Impact of neonatal pain and opiate administration in animal models: A meta-analysis concerning pain threshold.

BACKGROUND AND AIM: Neonatal intensive care treatment, including frequently performed painful procedures and administration of analgesic drugs, can have different effects on the neurodevelopment. This systematic review and meta-analysis aimed to investigate the influence of pain, opiate administration, and pre-emptive opiate administration on pain threshold in animal studies in rodents, which had a brain development corresponding to preterm and term infants. METHODS: A systematic literature search of electronic data bases including CENTRAL (OVID), CINAHL (EBSCO), Embase.com, Medline (OVID), Web of Science, and PsycInfo (OVID) was conducted. A total of 42 studies examining the effect of pain (n = 38), opiate administration (n = 9), and opiate administration prior to a painful event (n = 5) in rodents were included in this analysis. RESULTS: The results revealed that pain (g = 0.42, 95%CI 0.16-0.67, p = 0.001) increased pain threshold leading to hypoalgesia. Pre-emptive opiate administration had the opposite effect, lowering pain threshold, when compared to pain without prior treatment (g = -1.79, 95%CI -2.71-0.86, p = 0.0001). Differences were found in the meta regression for type of stimulus (thermal: g = 0.66, 95%CI 0.26-1.07, p = 0.001; vs. mechanical: g = 0.13, 95%CI -0.98-1.25, p = 0.81) and gestational age (b = -1.85, SE = 0.82, p = 0.027). In addition, meta regression indicated an association between higher pain thresholds and the amount of cumulative pain events (b = 0.06, SE = 0.03, p = 0.05) as well as severity of pain events (b = 0.94, SE = 0.28, p = 0.001). CONCLUSION: Neonatal exposure to pain results in higher pain thresholds. However, caution is warranted in extrapolating these findings directly to premature infants. Further research is warranted to validate similar effects in clinical contexts and inform evidence-based practices in neonatal care.

[The unconscious child]. / Das bewusstlose Kind.

Acute disturbance of consciousness in a child is a potentially life-threatening condition. There are a variety of possible causes - traumatic, infectious, toxic, metabolic/endocrine, cardio-circulatory - to name a few. The history often provides important clues to narrow down the differential diagnoses. The recognition of reversible causes and a structured diagnostic process are life-saving in an emergency.

Perceived stress of mothers and fathers on two NICUs before and during the SARS-CoV-2 pandemic.

Parents of very low birth weight (VLBW) infants in a neonatal intensive care unit experienced additional stress during the SARS-CoV-2 pandemic due to the related restrictions in hospital visiting policies. Our study aimed to compare parents' burdens before and during the pandemic. This survey included 121 parents of 76 VLBW infants in two European Level IV perinatal centers before and during the pandemic. We performed standardized parent questionnaires with mothers and fathers separately to evaluate their emotional stress and well-being. The pandemic worsened the emotional well-being of parents of VLBW infants, particularly of mothers. During the pandemic, mothers reported significantly higher state anxiety levels (48.9 vs. 42.9, p = 0.026) and hampered bonding with the child (6.3 vs. 5.2, 0 = 0.003) than before. In addition, mothers felt more personally restricted than fathers (6.1 vs. 5.2, p = 0.003). Fathers experienced lower levels of stress than mothers; they were equally burdened before and during the pandemic. Restrictions in visiting policies for families of VLBW infants during the SARS-CoV-2 pandemic have a significant negative impact on parental stress and should therefore be applied cautiously.

Pilot study of an interprofessional pediatric mechanical ventilation educational initiative in two intensive care units.

INTRODUCTION: Inappropriate ventilator settings, non-adherence to a lung-protective ventilation strategy, and inadequate patient monitoring during mechanical ventilation can potentially expose critically ill children to additional risks. We set out to improve team theoretical knowledge and practical skills regarding pediatric mechanical ventilation and to increase compliance with treatment goals. METHODS: An educational initiative was conducted from August 2019 to July 2021 in a neonatal and pediatric intensive care unit of the University Children's Hospital, Hamburg-Eppendorf, Germany. We tested baseline theoretical knowledge using a multiple choice theory test (TT) and practical skills using a practical skill test (PST), consisting of four sequential Objective Structured Clinical Examinations of physicians and nurses. We then implemented an educational bundle that included video self-training, checklists, pocket cards, and reevaluated team performance. Ventilators and monitor settings were randomly checked in all ventilated patients. We used a process control chart and a mixed-effects model to analyze the primary outcome. RESULTS: A total of 47 nurses and 20 physicians underwent assessment both before and after the implementation of the initiative using TT. Additionally, 34 nurses and 20 physicians were evaluated using the PST component of the initiative. The findings revealed a significant improvement in staff performance for both TT and PST (TT: 80% [confidence interval (CI): 77.2-82.9] vs. 86% [CI: 83.1-88.0]; PST: 73% [CI: 69.7-75.5] vs. 95% [CI: 93.8-97.1]). Additionally, there was a notable increase in self-confidence among participants, and compliance with mechanical ventilation treatment goals also saw a substantial rise, increasing from 87.8% to 94.5%. DISCUSSION: Implementing a pediatric mechanical ventilation education bundle improved theoretical knowledge and practical skills among interprofessional pediatric intensive care staff and increased treatment goal compliance in ventilated children.

Recommendations for endotracheal tube insertion depths in children.

BACKGROUND: Endotracheal tube (ETT) malposition is frequent in paediatric intubation. The current recommendations for ETT insertion depths are based on formulae that hold various limitations. This study aimed to develop age-based, weight-based and height-based curve charts and tables for ETT insertion depth recommendations in children. METHODS: In this retrospective single-centre study, we determined the individual optimal ETT insertion depths in paediatric patients by evaluating postintubation radiographic images. Age-based, weight-based and height-based ETT insertion depth recommendations were developed using regression analysis. We compared the insertion depths predicted by the models with previously published formulae. RESULTS: Intubations of 167 children (0-17.9 years) were analysed. Best-fit curves generated with logistic regression analysis revealed R2 values between 0.784 and 0.880. The insertion depths predicted by the models corresponded well with published age-based and height-based formulae. However, they demonstrated the unsuitability of weight-related linear formulae to predict ETT depth in children. CONCLUSION: The recommendations developed in this study facilitate a fast and accurate determination of recommended ETT insertion depths in children. Our recommendations provide greater accuracy than previously published formulae and demonstrate that weight-related linear formulae are unsuitable for predicting ETT depth in children.

Impact of probe-induced abdominal compression on two-dimensional shear wave elastography measurement of split liver transplants in children.

PURPOSE: To evaluate the effect of probe-induced abdominal compression of split liver transplants (SLT) in children on 2D-shear wave elastography (SWE) values. MATERIALS AND METHODS: Data from 11 children (4.7 ±â€Š4.8 years) who had undergone SLT and SWE were evaluated retrospectively. Elastograms were obtained with probes placed in an epigastric, midline position on the abdominal wall, with no and slight compression, using convex and linear transducers. For each identically positioned probe and condition, 12 serial elastograms were obtained and the SLT diameter was measured. Liver stiffness and degree of SLT compression were compared. RESULTS: Slight probe pressure resulted in SLT compression, with a shorter distance between the cutis and the posterior margin of the liver transplant than in the measurement with no pressure (curved array, 5.0 ±â€Š1.1 vs. 5.9 ±â€Š1.3 cm, mean compression 15 %±â€Š8 %; linear array, 4.7 ±â€Š0.9 vs. 5.3 ±â€Š1.0 cm, mean compression 12 %±â€Š8 %; both p < 0.0001). The median liver stiffness was significantly greater with slight pressure than with no pressure (curved transducer, 13.38 ±â€Š3.0 vs. 7.02 ±â€Š1.7 kPa, p < 0.0001; linear transducer, 18.53 ±â€Š7.1 vs. 9.03 ±â€Š1.5 kPa, p = 0.0003). CONCLUSION: Slight abdominal compression can significantly increase SWE values in children with left-lateral SLT. To obtain meaningful results and reduce operator dependency in free-hand examinations, probe pressure must be controlled carefully. KEY POINTS: · Probe-induced compression can increase elastography values in split liver transplants in children. · In free-hand examination, probe pressure must be controlled carefully. · Pressure loading can be determined indirectly by the anteroposterior transplant diameter. CITATION FORMAT: · Groth M, Fischer L, Herden U et al. Impact of probe-induced abdominal compression on two-dimensional shear wave elastography measurement of split liver transplants in children. Fortschr Röntgenstr 2023; 195: 905 - 912.

Living in a box: Understanding acoustic parameters in the NICU environment.

Background: In the last years, a significant body of scientific literature was dedicated to the noisy environment preterm-born infants experience during their admission to Neonatal Intensive Care Units (NICUs). Nonetheless, specific data on sound characteristics within and outside the incubator are missing. Therefore, this study aimed to shed light on noise level and sound characteristics within the incubator, considering the following domain: environmental noise, incubator handling, and respiratory support. Methods: The study was performed at the Pediatric Simulation Center at the Medical University of Vienna. Evaluation of noise levels inside and outside the incubator was performed using current signal analysis libraries and toolboxes, and differences between dBA and dBSPL values for the same acoustic noises were investigated. Noise level results were furthermore classed within previously reported sound levels derived from a literature survey. In addition, sound characteristics were evaluated by means of more than 70 temporal, spectral, and modulatory timbre features. Results: Our results show high noise levels related to various real-life situations within the NICU environment. Differences have been observed between A weighted (dBA) and unweighted (dBSPL) values for the same acoustic stimulus. Sonically, the incubator showed a dampening effect on sounds (less high frequency components, less brightness/sharpness, less roughness, and noisiness). However, a strong tonal booming component was noticeable, caused by the resonance inside the incubator cavity. Measurements and a numerical model identified a resonance of the incubator at 97 Hz and a reinforcement of the sound components in this range of up to 28 dB. Conclusion: Sound characteristics, the strong low-frequency incubator resonance, and levels in dBSPL should be at the forefront of both the development and promotion of incubators when helping to preserve the hearing of premature infants.

The impact of pandemic restrictive visiting policies on infant wellbeing in a NICU.

BACKGROUND: Given the countrywide lockdown in the first pandemic period and the respective Hospital restrictive policies, we aimed to investigate if the SARS-COV-2 pandemic was associated to a reduced parental presence in the NICU and in which form this had an impact on infant wellbeing. METHODS: Retrospective cohort study about altered NICUs parental presence (measured by number of visits and kangaroo care time) due to pandemic restrictive policies and its impact on infant wellbeing (measured through The Neonatal Pain Agitation and Sedation scale and nurses' descriptive documentation). RESULTS: Presence of both parents at the same time was significantly lower during pandemic. Contrary, maternal presence only and total kangaroo-care time were higher within the pandemic (163.36 ± 94.07 vs 122.71 ± 64.03; p = 0.000). Lower NPASS values were documented during the lookdown (1.28 ± 1.7 vs 1.78 ± 2.2; p = 0.000). CONCLUSION: Data collected through the pandemic confirm the importance of parental presence for infants' wellbeing in a NICU setting. IMPACT: Parental support is an extremely important aspect for infants hospitalized in an intensive care unit. Their presence was limited in many NICUs worldwide during the SARS-COV-2 pandemic. This study confirm the importance of parental presence for infants' wellbeing also in a pandemic situation. Our results support a family-centered newborn individualized developmental care approach in the NICU.

Pain and neurodevelopmental outcomes of infants born very preterm.

AIM: To investigate the impact of the level of pain experienced by infants born preterm on neurodevelopmental outcomes during their stay in a neonatal intensive care unit. METHOD: In this retrospective data analysis we included all surviving infants born preterm with a gestational age between 23 and 32 weeks from 2011 to 2015, who were assessed using the Neonatal Pain, Agitation, and Sedation Scale and examined at 1 year of age using the Bayley Scales of Infant Development. We excluded all infants who had suffered severe neurological morbidities and undergone surgical interventions. RESULTS: A total of 196 infants born preterm were included in the analyses: 105 in the 'no pain group' and 91 in the 'pain group'. Significant differences between the groups were detected for both mental and motor development (p = 0.003, 95% confidence interval [CI] 2.23-10.92; p = 0.025, 95% CI 0.64-9.78). The results remained significant after controlling for other important medical conditions (p = 0.001, 95% CI -19.65 to -5.40; p = 0.010, 95% CI -16.18 to -2.29). INTERPRETATION: Neonatal pain exposure was associated with altered neurodevelopmental outcomes of infants born very preterm at a corrected age of 12 months. This observation highlights the importance of adequate pain management to reduce the risk of poor neurodevelopmental outcomes in these vulnerable patients.

Recommendations for Peripherally Inserted Central Catheter Insertion Depths in Neonates.

OBJECTIVE: Malposition of peripherally inserted central catheters (PICCs) is common. Recommendations for PICC insertion depths are scarce and comprise complex equations. This study aimed to develop diagrams and tables for the recommendation of PICC insertion depths in neonates based on anthropometric parameters. STUDY DESIGN: In this retrospective single-center study, the individual optimal PICC insertion depths were correlated with body weight, length, and head circumference. Using linear regression analysis, line charts and tables for the recommendation of PICC insertion depth were generated and compared with previously published recommendations. RESULT: PICC insertion depths of 204 infants (gestational age at PICC installation: 24.0-44.9 weeks) with 131 (64%) PICC in the upper extremities and 73 (36%) in the lower extremities were analyzed. Linear logistic regression models revealed R2 values between 0.387 and 0.884. CONCLUSION: The charts and table developed in this study enable a fast and accurate determination of recommended PICC insertion depths in neonates.

Recommendations for nasotracheal tube insertion depths in neonates.

Background: Endotracheal tube (ETT) malposition is common in neonatal intubation. Recommendations for ETT insertion depths predominantly address orotracheal intubation. The aim of this study was to develop gestational age-, weight-, and length-based curve charts and tables for nasotracheal ETT insertion depth recommendations in neonates. Method: In this retrospective single-center study, the individual optimal ETT insertion depths in neonates were determined by evaluating postintubation radiographic images. Gestational age-, weight-, and length-based best-fit curves and tables were generated using regression analysis to calculate related ETT insertion depths. The insertion depths predicted by the models were compared with previously published recommendations. Results: We analyzed intubations of 178 neonates (gestational age range at intubation: 23.7-43.0 weeks). Applying sigmoidal logistic regression models, curves, and tables revealed R 2 values between 0.766 and 0.837. The insertion depths predicted by the models revealed certain deviations when compared with four previously published recommendations for nasotracheal ETT depth estimation in neonates. Conclusion: The charts and tables developed in this study enable a fast and accurate determination of recommended nasotracheal ETT insertion depths in neonates.

Audio Feature Analysis for Acoustic Pain Detection in Term Newborns.

INTRODUCTION: Crying newborns signal a need or discomfort as part of the innate communication system. Exposure to pain is related to infants' unfavorable neurodevelopmental outcomes. There is a tremendous need for more objective methods to assess neonatal pain. An audio analysis of acoustic utterances could provide specific information on the patient's pain level. METHODS: We analyzed 67 videos of 33 term-born newborns recorded during a planned capillary blood sample, including the stimuli, non-noxious thermal stimulus, short noxious stimulus, and prolonged unpleasant stimulus, between December 2020 and March 2021. Two expert raters evaluated the infants' pain responses using the Neonatal Facial Coding System (NFCS). The mean values of 123 timbre features of the recorded audio data were analyzed by using specific toolboxes and libraries from the following programming environments: MIRtoolbox (MATLAB), MiningSuite (MATLAB), Essentia (Python), AudioCommons timbral models (Python), and Librosa (Python). RESULTS: The NFCS values were significantly higher during the short noxious stimulus (p < 0.001) and prolonged unpleasant stimulus (p < 0.001) than during the non-noxious thermal stimulus, whereas NFCS values during the short noxious stimulus and prolonged unpleasant stimulus were similar (p = 0.79). Brightness, roughness, percussive energy, and attack times were identified as the features having the highest impact on the NFCS. CONCLUSION: This hypothesis-generating study identified several salient acoustic features highly associated with pain responses in term newborns. Our analysis is an encouraging starting point for the targeted analysis of pain-specific acoustic features of neonatal cries and vocalizations from the perspective of real-time acoustic processing.

Teaching fiberoptic-assisted tracheoscopy in very low birth weight infants: A randomized controlled simulator study.

Objective: We developed a fiberoptic-assisted tracheoscopy (FAST) method to avoid direct laryngoscopy during surfactant replacement therapy and compared two training approaches on a very low birth weight (VLBW) infant simulator. Design: This prospective randomized controlled study was conducted at the Department of Neonatology and Pediatric Intensive Care Medicine of the University Medical Center Hamburg-Eppendorf, Germany. Participants: We recruited physicians, trainees, students, and nurses without prior experience in endoscopic techniques. Interventions: Participants were assigned randomly to a group that received instructions according to Peyton's Four-Step Approach and a control group that received standard bedside teaching only. Main outcome measures: Primary endpoints were the total and the component times required to place the bronchoscope and the method success. Results: We recruited 186 participants. Compared with the control group, the Peyton group had a lower mean (±standard deviation) FAST completion time (33.2 ± 27.5 s vs. 79.5 ± 47.9 s, p < 0.001; d = 1.12) and a higher FAST success rate (95% vs. 84%, p = 0.036, V = 0.18). Conclusion: After standardized training, the vast majority of novices completed FAST successfully. Peyton's four-step approach resulted in faster and more successful performance than standardized training.

Therapeutic Management of COVID-19 in a Pediatric Patient with Neurodegenerative CLN2 Disease and ICV-Enzyme Replacement Therapy: A Case Report.

The 12 years old male patient presented here suffers from neuronal ceroid lipofuscinoses 2 (CLN2) (MIM# 204500) and receives intracerebroventricular enzyme replacement therapy (ICV-ERT) every 14 days. After the emergence of the coronavirus disease 2019 (COVID-19) pandemic, routine care of children and adolescents with rare chronic diseases has become challenging. Although, in general, children do not develop severe COVID-19, when severe acute respiratory syndrome coronavirus 2 infection was detected by polymerase chain reaction-screening examination in our CLN2 patient before hospital admission for ICV-ERT, he was regarded to be at risk. Upon diagnosis, the patient developed respiratory deterioration symptoms and was admitted to our pediatric intensive care unit to receive oxygen, remdesivir, and steroids. As far as we know, this is the first CLN2 patient receiving intraventricular enzyme therapy with COVID-19 who required intensive care treatment and specific therapy.

Discriminant properties of the Behavioral Pain Scale for assessment of procedural pain-related distress in ventilated children.

OBJECTIVES: Children hospitalized in a pediatric intensive care unit (PICU) are frequently exposed to distressing and painful medical procedures and interventions. There is a lack of clinical scales to measure procedural pain-related distress in ventilated children. The Behavioral Pain Scale (BPS) was initially developed to detect procedural pain in critically ill adults. This study aims to assess the BPS's discriminant properties for measuring procedural pain-related distress in ventilated pediatric patients incorporating two instruments validated for pediatric patients. METHODS: This prospective exploratory study was performed with ventilated children admitted to the interdisciplinary 14-bed PICU of the University Children's Hospital, University Medical Center Hamburg-Eppendorf, Germany. The nurse in charge and an independent observer simultaneously assessed the patients using German versions of the BPS, the COMFORT-B scale (CBS), and the modified Face, Legs, Activity, Cry, Consolability (mFLACC) scale immediately before and during endotracheal suctioning. RESULTS: We analyzed 170 parallel assessments in n=34 ventilated children. Patients were (mean ± SD) 9.5 ± 4.8 years old. Internal consistency for the BPS was excellent (α=0.93). We found a high rater agreement for all clinical scales (BPS: k=0.73, CBS: k=0.80, mFLACC: k=0.71). Strong correlations were identified between BPS and CBS (r=0.89) and BPS and mFLACC (r=0.79). The BPS cutoff values showed likewise excellent results (area under the curve CBS >16: 0.97; mFLACC >2: 0.91). CONCLUSIONS: In our population of ventilated children, the BPS was well suited to detect procedural pain-related distress compared with two validated pain scales. Further extensive validation studies should follow to support our findings.

The consequences of neonatal pain, stress and opiate administration in animal models: An extensive meta-analysis concerning neuronal cell death, motor and behavioral outcomes.

This systematic review and meta-analysis aimed to investigate the association of neonatal exposure to pain, stress, opiate administration alone, as well as opiate administration prior to a painful procedure on neuronal cell death, motor, and behavioral outcomes in rodents. In total, 36 studies investigating the effect of pain (n = 18), stress (n = 15), opiate administration (n = 13), as well as opiate administration prior to a painful event (n = 7) in rodents were included in our meta-analysis. The results showed a large effect of pain (g = 1.37, 95% CI 1.00-1.74, p < .001) on neuronal cell death. Moreover, higher number of neonatal pain events were significantly associated with increased neuronal cell death, increased anxiety (b = -1.18, SE = 0.43, p = .006), and depressant-like behavior (b = 1.74, SE = 0.51, p = .027) in rodents. Both opiates and pain had no impact on motor function (g = 0.26, 95% CI 0.18-0.70, p = .248).