The Challenge of Surgical Sepsis

Infection is the result of the local activation of human inflammation due to the proliferation of microbial pathogens in tissue. The microbial exotoxins and endotoxins from the pathogens activate the coagulation cascade, platelets, the bradykinin pathway, mast cells, the complement cascade, and other responses of the innate immune response that are the component parts of the inflammatory cascade [1]. The result of these host responses to microbial cell products and pro-inflammatory signals is local vasodilation, increased microcirculatory permeability, and soft tissue edema. Microcirculatory vasodilation increases bulk flow to the tissue but reduces flow velocity, increased vascular permeability permits exit routes for serum proteins and phagocytic cells, and edema in the adjacent tissues provides conduits for leukocyte trafficking. The clinical result of local inflammation is the rubor, calor, dolor, and tumor that are characteristics of local infection. This local response serves the important role for containment and eradication of the infection pathogens.

Sepsis occurs when containment and eradication have failed, and the infection becomes systemic in domain. The pathogen, the pathogen cell products, or the pro-inflammatory signals achieve a systemic distribution. The normally beneficial inflammatory response of local infection becomes activated systemically with toxic consequences for the host. The results are tachycardia, tachypnea, leukocytosis, fever, and lactic acidemia. Pathophysiologic changes of the hyperdyanamic circulation and reductions of peripheral vascular resistance of the septic response then transition to cardiac suppression and vasoconstriction [2]. Metabolic changes of hypermetabolism, exaggerated gluconeogenesis, increased hepatic ureogenesis, and increased urinary nitrogen losses follow [3]. End-organ injury becomes the hallmark of full-blown human sepsis as the process continues. If not treated effectively, hypotension and hypoxemia will follow with septic shock being the result. Multiple mechanisms have been proposed for the pathologic pathways of human sepsis, but specific treatments with endotoxin inhibitors, monoclonal antibodies against specific cytokines, receptor antagonists, and other efforts have failed to improve outcomes.

The impact of sepsis in the United States has been estimated at 250,000 deaths annually and billions of dollars in healthcare costs [4]. For the US Medicare program, there were over 700,000 patient admissions for medical sepsis Medicare Severity, Diagnosis Related Groups (MS DRGs) at an inpatient expenditure of nearly $10 billion dollars in 2015 [5]. The frequency of sepsis in hospital admissions is increasing and is currently the most common MS DRG group (870–872) among hospital discharges for Medicare. The Surviving Sepsis Campaign has developed management guidelines to improve outcomes in the estimated 30% mortality rate for this population of patients [6]. Prevention would be the best strategy but the emergence of increasingly resistant pathogens, and the clinical dilemma of severely comorbid medical conditions and immunosuppressed patients makes this objective a formidable challenge.

This grim overview of sepsis in the United States understates the problem because it is not inclusive of all surgical sepsis patients. Because sepsis that is associated with the operation for treatment is not categorized as “sepsis” by the Medicare MS DRG methodology but rather is classified by the operation that is performed, the impact of surgical sepsis is not well defined. Surgeons are challenged with the management of community-acquired intra-abdominal infection and necrotizing soft tissue infections of which virtually all will meet sepsis criteria. Surgical site infections in the organ/space location will have sepsis as a usual accompaniment. Post-operative surgical patients will have pneumonias, urinary tract infections, intra-vascular catheter infections, and others that have sepsis consequently but may not be coded as such on the discharge summary, and even if appropriately recognized, will not change the MS DRG of the primary surgical procedure. Surgical sepsis is common but the diagnosis is often obscured by the primary surgical disease (e.g., perforated colon) or by the primary operation (e.g., colon resection).

This issue of Surgical Infections is dedicated to the theme of surgical sepsis. The unique issues of sepsis in the surgical patient will be emphasized. While specific antibiotic therapy and physiologic support of the host with contemporary critical care management are important for medical and surgical patients alike, surgical sepsis often requires control of the source of infection that is driving the response of the host. Drainage (i.e., abscesses), debridement (necrotic tissue), and controlling the primary source of microbial contamination (e.g., gastrointestinal perforation) remain essential objectives for the treatment of the septic surgical patient. Antibiotic therapy alone is sure to fail if source control is not achieved. The enhancement of overall patient outcomes by timely intervention with effective source control, effective supportive care, and appropriate antibiotics become paramount for rescue of the patient with evolving surgical sepsis.