Does meloxicam provide adequate pain management as a post-operative analgesic in canine ovariohysterectomy patients?

Literature review

Use of pain scales

The presence of pain compromises a patient's recovery (Weber et al, 2012). It causes disrupted sleep, extended wound healing time and in-appetence (Weber et al, 2012). Morton et al (2005) and Ferreira-Valente et al (2011) agreed on the need to assess pain to guard patient welfare, assessing analgesia protocols and developing care plans specific to each patient and that the main purpose of pain scales is to pick up on changes in pain throughout analgesia therapy.

There are numerous subjective pain scales, some of which have been modified for specific use within veterinary practice (Matthews et al, 2014); these include the visual analogue scale (VAS), numerical rating scale and Glasgow composite pain scale (CMPS). The VAS is based on a 100 mm line used to mark the perception of pain between ‘no pain’ and ‘worst possible pain’ (Murphy, 2016: 335). Benefits of this system include the flexibility of the scoring system (Smith, 2009), but it can cause an over or underestimation of scores leading to discrepancies within the observer's variability (Anil et al, 2002). In addition, Smith (2009) identified the scale can only measure pain at the specific time of assessment with no consideration of stress or supportive care. However, a modification to the scale, the dynamic and interactive visual analogue scale (DIVA), allows the use of behavioural and interactive factors in the assessment to improve reliability (Flaherty, 2012). Nevertheless, research suggests that the VAS is less sensitive to post-operative pain assessment than the CMPS (Kalchofner et al, 2015). Hawker et al (2011) and Anil et al (2002) agreed suggesting the VAS should be used in conjunction with other scales for the best results.

The CMPS for dogs, is a multidimensional method of pain assessment developed by Holton et al (2001). The design allows the assessor to choose the most appropriate phrase from each category, allowing them to create an overall score of the patient's pain. Each phrase was selected by veterinary surgeons (VS), and linked pain in combination with behavioural change (Murphy, 2016). Comparing physiological parameters and behavioural changes elicits more accurate results than using either model by itself. In addition, the VAS is not designed specifically for veterinary use unlike the Glasgow pain score model. Reid et al (2007) developed the short-form version of the CMPS (Figure 1), as the full version was considered time consuming. RVNs are at the forefront of helping to manage pain in their patients using their skills and knowledge to improve current clinical practice.

Methodology

All procedures were performed in compliance with relevant laws and institutional guidelines and the research project was approved by University Centre Askham Bryan ethics committee. All owners gave written consent to take part in the study.

The methodology chosen was like that of the study conducted by Slingsby and Waterman-Pearson (2000) on feline patients undergoing ovariohysterectomy and underwent an initial pilot study prior to data collection commencing.

The observational study was conducted at Eden Hill veterinary surgery (Westway Veterinary Group), county Durham, with a sample size of 13 canines that were admitted for ovariohysterectomies and that had been assessed as healthy with no prior conditions that could be considered painful. Routine practice protocol was followed throughout, and the meloxicam was prescribed by a veterinary surgeon pre and post-operatively for each patient with all patients having a subcutaneous injection (SC) of meloxicam given on induction at a dose rate of 0.2 mg/kg (5 mg/ml), 5 to 10 minutes prior to the surgery, because tissue trauma could have resulted in inflammation. Each patient received the same premedication at the appropriate dose rate of 0.02 mg/kg acepromazine and 0.03 mg/kg buprenorphine intravenously (IV) 5 to 10 minutes prior to induction of anaesthesia using propofol at a dose rate of 4 ml/10 kg IV to effect. Each patient was dispensed oral meloxicam and no rescue analgesia was required by any of the patients. Each patient was assessed using the CMPS when admitted to the veterinary practice, and then 15 minutes post-surgery, at discharge and at their post-operative check (POC) 3–5 days post-surgery (Figure 2). Pain scores were completed by different veterinary professionals to ensure there was a sample size large enough because of time constraints. In addition, research by Murphy (2016) on pain scales, found them to be subjective therefore limiting the number of assessors conducting them during the study would not eliminate subjectivity. Minitab 17 software was used to statistically analyse the data. As the data were not suitable for parametric tests, non-parametric tests were utilised.

Results

Data were statistically analysed to determine the overall effectiveness of meloxicam in reducing pain following canine ovariohysterectomies. The results showed a statistically significant difference (Kruskal-Wallis test: H3 =12.98, p=0.005) in pain scores between admission, 15 minutes post op, discharge and 3–5 days POC (Figure 3). The greatest decrease in pain score was between 15 minutes post-operatively and POC (Mann-Whitney U test: W=236, n=13, 13, p=0.0014) and between discharge and POC (Mann-Whitney U test: W=227, n=13, 13, p =0.0060). Overall this demonstrated that there was an improvement in pain suggesting meloxicam is effective between these time frames. In addition, none of the patients required rescue analgesia and 69.2% (n=9) of patients in the study showed a pain score of 0, indicating an absence of pain, on their final POC. Statistical analysis was also used to determine if there was any difference in pain score between the 3, 4 or 5-day POC pain score. The results show no significant difference (Kruskal-Wallis test: H2 =0.090, p=0.638) suggesting that meloxicam's effectiveness was similar across this range of time, post surgery (Figure 4).

Discussion

There was a significant statistical difference between the scores recorded 15 minutes post-operatively and the POC completed 3–5 days later, as well as between the scores taken at discharge and the POC (Figure 3). This was predicted as the time when a difference should be evident if the drug was an effective analgesic agent for canine ovariohysterectomy. The results also showed that 69.2% (n=9) of the patients scored a pain score of zero, suggesting an absence of pain, at their POC. Wanamaker and Massey (2015) and Cracknell (2011) both discussed the drug's versatility because of not only its analgesic effects but also through its ability to promote blood supply and its anti-inflammatory properties.

All patients received a subcutaneous injection of meloxicam given on induction, and 5–10 minutes prior to the surgery. This is because tissue trauma could have resulted in inflammation. Cracknell (2011) suggested that meloxicam had improved effectiveness when given prior to inflammation. These findings are also supported by Slingsby and Waterman-Pearson (2002), whose research found that meloxicam and carprofen provided an overall substantially lower pain score throughout their study when given prior to tissue trauma during intubation

Future research could be to compare meloxicam's effectiveness with other post-operative analgesia to further evaluate its effectiveness in given scenarios, as well as examining meloxicam's effectiveness for both short- and long-term management in canines.

There was no significant difference between the pain scores at either the 3, 4 or 5-day POC (Figure 4). This result suggests there was no difference in level of pain (pain score) whether the POC occurred on day 3, day 4 or day 5. This gives us confidence that the animal's pain level is the same no matter which day the POC occurs post surgery, which is similar findings to research by Wanamaker and Massey (2015) and Lascelles (2001).

It is important to note that because of ethical considerations and in order to uphold animal welfare, a limitation of this study is the absence of a control group, also encountered by Tsai et al (2013) and Laredo et al (2004) in extrapolating findings. Research however has established that there is moderate post-operative pain in dogs undergoing an ovariohysterectomy (Luna et al. 2007; Leece and Brearley 2005; Tsai et al, 2013) and this research also suggests that the protocol within this study using meloxicam, provides adequate pain management both during and after ovariohysterectomy surgeries in dogs.

The study's limitations also included subjectivity of the pain score models as well as limitations with the CMPS model used in the study, particularly as the shortened version of the scale was tested. The results from the study used to determine its effectiveness as a post-operative pain assessment in practice (Guillot et al, 2011), had limitations including inter-observer variance as different people conducted the pain scores (Murphy, 2016), leading to a loss of consistency and reliability.

The biggest limitation to the study was the small sample size. With just 13 patients the sample was not representative of the wider population. This number also fell short of Dytham's (2011) suggestion of a minimum of 20 participants required to make the statistical analyses meaningful.

Some variables also proved difficult to control, which could have impacted the results. These included the skill of the surgeon and nature of the surgery, potentially reducing or increasing the amount of tissue trauma. The temperament of the animal may also affect the pain score, for example as one of the measurements suggests that any nervous behaviour can indicate pain, however the patient may display such behaviour as a result of being in a novel environment. In addition, the effects of sedation could also affect the pain score, as the pre-medication protocol included a sedative and analgesic combination. The research also acknowledges that certain other factors were not considered when conducting the clinical trial, including the age of the patient.

The use of multimodal analgesia was adopted throughout the study, as Leach et al (2009) and Cracknell (2011) both suggested a multimodal analgesia approach for effective control of post-operative pain. This is further evidenced by Kelly et al (2001) whose research suggested that meloxicam and other NSAIDs had a greater effect when used in conjunction with opioids when managing post-operative pain in dogs and cats. This was particularly relevant in this study, as an opioid was used in the pre-medication protocol. This could have influenced the pain score assessment and ultimately the results. This study's findings therefore suggest that meloxicam may be more effective because of a multimodal approach to analgesia, rather than any effect it had on its own. This is in line with research by Tsai et al (2013) and Corletto (2007) which indicated that the process of pain reception involves numerous pathways and therefore a single analgesia agent may not be sufficient to alleviate pain adequately. Therefore, using a combination of drugs with multiple mechanisms should be deemed more effective as pain management.

There is also debate over the effects of meloxicam and NSAIDs on the renal system. The COX enzyme system consists of two isoforms COX-1 and COX-2. COX-1 activity is involved in the maintenance of normal renal and platelet function and COX-2 activates when there is inflammation (Caulkett et al, 2003). Meloxicam has both COX-1 and COX-2 selectivity and COX-2 isoforms may be able to produce pain relief and anti-inflammatory response without any adverse renal effects (Caulkett et al 2003; Doig et al 2000; Slingsby and Waterman-Pearson, 2000; Thompson et al, 2000; Vane and Botting, 1997). A study by Caulkett et al (2003) compared the analgesic effects of butorphanol with those of meloxicam after ovariohysterectomies in dogs, and found that the meloxicam, as it was a specific COX-2 inhibitor, had less potential to impair renal function and that therefore demonstrated advantages for its use, although they state caution should be exercised for its use in patients with renal disease. Similar findings are also evidenced by Doig et al (2000) where meloxicam was used over time (4 weeks) for management of chronic pain in dogs. When they examined renal function, serum urea and creatinine levels were not affected. A study by Matthews et al (2001) exploring safety and efficacy of administration of meloxicam in dogs undergoing abdominal surgery showed no renal changes that could be attributed to drug administration at necropsy. However, dogs are susceptible to adverse effects of NSAIDS because of their mode of action (Doig et al, 2000) and it has been documented that their use can cause compromised renal perfusion (Doig et al, 2000). Although urine and creatine concentrations may be used to evaluate renal function, they are not sensitive markers of renal failure because they only increase if renal damage is severe (Luna et al, 2007). In Caulkett et al's (2003) study, renal function was not measured, and caution should be considered with meloxicam use in compromised patients such as those with renal or hepatic disease and gastrointestinal disorders. From this, further research is encouraged to examine any renal side effects of meloxicam in order to fully determine its safety as well as its efficacy.

Overall the study has suggested that meloxicam is an effective post-operative analgesic for canine ovariohysterectomy, providing justification for its current common use in practice. This is in line with findings by Caulkett et al (2003), Leece and Brearley (2005) and Tsai et al (2013). Further research is recommended to repeat the methodology of this study to determine if similar results are achieved improving reliability of the findings (Shuttleworth, 2018).

Conclusion

Meloxicam is an overall quick, and effective post-operative analgesic for short-term management of pain in canines following surgery for ovariohysterectomy. Further research should examine meloxicam's effectiveness for a variety of species, surgical procedures and comparison to other commonly used analgesics as well as utilising additional assessment methods including the use of a mechanical nociceptive threshold device as suggested by Benito-de-la-Vibora et al. (2008), to provide further clarification of the drug's overall effectiveness.

With post-operative analgesia use being varied between different practices, further research can help build on current results to help develop and expand the use of pain scales in veterinary practice.

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