Adhikari – Challenge and opportunities for sepsis research in resource-limited settings

Clinical Pearls (Assistance from Dr. Tony Basel)

• First issue notes that there is very little historical data on the incidence of sepsis in low income countries (LIC) and middle income countries (MIC), so it is difficult to truly understand the gravity of the problem.
  • However, the amount of studies in LIC studies as grown exponentially over the last several years.
• Definition of Sepsis
  • Consensus definition (updated in the last couple years)
    • Suspected infection + Change in SOFA >2
      • Issue: need Labs/interventions to get obtain SOFA scores
  • WHO diagnosis (no labs, all clinically bsed)
    • Suspected infection + 1 or more of:
      • HR >100 bpm
      • RR >24 Bpm
      • Temp <36 or >38
  • New developments for Sepsis 3
    • Suspected infection + qSOFA >2
      • AMS
      • RR >20
      • SBP <90
    • Is QSOFA good or bad?
      • Was created to prognosticate mortality, not for sepsis diagnosis
      • Recent study in Gabon shows that
        • Fever or hypothermia + 1 other SIRS + abx = mortality of 4.8%
          • Sensitivity 87% + Specificity 75% (AUC 0.83)
        • Minimally change to post-test probability
  • The future is a study of qSOFA in low middle income countries with a wide variety of sepsis causing a:

• ARDS
  • Berlin definition
    • Requires CXR, ABG (P/F ratio), and access to echocardiography
      • Not practical with minimal resources
    • Kigali Modification of Berlin definition
      • SpO2/FiO2 ratio (no ABG needed)
      • Allows CXR or US
      • More useful in resource limited countries (RLC)
• Epidemiology
  • Sepsis is very underestimated in Global Data Base
    • Example: A population of 850 million in Africa/Asia showed:
      • 43 studies from 15 countries
      • 36 ICUS in 31 cities
        • Median admission rate: 461/yr
        • Median ICU size: 8 beds
    • Consensus data then shows that most sepsis does not occur in the ICUs of LICs or MICs, because it can’t (no ICU beds to hold them)
  • Unfortunately we do not have adequate population based data on Sepsis in resource limited countries
    • From different sources we estimate that the LIC and MIC sepsis rate  is about 13 million cases per year
  • Measurement challenges
    • Clinical databases don’t exist
    • Hospital discharge databases don’t exist
    • All we have is a death registry
      • 5.3 million deaths per year GLOBALLY
      • Difficult to stratify in LIC/MICs as “coding” and nomenclature is often complicated
  • Data has shown that:
    • Deaths from severe sepsis is falling
    • Mortality from malaria is falling
    • Admission for malaria related bacteremia are falling
• Microbiology and Antimicrobial Resistance

• • Bacteremia is difficult to diagnose in the LIC and MIC countries either due to lack of access to culturing materials or due to a simple lack of bacterial growth.
    • The current antibiotic use is highest in higher income countries, but resistance is greatest in LIC! Why?
      1. Higher incidence of infection
      2. Higher prevalence of resistant bacteria
      3. High growth in antibiotic prescribing
      4. Lack of prescription controls
      5. Counterfeit drugs
      6. Poor infection prevention controls
      7. Laboratory capacities are limited and expensive (lack of vital antibiograms)
    • Limit effect of the spread of disease with improvements to hospital cleaning protocols as well as cohort patients together with similar disease (ex: Cholera ward)
  • Approaches to limit Antibiotic resistance in the ICU
    • Infection control
      • Hand Hygiene
      • Active surveillance
      • Contact precautions
      • Cohorting
    • Patient level
      • Skin chlorhexidine
      • Oral chlorhexidine
      • SDD
      • (No) ulcer Prophylaxis
    • Proper antibiotic use
      • Stewardship teams
      • ‘Rotation’
    • Better diagnostics
      • Limit decision to start or duration of empiric therapy
      • Microbiology labs
• Treatment considerations in resource limited countries
  • The current treatment guidelines available rely on data from High income countries and expert opinion, few are based on data from LICs
    • One recent study from Haiti showed that standard sepsis goals (IVF, abx, etc) are rarely able to be met due to system limitations
  • Very few studies in low income nations look at fluid resuscitation and antibiotic use, however nearly all show that:
    • Fluid resuscitation is very sporadic, with some patients getting little fluid, while others getting a too much
    • Antibiotic use differs wildly with up to >50 different antibiotic regimens
  • Fixing the fluid problem with POC US with tele-medicine guidance, is this the future?