Vito Giordano

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.

The implementation of systematic pain and sedation management has no impact on outcome in extremely preterm infants.

This study compared the short‐term and neurodevelopmental outcomes of extremely preterm infants before and after the implementation of a protocol to manage neonatal pain and sedation.

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.

Decompressing posthaemorrhagic ventricular dilatation significantly improves regional cerebral oxygen saturation in preterm infants

This study aimed to delineate the impact of posthaemorrhagic ventricular dilatation (PHVD) on regional cerebral oxygen saturation (rcSO2) in preterm infants before and after ventricular decompression using near‐infrared spectroscopy (NIRS).

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.

Being Born Small for Gestational Age Influences Amplitude-Integrated Electroencephalography and Later Outcome in Preterm Infants

Background: The impact of growth restriction on perinatal morbidity is well known, but electroencephalographic (EEG) data on its influence are still scarce. Objectives: We aimed to analyze the influence of being born small for gestational age (SGA; defined as a birth weight <10th percentile) on the amplitude-integrated EEG (aEEG) score in the first 2 weeks of life in preterm infants born before 30 weeks of gestation, and its impact on later outcome. Methods: aEEG data obtained within the first 2 weeks of life on preterm infants born SGA and before 30 weeks of gestational age (GA) were analyzed retrospectively using a combined score [including background activity, occurrence of sleep-wake cycles (SWC) and suspected seizure activity]. Neurodevelopmental outcome was evaluated at 24 months by means of the Bayley Scales of Infant Development II and a standardized neurological examination. Results: One hundred and thirty-six patients were included (47 SGA and 89 controls). Infants with SGA had abnormal aEEG scores significantly more often (57 vs. 24%, p = 0.002) than infants born appropriate for gestational age (AGA). They also displayed SWC less frequently (65 vs. 96%, p = 0.001), were more likely to develop seizure activity (15 vs. 4%, p = 0.013) and had a normal neurodevelopmental outcome at the age of 2 years less frequently (36.2 vs. 59.6%, p = 0.02). Conclusion: Preterm infants born SGA and before 30 weeks of GA had less optimal scores on early aEEG and a poorer neurodevelopmental outcome at 24 months than the AGA controls.

The Neonatal Pain, Agitation and Sedation Scale reliably detected oversedation but failed to differentiate between other sedation levels.

The aim of this study was to analyse the sedation subscale of the Neonatal Pain, Agitation and Sedation Scale (N‐PASS), because the N‐PASS has only been validated for the assessment of acute and prolonged pain.

Prediction of Outcome in Neonates with Hypoxic-Ischemic Encephalopathy II: Role of Amplitude-Integrated Electroencephalography and Cerebral Oxygen Saturation Measured by Near-Infrared Spectroscopy

Background: Few data have been published on the combined use of amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy (NIRS) for outcome prediction in neonates cooled for hypoxic-ischemic encephalopathy (HIE). Objective: Our aim was to evaluate the predictive values and the most powerful predictive combinations of single aEEG and NIRS parameters and the respective cut-off values with regard to short-term outcomes in HIE II. Methods: aEEG and NIRS were prospectively studied at the Medical University of Vienna in the first 102 h of life with regard to magnetic resonance imaging (MRI). Thirty-two neonates diagnosed with HIE II treated with hypothermia were investigated. The measurement period was divided into 6-h epochs. According to MRI, 2 outcome groups were defined and predictive values of aEEG parameters, regional cerebral oxygen saturation (rScO2), and the additional value of both methods combined were studied. Receiver operating curves (ROC) were obtained and area under the curve (AUC) values were calculated. ROC were then used to detect the optimal cut-off points, sensitivity, specificity, positive predictive values, and negative predictive values. Results: At all time epochs, combined parameter scores were more predictive than single parameter scores. The highest AUC were observed between 18 and 60 h of cooling for the aEEG summation score (0.72-0.84) and for (background pattern + seizures) × rScO2 (0.79-0.85). At 42-60 h sensitivity was similar between those 2 scores (87.5-90.0%), but the addition of NIRS to aEEG led to an increase in specificity (from 52.4-59.1% to 72.7-90.5%). Conclusions: In HIE II, aEEG and NIRS are important predictors of short-term outcome. The combination of both methods improves prognostication. The highest predictive abilities were observed between 18 and 60 h of cooling.

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.

Effect of increased opiate exposure on three years neurodevelopmental outcome in extremely preterm infants

BACKGROUND International guidelines recommend the use of item based scales for the assessment of pain and sedation. In our previous study, the implementation of the Neonatal Pain Agitation and Sedation Scale (N-PASS), and the associated systematic assessment and treatment of pain and sedation reduced pain and over-sedation in our intervention group, but lead to a significant increase of individual opiate exposure. This increased opiate exposure was not associated with impaired motor and mental development at one year of age. As one-year follow-up is not necessarily representative for future outcomes, we retested our sample at three years of age. METHODS Fifty-three patients after (intervention group) and 61 before implementation (control group) of the N-PASS and the Vienna Protocol for the Management of Neonatal Pain and Sedation (VPNPS), were compared for motor, mental and behavioural development at three-years follow-up using the Bayley Scales of Infant Development. RESULTS Cumulative opiate exposure was not associated with mental (p = .31) and motor (p = .20) problems when controlling for other important medical conditions, but was associated to lower behavioural scores (p = .007). No statistically significant differences were found with regard to mental (p = .65), psychomotor (p = .12) and behavioural (p = .61) development before and after the implementation of the N-PASS and the VPNPS. CONCLUSION Implementing a neonatal pain and sedation protocol increased opiate exposure without affecting neurodevelopmental outcome at three-years of age.