Evidence-Based Guidelines for Acute Stabilization and Management of Neonates with Persistent Pulmonary Hypertension of the Newborn.

Persistent pulmonary hypertension of the newborn, or PPHN, represents a challenging condition associated with high morbidity and mortality. Management is complicated by complex pathophysiology and limited neonatal specific evidence-based literature, leading to a lack of universal contemporary clinical guidelines for the care of these patients. To address this need and to provide consistent high-quality clinical care for this challenging population in our neonatal intensive care unit, we sought to develop a comprehensive clinical guideline for the acute stabilization and management of neonates with PPHN. Utilizing cross-disciplinary expertise and incorporating an extensive literature search to guide best practice, we present an approachable, pragmatic, and clinically relevant guide for the bedside management of acute PPHN. KEY POINTS: · PPHN is associated with several unique diagnoses; the associated pathophysiology is different for each unique diagnosis.. · PPHN is a challenging, dynamic, and labile process for which optimal care requires frequent reassessment.. · Key management goals are adequate tissue oxygen delivery, avoiding harm..

Evaluation of the Efficacy of Enoxaparin in the Neonatal Intensive Care Unit.

OBJECTIVE: This article evaluates the efficacy of enoxaparin when targeting anti-factor Xa levels of 0.5 to 1 units per milliliter in the neonatal intensive care unit. STUDY DESIGN: This is a retrospective chart review of 45 neonates receiving enoxaparin for the treatment of venous thromboembolism. Enoxaparin dosing and corresponding anti-factor Xa levels were collected. Time to resolution of clot was confirmed by imaging and compared between clots in various locations. RESULTS: The median time to clot resolution was 76 days (interquartile range 40-91 days). Clot location, postnatal age, and sex at the clot onset were significantly associated with time to clot resolution in a multivariable Cox model (p-value: 0.03, 0.03, and < 0.01, respectively). Of the 54 patients analyzed for safety, 5 patients (9.3%) experienced bleeding events resulting in the discontinuation of enoxaparin. CONCLUSION: Based on our findings, 50% of all patients evaluated, regardless of thrombus location, achieved resolution within the first 76 days of therapy. Clots located in the extremities tended to resolve sooner, hence earlier reimaging should be considered.

Implementation of an electronic pharmacy scoring tool to prioritize clinical pharmacists' daily workflow at a pediatric institution.

PURPOSE: To describe the development and implementation of an electronic pharmacy scoring tool (PST) to prioritize patients requiring clinical pharmacy intervention and assist in workload management in a freestanding pediatric hospital using quality improvement methodology. SUMMARY: The department of pharmacy at Nationwide Children's Hospital developed a pediatric-specific PST within the electronic medical record to aid in patient prioritization and ensuring proficient daily workflow and qualifying workload for clinical pharmacists. The PST identifies patients for monitoring of high-risk medications, complex medication regimens, or abnormal laboratory values related to medication management. Application of the scoring tool ensures each patient is reviewed by clinical pharmacy staff each day, with initial efforts focused on patients with significant clinical pharmacy needs. This tool reduces the need for time-intensive manual chart review for identification of patients whose medication use and/or laboratory values afford greater opportunity for pharmacist intervention. Additionally, clinical pharmacist productivity metrics and workloads are considered, with the qualifying of patient care activities and quantification of time spent on patient review. CONCLUSION: A PST enhances pediatric patient prioritization for clinical pharmacists by identifying patients most likely to require intervention in real time. The scoring tool enables future assessment of clinical pharmacists' workload assignments and better quantifies time spent on patient care activities.

Short-course empiric antibiotic therapy for possible early-onset sepsis in the NICU.

OBJECTIVE: On 2/2019, the Neonatal Antimicrobial Stewardship Program at Nationwide Children's Hospital recommended reducing empirical antibiotic therapy for early-onset sepsis (EOS) from 48 to 24 hours with a TIME-OUT. We describe our experience with this guideline and assess its safety. METHODS: Retrospective review of newborns evaluated for possible EOS at 6 NICUs from 12/2018-7/2019. Safety endpoints were re-initiation of antibiotics within 7 days after discontinuation of the initial course, positive bacterial blood or cerebrospinal fluid culture in the 7 days after antibiotic discontinuation, and overall and sepsis-related mortality. RESULT: Among 414 newborns evaluated for EOS, 196 (47%) received a 24 hour rule-out sepsis antibiotic course while 218 (53%) were managed with a 48 hour course. The 24-hour rule-out group were less likely to have antibiotics re-initiated and did not differ in the other predefined safety endpoints. CONCLUSION: Antibiotic therapy for suspected EOS may be discontinued safely within 24 hours.

Short-course antibiotic therapy for pneumonia in the neonatal intensive care unit.

OBJECTIVE: To determine the adherence and safety outcomes of a 5-day antibiotic course with a "time-out" for treatment of "blood culture-negative" pneumonia in the NICU. STUDY DESIGN: Prospective surveillance of all infants diagnosed with pneumonia at 7 NICUs from 8/2020-12/2021. Safety outcomes were defined a priori by re-initiation of antibiotic therapy within 14 days after discontinuation and overall and sepsis-related mortality. RESULTS: 128 infants were diagnosed with 136 episodes of pneumonia; 88% (n = 119) were treated with 5 days of definitive antibiotic therapy. Antibiotics were restarted within 14 days in 22 (16%) of the 136 pneumonia episodes. However, only 3 (3%) of the 119 episodes of pneumonia treated for 5 days had antibiotics restarted for pneumonia. Mortality was 5% (7/128); 5 of the 7 deaths were assessed as sepsis-related. CONCLUSION: Adherence to the 5-day definitive antibiotic treatment for "culture-negative" pneumonia was high and the intervention seemed safe.

Safety and Efficacy of Nafcillin for Empiric Therapy of Late-Onset Sepsis in the NICU.

BACKGROUND AND OBJECTIVE: In 2014 at Nationwide Children's Hospital, the Neonatal Antimicrobial Stewardship Program recommended nafcillin over vancomycin for empirical therapy of possible late-onset sepsis (LOS) in infants without a history of methicillin-resistant Staphylococcus aureus colonization or infection. We report our experience with this guideline and assess its safety. METHODS: We retrospectively reviewed all infants who received nafcillin or vancomycin for empirical treatment of possible LOS at 3 NICUs before (January 2013-May 2014) and after (January 2017-March 2019) implementation of a vancomycin reduction guideline. Safety measures included duration of blood culture positivity, recurrence of infection with the same previously identified pathogen in the 14 days after discontinuation of antibiotic therapy, and mortality. RESULTS: Among 366 infants who received a first antibiotic course for possible LOS, 84% (95 of 113) and 25% (62 of 253) received empirical therapy with vancomycin before and after the guideline implementation, respectively, representing a 70% reduction. Nafcillin use increased by 368%. Duration of blood culture positivity did not differ before and after the guidance. In 2 infants, antibiotic therapy was restarted within 14 days of discontinuation of the initial therapy for recurrence of the same infection; both had received empirical vancomycin. Overall in-hospital mortality was 10%, and there was no difference before (9%) and after (10%) implementation of the vancomycin reduction guidance (odds ratio, 0.97). CONCLUSIONS: Nafcillin can be a safe alternative to vancomycin for empirical therapy of LOS among NICU infants who do not have a history of methicillin-resistant S aureus infection or colonization.

Nephrotoxic medications and associated acute kidney injury in hospitalized neonates.

OBJECTIVES: Hospitalized neonates are often treated with nephrotoxic medications, a known risk factor for acute kidney injury (AKI). Nephrotoxic medications and AKI, especially in periviable neonates, could be detrimental to nephrogenesis. Our objectives were to evaluate the prevalence of neonatal treatment with nephrotoxic medications and its relationship with AKI in in the first 28 days of life, and to delineate the associated demographics and diagnoses. STUDY DESIGN: Multicenter retrospective analysis using the national Pediatric Hospital Information System database, including 49 pediatric hospitals. Neonates admitted within the first two postnatal days were included. Treatment with 37 nephrotoxic medications across demographics and clinical variables, and relationship with AKI were evaluated. AKI was determined by using the International Classification of Diseases codes. RESULTS: Of 192,229 neonates, 74% were treated with at least one nephrotoxic medication. Incidence of AKI was significantly higher in the treated group (aRR 3.68 [95% CI: 2.85, 4.75]). The aRRs of treatment were increased in infants born < 32-week, and < 2000 g. Nephrotoxic medications were prescribed to 90-95% of neonates born ≤ 28-week gestational age. Most treatments (95-98%) occurred in the first 3 days. Intravascular aminoglycosides were the most frequent type; 28% of neonates were treated for ≥ 4 calendar days. Most common diagnoses were infections (25%) and patent ductus arteriosus (20%). CONCLUSIONS: Neonatal treatment with nephrotoxic medications is common, especially among the smallest, most immature preterm neonates and demonstrates a need for initiatives to reduce neonatal exposure to these agents, when feasible. Across all gestational age categories, the prevalence of AKI is higher in the neonates treated with nephrotoxic drugs. The long-term effects of treatment with nephrotoxic medications and subsequent AKI on nephrogenesis and nephron endowment will need to be evaluated.

Effects of prophylactic indomethacin on intraventricular hemorrhage and adverse outcomes in neonatal intensive care unit.

OBJECTIVE: To identify the relationship between prophylactic indomethacin (PI) administration and incidence of intraventricular hemorrhage. STUDY DESIGN: A retrospective analysis of extremely premature infants <27 weeks gestational age born between January 2014 and September 2020. RESULTS: A total of 421 infants were included from three of Nationwide Children's Hospital delivery centers. Of those 255 (61%) received PI. After adjustment by inverse proportionality treatment weighting (IPTW), no differences were found in incidence of intraventricular hemorrhage (IVH) at the time of the first ultrasound, 31% vs. 33% in PI and control groups respectively (p = 0.68). The rate of rise of serum creatinine from baseline to day of life four was significantly higher in the PI group (0.14 mg/dl PI and 0.03 mg/dl control, p < 0.001). CONCLUSION: PI was not associated with any benefit in prevention of IVH, but is associated with adverse effects including acute rise in creatinine.

Parenteral Nutrition in Moderately Preterm, Otherwise Healthy Neonates Is Not Associated With Improved Short-Term Growth Outcomes.

BACKGROUND: Parenteral nutrition (PN) serves a crucial role in providing nutrition to extremely premature infants who are at high risk for malnutrition. However, little is known about the impact of PN on short-term growth outcomes in moderately preterm infants. METHODS: In this retrospective cohort analysis, patients were included in the study if they were born at ≥32 but <34 weeks gestational age and had no major comorbidities. The primary outcome of this study was to determine whether initiation of early PN for these patients has any effect on daily weight gain compared with standard dextrose-containing fluids (DCFs). Secondary outcomes were to evaluate the differences in time to regain birth weight, length of stay, and change in weight, length, and head circumference percentiles from birth to discharge. Incidence of necrotizing enterocolitis, antibiotic usage, or supplemental oxygen utilization was also evaluated. RESULTS: There were 89 patients in the PN group and 35 patients in the DCF group. The mean daily weight gain was not different between PN and DCF groups when calculated from birth to discharge (11.8 vs 10 g/kg/d, respectively; P = .09). There were also no differences when weight gain was calculated from nadir to discharge: 16.8 vs 15.2 g/kg/d, respectively (P = .1). Lack of differences persisted even when propensity matching was performed. CONCLUSION: Based on the study findings, neonates born ≥32 weeks of gestational age without any major comorbidities are unlikely to benefit from PN supplementation.

A quality improvement project to reduce length of stay for neonatal abstinence syndrome.

BACKGROUND AND OBJECTIVE: Neonatal abstinence syndrome (NAS), a self-limiting condition, is associated with clinical symptoms that may require pharmacological intervention. Optimal treatment of NAS remains undetermined, but the hospital length of stay (LOS) for patients with NAS is partially dependent upon a standard treatment protocol used. Prolonged LOS for patients with NAS can lead to adverse patient harm, impaired maternal-infant attachment, and significant health care costs. Therefore, we conducted a quality improvement study to reduce the LOS for infants with NAS. METHODS: In 2009, a multidisciplinary NAS Taskforce was created to implement a standardized treatment protocol, discuss the strengths and weaknesses of the current medical and nursing management, and improve communication among staff. Infants with NAS that required pharmacological intervention were followed throughout their hospitalization. Readmission within 30 days of hospital discharge was tracked as a balancing measure. RESULTS: Ninety-two infants were eligible for the project including 23 infants from a baseline period (January 2007-August 2009). Reliable monitoring of symptoms and the administration of a standardized morphine protocol effectively reduced LOS from 36 days to 18 days by June 2012. This improvement was sustained through December 2012. No patients were readmitted for NAS treatment. CONCLUSIONS: The most effective interventions that impacted LOS for infants with NAS were the development of a staff NAS education program and the implementation of a standard treatment protocol. The formation of the NAS Taskforce was also essential because it facilitated communication and the dissemination of vital treatment information among all clinical staff.