The IAHPC Manual of Palliative Care
2nd Edition

III. PAIN CON'T

Table of Contents

The opioid analgesics are defined as drugs having morphine-like effects and act by interaction with the opioid receptors.

Classification

• Weak opioids—opioids for mild to moderate pain
  • codeine
  • tramadol
• Strong opioids—opioids for moderate and severe pain
  • buprenorphine
  • fentanyl
  • diamorphine
  • hydromorphone
  • methadone
  • morphine
  • oxycodone
  • pethidine

Equianalgesic doses of opioids

• The equianalgesic doses of different opioid drugs
• are only approximations
• do not take into account individual patient variation (differences in absorption, metabolism, excretion) some are derived from studies of single doses rather than continued therapy
• Each drug must be titrated against pain and side effects for each individual patient

Opioid substitution: switching from one drug to another

With the increasing availability of a range of opioid drugs, it has become common practice for patients with inadequate analgesia or troublesome adverse effects to be tried on a different drug. Substitution of one opioid drug for another has been termed opioid switching or opioid rotation. Opioid substitution results in improved analgesia and fewer adverse effects for many patients.

Opioid overdosage

Severe sedation or narcosis, with loss of consciousness and respiratory depression, can occur

• if the dose prescribed is too large
• if the patient takes an intentional overdose (likely to be more severe)

The risk factors for narcosis are

• elderly or frail patients
• renal impairment
• other causes of CNS depression, including other medications
• opioid naive patients
• patients with only mild pain
• patients whose pain has been acutely relieved by a procedure such as a nerve block

Opioid overdosage is very uncommon in palliative care if appropriate care is taken with selecting and titrating the dose.

Assessment of narcosis

• respiration rate (RR)
• oxygen saturation: SaO2. Is the patient cyanosed?
• is the patient rousable?
• has time of peak plasma level of last dose of opioid been reached?

Treatment of narcosis

• General
  • stimulate the patient
  • give oxygen
  • stop/withhold further opioid therapy
• RR < 5/min
  • naloxone 0.4mg IV or SC stat
• RR 5-7/min ± barely rousable/unconscious ± SaO2 <90%
  • naloxone 0.4mg in 10ml saline: 1-2ml IV or SC, q2-3min
  • the minimum effective dose of naloxone should be used
  • the aim is to improve respiratory function without causing recurrent pain or physical withdrawal
• RR = 8/min + rousable + SaO2 = 90%
  • Careful observation

Adverse effects of opioids

• Gastrointestinal
  • nausea and vomiting
    • usually settles after several days
    • give antiemetic, either regularly or PRN
    • if persistent, change to a different opioid
  • constipation
    • laxatives and dietary advice are required for the duration of opioid therapy
  • gastric stasis
    • metoclopramide or cisapride
• CNS
  • narcosis - see Overdosage
  • sedation
    • may resolve after a few days
    • reduce opioid dose
    • withhold less necessary drugs that are CNS depressants
    • consider an alternative opioid
  • psychotomimetic (agitated delirium)
    • reduce opioid dose
    • haloperidol
    • consider an alternative opioid
  • myoclonus
    • reduce opioid dose
    • benzodiazepine
• Respiratory
  • severe respiratory depression - see Overdosage
  • mild/moderate respiratory depression
    • reduce opioid dose
    • withhold less necessary drugs that are CNS depressants
    • consider an alternative opioid
  • suppression of cough reflex
  • Note: the respiratory effects may not be seen as adverse if opioids are being used to treat cough or breathlessness

Tolerance, physical dependence and psychological dependence

• Tolerance
• is a normal physiological response to chronic opioid therapy in which increasing doses are required to produce the same effect
• is uncommon in cancer patients with chronic pain in whom the need for increasing doses usually relates to disease progression
• is not a reason for "saving up" the use of opioid drugs until the terminal phase
• patients concerned that there will be "nothing left" for more severe pain should be reassured that the therapeutic range of morphine is very broad and that there is adequate scope to treat more severe pain if it occurs

• Physical Dependence
• is a normal physiological response to chronic opioid therapy which causes withdrawal symptoms if the drug is abruptly stopped or an antagonist administered
• patients whose pain has been relieved by surgical or other means should have their opioid reduced by about 25% per day
• patients should be reassured that physical dependence does not prevent withdrawal of the medication if their pain has been relieved by other means, providing it is weaned slowly

• Psychological dependence and addiction
• is a pathological psychological condition characterised by abnormal behavioural and other responses that always include a compulsion to take the drug to experience its psychic effects
• is rare in patients with cancer and pain even if it is anticipated that pain will be relieved by other means, opioids should not be withheld because of any concerns related to psychological dependence, although patients with a history of drug abuse should be managed carefully

In palliative care, concerns about tolerance, physical dependence or psychological dependence are never a reason to withhold opioid therapy if it is clinically indicated

The Underutilisation of Opioids: Opiophobia

1. Professional opiophobia

Reasons why doctors underprescribe and nurses underadminister opioid drugs

• belief that morphine hastens death
  • morphine may be used for months or years and, correctly administered, is compatible with a normal lifestyle
  • used properly, it does not hasten death
• fear of respiratory depression
  • used properly, morphine should not cause respiratory depression, although care must be taken with patients who are at risk of respiratory depression for other reasons
• "Morphine doesn't work"
  • morphine will be ineffective in controlling pain if
    • it is incorrectly administered
    • it is used for morphine-insensitive pain
    • matters of psychosocial concern have not been addressed
• Morphine causes unacceptable side effects
  • side effects should not be severe
  • respiratory depression is uncommon except in opioid naïve patients commenced on parenteral therapy
  • constipation occurs inevitably and requires explanation and advice about diet and laxative therapy
  • somnolence and nausea usually improve after several days
• Fear of tolerance, physical dependence, psychological dependence
  • concerns about these are never a reason to delay treatment with an opioid if it is clinically indicated

2. Patient opiophobia

Patients and their families may express concerns about opioid therapy, including

• "That means I'm going to die soon"
  • requires explanation that morphine can be used for months or years and is entirely compatible with a normal lifestyle
• "Nothing left for when the pain gets worse"
  • requires reassurance that the therapeutic range of morphine is sufficient to allow escalation of the dose if necessary
• "I'll become an addict"
  • requires explanation and reassurance about physical and psychological dependence
• "The morphine didn't work"
  • morphine may not relieve pain if
    • the dose was too low
    • it was given too infrequently
    • there were no instructions for breakthrough pain
    • it was given for opioid-insensitive pain
    • matters of psychosocial concern have not been addressed
• "I couldn't take the morphine"
  • unacceptable side effects should not occur
  • patients should be warned about somnolence and nausea and reassured that they are likely to improve after several days
  • constipation occurs inevitably and requires explanation and advice about diet and laxative therapy.
    
• "I'm allergic to morphine"
  • usually relates to nausea or vomiting that occurred when parenteral morphine was given to an opioid naïve patient for acute pain
  • immunological allergy to morphine is rare

Given explanation, reassurance and the cover of antiemetics, most patients can be started on morphine without ill effect.

Weak opioid drugs—drugs for mild to moderate pain

• codeine
• tramadol

Strong opioids—opioids for severe pain

• buprenorphine
• diamorphine
• fentanyl
• hydromorphone
• methadone
• morphine
• oxycodone
• pethidine (meperidine)

Fentanyl

Oral transmucosal fentanyl citrate (OTFC)

• is a ‘lozenge on a stick’ containing fentanyl in a hard sweet matrix
• used by placing it against the mucosa of one cheek and constantly moving it up and down, and changed at intervals from one cheek to the other
• provided safe and effective treatment for breakthrough pain in 75% of patients studied in trials
• 25% of patients either do not achieve analgesia with the highest dose (1600µg) or suffer unacceptable adverse effects
• there is no relationship between the effective dose of OTFC for breakthrough pain and the dose of opioid being used for background analgesia
  • each patient has to be individually titrated to find the appropriate OTFC dose
• OTFC lozenges are expensive.

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©2008 Published by IAHPC Press