Sepsis remains a global health burden, can vitamin C help?

Sepsis continues to be a chief cause of health loss across the globe despite decreasing age-standardized incidence and mortality, according to a study presented at the Asia Pacific Intensive Care Symposium (APICS) 2021 virtual conference. Moreover, the disorder has particularly high health-related burden in Southeast Asia, South Asia, East Asia, Oceania, and sub-Saharan Africa.

“We have shown a global trend of decreasing sepsis burden but, importantly, substantial differences between regions remain, in total number of sepsis deaths, age distribution of sepsis deaths, and case-fatality,” said lead author Kristina Rudd, assistant professor at University of Pittsburgh School of Medicine, Pennsylvania, US. [Lancet 2018;392:1736-1788]

“These differences by location are alarming and deserve urgent attention from the global health, research, and policy communities,” she added.

Multiple cause-of-death data from 109 million individual death records were used to calculate sepsis-related mortality among each of the 282 underlying causes of death in the Global Burden of Disease (GBD) Study 2017. Mixed-effects linear regression was used to model the percentage of deaths by underlying GBD cause in each location worldwide.

Rudd and her team also used data for 8.7 million individual hospital records to calculate in-hospital sepsis-related case-fatality, stratified by underlying GBD cause. They modelled this for each location using linear regression and estimated sepsis incidence by applying modelled case-fatality to sepsis-related mortality estimates.

Some 48.9 million (95 percent uncertainty interval [UI], 38.9–62.9) incident sepsis cases were recorded worldwide in 2017, including 11.0 million (95 percent UI, 10.1–12.0) sepsis-related deaths, which accounted for 19.7 percent (95 percent UI, 18.2–21.4) of all global deaths. [Lancet 2020;395:200-211]

Interestingly, age-standardized sepsis incidence decreased by 37.9 percent (95 percent UI, 11.8–54.5) and mortality by 52.8 percent (95 percent UI, 47.7–57.7) from 1990 to 2017. Significant variation was noted in sepsis incidence and mortality across regions, with the highest burden in Southeast Asia, South Asia, East Asia, Oceania, and sub-Saharan Africa.

“Patients with sepsis frequently present for urgent medical care with undifferentiated infection,” the researchers said. “All sepsis patients, regardless of underlying source, have a shared need for access to basic acute care services such as timely and appropriate antibiotic administration, microbiology facilities, and capacity for organ support.”

Vitamin C for sepsis?

In another presentation at APICS 2021, Tomoko Fujii, assistant professor at Jikei University, Tokyo, Japan, shared recent trials concerning the use of vitamin C for sepsis.

“Vitamin C is a water-soluble essential vitamin and works as an antioxidant in the cell,” Fujii said, adding that it is also a cofactor to catalyse the conversion of dopamine to noradrenaline. [Intensive Care Med 2020;46:2061-2063]

However, in one of these trials, treatment with intravenous (IV) vitamin C, hydrocortisone, and thiamine compared with IV hydrocortisone alone did not significantly improve the duration of time alive and free of vasopressor administration over 7 days in patients with septic shock. [JAMA 2020;323:423-431]

Other recent studies also failed to show significant benefits with the use of vitamin C to treat septic shock. [JAMA 2020;423:642-650; Intensive Care Med 2020;46:2015-2025; JAMA 2020;323:2204-2205; JAMA 2021;325:742-750; Chest 2020;158:174-182]

“Robust data from clinical trials are needed before implementing a new therapy,” Fujii said, “Clinicians [must] remain focused on appropriate usual care for sepsis, [namely] prompt resuscitation with antibiotics and source control.”

Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection.