Sepsis & Toxic Shock in Horses: Pathophysiology, Causes & Prognosis

Sepsis is a severe and rapidly life-threatening condition that develops in response to an infection of the horse’s bloodstream, triggering a widespread inflammatory response that affects multiple organs. Any infection has the potential to develop into sepsis if left untreated.

Toxic shock is a specific type of sepsis caused by bacterial toxins that trigger a sudden and extreme immune response.

Signs of sepsis and toxic shock in horses include fever, rapid heart rate, rapid breathing, and dark red gums. Veterinary intervention is necessary to prevent organ failure and death, which can occur within a matter of hours or days.

The high risk of rapid fatality underscores the importance of horse owners and caretakers familiarizing themselves with the signs and symptoms of common equine diseases to ensure prompt treatment before sepsis can develop.

Read on to learn the terminology surrounding sepsis and toxic shock in horses, causes of these condition, diagnosis, treatment, and prevention strategies.

Sepsis and Toxic Shock in Horses

Sepsis in horses can develop from any source of infection that allows bacteria to enter the bloodstream. ^[1]

During an infection, bacteria proliferate within the affected tissue and eventually gain access to a blood vessel, allowing them to enter the bloodstream. ^[1] Bacteria circulating in the bloodstream is known as bacteremia. ^[1]

Some bacteria such as Staphylococcus or Streptococcus can release toxins into the bloodstream and trigger toxic shock. In such cases, the body reacts to the toxins rather than the bacteria themselves, leading to rapid-onset symptoms and potentially more severe shock than standard sepsis.

Sometimes, bacteria replicate and spread to other tissues once they enter the bloodstream. This is a much more serious condition, as new areas of infection can develop rapidly and may affect many organs. This scenario is called septicemia. ^[1] Veterinarians diagnose septicemia by performing bacterial culture on a blood sample. ^[1]

Common locations where additional infections may develop during septicemia include: ^[2]

• Lungs
• Eyes
• Joints
• Bones
• Intestinal tract
• Umbilical stump in foals
• Brain and meninges (covering of the brain)
• Heart

Septicemia typically triggers an immune system response to try and clear the bacteria from the bloodstream and resolve the infection. ^[1] Since infected blood distributes throughout the entire body, the inflammation produced by the activated immune system affects all tissues. ^[1]

Sepsis, SIRS & Septic Shock

The symptoms associated with the widespread inflammation triggered by septicemia are sometimes called systemic inflammatory response syndrome (SIRS). ^[1] Affected horses are septic (have sepsis). ^[1] Sepsis is a more severe condition as the inflammatory response can cause tissue damage and organ failure.

Septic horses may go into septic shock, also referred to as toxic shock, a condition where they have poor blood flow to their tissues. ^[1] This condition occurs because the inflammatory proteins in the bloodstream trigger the blood vessels to expand, lowering their blood pressure and preventing adequate blood flow. ^[1]

Inflammation can also damage endothelial cells, the cells that compose blood vessel walls. ^[3] This damage further lowers blood pressure by allowing fluid to leak into the tissues surrounding vessels. ^[3] Clinically, veterinarians identify edema (excessive fluid in the tissues) as the end result of this fluid imbalance. ^[3]

The combination of poor blood flow and widespread inflammation can trigger multiple organ dysfunction syndrome, where the horse’s internal organs begin to fail. ^[1] This condition most commonly affects the kidneys, liver, and lungs, but any organ may show signs of failure. ^[1][3]

Many horses also develop laminitis during this stage of sepsis. ^[1]

Endotoxemia

Gram-negative bacteria, a specific class of bacteria, have a special structure in their cell wall called lipopolysaccharide (LPS). ^[1] LPS, also called endotoxin, is a highly potent activator of the immune system, resulting in a widespread inflammatory response if these bacteria cause septicemia. ^[1]

Sepsis caused by Gram-negative bacteria in the bloodstream is called endotoxemia, and typically causes more severe symptoms than sepsis caused by other bacteria due to strong activation of the immune system. ^[1] Diagnosing the type of bacteria present on blood culture can help differentiate endotoxemia from other causes of sepsis. ^[1]

In horses, most cases of sepsis result from Gram-negative bacterial infections, with many studies showing that over 90% of bacterial cultures from septic foals are Gram-negative. ^[4]

Causes

Any source of infection can potentially lead to sepsis, if the bacteria successfully enter the bloodstream. ^[1]

Common causes in adult horses include: ^[1][5][6][7]

• Pleuropneumonia (shipping fever)
• Peritonitis
• Compromised intestinal tract during colic, allowing normal intestinal flora to enter the blood
• Colitis caused by bacterial infections such as Clostridium, Salmonella and Potomac horse fever
• Joint infections
• Infected wounds
• Retained placenta

Common causes in foals include: ^[1][5][6][7]

• Colitis caused by bacterial infections such as Clostridium and Salmonella
• Umbilical infections
• Aspiration pneumonia or inhaling bacteria from the environment
• Patent urachus

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Symptoms

Horses with bacteremia or septicemia typically show signs associated with infection. Common signs include: ^[1]

• Fever
• Lethargy
• Yellow-green discharge, pain, heat, and swelling at the infected site

If immune system responds to the bacteremia or septicemia, horses can rapidly develop systemic inflammatory response syndrome and become septic.

Symptoms of the SIRS include: ^[1][6]

• Fever or hypothermia (low body temperature)
• Rapid heart rate
• Rapid breathing or excessively slow breathing
• Dark red gums which may have pinpoint spots
• Bleeding from the nostrils

Horses with poor blood flow due to septic shock may show additional symptoms such as: ^[5][6]

• Cold limbs and ears
• Little to no digital pulses
• Poor filling of the jugular vein when compressed
• Pale gums
• Slow capillary refill time when pressing on the gums

Foals

Foals have relatively weak immune systems, which predisposes them to severe sepsis. They can also develop sepsis very rapidly, with few warning signs.

Symptoms often seen in septic foals include: ^[3]

• Sleeping more than usual
• Not nursing
• Diarrhea
• Tacky, dry gums
• Rapid heart rate
• Rapid breathing
• Cold limbs and ears
• Hypothermia
• Weakness

In some cases, foals die before noticeable symptoms develop. ^[3]

Diagnosis

Veterinarians can make an initial diagnosis of septicemia or sepsis based on the horse’s clinical signs and the presence of an infection. ^[1]

Bloodwork showing changes in white blood cell concentrations can support this diagnosis. ^[1] White blood cells are the body’s major immune cell, and their levels change significantly during sepsis. ^[1]

Other bloodwork changes that can indicate sepsis include: ^[1][7]

• Lactic acidosis (acidification of the blood by lactate)
• Increased serum amyloid A, an indicator of inflammation
• Low blood glucose
• Prolonged blood clotting times

Veterinarians also monitor blood components such as liver enzymes, creatinine, and urea to check on the health of the liver and kidneys, as these organs commonly fail during sepsis. ^[1]

Confirming a diagnosis of septicemia and sepsis requires a blood culture, where diagnostic labs measure the amount and type of bacterial growth from a blood sample. ^[1] However, these tests often fail to show a positive result, even in septic horses. ^[8]

A false negative result can occur due to contamination of the sample, poor sample handling, incorrect timing of the sample, or a low volume of blood collected. ^[8]

Treatment

Treatment of sepsis is complex, as affected horses have many abnormalities in their physiology that the veterinary team must counteract. Sepsis treatment protocols are usually individual to the horse’s specific needs and may change frequently as the horse’s condition changes.

Most horses require hospitalization due to the intensive nature of treating sepsis. ^[1]

Fluid Therapy

Fluid therapy is necessary for horses with sepsis to counteract the effects of septic shock. ^[1][4] Providing additional fluids helps maintain blood flow to the organs to reduce the risk of organ failure. ^[1]

Common fluids used for sepsis treatment include: ^[1]

• Saline solutions
• Blood plasma
• Hetastarch-containing fluids, which have a longer lasting effect compared to other fluids

Depending on the horse’s bloodwork, veterinarians may also add sodium bicarbonate to fluid solutions to help balance the horse’s blood acidity. ^[1] Electrolytes and glucose may also be necessary to replenish the bloodstream. ^[1][4]

Anti-Inflammatories

Anti-inflammatory medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs) are common medications used in managing equine sepsis. ^[1] These medications inhibit the production of inflammatory mediators that activate the immune system. ^[1] They also help reduce pain associated with the infectious condition that triggered the sepsis episode initially. ^[4]

The most common NSAID used for sepsis is flunixin meglumine. ^[1] However, other NSAIDs such as ketoprofen, phenylbutazone, and eltenac are also options. ^[4]

Antibiotics

Since the underlying cause of sepsis is a bacterial infection, antibiotics are a common component of treatment protocols for this condition. ^[4]

Common antibiotics include: ^[4]

• Penicillin
• Gentamicin
• Enrofloxacin
• Ceftiofur

Veterinarians must be cautious about the type of antibiotic chosen, as some antibiotics may cause an increased release of LPS from dying bacteria and exacerbate the horse’s condition. ^[1]

Hyperimmune Serum

Hyperimmune serum is an equine blood product harvested from horses vaccinated against endotoxin. ^[1] Vaccinated horses develop a robust antibody response against LPS, and injecting their serum into a septic horse can boost that horse’s immune response against bacteria. ^[1]

Dimethyl Sulfoxide

Dimethyl sulfoxide (DMSO) is an antioxidant medication that can bind and neutralize reactive oxygen species produced during endotoxemia. ^[4] DMSO can also reduce blood clotting, which can improve circulation and blood flow to the tissues. ^[4]

Polymyxin B

Polymyxin is an antimicrobial that can bind to the LPS component of Gram-negative bacteria. ^[4] Binding LPS reduce the inflammatory response by preventing LPS from interacting with immune cells, preventing activation of the immune system. ^[4]

For this reason, polymyxin is most effective before SIRS develops, but it may have some effects in already septic horses. ^[4]

Clotting Medications

Some horses with sepsis develop blood clotting abnormalities. These abnormalities can either result in too much clotting, producing blockages within blood vessels, or inadequate clotting if bleeding occurs. ^[1] In some cases, both conditions can occur in short succession, requiring careful management by the veterinary team. ^[1]

Treatments that alter blood clotting include: ^[1]

• Blood plasma administration
• Heparin
• Aspirin

Blood Flow Medications

Some veterinarians use drugs to directly counteract the effects of septic shock, which may allow them to use lower doses of fluid therapy. ^[1] These drugs increase the strength of heart contractions and raise blood pressure, increasing blood flow to organs. ^[1]

Some also include drugs that trigger dilation of blood vessels supplying critical organs, such as the kidneys and brain. ^[1]

Prognosis

Sepsis generally has a poor prognosis, particularly in affected foals. ^[7] Survival rates are typically around 50%, although individual factors can have a significant effect. ^[7] Early detection and treatment can improve the overall prognosis. ^[7]

Factors associated with a poorer prognosis include: ^[1][2][7]

• Having a Gram-negative bacterial infection
• Developing a joint infection or brain infection due to sepsis
• Laminitis
• Longer duration of clinical signs prior to treatment
• Signs of organ failure

Foals

Factors influencing the prognosis in foals specifically include: ^[3]

• Location of infection
• Age when they develop sepsis
• Presence of hypothermia
• Development of diarrhea
• Quality of the immune system response to the infecting bacteria

Another consideration regarding the prognosis in foals is their long-term performance capability if they recover from the infection. ^[3] Studies show that septic foals that recover from their illness have the same likelihood of starting a performance career as their peers. ^[3]

However, some studies in racehorses show that septic foals have lower career earnings as adults than foals who were healthy. ^[3]

Prevention

Preventing sepsis involves preventing conditions that may lead to sepsis, and prompt treatment of any conditions that do arise.

Preventative measures targeting known causes of sepsis include: ^[1]

• Sterile cleaning by the veterinarian prior to any joint injections
• Prompt cleaning and treatment of any wounds
• Early recognition and removal of retained placenta
• Allowing frequent breaks during trailering to allow horses to put their heads down and reduce the risk of shipping fever
• Proper management of surgical sites to reduce contamination

Foals are particularly susceptible to sepsis when they experience failure of passive transfer, or inadequate acquisition of antibodies from their dam’s colostrum. ^[7]

Early detection of failure of passive transfer by measuring blood antibody levels is crucial in preventing sepsis. ^[7] Breeders should ensure that foals receive an adequate amount of high-quality colostrum within the first 24 hours of life. ^[7]

Summary

Sepsis is a rapidly life-threatening inflammatory condition in horses caused by infection of the bloodstream.

• Left untreated, sepsis can cause organ failure and death in affected horses.
• Common symptoms include fever, rapid heart rate, rapid breathing, and dark red gums.
• Prompt veterinary intervention is necessary for survival.
• Treatment frequently requires hospitalization and intensive care.
• The overall prognosis for affected horses is poor with about 50% survival rates.