Autonomic markers of extubation readiness in premature infants.

BACKGROUND: In premature infants, extubation failure is common and difficult to predict. Heart rate variability (HRV) is a marker of autonomic tone. Our aim is to test the hypothesis that autonomic impairment is associated with extubation readiness. METHODS: Retrospective study of 89 infants <28 weeks. HRV metrics 24 h prior to extubation were compared for those with and without extubation success within 72 h. Receiver-operating curve analysis was conducted to determine the predictive ability of each metric, and a predictive model was created. RESULTS: Seventy-three percent were successfully extubated. The success group had significantly lower oxygen requirement, higher sympathetic HRV metrics, and a lower parasympathetic HRV metric. α1 (measure of autocorrelation, related to sympathetic tone) was the best predictor of success-area under the curve (AUC) of .73 (p = 0.001), and incorporated into a predictive model had an AUC of 0.81 (p < 0.0001)-sensitivity of 81% and specificity of 78%. CONCLUSIONS: Extubation success is associated with HRV. We show an autonomic imbalance with low sympathetic and elevated parasympathetic tone in those who failed. α1, a marker of sympathetic tone, was noted to be the best predictor of extubation success especially when incorporated into a clinical model. IMPACT: This article depicts autonomic markers predictive of extubation success. We depict an autonomic imbalance in those who fail extubation with heightened parasympathetic and blunted sympathetic signal. We describe a predictive model for extubation success with a sensitivity of 81% and specificity of 78%.

Renal versus cerebral saturation trajectories: the perinatal transition in preterm neonates.

BACKGROUND: The aim of this study was to develop reference renal saturation (rSrO2) curves in premature infants, depict how they differ from cerebral saturation (rScO2) curves, and evaluate the effect of blood pressure on these values using near-infrared spectroscopy (NIRS). METHODS: This is a prospective cohort study of 57 inborn infants <12 h and <30 weeks gestation. rScO2, rSrO2, fractional tissue oxygen extraction (FTOE), and mean arterial blood pressure (MAP) were continuously monitored every 30 s for 96 h. Quantile regression was used to establish nomograms, and mean saturation values were evaluated for different MAP ranges. RESULTS: Median rSrO2 at the start of monitoring was ~10% higher than rScO2. rSrO2 showed a significant decline over time while rScO2 peaked at 26 h. FTOE demonstrated a similar but inverse trend to their saturation counterparts. rScO2 declined as MAP increased, while rSrO2 showed a peak and decline as MAP increased. CONCLUSIONS: We provide rSrO2 reference curves for the first 4 days of life, which differ in their trajectory from rScO2 and from what has previously been reported for rSrO2 in the full-term population. In addition, we observed a peak and decline in renal saturation with increasing MAP, suggesting a renovascular response to blood pressure changes. IMPACT: This article depicts reference renal saturation curves during the perinatal transition in preterm infants. We show how renal saturation compares to cerebral saturation trends over time. We describe a peak and decline in renal saturation with increasing MAP, suggesting a renovascular response to blood pressure changes.

Point-of-Care Ultrasound to Confirm Umbilical Line Placement: Impact of a Simulation Enhanced Curriculum on Neonatal Intensive Care Unit Provider Competency.

INTRODUCTION: Neonatal intensive care unit (NICU) provider point-of-care ultrasound (POCUS) procedural competency for umbilical line placement confirmation has not been defined, and the necessary training to achieve competency has not been previously studied. This study's objective was to test the hypothesis that a simulation-enhanced curriculum will improve NICU providers' POCUS competency to confirm umbilical line placement. METHODS: Neonatal intensive care unit providers without prior ultrasound experience were randomized to a curriculum with or without simulation-based training. Competency for catheter detection, tip localization, and scan interpretation on patients was determined using learning curve-cumulative summation, a specific statistical tool designed to indicate when a predefined level of performance is reached. Differences in success rates were analyzed by χ2 test. RESULTS: Two thirds (22/33) of participants completed 10 scans. Three (simulation) and 1 (control) attained catheter detection competency (P = 0.28). The simulation group was more successful for catheter detection (81% vs. 69%, P = 0.04) and scan interpretation (61% vs. 48%, P = 0.04). Success did not differ by umbilical vessel location, provider role, or duration of NICU experience. CONCLUSIONS: A simulation-enhanced POCUS curriculum improved catheter detection rate and scan interpretation, but there was no difference in procedural competency between groups on ultrasound scans performed on patients with umbilical catheters. We speculate that more than 10 scans may be needed for NICU providers to obtain POCUS competency.

Association between dopamine and cerebral autoregulation in preterm neonates.

BACKGROUND: To test the hypothesis that dopamine is associated with impaired cerebral autoregulation (ICA) in a dose-dependent fashion. METHODS: Non a priori designed secondary analysis of a prospectively enrolled cohort study subjects <12 h of life between 240 and 296 weeks gestation. Cerebral saturations (rScO2) and mean arterial blood pressure (MAP) were continuously monitored every 30 s for 96 h. ICA was defined by a 10 min epoch rScO2-MAP correlation coefficient of >0.5. RESULTS: Twenty-three of 61 subjects (38%) required dopamine. Time spent with ICA was 23% in dopamine-exposed subjects vs. 14% in those not exposed (p = 0.0001). On the epoch level, time spent with ICA was 15%, 29%, 34%, 37%, and 23% in epochs with dopamine titration of 0, 1-5, 6-10, 11-15, and 16-20 µg/kg/min, respectively. Using mixed-effect modeling, ICA for each dopamine titration was significantly higher than unexposed times when controlling for gestation, presence of a patent ductus arteriosus, day of life, MAP less than gestational age, and illness severity score (p < 0.02). CONCLUSIONS: Dopamine exposure during the first 96 h was associated with ICA. Time periods with ICA increased with dopamine exposure in a dose-dependent fashion peaking at a concentration of 11-15 µg/kg/min.

Association of PDGFRB Mutations With Pediatric Myofibroma and Myofibromatosis.

IMPORTANCE: Myofibroma is the most frequent fibrous tumor in children. Multicentric myofibroma (referred to as infantile myofibromatosis) is a life-threatening disease. OBJECTIVE: To determine the frequency, spectrum, and clinical implications of mutations in the PDGFRB receptor tyrosine kinase found in sporadic myofibroma and myofibromatosis. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective study of 69 patients with sporadic myofibroma or myofibromatosis, 85 tumor samples were obtained and analyzed by targeted deep sequencing of PDGFRB. Mutations were confirmed by an alternative method of sequencing and were experimentally characterized to confirm gain of function and sensitivity to the tyrosine kinase inhibitor imatinib. MAIN OUTCOMES AND MEASURES: Frequency of gain-of-function PDGFRB mutations in sporadic myofibroma and myofibromatosis. Sensitivity to imatinib, as assessed experimentally. RESULTS: Of the 69 patients with tumor samples (mean [SD] age, 7.8 [12.7] years), 60 were children (87%; 29 girls [48%]) and 9 were adults (13%; 4 women [44%]). Gain-of-function PDGFRB mutations were found in samples from 25 children, with no mutation found in samples from adults. Mutations were particularly associated with severe multicentric disease (13 of 19 myofibromatosis cases [68%]). Although patients had no familial history, 3 of 25 mutations (12%) were likely to be germline, suggesting de novo heritable alterations. All of the PDGFRB mutations were associated with ligand-independent receptor activation, and all but one were sensitive to imatinib at clinically relevant concentrations. CONCLUSIONS AND RELEVANCE: Gain-of-function mutations of PDGFRB in myofibromas may affect only children and be more frequent in the multicentric form of disease, albeit present in solitary pediatric myofibromas. These alterations may be sensitive to tyrosine kinase inhibitors. The PDGFRB sequencing appears to have a high value for diagnosis, prognosis, and therapy of soft-tissue tumors in children.

Cerebral autoregulation in premature infants during the first 96 hours of life and relationship to adverse outcomes.

OBJECTIVE: To test the hypothesis that impaired cerebral autoregulation (ICA) increases the susceptibility of premature infants to adverse outcomes, we determined the relationship of ICA and cerebral reactivity (CR) measured in the first 96 hours of life to the outcome of grade 3 or 4 intraventricular haemorrhage (IVH) and/or death within 1 month. SETTING: Single-centre level IV neonatal intensive care unit. PATIENTS: Neonates 24-29 weeks' gestation less than 12 hours old with invasive blood pressure monitoring. DESIGN: Cerebral saturations and mean arterial blood pressure were recorded every 30 s for 96 hours. For each 10 min epoch, the correlation coefficient (r) was calculated for mean arterial blood pressure versus cerebral saturations. The epoch was considered to have ICA if r>0.5 and CR if r<0. RESULTS: Sixty-one subjects were included. During the first 96 hours, ICA occurred 17.6% and CR occurred 41% of recorded time. In those without adverse outcomes, ICA decreased and CR increased by postnatal day (p<0.05). Adjusted for birth weight and gestational age, those with IVH and those who died spent more time with ICA and less time with CR (p<0.05) over the entire recording period. Those with IVH had 1.5-fold increase in time with ICA on day 2 (p=0.021), and decrease in time with CR on day 3 (p=0.036). Compared with survivors, non-survivors spent more time with ICA on days 3 and 4 (p<0.005), and less with CR on day 3 (p=0.032). CONCLUSION: ICA and CR vary by postnatal day and these patterns are associated with adverse outcomes.

Utility of prenatal Doppler ultrasound to predict neonatal impaired cerebral autoregulation.

OBJECTIVE: Determine if abnormal prenatal Doppler ultrasound indices are predictive of postnatal impaired cerebral autoregulation. STUDY DESIGN: Prospective cohort study of 46 subjects, 240-296 weeks' gestation. Utilizing near-infrared spectroscopy and receiver-operating characteristic analysis, impaired cerebral autoregulation was defined as >16.5% time spent in a dysregulated state within 96 h of life. Normal and abnormal Doppler indices were compared for perinatal outcomes. RESULTS: Subjects with abnormal cerebroplacental ratio (n = 12) and abnormal umbilical artery pulsatility index (n = 13) were likely to develop postnatal impaired cerebral autoregulation (p ≤ 0.02). Abnormal cerebroplacental ratio was associated with impaired cerebral autoregulation between 24 and 48 h of life (p = 0.016). These subjects have increased risk for fetal growth restriction, lower birth weight, lower Apgar scores, acidosis, and severe intraventricular hemorrhage and/or death (p < 0.05). CONCLUSION: Abnormal cerebroplacental ratio and umbilical artery pulsatility index are associated with postnatal impairment in cerebral autoregulation and adverse outcome.

Hypotension and Adverse Outcomes in Prematurity: Comparing Definitions.

BACKGROUND: In the premature neonate, there is no consensus regarding normal blood pressure (BP). The most common definition used is a mean arterial BP (MAP) less than the gestational age (GA); however, studies indicate that the neuroprotective mechanism of autoregulation is lost below a MAP of 30 mm Hg. OBJECTIVE: To determine whether hypotension defined as MAP <30 mm Hg or MAP less than the infant's GA better predicts adverse outcomes of intraventricular hemorrhage (IVH) and death. STUDY DESIGN: For this retrospective study, demographic, clinical, and BP data in epochs of 12 h were collected during the first 72 h of life in 188 subjects 24-28 weeks of gestation. For each definition, outcomes of severe IVH (grade 3 or 4), death, or the composite outcome of either were evaluated using bivariate testing. Logistic regression determined independent predictors of composite outcome of death and/or grade 3 or 4 IVH. RESULTS: Hypotension by either definition was significant for death and the composite outcome (p < 0.0001). Only the MAP <30 mm Hg definition was associated with severe IVH (p = 0.02). On logistic regression, significant predictors of the composite outcome were GA (OR 0.59, 95% CI 0.39-0.89) and vasopressor therapy (OR 5.5, 95% CI 2-17). CONCLUSIONS: Neither definition of hypotension independently predicts adverse outcome in multivariate logistic regression. Vasopressor therapy, however, is an independent predictor of IVH and death in premature infants.

Impact of High-Flow Nasal Cannula Use on Neonatal Respiratory Support Patterns and Length of Stay.

BACKGROUND: Heated humidified high-flow nasal cannula (HFNC) is thought to be comparable with nasal CPAP. The effect of multimodality mid-level respiratory support use in the neonatal ICU is unknown. The objective of this work was to evaluate the effect of introducing HFNC on length of respiratory support and stay. METHODS: A chart review was conducted on subjects at 24-32 weeks gestation requiring mid-level support (HFNC/nasal CPAP) 1 y before and after HFNC implementation. The 2 groups were compared for clinical and demographic data using t test or chi-square analysis. Further, multivariate linear and logistic regression was done to determine significant risk factors for outcomes controlling for covariates. RESULTS: Eighty subjects were eligible in the pre-HFNC group, and 83 were eligible in the post-HFNC group. Subjects were similar in their baseline characteristics. In clinical outcomes, the post-HFNC group had higher rates of retinopathy of prematurity (P = .02) and a trend toward higher bronchopulmonary dysplasia rates (P = .063). The post-HFNC subjects had longer duration of mid-level support and were older at the time they were weaned to stable low-flow nasal cannula (P < .05). Although the length of respiratory support and stay and corrected gestational age at discharge were similar, those in the pre-HFNC period were more likely to be receiving full oral feeds and be discharged home versus being transferred to an intermediate care facility (P < .05). CONCLUSIONS: HFNC introduction was significantly associated with a longer duration of mid-level respiratory support, decrease in oral feeding at discharge, increased retinopathy of prematurity rates, and higher use of intermediate care facilities, leading us to examine our noninvasive ventilation and weaning strategies.

Survival in congenital diaphragmatic hernia: use of predictive equations in the ECMO population.

BACKGROUND: Equations have been proposed by the Wilford Hall/Santa Rosa (WHSR) and Congenital Diaphragmatic Hernia Study Group (CDHSG) for predicting survival in patients with CDH. The CDHSG stratifies risk based on a logistic regression equation incorporating birth weight and 5-min Apgar score, while the WHSR group uses the difference between maximum pO(2) and maximum pCO(2) as an index of risk. These models have not been applied specifically to the CDH ECMO (extracorporeal membrane oxygenation) population, a group at highest mortality risk. OBJECTIVES: To evaluate the WHSR and CDHSG predictive equations when applied to a population of patients with CDH requiring ECMO life support. METHODS: A single-center retrospective review was conducted on infants with CDH treated with ECMO between 1993 and 2007. Predicted and actual outcomes were compared using receiver operating curve (ROC) analyses in which an area under the curve (AUC) of 1 denotes 100% agreement between predicted and actual outcomes. Kaplan-Meier analyses were also used to compare survival of patients who were risk-categorized according to each prediction model. Minimum pre-ECMO pCO(2) was likewise evaluated as a predictor of survival. RESULTS: Overall survival was 50% in 62 CDH patients treated with ECMO during the study period. The CDHSG equation did not discriminate between survivors and nonsurvivors (AUC 0.55, p = 0.499). The modified WHSR formula showed better discrimination of survival (AUC 0.71, p = 0.004). Lowest achievable pre-ECMO pCO(2) had the highest AUC (0.723, p = 0.003). Patients with minimum pre-ECMO pCO(2) <50 mm Hg had 56% survival, while those with >70 mm Hg had 0% survival. CONCLUSIONS: Equations proposed to predict survival in CDH patients may not discriminate survivors from nonsurvivors in the ECMO population. In this highest risk group, factors such as birth weight and Apgar score are less critical in estimating mortality risk than indicators of ventilation and oxygenation that reflect the degree of pulmonary hypoplasia.