The Global Burden of Sepsis: Barriers and Potential Solutions

Kristina E. Rudd; Niranjan Kissoon; Direk Limmathurotsakul; Sotharith Bory; Birungi Mutahunga; Christopher W. Seymour; Derek C. Angus; T. Eoin West


Crit Care. 2018;22(232) 

In This Article

Quantifying the Global Burden of Sepsis

Challenges in Definitions

Early, accurate identification of patients with sepsis is critical to improving outcomes through better targeted medical management,[7] yet remains challenging. There is no single "gold standard" diagnostic test for sepsis, and case definitions vary widely. Use of nonspecific terminology such as "septicemia" remains pervasive. A consensus definition of adult sepsis, originally proposed in 1991, was most recently revised in 2016 (Sepsis-3).[8,9] Sepsis-3 defined sepsis as a syndrome of "life-threatening organ dysfunction caused by a dysregulated host response to infection",[9] and the authors proposed that organ dysfunction be identified by a change in organ failure score relative to baseline. The analyses underpinning these clinical criteria were based on data exclusively drawn from the United States and Germany.[10] The validity of one Sepsis-3 clinical prompt, the Quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) score, has now been retrospectively evaluated in multiple datasets from LMICs.[11] However, neither the qSOFA score nor other Sepsis-3 criteria have been tested prospectively in low-resource settings. Until these clinical criteria are more fully validated in more diverse populations, their utility elsewhere in the world remains uncertain. Additionally, the Sepsis-3 Task Force explicitly did not examine definitions of infection and did not specify which infections, when leading to life-threatening organ dysfunction, should be considered as causes of sepsis.[9] There is some disagreement within sepsis and infectious disease communities regarding this issue; for example, some authors consider malaria to be a potential cause of sepsis, whereas others do not. This disagreement has important implications for comparability of patient populations in research studies and for the clinical application of sepsis treatment guidelines.

The definition of pediatric sepsis is also challenging. Last revised in 2005 and based heavily on the 1991 adult sepsis consensus definition, the pediatric definition offers age-appropriate values for the systemic inflammatory response syndrome (SIRS) criteria.[12] Combined with suspected infection, the presence of these modified SIRS criteria is used to identify pediatric patients with sepsis. This definition has not been revisited in over a decade and has posed problems in implementation, especially in low-resource settings, due to its low specificity and requirement for a leukocyte count.[13]

Heterogeneous Clinical use of Definitions

While the adult and pediatric consensus sepsis definitions are endorsed by multiple professional societies, clinicians show high levels of disagreement regarding the application of the definitions to clinical cases.[14] Additionally, the sepsis definitions are currently operationalized through the use of various clinical scoring systems (such as the qSOFA score, SOFA score, or SIRS criteria), some of which may be impractical to use at the bedside in low-resource settings. Moreover, the burden of sepsis is very difficult to quantify when clinicians do not uniformly document it in their practice. Often patients are classified based on the primary source of infection, such as pneumonia or meningitis, but are not explicitly deemed to have sepsis.[15] Accurate assessment of sepsis epidemiology is most feasible on a broad scale through the use of International Classification of Diseases (ICD) coding in administrative data or vital records, but this is impossible without more uniform coding practices worldwide.

Initiatives to Quantify the Burden

As a result of these issues related to sepsis definition and documentation, most estimates of the global burden of sepsis are likely to be inaccurate. Further, it is likely that many sepsis deaths occur at home, particularly in low-resource settings, and thus are less likely to be identified and documented as sepsis related. Two of the most comprehensive and rigorous efforts to document the worldwide burden of disease, the Global Burden of Disease study by the Institute for Health Metrics and Evaluation (IHME)[16] and the World Health Organization's (WHO) World Health Statistics,[17] have not previously quantified the burden of sepsis beyond neonatal or maternal sepsis. Encouragingly, the IHME has recently indicated that it will produce estimates for the burden of sepsis for the first time, and the World Health Assembly of the WHO passed a resolution on Improving the Prevention, Diagnosis, and Management of Sepsis in May 2017.[18]