Necrotising Enterocolitis in Neonates - Guideline for the Management of

Publication: 14/05/2013  --
Last review: 16/05/2019  
Next review: 02/05/2022  
Clinical Guideline
CURRENT 
ID: 3329 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2019  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for the Management of Necrotising Enterocolitis in Neonates

Summary
Necrotising Enterocolitis in Neonates

Necrotising eneterocolitis (NEC) is seen primarily in preterm babies. Diagnosis depends on a constellation of signs. Rapid and adequate resuscitation should take place and close monitoring of fluid balance is vital. Non-antimicrobial measures alongside antibiotics are the mainstay of treatment. Surgical intervention is sometimes necessary both in the acute or recovery phases.
History and examination can be non-specific but NEC should be considered in any infant with feed intolerance, abdominal distension or bloody stools.


Symptoms and signs in NEC

Temperature instability

Increased NG aspirates

Increased apnoeas

Abdominal distension

Increased bradycardias

Fresh blood PR

Mild acidosis

Mucoid stools

Lethargy or quietness

Abdominal cellulitis

Investigations required:

  • Abdominal x-ray: supine and lateral shoot-through (if perforation is suspected). Supine x-ray should be repeated within 24 hours of initial diagnosis and no more than 12 hourly unless clinical signs change
  • Blood tests: (minimum)

Haematology

Biochemistry

Microbiology

Other

FBC

U&E

Blood Cultures

Blood Gas (including Lactate)

Coagulation

CRP

 

 

Group & Save

 

 

 

Remember, if infant is to be transferred to surgical unit, to ensure a sample of maternal blood for group and save is taken.
Non-Antimicrobial Management

  • Stabilise and resuscitate as required
  • Consider intubation and ventilation if hypotensive, acidotic or having recurrent apnoeas
  • 8-10F NG/OG tube on free drainage
  • Measure NG/OG losses (if aspirates replace “mL for mL” with 0.9% sodium chloride with 20 mmol/L potassium)
  • Correct any shock present with 10-20 mL/kg of 0.9% sodium chloride. If further fluid boluses required consider 4.5% HAS. Significant amounts of fluids may be required.
  • Measure urine output (consider urinary catheterisation)
  • Calculate fluid balance and monitor regularly
  • Obtain secure central venous access (oedema may develop quickly making central access difficult to obtain)
  • Serial bloods and AXR may be necessary

Non-Antimicrobial Treatment

  • Nil by mouth (NBM) for up to 2 weeks
  • IV fluids with regular assessment of fluid balance: these infants can require multiple fluid boluses
  • IV antibiotics (see below)
  • Correct coagulopathy: may require FFP, cryoprecipitate or vitamin K - see Blood products on the Neonatal Unit - Use of guideline
  • Maintain adequate blood pressure - see Hypotension in the newborn infants guideline
  • Maintain adequate nutrition: Parenteral nutrition (PN - see main guideline)
  • Surgical review may be required (see below)

Empirical (initial) antimicrobial treatment
Intravenous triple antibiotic combination therapy is routine, however the chosen regime should take into consideration patterns of resistance among Gram-negative enteric organisms for each patient:

First line:
Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin: Amoxicillin monograph
Neonate under 7 days: 30 mg/kg every 12 hours; dose can doubled in severe infection
Neonate 7–28 days: 30 mg/kg every 8 hours; dose can doubled in severe infection
Child 1 month or older: 30 mg/kg every 8 hours; dose can doubled in severe infection;

Gentamicin: Gentamicin monograph

Neonate less than 7 days old 5 mg/kg every 36 hours
Neonate 7 days old and over 5 mg/kg every 24 hours

Metronidazole Description: electronic Medicines Compendium information on Metronidazole: Metronidazole monograph

Neonate less than 26 weeks corrected gestational age:15 mg/kg as a single loading dose followed after 24 hours by 7.5 mg/kg ONCE daily
Neonate 26–34 weeks corrected gestational age: 15 mg/kg as a single loading dose followed after 12 hours by 7.5 mg/kg every 12 hours
Neonate over 34 weeks corrected gestational age: 15 mg/kg as a single loading dose followed after 8 hours by 7.5 mg/kg every 8 hours
Child 1–2 months: 15 mg/kg as a single loading dose followed after 8 hours by 7.5 mg/kg every 8 hours
Child over 2 months : 7.5 mg/kg (max. 500 mg) every 8 hours

Second line: to be used if first line treatment has recently been used in this baby or previous Microbiology suggests need for broader spectrum antibiotics.

Vancomycin Description: electronic Medicines Compendium information on Vancomycin: as per guideline Vancomycin monograph
Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime: Ceftazidime monograph By intravenous injection or infusion
Neonate under 7 days 25 mg/kg every 24 hours;
Neonate 7–21 days 25 mg/kg every 12 hours;
Neonate 21–28 days 25 mg/kg every 8 hours;
Child 1 month–18 years 25 mg/kg every 8 hours;
Metronidazole Description: electronic Medicines Compendium information on Metronidazole: Metronidazole monograph (as above)

Referral for surgical review

  • Free air on x-ray
  • Abdominal wall cellulitis
  • Fixed dilated intestinal segment on x-ray
  • Palpable abdominal mass
  • On-going platelet consumption
  • Clinical condition refractory to medical management

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Background

NEC is the most common gastrointestinal emergency occurring within the neonatal population. It occurs in 1-3 per 1000 live births and is most common in very low birth weight (VLBW) infants in whom the incidence rises to 6-7%.
The aetiology of NEC remains uncertain although numerous risk factors have been implicated in the pathogenesis of NEC, including:

  • Prematurity
  • Milk feeding
  • Impaired mucosal defence
  • Circulatory compromise

NEC is characterised by ischaemic necrosis of the intestinal mucosa, which is associated with inflammation, invasion of enteric gas forming organisms and dissection of gas into the muscularis and portal venous system.1
The gastrointestinal tract of the newborn infant is sterile but colonised within 12-24hours. Colonisation is affected by the feeding practices and use of broad spectrum antibiotics in neonatal intensive care. No single pathogen has been implicated as the cause of NEC, both aerobic and anaerobic micro-organisms including Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae & Enterobacter cloacae), Bacteroides fragilis , Clostridia and Gram positive cocci (Streptococci, Enterococci & Staphylococci) have been identified. Viral pathogens and yeasts have also been implicated in the development of NEC.. Despite conflicting data as to whether culture positivity affects management or outcome, antibiotic therapy needs to target a broad range of both aerobic and anaerobic microbes to cover the spectrum of potential pathogens.
Prevention is better than cure and several factors have been shown to be associated with decreased incidence of NEC

  1. Exclusive use of breast milk to feed infant
  2. Avoidance of use of ant-acids
  3. Adherence to a feeding protocol
  4. Some early evidence showing the use of probiotics is beneficial

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Clinical Diagnosis

NEC should be suspected in any infant with feed intolerance (increasing volume of aspirates or bilious aspirates) abdominal distension and bloody stools (or acute change in stools), however, the early signs can be much less specific (see table below) and it is important to remember that it does not only occur in premature infants.


Symptoms and signs in NEC

Temperature instability

Increased NG aspirates

Increased apnoeas

Abdominal distension

Increased bradycardias

Fresh blood PR

Mild acidosis

Mucoid stools

Lethargy or quietness

Abdominal cellulitis

Differential Diagnosis includes:

  • Sepsis
  • Focal intestinal perforation
  • Volvulus / malrotation
  • Intestinal atresia or stenosis
  • Swallowed maternal blood

Diagnosis Staging modified from 2, 3,4


Modified Bell Staging

Classification

Systemic signs

Abdominal signs

Radiological signs

Ia

Suspected NEC

Temperature instability
Apnoea
Bradycardia
Lethargy

Aspirates
Mild abdominal distension
Positive faecal occult blood

Normal
Mild intestinal dilatation
Mild ileus

Ib

Suspected NEC

As above

Fresh blood PR

As above

IIa

Proven NEC
– mildly ill

As above

As above, plus
Absent bowel sound
+/- abdo tenderness

Intestinal dilatation
Ileus
Pneumatosis intestinalis

IIb

Proven NEC
– moderately ill

As above, plus
Mild metabolic acidosis
Mild thrombocytopenia

As above, plus
Definite tenderness
+/- abdominal cellulitis
+/-RLQ mass

As above, plus
Portal vein gas
+/- ascites

IIIa

Advanced NEC
– severely ill,
– bowel intact

As above, plus
Hypotension
Bradycardia
Severe apnoea
More severe acidosis
DIC
neutropaenia

Generalised peritonitis
Marked tenderness
Marked distension

As above, plus
Definite ascites

IIIb

Advanced NEC
– severely ill,
– bowel perforated

As above
Deteriorating vital signs

As above

As above
pneumoperitoneum

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Investigation
  • Full history review and examination may help differentiate between differential diagnoses
  • Abdominal x-ray: supine and lateral shoot-through (if perforation is suspected).Supine x-ray should be repeated within 24 hours of initial diagnosis and no more than 12 hourly unless clinical signs change
    • Findings on abdominal x-ray: Pneumatosis intestinalis (gas within the bowel wall), free air, portal venous gas, ileus or diffusely dilated bowel loops
  • Ultrasound scan by an experienced sonographer may be useful in some cases to identify portal venous gas and thickened bowel wall.
  • Blood tests: (minimum)

Haematology

Biochemistry

Microbiology

Other

FBC

U&E

Blood Cultures

Blood Gas (including Lactate)

Coagulation

CRP

 

 

Group & Save

 

 

 

Remember, if infant is to be transferred to surgical unit, to ensure a sample of maternal blood for group and save is taken.
Blood results:

  • Coagulopathy

)

 

  • Thrombocytopenia / neutropenia

)

all indicate severe disease

  • Acidosis

)

 

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Treatment
Non-Antimicrobial Treatment

Management

  • Stabilise and resuscitate as required
  • Consider intubation and ventilation if hypotensive, acidotic or having recurrent apnoeas
  • 8-10F NG/OG tube on free drainage
  • Measure NG/OG losses (if aspirates replace “mL for mL” with 0.9% sodium chloride with 20 mmol/L potassium)
  • Correct any shock present with 10-20 mLs/kg of 0.9% sodium chloride. If further fluid boluses required consider 4.5% HAS. Significant amounts of fluids may be required.
  • Measure urine output (consider urinary catheterisation)
  • Calculate fluid balance and monitor regularly
  • Obtain secure central venous access (oedema may develop quickly making central access difficult to obtain)
  • Serial bloods and AXR may be necessary

If umbilical lines in situ, do not remove unless discussed with senior colleague. Central access is often essential and this can necessitate the ongoing use of umbilical lines initially.
Treatment
The guiding principles of treatment can be summarised as resting the gut, nutrition and prevention/treatment of bacteraemia, or more specifically:

  • Nil by mouth (NBM) for up to 2 weeks
  • IV fluids with regular assessment of fluid balance: these infants can require multiple fluid boluses
  • IV antibiotics (see below)
  • Correct coagulopathy: may require FFP, cryoprecipitate or vitamin K - see Blood products on the Neonatal Unit - Use of guideline
  • Maintain adequate blood pressure - see hypotension in the newborn infants guideline
  • Maintain adequate nutrition: Parenteral nutrition (PN - see below)
  • Surgical review may be required (see below)

Early discussion with Paediatric surgical SpR is preferable in all cases of advanced NEC and should be considered in cases of proven NEC.
Indications for Surgical consultation include:

  • Free air on x-ray
  • Abdominal wall cellulitis
  • Fixed dilated intestinal segment on x-ray
  • Palpable abdominal mass
  • Ongoing platelet consumption
  • Clinical condition refractory to medical management

Parenteral Nutrition:
In many cases of confirmed NEC infants will remain NBM for prolonged periods and may be slow to tolerate full enteral feeds and therefore require parenteral nutrition (PN) to maintain adequate nutrition. Secure central access should be placed at the earliest opportunity LINK TO GUIDELINE 217

Long-term management
Reintroduction of enteral feeds

  • feeds should be reintroduced after completion of antibiotic course
  • feeds should be reintroduced slowly, AS PER THE ENTERAL NUTRITION GUIDELINE 1139
  • monitor NG aspirates (feed intolerance occurs frequently in early stages but if persistent may indicate a stricture or other complication)
  • EBM (expressed breast milk) is the preferred milk to recommence feeding with and consideration should be given to the use of Donor EBM if no maternal EBM is available.
  • Some infants may require the use of specialist feeds

Cranial Ultrasound
In cases of proven NEC, consideration should be given to performing a repeat Cranial Ultrasound during the acute illness and 3-4 weeks later to try and identify any new abnormalities such as periventricular leukomalacia (PVL.)
Observe for complications

  • intestinal strictures

)

 

  • enterocolic fistulae

)

all are rare and may not present immediately

  • recurrent NEC

)

 

Outcome
Overall survival after NEC is 70-90%, with mortality being higher in infants less than 28 weeks gestation. Mortality is also higher in infants with birth weight <1000g. Extensive disease, DIC and persistent ascites are all bad prognostic markers.
Nutrition, growth and gastrointestinal function of survivors depend upon the site and extent of the disease5 and if there was any bowel resected. Specific nutritional deficiencies may occur following resection.
There is a link between NEC and PVL and neurodevelopmental problems are more common in survivors of severe NEC.

 

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Empirical Antimicrobial Treatment


Intravenous triple antibiotic combination therapy is routine, however the chosen regime should take into consideration patterns of resistance among Gram-negative enteric organisms for each patient.

First line: Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin: Amoxicillin monograph

Neonate under 7 days: 30 mg/kg every 12 hours; dose can doubled in severe infection
Neonate 7–28 days: 30 mg/kg every 8 hours; dose can doubled in severe infection
Child 1 month or older: 30 mg/kg every 8 hours; dose can doubled in severe infection;

Gentamicin: Gentamicin monograph

Neonate less than 7 days old 5 mg/kg every 36 hours
Neonate 7 days old and over 5 mg/kg every 24 hours

Metronidazole Description: electronic Medicines Compendium information on Metronidazole: Metronidazole monograph

Neonate less than 26 weeks corrected gestational age:15 mg/kg as a single loading dose followed after 24 hours by 7.5 mg/kg ONCE daily
Neonate 26–34 weeks corrected gestational age: 15 mg/kg as a single loading dose followed after 12 hours by 7.5 mg/kg every 12 hours
Neonate over 34 weeks corrected gestational age: 15 mg/kg as a single loading dose followed after 8 hours by 7.5 mg/kg every 8 hours
Child 1–2 months: 15 mg/kg as a single loading dose followed after 8 hours by 7.5 mg/kg every 8 hours
Child over 2 months : 7.5 mg/kg (max. 500 mg) every 8 hours

Second line: to be used if first line treatment has recently been used in this baby or previous Microbiology suggests need for broader spectrum antibiotics.

Vancomycin Description: electronic Medicines Compendium information on Vancomycin: as per guideline Vancomycin monograph

Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime: Ceftazidime monograph
By intravenous injection or infusion

Neonate under 7 days 25 mg/kg every 24 hours;
Neonate 7–21 days 25 mg/kg every 12 hours;
Neonate 21–28 days 25 mg/kg every 8 hours;
Child 1 month–18 years 25 mg/kg every 8 hours;

Metronidazole Description: electronic Medicines Compendium information on Metronidazole: Metronidazole monograph (as above)

Candida species may be important pathogens in occasional cases where focal intestinal perforation is associated with NEC, please Discuss with Microbiology regarding antifungals.

Antifungals should be considered in the infant failing to respond to triple antibiotics and other features such as thrombocytopenia or fungus in the urine.
Fluconazole is the first line anti-fungal agent - see guideline Invasive Candidiasis in Neonates

When infants have just completed a course of second line antibiotics and relapse, consideration should be given to re-starting second line antibiotics. Each case will need to be decided individually, if uncertain discuss with senior neonatologist (Consultant or SpR.)

Failure to respond (i.e. further deterioration or no significant improvement) after 48 hours treatment or at risk of multiple antibiotic resistance

Vancomycin Description: electronic Medicines Compendium information on Vancomycin: as per guideline Vancomycin monograph

Meropenem Description: electronic Medicines Compendium information on MeropenemMeropenem monograph

Neonate under 7 days 20 mg/kg every 12 hours
Neonate 7–28 days 20 mg/kg every 8 hours
Child 1 month–12 years 20mg/kg every 8 hours

A risk assessment needs to be done at this stage to review the need for surgical intervention in cases of clinical deterioration before escalating to meropenem.

Please note Metronidazole Description: electronic Medicines Compendium information on Metronidazoleshould not be routine with this regime as meropenem covers anaerobic organisms, individual cases may need to be discussed with Microbiology.

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Directed Antimicrobial Treatment (when microbiology results are known)

Antimicrobials may be modified depending on Microbiology results, note documented bacteraemia in 20-30% of cases and pathogenic bacteria may be recovered from surgical specimen or peritoneal fluid.

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Duration of Treatment

Duration: up to 14 days in confirmed cases of NEC

Frequently blood cultures are negative however this should not alter the clinical decision to continue IV antibiotics for a specified duration.

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Switch to oral agent(s)
Not appropriate

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Treatment Failure

In infants failing to respond to treatment the infant requires senior review by both the medical and surgical teams and further consultation with microbiology.

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Provenance

Record: 3329
Objective:

Aims
To improve the diagnosis and management of necrotising enterocolitis in newborn infants.

Objectives

  • To provide evidence-based recommendations for appropriate diagnosis and investigation of NEC
  • To provide evidence-based recommendations for appropriate non-antimicrobial management of NEC
  • To provide evidence-based recommendations for appropriate empirical and directed antimicrobial therapy of NEC
  • To recommend appropriate dose, route of administration and duration of antimicrobial agents.
  • To advise in the event of antimicrobial allergy.
  • To set-out criteria for referral for surgical opinion.
Clinical condition:

Necrotising Enterocolitis (NEC)

Target patient group: Newborn infants who develop NEC
Target professional group(s): Secondary Care Doctors
Pharmacists
Secondary Care Nurses
Adapted from:

Evidence base

Evidence base

  1. Neu, J. Necrotizing enterocolitis: The search for a unifying pathogenic theory leading to prevention. Pediatr Clin North Am 1996; 43:409. (c)
  2. Bell MJ. Neonatal necrotizing Enterocolitis. N Engl J Med. 1978 Feb 2;298(5):281-1. (B)
  3. Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing Enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978 Jan;187(1):1-7 [abstract]
  4. Walsh MC, Kleigman RM. Necrotizing Enterocolitis: treatment based on staging criteria. Pediatr Clin North Am 1986; 33:179 (C)
  5. Newell SJ. Gastrointestinal disorders. Roberton’s Textbook of Neonatology. Fourth Edition. (c)
  6. Michael J. Morowitz et al. Redefining the Role of Intestinal Microbes in the Pathogenesis of Necrotizing Enterocolitis. Pediatrics 2010;125:777-785 (c)
  7. C Rees, N Hall, S Eaton, and A. Pierro. Surgical strategies for necrotising enterocolitis: a survey of practice in the United Kingdom. Arch Dis Child Fetal Neonatal Ed. 2005 March; 90(2): F152F155

Evidence levels:
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

Not supplied

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