The use of analgesic drugs by South African veterinarians

INTRODUCTION The use of analgesics by veterinarians worldwide has been inadequately addressed. Only 40 % of dogs admitted to the North Carolina State University Hospital for major surgery received analgesics. A more recent Canadian survey (1996) concluded that only 50 % of veterinary practitioners used analgesics perioperatively. Pain is a subjective parameter and hence is difficult to quantify objectively. A number of pain rating scales and behavioural assessment scores are available for the evaluation of pain. The use of analgesic drugs by South African veterinarians is unknown and anecdotal. This survey was undertaken to assess the use of analgesics for routine sterilisations, acute post-operative pain and general pain management. No information on the assessment of pain by veterinarians or the basis for administration of analgesic drugs was obtained.


INTRODUCTION
The use of analgesics by veterinarians worldwide has been inadequately addressed 6,7,14 .Only 40 % of dogs admitted to the North Carolina State University Hospital for major surgery received analgesics 14 .A more recent Canadian survey (1996) concluded that only 50 % of veterinary practitioners used analgesics perioperatively 7 .Pain is a subjective parameter and hence is difficult to quantify objectively.A number of pain rating scales and behavioural assessment scores are available for the evaluation of pain 10,13 .The use of analgesic drugs by South African veterinarians is unknown and anecdotal.This survey was undertaken to assess the use of analgesics for routine sterilisations, acute post-operative pain and general pain management.No information on the assessment of pain by veterinarians or the basis for administration of analgesic drugs was obtained.

MATERIALS AND METHODS
The sales representatives of a pharmaceutical company distributed 600 questionnaires to veterinary practices in South Africa between February and April 1999.The questionnaires were completed by the veterinarian in the practice and returned either via the company or by post to the author.Analgesic-type drugs available in South Africa were listed and the respondent was asked which of those drugs were administered routinely during sterilisation of dogs and cats.The list included non-steroidal anti-inflammatory agents, opioids and other drugs with analgesic properties.A similar question was asked as to which analgesic drugs were given for acute post-operative pain after any procedure.Lastly, drugs including non-steroidal anti-inflammatory agents, opioids, anaesthetic drugs, premedication and other analgesic drugs were listed, and the respondent was asked to identify the drugs with analgesic properties that they used for pain control.The survey is contained in Appendix 1.The list of drugs for each question was compiled from the South African Medicines Council list of registered drugs.The list of drugs has been omitted from certain questions where the drugs would be selfexplanatory.Several phenylbutazonecontaining drugs are available in South Africa and these drugs were grouped together.
The data were entered into a spreadsheet (Excel 97 SR-1, Microsoft Corporation).Tables and descriptive statistics were used to describe the data.Statistical analysis was performed with SigmaStat for Windows, Version 2.00 (Jandel Corporation).

RESULTS
In total, 162 questionnaires were completed.This represents a response rate of 27 %.One questionnaire was rejected, as it was incomplete.The remain-ing questionnaires (161) were used for analysis.

Use of analgesic drugs
The results indicate that 139 (86.3 %) respondents did not include any drugs specifically for their analgesic properties in the premedication and induction of cats undergoing routine sterilisation.However, when the author included premedication and induction agents with analgesic properties, this percentage was reduced to 34.2 % (55).This indicates that a large number of practitioners are unaware of the pharmacology of many drugs.A number of practitioners used more than one drug with analgesic properties in a case.The analgesic drugs used in cats are given in Table 1.A similar situation was reported for dogs.One hundred and thirty (80.75 %) respondents indicated that they did not intentionally give analgesic drugs to dogs undergoing sterilisation.Again, analysis of premedication and induction agents revealed that 111 (68.9 %) of the respondents did not administer any with analgesic properties.These results are presented in Table 2.
The 4 most commonly used drugs for acute post-operative pain were flunixin meglumine (87, 54.0 %), phenylbutazone (79, 49.1 %), pethidine, (41, 25.5 %) and buprenorphine (23, 14.3 %).Five practitioners indicated that they did not administer any drugs for acute post-operative pain.All the drugs used for acute postoperative pain are listed in Table 3.The drugs most commonly used for the treatment of pain in general practice in South Africa are flunixin meglumine (134, 83.2 %) followed by phenylbutazone (112, 69.6 %).Aspirin, pethidine, ibuprofen, xylazine and meloxicam were commonly used.The remaining drugs are listed in Table 4.A number of respondents identified drugs that have limited analgesic effect as having analgesic properties.Drugs included in this group are thiopentone, alphaxalone/alphadolone, diazepam, halothane, acetylpromazine, pentobarbitone, atropine, phenobarbitone, propofol and isoflurane.Details are given in Table 4.

DISCUSSION
Most respondents in this study indicated that they did not actively administer analgesics to animals during routine sterilisation.In a British study, 53 % of ovariohysterectomies and 32 % of castrations received peri-operative analgesics 3 .The lower incidence of the use of analgesics in ovariohysterectomies compared to laparotomy (71 %) in the British study was attributed to the fact that an ovariohysterectomy is considered routine 3 .
What is interesting about this study is that a laparotomy was considered to be as painful as an ovariohysterectomy 3 .A Canadian study showed dismal results for peri-operative use of analgesics in the sterilisation of cats and dogs (ovariohysterectomy cats 16.6 %, dogs 12.6 %, castrations cats 9.3 %, dogs 10.5 %) 7 .
From our study it initially appeared that only 13.7 % of cats received peri-operative analgesics for routine sterilisation.When the premedications were considered, 43.5 % of cats received xylazine.Xylazine and medetomidine, both alpha2-adrenergic agonists, are known to have potent analgesic properties 22 .This had a dramatic impact on the number of cats receiving analgesics for sterilisation (65.8 %).The analgesic effect of alpha2adrenergic agonists does not last as long as the sedative effect 22 , therefore this drug is unlikely to have contributed much to post-operative analgesia.Dogs did not benefit as much from the inclusion of alpha2-adrenergic agonists.
The most commonly-used opioid for pain control during sterilisation in this study was pethidine.In Britain, buprenorphine was the most common, followed by butorphanol 3 .In Canada, butorphanol ranks above buprenorphine 7 .The most commonly used non-steroidal antiinflammator y agent was flunixin meglumine followed by phenylbutazone.The most commonly used non-steroidal anti-inflammatory agent in Britain for sterilisation is carprofen 3 .Although use of butorphanol and carprofen was reported in this study, neither drug is currently registered by the South African Medicines and Drug Related Authority.
To manage acute post-surgical pain, flunixin meglumine and phenylbutazone were the most popular choices.It is important to realise that non-steroidal antiinflammatory agents seldom relieve pain immediately as they take 45-60 minutes to achieve their full effect after administration 20 .Opioids or other drugs with a rapid mechanism of action should be used initially for acute post-operative pain.Non-steroidal anti-inflammatory agents are synergistic with opioids and several benefits can be derived from using these drugs in combination 20 .
Non-steroidal anti-inflammatory agents pose several risks to patients, of which acute renal failure and gastric ulceration probably cause the most concern.Flunixin meglumine and phenylbutazone have been reported to cause peri-operative renal failure 5,9,16,20,21,26 .Older animals should be monitored for adverse renal side-effects 4 .Non-steroidal anti-inflammatory drugs should be used with caution when creatinine levels are raised 20 .The median value of creatinine is used as the upper limit when considering non-steroidal anti-inflammatory drugs.When creatinine is in the top normal range, up to two-thirds of renal function can already be lost.
Non-steroidal anti-inflammatory drugs should not be given to patients with known renal insufficiency, dehydration, hypotension, relative and absolute hypovolaemia, ascites, heart failure, thrombocytopenia, known coagulation   20 .Gastric ulceration can occur with all non-steroidal anti-inflammatory drugs and prophylaxis should be instituted 20 .Drugs that can be used are sucralfate (0.25 g p/o tid or bid), misoprostol (2-5 g/kg p/o tid) and ranitidine (3.5 mg/kg p/o bid, 2.5 mg/kg i/v bid) 20 .Non-steroidal anti-inflammatory drugs are safe in normovolaemic, normotensive patients.
The most commonly-used opioidtype drug for post-operative pain was pethidine, followed by buprenorphine.The most commonly-cited factors affecting the use of opioids are: analgesic potency, legal requirements, and sideeffects 3,7 .Pethidine has been shown to be a useful analgesic in dogs and cats 1,17 .Pethidine has one third to half the potency of morphine 23 .The major problem associated with pethidine is its short duration of action, and it is in this respect an ineffective analgesic in small animal patients 7 .Buprenorphine is as effective as morphine for the relief of postarthrotomy pain 2 .Buprenorphine is a mixed agonist-antagonist opioid and as such has a ceiling effect 2,7 .The major disadvantage of this is that once buprenorphine has been given, another more potent opioid cannot be given for anaesthesia or analgesia.As a result of this buprenorphine has been used to reverse opioid overdoses.Buprenorphine has a duration of action of up to 8 hours 2 .Mixed agonist-antagonist opioids are not considered adequate for moderate to severe post-operative pain 7 .A potent µ agonist, e.g.morphine, is more suitable for severe pain, as increasing the dose increases the analgesic effect 7 .Few practitioners in this survey used morphine or any of the other potent µ agonists.Major concerns exist about the use of µ agonists in cats, as they may cause excitement.This concern has been shown to be unfounded when they are used at clinically relevant doses 7 .Morphine has a duration of action of approximately 4 hours 2 .
Veterinarians identified several anaesthetic drugs as having analgesic properties.The drugs included thiopentone, alphaxalone/alphadolone, diazepam, halothane, acetylpromazine, pentobarbitone, atropine, phenobarbitone, propofol and isoflurane.In fact, thiopentone and halothane have been shown to potentiate painful stimuli or have limited analgesic properties 11,24,28 .Propofol may have moderate analgesic properties and does not increase sensitivity to pain 24 .Anaesthesia is defined as a state of reversible unconsciousness, amnesia, muscle relaxation and analgesia.Acepromazine, thiopentone and halothane constitute the most commonlyused anaesthetic protocol for sterilisation in dogs and alphaxalone/alphadolone in cats.None of these anaesthetic protocols meet all the requirements for anaesthesia.Veterinarians should critically review their anaesthetic practices in order to achieve a more balanced anaesthetic protocol.
Ketamine is an anaesthetic agent with potent analgesic properties, and has most commonly been used as an analgesic in burn wound patients 12,15,19,29 .Subanaesthetic doses of ketamine given pre-operatively have been shown to be effective in reducing post-operative pain 25 .
A few practitioners indicated that they used corticosteroids for acute postoperative pain and during sterilisation.Corticosteroids have a limited role to play in peri-operative analgesia.They affect the inflammatory pathways and may exert effects similar to non-steroidal antiinflammatory agents 27 .Corticosteroids produce multiple effects in various organ systems and are thus associated with numerous side-effects 27 .Their use is indicated in cases of immune-mediated and rheumatoid arthritis, but is seldom indicated as the primary choice in other types of chronic pain.The routine use of corticosteroids as an analgesic cannot be justified.
It has been demonstrated that sex is one of the important factors dictating the prescription of analgesic drugs 6 .Female members of staff are far more likely to give analgesic drugs than male counterparts 3,6 .Nurses in general increase the use of analgesic drugs 6,8 .Even in teaching hospitals, the knowledge and use of analgesic drugs has been shown to be poor, ineffectual and inappropriate in many cases 14 .In order to relieve pain effectively, a multimodal approach is frequently required 17,18 .This includes the use of non-steroidal anti-inflammatory agents, opioids and other adjuncts.
The analgesic care of patients can be dramatically improved through continuing education, creating more awareness amongst veterinarians about pain and increasing their knowledge about analgesic drugs.