The role of cytokines in acute and chronic postsurgical pain after major musculoskeletal surgeries in a quaternary pediatric center.

STUDY OBJECTIVE: To determine if baseline cytokines/chemokines and their changes over postoperative days 0-2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery. DESIGN: Prospective, observational, longitudinal nested study. SETTING: University-affiliated quaternary children's hospital. PATIENTS: Subjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure. MEASUREMENTS: Demographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and up to two weeks after surgery, using Luminex bead arrays. After data preparation, relationships between pre- and post-surgical cytokine concentrations with acute (% time in moderate-severe pain over POD0-2) and chronic (pain score > 3/10 beyond 3 months post-surgery) post-surgical pain were analyzed using univariable and multivariable regression analyses with adjustment for covariates and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes. MAIN RESULTS: Analyses included 3,164 repeated measures of 16 cytokines/chemokines from 112 subjects (median age 15.3, IQR 13.5-17.0, 54.5 % female, 59.8 % pectus). Acute postsurgical pain was associated with higher baseline concentrations of GM-CSF (ß = 0.95, SE 0.31; p = 0.003), IL-1ß (ß = 0.84, SE 0.36; p = 0.02), IL-2 (ß = 0.78, SE 0.34; p = 0.03), and IL-12 p70 (ß = 0.88, SE 0.40; p = 0.03) and longitudinal postoperative elevations in GM-CSF (ß = 1.38, SE 0.57; p = 0.03), IFNγ (ß = 1.36, SE 0.6; p = 0.03), IL-1ß (ß = 1.25, SE 0.59; p = 0.03), IL-7 (ß = 1.65, SE 0.7; p = 0.02), and IL-12 p70 (ß = 1.17, SE 0.58; p = 0.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (ß = -0.39, SE 0.17; p = 0.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (ß = -0.57, SE 0.26; p = 0.03), IL-8 (ß = -0.68, SE 0.24; p = 0.006), and IL-13 (ß = -0.48, SE 0.22; p = 0.03). Covariates female (vs. male) sex and surgery type (pectus surgery vs. spine) were associated with higher odds for CPSP in baseline adjusted cytokine-CPSP association models for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNFα, and IL-8, IL-10, respectively. CONCLUSION: We identified pro-inflammatory cytokine profiles associated with higher risk of acute postoperative pain. Interestingly, pleiotropic cytokine IL-6, chemokine IL-8 (which promotes neutrophil infiltration and monocyte differentiation), and monocyte-released anti-inflammatory cytokine IL-13, were associated with lower CPSP risk. Our results suggest heterogenous outcomes of cytokine/chemokine signaling that can both promote and protect against post-surgical pain. These may serve as predictive and prognostic biomarkers of pain outcomes following surgery.

A survey of practice in the anesthetic management of adolescent idiopathic scoliosis spine fusion by the North American Pediatric Spine Anesthesiologists Collaborative.

BACKGROUND: Adolescent Idiopathic Scoliosis (AIS) affects 2%-4% of the general pediatric population. While surgical correction remains one of the most common orthopedic procedures performed in pediatrics, limited consensus exists on the perioperative anesthetic management. AIMS: To examine the current state of anesthetic management of typical AIS spine fusions at institutions which have a dedicated pediatric orthopedic spine surgeon. METHODS: A web-based survey was sent to all members of the North American Pediatric Spine Anesthesiologists (NAPSA) Collaborative. This group included 34 anesthesiologists at 19 different institutions, each of whom has a Harms Study Group surgeon performing spine fusions at their hospital. RESULTS: Thirty-one of 34 (91.2%) anesthesiologists completed the survey, with a missing response rate from 0% to 16.1% depending on the question. Most anesthesia practices (77.4%; 95% confidence interval [CI], 67.7-93.4) do not have patients come for a preoperative visit prior to the day of surgery. Intravenous induction was the preferred method (74.2%; 95% CI 61.3-89.9), with the majority utilizing two peripheral IVs (93.5%; 95% CI 90.3-100) and an arterial line (100%; 95% CI 88.8-100). Paralytic administration for intubation and/or exposure was divided (51.6% rocuronium/vecuronium, 45.2% no paralytic, and 3.2% succinylcholine) amongst respondents. While tranexamic acid was consistently utilized for reducing blood loss, dosing regimens varied. When faced with neuromonitoring signal issues, 67.7% employ a formal protocol. Most anesthesiologists (93.5%; 95% CI 78.6-99.2) extubate immediately postoperatively with patients admitted to an inpatient floor bed (77.4%; 95% CI 67.7-93.3). CONCLUSION: Most anesthesiologists (87.1%; 95% CI 80.6-99.9) report the use of some form of an anesthesia-based protocol for AIS fusions, but our survey results show there is considerable variation in all aspects of perioperative care. Areas of agreement on management comprise the typical vascular access required, utilization of tranexamic acid, immediate extubation, and disposition to a floor bed. By recognizing the diversity of anesthetic care, we can develop areas of research and improve the perioperative management of AIS.

The Role of Cytokines in Acute and Chronic Postsurgical Pain in Pediatric Patients after Major Musculoskeletal Surgeries.

Study Objective: To determine if baseline cytokines and their changes over postoperative days 0-2 (POD0-2) predict acute and chronic postsurgical pain (CPSP) after major surgery. Design: Prospective, observational, longitudinal nested study. Setting: University-affiliated quaternary children's hospital. Patients: Subjects (≥8 years old) with idiopathic scoliosis undergoing spine fusion or pectus excavatum undergoing Nuss procedure. Measurements: Demographics, surgical, psychosocial measures, pain scores, and opioid use over POD0-2 were collected. Cytokine concentrations were analyzed in serial blood samples collected before and after (up to two weeks) surgery, using Luminex bead arrays. After data preparation, relationships between pre- and post-surgical cytokine concentrations with acute (% time in moderate-severe pain over POD0-2) and chronic (pain score>3/10 beyond 3 months post-surgery) pain were analyzed. After adjusting for covariates, univariate/multivariate regression analyses were conducted to associate baseline cytokine concentrations with postoperative pain, and mixed effects models were used to associate longitudinal cytokine concentrations with pain outcomes. Main Results: Analyses included 3,164 measures of 16 cytokines from 112 subjects (median age 15.3, IQR 13.5-17.0, 54.5% female, 59.8% pectus). Acute postsurgical pain was associated with higher baseline concentrations of GM-CSF (ß=0.95, SE 0.31; p=.003), IL-1ß (ß=0.84, SE 0.36; p=.02), IL-2 (ß=0.78, SE 0.34; p=.03), and IL-12 p70 (ß=0.88, SE 0.40; p=.03) and longitudinal postoperative elevations in GM-CSF (ß=1.38, SE 0.57; p=.03), IFNγ (ß=1.36, SE 0.6; p=.03), IL-1ß (ß=1.25, SE 0.59; p=.03), IL-7 (ß=1.65, SE 0.7, p=.02), and IL-12 p70 (ß=1.17, SE 0.58; p=.04). In contrast, CPSP was associated with lower baseline concentration of IL-8 (ß= -0.39, SE 0.17; p=.02), and the risk of developing CPSP was elevated in patients with lower longitudinal postoperative concentrations of IL-6 (ß= -0.57, SE 0.26; p=.03), IL-8 (ß= -0.68, SE 0.24; p=.006), and IL-13 (ß= -0.48, SE 0.22; p=.03). Furthermore, higher odds for CPSP were found for females (vs. males) for IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNFα, and for pectus (vs. spine) surgery for IL-8 and IL-10. Conclusion: We identified pro-inflammatory cytokines associated with increased acute postoperative pain and anti-inflammatory cytokines associated with lower CPSP risk, with potential to serve as predictive and prognostic biomarkers.

Multisite prospective study of perioperative pain management practices for anterior cruciate ligament reconstruction in adolescents: Society for Pediatric Anesthesia Improvement Network (SPAIN) Project Report.

INTRODUCTION: Although 200 000 adolescents undergo anterior cruciate ligament reconstruction (ACLR) surgery annually, no benchmarks for pediatric post-ACLR pain management exist. We created a multicenter, prospective, observational registry to describe pain practices, pain, and functional recovery after pediatric ACLR. METHODS: Participants (n=519; 12-17.5 years) were enrolled from 15 sites over 2 years. Data on perioperative management and surgical factors were collected. Pain/opioid use and Lysholm scores were assessed preoperatively, on postoperative day 1 (POD1), POD3, week 6, and month 6. Descriptive statistics and trends for opioid use, pain, and function are presented. RESULTS: Regional analgesia was performed in 447/519 (86%) subjects; of these, adductor canal single shot was most frequent (54%), nerve catheters placed in 24%, and perineural adjuvants used in 43%. On POD1, POD3, week 6, and month 6, survey response rates were 73%, 71%, 61%, and 45%, respectively. Over these respective time points, pain score >3/10 was reported by 64% (95% CI: 59% to 69%), 46% (95% CI: 41% to 52%), 5% (95% CI: 3% to 8%), and 3% (95% CI: 1% to 6%); the number of daily oxycodone doses used was 2.8 (SD 0.19), 1.8 (SD 0.13), 0, and 0. There was considerable variability in timing and tests for postdischarge functional assessments. Numbness and weakness were reported by 11% and 4% at week 6 (n=315) and 16% and 2% at month 6 (n=233), respectively. CONCLUSION: We found substantial variability in the use of blocks to manage post-ACLR pain in children, with a small percentage experiencing long-term pain and neurological symptoms. Studies are needed to determine best practices for regional anesthesia and functional assessments in this patient population.

Current Evidence for Biological Biomarkers and Mechanisms Underlying Acute to Chronic Pain Transition across the Pediatric Age Spectrum.

Chronic pain is highly prevalent in the pediatric population. Many factors are involved in the transition from acute to chronic pain. Currently, there are conceptual models proposed, but they lack a mechanistically sound integrated theory considering the stages of child development. Objective biomarkers are critically needed for the diagnosis, risk stratification, and prognosis of the pathological stages of pain chronification. In this article, we summarize the current evidence on mechanisms and biomarkers of acute to chronic pain transitions in infants and children through the developmental lens. The goal is to identify gaps and outline future directions for basic and clinical research toward a developmentally informed theory of pain chronification in the pediatric population. At the outset, the importance of objective biomarkers for chronification of pain in children is outlined, followed by a summary of the current evidence on the mechanisms of acute to chronic pain transition in adults, in order to contrast with the developmental mechanisms of pain chronification in the pediatric population. Evidence is presented to show that chronic pain may have its origin from insults early in life, which prime the child for the development of chronic pain in later life. Furthermore, available genetic, epigenetic, psychophysical, electrophysiological, neuroimaging, neuroimmune, and sex mechanisms are described in infants and older children. In conclusion, future directions are discussed with a focus on research gaps, translational and clinical implications. Utilization of developmental mechanisms framework to inform clinical decision-making and strategies for prevention and management of acute to chronic pain transitions in children, is highlighted.

Error traps and preventative strategies for adolescent idiopathic scoliosis spinal surgery.

Anesthesia for posterior spinal fusion for adolescent idiopathic scoliosis remains one of the most common surgeries performed in adolescents. These procedures have the potential for significant intraprocedural and postoperative complications. The potential for pressure injuries related to prone positioning must be understood and addressed. Additionally, neuromonitoring remains a mainstay for patient care in order to adequately assess patient neurologic integrity and alert the providers to a reversible action. As such, causes of neuromonitoring signal loss must be well understood, and the provider should have a systematic approach to signal loss. Further, anesthetic design must facilitate intraoperative wake-up to allow for a definitive assessment of neurologic function. Perioperative bleeding risk is high in posterior spinal fusion due to the extensive surgical exposure and potentially lengthy operative time, so the provider should undertake strategies to reduce blood loss and avoid coagulopathy. Pain management for adolescents undergoing spinal fusion is also challenging, and inadequate analgesia can delay recovery, impede patient/family satisfaction, increase the risk of chronic postsurgical pain/disability, and lead to prolonged opioid use. Many of the significant complications associated with this procedure, however, can be avoided with intentional and evidence-based approaches covered in this review.

Association of race and socioeconomic status with time to pain control among pediatric trauma patients managed nonoperatively.

BACKGROUND: Few studies have evaluated racial/ethnic inequities in acute pain control among hospitalized injured children. We hypothesized that there would be inequities in time to pain control based on race/ethnicity and socioeconomic status. METHODS: We performed a retrospective cohort study of all injured children (7-18 years) admitted to our level 1 trauma center between 2010 and 2019 with initial recorded numerical rating scale (NRS) scores of >3 who were managed nonoperatively. A Cox regression survival analysis was used to evaluate the time to pain control, defined as achieving an NRS score of ≤3. RESULTS: Our cohort included 1,787 admissions. The median age was 14 years (interquartile range, 10-18), 59.5% were male, 76.6% identified as White, 19.9% as Black, and 2.4% as Hispanic. The median initial NRS score was 7 (interquartile range, 5-9), and the median time to pain control was 4.9 hours (95% confidence interval, 4.6-5.3). Insurance status, as a marker of socioeconomic status, was not associated with time to pain control ( p = 0.29). However, the interaction of race/ethnicity and deprivation index was significant ( p = 0.002). Specifically, the socioeconomic deprivation of a child's home neighborhood was an important predictor for non-White children ( p <0.003) but not for White children ( p = 0.41) and non-White children from higher deprivation neighborhoods experienced greater times to pain control (hazard ratio, 1.55; 95% confidence interval, 1.16-2.07). Being female, older, presenting with higher initial NRS scores, and having history of attention-deficit/hyperactivity disorder were all associated with longer times to pain control. Other injury characteristics and psychiatric history were evaluated but ultimately excluded, as they were not significant. CONCLUSION: Greater neighborhood socioeconomic deprivation was associated with prolonged time to pain control for non-White children admitted after injury and managed nonoperatively. Further work is needed to understand inequities in pain control for injured patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Implementation of CYP2D6-guided opioid therapy at Cincinnati Children's Hospital Medical Center.

PURPOSE: We describe the implementation of CYP2D6-focused pharmacogenetic testing to guide opioid prescribing in a quaternary care, nonprofit pediatric academic medical center. SUMMARY: Children are often prescribed oral opioids after surgeries, for cancer pain, and occasionally for chronic pain. In 2004, Cincinnati Children's Hospital Medical Center implemented pharmacogenetic testing for CYP2D6 metabolism phenotype to inform codeine prescribing. The test and reports were updated to align with changes over time in the testing platform, the interpretation of genotype to phenotype, the electronic health record, and Food and Drug Administration (FDA) guidance. The use of the test increased when a research project required testing and decreased as prescribing of oxycodone increased due to FDA warnings about codeine. Education about the opioid-focused pharmacogenetic test was provided to prescribers (eg, the pain and sickle cell teams) as well as patients and families. Education and electronic health record capability increased provider compliance with genotype-guided postsurgical prescribing of oxycodone, although there was a perceived lack of utility for oxycodone prescribing. CONCLUSION: The implementation of pharmacogenetic testing to inform opioid prescribing for children has evolved with accumulating evidence and guidelines, requiring changes in reporting of results and recommendations.

Evaluating the role for regional analgesia in children with spina bifida: a retrospective observational study comparing the efficacy of regional versus systemic analgesia protocols following major urological surgery.

INTRODUCTION: Regional techniques are a key component of multimodal analgesia and help decrease opioid use perioperatively, but some techniques may not be suitable for all patients, such as those with spina bifida. We hypothesized peripheral regional catheters would reduce postoperative opioid use compared with no regional analgesia without increasing pain scores in pediatric patients with spina bifida undergoing major urological surgery. METHODS: A retrospective review of a multicenter database established for the study of enhanced recovery after surgery was performed of patients from 2009 to 2021 who underwent bladder augmentation or creation of catheterizable channels. Patients without spina bifida and those receiving epidural analgesia were excluded. Opioids were converted into morphine equivalents and normalized to patient weight. RESULTS: 158 patients with pediatric spina bifida from 7 centers were included, including 87 with and 71 without regional catheters. There were no differences in baseline patient factors. Anesthesia setup increased from median 40 min (IQR 34-51) for no regional to 64 min (IQR 40-97) for regional catheters (p<0.01). The regional catheter group had lower median intraoperative opioid usage (0.24 vs 0.80 mg/kg morphine equivalents, p<0.01) as well as lower in-hospital postoperative opioid usage (0.05 vs 0.23 mg/kg/day morphine equivalents, p<0.01). Pain scores were not higher in the regional catheters group. DISCUSSION: Continuous regional analgesia following major urological surgery in children with spina bifida was associated with a 70% intraoperative and 78% postoperative reduction in opioids without higher pain scores. This approach should be considered for similar surgical interventions in this population. TRIAL REGISTRATION NUMBER: NCT03245242.

Retrospective study comparing outcomes of multimodal epidural and erector spinae catheter pain protocols after pectus surgery.

INTRODUCTION: There are no optimal postoperative analgesia regimens for Nuss procedures. We compared the effectiveness of thoracic epidurals (EPI) and novel ambulatory erector spinae plane (ESP) catheters as part of multimodal pain protocols after Nuss surgery. METHODS: Data on demographics, comorbidities, perioperative details, length of stay (LOS), in hospital and post discharge pain/opioid use, side effects, and emergency department (ED) visits were collected retrospectively in children who underwent Nuss repair with EPI (N = 114) and ESP protocols (N = 97). Association of the group with length of stay (LOS), in hospital opioid use (intravenous morphine equivalents (MEq)/kg over postoperative day (POD) 0-2), and oral opioid use beyond POD7 was analyzed using inverse probability of treatment weighting (IPTW) with propensity scores, followed by multivariable regression. RESULTS: Groups had similar demographics. Compared to EPI, ESP had longer block time and higher rate of ketamine and dexmedetomidine use. LOS for ESP was 2 days IQR (2, 2) compared to 3 days IQR (3, 4) for EPI (p < 0.01). Compared to EPI, ESP group had higher opioid use (in MEq/kg) intraoperatively (0.32 (IQR 0.27, 0.36) vs. 0.28 (0.24, 0.32); p < 0.01) but lower opioid use on POD 0 (0.09 (IQR 0.04, 0.17) vs. 0.11 (0.08, 0.17); p = 0.03) and POD2 (0.00 (IQR 0.00, 0.00) vs. 0.04 (0.00, 0.06) ; p < 0.01). ESP group also had lower total in hospital opioid use (0.57 (IQR 0.42, 0.73) vs.0.82 (0.71, 0.91); p < 0.01), and shorter duration of post discharge opioid use (6 days (IQR 5,8) vs. 9 days (IQR 7,12) (p < 0.01). After IPTW adjustment, ESP continued to be associated with shorter LOS (difference -1.20, 95% CI: -1.38, -1.01, p < 0.01) and decreased odds for opioid use beyond POD7 (OR 0.11, 95% CI: 0.05, 0.24); p < 0.01). However, total in hospital opioid use in MEq/kg (POD0-2) was now similar between groups (difference -0.02 (95% CI: -0.09, -0.04); p = 0.50). The EPI group had higher incidence of emesis (29% v 4%, p < 0.01), while ESP had higher catheter malfunction rates (23% v 0%; p < 0.01) but both groups had comparable ED visits/readmissions. DISCUSSION/CONCLUSION: Compared to EPI, multimodal ambulatory ESP protocol decreased LOS and postoperative opioid use, with comparable ED visits/readmissions. Disadvantages included higher postoperative pain scores, longer block times and higher catheter leakage/malfunction. LEVELS OF EVIDENCE: Level III.

Design and implementation of a novel patient-centered empowerment approach for pain optimisation in children undergoing major surgery.

BACKGROUND: Paediatric surgery is a stressful experience for patients and caregivers. While standardised protocols are the norm, patient-centred approaches are needed to empower patients/caregivers for an optimal perioperative pain experience. To address this gap, we employed a patient-centred approach using design thinking (DT) methodology to develop insights, map processes, identify opportunities and design solutions for individualised empowerment tools. METHODS: In consultation with DT experts, a multidisciplinary team of stakeholders (healthcare providers, patients who underwent pectus excavatum/scoliosis surgery and their caregivers), were invited to participate in surveys, interviews and focus groups. The project was conducted in two sequential stages each over 24 weeks-involving 7 families in stage 1 and 16 patients/17 caregivers in stage 2. Each stage consisted of three phases: design research (focus groups with key stakeholders to review and apply collective learnings, map processes, stressors, identify influencing factors and opportunities), concept ideation (benchmarking and co-creation of new solutions) and concept refinement. RESULTS: In stage 1, mapping of stress/anxiety peaks identified target intervention times. We identified positive and negative influencers as well as the need for consistent messaging from the healthcare team in our design research. Current educational tools were benchmarked, parent-child engagement dyads determined and healthcare-based technology-based solutions conceived. The 'hero's journey' concept which has been applied to other illness paradigms for motivation successfully the was adapted to describe surgery as a transformative experience. In stage 2, patient and caregiver expectations, distinct personas and responses to perioperative experience were categorised. Educational tools and an empowerment tool kit based on sensorial, thinking, relaxation and activity themes, tailored to parent/child categories were conceptualised. CONCLUSION: DT methodology provided novel family centred insights, enabling design of tailored empowerment toolkits to optimise perioperative experience. Adapting the hero's journey call to adventure may motivate and build resilience among children undergoing surgery.

Genetic and epigenetic mechanisms influencing acute to chronic postsurgical pain transitions in pediatrics: Preclinical to clinical evidence.

Background: Chronic postsurgical pain (CPSP) in children remains an important problem with no effective preventive or therapeutic strategies. Recently, genomic underpinnings explaining additional interindividual risk beyond psychological factors have been proposed. Aims: We present a comprehensive review of current preclinical and clinical evidence for genetic and epigenetic mechanisms relevant to pediatric CPSP. Methods: Narrative review. Results: Animal models are relevant to translational research for unraveling genomic mechanisms. For example, Cacng2, p2rx7, and bdnf mutant mice show altered mechanical hypersensitivity to injury, and variants of the same genes have been associated with CPSP susceptibility in humans; similarly, differential DNA methylation (H1SP) and miRNAs (miR-96/7a) have shown translational implications. Animal studies also suggest that crosstalk between neurons and immune cells may be involved in nociceptive priming observed in neonates. In children, differential DNA methylation in regulatory genomic regions enriching GABAergic, dopaminergic, and immune pathways, as well as polygenic risk scores for enhanced prediction of CPSP, have been described. Genome-wide studies in pediatric CPSP are scarce, but pathways identified by adult gene association studies point to potential common mechanisms. Conclusions: Bench-to-bedside genomics research in pediatric CPSP is currently limited. Reverse translational approaches, use of other -omics, and inclusion of pediatric/CPSP endophenotypes in large-scale biobanks may be potential solutions. Time of developmental vulnerability and longitudinal genomic changes after surgery warrant further investigation. Emergence of promising precision pain management strategies based on gene editing and epigenetic programing emphasize need for further research in pediatric CPSP-related genomics.

Contexte: La douleur chronique post-chirurgicale (DCPC) chez l'enfant reste un problème important pour lequel il n'y a pas de stratégies préventives ou thérapeutiques efficaces. Récemment, des fondements génomiques expliquant des risques interindividuels additionnels, au-delà des facteurs psychologiques, ont été proposés. Objectifs: Nous présentons une revue compléte des données probantes précliniques et cliniques actuelles pour les mécanismes génétiques et épigénétiques pertinents en matiére de DCPC pédiatrique. Méthodes: Revue narrative.Les modéles animaux sont pertinents pour la recherche translationnelle afin de déchiffrer les mécanismes génomiques. Par exemple, les souris mutantes Cacng2, p2rx7 et bdnf présentent une hypersensibilité mécanique altérée à des lésions et des variantes des mêmes génes ont été associées à la sensibilité à la DCPC chez l'humain; de même, la méthylation différentielle de l'ADN (H1SP) et les miARN (miR-96/7a) ont montré des implications translationnelles. Des études menées sur des animaux indiquent également que la diaphonie entre les neurones et les cellules immunitaires peut être impliquée dans l'amorçage nociceptif observé chez les nouveau-nés. Chez les enfants, la méthylation différentielle de l'ADN dans les régions génomiques régulatrices enrichissant les voies GABAergiques, dopaminergiques et immunitaires, ainsi que des scores de risque polygénique pour une prédiction améliorée de la PCSP, ont été décrits. Les études pangénomiques en matiére de DCPC pédiatrique sont rares, mais les voies identifiées par les études d'association de génes chez l'adulte indiquent de possibles mécanismes communs. Conclusions: La recherche en génomique du laboratoire au patient dans le cadre de la DCPC pédiatrique est actuellement limitée. Les approches translationnelles inversées, l'utilisation d'autres -omiques et l'inclusion d'endophénotypes pédiatriques/DCPC dans les biobanques à grande échelle peuvent être des solutions possibles. La durée de la vulnérabilité développementale et des changements génomiques longitudinaux aprés la chirurgie justifie des recherches plus approfondies. L'émergence de stratégies de précision prometteuses basées sur lé'dition de génes et la programmation épigénétique pour la prise en charge de la douleur font valoir la nécessité de poursuivre les recherches sur la génomique pédiatrique liée à la DCPC.

Timely completion of spinal fusion: A multidisciplinary quality improvement initiative to improve operating room efficiency.

BACKGROUND: Failure to complete surgery within the scheduled timeframe impairs operating room efficiency leading to patient dissatisfaction and unplanned labor costs. We sought to improve timely completion (within 30 min of scheduled time) of first-case spine fusion surgery (for idiopathic scoliosis) from a baseline of 25%-80% over 12 months. We also targeted timely completion of perioperative stages within predetermined target completion times. METHODS: The project was conducted in three overlapping phases over 16 months. A simplified process map outlining five sequential perioperative stages, preintervention baselines (N = 24) and time targets were defined. A multidisciplinary team conducted a series of tests of change addressing the aims. The key drivers included effective scheduling, team communications, family engagement, data collection veracity, standardized pathways, and situational awareness. Data collected by an independent data collector and from electronic medical records were analyzed using control charts and statistical process control methods. RESULTS: Post-intervention, timely case completion increased from 25% to 68% (N = 49) (95% CI 15.1-62.7), (p = 0.003) and was sustained (N = 14). Implementation of prediction model for case-scheduling decreased difference between scheduled and actual case end-time (33 vs. 53 min [baseline]) and variance [lower/upper control limits ([-26, 51] vs. [-109, 216] min [baseline]). Average start time delay decreased from 6 to 2 min and on-time surgical starts improved from 50% to 70% (95% CI 3.2-41.6%). Timely completion increased for anesthesia induction (60% to 85%), surgical procedure (26% to 48%) and emergence from anesthesia (44% to 80%) but not for intraoperative patient preparation (30% to 25%) perioperative stages. Families reported satisfaction with preoperative processes (N = 14), and no untoward intraoperative safety events occurred. CONCLUSIONS: Application of QI methodology reduced time variation of several tasks and improved timely completion of spine surgery. Beyond the study period, sustained team behavior, adaptive changes, and vigilant monitoring are imperative for continued success.

Association of CYP2D6 genotype predicted phenotypes with oxycodone requirements and side effects in children undergoing surgery.

Background: Oxycodone is a commonly used oral opioid in children for treating postoperative pain. Highly polymorphic gene CYP2D6 metabolizes oxycodone into its more potent metabolite, oxymorphone. We hypothesized that altered activity due to CYP2D6 polymorphisms will influence oxycodone requirements {relative oxycodone use [oxycodone morphine equivalents (MEq)/total MEq] to maintain analgesia} (primary outcome) and risk for oxycodone induced side-effects such as respiratory depression (RD) and emesis (secondary outcomes). We also explored the influence of genotype availability and provider guidance on oral opioid prescription patterns. Methods: Patients who underwent Nuss procedure and spine fusion with CYP2D6 genotyping results available preoperatively were included. Data on demographics, genotypes, oral opioids, pain scores, RD and emesis were collected. Univariate and multivariable regression for comparison of CYP2D6 genotype predicted poor, ultrarapid, intermediate metabolizers (PM, UM and IM) phenotype with normal metabolizers (NM) for outcomes were performed. Stratified logistic regression was conducted in low (oxycodone/total MEq <0.5) and high (and oxycodone/total MEq >0.5) oxycodone use groups for RD and emesis, with application of firth correction due to quasi-complete separations. Breslow-Day test was used to evaluate odds ratios for prescribing genotype directed opioid between control group (2012-15) (where providers were alerted to genotyping results availability but not directed to use them while prescribing) and genotype directed groups (2016-18) (where providers were directed to use the genotyping results available to them while prescribing oxycodone after surgery). Results: Of 193 subjects (age 15.9±0.25 years, 28.5% female, 93.78% White; 101 NM, 76 IM, 10 PM and 6 UM), 77.72% underwent pectus surgery. CYP2D6 phenotype was associated with oxycodone MEq/total MEq requirements (P<0.001). Both PM and UM phenotypes had lower oxycodone requirements compared to NM [-0.316 (SE 0.098), P=0.005 and -0.432 (SE 0.113), P<0.001 respectively]. CYP2D6 phenotype was associated with RD in high use oxycodone group (P=0.018) but not low use oxycodone groups (P=0.634). No phenotype association was found for emesis. Oxycodone was prescribed to 91.24% of NM/IM vs. 66.67% of PM/UM (P=0.129) in control group and 94.64% of NM/IM vs. 28.57% of PM/UM (P<0.001) in the genotype-directed group. PM/UM phenotypes in genotype directed group had a lower chance of being prescribed oxycodone (effect size =-2.775; SE 1.566; P=0.076). Conclusions: Our findings suggest CYP2D6 genotypes are associated with oxycodone requirements for analgesia and may influence risk for RD. Genotype availability and guidance likely influence oral opioid prescription pattern after surgery. Our findings are limited by small sample size for UM/PM groups.

Fascia Iliaca Pain Block Results in Lower Overall Opioid Usage and Shorter Hospital Stays than Epidural Anesthesia After Hip Reconstruction in Children With Cerebral Palsy.

INTRODUCTION AND OBJECTIVE: Epidural anesthesia (EA) is often used for pain control in children with cerebral palsy (CP) who undergo hip reconstructions. The purpose of this study is to determine if preoperative fascia iliaca (FI) pain blocks would improve pain scores, decrease opioid use, and result in shorter hospital stays in comparison to the use of EA. METHODS: This is a nonrandomized retrospective cohort study examining 60 consecutive patients with CP who underwent hip reconstruction utilizing either a fascia iliac compartment nerve block (FICNB) (N=37) or continuous lumbar epidural (N=22) from January 2017 to March 2019. Age at surgery was 8.5±4.6 years. We recorded age, weight, operating room (OR) time, FLACC (Face, Legs, Activity, Cry, Consolability scale) scores on postoperative days (PODs) 0, 1, 2, and 3, opioid doses, overall opioid (mg) used, and length of stay. We compared pain scores, opioid usage, OR time, and lengths of stay between our 2 patient groups. RESULTS: Pain scores were similar between groups on POD #0, 2, and 3 but were statistically improved on POD #1 (1.8±1.3 vs. 3.1±1.4, P<0.001). Total number of opiod doses (7.9±4.4 vs. 10.7±2.3, P=0.004), total milligram given (18.3±11.8 vs. 24.7±12.3, P<0.05), and milligram per kilogram given (0.77±0.42 vs. 1.11 mg/kg±0.36 mg/kg, P=0.001) were less for the FI group versus the epidural group. The OR time (which includes time for blocks/epidurals) was lower in the FI group (4.6±1.2 vs. 5.7±1.1 h, P=0.0002). Overall hospital stays were lower in the FI group (3.4±1.5 vs. 4.1±1.0 d, P<0.05). CONCLUSIONS: This study demonstrates that in the setting of hip reconstruction, patients that received preoperative FI blocks used a lower amount of opioids, required fewer rescue doses and ultimately had a shorter hospital length of stay than those undergoing EA.

Pediatric Pain Screening Tool: A Simple 9-Item Questionnaire Predicts Functional and Chronic Postsurgical Pain Outcomes After Major Musculoskeletal Surgeries.

Reliable, clinic-friendly screening for Chronic postsurgical pain (CPSP) risk is unavailable. Within a prospective, observational study, we evaluated Pediatric Pain Screening Tool (PPST), a concise 9-item questionnaire, as a preoperative screening tool to identify those at higher risk for CPSP (Numerical Rating Scale > 3/10 beyond 3 months post-surgery) and poor function (disability/Functional Disability Inventory [FDI]/quality of life/ Pediatric Quality of Life) after spine fusion and Nuss procedures. Incidence of CPSP was 34.86% (38/109). We confirmed PPST scale stability, test re-test reliability (ICC = 0.68; P< .001); PPST measures were positively correlated with known CPSP risk factors (P< .001) preoperative pain (Pearson or Spearman Correlation Coefficient [SCC]:0.672), Child anxiety sensitivity index (SCC:0.357), Patient Related Outcome Measures Information System pain interference (SCC:0.569), Patient Related Outcome Measures Information System depression (SCC:0.501), Pediatric Quality of Life (SCC:-0.460) and insomnia severity index (SCC0.567). Preoperative PPST and PPST physical sub-scores (median(IQR) were higher in CPSP (2[0.5,4], 1[0,2]) compared to non-CPSP (1[0,3], 0[0,1.5]) groups (P= .026, P= .029) respectively. PPST scores/sub-scores positively correlated with higher FDI at 6 months but only PPST total and PPST psychosocial subscore correlated with higher FDI at 12 months. Based on ROC, optimal PPST cutoff for CPSP was 2 (63.9% sensitivity, 64.7% specificity). CPSP risk was high (48.94% risk) if PPST ≥ 2 (n = 47) and medium (22.81%) if PPST < 2 (n = 57) after spine/pectus surgery. General and risk-strata specific, targeted psychosocial non-pharmacological interventions, need to be studied. Findings need validation in diverse, larger cohorts. CLINICALTRIALS.GOV IDENTIFIER: NCT02998138. PERSPECTIVE: The article supports Pediatric Pain Screening Tool, a simple 9-item questionnaire, as a preoperative screening tool for CPSP and function 6-12 months after spine/pectus surgeries. PPST measures correlate with known risk factors for CPSP. Risk stratification and targeted preventive interventions in high-risk subjects are proposed.