While non-steroidal anti-inflammatory drugs remain the first line treatment for lameness and the mainstay of postoperative orthopaedic pain relief, for perioperative analgesia it is important that a comprehensive preventive and multimodal approach be considered. Preventive, meaning we try to avoid the build-up of a ‘pain memory’ in the peripheral and central nervous system that can make pain much harder to treat; and multimodal, meaning we try to combine different drugs acting via different pathways and/or at different levels of the nociceptive pathway, to achieve better analgesia while limiting side effects.
In addition to clear benefits in terms of patient comfort (welfare), it has been shown that recovery from general anaesthesia will be smoother when patients are less painful. In addition, as pain acts as a stressor, diverting blood flow away from the skin and subcutis as well as the GI tract, wound healing and GI function will be favoured by adequate analgesia provision, contributing to enhanced recovery after surgery (‘ERAS’). There may be several reasons why one may be reluctant to consider multimodal approaches in individual orthopaedic cases:
A tiered step-up and step-down approach, following the thinking behind the WHO revised pain ladder, can be helpful to guide clinical decision making in analgesia provision for surgical procedures. The original emphasis that the WHO ladder put on opioids has been challenged, and we now try to incorporate more locoregional techniques and ancillary analgesics to reduce our reliance on opioids with their potential for adverse effects; they remain the gold standard analgesic drugs for moderate to severe pain however (Bowen et al. 2020). The ladder approach to perioperative analgesia entails identifying the likelihood of mild/moderate/severe pain from both the planned surgical procedure and any pre-existing painful condition, to determine the most appropriate peri-operative analgesic strategy. The aim is to select the approach that is most likely to achieve optimal pain relief while minimizing adverse effects of analgesics.
NSAIDs remain our first line agents both for analgesic, antipyretic and anti-inflammatory effects. NSAID selection for orthopaedic cases will very often be affected by pricing and availability or clinic buying preferences rather than scientific evidence perse. A recent narrative review on NSAID use for orthopaedic cases collected a large body of literature but no conclusive overall evidence for or against a particular NSAID for orthopaedic pain in horses (Jacobs et al. 2021). Flunixin and phenylbutazone remain the most commonly used. While phenylbutazone has classically been reported as the most efficacious for orthopaedic pain, in reality the better term would be most cost-effective (Jacobs et al. 2021). While studies showed flunixin to be equally efficacious for orthopaedic pain, its traditional use is in medical cases (colic pain, fever, endotoxaemia), without convincing scientific underpinning for the preference (Citarella et al. 2023).There is a big risk of publication bias with studies using newer more selective NSAIDs trying to establish superiority of effect vs. phenylbutazone as the benchmark orthopaedic NSAID. In terms of possible subsets of patients benefitting more from one NSAID than another, high-risk patients such as foals or geriatric ponies may benefit from more COX-2 preferential or -selective NSAIDs instead of phenylbutazone, which has the smallest safety margin, though the evidence to support this notion is currently lacking (Ziegler and Blikslager 2020). There is some evidence suggesting meloxicam may be preferred in cases with synovial inflammation for analgesia (UCVM Class of 2016, 2017) and more effective suppression of inflammatory changes in cartilage turnover (de Grauw et al. 2009, de Grauw et al. 2014), while phenylbutazone may be superior for distal foot pain (pedal bone osteitis, laminitis; UCVM Class of 2016, 2017).
The second step encompasses adjunct analgesics, e.g. paracetamol or gabapentin. While gabapentin has been trialled in (presumed) neuropathic pain, the evidence for acute postoperative pain relief is scant at best, and PK/PD studies in horses have so far not been successful at suggesting the most effective dosing regimen. While it can be considered in individual cases, blanket prescription whenever nerve damage may feature is not the way forward, particularly as this drug carries the risk for human diversion.
Paracetamol or acetaminophen has recently seen a resurgence in popularity for management of (orthopaedic) pain. Paracetamol (or ‘acetaminophen’) is not classified as a traditional NSAID. It has a varied mode of action and can affect serotonin, cannabinoid, and opioid receptors as well as COX-produced intermediates including prostaglandins. It is a very effective antipyretic. Paracetamol was recently shown to cause more rapid improvement in lameness scores over phenylbutazone alone when dosed at 30 mg/kg (single dose) in a sole pressure horseshoe model (Mercer et al. 2023), and to be safe to use at this dose twice daily up to 21 days (Mercer et al. 2024). It should not be considered a like-for-like replacement of NSAIDs, for which we have a much stronger body of evidence to support efficacy, and also since paracetamol lacks strong peripheral anti-inflammatory effect. While it was tolerated well at 30 mg/kg BID, it should not be used as a standalone analgesic for osteoarthritic horses (Mercer et al. EVJ 2024). In horses, combination of NSAID + paracetamol has not (yet) been proven to improve postoperative pain relief over NSAID alone. Perioperatively, it would best be reserved for those horses in which pain is anticipated to be severe, where no local block can be incorporated, and/or where NSAIDs are contraindicated.
Opioids should be considered for all procedures that likely result in more than mild pain (Bowen et al. 2020); where butorphanol is licensed and helpful for mild to moderate visceral pain as a bolus or CRI, its limited efficacy for somatic pain and short duration of action limit utility for postoperative orthopaedic pain (Bowen et al. 2020). A recent equine study identified prolonged (>24 hr) systemic morphine use, but not methadone or butorphanol CRI, as a risk factor for colic/impaction in horses after emergency non-colic or elective surgery, or imaging under general anaesthesia. Methadone also acts via non-opioid pathways, including NMDA and serotonin signalling (Haralambus et al. 2024). Importantly, results of this study also highlighted that the presence of postsurgical pain in itself increases post-anaesthetic colic risk, as does pre-operative starvation (Haralambus et al. 2024).
For invasive procedures (e.g. fracture repair, bone and joint surgery with extensive debridement), the analgesic ladder suggests to start on step 4: NSAID +/- adjunct + opioid + locoregional technique. By incorporating a locoregional technique (simple local anaesthetic infiltration, perineural nerve block, intra-articular or epidural analgesia with morphine), the aim is to provide optimal local or regional pain relief, while limiting systemic levels of analgesic agents and their potential systemic side effects (e.g. on GI motility). By adding a block, importantly, we are preventing ‘priming’ of the nociceptive pathways, and we can end up with an analgesic effect far outlasting the duration of action of the drug itself (Abass et al. 2018).
Waiving the benefit of a pre-emptive epidural for a hindlimb procedure hoped to be smooth yet turning out to be more difficult is not an uncommon scenario – more difficult surgery often means longer anaesthetic time which can negatively affect outcome, but also, more manipulation leads to a bigger surgical stress response. The notion to optimize rather than minimize would be imperative here: Adequate postoperative pain relief leads to shorter hospitalisation times, and research shows the single most predictive factor for persistent postsurgical pain to be the severity of acute postoperative pain. Nerve blocks with local anaesthetics would typically be kept below carpus or tarsus level to not affect quality of recovery from anaesthesia (avoid high proprioceptive and motor deficit). Epidural analgesia for the hindquarters can involve a single injection via a spinal needle, and/or epidural catheter placement for prolonged postoperative pain relief (most commonly placed postoperatively to avoid catheter dislodgement during recumbency and/or recovery).
To improve postoperative pain relief and help guide clinical decision making, it should be recommended to incorporate pain scoring at sensible (i.e. clinically relevant) intervals (e.g. at wear-off time of analgesics) for all post-operative patients, using a pain score that has been validated for postoperative use (e.g. CPS, EQUUS-COMPASS, EQUUS-FAP, HGS) – training is available online for these tools. Discussion between surgeons and anaesthetists should be encouraged to avoid monodisciplinary dogma and blind spots, and/or top-down decision making; there is always a gain in the crosstalk!
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