FRANK J. MILNE STATE-OF-THE-ART LECTURE


ideally be based upon culture and sensitivity results from hepatic biopsy material but clinicians are fre- quently required to select an initial antimicrobial agent empirically or when the culture results are negative. The isolation of predominantly Gram- negative enteric and mixed anaerobic organisms from cases of CL30,40,44 suggests that antibiotics with good Gram-negative activity (enrofloxacin, third-generation cephalosporins, aminoglycosides, and possibly trimethoprim sulfa) in addition to an- timicrobials effective against enteric anaerobes (penicillin, metronidazole, chloramphenicol) would be reasonable choices. Although the liver metabo- lizes nearly 50% of metronidazole, its use in CH is unlikely to be a problem or require a dose adjust- ment unless there is marked liver fibrosis. In the absence of positive culture results, clinicians may not only have to select an agent empirically but should also be prepared to change antibiotics accord- ing to clinical response. In one study, in all horses that improved, clinical improvement was seen days to several weeks before normalization of serum bio- chemical indices of hepatobiliary disease/function occurred (GGT, alkaline phosphatase [AP], biliru- bin, and bile acids).30 Furthermore in that study, serum GGT actually increased during the initial period of clinical improvement in all horses. I do not believe that there is a level of GGT that accu- rately predicts treatment failure in CH, as long as the horse is clinically stable, the ultrasound exami- nation does not reveal numerous obstructing stones or diffuse fibrosis, fever abates, and laboratory tests improve within 7–10 days after medical therapy commences. The highest GGT in an affected horse that I have successfully treated with medical ther- apy was 2,270 IU/L but I consulted on a case in Virginia where the horse recovered despite a GGT of 3,200 IU/L. Continuing antimicrobial therapy un- til both clinical and biochemical recovery has oc- curred may be important in achieving a successful outcome and I suggest monitoring serum GGT ac- tivity as a biochemical marker of recovery. Sup- portive medical care using intravenous fluids and anti-inflammataory drugs was a critical part of the treatment of several cases in our reports. Therapeutic agents, such as the bile salts cheno- deoxycholic acid and ursodeoxycholic acid (ursodiol), that are specifically used to encourage dissolution of cholesterol-rich stones in man, have no effect on calcium bilirubinate calculi but, as anti-inflamma- tory and choleretic agents that increase bile produc- tion, their use may make bile more liquid and easier to excrete.59 These bile salts were initially pre- dicted to be potentially toxic in horses due to their ability to be metabolized to the hepatotoxic com- pound lithocholic acid by intestinal bacteria in an- other hindgut fermenter, the rabbit.60 During the past 4 years we have now used ursodiol in eight horses with CH when standard medical treatments as listed above were not providing a favorable re- sponse. Five of these horses had somewhat sur-


prising recoveries, including one that clearly had an obstructing stone and others with “sludge” visual- ized on ultrasound examination. There has been no recognizable evidence of toxic effects in any case but additional studies on safety and efficacy are needed. Administration of ursodiol may increase se- rum bile acid concentrations. There is direct experi- mental support for the use of dimethyl sulfoxide (DMSO) in the treatment of brown pigment stones in man because it is a direct solubilizer of calcium biliru- binate61 and I still recommend its use for CH and CL. Previous reports have described the surgical treatment of cholelithiasis.48,53,54,57,62 Unfortu- nately, intrahepatic calculi are largely inaccessible to the surgeon and the fact that many cases of equine cholelithiasis possess multiple intrahepatic and extrahepatic choleliths means that recurrent biliary obstruction would be likely even if an ob- structing stone is removed. The best surgical out- come has been when there is thought to be a single stone obstructing the bile duct and when hepatic fibrosis is not severe. Surgery should be considered for horses that have intermittent or persistent ab- dominal pain, ultrasonographic evidence of obstruc- tion to biliary outflow, moderate-to-no hepatic fibrosis, few or no stones visible on ultrasound, and an unsuccessful response to medical therapy. Rec- ommending surgery when you are uncertain whether it is a single obstructing stone causing the clinical disease can be difficult so one must use all of the information above to make that decision. In addition, consultation with a voice of experience such as the one Dr. Jim Becht and I received on a case in 1985 is always helpful. In that case we were struggling to make a diagnosis as to the reason for persistent colic and liver failure when Dr. Whit- lock suggested, “if I were you boys I would consider cholelithiasis in that mare and explore her,” the mare did well following a choledocholithotripsy and went on in later years to deliver a foal by Seattle Slew. Thanks to Dr. Whitlock for the “suggestion.” Right dorsal displacement of the large colon (RDDLC) can cause nonstrangulating obstructions, preventing the normal flow of ingesta through the bowel lumen without resulting in intestinal vascular compromise.41 It may be difficult to make a defin- itive diagnosis of a RDDLC because of the vague clinical findings (often mild colic, questionable ab- normalities on rectal exam, etc.) although the diag- nosis is easier in horses that have the highly specific but not highly sensitive ultrasound examination finding of horizontally flowing mesenteric blood ves- sels in the right cranial to mid-abdomen.63 In the late 1980s we initially noticed that some horses with RDDLC had intense icterus and marked elevations in the serum activity of GGT, often accompanied by an increase in concentration of conjugated bilirubin. The elevations in GGT returned to normal after surgical correction of the displacement and liver bi- opsies showed minimal pathology, suggesting that the elevations are due to some feature of the colic


AAEP PROCEEDINGS  Vol. 61  2015 73


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