NEC Flashcards
Define NEC
Ischemic and inflammatory necrosis of the bowel
When was NEC first recognized?
1960-1970’s-when younger babies were being saved (especially cardiac babies)
What was the mortality rate in 1960-1970’s?
Mortality >70%
Has the Medical or Surgical Management changed since 1970?
No
What is the Medical Management of NEC?
5 things
- NPO
- NG suction (replogyl to LIS)
- Systemic Antibiotics
- IV Fluids (d/t 3rd spacing)
- Monitoring clinical signs & X-ray findings
What is the surgical Management of NEC?
3 things
- Removal of Necrotic/Non-viable bowel
- Enterostomy Formation
- Reanastomosis at a later time
What is the current Mortality rate of NEC?
What is the Mortality rate w/Surgical NEC?
~30%
As high as 50% (w/surgical NEC)
Current Morbidity of NEC is high/low?
High
What are the Morbidities of NEC?
- Short Bowel Syndrome
- Parenteral Nutrition-related Liver Dz
- Poor Growth (they are growth restricted later on-don’t do as well)
< 10% on Wt, Length, and OFC - Poor Neurodevelopmental Outcome
Describe the ND outcomes of NEC
1. Mental Retardation < 70 on MDI Mental Developmental Index < 70 on PDI Psychomotor Dev. Index 2. PVL/Cerebral Palsy/Motor Problems 3. Vision & Hearing Impairment
What is one of the worst sequellae of NEC?
Which babies usually get this?
Poor ND outcome
Usually babies w/Surgical intervention from NEC
What is sometimes noted on Clinic F/U?
What can cause this?
Microcephaly
Gram Negative Rod Sepsis (has a predilection to cause it)
What causes the Microcephaly after NEC?
Lipopolysaccharides (LPS) release endotoxins in the outer Gram Negative cell wall.
-There are receptor sites on the Microglia in the White Matter that pick up the Endotoxins.
T/F: In NEC, there is Bacterial invasion of the intestinal wall?
True
With Bacterial invasion of the intestinal wall, what do the bacteria do?
Set up “camp” and Eat the Intestine : (
What metabolic by-product is produced by the invading intestinal wall bacteria?
What does this create?
Hydrogen gas
Creates the linear tracks of air bubbles (Pneumotosis intestinalis)
What does KUB stand for? (old term)
Kidneys, Ureters, Bladder (Abdominal X-ray)
What might be seen on abdominal X-ray of an infant w/NEC?
- Portal Venous Air
2. Pneumatosis Intestinales
What is Portal Venous Air?
What might it look like on Abdominal X-ray?
Does Portal Venous Air stay or is it transient?
The Hydrogen has dissected into the blood vessels and into the portal venous system & is in the Liver
- the Liver should be white/solid, w/air it has little lines or black dots.
- it can be Transient
Pneumatosis Intestinales is a ____________ sign.
Pathognomonic sign
sign specific to NEC
T/F: When Pneumatosis Intestinales is seen, you can definitively say the pt has NEC?
True
The predominant Lesion of NEC is what type?
Necrosis–either coagulative or ischemic
What is the spread of a NEC lesion?
Is there a distinct pattern?
Location: May be longitudinal or transmural
May be Patchy w/no pattern
Where are NEC lesions typically located?
Usually terminal ileum & ascending Colon
What is the most likely site for perforation?
Ileocecal valve
Is a Spontaneous Intestinal Perforation (SIP) the same as NEC?
No
Are babies w/sponatneous intestinal perf. as sick as babies w/NEC?
No, they are sick but not AS sick as those w/NEC (septic shock, etc).
Describe Spontaneous Intestinal Perforation
- Occurs earlier (1-2 wks of life)
- A/W: Indomethicin, Steroids, Umb. Catheters
- ISOLATED AREA of hemorrhagic necrosis often w/perforation in Terminal Ileum
- Generally less morbidity/mortality than NEC
Up to 10% of babies who develop NEC are _____.
Term
What types of babies (generally term) are at High Risk of NEC?
Why?
Gastroschesis–5% incidence
Cong. Heart Dz–3-7% Incidence
The risk is from perfusion problems
Is Preterm NEC different than Term NEC?
Yes
Which Preemies are at greatest Risk of NEC?
< 1000 gms & < 28 wks
The age of onset of NEC varies ________ with ____.
Inversely w/ GA
What is the Mean Postmenstrual Age of NEC?
29-32 wks
The younger GA at birth, the ______the onset of NEC may be.
later
What is the usual time babies develop NEC?
When they are just about up to full feedings
What is the Biggest Problem with a Preemies GI system, leaving them vulnerable to NEC?
The Immaturity of the Intestinal Tract
Name the 6 things of a premature Intestinal Tract.
- Decreased GI Motility–>bacterial overgrowth
- Patchy Protective Mucus coat
- Not tight junctions in intestinal wall structure
- Immature Immune system
- Decreased gastric acidity (increased pH)
- Altered Circulatory Regulation (dilation/vasoconstriction)
What does decreased gastric acidity (increased pH) do?
Alters Bacterial Flora
What medications are A/W NEC?
H2 Blockers—absolute no-no
i.e. Pepcid, Zantac
One study found a ___ - fold increase in NEC when H2 blockers were used.
6.6 x’s
The intestinal Avascular Area (watershed area) depends on what?
Vessels coming across Avascular Area to perfuse it
If you stretched out the Surface area of Microvilli of a term baby, it would be the size of what?
1/2 a Tennis Court
The Microvilli are ___ cells deep.
They measure ____-____ in Length.
1
0.5-1.6mm in Length
The Intestinal Epithelium is a single layer of _________.
Enterocytes
How do the single Enterocyte cells move along the Villus?
They move up as other cell die via Apoptosis
Each Villi has a ______, _______, & _______.
Vein, Artery, & Lymphatic vessel
What sits on top of the Enterocyte that works on protein recognition of pathogens?
TLR’s (Toll-Like Receptors)
What is the principal sensor of infection?
TLR’s (toll-like receptors)
TLR’s are _______ Receptors.
What do TLR’s do?
Signaling receptors.
They Recognize pathogens & Activate the immune system
When TLR’s recognize a pathogen, and the immune system is activated, what happens next?
Is this beneficial?
What happens to this system in a preemie?
This sets up an inflammatory reaction
Yes, it’s beneficial as long as it is CONTROLLED.
The premature body can’t regulate the inflammatory reaction well.
What does an inflammatory reaction produce?
heat
increased blood flow
WBC’s
What is the Proposed Mechanism of NEC?
- Intestinal wall immaturity
- Enteral feeding = bacterial proliferation (microbial dysbiosis)
- Abnormal Colonization
- Low Microbiota Diversity - Bacterial Adhesion (TLR’s stimulated)
- Inflammatory cascade triggered (Macrophages and Polyneutrophils arrive–>Release of inflammatory mediators)
What is an essential component of NEC?
Bacteria
- can be Bacteria, Virus, Fungus
- can be normal flora or probiotic (lactobacillus sepsis)
Preemies are a set up for NEC from inappropriate colonization with pathogenic organisms due to?
- Lack of contact with mother
- Exposure to NICU environment
- Exposure to Antibiotics
- Exposure to H2 Blockers
Preemies have a ______ in development of commensal bacteria (normal flora)
Delay
Preemies have an increase/decrease colonization of potential pathogenic bacteria.
Increase Colonization
Preemies have increased/reduced microbiota diversity
Reduced
-Preemies who develop NEC may show altered microbiota several weeks before Dx (they usually only have a few types of normal flora, and an increased build up of certain ones)
The ability to _____ pain comes before the ability to _________ pain.
Preemies have an Increased/Decreased pain sensation vs. Term. Why?
Feel
Modulate
Increased pain sensation b/c they can’t suppress any of it.
T/F: Preemies are skewed toward UNbalanced pro-inflammatory (injury vs/ repair) response
True.
-The balance between the 2 happens later in development
Name the 2 Inflammatory Mediators involved in NEC
- PAF-Platelet Activating Factor
2. TNF-Tumor Necrosis Factor
Inflammatory Mediators PAF & TNF lead to increased what? (3 things)
- Inflammation
- Vasoconstriction
- Permeability
When the intestinal barrier is broken, injury/repair balance is altered favoring ___________ leading to ______ _______.
Vasoconstriction Tissue Injury (via hypoxia & ischemia-->tissue necrosis)
The vasoconstriction that happens after intestinal barrier is broken is ____ of ______.
Out of Control
Inflammatory and vasoconstrictive prostanoids result in:
Increased production of Nitric Oxide
Low levels of NO = ?
High levels of NO = ?
Vasodilatory & Beneficial
Injure intestinal epithelium (what you get with a preemie from vasoconstrictive prostanoids)
Injury to intestinal epithelium—>_____ _____—>__________ ________—>________.
If it continues, —>_______—>_____ _____
Bacterial Invasion–>Pneumotosis Intestinales–>Necrosis–>Septicemia–>Septic Shock
Name 10 Risk factors for NEC
- Black and Hispanic race (vs. Caucasian)
- Outborn
- NICU NEC rate
- Abnormal bacterial colonization
- H2 Blockers/PPI’s/Jejunal feedings
- Hypertonic formula/meds (osmolarity)
- No standardized feeding protocol
- NPO Status
- Non-Human Milk
- Blood transfusions (or anemia?)
What is the osmolarity of term formula?
Breastmilk?
Fortified Breastmilk?
275-295 miliosmols
~ 300
> 400
What is the 1 thing we KNOW can prevent NEC?
Maternal Breastmilk
What standard feeding protocol is best?
Any (is better than none)
What items should be included in a standardized feeding protocol?
When to start feeds
When to advance feeds
When to add fortifier
When to hold feeds
Can NEC happen in UNfed infants?
Yes, but rare
NPO can be BAD to the gut, why?
- Intestinal Atrophy
- Cellular Death
- Increased Permeability of Intestine
- Bacterial Translocation
Do early trophic feedings decrease NEC?
No, not specifically but they do have many benefits
What are the benefits of early trophic feeds?
Increased:
- Digestive Hormone release
- Intestinal blood flow
- GI Motility
- Feeding Tolerance
- Growth
Decreased:
- Sepsis
- Hospital Stay
A study conducted by Henri Ford MD showed that mice fed Formula in a hypoxic state had what compared to their breastmilk fed counterparts?
Apoptotic Enterocytes
Is the incidence of NEC higher or lower in breastmilk fed babies vs formula?
Lower.
formula = highest
formula + breastmilk = lower
breastmilk only = lowest
In breastmilk fed infants with NEC, what is the course like?
less fulminant course
In a study done by Lucas et. al, in Lancet, any addition of human milk did what?
The more human milk, the ________
helped and protected the babies
better
What % of NEC follows a blood transfusion?
Is there a proven pathogenic pathway?
What is the consensus on what to do about blood transfusion associated NEC?
25-35%
No
None
Anemia itself could be the pathway to NEC instead of the blood transfusion, what is the thought behind this?
In Anemia, there is reperfusion injury w/transfusion.
Maybe we should transfuse earlier
Any condition that causes hypoperfusion-hypoxia is a ________ risk factor
secondary
After what GA are feedings able to be advanced faster?
34 wks
NEC can present with ____ to _____ symptoms
mild to severe
NEC courses can vary from what to what?
slow & paroxysmal
rapid & fulminant
Name the 8 non-specific signs of NEC
- temp instability
- A & B’s
- Lethargy
- Mild GI problems
- Increased residuals
- Low PCV (% of RBC’s)
- Low Platelets (unless mom had PHTN, low plts can be a sign of NEC)
- Metabolic Acidosis
What is the only non-specific sign that can be an actual sign of NEC?
Low platelets
Name 7 more specific signs of NEC
- Abdominal tenderness
- Abdominal distension
- Decreased or Absent bowel sounds
- Emesis
- Frank or occult blood in stools
- Visible loops of bowel
- Discoloration of abdomen
In a term baby w/CHD, what sign can herald NEC?
Frank or occult stools
There are lots of late non-specific symptoms of NEC. What are the triad of signs?
- Thrombocytopenia
- Increased Lactate
- Hyponatremia
Why is oliguria a late non-specific sign?
they 3rd space and have decreased blood flow to kidneys
Why is hyperkalemia a late non-specific sign?
K+ is released from dead cells
In Diagnosing NEC severity what criteria is used (in general).
Has it changed much since 1978?
Modified Bells staging criteria
No, it has not changed much
What is blood in stool usually caused from? What can be used for it?
From an anal fissure
Vaseline
Stage 1 NEC is __________
Stage 2 is ______ by ____
Suspected
Definite by x-ray
What % NEC can be Medically managed?
50-75%
What is the 1st thing that should be done to medically manage NEC?
Why?
Replogyl tube to LIS
Gastric Decompression–try to prevent perforation
When would it be ok to use a feeding tube vs/replogyl?
on transport
-connect fdg tube to syringe
What does Medical Management of NEC involve?
- Blood Gas
- Blood Culture
- CBC, diff, plts
- CRP
- Electrolytes
- Vanc/Gent/Flagyl
- NPO 10-14 days after normal x-ray
- Ventilator support PRN
- Volume expanders
- Pressors
- TPN/IL
- Pain meds
- Serial x-rays
- Surgical consult
How often are serial X-rays done w/NEC?
every 6-8 hours
What abnormal gas patterns are looked for on the AP w/NEC?
Dilated loops of bowel Bowel wall edema Sentinel loop (fixed loop of bowel) Pneumatosis intestinales Portal venous air Football sign Pneumoperitoneum
With the Left lateral decubitus view, why do we use this?
How do you position baby?
Best film to detect pneumoperitoneum
Left side down
“Soap bubbles” is a term used to describe what condition?
CF, not NEC
air mixed w/mec
On abdominal x-ray you might see:
Bowel wall edema Grossly dilated loops Pneumatosis intestinales-"railroad track sign" Portal venous gas Sentinel loop Footbal sign - Falciform ligament Pneumoperitoneum
What i the “railroad track” sign caused from?
Coalesced Hydrogen gas.
The tracks are in the bowel walls themselves.
What is a Sentinel Loop?
Seen on every serial x-ray, the same loop is noted. It means the area is necrotic and gas can’t pass the area.
What is the Football sign a/w the falciform ligament?
The faliciform ligament sticks the liver to the anterior intestinal wall. You can visualize the ligament when air is surrounding it on x-ray.
Ultrasound can be very helpful in Dx NEC. What can it detect?
- ID loculated/absscessed areas consistent w/walled off perforation
- ID and quantify ascites (a gasless abdomen is not good either = fluid/blood in peritoneum)
- May be better at identifying pneumatosis and portal venous air than x-ray
(US w/doppler):
- Detects absence of flow in intestinal wall–>possible ischemia
- Detects increased vascularization–>inflammatory process
T/F: the timing of surgery is controversial
True (too early vs. too late)
What is the traditional surgical management?
Laparotomy w/resection & stoma formation
What is the goal of Surgical Management for NEC?
Save as much intestine as possible
Do they keep the “Leopard Skinning” parts of the intestine during surgery?
Yes, some-they think it will heal
Stomas are very ____________.
hypervascular
Risk of postoperative complications is ____-____%
20-40%
Name 4 surgical wound complications
- Infection
- Dehiscense
- Abscess
- Fistula
Name 3 Stoma complications
- Retraction
- Prolapse
- Hernia
Preterms have ________ tissue strength
Preterms have ________ immune response
Decreased
Decreased
-they don’t heal well, depends on nutrition
Bedside peritoneal drainage was originally what?
Palliative procedure–used to stabilize infants too sick for immediate laparotomy
What % babies actually get better with peritoneal drainage?
~50%
Is peritoneal drainage used as primary tx vs. surgery?
yes, sometimes
What does bedside peritoneal drainage eliminate?
- Stress of transfer to OR
2. Use of general anesthesia
Bedside peritoneal drainage uses Local/General anesthesia?
Local
What does bedside peritoneal drainage do?
- Decompresses pertoneal cavity of gas, necrotic debris, & stool
- Peritoneal cavity can be irrigated w/NS/antibiotics
If there is no improvement or is deterioration in 12-48 hrs of peritoneal drainage, what is the course of action?
Taken to OR for Laparotomy and Resection
What would be 2 signs of worsening NEC w/drain in place?
Decreasing Plts
Decreasing B/P, etc.
50% babies post-op have Gastric Acid hypersecretion. What can this do?
What might be used in this situation, for how long?
Disrupt surgical site
Cause Peptic ulcer
Inactivate Pancreatic Enzymes
H2 blocker might be used for a few days
Name 4 NEC Sequelae
- Recurrent NEC 5%
- Strictures 10-30%
- Malabsorption (d/t bacterial overgrowth)
- Short Bowl Syndrome
How is Malabsorption from bacterial overgrowth treated?
Rotating courses of enteral antibiotics
Tapering of bowel (Bianchi procedure-at about 1 yr for max intestinal growth)
Determining Short Bowel Syndrome depends on what?
What segments were removed
Presence of Ileocecal valve
FUNCTION of remaining bowel
Poor outcomes of Short Bowel Syndrome are associated w/?
Residual length <10% for GA
How much small intestine does a Term infant have?
240-300 cms
A 23 wkr’s small intestine doubles in length by what GA?
35 wks
The small intestine doubles in length from Birth to ____
1 yr
The small intestine has the ability to ______ by increasing the _____ ___ as much as 4 x’s
Adapt
Surface Area
When does compensatory hyperplasia begin?
At time of resection and continues for 3-4 years.
Mortality from short bowel syndrome is primarily due to what?
Parenteral Nutrition sequelae
Length of time on parenteral nutrition matters. Usually don’t want them on it longer than ______.
5 years
What are the side effects of long-term parenteral nutrition?
Central line sepsis
Steatosis (fatty Liver)
Cholestasis (persistent direct bili >2 mg/dL)
How can Cholestasis be prevented?
20-30% parenteral nutrition
How is Cholestatsis treated?
Actigall
Omegaven-life saving in some situations
Cycling TPN-Liver rest
Early ____ _______ is very important w/short bowel syndrome.
Why?
Enteral nutrition
Prevent Atrophy of the gut
Traditional centers wait ___ - ____ days to restart feeds
10-14 days
Centers of Excellence start feeds around ____ days post-op
~4 days–may be able to start as early as 12 hrs
Semi-elemental formula (elecare) is more trophic than breastmilk but may not provide a ________ _______
Functional workload
What is theoretically the best method for feeds w/short bowel syndrome?
Increase feeds ________ & ______
Continuous drip feeds–saturates the whole gut
Carefully & slowly
Breastmilk provides a _______ _______ stimulating adaptation
Functional workload
Presence of Lactose, Complex fats, Protein in Breastmilk can lead to _______ _________
Feeding Intolerance
____% babies with short bowel syndrome will have Dumping Syndrome.
What needs to be monitored carefully (depends a lot on where the stoma is)
80%
Na & K (growth)
Acidosis
To “grow your baby” refeed ostomy output through the ______ _______.
Mucus fistula
What Vitamins are deficient in Short Bowel Syndrome?
Fat-soluble vits A,D,E,& K Vit B12 (absorbed in distal ileum)
What can deficiency of fat soluble vits cause?
Anemia
Bleeding
Rickets
The ileum can compensate for loss of _______ but not the other way around.
loss of Jejunum
Nothing can compensate for loss of the _____
Ileum
Name 3 surgical procedures to improve outcome of short bowel syndrome
- Stricture Resection
- Bowel Tapering
- Bowel Lengthening
The Bianchi Procedure does what?
Dissects the length of bowel into 2 sections
The STEP procedure provides what?
What area is it typically used for?
Lengthening and tapering
(serial transverse enteroplasty)
A very dilated area to increase the surface area and prevent stasis of food
Intestinal transplants have ____ 1 yr survival , ____ 3 yr survival
~87% 1 yr
~75% 3 yr
What is the only known preventive measure for NEC?
Human Breast Milk
T/F: KC is very beneficial for GI colonization
True
What cells are noted in breastmilk?
Neutrophils
Lymphocytes
Macrophages
What enzyme in breastmilk is Anti-Inflammatory?
Lysozyme
What 3 immunoglobulins are in breastmilk?
Which is correlates with decrease in bacterial translocation?
IgG, IgM, IgA
IgA (it’s like a paint brush for the GI system–>protects it, pathogens can’t get through easily & it encourages intestinal growth)
What antibacterial/antiviral in high concentrations in colostrum is 1/3 protein?
Lactoferrin
What 2 growth factors are in breastmilk?
Insulin-like growth factor
Epidermal growth factor
________ encourages replication of Bifidobacteria and decreases colonization w/lactose-fermenting bacteria (that produce H gas and pneumatosis)
Oliogofructose
Oligofructose is a ____biotic
Pre-biotic
What do Prebiotics do?
Feed normal bacteria already in our bodies
What do Probiotics do?
Colonize GI tract w/normal bacteria
- limit # of pathogenic bacteria
- compete for binding sites & nutrition
Produce acid environment hostile to bacteria
Fortify mucosal barrier
Multiple studies show decreased _________ & ________ of NEC when using probiotics
Incidence & severity
Which 2 probiotics look promising?
Lactobacillus & Bifidobacteria
Must probiotics be FDA regulated?
Yes, they are considered a treatment now not a food supplement so they are FDA regulated.
What might be the best balance?
Use of Prebiotics and Probiotics
What are we hoping will happen with the Human Microbiome project?
Find the actual genome that causes NEC
ID microbial patterns prior to developing NEC
ID microbes that currently can’t be cultured
Sensitivity =
Ability of a test to correctly identify those w/the disease (True Positive)
Specificity =
Ability of a test to correctly identify those w/o the disease (True Negative rate)
Name 4 potential biomarkers of NEC
- High-risk colonization patterns
- Serum proteins
- Urine proteins (enterocyte damage)
- Fecal Bile salts (more in babies who develop NEC)
Synthetic Amniotic-like fluid has been trialed and used to do what?
Prevent atrophy of the gut
