Evaluation of Initial Enoxaparin Dosing and Antifactor Xa Levels in Infants Admitted to the Neonatal Intensive Care Unit.

Introduction: Infants are at risk for thrombotic conditions due to multiple risk factors such as congenital heart defects and sepsis. According to the American College of Chest Physicians (ACCP) 2012 guidelines, enoxaparin may be given for thrombotic conditions at a dose of 1.5 mg/kg/dose every 12 h for patients less than 2 months of age and 1 mg/kg/dose every 12 h for those older than 2 months. Several studies have reported that infants typically require a higher initial dose of enoxaparin to reach therapeutic antifactor Xa levels than what is currently recommended. Methods: This is a single-center retrospective case-control study of hospitalized infants less than 12 months of age who received treatment with enoxaparin while admitted to the neonatal intensive care unit (NICU) at a freestanding children's hospital. The primary objective was the difference between the initial enoxaparin dose (mg/kg) compared to the enoxaparin dose in which the patient first achieved a therapeutic antifactor Xa level of 0.5-1.0 units/mL. Results: A total of 56 infants were included in this study. The median enoxaparin dose at initiation was 1.5 mg/kg/dose, and the median enoxaparin dose at the first therapeutic antifactor Xa level was 1.9 mg/kg/dose (z = -12.7, p < 0.0001). There was no correlation between gestational age and weight with the enoxaparin dose required to reach a therapeutic antifactor Xa level. Conclusion: Infants admitted to the NICU, specifically those less than 4 months of age, require higher initial enoxaparin dosing to reach therapeutic antifactor Xa levels than what is currently recommended.

Recognition and Management of Delirium in the Neonatal Intensive Care Unit: Case Series From a Single-Center Level IV Intensive Care Unit.

Delirium often goes unrecognized in neonates and children because of lack of experience in evaluating behavior and cognition, insufficient awareness of the prevalence, and nondistinctive symptoms in this population. Although there are increasing reports of the presence of delirium in neonates, there are little data to guide the pharmacologic treatment in this population. In this retrospective single-center case series, we present our experience using quetiapine to treat delirium in 9 medically complex neonates. Based on an extensive literature review, expert opinion, and institutional experience, we propose an approach for monitoring and treating delirium in neonates and infants.

Propofol Sedation Washouts in Critically Ill Infants: A Case Series.

Medically complex infants are experiencing longer hospital stays, more invasive procedures, and increasingly involved therapeutic interventions that often require long-term analgesia and sedation. This is most commonly achieved with continuous intravenous infusions of opioids and benzodiazepines. There are times when patients develop a tolerance for these medications or the clinical scenario necessitates a rapid wean of them. A rapid wean of either class of medication can lead to increased signs of pain and agitation or withdrawal symptoms. As a result, when a rapid wean is needed or there has been a failure to control symptoms with conventional measures, alternative therapies are considered. Propofol, a sedative hypnotic typically used for general anesthesia and procedural sedation, is one such medication. It has effectively been used for short-term sedation in adults and children to facilitate weaning benzodiazepines and opioids. There is a paucity of data on the use of propofol in infants for this purpose. Here we describe the use of propofol to rapidly wean high-dose sedation and analgesia medications, a propofol sedation washout, in 3 infants. The washouts proved to be safe and efficacious. Based on institutional experience and a literature review, considerations and recommendations are made for propofol sedation washouts in infants.

Impact of Patient-Specific Aminoglycoside Monitoring for Treatment of Pediatric Cystic Fibrosis Pulmonary Exacerbations.

OBJECTIVE: Aminoglycosides are frequently used for empiric and definitive treatment of cystic fibrosis (CF) pulmonary exacerbations. Various methods have been described for aminoglycoside therapeutic drug monitoring. The objective of this study is to evaluate the effect of patient-specific pharmacokinetic calculations for aminoglycosides used to treat CF pulmonary exacerbations. METHODS: Ambidirectional cohort study of patients admitted to a children's hospital from June 1, 2018, through February 28, 2019, and June 1, 2019, through February 8, 2021. The primary outcome was the occurrence of dosing changes after analysis of initial serum concentrations in either group. Secondary outcomes included occurrence of nephrotoxicity, duration of antibiotics, and length of stay. RESULTS: Twenty-four patients (75%) in the intervention group versus zero in the control group required dosing adjustments after initial analysis of serum concentrations were completed (p < 0.001). There was not a statistically significant between-group difference for duration of antibiotics in days (median, 14 vs 13.5; Z, 1.07; p = 0.29) or length of stay (median, 11 vs 11; Z, -0.31; p = 0.76). There was also not a statistically significant between-group difference in forced expiratory volume in one second (FEV1) change from admission to discharge (11.4% vs 13.9%; t, 0.61; Degrees of Freedom, 39; p = 0.55). Two patients (6.25%) in the intervention group experienced nephrotoxicity compared with zero patients in the control group (risk difference, 6.25%; 95% CI, -2.14 to 14.64; number needed to harm, 16). CONCLUSIONS: Patient-specific pharmacokinetic monitoring led to significantly more dosing changes and was associated with similar patient outcomes as trough-only monitoring. Further studies are needed to identify methods to optimize aminoglycoside dosing and monitoring for these patients with the goal of reducing toxicities while maximizing efficacy.

Impact of Early Fortification in Very Low Birth Weight Infants on the Incidence of Malnutrition During a Trophamine Shortage.

OBJECTIVE: The devastation of pharmaceutical production facilities from Hurricane Maria caused a national shortage of parenteral amino acids in October 2017. Our institution decreased trophamine in very low birth weight (VLBW) infants and initiated human milk fortification at a lower feeding volume to increase enteral protein intake more quickly. The objective of this study was to assess how protein management during the shortage period affected the incidence of malnutrition. METHODS: This was a retrospective cohort study of infants admitted to 2 neonatal intensive care units from June 1, 2017 to May 31, 2018. Infants between 23 and 32 weeks' gestation were included in this study. The primary outcome was the incidence of malnutrition at 14 days, defined as a z score decline of ≥0.8 SDs, in the pre-shortage period compared with the shortage period. Clinical data regarding adverse effects associated with early fortification and pharmacy costs were recorded. RESULTS: There were 68 infants prior to and 65 during the shortage who met inclusion criteria. There was no difference in malnutrition between the pre-shortage and shortage groups; however, a significant increase in malnutrition was observed in infants who did not receive early fortification during the shortage. No difference in time to full enteral feeds or necrotizing enterocolitis was observed with early fortification. CONCLUSIONS: Early fortification in VLBW infants receiving less trophamine during the shortage was not associated with an increase in malnutrition. Restricting trophamine in neonates during the shortage allowed for distribution to other critically ill patients.

Presumed adrenal insufficiency in neonates treated with corticosteroids for the prevention of bronchopulmonary dysplasia.

OBJECTIVE: To determine if extremely preterm (EPT) neonates receiving dexamethasone for the prevention of BPD have a higher incidence of presumed adrenal insufficiency (PAI). STUDY DESIGN: Retrospective cohort study of neonates <28 weeks gestation examining PAI after dexamethasone use and PAI after intratracheal budesonide with surfactant administration. RESULT: Of 332 neonates, 38% received dexamethasone. The incidence of PAI was higher in neonates who had received dexamethasone (20.8% vs 2.9%, p < 0.001). However, for intubated babies receiving surfactant, dexamethasone was not independently associated with increased PAI after adjusting for gestational age, birthweight, and race (aOR 2.92, 95% CI: 0.79-10.85). Dexamethasone was independently associated with increased PAI in infants previously receiving budesonide/surfactant treatment (aOR 5.38, 95% CI: 1.38-20.90). CONCLUSION: The use of dexamethasone alone was not associated with increased PAI, when adjusted for prematurity-related factors. The combination of budesonide with dexamethasone was significantly associated with increased PAI.