Kristina Rudd 18 th June, 2013

1. Sepsis Management and Outcomes in a Rural Ugandan Hospital: A Prospective Observational Cohort Study Kristina Rudd 18th June, 2013

2. Outline • Introduction and Background • Terminology • Epidemiology • Considerations for resource-limited settings • Bwindi Sepsis Study • Goals, objectives, and hypothesis • Logistics • Methods • Results • Challenges and observations

3. Introduction and Background Terminology Epidemiology Considerations for resource-limited settings

4. Adult Sepsis Definition • Suspected infection PLUS • Systemic Inflammatory Response Syndrome (SIRS): • 2 or more of the following: • Temp >38ºC or <36ºC • HR >90 beats/min • RR >20 breaths/min • WBC >12,000 or <4000 cells/mm3, or >10% immature (band) forms

5. Pediatric Sepsis Definition • Suspected infection PLUS • Systemic Inflammatory Response Syndrome (SIRS): • 2 or more of the following (MUST have abnormal temp or WBC count): • Core temp >38.5ºC or <36ºC • WBC elevated or depressed for age, or >10% bands • HR >2 SD above normal for age in absence of external stimulus • RR >2 SD above normal for age in absence of external stimulus

6. Epidemiology • Infectious diseases account for 4 of 5 top causes of death in Uganda • HIV/AIDS, lower respiratory infections, diarrheal diseases, malaria • Similar to other low-income countries (LIC) • ischemic heart disease rather than stroke, different rank order • Account for about 40% of deaths in LIC • More than 3.6 million deaths in LIC annually due to severe infections

7. Epidemiology • Unknown burden of sepsis in low- and middle-income countries (LMIC); extrapolate based on physiology and data from high-income countries (HIC) • Limited published data: • Brazilian ICUs: 61.4% incidence, 34.7% mortality • Zambian rural district hospital: 30% incidence

8. Surviving Sepsis Campaign • Global program to improve sepsis-related mortality and morbidity • Early identification • Early antibiotics and cultures • Early goal-directed therapy for resuscitation

9. Surviving Sepsis Campaign

10. Resource-limited Settings

11. Resource-limited Settings • Several recent guidelines • Expert opinion, extrapolation • Need to be tested

12. Resource-limited Settings • Ugandan sepsis studies – PRISM-U Study Group • Urban • Kampala (Mulago) • Masaka • Public • Descriptive

13. Bwindi Sepsis Study Goals, objectives, and hypothesis Logistics Methods Results Challenges and observations

14. Bwindi Sepsis Study Sepsis Management and Outcomes in a Rural Ugandan Hospital: A Prospective Observational Cohort Study

15. Goals and Objectives • Describe the current presentation, management, and outcome of sepsis in adult and pediatric inpatients in a private, rural Ugandan hospital • Determine the correlates of in-hospital mortality and length of stay • Assess the frequency of acute lung injury based on SpO2-to-FiO2 ratio • Evaluate a modified SIRS/sepsis criteria excluding change in WBC to be used in low-resource settings

16. Hypothesis • Adult and pediatric patients presenting to Bwindi Community Hospital with sepsis syndromes will have high in-hospital mortality rates and rates of hypoxemia and the major predictors of mortality will be AVPU Score, Glasgow Coma Score, and point-of-care venous lactate and glucose • Initial hypothesis based on mortality  underpowered  additional primary hypotheses based on length of stay • Continuous outcome rather than binary

17. Bwindi Community Hospital • 112 beds • Inpatient, outpatient, surgery, maternity, HIV, nutrition • 1 HDU bed (pediatric) • Oxygen, x-ray, ultrasound, limited lab, IV fluid, blood transfusion, antibiotics • No ventilators, CT, central lines, cultures, cardiac monitors, ECG, lactate

28. Study Team • From Bwindi Community Hospital: • Leonard Tutaryebwa, Head of Clinical Services • Birungi Mutahunga, Medical Director • From the University of Washington: • Kristina Rudd, Resident, Department of Medicine • Eoin West, Assistant Professor, Division of Pulmonary and Critical Care

29. Logistics • Time: • 2 months • No more than 1 month away • Funding: • International Respiratory and Severe Illness Center (INTERSECT) • INTERSECT – Ellison Fellowship • Ethics oversight: • University of Washington • Mbarara University of Science and Technology (MUST)

30. Logistics • Language: • Medical – English • Patients – Rukiga • Nurses, hospital staff as translators • Data collection • One person, consecutive enrollment • Chart screening – IRB waiver of consent

31. Methods • Inclusion and exclusion criteria • Chart review • Primary data collection

32. Inclusion and Exclusion Criteria • Inclusion: • Consecutive enrollment • Sepsis (including severe sepsis and septic shock) • Inpatient admission • Exclusion: • Surgical patient • Pregnancy • Neonate (less than 28 days)

33. Chart Review • Timing • Within 24hr of admission • 24-48hr after admission • Discharge • Content • Demographics: age, gender, language, ethnic group • Admit and discharge diagnoses and comorbidities • Vital signs, labs, radiographic findings, IV fluids, O2, antibiotics • Disposition and complications

34. Chart Review

35. Primary Data Collection • Timing • Initial assessment (within 24hr of admission) • Follow-up assessment (24-48hr after admission) • Content • AVPU, GCS • SpO2 and FiO2 • Point-of-care blood glucose, venous lactate

36. Primary Data Collection

37. Results • 56 patients • 1 missing data • 3 erroneously included • 6 qualified but not enrolled • 1 declined • 1 adolescent without parents to consent • 1 died prior to enrollment • 3 missed or no translator available

38. Results • 56 patients • Vast majority pediatric • Majority sepsis, not severe sepsis or shock • Low mortality rate, relatively low length of stay • Most common diagnoses malaria, respiratory tract infections • Low HIV prevalence among pediatrics, high among adults

39. Challenges and Observations • Confusion on sepsis definition and management • Reported findings  first set of primary data potentially influenced follow-up data (many examples of changes in management) • Difficult to remain completely separate from clinical care • Paper charting • Higher severity of illness and mortality among patients who developed sepsis while inpatient – not included in study • Differences in consent • Age • Familial relationship

40. Questions and Comments

41. Thank You! • Eoin West, Mentor • Leonard Tutaryebwa, Research Collaborator • Medical leadership and staff of Bwindi Community Hospital • INTERSECT-Ellison Fellowship

42. Pediatric Sepsis Definition

43. Additional Definitions • Severe sepsis: sepsis associated with hypotension, hypoperfusion, and/or end-organ dysfunction • Examples of end-organ dysfunction: cardiac (ACS), renal (decreased urine output), hepatic (shock liver), CNS (somnolence, decreased GCS not directly due to infection), hematological (DIC) • Septic shock: sepsis with hypotension despite adequate fluid resuscitation

44. Overview of SIRS, Sepsis, Severe Sepsis, and Septic Shock Severe sepsis Infection Sepsis SIRS Septic shock

45. FEAST Trial • FEAST = Fluid Expansion As Supportive Therapy • Large RCT • > 3000 children, severe febrile illness with evidence of impaired perfusion or respiratory distress (but not severe hypotension) • Multiple sites in Kenya, Uganda, Tanzania • 3 arms: • Immediate volume resuscitation with normal (0.9%) saline • Immediate volume expansion with 5% human albumin solution (HAS) • Control: no immediate volume expansion • Outcomes: • Fluid boluses significantly increased mortality at 48hr