Starting strong opioids – titrating the dose
☛ When starting treatment with strong opioids, offer patients with advanced and progressive disease regular oral sustained-release or oral immediate-release morphine (depending on patient preference), with rescue doses of oral immediate-release morphine for breakthrough pain.
☛ For patients with no renal or hepatic comorbidities, offer a typical total daily starting dose schedule of 20–30 mg of oral morphine (for example, 10–15 mg oral sustained-release morphine twice daily), plus 5 mg oral immediate-release morphine for rescue doses during the titration phase.
☛ Adjust the dose until a good balance exists between acceptable pain control and side effects. If this balance is not reached after a few dose adjustments, seek specialist advice. Offer patients frequent review, particularly in the titration phase.
☛ Seek specialist advice before prescribing strong opioids for patients with moderate to severe renal or hepatic impairment.
First-line maintenance treatment
☛ Offer oral sustained-release morphine as first-line maintenance treatment to patients with advanced and progressive disease who require strong opioids.
☛ Do not routinely offer transdermal patch formulations as first-line maintenance treatment to patients in whom oral opioids are suitable.
☛ If pain remains inadequately controlled despite optimising first-line maintenance treatment, review analgesic strategy and consider seeking specialist advice.
First-line treatment if oral opioids are not suitable – transdermal patches
☛ Consider initiating transdermal patches with the lowest acquisition cost for patients in whom oral opioids are not suitable and analgesic requirements are stable, supported by specialist advice where needed.
☛ Use caution when calculating opioid equivalence for transdermal patches: A transdermal fentanyl 12 microgram patch equates to approximately 45 mg oral morphine daily. A transdermal buprenorphine 20 microgram patch equates to approximately 30 mg oral morphine daily.
First-line treatment if oral opioids are not suitable – subcutaneous delivery
☛ Consider initiating subcutaneous opioids with the lowest acquisition cost for patients in whom oral opioids are not suitable and analgesic requirements are unstable, supported by specialist advice where needed.
First-line treatment for breakthrough pain in patients who can take oral opioids
☛ Offer oral immediate-release morphine for the first-line rescue medication of breakthrough pain in patients on maintenance oral morphine treatment.
☛ Do not offer fast-acting fentanyl as first-line rescue medication.
☛ If pain remains inadequately controlled despite optimising treatment, consider seeking specialist advice.
- • When starting an opioid, use immediate release (IR) until dose is stabilized. Alternatively, some clinicians may choose to start with an oral controlled-release (CR) formulation, with an IR form available for breakthrough pain.
- • In opioid naïve patients start with 2.5 to 5 mg of morphine or 0.5 to 1 mg of hydromorphone q4h with breakthrough medication ordered at 1.25 to 2.5 mg of morphine or 0.25 to 0.5 mg hydromorphone q1h prn.
- • Analgesic effectiveness can be reassessed after 24 hours as it takes five half lives to reach a steady state (5 x 4 hrs = 20 hrs).
- • Total all the regular and breakthrough opioid used in the last 24 hours to get the total daily dose (TDD).
- • Divide this amount by the number of doses for the next 24 hours (normally 6=q4h) and give this dose regularly q4h with 10% of the TDD given q1h p.r.n. as a breakthrough/rescue dose (BTD) for breakthrough/rescue pain.
- • Dose adjustments should not be made more frequently than every 24 hours. Also assess for end of dose pain, and the presence of incident pain, which may require further titration.
- • Use IR opioid formulations for breakthrough doses (BTD) and remember to increase the breakthrough dose proportionately when the regular dose is increased.
- • When full pain relief is achieved, yet adverse effect have developed, employ a dose reduction to try and maintain adequate pain control with diminished adverse effects.
- • Doubling the nightime dose will avoid wakening the patient in the early morning for a scheduled q4h dose, however, night loading doses should be considered only for patients with good pain control. The use of sustained release opioids appears to be a better dosing strategy, as shown in a study with SR morphine.
- • When good pain control is achieved with a stable dose with an immediate release formulation, consider use of a long acting product to improve compliance.
- • When the patient is on sustained release opioids or fentanyl patches it is usual to titrate the dose every 48 and 72 hours respectively. If fentanyl is used, total the amount of breakthrough opioid analgesic given in the last 24 hours and convert that amount to an additional equivalent size fentanyl patch. If titration is done frequently switch to a short acting preparation.
- • If pain is rapidly escalating or pain is requiring frequent titration use short acting opioids q4h until pain is controlled and opioid needs are stabilized. Consider development of tolerance (which may require opioid rotation) or reassessment for a new or progressive medical problem.
- • When patients are elderly or frail, titrate over a number of days rather than rapidly over 1 to 2 days.
- • For severe pain the rate of titration may need to be more aggressive.
Initiating morphine
• Reassure the patient about the safety and efficacy of opioids
• Prescribe a laxative and antiemetic
• For opioid naive patients:
– 2.5–5.0 mg of morphine elixir/immediate release tablet 4 hourly + equal dose to be taken PRN between regular doses if pain is not controlled
– if pain is not controlled, increase each dose by 25–50%
– when dosing is stable with good pain control, convert daily dose to a once or twice daily slow release preparation
• review daily during the titration phase (this can be done by phone)
Calculating breakthrough doses
• Traditionally 1/6 of the total daily opioid requirement has been used for PRN dosing. This does give an idea of the starting dose, which can be adjusted according to effect. Some patients will need smaller doses, some larger
https://web.archive.org/web/20200909090614/https://www.racgp.org.au/afpbackissues/2006/200610/20061004auret.pdf
OPIOID DOSE CONVERSION
The numerous available opioid dose conversion charts and tools show considerable variation. There are a number of reasons for this:
- there is wide interindividual variation in response to different opioids, so no equivalence value will be right for every patient
- supporting data is often extrapolated from single-dose studies (rather than continuous)
- some manufacturers have recommended “one-way” conversion values (i.e. from morphine to their drug) which are “cautious” and overestimate the relative potency of their drug; these values are not ideal if converting the other way (i.e. from their drug to morphine)
- incomplete cross-tolerance means that data from clinical cross-over studies do not necessarily give potency ratios which can be used for converting in both directions
Conversion values from different sources conflict:
- morphine PO 30mg = oxycodone PO 15mg (BNF, as per manufacturer’s SPC)
- morphine PO 30mg = oxycodone PO 20mg (Palliative Care Formulary)
Even from a single source, values may not be internally consistent e.g. the Palliative Care Formulary (an excellent authority on this matter) recommends:
- morphine PO 300mg = oxycodone PO 200mg (1:1.5) = oxycodone SC 133mg (1:1.5)
- morphine PO 300mg = oxycodone SC 150mg (1:2)
- morphine PO 300mg = diamorphine SC 100mg (1:3) = oxycodone SC 100mg (1:1, DoH)
Therefore values often need to be rounded up or down to make a consistent table. The on-line opioid conversion tool uses some values which would not be easy for day-to-day conversions without a calculator e.g. for morphine PO to morphine SC, many people use a 1:2 ratio, whereas a value of 1:2.25 is used in the calculator for more consistent results.
The important thing is to remember that all these conversions are approximations only.
https://book.pallcare.info/index.php?tid=125&dg=8
Wessex Palliative Physicians Handbook of Palliative Care 9th Edition 2019
Opioid Conversion Chart
OPIOID TOXICITY IN PALLIATIVE CARE
https://pharmacopallcare.blogspot.com/2020/09/opioid-toxicity-in-palliative-care-ika.html
↓↓↓↓↓↓↓
- ☛ Steroids have many indications for use in palliative care. Dexamethasone is the most commonly used corticosteroid due to the smaller number of tablets at higher doses, and the option for subcutaneous route if necessary. Dose used and duration of treatment varies depending on indication.
- ☛ Although the short life expectancy of some palliative patients means they are unlikely to be affected by more long-term side effects such as muscle wasting, weakness and osteoporosis, they can still experience diabetes and the more distressing symptoms of insomnia, agitation and psychosis.
- ☛ Choose dose of Dexamethasone based on indication, and document indication clearly in medical notes.
- ☛ Give dexamethasone as single morning dose, or if higher dose needed give in 2 divided doses, the second being no later than 2pm to minimize risk of sleep disturbance.
- • Dexamethasone has a long duration of action and can be prescribed as a single morning dose. At higher doses, the tablet burden may be reduced by giving two divided doses. Do not give later than 2pm to minimise sleep disturbance. In an emergency situation, the dose can be given at any time.
- • Higher doses given by SC injection may need to be divided with the recommended maximum volume of 2ml for a single SC bolus injection.
- • Dexamethasone may be stopped abruptly in those whose symptoms are unlikely to relapse if it has been taken for less than 3 weeks at a maximum dose of 6mg (unless the patient has had repeated courses or are within 1 year of stopping long term treatment).
- • Following high dose or prolonged treatment, the dose should be reduced gradually, under supervision, and be guided by whether the disease is likely to relapse as steroids are reduced. The dose can be reduced fairly rapidly, for example by 50% every 3-5 days to2mg daily, then more slowly as the physiological dose is reached, for example reduce by0.5mg every 5-7 days.
- • A more gradual dose reduction may be required in some patients. Monitor for symptom recurrence and consider maintaining at the lowest dose which controls symptoms.
- • When a patient is no longer able to take oral medications, the balance of benefit and burden of SC injections versus the potential for withdrawal reaction should be taken into consideration.
- • In dying patients it is usually appropriate to discontinue corticosteroids. However, all cases should be assessed individually and it may be beneficial to continue to achieve symptom control.
THE DOUBLE EFFECT
The Double Effect (sometimes called a rule, principle or doctrine) states that “The risk of a potential, known (foreseen), unintended consequence or side-effect of treatment is justified only if all the following criteria are met:
☛ The intended effect is good in itself
☛ The clinician’s intention is solely to produce the good effect
☛ The intervention is proportionate to the situation
☛ The good effect is not achieved through the bad effect”
There is a misconception that morphine related drugs and sedative drugs bring about death more quickly and that doctors both know this and in some way condone their use with the double effect.
It knows of no credible research evidence to suggest that a patient’s life is shortened either by opioids or sedatives when used in line with accepted palliative care practice.
The Double Effect is unnecessary to justify the use or dosing regimes necessary to manage pain or distress in all but the most exceptional circumstances.
According to ASCO, essential components of palliative care may include the following:
- Building rapport and relationships with patients and family caregivers
- Managing symptoms, distress, and functional status (eg, pain, dyspnea, fatigue, sleep disturbance, mood, nausea, constipation)
- Exploration of understanding and education about illness and prognosis
- Clarification of treatment goals
- Assessment and support of coping needs (eg, provision of dignity therapy)
- Assistance with medical decision making
- Coordination with other care providers
- Provision of referrals to other care providers as indicated
The Palliative Care Handbook: A Good Practice Guide Wessex Palliative Physicians Ninth Edition 2019
http://bswformulary.nhs.uk/chaptersSubDetails.asp?FormularySectionID=21&SubSectionRef=21&SubSectionID=A100&FC=1
http://eolp.co.uk/SIXSTEPS/
http://www.sixsteps.net/
Standards and Norms of Practice
https://www.chpca.net/professionals/norms.aspx
Resources to support good palliative and end of life care
https://www.palliativecarescotland.org.uk/content/links/
An electronic version of the INCTR Palliative Care Handbook
http://inctr-palliative-care-handbook.wikidot.com/
The GSF Centre in End of life Care Enabling generalist frontline staff to provide a gold standard of care for people in the last years of life: "End of Life Care is everyone's business"
http://www.goldstandardsframework.org.uk/
Signs and symptoms that suggest a person may be in the last days of life include:
- Signs such as agitation, Cheyne–Stokes breathing, deterioration in level of consciousness, mottled skin, noisy respiratory secretions and progressive weight loss
- Symptoms such as increasing fatigue, reduced desire for food and fluid, and deterioration in swallowing function
- Functional observations such as changes in communication, deteriorating mobility or performance status, or social withdrawal.
