SEPSIS
Sepsis has two definitions:
The old school definition - a really severe infection
The new definition - a self-harming cytokine cascade commonly seen in the setting of a severe infection
The purpose of the new definition is to draw attention to the immune system’s role in the pathophysiology of sepsis. But the old definition is suitable for most practicing physicians. So how do you tell a regular infection apart from sepsis? That’s a controversial question, but there are two popular decision making tools to answer this: SIRS and qSOFA.
SIRS stands for Systemic Inflammatory Response System. It allows doctors to glance at the patient’s vital signs and CBC to help make the sepsis diagnosis. You are considered “SIRS positive” if you meet 2 of the following in the setting of an infection: fever, tachycardia, tachypnea and leukocytosis.
Some evidence suggests that qSOFA (Quick Sequential Organ Failure Assessment) may be better than SIRS. The patient needs to meet only one of the following in the setting of an infection: confusion, tachypnea or hypotension (SBP < 110).
Bacteria or Virus? The vast majority of sepsis is caused by a bacterial infection. The viral exceptions are coronavirus and the other colds, an immunocompromised host with CMV or EBV or a neonate with HSV1. Fungal sepsis only occurs in an immunocompromised host. Bacterial sepsis can be confirmed with the Procalcitonin serum test (aka the bacteria test).
Risk Factors? One of the best predictors of sepsis is the presence of plastic. What I mean by plastic is plastic medical instruments that have been inserted into the patient, like IV lines, breathing tubes or urinary catheters.
Lung infections 35% (Strep pneumo, H influenzae, E coli, Pseudomonas, Klebsiella, Legionella)
UTIs 25% (E. coli, Klebsiella, Enterobacter, Enterococcus, Staph epidermidis, Proteus)
Other abdominal infections 10% (E. coli, Bacteroides fragilis, Candida)
Skin infections 10% (Strep pyogenes, Staph aureus, aerobic G- rods, Clostridium, Pseudomonas)
Other 20% (Meningitis - Strep pneumo, Neiserria meningitidis, E coli, Listeria monocytogenes)
Other factors include extremes of age, immunosuppression (including diabetes) and comorbidities like CHF or COPD. Sepsis in a healthy 20 year old is very uncommon.
Bacterial virulence factors - Gram negative bugs cause the most / worst sepsis. That’s because they all contain a nasty little fat molecule called Lipopolysaccharide (LPS). There are 3 different parts of the LPS molecule, but the most important is Lipid A. That’s because Lipid A is INCREDIBLY antigenic. It sends our immune system into a frenzy. The cytokine storm it unleashes in a large gram negative infection is often more damaging than the infection itself! Most gram positive bugs aren’t as antigenic, and thus aren’t as implicated in sepsis. But they can definitely still cause sepsis. Some bugs have superantigens, which unleash sepsis in even small amounts (they activate every T helper cell they come across). Most antigens can mobilize about 0.0001% of the immune system. Superantigens can mobilize 20%. Superantigens are associated with INF-alpha. A classic example is Toxic Shock Syndrome, which is sometimes released by Staph aureus or Strep pyogenes. Viruses can also lead to a cytokine storm, especially in severe cases of respiratory viruses like coronavirus or the flu.
How do you treat sepsis? The best treatment is EARLY treatment. Give antibiotics, fluids, vasopressors and consider steroids (controversial). Surgically remove the source of the infection, if that’s possible.