Early continuous renal replacement therapy during infant extracorporeal life support is associated with decreased lung opacification.

Lung opacification on chest radiography (CXR) is common during extracorporeal life support (ECLS), often resulting from pulmonary edema or inflammation. Concurrent use of continuous renal replacement therapy (CRRT) during ECLS is associated with improved fluid balance and cytokine filtration; through modification of these pathologic states, CRRT may modulate lung opacification observed on CXRs. We hypothesize that early CRRT use during infant ECLS decreases lung opacification on CXR. We conducted a retrospective cohort study comparing CXRs from infants receiving ECLS and early CRRT (n = 7) to matched infants who received ECLS alone (n = 7). The CXR obtained prior to ECLS, all CXRs obtained within the first 72 h of ECLS, and daily CXRs for the remainder of the ECLS course were analyzed. The outcome measure was the degree of opacification, determined by independent assessment of two, blinded pediatric radiologists using a modified Edwards et al.'s lung opacification scoring system (from Score 0: no opacification to Score 5: complete opacification). 220 CXRs were assessed (cases: 93, controls: 127). Inter-rater reliability was established (Cohen's weighted к = 0.74; p < 0.0001, good agreement). At baseline, the mean opacification score difference between cases and controls was 1 point (cases: 1.8, controls 2.8; p = 0.049). Using mixed modeling analysis for repeated measures accounting for differences at baseline, the average overall opacification score was 1.2 points lower in cases than controls (cases: 2.1, controls: 3.3; p < 0.0001). The overall distribution of scores was lower in cases than controls. Early CRRT utilization during infant ECLS was associated with decreased lung opacification on CXR.

Implementing a practice change: early initiation of continuous renal replacement therapy during neonatal extracorporeal life support standardizes care and improves short-term outcomes.

PURPOSE: We hypothesized that a standardized approach to early continuous renal replacement therapy (CRRT) during neonatal extracorporeal life support (ECLS) results in greater homogeneity of CRRT initiation times with improvements in fluid balance and outcomes. METHODS: Retrospective analysis of data (2007-2015) obtained from neonates treated prior to (E1; n = 32) and after (E2; n = 31) a 2011 practice change: CRRT initiation within 48 h of ECLS. RESULTS: Birthweight, gestational age, ECLS mode, and age at ECLS initiation were similar to each epoch. Survival [E1: median 75%, E2: 71%] and length of ECLS [E1: median 221 h, E2: 180 h] were comparable. During E2, 100% of infants received CRRT (vs. E1: 37%; p < 0.001) and 97% of infants initiated CRRT within 48 h of ECLS (vs. E1: 13%; p < 0.001). Control charts demonstrate reduced practice variation. Elapsed time from ECLS to CRRT differed between Epochs [E1: median 105 h, E2: 9 h; p < 0.001] as did weight at CRRT initiation [E1: 4.13 kg (29% above baseline), E2: 3.19 kg (0%); p < 0.001]. Significant differences in weight change were noted on days 6 and 7 (E1: 14%, E2: 2%; raw data comparison yielded p < 0.05) and curves were different (p < 0.05). CONCLUSIONS: We successfully implemented a practice change, initiating CRRT within 48 h of ECLS cannulation, leading to decreased practice variation and improved short-term outcomes including decreased weight gain at CRRT initiation and faster return to baseline weight during the first 7 days of ECLS. We did not demonstrate changes in duration of ECLS, invasive ventilation, or survival.

Early Continuous Renal Replacement Therapy Improves Nutrition Delivery in Neonates During Extracorporeal Life Support.

OBJECTIVE: Optimizing nutrition in neonatal patients as soon as possible after extracorporeal life support (ECLS) initiation is imperative as malnutrition can worsen both short- and long-term outcomes. Fluid restriction, used to manage the fluid overload that commonly complicates neonatal ECLS, severely impairs nutrition delivery. Continuous renal replacement therapy (CRRT) can be used to help manage fluid overload. We hypothesize that early CRRT utilization ameliorates the need for fluid restriction and allows providers to prescribe higher parenteral nutrition (PN) volumes leading to better nutrition delivery. DESIGN: The design of the study was a retrospective chart review, and the setting was a single, level III neonatal intensive care unit. SUBJECTS: Neonatal patients (n = 42) treated with ECLS between January 1, 2008, and December 31, 2013. INTERVENTIONS: Comparisons were made between 2 groups: neonates who received ECLS without early CRRT initiation (group 1; n = 23) and with early CRRT initiation (group 2; n = 19). MAIN OUTCOME MEASURES: The main outcome measures were goal total fluid intake, prescribed PN volume, protein, glucose infusion rate, intralipid, and kilocalories. RESULTS: Infants who received early CRRT were prescribed higher mean total fluid intake goals (group 1: 99 mL/kg/day vs. group 2: 119 mL/kg/day, P < .001) and higher mean volumes of PN (group 1: 61 mL/kg/day vs. group 2: 81 mL/kg/day, P < .001) over the first 72 hours of ECLS compared with infants who did not receive early CRRT. Early CRRT receivers also were prescribed greater mean amounts of protein during the first 72 hours of ECLS (group 1: 2.7 g/kg/day vs. group 2: 3 g/kg/day, P = 0.03). There were no significant changes noted in prescribed glucose infusion rates, intralipid, or total kilocalories. CONCLUSIONS: Institution of early CRRT in neonates on ECLS allows for administration of greater volumes of PN with improved protein delivery. This study characterizes one benefit of early CRRT initiation in neonates on ECLS and suggests these patients could experience improved nutritional outcomes.

Novel FOXF1 mutations in sporadic and familial cases of alveolar capillary dysplasia with misaligned pulmonary veins imply a role for its DNA binding domain.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

Levofloxacin secretion in breast milk: a case report.

OBJECTIVE: To evaluate levofloxacin secretion in human breast milk. METHODS: Breast milk was collected from a lactating woman during a 23-day period in which she received levofloxacin 500 mg/day and for 5 days after discontinuation of levofloxacin. The levofloxacin concentration was assayed by high-performance liquid chromatography. A two-compartment pharmacokinetic model was used to estimate peak and total levofloxacin exposure. RESULTS: At steady state, peak levofloxacin exposure in breast milk was 8.2 microg/ml at 5 hours after dosing. Elimination pharmacokinetics followed the anticipated pattern. CONCLUSION: Peak levofloxacin concentration in human breast milk is similar to levels attained in plasma. However, breast-feeding mothers who take levofloxacin will expose their infants to levofloxacin in concentrations below those being studied in the pediatric population.

Preparation of the critically ill neonate for transport.

Transport of a critically ill neonate is stressful for all involved. Adequate communication and stabilization will reduce stresses and improve outcomes. Periodic review of the stabilization and care provided to neonates prior to transport can help in further improving the process. Such reviews can be done in conjunction with the Regional Perinatal Center.