Simplified Severe Sepsis Protocol in Zambia (SSSP)

National Institutes of Health (NIH), Fogarty International Center of the National Institute of Health

This study is a randomized control trial assessing the impact of a simple evidence-based protocol for the treatment severe sepsis in Zambia. The intervention protocol consists of a scheduled fluid regimen, early blood culture and antibiotics, and dopamine and blood transfusion when necessary. It is hypothesized that the protocol will significantly decrease in-hospital mortality in patients with severe sepsis.

In recent years, evidence-based protocols of bundled therapies have improved survival of severe sepsis in developed countries. However, in sub-Saharan Africa, simple therapies such as IV fluids and early antibiotics are frequently under-utilized. Furthermore, although tuberculosis is a common cause of severe sepsis in the region, accurate and timely diagnosis of tuberculosis-associated severe sepsis remains elusive. The aims of this study are (1) To assess the impact on survival of a simple evidence-based protocol for severe sepsis, (2) To evaluate the cost of implementation for a simplified severe sepsis protocol (3) To develop a clinical diagnostic score for identifying tuberculosis in HIV positive patients with severe sepsis (4) To assess the performance of the Xpert TB/RIF rapid PCR system for diagnosing tuberculosis in HIV positive patients with severe sepsis.

This protocol consists of an early aggressive fluid strategy, early blood cultures and antibiotics, and, when appropriate, blood transfusion and titratable dopamine. Monitoring is based on physical exam findings.

Early blood cultures and antibiotics. Monitoring by study nurses as in experimental arm. Other interventions are according to admitting (non-study) doctors' orders.

Early fluid protocol, early blood cultures and antibiotics; blood cultures and titrated dopamine in selected patients; monitoring based on vital signs and physical examination

A composite outcome consisting of dopamine extravasation, dopamine-associated tissue ischemia or necrosis, iatrogenic pulmonary oedema, and transfusion-related adverse events.

A budget impact analysis will determine the cost of treatment per patient using a mix of direct measurements and micro-cost observation.

The proportion of patients whose antibiotic regimen was changed due to information obtained from blood culture results.

Inclusion Criteria: Age 18 or older Suspected infection 2 or more of SIRS criteria: Heart rate >90/min Respiratory rate >20/min Temperature >= 38° C or <= 36° C White blood count > 12,000 or < 4,000/µL 1 or more of the following signs of end-organ dysfunction Systolic blood pressure < 90 mm Hg Mean arterial blood pressure (MAP) < 65 mm Hg Confusion/altered mentation Urine output < 0.5 mL/kg/hr Creatinine increase > 0.5 mg/dL Creatinine > 0.5 mg/dL above upper limit of normal Platelet < 100x109/L Respiratory rate > 40/min Jaundice Exclusion Criteria: GI bleed Need for urgent surgery