title: Simplified severe sepsis protocol: a randomized controlled trial of modified early goal-directed therapy in Zambia.
abstract: OBJECTIVE
  To assess the efficacy of a simple, goal-directed sepsis treatment protocol for reducing mortality in patients with severe sepsis in Zambia.
  
  
  METHODS
  Single-center nonblinded randomized controlled trial.
  
  
  METHODS
  Emergency department, ICU, and medical wards of the national referral hospital in Lusaka, Zambia.
  
  
  METHODS
  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
  
  
  METHODS
  : 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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors: 1Institute 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.
authors: Ben
authors: B
authors: Andrews
authors: Levy
authors: L
authors: Muchemwa
authors: Paul
authors: P
authors: Kelly
authors: Shabir
authors: S
authors: Lakhi
authors: Douglas C
authors: DC
authors: Heimburger
authors: Gordon R
authors: GR
authors: Bernard
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001803:Blood Transfusion / Q000379:methods; D003131:Combined Modality Therapy; D003422:Critical Care / Q000379:methods*; D003906:Developing Countries; D004298:Dopamine / Q000627:therapeutic use; D004636:Emergency Service, Hospital; D005260:Female; D005440:Fluid Therapy / Q000379:methods; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018570:Risk Assessment; D018805:Sepsis / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D012772:Shock, Septic / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D016019:Survival Analysis; D016896:Treatment Outcome; D015024:Zambia
chemical_list: D000900:Anti-Bacterial Agents; D004298:Dopamine