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Objective: This article reviews pain disorders encountered in pediatric neurology practice and provides current information regarding the assessment and treatment of pediatric chronic pain., Latest Developments: Data about pediatric pain management remain sparse, owing to a dearth of controlled trials and longitudinal studies in these patients. However, the field of pain management and understanding of central and peripheral pain processing has expanded to allow more effective treatment of a broad group of children and adolescents with pain associated with neurologic disease. Neuroimaging visualizes sensory and nonsensory systems, and genetic markers of sensitivity and disease may guide specific therapy. The concept of central sensitization in chronic pain disorders has supported the development of multidisciplinary paradigms for the comprehensive care of these patients., Essential Points: Pain involves sensory activation and central nervous system modulation in pediatric patients. Pediatric neurologists should be prepared to define, investigate, and treat pain disorders in this complex patient population. Appropriate interventions during childhood may attenuate or prevent chronic pain later in life. Current interventions include behavioral, physical, and pharmacologic approaches, as well as potential noninvasive tools for neuromodulation. Research is progressing in sensory measurement, neuroimaging, genetics, and neuroinflammation to guide future targeted therapies., (Copyright © 2024 American Academy of Neurology.)

Pain in newborn children should be prevented due to negative short- and long-term consequences. A good understanding of the development of the nociceptive system in newborns is necessary to enable optimal pain assessment, and most importantly to treat and prevent pain adequately in neonates. So far, preclinical juvenile animal studies have led to a tremendous amount of information regarding the development of the nociceptive system. In addition, they have made clear that the developmental stage of the nociceptive system may influence the mechanism of action of different classes of analgesics. Age specific analgesic therapy, based on post-menstrual age, should therefore be considered by incorporating information on the developmental stages of the nociceptive system in combination with knowledge from pharmacokinetic and -dynamic studies in neonates., (© 2019 Elsevier Ltd. All rights reserved.)

Background: Although opioids are effective for neonatal postoperative pain management, cumulative opioid exposure may be detrimental. Pain management practices vary among providers, but practice guidelines may promote consistency and decrease opioid use., Purpose: To develop a pain management guideline (PMG) for neonates undergoing minor surgical procedures with the overarching goal of reducing opioid use without compromising the pain experience. The specific aim was for neonatal intensive care unit providers to adhere to the PMG at least 50% of the time., Methods: An interdisciplinary pain and sedation work group in a large level IV neonatal intensive care unit developed an evidence-based PMG for minor surgical procedures. Nurses and providers were educated on the new guideline, and rapid cycle quality improvement methodology provided an opportunity to adjust interventions over 3 months., Results: The PMG was used for 32 neonates following minor surgical procedures: 18 (56%) of the neonates received only acetaminophen and no opioids, 32% required 0.15 mg/kg dose equivalent of morphine or less, and only 9% required more than 0.15 mg/kg dose equivalent of morphine. Overall, opioid use decreased by 88% compared with rates before implementation of the PMG. Providers adhered to the PMG approximately 83.3% of time., Implications for Practice: A PMG is a systematic approach to direct nurses and providers to appropriately assess, prevent, and treat neonatal pain following minor surgery while alleviating opioid overuse., Implications for Research: Future research should focus on determining and mitigating barriers to nurse/provider use of the PMG and developing and implementing a PMG for major surgical procedures., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 by The National Association of Neonatal Nurses.)

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. [ABSTRACT FROM AUTHOR]

Less invasive surfactant administration (LISA) is an effective, minimally invasive technique of administering surfactant to infants with respiratory distress syndrome. While termed less invasive, LISA still requires airway instrumentation with direct laryngoscopy, thus may be considered painful. However, the issue of whether or not to routinely sedate infants for LISA remains contentious, with significant variation in practice between centres. Proponents for giving pharmacological analgesia and/or sedation predominantly focus on patient comfort during the procedure. However, those who favour non-pharmacological measures of pain management focus on the potential for procedural success without the risk of adverse events, such as respiratory depression and potentially the need for escalation to intubation, which may occur with pharmacological agents. The neonatal population who may benefit from LISA is varied. Due to this variety in presentation type, gestational age, and unit experience, there is a need to provide an individualized, tailored approach to sedation and analgesia for these infants. Using a blanket approach to sedation will lead to infants being exposed to sedative medications on the assumption of potential distress, rather than in response to signs of actual distress. This places the infant at risk of the adverse reactions, potentially without them ever having needed the beneficial effect of the medications. This seems an unnecessary risk. This article explores the ethical arguments pertaining to analgesia and sedation during the LISA technique, concluding that a standardized approach to the usage of pharmacological sedation is undesirable. Moreover, we maintain that procedural analgesia and sedation should be based on individualized, infant-centred assessment, rather than on a rigid, standardized approach. [ABSTRACT FROM AUTHOR]

We aimed to compare ratings of self‐reported and parent‐reported pain sensitivity between early preterm (EP), moderately‐late preterm (MLP), and full‐term (FT) adolescents. For EP adolescents, we aimed to determine whether pain sensitivity was associated with early‐life events. EP (n = 68, response rate 47.4%), MLP (n = 128, response rate 33.0%), and FT (n = 78, response rate 31.1%) adolescents and their parents (n = 277) answered an author‐generated question on pain sensitivity at 14‐15 years of age within a community‐based cohort study. Differences between groups were determined using the chi‐square test for trends. For EP adolescents, we assessed associations of treatment modalities (inotrope treatment, mechanical ventilation, and C‐section) and neonatal morbidities (sepsis/necrotizing enterocolitis, small‐for‐gestational age status, asphyxia, and cerebral pathologies) with adolescent pain sensitivity using logistic regression analyses. Increased pain sensitivity was reported by 18% of EP adolescents, compared with 12% of MLP adolescents, and 7% of FT adolescents (P = 0.033). Parent‐reported pain sensitivity did not differ by gestational age group. For EP adolescents, inotrope treatment was associated with increased pain sensitivity (odds ratio, 5.00, 95% confidence interval, 1.23‐20.4, P = 0.025). No other neonatal treatment modalities or morbidities were associated with pain sensitivity in adolescence. In conclusion, we observed higher proportions of increased pain sensitivity for EP and MLP adolescents. Physicians treating preterm adolescents should be aware of altered pain sensitivity. [ABSTRACT FROM AUTHOR]

Recent years have seen the increasing use of noninvasive respiratory support in preterm infants with the aim of minimizing the risk of mechanical ventilation and subsequent bronchopulmonary dysplasia. Respiratory distress syndrome is the most common respiratory diagnosis in preterm infants, and is best treated by administration of surfactant. Until recently, this has been performed via an endotracheal tube using premedication, which has often included opiate analgesia; subsequently, the infant has been ventilated. Avoidance of mechanical ventilation, however, does not negate the need for surfactant therapy. Less invasive surfactant administration (LISA) in spontaneously breathing infants is increasing in popularity, and appears to have beneficial effects. However, laryngoscopy is necessary, which carries adverse effects and is painful for the infant. Conventional methods of premedication for intubation tend to reduce respiratory drive, which increases the likelihood of ventilation being required. This has led to intense debate about the best strategy for providing appropriate treatment, taking into account both the respiratory needs of the infant and the need to alleviate procedural pain. Currently, clinical practice varies considerably and there is no consensus with respect to optimal management. This review seeks to summarize the benefits, risks, and challenges associated with this new approach. [ABSTRACT FROM AUTHOR]

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Objective: Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population. Study design: Term and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008–2010 (SHIVER) and 2010–2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants. Results: 244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C– 8.41%/°C, p<0.001) and metabolite clearance by 4.91%/°C (95% CI 3.53%/°C– 6.22%/°C, p<0.001) compared to normothermia (36.5°C). Simulations showed that a loading dose of 50 μg/kg followed by continuous infusion of 5 μg/kg/h resulted in morphine plasma concentrations in the desired range (between 10 and 40 μg/L) during hypothermia. Conclusions: Clearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect. Trial registration: . [ABSTRACT FROM AUTHOR]

Introduction: Pharmacologic pain management in newborns and infants is often based on limited scientific data. To close the knowledge gap, drug-related research in this population is increasingly supported by the authorities, but remains very challenging. This review summarizes the challenges of analgesic studies in newborns and infants on morphine and paracetamol (acetaminophen). Areas covered: Aspects such as the definition and multimodal character of pain are reflected to newborn infants. Specific problems addressed include defining pharmacodynamic endpoints, performing clinical trials in this population and assessing developmental changes in both pharmacokinetics and pharmacodynamics. Expert commentary: Neonatal and infant pain management research faces two major challenges: lack of clear biomarkers and very heterogeneous pharmacokinetics and pharmacodynamics of analgesics. There is a clear call for integral research addressing the multimodality of pain in this population and further developing population pharmacokinetic models towards physiology-based models. [ABSTRACT FROM AUTHOR]

Background: Necrotizing enterocolitis (NEC) is known as an extremely painful childhood condition. Objectives: The objective of this study was to explore pain management around NEC-related surgery in our neonatal intensive care unit (NICU) from a chart review of prospectively collected data on 60 operated NEC patients admitted between 2008 and 2013 with a median (IQR) gestational age of 28.3 (25.5-31.6) weeks. Methods: Pain medication data and pain scores (i.e. COMFORTneo and Numerical Rating Scale pain and distress scores) from 72 h before until 72 h after surgery were collected. Results: Preoperatively, 95% of the patients received morphine versus 100% postoperatively, with a median dosage of 10.0 (IQR 9.7-14.5) and 16.9 (IQR 10.1-20.0) μg/kg/h, respectively. Postoperatively, 28 patients (46.7%) received additional fentanyl intermittently and 14 (23.3%) received midazolam, which was part of palliative treatment for 6 patients (42.9%). In patients receiving pain medication, median COMFORTneo scores were 10 (IQR 10-11) preoperatively and 11 (10-12) postoperatively. The pain scores were comparable with those of other patients admitted to the NICU in the same time period. Conclusions: Continuous morphine of 10 μg/kg/h preoperatively, with an increase to 15 μg/kg/h postoperatively, seems to constitute a good starting dose for further individualized pain management guided by pain scores. [ABSTRACT FROM AUTHOR]

Background: Traditionally, 10 years ago, children born preterm often routinely received morphine, especially during mechanical ventilation. Studies in neonatal rats, whose stage of brain development roughly corresponds to that of children born preterm, found negative long-term effects after pain and opioid exposure. Objectives: We studied possible effects of prematurity, procedural pain and opioids in humans 10 years later. We hypothesized that these factors would negatively influence neurobiological, neuropsychological and sensory development later in life. Methods: We included 19 children born preterm who as neonates participated in an RCT on the short-term effects of morphine administration and who previously participated in our follow-up studies at ages 5 and 8/9 years. We assessed associations between brain morphology (n = 11), neuropsychological functioning (n = 19) and thermal sensitivity (n = 17) and prematurity, opioid exposure and neonatal pain. Results: Significant correlations (coefficients 0.60-0.85) of gestational age, number of painful procedures and morphine exposure with brain volumes were observed. Significant correlations between these factors and thermal sensitivity were not established. Neuropsychological outcome was significantly moderately correlated with morphine exposure in only two subtests, and children performed in general 'average' by Dutch norms. Conclusions: Although prematurity, opioid exposure and neonatal pain were significantly associated with brain volume, no major associations with neuropsychological functioning or thermal sensitivity were detected. Our findings suggest that morphine administration during neonatal life does not affect neurocognitive performance or thermal sensitivity during childhood in children born preterm without brain damage during early life. Future studies with larger sample sizes are needed to confirm these findings. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Pain is a predictable consequence following operations, but the management of postoperative pain is another challenge for anesthesiologists and inappropriately controlled pain may lead to unwanted outcomes in the postoperative period. Opioids are indeed still at the mainstream of postoperative pain control, but solely using only opioids for postoperative pain management may be connected with risks of complications and adverse effects. As a consequence, the concept of multimodal analgesia has been proposed and is recommended whenever possible. Acetaminophen is one of the most commonly used analgesic and antipyretic drug for its good tolerance and high safety profiles. The introduction of intravenous form of acetaminophen has led to a wider flexibility of its use during peri- and postoperative periods, allowing the early initiation of multimodal analgesia. Many studies have revealed the efficacy, safety and opioid sparing effects of intravenous acetaminophen. Intravenous ibuprofen has also shown to be well tolerated and demonstrated to have significant opioid sparing effects during the postoperative period. However, the number of randomized controlled trials confirming the efficacy and safety is small and should be used in caution in certain group of patients. Intravenous acetaminophen and ibuprofen are important options for multimodal postoperative analgesia, improving pain and patient satisfaction. [ABSTRACT FROM AUTHOR]

Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever in children. This drug has multiple mechanisms of action, but its pharmacodynamic is still not well known. The central nervous system is the main site of action and it mirrors the paracetamol effect compartment. The recommended dosages and routes of administration should be different whether paracetamol is used for the treatment of pain or fever. For example, the rectal route, while being efficacious for the treatment of fever, should be avoided in pain management. Paracetamol is a safe drug, but some clinical conditions and concomitant drugs, which are frequent in clinical practice, may increase the risk of paracetamol toxicity. Therefore, it is important to optimize its administration to avoid overdoses and maximize its effect. The principal mediator of the paracetamol toxicity is the N-acetyl- p-benzo-quinone imine (NAPQI), a toxic product of the paracetamol metabolism, which could bind cysteine groups on proteins forming paracetamol-protein adduct in the liver. Conclusion: Although frequently prescribed, the concept of 'effect compartment concentration' and the possible co-factors that could cause toxicity at recommended doses are not familiar to all pediatricians and general practitioners. We reviewed the literature concerning paracetamol mechanisms of action, we highlighted some relevant pharmacodynamic concepts for clinical practice, and we summarized the possible risk factors for toxicity at therapeutic dosages. [ABSTRACT FROM AUTHOR]

Background: Morphine is worldwide the analgesic of first choice after cardiac surgery in children. Morphine has unwanted hemodynamic and respiratory side effects. Therefore, post-cardiac surgery patients may potentially benefit from a non-opioid drug for pain relief. A previous study has shown that intravenous (IV) paracetamol is effective and opioid-sparing in children after major non-cardiac surgery. The aim of the study is to test the hypothesis that intermittent IV paracetamol administration in children after cardiac surgery will result in a reduction of at least 30% of the cumulative morphine requirement.Methods: This is a prospective, multi-center, randomized controlled trial at four level-3 pediatric intensive care units (ICUs) in the Netherlands and Belgium. Children who are 0-36 months old will be randomly assigned to receive either intermittent IV paracetamol or continuous IV morphine up to 48 h post-operatively. Morphine will be available as rescue medication for both groups. Validated pain and sedation assessment tools will be used to monitor patients. The sample size (n = 208, 104 per arm) was calculated in order to detect a 30% reduction in morphine dose; two-sided significance level was 5% and power was 95%.Discussion: This study will focus on the reduction, or replacement, of morphine by IV paracetamol in children (0-36 months old) after cardiac surgery. The results of this study will form the basis of a new pain management algorithm and will be implemented at the participating ICUs, resulting in an evidence-based guideline on post-operative pain after cardiac surgery in infants who are 0-36 months old.Trial Registration: Dutch Trial Registry ( www.trialregister.nl ): NTR5448 on September 1, 2015. Institutional review board approval (MEC2015-646), current protocol version: July 3, 2017. [ABSTRACT FROM AUTHOR]

Author(s): Julia Harris [sup.1], Anne-Sylvie Ramelet [sup.2], Monique van Dijk [sup.3] [sup.4], Pavla Pokorna [sup.3] [sup.5] [sup.6], Joke Wielenga [sup.7], Lyvonne Tume [sup.8], Dick Tibboel [sup.3], Erwin Ista [sup.3] Author [...], Background This position statement provides clinical recommendations for the assessment of pain, level of sedation, iatrogenic withdrawal syndrome and delirium in critically ill infants and children. Admission to a neonatal or paediatric intensive care unit (NICU, PICU) exposes a child to a series of painful and stressful events. Accurate assessment of the presence of pain and non-pain-related distress (adequacy of sedation, iatrogenic withdrawal syndrome and delirium) is essential to good clinical management and to monitoring the effectiveness of interventions to relieve or prevent pain and distress in the individual patient. Methods A multidisciplinary group of experts was recruited from the members of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC). The group formulated clinical questions regarding assessment of pain and non-pain-related distress in critically ill and nonverbal children, and searched the PubMed/Medline, CINAHL and Embase databases for studies describing the psychometric properties of assessment instruments. Furthermore, level of evidence of selected studies was assigned and recommendations were formulated, and grade or recommendations were added on the basis of the level of evidence. Results An ESPNIC position statement was drafted which provides clinical recommendations on assessment of pain (n = 5), distress and/or level of sedation (n = 4), iatrogenic withdrawal syndrome (n = 3) and delirium (n = 3). These recommendations were based on the available evidence and consensus amongst the experts and other members of ESPNIC. Conclusions This multidisciplinary ESPNIC position statement guides professionals in the assessment and reassessment of the effectiveness of treatment interventions for pain, distress, inadequate sedation, withdrawal syndrome and delirium.