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Exploratory laparotomy in the management of confirmed necrotizing enterocolitis

Lakhoo, Kokilaa; Morgan, Robert D.a; Thakkar, Hemanshooa; Gupta, Amitb; Grant, Hugh W.a; Wagener, Silkea; Willetts, Ian E.a

doi: 10.1097/01.XPS.0000463166.88394.24
ORIGINAL ARTICLES
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Introduction Necrotizing enterocolitis (NEC) is a serious gastrointestinal emergency in newborn infants. Surgical management includes primary peritoneal drainage and/or exploratory laparotomy with bowel resection. This study describes obstetric complications, postnatal comorbidities, surgical care and intermediate postoperative outcomes in all infants with surgically and/or histologically proven NEC, who underwent exploratory laparotomy at our tertiary referral centre.

Materials and methods We conducted a retrospective review between January 2005 and December 2010. Results are reported as median (range). Fisher’s exact test (two tailed) was used for statistical analysis. A P-value of 0.05 or less was considered statistically significant.

Results A total of 71 infants had suspected (Bell’s stage≥1) NEC. Of them, 32 infants underwent laparotomy for stage 2–3 NEC. We excluded 11 infants with surgically and/or histologically proven spontaneous intestinal perforation. In the remaining 21 infants with confirmed NEC, median gestational age was 27 weeks (23–39 weeks) and median birth weight was 720 g (440–3510 g). NEC was suspected after a median 14 days of life (1–49 days of life). Fifteen patients (71%) were initially managed medically for a median total of 8 days (1–25 days). Laparotomy was performed after a median of 7 days (<1–35 days) from the suspicion of NEC. Eleven infants (52%) underwent bowel resection and enterostomy, four infants (19%) underwent bowel resection with primary anastomosis and one infant (5%) underwent proximal diverting jejunostomy. Bowel perforation was seen in seven patients (33%). Necrosis totalis was evident in five patients (24%). There were 12 postoperative deaths (57% mortality), and seven deaths (58%) occurred during the first 30 days. Infants who died were more likely to have had absent/reversed end-diastolic flow (n=5, P=0.64), intrauterine growth retardation (n=5, P=0.18) or a gestational birth weight between 501 and 750 g (n=9, P=0.08). In the surviving children (n=9), the median length of hospital stay was 134 days (87–190 days) and postoperative sequelae were frequently seen.

Conclusion The morbidity and mortality for infants with confirmed NEC who undergo laparotomy remain high in infants despite optimal medical and surgical care.

Departments of aPaediatric Surgery

bNeonatology, Oxford University Hospitals NHS Trust, Oxford, UK

Correspondence to Kokila Lakhoo, MD, Department of Paediatric Surgery, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK e-mail: kokila.lakhoo@ouh.nhs.uk

Received November 30, 2014

Accepted March 12, 2015

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Introduction

Necrotizing enterocolitis (NEC) is a serious gastrointestinal emergency in neonates, associated with significant morbidity and mortality 1. It primarily affects preterm infants and those with very low birth weight (VLBW – i.e., birth weight<1500 g) 2,3. Bell’s staging criteria is used to define the severity of NEC based on clinical, laboratory and radiographic signs. Patients can be classified with stage 1 (suspected), stage 2 (confirmed) or stage 3 (advanced) disease 4. Surgery is considered in children with Bell’s stage 2–3 NEC and includes primary peritoneal drainage (PPD) and/or exploratory laparotomy with bowel resection 5, although no consensus exists about the optimal intervention 6–8. At our institution, PPD is used to stabilize a patient before laparotomy, but not as a definitive treatment. The aims of exploratory laparotomy are to control intra-abdominal sepsis, remove necrotic bowel and preserve as much bowel length as possible 5. Resection of bowel necrosis is followed by either primary anastomosis or enterostomy.

This retrospective review outlines the obstetric complications, postnatal comorbidities, surgical care and postoperative outcomes in infants with surgically and/or histologically proven NEC at our tertiary referral centre between January 2005 and December 2010.

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Materials and methods

The institutional review board of the John Radcliffe Hospital, Oxford, approved this study. All neonates with clinical, laboratory and radiographic signs of Bell’s stage 2–3 NEC who underwent exploratory laparotomy at our institution between January 2005 and December 2010 were identified using the hospital database.

Patient demographics, obstetric complications, postnatal comorbidities, clinical, laboratory and radiographic signs of NEC, operative procedures, surgical findings and intermediate postoperative outcomes were reviewed using inpatient and outpatient records. The standardized electronic neonatal database was used to retrieve missing antenatal data. All infants with a surgically or histologically proven spontaneous intestinal perforation (SIP) were excluded from the study.

The following definitions are used throughout this study: for extreme prematurity, a gestation of less than 28 weeks; for intrauterine growth retardation (IUGR), an estimated foetal weight less than 10th centile for gestational age; for neonatal hypoglycaemia, a serum glucose of less than 2.5 mmol/l during the first 24 h of life; for severe thrombocytopenia, a platelet count less than 50×109/l; and for VLBW, a birth weight less than 1500 g. Grades 3 and 4 intraventricular haemorrhage (IVH) was diagnosed on the basis of cranial ultrasonography (US), with grade 3 IVH diagnosed if the ventricles were enlarged by the blood, and grade 4 if there was bleeding into the brain tissues around the ventricles 9. Results are reported as median (range). Statistical analysis involved the two-tailed Fisher’s exact test, with a P-value of 0.05 or less considered to indicate statistical significance.

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Results

A total of 71 infants had suspected (Bell’s stage≥1) NEC at our institution between January 2005 and December 2010. Of them, 32 underwent exploratory laparotomy. We excluded 11 patients who had surgically or histologically proven SIP, leaving 21 infants (30% of original cohort) with confirmed surgical NEC.

In the cohort of infants with surgical NEC, there were 12 boys (57%). The median gestational age was 27 weeks (23–39 weeks) and median birth weight was 720 g (440–3510 g). Sixteen neonates (76%) were classified as extremely premature and 19 (90%) infants had VLBW. There were six twin pregnancies, with only one set of twins in whom both infants were diagnosed with NEC stage 1 or higher. Fourteen patients (67%) were born through Caesarean section; of which, eight were emergency procedures. All obstetric complications are outlined in Table 1. The most common obstetric complications were absent or reversed end-diastolic flow [n=7 (33%)], pre-eclamptic toxaemia [n=7 (33%)] and IUGR [n=6 (29%)].

Table 1

Table 1

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Perinatal comorbidities

Median Apgar scores at 1 and 5 min were 6 (1–10) and 9 (3–10), respectively. Twenty infants (95%) had respiratory distress syndrome requiring mechanical ventilation on the first day of life. Neonatal hypoglycaemia was diagnosed in five babies (24%). Cranial US revealed grades 3 or 4 IVH in three infants (14%). Fourteen patients (67%) were diagnosed with patent ductus arteriosus, and four (19%) received indomethacin therapy. Severe thrombocytopenia was noted in six cases (29%) and disseminated intravascular coagulopathy occurred in two patients (10%). Sepsis was suspected initially in all cases. Eleven patients (52%) had positive blood cultures, including coagulase-negative Staphylococcus (n=9), Enterobacter cloacae (n=2) and Candida spp. (n=1). One infant had two or more microorganisms.

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Enteral feeding

Eighteen (86%) infants were started on enteral feeds before NEC was suspected. Enteral feeds were started after a median of 3 days of life (1–17 days of life) and consisted of breast milk (n=13) or formula milk (n=5).

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Necrotizing enterocolitis

NEC was suspected after a median of 14 days of life (1–49 days of life), with 81% of infants suspected to have NEC within 30 days of birth. A total of 21 patients (95%) presented with abdominal distension and six (29%) had rectal bleeding. Fifteen patients (71%) were treated conservatively with bowel rest, bowel decompression and broad-spectrum antibiotics. The medical treatment given to these patients lasted a median of 8 days (1–25 days). Seven patients (33%) received total parental nutrition preoperatively.

Indications for laparotomy included pneumoperitoneum, portal venous gas and/or pneumatosis intestinalis [n=15 (71%)], failed medical treatment [n=4 (19%)] or severe peritonitis [n=2 (10%)]. Failed medical treatment was defined as failure to demonstrate a clinical improvement despite resuscitation, gut rest and treatment with intravenous antibiotics. Four infants (19%) had PPD before exploratory laparotomy, and all these infants had VLBW. Exploratory laparotomy was performed after a median of 21 days of life (1–52 days of life) and 7 days (<1–35 days) after NEC was suspected. The surgical findings and operative procedures are outlined in Table 2. Eleven patients (52%) underwent bowel resection and enterostomy and four patients (19%) underwent a resection and primary anastomosis. One patient underwent a proximally diverting jejunostomy. Bowel perforation was found in seven patients (33%): four (19%) with a single perforation and three (14%) with multiple perforations. Necrosis totalis was evident in five neonates (24%) in whom care was subsequently withdrawn.

Table 2

Table 2

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Postoperative morbidity and mortality

Postoperative morbidities are outlined in Table 3. Two infants (10%) required planned relook laparotomy: both within 5 days of their initial laparotomy. In the first patient, more necrotic bowel (3 cm in the jejunum) was resected and additional enterostomies were formed. In the second patient, necrosis totalis was seen and care was withdrawn. Postoperative sepsis was confirmed in 11 patients (52%), and blood cultures were positive for coagulase-negative Staphylococcus (n=6), Klebsiella spp. (n=3), E. cloacae (n=2), Enterococcus faecalis (n=1) and Serratia marcescens (n=1). Three patients had two or more bacteria.

Table 3

Table 3

There were 12 postoperative deaths (57% mortality). Seven deaths occurred during the first 30 days postoperatively. Factors that correlated with higher mortality included absent or reversed end-diastolic flow (n=5), IUGR (n=5) or a gestational birth weight between 501 and 750 g (n=9) (Table 4), although none of these factors reached statistical significance (P>0.05); probably due to the small size of our cohort. In the infants who survived (n=9), the median length of hospital stay was 134 days (87–190 days). One patient was lost to follow-up.

Table 4

Table 4

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Discussion

Despite advances in neonatal intensive care, the surgical morbidity and mortality from NEC still remain a concern. Infants born prematurely and those of lower birth weights 2,3 are considered at risk. Term infants who develop NEC often have additional comorbidities such as congenital heart disease 10. In our study, most infants with surgical NEC had extreme prematurity or VLBW. Only one pregnancy reached term gestation, and this infant had no comorbidities.

Large population-based studies have evaluated perinatal risk factors for developing NEC, although limited data are available for infants requiring surgery 11–14. Guthrie et al.13 reported that mechanical ventilation on the first day of life and exposure to both glucocorticoids and indomethacin during the first week of life increased the risk for surgical NEC. The same authors found no significant association between birth weight or gestational age and the need for surgery. In our study, around 95% of neonates who required laparotomy were mechanically ventilated on the 1st day of life because of respiratory distress syndrome, but less than 20% of infants diagnosed with patent ductus arteriosus were treated with indomethacin before developing NEC. Our analysis also appears to show that most infants operated on had VLBW, with the majority weighing between 501 and 750 g at birth (P=0.08).

Studies have shown that up to 50% of infants with NEC require surgery 15. Our findings were similar to this, with 45% of patients with suspected stage 2–3 NEC taken to theatre. Overall, 30% had surgically or histologically proven NEC and 19% had NEC totalis at initial laparotomy. In all these patients NEC had been suspected within 24 h of surgery. It is not surprising that the most common reasons for surgery were suspected perforation or pneumatosis intestinalis; however, interestingly, 29% of patients developed severe thrombocytopenia, which has previously been linked to the severity of NEC 16,17.

In our study, laparotomy occurred following a median of 1 week after NEC was initially suspected. The majority of patients (76%) had focal NEC confined to the ileum and/or ascending colon (Table 1). Bowel perforations occurred infrequently (n=7) and were more likely to be single perforations (57%). Importantly, all perforations were confined to an area of necrotic bowel. Intestinal resection of the affected bowel and enterostomy formation were the mainstay of treatment, which was usually performed in neonates who needed rapid and effective surgical defunctioning.

It is widely accepted that infants with surgical NEC have higher morbidity and longer hospital stay compared with those treated nonsurgically 18,19. In our study, postoperative sequelae were frequently encountered, with the most common complication being sepsis from coagulase-negative Staphylococcus. Early complications such as metabolic acidosis and disseminated intravascular coagulopathy were rare; however intermediate sequelae such as intestinal stricture, short gut syndrome and neurodevelopmental delay were more frequently observed. In the surviving infants the median length of postoperative hospital stay exceeded 3 months. All affected neonates with suspected NEC were managed initially with gut rest, drainage of aspirates and intravenous antibiotics. However, despite maximal medical management and adequate resuscitation, a failure to demonstrate clinical improvement was considered an indication for surgery in our centre. Our findings further emphasize the delayed morbidity associated with surgical NEC and the importance of having a high threshold for surgical intervention in such cases.

In the UK, the number of deaths attributable to NEC has increased in recent years 7,20. It has been suggested that an increase in the number of births and an increase in the survival of preterm infants has lead to larger numbers of children at higher risk of developing NEC. In contrast, recent data from the US suggest that the mortality trend of NEC remains relatively constant 21. In our study the mortality rate of confirmed NEC was 57%. Interestingly, if the number of deaths for infants with SIP (n=0) is included in our analysis, the total mortality for babies with clinical, laboratory and/or radiographic signs of Bell’s stage 2–3 NEC who underwent laparotomy would be 38%. These results suggest that further research is needed to stratify infants on the basis of underlying intra-abdominal pathology to optimize surgical care.

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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