ShapeShapeauthorShapecrossShapeShapeShapeGrouphamburgerhomeGroupmagnifyShapeShapeShapeShape

What are the best options for pain management?

27 May 2019, at 9:30am

Analysing the pros and cons of the most commonly used medications and methods for managing pain in horses

Pain management is an essential component of veterinary practice but is often overlooked and underutilised in the equine industry. Defining the cause of the pain is integral to being able to treat the immediate pain and resolve the ongoing disease. Deep pain is frequently more difficult to control than superficial pain, whilst pain, broadly, can be caused by trauma, infection or inflammation, whether musculoskeletal or visceral in origin. Neurological pain is often the hardest to diagnose and treat, requiring long-term analgesics and a multimodal approach.

Critical assessment of orthopaedic pain is more routinely carried out, with various grading systems available, as well as recent advances in computer-generated assessments of lameness. The inherent problem in assessing pain is the non-verbal nature of horses as well as their often-inconsistent demonstration of pain.

Attempts have been made to formulate a pain recognition system via facial expressions. One study demonstrated changes in facial expression that were consistent through-out different noxious stimuli, including: low and/or asymmetrical ears, angled appearance of the eyes, withdrawn stare, mediolaterally dilated nostrils and tension of the facial muscles. The frustrating aspect is that these are all very subjective and have not been fully validated (Gleerup et al., 2014). That said, use of these pain score scales could help diagnose pain earlier than if not attempted.

Following recognition of pain in a patient, a treatment plan can be designed and built around the source of the pain, the animal involved and owner compliance. When designing the treatment plan for an equine patient, it is important to ascertain the severity of the pain as well as the type of pain, as this should alter treatment undertaken.

Multimodal analgesia is the most efficacious way to treat pain, but treatment should, ideally, follow the cascade with first-line treatment consisting of licensed equine products via the appropriate route. Due to a paucity of medication, there is often a need to utilise the cascade and use a product not licensed for equine patients. In these situations, consent should be gained from the owner prior to administration and risk of administration discussed.

Non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line therapy in the vast majority of equine cases, with a number of products and active ingredients licensed in the UK (Table 1). NSAIDs work by inhibiting cyclo-oxygenase (COX) with different active ingredients affecting COX-1 and COX-2 differentially, with a higher inhibition of COX-2 theoretically being beneficial with fewer side effects. By inhibiting COX enzymes, there will be an alteration in the arachidonic acid cascade, leading to a reduced production of inflammatory mediators. As the clear majority of pain dealt with daily is associated with inflammation, the use of NSAIDs should play a pivotal role in its treatment.

NSAIDs are not without their risk though, and chronic use should also involve ongoing monitoring for signs of toxicity.

Gastrointestinal ulceration and right dorsal colitis are the most frequently discussed side effects; albumin should therefore be monitored and any changes in faecal consistency should alert the owner and the veterinary surgeon to a potential toxicity. Renal papillary necrosis is another, albeit uncommon, side effect due to reduction in prostaglandin production leading to a decreased blood flow within the kidneys. Regular evaluation of creatinine is useful, although a large percentage of the kidney must be affected to lead to aberrant results. Urinalysis can also be useful if concerned, as can a urine GGT:creatinine ratio. Care should be taken when giving NSAIDs concurrently with other nephrotoxic drugs, such as gentamicin.

There is no indication to use different NSAIDs at the same time, and in fact this would probably be contraindicated due to the inability to dose correctly (and so a higher risk of toxicity). That said, it appears that some pain and some horses will respond better to different NSAIDs. If a change is required, a 24-hour washout should be allowed prior to the administration of the second medication.

Paracetamol

The exact mechanism of action of paracetamol is not fully known. There is an inhibitory effect on both COX-1 and COX-2, with an increased selectivity for COX-2 in humans, which likely leads to the anti-inflammatory effects of paracetamol. There is also a central action, thought to be due to activation of descending serotonergic pathways, but it may also act on opioid receptors

Although not a potent analgesic on its own, it clinically appears to have an excellent adjunctive effect in most painful cases, particularly laminitic cases. With limited side effects (liver function should be monitored when chronic use is planned), it can be given in cases where NSAIDs cannot be administered (colitis, gastric ulceration, renal compromise, etc).

It should be given at 20mg/kg orally twice daily. No licensed product is available for horses, but formulations are available for dogs and pigs with the latter as a liquid. The liquid for pigs anecdotally appears to cause oral ulceration and so the author washes the mouth out following administration.

Gabapentin

Gabapentin is a structural analogue of GABA, but it appears that the drug and its metabolites do not bind to the receptors. Therefore, its action appears to be associated with a reduction in neurotransmitter release. Various doses have been trialled in horses with up to 20mg/kg PO given with no adverse side effects. Humans and small animals frequently show evidence of ataxia and sedation but thankfully this does not appear to occur in horses. The author generally starts treatment at 10mg/kg PO q12h and this can be increased to 20mg/kg PO q8h – although this is rarely realised due to financial constraints.

The author generally uses gabapentin in cases that have been refractory to NSAID use (laminitics) or where NSAIDs are not appropriate (colitis). Just like paracetamol, it is more frequently used as an adjunct to other analgesics rather than a solitary treatment.

Local anaesthetic agents

Where possible, local anaesthetics applied topically, perineurally, systemically or epidurally can have a huge impact on pain control. The licensed products available in the UK include lidocaine, procaine and mepivacaine, but mepivacaine is the only product that can be preservative/adrenaline free, making it more useful for procedures such as epidurals. Lidocaine is available as solutions without adrenaline, but is not licensed in equids.

The most frequently used local anaesthetic is systemic lidocaine. It is frequently used as a continuous rate infusion (CRI) in post-op colic cases due to possible pro-motility/anti-inflammatory effects, but also in chronic colic or colitis due to the continuous pain relief provided. The author will often use this in cases such as severe colitis where a multimodal analgesia program is required. A load dose of 1.3mg/kg should be given followed by 0.05mg/kg/minute.

Care should be taken to not overdose as neurological side effects develop quite quickly. The therapeutic window is small so even slight changes in flow rate can lead to abnormalities. When a horse is treated with lidocaine, all personnel involved should be aware that if abnormal behaviour is noted, the lidocaine should be stopped and the patient reassessed after 20 minutes. In the author’s hospital, all lidocaine CRIs are run through a drip pump to reduce the risk of inadvertent overdose and this is the recommended administration method.

With opioids, care should be taken to record all use and wastage appropriately due to their controlled substance status

Opioids

This class of medication offers several licensed medications that can be given through various routes (Table 2). Each drug has a different mode of action via different receptor activity and affinity. The exact effect of each drug is beyond the scope of this article, but the primary effect is central (although opioid receptors are also found outside the CNS). Extended use in horses can lead to decreased GI motility and a risk of impaction. This should be weighed up against the analgesic effects that will increase GI motility in equids. Licensed products for horses include pethidine, butorphanol and buprenorphine but morphine, fentanyl and tramadol are unlicensed opioids often used in equine patients (Table 3).

With opioids, care should be taken to record all use and wastage appropriately due to their controlled substance status. When applying fentanyl patches, the author recommends using Elastoplast over the patch with the vet or vet nurse’s name, the amount applied and when it was applied written perpendicularly across multiple stripes to ensure there is a reduced risk of abuse.

Pethidine is licensed as an analgesic for the symptomatic relief of pain in spasmodic colic in horses and has a very short duration of action (one to four hours); its use in chronic pain is therefore limited. It must be given intramuscularly as intravenous administration can cause seizure-like activity due to histamine release. If this occurs, the clinical signs can be controlled by diazepam or pentobarbitone injections. The author rarely uses this medication primarily due to its short half-life.

Buprenorphine is licensed for post-operative analgesia in combination with sedation, as well as causing potentiation of the sedative effects of centrally acting agents. Although potent and theoretically lasting 6 to 12 hours, the cost can be prohibitive as the multi-dose vials only come as 10ml. Its use via an oral-transmucosal route has been researched and a dose of 6μg/kg provides extended analgesia and so can play a role in cases that are refractory to injections.

Butorphanol is licensed for moderate to severe pain in horses and has been shown to alleviate abdominal pain associated with torsion, impaction, intussusception, parturition and colic. More frequently, it is used in conjunction with detomidine to induce profound sedation. The author does use butorphanol intramuscularly in cases where additional analgesia is needed between administration of NSAIDs or when a colic is refractory to routine analgesics.

The remainder of the opioids discussed are not licensed in equine patients. Morphine is frequently used as a preoperative analgesic given intramuscularly or intravenously (following sedation to reduce the risk of excitation). Frequent administration is required as the duration of action is around four hours with no evidence of morphine systemically at seven hours post-administration. Therefore,a dosing regimen of q4h is required in very painful horses. Morphine is also regularly used in epidural medication and can be used for intra-synovial medication. Again, this is frequently used for colic or laminitic patients.

Transcutaneous administration of fentanyl is an excellent extended use opioid for chronic pain

Transcutaneous administration of fentanyl is an excellent extended use opioid for chronic pain. There is relatively rapid uptake with a peak concentration achieved 8 to 15 hours after application of the patch via the transdermal route, although there is a large variation in onset and maximal concentration reported. The author utilises fentanyl patches regularly for chronic pain, particularly laminitis, with anecdotally excellent response. Whilst awaiting peak concentrations, administration of morphine can reduce pain. Increased efficacy is seen when the patches are applied to the rump or pectoral region, but the author has found these difficult to maintain and therefore uses the antebrachium.

Tramadol has been used in patients with laminitis, but its oral bioavailability is highly variable depending on the study reviewed and ranges from 3 to 85 percent. With a short half-life in equids and risk of impaction, its use should be limited to cases that are refractory to other medications.

Corticosteroids

With profound effects on both COX and lipoxygenase pathways, these products have an excellent effect on inflammation. Therefore, when there is a definitive inflammatory focus, steroids can be useful as an adjunctive therapy.

The risk of using NSAIDs in conjunction with steroids appears to be small in equine patients when compared with small animal patients. The owners should be warned of the theoretical risks of laminitis, although recent research shows that there is not an increased risk of laminitis in cases that have been given steroids (Jordan et al., 2017). It should be noted that, as a retrospective study, there is inherent bias and therefore the author still warns of the risks when the patient is high risk (pituitary parsintermedia dysfunction or equine metabolic syndrome).

Systemic treatment options include dexamethasone at 0.1mg/kg IV/IM/PO q24h or prednisolone at 1mg/kg PO q24h. With equine licensed products available for both drugs, these should be used. Steroids can be administered intra-synovially if there is chronic pain such as osteoarthritis, with methylprednisolone and dexamethasone licensed for this, and triamcinolone frequently used off-label.

Epidural

Epidural-administered analgesia is an excellent technique in cases of severe hindlimb pain or surgeries including the perineum and tail. Various medications can be given including opioids, local anaesthetics, α-2 agonists and ketamine. Different combinations of these drugs will lead to variable analgesic levels as well as duration. This can be done as a one-off injection but in the more chronic cases, an epidural catheter can be placed. The latter requires hospitalisation due to the high risk of contamination and intensive nature of their maintenance. The exact methodology and drug doses/choices are beyond the scope of this article; these have been mentioned for reference.

Conclusions

Defining the painful patient, alongside the severity of the pain, can be difficult in horses, although common sense should apply following routine procedure. Most cases can be treated simply as long as medication is given in a timely manner (ideally prior to the painful stimulus during surgery) but in severe chronic pain cases, multimodal therapy will often be required. This can appear daunting, but with multiple analgesics available via multiple routes, a sensible plan can be created for most patients – although some of the medications will require hospitalisation.

Other complementary therapies should be considered, including hydrotherapy, ice, acupuncture or, if dealing with laminitis, appropriate bedding or farriery work. The exact treatment protocol for analgesia must be designed around the individual patient and disease and therefore will differ greatly between patients.

References
Author Year Title
Gleerup, K. B., Forkman, B., Lindegaard, C. and Andersen, P. H. 2015 An equine pain face. Veterinary Anaesthesia and Analgesia, 42, 103-114.
Jordan, V. J., Ireland, J. L. and Rendle, D. I. 2017 Does oral prednisolone treatment increase the incidence of acute laminitis? Equine Veterinary Journal, 49, 19-25.

Jamie Prutton, BSc (Hons), BVSc, DipACVIM, DipECEIM, MRCVS, completed an internship at Rossdales Equine Hospital before starting an internal medicine residency at UC Davis. He holds Diplomate status from the American College of Veterinary Internal Medicine and has been practising at Liphook Equine Hospital since 2015.

More from this author