Sepsis And Sepsis Related Syndrome:

Dr Saurav HamalMBBS.

Objectives• To know definitions of SIRS, sepsis, septic

shock, MODS.• To learn basic pathophysiology of sepsis.• Basic management of Sepsis.

‘SIRS’(Systemic inflammatory response syndrome);• A clinical response arising from a nonspecific insult manifested by 2 or more of the

following: a. Temp >38ºC or <36ºC b. HR >90 beats/minc. RR >20 breaths/min or PaCO2 <4.5kPa d. WBC >12,000 or <4000 cells/mm3, or >10% immature (band) forms

Definitions:

‘Sepsis’• SIRS in the presence of proven or suspected infection.

• Infection:– Presence of organisms in a closed space or location where not

normally found.

‘Severe Sepsis’• Sepsis associated with hypotension, hypoperfusion and/or organ-dysfunction.

‘Septic Shock’:- Sepsis with hypotension despite adequate fluid resuscitation.- May be ‘vasodilatory’ and/or ‘distributive’ shock.- Include all patients on vasopressors or inotropic support.

Sepsis: A Complex Disease

Infection/ SIRS Sepsis Severe Sepsis Trauma

Infection/ SIRS Sepsis Severe Sepsis Trauma

Sepsis: Defining a Disease Continuum

Disorder Due to Uncontrolled Inflammation?• Increased inflamatory mediators like IL-1, TNF,

IL-6.• Based on animal studies.• In a study in children with meningococcemia, TNF levels directly

correlated with mortality.• Clinical trials involving TNF anagonist, antiendotoxin antibodies, IL-1

receptor antagonists, cortocosteroids failed to show any benefits.

Pathophysiology of Sepsis

Failure of Immune System to EliminateMicroorganism?

• Shift from inflammatory (ThI) to antiinflammatory response (Th2).• Anergy.• Apotosis of B cells, T cells, Dendritic cells.• Loss of macrophage expression of MHC Class I and co-stimulatory

molecules. • Immunosuppressive effect of apoptotic cells.

Pathogenesis:-

• MODS occurs late and is the most common cause of death in patients with Sepsis.

• Lactic acidosis led investigators to think that this is due to tissue ischaemia.

• Minimal cell death in postmortem samples taken from the failed organs of patients with Sepsis.

• Recovery from Sepsis is associated with near complete recovery of organ function, even in organs whose cells have poor regenerative capacity.

• Increased tissue oxygen tensions in various organs (muscle, gut, bladder) in animals and patients with Sepsis.

Multiple Organ Dysfunction Syndrome (MODS)

Treatment of SepsisIdentify Sepsis as early as possible

Broad Spectrum antibiotics ASAP and Identify source(s) of infection

Identify severity: Vitals, mental status, Lactate, other labs.

Volume and physiologic resuscitation ASAP with GOALS.

Tweak your system so these things happen FAST. Train all providers.

Vital sign/Laboratory alerting systems.

?Biomarkers

Basic support:-• Airway; Assess the airway, respiration, and perfusion.

• Blood pressure; avoid hypotension, volume resuscitation.

1. Eradication of Infection:-Choice of Antibiotics; If pseudomonas is an unlikely pathogen, combine- Vancomycin with one of the following:• Cephalosporin, 3rd or 4th generation • Beta-lactam/beta-lactamase inhibitor • Fluroquinolones eg., Levofloxacin.

If pseudomonas is suspected, combine Vancomycin with two of the following :

• Antipseudomonal cephalosporin (e.g cefoperazone).• Antipseudomonal carbapenem (eg imipenem, ).• Antipseudomonal beta-lactam/beta-lactamase inhibitor

(e.g. pipercillin-tazobactam, ).• Aminoglycoside • Fluoroquinolone with good anti-pseudomonal activity .• Monobactam .

Other measure :-

2.Coticosteroids• Anti-inflammatory actions such as inhibiting the production of

proinflammatory cytokines, enhancing the release of anti-inflammatory mediators.

3.Tight Glycemic Control using insulin.

Does Everyone Know what to do?Established Core Rx:• Source Control• Antibiotics• Resuscitation• Supportive Care

Conclusions…• The incidence of Sepsis is increasing.• Possible contributing factors :

– Use of antibiotics leading to microbial resistance.– More invasive procedures.– Increasing use of immunosuppressants.

• There have been new insights into the pathogenesis of Sepsis which could be potential therapeutic targets in the future.

• Treatment of Sepsis includes early institution of antibiotics, volume resuscitation, tight glycemic control, steroids, protein C when indicated.