Sepsis and SIRS

Done by:

Mohammad Jomaa

Haneen Omar

Dua'a Migdadi

Sepsis: is an acute life-threatening condition, due to a dysregulated immune response to infection. Causes ….It is may be due to : Infectious Can be classified into: 1. A primary infection : Bacterial (most common), Viral, Fungal …(e.g

pneumonia) 2. Clinical interventions for other conditions (e.g immunosuppressive drugs,

chemotherapy) invasive lines (venous line or arterial ), urinary catheters ...etc.

Non-infectious: pancreatitis

Sepsis causes high rate of mortality… The mortality depends on more than one factor that include : 1- related to the person himself (age, immune state(DM,chemotherapy…),alchole) 2- Organism 3- Appropriateness of the empiric anti-infective therapy

# Infection: invasion of normally sterile tissue by microorganisms with inflammation # Bacteremia: viable bacteria in the blood

#Septicemia: is a serious bloodstream infection, It’s also known as blood poisoning. # SIRS ( systemic inflammatory response syndrome ): is the body’s systemic response to severe infection (systemic manifestation of sepsis) >> diagnosed by the presence of two or more of(criteria) :

• RR > 20/min // PaCO2 < 32mmHg // Temp > 38ْ C or < 36ْ C //

WBC > 12*10^9/L or <4*10^9/L or > 10% band cells(immature WBC) // HR > 90/min

### notes

**not SIRS positive mean patient have sepsis but increase your suspicion of sepsis (may be physiologically normal like when doing exercise)

** Fever is a good prognostic factor. The immune system and complement system

work more effectively at higher temperatures

** Hypothermia can occur with bacteremia; it is a bad prognostic factor.

** Wide pulse pressure, may be an early pointer to systemic sepsis ** Hypothermia ,endotoxinmia and septic neutopenia indicate more severe infection.

Extra note: as we say there is Infectious and non- Infectious cause of sepsis so in sepsis less than 40% have a positive culture because culture is not always accurate and SIRS may be caused by toxins of organisms in blood not the organism itself.

Terminology

# sepsis: SIRS + documented infection

# Severe sepsis or sepsis syndrome: is sepsis with evidence of failure of one or more organs that response to fluid resuscitation : respiratory (acute respiratory distress syndrome), cardiovascular (septic shock follows compromise of cardiac function and fall in peripheral vascular resistance), renal (usually acute tubular necrosis), hepatic, blood coagulation systems or central nervous system.

# MODS(multiple organ dysfunction syndrome): is the effect that SIRS produces systemically (>= 2 organ dysfunction)

# MSOF(multiple system organ failure): is the end stage of uncontrolled MODS

# Septic Shock (Vasodilatory Shock): Syndrome of profound hypotension due to sepsis (by releasing of endotoxins / TNF / vasoactive peptides following bacterial destruction) ,this shock is unresponsiveness to initial fluid expansion. The Hypotension is defined as systolic blood pressure <90 or a fall >40 from the baseline.(sepsis + hypotension)

• Two phases:

1) early phase (Pre-shock (reversible)) also called “Warm shock” :

Hyper-dynamic response, vasodilation, warm skin, oliguria, mental status changes

2) late phase (Shock (irreversible)) also called “Cold shock” :

hypodynamic response, cool skin, MODS, decompensated state

• Septic spectrum: arrange sepsis and its complication according to severity (mild sever)…..SIRS sepsis septic shock MODS

if there is some infective material in the bloodstream >> WBC will encounter this infective material >> WBC become active 1) WBC recruitment>> to eradicate the infective material. 2) WBC release NO >> dilate BV >> increase diameter & decrease the systemic vascular resistence (SVR) 3) increase permeability of the blood vessel # NOTE: You have the infecious material in the blood vessels all throughout the body. So, the vasodilation happen everywhere >> systemic vascular dilatation. Decreased SVR >> decreased Blood pressure. 4) low tissue perfusion due to 1- decreased BP 2- difficulty to get to the cells ( due to increased leakiness) So the cells become starved of O2.

Pathophysiology

5) releasing lytic enzymes and ROS to destroying the infective material, that may damage BV as well so…

several complications can occur >> damage to endothelium triggers coagulation cascade causing micro-clot of :- fibrin, neutrophils, platelets, RBCs.>> formation of “micro clot” that my:

• prevents BV rupture >> so blood does not spill into extravascular space.

• Also, there is coagulation happens in the vascular system

(disseminated intravascular coagulation -DIC-)

>>>>> this mechanisms can not keep up the breakage of BV. (due to depletion in platlet, fibrin and other factors)……

So>> blood spilling out of BV >> simultaneous bleeding

• poor nutrition

• Poor O2 delivary.

• Poor perfusion of vital organs.

Complication of that …..is organ failure mimics to that happen in sever sepsis

The amazing association O-O >>as organ starved from O2, they start to loss function.

6) Cardiac output: initially increase to compensate BP >> ( increased CO* decreased SVR = normal compensated BP)

• As septic shock goes on, the heart can become paralyzed and damage by these immune molecules so cardiac output start to be depressed >> so decreased CO * Decreased SVR >> decreased BP.

• Acid base disturbances:

** Lactic acid is elevated due to tissue ischemia (acidosis)

** Acidosis + cytokines: tachypnea (develops due to acidocis, cytokines, and fever) which will lead to respiratory alkalosis

** Metabolic acidosis develops just before or with hypotension; it signals the

beginning of a fatal downward course.

• Cell wall factors related to sepsis:

1) In gram negative bacteria: LPS (endotoxins)

**Inflammation and coagulation starts by interaction of LPS and mononuclear WBC

** Presence of endotoxemia is correlated with a more severe form of sepsis

2) Gram positive bacteria: Peptidoglycans

1. fever (first and most common manifestation)or may hypothermic ( more common in very young, elderly, immunocompromised ….)

2. sign of SIRS (increased RR, increased HR )……..( TACHYCARDIA is the 1st manifestation)

3. sign of shock ( hypotension, oliguria, lactic acidosis) >>as The BV still leaky, so still have decrease in tissue perfusion (hypotension and hypoxia)

4. manifestation related to the cause of sepsis. ( e.g pneumonia / breathing difficulty, UTI / urination problem.....)

5. flushing, warm skin due to BV dilatation >>> increase sympathetic innervation >> tries to increase BP by VC to improve SVR >>> so, with progression of septic shock, patient will eventually have cooler skin.

Clinical features

3) Other secreted factors: ** Some strain of Staph aureus secrete toxic shock syndrome toxin 1 (SSTS1) ** Some strains of group A beta hemolytic steptococcus secrete streptococcal pyogenic exotoxin A (SPEA). It causes necrotizing fascitis associated with hypotension. It is a superantigen that can bypass the macrophages to activate T-cells. Cytokines involves in sepsis:

TNF-alpha IL-1, 6, 8 Complement Coagulation pathways ROS Gamma interpheron

Diagnosis of sepsis • identify the actual infection source(Very difficult) however, most common sites include

lungs, bloodstream, abdomen, wounds, and UTI.

• Clinically >> SIRS criteria (by check the vital sign) with chills, lethargy, and hemorrhagic skin lesions (blood spilling out of blood vessel)

• Lab tests:

o Blood culture (before giving antibiotics)

#Negative blood culture with clinical symptoms maybe due to:

- prior antibiotic tx.

- the fact that an inflammatory state is not always due to infection.

o Urine culture(UTI)

o Sputum culture if abnormal chest X-ray (pneumonia)

o CBC with differential

o ABG, chemistry

o DIC work up by the following tests:

- CBC –platelets are low.

- PT–prolonged as coagulation factors are consumed

- PTT– may be prolonged

- D-dimer –protein that results from clot break-down; it is markedly

elevated with DIC

-Fibrinogen – one of the clotting factors; is low

The sequential organ failure assessment score (SOFA score)

• The sequential organ failure assessment score (SOFA score), previously known as the sepsis-related organ failure assessment score, is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure.

• The score is based on six different scores, one each for the I. Respiratory II. Cardiovascular III. Hepatic IV. Coagulation V. renal VI. neurological systems.

Goals of treatment 1. Central venous pressure (10-12 mmhg) 2. Urine output (>= 0.5 cc/kg/hour) 3. Mean arterial pressure (>= 65mmhg) 4. Central venous O2 satturation “Scvo2” (>= 70%)

Treatment • Always ABCs in any type of shock • 2 large IV bore • Fluid resuscitation (IV fluids at a dose of 30 mL/kg given within the first 3 h) • Supplemental oxygen • Empiric antibiotics, based on suspected source, as soon as possible Levofloxacin used in suspected patient with pneumonia since its cover most Aminoglycosides(eg. Gentamycin), Ceftriaxone in UTI suspected Ampicillin, Amoxicillin, Tetracyclines Vancomycin For MRSA >>> After the culture result >> specific antibiotic to the organism. • if not get better with antibiotics>> Antifungal (for candidemia) • Vasopressors as needed as following: - noradrenaline >> Vasoconstriction >> increase SVR & BP - dobutamine (high dose) >> inotropic effect >> maintain CO . • There is no useful pharmacological treatment for SIRS; however, some drugs with potential

benefits include NSAIDs, antibodies against LPS, antibodies against TNF alpha, IL-1 antagonists, and platelet activating factor antagonist.

• Steroids: they are given for patients who develop adrenal insufficiency. # monitor progress of the patient 1) CRP(c- reactive protein) normal < 1 mg/dL 2) ESR (erythrocyte sedimentation rate normal < 20-25 ml/h **Both markers increased in inflammation and downtrend(decrease) in resolution of septic shock

References

• Schwart's principles of surgery

• Baily & Love's short Practice of surgery

• Khan academy

• Jordan University SEPSIS lecture