Bio

Clinical Focus


  • Neonatal-Perinatal Medicine

Academic Appointments


Administrative Appointments


  • President, California Association of Neonatologists (2005 - 2006)
  • President, Board of Governors, Stanford University School of Med. Alumni Assoc. (2009 - 2011)
  • National Advisory Board Member, Vermont-Oxford Network NICQ (2007 - Present)
  • Medical Director, Neonatal ICU (2000 - Present)

Professional Education


  • Fellowship:Stanford University School of Medicine Registrar (1989) CA
  • Residency:Stanford University School of Medicine Registrar (1987) CA
  • Internship:Stanford University School of Medicine (1985) CA
  • Medical Education:Stanford University School of Medicine (1984) CA
  • Board Certification: Neonatal-Perinatal Medicine, American Board of Pediatrics (1989)
  • M.D., Stanford University, Medicine (1984)
  • M.S., Mass. Institute of Technology, Nutritional Biochemistry (1979)
  • B.S., Mass. Institute of Technology, Biology (1977)

Research & Scholarship

Current Research and Scholarly Interests


Neonatology, extracorporeal membrane oxygenation, nitric oxide therapy, mechanisms of bilirubin toxicity and brain injury, non-invasive biotechnologies to study cellular and organ metabolism.

Teaching

2018-19 Courses


Publications

All Publications


  • An Analysis of Time to Improvement in Oxygenation in Japanese Preterm and Late Preterm or Term Neonates With Hypoxic Respiratory Failure and Pulmonary Hypertension. Clinical therapeutics Rhine, W. D., Suzuki, S., Potenziano, J. L., Escalante, S., Togari, H. 2019

    Abstract

    PURPOSE: We analyzed data from an ongoing registry to determine time to improvement in oxygenation in preterm and late preterm or term neonates with hypoxic respiratory failure and pulmonary hypertension receiving inhaled nitric oxide (iNO) in Japan.METHODS: Registry neonates received iNO ≤7 days after birth (February 26, 2010, to October 9, 2012). Efficacy and safety profile data were collected up to 96h after iNO initiation and, if necessary, every 24h thereafter and before iNO discontinuation. Patients were stratified by gestational age (GA), oxygenation index (OI), and shunt direction at baseline.FINDINGS: Data were evaluated for 1106 neonates (431 with a GA <34 weeks and 675 with a GA of ≥34 weeks). Sixty percent of patients had improved OI; rates were similar for those with GAs of <34 versus ≥34 weeks (61% vs 59%). Overall, mean time to improvement was 11.4h and tended to be shorter in the groups with a GA <34 weeks versus ≥34 weeks (9.2 vs 12.9h). Thirty percent of responding neonates required >1h to achieve improvement in oxygenation. Neonates with higher baseline OI had the greatest decrease in OI during the first hour of treatment. The mortality rate was higher among iNO-treated patients with a baseline OI ≥25 versus those with OI ≥15 to <25 (25% vs 12%; P=0.0073).IMPLICATIONS: iNO treatment provided acute, sustained improvement in oxygenation in neonates with GAs <34 and≥34 weeks; 70% of patients had improvement within 1h, but the remaining 30% took >1h to respond. Initiation of iNO at lower OIs was associated with reduced mortality compared with higher OI.

    View details for PubMedID 30987776

  • Welcome and Opening Remarks. Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine Bode, L., Rhine, W. D. 2019; 14 (S1): S2

    View details for PubMedID 30985204

  • Welcome and Opening Remarks BREASTFEEDING MEDICINE Rhine, W. D., Bode, L. 2018; 13: S2

    View details for PubMedID 29624418

  • Technology - Considerations for the NICU of the Future NEWBORN AND INFANT NURSING REVIEWS Rhine, W. D. 2016; 16 (4): 208–12
  • Apolipoprotein E genotype and outcome in infants with hypoxic-ischemic encephalopathy. Pediatric research Cotten, C. M., Goldstein, R. F., McDonald, S. A., Goldberg, R. N., Salhab, W. A., Carlo, W. A., Tyson, J. E., Finer, N. N., Walsh, M. C., Ehrenkranz, R. A., Laptook, A. R., Guillet, R., Schibler, K., Van Meurs, K. P., Poindexter, B. B., Stoll, B. J., O'Shea, T. M., Duara, S., Das, A., Higgins, R. D., Shankaran, S. 2014; 75 (3): 424-430

    Abstract

    Background:Adults with the apolipoprotein E (APOE) gene alleles e4 and e2 are at high risk of poor neurological outcome after brain injury. The e4 allele has been associated with cerebral palsy (CP), and the e2 allele has been associated with worse neurological outcome with congenital heart disease. This study was done to test the hypothesis that the APOE genotype is associated with outcome among neonates who survive after hypoxic-ischemic encephalopathy (HIE).Methods:We conducted a cohort study of infants who survived HIE and had 18-22 mo standardized neurodevelopmental evaluations to assess associations between disability and the APOE genotypes e3/e3, e4/-, and e2/-.Results:A total of 139 survivors were genotyped. Of these, 86 (62%) were of the e3/e3, 41 (29%) were of the e4/-, and 14 (10%) were of the e2/- genotypes. One hundred and twenty-nine infants had genotype and follow-up data; 26% had moderate or severe disabilities. Disability prevalence was 30 and 19% among those with and without the e3/e3 genotype, 25 and 26% among those with and without the e2 allele, and 18 and 29% among those with and without the e4 allele, respectively. None of the differences were statistically significant. CP prevalence was also similar among genotype groups.Conclusion:Disability was not associated with the APOE genotype in this cohort of HIE survivors.

    View details for DOI 10.1038/pr.2013.235

    View details for PubMedID 24322171

  • Parental coping in the neonatal intensive care unit. Journal of clinical psychology in medical settings Shaw, R. J., Bernard, R. S., Storfer-Isser, A., Rhine, W., Horwitz, S. M. 2013; 20 (2): 135-142

    Abstract

    Fifty-six mothers of premature infants who participated in a study to reduce symptoms of posttraumatic stress disorder (PTSD) completed the Brief COPE, a self-report inventory of coping mechanisms, the Stanford Acute Stress Reaction Questionnaire to assess acute stress disorder (ASD) and the Davidson Trauma Scale to assess PTSD. 18 % of mothers had baseline ASD while 30 % of mothers met the criteria for PTSD at the 1-month follow-up. Dysfunctional coping as measured by the Brief COPE was positively associated with elevated risk of PTSD in these mothers (RR = 1.09, 95 % CI 1.02-1.15; p = .008). Maternal education was positively associated with PTSD; each year increase in education was associated with a 17 % increase in the relative risk of PTSD at 1 month follow-up (RR = 1.17, 95 % CI 1.02-1.35; p = .03). Results suggest that dysfunctional coping is an important issue to consider in the development of PTSD in parents of premature infants.

    View details for DOI 10.1007/s10880-012-9328-x

    View details for PubMedID 22990746

  • Impact of an EMR-Based Daily Patient Update Letter on Communication and Parent Engagement in a Neonatal Intensive Care Unit. Journal of participatory medicine Palma, J. P., Keller, H., Godin, M., Wayman, K., Cohen, R. S., Rhine, W. D., Longhurst, C. A. 2012; 4

    Abstract

    To evaluate the impact of using electronic medical record (EMR) data in the form of a daily patient update letter on communication and parent engagement in a level II neonatal intensive care unit (NICU).Parents of babies in a level II NICU were surveyed before and after the introduction of an EMR-generated daily patient update letter, Your Baby's Daily Update (YBDU).Following the introduction of the EMR-generated daily patient update letter, 89% of families reported using YBDU as an information source; 83% of these families found it "very useful", and 96% of them responded that they "always" liked receiving it. Rates of receiving information from the attending physician were not statistically significantly different pre- and post-implementation, 81% and 78%, respectively (p = 1). Though there was no statistically significant improvement in parents' knowledge of individual items regarding the care of their babies, a trend towards statistical significance existed for several items (p <.1), and parents reported feeling more competent to manage information related to the health status of their babies (p =.039).Implementation of an EMR-generated daily patient update letter is feasible, resulted in a trend towards improved communication, and improved at least one aspect of parent engagement-perceived competence to manage information in the NICU.

    View details for PubMedID 23730532

  • A Quality Improvement Project to Increase Breast Milk Use in Very Low Birth Weight Infants PEDIATRICS Lee, H. C., Kurtin, P. S., Wight, N. E., Chance, K., Cucinotta-Fobes, T., Hanson-Timpson, T. A., Nisbet, C. C., Rhine, W. D., Risingsun, K., Wood, M., Danielsen, B. H., Sharek, P. J. 2012; 130 (6): E1679-E1687

    Abstract

    To evaluate a multihospital collaborative designed to increase breast milk feeding in premature infants.Eleven NICUs in the California Perinatal Quality of Care Collaborative participated in an Institute for Healthcare Improvement-style collaborative to increase NICU breast milk feeding rates. Multiple interventions were recommended with participating sites implementing a self-selected combination of these interventions. Breast milk feeding rates were compared between baseline (October 2008-September 2009), implementation (October 2009-September 2010), and sustainability periods (October 2010-March 2011). Secondary outcome measures included necrotizing enterocolitis (NEC) rates and lengths of stay. California Perinatal Quality of Care Collaborative hospitals not participating in the project served as a control population.The breast milk feeding rate in the intervention sites improved from baseline (54.6%) to intervention period (61.7%; P = .005) with sustained improvement over 6 months postintervention (64.0%; P = .003). NEC rates decreased from baseline (7.0%) to intervention period (4.3%; P = .022) to sustainability period (2.4%; P < .0001). Length of stay increased during the intervention but returned to baseline levels in the sustainability period. Control hospitals had higher rates of breast milk feeding at baseline (64.2% control vs 54.6% participants, P < .0001), but over the course of the implementation (65.7% vs 61.7%, P = .049) and sustainability periods (67.7% vs 64.0%, P = .199), participants improved to similar rates as the control group.Implementation of a breast milk/nutrition change package by an 11-site collaborative resulted in an increase in breast milk feeding and decrease in NEC that was sustained over an 18-month period.

    View details for DOI 10.1542/peds.2012-0547

    View details for Web of Science ID 000314802000033

    View details for PubMedID 23129071

    View details for PubMedCentralID PMC3507251

  • Combining hand techniques with electric pumping increases the caloric content of milk in mothers of preterm infants JOURNAL OF PERINATOLOGY Morton, J., Wong, R. J., Hall, J. Y., Pang, W. W., Lai, C. T., Lui, J., Hartmann, P. E., Rhine, W. D. 2012; 32 (10): 791-796

    Abstract

    We previously reported that preterm mothers' milk production can exceed levels of term mothers by using early hand expression and hands-on pumping (HOP) with the highest production (955 ml per day) in frequent users of hand expression. In this study, we compared milk composition between mothers stratified by early hand expression frequency.A total of 67 mothers of infants <31 weeks gestation were instructed on hand expression and HOP. Subjects submitted expression records and 1-ml samples from each pumping session over 24 h once weekly for 8 weeks.78% (52/67) of mothers completed the study. But for Week 1, no compositional differences (despite production differences) were noted between the three groups. Protein and lactose tracked reported norms, but fat and energy of mature milk (Weeks 2-8) exceeded norms, 62.5 g l(-1) per fat and 892.7 cal l(-1) (26.4 cal oz(-1)), respectively.Mothers combining manual techniques with pumping express high levels of fat-rich, calorie-dense milk, unrelated to production differences.

    View details for DOI 10.1038/jp.2011.195

    View details for PubMedID 22222549

  • Prediction of Bronchopulmonary Dysplasia by Postnatal Age in Extremely Premature Infants AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Laughon, M. M., Langer, J. C., Bose, C. L., Smith, P. B., Ambalavanan, N., Kennedy, K. A., Stoll, B. J., Buchter, S., Laptook, A. R., Ehrenkranz, R. A., Cotten, C. M., Wilson-Costello, D. E., Shankaran, S., Van Meurs, K. P., Davis, A. S., Gantz, M. G., Finer, N. N., Yoder, B. A., Faix, R. G., Carlo, W. A., Schibler, K. R., Newman, N. S., Rich, W., Das, A., Higgins, R. D., Walsh, M. C. 2011; 183 (12): 1715-1722

    Abstract

    Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment.To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death.We assessed infants of 23-30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000-2004.Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and Fi(O(2)), and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at https://neonatal.rti.org.The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.

    View details for DOI 10.1164/rccm.201101-0055OC

    View details for Web of Science ID 000292305600024

    View details for PubMedID 21471086

    View details for PubMedCentralID PMC3136997

  • Improved outcomes with a standardized feeding protocol for very low birth weight infants JOURNAL OF PERINATOLOGY McCallie, K. R., Lee, H. C., Mayer, O., Cohen, R. S., Hintz, S. R., Rhine, W. D. 2011; 31: S61-S67

    Abstract

    The objective of this study was to evaluate the impact of a standardized enteral feeding protocol for very low birth weight (VLBW) infants on nutritional, clinical and growth outcomes.Retrospective analysis of VLBW cohorts 9 months before and after initiation of a standardized feeding protocol consisting of 6-8 days of trophic feedings, followed by an increase of 20 ml/kg/day. The primary outcome was days to reach full enteral feeds defined as 160 ml/kg/day. Secondary outcomes included rates of necrotizing enterocolitis and culture-proven sepsis, days of parenteral nutrition and growth end points.Data were analyzed on 147 VLBW infants who received enteral feedings, 83 before ('Before') and 64 subsequent to ('After') feeding protocol initiation. Extremely low birth weight (ELBW) infants in the After group attained enteral volumes of 120 ml/kg/day (43.9 days Before vs 32.8 days After, P=0.02) and 160 ml/kg/day (48.5 days Before vs 35.8 days After, P=0.02) significantly faster and received significantly fewer days of parenteral nutrition (46.2 days Before vs 31.3 days After, P=0.01). Necrotizing enterocolitis decreased in the After group among VLBW (15/83, 18% Before vs 2/64, 3% After, P=0.005) and ELBW infants (11/31, 35% Before vs 2/26, 8% After, P=0.01). Late-onset sepsis decreased significantly in the After group (26/83, 31% Before vs 6/64, 9% After, P=0.001). Excluding those with weight <3rd percentile at birth, the proportion with weight <3rd percentile at discharge decreased significantly after protocol initiation (35% Before vs 17% After, P=0.03).These data suggest that implementation of a standardized feeding protocol for VLBW infants results in earlier successful enteral feeding without increased rates of major morbidities.

    View details for DOI 10.1038/jp.2010.185

    View details for Web of Science ID 000289236900010

    View details for PubMedID 21448207

  • Brief Cognitive-Behavioral Intervention for Maternal Depression and Trauma in the Neonatal Intensive Care Unit: A Pilot Study JOURNAL OF TRAUMATIC STRESS Bernard, R. S., Williams, S. E., Storfer-Isser, A., Rhine, W., Horwitz, S. M., Koopman, C., Shaw, R. J. 2011; 24 (2): 230-234

    Abstract

    Parents of hospitalized premature infants are at risk for developing psychological symptoms. This randomized controlled pilot study examined the effectiveness of a brief cognitive-behavioral intervention in reducing traumatic and depressive symptoms in mothers 1 month after their infant's discharge from the hospital. Fifty-six mothers were randomly assigned to the intervention or control group. Results showed that mothers experienced high levels of symptoms initially and at follow-up. At follow-up, there was a trend for mothers in the intervention group to report lower levels of depression (p = .06; Cohen's f = .318), but levels of traumatic symptoms were similar for both groups. Brief psychological interventions may reduce depressive symptoms in this population. Estimates of the effect sizes can be used to inform future intervention studies.

    View details for DOI 10.1002/jts.20626

    View details for PubMedID 21438016

  • Combining hand techniques with electric pumping increases milk production in mothers of preterm infants JOURNAL OF PERINATOLOGY Morton, J., Hall, J. Y., Wong, R. J., Thairu, L., Benitz, W. E., Rhine, W. D. 2009; 29 (11): 757-764

    Abstract

    Pump-dependent mothers of preterm infants commonly experience insufficient production. We observed additional milk could be expressed following pumping using hand techniques. We explored the effect on production of hand expression of colostrum and hands-on pumping (HOP) of mature milk.A total of 67 mothers of infants <31 weeks gestation were enrolled and instructed on pumping, hand expression of colostrum and HOP. Expression records for 8 weeks and medical records were used to assess production variables.Seventy-eight percent of the mothers completed the study. Mean daily volumes (MDV) rose to 820 ml per day by week 8 and 955 ml per day in mothers who hand expressed >5 per day in the first 3 days. Week 2 and/or week 8 MDV related to hand expression (P<0.005), maternal age, gestational age, pumping frequency, duration, longest interval between pumpings and HOP (P<0.003). Mothers taught HOP increased MDV (48%) despite pumping less.Mothers of preterm infants may avoid insufficient production by combining hand techniques with pumping.

    View details for DOI 10.1038/jp.2009.87

    View details for PubMedID 19571815

  • A quality improvement project to improve admission temperatures in very low birth weight infants JOURNAL OF PERINATOLOGY Lee, H. C., Ho, Q. T., Rhine, W. D. 2008; 28 (11): 754-758

    Abstract

    To review the results of a quality improvement (QI) project to improve admission temperatures of very low birth weight inborn infants.The neonatal intensive care unit at Lucile Packard Children's Hospital underwent a QI project to address hypothermic preterm newborns by staff education and implementing processes such as polyethylene wraps and chemical warming mattresses. We performed retrospective chart review of all inborn infants with birth weight <1500 g during the 18 months prior to (n=134) and 15 months after (n=170) the implementation period. Temperatures were compared between periods. Multivariable logistic regression was used to account for potential confounding variables. We compared mortality rates and grade 3 or 4 intraventricular hemorrhage rates between periods.The mean temperature rose from 35.4 to 36.2 degrees C (P<0.0001) after the QI project. The improvement was consistent and persisted over a 15-month period. After risk adjustment, the strongest predictor of hypothermia was being born in the period before implementation of the QI project (odds ratio 8.12, 95% confidence interval 4.63, 14.22). Although cesarean delivery was a strong risk factor for hypothermia prior to the project, it was no longer significant after the project. There was no significant difference in death or intraventricular hemorrhage detected between periods.There was a significant improvement in admission temperatures after a QI project, which persisted beyond the initial implementation period. Although there was no difference in mortality or intraventricular hemorrhage rates, we did not have sufficient power to detect small differences in these outcomes.

    View details for DOI 10.1038/jp.2008.92

    View details for Web of Science ID 000260795100005

    View details for PubMedID 18580878

  • Inhaled nitric oxide in the treatment of preterm infants EARLY HUMAN DEVELOPMENT Miller, S. S., Rhine, W. D. 2008; 84 (11): 703-707

    Abstract

    Inhaled nitric oxide (iNO) has been used successfully in select term and near-term infants with respiratory failure. The use of iNO in the premature infant population, however, remains controversial. This article will review some of the current literature regarding the use of iNO in premature infants and discuss current recommendations and future research directions.

    View details for DOI 10.1016/j.earlhumdev.2008.08.005

    View details for PubMedID 18930359

  • Neonatal heparin overdose-a multidisciplinary team approach to medication error prevention. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG Arimura, J., Poole, R. L., Jeng, M., Rhine, W., Sharek, P. 2008; 13 (2): 96-98

    Abstract

    Despite the efforts of many hospitals, system failures can result in medication errors that may be life threatening. During 2006 and 2007, nine neonates received potentially fatal doses of heparin. This paper will review contributing factors to the heparin medication errors and ways to minimize the risk of heparin overdose.

    View details for DOI 10.5863/1551-6776-13.2.96

    View details for PubMedID 23055872

    View details for PubMedCentralID PMC3462065

  • A cluster-randomized trial of benchmarking and multimodal quality improvement to improve rates of survival free of bronchopulmonary dysplasia for infants with birth weights of less than 1250 grams PEDIATRICS Walsh, M., Laptook, A., Kazzi, S. N., Engle, W. A., Yao, Q., Rasmussen, M., Buchter, S., Heldt, G., Rhine, W., Higgins, R., Poole, K. 2007; 119 (5): 876-890

    Abstract

    We tested whether NICU teams trained in benchmarking and quality improvement would change practices and improve rates of survival without bronchopulmonary dysplasia in inborn neonates with birth weights of <1250 g.A cluster-randomized trial enrolled 4093 inborn neonates with birth weights of <1250 g at 17 centers of the National Institute of Child Health and Human Development Neonatal Research Network. Three centers were selected as best performers, and the remaining 14 centers were randomized to intervention or control. Changes in rates of survival free of bronchopulmonary dysplasia were compared between study year 1 and year 3.Intervention centers implemented potentially better practices successfully; changes included reduced oxygen saturation targets and reduced exposure to mechanical ventilation. Five of 7 intervention centers and 2 of 7 control centers implemented use of high-saturation alarms to reduce oxygen exposure. Lower oxygen saturation targets reduced oxygen levels in the first week of life. Despite these changes, rates of survival free of bronchopulmonary dysplasia were all similar between intervention and control groups and remained significantly less than the rate achieved in the best-performing centers (73.3%).In this cluster-randomized trial, benchmarking and multimodal quality improvement changed practices but did not reduce bronchopulmonary dysplasia rates.

    View details for DOI 10.1542/peds.2006-2656

    View details for Web of Science ID 000246153300002

    View details for PubMedID 17473087

  • The use of inhaled nitric oxide in the premature infant with respiratory distress syndrome. Minerva pediatrica Van Meurs, K., Hintz, S., Rhine, W., Benitz, W. 2006; 58 (5): 403-422

    Abstract

    The identification of the biologic properties of nitric oxide (NO) is one of the key scientific discoveries of the century, but its potential for treating human disease is yet to be fully realized. NO has a basic role in regulating vascular tone of the pulmonary circulation, and recent animal models have suggested a more wide reaching influence on perinatal lung development. In animal models, NO has effects on lung growth, angiogenesis, airway smooth muscle proliferation, vascular remodeling, surfactant function, inflammation, and pulmonary mechanics. However, despite extensive basic science investigation and completion of several large clinical trials, the role of NO in the treatment of the premature infant with respiratory distress syndrome remains unclear. One must conclude that the interaction of lung immaturity, ventilator and oxygen-induced lung injury, and NO biology in the premature newborn is incompletely understood. Clinical trial results of inhaled NO therapy in the premature infant are accumulating, but the results do not suggest a clear-cut advantage for the population at greatest risk for death and disability. Whether trial design, dose, duration of therapy, or other factors are responsible has not been determined. Further research is needed to answer these questions and more clearly define the population of premature infants who may derive benefit from this new therapy.

    View details for PubMedID 17008853

  • Eliminating nosocomial infections in the NICU: everyone's duty JOURNAL OF PERINATOLOGY Rhine, W. D. 2006; 26 (3): 141-143

    View details for DOI 10.1038/sj.jp.7211446

    View details for Web of Science ID 000241843100001

    View details for PubMedID 16493430

  • Implementing potentially better practices to reduce lung injury in neonates PEDIATRICS Burch, K., Rhine, W., Baker, R., Litman, F., Kaempf, J. W., Schwarz, E., Sun, S. Y., Payne, N. R., Sharek, P. J. 2003; 111 (4)

    Abstract

    Adherence to basic quality improvement principles enhances the implementation of potentially better practices (PBPs) and requires extensive planning and education. Even after PBPs have been identified and acknowledged as desirable, effective implementation of these practices does not occur easily. The objective of this study was to identify and assess implementation strategies that facilitate quality improvements in the respiratory care of extremely low birth weight infants.The 9 members of the Neonatal Intensive Care Quality Improvement Collaborative Year 2000 Reducing Lung Injury focus group identified 9 PBPs in a evidence-based manner to decrease chronic lung disease in extremely low birth weight newborns. Each site implemented several or all PBPs based on a site-specific selection process. Each site was asked to submit 1 or more examples of experiences that highlighted effective implementation strategies. This article reports these examples and emphasizes the principles on which they are based.The 9 participating institutions implemented a total of 57 PBPs (range: 1-9; median: 5). Including previous implementation, the 9 participating institutions implemented a total of 70 of a possible 81 PBPs before or during the study period (range: 5-9; median: 8). We report 7 approaches that facilitated PBP implementation: information availability, feedback, perseverance, collaboration, imitation, recognition of implementation complexity, and tracking of process indicators.Quality improvement efforts are enhanced by identifying and then implementing PBPs. In our experience, implementation of these PBPs can be difficult. Implementation strategies, such as those identified in this article, can improve the chances that quality improvement efforts will be effective.

    View details for Web of Science ID 000181960900006

    View details for PubMedID 12671163

  • Venoarterial versus venovenous extracorporeal membrane oxygenation in congenital diaphragmatic hernia: The Extracorporeal Life Support Organization Registry, 1990-1999 31st Annual Meeting of the Section-on-Surgery of the American-Academy-of-Pediatrics Dimmitt, R. A., Moss, R. L., Rhine, W. D., Benitz, W. E., Henry, M. C., VanMeurs, K. P. W B SAUNDERS CO-ELSEVIER INC. 2001: 1199–1204

    Abstract

    Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) traditionally has been the mode of support used in congenital diaphragmatic hernia (CDH). A few studies report success using venovenous (VV) ECMO. The purpose of this study is to compare outcomes in CDH patients treated with VA and VV.The authors queried the Extracorporeal Life Support Organization Registry for newborns with CDH treated with ECMO from January 1, 1990 through December 31, 1999. They analyzed the pre-ECMO data, ECMO course, and complications.VA was utilized in 2,257 (86%) and VV in 371 (14%) patients. The pre-ECMO status was similar, with greater use of nitric oxide, surfactant, and pressors in VV. Survival rate was similar (58.4% for VV and 52.2% for VA, P =.057). VA was associated with more seizures (12.3% v 6.7%, P =.0024) and cerebral infarction (10.5% v 6.7%, P =.03). Sixty-four treatments were converted from VV to VA (VV-->VA). Survival rate in VV-->VA was not significantly different than VA (43.8% v 52.2%, respectively; P =.23). VV-->VA and VA patients had similar neurologic complications.CDH patients treated with VV and VA have similar survival rates. VA had more neurologic complications. The authors identified no disadvantage to the use of VV as an initial mode of ECMO for CDH, although some infants may need conversion to VA.

    View details for DOI 10.1053/jpsu.2001.25762

    View details for PubMedID 11479856

  • Decreased use of neonatal extracorporeal membrane oxygenation (ECMO): How new treatment modalities have affected ECMO utilization PEDIATRICS Hintz, S. R., Suttner, D. M., Sheehan, A. M., Rhine, W. D., Van Meurs, K. P. 2000; 106 (6): 1339-1343

    Abstract

    Over the last decade, several new therapies, including high-frequency oscillatory ventilation (HFOV), exogenous surfactant therapy, and inhaled nitric oxide (iNO), have become available for the treatment of neonatal hypoxemic respiratory failure. The purpose of this retrospective study was to ascertain to what extent these modalities have impacted the use of neonatal extracorporeal membrane oxygenation (ECMO) at our institution.Patients from 2 time periods were evaluated: May 1, 1993 to November 1, 1994 (group 1) and May 1, 1996 to November 1, 1997 (group 2). During the first time period (group 1), HFOV was not consistently used; beractant (Survanta) use for meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN), and pneumonia was under investigation; and iNO was not yet available. During the second time period (group 2), HFOV and beractant treatment were considered to be standard therapies, and iNO was available to patients with oxygenation index (OI) >/=25 x 2 at least 30 minutes apart, or on compassionate use basis. Patients were included in the data collection if they met the following entry criteria: 1) OI >15 x 1 within the first 72 hours of admission; 2) EGA >/=35 weeks; 3) diagnosis of MAS, PPHN or sepsis/pneumonia; 4) <5 days of age on admission; and 5) no congenital heart disease, diaphragmatic hernia, or lethal congenital anomaly.Of the 49 patient in group 1, 21 (42.8%) required ECMO therapy. Of these ECMO patients, 14 (66.6%) had received diagnoses of MAS or PPHN. Only 3 of the patients that went on to ECMO received beractant before the initiation of bypass (14.3%). All ECMO patients in group 1 would have met criteria for iNO had it been available. Of all patients in group 1, 18 (36.7%) were treated with HFOV, and 13 (26.5%) received beractant. Of the 47 patients in group 2, only 13 (27.7%) required ECMO therapy (compared with group 1). Of these ECMO patients, only 5 (38.5%) had diagnoses of MAS or PPHN, with the majority of patients (61.5%) requiring ECMO for sepsis/pneumonia, with significant cardiovascular compromise. Only 5 of these ECMO patients, all outborn, did not receive iNO before cannulation because of the severity of their clinical status on admission. Of all patients in group 2, 41 (87.2%) were treated with HFOV (compared with group 1), 42 (89.3%) received beractant (compared with group 1), and 18 (44.7%) received iNO.The results indicate that ECMO was used less frequently when HFOV, beractant and iNO was more commonly used. The differences in treatment modalities used and subsequent use of ECMO were statistically significant. We speculate that, in this patient population, the diagnostic composition of neonatal ECMO patients has changed over time.

    View details for PubMedID 11099586

  • Tc-99m annexin V imaging of neonatal hypoxic brain injury STROKE D'Arceuil, H., Rhine, W., de Crespigny, A., Yenari, M., Tait, J. F., Strauss, W. H., Engelhorn, T., Kastrup, A., Moseley, M., Blankenberg, F. G. 2000; 31 (11): 2692-2699

    Abstract

    Delayed cell loss in neonates after cerebral hypoxic-ischemic injury (HII) is believed to be a major cause of cerebral palsy. In this study, we used radiolabeled annexin V, a marker of delayed cell loss (apoptosis), to image neonatal rabbits suffering from HII.Twenty-two neonatal New Zealand White rabbits had ligation of the right common carotid artery with reduction of inspired oxygen concentration to induce HII. Experimental animals (n=17) were exposed to hypoxia until an ipsilateral hemispheric decrease in the average diffusion coefficient occurred. After reversal of hypoxia and normalization of average diffusion coefficient values, experimental animals were injected with (99m)Tc annexin V. Radionuclide images were recorded 2 hours later.Experimental animals showed no MR evidence of blood-brain barrier breakdown or perfusion abnormalities after hypoxia. Annexin images demonstrated multifocal brain uptake in both hemispheres of experimental but not control animals. Histology of the brains from experimental animals demonstrated scattered pyknotic cortical and hippocampal neurons with cytoplasmic vacuolization of glial cells without evidence of apoptotic nuclei by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Double staining with markers of cell type and exogenous annexin V revealed that annexin V was localized in the cytoplasm of scattered neurons and astrocytes in experimental and, less commonly, control brains in the presence of an intact blood-brain barrier.Apoptosis may develop after HII even in brains that appear normal on diffusion-weighted and perfusion MR. These data suggest a role of radiolabeled annexin V screening of neonates at risk for the development of cerebral palsy.

    View details for PubMedID 11062296

  • Secondary infection presenting as recurrent pulmonary hypertension. Journal of perinatology Hintz, S. R., Benitz, W. E., Halamek, L. P., Van Meurs, K. P., Rhine, W. D. 2000; 20 (4): 262-264

    Abstract

    Primary infection in the neonate, especially group B streptococcal infection, has long been recognized as a cause of persistent pulmonary hypertension of the newborn (PPHN), sometimes requiring treatment with inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). However, secondary nosocomial infections in the neonatal period have not been widely reported as a cause of severe recurrent pulmonary hypertension (PHTN). We now present two cases of secondary infection in the neonate leading to significant PHTN. In both cases, the infants presented with PPHN soon after birth, requiring transfer to a level 3 neonatal intensive care unit and treatment with high-frequency oscillatory ventilation and iNO. After successful resolution of the initial PPHN, including extubation to nasal cannula, both infants developed signs of severe recurrent PHTN, leading to reintubation, high-frequency oscillatory ventilation and iNO therapy, and consideration of ECMO. In both cases, blood cultures taken at the time of recurrence of PHTN returned positive, one for Staphylococcus epidermidis, the other for methicillin-resistant Staphylococcus aureus. These unusual cases present the possibility of severe recurrent PHTN requiring iNO or ECMO in the setting of secondary infection. We speculate that these infants, although extubated after their first episodes of PHTN, were at risk for recurrence of PHTN due to continued pulmonary vascular reactivity.

    View details for PubMedID 10879342

  • Inhaled nitric oxide in term and near-term infants: Neurodevelopmental follow-up of The Neonatal Inhaled Nitric Oxide Study Group (NINOS) JOURNAL OF PEDIATRICS Finer, N. N., Vohr, B. R., Robertson, C. M., Ehrenkranz, R. A., Verter, J., Wright, L. L., Hoffman, H. J., Walsh-Sukys, M. C., Dusick, A. M., Fleisher, B. E., Steichen, J., Laadt, G., Yolton, K., Delaney-Black, V., Vohr, B. R., Whitfield, M. F., Blayney, M. P., Sauve, R. S., Casiro, O. G., Saigal, S., Riley, S. P., Robertson, C. M., Sankaran, K., Gosselin, R., Reynolds, A., Stork, E., Gorjanc, E., Verter, J., Powers, T., Sokol, G. M., Appel, D., Wright, L. L., Van Meurs, K., Rhine, W., Ball, B., Brilli, R., Moles, L., Crowley, M., Backstrom, C., Crouse, D., Hudson, T., Konduri, G. G., Bara, R., Kleinman, M., Hensmann, A., Rothstein, R. W., Ehrenkranz, R. A., Solimano, A., Germain, F., Walker, R., Ramirez, A. M., Singhal, N., Bourcier, L., Fajardo, C., Cook, V., Kirpalani, H., Monkman, S., Johnston, A., Mullahoo, K., Finer, N. N., Peliowski, A., Etches, P., Kamstra, B., Sankaran, K., Riehl, A., Blanchard, P., Gouin, R., Wearden, M. E., Gomez, M. R., Moon, Y. S., Avery, G. B., D'Alton, M. E., Bracken, M. B., Catz, C., Gleason, C. A., Maguire, M., Redmond, C. K., Sinclair, J. C., Verter, J. 2000; 136 (5): 611-617

    Abstract

    Inhaled nitric oxide (INO) improved oxygenation and reduced the occurrence of death or extracorporeal membrane oxygenation in term and near-term hypoxic neonates. We report the results of neurodevelopmental follow-up of infants enrolled in the NINOS trial.Hypoxic infants >/=34 weeks' gestation and <14 days of age were randomized to 20 ppm INO or 100% oxygen as control. Comprehensive neurodevelopmental assessment of survivors occurred at 18 to 24 months of age.A total of 235 infants were enrolled in the original trial. There were 36 deaths, 20 of 121 infants in the control group and 16 of 114 infants in the INO-treated group. Of the 199 surviving infants, 173 (86.9%) were seen for follow-up (88 members of the control group and 85 members of the INO-treated group), and 135 infants were normal (69 [79.3%] members of the control group and 66 [77.6%] members of the INO-treated group). Twenty-two infants had sensorineural hearing loss (12 members of the control group and 10 members of the INO-treated group). Moderate to severe cerebral palsy occurred in 13 infants (7 infants in the control group and 6 infants in the INO-treated group). Mental developmental index scores (87 +/- 18.7 in the control group vs 85 +/- 21.7 in the INO-treated group) and psychomotor developmental index scores (93.6 +/- 17.5 in the control group vs 85.7 +/- 21.2 in the INO-treated group) were not different. A total of 29.6% of the control group compared with 34.5% of the INO-treated group had at least one disability. Infants with congenital diaphragmatic hernia, enrolled in a separate but parallel trial, had similar outcomes with a higher incidence of sensorineural hearing loss.Inhaled nitric oxide is not associated with an increase in neurodevelopmental, behavioral, or medical abnormalities at 2 years of age.

    View details for Web of Science ID 000086985900011

    View details for PubMedID 10802492

  • Sonography, CT, and MR imaging: A prospective comparison of neonates with suspected intracranial ischemia and hemorrhage AMERICAN JOURNAL OF NEURORADIOLOGY Blankenberg, F. G., Loh, N. N., Bracci, P., D'Arceuil, H. E., Rhine, W. D., Norbash, A. M., Lane, B., Berg, A., Person, B., Coutant, M., Enzmann, D. R. 2000; 21 (1): 213-218

    Abstract

    Sonography, CT, and MR imaging are commonly used to screen for neonatal intracranial ischemia and hemorrhage, yet few studies have attempted to determine which imaging technique is best suited for this purpose. The goals of this study were to compare sonography with CT and MR imaging prospectively for the detection of intracranial ischemia or hemorrhage and to determine the prognostic value(s) of neuroimaging in neonates suspected of having hypoxic-ischemic injury (HII).Forty-seven neonates underwent CT (n = 26) or MR imaging (n = 24) or both (n = 3) within the first month of life for suspected HII. Sonography was performed according to research protocol within an average of 14.4 +/- 9.6 hours of CT or MR imaging. A kappa analysis of interobserver agreement was conducted using three independent observers. Infants underwent neurodevelopmental assessment at ages 2 months (n = 47) and 2 years (n = 26).CT and MR imaging had significantly higher interobserver agreement (P < .001) for cortical HII and germinal matrix hemorrhage (GMH) (Grades I and II) compared with sonography. MR imaging and CT revealed 25 instances of HII compared with 13 identified by sonography. MR imaging and CT also revealed 10 instances of intraparenchymal hemorrhage (>1 cm, including Grade IV GMH) compared with sonography, which depicted five. The negative predictive values of neuroimaging, irrespective of technique used, were 53.3% and 58.8% at the 2-month and 2-year follow-up examinations, respectively.CT and MR imaging have significantly better interobserver agreement for cortical HII and GMH/intraventricular hemorrhage and can reveal more instances of intraparenchymal hemorrhage compared with sonography. The absence of neuroimaging findings on sonograms, CT scans, or MR images does not rule out later neurologic dysfunction.

    View details for Web of Science ID 000085055900042

    View details for PubMedID 10669253

  • Serial magnetic resonance diffusion and hemodynamic imaging in a neonatal rabbit model of hypoxic-ischemic encephalopathy NMR IN BIOMEDICINE D'Arceuil, H. E., de Crespigny, A. J., Rother, J., Moseley, M., Rhine, W. 1999; 12 (8): 505-514

    Abstract

    Dynamic changes in relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were investigated, using high speed magnetic resonance imaging (MRI) in an acute neonatal rabbit model of hypoxic-ischemic encephalopathy (HIE). Serial rCBV imaging used a magnetic susceptibility blood pool contrast agent. Interleaved ADC and rCBV images were acquired with 9 s temporal resolution. Rabbits received unilateral common carotid artery (CCA) ligation followed by hypoxia. rCBV increased bilaterally within 1-2 min after the onset of hypoxia. A biphasic ADC decline was observed: a slowly declining phase (84 +/- 18% of baseline) followed by a rapid, focal drop to 55 +/- 8% of baseline in the ipsilateral cortex, which was paralleled by a rapid focal rCBV drop to 70 +/- 17% of baseline. ADC decline generally began in a small region of ipsilateral cortex and spread over the ipsilateral cortex, ipsilateral subcortical tissue and contralateral cortex. The initial ADC drop usually preceded the initial rCBV drop by approximately 60 s, however at later timepoints rCBV decline sometimes preceded ADC decline. Upon normoxia, rCBV recovered to about baseline values while ADC recovered to baseline or above. This method provides a sensitive means of non-invasively visualizing acute hemodynamic- and metabolic-related changes in HIE with good temporal and spatial resolution.

    View details for PubMedID 10668043

  • Bilirubin toxicity and differentiation of cultured astrocytes. Journal of perinatology Rhine, W. D., SCHMITTER, S. P., Yu, A. C., Eng, L. F., Stevenson, D. K. 1999; 19 (3): 206-211

    Abstract

    To study the toxicity of bilirubin in primary cultures of newborn rat cerebral cortical astrocytes.Primary cultures of newborn rat astrocytes were incubated at bilirubin concentrations of 0, 1, 5, 10, 25, 50, 100, 200, and 2000 microM, at a bilirubin:albumin molar ratio of 1.7. Bilirubin toxicity was determined by changes in cellular morphology, trypan blue staining, and lactate dehydrogenase (LDH) release into the culture medium at various times of incubation. To determine if differentiation of astrocytes affects bilirubin toxicity, cultures were treated with dibutyryl cyclic adenosine monophosphate.All three indices of toxicity showed a bilirubin concentration dependence. LDH release in experimental cultures was significantly elevated (p < 0.05) above that of control cultures by 24 hours at bilirubin concentrations of > or = 100 microM. The absolute amount of LDH release differed significantly between the 200 and 2000 microM cultures from 1.5 to 24 hours, after which duration of exposure appeared to take over and all cultures approached maximum. LDH release for the lower concentrations all reached maximum by 120 hours, except for the 1 microM cultures, which showed no significant elevation above control throughout the study period. At 100 and 200 microM bilirubin, LDH release by untreated cells was significantly higher (p < 0.05) than release by treated cells by 36 hours.Undifferentiated astrocytes appeared to be more sensitive to bilirubin toxicity, which may correlate with the greater susceptibility of newborns to kernicteric injury. Studies with primary astrocyte culture may provide insight into how bilirubin sensitivity changes with brain development as well as the cellular and biochemical mechanisms of bilirubin encephalopathy.

    View details for PubMedID 10685223

  • Inhaled nitric oxide for respiratory failure in pediatric patients Andrus, J. P., Derish, M. T., Rhine, W. D., Van Meurs, K. P. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1999: 37A
  • Strategy for lipid suppression in lactate imaging using STIR-DQCT: A study of hypoxic-ischemic brain injury MAGNETIC RESONANCE IN MEDICINE Nakai, T., Rhine, W. D., Okada, T., Stevenson, D. K., Spielman, D. M. 1998; 40 (4): 629-632

    Abstract

    In vivo lactate detection using gradient enhanced double quantum coherence transfer (DQCT) was significantly improved by addition of short-time-inversion-recovery (STIR). Phantom studies demonstrated lipid suppression down to the background noise level with 33% loss of lactate signal. In vivo studies using a rabbit model of hypoxic and unilateral-ischemic brain injury showed reduction down to 29 +/- 11% in lipids with inversion times between 140 and 170 ms. Lactate signals on the ischemic side were 51 +/- 53% higher than the nonischemic side at the peak of hypoxia. STIR-DQCT can be a useful robust method of obtaining metabolic maps of lactate in vivo.

    View details for PubMedID 9771580

  • Diffusion and perfusion magnetic resonance imaging of the evolution of hypoxic ischemic encephalopathy in the neonatal rabbit JOURNAL OF MAGNETIC RESONANCE IMAGING D'Arceuil, H. E., de Crespigny, A. J., Rother, J., Seri, S., Moseley, M. E., Stevenson, D. K., Rhine, W. 1998; 8 (4): 820-828

    Abstract

    Hypoxic-ischemic encephalopathy (HIE) can result from neonatal asphyxia, the pathophysiology of which is poorly understood. We studied the acute evolution of this disease, using magnetic resonance imaging in an established animal model. HIE was induced in neonatal rabbits by a combination of common carotid artery (CCA) ligation and hypoxia. Serial diffusion and perfusion-weighted magnetic resonance images were acquired before, during, and after the hypoxic interval. Focal areas of decreased apparent diffusion coefficient (ADC) were detected initially in the cortex ipsilateral to CCA ligation within 62 +/- 48 min from the onset of hypoxia. Subsequently, these areas of decreased ADC spread to the subcortical white matter, basal ganglia (ipsilateral side), and then to the contralateral side. Corresponding perfusion-weighted images showed relative cerebral blood volume deficits which closely matched those regions of ADC change. Our results show that MRI diffusion and perfusion-weighted imaging can detect acute cell swelling post-hypoxia in this HIE model.

    View details for PubMedID 9702883

  • Congenital diaphragmatic hernia associated with aortic coarctation 29th Annual Meeting of the Canadian-Association-of-Paediatric-Surgeons Eghtesady, P., Skarsgard, E. D., Smith, B. M., Robbins, R. C., Wexler, L., Rhine, W. D. W B SAUNDERS CO-ELSEVIER INC. 1998: 943–45

    Abstract

    Congenital diaphragmatic hernia (CDH) may be associated with other anomalies, most frequently cardiovascular in nature. Despite fetal echocardiography, diagnosis of an accompanying cardiac malformation often is not made until after birth and sometimes not until after extracorporeal membrane oxygenation (ECMO) has been instituted. Aortic coarctation associated with CDH may occur as an isolated, surgically correctable malformation or it may be a component of the usually fatal left heart "hypoplasia" or "smallness" syndrome. The authors present two cases of aortic coarctation associated with CDH requiring ECMO that illustrate the management challenges of these coincident diagnosis. In one case, the accompanying coarctation was suspected and required precannulation angiography for confirmation, whereas in the other case, the diagnosis of coarctation was not made until after ECMO cannulation. Depending on its anatomic location and severity, an aortic coarctation associated with life-threatening CDH may limit the physiological efficacy of venoarterial ECMO. Furthermore, arterial cannulation for extracorporeal support requires that flow through the remaining carotid artery be maintained during aortic reconstruction, which may prove difficult for lesions best treated by subclavian flap angioplasty. When the diagnosis of coincident aortic coarctation and CDH is suspected or proven before institution of extracorporeal support, serious consideration should be given to venovenous bypass, because this may provide better postductal oxygenation and facilitate aortic repair with the option of left carotid artery inflow occlusion.

    View details for Web of Science ID 000074327400034

    View details for PubMedID 9660236

  • Response of premature infants with severe respiratory failure to inhaled nitric oxide. Preemie NO Collaborative Group. Pediatric pulmonology Van Meurs, K. P., Rhine, W. D., Asselin, J. M., Durand, D. J. 1997; 24 (5): 319-323

    Abstract

    Elevated pulmonary vascular resistance is seen in premature infants with severe respiratory distress syndrome (RDS). Inhaled nitric oxide (NO) has been shown to decrease pulmonary vascular resistance and to improve oxygenation in some patients with respiratory failure. The purpose of this study was to determine whether premature infants with severe RDS would respond to inhaled NO with an improvement in oxygenation. Eleven premature infants (mean gestational age 29.8 weeks) with severe respiratory failure caused by RDS were treated with NO in four concentrations [1, 5, 10, 20 parts per million (ppm) NO] and with placebo (0 ppm NO). Arterial blood gas measurements were drawn immediately before and at the end of each of the 15-minute treatments and were used to determine the arterial/alveolar oxygen ratio (PaO2/PAO2). Ten of the 11 infants had a greater than 25% increase in PaO2/PAO2. Five of the 11 had a greater than 50% increase in PaO2/PAO2. Despite normal cranial ultrasound imaging prior to NO, 3 infants had intracranial hemorrhage (ICH) noted on their first ultrasound scan after this brief period of NO treatment, and 4 additional infants developed ICH later during their hospitalization. No infant had significant elevations of methemoglobin concentrations after the total 60-minute exposure to NO. NO may be an effective method of improving oxygenation in infants with severe RDS. The disturbing incidence of ICH in this small group of infants needs to be carefully evaluated before considering routine use or NO for preterm infants.

    View details for PubMedID 9407564

  • Response of premature infants with severe respiratory failure to inhaled nitric oxide 66th Annual Meeting of the Society-for-Pediatric-Research VanMeurs, K. P., Rhine, W. D., Asselin, J. M., Durand, D. J., Peverini, R., Dudell, G., Butler, S., Durand, D., Asselin, J., VANMEURS, K., Rhine, W. WILEY-LISS. 1997: 319–23

    Abstract

    Elevated pulmonary vascular resistance is seen in premature infants with severe respiratory distress syndrome (RDS). Inhaled nitric oxide (NO) has been shown to decrease pulmonary vascular resistance and to improve oxygenation in some patients with respiratory failure. The purpose of this study was to determine whether premature infants with severe RDS would respond to inhaled NO with an improvement in oxygenation. Eleven premature infants (mean gestational age 29.8 weeks) with severe respiratory failure caused by RDS were treated with NO in four concentrations [1, 5, 10, 20 parts per million (ppm) NO] and with placebo (0 ppm NO). Arterial blood gas measurements were drawn immediately before and at the end of each of the 15-minute treatments and were used to determine the arterial/alveolar oxygen ratio (PaO2/PAO2). Ten of the 11 infants had a greater than 25% increase in PaO2/PAO2. Five of the 11 had a greater than 50% increase in PaO2/PAO2. Despite normal cranial ultrasound imaging prior to NO, 3 infants had intracranial hemorrhage (ICH) noted on their first ultrasound scan after this brief period of NO treatment, and 4 additional infants developed ICH later during their hospitalization. No infant had significant elevations of methemoglobin concentrations after the total 60-minute exposure to NO. NO may be an effective method of improving oxygenation in infants with severe RDS. The disturbing incidence of ICH in this small group of infants needs to be carefully evaluated before considering routine use or NO for preterm infants.

    View details for Web of Science ID A1997YJ50900003

  • Hemopericardium from coronary artery laceration complicating extracorporeal membrane oxygenation. Journal of perinatology Rhine, W. D., Hartman, G. E., Shochat, S. J., Benitz, W. E., Van Meurs, K. P. 1997; 17 (3): 189-192

    Abstract

    We report the clinical course and successful surgical treatment of hemopericardium resulting from coronary artery (CA) laceration in two patients with congenital diaphragmatic hernia (CDH) undergoing extracorporeal membrane oxygenation (ECMO) bypass.Retrospective case review.Two neonates with CDH had needle aspiration for either pneumothorax or pericardial effusion before initiation of ECMO. While on bypass, progressive hemopericardium led to narrow pulse pressure and decreased venous return that limited bypass flow. Widened cardiac silhouette on chest radiographs suggested hemopericardium; echocardiography was confirmatory in one case. The underlying diagnosis of CA laceration was made during pericardiotomy and treated with surgical patching.Pre-ECMO history of cardiothoracic needle aspiration is important because complications such as hemothorax or hemopericardium may arise once ECMO bypass is initiated. Inadvertent CA laceration may lead to acute hemopericardium, compromising venous drainage. However, CA laceration can be successfully repaired while the patient is on bypass.

    View details for PubMedID 9210072

  • Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure NEW ENGLAND JOURNAL OF MEDICINE Stork, E., Gorjanc, E., Verter, J., Younes, N., Stenzel, B. A., Powers, T., Sokol, G., Wright, L. L., Yaffe, S. J., Catz, C., VANMEURS, K., Rhine, W., Ball, B., Brilli, R., Moles, L., Crowley, M., Backstrom, C., Crouse, D., Hudson, T., Konduri, G., Bara, R., Kleinman, M., Hensman, A., Rothstein, R. W., Ehrenkranz, R. A., Solimano, A., Germain, F., Walker, R., Ramirez, A. M., Singhal, N., Bourcier, L., Fajardo, C., Cook, V., Kirpalani, H., Monkman, S., Johnston, A., Mullahoo, K., Finer, N. N., Peliowski, A., Etches, P., Kamstra, B., Sankarhan, K., Riehl, A., Blanchard, P., Gouin, R., Wearden, M., Gomez, M., Moon, Y., Bauer, C. R., Donovan, E. F., Fanaroff, A. A., Korones, S. B., Lemons, J. A., Oh, W., Papile, L. A., Shankaran, S., Stoll, B. J., TYSON, J. E., Avery, G., DALTON, M., Bracken, M. B., Gleason, C. A., Maguire, M., Redmond, C., Silverman, W., Sinclair, J. 1997; 336 (9): 597-604
  • Nitrovasodilator therapy for severe respiratory distress syndrome. Journal of perinatology Benitz, W. E., Rhine, W. D., Van Meurs, K. P., Stevenson, D. K. 1996; 16 (6): 443-448

    Abstract

    Improved gas exchange in infants with severe respiratory distress syndrome has been reported in association with infusion of nitroprusside and during inhalation of nitric oxide. To evaluate the association between nitrovasodilator therapy and clinical improvement in premature neonates with severe respiratory distress syndrome, we reviewed the courses of 22 infants with severe respiratory distress syndrome who were treated with sodium nitroprusside for at least 24 hours. These infants had birth weights of 2049 +/- 828 gm (range 720 to 3430 gm), gestational ages of 32.5 +/- 3.5 weeks (range 25 to 38 weeks), high ventilator settings before treatment (FIO2 of 100%, peak inspiratory pressures of 37.8 +/- 6.1 cm H2O [range 30 to 50 cm H2O], and mean airway pressures of 18.0 +/- 3.3 cm H2O [range 12.3 to 26 cm H2O]), and low pretreatment PaO2 of 49.3 +/- 9.4 mm Hg (range 27 to 69 mm Hg). Baseline oxygenation indexes were 39.4 +/- 12.1 (range 18.6 to 66.7). Nitroprusside infusion was temporally associated with increased PaO2, decreased PaCO2, and reduced oxygenation index. Potentially beneficial changes were inconsistent in infants with pulmonary interstitial emphysema and were greatest in infants treated with end-expiratory pressures of at least 4 cm H2O. These observations provide a basis for the hypothesis that nitrovasodilator therapy produces improvement in gas exchange in premature infants with severe respiratory distress syndrome.

    View details for PubMedID 8979182

  • A model for detecting early metabolic changes in neonatal asphyxia by 1H-MRS JOURNAL OF MAGNETIC RESONANCE IMAGING Nakai, T., Rhine, W. D., Enzmann, D. R., Stevenson, D. K., Spielman, D. M. 1996; 6 (3): 445-452

    Abstract

    In newborn rabbits, the early cerebral metabolic changes caused by hypoxic-ischemic (H-I) insult was examined by using volume localized 1H-MRS (STEAM). Partial ischemia was caused by unilateral carotid artery ligation, and hypoxia was induced by 10% oxygen inspiration for 150 minutes. Lactate immediately increased after hypoxia induction and almost disappeared 120 to 150 minutes after removal of hypoxia in both H-I and hypoxia-only experiments. Lactate production correlated well with decrease of the blood oxygen saturation. More lactate was produced on ischemic side 50 minutes post-hypoxia induction in H-I study. Ischemia alone did not cause any significant lactate production. Lactate caused by hypoxia can be dynamically monitored by localized 1H-MRS. Existence of regional ischemia can induce greater anaerobic glycolysis and may affect the pattern of brain injury under hypoxia. 1H-MRS is a sensitive tool to detect the acute metabolic change caused by H-I insult.

    View details for PubMedID 8724409

  • NEONATAL JAUNDICE - WHAT NOW CLINICAL PEDIATRICS Dennery, P. A., Rhine, W. D., Stevenson, D. K. 1995; 34 (2): 103-107

    View details for PubMedID 7729104

  • LOBAR LUNG TRANSPLANTATION AS A TREATMENT FOR CONGENITAL DIAPHRAGMATIC-HERNIA JOURNAL OF PEDIATRIC SURGERY VanMeurs, K. P., Rhine, W. D., Benitz, W. E., Shochat, S. J., Hartman, G. E., Sheehan, A. M., Starnes, V. A. 1994; 29 (12): 1557-1560

    Abstract

    The mortality rate for infants severely affected with congenital diaphragmatic hernia (CDH) remains high despite significant advances in surgical and neonatal intensive care including delayed repair and extracorporeal membrane oxygenation (ECMO). Because of the increasingly successful experience with single-lung transplantation in adults; this approach has been suggested as a potential treatment for CDH infants with unsalvageable pulmonary hypoplasia. The authors report on a newborn female infant who was the product of a pregnancy complicated by polyhydramnios. At birth, she was found to have a right-sided CDH and initially was treated with preoperative ECMO, followed by delayed surgical repair. Despite the CDH repair and apparent resolution of pulmonary hypertension, the infant's condition deteriorated gradually after decannulation, and escalating ventilator settings were required as well as neuromuscular paralysis and pressor support because of progressive hypoxemia and hypercarbia. A lung transplant was performed 8 days after decannulation, using the right lung obtained from a 6-week-old donor. The right middle lobe was excised because of the size discrepancy between the donor and recipient. After transplantation, the patient was found to have duodenal stenosis and gastroesophageal reflux, which required duodenoduodenostomy and fundoplication. The patient was discharged from the hospital 90 days posttransplantation, at 3 1/2 months of age. Currently she is 24 months old and doing well except for poor growth. This case shows the feasibility of single-lung transplantation for infants with CDH, and the potential use of ECMO as a temporary bridge to transplantation. Lobar lung transplantation allowed for less stringent size constraints for the donor lung.

    View details for Web of Science ID A1994PW61200018

    View details for PubMedID 7877027

  • INTRACRANIAL ABNORMALITIES AND NEURODEVELOPMENTAL STATUS AFTER VENOVENOUS EXTRACORPOREAL MEMBRANE-OXYGENATION JOURNAL OF PEDIATRICS VanMeurs, K. P., Nguyen, H. T., Rhine, W. D., Marks, M. P., Fleisher, B. E., Benitz, W. E. 1994; 125 (2): 304-307

    Abstract

    Computed tomography scans of the head and early neurodevelopmental assessment (Bayley Scales of Infant development) were recorded for 24 surviving infants who received venovenous extracorporeal membrane oxygenation and were compared with those of infants treated with venoarterial bypass matched by diagnosis and oxygenation index before extracorporeal membrane oxygenation. A comparable neuroradiographic and early neurodevelopmental outcome was documented for survivors of venoarterial and venovenous extracorporeal membrane oxygenation.

    View details for Web of Science ID A1994PA95200025

    View details for PubMedID 8040782

  • MAGNETIC-RESONANCE (MR) DIFFUSION AND PERFUSION IMAGING STUDIES OF IMMATURE RABBIT HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE) RHINE, W. D., DECRESPIGNY, A., PELC, L. R., MOSELEY, M. E., STEVENSON, D. K. WILLIAMS & WILKINS. 1994: A386
  • GD-DTPA MR DETECTION OF BLOOD-BRAIN-BARRIER OPENING IN RATS AFTER HYPEROSOMOTIC SHOCK JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY Rhine, W. D., Benaron, D. A., Enzmann, D. R., Chung, C., GONZALESMENDEZ, R., Sayre, J. R., Stevenson, D. K. 1993; 17 (4): 563-566

    Abstract

    Detection of blood-brain barrier (BBB) opening in neonates has required invasive methods not clinically applicable. We set out to develop a noninvasive approach to detect such opening.Wistar rats were studied using MRI with Gd-DTPA contrast before and after injection of hyperosmotic solutions known to produce barrier opening. Arabinose was given via right carotid artery to produce unilateral barrier opening; urea was given via tail vein to produce bilateral opening; controls received normal saline. Next, all animals received Gd-DTPA via tail vein.Animals receiving carotid hyperosmotic injections showed increased signal in the ipsilateral brain hemisphere; those receiving venous hyperosmotic injections showed increased signal bilaterally. Similar increases were not found prior to administration of hyperosmotic agent or in saline controls. In both cases, barrier opening was detectable using the relative partitioning of Gd-DTPA between intrabarrier and extrabarrier structures, even in the absence of a hemispheric control.We conclude that MRI with Gd-DTPA contrast allows noninvasive detection of BBB opening in the rat.

    View details for PubMedID 8331226

  • BRAIN-STEM BILIRUBIN TOXICITY IN THE NEWBORN PRIMATE MAY BE PROMOTED AND REVERSED BY MODULATING PCO2 PEDIATRIC RESEARCH Wennberg, R. P., Gospe, S. M., Rhine, W. D., Seyal, M., Saeed, D., Sosa, G. 1993; 34 (1): 6-9

    Abstract

    The auditory brainstem response (ABR) was monitored during infusion of bilirubin in six ventilated newborn rhesus monkeys (138-145 d gestation) while acute changes in pH were produced by varying inspired CO2. Prolonged respiratory acidosis without bilirubin infusion produced minimal changes in the ABR (one animal). CO2 exposure, usually initiated when the bilirubin level reached approximately 20 mg/dL, decreased arterial pH to values ranging from 6.85 to 7.10. ABR changes, including prolongation of the wave II-IV peak to peak intervals and decreased wave amplitudes, first developed 2-4 h after initial exposure to CO2. Total and unbound bilirubin levels at this time ranged from 376 to 564 mumol/L (22-33 mg/dL) and 38 to 65 nmol/L (2.5-3.8 micrograms/dL), respectively. Correction of respiratory acidosis produced partial to complete reversal of ABR changes within 3 to 20 min. Reexposure to CO2 immediately reproduced the ABR abnormality. Production and reversal of the abnormal ABR was obtained through two to three cycles in three animals. Thus, when the brainstem bilirubin level was near the threshold for toxicity, the effect of changes in PCO2 on the ABR were immediate, suggesting that auditory pathway toxicity is initially mediated by a reversible pH-dependent bilirubin-membrane complex. In contrast to humans, in monkeys auditory toxicity appeared to be a late manifestation of bilirubin toxicity, inasmuch as all monkeys were obtunded and apneic 30-70 min before ABR abnormalities appeared. Notwithstanding these limitations, the results support the hypothesis that bilirubin toxicity can be both promoted and reversed by modulating brain pH.

    View details for Web of Science ID A1993LJ67900002

    View details for PubMedID 8356020

  • ANTICOAGULATION THERAPY ADVISER - A DECISION-SUPPORT SYSTEM FOR HEPARIN-THERAPY DURING ECMO 16th Annual Symposium on Computer Applications in Medical Care Peverini, R. L., Sale, M., Rhine, W. D., Fagan, L. M., Lenert, L. A. MCGRAW-HILL BOOK CO. 1993: 567–578
  • Where should the hemofiltration circuit be placed in relation to the extracorporeal membrane oxygenation circuit? ASAIO journal Yorgin, P. D., Kirpekar, R., Rhine, W. D. 1992; 38 (4): 801-803

    Abstract

    Patients requiring extracorporeal membrane oxygenation (ECMO) frequently experience hypervolemia and metabolic abnormalities that can be effectively managed by hemofiltration. Although several options for hemofiltration circuit placement exist, some may have the disadvantage of recirculation or shunting of poorly oxygenated blood to the patient. Attachment of the entire hemofiltration circuit to the pre-ECMO pump region is described. Despite the absence of pump generated pressure and a low blood flow rate, effective hemofiltration and diafiltration were achieved. This article examines whether placement of the hemofiltration circuit proximal to the ECMO pump has advantages over other hemofiltration circuit placements.

    View details for PubMedID 1450474

  • Anticoagulation therapy advisor: a decision-support system for heparin therapy during ECMO. Proceedings / the ... Annual Symposium on Computer Application [sic] in Medical Care. Symposium on Computer Applications in Medical Care Peverini, R. L., Sale, M., Rhine, W. D., Fagan, L. M., Lenert, L. A. 1992: 567-571

    Abstract

    We present a case study describing our development of a mathematical model to control a clinical parameter in a patient--in this case, the degree of anticoagulation during extracorporeal membrane oxygenation (ECMO) support. During ECMO therapy, an anticoagulant agent (heparin) is administered to prevent thrombosis. Under- or over-coagulation can have grave consequences. To improve control of anticoagulation, we developed a pharmacokinetic-pharmacodynamic (PK-PD) model that predicts activated clotting times (ACT) using the NONMEM program. We then integrated this model into a decision-support system, and validated it with an independent data set. The population model had a mean absolute error of prediction for ACT values of 33.5 seconds, with a mean bias in estimation of -14.3 seconds. Individualization of model-parameter estimates using nonlinear regression improved the absolute error prediction to 25.5 seconds, and lowered the mean bias to -3.1 seconds. The PK-PD model is coupled with software for heuristic interpretation of model results to provide a complete environment for the management of anticoagulation.

    View details for PubMedID 1482937

  • Fatal postoperative Legionella pneumonia in a newborn. Journal of perinatology Greene, K. A., Rhine, W. D., Starnes, V. A., Ariagno, R. L. 1990; 10 (2): 183-184

    Abstract

    This is a case of postoperative Legionella pneumonia in a full-term infant with hypoplastic left heart syndrome. The infant had an uncomplicated prenatal history, normal vaginal delivery, Apgars of 8 at 1 and 5 minutes, but was cyanotic at birth. At 3 days of age she had a stage 1 Norwood surgical procedure to palliate her congenital heart disease. A synthetic patch was placed over the thoracic midline because of difficulty in reapposing the sternum. Peritoneal dialysis was used to manage renal failure. At 20 days of age she had disseminated intravascular coagulopathy and pneumonia associated with sepsis. Four days later she died. Legionella pneumophila serogroup 1 was isolated from a lung culture taken at autopsy.

    View details for PubMedID 2358903

  • NEONATAL ASPERGILLOSIS - A CASE-REPORT AND REVIEW OF THE LITERATURE CLINICAL PEDIATRICS Rhine, W. D., Arvin, A. M., Stevenson, D. K. 1986; 25 (8): 400-403

    Abstract

    Neonatal aspergillosis is a rare, usually overwhelming multisystem infection diagnosed postmortem. We present a neonate who had a brain abscess diagnosed by CT scan that was found at surgical exploration to contain aspergillus. Treatment included prolonged antifungal medication and several surgical interventions. The child has neurologic sequelae, including a seizure disorder and hemiplegia. There are no previously reported survivors of neonatal aspergillosis.

    View details for Web of Science ID A1986D516900004

    View details for PubMedID 3731668

  • SCHISTOSOMA-MANSONI - REPRODUCTIVE POTENTIAL OF MALE AND FEMALE WORMS CULTURED INVITRO JOURNAL OF PARASITOLOGY Basch, P. F., Rhine, W. D. 1983; 69 (3): 567-569

    Abstract

    We studied the development of S. mansoni after various combinations of ex-vivo, cultured, and unisexual male and female worms were implanted into hamsters. Females of any type, co-implanted with ex-vivo males, were capable of developing to maturity and producing eggs containing viable miracidia. Cultured males often did not induce adequate growth and maturation of females, but viable miracidia were produced in some animals co-implanted with cultured males plus cultured, ex-vivo, or unisexual females. We concluded that both cultured males and females have the potential for full growth and reproductive maturation, but are retarded in vitro by inadequate culture conditions.

    View details for Web of Science ID A1983RP33400018

    View details for PubMedID 6631628