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..

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.

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.

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.

High surgical burden for infants with severe chronic lung disease (sCLD).

BACKGROUND/PURPOSE: Infants with severe chronic lung disease (sCLD) may require surgical procedures to manage their medical problems; however, the scope of these interventions is undefined. The purpose of this study was to characterize the frequency, type, and timing of operative interventions performed in hospitalized infants with sCLD. METHODS: The Children's Hospital Neonatal Database was used to identify infants with sCLD from 24 children's hospital's NICUs hospitalized over a recent 16-month period. RESULTS: 556 infants were diagnosed with sCLD; less than 3% of infants had operations prior to referral and 30% were referred for surgical evaluation. In contrast, 71% of all sCLD infants received ≥1 surgical procedure during the CHND NICU hospitalization, with a mean of 3 operations performed per infant. Gastrostomy insertion (24%), fundoplication (11%), herniorrhaphy (13%), and tracheostomy placement (12%) were the most commonly performed operations. The timing of gastrostomy (PMA 48±10 wk) and tracheostomy (PMA 47±7 wk) insertions varied, and for infants who received both devices, only 33% were inserted concurrently (13/40 infants). CONCLUSIONS: A striking majority of infants with sCLD received multiple surgical procedures during hospitalizations at participating NICUs. Further work regarding the timing, coordination, perioperative complications, and clinical outcomes for these infants is warranted.

The association of type of surgical closure on length of stay among infants with gastroschisis born≥34 weeks' gestation.

BACKGROUND/PURPOSE: The optimal surgical approach in infants with gastroschisis (GS) is unknown. The purpose of this study was to estimate the association between staged closure and length of stay (LOS) in infants with GS. DESIGN/METHODS: We used the Children's Hospital Neonatal Database to identify surviving infants with GS born ≥34 weeks' gestation referred to participating NICUs. Infants with complex GS, bowel atresia, or referred after 2 days of age were excluded. The primary outcome was LOS; multivariable linear regression was used to quantify the relationship between staged closure and LOS. RESULTS: Among 442 eligible infants, staged closure occurred in 68.1% and was associated with an increased median LOS relative to odds ration (OR):primary closure (37 vs. 28 days, p<0.001). This association persisted in the multivariable equation (ß=1.35, 95% CI: 1.21, 1.52, p<0.001) after adjusting for the presence of necrotizing enterocolitis, short bowel syndrome, and central-line associated bloodstream infections. CONCLUSIONS: In this large, multicenter cohort of infants with GS, staged closure was independently associated with increased LOS. These data can be used to enhance antenatal and pre-operative counseling and also suggest that some infants who receive staged closure may benefit from primary repair.

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.

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.

Improving hand hygiene compliance in health care workers: Strategies and impact on patient outcomes.

BACKGROUND: We described a systematic process for improving hand hygiene (HH) compliance in health care providers and assessed the impact of HH on patient outcomes. METHODS: This retrospective cohort study was conducted between July 2008 and September 2011 in a children's hospital. We employed failure mode effectiveness analysis to identify barriers for complying with HH requirements and instituted improvement measures. We conducted a subanalysis using methicillin-resistant Staphylococcus aureus (MRSA) acquisition data and HH compliance data collected in the neonatal intensive care unit (NICU) to demonstrate the impact of HH on patient outcomes. RESULTS: The overall HH compliance rate increased from 50.3% preintervention (July 2008-September 2008) to 84.0% postintervention (January 2009-September 2011) (relative risk [RR], 1.7; 95% confidence interval [CI]: 1.6-1.9). Compliance among physicians and nurses increased from 48.6% to 87.0% (RR, 1.4; 95% CI: 1.3-1.6) and from 46.5% to 77.9% (RR, 1.3; 95% CI: 1.2-1.4), respectively. Sustaining HH at 80% or higher was associated with a 48% further reduction of MRSA acquisition (incident rate ratio, -0.52; 95% CI: -0.31 to -0.90) in a unit that had comprehensive MRSA prevention measures. This reduction represents the prevention of 1.3 MRSA acquisitions per month, resulting in a saving of 11.6 NICU-days and $66,397 hospital charges. CONCLUSION: This study demonstrated the utility of failure mode effectiveness analysis to improve staff HH and suggested HH as a potential cost-effective means for preventing MRSA in hospitals.

Heparin inhibits angiotensin II-induced vasoconstriction on isolated mouse mesenteric resistance arteries through Rho-A- and PKA-dependent pathways.

Heparin is commonly used to treat intravascular thrombosis in children undergoing extracorporeal membrane oxygenation or cardiopulmonary bypass. These clinical circumstances are associated with elevated plasma levels of angiotensin II (Ang II). However, the mechanisms by which heparin modulates vascular reactivity of Ang II remain unclear. We hypothesized that heparin may offset Ang II-induced vasoconstriction on mesenteric resistance arteries through modulating the Rho-A/Rho kinase pathway. Vascular contractility was studied by using pressurized, resistance-sized mesenteric arteries from mice. Rho-A activation was measured by pull-down assay, and myosin light chain or PKA phosphorylation by immunoblotting. We found that heparin significantly attenuated vasoconstriction induced by Ang II but not that by KCl. The combined effect of Ang II with heparin was almost abolished by a specific Rho kinase inhibitor Y27632. Ang II stimulated Rho-A activation and myosin light chain phosphorylation, both responses were antagonized by heparin. Moreover, the inhibitory effect of heparin on Ang II-induced vasoconstriction was reversed by Rp-cAMPS (cAMP-dependent PKA inhibitor), blunted by ODQ (soluble guanylate cyclase inhibitor), and mimicked by a cell-permeable cGMP analogue, 8-Br-cGMP, but not by a cAMP analogue. PKC and Src kinase were not involved. We conclude that heparin inhibits Ang II-induced vasoconstriction through Rho-A/Rho kinase- and cGMP/PKA-dependent pathways.

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.

Survival in congenital diaphragmatic hernia: use of predictive equations in the ECMO population.

BACKGROUND: Equations have been proposed by the Wilford Hall/Santa Rosa (WHSR) and Congenital Diaphragmatic Hernia Study Group (CDHSG) for predicting survival in patients with CDH. The CDHSG stratifies risk based on a logistic regression equation incorporating birth weight and 5-min Apgar score, while the WHSR group uses the difference between maximum pO(2) and maximum pCO(2) as an index of risk. These models have not been applied specifically to the CDH ECMO (extracorporeal membrane oxygenation) population, a group at highest mortality risk. OBJECTIVES: To evaluate the WHSR and CDHSG predictive equations when applied to a population of patients with CDH requiring ECMO life support. METHODS: A single-center retrospective review was conducted on infants with CDH treated with ECMO between 1993 and 2007. Predicted and actual outcomes were compared using receiver operating curve (ROC) analyses in which an area under the curve (AUC) of 1 denotes 100% agreement between predicted and actual outcomes. Kaplan-Meier analyses were also used to compare survival of patients who were risk-categorized according to each prediction model. Minimum pre-ECMO pCO(2) was likewise evaluated as a predictor of survival. RESULTS: Overall survival was 50% in 62 CDH patients treated with ECMO during the study period. The CDHSG equation did not discriminate between survivors and nonsurvivors (AUC 0.55, p = 0.499). The modified WHSR formula showed better discrimination of survival (AUC 0.71, p = 0.004). Lowest achievable pre-ECMO pCO(2) had the highest AUC (0.723, p = 0.003). Patients with minimum pre-ECMO pCO(2) <50 mm Hg had 56% survival, while those with >70 mm Hg had 0% survival. CONCLUSIONS: Equations proposed to predict survival in CDH patients may not discriminate survivors from nonsurvivors in the ECMO population. In this highest risk group, factors such as birth weight and Apgar score are less critical in estimating mortality risk than indicators of ventilation and oxygenation that reflect the degree of pulmonary hypoplasia.