Neonatal Sepsis

Alicia Pacala, RN BSN

Prepared for MSN 621 Advanced Pathophysiology (Spring 2006)

Alverno College

pacalaay@alverno.edu

Welcome !!Instructions on use

of Tutorial:

To start Tutorial:

tutorial

InstructionsInstructions Causes

Symptoms

Diagnosis

Treatments

Summary

What is Neonatal Sepsis?

Objectives

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Tutorial Objectives

Completing this tutorial will provide the learner with a better

understanding of Neonatal Sepsis:

* Pathology

* Causes

* Symptoms

* Diagnosis

* Treatments

What will I learn?

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.

Image used with permission and provided by www.steliz.org/newborn_center.htm

More facts about Neonatal Sepsis

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

There are two types of Neonatal Sepsis:

Early Onset

Late Onset

* This tutorial will focus primarily on Early Onset Sepsis

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 [3&6]:

Immature immune response

Genetic predisposition

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 [3&6].

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 [6].

Prenatal Maternal Substance Abuse

Premature Rupture of Membranes (>18 Hours)

Maternal Infection

Perinatal Microbial Colonization at Birth

Maternal Infection

Vaginal Exam of Mother

Postnatal Invasive Catheters

Endotracheal Intubation

Exposure 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 [2&6].

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 [2&6].

Neonatal neutrophils have a

decreased ability to “deform” &

migrate into tissues [2&6]. Neutrophils

Red Blood Cells

Image provided with permission from http://en.wikipedia.org/wiki/Image:Segmented_neutrophils.jpg

Chemotaxis

Imagine: Being in a dark tunnel without any direction or a way out. Finally you see light. You move towards the light and get out of the tunnel. Well this is like chemotaxis. The sun is the chemoattractant attracting you out to the world!!

Neonatal neutrophils have

decreased chemotaxis due to

decreased chemoattractant

Production [2&6].

Chemoattractants attract

neutrophils to the site of infection

[2&6].

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 [2&6].

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

destroying pathogens [2&6].

Neonates have a decreased amount of opsonins (antibodies that promote

opsonization) [2&6].

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 [2], but because of a neonates deficiencies previously

discussed very few monocytes get to the site of infection.

Image provided with permission and copyrighted by amaxa GmbH at www.amaxa.com/mission3.html

What makes a neonate’s immune system susceptible to sepsis?

OR

Maturity

Immaturity

You’re Right!!!!

The immaturity of a neonate’s immune system makes them MORE SUSCEPTIBLE to sepsis.

Not Quite! Try Again

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 [3&14]. 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 [3&14].

Let’s look further into these two phases to see 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 [3].

Polymorphisms in genes coding for proteins involved in the recognition

of pathogens can influence the susceptibility to and/or outcome of neonatal sepsis [3].

Let’s look into two of these:Mannose-Binding Lectine (MBL)

Lipopolysaccharide (LPS)

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 [3]. This dual release of opposite cytokines helps the cytokines return to a baseline level and that enables the start of tissue repair to start [3].

It is generally accepted that an imbalance between proinflammatory and anti-inflammatory cytokines result in clinical manifestations of sepsis [3]. 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)

LPS, a major component of bacteria, is a powerful stimulator of the innate immune response [3].

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

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 [3]: – involved with opsonization– leads to activation of complement system, independent

of antibodies.

Polymorphisms cause deficiencies in MBL level [3].

This results in decreased levels of MBL. This deficiency

is associated with increased susceptibility to infections!

Tumor Necrosis Factor (TNF)

TNF is a proinflammatory cytokine that is responsible

for the initial activation of the inflammatory response [3&14].

There are several polymorphisms associated with an

increased secretion of TNF resulting in the susceptibility

to sepsis[3].

Interleukin 10 (IL-10)

IL-10 is an anti-inflammatory cytokine produced by primarily monocytes [3]. 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 [3].

What effect do polymorphisms have in Neonatal Sepsis?

They make a neonate more susceptible to sepsis.

They have no apparent effect.

They make a neonate less susceptible to sepsis.

Not quite! Try again.

Great answer! You’re correct!

Polymorphisms cause either an over expression or under expression of

proteins and/or genes that have significant roles in the immune

response to infection. This alters their ability to properly function which

makes a neonate more susceptible to sepsis.

This is not correct! Try again!

Symptoms of Neonatal SepsisThe symptoms of neonatal sepsis are not concrete and vary

widely [9].

Tachypnea Heart Rate Changes

Feeding difficulties

Difficulty Breathing Temperature Instability

Jaundice Irritability

Why are symptoms so broad?

Symptoms

Symptom variability occurs because of the metabolic and inflammatory processes that occur in neonatal sepsis.

A neonate’s symptoms are rooted in

these two processes.

Let’s look more into these areas: Metabolism

Inflammation

Metabolism in Neonatal Sepsis

Sepsis can alter a neonate’s metabolism [11].

The Ebb & Flow Metabolic Response [11] best describes how a neonate’s metabolism is affected by sepsis.

Flow Phase

Ebb Phase

Ebb FlowThis is the initial phase and last only 1-3 days. This is how a neonate’s body

initially tries to compensate for losses that occur during sepsis. The body slows things down in order to let the body recover.

The Ebb Phase consists of several clinical manifestations [11]: – Hypometabolism – Decreased energy expenditure– Decreased cardiac output– Lowered oxygen consumption– Vasoconstriction

Flow PhaseThis is the phase that occurs after the initial Ebb Phase. If the body

doesn’t recover it goes into hyperdrive. This is partly due to the exaggerated inflammatory response (further discussion in inflammatory

process section). This phase leads to much of the mortality and morbidity related to neonatal sepsis [11].

The Flow Phase consists of several clinical manifestations [11]:– Hypermetabolism– Increased energy expenditure– Increased cardiac output– High oxygen consumption

What metabolic phase causes a neonate’s body into “hyperdrive”?

Hyper Phase

Flow Phase

Ebb Phase

This is not right!!

Wow! You’re so smart!!

The flow phase DOES put the neonate’s body into hyperdrive. This

phase leads to much of the mortality and morbidity in neonatal sepsis.

Not quite. Try again.

Inflammation in Neonatal Sepsis

It is widely known that sepsis occurs

because of an exaggerated

systemic inflammatory response (SIR) [12].

Let’s find out how this is true Inflammatory Process

Inflammatory Process

[12]

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

Inflammation

Overall, the imbalance among inflammation, over coagulation, and decreased fibrinolysis are the cause for the majority of deaths in

sepsis [12].

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 [2]. What is included in a septic work up?

* Complete Blood Count (CBC)

* Blood & Urine cultures

* Lumbar Puncture (LP)

* Chest X-Ray

* Line cultures

Is there a diagnostic marker for neonatal sepsis?

True

False

Yeah!!! You are correct!

There is NOT a specific diagnostic marker, only determinants of infection (labs, x-rays).

Are you sure? Try again!

Treatments for Neonatal Sepsis

It is of vital importance that treatment is initiated as soon as sepsis is suspected, especially for those infants at risk.

Broad Spectrum Antibiotics (Ampicillin & Gentamycin) are the first line of defense against neonatal sepsis [2].

Why????

What are other recommendations/options?

Why is it so important to start antibiotic treatment?

If not treated as soon as sepsis is suspected a neonate is more likely to die from sepsis and it’s complications.

For this reason it is of vital importance that healthcare workers (nurses and physicians) notice and act upon even the most subtle changes in a neonates assessment, particularly those infants at risk (GBS+).

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.* Every hospital/organization has an antibiotic protocol specific to their site.

Although antibiotic therapy is vital, it is just as important to continue the overall support of the neonate (i.e. respiratory & cardiac).

Summary

Neonatal Sepsis is a severe infection in neonates that has the ability to cause death if not

recognized and treated appropriately. The primary causes of sepsis are pathogens, such

as Staphylococcus and Group Beta Strep [2&6]. These pathogens can enter a neonate’s

body during the prenatal, perinatal, and postnatal period [6]. Although pathogens are the

culprit in sepsis, neonates have factors that make them more susceptible to sepsis. One

of these factors is the immaturity of the neonate’s immune system [6]. The second factor

is related to a possible genetic predisposition that is caused by polymorphisms [3&14]. A

Neonate’s symptoms in sepsis are broad and vary [9]. This is due in part to the

metabolic and inflammatory processes that occur in neonatal sepsis. Because symptoms

are broad and not very concrete, it is of vital importance that the healthcare professional

notice even the most subtle changes in a neonate’s assessment. When sepsis is

suspected a neonate will undergo a septic work up [2], which includes lab work and x-

rays. After lab work is completed intravenous antibiotics are initiated immediately and will

continue until lab work demonstrates no infection and the neonate shows no further

symptoms.

Print

I hope you have enjoyed your experience and have learned some

new information about neonatal sepsis.

Contact Information: pacalaay@alverno.edu

References1. Amaxa Biosystems. (n.d.). “Mission #3: Transfect human monocytes”. [Online image]. Retrieved March 22, 2006

from www.amaxa.com/mission3.html

2. Bellig, L.L. & Ohning, B.L. (2004). Neonatal Sepsis. Retrieved February 8, 2006, from emedicine:http://wwwemedicine.com/ped/topic2630.htm

3. Dahmer, M.K., Randolph, A., Vitali, S., & Quasney, M.W. (2005). Genetic polymorphisms in sepsis. Pediatric Critical Care Medicine, 6(3), 61-73. Retrieved February 23, 2006 from PubMed database.

4. Farlex Inc. (n.d.). The Free Dictionary. Retrieved March 30, 2006, from www.thefreedictionary.com

5. LaRosa, S.P. (2002). Sepsis. Retrieved February 14,2006, from The Cleveland ClinicWebsite: http://www.clevelandclinicmeded.com/diseasemanagement/infectiousdisease/sepsis.htm

6. McKenney, W.M. (2001). Neonatal nursing: Understanding the neonatal immune system: High risk for infection. Crtitical Care Nurse, 21(6), 35-58. Retrieved February 14, 2006, from ProQuest database.

7. Microsoft Corp. (2006). Microsoft Clip Art. Retrieved March 30, 2006, from www.microsoftclipart.com

8. Mrozek, J.D., Georgieff, M.K., Blazer, B.R., Mammel, M.C., & Schwarzenburg, S.J. (2000). Effect of sepsis syndrome on neonatal protein and energy metabolism. [Electronic version] Journal of Perinatology, 2, 96-100.

References9. Neonatal Handbook:Sepsis. (n.d.). Retrieved February 14, 2006, from

http://www.netsvic.org.au/nets/handbook/index.cfm?doc_id=898

10. Oostdyk, R. (2005). “Neutrophil”. [Online image]. Retrieved April 20, 2006, fromhttp://en.wikipedia.org/wiki/Image:Segmented_neutrophils.jpg

11. Orr, P.A., Case, K.O., & Stevenson, J.J. (2002). Metabolic response and parenteral nutrition in trauma sepsis and burns. Journal of Infusion Nursing, 25(1), 45-53. Retrieved March 7, 2006 from Ovid database.

12. Sharma, S. & Mink, S. (2004). Septic shock. Retrieved February 14, 2006, from emedicine: http://www.emedicine.com/MED/topic2101.htm

13. St. Elizabeth Hospital. (n.d.). “The newborn center at St. Elizabeth’s”. [Online image]. Retrieved March 22, 2006 from www.steliz.org/newborn_center.htm

14. Villar, J., Maca-Meyer, N., Perez-Mendez, L., & Flores, C. (2204). Bench to bedside review: Understanding genetic predisposition to sepsis. Critical Care, 8(3), 180-189. Retrieved February 23, 2006, from PubMed database.

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