NECNEC

Nawaf Al-DajaniNawaf Al-Dajani

Disclosure Disclosure

NECNEC Definition Early history Epidemiology Pathophysiology Presentation Prevention Treatment

Definition Early history Epidemiology Pathophysiology Presentation Prevention Treatment

Definition Definition

Acute inflammatory disease process affecting GI tract of neonates.

Usually ass’ necrosis of affected part.

Unpredictable course.

Acute inflammatory disease process affecting GI tract of neonates.

Usually ass’ necrosis of affected part.

Unpredictable course.

History History

Not known prior 1950’s First described by Schmid &

Quaiser. Well recognized entity 1960-1970. High MR Idiopathic GI perforations.

Not known prior 1950’s First described by Schmid &

Quaiser. Well recognized entity 1960-1970. High MR Idiopathic GI perforations.

Epidemiology Epidemiology Affect 1-5% all NICU admissions. Up to 10% of prem. less than 1.5 kg. 10% occur in term neonates M=F Black > Onset inversely related to GA. 10* in infant who have been fed. Clusters may occur.

Affect 1-5% all NICU admissions. Up to 10% of prem. less than 1.5 kg. 10% occur in term neonates M=F Black > Onset inversely related to GA. 10* in infant who have been fed. Clusters may occur.

Pathophysiology Pathophysiology

NECROTIZING ENTEROCOLITISNECROTIZING

ENTEROCOLITIS Pathophysiology:

Pathophysiology:

UNKNOWN CAUSE…….

Preemies gut is differentPreemies gut is different

Inadequate IgAScanty T lymphocytesLack of adequate antibody responseHigher membrane permeabilityLower motility and emptyingMucin blanket Tight junction are deficient

PRIMARY INFECTIOUS AGENTS

Bacteria, Bacterial toxin, Fungus

CIRCULATORY INSTABILITY

Hypoxic-ischemic event Polycythemia

MUCOSAL INJURY

ENTERAL FEEDINGS

Hypertonic formula or medication, H2 gas production,

Endotoxin production

INFLAMMATORY MEDIATORS

Inflammatory cells (macrophage) Platelet activating factor (PAF) Tumor necrosis factor (TNF) Leukotriene C4, Interleukin 1; 6

Preemies gut Preemies gut

PMNM0

Immune cellsPAFTNF

Luminal flow

Mucin Inflammation

VasoconstrictionTissue permeability

Risk factorsRisk factors

IUGR RDS Cyanotic heart disease Blood Tx Gastroschisis

IUGR RDS Cyanotic heart disease Blood Tx Gastroschisis

Temperature instabilityApneaEpisodes of Bradycardias & DesaturationLethargyAcidosisThrombocytopenia Shock

Feeding intoleranceIncreased gastric residualsAbdominal distentionOccult blood/ HematocheziaPeritonitisDiscoloration of abdominal wallAbdominal mass

Presentation

Bell’s Stages

I. Suspected diseaseMild systemic signs (apnea, bradycardia, temperature instability)Mild intestinal signs (abdominal distention, gastric residuals, bloody stools)Nonspecific or normal radiological signs

II. Definite diseaseMild to moderate systemic illnessAdditional intestinal signs (absent bowel sounds, abdominal tenderness)Specific radiologic signs (pneumatosis intestinalis or portal venous air)Laboratory changes (metabolic acidosis, thrombocytopenia)

III. Advanced diseaseSevere systemic illness (hypotension)Additional intestinal signs (marked abdominal distention, peritonitis)Severe radiologic signs (pneumoperitoneum)Additional laboratory changes (metabolic and respiratory acidosis, DIC)

Radiographs Radiographs

Management “same same” Management “same same” Medical emergency: Cardiorespiratory support: Ventilation “avoid CPAP” Fluid +/- inotrops Invasive monitoring Maintain Sat. higher than acceptable for

GA. NPO, NG (IMS)

Medical emergency: Cardiorespiratory support: Ventilation “avoid CPAP” Fluid +/- inotrops Invasive monitoring Maintain Sat. higher than acceptable for

GA. NPO, NG (IMS)

CBC Coags Lytes & BG SWU Antibiotics Maintain Hg > 12 Maintain BS

CBC Coags Lytes & BG SWU Antibiotics Maintain Hg > 12 Maintain BS

Strict ins/out Surgical referral Serial X-ray is not advisable routinely Have a wise mind & strong arms to

push the surgeons when approriate Be aggressive when u have to B Optimize nutritional support

Strict ins/out Surgical referral Serial X-ray is not advisable routinely Have a wise mind & strong arms to

push the surgeons when approriate Be aggressive when u have to B Optimize nutritional support

Closely follow hg/plt/BG May need to use diuretics early Serial clinical assessment Follow SWU Watch for opportunistic infections Counsel the family about prognosis

Closely follow hg/plt/BG May need to use diuretics early Serial clinical assessment Follow SWU Watch for opportunistic infections Counsel the family about prognosis

Surgical approach???Surgical approach???

Free air remain the strongest indication??

Newer trend to use peritoneal drain initially!!

Free air remain the strongest indication??

Newer trend to use peritoneal drain initially!!Moss et al NEJM,2006

Rees et al, Ann Surg,2008

Emil et al, Eurp J Surg, 2008

Complication Complication

Death 20-40% (early/late) Bleeding Stricture Short bowel syndrome (27%) Abscess Neurodevelopmental delay

Death 20-40% (early/late) Bleeding Stricture Short bowel syndrome (27%) Abscess Neurodevelopmental delay

Breast Milk

Immuno-globulin

Antibiotics

Probiotics

Slow feeding

StandardizedFeedingprotocols

PreventionOf NEC

Prevention Prevention

Breast milk: Most “only” known safe preventive

measure. 926 pts in prospective study. 6-10* risk of NEC in formula vs BM 3 times if formula + BM

Breast milk: Most “only” known safe preventive

measure. 926 pts in prospective study. 6-10* risk of NEC in formula vs BM 3 times if formula + BM

Lucas & Cole, Lancet, 1990Schanler, 1999McGuire, 2003

Contin…Contin… Feeding strategies: One large trial showed benefit of slow

rate @ 20 cc/kg/d, stopped early.

Many other trials & meta-analyses; showed no difference

Kennedy,2003 Kamitsuka, 2000

Feeding strategies: One large trial showed benefit of slow

rate @ 20 cc/kg/d, stopped early.

Many other trials & meta-analyses; showed no difference

Kennedy,2003 Kamitsuka, 2000

Berseth et al, 2003

Feeding protocol: Modest evidence that protocol for

feeding may reduce the risk of NEC

Trophic feeds:

Feeding protocol: Modest evidence that protocol for

feeding may reduce the risk of NEC

Trophic feeds:

Schurr & Perkins, Cochrane review

Tyson & Kennedy

Feed #

1 2 3 4 5 6 7 8 9 10 11 12

1 1 1 1 1 1 1 1.5 1.5 1.5 1.5 1.5 1.5

2 2 2 2 2 2 2 2.5 2.5 2.5 2.5 2.5 2.5

Day 3 3 3 3 3 3 3 3.5 3.5 3.5 3.5 3.5 3.5

4 4 4 4 4 4 4 4.5 4.5 4.5 4.5 4.5 4.5

5 5 5 5 5 5 5 5.5 5.5 5.5 6 6 6

6 6 6.5 6.5 6.5 6.5 7 7 7 7 7.5 7.5 7.5

Example of guidelines

Probiotics: for life Dani et al, no difference Other, Lin, Bin-Nun 2 meta-analyses, Al-faleh, Deshpande Showed decrease NEC-II & Mortality Many unanswered Qs?

Probiotics: for life Dani et al, no difference Other, Lin, Bin-Nun 2 meta-analyses, Al-faleh, Deshpande Showed decrease NEC-II & Mortality Many unanswered Qs?

Probiotics

Amino acid supp: Arginine supp, Amin, 2002 Enteral glutamine, Vaughn, 2003

Immunoglobulin: IgG/IgA po, no difference, Foster, 2004 IVIG, Faranoff, 1994

Amino acid supp: Arginine supp, Amin, 2002 Enteral glutamine, Vaughn, 2003

Immunoglobulin: IgG/IgA po, no difference, Foster, 2004 IVIG, Faranoff, 1994

Antibiotics: Oral Gentamicin: Meta-analysis of 5 studies showed

efficacy in reduction of NEC (Bury, 2004)

Erythromycin PO/IV; Ng et al

Antibiotics: Oral Gentamicin: Meta-analysis of 5 studies showed

efficacy in reduction of NEC (Bury, 2004)

Erythromycin PO/IV; Ng et al

H2 hitamine blocker: Usage of H2 blocker ass’ NEC Guillet 2006

• Indomethacin****

H2 hitamine blocker: Usage of H2 blocker ass’ NEC Guillet 2006

• Indomethacin****

Conclusion Conclusion A disease of medical progress Encourage EBM Control multiple pregnancy

“induced” Standardized feeding protocol Probiotics looming around Medical care 1st & scalpel

A disease of medical progress Encourage EBM Control multiple pregnancy

“induced” Standardized feeding protocol Probiotics looming around Medical care 1st & scalpel