Related Experiment Video
Updated: Apr 26, 2026
Author Spotlight: Rehabilitation of Stroke Patients With a Digital Occupational Training System
Published on: December 29, 2023
Simplified severe sepsis protocol: a randomized controlled trial of modified early goal-directed therapy in Zambia
Ben Andrews1, Levy Muchemwa, Paul Kelly
11Institute for Global Health, Vanderbilt University, Nashville, TN. 2Division of General Internal Medicine and Public Health, Department of Internal Medicine, Vanderbilt University, Nashville, TN. 3Department of Internal Medicine, University of Zambia School of Medicine, Lusaka, Zambia. 4Barts and the London School of Medicine, London, United Kingdom. 5Department of Internal Medicine, University Teaching Hospital, Lusaka, Zambia. 6Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University, Nashville, TN.
Objective:
To assess the efficacy of a simple, goal-directed sepsis treatment protocol for reducing mortality in patients with severe sepsis in Zambia.
Design:
Single-center nonblinded randomized controlled trial.
Setting:
Emergency department, ICU, and medical wards of the national referral hospital in Lusaka, Zambia.
Patients:
One hundred twelve patients enrolled within 24 hours of admission with severe sepsis, defined as systemic inflammatory response syndrome with suspected infection and organ dysfunction
Interventions:
: Simplified Severe Sepsis Protocol consisting of up to 4 L of IV fluids within 6 hours, guided by jugular venous pressure assessment, and dopamine and/or blood transfusion in selected patients. Control group was managed as usual care. Blood cultures were collected and early antibiotics administered for both arms.
Measurements And Main Results:
Primary outcome was in-hospital all-cause mortality. One hundred nine patients were included in the final analysis and 88 patients (80.7%) were HIV positive. Pulmonary infections were the most common source of sepsis. In-hospital mortality rate was 64.2% in the intervention group and 60.7% in the control group (relative risk, 1.05; 95% CI, 0.79-1.41). Mycobacterium tuberculosis complex was isolated from 31 of 82 HIV-positive patients (37.8%) with available mycobacterial blood culture results. Patients in Simplified Severe Sepsis Protocol received significantly more IV fluids in the first 6 hours (2.7 L vs 1.7 L, p = 0.002). The study was stopped early because of high mortality rate among patients with hypoxemic respiratory failure in the intervention arm (8/8, 100%) compared with the control arm (7/10, 70%; relative risk, 1.43; 95% CI, 0.95-2.14).
Conclusion:
Factors other than tissue hypoperfusion probably account for much of the end-organ dysfunction in African patients with severe sepsis. Studies of fluid-based interventions should utilize inclusion criteria to accurately capture patients with hypovolemia and tissue hypoperfusion who are most likely to benefit from fluids. Exclusion of patients with severe respiratory distress should be considered when ventilatory support is not readily available.
