Informatics in medicine: Sepsis

Kenneth Baillie

Baillie Gifford Pandemic Science Hub,IRR
Intensive Care Unit, Royal Infirmary Edinburgh
Roslin Institute
MRC Human Genetics Unit, Institute for Genetics and Cancer

References

• Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet 2010;376:1339-1346
• Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009;302:2323-2329
• Singer et al JAMA. 2016 Feb 23; 315(8): 801–810.
• Bone RC, Balk RA, Cerra FB, et al. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20(6):864–874
• Singer et al JAMA. 2016 Feb 23; 315(8): 801–810.
• Shankar-Hari et al JAMA. 2016 Feb 23;315(8):775-87.
• Seymour et al JAMA. 2016;315(8):762-774.
• Marshall J. Trends in Molecular Medicine. Volume 20, Issue 4, April 2014, Pages 195-203
• Pool et al. Critical Care Clinics. 34(1), Pages 63-80 (2018)

How can we idenfity effective targets for drugs?

The knowledge gap

Incidence

• 19 million cases worldwide per year

Pathogens

Of patients with severe sepsis who had positive cultures:

• gram-negative bacteria: 62% (Staphylococcus aureus and Streptococcus pneumoniae)

• gram-positive bacteria: 47% (Escherichia coli, Klebsiella, and Pseudomonas aeruginosa)

• fungi: 19%

Sources

• Lungs: 64% of infections

• Abdomen: 20%

• Bloodstream: 15%

• Renal tract/genitourinary system: 14%

Science

** You can’t understand an entity until you can:**

• Define it
• Measure it

Sepsis

“Life-threatening

organ dysfunction caused by a

dysregulated host response

to infection.”

Treatment

• Antimicrobials
• Source control

Treatment: Supportive care

• Intravenous fluid (e.g. balanced crystalloid)
• Vasopressors (e.g. noradrenaline)
• Mechanical ventilation
• Sedation
• Renal replacement therapy

Treatment: targeting mechanisms

Treatment: trials conducted

• 121 Phase 2/3 trials
• How many effective treatments?

Medicine for scientists

• you shouldn’t really trust doctors
• you have to work with them

Sources of information

Investigations

Examination

History

Sources of information

90% History

Spectrum of clinical responses to SARS-CoV 2

• 6 - Environment Inherited
• 5 -
• 4 -
• 3 -
• 2 -
• 1 -

• Cardiovascular
• Cancer
• Infection

Choosing the right patients

INFA10

PLSCR1

eQTL