Opioid toxicity in palliative care

Introduction

Opioids can have unwanted side effects. These include constipation, nausea, drowsiness, itch, dry mouth, opioid toxicity and opioid-induced respiratory depression.

Opioid toxicity is caused by the accumulation of toxic opioid metabolites. It can occur when opioids are prescribed by any route, at any dose and for any indication and is often precipitated by deteriorating renal and/or liver function. Mild to moderate opioid toxicity is relatively common in people receiving palliative care. It is best to identify opioid toxicity early as it needs to be actively managed. All patients prescribed opioids should be monitored for the signs and symptoms of opioid toxicity (see table below).

Opioid-induced respiratory depression is a potentially life-threatening side effect of opioids. It is very rare when opioids are titrated carefully, as in palliative care, but may be seen in severe opioid toxicity. It is more commonly seen in the context of opioid overdose (deliberate or inadvertent) or in the acute care setting. If this is suspected, see the emergency guideline opioid induced respiratory depression.

Assessment

First check respiratory rate and oxygen saturations

IF respiratory rate (RR) <8 breaths/minute AND oxygen saturations <85% FOLLOW opioid induced respiratory depression guideline DO NOT USE THIS GUIDELINE

Opioid toxicity

Mild

Moderate

Severe

Symptoms and signs

Vivid dreams

Pseudohallucinations

Occasional myoclonus

Vivid dreams or nightmares

Hallucinations

Persistent myoclonus

Mild hyperalgesia

Hallucinations

Delirium

Severe myoclonus

Reduced conscious level or coma

Severe hyperalgesia

Respiratory depression (rare) opioid induced respiratory depression

Management

See mild toxicity management section

See moderate toxicity management section

See severe toxicity management section

Note

Pinpoint pupils in palliative patients are not necessarily a sign of opioid use or toxicity as this can occur due to other factors.
In very rare cases, respiratory depression can evolve from mild, moderate or severe toxicity and can become life threatening. Regular nursing observations and review are necessary to ensure that this is identified early.

Management

Severe toxicity management

If the patient is:

pain free, consider omitting the next dose of modified-release opioid. Reduce the background and as required opioid by 30–50%.
in pain, seek specialist advice for changing opioid and other analgesic approaches.

Continue to monitor respiratory rate and oxygen saturation. If RR <8/min and oxygen saturation <85%, refer to the opioid-induced respiratory depression palliative emergency guideline opioid induced respiratory depression.

For opioid-induced delirium or hallucinations, consider low-dose haloperidol until symptoms resolve, for example 500 micrograms every 8 hours, as required.
Consider appropriateness of checking bloods for urea and electrolytes (U&Es), calcium, liver function test (LFT), C-reactive protein (CRP) and full blood count (FBC).
Consider intravenous (IV) or subcutaneous (SC) fluids if appropriate to promote renal excretion of opioid metabolites.
Monitor the individual’s observations every 15-30 minutes for worsening toxicity for a minimum of the next 2 hours.
Review other risk factors addressing reversible causes where appropriate.
Review other medicines that may be contributing to the clinical picture of central nervous system (CNS) depression and may need to be withheld or stopped, such as gabapentin, pregabalin and benzodiazepines.

Moderate toxicity management

If the patient is:

pain free, consider omitting the next dose of modified-release opioid. Reduce the background and as required opioid by 30–50%.
in pain, consider changing opioid and maximising non-opioid adjuvant analgesic interventions (seek specialist advice if required).

Monitor for signs of respiratory depression.

For opioid-associated delirium or hallucinations, consider low-dose haloperidol until symptoms resolve, for example, 500 micrograms 8-hourly when required.
Consider appropriateness of checking bloods for U&Es, calcium, LFTs, CRP and FBC.
Consider IV or SC fluids if appropriate to promote renal excretion of opioid metabolites.
Monitor the individual’s observations for worsening toxicity.
Review other risk factors, addressing reversible causes where appropriate.
Review other medicines that may be contributing to the clinical picture of CNS depression and may need to be withheld or stopped, such as gabapentin, pregabalin or benzodiazepines.

Mild toxicity management

If the patient is:

pain free, consider omitting the next dose of modified-release opioid. Reduce the background and as required opioid by 30–50%.
in pain, consider changing opioid and maximising non-opioid adjuvant analgesic interventions. Caution with any further opioid up-titration (seek specialist advice if required).
Consider appropriateness of checking bloods for U&Es, calcium, LFTs, CRP and FBC.
Push oral fluids to promote renal excretion of opioid metabolites.
Review risk factors, addressing reversible causes where appropriate.
Review other medicines that may be contributing to the clinical picture of CNS depression that may need to be withheld or stopped, such as gabapentin, pregabalin or benzodiazepines.

Risk factors

Understanding contributory risk factors can help both assessment and ongoing management.

Opioid toxicity can arise due to several factors, including, but not limited to:

infection
high opioid dose or rapid increase in dose
frequent or excessive as required opioid dosing
inappropriate use of opioids for symptoms other than pain or dyspnoea
polypharmacy, especially co-prescription of benzodiazepines, gabapentinoids or sedatives
renal or liver impairment
pharmacokinetics in cachexia, which can amplify toxicity risk
non-medical opioid use, polysubstance or substance use disorder
opioid dose not reduced when pain is relieved by other interventions such as radiotherapy or nerve block.
depressive or anxiety disorders
frailty, older age
opioid naivety, and
drug errors.

Management of background opioid

The guidance below refers to the ongoing management of opioid following treatment of opioid toxicity.

Where pain is poorly controlled, seek specialist advice.

Transdermal opioid patches	Remove opioid patch. After 24 hours, can replace at 30–50% dose if the patient is apyrexial. If pyrexia remains a risk, consider changing to an alternative route of opioid administration.
Syringe pump	Stop opioid in syringe pump. Review the need for any other medicines being given by this route. Reduce opioid dose by 30–50% and consider changing opioid. Time to restarting opioid will depend on the half-life of the opioid and factors such as renal or liver function, therefore seek specialist palliative care advice.
Modified-release opioid	Omit next dose. Reduce opioid dose by 30–50% and consider changing opioid. A regular immediate-release opioid may be indicated instead of modified-release preparation, particularly in renal or liver failure.
Immediate-release opioid As required opioid	Reduce opioid dose by 30–50% and consider changing opioid.

It may be clinically appropriate to deviate from these guidelines in people who are in the last days of life to avoid worsening of symptoms or opioid withdrawal. Specialist palliative care opinion should be sought in this scenario to support decision making.

Practice points

For opioid-associated delirium or hallucinations, consider low-dose haloperidol until symptoms resolve, such as 500 micrograms 8-hourly when required.
Consider appropriateness of checking bloods for U&Es, calcium, LFTs, CRP and FBC.
Consider IV or SC fluids to promote renal excretion of opioid metabolites.
When reducing background opioid doses, remember to also reduce breakthrough opioid doses.

References

Blundell M, Gill R, Thanacoody R, et al. Joint RCEM and NPIS best practice guideline: assessment and management of acute opioid toxicity in adults in the emergency department. Emerg Med J. 2024;41(7):440–445. Available from: https://emj.bmj.com/content/41/7/440 [accessed June 2026].