Implicit Racial Bias in Evaluation of Neonatal Opioid Withdrawal Syndrome.

OBJECTIVE: To assess implicit bias by administrating the Modified Finnegan Score (MFS) for quantifying neonatal opioid withdrawal and to evaluate risk of decreased opioid treatment of Black versus White infants. STUDY DESIGN: Study participants were nurses recruited from a large tertiary care center who received three clinical vignettes portraying withdrawing infants and were randomized to receive an accompanying photo of either a Black or White infant. MFS results were compared for identical vignettes based on race of infant photo. RESULTS: Out of 275 nurses, 70 completed the survey. In vignette 2, nurses aged ≤35 years scored Black infants lower than White infants (MFS=8.3 ± 2 vs. 9.5 ± 1.2, p=0.012). Nurses with <5 years of experience and ≤10 years of experience also scored Black infants lower for the same vignette (8.2 ± 2.3 vs. 9.6 ± 1.2, p=0.032 and 8.3 ± 2 vs. 9.5 ± 1.2, p=0.0083). CONCLUSION: Implicit bias may contribute to the difference in opioid treatment.

Impact of Routine Gastric Aspirate Monitoring on Very Low Birth Weight Early Preterm Infants.

OBJECTIVES: Routine gastric aspirate (RGA) monitoring is a common yet controversial practice intended for early identification of gastrointestinal pathology in infants receiving gavage feeds. Our objectives were to evaluate the association of ceasing RGA monitoring on the incidence of necrotizing enterocolitis (NEC) as well as nutritional outcomes in a large population of very low birth weight (VLBW) and very preterm neonates. METHODS: Retrospective record review of neonates born ≤32 weeks and/or VLBW from 2 cohorts: (1) during pre-feed RGA monitoring (September 2015 to June 2018) and (2) after cessation of RGA ("non-RGA") monitoring (July 2018 to December 2020). We compared incidence of NEC, time-to-full enteral feeds, central line duration, and duration of parenteral nutrition (PN) in bivariate and multivariable models accounting for changes in feeding protocols over time. RESULTS: We identified 617 subjects, 53% in the RGA monitoring cohort (n = 327) and 47% in non-RGA cohort (n = 290). The non-RGA cohort had feeds initiated earlier ( P < 0.0001), achieved full enteral feeds more rapidly ( P < 0.0001), received a shorter duration of PN ( P = 0.0003), and had shorter central access duration ( P < 0.0001) without increasing NEC risk. In fact, the non-RGA cohort had a lower incidence of NEC ( P = 0.0345) compared to the RGA cohort. Even after adjusting for changes in feeding protocols over time in a multivariable model, the RGA cohort had significantly higher odds of NEC. CONCLUSIONS: Pre-feed RGA monitoring in the absence of concerning clinical exam findings is not indicated for neonates receiving gavage feeds as it does not improve NEC incidence but instead may delay important nutritional outcomes such as feed initiation and central line removal.

Predicting the likelihood of lower respiratory tract Ureaplasma infection in preterms.

OBJECTIVE: To develop predictive models of Ureaplasma spp lower airway tract infection in preterm infants. METHODS: A dataset was assembled from five cohorts of infants born <33 weeks gestational age (GA) enrolled over 17 years (1999-2016) with culture and/or PCR-confirmed tracheal aspirate Ureaplasma status in the first week of life (n=415). Seventeen demographic, obstetric and neonatal factors were analysed including admission white blood cell (WBC) counts. Best subset regression was used to develop three risk scores for lower airway Ureaplasma infection: (1) including admission laboratory values, (2) excluding admission laboratory values and (3) using only data known prenatally. RESULTS: GA and rupture of membranes >72 hours were significant predictors in all 3 models. When all variables including admission laboratory values were included in the regression, WBC count was also predictive in the resulting model. When laboratory values were excluded, delivery route was found to be an additional predictive factor. The area under the curve for the receiver operating characteristic indicated high predictive ability of each model to identify infants with lower airway Ureaplasma infection (range 0.73-0.77). CONCLUSION: We developed predictive models based on clinical and limited laboratory information available in the perinatal period that can distinguish between low risk (<10%) and high risk (>40%) of lower airway Ureaplasma infection. These may be useful in the design of phase III trials of therapeutic interventions to prevent Ureaplasma-mediated lung disease in preterm infants and in clinical management of at-risk infants.

Novel uses of ketamine in the emergency department.

INTRODUCTION: Ketamine is gaining renewed interest among healthcare providers in the emergency department (ED) setting due to its novel clinical applications. AREAS COVERED: This article provides a comprehensive discussion of ketamine's pharmacological properties, safety profile, and an overview of current evidence for ketamine in the management of ED patients with acute agitation, pain, depression/suicide ideation. EXPERT OPINION: Ketamine is an effective adjunct to opioids, providing greater pain relief than morphine alone. Ketamine (0.1-0.3 mg/kg IV) alone can provide analgesia similar to that of morphine in patients with acute visceral and musculoskeletal pain, as well as for chronic painful conditions (cancer, vaso-occlusive pain crisis associated with sickle cell disease, and in patients with high opioid tolerance and/or opioid dependency). Available literature shows that ketamine (1-2 mg/kg IV or 4-5 mg/kg IM) is a safe, rapid (<5 minutes) and effective tranquilization agent for ED patients with acute agitation. Finally, there is growing evidence that suggests ketamine may have potential utility in the management of patients with self-harm ideation or acute depressive episodes. Intravenous infusion of ketamine (0.5 mg/kg over 40 mins) has been shown to produce an antidepressant effect and decrease in suicidal ideation within 4 hours with effects lasting up to one week.

A hospital-based multidimensional intervention for high risk pediatric patients with asthma.

OBJECTIVE: To determine the effects of a multi-dimensional intervention (consisting of education, recommendations for medical management, and short-term case management) provided by pulmonology nurse practitioners(NP) on inpatient and post-discharge outcomes for patients admitted with asthma exacerbations to a Pediatric Intensive Care Unit(PICU). METHODS: A retrospective cohort study was completed on subjects with an asthma exacerbation admitted to the PICU from 1 January 2015 to 31 December 2018. Records were reviewed for 12-months post-discharge. We compared inpatient and post-discharge outcomes for those who did vs. did not receive NP consultation. The primary outcome evaluated was optimization of discharge medications. Rates of follow up, repeat ED visits and hospitalizations were also reviewed. RESULTS: Two hundred and twenty two subjects met inclusion and exclusion criteria; of those, 101 (45.5%) patients received NP consultation and 121 (54.5%) had PICU management only. Patients with NP consultation were more likely to have controllers initiated (34.6% vs. 15%) or adjusted (55.5% vs. 33.3%) per asthma guidelines (p < 0.001). The consult group were more likely to have an asthma follow-up appointment made prior to discharge (99% vs. 45%, p < 0.001), and were more likely to attend the appointment (51% vs. 21%, p < 0.001). There were no significant differences between groups for ED visits or readmission for asthma 12-months post-discharge. CONCLUSIONS: Patients with NP consultation were more likely to have controllers started or adjusted per guidelines and were more likely to attend specialty follow-up appointments post-discharge. No impact was seen on ED visits or readmissions. Implementation of such a program may aid in optimizing asthma management and continuity of care post hospitalization.

Randomized trial of azithromycin to eradicate Ureaplasma respiratory colonization in preterm infants: 2-year outcomes.

BACKGROUND: To assess the potential impact of azithromycin treatment in the first week following birth on 2-year outcomes in preterm infants with and without Ureaplasma respiratory colonization who participated in a double-blind, placebo-controlled randomized controlled trial. METHODS: Respiratory morbidity was assessed at NICU discharge and at 6, 12, and 22-26 months corrected age using pulmonary questionnaires. Comprehensive neurodevelopmental assessments were completed between 22 and 26 months corrected age. The primary and secondary composite outcomes were death or severe respiratory morbidity and death or moderate-severe neurodevelopmental impairment, respectively, at 22-26 months corrected age. RESULTS: One hundred and twenty-one randomized participants (azithromycin, N = 60; placebo, N = 61) were included in the intent-to-treat analysis. There were no significant differences in death or serious respiratory morbidity (34.8 vs 30.4%, p = 0.67) or death or moderate-severe neurodevelopmental impairment (47 vs 33%, p = 0.11) between the azithromycin and placebo groups. Among all trial participants, tracheal aspirate Ureaplasma-positive infants experienced a higher frequency of death or serious respiratory morbidity at 22-26 months corrected age (58%) than tracheal aspirate Ureaplasma-negative infants (34%) or non-intubated infants (21%) (p = 0.028). CONCLUSIONS: We did not observe strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes in preterm infants treated with azithromycin in the first week of life compared to placebo. IMPACT: No strong evidence of a difference in long-term pulmonary and neurodevelopment outcomes was identified at 22-26 months corrected age in infants treated with azithromycin in the first week of life compared to placebo. The RCT is the first study of 2-year pulmonary and neurodevelopmental outcomes of azithromycin treatment in ELGANs. Provides evidence that ELGANs with lower respiratory tract Ureaplasma have the most frequent serious respiratory morbidity in the first 2 years of life, suggesting that a Phase III trial of azithromycin to prevent BPD targeting this population is warranted.

A Multi-Modal Curriculum Teaching Opioid Use Disorder Management in Young Adult Populations.

BACKGROUND: The use of both prescription and illicit opioids among adolescents and young adults (AYA) is increasing. Barriers to effective treatment of opioid use disorders among AYA range from patients leaving against medical advice to decreased knowledge and experience of providers caring for those with opioid dependence. No formal curricula for residents on AYA opioid use disorder and management have been implemented despite rapidly increasing use in this population. OBJECTIVE: To develop a brief curriculum for trainees who encounter AYA that will increase knowledge and skills to treat opioid use in the AYA population.  Methods: Twenty-six pediatric and family medicine interns participated in this pilot study. The multimodal curriculum included standardized patient encounters, case-based learning sessions, didactics, and high-fidelity simulations. The curriculum encompasses five individual sessions, each with a different theme: motivational interviewing, naloxone administration, opioid withdrawal medications, complex overdoses, and infectious complications of intravenous drug use. A pre-survey was administered prior to the curriculum and a post-survey was administered at the conclusion to assess its effectiveness in improving knowledge for this specific population and increasing comfort levels providing medical interventions in AYA patients with opioid use disorders. RESULTS: Trainee comfort levels increased significantly in all four domains as measured by the average Likert scale, including interviewing AYA about opioid use (2.5 (standard deviation (SD) 1.2) to 4 (SD 0.9), p<0.0001)), prescribing medication for opioid use disorder (1.3 (SD 0.5) to 2.8 (SD 1.3), p<0.0001)), treating acute opioid overdose (1.5 (SD 0.8) to 3.7 (SD 0.9), p<0.0001)), and treating infectious complications of intravenous drug use (1.7 (SD 0.8) to 3 (SD 1.1), p <0.0001)). The Chi-square test showed similarly significant increases in comfort levels. CONCLUSIONS: Early trainees who provide care to young adults benefit from opioid education specific to this population. Participants described increased knowledge and comfort in interviewing and treating this vulnerable patient group.

Quantifying Medication Exposure in Very Low Birth Weight Neonates.

OBJECTIVE: Very low birth weight (VLBW) infants are exposed to medications with insufficient evidence describing pharmacokinetics and safety. Objective was to quantify and identify risk factors associated with the highest quartile of medication exposure. STUDY DESIGN: Retrospective record review of VLBW infants admitted to a level-IV neonatal intensive care unit (NICU). We obtained baseline clinical and demographic characteristics, as well as data on all medications received during admission. Characteristics of patients within the upper quartile of medication use were compared with remaining patients. RESULTS: Identified 106 infants, mean birth weight (BW) = 961 g, gestational age = 27.3 weeks. Infants received a median = 20 medications (range, 4-72). Those in the top quartile of medication use received ≥30 medications while in the NICU and had higher odds of being male sex, lower BW, longer length of hospital stay (LOHS), and bronchopulmonary dysplasia. Sepsis did not affect medication exposure. Antibiotics, opiates, and reflux medications were among the top prescribed. CONCLUSION: Infants are exposed to a large number of medications during NICU hospitalization, including potentially unnecessary antibiotics and reflux medications. Male sex, the presence of certain comorbidities such as necrotizing enterocolitis, and LOHS, are associated with higher exposure. Increased awareness of this issue may assist in decreasing medication exposure in VLBW populations.

A National Survey of Car Seat Tolerance Screening Protocols in Neonatal Intensive Care Units.

OBJECTIVE: A predischarge car seat tolerance screen (CSTS) is currently recommended for all infants born prematurely in the United States to monitor for adverse cardiorespiratory events while in the semi-upright car seat. However, specific guidelines for failure criteria, timing of testing, and follow-up of failed CSTS do not exist. Our objective was to perform a national survey of neonatal intensive care units (NICUs) in order to identify common features and variation in CSTS protocols. METHODS: We surveyed Level II-IV NICUs representing all 50 states to determine whether each performed CSTS, inclusion and failure criteria, timing of CSTS prior to discharge and in relation to feeds, follow-up of initial and subsequent CSTS failures, use of car beds, and outpatient referrals after failed CSTS. RESULTS: Of the 199 NICUs surveyed, 96.5% perform a CSTS. The most common failure saturation cutoff was <90%, but values ranged from <80% to <92%. The most common failure bradycardia definition was <80 bpm but ranged from <70 bpm to <100 bpm. After an initial failed CSTS, 86.5% will perform a repeat CSTS after a period of observation that ranged from <12 hours to 3 or more days. When discharging in a car bed, 20% do not routinely perform a car bed test, and >70% refer only to the primary care physician for car bed follow-up. CONCLUSIONS: Despite widespread implementation, significant variation exists in CSTS protocols and follow-up after NICU discharge. A stronger evidence base is needed to define appropriate testing parameters and inform more explicit guidelines.

Variation in Car Seat Tolerance Screen Performance in Newborn Nurseries.

BACKGROUND: Currently, car seat tolerance screens (CSTSs) are recommended for all infants born prematurely in the United States. Although many late-preterm infants are cared for exclusively in newborn nurseries (NBNs), data on implementation of CSTS in nurseries are limited. Our objective for this study was to determine management strategies and potential variation in practice of CSTS in NBNs across the nation. METHODS: We surveyed NBNs across 35 states using the Better Outcomes through Research for Newborns (BORN) network to determine what percentage perform CSTSs, inclusion and failure criteria, performance characteristics, follow-up of failed CSTSs including use of car beds, and provider attitudes toward CSTS. RESULTS: Of the 84 NBNs surveyed, 90.5% performed predischarge CSTSs. The most common failure criteria were saturation <90%, bradycardia <80 beats per minute, and apnea >20 seconds. More than 55% noted hypotonia as an additional inclusion criterion for testing, and >34% tested any infant who had ever required supplemental oxygen. After an initial failed CSTS, >93% of NBNs retested in a car seat at a future time point, whereas only ∼1% automatically discharged infants in a car bed. When asked which infants should undergo predischarge CSTS, the most common recommendations by survey respondents included infants with hypotonia (83%), airway malformations (78%), hemodynamically significant congenital heart disease (63%), and prematurity (61%). CONCLUSIONS: There is a large degree of variability in implementation of CSTS in NBNs across the United States. Further guidance on screening practices and failure criteria is needed to inform future practice and policy.

Patient and provider factors impacting referral for neonatal organ donation.

BACKGROUND: As determination of brain death is infrequent in neonates, the AAP endorses donation after circulatory determination of death as an acceptable alternative. Despite this recommendation, neonatal organ donation is infrequent. Timely referral to OPOs is a vital first step in the organ donation process. The aim of this study was to identify patient and provider factors impacting timely referral for neonatal organ donation. METHODS: Medical records were reviewed for deaths occurring in a Level IV NICU from 2007 to 2017. Clinical and demographic factors, provider type, timing of OPO referral (before or after death), and outcome were assessed. Bivariate and multivariable logistic regression models were utilized to identify predictors of OPO referral characteristics. RESULTS: Between 2007 and 2017, 329 deaths occurred in the NICU or delivery room. Of the 265 infants meeting inclusion criteria, 96% had late referrals (after death) and were declined for organ donation. Frequency of timely referrals (before death) improved when OPO contact was by an attending neonatologist, when withdrawal of life support was planned, and with increasing birthweight, gestational age, and PMA. Factors associated with decreased OPO referral included male sex, lower weight at death, earlier PMA, and deaths occurring while receiving maximal intensive care support. No organs or tissues were donated. CONCLUSIONS: This study is the first to report NICU referral patterns for organ donation. We found that timely provider referral of neonates to the OPO was rare. Exploration of provider knowledge will guide future educational interventions aimed to improve the referral process.

Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants.

OBJECTIVE: To test whether azithromycin eradicates Ureaplasma from the respiratory tract in preterm infants. DESIGN: Prospective, phase IIb randomised, double-blind, placebo-controlled trial. SETTING: Seven level III-IV US, academic, neonatal intensive care units (NICUs). PATIENTS: Infants 240-286 weeks' gestation (stratified 240-266; 270-286 weeks) randomly assigned within 4 days following birth from July 2013 to August 2016. INTERVENTIONS: Intravenous azithromycin 20 mg/kg or an equal volume of D5W (placebo) every 24 hours for 3 days. MAIN OUTCOME MEASURES: The primary efficacy outcome was Ureaplasma-free survival. Secondary outcomes were all-cause mortality, Ureaplasma clearance, physiological bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age, comorbidities of prematurity and duration of respiratory support. RESULTS: One hundred and twenty-one randomised participants (azithromycin: n=60; placebo: n=61) were included in the intent-to-treat analysis (mean gestational age 26.2±1.4 weeks). Forty-four of 121 participants (36%) were Ureaplasma positive (azithromycin: n=19; placebo: n=25). Ureaplasma-free survival was 55/60 (92% (95% CI 82% to 97%)) for azithromycin compared with 37/61 (61% (95% CI 48% to 73%)) for placebo. Mortality was similar comparing the two treatment groups (5/60 (8%) vs 6/61 (10%)). Azithromycin effectively eradicated Ureaplasma in all azithromycin-assigned colonised infants, but 21/25 (84%) Ureaplasma-colonised participants receiving placebo were culture positive at one or more follow-up timepoints. Most of the neonatal mortality and morbidity was concentrated in 21 infants with lower respiratory tract Ureaplasma colonisation. In a subgroup analysis, physiological BPD-free survival was 5/10 (50%) (95% CI 19% to 81%) among azithromycin-assigned infants with lower respiratory tract Ureaplasma colonisation versus 2/11 (18%) (95% CI 2% to 52%) in placebo-treated infants. CONCLUSION: A 3-day azithromycin regimen effectively eradicated respiratory tract Ureaplasma colonisation in this study. TRIAL REGISTRATION NUMBER: NCT01778634.

Choline ameliorates ethanol induced alterations in tyrosine phosphorylation and distribution in detergent-resistant membrane microdomains of L1 cell adhesion molecule in vivo.

BACKGROUND: Exposure to ethanol during pregnancy is the cause of fetal alcohol spectrum disorder. The function of L1 cell adhesion molecule (L1), critical for proper brain development, is dependent on detergent-resistant membrane microdomains (DRM). Ethanol at low concentrations disrupts L1 function measured by inhibition of downstream signaling and alterations in L1-DRM distribution in cerebellum in vivo and in cerebellar granule neurons (CGN) in vitro. We have previously shown that choline pretreatment of CGN partially prevents ethanol toxicity through improving L1 function in vitro. Here we show that choline supplementation reduces the impact of ethanol on L1 in cerebellum in vivo. METHODS: Pregnant rat dams were placed on choline free diet on gestational Day 5 (G5). Pups were treated with saline or choline from postnatal day (P) 1-5. On P5, pups were intubated twice 2 hr apart with ethanol or Intralipid® for a total dose of 6 g/kg/d and sacrificed 1 hr after the last intubation. The cerebella were harvested and L1 phosphorylation/dephosphorylation status and distribution in DRM were analyzed. RESULTS: Ethanol reduced L1 tyrosine phosphorylation and L1-Y1176 dephosphorylation in cerebella, and caused an increase in the percent of L1 in DRM. Choline supplementation of pups reduced the ethanol-induced changes in L1 phosphorylation status and ameliorated ethanol-induced redistribution of L1 into DRM. CONCLUSION: Choline supplementation before an acute dose of ethanol ameliorates changes in L1 in vivo.

Car Seat Tolerance Screening for Late-Preterm Infants.

BACKGROUND: The belief that late-preterm infants have similar cardiorespiratory maturity to term infants has led many institutions to limit car seat tolerance screens (CSTSs) to those born early preterm. The objective of this study was to evaluate the incidence and predictors of CSTS failure, focusing on late-preterm infants. METHODS: We performed a retrospective review of late-preterm infants born from 2013 to 2017 to identify the incidence and predictors of CSTS failure, focusing on location of admission. We performed multivariable linear regression to assess the effect of CSTS results on length of stay (LOS). RESULTS: We identified 918 subjects who underwent CSTSs, of whom 4.6% failed. Those infants who were admitted to both the NICU and nursery before discharge had the highest failure rate (8.5%). Of those who failed, 24% failed ≥2 CSTSs. Of these, 20% (all from the nursery) were found to have obstructive apnea and desaturations, and a total of 40% required supplemental oxygen for safe discharge from the hospital. Although crude LOS was longer for those who failed an initial CSTS, when accounting for location of admission, level of prematurity, and respiratory support requirements, the CSTS result was not a significant predictor of longer LOS. CONCLUSIONS: A concerning number of late-preterm infants demonstrated unstable respiratory status when placed in their car seat. Those who failed repeat CSTSs frequently had underlying respiratory morbidities that required escalation of care. Although further study is warranted, LOS was not associated with CSTS results but rather with the cardiorespiratory immaturity noted or discovered by performing a CSTS.

The Emergent Evaluation and Treatment of Neck and Back Pain.

Neck and back pain are among the most common symptom-related complaints for visits to the emergency department (ED). They contribute to high levels of lost work days, disability, and health care use. The goal of ED assessment of patients with neck and back pain is to evaluate for potentially dangerous causes that could result in significant morbidity and mortality. This article discusses the efficient and effective evaluation, management, and treatment of patients with neck and back pain in the ED. Emphasis is placed on vertebral osteomyelitis, epidural abscess, acute transverse myelitis, epidural compression syndrome, spinal malignancy, and spinal stenosis.

Use of car beds for infant travel: a review of the literature.

Discharging neonates in a proper car safety seat is standard of care in the United States and many other countries. However, not every neonate can be safely positioned in a standard semi-upright car seat. In these cases, providers may opt for a travel device that allows the infant to lie flat, either supine or prone, known as a car bed. Minimal evidence exists to guide providers on car bed safety and help determine which infants would benefit from discharge in a car bed. In this article, we provide a comprehensive summary of existing literature on the safety of car beds for motor vehicle travel, car bed use in specific patient populations, and car beds vs. car seats for infants at risk of adverse cardiorespiratory events, including preterm infants with Hg-O2 desaturations in the car seat. We discuss recommendations for the follow-up of infants discharged in a car bed in order to safely transition back to a car seat.

A Quality Improvement Project to Improve Evidence-Based Inhaled Nitric Oxide Use.

BACKGROUND: Inhaled nitric oxide (INO) reduces extracorporeal membrane oxygenation (ECMO) use in term and near-term neonates with persistent pulmonary hypertension of the newborn; however, its overutilization is increasing. We hypothesized that implementing a shared baseline protocol would safely improve evidence-based INO use in a Level IV neonatal ICU. METHODS: Through several plan-do-study-act cycles, a shared baseline protocol for initiation and weaning of INO was developed and implemented starting in August 2014. Based on user feedback, the shared baseline protocol was amended and re-evaluated at regular intervals. Significant changes for process and outcome measures related to utilization of INO were detected using statistical process control, bivariate analyses using t test or nonparametric Wilcoxon rank-sum test as appropriate, and chi-square and Fisher exact testing as appropriate. Comparisons between the pre-plan-do-study-act group (January 2012 to July 2014) and post-plan-do-study-act group (August 2014 to October 2015) were made. RESULTS: One hundred sixteen INO courses in 95 subjects were administered during the pre-plan-do-study-act period, and 44 episodes were initiated in 39 subjects during the post-plan-do-study-act period. Process control charts demonstrate significant reductions in the percentage of INO doses > 20 ppm and the percentage of prolonged (>4-d) INO courses. Prolonged INO courses decreased from 67.9 to 40% (P = .032), whereas the median duration of INO per course decreased from 8 to 4 d (P < .001). The percentage of INO courses that exceeded the dose of 20 ppm decreased from 18.1 to 2.3% (P = .009). Very delayed INO weaning (weaning at FIO2 ≤ 0.40) decreased from 41.9 to 21.2% (P = .038). There were no differences in the percentage of INO courses administered to non-sedated subjects or the percentage of INO courses administered to preterm infants. There was no difference for death or ECMO between groups. CONCLUSIONS: Implementation of a shared baseline protocol to encourage appropriate INO initiation and weaning safely decreased INO exposures. Focused efforts on reducing unapproved INO use in preterm infants are warranted.