What's new in medicating horses with colic (Proceedings)

Analgesics

Although there are a limited number of analgesics available, they can be divided into several categories based on mechanism of action:

There are other agents in each of the above categories, but these drugs can be used as examples in order to develop a treatment plan. For a horse that is actively showing signs of colic, an abbreviated physical examination (heart rate, mucous membrane color, and capillary refill time) should be performed before administering an analgesic. If the horse is extremely painful, an attempt at taking the heart rate should be made, since the α2-agonists will dramatically alter this parameter. Furthermore, heart rate remains one of the most useful predictors of the need for surgery. The first analgesic I administer is xylazine (150-200mg for an adult horse) because it is a moderately potent but short-duration analgesic. This gives the veterinarian an opportunity to determine whether or not the colic is going to recur within the time it takes to complete the remainder of the examination. If flunixin is used as the first line analgesic, it may not be possible to gauge whether or not colic will recur within the time of the initial visit because it is relatively long-acting. However, if the horse remains comfortable on the first dose of xylazine, and the remainder of the examination is normal or the veterinarian feels comfortable with the abnormal findings (such as a mild impaction) flunixin can be administered to control further mild or moderate pain. If the first dose of xylazine does not keep the horse comfortable, it can be repeated at the same dose. In addition, butorphanol can be combined to provide greater pain relief (typically 5-10mg for an adult horse). If xylazine and butorphanol have little or insufficient effect, the next drug I administer is detomidine (5-10mg for an adult horse). If the first dose of detomidine has little effect, I will repeat it. If detomidine fails to control pain, the horse should be referred as rapidly as possible. Large colon volvulus is the most likely diagnosis in a horse with intractable pain, and the horse has approximately 3-4 hours between onset of the volvulus and development of irreversible mucosal injury. Addition of flunixin to the pain treatment plan is of little benefit in these types of cases because the majority of pain results from distension and tension on the mesenteric attachments rather than from inflammation. In addition, all of the drugs mentioned in the table can be repeated as needed except flunixin, which should only be given once every 12 hours.

An additional aspect of pain management is treatment of horses that have had colic surgery. These horses may have significant gastrointestinal mucosal injury, so it is advantageous to use low doses of flunixin because NSAIDs have deleterious effects on mucosa. To keep these horses comfortable, we are currently evaluating the use of continuous infusion butorphanol (5-10mg/L at a rate of 2L/hr). Numerous studies in the human literature attest to the benefit of frequent or constant administration of analgesics, because pain is far easier to control if it is treated preemptively. It is also possible that this regime could be useful for pre-operative treatment of severe pain in conjunction with β2 agonists.

FluidTherapy

There are two major reasons horses with colic may require fluid therapy: hypovolemia and endotoxemia. Hypovolemia results from decreased intake, loss of fluid (typically sweat or reflux), and sequestration of fluid (typically in horses that have intestinal obstruction). Endotoxemia exacerbates hypovolemia by triggering sequestration and leakage of fluid in peripheral capillary beds. The most obvious example of this is a horse with congested gums, in which endotoxin-induced elaboration of prostanoids (particularly PGI2) results in inappropriate vasodilation of capillary beds. The blood that is pooled in these capillary beds becomes de-oxygenated, resulting in progressive deterioration of gum color (from red to purple). Some horses with severe colic will present with predominantly hypovolemia, particularly horses with volvulus of the large colon, in which fluid is sequestered in the large colon, but there has been insufficient duration of disease to trigger endotoxemia. Many horses will present with both hypovolemia and endotoxemia, such as a horse with a small intestinal strangulating obstruction, in which fluid may be sequestered in the lumen of the gut (hypovolemia) and endotoxin has started to leak from degenerating bowel.

Treatment of hypovolemia should begin with an estimate of the degree of dehydration, which can be based on the following:

The degree of dehydration can be confirmed by running a packed cell volume and total protein. Once the degree of dehydration has been estimated, the percentage is multiplied by the horses body weight to give the fluid deficit (e.g., 8% dehydration x 500kg = 40L). The first half of the fluid deficit should be administered rapidly (up to 100ml/kg/h, or 50L/ hr in an adult horse) followed by the remainder at a slower rate (e.g., 3-5L/ hr) and a re-check of the PCV/ TS. In the field, if fluids are going to be administered, the veterinarian should be prepared to give approximately 15-20L, which corresponds to half the fluid deficit for an adult horse that is 6-8% dehydrated. A lesser volume (such as 2L) is not worth taking the time to set up, and rapid referral is preferable.

In horses with concurrent endotoxemia, the fluid deficit calculations are the same as for hypovolemia. However, consideration should be given to administration of oncotic support because much of the fluid that is administered will continue to pool or leak from capillary beds. The aim of oncotic support is to keep administered fluids within the central circulating blood volume. There are 3 general options: hypertonic saline, polysaccharides, and plasma. Hypertonic saline (4-6ml/kg 7.2% NaCl, or 2-3L for an adult horse) has the same effect as administration of 20L of isotonic fluids on cardiovascular parameters such as central venous pressure. However, the horse should continue to receive its fluid deficit shortly after administration of hypertonic saline because the effects are short lived, and the horse continues to require fluid to normalize total body water. Dextrans (polysaccharide solutions) are clinically available in two molecular weights: dextran-40 (40,000 MW) and dextran-70 (70,000 MW). Dextran-70 is more effective because it exerts greater oncotic pressure, and dextrans are more effective than hypertonic saline because the duration of effect is longer (6-hour half-life for dextran-70). It is administered at a rate of 4ml/kg (2L for an adult horse). For maximal effect, it can be administered with hypertonic saline. The other class of polysaccharide solution is hetastarch, but these solutions are more expensive. The final type of oncotic support is plasma or hyperimmune serum. The latter is available commercially as either J5 E. coli hyperimmune serum, or Re mutant Salmonella hyperimmune serum. Such sera have the advantage of providing oncotic support in addition to antibodies directed at the core polysaccharide of endotoxin. Alternatively, plasma is particularly advantageous in horses that have established endotoxemia with 'vascular-leak syndrome,' in which protein is lost from the circulation into peripheral tissues.

Endotoxemia

The major problem with treatment of endotoxemia continues to be the inability to treat horses prior to development of severe shock. Many of the treatments that are used clinically have shown benefit in experimental studies in which horses are treated before onset of endotoxemia. Clinically, the clinician is always struggling to keep up with endotoxemia because an inordinately complex cascade of inflammatory mediators is set in motion. Nonetheless, treatments such as hyperimmune serum may be beneficial in that they bind endotoxin present in the circulation and may prevent further development of shock. Another agent that has shown promise because of its ability to bind endotoxin is polymixin (2,000U q12h for 3 days), which is used at doses lower than those required for antimicrobial efficacy. In addition, at low doses, the side effects of polymixin (primarily renal injury) are minimized.

Other agents that are used to combat endotoxemia include the adenylate cylase inhibitor pentoxifylline, which inhibits production of TNF?, one of the proximal-most mediators of endotoxic shock. However, inhibition of endotoxin-induced cytokine production has only been achieved experimentally at doses of up to 50mg/kg, which are much higher than those used clinically in horses (8mg/kg q12h). The drug that has the greatest apparent clinical effect on endotoxemia is the non-steroidal anti-inflammatory medication flunixin meglumine. Studies have shown that flunixin inhibits prostanoid production at doses as low as 0.25mg/kg, which in turn improves cardiovascular parameters such as capillary refill time primarily because of reduced levels of PGI2. However, recent studies suggest that prostanoids are required for mucosal recovery following severe colic, so flunixin may have the paradoxical effect of retarding mucosal repair and exacerbating endotoxemia in horses with severe colic. This dilemma may be resolved by the recent development of more selective COX inhibitors.

Given the shortcomings of individual agents utilized to treat endotoxemia, we (at NC State) are currently using all of the aforementioned methods of treating endotoxemia. Horses remain on flunixin meglumine since alternative NSAIDs (COX-2 inhibitors) are not yet available for use in the horse. We attempt to use the lowest dose possible while continuing to provide pain relief. This is also made possible by constant infusion butorphanol. We also use pentoxifylline, and will use hyperimmune serum in horses with moderate-to-severe signs of endotoxemia, particularly if there is evidence of capillary pooling and loss of protein. We have also begun to use polymixin in horses that we predict from surgery will have continued endotoxemia postoperatively.

Treatment update: ileal impaction

Although ileal impaction is generally regarded as surgical disease, it has become evident that such impactions may be resolved medically. Although the impaction may be difficult to diagnose, the finding of 2-3 loops of distended small intestine adjacent to the cecum is enough for a presumptive diagnosis in the southeastern United States, where this disease is most prevalent. As long as the horse can be kept comfortable on reasonable levels of analgesics, aggressive fluid therapy may resolve these impactions.

Treatment update: Nephrosplenic entrapment

Recently, non-surgical intervention has been successful in select cases of nephrosplenic entrapment. However, if such manipulations are to be attempted, the clinician should be reasonably certain of a diagnosis. This is aided by accurate palpation findings and ultrasonography. In order to attempt to relieve nephrosplenic entrapment by rolling, the horse is anesthetized and placed in right lateral recumbency. The horse is rotated up to dorsal recumbency, rocked back and forth for 5-10 minutes, and then rolled down into left lateral recumbency. The nephrosplenic space should be palpated per rectum to determine whether or not the entrapment has been relieved. Phenylephrine (3-6μg/kg/min over 15 minutes) may be administered to decrease the size of the spleen. If the entrapment remains, further attempts may be tried, but in cases where the displacement is not corrected, the horse should be taken to surgery. More recently, phenylephrine has been used in conjunction with 30-45 minutes of light exercise (jogging) to successfully reduce nephrosplenic entrapments in 4 of 6 horses.