Pain and opioid tolerance
Managing pain is a central tenet of our role as anaesthetists.
The motto of the RCOA itself is:
'Divinum sedare dolorem'
'It is divine to alleviate pain'
And it's not easy, especially when our surgical colleagues insist on cutting holes and drilling metalwork into our patients.
It's even more tricky, when your patient has been taking vast doses of opioids for a long period of time, and their nervous system has completely rewired its perception of pain.
If you ask anyone who has taken a dose of opioid (for whatever reason), they'll usually tell you the same thing.
- The first dose was amazing
- The second dose didn't feel the same
The human brain's reward system adapts unbelievably quickly to new stimuli, leading to tolerance, dependence and withdrawal symptoms if left unchecked.
It's not surprising that the more opioid you take, the higher the risk profile.
If you take over 100 mg oral morphine (or equivalent) per day, you have nine times the risk of accidentally overdosing or another adverse event than if you take less than 20 mg per day.
It's a straightforward concept
- Recognise patients that are in pain
- Use opioids early and proportionately for severe acute pain
- Employ as many other opioid-sparing techniques as possible
- Wean off the opioids as soon as possible
- Figure out who's at risk of dependence and get the right people involved early
It's not complicated, but it's far from easy.
The CRQ examiner's report states:
"A new question that was generally well answered. Most candidates did well on the practical aspects of pain management in the opioid dependent patient but marks were dropped on the risk factors for opioid tolerance (dose and duration) and the definition of opioid induced hyperalgesia."
Here are all the questions we think could come up in the exams.
What are opioids used for?
- Acute pain
- Cancer pain
- Chronic non-cancer pain
- Substitution therapy for substance abuse disorders
What opioid equivalent doses do you know?
When compared to oral morphine:
- Intravenous morphine is one third of the dose
- Oral oxycodone is half the dose
- Codeine is ten times the dose
- Tramadol is five to ten times the dose
- Fentanyl patch is a quarter of the dose in mcg/hour
- Buprenorphine patch is half the dose in mcg/hour
These numbers vary depending on what resource you're looking at, as with any number in medicine, so check your local trust's protocols to confirm.
The other thing to think about is incomplete cross-tolerance.
Just because you're super-tolerant to one opioid doesn't mean you're going to need an equal jump in dose of another. In patients on high doses of morphine, you might want to start with a lower-than-equivalent dose of oxycodone and assess the response first.
What is tolerance?
- A chronic adaptive process whereby increasing doses of drug are required to obtain the same clinical effect
- This increases the risk of side effects and harm*
- We think this process is mediated at least in part by the delta opioid receptor, rather than the mu receptor, which is responsible for the analgesic effects of opioids
*Analgesic tolerance and respiratory depression tolerance develop at different rates so they can still be sensitive to the side effects and harmful consequences of large doses of opioids.
Why might a patient taking chronic opioids present a challenge to the anaesthetist?
- High baseline opioid requirement
- Superadded acute surgical pain in a hypersensitive nervous system
- Clinicians undertreating pain due to fear of respiratory depression with such large doses
- Psychological distress and underlying anxiety worsens perception of pain and reduces satisfaction with analgesic regime
What are the harms associated with opioid medications?
- Side effects - nausea, vomiting, hypoventilation, pruritus, constipation, hallucinations
- Persistent postoperative opioid use*
- Opioid induced hyperalgesia
- Dependence and addiction
- Immunosuppression
*Persistent postoperative opioid use is defined as a previously opioid-naive patient taking any opioids for longer than 90 days after surgery.
What are the risk factors for opioid tolerance?
Characterise or die.
System / healthcare factors
- Long-term prescribing - more than 3 months
- High prescribed daily opioid doses - especially above more than 50 mg per 24 hours
- Use of long-acting or extended-release opioid formulations
- Regular rather than PRN opioids
- Multiple concurrent opioid prescriptions
Patient factors
- Chronic pain conditions requiring ongoing opioid exposure
- Previous opioid exposure or prior tolerance history
- History of substance abuse
- Genetic predisposition affecting opioid receptor sensitivity or metabolism
- Psychological stress, anxiety, depression, PTSD, or trauma-related disorders
- Sleep deprivation and chronic stress states
- Repeated cycles of withdrawal and re-exposure
- Returning to opioid use after abstinence (reduced tolerance increases overdose risk)
Pharmacological
- Higher potency opioids
- Prolonged exposure - tolerance develops within days to weeks
- Higher cumulative exposure
- Continuous around-the-clock dosing
- Rapid onset formulations that spike plasma concentration
- Cross-tolerance from exposure to other opioids
- Concurrent use of other sedatives
What are the core tenets of good opioid stewardship?
- Recognising the risks of opioids
- Patient and clinician education
- Managing expectations
- Employing multi-modal analgesic techniques
- Controlled prescribing
- Early involvement of pain specialists