging stat dose of dexamethasone 10-20mg I.V, s.c., p.o. followed by 16mg per day in single dose.
If diagnosis confirmed by imaging or clinical judgement refer for radiation or surgical decompression if available.
Superior Vena Cava Syndrome
Superior vena cava obstruction by tumor invasion or external compression and/or clotting.
Symptoms: headache, blurred vision, dizziness, dyspnea, coughing, dysphagia
Signs: swelling of face +/- edema of arm, neck +/- arm vein distention
An emergency if respiratory stridor or severe dyspnea
Chest X-ray or CT scan may help diagnosis
Management
- 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.
Tiredness/fatigue
Tiredness is closely related to cachexia/anorexia and may be due to advanced disease.
Start by determining if the tiredness could be due to reversible causes.
Reversible causes
Start by determining if the cause is reversible:
- pain or dyspnea
- insomnia
- anemia
- hypothyroidism
- medication side-effects
- distress: depression/anxiety
Medications
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
Other therapies
- 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).
Wound Care
Goals are to control symptoms (pain, odor) manage infection, exudate and preserve dignity.
Frequency of dressing change dependent on exudate, smell and comfort.
Pain
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.
Topical Opioids
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.
Odor
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.