INTRODUCTION

Sepsis, severe sepsis, and septic shock (see Chapter 107) are common causes of morbidity and mortality. The incidence of severe sepsis in humans in the United States is approximately 3 cases per 1000; the mortality rate is approximately 30% and is due to progression to septic shock and multiple organ failure.¹ The incidence of sepsis in veterinary medicine is unknown, but the mortality rates appear to be similar, ranging from 20% to 68%.^2-6 Recognition and early, aggressive intervention and supportive care are key to the treatment of sepsis and septic shock.

DEFINITIONS

DIAGNOSTIC CRITERIA FOR SEPSIS

Sepsis and the systemic inflammatory response syndrome(SIRS) are clinical syndromes, not diseases, and as such are inherently difficult to define. In 2001, the International Sepsis Definitions Conference produced consensus guidelines for definitions and terminology for syndromes associated with microbial infection and the host response to it.⁷ Because of the difficulty in defining universal physiologic derangements associated with sepsis, the Consensus Committee produced a list of clinical and physiologic derangements to “attempt to codify the physical and laboratory findings that prompt an experienced clinician to conclude that an infected patient ‘looks septic’”⁷ (Box 106-1). These criteria were proposed for human patients. Therefore, although conceptually useful for veterinary patients, specific values have not been validated in these species.

STAGING SEPSIS

Following the 2001 International Sepsis Definitions Conference, the concept called PIRO was adopted to stage sepsis and to describe clinical manifestations of the infection and the host response to it.⁷ In this model, PIRO is an acronym for predisposition, insult or infection, response, and organ dysfunction. This conceptual and clinical framework attempts to incorporate patient factors with the microbial insult in order to stage the disease process and to identify factors that may contribute to morbidity and mortality. The PIRO approach may employ advanced diagnostic techniques not yet available in veterinary medicine, but hopefully it can serve as a guideline until similar methods are available and validated (Table 106-1).

Table 106-1 PIRO System for Staging Sepsis⁷

Predisposition refers to the patient-specific factors that increase the risk of developing or dying from sepsis. Factors to be considered include genetic factors, comorbid conditions, age, species, breed, gender, and even socioeconomic factors. For example, an immunosuppressed patient may be more likely to contract an infection and less likely to mount an appropriate immune response. Socioeconomic factors may also play a role; inadequate vaccination against canine parvovirus in the individual and in the community would increase the risk of a given dog contracting parvoviral enteritis in its local environment.

Insult refers to site, type, and extent of infection. All of these factors may influence the extent and course of disease. For example, generalized peritonitis is more serious and extensive than an encapsulated infection at a feeding tube site. Compared with a community-acquired infection, a nosocomial infection may harbor bacteria that are more resistant to antimicrobial agents. A gram-positive or fungal infection will elicit a different host response than will a gram-negative infection.

Response refers to the host reaction to infection which may, in part, determine whether there is an adequate, inadequate, or overly exuberant inflammatory response. Additionally, there are regional and temporal differences in the immune response to infection, meaning that in some areas or times the response may be deficient (often termed immune paralysis) whereas in others the response may be overly exuberant, either of which may be harmful to the patient. The host response is characterized by biomarkers of inflammation (e.g., interleukin [IL]-6, C-reactive protein), measures of host responsiveness (e.g., CD11 and CD18, lymphocyte function), or detection of specific targets of therapy (e.g., protein C, antithrombin, cortisol response). Currently in veterinary medicine, relatively few biomarkers are available to assess host response.

Organ dysfunction refers to physiologic derangements secondary to the infection or to the host response or both. Organ dysfunction may be reversible. Classic examples of sepsis-associated organ dysfunction include DIC, acute respiratory distress syndrome, and acute renal failure.