Epidemiology, Acute Management, and Outcomes of Patients With Sepsis Presenting to a Referral Hospital in Western Kenya

Study Overview
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Brief Summary
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Sepsis is a clinical syndrome representing deranged hemodynamics (such as tachycardia) secondary to severe infection. In high-income countries (HICs), early resuscitation of septic patients with protocol-driven therapy, including quantitative fluid administration guided by invasive monitoring, has resulted in improved outcomes for septic patients. Prevalence and mortality of sepsis are thought to be higher in sub-Saharan Africa (SSA) than in high-income countries; however, most hospitals in SSA lack the technology and resources necessary to implement the resuscitation protocols used in HICs and therefore, mortality from sepsis remains high. The World Health Organization (WHO) has recently disseminated an algorithm for resuscitation of septic patients in low resource settings. This algorithm is based on expert consensus only, and its efficacy has never been tested. This study will be conducted in the Casualty Department of Moi Teaching and Referral Hospital (MTRH) in Eldoret, Kenya. The purpose of this study is to describe the epidemiology of patients presenting with severe sepsis, to examine the microbiology causing severe sepsis, to describe current management and outcomes for severe sepsis, and to test the effect of implementation of the WHO resuscitation algorithm at MTRH. The study design is a prospective before and after clinical trial. In an initial observational phase, adult patients presenting to the MTRH Casualty Department with sepsis and severe sepsis (the latter of which will be defined by elevated lactate) will be enrolled into a prospective observational cohort. Demographic data, medical characteristics, and microbiological studies will be obtained, then the management and outcomes of these patients will be observed. In a second phase, patients with sepsis will continue to be enrolled into a prospective observational cohort, while patients with severe sepsis will be enrolled into an intervention group. Patients in the intervention group will be managed according to the WHO resuscitation algorithm. Specifically, the WHO algorithm involves fluid boluses guided by vital signs and physical exam findings, rapid and early administration of empiric antibiotics, and frequent patient monitoring. The outcomes of interest are achievement of lactate clearance, which is a correlate of tissue perfusion, as well as 24-hour, in-hospital, and 30-day mortality.

Official Title
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Epidemiology, Acute Management, and Outcomes of Patients With Sepsis Presenting to a Referral Hospital in Western Kenya

Conditions
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Sepsis, Severe Sepsis, Septic Shock

Intervention / Treatment
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* Other: WHO algorithm of fluid boluses guided by physical examination
* Other: Frequent patient monitoring
* Other: Early administration of empiric antibiotics
* Other: Oxygen delivery
* Other: Correction of hypoglycemia
* Other: Correction of severe anemia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presenting to MTRH Casualty Department for acute medical care Suspected infection, in the judgment of the managing clinician At least 2 of the following: axillary temperature >37.5°C or <35.5°C or core temperature >38.0°C or <36.0°C; heart rate >90 beats per minute; respiratory rate >20 breaths per minute; or systolic blood pressure <100 mmHg Exclusion Criteria: Lack of basic language skills in either English or Kiswahili Pregnancy Congestive heart failure or valvular heart disease (as a known prior diagnosis or in the judgment of the managing clinician) Need for immediate surgery (within 6 hours) in the judgment of the managing clinician Inability to consent to study participation and lack of accompaniment by a family member or other surrogate who can provide consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: WHO intervention<br>This arm will be treated with the 2011 WHO sepsis recommendations for the first 6 hours of their hospitalization. The WHO recommendations involve fluid boluses guided by vital signs and physical exam, frequent patient monitoring, rapid and early administration of empiric antibiotics, oxygen delivery, correction of hypoglycemia, and correction of severe anemia. | Other: WHO algorithm of fluid boluses guided by physical examination<br> <br> Other: Frequent patient monitoring<br>* Vital signs and physical exam every 30-60 minutes<br>Other: Early administration of empiric antibiotics<br>* Clinician will be prompted to administer antibiotics within 60 minutes<br>Other: Oxygen delivery<br> <br> Other: Correction of hypoglycemia<br>* If blood glucose is less than 3.0 mmol/L, IV dextrose will be administered<br>Other: Correction of severe anemia<br>* If hemoglobin is less than 7 mg/dL, clinician will be prompted to offer blood transfusion<br>|
| No Intervention: Standard care<br>This arm will be managed per standard care by the hospital clinicians. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactate clearance (difference in lactate [mmol/L] at study enrollment and 6 hours after study enrollment) as a measure of efficacy | Lactate level will be measured at study enrollment (time 0) and 6 hours after study enrollment (time 6). Lactate clearance will be reported as the difference between time 0 and time 6 lactate, as a fraction of time 0 lactate. | enrollment, 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 24 hours, in-hospital, and 30 days | 
| Number of subjects with adverse effects as a measure of safety |  | 6 hours, 24 hours, in-hospital, and 30 days |