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Buprenorphine versus butorphanol in cat spays

Clinical Scenario

Over pizza at a vet meeting in your practice you are talking about your peri-operative analgesia for cat spays. You currently use butorphanol with ACP as your pre-medication, followed by propofol and isoflurane. One of the team has just been to a course about pain in cats and it was suggested that replacing butorphanol with buprenorphine may be superior at providing post-operative analgesia. You don’t seem to have had a problem with the cats undergoing surgery currently, but you wonder if buprenorphine would be a better choice.

3-Part Question (PICO)

In [female cats that are being neutered] does the use of [peri-operative buprenorphine compared to peri-operative butorphanol] provide [better post-operative analgesia]?

Search Strategy and Summary of Evidence

Search Strategy

MEDLINE(R) In-Process & Other Non-Indexed Citations and MEDLINE(R) 1946 to Present using the OVID interface

(cat.mp. OR cats.mp. OR feline.mp. OR felines.mp. OR felis.mp. OR exp Cats/)

AND

(neuter.mp. OR neutering.mp. OR sterilise.mp. OR sterilize.mp. OR sterilising.mp. OR sterilizing.mp. OR sterilisation.mp. OR sterilization.mp. OR sterilisations.mp. OR sterilizations.mp. OR spay.mp. OR spays.mp. OR spey.mp. OR speys.mp. OR desex.mp. OR desexed.mp. OR desexing.mp. OR de sex.mp. OR de sexed.mp. OR de sexing.mp. OR ovariectomy.mp. OR ovariectomies.mp. OR hysterectomy.mp. OR hysterectomies.mp. OR ovariohysterectomy.mp. OR ovariohysterectomies.mp. OR gonadectomy.mp. OR gonadectomise.mp. OR exp Sterilization, Reproductive/ OR exp Ovariectomy/ OR exp Hysterectomy/)

AND

(buprenorphine.mp. OR vetergesic.mp. OR temgesic.mp. OR exp Buprenorphine/ OR butorphanol.mp. OR torbugesic.mp. OR exp Butorphanol/ OR opiod.mp. OR opiods.mp.)

CAB Abstracts 1910 to Present using the OVID interface

(cat.mp. OR cats.mp. OR feline.mp. OR felines.mp. OR felis.mp. OR exp cats/)

AND

(neuter.mp. OR neutering.mp. OR sterilise.mp. OR sterilize.mp. OR sterilising.mp. OR sterilizing.mp. OR sterilisation.mp. OR sterilization.mp. OR sterilisations.mp. OR sterilizations.mp. OR spay.mp. OR spays.mp. OR spey.mp. OR speys.mp. OR desex.mp. OR desexed.mp. OR desexing.mp. OR de sex.mp. OR de sexed.mp. OR de sexing.mp. OR ovariectomy.mp. OR ovariectomies.mp. OR hysterectomy.mp. OR hysterectomies.mp. OR ovariohysterectomy.mp. OR ovariohysterectomies.mp. OR gonadectomy.mp. OR gonadectomise.mp. OR exp sterilization/ OR exp ovariectomy/ OR exp hysterectomy/ OR exp gonadectomy/)

AND

(buprenorphine.mp. OR vetergesic.mp. OR temgesic.mp. OR butorphanol.mp. OR torbugesic.mp. OR exp Butorphanol/ OR opiod.mp. OR opiods.mp.)

Search Outcome

MEDLINE

  • 44 papers found in MEDLINE search
  • 40 papers excluded as they don't meet the PICO question
  • 0 papers excluded as they are in a foreign language
  • 0 papers excluded as they are review articles/in vitro research/conference proceedings
  • 4 total relevant papers from MEDLINE

CAB Abstracts

  • 57 papers found in CAB search
  • 53 papers excluded as they don't meet the PICO question
  • 0 papers excluded as they are in a foreign language
  • 0 papers excluded as they are review articles/in vitro research/conference proceedings
  • 4 total relevant papers from CAB

Total relevant papers

4 relevant papers from both MEDLINE and CAB Abstracts

Summary of Evidence

Slingsby et al. (2015) UK

Title:

Methadone in combination with medetomidine as premedication prior to ovariohysterectomy and castration in the cat

Patient group:

Healthy male and female cats presented for routine neutering in the United Kingdom. Females neutered via flank route. 

Study Type:

Randomised controlled trial

Outcomes:

Three groups compared - medetomidine + methadone/butorphanol/buprenorphine. 

  • Sedation (using both visual analogue and four point simple descriptive scales)
  • Ease of restraint for catheter placement
  • Post-operative pain (using an interactive visual analogue scale)
  • Mechanical nociceptive threshold (using a Pressure Rate Onset Device [PROD])
  • Recovery time from anaesthesia to first head lift, first sternal recumbency and first time standing
  • Adverse events
Key Results:
  • A flank approach was used in all female cats. 
  • There was no significant difference between treatment groups in the need for rescue analgesia, and pain scores were low at all time points for all treatments.
  • Mechanical nociceptive threshold tests were significantly lower (i.e. less pressure was needed to exert the same response) at all time points in all cats in the 24 hours after surgery compared to the 24 hours before surgery, but there was no significant difference between analgesia groups post-operatively.
  • IVAS pain scores for female cats were significantly higher (i.e. more painful) at 3 hours post-operatively in the butorphanol group than the buprenorphine group. 
  • IVAS pain scores for female cats, when corrected for the administration of rescue analgesia, were significantly higher at 3, 4, 5 and 6 hours post-operatively in the butorphanol group compared to the buprenorphine group. 
  • IVAS pain scores for female cats showed a significant interaction between treatment and time, i.e. pain scores increased over time following analgesic administration.
  • No other significant differences were identified between treatment groups. 
  • No adverse events were noted for any treatment group. 
  • The company that produces methadone supported the study.
Study Weaknesses:
  • The primary aim of this study was not the same as the primary aim of our BET question.
  • NSAIDs are not reported to have been given as part of the analgesia protocols.
  • There were insufficient female cats included in the study to meet the sample size requirement for adequate power using their data alone. 
  • There are a lot of missing physiological parameter data (particularly in Tables 1 and 2) which according to the authors is due to the time taken to set up the equipment and the variability in anaesthetic length. 
  • The data presented in the figures are somewhat difficult to interpret. 
  • The scores used for sedation are not referenced therefore may not be validated. 
Attachment:
No attachments.

Warne et al. (2014) USA

Title:

Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats

Patient group:

Healthy female cats in Australia under 4 years of age presented for midline ovariohysterectomy. 

Study Type:

Randomised controlled trial

Outcomes:

Two groups compared: medetomidine + butorphanol/buprenorphine.

Phase 1 – Cats received either buprenorphine or butorphanol during pre-medication only.

  • Anaesthesia time
  • Length of time of surgery
  • Pain assessments at time 0, 20, 60, 120, 180, 240, 300 and 360 minutes after extubation
  • Requirement for rescue analgesia

Phase 2 – Cats were given a second dose of analgesic at wound closure.

  • Anaesthesia time
  • Length of time of surgery
  • Pain on injection
  • Sedation levels
  • Rectal temperature
  • Blood pressure
  • Anaesthetic sparing effect
  • Anaesthesia depth
  • Other physiologic variables e.g. heart rate, respiratory rate, oxygen saturation
  • Pre and post-operative pain levels (20, 60, 120, 180, 240, 300, 360 mins)
  • Requirement for rescue analgesia
Key Results:
  • A midline approach was used in all cats. 
  • Ten cats were recruited for Phase 1 of the trial. Nine required rescue analgesia after 20 minutes, and the other cat required rescue analgesia at 120 minutes.
  • Thirty cats were recruited for Phase 2 of the trial (the authors had aimed for 40); 29 cats completed the trial.
  • In Phase 2, cats receiving butorphanol had significantly higher pain scores at 20 minutes than cats receiving buprenorphine; pain scores were not subsequently compared.
  • In Phase 2, all cats receiving butorphanol required rescue analgesia at 20 minutes post-operatively, but none of the cats receiving buprenorphine required rescue analgesia at any point in time. 
  • No significant differences were identified between any of the other outcomes reported. 
Study Weaknesses:
  • NSAIDs were given only as part of the rescue analgesia or at 6 hours post-operatively. 
  • There was no sample size calculation undertaken; the authors state that insufficient cats were recruited for the study. 
  • Only the pain score methodology has previously been reported, so the validity of the other scoring systems is unknown. 
  • The pain assessment tool used is not described in adequate detail within this manuscript for the results to be easily interpreted. 
  • Phase 1 had to be halted prematurely as all cats required rescue analgesia so not all parameters were measured. 
  • All cats receiving butorphanol rescue analgesia at 20 minutes post-operatively in Phase 2 significantly limited the comparisons possible between groups.
  • Data on the pain scores after the rescue dose of butorphanol was administered are not presented. 
  • It is unclear whether it was the dose amount given or the increased dose frequency that made the difference in the buprenorphine efficacy noted in Phases 1 and 2. 
  • The company that makes buprenorphine supported the study.
Attachment:
No attachments.

Bortolami et al. (2013) UK

Title:

Methadone in combination with acepromazine as premedication prior to neutering in the cat

Patient group:

45 cats visiting a single clinic for elective neutering (24 females)

Study Type:

Randomised controlled trial

Outcomes:
  • Three groups compared (acepromazine + methadone/buprenorphine/butorphanol)
  • Level of sedation
  • Clinical parameters (temperature, pulse rate, respiratory rate)
  • Ease of restraint for intravenous (IV) catheter placement
  • Anaesthetic recovery
  • Degree of pain at surgical site using a visual analogue scale, mechanical nociceptive threshold and behavioural indicators
  • Any adverse events
Key Results:
  • A flank approach was used for all cats.
  • No statistically significant differences between groups in relation to timing or recovery from anaesthesia, although cats in the butorphanol group had significantly shorter surgery durations than cats in the buprenorphine group.
  • No significant differences between groups in relation to ease of restraint for IV catheter placement, clinical parameters (although blood pressure was not measured in all cats) or sedation scores 2-6 hours after premedication.
  • No significant differences between groups in relation to degree of pain at surgical site using a visual analogue scale or mechanical nociceptive threshold.
  • No adverse effects were seen.
  • 6 cats required rescue analgesia (1 in buprenorphine group, 3 in butorphanol group - not significantly different).
Study Weaknesses:
  • The primary aim of this study was not the same as the primary aim of our BET question.
  • Inclusion criteria state that only cats over 5 months were eligible to be included in the study; however, in the results the mean age was stated as 7 months +/- standard deviation of 4 months.  After contacting one of the authors for clarification, it appears that there may have been cats younger than 5 months in the final analysis.
  • It is unknown whether the person who administered the intervention was blinded.
  • The methods used to measure pain do not appear to have been previously published.
  • Further analgesia was provided to all cats at 6 hrs (methadone) and 8 hrs (meloxicam) after premedication, respectively - this is likely to affect the interpretation of pain scores for the subsequent time points.
  • Assessor was aware from the 7 hrs time point onwards that all cats had been given methadone at 6 hrs.
  • It is unknown how many different surgeons were involved; in the discussion section it states that the surgeons were experienced but the average length of time for surgery seemed reasonably long (37 minutes +/- 13 minutes). However, it does not state how surgery length was determined, i.e. from induction to end of anaesthesia or induction to extubation etc.  One of the authors after being contacted confirmed that the surgeons were experienced.
  • There were some missing values across the time points (see Table 2, Table 3 and text), although explanations were given for some of these by the authors.
  • It was introduced in the discussion that the study was designed for regulatory purposes in order to obtain a marketing authorisation for use of methadone in cats; the study was funded by Eurovet Animal Health BV (subsequently acquired by Dechra) who manufacture methadone.
Attachment:
No attachments.

Polson et al. (2012) UK

Title:

Analgesia after feline ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia with buprenophine or butorphanol, and carprofen or meloxicam: a prospective, randomised clinical trial

Patient group:

100 female cats at two RSPCA hospitals

Study Type:

Randomised controlled trial (Factorial design - comparison of two different NSAIDs and two different opioids)

Outcomes:
  • Four groups compared (Ketamine, midazolam and medetomine + carprofen/buprenorphine or meloxicam/buprenorphine or carprofen/butorphanol or meloxicam/butorphanol)
  • Duration of surgery and recovery
  • Surgical condition as judged by the surgeon
  • Any abnormalities (e.g. pregnancy) noted
  • Clinical parameters (heart and respiratory rate)
  • Level of sedation
  • Pain using a descriptive scale based on the cats appearance, a visual scale and mechanical nociceptive threshold
Key Results:
  • A midline approach was used for all cats.
  • There were no significant differences between groups in relation to duration of surgery or recovery, or surgical condition as judged by the surgeon.
  • There were no significant differences between groups in relation to abnormalities noted or clinical parameters.
  • The level of sedation, or pain using any of the 4 methods, were not significantly lower or higher on comparison between groups.
Study Weaknesses:
  • The aim of the study was not the same as the aim of our BET.
  • It is unknown whether the person who administered the interventions was blinded.
  • Mostly aggregated data were given so it is difficult to determine absolute numbers and whether all cats were assessed at all time points.
  • The authors did not state the statistical significance level that was to be used in the methods section.
  • The standard deviation in Table 2 suggests an age less than zero is possible. The authors were contacted and stated that a median and interquartile range should have been used; most cats in the study were young with a few older cats.
  • The lack of difference between the groups in relation to the level of pain could be due to the drugs used in the anaesthetic protocol having analgesic properties (medetomidine, ketamine) and the use of a multimodal regime (NSAID and opiod peri-operatively); the authors also conclude this.
  • Some conflict of interest is declared (one of the authors works for the company that produces the nociceptive threshold measuring device).
Attachment:
No attachments.

Comments

This is an updated version of the BET originally published in September 2014 and authored by Dr Marnie Brennan and Dr Jenny Stavisky.

This BET now includes 4 randomised controlled trials that perform a comparison of the efficacy of butorphanol versus buprenorphine in feline ovariohysterectomy (two using a midline approach, two using a flank approach).

The studies are difficult to compare as each study uses a different anaesthetic protocol, and different methods and timings of post-operative pain scoring. Only one of the studies (Warne) sought specifically to compare the efficacy of butorphanol versus buprenorphine; the other three studies had different aims to our BET question which may have had an effect on the study results. The use of NSAIDs also varied between the four studies: NSAIDs were administered peri-operatively in the Polson study, were given 8 hours after pre-medication in the Bortolami and Slingsby studies, and were given either with rescue analgesia or at 6 hours after pre-medication in the Warne study.  The use of NSAIDs in addition to opiods for post-surgical analgesia is common in clinical practice, but makes the singling out of the analgesic contribution of each opiod more difficult.

All the studies reviewed have weaknesses which mean the significance of these results is difficult to interpret. However, the two newer studies (Warne and Slingsby) both suggest that buprenorphine may provide superior post-operative analgesia to butorphanol since cats who received butorphanol were significantly more likely to require additional analgesia than those given buprenorphine. Unfortunately, those two studies provide conflicting data on the analgesic efficacy of a single pre-operative dose of buprenorphine in combination with medetomidine, and all 4 studies use different dosages of opiods, making comparison difficult.

Bottom line

The authors found it very difficult to compare the overall effects of these analgesics across the 4 studies.  There is a suggestion that peri-operative buprenorphine may be superior to butorphanol in providing cats with adequate post-operative analgesia following ovariohysterectomy.  However, additional high quality, large randomised controlled trials are required to definitively confirm this.

In the absence of robust evidence, clinicians should continue to monitor post-operative pain in individual animals and respond with additional analgesia as required.

Disclaimer

The BETs on this website are a summary of the evidence found on a topic and are not clinical guidelines. It is the responsibility of the individual veterinary surgeon to ensure appropriate decisions are made based on the specific circumstances of patients under their care, taking into account other factors such as local licensing regulations. Read small print

References

Slingsby LS, Bortolami E, Murrell JC (2015) Methadone in combination with medetomidine as premedication prior to ovariohysterectomy and castration in the cat. Journal of Feline Medicine and Surgery 17: 864-872.

Warne LN, Beths T, Holm M, Carter JE, Bauquier SH (2014) Evaluation of the perioperative analgesic efficacy of buprenorphine, compared with butorphanol, in cats. Journal of the American Veterinary Association 245: 195-202.

Bortolami E, Murrell JC, Slingsby LS (2013) Methadone in combination with acepromazine as premedication prior to neutering in the cat.  Veterinary Anaesthesia & Analgesia 40: 181-93.

Polson S, Taylor PM, Yates D (2012) Analgesia after feline ovariohysterectomy under midazolam-medetomidine-ketamine anaesthesia with buprenophine or butorphanol, and carprofen or meloxicam: a prospective, randomised clinical trial.  Journal of Feline Medicine and Surgery 14: 553-9.

About this BET

First author:
Marnie Brennan
Second author:
Zoe Belshaw
Institution:

CEVM, University of Nottingham

Search last performed:
2018-05-08 15:23:50
Original publication date:
2018-05-31 15:23:50
Last updated:
2018-05-31 15:23:50
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