Biomarkers for assessing pain and pain relief in the neonatal intensive care unit

Newborns admitted to the neonatal intensive care unit (NICU) regularly undergo painful procedures and may face various painful conditions such as postoperative pain. Optimal management of pain in these vulnerable preterm and term born neonates is crucial to ensure their comfort and prevent negative consequences of neonatal pain. This entails accurate and timely identification of pain, non-pharmacological pain treatment and if needed administration of analgesic therapy, evaluation of treatment effectiveness, and monitoring of adverse effects. Despite the widely recognized importance of pain management, pain assessment in neonates has thus far proven to be a challenge. As self-report, the gold standard for pain assessment, is not possible in neonates, other methods are needed. Several observational pain scales have been developed, but these often rely on snapshot and largely subjective observations and may fail to capture pain in certain conditions. Incorporation of biomarkers alongside observational pain scores holds promise in enhancing pain assessment and, by extension, optimizing pain treatment and neonatal outcomes. This review explores the possibilities of integrating biomarkers in pain assessment in the NICU.</p

Acute Pain Assessment in Prematurely Born Infants Below 29 Weeks A Long Way to Go

Objectives: Neonates born extremely prematurely are at high risk of acute and prolonged pain. Effective treatment requires reliable pain assessment, which is currently missing. Our study explored whether existing pain assessment tools and physiological indicators measure pain and comfort accurately in this population. Materials and Methods: We prospectively collected data in 16 neonates born at less than 29 weeks’ gestational age during 3 conditions: skin-to-skin care, rest, and heelstick procedure for capillary blood sampling in the incubator. The neonates were video recorded in these situations, and recordings were coded using 5 observational pain assessment tools and numeric rating scales for pain and distress. We simultaneously collected heart rate, respiratory rate, arterial oxygen saturation, regional cerebral oxygenation, and the number of skin conductance peaks. All measures across the 3 conditions were compared using general linear modeling. Results: The median gestational age was 27.1 weeks (range: 24.1 to 28.7). Forty measurement periods across the 3 conditions were analyzed. Heart rate was significantly higher during heelstick procedures compared with during rest, with a mean difference of 10.7 beats/min (95% confidence interval [CI]: 2.7-18.6). Oxygen saturation was significantly higher during skin-to-skin care compared with during heelstick procedures with a mean difference of 5.5% (95% CI: 0.2-10.8). The Premature Infant Pain Profile-revised (PIPP-R) score was significantly higher during heelstick procedures compared with skin-to-skin care with a mean difference of 3.2 points (95% CI: 1.6-5.0). Discussion: Pain measurement in clinical practice in prematurely born infants below 29 weeks remains challenging. The included behavioral and physiological indicators did not adequately distinguish between a painful situation, rest, and skin-to-skin care in premature neonates

A “Wear and Tear” Hypothesis to Explain Sudden Infant Death Syndrome

Sudden infant death syndrome (SIDS) is the leading cause of death among USA infants under 1 year of age accounting for ~2,700 deaths per year. Although formally SIDS dates back at least 2,000 years and was even mentioned in the Hebrew Bible (Kings 3:19), its etiology remains unexplained prompting the CDC to initiate a sudden unexpected infant death case registry in 2010. Due to their total dependence, the ability of the infant to allostatically regulate stressors and stress responses shaped by genetic and environmental factors is severely constrained. We propose that SIDS is the result of cumulative painful, stressful, or traumatic exposures that begin in utero and tax neonatal regulatory systems incompatible with allostasis. We also identify several putative biochemical mechanisms involved in SIDS. We argue that the important characteristics of SIDS, namely male predominance (60:40), the significantly different SIDS rate among USA Hispanics (80% lower) compared to whites, 50% of cases occurring between 7.6 and 17.6 weeks after birth with only 10% after 24.7 weeks, and seasonal variation with most cases occurring during winter, are all associated with common environmental stressors, such as neonatal circumcision and seasonal illnesses. We predict that neonatal circumcision is associated with hypersensitivity to pain and decreased heart rate variability, which increase the risk for SIDS. We also predict that neonatal male circumcision will account for the SIDS gender bias and that groups that practice high male circumcision rates, such as USA whites, will have higher SIDS rates compared to groups with lower circumcision rates. SIDS rates will also be higher in USA states where Medicaid covers circumcision and lower among people that do not practice neonatal circumcision and/or cannot afford to pay for circumcision. We last predict that winter-born premature infants who are circumcised will be at higher risk of SIDS compared to infants who experienced fewer nociceptive exposures. All these predictions are testable experimentally using animal models or cohort studies in humans. Our hypothesis provides new insights into novel risk factors for SIDS that can reduce its risk by modifying current infant care practices to reduce nociceptive exposures

PATTERN: Pain Assessment for paTients who can't TEll using Restricted Boltzmann machiNe.

BackgroundAccurately assessing pain for those who cannot make self-report of pain, such as minimally responsive or severely brain-injured patients, is challenging. In this paper, we attempted to address this challenge by answering the following questions: (1) if the pain has dependency structures in electronic signals and if so, (2) how to apply this pattern in predicting the state of pain. To this end, we have been investigating and comparing the performance of several machine learning techniques.MethodsWe first adopted different strategies, in which the collected original n-dimensional numerical data were converted into binary data. Pain states are represented in binary format and bound with above binary features to construct (n + 1) -dimensional data. We then modeled the joint distribution over all variables in this data using the Restricted Boltzmann Machine (RBM).ResultsSeventy-eight pain data items were collected. Four individuals with the number of recorded labels larger than 1000 were used in the experiment. Number of avaliable data items for the four patients varied from 22 to 28. Discriminant RBM achieved better accuracy in all four experiments.ConclusionThe experimental results show that RBM models the distribution of our binary pain data well. We showed that discriminant RBM can be used in a classification task, and the initial result is advantageous over other classifiers such as support vector machine (SVM) using PCA representation and the LDA discriminant method

Long-term continuous monitoring of the preterm brain with diffuse optical tomography and electroencephalography: A technical note on cap manufacturing

open12noDiffuse optical tomography (DOT) has recently proved useful for detecting whole-brain oxygenation changes in preterm and term newborns' brains. The data recording phase in prior explorations was limited up to a maximum of a couple of hours, a time dictated by the need to minimize skin damage caused by the protracted contact with optode holders and interference with concomitant clinical/nursing procedures. In an attempt to extend the data recording phase, we developed a new custom-made cap for multimodal DOT and electroencephalography acquisitions for the neonatal population. The cap was tested on a preterm neonate (28 weeks gestation) for a 7-day continuous monitoring period. The cap was well tolerated by the neonate, who did not suffer any evident discomfort and/or skin damage. Montage and data acquisition using our cap was operated by an attending nurse with no difficulty. DOT data quality was remarkable, with an average of 92% of reliable channels, characterized by the clear presence of the heartbeat in most of them.openopenAlfonso Galderisi; Sabrina Brigadoi; Simone Cutini; Sara Basso Moro; Elisabetta Lolli; Federica Meconi; Silvia Benavides-Varela; Eugenio Baraldi; Piero Amodio; Claudio Cobelli; Daniele Trevisanuto; Roberto Dell'AcquaGalderisi, Alfonso; Brigadoi, Sabrina; Cutini, Simone; BASSO MORO, Sara; Lolli, Elisabetta; Meconi, Federica; Silvia, Benavides-Varela; Baraldi, Eugenio; Amodio, Piero; Cobelli, Claudio; Trevisanuto, Daniele; Dell'Acqua, Robert

Respiratory Management of Newborns

In this book, you'll learn multiple new aspects of respiratory management of the newborn. For example, ventilator management of infants with unusually severe bronchopulmonary dysplasia and infants with omphalocele is discussed, as well as positioning of endotracheal tube in extremely low birth weight infants, noninvasive respiratory support, utilization of a protocol-driven respiratory management, and more. This book includes a chapter on noninvasive respiratory function monitoring during chest compression, analyzing the efficacy and quality of chest compression and exhaled carbon dioxide. It also provides an overview on new trends in the management of fetal and transitioning lungs in infants delivered prematurely. Lastly, the book includes a chapter on neonatal encephalopathy treated with hypothermia along with mechanical ventilation. The interaction of cooling with respiration and the strategies to optimize oxygenation and ventilation in asphyxiated newborns are discussed

The consideration of individual contextual factors in neonatal pain assessment : validation and revision of the Bernese Pain Scale for Neonates

Neonates are dependent on a caregiver to discover that they are in pain and to manage it. Numerous pain assessment scales have been developed, but pain assessment is challenging because neonates of different gestational ages (GAs) have widely varied pain responses. Individual contextual factors such as GA or health status may account for this variability in pain response. The aim of the present dissertation was the validation and revision of the Bernese Pain Scale for Neonates (BPSN) by testing its psychometric properties and analyzing the influence of individual contextual factors on the variability in pain response. The BPSN is a pain assessment tool that is widely used in Swiss neonatal intensive care units. In this prospective multisite validation study, 154 neonates between 24 2/7 and 41 4/7 weeks of gestation were videotaped during 1-5 routine capillary heel sticks in their first 14 days of life. For each heel stick, three video sequences were produced: baseline, heel stick, and recovery. Comprehensive psychometric testing was conducted to examine the BPSN’s underlying factor structure, interrater reliability, concurrent and construct validity, sensitivity and specificity. Single and multiple linear mixed effects analyses were used to examine the influence of individual contextual factors on variability in pain response. The results of the psychometric testing indicated a significant reduction of the scale from nine to four items: crying, facial expression, posture and heart rate. This modified BPSN showed promising reliability and validity, especially when the cut-off that discriminates between no or low pain and moderate to severe pain is adjusted to increase with increasing GA. Apart from the GA, baseline behavioral state and ventilation status were the individual contextual factors which the revised BPSN should account for. The BPSN-Revised is a promising tool for acute procedural pain assessment in full-term and preterm neonates with different GAs. Future studies should test its validity, feasibility and clinical utility