Accuracy of the American College of Surgeons Minimum Criteria for Full Trauma Team Activation for Children.

OBJECTIVE: Pediatric trauma centers use reports from emergency medical service providers to determine if a trauma team should be sent to the emergency department to prepare to care for the patient. Little scientific evidence supports the current American College of Surgeons (ACS) indicators for trauma team activation. The objective of this study was to determine the accuracy of the ACS Minimum Criteria for Full Trauma Team Activation for children as well as the accuracy of the modified criteria used at the local sites for trauma activation. METHODS: Emergency medical service providers who transported an injured child aged 15 years or younger to a pediatric trauma center in 1 of 3 cities were interviewed after emergency department arrival. Emergency medical service providers were asked if each of the activation indicators were present based on their evaluation. The need for full trauma team activation was determined through a medical record review using a published criterion standard definition. Undertriage and overtriage rates and positive likelihood ratios (+LRs) were calculated. RESULTS: Emergency medical service provider interviews were conducted and outcome data were obtained for 9483 children. There were 202 (2.1%) cases that met the criterion standard for need for trauma team activation. Based on the ACS Minimum Criteria, 299 (3.0%) cases should have received a trauma activation. The ACS Minimum Criteria undertriaged 44.1% and overtriaged 20% (+LR, 27.9; 95% confidence interval, 23.1-33.7). Based on the actual activation status using the local criteria, 238 cases received a full trauma activation, 45% were undertriaged, and 1.4% were overtriaged (+LR, 40.1; 95% confidence interval, 32.4-49.7). There was 97% agreement between the ACS Minimum Criteria and the actual local activation status at the receiving institution. CONCLUSIONS: The ACS Minimum Criteria for Full Trauma Team Activation for children have a high rate of undertriage. Changes that individual institutions have made to improve the accuracy of activations at their institutions seem to have had a limited effect on decreasing undertriage.

Imaging of Right Lower Quadrant Pain in Children and Adolescents: AJR Expert Panel Narrative Review.

Right lower quadrant (RLQ) pain is a common clinical presentation in children, and accurate clinical diagnosis remains challenging given that this nonspecific presentation is associated with numerous surgical and nonsurgical conditions. The broad differential diagnosis varies by patient age and sex. Important considerations in the selection of a diagnostic imaging strategy include the sequencing, performance, and cost of tests. This article provides a comprehensive narrative review of the diagnostic imaging of RLQ pain in children and adolescents, including a discussion of the complementary roles of ultrasound, CT, and MRI; description of key imaging findings based on available evidence; and presentation of salient differential diagnoses. Subspecialized pediatric emergency medicine and surgical perspectives are also provided as further clinical insight into this common, but often challenging, scenario. Finally, the current status of imaging of RLQ pain in children and adolescents is summarized on the basis of expert consensus.

Lipofibromatosis-like neural tumors: Report of a case and review of 73 reported cases.

Lipofibromatosis-like neural tumors (LPF-NTs) are a recently discovered group of spindle cell tumors defined by the presence of a lipofibromatosis-like pattern, CD34 and/or S100 reactivity, and frequent neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangements. As new cases emerge, the spectrum of features observed in LPF-NTs continues to evolve. Here we describe the case of an 11-year-old with LPF-NT with a dermatofibrosarcoma protuberans-like honeycomb pattern, CD34 and S100 co-expression, and an NTRK1 rearrangement. We also review the clinical and molecular features of the 73 cases of LPF-NT previously described in the literature.

Utilizing Near-Infrared Spectroscopy to Identify Pediatric Trauma Patients Needing Lifesaving Interventions: A Prospective Study.

OBJECTIVES: The aim of this study was to prospectively investigate the role of near-infrared spectroscopy (NIRS) in identifying pediatric trauma patients who required lifesaving interventions (LSIs). METHODS: Prospective cohort study of children age 0 to 18 years who activated the trauma team response between August 15, 2017, and February 12, 2019, at a large, urban pediatric emergency department (ED).The relationship between the lowest somatic NIRS saturation and the need for LSIs (based on published consensus definition) was investigated. Categorical variables were analyzed by χ 2 test, and continuous variables were analyzed by Student t test. RESULTS: A total of 148 pediatric trauma patients had somatic NIRS monitoring and met the inclusion criteria. Overall, 65.5% were male with a mean ± SD age of 10.9 ± 6.0 years. Injuries included 67.6% blunt trauma and 28.4% penetrating trauma with mortality of 3.4% (n = 5). Overall, the median lowest somatic NIRS value was 72% (interquartile range, 58%-88%; range, 15%-95%), and 43.9% of patients had a somatic NIRS value <70%. The median somatic NIRS duration recorded was 11 minutes (interquartile range, 7-17 minutes; range, 1-105 minutes). Overall, 36.5% of patients required a LSI including 53 who required a lifesaving procedure, 17 required blood products, and 17 required vasopressors. Among procedures, requiring a thoracostomy was significant.Pediatric trauma patients with a somatic NIRS value <70% had a significantly increased odds of requiring a LSI (odds ratio, 2.11; 95% confidence interval, 1.07-4.20). Somatic NIRS values <70% had a sensitivity and specificity of 56% and 63%, respectively. CONCLUSIONS: Pediatric trauma patients with somatic NIRS values <70% within 30 minutes of ED arrival have an increased odds of requiring LSIs. Among LSIs, pediatric trauma patients requiring thoracostomy was significant. The role of NIRS in incrementally improving the identification of critically injured children in the ED and prehospital setting should be evaluated in larger prospective multicenter studies.

Utilizing Near-Infrared Spectroscopy (NIRS) to Identify Pediatric Trauma Patients Needing Lifesaving Interventions (LSIs): A Retrospective Study.

OBJECTIVES: The aim of this study was to investigate the role of near-infrared spectroscopy (NIRS) in identifying pediatric trauma patients who required lifesaving interventions (LSIs). METHODS: Retrospective chart review of children age 0 to 18 years who activated the trauma team response between January 1, 2015 and August 14, 2017, at a large, urban pediatric emergency department. The lowest somatic NIRS saturation and the need for LSIs (based on published consensus definition) were abstracted from the chart. χ2 and descriptive statistics were used for analysis. RESULTS: The charts of 84 pediatric trauma patients were reviewed. Overall, 80% were boys with a mean age of 10.4 years (SD, 6.2 years). Injuries included 56% blunt trauma and 36% penetrating trauma with mortality of 10.7% (n = 9). Overall, the median lowest NIRS value was 67% (interquartile range, 51-80%; range, 15%-95%) and 54.8% of the patients had a NIRS value less than 70%. The median somatic NIRS duration recorded was 12 minutes (interquartile range, 6-17 minutes; range, 1-59 minutes). Overall, 50% of patients required a LSI, including 39 who required a lifesaving procedure, 11 required blood products, and 14 required vasopressors. Pediatric trauma patients with NIRS less than 70% had a significantly increased odds of requiring a LSI (odds ratio, 2.67; 95% confidence interval, 1.10-6.47). NIRS less than 70% had a sensitivity and specificity of 67% and 57% respectively. CONCLUSIONS: Pediatric trauma patients with somatic NIRS less than 70% within 30 minutes of emergency department arrival are associated with the need for LSIs. Continuous NIRS monitoring in the pediatric trauma population should be evaluated prospectively.

Does Mechanism of Injury Predict Trauma Center Need for Children?

OBJECTIVE: To determine if the Mechanism of Injury Criteria of the Field Triage Decision Scheme (FTDS) are accurate for identifying children who need the resources of a trauma center. METHODS: EMS providers transporting any injured child ≤15 years, regardless of severity, to a pediatric trauma center in 3 midsized communities over 3 years were interviewed. Data collected through the interview included EMS observed physiologic condition, suspected anatomic injuries, and mechanism. Patients were then followed to determine if they needed the resources of a trauma center by reviewing their medical record after hospital discharge. Patients were considered to need a trauma center if they received an intervention included in a previously published consensus definition. Data were analyzed with descriptive statistics including positive likelihood ratios (+LR) and 95% confidence intervals (95%CI). RESULTS: 9,483 provider interviews were conducted and linked to hospital outcome data. Of those, 230 (2.4%) met the consensus definition for needing a trauma center. 1,572 enrolled patients were excluded from further analysis because they met the Physiologic or Anatomic Criteria of the FTDS. Of the remaining 7,911 cases, 62 met the consensus definition for needing a trauma center (TC). Taken as a whole, the Mechanism of Injury Criteria of the FTDS identified 14 of the remaining 62 children who needed the resources of a trauma center for a 77% under-triage rate. The mechanisms sustained were 36% fall (16 needed TC), 28% motor vehicle crash (MVC) (20 needed TC), 7% struck by a vehicle (10 needed TC), <1% motorcycle crash (none needed TC), and 29% had a mechanism not included in the FTDS (16 needed TC). Of those who sustained a mechanisms not listed in the FTDS, the most common mechanisms were sport related injuries not including falls (24% of 2,283 cases with a mechanism not included) and assault (13%). Among those who fell from a height greater than 10 feet, 4 needed a TC (+LR 5.9; 95%CI 2.8-12.6). Among those in a MVC, 41 were reported to have been ejected and none needed a TC, while 31 had reported meeting the intrusion criteria and 0 needed a TC. There were 32 reported as having a death in the same vehicle, and 2 needed a TC (+LR 7.42; 95%CI: 1.90-29.0). CONCLUSION: Over a quarter of the children who needed the resources of a trauma center were not identified using the Physiologic or Anatomic Criteria of the Field Triage Decision Scheme. The Mechanism of Injury Criteria did not apply to over a quarter of the mechanisms experienced by children transported by EMS for injury. Use of the Mechanism Criteria did not greatly enhance identification of children who need a trauma center. More work is needed to improve the tool used to assist EMS providers in the identification of children who need the resources of a trauma center.

COVID-19 pre-procedural testing strategy and early outcomes at a large tertiary care children's hospital.

PURPOSE: With the emergence of the coronavirus disease-2019 (COVID-19) pandemic, institutions were tasked with developing individualized pre-procedural testing strategies that allowed for re-initiation of elective procedures within national and state guidelines. This report describes the experience of a single US children's hospital (Children's Wisconsin, CW) in developing a universal pre-procedural COVID-19 testing protocol and reports early outcomes. METHODS: The CW pre-procedural COVID-19 response began with the creation of a multi-disciplinary taskforce that sought to develop a strategy for universal pre-procedural COVID-19 testing which (1) maximized patient safety, (2) prevented in-hospital viral transmission, (3) conserved resources, and (4) allowed for resumption of procedural care within institutional capacity. RESULTS: Of 11,209 general anesthetics performed at CW from March 16, 2020 to October 31, 2020, 11,150 patients (99.5%) underwent pre-procedural COVID-19 testing. Overall, 1.4% of pre-procedural patients tested positive for COVID-19. By June 2020, CW was operating at near-normal procedural volume and there were no documented cases of in-hospital viral transmission. Only 0.5% of procedures were performed under augmented COVID-19 precautions (negative pressure environment and highest-level personal protective equipment). CONCLUSION: CW successfully developed a multi-disciplinary pre-procedural COVID-19 testing protocol that enabled resumption of near-normal procedural volume within three months while limiting in-hospital viral transmission and resource use.

Single-Immunoglobulin Interleukin-1-Related Receptor regulates vulnerability to TLR4-mediated necrotizing enterocolitis in a mouse model.

BackgroundThe mechanisms underlying aberrant activation of intestinal Toll-like receptor 4 (TLR4) signaling in necrotizing enterocolitis (NEC) remain unclear. In this study, we examined the role of single-immunoglobulin interleukin-1 receptor-related molecule (SIGIRR), an inhibitor of TLR signaling, in modulating experimental NEC vulnerability in mice.MethodsExperimental NEC was induced in neonatal wild-type and SIGIRR-/- mice using hypoxia, formula-feeding, and lipopolysaccharide administration. Intestinal TLR canonical signaling, inflammation, apoptosis, and severity of experimental NEC were examined at baseline and after NEC induction in mice.ResultsSIGIRR is developmentally regulated in the neonatal intestine with a restricted expression after birth and a gradual increase by day 8. At baseline, breast-fed SIGIRR-/- mouse pups exhibited low-grade inflammation and TLR pathway activation compared with SIGIRR+/+ pups. With experimental NEC, SIGIRR-/- mice had significantly more intestinal interleukin (IL)-1ß, KC (mouse homolog to IL-8), intercellular adhesion molecule-1 (ICAM-1), and interferon-beta (IFN-ß) expression in association with the amplified TLR pathway activation. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, cleaved caspase 3, and severity of intestinal injury with NEC were worse in SIGIRR-/- mice in comparison with SIGIRR+/+ mice.ConclusionSIGIRR is a negative regulator of TLR4 signaling in the developing intestine, and its insufficiency results in native intestinal TLR hyper-responsiveness conducive to the development of severe experimental NEC in mice.

Role of intestinal Hsp70 in barrier maintenance: contribution of milk to the induction of Hsp70.2.

BACKGROUND: Necrotizing enterocolitis (NEC) is a gastrointestinal disease of complex etiology resulting in devastating systemic inflammation and often death in premature newborns. We previously demonstrated that formula feeding inhibits ileal expression of heat shock protein-70 (Hsp70), a critical stress protein within the intestine. Barrier function for the premature intestine is critical. We sought to determine whether reduced Hsp70 protein expression increases neonatal intestinal permeability. METHODS: Young adult mouse colon cells (YAMC) were utilized to evaluate barrier function as well as intestine from Hsp70-/- pups (KO). Sections of intestine were analyzed by Western blot, immunohistochemistry, and real time PCR. YAMC cells were sub-lethally heated or treated with expressed milk (EM) to induce Hsp70. RESULTS: Immunostaining demonstrates co-localized Hsp70 and tight junction protein zona occludens-1 (ZO-1), suggesting physical interaction to protect tight junction function. The permeability of YAMC monolayers increases following oxidant injury and is partially blocked by Hsp70 induction either by prior heat stress or EM. RT-PCR analysis demonstrated that the Hsp70 isoforms, 70.1 and 70.3, predominate in WT pup; however, Hsp70.2 predominates in the KO pups. While Hsp70 is present in WT milk, it is not present in KO EM. Hsp70 associates with ZO-1 to maintain epithelial barrier function. CONCLUSION: Both induction of Hsp70 and exposure to EM prevent stress-induced increased permeability. Hsp70.2 is present in both WT and KO neonatal intestine, suggesting a crucial role in epithelial integrity. Induction of the Hsp70.2 isoform appears to be mediated by mother's milk. These results suggest that mother's milk feeding modulates Hsp70.2 expression and could attenuate injury leading to NEC. LEVEL OF EVIDENCE: Level III.

Intestinal alkaline phosphatase: a summary of its role in clinical disease.

Over the past few years, there is increasing evidence implicating a novel role for Intestinal Alkaline Phosphatase (IAP) in mitigating inflammatory mediated disorders. IAP is an endogenous protein expressed by the intestinal epithelium that is believed to play a vital role in maintaining gut homeostasis. Loss of IAP expression or function is associated with increased intestinal inflammation, dysbiosis, bacterial translocation and subsequently systemic inflammation. As these events are a cornerstone of the pathophysiology of many diseases relevant to surgeons, we sought to review recent research in both animal and humans on IAP's physiologic function, mechanisms of action and current research in specific surgical diseases.

Intestinal alkaline phosphatase to treat necrotizing enterocolitis.

BACKGROUND: Intestinal alkaline phosphatase (IAP) activity is decreased in necrotizing enterocolitis (NEC), and IAP supplementation prevents NEC development. It is not known if IAP given after NEC onset can reverse the course of the disease. We hypothesized that enteral IAP given after NEC induction would not reverse intestinal injury. MATERIALS AND METHODS: NEC was induced in Sprague-Dawley pups by delivery preterm followed by formula feedings with lipopolysaccharide (LPS) and hypoxia exposure and continued up to 4 d. IAP was added to feeds on day 2 until being sacrificed on day 4. NEC severity was scored based on hematoxylin and eosin-stained terminal ileum sections, and AP activity was measured using a colorimetric assay. IAP and interleukin-6 expression were measured using real time polymerase chain reaction. RESULTS: NEC pups' alkaline phosphatase (AP) activity was decreased to 0.18 U/mg compared with controls of 0.57 U/mg (P < 0.01). Discontinuation of LPS and hypoxia after 2 d increased AP activity to 0.36 U/mg (P < 0.01). IAP supplementation in matched groups did not impact total AP activity or expression. Discontinuing LPS and hypoxia after NEC onset improved intestinal injury scores to 1.14 compared with continued stressors, score 2.25 (P < 0.01). IAP supplementation decreased interleukin-6 expression two-fold (P < 0.05), though did not reverse NEC intestinal damage (P = 0.5). CONCLUSIONS: This is the first work to demonstrate that removing the source of NEC improves intestinal damage and increases AP activity. When used as a rescue treatment, IAP decreased intestinal inflammation though did not impact injury making it likely that IAP is best used preventatively to those neonates at risk.

Intestinal alkaline phosphatase prevents the systemic inflammatory response associated with necrotizing enterocolitis.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with an incidence of 0.5-2.4 cases per 1000 live births and a mortality rate between 10% and 50%. Neonates affected by NEC develop a septic injury that is associated with increased risk of neurological impairment due to intraventricular bleeding and chronic lung disease. Intestinal alkaline phosphatase (IAP) is an endogenous protein that has been shown to inactivate the endotoxin lipopolysaccharide (LPS), and has recently been used successfully as an adjunct to treat sepsis in adult patients. We tested the hypothesis that systemic, exogenous IAP will mitigate the inflammatory response as measured by serum levels of proinflammatory cytokines in a rat model of NEC. METHODS: Newborn Sprague-Dawley rats were divided into groups. Control pups were dam fed. NEC was induced by feeding formula containing LPS and exposure to intermittent hypoxia. NEC pups were given intraperitoneal injections of 4 or 40 glycine units (U) of IAP or placebo twice daily. Intestine and serum was collected for cytokine analysis as well as measurement of alkaline phosphatase activity. RESULTS: Systemic IAP administration significantly increased serum alkaline phosphatase activity in a dose- and time-dependent fashion. The proinflammatory cytokines tumor necrosis factor α, interleukin 6, and interleukin 1ß were significantly increased in NEC rats versus controls on days 2 and 3. Importantly, treatment with 40 U systemic IAP decreased these proinflammatory cytokines back to near-control levels. CONCLUSIONS: Systemic IAP administration appears effective in mitigating the systemic inflammatory response associated with NEC, and may prove to be a valuable adjunctive treatment for NEC.

Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model.

BACKGROUND: Supplementation of intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, decreases the severity of necrotizing enterocolitis (NEC)-associated intestinal injury and permeability. We hypothesized that IAP administration is protective in a dose-dependent manner of the inflammatory response in a neonatal rat model. MATERIALS AND METHODS: Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day of life 3. Control pups were vaginally delivered and dam fed. Preterm pups were delivered via cesarean section and exposed to intermittent hypoxia and formula feeds containing lipopolysaccharide (NEC) with and without IAP. Three different standardized doses were administered to a group of pups treated with 40, 4, and 0.4U/kg of bovine IAP (NEC+IAP40, IAP4, or IAP0.4U). Reverse transcription-real-time polymerase chain reaction (RT-PCR) for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α on liver and lung tissues and serum cytokine analysis for interleukin (IL)-1ß, IL-6, IL-10, and TNF-α were performed. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests, expressed as mean±standard error of the mean and P≤0.05 considered significant. RESULTS: Levels of cytokines IL-1ß, IL-6, and TNF-α increased significantly in NEC versus control, returning to control levels with increasing doses of supplemental enteral IAP. Hepatic and pulmonary TNF-α and iNOS messenger ribonucleic acid expressions increased in NEC, and the remaining elevated despite IAP supplementation. CONCLUSIONS: Proinflammatory cytokine expression is increased systemically with intestinal NEC injury. Administration of IAP significantly reduces systemic proinflammatory cytokine expression in a dose-dependent manner. Early supplemental enteral IAP may reduce NEC-related injury and be useful for reducing effects caused by a proinflammatory cascade.

Same-day discharge after appendectomy for uncomplicated appendicitis in children: Potential barriers to increased utilization.

BACKGROUND: Utilization of same-day discharge (SDD) after appendectomy for uncomplicated appendicitis (UA) was closely examined to explore potential barriers to greater use of SDD. METHODS: Children (≤18 years) who underwent appendectomy for UA between 2015 and 2019 at a tertiary care children's hospital were reviewed. Associations with SDD were evaluated using multivariable regression models. RESULTS: Among 973 children, SDD was less frequently utilized after appendectomy performed between 12pm and 5pm (aOR 0.14, p < 0.001) and after 5pm (aOR 0.01, p < 0.001) compared to before 12pm. SDD utilization was also less frequent in those from lower resource neighborhoods (adjusted odds ratio [aOR] 0.90 per decile increase in Area Deprivation Index, p = 0.04), females (aOR 0.53, p = 0.005), and patients residing 30-60 min away (aOR 0.56, p = 0.04) compared to <30 min away. CONCLUSIONS: SDD utilization was primarily impacted by operative timing and socioeconomic and travel factors, focuses for quality improvement efforts to further increase utilization of SDD.

Endothelial microparticles induce inflammation in acute lung injury.

BACKGROUND: Previously, we have shown that endothelial microparticles (EMPs) injected into mice induce acute lung injury (ALI) [1]. In this study, we hypothesize that EMPs induce ALI by initiating cytokine release in the lung, leading to recruitment and activation of neutrophils. MATERIALS AND METHODS: C57BL/6J male mice (8-10 wk old) were intravenously injected with EMPs (200,000/mL), LPS (2 mg/kg), or both. Bronchoalveolar lavage (BAL) and serum levels of IL-1ß and TNF-α were analyzed by enzyme-linked immunoassay (ELISA). Morphometric analysis was performed on H and E stained lung sections. Myeloperoxidase (MPO) levels were determined via an enzymatic assay and immunofluorescence of stained sections. RESULTS: EMPs led to significantly increased pulmonary and systemic IL-1ß and TNF-α levels, which correlated with increased neutrophil recruitment to the lung. MPO levels in the lungs were increased significantly following injection of EMPs or LPS, compared to PBS. In mice treated with EMPs and LPS either simultaneously or successively, the cytokine and MPO levels were significantly increased over that of either treatment alone. CONCLUSION: EMPs contribute to lung injury through the initiation of a cytokine cascade that increases recruitment of neutrophils and subsequent release of MPO. Furthermore, treatment of mice with both EMPs and LPS induced greater lung injury than either treatment alone, suggesting that EMPs prime the lung for increased injury by other pathogens. Therapies aimed at reducing or blocking EMPs may be a useful strategy for attenuating lung injury.

Outcomes of gastrostomy placement with and without concomitant tracheostomy among ventilator dependent children.

INTRODUCTION: Simultaneous gastrostomy tube (GT) and tracheostomy placement in young children offers potential benefit in limiting anesthetic exposure, but it is unknown whether combining these procedures introduces additional morbidity. This study compared outcomes after combined GT and tracheostomy placement versus GT placement alone among similar ventilator-dependent patients. METHODS: Ventilator-dependent children <2-years-old who underwent GT placement alone (MV-GT), simultaneous GT and tracheostomy placement (GT+T), and GT placement alone with a pre-existing tracheostomy (T-GT) were identified using 2012-2018 NSQIP-Pediatric Participant User Files. Multiple logistic regression models were used to compare outcomes while adjusting for other group differences. RESULTS: Among 1100 children, 351 underwent MV-GT, 494 GT+T, and 255 T-GT. Major complications occurred in 23.6%, 17.0%, and 14.5% of the respective groups (p = 0.01). Major complications with GT+T were similar to T-GT (adjusted odds ratio [aOR]=1.19, 95%CI:0.78-1.83, p = 0.4) and lower than MV-GT (aOR=0.67, 95%CI:0.47-0.95, p = 0.02). Severe complications including mortality, cardiac arrest, and stroke were similar between the three groups (p = 0.8). CONCLUSIONS: Children <2-years-old undergoing GT+T did not experience higher post-operative complications compared to children undergoing T-GT or MV-GT. Utilizing GT+T to limit anesthetic exposure may be reasonable within this high-risk population. TYPE OF STUDY: Treatment Study LEVEL OF EVIDENCE: Level III.

The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis.

BACKGROUND: Enterocytes produce intestinal alkaline phosphatase (iAP), which detoxifies lipopolysaccharide (LPS), a mediator in necrotizing enterocolitis (NEC) pathogenesis. We hypothesize that aberrant expression or function of iAP contributes to the pathogenesis of NEC. MATERIALS AND METHODS: Newborn Sprague Dawley rat pups were divided into three main groups. Control pups were breast fed, while two groups were exposed to intermittent hypoxia, LPS, and formula feeding for 4 d to induce NEC. Bovine iAP, with and without the presence of LPS, was administered orally to one of the NEC groups. The intestine was harvested and used to detect alkaline phosphatase (AP) activity and protein expression. Terminal ileum sections were used to grade intestinal injury and stained for AP. Comparisons were made with adult rat duodenum. RESULTS: Compared with adult rats, control pups expressed significantly less AP protein but had 2-fold higher AP activity. NEC pup AP activity was significantly decreased compared to controls (P < or = 0.05), which paralleled both the AP protein expression and immunofluorescence assay results. Following iAP administration, immunofluorescence, protein expression, and activity of AP were significantly increased compared with NEC pups without iAP supplementation. All NEC pups had intestinal injury grades > or = 2 on a 4-point scale, while control and iAP-treated pups had grades < 0.25 (P < 0.001). CONCLUSIONS: Enteral administration of iAP to rat pups with experimental NEC increased AP activity levels to that of controls, and appears to protect the intestine. This opens up a new area of study in NEC pathophysiology as well as a potential novel treatment strategy to prevent the development of NEC.

Mesenteric nitric oxide and superoxide production in experimental necrotizing enterocolitis.

BACKGROUND: A proposed mechanism of intestinal injury in necrotizing enterocolitis (NEC) involves vascular dysfunction through altered nitric oxide synthase (NOS) activity. We hypothesize that this dysfunction results in an imbalance in nitric oxide (*NO) and superoxide (O(2)(*-)) production by the intestinal vascular endothelium, which contributes to the intestinal injury seen in NEC. MATERIALS AND METHODS: Neonatal rat pups were divided into two groups. Control pups were breast fed and housed with their mother. Experimental NEC pups were housed separately and either exposed to formula feeding and 5% to 10% hypoxia alone (FF/H) or with the addition of lipopolysaccharide (FF/H/LPS). Mesenteries from each group were analyzed for *NO and O(2)(*-) production with and without NOS inhibition by N(G)-monomethyl-L-arginine (L-NMMA). Western blot analysis for eNOS, phosphorylated eNOS (phospho-eNOS), and inducible NOS (iNOS) was performed, and each terminal ileum was graded for intestinal injury by histology. RESULTS: Histology revealed mild intestinal injury (grade 1-2 on a 4-point scale) in the FF/H group and severe injury (grade 3-4) in the FF/H/LPS group. The FF/H cohort had significantly increased *NO and lower O(2)(*-) production, while the FF/H/LPS group shifted to significantly decreased *NO and increased O(2)(*-) production. L-NMMA inhibited >50% of O(2)(*-) production in all three groups but only inhibited *NO production in control and FF/H pups. Western blot analysis revealed increased levels of phospho-eNOS in FF/H pups and increased iNOS in FF/H/LPS pups. CONCLUSIONS: This study demonstrates in the progression of NEC, intestinal ischemia is associated with a shift from *NO to O(2)(*-) production, which is NOS-dependent. Potentially greater injury results from impaired vasodilatation and over-production of reactive oxygen species.

Reducing opioid utilization after appendectomy: A lesson in implementation of a multidisciplinary quality improvement project.

BACKGROUND: Perioperative care after appendectomy may be the first exposure to opioids for many children. A quality improvement project was implemented to assess current practice of prescribing pain medications after a laparoscopic appendectomy to decrease unnecessary opioid use via simple, targeted steps. METHODS: Three measures were implemented in patients undergoing laparoscopic appendectomy for acute appendicitis: (1) ice packs to incision in postanesthesia care unit, (2) standard pain scores within 30 minutes of admission to ward postoperatively, and (3) standardized postoperative order set minimizing opioid utilization and limited number of opioids prescribed at discharge. Pre- and postimplementation data were compared with the primary outcome variable: opioid utilization during the postoperative period. RESULTS: There were no statistically significant differences in age or gender between the 814 preimplementation and 263 postimplementation patients. Postimplementation compliance is 66.9% for icepacks, 88% for pain scores, and 94.7% for postoperative order set. There were statistically significant decreases in intravenous and enteral opioids administered, number of opioid doses prescribed at discharge, and patients discharged with an opioid prescription. CONCLUSION: By using a multidisciplinary assessment of current state, culture, and management of parental, patient, and nursing expectations, our institution was able to reduce overall opioid consumption.