Sepsis

Kenneth Baillie
Roslin Institute, University of Edinburgh
Intensive Care Unit, Royal Infirmary Edinburgh

#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. - 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)

# Incidence - 19 million cases worldwide per year

Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD. Critical care and the global burden of critical illness in adults. Lancet 2010;376:1339-1346

# 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%

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

# Sources - Lungs: 64% of infections - Abdomen: 20% - Bloodstream: 15% - Renal tract/genitourinary system: 14%

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

# 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.

Singer et al JAMA. 2016 Feb 23; 315(8): 801–810.

# Infection * Your doctor thinks you have an infection

# Organ dysfunction * Definable and measurable

# Organ dysfunction ## Systemic inflammatory response syndrome (SIRS) - Heart rate >90/min - Respiratory rate >20/min or PaCO2 <32 mm Hg (4.3 kPa) - Temperature >38°C or <36°C - White cell count >12e3/mm3 or <4e3/mm3 or >10% immature bands

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

# Organ dysfunction ## qSOFA - Hypotension SBP < 100mmHg - Glasgow Coma Scale (GCS) below 15 - Tachypnoea > 22/min

Singer et al JAMA. 2016 Feb 23; 315(8): 801–810.

Life-threatening Organ dysfunction

## Predictive validity - *not* an attempt to predict mortality - an quantitative test for the definition

Shankar-Hari et al JAMA. 2016 Feb 23;315(8):775-87.

Life-threatening Organ dysfunction

## Septic shock - hypotension requiring vasopressors to maintatin mean BP > 65 mm Hg AND - serum lactate level > 2 mmol/L

Shankar-Hari et al JAMA. 2016 Feb 23;315(8):775-87.

Life-threatening Organ dysfunction

## Mortality - 10-fold variation for in-hospital mortality across deciles of baseline risk

Seymour et al JAMA. 2016;315(8):762-774.

Pool et al. Critical Care Clinics. 34(1), Pages 63-80 (2018)

# Sepsis pathophysiology - hypoxia/ischaemia

Physiological mechanisms of hypoxia

	Inspired gas	Ventilation	Uptake into arterial blood	Transport in blood	Utilisation in cells
Hypoxic gas	↓
Type II RF		↓
Type I RF			↓
Stagnant				↓
Cytotoxic					↓

# Sepsis pathophysiology - hypoxia/ischaemia; mitochondrial failure - "cytokine storm"

# Sepsis pathophysiology - hypoxia/ischaemia; mitochondrial failure - "cytokine storm" - inflammatory cell recruitment - endothelial permeability

# Treatment - Antimicrobials - Source control

# Treatment: Supportive care - Intravenous fluid (e.g. balanced crystalloid) - Vasopressors (e.g. noradrenaline) - Mechanical ventilation - Sedation - Renal replacement therapy

# Treatment: specific interventions to modify pathogenesis

# Treatment failures - Activated protein C - Anti-endotoxin antibodies - Anti-TNF antibodies