Systemic inflammatory response syndrome refers to out-of-control inflammation that has overwhelmed the body’s endogenous anti-inflammatory mechanisms. This syndrome is associated with observable clinical signs and substantial morbidity and mortality in both human and non-human animal patients. Sepsis is the systemic inflammatory response syndrome (SIRS) associated with a documented infection.
In SIRS, there is a hypercytokinemia. Cytokines are protein, peptide, or glycoprotein molecules that are produced by a cell, interact with a receptor on a cell, and bring about a change in the behavior of a target cell. Unlike hormones, which are produced by specific cells or tissues, cytokines are produced by most cells, and are actually much more potent than hormones on a molar basis. Cytokines have diverse biologic effects; some are pro-inflammatory and some are anti-inflammatory. They are produced in response to the recognition of a danger signal, either from an endogenous molecule or a molecule associated with a pathogen, by an immune system cell. Most cytokines are released from activated monocytes, macrophages, and neutrophils, and the result is alterations in thermoregulation, heart rate, respiratory rate, and white blood cell counts.
Activated neutrophils may be recruited and go to sites distant from the original lesion, causing significant tissue and organ damage and destruction when inflammation or injury is ongoing; when there are new insults to the organism such as hypoxia or surgery; or if there is immune-mediated or immunodeficiency disease. At this point there are recognizable clinical signs that indicate the inflammatory response has spiraled out of control, and that SIRS is present.
In humans, severe sepsis is the third leading cause of death, with a mortality rate of 28-50% or greater. If sepsis is recognized early, there is a greater probability of being able to save the patient. Once septic shock and multiple organ failure occur, the mortality rate increases dramatically. Much less is known about the epidemiology of sepsis in veterinary patients than in humans. A single study of hospitalized dogs in the intensive care unit (ICU) of a veterinary teaching hospital demonstrated that dogs with sepsis were hospitalized longer, incurred higher treatment costs, and had a higher mortality rate than critically ill dogs without sepsis. Even less is known about sepsis in cats, but cats with infectious diseases, such as pyothorax, hepatic abscesses, and septic peritonitis, have a high mortality rate.
In this 3-month observational study of 246 client-owned cats hospitalized in a veterinary teaching hospital, these researchers were interested in identifying cases of community-acquired sepsis at hospital admission, as well as hospital-associated sepsis, and determining the epidemiology of SIRS and sepsis in cats within the greater population of hospitalized cats in the same institution. They hypothesized that the mortality rate for cats with sepsis would be significantly higher than that for other hospitalized cats. All patient care and diagnostics, treatment, and monitoring of the animals was determined by the primary care clinician.
Criteria for the diagnosis for SIRS in feline patients were defined as the presence of two or more of the following clinical signs: rectal temperature > 39.7 degrees C (103.5 degrees F) or <37.8 degrees C (100 degrees F); heart rate > 225 beats/minute or < 140 beats/minute; respiratory rate > 40 breaths/minute; or white blood cell count (WBC) >19,500/microliter or <5,000/microliter, or a band neutrophil fraction > 5%. The patients were evaluated for SIRS criteria and the number of SIRS criteria met for each cat on a given day was recorded. Also recorded was the number of cats that met two or more and three or more of the four listed SIRS criteria on each day.
Those cats that met the criteria for SIRS diagnosis and also had a documented source of infection identified by culture, cytology, histology, or serology and had clinical signs of disease were labeled as septic. Community-acquired sepsis was diagnosed in patients with evidence of SIRS and an infection at the time of hospital admission. Those cats who developed SIRS and an infection more than 24 hours after hospital admission were considered to have hospital-associated sepsis.
During the observation period, 26 cats were hospitalized twice and 3 cats were hospitalized 3 times, so 246 cats involved in 275 hospital admissions were studied. Median age of 236 of the cats for which age was recorded was 8.0 years (range 0.1-21.4 years). Most cats were either castrated males (n=135) or spayed females (n=79); there were also some sexually intact females (n=18) and males (n=13). The vast majority of patients were mixed breeds (147 domestic shorthair and 47 domestic longhair); a variety of pedigreed cats were also included. Median duration of hospitalization for all patients was 2 days (range, 0 to 26 days).
Four disease categories were defined: sepsis, infection, noninfectious SIRS (NSIRS), or no SIRS. Infection was diagnosed in 33 of the 275 (12%) hospitalizations evaluated in the study. Seventeen of the 33 cats with infection met at least two of the criteria for SIRS and were diagnosed as septic. Peritonitis was found in 6/17; a urinary tract infection in 5/17; systemic infection in 3/17; respiratory tract infection in 2/7, and hepatobiliary disease in 1/17. All of these cats were septic at hospital admission and were considered to have community-acquired sepsis. Four other cats developed sepsis after hospital admission, giving an incidence of 1.5 cases/100 hospital admissions, as opposed to 6.2 cases/100 hospital admissions for those cats with community-acquired sepsis.
Cats survived to hospital discharge in 239/275 (86.9%) of hospitalizations; in 36/275 (13.1%) of the hospitalizations, the patient either died of natural causes (n=8; 2.9%) or was euthanized (n=28;10.2%). No patients died or were euthanized due to iatrogenic adverse events. The prevalence and incidence of sepsis in the study cats was similar to that in dogs, and the prevalence of sepsis in the study cats was similar to that reported in human patients. Humans with sepsis, however, often have respiratory tract infections; respiratory tract infections were uncommon in those study cats who were septic. The most important causes of sepsis in the study cats were peritonitis and urinary tract infections.
Gram-negative organisms, particularly E. coli, were the most common cause of sepsis in the cats enrolled in this study. In humans, gram-positive organisms, especially those that are antimicrobial-resistant, are important in the etiology of sepsis. As in humans with sepsis, the study cats with sepsis often had chronic, serious comorbidities such as diabetes mellitus, neoplasia, and chronic kidney disease.
Hitherto, cats were diagnosed with SIRS only when they met three or more of the SIRS criteria defining derangements in rectal temperature, heart rate, respiratory rate, or WBC count. This definition of feline SIRS was established from a study of cats with presumptive severe sepsis that were evaluated with postmortem examination. These guidelines may actually be somewhat insensitive for the population of cats with less severe sepsis, and this is why these researchers adjusted their definition of SIRS to mean that > 2 of the 4 SIRS criteria were present in the patient, just as in dogs. Based on the results of this study, sepsis should be considered an important clinical entity in cats, one that is associated with a high mortality rate. Clinicians who care for critically ill cats should be vigilant in monitoring these patients for signs of SIRS and infections, and be prepared to intervene proactively as early as possible when as few as two of the four SIRS criteria are present in a patient. [PJS]
Costello ME, Drobatz KJ, et al. Underlying cause, pathophysiologic abnormalities, and response to treatment in cats with septic peritonitis: 51 cases (1990-2001). J Am Vet Med Assoc 2004;225:897-902.