Sepsis is a health puzzle in human history: "When in continued fever, the external surface of the body is cold and internally great heat is felt; with thirst; the affection is mortal" (Hippocrates, 460–370 BC).

The Third International Consensus Definitions for Sepsis and Septic Shock in 2016 (Sepsis-3) defines sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection. Clinically organ dysfunction can be represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more and an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dl) in the absence of hypovolemia.

Another concept that arose from this recent consensus conference was a classification scheme for sepsis.

This approach is recognized as PIRO and incorporates 4 factors in the stratification:

1.  Predisposition to develop sepsis and septic shock and involves individual genetic variations or polymorphisms appear to further contribute to susceptibility.

2.  Infection as the presence of bacteria and the inflammatory process associated.

3.  Response is the individual reaction to the septic challenge. No specific biomarkers have been found to be reliable in veterinary medicine.

4.  Organ dysfunction is the presence of some degree of organ dysfunction in dogs and cats, and it correlated closely with the outcome.

Septic shock is defined as sepsis with unresponsive hypotension that require vasopressor therapy after volume-resuscitation. Septic shock is actually a combination of hypovolemic, cardiogenic and distributive classes of shock that occur as a result of systemic infection. It often has signs characteristic of SIRS in addition to a finding of hypotension (systolic blood pressure <90 mm Hg) unresponsive to fluid therapy and often with some degree of organic failure.

Clinical Signs

Patients that are in early septic shock may have "injected" or brick red mucous membranes with a shortened capillary refill time (CRT< 1 second), tachycardia, tachypnea, fever, bounding pulses and may feel warm to the touch due to peripheral vasodilation. As septic shock progresses, mucous membranes may take on a "muddy appearance, CRT becomes prolonged (>2 seconds), pulses become weak and the extremities may become cool to the touch.

Owners of pets that present with any of the above clinical signs should be questioned closely to determine if there are predisposing factors in the patient history, as Immunosuppressive therapy for immune-mediated disease and/or chemotherapy for cancer. Underlying diseases such as hyperadrenocorticism, diabetes mellitus and viral infections such as parvovirus can place an animal at risk for the development of sepsis.

Owners of intact female pets should be questioned about recent pregnancies and estrus cycles. Additionally it should be determined if the animal is exposed to other animals (wild or domestic) and whether it has had any recent medical or surgical procedures (biopsies, foreign body removal, etc.).

The goals of treatment of patients with septic shock are to maximize oxygen delivery to the tissues to address the increased tissue demand. To achieve this goal, hemodynamic and metabolic abnormalities must be corrected. Finally, the site of infection must be determined and eliminated.

Common sites for septic foci include the abdominal cavity and the GI tract, the reproductive tract, the urinary tract, the thoracic cavity and the heart valves. The patient should be examined closely for evidence of heat, pain or swelling that may suggest presence of abscess or cellulitis.

On auscultation, muffling of heart and lung sounds can occur with pyothorax and crackles may be heard in patients with pneumonia. Alternatively, a new murmur may be ausculted with endocarditis. Pain on palpation of the abdomen may be seen with peritonitis, pancreatitis, pyelonephritis, and blunt or penetrating trauma. Palpation of the spine may demonstrate neck pain suggestive of meningitis, or thoracolumbar pain consistent with pyelonephritis. Discospondylitis may cause pain anywhere along the spine.

Diagnosis

Blood should be obtained for complete CBC, lactate assessment, electrolytes, coagulation (PT, aPTT), clinical chemistry panel and blood gas evaluation. Ideally blood samples should be taken aseptically hourly for 2–3 hours to be submitted for culture. Additionally a urine sample should be obtained by cystocentesis for urinalysis, sediment and culture.

If fever and leukocytosis are present, a rational approach to find a source of infections should be made: Thorax radiographs and Abdominal Ultrasound could be a performed whenever possible.

Therapy

A couple of large bore, peripheral catheter should be placed for fluid administration. The usage of central catheters has been questioned.

There is no single "right" choice for fluid therapy. The classic approach of a "shock" dose of a sodium- containing crystalloid can be given (70–90 ml/kg in dogs, 45–60 ml/kg in cats) is very rarely recommended anymore.

Multiple strategies, including Early-goal therapy has been proposed for the treatment of these patients. Bolus therapy with 10 ml/kg of a crystalloid followed by a reassessment of the patient is commonly recommended today, pursuing clear end-goals as lactate or target blood pressure. If the patient does not seem to be responding, new bolus attempts with same volume maybe attempted. If no response is observed a colloid such as hetastarch (10–20 ml/kg/day) may be given.

Some data from human volunteers and experimental animals proves that 3–4 times as much crystalloid as colloid infusion are needed to achieve an equivalent increase in intravascular volume. Silverstein et al. investigate the effect of different type of fluids. 80 ml/kg of saline, 4 ml/kg of hypertonic saline (7.5%), 20 ml/kg of dextran-70, and 20 ml/kg of 6% HES were compared.

The saline resulted in the largest immediate increase in blood volume, with a direct correlation with the volume infused. However, this increase was transient and followed by a rapid decline, attributed to prompt fluid redistribution into the interstitial space.

The synthetic colloidal solutions generated the largest cumulative effects between 30 and 240 minutes, with blood volumes that continued to increase beyond the administration interval.

However, through the total study period (0–240 min), there was no statistically significant difference in the volume expanding efficiency of either synthetic colloid compared with normal saline.

A veterinary research study evaluated the effect of tetrastarch administration on hemodynamic and laboratory variables in healthy dogs and dogs with lipopolysaccharide (LPS)-induced systemic inflammation, as compared with an equal volume of saline. Comparable volume-expanding efficacy was found after administration of saline or HES in both healthy and LPS-treated dogs.

Tetrastarch administration led to an expected increase in plasma COP, whereas saline led to a dilutional-associated decrease in COP. Despite the provision of oncotic support, no significant beneficial effect on hemodynamic stabilization (HDS) in the LPS-treated dogs was demonstrated with the colloid over normal saline.

Colloids (plasma, hetastarch or dextrans) should also be considered if the total protein is <3.5 gm/dl or the albumin is <2 mg/dl. Also patients evidencing hypoglycemia (BG <60 mg/dl) should receive a bolus of 50% dextrose at 0.5–1 ml/kg, diluted 1:1 with saline.

Once cultures have been submitted, antibiotic therapy should be instituted pending the culture and sensitivity results. Broad-spectrum antibiotics should be selected based on the suspected pathogen(s).

Hypotension, sepsis and systemic inflammation can predispose septic patients to GI ulceration. Use of H₂ blockers such as famotidine, ranitidine or cimetidine may help to reduce the risk of ulceration. If evidence of GI hemorrhage is seen, sucralfate can be used to coat and protect the ulcerated mucosa. Antiemetics may be needed in patients with persistent vomiting.

Nutrition is critical in septic patients. Enteral nutrition is the best way to provide nutrients both to the patient and to the enterocytes, enhancing the health of the GI mucosa and preventing bacterial dysbiosis.

Nausea should be evaluated and treated. Maropitant and ondansetron a regular dosages can be used safely.

Finally, good nursing care is essential for the patient's wellbeing. Recumbent patients should be turned every 4 hours to prevent decubital ulcers. Additionally, recumbent patients should be kept on well-padded surfaces that are covered with absorbent material to prevent scalding by urine and feces. Catheters should be checked daily for signs of infection or phlebitis and changed as needed. If possible allow extended periods of time in which the patient can rest (turn down lights, limit invasive treatments/monitoring after midnight).

Sepsis and septic shock/SIRS are life-threatening disorders that carry a guarded prognosis. Care of septic patients is time consuming and expensive so clients should be fully informed of the prognosis and possible complications before embarking on such an endeavor. However, with close monitoring and intensive care septic patients can be treated successfully.

References

References are available upon request