Twice as Many Individuals Die of Sepsis Than Previously Estimated

It is well known that sepsis accounts for many deaths around the world and as such, sepsis-related mortality is of particular concern for infectious disease specialists.

Investigators of a new study published in The Lancet report that sepsis is associated with 1 in 5 deaths globally, twice the amount that some previous estimates indicated. Despite declining incidence, the investigators discovered that sepsis remains a substantial cause of mortality worldwide.

Data for the global burden of sepsis are limited, given the syndrome is caused by underlying infection. Therefore, it is not a cause of death in the GBD (Global Burden of Diseases, Injuries, and Risk Factors) study.

Investigators of the study used cause of death data from 109,000,000 deaths to estimate morality related to sepsis. The study team also looked at past data concerning sepsis-related mortality to evaluate change in incidence.

Sepsis cases were defined within 2 mutually exclusive groups, explicit and implicit.

Explicit cases of sepsis were defined as those with an International Classification of Diseases (ICD) 9 or 10 revision code explicitly referencing sepsis.

Implicit cases of sepsis were defined as those with an infection code listed as the underlying cause of death alongside an organ dysfunction code in the chain cause of death or primary admission diagnosis.

Locations of sepsis-related mortality were classified using the Sociodemographic Index, a measure which identifies countries and geographic areas according to low, low-middle, middle, high-middle, and high levels on the spectrum of economic development.

Global sepsis incidence was evaluated by dividing estimated sepsis deaths by modelled in-hospital sepsis case fatalities established using GBD Study hospital data. The percentage of sepsis-related mortality was modelled using mixed effects linear regression.

Results indicate that overall sepsis cases declined from an estimated 60.2 million cases in 1990 to 48.9 million cases in 2017. The 48.9 million cases led to approximately 11 million deaths. Despite the decline, this figure represents 19.7% of all global deaths in 2017.

Consistently from 1990 to 2017, the most common underlying cause of sepsis-related death across demographics was lower respiratory infection.

Sepsis incidence peaked in early childhood, with an estimated 20.3 million cases among children younger than 5 years. There was a second peak among older adults.

An estimated 41.5 million of 48.9 million total 2017 cases of sepsis took place in countries with low, low-middle, or middle Sociodemographic Index classification. Of the 11 million sepsis related deaths in 2017, 8.2 million took place within such countries.

The inclusion of lower income countries was pointed to by investigators as a key strength of their study.

“These estimates are more than double previous global figures, which is probably attributable to inclusion of more data from low-income and middle-income countries, locations where sepsis incidence and mortality are considerably higher and for which data were previously under-represented,” authors of the study wrote.

In a sensitivity analysis in which only explicit sepsis related ICD codes were modelled, there were still an estimated 9.2 million sepsis-related deaths in 2017, representing 16.5% of global deaths.

Study authors concluded by identifying several key implications of their work. The global sepsis burden is larger than previously established, they pointed out, and deserves urgent attention. In addition, they pointed to substantial variation in incidence and mortality regionally, calling attention to underlying disparities in the areas least equipped to treat and prevent sepsis.

Finally, the study authors argued that more robust infection prevention measures should be implemented in areas with disproportionate burden. Particular attention should be paid to caring for neonates, given the new results indicate a higher burden among very young children than previously established.

“Research and policy interventions targeting antimicrobial resistance, an important driver of sepsis (particularly in health care settings), are imperative,” study authors wrote.