Alix Paget-Brown

Responding to Compliance Changes in a Lung Model During Manual Ventilation: Perhaps Volume, Rather Than Pressure, Should be Displayed

Objective. The standard technique for positive-pressure ventilation is to regulate the breath size by varying the pressure applied to the bag. Investigators have argued that consistency of peak inspiratory pressure is important. However, research shows that excessive tidal volume delivered with excessive pressure injures preterm lungs, which suggests that inspiratory pressure should be varied during times of changing compliance, such as resuscitation of newborns or treatment after surfactant delivery. Methods. We modified a computerized lung model (ASL5000 [IngMar Medical, Pittsburgh, PA]) to simulate the functional residual capacity of a 3-kg neonate with apnea and programmed it to change compliance during ventilation. Forty-five professionals were blinded to randomized compliance changes while using a flow-inflating bag, a self-inflating bag, and a T-piece resuscitator. We instructed subjects to maintain a constant inflation volume, first while blinded to delivered volume and then with volume displayed, with all 3 devices. Results. Subjects adapted to compliance changes by adjusting inflation pressure more effectively when delivered volume was displayed. When only pressure was displayed, sensing of compliance changes occurred only with the self-inflating bag. When volume was displayed, adjustments to compliance changes occurred with all 3 devices, although the self-inflating bag was superior. Conclusions. In this lung model, volume display permitted far better detection of compliance changes compared with display of only pressure. Devices for administration of positive-pressure ventilation should display volume rather than pressure.

A new algorithm for detecting central apnea in neonates

Apnea of prematurity is an important and common clinical problem, and is often the rate-limiting process in NICU discharge. Accurate detection of episodes of clinically important neonatal apnea using existing chest impedance (CI) monitoring is a clinical imperative. The technique relies on changes in impedance as the lungs fill with air, a high impedance substance. A potential confounder, however, is blood coursing through the heart. Thus, the cardiac signal during apnea might be mistaken for breathing. We report here a new filter to remove the cardiac signal from the CI that employs a novel resampling technique optimally suited to remove the heart rate signal, allowing improved apnea detection. We also develop an apnea detection method that employs the CI after cardiac filtering. The method has been applied to a large database of physiological signals, and we prove that, compared to the presently used monitors, the new method gives substantial improvement in apnea detection.

Anemia, Apnea of Prematurity, and Blood Transfusions

OBJECTIVE To compare the frequency and severity of apneic events in very low birth weight (VLBW) infants before and after blood transfusions using continuous electronic waveform analysis. STUDY DESIGN We continuously collected waveform, heart rate, and oxygen saturation data from patients in all 45 neonatal intensive care unit beds at the University of Virginia for 120 weeks. Central apneas were detected using continuous computer processing of chest impedance, electrocardiographic, and oximetry signals. Apnea was defined as respiratory pauses of >10, >20, and >30 seconds when accompanied by bradycardia (<100 beats per minute) and hypoxemia (<80% oxyhemoglobin saturation as detected by pulse oximetry). Times of packed red blood cell transfusions were determined from bedside charts. Two cohorts were analyzed. In the transfusion cohort, waveforms were analyzed for 3 days before and after the transfusion for all VLBW infants who received a blood transfusion while also breathing spontaneously. Mean apnea rates for the previous 12 hours were quantified and differences for 12 hours before and after transfusion were compared. In the hematocrit cohort, 1453 hematocrit values from all VLBW infants admitted and breathing spontaneously during the time period were retrieved, and the association of hematocrit and apnea in the next 12 hours was tested using logistic regression. RESULTS Sixty-seven infants had 110 blood transfusions during times when complete monitoring data were available. Transfusion was associated with fewer computer-detected apneic events (P < .01). Probability of future apnea occurring within 12 hours increased with decreasing hematocrit values (P < .001). CONCLUSIONS Blood transfusions are associated with decreased apnea in VLBW infants, and apneas are less frequent at higher hematocrits.

Accurate automated apnea analysis in preterm infants.

OBJECTIVE In 2006 the apnea of prematurity (AOP) consensus group identified inaccurate counting of apnea episodes as a major barrier to progress in AOP research. We compare nursing records of AOP to events detected by a clinically validated computer algorithm that detects apnea from standard bedside monitors. STUDY DESIGN Waveform, vital sign, and alarm data were collected continuously from all very low-birth-weight infants admitted over a 25-month period, analyzed for central apnea, bradycardia, and desaturation (ABD) events, and compared with nursing documentation collected from charts. Our algorithm defined apnea as > 10 seconds if accompanied by bradycardia and desaturation. RESULTS Of the 3,019 nurse-recorded events, only 68% had any algorithm-detected ABD event. Of the 5,275 algorithm-detected prolonged apnea events > 30 seconds, only 26% had nurse-recorded documentation within 1 hour. Monitor alarms sounded in only 74% of events of algorithm-detected prolonged apnea events > 10 seconds. There were 8,190,418 monitor alarms of any description throughout the neonatal intensive care unit during the 747 days analyzed, or one alarm every 2 to 3 minutes per nurse. CONCLUSION An automated computer algorithm for continuous ABD quantitation is a far more reliable tool than the medical record to address the important research questions identified by the 2006 AOP consensus group.

Breath-by-breath analysis of cardiorespiratory interaction for quantifying developmental maturity in premature infants

In healthy neonates, connections between the heart and lungs through brain stem chemosensory pathways and the autonomic nervous system result in cardiorespiratory synchronization. This interdependence between cardiac and respiratory dynamics can be difficult to measure because of intermittent signal quality in intensive care settings and variability of heart and breathing rates. We employed a phase-based measure suggested by Schäfer and coworkers (Schäfer C, Rosenblum MG, Kurths J, Abel HH. Nature 392: 239-240, 1998) to obtain a breath-by-breath analysis of cardiorespiratory interaction. This measure of cardiorespiratory interaction does not distinguish between cardiac control of respiration associated with cardioventilatory coupling and respiratory influences on the heart rate associated with respiratory sinus arrhythmia. We calculated, in sliding 4-min windows, the probability density of heartbeats as a function of the concurrent phase of the respiratory cycle. Probability density functions whose Shannon entropy had a <0.1% chance of occurring from random numbers were classified as exhibiting interaction. In this way, we analyzed 18 infant-years of data from 1,202 patients in the Neonatal Intensive Care Unit at University of Virginia. We found evidence of interaction in 3.3 patient-years of data (18%). Cardiorespiratory interaction increased several-fold with postnatal development, but, surprisingly, the rate of increase was not affected by gestational age at birth. We find evidence for moderate correspondence between this measure of cardiorespiratory interaction and cardioventilatory coupling and no evidence for respiratory sinus arrhythmia, leading to the need for further investigation of the underlying mechanism. Such continuous measures of physiological interaction may serve to gauge developmental maturity in neonatal intensive care patients and prove useful in decisions about incipient illness and about hospital discharge.

Sensing and responding to compliance changes during manual ventilation using a lung model: can we teach healthcare providers to improve?

OBJECTIVE To test the hypothesis that an educational intervention would improve the resuscitators ability to provide on-target volume ventilation during pulmonary compliance changes. STUDY DESIGN Neonatal professionals (n = 27) ventilated an electromechanical lung model simulating a 3-kg baby while targeting a tidal volume of 4-6 mL/kg. In this preintervention and postintervention study, a one-on-one educational intervention aimed to improve the primary outcome of on-target tidal volume delivery during high and low compliance. Seventeen subjects were retested 8 months later. RESULTS When only pressure was displayed, and using a self-inflating bag, participants improved from a mean of 6% of breaths on-target to 21% immediately after education (P < .01). Using a flow-inflating bag, participants improved from 1% to 7% of breaths on-target (P < .01). Eight-month retention testing demonstrated no difference compared with baseline. With volume displayed, the mean baseline success rate was 84% with the self-inflating bag and 68% with the flow-inflating bag. There was no significant change after education or at 8-month follow-up. CONCLUSION When pressure is displayed, resuscitators can improve their ability to respond to changes in compliance after an educational intervention. When volume is displayed, performance is markedly better at baseline, but not improved after the intervention. Our findings reconfirm that resuscitation bags should have volume displays.

Clinical associations of immature breathing in preterm infants: part 1—central apnea

Background:Apnea of prematurity (AOP) is nearly universal among very preterm infants, but neither the apnea burden nor its clinical associations have been systematically studied in a large consecutive cohort.Methods:We analyzed continuous bedside monitor chest impedance and electrocardiographic waveforms and oxygen saturation data collected on all neonatal intensive care unit (NICU) patients <35 wk gestation from 2009 to 2014 (n = 1,211; >50 infant-years of data). Apneas, with bradycardia and desaturation (ABDs), defined as central apnea ≥10 s associated with both bradycardia <100 bpm and oxygen desaturation <80%, were identified using a validated automated algorithm.Results:Number and duration of apnea events decreased with increasing gestational age (GA) and postmenstrual age (PMA). ABDs were more frequent in infants <31 wk GA at birth but were not more frequent in those with severe retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), or severe intraventricular hemorrhage (IVH) after accounting for GA. In the day before diagnosis of late-onset septicemia and necrotizing enterocolitis, ABD events were increased in some infants. Many infants continued to experience short ABD events in the week prior to discharge home.Conclusion:Frequency of apnea events is a function of GA and PMA in infants born preterm, and increased apnea is associated with acute but not with chronic pathologic conditions.

Predictive monitoring for respiratory decompensation leading to urgent unplanned intubation in the neonatal intensive care unit

Background:Infants admitted to the neonatal intensive care unit (NICU), and especially those born with very low birth weight (VLBW; <1,500 g), are at risk for respiratory decompensation requiring endotracheal intubation and mechanical ventilation. Intubation and mechanical ventilation are associated with increased morbidity, particularly in urgent unplanned cases.Methods:We tested the hypothesis that the systemic response associated with respiratory decompensation can be detected from physiological monitoring and that statistical models of bedside monitoring data can identify infants at increased risk of urgent unplanned intubation. We studied 287 VLBW infants consecutively admitted to our NICU and found 96 events in 51 patients, excluding intubations occurring within 12 h of a previous extubation.Results:In order of importance in a multivariable statistical model, we found that the characteristics of reduced O2 saturation, especially as heart rate was falling; increased heart rate correlation with respiratory rate; and the amount of apnea were all significant independent predictors. The predictive model, validated internally by bootstrap, had a receiver-operating characteristic area of 0.84 ± 0.04.Conclusion:We propose that predictive monitoring in the NICU for urgent unplanned intubation may improve outcomes by allowing clinicians to intervene noninvasively before intubation is required.

Hyperpolarized Helium-3 Diffusion-weighted Magnetic Resonance Imaging Detects Abnormalities of Lung Structure in Children With Bronchopulmonary Dysplasia

Purpose: The aim of the study was to determine whether hyperpolarized 3He diffusion-weighted magnetic resonance imaging detects abnormalities in the lungs in children with bronchopulmonary dysplasia (BPD) as compared with age-matched normal children. Materials and Methods: All experiments were compliant with Health Insurance Portability and Accountability Act (HIPAA) and performed with Food and Drug Administration approval under an IND application. The protocol was approved by our Institutional Review Board, and written informed consent was obtained. Hyperpolarized 3He diffusion-weighted magnetic resonance imaging was performed in 16 subjects with a history of preterm birth complicated by BPD (age range, 6.8 to 13.5 y; mean, 9.0 y) and in 29 healthy term-birth subjects (age range, 4.5-14.7 y; mean, 9.2 y) using a gradient-echo sequence with bipolar diffusion gradients and with measurements at 2 b values (0 and 1.6 s/cm2). Age-related comparison of the whole-lung mean apparent diffusion coefficient (ADC), 90th percentile ADC, and percentage of whole-lung volume with ADC>0.2 cm2/s between the 2 groups was examined using ordinary least-squares multiple regression. Results: The mean ADC was significantly greater in subjects with BPD (0.187 vs. 0.152 cm2/s, P<0.001). The 90th percentile ADC and mean percentage lung volume with ADC>0.2 cm2/s were also higher in the BPD group (0.258 vs. 0.215 cm2/s, 30.3% vs. 11.9%, P<0.001 for both). The body surface area–adjusted ventilated lung volume was similar in the 2 groups (1.93 vs. 1.91 L, P=0.90). Conclusions: Children with BPD had higher ADCs and the same lung volumes when compared with age-matched healthy subjects, suggesting that children with BPD have enlarged alveoli that are reduced in number.

Safety of an Alkalinizing Buffer Designed for Inhaled Medications in Humans

BACKGROUND: Airway acidification plays a role in disorders of the pulmonary tract. We hypothesized that the inhalation of alkalinized glycine buffer would measurably alkalinize the airways without compromising lung function or causing adverse events. We evaluated the safety of an inhaled alkaline glycine buffer in both healthy subjects and in subjects with stable obstructive airway disease. METHODS: This work includes 2 open-label safety studies. The healthy controls were part of a phase 1 safety study of multiple inhalations of low-dose alkaline glycine buffer; nebulized saline was used as a comparator in 8 of the healthy controls. Subsequently, a phase 2 study in subjects with stable obstructive airway disease was completed using a single nebulized higher-dose strategy of the alkaline inhalation. We studied 20 non-smoking adults (10 healthy controls and 10 subjects with obstructive airway disease), both at baseline and after inhalation of alkaline buffer. We used spirometry and vital signs as markers of clinical safety. We used changes in fraction of exhaled nitric oxide (NO) and exhaled breath condensate (EBC) pH as surrogate markers of airway pH modification. RESULTS: Alkaline glycine inhalation was tolerated by all subjects in both studies, with no adverse effects on spirometric parameters or vital signs. Airway alkalinization was confirmed by a median increase in EBC pH of 0.235 pH units (IQR 0.56–0.03, P = .03) in subjects after inhalation of the higher-dose alkaline buffer (2.5 mL of 100 mmol/L glycine). CONCLUSIONS: Alkalinization of airway lining fluid is accomplished with inhalation of alkaline glycine buffer and causes no adverse effects on pulmonary function or vital signs.