eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology
Necrotizing Enterocolitis: Treatment & Medication
Updated: Sep 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Diagnosis of necrotizing enterocolitis (NEC) is based on clinical suspicion supported by findings on radiologic and laboratory studies. Treatment of necrotizing enterocolitis depends on the degree of bowel involvement and severity of its presentation. Objective staging criteria developed by Bell have been widely adopted or modified to help tailor therapy according to disease severity.
- Bell stage I - Suspected disease
- Stage IA
- Mild nonspecific systemic signs such as apnea, bradycardia, and temperature instability are present.
- Mild intestinal signs such as increased gastric residuals and mild abdominal distention are present.
- Radiographic findings can be normal or can show some mild nonspecific distention.
- Treatment is kept on a diet of nothing-by-mouth (NPO) with antibiotics for 3 days.
- Intravenous (IV) fluids, including total parenteral nutrition (TPN)
- Stage IB
- Stage IA
- Bell stage II - Definite disease
- Stage IIA
- Patient is mildly ill.
- Diagnostic signs include the mild systemic signs present in stage IA.
- Intestinal signs include all of the signs present in stage I, with the addition of absent bowel sounds and abdominal tenderness.
- Radiographic findings show ileus and/or pneumatosis intestinalis. This diagnosis is sometimes referred to as "medical" necrotizing enterocolitis as surgical intervention is not needed to successfully treat the patient.
- Treatment includes support for respiratory and cardiovascular failure, including fluid resuscitation, NPO, and antibiotics for 14 days. Surgical consultation should be considered. After stabilization, TPN should be provided during the period that the infant is NPO.
- Stage IIB
- Patient is moderately ill.
- Diagnosis requires all of stage I signs plus the systemic signs of moderate illness, such as mild metabolic acidosis and mild thrombocytopenia.
- Abdominal examination reveals definite tenderness, perhaps some erythema or other discoloration, and/or right lower quadrant mass.
- Radiographs show portal venous gas with or without ascites.
- Treatment includes support for respiratory and cardiovascular failure, including fluid resuscitation, NPO, and antibiotics for 14 days. Surgical consultation should be considered. After stabilization, TPN should be provided during the period that the infant is NPO.
- Stage IIA
- Bell stage III - Represents advanced necrotizing enterocolitis with severe illness that has a high likelihood of progressing to surgical intervention
- Stage IIIA
- Patient has severe necrotizing enterocolitis with an intact bowel.
- Diagnosis requires all of the above conditions, with the addition of hypotension, bradycardia, respiratory failure, severe metabolic acidosis, coagulopathy, and/or neutropenia.
- Abdominal examination shows marked distention with signs of generalized peritonitis.
- Radiographic examination reveals definitive evidence of ascites.
- Treatment involves NPO for 14 days, fluid resuscitation, inotropic support, and ventilator support. Surgical consultation should be obtained. TPN should be provided during the period of NPO.
- Stage IIIB
- This stage is reserved for the severely ill infant with perforated bowel observed on radiograph in addition to the findings and treatment recommendations for IIIA.
- Surgical intervention as outlined below.
- Stage IIIA
Surgical Care
- Free air visible on abdominal radiograph is an indication for surgery. Surgical treatment includes resecting the affected portion of the bowel, which may be extensive. Initially, an ileostomy with a mucous fistula is typically performed, with reanastomosis performed later. Strictures may occur, with or without a history of surgical intervention, which may require surgical treatment.
- Patients who are extremely small and ill may not have the stability to tolerate laparotomy. If free air develops in such a patient, one may consider inserting a peritoneal drain under local anesthesia in the nursery.
- The surgical community remains divergent on the risks and benefits of open laparotomy versus peritoneal drain placement. Two retrospective reviews of the use of peritoneal drains as initial therapy for perforated bowel concluded that, although most patients ultimately require open laparotomy, initial peritoneal drainage may allow systemic stabilization and recovery in the smallest, sickest infants until they become better surgical candidates.17,18 More recent prospective randomized trials have failed to show a difference in outcomes between the 2 approaches, although local custom may continue to impact the decision for surgical intervention in patients who are surgical candidates.
- Any patient requiring surgical intervention and many of those patients not progressing to surgery require protracted courses of parenteral nutrition and IV antibiotics.
- Secure central venous access is optimal for ensuring uninterrupted delivery of antibiotics and nutrition as well as maximizing nourishment with central venous formulations.
- Some units successfully use percutaneously inserted central venous catheters (PCVCs), whereas other units prefer surgically placed central lines such as Broviac catheters. Both types carry an increased risk of infection, particularly if they are used to administer lipids.
Consultations
- Consult with a pediatric surgeon at the earliest suspicion of developing necrotizing enterocolitis. This may require transferring the patient to another facility where such services are available.
Diet
- When necrotizing enterocolitis is suspected, enteral feedings are withheld and parenteral nutrition is initiated. Centrally delivered formulations with appropriate nutritional components are infused for optimal IV nutrition (see Surgical Care). Enteral feedings are traditionally restarted 10-14 days after findings on abdominal radiographs normalize in the case of nonsurgical necrotizing enterocolitis. However, balancing the risks and benefits of NPO versus enteral feeds may alter this timeline. Reinitiating enteral feeds in postsurgical babies may take longer and may also depend on issues such as the extent of surgical resection, return of bowel motility, timing of reanastomosis, and preference of the consulting surgical team.
- Because of the high incidence of postsurgical strictures, some clinicians prefer to evaluate intestinal patency via contrast studies prior to initiating enteral feeds. When feeds are restarted, if human milk is not available, formulas containing casein hydrolysates, medium-chain triglycerides, and safflower/sunflower oils (eg, Alimentum, Pregestimil, Nutramigen) may be better tolerated and absorbed than standard infant formulas.
Medication
Pharmacologic therapy for necrotizing enterocolitis (NEC) includes agents to treat the developing disease and those to provide supportive and symptomatic relief. Probiotics are emerging as a possible preventive therapy.
Antibiotic, Miscellaneous
Although no single infectious etiology is known to cause necrotizing enterocolitis, clinical consensus finds that antibiotic treatment is appropriate. Broad-spectrum parenteral therapy is initiated at the onset of symptoms after obtaining blood, spinal fluid, and urine for culture. Antibiotic coverage for staphylococcus should be considered in neonatal ICUs (NICUs) that have a high colonization rate. Antifungal therapy should be considered for premature infants with a history of recent or prolonged antibacterial therapy or for babies who continue to deteriorate clinically or hematologically despite adequate antibacterial coverage.
Various antibiotic regimens can be used; one frequently used regimen includes ampicillin, aminoglycoside (eg, gentamicin) or third-generation cephalosporin (cefotaxime), and clindamycin or metronidazole. Vancomycin should be included if staphylococcus coverage is deemed appropriate. This combination provides broad gram-positive coverage (including staphylococcal species), excellent gram-negative coverage (with the exception of pseudomonads), and anaerobic coverage.
Doses are adapted from Neofax.19 Postmenstrual age (PMA) is equivalent to gestational age plus postnatal age. Postnatal age is used as a secondary qualifier to determine dose.Cefotaxime (Claforan)
Broad-spectrum third-generation cephalosporin with excellent nonpseudomonal gram-negative coverage at the expense of gram-positive effects. Safety profile is more favorable than aminoglycosides. Penetrates cerebrospinal fluid to treat meningitis.
Adult
Pediatric
Neonatal dosage depends on PMA and postnatal age
PMA <29 weeks and postnatal age 0-28 days: 50 mg/kg/dose IV q12h
PMA <29 weeks and postnatal age >28 days: 50 mg/kg/dose IV q8h
PMA 30-36 weeks and postnatal age 0-14 days: 50 mg/kg/dose IV q12h
PMA 30-36 weeks and postnatal age >14 days: 50 mg/kg/dose IV q8h
PMA 37-44 weeks and postnatal age 0-7 days: 50 mg/kg/dose IV q12h
PMA 37-44 weeks and postnatal age >7 days: 50 mg/kg/dose IV q8h
PMA >45 weeks (any postnatal age): 50 mg/kg/dose IV q6h
Probenecid may increase cefotaxime levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in severe renal impairment; has been associated with severe colitis
Ampicillin
Broad-spectrum penicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally. Until recently, the HACEK bacteria were uniformly susceptible to ampicillin. However, beta-lactamase–producing strains of HACEK have recently been identified.
Adult
Pediatric
Neonatal dosage depends on PMA and postnatal age
PMA <29 weeks and postnatal age 0-28 days: 25-50 mg/kg/dose IV q12h
PMA <29 weeks and postnatal age >28 days: 25-50 mg/kg/dose IV q8h
PMA 30-36 weeks and postnatal age 0-14 days: 25-50 mg/kg/dose IV q12h
PMA 30-36 weeks and postnatal age >14 days: 25-50 mg/kg/dose IV q8h
PMA 37-44 weeks and postnatal age 0-7 days: 25-50 mg/kg/dose IV q12h
PMA 37-44 weeks and postnatal age >7 days: 25-50 mg/kg/dose IV q8h
PMA >45 weeks (any postnatal age): 25-50 mg/kg/dose IV q6h
Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of PO contraceptives
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction
Gentamicin
Aminoglycoside antibiotic for gram-negative coverage bacteria including Pseudomonas species. Synergistic with beta-lactamase against enterococci. Interferes with bacterial protein synthesis by binding to 30S and 50S ribosomal subunits. Dosing regimens are numerous and are adjusted based on CrCl and changes in volume of distribution, as well as body space into which agent needs to distribute. Monitor by serum levels obtained before third or fourth dose (0.5 h before dosing); may draw peak level 0.5 h after 30-min infusion.
Adult
Pediatric
Neonatal dosage depends on PMA and postnatal age
PMA <29 weeks and postnatal age 0-7 days: 5 mg/kg/dose IV q48h
PMA <29 weeks and postnatal age 8-28 days:4 mg/kg/dose IV q36h
PMA <29 weeks and postnatal age >29 days: 4 mg/kg/dose IV q24h
PMA 30-34 weeks and postnatal age 0-7 days: 4.5 mg/kg/dose IV q36h
PMA 30-34 weeks and postnatal age >8 days: 4 mg/kg/dose IV q24h
PMA >35 weeks (any postnatal age): 4 mg/kg/dose IV q24h
Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular blocking agents prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Documented hypersensitivity; non-dialysis dependent renal insufficiency
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment
Vancomycin (Vancocin, Vancoled)
Provides excellent gram-positive coverage, including methicillin-resistant Staphylococcus species and Streptococcus species. Blocks bacterial cell wall synthesis. The parenteral formulation is widely bioavailable throughout all body tissues and fluids, including cerebrospinal fluid. Recommended for empiric use in patients with central lines, VP shunts, and for those with probable staphylococcal or streptococcal infection. Enteral administration for Clostridium difficile intoxication.
Adult
Pediatric
Neonatal dosage depends on PMA and postnatal age
PMA <29 weeks and postnatal age 0-14 days: 10 mg/kg/dose IV q18h
PMA <29 weeks and postnatal age >14 days: 10 mg/kg/dose IV q12h
PMA 30-36 weeks and postnatal age 0-14 days: 10 mg/kg/dose IV q12h
PMA 30-36 weeks and postnatal age >14 days: 10 mg/kg/dose IV q8h
PMA 37-44 weeks and postnatal age 0-7 days: 10 mg/kg/dose IV q12h
PMA 37-44 weeks and postnatal age >7 days: 10 mg/kg/dose IV q8h
PMA >45 weeks (any postnatal age): 10 mg/kg/dose IV q6h
Concurrent administration with anesthetic agents can cause erythema, hypotension, and hypothermia; concurrent administration of other ototoxic or nephrotoxic drugs, including loop diuretics and aminoglycosides
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use caution with compromised renal function; monitor trough levels (5-10 mcg/mL) and adjust regimen to maintain safe and effective serum levels
Clindamycin (Cleocin)
Inhibits bacterial protein synthesis and is bacteriostatic or bacteriocidal depending on drug concentration and organism. Coverage includes anaerobes commonly found in the intestinal tract and many staphylococcal and streptococcal species.
Adult
Pediatric
Neonatal dosage depends on PMA and postnatal age
PMA <29 weeks and postnatal age 0-28 days: 5-7.5 mg/kg/dose IV/PO q12h
PMA <29 weeks and postnatal age >28 days: 5-7.5 mg/kg/dose IV/PO q8h
PMA 30-36 weeks and postnatal age 0-14 days: 5-7.5 mg/kg/dose IV/PO q12h
PMA 30-36 weeks and postnatal age >14 days: 5-7.5 mg/kg/dose IV/PO q8h
PMA 37-44 weeks and postnatal age 0-7 days: 5-7.5 mg/kg/dose IV/PO q12h
PMA 37-44 weeks and postnatal age >7 days: 5-7.5 mg/kg/dose IV/PO q8h
PMA >45 weeks (any postnatal age): 5-7.5 mg/kg/dose IV/PO q6h
Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Dosage may require adjustment if patient has hepatic impairment; overgrowth of C difficile and associated development of pseudomembranous colitis can occur; C difficile infection has been associated with the development of postinflammatory adhesions and/or stricture; metronidazole also has anaerobic coverage and may be an acceptable substitute
Metronidazole (Flagyl)
Used to treat susceptible anaerobic bacterial and protozoal intraabdominal, systemic, or CNS infections.
Adult
Pediatric
Neonatal dosing adjusted by PMA and postnatal age
Loading dose: 15 mg/kg IV/PO
Maintenance doses: 7.5
PMA <29 weeks and postnatal age 0-28 days: 7.5 mg/kg/dose IV/PO q48h
PMA <29 weeks and postnatal age >28 days: 7.5 mg/kg/dose IV/PO q24h
PMA 30-36 weeks and postnatal age 0-14 days: 7.5 mg/kg/dose IV/PO q24h
PMA 30-36 weeks and postnatal age >14 days: 7.5 mg/kg/dose IV/PO q12h
PMA 37-44 weeks and postnatal age 0-7 days: 7.5 mg/kg/dose IV/PO q24h
PMA 37-44 weeks and postnatal age >7 days: 7.5 mg/kg/dose IV/PO q12h
PMA >45 weeks (any postnatal age): 7.5 mg/kg/dose IV/PO q8h
May increase toxicity of anticoagulants, cyclosporine, lithium, phenytoin, tacrolimus, and carbamazepine; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol; coadministration increases amiodarone toxicity (QT prolongation); increases disulfiram toxicity (psychotic symptoms) with concurrent use; phenobarbital and rifampin may increase metabolism of metronidazole
Documented hypersensitivity; first trimester of pregnancy
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in liver impairment, blood dyscrasias, or CNS disease; reduce dosage in severe liver impairment; monitor for seizures and development of peripheral neuropathy
Vasopressors
Babies with serious illness may progress to shock and require pharmacologic blood pressure support.
Dopamine (Intropin)
An adrenergic agonist that increases blood pressure by stimulating alpha-adrenergic vascular receptors resulting in vasoconstriction. Has some inotropic effects via beta1 cardiac receptors and, at low doses, increases glomerular filtration via renal dopaminergic receptors. Useful for babies with hypotension not responsive to volume repletion. May be mixed in dextrose so that glucose delivery is not compromised.
Adult
Pediatric
2-20 mcg/kg/min continuous IV infusion; initiate at low dose and titrate to effect
Phenytoin, alpha-blocking and beta-adrenergic blockers, general anesthesia, and MAOIs increase and prolong effects of dopamine
Documented hypersensitivity; pheochromocytoma; ventricular fibrillation
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Extravasation can cause tissue necrosis, treat with phentolamine as quickly as possible after the event; correct hypovolemia before infusion
Dobutamine (Dobutrex)
Adrenergic agonist with specific effects on beta1-receptors in the heart, resulting in increased contractility. Has minimal alpha-adrenergic activity. Can be used for babies in shock, usually adjunctively with dopamine, to increase cardiac output. May be mixed in dextrose so that glucose delivery is not compromised.
Adult
Pediatric
2-25 mcg/kg/min continuous IV infusion; initiate at low dose and titrate to effect
Beta-adrenergic blocking agents antagonize effects; general anesthetics may increase toxicity
Documented hypersensitivity; idiopathic hypertrophic subaortic stenosis; atrial fibrillation or flutter
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hypovolemic state should be corrected before using this drug
Epinephrine (Adrenaline)
Nonspecific adrenergic agonist that stimulates alpha-receptors, beta1-receptors, and beta2-receptors. Can be used to support blood pressure in severe hypotension refractory to other treatment modalities.
Adult
Pediatric
0.1 mcg/kg/min continuous IV infusion initially; may increase to optimal effect; not to exceed 1 mcg/kg/min
Increases toxicity of beta-blocking and alpha-blocking agents and that of halogenated inhalational anesthetics
Documented hypersensitivity; cardiac arrhythmias or angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; do not use during labor (may delay second stage of labor)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hypertension, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias
Naloxone (Narcan)
Opioid receptor blocker. Experimental evidence suggests that it may increase blood pressure for babies in shock, perhaps by blocking the binding of endogenously produced endorphins released in sepsis, particularly from gram-negative organisms.
Adult
Pediatric
Bolus: 0.1 mg/kg IV push
For continuous IV infusion, administer a test dose as above, observe for magnitude and duration of effect, and calculate continuous dose appropriately
Reported dosage range 2.5-160 mcg/kg/h IV
Blocks the effects of narcotic analgesics and those of endogenous endorphins that may be involved in intrinsic pain relief pathways
Documented hypersensitivity; opioid addiction in baby or mother if baby is <7 d
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in cardiovascular disease; naloxone may precipitate withdrawal symptoms in patients addicted to opiates
Volume expanders
Patients with severe illness may experience fluid shifts to the extracellular space, resulting in intravascular depletion requiring expansion.
Albumin (5% and 25%)
Used to increase intravascular oncotic pressure in hypovolemia and helps mobilize fluids from the interstitial to the intravascular space. Concentration can be either 5% (5 g/100 mL) or 25% (25 g/100 mL), depending on the desired effect.
Adult
Pediatric
Typical dose: 0.5-1 g/kg
Use 5% to replete the intravascular space
Use 25% to move fluid from the extravascular to the intravascular space
None reported
Documented hypersensitivity; severe anemia; cardiac failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
If the patient has an ongoing capillary leak, exogenous albumin also moves into the interstitium; administer IV slowly, rapid administration can cause fluid shifts, exacerbating the risk of intraventricular hemorrhage in premature neonates; carries all of the risks and restrictions associated with administering blood products; protein load may exacerbate renal insufficiency, a potential complication of septic shock
Sodium chloride 0.9% (Normal saline, NS, Isotonic saline)
Can be used as a volume expander and be as effective as albumin in acute hypovolemia.
Adult
Pediatric
10-20 mL/kg IV infused over 30 min
None reported
Fluid retention; hypernatremia; cardiac failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in congestive heart failure, hypertension, edema, liver cirrhosis, renal insufficiency, and sodium toxicity
Fresh frozen plasma
Used as a volume expander, especially helpful for patients with concomitant coagulopathy.
Adult
Pediatric
10-15 mL/kg IV infused over 1 h
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Carries all of the risks and restrictions associated with administering blood products
Glucocorticosteroids
These agents correct the inappropriate adrenal response that is often present in very ill neonates. Once hydrocortisone therapy is initiated, hypotension typically resolves.
Hydrocortisone sodium succinate (Solu-Cortef)
Elicits mineralocorticoid activity and glucocorticoid effects.
Adult
Pediatric
Stress dose for hypotension resistant to pressors or fluids: 20-30 mg/m2/d IV divided bid/tid (ie, approximately 1 mg/kg/dose IV q8h)
CYP450 2D6 and 3A3/4 substrate; corticosteroid clearance may increase with phenytoin, barbiturates, or rifampin treatment or decrease with estrogens; cholestyramine may decrease AUC; corticosteroids may increase digitalis toxicity secondary to hypokalemia; coadministration with potassium depleting agents (eg, diuretics) may increase risk of hypokalemia; corticosteroids may decrease growth-promoting effect of GH; decreases effects of salicylates and vaccines used for immunization; monitor for hypokalemia with coadministration of diuretics or amphotericin B; antagonizes effects of anticholinergics; may increase anticoagulant effects of warfarin; decreases hypoglycemic effects of sulfonylureas and insulin; increases toxicity of cyclosporine
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis
Opioid analgesics
Although difficult to assess, premature infants presumably experience pain with severe illness and invasive procedures. Narcotic analgesics are safe and effective in premature infants and have a long history of clinical experience.
Morphine sulfate (Duramorph, Astramorph)
Opioid analgesic with a long history of safe and effective use in neonates. Inhibits ascending pain pathways by binding to the opiate receptors in the CNS. Causes generalized CNS depression. It is used for sedation and analgesia.
Adult
Pediatric
Administer as a bolus or a continuous infusion
Bolus: 0.05-0.2 mg/kg IV q4h prn; not to exceed 0.1 mg/kg q1h
Continuous infusion: Administer loading dose of 100-150 mcg/kg (ie, 0.1-0.15 mg/kg) IV infused over 1 h, then 10- 20 mcg/kg/h continuous IV infusion (ie, 0.01-0.02 mg/kg/h)
Other CNS depressants (eg, drugs typically not used in neonates) can potentiate the adverse effects of morphine; naloxone reverses morphine
Documented hypersensitivity; hypotension; potentially compromised airway when establishing rapid airway control would be difficult
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Causes respiratory depression/apnea at higher doses; use only preservative-free preparations in neonates; may cause systemic hypotension secondary to histamine release; prolonged use causes physiologic dependence and abrupt cessation can cause severe neonatal abstinence syndrome
Fentanyl (Sublimaze)
Opioid analgesic 50-100 times more potent than morphine; mechanism of action and indications for use are similar; has less hypotensive effects than morphine because of minimal-to-no associated histamine release.
Administered bolus IV or as a continuous infusion. Because of small volumes used in neonates for bolus administration, it is not usually cost-effective to administer bolus.
Adult
Pediatric
Bolus: 0.5-4 mcg/kg/dose slow IV push
Continuous infusion: 0.5-1 mcg/kg/h IV initially; titrate to desired effect; not to exceed 5 mcg/kg/h
If used during ECMO, higher doses can be anticipated, typically 1-5 mcg/kg/h initially
Because of tachyphylaxis, dose may need to be increased during the ECMO run, with doses as high as 20 mcg/kg/h reported by day 7 of treatment
Other CNS depressants (eg, drugs not typically used in neonates) and MAOIs may potentiate adverse effects; naloxone reverses fentanyl
Documented hypersensitivity; hypotension; potentially compromised airway when establishing rapid airway control would be difficult
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Rapid IV administration may result in chest wall rigidity, severely compromising ability to ventilate the baby; higher doses are associated with respiratory depression/apnea; should be administered by qualified health care professionals trained in the use of general anesthetic agents; patient should be closely monitored, dose should be titrated, and lowest effective dose should be used; prolonged use (>5 d continuous infusion) results in physiologic dependence and abrupt cessation precipitates neonatal abstinence syndrome
Antifungal agents
The mechanism of action in these agents may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide, which is toxic to the fungal cell.
If antifungal therapy is warranted, fluconazole can be initiated. Fluconazole is less toxic than amphotericin B, which is substituted if no clinical response to fluconazole occurs or if evidence of microbiological resistance is present.
Fluconazole (Diflucan)
Antifungal agent with good activity against Candida albicans. Associated with less toxicity and easier to administer than amphotericin B; however, fluconazole-resistant candidal species are being isolated with increasing frequency. This agent can be administered enterally or parenterally.
Adult
Pediatric
Neonatal dosage depends on PMA and postnatal age
Loading dose: 12 mg/kg IV/PO
PMA <29 weeks and postnatal age 0-14 days: 6 mg/kg/dose IV/PO q72h
PMA <29 weeks and postnatal age >14 days: 6 mg/kg/dose IV/PO q48h
PMA 30-36 weeks and postnatal age 0-14 days: 6 mg/kg/dose IV/PO q48h
PMA 30-36 weeks and postnatal age >14 days: 6 mg/kg/dose IV/PO q24h
PMA 37-44 weeks and postnatal age 0-7 days: 6 mg/kg/dose IV/PO q48h
PMA 37-44 weeks and postnatal age >7 days: 6 mg/kg/dose IV/PO q24h
PMA >45 weeks (any postnatal age): 6 mg/kg/dose IV q24h
Levels may increase with hydrochlorothiazide; fluconazole levels may decrease with chronic coadministration of rifampin; coadministration of fluconazole may decrease phenytoin clearance; inhibits CYP2C19 and CYP3A4; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration; increases in cyclosporine concentrations may occur when administered concurrently
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use caution in impaired renal function (dosage may require adjustment); monitor liver enzymes and liver function tests during protracted therapy; discontinue use if clinical signs of hepatic failure develop
Probiotics
Oral administration of nonpathogenic bacterial species may result in beneficial alteration of intestinal bacterial flora, reducing risk and severity of disease.20,21,22,23,24,25,26,27
Lactobacillus acidophilus/Bifidobacterium infantis (Infloran)
Lactic acid–producing organisms thought to acidify the intestinal contents and to prevent selective bacterial growth. Probiotic live cultures are intended to restore or maintain healthy microbial flora. Data are currently emerging regarding use in NEC. Various products are available and doses may vary between products. Infloran has specifically been studied in NEC among VLBW infants. It has completed phase II clinical trials.
Adult
Pediatric
Varies with preparation
Infloran: 125 mg/kg PO bid; mix in breast milk/formula
Data limited, none reported
Documented hypersensitivity; sensitivity to lactose or milk
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
L acidophilus has been reported to cause metabolic acidosis; may cause burping, diarrhea, gas, hiccups, or vomiting; Lactobacillus sepsis occurred in 2 infants with short bowel syndrome who were administered Lactobacillus GG as a probiotic to prevent bacterial overgrowth (both infants had short gut, cholestasis, and chronic intestinal inflammation; DNA fingerprinting was used to verify the suspicion that probiotic treatment was the source of the septicemia in one of the infants)
More on Necrotizing Enterocolitis |
| Overview: Necrotizing Enterocolitis |
| Differential Diagnoses & Workup: Necrotizing Enterocolitis |
 Treatment & Medication: Necrotizing Enterocolitis |
| Follow-up: Necrotizing Enterocolitis |
| Multimedia: Necrotizing Enterocolitis |
| References |
| « Previous Page | Next Page » |
References
Hunter, CJ, Camerini V, Boyle A, et al. Bacterial Flora Enhance Intestinal Injury and Inflammation in the Rat Pup Model of Necrotizing Enterocolitis [dissertation/master's thesis]. Presented at PAS 2007, Toronto: Childrens hospital Los Angeles, CA; 2007.
Hoyos AB. Reduced incidence of necrotizing enterocolitis associated with enteral administration of Lactobacillus acidophilus and Bifidobacterium infantis to neonates in an intensive care unit. Int J Infect Dis. 1999;3(4):197-202. [Medline].
Alfaleh K, Anabrees J, Bassler D. Probiotics Reduce the Risk of Necrotizing Enterocolitis in Preterm Infants: A Meta-Analysis. Neonatology. Aug 25 2009;97(2):93-99. [Medline].
Pickard SS, Feinstein JA, Popat RA, Huang L, Dutta S. Short- and long-term outcomes of necrotizing enterocolitis in infants with congenital heart disease. Pediatrics. May 2009;123(5):e901-6. [Medline]. [Full Text].
Moya FR, Eguchi H, Zhao B, et al. Platelet-activating factor acetylhydrolase in term and preterm human milk: a preliminary report. J Pediatr Gastroenterol Nutr. Aug 1994;19(2):236-9. [Medline].
Moonen RM, Paulussen AD, Souren NY, Kessels AG, Rubio-Gozalbo ME, Villamor E. Carbamoyl phosphate synthetase polymorphisms as a risk factor for necrotizing enterocolitis. Pediatr Res. Aug 2007;62(2):188-90. [Medline].
Treszl A, Heninger E, Kalman A, Schuler A, Tulassay T, Vasarhelyi B. Lower prevalence of IL-4 receptor alpha-chain gene G variant in very-low-birth-weight infants with necrotizing enterocolitis. J Pediatr Surg. Sep 2003;38(9):1374-8. [Medline].
Young C, Sharma R, Handfield M, Mai V, Neu J. Biomarkers for Infants at Risk for Necrotizing Enterocolitis: Clues to Prevention?. Pediatr Res. Jan 28 2009;[Medline].
Kovacs L, Papageorgiou, A. Incidence, Predisposing Factors and Outcome of NEC in Infants <32 Weeks' Gestation [dissertation/master's thesis]. Presented at PAS 2007, Toronto: SMBD-Jewish General Hospital, McGill University, Montreal; 2007.
Wiswell TE, Robertson CF, Jones TA, Tuttle DJ. Necrotizing enterocolitis in full-term infants. A case-control study. Am J Dis Child. May 1988;142(5):532-5. [Medline].
Brotschi B, Baenziger O, Frey B, Bucher HU, Ersch J. Early enteral feeding in conservatively managed stage II necrotizing enterocolitis is associated with a reduced risk of catheter-related sepsis. J Perinat Med. Aug 13 2009;[Medline].
McKeown RE, Marsh TD, Amarnath U, et al. Role of delayed feeding and of feeding increments in necrotizing enterocolitis. J Pediatr. Nov 1992;121(5 Pt 1):764-70. [Medline].
Shorter NA, Liu JY, Mooney DP, Harmon BJ. Indomethacin-associated bowel perforations: a study of possible risk factors. J Pediatr Surg. Mar 1999;34(3):442-4. [Medline].
Adderson EE, Pappin A, Pavia AT. Spontaneous intestinal perforation in premature infants: a distinct clinical entity associated with systemic candidiasis. J Pediatr Surg. Oct 1998;33(10):1463-7. [Medline].
Stark AR, Carlo WA, Tyson JE, et al. Adverse effects of early dexamethasone in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network. N Engl J Med. Jan 11 2001;344(2):95-101. [Medline].
Deeg KH, Rupprecht T, Schmid E. Doppler sonographic detection of increased flow velocities in the celiac trunk and superior mesenteric artery in infants with necrotizing enterocolitis. Pediatr Radiol. 1993;23(8):578-82. [Medline].
Ahmed T, Ein S, Moore A. The role of peritoneal drains in treatment of perforated necrotizing enterocolitis: recommendations from recent experience. J Pediatr Surg. Oct 1998;33(10):1468-70. [Medline].
Rovin JD, Rodgers BM, Burns RC, McGahren ED. The role of peritoneal drainage for intestinal perforation in infants with and without necrotizing enterocolitis. J Pediatr Surg. Jan 1999;34(1):143-7. [Medline].
Young TE, Mangum B. Neofax. Twenty-first edition. Montvale, NJ: Thomson Reuters; 2008.
Alfaleh K, Bassler D. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev. Jan 23 2008;CD005496. [Medline].
Bin-Nun A, Bromiker R, Wilschanski M, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr. Aug 2005;147(2):192-6. [Medline].
Carlson K, Schy RB, Jilling T, Lu J, Caplan MS. The Two Probiotic strains, L acidophilus and S thermophilus, down-regulate Toll-like Receptor 4 Expression in Enterocytes [dissertation/master's thesis]. Presented at PAS Toronto, 2007: Evanston Northwestern Hospital, IL; 2007.
Dani C, Biadaioli R, Bertini G, Martelli E, Rubaltelli FF. Probiotics feeding in prevention of urinary tract infection, bacterial sepsis and necrotizing enterocolitis in preterm infants. A prospective double-blind study. Biol Neonate. Aug 2002;82(2):103-8. [Medline].
Hammerman C, Bin-Nun A, Kaplan M. Germ warfare: probiotics in defense of the premature gut. Clin Perinatol. Sep 2004;31(3):489-500. [Medline].
Lin HC, Su BH, Chen AC, et al. Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in very low birth weight infants. Pediatrics. Jan 2005;115(1):1-4. [Medline].
Millar M, Wilks M, Costeloe K. Probiotics for preterm infants?. Arch Dis Child Fetal Neonatal Ed. Sep 2003;88(5):F354-8. [Medline].
Lin HC, Hsu CH, Chen HL, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics. Oct 2008;122(4):693-700. [Medline].
Lucas A, Cole TJ. Breast milk and neonatal necrotising enterocolitis. Lancet. Dec 22-29 1990;336(8730):1519-23. [Medline].
Eyal F, Sagi E, Arad I, Avital A. Necrotising enterocolitis in the very low birthweight infant: expressed breast milk feeding compared with parenteral feeding. Arch Dis Child. Apr 1982;57(4):274-6. [Medline].
Berseth CL. Effect of early feeding on maturation of the preterm infant's small intestine. J Pediatr. Jun 1992;120(6):947-53. [Medline].
Meetze WH, Valentine C, McGuigan JE, et al. Gastrointestinal priming prior to full enteral nutrition in very low birth weight infants. J Pediatr Gastroenterol Nutr. Aug 1992;15(2):163-70. [Medline].
Rayyis SF, Ambalavanan N, Wright L, Carlo WA. Randomized trial of "slow" versus "fast" feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants. J Pediatr. Mar 1999;134(3):293-7. [Medline].
Kennedy KA, Tyson JE, Chamnanvanakij S. Rapid versus slow rate of advancement of feedings for promoting growth and preventing necrotizing enterocolitis in parenterally fed low-birth-weight infants. Cochrane Database Syst Rev. 2000;(2):CD001241. [Medline].
[Guideline] Cincinnati Children's Hospital Medical Center. Evidence-based care guideline for necrotizing enterocolitis (NEC) among very low birth weight infants. Cincinnati (OH): Cincinnati Children's Hospital Medical Center; 2007 Feb.
Avila-Figueroa C, Goldmann DA, Richardson DK, et al. Intravenous lipid emulsions are the major determinant of coagulase- negative staphylococcal bacteremia in very low birth weight newborns. Pediatr Infect Dis J. Jan 1998;17(1):10-7. [Medline].
Berseth CL, Abrams SA. Special gastrointestinal concerns. In: Taeusch W, Ballard RA, eds. Avery's Diseases of the Newborn. 7th ed. Philadelphia, PA: WB Saunders Co; 1998:965-70.
Bhandari V, Bizzarro MJ, Shetty A, Zhong X, Page GP, Zhang H. Familial and genetic susceptibility to major neonatal morbidities in preterm twins. Pediatrics. Jun 2006;117(6):1901-6. [Medline].
Butel MJ, Waligora-Dupriet AJ, Szylit O. Oligofructose and experimental model of neonatal necrotising enterocolitis. Br J Nutr. May 2002;87 Suppl 2:S213-9. [Medline].
Freeman J, Wilcox MH. Antibiotics and Clostridium difficile. Microbes Infect. Apr 1999;1(5):377-84. [Medline].
Furukawa M, Lee EL, Johnston JM. Platelet-activating factor-induced ischemic bowel necrosis: the effect of platelet-activating factor acetylhydrolase. Pediatr Res. Aug 1993;34(2):237-41. [Medline].
Guner Y, Friedlich Ph, Dorey F, et al. Mortality From Necrotizing Enterocolitis Is Increased in the Presence of Patent Ductus Arteriosus [dissertation/master's thesis]. Presented at PAS 2007, Toronto: Childrens Hospital Los Angeles, CA; 2007.
Halkais J, Podd B, Goth K, Camerini V. Small Lymphoid Aggregatres in the Intestine Are Sites of Antigen Presentation and Regulatory T-cell Accumulation [dissertation/master's thesis]. Presented at PAS 2007, Toronto: Childrens Hospital Los Angeles/LAC-USC, Los Angeles, CA; 2007.
Halpern MD, Khailova L, Hosseini DM, Arganbright K, Dvorak B. Reduction of Necrotizing Enterocolitisin IL-18 Knockout Mice [dissertation/master's thesis]. Presented at PAS 2007, Toronto: University of Arizona, Tucson; 2007.
Hartman GE, Boyajian MJ, Choi SS, et al. General surgery. In: Neonatology: Pathophysiology & Management of the Newborn. 5th ed. Philadelphia, PA: Lippincott; 1999:1005-44.
Hsueh W, Caplan MS, Qu XW, et al. Neonatal necrotizing enterocolitis: clinical considerations and pathogenetic concepts. Pediatr Dev Pathol. Jan-Feb 2003;6(1):6-23. [Medline].
Kafetzis DA, Skevaki C, Costalos C. Neonatal necrotizing enterocolitis: an overview. Curr Opin Infect Dis. Aug 2003;16(4):349-55. [Medline].
Kanto WP Jr, Hunter JE, Stoll BJ. Recognition and medical management of necrotizing enterocolitis. Clin Perinatol. Jun 1994;21(2):335-46. [Medline].
Khailova L, Hosseini DM, Reynolds C, Dvorak B, HalpernMD. Ileal Bile Acid Accumulation Precedes Ileal Damage and Inflammation in Experimental Necrotizing Enterocolitis [dissertation/master's thesis]. Presented at PAS 2007, Toronto: University of Arizona, Tucson; 2007.
Khailova L, Reynolds CM, Hosseini DM, Halpern MD, Dvorak B. Changes in Hepatic Cell Junctions Structure During Experimental Necrotizing Enterocolitis: Effect of EGF Treatment [dissertation/master's thesis]. Presented at PAS 2007, Toronto: University of Arizona, Tucson; 2007.
Khaliova L, Hosseini DM, Dvorak B, Halpern MD. Inhibition of Bile Acid Uptake Reduces Incidence and Severity of Necrotizing Enterocolitis [dissertation/master's thesis]. Presented at PAS 2007, Toronto: University of Arizona, Tucson; 2007.
Krimmel G, Baker R, Yanowitz T. Blood Transfusion Alters the Superior Mesenteric Artery Blood Flow Velocity (MBFV) Response to Feeding in Premature Infants [dissertation/master's thesis]. Presented at PAS Toronto, May 2007: University Pittsburgh, PA; 2007.
Nash PL. Naloxone and its use in neonatal septic shock. Neonatal Netw. Jun 1990;8(6):29-34. [Medline].
Powell SB, Silvestri JM, Griffin AHJ. Bokowski JW, Holterman MJ. Patent Ductus Arteriosus (PDA), Aortic Reversed Diastolic Flow, Indomethacin and Intestinal Perforation/Nectorizing Enterocolitis (IP/NEC) in Extremely Low Birth-weight Infants [dissertation/master's thesis]. Presented at PAS 2007, Toronto: Rush Children's Hospital, Chicago, IL; 2007.
Ramasamy V, Sriram B, Bindu M, Agarwal P. Postoperative Outcomes of Very Low Birthweight (VLBW) Neonates with Necrotising Enterocolitis (NEC) or Solitary Intestinal Perforation (SIP) [dissertation/master's thesis]. Presented at PAS 2007, Toronto: KK Women's and Children's Hospital, Singapore; 2007.
Reber KM, Nankervis CA. Necrotizing enterocolitis: preventative strategies. Clin Perinatol. Mar 2004;31(1):157-67. [Medline].
Richter JM, Schanbacher BL, Reber KM, Bajuer JA, Giannone PJ. Effectof Lipopolysaccharide (LPS) on Intestinal Injury and Restitution: Implication for Innate Immune Mechanisms [dissertation/master's thesis]. Presented at PAS 2007, Toronto: Columbus Children's Hospital, Columbus, OH; 2007.
Riskin A, Hochwald O, Bader D, et al. The Effects of Lactulose Supplementation to Enteral Feedings in Premature Infants -- A Pilot Study [dissertation/master's thesis]. Presented at PAS 2007, Toronto: Bnai Zion Medical Center, Haifa, Israel; 2007.
Schutzman DL, Porat R. G6PD Deficience -- Yet Another Association with Necrotizing Enterocolitis? [dissertation/master's thesis]. Presented at PAS 2007, Toronto: Albert Einstein Medical center, Philadephia, PA; 2007.
Shim Sy, Kim HS, Kim SD, et al. Cow's Milk Protein-Induced Enterocolitis in Near-term and Full-term Infants with Preceding Necrotizing Enterocolitis [dissertation/master's thesis]. Presented at PAS 2007, Toronto: Seoul National University College of Medicine, Seoul, Korea; 2007.
Simmonds A, LaGamma E. rhG-CSF + IVIG: A Rational Treatment for the "New" NEC? [dissertation/master's thesis]. Presented at PAS 2007, Toronto: NYMC/Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, NY; 2007.
Stoll BJ. Epidemiology of necrotizing enterocolitis. Clin Perinatol. Jun 1994;21(2):205-18. [Medline].
Taketomo CK, Hodding JH, Kraus DM. Pediatric Dosage Handbook. 6th ed. Lexi-Comp, Inc; 1999.
Untalan PB, Keeney SE, Rivera A, Goldman AS. The Effect of Holder Pasteurization on Cytokine Levels in Donor Human Milk [dissertation/master's thesis]. Presented at PAS 2007, Toronto: University of Texas Medical Branch, Galveston, TX; 2007.
Further Reading
Keywords
necrotizing enterocolitis, NEC, inflammation of the intestinal tissues, enteral feeding, sepsis, feeding intolerance, delayed gastric emptying, abdominal wall erythema, hematochezia, apnea, decreased peripheral perfusion, cardiovascular collapse, bleeding diathesis, hyponatremia, consumption coagulopathy, metabolic acidosis, thrombocytopenia, leukopenia, leukocytosis, neutropenia, oligofructose, Staphylococcus aureus, Escherichia coli, intestinal ischemia, maternal hypertension, preeclampsia, cocaine exposure, patent ductus arteriosus, congenital heart disease, splanchnic ischemia, perinatal asphyxia, thromboembolic events, nosocomial infections, cholestasis, direct hyperbilirubinemia, strictures, hyperalimentation hepatitis, cow's milk protein–induced enterocolitis, glucose-6-phosphate dehydrogenase deficiency, birth asphyxia, respiratory distress, abnormal fetal growth pattern, anemia of prematurity
