Surgical decision making in NEC
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1 Surgical decision making in NEC (the role of ultrasound) Nigel Hall Associate Professor of Paediatric Surgery University of Southampton Consultant Paediatric and Neonatal Surgeon Southampton Children s Hospital SIGNEC Meeting, London, September 2016
2 Challenging current indications and timing of surgery in NEC
3 Overview NEC epidemiology and outcomes Current practice Smarter surgery Time critical surgery
4 NEC is not going away (Ahle et al: Pediatrics 2013)
5 NEC mortality (UK data) Year ELBW (p=0.0005) infant (p<0.0001) NEC (p<0.0001) (p=ns) Mortality rate (deaths/1000 live births)
6 Surgical NEC mortality 1990s vs 2000s (Fasoli et al: JPS 1999; Thyoka et al: Eur J Pediatr Surg 2012)
7 Neurodevelopmental Impairment N0 NEC vs. NEC Chacko et al ns Hintz et al Holmsgaard et al ns Sonntag et al Tobiansky et al ns Walsh et al ns Combined 1.3 < RR p (Rees et al: Arch Dis Child 2009)
8 NEC outcomes Incidence is increasing Despite improvements in neonatal care and an overall decrease in infant mortality, mortality from NEC has not changed In survivors, NEC is increasingly recognised as a risk factor for neurodevelopmental impairment Current approach to treatment of NEC, including surgery, is inadequate
9 Surgery for NEC 30-40% of infants required surgery
10 There are few (any?) other surgical conditions where we wait for the endpoint of the disease process to become evident before offering surgical intervention
11 Surgery for NEC 30-40% of infants required surgery How many would benefit from surgery? Would babies have improved survival, or get better quicker, or have improved long term outcomes if they had surgery earlier?
12 Smarter surgery? Can we limit adverse effects of severe intestinal disease earlier? Can we identify infants with critical intestinal ischaemia or necrosis earlier? Should we operate earlier? May improve survival May reduce gastrointestinal consequences May reduce neurological injury
13 Why do surgeons operate on babies with NEC?
14 Indications for laparotomy in NEC UK surgeon survey Universally accepted Respondents Perforation 75% Failure of medical treatment 71% More controversial Fixed intestinal loop 39% Abdominal mass 36% Portal venous gas 8% Thrombocytopenia 3% (Rees et al: Arch Dis Child 2005)
15 Why don t surgeons operate on babies with NEC? Concern of doing harm Can be difficult to identify those who need it
16 Cause of death in NEC n= had surgery 66 died (Thyoka et al: Eur J Pediatr Surg 2012)
17 How to identify those who would benefit.. Operate on all? Attempt to identify those with significant intestinal disease earlier - significant intestinal ischaemia or necrosis
18 How to identify intestinal ischaemia? Laparotomy / Laparoscopy Imaging plain radiographs usually unhelpful ultrasound Biochemical markers lactate non-specific intestine specific biomarkers Near infra-red spectroscopy
19 Biomarkers of intestinal ischaemia Candidate biomarkers Intestinal Fatty Acid Binding Protein (ifabp) mucosal marker Smooth muscle actin (SMA) full thickness? Claudin family tight junction proteins IL-8 less gut specific but may be useful Some known to be raised in NEC vs controls with sepsis
20 i-fabp Plasma Urine (Ng et al Ann Surg 2013; Evenett et al JPS 2010)
21 i-fabp surgical vs non-surgical NEC (Ng et al Ann Surg 2013; Thujls et al Ann Surg 2010)
22 IL-8 (Benkoe et al: JPS 2014)
23 IL-8 correlates with extent of disease Focal vs Multifocal vs Pan-intestinal But presence of ischaemia or necrosis not investigated (Benkoe et al JPS 2012)
24 Current barriers to using biomarkers Existing studies - small numbers Most have distinguished NEC and sepsis vs controls Surgical vs non-surgical NEC not optimum comparison Normal data reference range unknown Can they be used clinically? Are they valid markers of condition of intestine?
25 INTestinal ischaemia Early REecognition STudy Aims to correlate biomarker concentrations with findings at laparotomy to generate normal range of biomarkers in healthy control population Prelude to secondary study to determine if using biomarkers is effective
26 Can ultrasound help identify babies who would benefit from surgery? Attactive tool readily available non-invasive, no ionising radiation cheap repeatable BUT user dependent requires interested radiologist
27 Ultrasound in NEC Limited literature Pneumatosis intestinalis Portal venous gas Free intra-peritoneal gas All visible on US US more sensitive for these than plain radiography
28 Normal neonatal bowel US Epelman et al Radiographics 2007
29 Pneumatosis intetsinalis
30 Gas within lumen or bowel? Epelman et al, Radiographics 2007
31 Additional benefits of US over AXR Free fluid Bowel wall characteristics Dynamic evaluation Peristalsis Blood flow
32 US to define necrotic bowel Patterns of blood flow normal hyperaemic absent Features of bowel wall thick thin peristalsis Faingold et al, Radiology 2005
33 Patterns of hyperaemia
34 Patterns of hyperaemia
35 Absent flow
36 US findings in infants with NEC Absent flow on US: 100% sensitivity for necrotic bowel 95% specificity
37
38 Using ultrasound to guide surgical treatment Prospective, 26 infants with Bell stage II or III NEC none had pneumoperitoneum At least one abdominal US Surgery based on clinical and imaging findings Comparison of US and surgical findings
39 Ultrasound Findings Anechoic free fluid Free fluid with echoes Focal echogenic fluid collection Portal venous gas Increased wall echogenicity Bowel wall thickening Bowel wall thinning Intramural gas Increased perfusion Decreased perfusion Absent perfusion Decreased peristalsis Suspected bowel necrosis on basis of US
40 Ultrasound Findings No. of Patients Anechoic free fluid 10 Free fluid with echoes 6 Focal echogenic fluid collection 3 Portal venous gas 5 Increased wall echogenicity 5 Bowel wall thickening 20 Bowel wall thinning 2 Intramural gas 16 Increased perfusion 7 Decreased perfusion 7 Absent perfusion 5 Decreased peristalsis 10 Suspected bowel necrosis on basis of US 5
41 B A C
42 Comparison of US and surgical findings Evidence of necrosis Positive Negative US diagnosis of necrosis Positive 4 1 Negative 0 21 Sensitivity = 100% Specificity = 95.4% (Yikilmaz et al: PSI 2014)
43 US as an indication for surgery Accurately identified infants with established NEC and necrotic bowel Provided additional information to plain radiography Informed surgical decision making Needs: replicating, larger numbers, prove generalisability
44 Timing of surgery Neurological injury in NEC likely mediated by inflammatory pathways Prolonged inflammation greater neurological damage IL-8 during NEC significantly associated with abnormal development at 2 years Further justification for earlier surgery Once decision made, operate immediately (Lodha et al Acta Paediatr 2010)
45 In conclusion.. Need to improve outcomes from NEC Consider whether current surgical indication appropriate Gather evidence to inform surgical decision making Subsequently important to monitor benefit
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