Clare M. Rees

Peritoneal drainage or laparotomy for neonatal bowel perforation? A randomized controlled trial.

Objective:To determine whether primary peritoneal drainage improves survival and outcome of extremely low birth weight (ELBW) infants with intestinal perforation. Summary Background Data:Optimal surgical management of ELBW infants with intestinal perforation is unknown. Methods:An international multicenter randomized controlled trial was performed between 2002 and 2006. Inclusion criteria were birthweight ≤1000 g and pneumoperitoneum on x-ray (necrotizing enterocolitis or isolated perforation). Patients were randomized to peritoneal drain or laparotomy, minimizing differences in weight, gestation, ventilation, inotropes, platelets, country, and on-site surgical facilities. Patients randomized to drain were allowed to have a delayed laparotomy after at least 12 hours of no clinical improvement. Results:Sixty-nine patients were randomized (35 drain, 34 laparotomy); 1 subsequently withdrew consent. Six-month survival was 18/35 (51.4%) with a drain and 21/33 (63.6%) with laparotomy (P = 0.3; difference 12% 95% CI, −11, 34%). Cox regression analysis showed no significant difference between groups (hazard ratio for primary drain 1.6; P = 0.3; 95% CI, 0.7–3.4). Delayed laparotomy was performed in 26/35 (74%) patients after a median of 2.5 days (range, 0.4–21) and did not improve 6-month survival compared with primary laparotomy (relative risk of mortality 1.4; P = 0.4; 95% CI, 0.6–3.4). Drain was effective as a definitive treatment in only 4/35 (11%) surviving neonates, the rest either had a delayed laparotomy or died. Conclusions:Seventy-four percent of neonates treated with primary peritoneal drainage required delayed laparotomy. There were no significant differences in outcomes between the 2 randomization groups. Primary peritoneal drainage is ineffective as either a temporising measure or definitive treatment. If a drain is inserted, a timely “rescue” laparotomy should be considered. Trial registration number ISRCTN18282954; http://isrctn.org/

National prospective surveillance study of necrotizing enterocolitis in neonatal intensive care units.

PURPOSE There is scant epidemiological data on necrotizing enterocolitis (NEC), so we conducted a national study to characterize prevalence, surgical management, and mortality. METHODS A prospective cross-sectional survey was performed in the United Kingdom requesting data from 158 level 2 and 3 neonatal intensive care units (NICUs) during 2 winter and 2 summer months in 2005 to 2006; 51% of questionnaires were returned. Results are given as percentage with 95% confidence intervals. RESULTS (1) Period prevalence: 211 infants were diagnosed with NEC (45% Bells stage I, 21% stage II, and 33% stage III) from a total of 10,946 NICU admissions, with a period prevalence of 2% (1.7-2.2). In infants less than 1000 g birth weight, the prevalence was 14% (12-16), and in less than 26 weeks of gestation, 14% (11-17). Prevalence decreased significantly with increasing birth weight (P < .0001) and increasing gestation (P < .0001). (2) SURGERY: 66 infants received surgical procedures; peritoneal drain in 13 (followed by laparotomy in 8) and in 53, laparotomy alone. (3) Mortality: 27 infants died with NEC of a total 283 deaths, thus, accounting for 9.5% of NICU mortality. Eight (30%) infants with NEC died without surgery. CONCLUSIONS Prevalence of NEC in the United Kingdom is high and comparable to published series in other countries from the 1990s. There may be a hidden mortality in patients who do not receive surgery.

Trends in infant mortality from necrotising enterocolitis in England and Wales and the USA

Necrotising enterocolitis (NEC) is a devastating disease that affects up to 5% of infants in neonatal units and overall affects 0.5–5/1000 live births1 (33/1000 very-low-birthweight (VLBW) infants2). Mortality remains high at 35%.3 We hypothesised that improvements in neonatal care would reduce NEC mortality. National population registries of births and deaths for England and Wales and the USA were consulted, and data were extracted from 1999 to 2005. Data extracted for each year, based on linked registrations of births and deaths, included numbers of live births, births stratified by birth weight, infant deaths from NEC (main cause of death coded by ICD-9/ICD-10), and infant deaths linked to birth weight. USA data were available to 2004. Infant mortality was calculated as the …

Current research in necrotizing enterocolitis

Despite decades of research on necrotizing enterocolitis, we still do not fully understand the pathogenesis of the disease, how to prevent or how to treat the disease. However, as a result of recent significant advances in the microbiology, molecular biology, and cell biology of the intestine of premature infants and infants with necrotizing enterocolitis, there is some hope that research into this devastating disease will yield some important translation into improved outcomes.

Current Research on the Epidemiology, Pathogenesis, and Management of Necrotizing Enterocolitis

Despite decades of research on necrotizing enterocolitis, we still do not fully understand the pathogenesis of the disease, or how to prevent or how to treat it. However, as a result of recent significant advances in the microbiology, molecular biology, and cell biology of the intestine of preterm infants and infants with necrotizing enterocolitis, there is some hope that research into this devastating disease will yield some important translation into effective prevention, more rapid diagnosis, and novel therapies.

Is there a benefit of peritoneal drainage for necrotizing enterocolitis in newborn infants

Primary peritoneal drainage in infants with perforated necrotizing enterocolitis (NEC) has been used for many years [1-3]. Pediatric surgeons have viewed peritoneal drainage as a definitive treatment in some patients [3] but also as a temporizing measure, facilitating stabilization of very sick infants for a subsequent laparotomy before or after transfer to a pediatric surgical center [1,2]. Two multicenter randomized controlled trials comparing survival after primary peritoneal drainage or primary laparotomy have recently been published [4,5] Neither trial reached the recruitment target nor showed a significant benefit from drain or laparotomy. A meta-analysis of these 2 trials indicates no clear benefit from either treatment [4]. A third randomized controlled trial has been initiated in the United States (ClinicalTrials.gov Identifier: NCT01029353) with the primary outcome of death or neurodevelopmental impairment at 18 to 22 months of corrected age. Unless this current trial shows a dramatically different result from the others, it would seem unlikely that peritoneal drainage has a role in the future as a definitive treatment in NEC. The value of peritoneal drainage as a temporizing measure is less clear. The trial protocol of Moss et al [5] did not encourage early laparotomy following drain placement in patients with persistent metabolic acidosis, hemodynamic instability, and respiratory failure (although it did allow it). Consequently, only 9% of drain patients had a rescue laparotomy, and the trial of Moss et al was therefore mainly a trial of peritoneal drain as a definitive treatment [5]. In contrast, in the trial of Rees et al [4], 74% of the patients randomized to a drain required rescue laparotomy for clinical deterioration after 2.5 days (range, 0.4-21 days). Importantly, only 4 patients survived with a drain as definitive treatment [4]. Rees et al [4] concluded that primary peritoneal drainage is ineffective as either a temporizing measure or definitive treatment and that if a drain is inserted, a timely “rescue” laparotomy should be considered [4]. A survey of pediatric surgeons in the UK [6] showed that 95% used drains, with the indications being (i) stabilization

Probiotics for the prevention of surgical necrotising enterocolitis: systematic review and meta-analysis

Aim of the study Probiotic administration to preterm infants has the potential to prevent necrotising enterocolitis (NEC). Data from randomised controlled trials (RCT) are conflicting but meta-analyses seem to support this intervention. To date, these analyses have not focused on surgical NEC. We aimed to determine the effect of probiotic administration to preterm infants on prevention of surgical NEC. Methods A systematic review of RCTs of probiotic administration to preterm infants was performed. Studies were included if RCT outcomes included any of (1) Bell’s stage 3 NEC; (2) surgery for NEC; and (3) deaths attributable to NEC. Article selection and data extraction were performed independently by two authors; conflicts were adjudicated by a third author. Data were meta-analysed using Review Manager V.5.3. A random effects model was decided on a priori because of the heterogeneity of study design; data are risk ratio (RR) with 95% CI. Main results Thirty-five RCTs reported NEC as an outcome. Seventeen reported surgical NEC; all RCTs were included. A variety of probiotic products was administered across studies. Description of surgical NEC in most studies was poor. Only 6/16 specifically reported incidence of surgery for NEC, 12/17 Bell’s stage 3 and 13/17 NEC-associated mortality. Although there was a trend towards probiotic administration reducing stage 3 NEC, this was not significant (RR 0.74 (0.52–1.05), p=0.09). There was no effect of probiotics on the RR of surgery for NEC (RR 0.84 (0.56–1.25), p=0.38). Probiotics did, however, reduce the risk of NEC-associated mortality (RR 0.56 (0.34–0.93), p=0.03). Conclusion Despite 35 RCTs on probiotic prevention of NEC, evidence for prevention of surgical NEC is not strong, partly due to poor reporting. In studies included in this meta-analysis, probiotic administration was associated with a reduction in NEC-related mortality.

Morgagni hernia repair in children over two decades: Institutional experience, systematic review, and meta-analysis of 296 patients

BACKGROUND/PURPOSE Morgagni diaphragmatic hernia (MH) is rare. We report our experience based on routine patch use in MH repair to curb recurrence. A systematic review and meta-analysis were performed to study the recurrence and complications associated with minimally invasive surgery and the use of patch. METHODS We retrospectively reviewed all cases of MH who underwent first-time repair in 2012-2017 in our institution to determine recurrence and complication rate. A MEDLINE search related to minimally invasive surgery (MIS) and patch repair of MH was conducted for systematic review. Eligible articles published from 1997-2017 with follow-up data available were included. Primary outcomes measured were recurrence and complication. Meta-analysis to compare open versus MIS and primary versus patch repair in the MIS group were performed in comparative cohorts. Continuous data were presented as median (range), and statistical significance was P<0.05. RESULTS In our institution, 12 consecutive patients aged 17-month-old (22 days-7 years), underwent laparoscopic patch repair of MH, with one conversion to laparotomy. No recurrence or significant complication occurred over a follow-up period of 8 months (1-48 months). Thirty-six articles were included from literature review and were combined with the current series. All were retrospective case reports or series, of which 6 were comparative cohorts with both MIS and open repairs. A total of 296 patients from 37 series were ultimately used for analysis: 80 had open repair (4 patch) and 216 had MIS repair (32 patch), with a patch rate of 12%. There were 13 recurrences (4%): no difference between open and MIS repairs (4/80 vs 9/216, p=0.75); recurrence rate following primary repair was 13/260 (5%), but no recurrence occurred with 36 patch repairs. Meta-analysis showed no difference in recurrence between open and MIS repair (p=0.83), whereas patch repair was associated with 14% less recurrence compared with primary repair, although it did not reach statistical significance (p=0.12). There were 13 complications (5%): no difference between open and MIS repairs (5/80 vs 8/216, p=0.35). One small bowel obstruction occurred in a patient who had laparoscopic patch repair. CONCLUSION In MH, recurrence and complication rates are comparable between MIS and open repairs. Use of patch appeared to confer additional benefit in reducing recurrence. TYPE OF STUDY Systematic review LEVEL OF EVIDENCE: 3A.

Primary versus Staged Closure of Exomphalos Major: Cardiac Anomalies Do Not Affect Outcome

Aim The objective of the study is to describe management of exomphalos major and investigate the effect of congenital cardiac anomalies. Methods A single‐center retrospective review (with audit approval) was performed of neonates with exomphalos major (fascial defect ≥ 5cm ± liver herniation) between 2004 and 2014. Demographic and operative data were collected and outcomes compared between infants who had primary or staged closure. Data, median (range), were analyzed appropriately. Results A total of 22 patients were included, 20 with liver herniation and 1 with pentalogy of Cantrell. Gestational age was 38 (30‐40) weeks, birth weight 2.7 (1.4‐4.6) kg, and 13 (60%) were male. Two were managed conservatively due to severe comorbidities, 5 underwent primary closure, and 15 had application of Prolene (Ethicon Inc) mesh silo and serial reduction. Five died, including two managed conservatively, none primarily of the exomphalos. Survivors were followed up for 38 months (2‐71). Cardiac anomalies were present in 20 (91%) patients: 8 had minor and 12 major anomalies. Twelve (55%) patients had other anomalies. Primary closure was associated with shorter length of stay (13 vs. 85 days, p = 0.02), but infants had similar lengths of intensive care stay, duration of parenteral feeds, and time to full feeds. Infants with cardiac anomalies had shorter times to full closure (28 vs. 62 days, p = 0.03), but other outcomes were similar. Conclusion Infants whose defect can be closed primarily have a shorter length of stay, but other outcomes are similar. Infants with more significant abdominovisceral disproportion are managed with staged closure; the presence of major cardiac anomalies does not affect surgical outcome.

43 Superheroes and sepsis 6 – quality improvement and leadership to improve patient care

Background An introduction to QI methodology and how it has driven system-wide change in the management of sepsis at GOSH. We explore the role of leadership and a multi-disciplinary approach to embed a standardised response and escalation in children with sepsis. Through sharing the tools and methods of engagement with staff, patients and families, we explore how learning from this case study can be applied to implementing organisation-wide improvement initiatives. Objectives To share experience and learning to: 1. Apply Quality Improvement methodology to implementation of organisation-wide projects. 2. Understand the role of leadership in driving change across multi-disciplinary staff groups. 3. Take away ideas and methods for gaining widespread engagement in multidisciplinary teams to implement projects such as Sepsis 6. Involvement of patients and families: We have involved patients and families throughout the quality improvement project, shaping the training materials for staff and co-creating engagement materials for patients and families. Results 6 months post-project launch: – Increase from 45% – 64% Sepsis 6 bundles completed in 1 hour trust-wide (International bundle compliance average 47%) – No unnecessary increase in use of broad-spectrum antibiotics trust-wide. – Increased confidence and empowerment of staff to recognise and treat sepsis. – Innovative tools and technology designed to support the recognition of the Septic child. – 1000 multidisciplinary staff trained in sepsis recognition and management. – Dashboards created to enable local improvements in all areas. Conclusions Sepsis 6 has improved the recognition and management of paediatric inpatients in a tertiary hospital, with 65% of patients receiving the bundle within 1 hour. Leadership and quality improvement methodology are powerful tools to drive improvements in clinical services.