Side-effects of opioids what are they, are they common, and how do I deal with them?

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1 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

2 Opioid side-effects many of the perceived side-effects of opioids in animals are based on what happens in humans significant opioid sideeffects are rare in animals when appropriate doses are used

3 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

4 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)

5 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

6 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

7 Is it ever an issue? although clinical respiratory depression is rare with opioids, they do usually cause a mild increase in PaCO 2 inconsequential in healthy animals but, this may be problematic with some conditions

8 Is it ever an issue? PaCO 2 cerebral blood flow may intracranial pressure (ICP) may brain herniation and death Image courtesy of the Scottish Intensive Care Society

9 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 longeracting opioid is more practical

10 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

11 Opioid cardiac effects cardiovascularly stable negligible effects on cardiac contractility reduction in heart rate potential bradycardia (esp. high doses / IV administration) atropine responsive

12 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)

13 Opioid-induced sedation occasionally, this sedation can become excessive slow recovery from anaesthesia where additional opioid has been given during the procedure (doserelated)

14 Opioid excitement in cats originally reported following morphine at around 200 x the clinical dose!

15 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

16 Opioid excitement in cats more common to see some euphoria in cats kneading purring occasionally, hyperthermia (?)

17 Pupillary effects pupillary effects miosis in dogs (? significant for intraocular procedures) mydriasis in cats

18 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

19 Other effects salivation lip licking both may be associated with pain!

20 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

21 If there is a problem... reversal is rarely indicated unless there is significant respiratory depression and oxygenation cannot be maintained with supplemental O 2 the animal is flat and causing concern

22 If there is a problem... supportive therapy is usually all that is required maintenance of body T regular turning if recumbent toileting

23 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

24 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

25 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

26 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