11 May 2022
Nicola Menzies-Gow
Job Title
Image: © Rita Kochmarjova / Adobe Stock
Laminitis is now considered to be a clinical syndrome associated with systemic disease or altered weight bearing rather than being a discrete disease entity. Three types of laminitis exist, namely sepsis-associated, endocrinopathic and supporting limb laminitis. Endocrinopathic laminitis is the most common form of laminitis, and it encompasses laminitis associated with insulin dysregulation (ID). Therefore, it includes laminitis associated with the two common endocrine disorders, equine metabolic syndrome (EMS) and pituitary pars intermedia dysfunction (PPID). Treatment of the laminitis, regardless of type, consists of providing foot support and adequate analgesia.
Additionally, sepsis-associated laminitis requires treatment of the primary condition, anti-endotoxic therapy and use of digital cryotherapy. Endocrinopathic laminitis requires management of the ID, regardless of whether it is associated with EMS or PPID, primarily through a combination of diet and exercise (if no active laminitis is evident). Pharmacologic agents are used in the short-term in animals with EMS that are refractory to management changes alone. Those cases with PPID are also treated with the dopamine agonist pergolide.
Supporting limb laminitis requires treatment of the primary condition. Prevention of all types of laminitis requires prompt treatment of the primary/underlying condition and the use of prophylactic digital cryotherapy in animals at risk of sepsis-associated laminitis.
Laminitis is now considered to be a clinical syndrome associated with systemic disease (sepsis or systemic inflammatory response syndrome; SIRS, or endocrine disease) or altered weight bearing rather than being a discrete disease entity.
Three forms of laminitis exist.
Treatment of the acute laminitis, regardless of type, involves providing analgesia and foot support. Additionally, digital cryotherapy can be used in cases of sepsis-associated laminitis.
NSAIDs are the first choice for analgesia and no evidence exists to suggest that any one specific NSAID is superior to the next2. Although not a potent analgesic on its own, paracetamol (20mg/kg orally twice daily) clinically appears to have an excellent adjunctive effect in laminitic cases3.
The exact mechanism of action of paracetamol is not fully known; an inhibitory effect exists 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. A central action also exists, thought to be due to activation of descending serotonergic pathways, but it may also act on opioid receptors.
If NSAIDs do not provide enough pain relief, then opiates can be used in addition; for example, butorphanol, pethidine and morphine.
Transdermal fentanyl can also be considered; it was effective in horses with pain refractory to NSAID analgesia in one small clinical report4. However, uptake of fentanyl from a transdermal patch is highly variable in adult horses5.
Tramadol has also been advocated as it decreased forelimb offloading in four cases of chronic laminitis6, but current evidence does not support its use alone as it has a low oral bioavailability (approximately 9%), a short half-life (approximately two hours)7, and did not alter hoof withdrawal or skin-twitch latency to a thermal stimulus8.
If single drugs do not provide adequate analgesia, then multimodal therapy can be used in the hospital setting. Possible combinations typically involve NSAID administration in combination with a CRI of lidocaine, ketamine, butorphanol, a2 agonists or combinations thereof.
A neuropathic component to the pain associated with laminitis has been demonstrated, making ketamine and gabapentin potentially suitable drugs. In one study, the combination of tramadol and ketamine resulted in decreased forelimb offloading frequency and increased forelimb loading in horses with naturally occurring laminitis9.
Gabapentin improved hindlimb pain that was probably associated with femoral neuropathy in one horse10 and had no apparent adverse effects following oral administration in horses11.
Newer therapies, such as soluble epoxide hydrolase inhibitors and vanilloid receptor antagonists, may prove useful in the future12, but again further work is needed.
Supporting the foot is essential. Additional support should be applied to the caudal two-thirds of the foot to provide pain relief and minimise the mechanical forces on the laminae, and hence pedal bone movement.
The simplest method is to increase the depth of the bedding, ensuring the bedding extends to the door where the horse will spend most of its day. Alternatively, or additionally, extra support can be applied directly to the foot itself using methods that can be broadly divided into frog only supports, and combined frog and sole supports.
No evidence exists to suggest that any one foot support method is superior2.
Good evidence exists to support the use of cryotherapy in the treatment of sepsis-associated laminitis.
Continuous cooling (cryotherapy) of the equine digit was beneficial in experimentally induced sepsis-associated laminitis when initiated after the onset of clinical signs of laminitis13, and prophylactic cryotherapy was associated with a decreased incidence of laminitis in horses with colitis14.
The hoof temperature should be maintained at less than 10°C for 72 hours, which can be achieved by immersing the foot and pastern region in ice and water.
More recently, continuous digital hypothermia has been demonstrated to reduce the severity of laminitis and prevented histological lesions compatible with lamellar structural failure in the hyperinsulinaemic model when the cooling was initiated at the same time as the hyperinsulinaemia15.
However, no published studies exist to date evaluating its use when initiated either after the onset of clinical signs in experimental hyperinsulinaemia associated laminitis or in naturally occurring cases of endocrinopathic laminitis.
In addition, no published evidence exists relating to the use of cryotherapy for treatment of supporting limb laminitis.
Management of a case of endocrinopathic laminitis involves managing the underlying endocrinopathy as well as the laminitis itself.
The management of the ID, regardless of whether it is associated with EMS or ID, primarily consists of dietary modification and exercise. Pharmacologic agents can be used in the short-term in certain cases with EMS.
Dietary modification recommendations depend on whether the animal is obese or lean.
Obesity is managed primarily via energy restriction through limiting intake. An ideal target for weight loss is 0.5% to 1% of body mass (BM) weekly. A daily allowance of 1.25% to 1.5% of actual BM as dry matter intake (DMI), or 1.4% to 1.7% of actual BM as fed is widely recommended.
In horses with weight loss resistance, a further forage restriction to 1% BM as DMI or 1.15% BM as fed may be considered if appropriately monitored. Grains or cereal-based feeds should be excluded due to their high content of non-structural carbohydrate (NSC), and high-fat feeds should be avoided due to their high energy content. Additionally, large amounts of fruit or vegetables such as carrots, apples, or treats with a high glycaemic load should be avoided.
The nutrient composition of the forage should be determined where possible and hays with low NSC content (less than 10%) are recommended to limit postprandial insulin responses. Soaking for one hour in warm water or six hours in cold water is advised to reduce the NSC content of the hay if necessary. Straw is a cost-effective and low-energy forage that may be used as an alternative to hay alone. As forages can be low in protein, and mineral and vitamin leaching occurs after soaking, these nutrients must be balanced by low-calorie supplements to cover requirements.
During the initial 6 to 12 weeks of dietary restriction, pasture access should be prevented, as even partial access is very difficult to quantify. However, successful long-term management of EMS cases can still include some grazing provided that the ID, especially assessed by the insulin response to oral carbohydrates or grazing, is under control and that grazing is also carefully controlled.
The use of dietary supplements such as cinnamon, magnesium and chromium to facilitate weight loss or to improve ID is popular, but their efficacy remains questionable or unproven.
Lean animals should be fed a low glycaemic diet to minimise the postprandial insulin response. The diet should be based on forage with a low NSC content (ideally less than 10%) and additional calories provided in the form of fat (for example, vegetable oil) and high-quality fibre such as beet pulp. A low-calorie vitamin, mineral and protein ration balancer should be fed as required.
Exercise has been shown to improve insulin sensitivity in people; however, studies in horses have shown variable results. Exercise should only be considered in animals without current laminitis and should be gradually increased based on fitness. The optimal exercise regime has yet to be determined; however, half-hour sessions of exercise that raise heart rate to more than 150 beats per minute performed five days per week are recommended16.
Use of pharmacologic agents should be reserved for those cases with EMS that fail to improve following management changes. Their use should be restricted to the short-term (that is, three to six months).
Metformin is the most common drug that has been prescribed for managing ID in horses. Doses range from 15mg/kg to 30mg/kg given two to three times by mouth daily, and it is recommended that the drug is ideally administered 30 to 60 minutes prior to feeding. However, the oral bioavailability is extremely poor, and the drug does not appear to improve insulin sensitivity in equines – although, it had a beneficial effect through blunting of postprandial increases in glucose and insulin concentrations in a single study17.
Levothyroxine (0.1mg/kg to 0.15mg/kg by mouth daily) may be used in obese animals only to accelerate weight loss through increasing the metabolic rate, but must be used in conjunction with diet and exercise changes, as reported side effects include polyphagia. The dose should be gradually reduced and then treatment discontinued after the weight loss has been achieved, or after three to six months of therapy.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors may prove useful once more scientific evidence is available. Velagliflozin is an SGLT2 inhibitor that reduces renal glucose reabsorption, promotes glucosuria and, consequently, decreases blood glucose and insulin concentrations in humans. It has been shown to reduce hyperinsulinaemia and prevent laminitis in insulin-dysregulated ponies fed a challenge diet high in non-structural carbohydrates in two studies with small numbers of animals18,19; however, it is not currently commercially available.
Canagliflozin was reported to be effective at decreasing the insulin response to an oral sugar test in a preliminary US study using six horses20 and ertugliflozin has been shown to have a similar effect in an unpublished study using 11 animals.
Lipid mobilisation is stimulated in many horses treated with SGLT2 inhibitors and hypertriglyceridaemia may develop as a consequence. Therefore, horses with marked hypertriglyceridaemia should not be treated with these drugs.
None of these drugs are licensed for use in horses and each is used in accordance with the cascade.
PPID is a slowly progressive, lifelong condition. The aim of treatment is not to cure the condition, but to increase the quality of life through reducing the clinical signs, including those that have the potential to be life threatening.
Laminitis is the most common clinical sign that will enforce the use of pharmacological agents to help control the disease. Pergolide is a dopamine agonist that is available as a product licensed in the UK for the treatment of PPID in horses. It is reported to be effective in 65% to 80% of cases.
Side effects include anorexia, diarrhoea, depression and colic; however, only anorexia and depression are reported with any frequency.
If compliance with pergolide tablets is limiting, pergolide is also available as an unlicensed paste formulation.
Although a licensed medicine should be the first choice for treating any medical condition, if another product is more suitable for an individual horse, that product can be used if there is “clinical justification” for doing so, for example, if not taking the licensed medicine could lead to welfare issues/a decline in a horse’s clinical condition. Some horses will not eat pergolide tablets in any form, or may need dosing increments less than what some tablets can be split into. The pergolide paste can be dispensed in 0.2mg increments and being molasses-flavoured has been found to be readily accepted by horses in trials21.
Cabergoline is also a dopamine agonist that may be a potential replacement for pergolide for use in horses with PPID under certain circumstances, due to its long-acting nature. In one study, a single injection of 5mg cabergoline (in a slow-release vehicle) effectively applied dopaminergic activity to healthy horses for 7 to 10 days22.
No licensed product for use in the horse exists, but it is available in an unlicensed injectable formulation.
Prevention of sepsis-associated laminitis involves early and effective treatment of the cause of the sepsis or SIRS, the use of appropriate anti-endotoxic therapy, and the prophylactic use of digital cryotherapy.
Prevention of endocrinopathic laminitis centres on appropriately treating the underlying endocrinopathy, maintaining an optimum body condition and limiting intake of pasture NSC that may exacerbate ID.
A diet based on grass hay (or hay substitute) with low NSC content (less than 10%) should be fed and cereals avoided. The NSC content of pasture fluctuates widely; therefore, zero grazing might be necessary.
If an animal is to be turned out, steps should be taken to minimise NSC intake, such as the use of a grazing muzzle, strip grazing, rotation of paddocks to keep them at the ideal height or limiting the time spent at pasture. Forage-only diets do not provide adequate protein, minerals or vitamins, and so a low-calorie commercial ration balancer product that contains high-quality protein, and a mixture of vitamins and minerals is recommended.
If weight gain is required or the animal is undertaking a large amount of exercise, then caloric intake can be increased by adding unmolassed soaked sugar beet pulp to the diet (0.2kg/day to 0.7kg/day) or by feeding vegetable oil (100ml to 225ml once or twice daily up to a maximum of 100ml/100kg of bodyweight).
Several supplements containing magnesium, chromium or cinnamon, and a variety of herbs are marketed with claims for improved insulin sensitivity, but scientific evidence of their efficacy in horses is lacking23.
Exercise is also essential in the prevention of laminitis, as it has been shown to improve insulin sensitivity and decrease food intake. Light exercise is sufficient to improve insulin sensitivity, but this probably needs to be maintained on a daily basis for the improvement to persist.
More research is needed to allow specific recommendations for prevention of SLL to be made.
Some suggest that as limb cycling is an essential component of the circulation, it would be prudent to institute, whenever practicable, measures to improve foot circulation in horses at risk of SLL via either controlled exercise (walking) or physical therapy24. However, the ideal frequency and duration remains unknown24, and this is not possible in the majority of at-risk animals.
