Side-effects of opioids – what are they, are they common...
Transcript of Side-effects of opioids – what are they, are they common...
Side-effects of opioids – what are they, are they common, and how
do I deal with them?
Professor Derek Flaherty BVMS, DVA, DipECVAA, MRCA, MRCVS
RCVS and European Specialist in Veterinary
Anaesthesia
Opioid side-effects
• many of the perceived side-effects of opioids in animals are based on what happens in humans
• significant opioid side-effects are rare in animals when appropriate doses are used
Opioid side-effects
• respiratory depression • humans are extremely sensitive to the
respiratory depressant effects of opioid drugs • dogs and cats are much more resistant • i.e. it is not a clinical problem in these species in
the way it is in humans • panting may be seen in both dogs and cats
following opioid administration – ‘re-setting’ of the thermoregulatory centre in the
brain
Respiratory depression
• respiratory depression may be seen when either:
– high doses of opioids are used (especially if given IV)
– they are used in conjunction with other respiratory depressant drugs (e.g. anaesthetic agents)
Respiratory depression
What exactly do we mean by ‘respiratory depression’?
• we do not mean that a conscious animal will ever become apnoeic (unless massively overdosed with opioid)
• apnoea is possible if the animal is anaesthetised and opioids are given rapidly IV (especially doses at the higher end of the dose range) – can be overcome by positive pressure ventilation
Respiratory depression
• animals that do develop respiratory depression with opioids are only likely to be detected by capnography (or arterial blood gas analysis) – i.e. it is usually a sub-clinical problem and should
never be an excuse for withholding opioids from any animal that needs them
Is it ever an issue?
• although clinical respiratory depression is rare with opioids, they do usually cause a mild increase in PaCO2
• inconsequential in healthy animals
• but, this may be problematic with some conditions
Is it ever an issue?
• PaCO2 cerebral blood flow
• may intracranial pressure (ICP)
• may brain herniation and death
Image courtesy of the Scottish Intensive Care Society
Opioids and intracranial disease
• lots of conflicting information in the human literature
• if there is a significant chance the animal may require neurosurgical intervention, best to use a short-acting opioid such as pethidine IM
• if this is unlikely / not an option, a longer-acting opioid is more practical
Which opioid to use with intracranial disease?
• vomiting highly likely to ICP morphine should definitely be avoided (unlicensed anyway)
• absence of emesis with methadone
• start with low doses and titrate upwards
– 0.1 mg/kg slowly IV, repeated as required q 10 min
– N.B. this is less than the licensed dose and the IV route is off licence in cats
Opioid cardiac effects
• “cardiovascularly stable”
• negligible effects on cardiac contractility
• reduction in heart rate
– potential bradycardia (esp. high doses / IV administration)
– atropine responsive
Opioid-induced sedation
• by themselves, opioids induce minimal sedation in healthy animals
• synergistic sedative effect when combined with other drugs (e.g. premedicants, anaesthetic agents)
Opioid-induced sedation
• occasionally, this sedation can become excessive
– slow recovery from anaesthesia where additional opioid has been given during the procedure (dose-related)
Opioid excitement in cats
• originally reported following morphine at around 200 x the clinical dose!
Opioid excitement in cats
• in healthy, pain-free cats given opioids alone, you may see some signs of over-alertness
• ‘excitation’ not observed unless very high doses administered
Opioid excitement in cats
• more common to see some euphoria in cats
– kneading
– purring
• occasionally, hyperthermia (?)
Pupillary effects
• pupillary effects
– miosis in dogs (? significant for intra-ocular procedures)
– mydriasis in cats
Gastro-intestinal (GI) effects
• vomiting – common with all
opioids in humans
– only really seen with morphine in animals
• decreased GI motility – radiographic contrast
studies?
– possible constipation with chronic use
Other effects
• salivation
• lip licking
• both may be associated with pain!
Other effects
• histamine release
– most common with pethidine
– (IV) morphine
• does not occur with methadone
• is this an issue anyway?
Image courtesy of International Cat Care
If there is a problem...
• reversal is rarely indicated unless
– there is significant respiratory depression and oxygenation cannot be maintained with supplemental O2
– the animal is ‘flat’ and causing concern
If there is a problem...
• supportive therapy is usually all that is required
– maintenance of body T
– regular turning if recumbent
– toileting
If there is a problem...
• naloxone (Narcan®), starting dose of 0.01 mg/kg IV and titrated upwards
• butorphanol 0.1 mg/kg diluted to 1-2 ml and titrated slowly IV in 0.1 ml increments
• can remove undesirable effect but maintain some analgesia (μ and κ receptors)
• buprenorphine 0.01 mg/kg
diluted and titrated slowly IV
N.B. naloxone is not licensed for veterinary use, and butorphanol and buprenorphine are not licensed for
opioid antagonism
Opioid tolerance and dependence
• tolerance – increasing dose required over time to achieve the
same effect
– occurs rapidly with morphine
– does not seem to occur with methadone
• dependence – common in humans (variable time to occur)
– not recognised in animals
– most animals probably not on opioids for long enough
Opioid dependence
• if opioids have been administered for prolonged periods (? over 1 week), they should probably be withdrawn slowly
– halving dose on consecutive days
– withdraw over 2-3 days
• these are just suggestions as we don’t know whether this occurs in animals
In summary...
although opioids have a range of effects in the
body aside from provision of analgesia,
significant side-effects are very uncommon when
these drugs used appropriately