What Is Sepsis?

Sepsis is a syndrome caused by over-activation of the immune response secondary to an overwhelming infection. This inflammatory reaction leads to physiologic and biochemical abnormalities in the body, which define the clinical diagnosis of sepsis and septic shock. Sepsis and septic shock are leading causes of mortality in critical care medicine and can significantly raise the risk of anesthetic and surgical mortality.

What Is Systemic Inflammatory Response Syndrome (SIRS)?

Recent revisions of the definition of the systemic inflammatory response syndrome (SIRS) have simplified the definition of the inflammation associated with infection, which, when combined, define sepsis. The new definition of SIRS includes two or more of the following: temperature >38°C or <36°C, heart rate >90/min, respiratory rate >20/min or PaCO₂ <32 mmHg, or white blood cell count >12,000/mm³ or <4,000/mm³ or >10% immature bands. This definition currently applies to adults only, but similar criteria are used for children. These were set forth along with age specific vital signs and were defined in 2005 by an international consensus conference. These vital signs, listed in Table 11.1, are used to define the SIRS response for pediatrics.

What Is the Definition of Septic Shock?

When patients meet the criteria for SIRS and there are signs of end-organ dysfunction, patients meet criteria for septic shock. When patients have multiple organ systems affected, they meet the criteria for multiorgan dysfunction syndrome (MODS), a syndrome which significantly increases overall mortality.

What Are Important Diagnoses to Consider in a Child with Sepsis?

The clinical presentation of sepsis emerges from a combination of host factors, such as genetics and predisposing conditions, and pathogenic factors, including virulence and pathogen load. The pathogen can be a wide range of infections, including all variety of viral, bacterial, and fungal disease. The likelihood of each different pathogen to cause infection varies by patient comorbidity. For example, the youngest children and babies are more vulnerable to viral illness and spontaneous bacterial infection, while older patients can have medical comorbidities such as rheumatologic or oncologic disease that can predispose to sepsis because of a weakened immune response.

Viral illnesses such as influenza, rhinovirus, and Epstein-Barr virus can all present with symptoms that can meet clinical criteria for sepsis. The most common and obvious cause of sepsis include bacterial infections. These can occur in many different sites as manifestation of pneumonia, urogenital tract infection, and blood stream infections.

Fungal infection can also cause sepsis, though the presentation of this type of disease tends to be more indolent and is significantly more dependent on a previously weakened immune response.

The patient in the vignette at the beginning of the chapter meets clinical criteria for septic shock with end-organ dysfunction including respiratory compromise, renal dysfunction, and hemodynamic failure. She also has leukemia and has recently undergone chemotherapy, leading to significant immunosuppression. Both of these represent significant predisposing comorbidities. Typhlitis is a neutropenic colitis seen in oncologic patients leading to a dilated large bowel, with high chance of perforation, which is the likely cause of septic shock in this patient.

What Are the Most Common Sites for Infection Leading to Sepsis?

The cause of severe sepsis can vary significantly by location, age, and institution. The most common site of primary infection in severe sepsis is the respiratory system followed by bloodstream infection, genitourinary tract infections, abdominal, and central nervous system infections.

What Are the Most Common Pathogens Leading to Severe Sepsis?

Common bacterial causes include both gram-negative bacteria including Escherichia coli, Klebsiella species and Pseudomonas aeruginosa and gram-positive bacteria such as Staphylococcus and Streptococcus. It is important to consider early involvement of infectious disease specialists and to follow local antibiotic guidelines for appropriate treatment of at-risk populations to ensure broad coverage to cover all likely causative agents. Without appropriate source control, septic shock will continue to worsen and will lead to severe morbidity.

What Is the Incidence and Most Common Age of Presentation of Sepsis?

Sepsis and septic shock are leading causes of worldwide morbidity and mortality and a leading cause of critical illness. Approximately 1/3 of mortality in tertiary pediatric intensive care units (PICUs) is attributable to sepsis. A recent international survey of PICUs demonstrated a prevalence of 8.2% among patients admitted to a PICU with a median age of 3 years and a range from 0.7 years to 11 years.

What Is the Pathophysiology of Septic Shock?

The understanding of the cause of sepsis is incomplete, but the fundamental etiology is a significant release of vasoactive cytokines and bacterial derived products. Certain pathogens contain products such as lipopolysaccharides that have a higher potential to cause this cytokine storm. Similarly, certain individuals will have a more exaggerated response to pathogenic products, which will also lead to a higher cytokine response.

The specific response of each individual patient varies widely and depends on the pathogen load and virulence, and on the host with significant genetic variation and coexisting disease. The initial immune response also triggers several other cascades including complement and coagulation activation and catecholamine release.

What Are the Major Hemodynamic Consequences of Septic Shock?

Septic shock is most commonly seen in adults as warm shock with significant peripheral vasodilation leading to a high-output shock state. Tachycardia will increase total cardiac output to compensate for a greater volume of distribution secondary to vasoplegia caused by cytokine release. While warm shock is still the most common presentation in pediatrics, a considerable proportion of patients may also present in a cold shock state with decreased perfusion and delayed capillary refill. This version of septic shock is associated with depressed cardiac function and decreased cardiac output. The cause of this variation is incompletely understood but the consequences are the same as the majority of cases present with metabolic acidosis and end-organ dysfunction.

During early resuscitation, it is important to distinguish between warm and cold shock. Both instantaneous capillary refill and delayed capillary refill are seen in sepsis and management of septic shock should be adapted accordingly. Current guidelines for septic shock recommend initial volume resuscitation with crystalloid, up to 200 mL/kg, though most children will be given 40–60 mL/kg. Central venous pressure monitoring is useful to guide volume resuscitation with a common goal of approximately 8–12 cm H₂O, while monitoring for signs of fluid overload. There do not seem to be any advantages to colloid therapy.

Early initiation of inotropic support is recommended, preferably via central access if available. Epinephrine is the first-line choice for cold vasoconstricted shock, but dopamine has also been used successfully. Norepinephrine is the first-line therapy for warm vasodilatory shock. The role for other vasoactive medications in pediatrics has not been defined, though phenylephrine may provide peripheral vasoconstriction to treat hypotension secondary to warm shock, while dobutamine often provides significant inotropy.