Introduction

Sepsis is responsible for a large percentage of human deaths each year and the mortality has remained unchanged despite advances in critical care. In small animals, sepsis is also a frequent contributor to morbidity and mortality. Septic peritonitis in animals may be the presenting complaint to the emergency service, or may be a complication of a surgical procedure such as enterotomy or gastric resection.

Pathophysiology

In sepsis, the local systemic response to infection that is designed to be protective becomes systemic and affects other body systems. The classic scenario for the cascade of events that result in sepsis begins with exposure to endotoxin, a component of the cell wall of gram-negative bacteria (or lipoteichoic acid in the case of gram-positive bacteria). Exposure to endotoxin activates neutrophils and macrophages to secrete inflammatory cytokines, the most well studied cytokines being tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin 6 (IL-6). Under normal circumstances, cytokines and other inflammatory mediators are responsible for the early clinical signs of sepsis (fever, neutropenia) and normally interact to neutralize the infection and generate a mild inflammatory response. If this immune response is overwhelmed, excessive inflammatory mediators are released leading ultimately to organ failure, shock and death.

The key changes associated with massive release of inflammatory mediators have important therapeutic implications and include disruption of microvascular permeability, nitric oxide mediated vasodilation, activation of coagulation with consumption of endogenous anticoagulants, and myocardial depression.

Terminology

Systemic Inflammatory Response Syndrome (SIRS) is described as the systemic response to a variety of clinical insults including bacteria, fungal, or tissue injury. In order for a dog to have SIRS, 2 out of the following 4 criteria should be present: tachycardia, leukocytosis or leukopenia, hypo-or hyperthermia, and tachypnea. A big limiting factor to the clinical usefulness of these criteria is that dogs, unlike people, pant and therefore the respiratory component of these criteria is subjectively evaluated. In cats, similar criteria have been proposed (but not validated), with a tentative diagnosis of SIRS if 3 out of 4 criteria are fulfilled. Cats have a tendency to be bradycardic when shock is present, so in cats tachycardia or bradycardia is included for the diagnosis of SIRS. It is important to note that these criteria are far from ideal. Sepsis is considered the systemic response to a documented infection. Animals are septic if they have an infection in addition to SIRS. Because of this, the definition of sepsis in people includes evidence of SIRS (2/4 criteria listed above), along with 'gross, histopathological, or microbiological evidence of infection or a strong suspicion of infection'.

Severe sepsis describes sepsis along with evidence of organ dysfunction (hyperbilirubinemia, thrombocytopenia, azotemia, altered mental state). Septic shock describes sepsis along with hypotension that is refractory to therapy and requires vasopressor therapy. Many dogs that present to the emergency room collapsed with evidence of sepsis are erroneously diagnosed with septic shock. They may be experiencing shock, and they may be septic, but they can only be diagnosed with septic shock if hypotension persists despite adequate fluid resuscitation. Parameters that can be used to guide fluid therapy include calculation of a shock dose of crystalloids or colloids, central venous pressure monitoring (difficult to use in an emergency situation due to the need for a central line), lactate concentration, and echocardiography to look for left ventricular filling.

Recognition of Sepsis

Sepsis should be considered a possibility in any dog or cat presenting with a fever. Clinical signs are often non-specific and may include lethargy, anorexia, vomiting, or collapse. On physical examination, fever, tachycardia and tachypnea are classic findings. Brick red mucous membranes, tachycardia and normal blood pressure are classic findings of the hyperdynamic phase of sepsis. As fluid shifts and volume depletion occurs, this hyperdynamic phase is replaced by a hypodynamic state characterized by pale mucous membranes, cold extremities, tachycardia, and hypotension. When treatment (such as resuscitation with intravenous fluids) is administered, the hypodynamic phase can be reversed, but untreated animals often progress to septic shock and death. Interestingly, septic cats are rarely hyperdynamic, and typically display characteristics of hypodynamic state (pale mucous membranes, hypotension, cold extremities). Hypotension is common in cats and can be difficult to treat. It is also important to remember that some dogs with sepsis may not show all the classic signs.

As with any dog or cat that presents to the emergency service, initial diagnostics consist of a brief physical examination (TPR) and point of care testing consisting of packed cell volume and total protein concentration, lactate concentration, electrolytes, and BUN assessment. In animals with septic peritonitis, evaluation of coagulation would also be indicated prior to surgery. Complete blood count (CBC) and chemistry profile results may be helpful in the recognition of sepsis. Classic changes associated with sepsis include a leukocytosis or leukopenia. Neutrophilic leukocytosis is often present, with or without a left shift. Toxic neutrophils may be present, and the platelet count is often decreased. Due to volume depletion, signs of hemoconcentration are also often present. Hypoglycemia, hypoalbuminemia, and elevated liver enzymes (ALP, ALT, AST) are often found on the chemistry profile. Of these, hypoalbuminemia is most prevalent. Other findings parallel organ dysfunction and can include azotemia or hyperbilirubinemia.

Diagnosing sepsis typically involves localizing a source of suppurative, septic exudate in a patient with systemic illness. Suppurative inflammation indicates the finding of inflammatory cells (mainly neutrophils), and septic indicates the finding of bacteria around and within the neutrophils. In a patient with signs of abdominal pain on physical examination, an abdominocentesis might yield turbid or blood tinged fluid that is septic on cytological examination. If no fluid is obtained but an abdominal source of sepsis is strongly suspected, the belly tap should be repeated after fluid resuscitation. Examination of the pellet after centrifugation may also be helpful. Abdominal diseases predisposing to sepsis include ruptured gastrointestinal foreign bodies, abdominal neoplasia, pyometra, and hepatic or renal abscesses. It is important to remember that an abdominocentesis should NOT be performed in a female dog that has not been spayed, despite an index of suspicion for abdominal disease, as perforation of the uterus will lead to septic peritonitis.

If a source of sepsis isn't immediately evident, imaging may be required. Abdominal ultrasound can help localize the source of sepsis once the animal is considered hemodynamically stable. Oxygen should be supplemented by mask if necessary. If at any point during the positioning for radiographs or ultrasound the animal becomes distressed or if the clinical signs worsen, attempts at obtaining radiographs should be abandoned until the patient is more stable.

Treatment

An intravenous catheter should be placed in all septic patients. If the patient is assessed as volume contracted (as judged by hemoconcentration or elevated lactate), rapid volume administration may be required. Crystalloids (Lactated Ringer's or 0.9% Sodium Chloride) are the fluid of choice for resuscitation unless the patient has underlying cardiac disease. Depending on the initial assessment, a shock dose (90 ml/kg in the dog and 40-60 ml/kg in the cat) or some portion of that is rapidly administered. Studies in people have identified improved survival in patients with aggressive protocol driven therapy. In dogs, empiric broad spectrum antibiotics should be administered as soon as sepsis is suspected and later changed according to culture and sensitivity results.

Septic peritonitis represents a surgical emergency during which the source of sepsis should be identified and removed. These animals may be managed using a closed suction drain (most common, for localized peritonitis), or by leaving the abdominal incision partially closed so that drainage can occur (for diffuse peritonitis). In the latter case, a sterile abdominal bandage is applied, and must be rewrapped at least daily, or whenever fluid is seen seeping through the bandage. The loss of fluid and protein in the septic patient treated as an open abdomen results in greater volume requirements, and these patients are often on high rates of intravenous fluids. Typically, a second surgery is performed 2-3 days after the initial exploratory surgery, and the abdomen is ravaged and closed at that time. In general, post-operative patients with abdominal sepsis may experience large volume losses due to severe peritonitis, and the importance of accounting for these fluid losses cannot be overemphasized. Fluid therapy consisting of crystalloids, colloids, or both, are necessary to maintain intravascular volume; however, the presence of vasculitis may make it difficult to administer aggressive fluid therapy without developing peripheral edema. Methods used to monitor intravascular volume status include serial body weights, urine specific gravity, echocardiography, central venous pressure, packed cell volume/total protein trends, and physical examination. Fresh frozen plasma may be administered to replenish clotting factors if a coagulopathy is documented. Fresh frozen plasma should not be used as a source of albumin due to the large volumes that are required for small changes in albumin concentration (except in the very small dog or cat). Vasopressors (dopamine) or inotropes (dobutamine) may be added if needed. Other infusions may include partial or total parenteral nutrition. The use of multiple fluid types may become confusing and may require multiple catheters. While peripheral catheters are typically placed during resuscitation, central venous access is important in the management of the critically ill patient. Central venous access is typically performed using the jugular vein, and allows for central venous pressure monitoring, as well as frequent blood sampling with minimal stress to the patient. Successful management of the septic patient relies heavily on attentive nursing care and attention to detail. Continuous re-assessment of these patients highlights subtle changes in their condition, and prompt attention may avoid progressive deterioration and ultimately multiple organ failure and death. The mortality rate for dogs with sepsis is reportedly 50-60%, and those that are saved are a reflection of hard work and attention to detail on the part of every member of the critical care team.