Neonatal Sepsis

Alicia Pacala, RN BSN

pacalaay@alverno.edu

Prepared for MSN 621 Advanced Pathophysiology (Spring 2006)

Alverno College

Welcome !!
Instructions on use of Tutorial:
Instructions What is Neonatal Sepsis? Objectives Causes Symptoms

To start Tutorial:
Diagnosis tutorial Treatments Summary

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Tutorial Objectives
Completing this tutorial will provide the learner with a better understanding of Neonatal Sepsis: * Pathology * Causes What will I learn? * Symptoms * Diagnosis * Treatments

What is Neonatal Sepsis?

Neonatal Sepsis is a term used for a severe infection in newly born infants.

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

It can cause death if not recognized and treated properly.

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 neonates immune system immature?

Pathogen enters body

Neutrophils move in

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].

Chemotaxis occurs

Opsonization causes phagocytosis

Monocytes kill pathogen

pathogens can enter a neonates 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

Invasive Catheters Endotracheal Intubation Exposure to Nosocomial Microorganisms

Postnatal

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]. Red Blood Cells

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

Chemotaxis
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.

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!!

Opsonization
Opsonization is the coating of a pathogen with antibodies that makes it susceptible to phagocytosis [2&6].
Opsonization

Phagocytosis is the process of cells (phagocytes) engulfing, ingesting, & destroying pathogens [2&6].
Pathogen

Neonates have a decreased amount of opsonins (antibodies that promote opsonization) [2&6].

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 neonates immune system susceptible to sepsis?

Maturity

OR
Immaturity

Youre Right!!!!

The immaturity of a neonates immune system makes them MORE SUSCEPTIBLE to sepsis.

Not Quite! Try Again

Genetic Predisposition to Sepsis

Multiple factors play into a neonates 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 bodys 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].

Lets look further into these two phases to see the effect polymorphisms have on neonatal sepsis:
Recognition Phase Response Phase

Recognition Phase
The bodys 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].

Lets look into two of these:

Lipopolysaccharide (LPS)

Mannose-Binding Lectine (MBL)

Response Phase
After 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.

Lets look into two of these :

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

Lipopolysaccharide (LPS)
LPS, a major component of bacteria, is a powerful stimulator of the innate immune response [3]. LPS elicits its 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!

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 less susceptible to sepsis.

They make a neonate more susceptible to sepsis.

They have no apparent effect.

Not quite! Try again.

Great answer! Youre 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 Sepsis

The 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 neonates symptoms are rooted in these two processes.

Lets look more into these areas:

Metabolism

Inflammation

Metabolism in Neonatal Sepsis

Sepsis can alter a neonates metabolism [11]. The Ebb & Flow Metabolic Response [11] best describes how a neonates metabolism is affected by sepsis.

Ebb Phase

Flow Phase

Ebb Flow
This is the initial phase and last only 1-3 days. This is how a neonates 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 Phase
This is the phase that occurs after the initial Ebb Phase. If the body doesnt 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 neonates body into hyperdrive?

Hyper Phase

Flow Phase

Ebb Phase

This is not right!!

Wow! Youre so smart!!

The flow phase DOES put the neonates 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].

Lets find out how this is true

Inflammatory Process

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 [12]

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.
Why????

Broad Spectrum Antibiotics (Ampicillin & Gentamycin) are the first line of defense against neonatal sepsis [2].
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 its 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 neonates 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 neonates 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 neonates immune system [6]. The second factor is related to a possible genetic predisposition that is caused by polymorphisms [3&14]. A Neonates 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 neonates assessment. When sepsis is suspected a neonate will undergo a septic work up [2], which includes lab work and xrays. 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.
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I hope you have enjoyed your experience and have learned some new information about neonatal sepsis.

Contact Information:

pacalaay@alverno.edu

References
1. 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.

References
9. 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, from http://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. Elizabeths. [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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