Lukić Stefanstefanlukic@gmail.com

Uvod Nekrotični Enterokolitis (NEC) je najčešća životno

ugrožavajuća bolest gastrointestinalnog sistemaneonatusa i karakteriše se varijabilnim stepenomnekroze mukoze ili celog zida creva.

NEC je bolest nepoznate etiologije

Epidemiologija SRBIJA – nepoznata epidemiologija Oko 2500 slučajeva godišnje u SAD, 20-28 % ne

prežive1

90% preterminska novorođenčad, 10% terminska2

1-5% sve dece primljene u NIN razvija NEC2

24-27 g.n. VS 27-31 g.n. incidenca 6.6% vs 2.6%3

(P<0.001) 47-14% dece u grupi veoma niske TM oboli od NEC1-3

1.Young C, Sharma R, Handfield M, Mai V, Neu J. Biomarkers for Infants at Risk for Necrotizing Enterocolitis: Clues to Prevention? Pediatric Research. 2009;65:91R-97R.2. Schnabl K-L. Necrotizing enterocolitis: A multifactorial disease with no cure. World Journal of Gastroenterology. 2008;14:2142.3. Luig M, Lui K. Epidemiology of necrotizing enterocolitis--Part II: Risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health. 2005;41(4):174-179.

ID#: 856 Description: Gross pathology of neonatal necrotizing enterocolitis.Alimentary tract of infant showing intestinal necrosis, pneumatosis intestinalis, and perforation site (arrow). Autopsy.Content Providers(s): CDC/Dr. Edwin P. Ewing, Jr. Creation Date: 1972

Epelman M, Daneman A, Navarro OM, et al. Necrotizing Enterocolitis: Review of State-of-the-Art Imaging Findings with Pathologic Correlation.

Radiographics. 2007;27:285-305.

Etiologija Sigurno: Mala porođajna masa, prematuritet, ishrana

formulom, perinatalna asfiksija1-6

Verovatno: Prethodne infekcije, hiposekrecija HCl u želucu i upotreba H2 blokatora, upotreba mehaničke ventilacije, crna rasa i profilaktička upotreba antibiotske terapija duže od 5 dana (neonatusi ispod 1000g) 1-6

1. Piazza A, Stroll B. Neonatal Necrotizing Enterocolitis (NEC). In: Kliegman R, ed. Nelson textbook of pediatrics. 18th E ed. Philadelphia :: Saunders Elsevier,; 2007. 2. Neu J, Walker WA. Necrotizing Enterocolitis. N Engl J Med. 2011;364(3):255-264.3. Schnabl K-L. Necrotizing enterocolitis: A multifactorial disease with no cure. World Journal of Gastroenterology. 2008;14:2142.4. Luig M, Lui K. Epidemiology of necrotizing enterocolitis--Part II: Risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health. 2005;41(4):174-179.5. Carter BM, Holditch-Davis D. Risk factors for necrotizing enterocolitis in preterm infants: how race, gender, and health status contribute. Adv Neonatal Care. 2008;8(5):285-290.6. Cotten CM, Taylor S, Stoll B, et al. Prolonged Duration of Initial Empirical Antibiotic Treatment Is Associated With Increased Rates of Necrotizing

Enterocolitis and Death for Extremely Low Birth Weight Infants. Pediatrics. 2009;123:58-66.

Etiologija Klasične Mikrobiološke tehnike ne otkrivaju 80%

enteričke flore 1

Cum hoc ergo propter hoc Vs Koch Bifidobacter-Lactobacillus Vs Enterobacteriae 2,3

1.Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635-1638.2. Claud EC. Neonatal Necrotizing Enterocolitis -Inflammation and Intestinal Immaturity. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents). 2009;8:248-2593. Lawrence G, Bates J, Gaul A. Pathogenesis of neonatal necrotising enterocolitis. Lancet.1982;1(8264):137–139.

EtiologijaEscherichia coli Klebsiella Clostridium perfringens

Clostridium difficile Clostridium butyricum Clostridium neonatale

Cronobacter sakazakii Pseudomonasaeruginosa

Staphylococcusepidermidis

Coronavirus Rotavirus Coxsackie B2

Adenovirus Torovirus Echovirus 22

Tabela 1 – Mikroorganizmi optuženi za izazivanje NEC-a 1,2,3,4,5

1.Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308(5728):1635-1638.2. Claud EC. Neonatal Necrotizing Enterocolitis -Inflammation and Intestinal Immaturity. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents). 2009;8:248-2593. Lawrence G, Bates J, Gaul A. Pathogenesis of neonatal necrotising enterocolitis. Lancet.1982;1(8264):137–1394.Piazza A, Stroll B. Neonatal Necrotizing Enterocolitis (NEC). In: Kliegman R, ed. Nelson textbook of pediatrics. 18th E ed. Philadelphia :: Saunders Elsevier,; 2007. 5. Neu J, Walker WA. Necrotizing Enterocolitis. N Engl J Med. 2011;364(3):255-264.

Intestinalna nezrelost:

Prematuritet

Smanjena digestivna

sposobnostSmanjen motilitet

Smanjena regulacijacirkulacije

Smanjena barijerna funkcija

Nezreo imunitet

NECHipoksično ishemična

povredaAbnormalna bakterijska

kolonizacija

Ishrana mlečnom formulom

Patogeneza

Patogeneza Nf-Kb LPS TLR4 Il-8 IFN-y ET1 NO PAF

1. Cetin S, Leaphart CL, Li J, et al. Nitric oxide inhibits enterocyte migration through activation of RhoA-GTPase in a SHP-2-dependent manner. American Journal of Physiology - Gastrointestinal and Liver Physiology. 2007;292(5):G1347 -G1358.

Nitrotyrosine

Patogeneza Leaphart CL, Cavallo J, Gribar SC, et al. A Critical Role

for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair. The Journal of Immunology. 2007;179(7):4808 -4820.

1. Claud EC. Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. The FASEB Journal. 2001;15:1398-1403.

Prezentacija Veća gestaciona starost – ranija prezentacije, niža

gestaciona starost - kasnija prezentacija 1,2,3

GIT tetrada: povraćanje, odbijanje hrane, distenzija abdomena i krv u stolici 1,2,3

Sistemski znaci i simptomi: apnea, bradikardija, poremećaj svesti, letargija, hipotenzija, Kusmaul-ovo disanje (metabolička acidoza) 1,2,3

1. Piazza A, Stroll B. Neonatal Necrotizing Enterocolitis (NEC). In: Kliegman R, ed. Nelson textbook of pediatrics. 18th E ed. Philadelphia :: Saunders Elsevier,; 2007. 2. Neu J, Walker WA. Necrotizing Enterocolitis. N Engl J Med. 2011;364(3):255-264.3. Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann. Surg.

1978;187(1):1-7.

1. Anon. MIcrobiologySpring2010 - Necrotizing Enterocolitis. Available at: http://microbiologyspring2010.wikispaces.com/Necrotizing+Enterocolitis. Accessed November 21, 2011.

Prezentacija Nativna radiografija, CT, MRI abdomena: slobodan

vazduh, pneumatosis intestinalis, portalni gas (1,2,3)

Laboratorija: povišen CRP, prokalcitonin, sniženje albumina, elevaciju jetrinih enzima... (1,2,3)

DIK : Protrombinsko vreme (PT), parcijalno tromboplastinsko vreme (PTT) i fibrin degradacioni produkti (FDP) (1,2,3)

Specifični markeri samo u istraživačke svrhe: IL-8, H2 izdisajni test, PAF, TNFa, uEGF, sEGF 2,4,5

1.Piazza A, Stroll B. Neonatal Necrotizing Enterocolitis (NEC). In: Kliegman R, ed. Nelson textbook of pediatrics. 18th E ed. Philadelphia :: Saunders Elsevier,; 2007. 2. Neu J, Walker WA. Necrotizing Enterocolitis. N Engl J Med. 2011;364(3):255-264.3. Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann. Surg.1978;187(1):1-7.4. Schnabl K-L. Necrotizing enterocolitis: A multifactorial disease with no cure. World Journal of Gastroenterology. 2008;14:21425. Claud EC. Neonatal Necrotizing Enterocolitis -Inflammation and Intestinal Immaturity. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents). 2009;8:248-259.

1. Sebastià C, Quiroga S, Espin E, et al. Portomesenteric Vein Gas: Pathologic Mechanisms, CT Findings, and Prognosis1. Radiographics. 2000;20(5):1213 -1224.

1. Anon. Welcome to LearningRadiology - portal, venous, gas, air, biliary, system, pneumatosis, intestinalis, pneumobilia, necrosis, death, bowel, wall, ischemia, ischemic, mesenteric, arterial, causes, CT, US, plain, film, infarction, best, radiology, podcast, teaching, website, web, site, image, imaging, radiology, xray, x-ray, student, medical, video, vodcast, jpg, jpeg. Available at: http://www.learningradiology.com/archives2009/COW%20360-Portal%20venous%20gas/portalgascorrect.htm. Accessed November 21, 2011.

1. Anon. LearningRadiology.com - necrotizing enterocolitis, NEC. Available at: http://www.learningradiology.com/archives05/COW%20156-NEC/neccorrect.htm. Accessed November 21, 2011.

Dijagnostika Ne čekati potvrdu dijagnoze već otpočeti terapiju.

(1,2,3) Koristiti Bell kriterijume (1,2,3)

1.Piazza A, Stroll B. Neonatal Necrotizing Enterocolitis (NEC). In: Kliegman R, ed. Nelson textbook of pediatrics. 18th E ed. Philadelphia :: Saunders Elsevier,; 2007. 2. Neu J, Walker WA. Necrotizing Enterocolitis. N Engl J Med. 2011;364(3):255-264.3. Bell MJ, Ternberg JL, Feigin RD, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann. Surg.1978;187(1):1-7.

Stadijum Sistemski znaci Intestinalni znaci Radiološki znaci

IA (Sumnjiv) Nestabilnosttemperature, apnea,bradikardija, letargija

Otežano hranjenje,povraćanje, Poorfeeding, povraćanje,blaga abdominalnadistenzija

Normalno iliintestinalna dilatacija,blagi ileus

IB (Sumnjiv) Isto kao iznad Isto kao iznad + svežakrv u stolici

Isto kao iznad

IIA (Dokazan) Isto kao iznad Isto kao iznad Iodsutna peristaltika +abdominalni bol napalpaciju

Intestinalna dilatacija,ileus, pneumatosisintestinalis

IIB (Dokazan) Iznad + metaboličkaacidoza +trombocitopenia

Isto kao iznad + jačiabdominalni bol

Isto kao iznad + gas uportalnoj veni + ascites

IIIA (Razvijen) Iznad + hipotenzija,respiratorna acidoza,neutropenia

Isto kao iznad +peritonitis, izrazitadistenzija abdomena

Isto kao iznad + većakoličina ascitesa

IIIB (Razvijen) Isto kao iznad Isto kao iznad Iznad +pneumoperitoneum

Terapija Preporuke se baziraju na “konsenzusu stručnjaka” Ne postoje korektni klinički trajali Prva mera mora biti uvođenje Nil per os i izolacija

pacijenta uz primeni higijenskig mera pri kontaktu 1,2

Upotreba antibiotika sa dejstvom protiv G+, G- i anaeroba je opravdana 1,2

Potrebna je energična borba protiv šoka, korekcija acidoze, nadoknada tečnosti i dekompresija plasiranjem NG sonde 1,2

DIK je stalni pratioc pa treba pratiti PT, PTT i FDP i energično se boriti protiv DIK-a 1,2

1.Piazza A, Stroll B. Neonatal Necrotizing Enterocolitis (NEC). In: Kliegman R, ed. Nelson textbook of pediatrics. 18th E ed. Philadelphia :: Saunders Elsevier,; 2007. 2. Neu J, Walker WA. Necrotizing Enterocolitis. N Engl J Med. 2011;364(3):255-264

Terapija Serijske radiografije se preporučuju ali ne postoje

dokazi da potvrde ili opovrgnu 1,2

Perforacija i prisustvo bakterija u ascitu indikacija za hiruršku terapiju 1,2

Ne preporučuje se peritonealna drenaža već “klasična” laparotomija sa eventualnom resekcijom 1,2,3

1.Piazza A, Stroll B. Neonatal Necrotizing Enterocolitis (NEC). In: Kliegman R, ed. Nelson textbook of pediatrics. 18th E ed. Philadelphia :: Saunders Elsevier,; 2007. 2. Neu J, Walker WA. Necrotizing Enterocolitis. N Engl J Med. 2011;364(3):255-2643. Blakely ML, Tyson JE, Lally KP, et al. Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated intestinal perforation in extremely low birth weight infants: outcomes through 18 months adjusted age. Pediatrics. 2006;117(4):e680-687

Prevencija

Tabela 2 – Preporuke po Neau i Walker-u (1)

2. Neu J, Walker WA. Necrotizing Enterocolitis. N Engl J Med. 2011;364(3):255-264

Prevencija

1.in 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 2008;122:693-7002. Bin-Nun A, Bromker R, Wilschanski M, et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight infants. J Pediatr2005;147:192-196