Pain should be assessed with the aim to identify the underlying cause and treat appropriately.
Specific non-malignant causes of pain in relation to kidney disease include:
- Complications of underlying conditions e.g. polycystic kidney disease, diabetic neuropathy
- Complications of long term renal treatments e.g. calciphylaxis (tissue ischaemia due to calcification of tissue and small arteries in dialysis patients); ischaemic neuropathy due to arteriovenous fistulae; peritonitis with peritoneal dialysis
Most analgesia is excreted by the kidneys and any degree of renal impairment can reduce drug clearance. We use eGFR as a marker of how much drug clearance is likely to be affected by renal impairment.
Stage 4 and 5 kidney disease (eGFR <30) have the highest increased risk of toxicity from analgesia.
If a patient is still receiving dialysis, specialist renal advice should be sought regarding appropriate medication choice, dose and dose interval.
In general when prescribing analgesia in renal impairment:
- Immediate release preparations are safer than modified release preparations
- As required (PRN) administration of analgesia is safer than regular administration
- Starting with lower doses and increasing the interval between doses will be better tolerated
No opioid is completely safe in renal impairment.
All patients should be monitored for signs of opioid toxicity (i.e. respiratory depression, myoclonic jerks, hallucinations, altered mental state).
WHO Ladder Step 1 analgesics
Generally safe.
Metabolism: Extensively metabolised by the liver
Dose adjustments: Maximum 3g/24hrs. Minimum dose interval 6hrs.
Comments: Avoid dispersible/effervescent tablets (high sodium content), chronic use increases risk of renal impairment
Avoid if possible. (unless NSAID analgesia effective in last days of life and benefit outweighs risk).
Mechanism of action: Inhibit production of COX, reducing prostaglandin synthesis and therefore reduce inflammation.
Comments: Avoid in severe renal impairment. Can cause acute renal failure, increase risk of GI bleeding and increase cardiovascular risk.
WHO Ladder Step 2 analgesics
Avoid if possible.
Metabolism: Metabolites excreted by the kidneys and accumulate.
Comments: Most of its analgesic effect is from conversion to morphine by liver, with individual variation. Active metabolites will accumulate in renal impairment, so should be avoided.
Use with caution.
Metabolism: Metabolised by liver and excreted by kidneys.
Dose adjustments: Start with immediate release tramadol 50mg BD, maximum 200mg / 24 hours
Comments: Generally tolerated with dose reduction. As tramadol has both opioid and non-opioid analgesic effects, generally has fewer opioid side effects than other opioids at equivalent dose.
WHO Ladder Step 3 analgesics
Generally safe.
Metabolism: Metabolised by liver, no active metabolites.
Dose adjustments: No change in dose required.
See Section Relative Doses of Opioids in Pain Chapter
Comments: Rapid onset (< 5 minutes) but shorter duration of action so less useful for PRN analgesia.
Availability in concentrated form makes it suitable for administering large doses via syringe pump.
Generally safe.
Metabolism: Metabolised by liver, excreted by kidneys and GI tract
Dose adjustments: If using SL/SC to reduce initial starting dose by 50%, transdermal use only appropriate if pain stable.
Comments: Available as transdermal patch and sublingually. Long duration of action and only partially reversed by naloxone so if opioid toxicity may require naloxone infusion.
Generally safe.
Transmucosal preparations are licensed for cancer-related incident pain and should not be used in patients who are opioid naïve. Patients need to be on a minimum of 60mg oral morphine /24 hours (or equivalent) before transmucosal fentanyl can be considered. Seek specialist advice.
Metabolism: Metabolised by liver to inactive metabolites, excreted by kidneys. Less than 7% excreted unchanged/active.
Dose adjustments: No adjustment necessary as it does not appear to significantly accumulate in renal failure.
See Section Relative Doses of Opioids in Pain Chapter
Comments: Available as immediate release transmucosal preparations, parenteral (SC/IV) and as a transdermal patch.
If large doses fentanyl required via syringe pump, may require switch to alfentanil due to volume of medication.
Use with caution.
Metabolism: Primarily metabolised in the liver but excreted in the urine.
Dose adjustments: Use immediate release preparation 4–6 hourly initially and titrate cautiously. Remember that the lowest oral dose is 1.3mg which is equivalent to 10mg morphine.
Comments: Theoretically may cause similar problems to morphine but in practice often better tolerated than morphine. Available in immediate release and slow release oral preparations and s.c.
Use with caution.
Metabolism: Metabolised by liver, excreted by kidneys. Around 20% excreted unchanged in urine.
Dose adjustments: Lower starting doses advised in renal impairment with increased dose interval.
Comments: Clearance reduced in renal impairment. Often used as first line PRN in mild-moderate renal impairment as felt to be safer than morphine. Although metabolites can still accumulate.
Requires specialist input.
Metabolism: Metabolised in liver, excreted equally by kidneys and GI tract.
Dose adjustments: Significant individual variation, large volume of distribution and interaction with other medications makes titration of doses complex.
Comments: May have a role as analgesia in renal impairment, predominantly where patients cannot tolerate other opioids and there is a neuropathic element to the pain being reported. Requires specialist palliative care input and close monitoring when initiated.
Avoid if possible.
Metabolism: Metabolised by liver. Active metabolites (morphine-3-glucuronide and morphine-6-glucuronide) are excreted by kidneys.
Dose adjustments: If no other safer opioid available, start with immediate release morphine in low doses and increased dose intervals (e.g. 1.25mg – 2.5mg PO morphine every 4-6 hours).
Comments: Accumulation of active metabolites will significantly increase risk of opioid toxicity.
Should be avoided in severe renal impairment (EGFR <30).
Avoid if possible.
Metabolism: Pro-drug metabolised to morphine by liver, excreted by kidneys.
Dose adjustments: If no other safer opioid available, start with diamorphine in low doses and increased dose intervals (e.g. 1.25mg – 2.5mg SC diamorphine every 4-6 hours).
Comments: Available for parenteral administration (SC/IV/IM). Diamorphine and morphine doses are not equivalent.
Accumulation of active metabolites will significantly increase risk of opioid toxicity. Should be avoided in severe renal impairment (EGFR <30).
Adjuvant analgesics for Neuropathic Pain
Gabapentin and pregabalin are recommended first line agents for neuropathic pain but should be used with caution in lower doses in renal impairment. Recommended to start low and titrate slowly. Risk of respiratory depression particularly alongside opioids (MHRA)
Carbamazepine is commonly used for trigeminal neuralgia.
If an antidepressant type medication is being used for neuropathic pain, amitriptyline is generally safer than duloxetine in renal impairment, but has more antimuscarinic side effects.
Use with caution.
Metabolism: Metabolised by liver, some active metabolites.
Dose adjustments: Start with low dose (i.e. 10mg ON) and uptitrate slowly. Lower doses may be sufficient.
Comments: To be aware of increased cardiovascular risk and antimuscarinic side effects.
Generally safe.
Metabolism: Metabolised by liver, no active metabolites.
Dose adjustments: No dose adjustment required. Start with 100mg BD and uptitrate as necessary.
Comments: Usually well tolerated. To be aware has multiple drug interactions (CYP3A4 inhibitors will increase plasma concentration)
Use with caution.
Metabolism: Metabolised by liver, excreted by kidneys.
Dose adjustments: Start with low dose (i.e. 0.5mg ON PO).
Comments: Some active metabolites and long half life (20-60 hours) so may accumulate in severe renal impairment.
Avoid if possible.
Metabolism: Metabolised by liver, excreted by kidneys and GI tract.
Dose adjustments: If no other option, start low dose (15-30mg ON), but in general avoid use.
Comments: May accumulate in renal impairment. Risk of GI bleeds.
Use with caution.
Metabolism: Excreted by kidneys unchanged.
Dose adjustments:
Dose reduction in relation to severity of renal failure:
if EGFR <15 start with 100mg alternate nights and increase to maximum 300mg ON,
if EGFR 15-29 start with 100mg ON and increase to maximum 300mg BD.
Comments: May accumulate in severe renal impairment.
Use with caution.
Metabolism: Excreted by kidneys unchanged.
Dose adjustments:
Dose reduction in relation to severity of renal failure:
if EGFR <15 start with 25mg OD and increase to maximum 75mg OD,
if EGFR 15-29 start with 25-50mg OD and increase to maximum 150mg OD.
Comments: May accumulate in severe renal impairment.
Disclaimer
This Guide is intended for use by healthcare professionals and the expectation is that they will use clinical judgement, medical, and nursing knowledge in applying the general principles and recommendations contained within. They are not meant to replace the many available texts on the subject of palliative care.
Some of the management strategies describe the use of drugs outside their licensed indications. They are, however, established and accepted good practice. Please refer to the current BNF for further guidance.
While WMPCPS takes every care to compile accurate information , we cannot guarantee its correctness and completeness and it is subject to change. We do not accept responsibility for any loss, damage or expense resulting from the use of this information.