Severe colic is characterized by intractable pain and signs of septic shock, which is any type of loss or poor distribution of blood supply caused by bacteria or their toxins. The bacterial toxin we most commonly think about is endotoxin, so horses are usually called endotoxemic when their gum color changes, the time it takes for the capillaries of the gums to refill after pressure from a finger (called capillary refill time) increases, and the heart rate remains elevated despite treatment for pain.
However, there are many different bacteria and toxins that can trigger the same reaction.
Septic shock is the horse's body mounting a massive immune response to bacterial toxins that, in horses with colic, have escaped from the intestine. In order to escape, the gut lining or barrier has to be broken down, and this happens when the bowel is strangulated (the intestine has become twisted or entrapped in an area of the abdomen that pinches off the blood supply).
If a horse with a strangulating obstruction of the intestine is not attended by a veterinarian and taken to surgery, it will die from the body's response to bacterial toxins that escape from the intestine. That is why endotoxemia has been so extensively researched.
However, despite an in-depth knowledge of how endotoxin and the immune system work, we have not been able to develop a specific treatment to combat this syndrome. This is because veterinarians rarely get the chance to treat the horse early enough--signs of severe pain and shock remain common amongst horses referred to veterinary hospitals, and progress over the last decade has been slow in reducing the time it takes for the referral of the horse by the treating veterinarian to a surgical facility.
That means the newest treatment is really the oldest treatment--early recognition of colic, early treatment, and rapid referral for possible surgery.
In other words, always notify the veterinarian as soon as possible, resist the urge to try to treat the horse yourself, and be prepared to refer the horse for advanced treatment. Generally, the population of horses that develop severe colic includes the ones that don't respond to the veterinarian's initial treatment. Almost all severe colics start as mild colics that are simply left too long.
Treatment for Shock
Medications used to treat horses that have severe shock are painkillers (analgesics), fluids, and drugs that can reduce the effects of endotoxin. The mainstay of treatment for endotoxemia has been twofold: fluids and non-steroidal anti-inflammatory drugs (NSAIDs). Of the two, fluids are the most important because without enough fluid in circulation, the horse will expire from lack of blood flow.
With severe colic, fluid has to be given intravenously with close attention to how well-hydrated the horse is. This can be based on physical examination findings and laboratory tests. Horses in endotoxemic shock are not just dehydrated, they have an abnormal distribution of blood flow. This means that a lot of the blood that should be circulated to the vital organs is trapped in capillary beds such as the gums (which is why gum color starts off as excessively red in horses with endotoxemia, see page 37). This occurs because mediators of inflammation--such as hormonelike substances called prostaglandins--dilate peripheral capillaries when the appropriate response would be to constrict capillaries and shunt blood back to the heart.
This raises the issue of the second major treatment for endotoxemic shock, NSAIDs. These drugs are capable of preventing production of prostaglandins. Since prostaglandins are also involved in pain, horses have improved gum color and are less painful once treated with an NSAID medication such as flunixin meglumine (Banamine). However, recent studies have shown that while flunixin is very effective for reducing pain and restoring gum color, it can delay repair of injured intestine. This appears to be more of a problem in the small intestine.
The reason for reduced intestinal recovery is that some of the prostaglandins that are produced are good because they aid repair of the gut barrier. So, in a very simplified way of speaking, you need to target the "bad" prostaglandins (cyclooxygenase-2, or COX-2) and preserve the "good" prostaglandins (COX-1).
The new COX-2 inhibitors, which have been on the human market since the release of Celebrex, might be a new option for horses. These drugs inhibit excessive production of prostaglandins from the pro-inflammatory enzyme COX-2, but they preserve prostaglandins from COX-1 involved in maintaining and repairing the gut. At this time there is one such drug available for horses in the United States (Equioxx), but it is only available as an oral agent. Equioxx is highly selective for COX-2, and we hope it will become available in an intravenous form.
Another drug that is available as an intravenous agent in surrounding countries and the European Union is Metacam (meloxicam). Although this drug is only moderately selective for COX-2, experimental trials have shown this drug provides adequate pain control and allows the intestine to repair more rapidly as compared to Banamine. The more rapid repair corresponds to quicker blockage of endotoxin absorption, which means you are keeping endotoxins out of circulation.
More Treatments for Endotoxemia
There has been a lot of interest in drugs that can bind endotoxin, thereby preventing contact with the cells that initiate the horse's immune response. One class of these drugs includes antibodies directed at endotoxin. These were made by immunizing horses with fragments of endotoxin molecules and collecting the antibodies made by the horses. These studies were initiated in the 1980s, but to date we haven't been able to use these antibodies effectively because by the time severe colic is evident, endotoxin has already set off the immune response. This response is so strong that once it starts, it is hard to control, even if endotoxin is no longer present.
Another drug that binds endotoxin is polymixin, an antibiotic that has been on the market for years. However, it cannot be used as an antibiotic in horses because it upsets the balance of bacteria in the gut, making them develop diarrhea. Recent studies have shown it can be used at low doses without this complication, and it has been shown to bind endotoxin.
Polymixin is most frequently used during surgery and immediately following surgery. For example, if an intestinal twist is found once surgery has been started, polymixin can be given prior to untwisting the intestine in an attempt to bind endotoxin that will be released from the damaged bowel. Once again, the earlier these treatments are used, the better.
Novel Effects of Lidocaine
The local anesthetic lidocaine, which has been used for years to perform nerve blocks or to anesthetize the skin before repairing a wound, has recently been shown to have positive effects in horses following surgery. In particular, lidocaine administration, when given as a constant infusion, reduces the prevalence of a postoperative complication called ileus. In equine terminology, ileus means an inability of the intestine to properly function, with reflux of fluid back into the stomach.
This result from lidocaine was at first thought to be attributable to the nerves supplying and lying within the intestine, with lidocaine suppressing the inhibitory action of some of these nerves. However, it now appears more likely that lidocaine is actually serving as a novel anti- inflammatory drug that stops white blood cells from infiltrating the wall of the intestine following injury.
This is important, because white blood cells release mediators of inflammation that likely make the gut ineffective at propelling contents downstream.
Another interesting effect of lidocaine is its ability to offset the effect of flunixin on preventing gut repair, so in a number of small intestine cases, we might be getting two benefits from one drug. The mechanism for improved intestinal repair with lidocaine is also thought to be its ability to prevent infiltration of white blood cells more than flunixin. However, additional studies are needed to fully understand the effects of lidocaine.
Another relatively new treatment used to combat inflammation following surgery, this time on the outside surface of the intestine, is carboxymethylcellulose ("belly jelly"). This is the same material that is used as a lubricant for rectal palpation, but it can be prepared so that it can be used safely at surgery. When poured on the intestine during surgery, it not only allows the surgeon to manipulate the intestine more easily, but it also appears to prevent infiltration of white blood cells.
This is critical because it is the accumulation of white blood cells on the exterior surface of the intestine that leads to adhesions (the gut sticking to itself or other organs).
This complication is the most important cause of long-term loss of horses that have had surgery. In other words, complications such as shock and postoperative ileus most often occur during hospitalization, but adhesions tend to occur within two months of surgery. Studies have repeatedly shown that carboxymethylcellulose reduces the number and severity of adhesions. Now there is new data to show that application of this agent increases survival of horses following surgery for severe colic.
In a more advanced world, colic would not be allowed to become severe. Once colic becomes severe, horses continue to have a reasonable survival rate (approximately a 75-90% chance of being discharged, and approximately 60-75% survive in the long term). These statistics have continued to improve, which is largely a testament to improved surgical and anesthetic techniques, as well as new treatments.
Now we need to maximize these numbers by shortening referral time. This, in large part, is in the hands of the owner, so ask your veterinarian to help you manage your colicking horse before the case becomes severe.
About the Author
Anthony Blikslager, DVM, PhD, Dipl. ACVS, is a professor of equine surgery and gastroenterology at North Carolina State University’s College of Veterinary Medicine. His research interest is gastrointestinal physiology in horses, studying the mechanisms of injury and repair in the gut with the clinical outlook of enhancing recovery of horses with colic.
POLL: Complementary Therapies