Sepsis is one of the most significant worldwide causes of morbidity and mortality, totaling 48.9 million annual cases and accounting for 11 million annual deaths, 19.7% of all global deaths, in the most recent analysis of the Global Burden of Disease Study from 2017 data.1 Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, while septic shock is a subset of sepsis in which there are underlying circulatory, cellular, and metabolic abnormalities that are associated with an even greater risk of mortality.2 These conditions disproportionately impact persons in low-and-middle income countries (LMICs).1,3 While in-hospital mortality rates can be greater than 25–30% across resource settings, mortality rates of up to 38% are reported in LMICs, particularly in patients who have confirmed bacteremia.2−4 In Uganda, a low-income country in sub-Saharan Africa, the primary causes of death are all infectious in nature—namely malaria, HIV/AIDs, pneumonia, tuberculosis and diarrheal-associated diseases, all of which can lead to sepsis.5,6 Studies in Uganda have shown sepsis mortality rates between 34–43% and 59% in those characterized as having septic shock.7,8 The World Health Organization (WHO) has identified sepsis as an international priority, adopting a resolution in 2017 to improve the prevention, diagnosis and clinical management of sepsis.9
Identifying patients with sepsis and septic shock presents a significant challenge. Clinical criteria to identify patients with these syndromes have evolved over time. The most recent Sepsis-3 consensus recommendations suggest using bedside clinical criteria, termed the quick Sequential Organ Failure Assessment (qSOFA) score, which utilizes respiratory rate ≥ 22/min, altered mentation, and systolic blood pressure ≤ 100 mm Hg.2 Adult patients with suspected infection and two or more of these findings are determined to meet sepsis criteria. Using the qSOFA score in a low-resource setting is of particular value because it does not rely on advanced diagnostic testing or resources and provides opportunity for a rapid objective clinical evaluation of the patient by a variety of providers including nurses, mid-level providers, and physicians. One study in Uganda found that stratifying patients with sepsis based on vital signs can assist in prioritizing patients who are more acutely ill.10
Management of sepsis globally has changed significantly over the past two decades. In the US and other high-resource settings, a single-center randomized trial published in 2001 that reported improvement in sepsis outcomes with “early goal-directed therapy” sparked widespread interest and change in practice patterns for sepsis management, yet subsequent trials published in the current era of sepsis management have failed to find similar benefits.11−15 As such, specific interventions that may improve outcomes continue to be debated,16 and many agree that sepsis management may need to be tailored based on patient population, disease patterns, practice environment, and resource availability.5
The current standard of care for managing sepsis in high-resource settings follow guidelines established by the Surviving Sepsis Campaign.17 However, these guidelines have been deemed not only impractical in sub-Saharan Africa (SSA) due to limited resources, but also potentially detrimental as “early goal-directed therapy” interventions that increased fluid resuscitation were found to increase mortality in SSA.18,19 This difference in impact of fluid resuscitation on septic patients across settings may be related to a difference in patient populations that carry a high burden of malaria and other co-morbidities as well as a lack of intensive care facilities to provide supportive treatment in cases where fluids may exacerbate respiratory failure, heart failure, or renal failure.7,8,19−22 In LMICs overall, recommendations for sepsis management have included early administration of antibiotics, fluid resuscitation, using epinephrine and dopamine administration to optimize tissue perfusion in those refractory to fluid resuscitation, frequent vital sign monitoring, corticosteroid administration when necessary, supplemental oxygenation, and identification of infectious sources.23 However, these interventions can be challenging to implement with limited staff, training, and supplies.24 Therefore, it remains unclear if any specific sepsis-care bundle can be applied across settings due to variations in patient populations, pathogens, and clinical environments.5
Despite these challenges, limited studies have shown some reduction in sepsis mortality in Uganda with increased adherence to sepsis protocols including fluid resuscitation, early antimicrobial treatment, and close monitoring of patients.21 For septic patients with Human Immunodeficiency Virus (HIV) infection, early antiretroviral therapy is recommended, in order to reduce mortality.25,26 In patients with HIV and severe sepsis, early anti-tuberculosis therapy and intravenous fluids have demonstrated a reduction in mortality.8,27 Although these studies suggest some approaches to sepsis management, there is still overall limited research into effective sepsis-related interventions and their outcomes in SSA and in Uganda in particular.19 In this study, we describe patients with sepsis and their management and outcomes in a rural Ugandan Emergency Department staffed by non-physician clinicians over a nine-year period.