Tobias Werther

Successful Implementation of a Neonatal Pain and Sedation Protocol at 2 NICUs

OBJECTIVE: To evaluate the implementation of a neonatal pain and sedation protocol at 2 ICUs. METHODS: The intervention started with the evaluation of local practice, problems, and staff satisfaction. We then developed and implemented the Vienna Protocol for Neonatal Pain and Sedation. The protocol included well-defined strategies for both nonpharmacologic and pharmacologic interventions based on regular assessment of a translated version of the Neonatal Pain Agitation and Sedation Scale and titration of analgesic and sedative therapy according to aim scores. Health care staff was trained in the assessment by using a video-based tutorial and bedside teaching. In addition, we performed reevaluation, retraining, and random quality checks. Frequency and quality of assessments, pharmacologic therapy, duration of mechanical ventilation, and outcome were compared between baseline (12 months before implementation) and 12 months after implementation. RESULTS: Cumulative median (interquartile range) opiate dose (baseline dose of 1.4 [0.5–5.9] mg/kg versus intervention group dose of 2.7 [0.4–57] mg/kg morphine equivalents; P = .002), pharmacologic interventions per episode of continuous sedation/analgesia (4 [2–10] vs 6 [2–13]; P = .005), and overall staff satisfaction (physicians: 31% vs 89%; P < .001; nurses: 17% vs 55%; P < .001) increased after implementation. Time on mechanical ventilation, length of stay at the ICU, and adverse outcomes were similar before and after implementation. CONCLUSIONS: Implementation of a neonatal pain and sedation protocol at 2 ICUs resulted in an increase in opiate prescription, pharmacologic interventions, and staff satisfaction without affecting time on mechanical ventilation, length of intensive care stay, and adverse outcomes.

Automated classification of neonatal sleep states using EEG

OBJECTIVE To develop a method for automated neonatal sleep state classification based on EEG that can be applied over a wide range of age. METHODS We collected 231 EEG recordings from 67 infants between 24 and 45weeks of postmenstrual age. Ten minute epochs of 8 channel polysomnography (N=323) from active and quiet sleep were used as a training dataset. We extracted a set of 57 EEG features from the time, frequency, and spatial domains. A greedy algorithm was used to define a reduced feature set to be used in a support vector machine classifier. RESULTS Performance tests showed that our algorithm was able to classify quiet and active sleep epochs with 85% accuracy, 83% sensitivity, and 87% specificity. The performance was not substantially lowered by reducing the epoch length or EEG channel number. The classifier output was used to construct a novel trend, the sleep state probability index, that improves the visualisation of brain state fluctuations. CONCLUSIONS A robust EEG-based sleep state classifier was developed. It performs consistently well across a large span of postmenstrual ages. SIGNIFICANCE This method enables the visualisation of sleep state in preterm infants which can assist clinical management in the neonatal intensive care unit.

Bispectral Index and Lower Margin Amplitude of the Amplitude-Integrated Electroencephalogram in Neonates

Background: The lower margin amplitude (LMA) of the amplitude-integrated electroencephalogram (aEEG) is suppressed in neonates during deep sedation, a feature that is attributed to the bispectral index (BIS) in adults. Objective: We compare the BIS and the LMA of the aEEG in neonates. Methods: Thirty neurologically healthy neonates between 37 and 44 weeks postmenstrual age were included in this study. Twenty patients received sedoanalgesic therapy for various reasons. BIS and aEEG recordings were performed simultaneously. The digital data were imported in the numerical software environment Matlab®. The LMA of the aEEG was computed on a 1-min time scale and synchronized with the BIS data. The correlation between the time-dependent variables BIS and LMA was estimated using the Spearman rank correlation index. Results: The median correlation between BIS and LMA was 0.3. Inclusion of recordings of high signal quality only into analysis improved the median correlation index to 0.6. Conclusions: We found a light-to-moderate correlation between BIS and LMA in our study cohort and a good correlation in the subgroup with high signal quality.

Functional maturation in preterm infants measured by serial recording of cortical activity

Minimally invasive, automated cot-side tools for monitoring early neurological development can be used to guide individual treatment and benchmark novel interventional studies. We develop an automated estimate of the EEG maturational age (EMA) for application to serial recordings in preterm infants. The EMA estimate was based on a combination of 23 computational features estimated from both the full EEG recording and a period of low EEG activity (46 features in total). The combination function (support vector regression) was trained using 101 serial EEG recordings from 39 preterm infants with a gestational age less than 28 weeks and normal neurodevelopmental outcome at 12 months of age. EEG recordings were performed from 24 to 38 weeks post-menstrual age (PMA). The correlation between the EMA and the clinically determined PMA at the time of EEG recording was 0.936 (95%CI: 0.932–0.976; n = 39). All infants had an increase in EMA between the first and last EEG recording and 57/62 (92%) of repeated measures within an infant had an increasing EMA with PMA of EEG recording. The EMA is a surrogate measure of age that can accurately determine brain maturation in preterm infants.

Left ventricular pumping during the transition–adaptation sequence in preterm infants: impact of the patent ductus arteriosus

BackgroundPostnatally, the immature left ventricle (LV) is subjected to high systemic afterload. Hypothesizing that LV pumping would change during transition–adaptation, we analyzed the LV in preterm infants (GA≤32+6), clinically stable or with a hemodynamically significant patent ductus arteriosus (hPDA) by applying a pump model.MethodsPumping was characterized by EA (effective arterial elastance, reflecting afterload), EES (end-systolic LV elastance, reflecting contractility), EA/EES coupling ratios, descriptive EA:EES relations, and EA/EES graphs. Data calculated from echocardiography and blood pressure were analyzed by diagnosis (S group: clinically stable, no hPDA, n=122; hPDA group, n=53) and by periods (early transition: days of life 1–3; late transition: 4–7; and adaptation: 8–30).ResultsS group: LV pumping was characterized by an increased EA/EES coupling ratio of 0.65 secondary to low EES in early transition, a tandem rise of both EA and EES in late transition, and an EA/EES coupling ratio of 0.45 secondary to high EES in adaptation; hPDA group: time-trend analyses showed significantly lower EA (P<0.0001) and EES (P=0.006). Therefore, LV pumping was characterized by a lower EA/EES coupling ratio (P=0.088) throughout transition–adaptation.ConclusionsIn stable infants, facing high afterload, the immature LV, enhanced by the physiological PDA, increases its contractility. In hPDA, facing low afterload, the overloaded immature LV exhibits a consistently lower contractility.

The impact of extrauterine life on visual maturation in extremely preterm born infants

BackgroundExtrauterine life is an important factor when considering brain maturation. Few studies have investigated the development of visual evoked potentials (VEP) in extremely preterm infants, and only a minority have taken into consideration the impact of extrauterine life. The aim of this study was to assess the normal maturation of VEP in infants born prior to 29 weeks gestational age (GA) and to explore the potential influence of extrauterine life.MethodsVEP were prospectively recorded in extremely preterm infants, and principal peaks (N0, N1, P1, N2, P2, N3) were identified. The mean of peak-time and percentages of peak appearances were assessed for three GA groups (23/24, 25/26, 27/28 weeks) and four subgroups of increasing postnatal age (PNA), up to 8 weeks after birth.ResultsA total of 163 VEP recordings in 38 preterm infants were analyzed. With increasing GA at birth, peak-times decreased. When comparing infants with equal GA but longer extrauterine life, those with the highest PNA demonstrated the shortest VEP peak-times. However, this effect was less present in infants born prior to 25 weeks GA.ConclusionProvided that a certain maturational threshold is reached, extrauterine life appears to accelerate maturation of the visual system in preterm infants.

Are All Amplitude-Integrated Electroencephalogram Systems Equal?

Background: Filter and peak detection algorithms implemented in amplitude-integrated electroencephalogram (aEEG) systems are not standardized. New aEEG systems are continuously enriching the market and clinicians are faced with different aEEG devices whose tracings may vary. Objectives: The aim of this work was to determine the role of different aEEG systems on quantitative measurements of the aEEG. Methods: In this observational study, a single-channel aEEG recording (Olympic CFM 6000) with corresponding EEG signal was obtained from 32 infants at a gestational age of 36-44 weeks. The signals were split into 334 episodes of 4 h. New aEEG tracings were generated using the NicoletOne Reader Software and aEEG emulations with varying filter profiles and peak detection settings. The aEEG amplitude margins and automated annotation of continuous normal voltage (CNV) were compared. Results: The output of the Olympic and the NicoletOne systems are very similar but not identical; the Spearman rank correlations of the aEEG amplitude margins exceeded 0.9 and the differences in the lower and upper amplitude margins were 1.55 μV (SD 1.47) and -2.12 μV (SD 1.44) on average (n = 309), respectively. The aEEG emulation showed that the differences between the output of the Olympic and the NicoletOne system could be primarily ascribed to the peak detection algorithm. The differences in output can affect automated analyses with agreement rates in CNV detection of 76% (n = 32, positive) and 92% (n = 32, negative) when comparing the Olympic to the NicoletOne outputs. Conclusions: Commercial aEEG systems have similar but not identical outputs. Care is advised when interpreting automated aEEG classifications across different devices.

PO-0454 Impact Of Systematic Pain And Sedation Management On Outcome Of Very Low Birth Weight Infants

Background and objectives We retrospectively compared short-term and neurodevelopmental outcome of very low birth weight infants (VLBWI) before (n = 84) and after implementation (n = 69) of a protocol for the management of neonatal pain and sedation. Methods Opiate exposure, time on mechanical ventilation, inotropic support, details on nutritional aspects, and growth were compared between baseline and after protocol implementation. Infants were evaluated at 12 months corrected age using standardised neurologic examination and Bayley Scales of Infant Development-II. Results Cumulative mean ± SD opiate dose (baseline dose of 14 ± 39 mg/kg vs. intervention group dose of 84 ± 222 mg/kg morphine equivalents; p < 0. 0001) increased after implementation. Time on mechanical ventilation, inotropic support, time on parenteral nutrition, growth, and length of stay were similar before and after implementation. There were no differences in neurodevelopmental outcome variables before and after intervention (MDI: 85 ± 14 vs. 84 ± 16, p = 0.6; PDI: 87 ± 19 vs. 83 ± 19, p = 0.2; BRS: 74 ± 27 vs. 68 ± 32, p = 0.2). Multiple linear regression analysis identified opiate exposure as a possible risk factor for lower MDI (estimate = -0.15; p = 0.004) and Behaviour Rating Scale (BRS) scores (estimate = -0.39; p = 0.012). Conclusions Implementation of a neonatal pain and sedation protocol results in an increase in opiate prescription without affecting short-term outcome and neurodevelopmental performance of VLBWI at 12 months corrected age.

O-114 Validation Of The Neonatal Pain, Agitation And Sedation Scale For The Assessment Of Sedation In Neonatal Intensive Care Patients

Background Implementation of sedation protocols based on regular sedation assessment using item-based scales can improve sedative treatment in children. There is a lack of validated tools to assess sedation in neonates. Objective To validate the Neonatal Pain, Agitation and Sedation Scale (N-PASS) for the assessment of sedation in preterm and term neonates. Methods The Nurse Interpretation of Sedation Score (NISS) was used to validate the N-PASS with regard to neonatal sedation. Paired assessments of both the N-PASS and the NISS were performed in 50 sedated neonates from 23 to 44 weeks’ postmenstrual age. Results A total set of 503 paired observations were included into analysis. The median N-PASS scores were significantly different for the three NISS categories (over-sedation (-8), adequate sedation (-2), under-sedation (0); p <.0001). Inter-observer agreement for the N-PASS sedation subscale was excellent (linearly weighted Cohen’s Kappa:. 93), as was the internal consistency estimated by a Cronbach’s alpha of 0.88, which increased to.90 when the vital sign item was excluded from the N-PASS. There was no risk of under-sedation in patients with an N-PASS score <-5 and no risk of over-sedation with an N-PASS score > -2. The N-PASS reliably detected over-sedation. Detection of under-sedation was markedly improved by simultaneous assessment of N-PASS pain scores which were significantly different in patients being considered adequately sedated vs. inadequately sedated (median N-PASS pain subscale score: 2 vs. 5). Conclusion The N-PASS meets the requirements of a valid clinical tool to assess sedation in neonates and may facilitate the use of sedation algorithms in the neonatal intensive care unit.