Comparison of epidural morphine and buprenorphine for hindlimb orthopaedic surgery in dogs

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Appraisal, application and reflection

There is a dearth of high-quality evidence to compare the treatments in this PICO. Although the paper by Smith & Yu (2001) is a randomised controlled trial, sitting high in the hierarchy of evidence, it has some flaws that mean application to day-to-day clinical practice may be challenging.

Most significantly, the paper presented has a low power; post-hoc power calculations suggest that to give a 20 % chance of detecting a statistically significant difference in pain scores over the first 2 hours, to P = 0.05, a sample size of 69 dogs per group is required – much larger than the 10 dogs per group utilised in the study. Ideally, such sample size calculations should have been performed prior to commencement, or after a brief pilot study.

The pain score used during the study is not validated, although the current validated pain scoring systems (such as the Glasgow Composite Measure Pain Scale – Short Form (Reid et al., 2007)) were not available in 2001. As the systems are not validated, they may not be best designed for the detection of pain or may demonstrate observer bias and reduce the reproducibility of this study; further, the effect size (significant difference in scores) chosen of 0.5 pain score units may not reflect a clinically significant difference in analgesia and the authors do not address the confounding sedation due to acepromazine dosing.

A further flaw is the lack of knowledge of the extent of systemic absorption of epidural buprenorphine; Smith & Yu (2001) provide a brief literature review in this regard and summarise good evidence for the lack of absorption for morphine but limited data for buprenorphine in dogs. The author of this Knowledge Summary was also unable to find published studies on the bioavailability of epidural buprenorphine in dogs. Therefore, it cannot be ruled out that the treatment effect seen for buprenorphine is attributable to a systemic effect. Should this be the case, the higher risk of epidural drug administration would preclude this route of administration in patients in favour of other parenteral routes.

Although an attempt is made to compare the end-tidal CO₂ tensions between groups, the methodology states that an unspecified proportion of dogs in each study arm were mechanically ventilated. Ventilation would be expected to reduce differences between groups so must be taken into account when interpreting this data. The requirement for ventilation may be due to blunting of physiological ventilatory responses caused by halothane, which in this study is seen at mean ± SD end-tidal concentrations (%) of 1.04 ± 0.26 (buprenorphine) and 1.06 ± 0.18 (morphine). These end-tidal halothane tensions are higher than previously reported minimum alveolar concentrations (MAC) for halothane with 0.1 mg kg^-1 epidural morphine (as in (Smith & Yu, 2001)) of 0.6 ± 0.017 (Valverde et al., 1989) and despite the use of large doses of acepromazine as a premedicant, which has been shown to be MAC sparing, producing end-tidal concentrations of 0.58 ± 0.044 with acepromazine doses of 0.1 mg kg^-1 in one study (Heard et al., 1986).

Additional to these clinical concerns regarding end-tidal CO₂ and halothane tensions, the statistical handling of both variables is unclear. The data sets for each variable would consist of a series of numbers for every dog in both study arms but the ANOVA analysis applied requires one data point from each dog; the authors do not elaborate on the methodology used to derive that number. As anaesthetic and ventilatory requirements may be expected to vary over time in response to surgical stimulus, this statistical approach is unlikely to be appropriate for these data.

In terms of application to clinical practice, there are some deviations that may be significant. No analgesic medication was administered to these patients other than the treatments being studied, which contrasts current anaesthetic practice where systemic opioid analgesics are often employed (Epstein et al., 2015). The 50% requirement for rescue analgesia in both trial arms may reflect inadequate perioperative analgesia.

Current surgical preferences may lie towards more invasive osteotomy techniques (such as tibial tuberosity transposition or TPLO) rather than extracapsular imbrication (Bergh et al., 2014) so it is feasible that the analgesic requirements of different surgical techniques will differ.

Unfortunately, the only paper obtained from the literature search did not utilise local anaesthetic in the epidural protocols tested and is therefore not completely relevant to the PICO question posed.

Therefore, it is not possible to make a recommendation to utilise buprenorphine epidurally in hindlimb orthopaedic surgery in dogs over morphine, although the reduced abuse potential and regulatory burden may make this attractive to individual practitioners. Further randomised controlled trials are needed to answer this PICO question.

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