Symbols:

• * Indicates not covered by ODB
• √ Indicates see website for reference &/ or additional information

Pain Management

• screen for pain: ask regularly (i.e., the 5th vital sign, use ESAS √ and observe for behaviours indicative of pain.
• assess to determine the etiology of the pain √
• initiate interventions considering the patient’s goals, PPS√ , pain type, kidney/liver function.
• monitor and document the efficacy of each intervention using a pain intensity scale of 0 – 10.
• assess efficacy of breakthrough doses one hour post oral dose, half hour post SC dose, 5 – 10 minutes post IV dose.
• reassess & revise the plan as necessary until goals are met.
• consult with a palliative care expert when comfort goals are not being met. √

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• start with q4h around the clock (ATC) dosing with immediate release (IR) opioid and titrate to effect or until side effects become unmanageable
• when titrating, allow the opioid to reach steady state before increasing the regular around the clock (ATC) dose
  • steady state occurs at 4 – 5 times the drug half-life. Half-life depends on the particular opioid and whether it is immediate release or long acting
• generally, immediate release opioids can be titrated every 24 hrs and long acting opioids can be titrated every 48 – 60 hrs
• once the steady state has been reached, a new order for the ATC dose of opioid is calculated based on the TOTAL opioid dose administered in the previous 24 hours [TOTAL = break through (BT) doses used plus regular ATC doses in 24 hours]. Use clinical judgment in determining the new ATC order
• always order a BT, immediate release dose:
  • whenever possible use the same opioid as is being administered on a regular basis
  • calculate approximately 10 % of the TOTAL daily dose of the scheduled ATC opioid and order it prn for uncontrolled pain (see page 17)
  • the breakthrough dose is calculated in the same way no matter which route of administration is being used
• consider opioid rotation for unmanageable side effects and adjuvant interventions for difficult to manage pain
• the fentanyl patch (LU 201) is a slow release form of a quick acting medication (fentanyl). Do not titrate to a stronger patch more rapidly than every 6 days
  • if pain is not managed, increase BT doses, using IR opioids (e.g., morphine, hydromorphone) until it is safe to titrate the patch √

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Opioid Toxicity

• metabolites of morphine and to a lesser extent, hydromorphone must be cleared renally; anyone with renal compromise (including the elderly) is at increased risk for toxicity
• suspect opioid toxicity if increased agitation occurs
• myoclonus may be an early warning sign of opioid toxicity
• dehydration may increase risk of toxicity

Consider Opioid Rotation if One of the Following Occurs

• decreased renal function (neurotoxic metabolite build up associated with morphine and hydromorphone)
• intractable nausea and/or vomiting
• delirium (hyperactive or hypoactive)
• myoclonus
• dysphoria
• persistent intolerable sedation

Opioid Rotation (Switching to Another Opioid)

When rotating opioids:

• determine the equianalgesic dose
• consider decreasing the dose of new drug by 30% to account for incomplete cross-tolerance √ .
• use breakthrough (BT) doses and titrate to effect.

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Equianalgesic Dose (Approximate Only)

• three Tylenol # 3s are approximately equal to morphine 10 mg PO plus acetaminophen 900 mg PO
• two Percocet are approximately equal to morphine 20 mg PO plus acetaminophen 650 mg PO
• remember incomplete cross-tolerance √
• methadone is used for analgesia. It has unusual pharmacodynamics and pharmacokinetics and multiple interactions with other drugs √ . Physicians require an exemption license to prescribe methadone for pain.

Fentanyl Patch

• do not use for rapidly escalating pain
• do not use in an opioid naïve person √
• do not cut reservoir patch
• patches are changed q72h (occasionally q48h); fentanyl does not have a short acting oral equivalent for BT pain √

  Starting Fentanyl:

  • starting dose: 60 - 134 mg oral morphine per day is approximately equal to fentanyl 25 mcg patch q 72h √
  • an appropriate BT dose for fentanyl 25 mcg patch would be morphine 10 mg PO q1h prn or hydromorphone 2 mg PO q1h prn
  • regular dosing of the q4h (IR) oral opioid is continued for 12 hours after applying a fentanyl patch
  • the patch can be applied simultaneously with the administration of the last dose of a long acting (q12h) oral opioid or 12 hours after administration of a q24h opioid

Stopping Fentanyl:

• fentanyl patch has 12-18 hour half-life
• commence regular ATC opioid dosing 12 hours after removing the patch; give BT doses as required

Analgesics to avoid

• Fiorinal® not for use in palliative care
• meperidine (Demerol®)- neurotoxic metabolite accumulation √
• pentazocine (Talwin®) - agonist-antagonist with severe psychotomimetic effects
• propoxyphene - increased risk of side effects profile in the elderly

Opioid Overdose

• use sedation scale to determine level of sedation √
• consider the PPS
• step 1: stimulate the person if sedation is increasing
• step 2: if sedation is unexpected and the sedation score is 3 and respiratory rate is ≤ 6/min and this is unexpected, consider judicious use of naloxone. If too much naloxone is given, it will precipitate a pain crisis. Starting IV dose: dilute naloxone 0.4 mg/ml with N/S 9 ml and give 1ml IV q 5-10 minutes until respirations > 6 and sedation level <3 √
• physician consultation required

Common Opioid Side Effects

• constipation: is universal and tolerance does not occur
• consider osmotic & stimulant laxatives daily, titrate to effect
• nausea / vomiting: consider CTZ, D-2 antagonist as a prophylactic measure; tolerance may develop
• sedation √ : usually temporary. If sedation is persistent, consider opioid rotation or use of methylphenidate. Consider the PPS

Must Know

• if treatment (e.g., radiation) results in decreased pain, then gradually decrease opioids. Too much opioid may lead to sedation as the pain level decreases

Pseudoaddiction / Tolerance / Dependence

• pseudoaddiction describes behaviours that may be perceived as drug-seeking but actually only occur when pain is under treated; the behaviours resolve when pain is effectively managed
• most patients over time do become physiologically dependent on opioids and will have withdrawal symptoms with abrupt discontinuation or major dose reduction √
• opioid tolerance and physical dependence are physiological and do NOT equate with addiction √

Wounds:

• morphine in intrasite gel for local analgesia √

Incident Pain / Procedural Pain

• pre-empt predictably occurring pain by using a prn dose in advance
• use a short acting opioid and administer prior to the procedure or event. Allow 1 hour following PO administration and ½ hour following SC for the opioid to reach peak effect
• first choice is sufentanil 12.5 -50 mcg SL 15 minutes prior to procedure; if sufentanil not available may use fentanyl injectable * can be used sublingually for incident or procedural pain √ 25-50 mcg SL 30 minutes prior to procedure
• consider EMLA ® topical cream for painful IV starts
  

Adjuvant / Co- Analgestic Pain Management

Consideration of the Etiology of Pain is Essential In Selectecting the Most Effective Adjuvant Medication

• opioids are first line, then consider appropriate co-analgesic/ adjuvant for each pain syndrome (e.g., bone, nerve, inflammatory, intracranial pressure, ischemia, muscle spasms)

Adjuvant Interventions

Bone Pain:

• NSAIDs
• bisphosphonates
• corticosteroids
• radiation
• consider orthopedic stabilization

Neuropathic Pain:

• radiation of tumour to relieve tumour pressure
• TCA and/or anti-convulsant meds; common drugs used are:
  • nortriptyline, amitriptyline
  • carbamazepine, valproic acid
  • gabapentin * √: for starting dose and titration guidelines
  • Pregabalin* √: indicated for diabetic peripheral neuropathy and postherpetic neuralgia
• consult anesthesia or interventional radiology for nerve block
• methadone √ is an excellent drug but requires a methadone exemption license for pain management; consult with a palliative care physician

Liver Capsule Pain:

• corticosteroids

Tumour expanding in a small space:

• corticosteroids
• radiation

Inflammatory Pain:

• NSAIDs
• corticosteroids

Raised Intracranial Pressure: (from intracranial tumours)

• corticosteroid
• radiation, neurosurgery

Muscle Spasms:

• benzodiazepine
• baclofen

Symptom Management

G.I. Protection √

• H2 antagonist (e.g., ranitidine 150 mg PO bid)
• cytoprotector (e.g., misoprostol 200 mg PO tid – qid)
• proton pump inhibitor (PPI), (e.g., rabeprazole 20 mg PO od)

Nausea (Consider Etiology)

Prokinetics (may be contraindicated in complete bowel obstruction):

• metoclopramide (10 – 20 mg PO/ SC */ IV *q 4h – 6h)
• domperidone 10 – 20 mg PO qid

CTZ, D2 Receptor or Antagonist:

• haloperidol 0.5 – 2.5 mg PO/ SC bid – tid

Steroid:

• dexamethasone 2 – 8 mg PO/ SC/ IV od

5HT3 Antagonist:

• ondansetron * √ 4 – 8 mg PO/SC/ IV bid – tid (main indication for use in early radiation/chemo induced nausea & vomiting)

Antihistamine:

• diphenhydramine 25 – 50 mg PO/SC/IV q4h prn

Cannabinoids:

• nabilone 0.25 mg – 2 mg PO bid

Vestibular Etiology:

• scopolamine 0.3mg SC q3-4h prn
• meclizine 25-50 mg PO tid prn
• Transderm-V Patch* change q 72h

Broad Spectrum:

• methotrimeprazine 2.5 – 12.5 mg PO/SC q6h prn
• prochlorperazine 5 -10 mg PO/PR/IV q4h prn (do not give SC)

Note: prochlorperazine and dimenhydrinate generally not very effective in patients receiving palliative care

Mouth Care √

• local institutions may have preferred formulations √
• saline or soda bicarbonate rinse and spit q1h prn
• chlorhexidine 0.2% rinse and spit q8h
• artificial saliva

Thrush (candidiasis):

• nystatin suspension 500,000 units qid (topical or swish and swallow); clean and soak dentures
• fluconazole 100 mg PO od x 10-14 days (LU #202); for maintenance dose 100 mg PO weekly

Painful Mouth:

• lidocaine viscous, swish and spit (caution: assess swallowing)
• morphine 5- 10 mg rinse and spit; morphine is not lipophilic and binds to raw wounds in mouth

Bowel Routine (daily dosing and prn)
Consider etiology of constipation √

Start concurrently with opioids & titrate individually or in combination:

• sennosides (1-8 tablets) PO bid - tid (mild stimulant)
• lactulose 15 – 60 ml PO od to qid (osmotic laxative)
• bisacodyl 5 mg (1 – 4 tablets) PO od – bid (stronger stimulant)
• bisacodyl suppository 10 mg PR prn
• milk of magnesia 15 – 60 ml PO od to qid (osmotic laxative caution in renal failure)
• Fleet Enema prn (caution in renal failure)
• methylnaltrexone *√ : consider etiology; use only in opioid induced constipation; if weight is: 38- 62 kg give mg SC for 62-114 kg give 12 mg SC; if weight falls outside these ranges dose is 0.15 mg/kg SC. Give SC 2 days for 2 weeks. If inadequate laxation response after 4 doses then discontinue. Can be given on a prn basis SC; may only be needed q 3-4 days

Malignant Non-operable Bowel Obstruction

• rule out obstipation versus other causes of mechanical obstruction
• assess current medications for administration by non-oral route

First choice is pharmacological management:

• consider NG tube decompression for short periods (i.e., 24-48h) to enhance efficacy of medication

Partial Bowel Obstruction:

• prokinetic: metoclopramide 10 – 20 mg SC*/IV * q4-6h
• steroid: dexamethasone 2 – 4 mg SC/IV od - bid
• antiemetic: haloperidol 0.5 – 1.0 mg SC/PO q 8-12h
• antispasmodic: hyoscine butylbromide * 10 – 20 mg SC/IV q 4-6h

Complete Bowel Obstruction:

• consider stopping prokinetic medications if there is increased abdominal cramping/pain with their use
• continue anti-inflammatory (dexamethasone), antiemetic
• consider IV fluids
• octreotide * 100 – 300 mcg SC bid or tid (reduces gastro- intestinal secretions)
• consider venting gastrostomy tube √

Malignant Ascites

Before paracentesis, maximize diuretics usage to decrease albumin loss:

• furosemide 40- 80 mg PO/IV* bid (0800h and 1400h) plus spironolactone 50 – 200 mg PO bid (0800 h and 1400 h)
• paracentesis is only for symptom relief

Hiccups (note–chlorpromazine causes orthostatic hypotension v)

• haloperidol 1 – 2.5 PO/ SC q4h prn
• metoclopramide 10 – 20 mg SC */PO qid
• baclofen 10 – 20 mg PO q4h prn
• methotrimeprazine 12.5 – 25 mg PO/SC q6h prn
• chlorpromazine 12.5 – 50 mg PO/IV q4h prn

Dyspnea

First Line:

• fan (air movement)
• oxygen √ for ODB criteria
• positioning of patient for ease of breathing & comfort
• emotional support and safety
• physiotherapy

Second Line:

• recent studies have indicated that the use of systemic opioid is more effective than nebulized opioid √
• if opioid naÏve, start with low dose, short acting opioid q4h for dyspnea control (e.g., morphine 2.5 - 5 mg PO q4h)
• if on long acting opioid for pain, increase the baseline by 30% for dyspnea control and adjust breakthrough dose
• use the adjusted breakthrough opioid dose for pain or dyspnea
• titrate opioid using pain management principles √

Other measures to consider based on etiology of dyspnea:

• nebulized normal saline q4 - 6h
• nebulized salbutamol and ipratropium (LU #258) q4 - 6h
• lorazepam 1 – 2 mg SL q1h prn for accompanying anxiety
• dexamethasone 4 – 8 mg PO/SC od and adjust according to response

Severe Progressive Dyspnea √

• consult with a Palliative Medicine Expert
• protocol for sedation for intractable symptoms at the end of life may be required √

Respiratory Secretions

• atropine 1% ophthalmic 3 gtts SL/Buccal Space q1-2h prn
• glycopyrrolate * 0.2 – 0.4 mg SC (each ml = 0.2 mg) q4h (non-sedating as does not cross blood-brain barrier)
• hyoscine hydrobromide * 0.4 mg SC q3h (also available as Transderm V patch * q 3 days – paranoia and confusion may develop in elderly patients)
• consider repositioning
• suctioning is not usually indicated

Hypercalcemia (Corrected value over 2.65 mmol √)

To calculate corrected calcium level =
       total serum calcium level + [(40 minus serum albumin level) x .02]
OR to correct, add 0.02 mmol for every gm albumin below normal

• hydrate with normal saline
• pamidronate 60 – 90 mg IV in 500 ml normal saline over 4 hours, q3-4 weeks – wait 72 hours post infusion to recheck levels
• zoledronic acid * 4 mg in 50 cc normal saline IV over 15 minutes q 3- 4 weeks

Excessive Sedation

• assess analgesic and reduce if possible
• consider opioid rotation
• methylphenidate 2.5 - 15 mg PO 0800 h & 12 noon (start low & titrate to maximum effect 30-60 mg od); may also improve cognitive function, activity (consider PPS, prior to initiation)

Delirium (consider etiology and treat appropriately)

Hyperactive, hypoactive (may masquerade as depression) and mixed √

• look for disordered thinking, fluctuating course, altered cognition
• consider opioid rotation
• haloperidol 0.5 – 5.0 mg PO/SC q4-6h prn as interim (first line)
• methotrimeprazine 5 - 50 mg PO/SC q4h prn

Depression

• consult PC team for emotional, psychosocial support
• antidepressants (SSRI & SNRI) (consider PPS before initiating)
• consider concurrent use of SSRI/SNRI with methylphenidate 10 – 20 mg PO bid 0800h & noon; suggested maximum 1 mg/kg/day; d/c when SSRI/SNRI effective

Acute Seizure Control (If patient is actively seizuring √)

• lorazepam 2 mg Buccally or SC stat and 2 mg Buccally or SC q30 min prn until controlled
• Or midazolam * 5 – 10 mg SC stat and q30 min until controlled

Ongoing maintenance if / when patient no longer able to swallow:

• phenobarbital 30 – 240 mg SC q 8-12h (not available in community above 30 mg/ml)
• midazolam 20 – 60 mg /24h per CSCI
• carbamazepine supp * 25% increase from oral dose; or 8 – 20 mg/kg/day, bid or qid
• valproic acid liquid 15 – 60 mg kg/day PR bid or qid
• diazepam 10-20 mg PR q 15 min prn

Myoclonic Jerking (can be due to opioid toxicity √)

• consider hydration
• consider side effects of medications
• check calcium and creatinine blood levels
• reduce or rotate opioid
• lorazepam 1 – 2 mg PO/SL/SC q6h
• clonazepam 0.5 – 2 mg PO qhs (or 0.5 mg PO q6h prn)

Terminal Restlessness

• eliminate all possible causes (e.g., urinary retention, fecal impaction)
• consult with person and family regarding intent of interventions
• haloperidol 1.0 mg – 5.0 mg SC q 6h
• haloperidol 1.0 mg – 5.0 mg SC q6h plus lorazepam 1 - 4 mg SC/SL q6h (or midazolam* 2.5- 5mg SC q 6h)
• methotrimeprazine 5 - 50 mg PO/SC od and q4h prn
• midazolam,* lorazepam (same as dosage for seizures)

Intractable Symptoms at End of Life

Criteria for sedation for intractable symptoms √:

• verify that symptoms are intractable; palliative medicine consultation highly recommended
• patient/family conference with PC team to inform and obtain consent for sedation as sedation precludes communication with patient; and suggest d/c IV/parenteral feeding
• possible medications that can be used for intractable symptoms at EOL include midazolam, methotrimeprazine, propofol, phenobarbital