Simplified Severe Sepsis Protocol-2 (SSSP-2) in Zambia (SSSP-2)

Simplified Severe Sepsis Protocol-2 (SSSP-2): A Randomized Controlled Trial of a Bundled Intervention for Severe Sepsis at the University Teaching Hospital in Zambia

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 with hypotension in Zambia. This is a follow-up study to the Simplified Severe Sepsis Protocol (SSSP) study. 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 and hypotension.

In recent years, evidence-based protocols of bundled therapies have improved survival of severe sepsis in developed countries. In sub-Saharan Africa, simple therapies such as IV fluids and early antibiotics are frequently under-utilized. Studies of fluid interventions in the region, however, have demonstrated conflicting results. Outcomes in septic patients may be further affected by delays in the diagnosis of tuberculosis-associated severe sepsis. The aims of this study are (1) To assess the impact on survival of a simple evidence-based protocol for severe sepsis with hypotensionor septic shock, (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, and (4) To assess the performance of the Xpert TB/RIF rapid PCR system and urine lipoarabinomannan assay for diagnosing tuberculosis in HIV positive patients with severe sepsis.

Patients are managed according to admitting doctors' orders. Blood cultures are drawn in all patients. Antibiotics are specified by the admitting doctors.

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. Antibiotics are specified by the admitting doctors.

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

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: infection suspected by the treating physician 2 or more of the following 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 of the following: Systolic blood pressure (SBP) ≤ 90 mm Hg Mean arterial blood pressure (MAP) ≤ 65 mm Hg Exclusion Criteria: Gastrointestinal bleed in the absence of fever Need for immediate surgery Respiratory rate greater than 40/min with oxygen saturation less than 90% Suspected congestive heart failure exacerbation End-stage renal disease Raised jugular venous pressure (JVP) at baseline Currently incarcerated

Requests for data sharing should be directed to PI. PI will then confer with Zambian co-PI to confirm that data sharing is allowable by Zambian law.

Andrews B, Semler MW, Muchemwa L, Kelly P, Lakhi S, Heimburger DC, Mabula C, Bwalya M, Bernard GR. Effect of an Early Resuscitation Protocol on In-hospital Mortality Among Adults With Sepsis and Hypotension: A Randomized Clinical Trial. JAMA. 2017 Oct 3;318(13):1233-1240. doi: 10.1001/jama.2017.10913.