Simplified severe sepsis protocol: a randomized controlled trial of modified early goal-directed therapy in Zambia.

In the United States, 750,000 people die each year from sepsis.(1) Although available data are limited, the number of sepsis-related deaths is likely much higher in sub-Saharan Africa, where more than half of all deaths are attributed to infections.(2) Cohort studies from the region have found sepsis to be the third leading cause of death among HIV-infected adults, after tuberculosis and cryptococcal meningitis,(3) and an unpublished audit at the University Teaching Hospital in Zambia showed sepsis to be the leading cause of death among hospitalized medical patients. However, optimal management strategies for septic patients in Africa remain controversial.(4-7) Protocol-based management of sepsis has had wide uptake in North America and Europe.(8,9) Studies of early goal directed therapy have demonstrated that aggressive intravenous (IV) fluid administration, hemodynamic support, and blood transfusion can significantly reduce mortality due to sepsis. Central venous pressure or serum-lactate-guided approaches have generally resulted in patients receiving between 4 and 5 liters of fluid in the first 6 hours of admission.(10,11) In sub-Saharan Africa, however, uptake has been generally non-existent due to resource limitations.(12) Central venous catheters and lactic acid tests are not widely available, and the use of IV fluids for volume resuscitation has been much more conservative than guidelines recommend.(13,14) There are also questions regarding the generalizability of existing evidence to the sub-Saharan African setting, considering the under-representation of resource-limited study sites and HIV/AIDS patients in most sepsis trials.(15) Furthermore, the limited existing evidence from the region is conflicting regarding the potential benefits and harms of aggressive fluid resuscitation.(4,6) We hypothesized that a novel simplified treatment protocol, based on existing early goal directed therapy protocols, would reduce mortality compared with usual care in African patients with severe sepsis. The simplified severe sepsis protocol (SSSP) intervention consisted of early goal-directed fluid administration, plus dopamine and/or blood transfusion when indicated. Patients in both arms received close nurse monitoring with early blood cultures and antibiotics.