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The Systemic Inflammatory Response Syndrome, Sepsis, and Septic Shock


Epidemiology

Sepsis remains a major cause of morbidity and mortality among children across the globe. In the US, the estimated incidence annually is 1 case per 1000 persons, an increase compared with prior years. , , Sepsis now accounts for 4.4% of children’s hospital admissions and 7% of patients treated in US PICUs. , Global estimates for sepsis are limited; however, the Sepsis Prevalence, Outcomes, and Therapies (SPROUT) study used prospective point prevalence estimates among 128 sites in 26 countries and found variability in prevalence and mortality. For example, 6%–8% of patients were treated in PICUs in North America, Europe, Australia, and New Zealand with 21%–32% mortality compared with 15%–16% of patients treated in Asia with 40% mortality. A systematic review of the global burden of pediatric and neonatal sepsis confirmed that sepsis is common, with high mortality, but that data from low-income settings and lack of standardization of diagnostic criteria and definitions are challenging. The economic impact of pediatric sepsis is large. One study estimated a median hospital stay of 17 days and a median total hospitalization cost of $77,446, and another estimated the annual health care expenditures in the US as $4.8 billion.

Most cases of sepsis worldwide are due to lower respiratory tract and bloodstream infections. The incidence of sepsis is highest in neonates (9.70 per 1000) and falls significantly in older children (0.48 per 1000 in 10- to 14-year-olds). Underlying comorbidities vary by age; however, neuromuscular, cardiovascular, and respiratory comorbidities were most common in all age groups. Endocarditis and central nervous system infections had the highest case-fatality rates (16.7% and 15.2%, respectively), whereas genitourinary and wound and soft tissue infections had the lowest (3.7% and 3.9%, respectively).

While the advancement in critical care medicine has improved child survival, long-term outcomes, including functional disabilities, continue to be of concern. Post-intensive care syndrome (PICS) refers to the disability that remains after surviving a critical illness. PICS includes impairment in cognition, psychological health, and physical function of the survivor and family. Long-term follow-up of these patients may help delineate the optimal care for ICU survivors.

Definitions

The consensus definitions for systemic inflammatory response syndrome (SIRS), infection, sepsis, severe sepsis, septic shock, and multiple organ dysfunction syndrome in children were developed by the International Consensus Conference on Pediatric Sepsis and are listed in Box 11.1 . , It is important to recognize that these definitions were initially created for use in the design, conduct, and analysis of large, multicenter, international therapeutic trials and may be helpful to clinicians in determining severity and monitoring response to therapy. Intra-individual and inter-individual differences in the time course of disease progression exist, and thus a clinical concern for sepsis may supersede laboratory and physiologic cutoffs. Ranges of vital signs, such as those used by the Pediatric Advanced Life Support septic shock guidelines, may be clinically useful to help guide diagnostic and therapeutic decisions.

BOX 11.1
Definitions of Systemic Inflammatory Response Syndrome, Infection, Sepsis, Severe Sepsis, and Septic Shock
Modified from Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med . 2005;6(1):2–8 and Weiss SL, Peters MJ, Alhazzani W, et al. Surviving Sepsis Campaign international guidelines for the management of septic shock and sepsis-associated organ dysfunction in children. Pediatr Crit Care Med . 2020;21(2):e52–106

Systemic Inflammatory Response Syndrome (Sirs)

Presence of ≥2 of the following criteria, one of which must be abnormal temperature or leukocyte count:

  • Core temperature by rectal, oral, or central catheter probe of >38.5°C or <36°C

  • Tachycardia, defined as a mean heart rate >2 SD above normal for age in the absence of external stimulus, chronic drugs, or painful stimuli; or otherwise unexplained persistent elevation over a 0.5- to 4-hour time period or for children <1 year old: bradycardia, defined as a mean heart rate <10th percentile for age in the absence of external vagal stimulus, β-blocker drugs, or congenital heart disease; or otherwise unexplained persistent depression over a 0.5-hour time period

  • Mean respiratory rate >2 SD above normal for age or mechanical ventilation for an acute process not related to underlying neuromuscular disease or the receipt of general anesthesia

  • Leukocyte count elevated or depressed for age (not secondary to chemotherapy-induced leukopenia) or >10% immature neutrophils

Infection

Suspected or proven (by positive culture, tissue stain, or polymerase chain reaction test) infection caused by any pathogen or a clinical syndrome associated with a high probability of infection

Evidence of infection includes positive findings on clinical examination, imaging, or laboratory tests (e.g., white blood cells in a normally sterile body fluid, positive cultures or molecular tests, perforated viscus, chest radiograph consistent with pneumonia, petechial or purpuric rash, or purpura fulminans)

Sepsis

SIRS in the presence of or as a result of suspected or proven infection

Severe Sepsis

Sepsis plus the following: cardiovascular organ dysfunction, acute respiratory distress syndrome (ARDS), or two or more other organ dysfunctions

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