Endotoxemia in Horses
By James Moore, DVM, PhD, Dipl. ACVS, and Jarred Williams, DVM, PhD, Dipl. ACVS-LA, ACVECC

It’s a normal day. You wake up, feed the horses, go to work, come home, head to the barn. Your 16-year-old gelding stands in the pasture, head down, lethargic and dull. He didn’t finish his breakfast and has no interest in dinner. You call your veterinarian arrives, she arrives, examines the gelding, and tells you he might have colitis and appears “toxic.” What does this mean, where did it start?
Understanding Endotoxemia
Endotoxemia is a complication that occurs when Gram-negative bacteria or parts of their walls access blood, such as in horses diagnosed with colitis, pneumonia/pleuropneumonia, neonatal sepsis, or endometritis.
Gram-negative bacteria have small structures in their cell walls called lipopolysaccharides or endotoxin. Intestinal ischemia (loss of blood supply) and inflammatory conditions such as colitis can compromise the inner lining of the gastrointestinal (GI) tract (the mucosal barrier), allowing endotoxin to enter the bloodstream. Though the horse is technically endotoxemic, problems don’t arise until the immune system recognizes the breach. A protein the liver synthesizes—called lipopolysaccharide-binding protein—has a strong affinity for endotoxin and a receptor on surfaces of specific immune cells.
When this protein encounters endotoxin, it handcuffs itself to the culprit and brings it to the immune cells, which interpret this as the worst news. These cells quickly produce a variety of pro-inflammatory mediators, including tumor necrosis factor, prostaglandins, interleukins, and tissue factor, that result in many of the clinical signs and responses associated with endotoxemia.
Clinical Signs and Findings
Endotoxemia causes a wide array of clinical signs:
- Poor tissue perfusion, signs of which include discolored oral mucous membranes, prolonged capillary refill time (how long it takes for color to return after pressing/releasing a finger on the horse’s gums), and cool extremities (i.e., ears, limbs).
- Fever, which is a common indicator of an immune response.
- Signs associated with abdominal pain caused by the underlying intestinal problem. In many cases reduced intestinal motility results in a decrease in or absence of intestinal sounds.
- Increased heart and respiratory rates as the body tries to cope.
- Lethargy and depression as poor perfusion and shock set in.
- Bloodwork changes, such as hematocrit (red blood cell concentration) increases; plasma protein concentration increases/decreases, abrupt decreases in white blood cells, notably neutrophils, and degenerative or “toxic” changes to their appearance.
- While not a sign of endotoxemia, laminitis, a painful inflammatory condition affecting the hooves, can occur due to decreased blood flow to the hooves.
Endotoxemia can rapidly lead to shock and cardiovascular collapse and, insidiously, laminitis. Given these severe outcomes, early intervention is paramount. If you suspect your horse exhibits any of the signs listed, consult a veterinarian immediately. Timely diagnosis and treatment can significantly improve the horse’s chances of recovery.
Treatment for Endotoxemia
Vets can treat endotoxemia by decreasing the amount of circulating endotoxin lipopolysaccharide-binding protein can bind to; immune cell ability to mount an inflammatory response; and immune cell signals to tissues responsible for clinical signs. Therapies include:
- Polymixin B: Vets can administer this antibiotic in small doses that don’t kill bacteria. It binds directly to lipopolysaccharide, rendering it unable to be bound by lipopolysaccharide-binding protein.
- Flunixin meglumine (Banamine): This non-steroidal anti-inflammatory decreases prostaglandin production and other aspects of the inflammatory response.
- Antibiotic therapy: This is an important part of treating known or suspected infection, such as in neonates with sepsis or adult horses with pleuropneumonia. Using antibiotics in adults with GI inflammation can be controversial because the drugs adversely affect the health of other microorganisms living in the intestines. Certain antibiotics can damage the intestinal mucosa, leading to colitis and endotoxemia.
- Cryotherapy: While cooling the hooves with ice water isn’t a direct therapy against endotoxin, it can decrease metabolism of the cells in the hoof, allowing them to better tolerate changes in blood flow and, optimally, prevent laminitis.
Endotoxemia is a critical condition that demands vigilance and awareness. Understanding its causes, symptoms, and the significance of early intervention can make all the difference in safeguarding equine health and well-being.
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