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