Risk Factors for Brain Injury in Newborns Treated with Extracorporeal Membrane Oxygenation.

OBJECTIVE: This study aimed to assess the association of clinical risk factors with severity of magnetic resonance imaging (MRI) brain injury in neonatal extracorporeal membrane oxygenation (ECMO) patients. STUDY DESIGN: This is a single-center retrospective study conducted at an outborn level IV neonatal intensive care unit in a free-standing academic children's hospital. Clinical and MRI data from neonates treated with ECMO between 2005 and 2015 were reviewed. MRI injury was graded by two radiologists according to a modified scoring system that assesses parenchymal injury, extra-axial hemorrhage, and cerebrospinal fluid spaces. MRI severity was classified as none (score = 0), mild/moderate (score = 1-13.5), and severe (score ≥ 14). The relationship between selected risk factors and MRI severity was assessed by Chi-square, analysis of variance, and Kruskal-Wallis tests where appropriate. Combinative predictive ability of significant risk factors was assessed by logistic regression analyses. RESULTS: MRI data were assessed in 81 neonates treated with ECMO. Veno-arterial (VA) patients had more severe injury compared with veno-venous patients. There was a trend toward less severe injury over time. After controlling for covariates, duration of ECMO remained significantly associated with brain injury, and the risk for severe injury was significantly increased in patients on ECMO beyond 210 hours. CONCLUSION: Risk for brain injury is increased with VA ECMO and with longer duration of ECMO. Improvements in care may be leading to decreasing incidence of brain injury in neonatal ECMO patients. KEY POINTS: · Veno-arterial ECMO is associated with more brain injury by MRI compared with veno-venous ECMO.. · Longer duration of ECMO is significantly associated with severe brain injury by MRI.. · Risk for neurologic injury may be decreasing over time with advances in neonatal ECMO..

Postnatal weight gain in preterm infants with severe bronchopulmonary dysplasia.

OBJECTIVES: To characterize postnatal growth failure (PGF), defined as weight < 10th percentile for postmenstrual age (PMA) in preterm (≤ 27 weeks' gestation) infants with severe bronchopulmonary dysplasia (sBPD) at specified time points during hospitalization, and to compare these in subgroups of infants who died/underwent tracheostomy and others. STUDY DESIGN: Retrospective review of data from the multicenter Children's Hospital Neonatal Database (CHND). RESULTS: Our cohort (n = 375) had a mean ± standard deviation gestation of 25 ± 1.2 weeks and birth weight of 744 ± 196 g. At birth, 20% of infants were small for gestational age (SGA); age at referral to the CHND neonatal intensive care unit (NICU) was 46 ± 50 days. PGF rates at admission and at 36, 40, 44, and 48 weeks' PMA were 33, 53, 67, 66, and 79% of infants, respectively. Tube feedings were administered to > 70% and parenteral nutrition to a third of infants between 36 and 44 weeks' PMA. At discharge, 34% of infants required tube feedings and 50% had PGF. A significantly greater (38 versus 17%) proportion of infants who died/underwent tracheostomy (n = 69) were SGA, compared with those who did not (n = 306; p < 0.01). CONCLUSIONS: Infants with sBPD commonly had progressive PGF during their NICU hospitalization. Fetal growth restriction may be a marker of adverse outcomes in this population.

Perioperative hypothermia in NICU infants: its occurrence and impact on infant outcomes.

Infants admitted to the neonatal intensive care unit (NICU) often require surgical intervention and maintaining normothermia perioperatively is a major concern. In our preliminary study of 31 normothermic infants undergoing operative procedures in the operating room (OR), 58% (N = 18) returned hypothermic while all 5 undergoing procedures in the NICU remained normothermic (P = .001). To describe perioperative thermal instability (temperatures lower than 36.0°C) and frequency of associated adverse events, support interventions, and diagnostic tests in infants undergoing operative procedures in the OR and the NICU. This prospective, case-control study included 108 infants admitted to the NICU who were sequentially scheduled for an operative procedure in the OR (50.93%; N = 55) or the NICU (49.07%; N = 53). Existing data from the medical record were collected about temperatures and frequency of adverse cardiovascular, respiratory, and metabolic events, associated support interventions, and diagnostic tests during the perioperative period. Analyses examined the relative risks and proportional differences in rates of hypothermia between the OR group and the NICU group and associated adverse events, support interventions, and diagnostic tests between hypothermic and normothermic infants. Hypothermia developed in 40% (N = 43) of infants during the perioperative period. The OR group had a higher rate of perioperative hypothermia (65.45%, N = 36; P < .001) and were 7 times more likely to develop perioperative hypothermia (P = .008) than the NICU group (13.21%, N = 7). Likewise, infants in the OR group were 10 times more likely to develop hypothermia during the intra- and postoperative periods than those in the NICU group (P = .001). The hypothermic group had significantly more respiratory adverse events (P = .025), were 6 times more likely to require thermoregulatory interventions (P < .001), 5 times more likely to require cardiac support interventions (P < .006), and 3 times more likely to require respiratory interventions (P = .02) than normothermic infants. Although infants undergoing operative procedures in the OR experienced significantly higher rates of hypothermia than those undergoing procedures in the NICU, both groups experienced unacceptable rates of clinical hypothermia. Hypothermic infants experienced more adverse events and required more support interventions during the intra- and postoperative periods than normothermic infants, thereby demonstrating the negative sequelae associated with thermal instability. As a result, a translational team of key stakeholders has been created to explore multifaceted strategies based on translation science to implement, embed, and sustain perioperative thermoregulation best practices for the infant, regardless of the operative setting.

The impact of ethnic population dynamics on neonatal ECMO outcomes: a single urban institutional study.

INTRODUCTION: Neonatal extracorporeal membrane oxygenation ECMO has been clinically used for the last 25 y. It has been an effective tool for both cardiac and non cardiac conditions. The impact of ethno-demographic changes on ECMO outcomes however remains unknown. We evaluated a single institution's experience with non cardiac neonatal ECMO over a 28-y period. METHODS: A retrospective review of all neonates undergoing noncardiac ECMO between the y 1984 and 2011 was conducted and stratified into year groups I, II, III (≤1990, 1991-2000, and ≥2001). Demographic, clinical, and outcome data were collected. The patient specifics, ECMO type, ECMO length, blood use, complications, and outcomes were analyzed. Univariate, bivariate, and multivariate analyses were then performed. RESULTS: Data was available for 827 patients. The number of African-American and Hispanic patients increased over the last 27 y (27.5% versus 45.0% and 3.3% versus 21.5%, year group I versus year group III, respectively). The proportion of congenital diaphragmatic hernia (CDH) patients by ethnicity also increased for African-Americans and Hispanics between the two year groups (22.0% to 33.0% and 4.9% to 33.0%, respectively). Similar pattern was noted for non-CDH diagnoses. Low birth weight, low APGAR scores, CDH, primary pulmonary hypertension, central nervous system hemorrhage, and ECMO were independent predictors of mortality. Ethnicity, in itself however, was not associated with mortality on adjusted analysis. CONCLUSION: More African-Americans and Hispanics have required ECMO over the years with a concurrent decrease in the number of Caucasians. While ethnicity was not an independent predictor of mortality, it appears to be a surrogate for fatal but sometime preventable diagnoses among minorities. Further investigations are needed to better delineate the reason behind this disparity.

Effect of a dedicated percutaneously inserted central catheter team on neonatal catheter-related bloodstream infection.

PURPOSE: To evaluate whether the establishment of a dedicated percutaneously inserted central catheter (PICC) team is associated with reduced risk of catheter-related bloodstream infection (CRBSI) in the neonatal intensive care unit. SUBJECTS: Participants were extremely low-birth-weight infants admitted to a level IIIC neonatal intensive care unit. DESIGN: A before- versus after-intervention study design was implemented. Intervention group participants were admitted after April 2006 when the PICC team was established, dedicating line insertion and maintenance responsibilities to the team. Historical control group participants were managed via the previous standard of care. METHODS: The risk of CRBSI over time was estimated by Kaplan-Meier analyses and the effect of the PICC team on CRBSI risk was evaluated after controlling for covariables in a Cox proportional hazards model. PRINCIPAL RESULTS: Mean birth weight and gestational age were similar between groups. After controlling for gestational age, central line days, respiratory support days, and average daily census at time of admission in a Cox regression model, the intervention group had 49% lower risk of CRBSI in patients who had a central line in place for more than 30 days. There was no difference in rate of CRBSI between groups that had central lines of short or intermediate duration (<30 days). CONCLUSIONS: Catheter-related bloodstream infection in extremely low-birth-weight infants requiring long-term central venous access was reduced by nearly half after the institution of a dedicated PICC team in the neonatal intensive care unit. Standardizing PICC line placement is important, but standardizing line maintenance is essential to improvement of CRBSI rates.

Therapeutic hypothermia for neonatal encephalopathy and extracorporeal membrane oxygenation.

This case series describes the clinical management of 5 infants who underwent whole-body cooling during extracorporeal membrane oxygenation (ECMO). In all 5 infants, systemic hypothermia was maintained during ECMO with acceptable clinical outcomes.

A New Approach to Recognize Neonatal Impaired Kidney Function.

INTRODUCTION: Previous studies in term newborns with hypoxic ischemic encephalopathy showed that the rate of serum creatinine (SCr) decline during the first week of life could be used to identify newborns with impaired kidney function (IKF) who are missed by standard definitions of neonatal acute kidney injury (nAKI). METHODS: Retrospective review of the medical records of 329 critically ill newborns ≥27 weeks of gestational age (GA) admitted to a level 4 neonatal intensive care unit (NICU). We tested the hypothesis that the rate of SCr decline combined with SCr thresholds provides a sensitive approach to identify term and preterm newborns with IKF during the first week of life. RESULTS: Excluding neonates with nAKI, an SCr decline <31% by the seventh day of life, combined with an SCr threshold ≥0.7 mg/dl, recognized newborns of 40 to 31 weeks of GA with IKF. An SCr decline <21% combined with an SCr threshold ≥0.8 mg/dl identified newborns of 30 to 27 weeks of GA with IKF. Neonates with IKF (∼17%), like those with nAKI (7%), showed a more prolonged hospital stay and required more days of mechanical ventilation, vasoactive drugs, and diuretics, when compared with the controls. Changes in urine output did not distinguish newborns with IKF. CONCLUSION: The rate of SCr decline combined with SCr thresholds identifies newborns with IKF during the first week of life. This distinctive group of newborns that is missed by standard definitions of nAKI, warrants close monitoring in the NICU to prevent further renal complications.

A tale of two bridges: effect of the bloodless bridge on renal function and blood pressure in neonates managed with venoarterial extracorporeal membrane oxygenation.

OBJECTIVE: To investigate if a change in bridge design of the extracorporeal membrane oxygenation (ECMO) circuit had an impact on renal function and blood pressure in neonates requiring venoarterial ECMO support. DESIGN: : Retrospective chart review. SETTING: A tertiary care neonatal intensive care unit and ECMO center. PATIENTS: The medical records of neonates admitted to the neonatal intensive care unit and treated with venoarterial ECMO were reviewed. Data were collected on 50 consecutive neonates treated previous to (prebridge group) and following (postbridge group) transition to a new bridge design on the ECMO circuit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Gestational age, gender, racial distribution, and use of hypertensive therapy were similar between the two groups. Daily blood urea nitrogen, serum creatinine, urine output, fluid balance, and average and maximum systolic and mean arterial blood pressures were recorded for the first 3 days on bypass. The postbridge group had lower maximum mean arterial blood pressure and systolic blood pressure on day 2 of ECMO and lower average mean arterial blood pressure and systolic blood pressure on days 2 and 3 of ECMO. These differences remained significant after controlling for covariates in a multiple regression model. A higher percentage of patients were hypertensive (mean arterial blood pressure >60) in the prebridge group compared with the postbridge group. There were no differences in blood urea nitrogen, serum creatinine, fluid balance, and urine output between the two groups. CONCLUSIONS: Patients managed on venoarterial ECMO after the transition to the "bloodless" bridge had less hypertension compared with those managed before the bridge change. This may reflect improved maintenance of renal perfusion associated with transition to an ECMO bridge design that does not require intermittent circulation with associated arterial-venous shunting.

Impact of decolonization on methicillin-resistant Staphylococcus aureus transmission and infection in a neonatal intensive care unit.

BACKGROUND: The value of decolonization as a strategy for preventing methicillin-resistantStaphylococcus aureus (MRSA) in the neonatal intensive care unit (NICU) remains to be determined. OBJECTIVE: After adding decolonization to further reduce MRSA transmission in our NICU, we conducted this retrospective review to evaluate its effectiveness. METHOD: The review included patients who were admitted to our NICU between April 2015 and June 2018 and were eligible for decolonization including twice daily intranasal mupirocin and daily chlorhexidine gluconate bathing over 5 consecutive days. Patients were considered successfully decolonized if 3 subsequent MRSA screenings conducted at 1-week intervals were negative. The MRSA acquisition rate (AR) was calculated as hospital-acquired (HA) MRSA per 1,000 patient days (PD) and was used to measure the effectiveness of the decolonization. RESULTS: Of the 151 MRSA patients being reviewed, 78 (51.6%) were HA-MRSA, resulting in an overall AR of 1.27 per 1,000 PD. Between April 2015 and February 2016, when only the decolonization was added, the AR was 2.38 per 1,000 PD. Between March 2016 and June 2018 after unit added a technician dedicated to the cleaning of reusable equipment, the AR decreased significantly to 0.92 per 1,000 PD (P < .05). Of the 78 patients who were started on the decolonization, 49 (62.8%) completed the protocol, 11 (14.1%) remained colonized, and 13 (16.7%) were recolonized prior to NICU discharge. CONCLUSION: In a NICU with comprehensive MRSA prevention measures in place, enhancing the cleaning of reusable equipment, not decolonization, led to significant reduction of MRSA transmission.

Reduction in Unintended Extubations in a Level IV Neonatal Intensive Care Unit.

OBJECTIVES: Unintended extubations (UEs) lead to significant morbidity in neonates. A quality improvement project was initiated in response to high rates in our level IV NICU. We targeted creating and sustaining UE rates below the published standard of 1 per 100 ventilator days. METHODS: This project spanned 4 time periods: baseline, epoch 1 (December 2010-May 2012), sustain, and epoch 2 (May 2015-December 2017) by using standard quality improvement methodology. Epoch 1 interventions included real-time analysis of UE events, standardization of taping, patient positioning and movement, accurate event reporting, and change in nomenclature. Epoch 2 interventions included reduction in daily chest radiographs (CXRs) and development of a high-risk tool. Patient and event characteristics were statistically compared across time points. RESULTS: Of the 612 UE events recorded over 10 years, 249 UEs occurred from May 2011 to 2017 involving 184 unique patients. UE rates decreased by 43% (from 1.75 to 0.99 per 100 ventilator days; epoch 1) and were sustained until a notable spike. Epoch 2 interventions led to a further 31% rate reduction. Single CXR use decreased by half. Median corrected gestational age at the time of an event was 35 weeks (interquartile range: 29-41). Seventy percent of infants experiencing an UE required reintubation, 29% had a previous event, and 9% had a code event. CONCLUSIONS: A decrease in UE below benchmarks can be achieved and sustained by standardization and mitigation interventions. This decline was also accompanied by a reduction in use of CXRs without increasing UE events.

Molecular and descriptive epidemiologyof multidrug-resistant Enterobacteriaceae in hospitalized infants.

OBJECTIVE: To investigate the epidemiology of multidrug-resistant Enterobacteriaceae (MDRE) in hospitalized infants. METHODS: From 2000 through 2005, active surveillance cultures for MDRE were performed for patients admitted to a 40-bed neonatal intensive care unit (NICU) that provides care for critically ill infants 6 months of age or younger. MDRE epidemiology and the genetic relatedness of MDRE strains determined by repetitive-sequence polymerase chain reaction were analyzed. RESULTS: Active surveillance cultures revealed that 759 (23%) of 3,370 NICU infants (or approximately 1 in 5) developed MDRE colonization or infection and that 613 (72%) of the 853 isolates with epidemiologic data available were healthcare acquired. MDRE colonization occurred more frequently (in 653 infants [86%]) than did MDRE infection (in 106 [14%]). Of the 653 infants with MDRE colonization, 119 (18%) eventually became infected, with 29 (4%) acquiring sterile site infections. The most commonly isolated organisms were the Enterobacter species, accounting for 612 (71%) of the 862 isolates. Molecular epidemiologic analysis revealed that genetic-relatedness clustering (related clusters defined as having a genetic similarity coefficient greater than 95%) varied depending on microbial species. Clustering was detected for 36 (78%) of the 46 Enterobacter aerogenes isolates, 22 (45%) of the 49 Enterobacter cloacae isolates, and 13 (59%) of the 22 Klebsiella pneumoniae isolates. CONCLUSION: Hospitalized infants are at significant risk of acquiring MDRE, specifically Enterobacter species, at the study institution. Active surveillance cultures identified colonized patients who likely contributed to the institutional reservoir of MDRE. Molecular epidemiologic studies suggest that both patient-to-patient transmission and de novo acquisition of resistance play a role in the acquisition of these organisms, and that the clinical significance of such acquisition varies by species. The high percentage of E. aerogenes isolates that demonstrated genetic clustering suggests that monitoring the prevalence of this organism could serve as a useful measure of compliance with infection control procedures.

Reassessing the need for active surveillance of extended-spectrum beta-lactamase-producing Enterobacteriaceae in the neonatal intensive care population.

OBJECTIVE: To determine the continued need for active surveillance to prevent extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) transmission in a neonatal intensive care unit (NICU). DESIGN: This retrospective observational study included patients with ESBL-E colonization or infection identified during their NICU stay at our institution between 1999 and March 2018. Active surveillance was conducted between 1999 and March 2017 by testing rectal swab specimens collected upon admission and weekly thereafter. The overall incidence rates, of ESBL-E colonization or infection (including hospital acquired) before and after active surveillance were calculated. The cost associated with active surveillance was then estimated. RESULTS: Overall, 171 NICU patients were found to have ESBL-E colonization or infection, and 150 of those patients (87.7%) were detected by active surveillance. The overall incidence rate was 1.4 per 100 patient admissions. The hospital-acquired incidence rate was 0.41 per 1,000 patient days, and this rate had decreased since 2002, with an average of 6 cases detected annually. A significant decrease was observed in 2009 when the unit moved to a new single-bed unit featuring private rooms. Active surveillance was discontinued with no increase in the number of infections. Of the 150 ESBL-E colonized patients, 14 (9.3%) subsequently developed an infection. Active surveillance resulted in a total of 50,950 specimen collections and a cost of $127,187 for processing, an average of $848 to detect 1 ESBL-E colonized patient. CONCLUSION: ESBL-E transmission and infection in our NICU remains uncommon. Active surveillance may have contributed to the decline of ESBL-E transmission when used in conjunction with contact precautions and private rooms, but its relatively high cost could be prohibitive.

Cardiovascular support in preterm infants.

BACKGROUND: Despite increasing investigation in the area of cardiovascular instability in preterm infants, huge gaps in knowledge remain. None of the current treatments for hypotension, including the use of inotropic agents, have been well studied in the preterm population, and data regarding safety and efficacy are lacking. Thus, the labeling information regarding the use of inotropes as therapeutic agents in this population is inadequate. OBJECTIVE: This article reviews the current deficiencies in knowledge with respect to measuring and achieving normal organ perfusion; summarizes the clinical, methodological, and ethical issues to consider when designing trials to evaluate medications for hemodynamic instability in the preterm neonate; and proposes 2 possible trial designs. Unanswered questions and potential obstacles for the systematic study of drugs to treat cardiovascular instability in preterm neonates are discussed. METHODS: The neonatal Cardiology Group was established in 2003 by the US Food and Drug Administration (FDA) and the National Institute of Child Health and Human Development (NICHD) as part of the Newborn Drug Development Initiative. The Cardiology Group conducted a number of teleconferences and one meeting to develop a document addressing gaps in knowledge regarding cardiovascular drugs commonly used in low-birth-weight neonates and possible approaches to investigate these drugs. This work was presented at a workshop cosponsored by the NICHD and the FDA held in March 2004 in Baltimore, Maryland. Information for this article was gathered during this initiative. RESULTS: To develop rational, evidence-based guidelines corroborated by robust scientific data for cardiovascular support in newborns, well-designed and adequately powered pharmacologic studies and clinical trials are needed to evaluate the safety and efficacy of inotropic agents and to determine the short- and long-term effects of these drugs. Trials investigating the currently available and novel therapies for cardiovascular instability in neonates will provide information that can be incorporated into product labeling and a scientific framework for cardiovascular management in critically ill neonates. The Cardiology Group identified and prioritized 2 conditions for investigation of therapeutic options for the management of neonatal cardiovascular instability: (1) cardiovascular instability in preterm neonates; and (2) cardiac dysfunction in neonates after cardiopulmonary bypass surgery. Key research questions in the area of cardiovascular instability in the preterm infant include determining optimal blood pressure (BP) in preterm infants; identifying better measures than BP to determine organ perfusion; optimizing hemodynamic treatments; and clarifying any associations between BP or therapy for low BP and mortality, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity, and neurodevelopmental outcome. The Cardiology Group concluded that the study of inotropic agents in neonates using outcomes of importance to patients will require a complicated trial design to address the elements discussed. The group proposed 2 clinical trial designs: (1) a placebo-controlled trial with rescue therapy for symptomatic infants; and (2) a targeted BP trial. CONCLUSION: This summary is intended to stimulate and assist future research in the area of cardiovascular support for preterm infants.

Altered cerebrovascular responses after exposure to venoarterial extracorporeal membrane oxygenation: role of the nitric oxide pathway.

BACKGROUND: Previous studies in our laboratory on newborn lambs have shown cerebral autoregulation impairment after exposure to venoarterial extracorporeal membrane oxygenation (VA ECMO), with additional studies showing an altered cerebrovascular response to NG-nitro-L-arginine methyl ester in lamb cerebral vessels in this same model. OBJECTIVE: To further study the mechanisms involved in altered cerebrovascular responses in vessels exposed to VA ECMO. DESIGN: Prospective study. SETTING: Research Animal Facility at Children's National Medical Center, Washington, DC. SUBJECT: Newborn lambs, 1-7 days of age, 4.76 +/- 0.8 kg (n = 10). METHODS: Animals randomly assigned two groups, control and VA ECMO, were anesthetized, ventilated, heparinized, and kept in a normal physiologic condition. Control animals were continued on ventilatory support, whereas animals in the VA ECMO groups were placed on VA ECMO, with bypass flows maintained between 120 and 200 mL x kg x min(-1) for 2.5 hrs. Isolated third-order branches of the middle cerebral arteries were studied for myotonic reactivity to increasing intraluminal pressure changes, response to acetylcholine, an endothelium-dependent vasodilator, 3-morpholinyl-sydnoneimine chloride, an endothelium-independent vasodilator, and serotonin, a direct vascular vasoconstrictor. Arterial caliber was monitored using video microscopy. RESULTS: Myogenic constriction response was significantly decreased in the VA ECMO group compared with the control group (p = .03). Intraluminal acetylcholine caused concentration-dependent arterial dilation in the control group, whereas it resulted in vasoconstriction in the VA ECMO group (p = .008). There were no significant differences in dilation responses to 3-morpholinyl-sydnoneimine chloride and contractile responses to serotonin among the groups. CONCLUSION: Cerebral arteries exposed to VA ECMO had impaired myogenic responses combined with altered endothelial function. The endothelial alteration seems to be mediated through the nitric oxide pathway, with recovery noted after addition of a nitric oxide donor. It can be postulated that these changes may reflect the mechanisms for the impairment of cerebral autoregulation previously reported in this lamb model.

NF-kappaB activation plays a role in superoxide-mediated cerebral endothelial dysfunction after hypoxia/reoxygenation.

BACKGROUND AND PURPOSE: Cerebral vascular injury occurs in response to hypoxia/reoxygenation (H/R). However, the cellular signaling pathways that regulate this event remain unclear. The present study was designed to determine whether reactive oxygen species (ROS) mediate endothelial dysfunction after H/R in cerebral resistance arteries and, if so, the relative contribution of ROS, NADPH oxidase, and a nuclear factor-kappaB (NF-kappaB) pathway. METHODS: Arterial diameter and intraluminal pressure were simultaneously measured on rat posterior cerebral arteries (PCA). Superoxide was measured by 5-micromol/L lucigenin-enhanced chemiluminescence. RESULTS: Hypoxia/reoxygenation selectively inhibited cerebral vasodilation to the endothelium-dependent agonist acetylcholine (Ach) (0.01 to 10 micromol/L) by approximately 50%. Impaired vasodilation after H/R was reversed by 2,2,6,6-tetramethylpiperidine-N-oxyl (Tempo) (100 micromol/L), a cell-permeable superoxide dismutase mimetic, and partially by ebselen (10 micromol/L), a peroxynitrite scavenger. H/R-impaired vasodilation to Ach was also preserved by apocynin (1 mmol/L), a specific inhibitor for NADPH oxidase. Correspondingly, H/R significantly increased lucigenin-detectable superoxide, which was reduced by either Tempo or apocynin, but not by allopurinol (10 micromol/L), an inhibitor of xanthine oxidase. Finally, the NF-kappaB inhibitors helenalin (10 micromol/L) and MG-132 (1 micromol/L) independently antagonized H/R-impaired Ach-induced vasodilation without affecting dilator response to sodium nitroprusside, an endothelium-independent vasodilator. CONCLUSIONS: These results indicate that superoxide mediates cerebral endothelial dysfunction after hypoxia/reoxygenation largely via activation of NADPH oxidase and possibly activation of NF-kappaB pathway.

Control of vancomycin-resistant enterococci in the neonatal intensive care unit.

BACKGROUND AND OBJECTIVE: Multidrug-resistant organisms (MDROs), such as vancomycin-resistant enterococci (VRE), cause serious infections, especially among high-risk patients in NICUs. When VRE was introduced and transmitted in our NICU despite recommended infection control practices, we instituted active surveillance cultures to determine their efficacy in detecting and controlling spread of VRE among high-risk infants. METHODS: Active surveillance cultures, other infection control measures, and a mandatory in-service education module on preventing MDRO transmission were implemented. Cultures were performed on NICU admission and then weekly during their stay. Molecular DNA fingerprinting of VRE isolates facilitated targeting efforts to eliminate clonal spread of VRE. Repetitive sequence PCR (rep-PCR)-based DNA fingerprinting was used to compare isolates recovered from patients with VRE infection or colonization. Environmental VRE cultures were performed around VRE-colonized or -infected patients. DNA fingerprints were prepared from the products of rep-PCR amplification and analyzed using software to determine strain genetic relatedness. RESULTS: Active surveillance cultures identified 65 patients with VRE colonization or infection among 1,820 admitted to the NICU. Rep-PCR performed on 60 VRE isolates identified 3 clusters. Cluster 1 included isolates from 21 patients and 4 isolates from the environment of the index patient. Clusters 2 and 3 included isolates from 23 and 3 patients, respectively. Similarity coefficients among the members of each cluster were 95% or greater. CONCLUSIONS: Control of transmission of multi-clonal VRE strains was achieved. Active surveillance cultures, together with implementation of other infection control measures, combined with rep-PCR DNA fingerprinting were instrumental in controlling VRE transmission in our NICU.