PEDIATRIC SEPSIS

OVERVIEW

Sepsis Syndrome

Hypothermia (temperature less than 96 ◦F (35.5 ◦C)) or hyperthermia (greater than 101 ◦F (38.3 ◦C)), Tachycardia (greater than 90 beat/min), tachypnea (greater than 20 breaths/min), clinical evidence of an infection site, and at least one end-organ demonstrating inadequate perfusion or dysfunction

Sepsis is a common, life-threatening condition in the pediatric ICU. Severe sepsis and septic shock occur in all settings and age groups though these

children often have associated co-morbidities such as prematurity or malignancy

OVERVIEW

SIRS: SystemicInflammatory

ResponseSyndrome

Presence of two or more of the following symptoms (seeTable 1): temperature instability (core temp > 38.5 / <36), tachycardia / bradycardia, tachypnea or mechanical ventilation, leukocytosis/leucopenia.

Sepsis SIRS with infection

Severe SepsisSepsis with one other organ dysfunction:cardiovascular dysfunction, mechanical ventilation, change in mental status, rising creatinine, rising hepatic enzymes TBili or ALT

Septic ShockFluid refractory hypotension: hypotension or Hypoperfusion despite fluid resuscitation

MODS / MOFSMulti-organ dysfunction syndrome / multi-organ failuresyndrome – at least two organ system failures

OVERVIEW

What is Neonatal Sepsis?Neonatal Sepsis is a term used for a severe infection

in newly born infants.

It can cause death if not recognized and treated properly.

Facts about neonatal sepsis

Neonatal Sepsis affects approximately 2 infants per 1000 births with a higher incidence in premature & low birth weight infants

Causes of Neonatal Sepsis

The primary causes of Neonatal Sepsis are bacteria, such as Staphylococcus and Group Beta Strep (GBS).

Bacteria may be the cause of neonatal sepsis, but neonates are more susceptible to these bacteria for two reasons :

Immature immune response

Genetic predisposition

STRUKTUR UMUM AGEN

Structural features of the cell wall that distinguishes the Gram-positive from the Gram-negative bacteria, which are two principal classes of pathogenic bacteria.

What makes a neonate’s immune system immature?

Normally an immune system responds to a pathogen in a specific manner, but if there are problems with any element

the immune system is unable to function properly.

Pathogen enters body

Neutrophils move in

Chemotaxis occurs

Opsonization causes phagocytosis

Monocytes kill pathogen

pathogens can enter a neonate’s body in many ways !

Pathogens can enter through the prenatal, perinatal, and postnatal periods.

Prenatal Maternal Substance AbusePremature Rupture of Membranes (>18 Hours)Maternal Infection

Perinatal Microbial Colonization at BirthMaternal InfectionVaginal Exam of Mother

Postnatal Invasive CathetersEndotracheal IntubationExposure to Nosocomial Microorganisms

Neutrophils: An important cell in immunity against pathogens

Neonatal neutrophils are deficient in their ability to adhere to vessel walls at site of infection

Further release of neutrophils depletes a neonatal storage pool because the bone marrow

storage of a neonate is only 20-30% of the pool in an adult

Neonatal neutrophils have a decreased ability to “deform” &

migrate into tissuesNeutrophils

Red Blood Cells

ChemotaxisNeonatal neutrophils have

decreased chemotaxis due to decreased chemoattractant

Production.

Chemoattractants attract neutrophils to the site of infection.

Neonatal neutrophils therefore cannot reach the site of infection

because of the chemotaxis deficiency

caused by decreased chemoattractant production.

OpsonizationOpsonization is the coating of a

pathogen with antibodies that makes it susceptible to phagocytosis.

Phagocytosis is the process of cells (phagocytes) engulfing, ingesting, &

destroying pathogens.

Neonates have a decreased amount of opsonins (antibodies that promote

opsonization).

Opsonization

Pathogen

Monocytes: Another important cell in the fight against pathogens

Monocytes are a type of White Blood Cell that ingests pathogens.

Neonates have a sufficient amount of

monocytes and full capability to kill organisms,

but because of a neonates deficiencies

previously discussed very few

monocytes get to the site of infection.

Genetic Predisposition to Sepsis

Multiple factors play into a neonate’s response to infection and the possible development of sepsis. One of these factors is genetics. As science has moved into recognizing the human genome there have also been advances with finding genetic contributions to sepsis.

The body’s first response to infection requires recognition of the presence of a pathogen.After recognition has occurred the body responds appropriately to resolve the problem.Many polymorphisms have been recognized within both of these phases and they have

been implicated in influencing the susceptibility to and/or outcome from sepsis.

two phases the effect polymorphisms have on neonatal

sepsis:

Recognition Phase Response Phase

Recognition Phase

The body’s initial response to infection requires recognition of the presence of a pathogen.

Polymorphisms in genes coding for proteins involved in the recognition

of pathogens can influence the susceptibility to and/or outcome of neonatal sepsis.

look into two of these:

Mannose-Binding Lectine (MBL)

Lipopolysaccharide (LPS)

LPS, a major component of bacteria, is a powerful stimulator of the innate immune response.

LPS elicits it’s response by binding to a cell surface receptor that is compromised of 3 proteins.

One of these proteins is TLR4.

TLR4 is required for LPS to respond.

When there are polymorphisms in TLR4 there is a reduced response to LPS and that enhances the

susceptibility to infection!

Lipopolysaccharide (LPS)

Mannose-Binding Lectin (MBL)

MBL has two primary immunodefensive roles:– involved with opsonization– leads to activation of complement system,

independent of antibodies.

Polymorphisms cause deficiencies in MBL level.

This results in decreased levels of MBL. This deficiency is associated with increased susceptibility to infections!

Response PhaseAfter the initial recognition of a pathogen occurs the body responds by releasing elevated levels of proinflammatory cytokines followed by a release of anti-inflammatory cytokines. This dual release of opposite cytokines helps the cytokines return to a baseline level and that enables the start of tissue repair to start.

It is generally accepted that an imbalance between proinflammatory and anti-inflammatory cytokines result in clinical manifestations of sepsis.This Imbalance is due to polymorphisms in various proteins involved in the response to pathogens.

Let’s look into two of these :

Tumor Necrosis Factor (TNF) Interleukin 10 (IL-10)

Tumor Necrosis Factor (TNF)

TNF is a proinflammatory cytokine that is responsible

for the initial activation of the inflammatory response.

There are several polymorphisms associated with an

increased secretion of TNF resulting in the susceptibility to sepsis.

Interleukin 10 (IL-10)

IL-10 is an anti-inflammatory cytokine produced by primarily monocytes . IL-10 helps regulate the over

expression of proinflammatory cytokines.

There are three polymorphisms noted that result in an over expression of IL-10. This over

expression is proposed to induce immunosuppression in bacterial sepsis and therefore increasing mortality by inhibiting

bacterial clearance.

Symptoms of Neonatal Sepsis

The symptoms of neonatal sepsis are not concrete and vary Widely.

Tachypnea Heart Rate Changes

Feeding difficulties

Difficulty Breathing Temperature Instability

Jaundice Irritability

Why are symptoms so broad?

Inflammation in Neonatal Sepsis

It is widely known that sepsis occurs because of an exaggerated

systemic inflammatory response (SIR)

Inflammatory Process

Pathogen enters body

Inflammatory mediators released (cytokines)

Injury to endothelium

Tissue factors released

Production of thrombin

Coagulation promotes clot formation

Increased activity of fibrinolysis inhibitors

Decreased fibrinolysis

How is Neonatal Sepsis Diagnosed?

There is no definite marker in neonatal sepsis, but there are determinants of infection.

When a neonate presents with sepsis symptoms a septic work-up

is completed . What is included in a septic work up?* Complete Blood Count (CBC)* Blood & Urine cultures* Lumbar Puncture (LP)* Chest X-Ray* Line cultures

Prognosis

• Prognosis can be estimated with the MEDS score. Approximately 20–35% of patients with severe sepsis and 40–60% of patients with septic shock die within 30 days. Others die within the ensuing 6 months

• Prognostic stratification systems such as APACHE II indicate that factoring in the patient's age, underlying condition, and various physiologic variables can yield estimates of the risk of dying of severe sepsis.

Treatment Recommendations

Antibiotics should be initiated after all cultures and lab work is completed to ensure proper diagnosis.

All neonates will remain on IV antibiotics until blood/urine culture results come back in approximately 2-3 days. Further therapy will depend on lab work results and the neonate’s response to treatment.

Broad Spectrum Antibiotics are the first line of defense against neonatal

sepsis.

Septic Shock Algorithm

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