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Background Minimally invasive repair of pectus excavatum (MIRPE) is associated with less tissue trauma; however, it may result in increased postoperative pain. Pain experience is a known risk factor for the development of posttraumatic stress symptoms, though there are little data on its relationship with long-term psychological outcomes following major surgery in pediatric patients. Aims In this study, we examined the relationship between immediate postoperative pain and psychological outcomes at 2 weeks and three months after discharge in a cohort of pediatric patients who underwent MIRPE. We sought to determine whether immediate postoperative pain levels were associated with ongoing distress related to aspects of surgery at both time points. We were also interested in how psychological symptoms related to persistent pain concerns. Methods Data on patients undergoing MIRPE across 14 institutions were collected as part of the Society for Pediatric Anesthesia Improvement Network (SPAIN). Patients were contacted at 2 weeks and three months following discharge to track pain levels and assess psychological distress using a self-report questionnaire. Patients were grouped into cohorts based on self-report of distress related to aspects of surgery, nonsurgical distress, or absence of distress. Results Analysis revealed that a higher proportion of children reporting ongoing distress related to surgery at both 2 weeks and 3 months experienced higher immediate postoperative pain levels. A subset of patients with complete data sets for 2 weeks and 3 months (N = 76) was further examined. Among the 47 patients who endorsed surgical distress at 2 weeks, 25 (53.2%) continued to endorse surgical distress at 3 months. Additionally, report of surgical distress at 3 months was associated with longer-term postoperative pain. Conclusions Our data suggest that, in patients undergoing MIRPE, the presence of distress at 2 weeks and 3 months may be associated with higher immediate postoperative pain levels.

Summary Opioids have long held a prominent role in the management of perioperative pain in adults and children. Published reports concerning the appropriate, and inappropriate, use of these medications in pediatric patients have appeared in various publications over the last 50 years. For this document, the Society for Pediatric Anesthesia appointed a taskforce to evaluate the available literature and formulate recommendations with respect to the most salient aspects of perioperative opioid administration in children. The recommendations are graded based on the strength of the available evidence, with consensus of the experts applied for those issues where evidence is not available. The goal of the recommendations was to address the most important issues concerning opioid administration to children after surgery, including appropriate assessment of pain, monitoring of patients on opioid therapy, opioid dosing considerations, side effects of opioid treatment, strategies for opioid delivery, and assessment of analgesic efficacy. Regular updates are planned with a re‐release of guidelines every 2 years.

Background It is not known whether the neurotoxicity produced by anaesthetics administered to young animals can also occur in children. Exposure of infant macaques to ketamine impairs performance in selected domains of the Operant Test Battery (OTB), which can also be administered to children. This study determined whether a similar pattern of results on the OTB is found in children exposed to procedures requiring general anaesthesia before age 3 yr. Methods We analysed data from the Mayo Anesthesia Safety in Kids (MASK) study, in which unexposed, singly-exposed, and multiply-exposed children born in Olmsted County, MN, USA, from 1994 to 2007 were sampled using a propensity-guided approach and prospectively underwent OTB testing at ages 8–12 or 15–20 yr, using five tasks that generated 15 OTB test scores. Results In primary analysis, none of the OTB test scores depended upon anaesthesia exposure status when corrected for multiple comparisons. Cluster analysis identified four clusters of subjects, with cluster membership determined by relative performance on the OTB tasks. There was no evidence of association between exposure status and cluster membership. Exploratory factor analysis showed that the OTB scores loaded onto four factors. The score for one factor was significantly less in multiply-exposed children (mean standardised difference –0.28 [95% confidence interval, –0.55 to –0.01; P=0.04]), but significance did not survive a sensitivity analysis accounting for outlying values. Conclusions These findings provide little evidence to support the hypothesis that children exposed to procedures requiring anaesthesia show deficits on OTB tasks that are similar to those observed in non-human primates.

BACKGROUND There are few comparative data on the analgesic options used to manage patients undergoing minimally invasive repair of pectus excavatum (MIRPE). The Society for Pediatric Anesthesia Improvement Network was established to investigate outcomes for procedures where there is significant management variability. For our first study, we established a multicenter observational database to characterize the analgesic strategies used to manage pediatric patients undergoing MIRPE. Outcome data from the participating centers were used to assess the association between analgesic strategy and pain outcomes. METHODS Fourteen institutions enrolled patients from June 2014 through August 2015. Network members agreed to an observational methodology where each institution managed patients based on their institutional standards and protocols. There was no requirement to standardize care. Patients were categorized based on analgesic strategy: epidural catheter (EC), paravertebral catheter (PVC), wound catheter (WC), no regional (NR) analgesia, and intrathecal morphine techniques. Primary outcomes, pain score and opioid consumption by postoperative day (POD), for each technique were compared while adjusting for confounders using multivariable modeling that included 5 covariates: age, sex, number of bars, Haller index, and use of preoperative pain medication. Pain scores were analyzed using repeated-measures analysis of variance with Bonferroni correction. Opioid consumption was analyzed using a multivariable quantile regression. RESULTS Data were collected on 348 patients and categorized based on primary analgesic strategy: EC (122), PVC (57), WC (41), NR (120), and intrathecal morphine (8). Compared to EC, daily median pain scores were higher in patients managed with PVC (POD 0), WC (POD 0, 1, 2, 3), and NR (POD 0, 1, 2), respectively (P < .001-.024 depending on group). Daily opioid requirements were higher in patients managed with PVC (POD 0, 1), WC (POD 0, 1, 2), and NR (POD 0, 1, 2) when compared to patients managed with EC (P < .001). CONCLUSIONS Our data indicate variation in pain management strategies for patients undergoing MIRPE within our network. The results indicate that most patients have mild-to-moderate pain postoperatively regardless of analgesic management. Patients managed with EC had lower pain scores and opioid consumption in the early recovery period compared to other treatment strategies.

Background Pediatric anesthesiology has been greatly impacted by COVID‐19 in the delivery of care to patients and to the individual providers. With this study, we sought to survey pediatric centers and highlight the variations in care related to perioperative medicine during the COVID‐19 pandemic, including the availability of protective equipment, the practice of pediatric anesthesia, and economic impact. Aim The aim of the survey was to determine how COVID‐19 directly impacted pediatric anesthesia practices during the study period. Methods A survey concerning four major domains (testing, safety, clinical management/policy, economics) was developed. It was pilot tested for clarity and content by members of the Pediatric Anesthesia COVID‐19 Collaborative. The survey was administered by email to all Pediatric Anesthesia COVID‐19 Collaborative members on September 1, 2020. Respondents had six weeks to complete the survey and were instructed to answer the questions based on their institution's practice during September 1 ‐ October 13, 2020. Results Sixty‐three institutions (100% response rate) participated in the COVID‐19 Pediatric Anesthesia Survey. Forty‐one hospitals (65%) were from the United States, and 35% included other countries. N95 masks were available to anesthesia teams at 91% of institutions (n = 57) (95% CI: 80%–96%). COVID‐19 testing criteria of anesthesia staff and guidelines to return to work varied by institution. Structured simulation training aimed at improving COVID‐19 safety and patient care occurred at 62% of institutions (n = 39). Pediatric anesthesiologists were economically affected by a reduction in their employer benefits and restriction of travel due to employer imposed quarantine regulations. Conclusion Our data indicate that the COVID‐19 pandemic has impacted the testing, safety, clinical management, and economics of pediatric anesthesia practice. Further investigation into the long‐term consequences for the specialty is indicated.

BACKGROUND: Two prior population-based (children born in Olmsted County, MN), retrospective cohort studies both found that multiple exposures to anesthesia prior to age 3 were associated with a significant increase in the frequency of attention deficit hyperactivity disorder (ADHD) and learning disabilities (LD) later in life. The primary purpose of this secondary analysis of these data was to test the hypothesis that a single exposure to anesthesia prior to age 3 was associated with an increased risk of ADHD. We also examined the association of single exposures with LD and the need for individualized educational plans as secondary outcomes. METHODS: This analysis includes 5,339 children who were unexposed to general anesthesia prior to age 3 (4,876 born from 1976–1982 and 463 born from 1996–2000), and 1,054 children who had a single exposure to anesthesia prior to age 3 (481 born from 1976–1982 and 573 born from 1996–2000). The primary outcome of interest was ADHD. Secondary outcomes included learning disabilities (reading, mathematics, and written language) and the need for individualized educational programs (speech/language and emotion/behavior). To compare the incidence of each outcome between those who were unexposed and singly-exposed to anesthesia prior to the age of 3 years an inverse probability of treatment weighted proportional hazards model was used. RESULTS: For children not exposed to anesthesia, the estimated cumulative frequency (95% CI) of ADHD at age 18 was 7.3% (95% CI 6.5% to 8.1%) and 13.0% (95% CI 10.1% to 16.8%) for the 1976–1982 and 1996–2000 cohorts respectively. For children exposed to a single anesthetic prior to age 3, the cumulative frequency of ADHD was 8.1% (95% CI 5.3% to 12.4%) and 17.6% (95% CI 14.0% to 21.9%) for the 1976–1982 and 1996–2000 cohorts respectively. In weighted analyses, single exposures were not significantly associated with an increased frequency of ADHD (hazard ratio [HR] 1.21, 95% CI 0.91 to 1.60, p=0.184). Single exposures were also not associated with an increased frequency of any LD (HR 0.98, 95% CI 0.78 to 1.23), or the need for individualized education plans CONCLUSION: This analysis did not find evidence that single exposures to procedures requiring general anesthesia prior to age three are associated an increased risk of developing ADHD, LD, or the need for individualized educational plans in later life.

Background Few studies of how exposure of children to anesthesia may affect neurodevelopment employ comprehensive neuropsychological assessments. This study tested the hypothesis that exposure to multiple, but not single, procedures requiring anesthesia before age 3 yr is associated with adverse neurodevelopmental outcomes. Methods Unexposed, singly exposed, and multiply exposed children born in Olmsted County, Minnesota, from 1994 to 2007 were sampled using a propensity-guided approach and underwent neuropsychological testing at ages 8 to 12 or 15 to 20 yr. The primary outcome was the Full-Scale intelligence quotient standard score of the Wechsler Abbreviated Scale of Intelligence. Secondary outcomes included individual domains from a comprehensive neuropsychological assessment and parent reports. Results In total, 997 children completed testing (411, 380, and 206 unexposed, singly exposed, and multiply exposed, respectively). The primary outcome of intelligence quotient did not differ significantly according to exposure status; multiply exposed and singly exposed children scoring 1.3 points (95% CI, −3.8 to 1.2; P = 0.32) and 0.5 points (95% CI, −2.8 to 1.9; P = 0.70) lower than unexposed children, respectively. For secondary outcomes, processing speed and fine motor abilities were decreased in multiply but not singly exposed children; other domains did not differ. The parents of multiply exposed children reported increased problems related to executive function, behavior, and reading. Conclusions Anesthesia exposure before age 3 yr was not associated with deficits in the primary outcome of general intelligence. Although secondary outcomes must be interpreted cautiously, they suggest the hypothesis that multiple, but not single, exposures are associated with a pattern of changes in specific neuropsychological domains that is associated with behavioral and learning difficulties.

Background Exposure of young animals to general anesthesia causes neurodegeneration and lasting behavioral abnormalities; whether these findings translate to children remains unclear. This study used a population-based birth cohort to test the hypothesis that multiple, but not single, exposures to procedures requiring general anesthesia before age 3 yr are associated with adverse neurodevelopmental outcomes. Methods A retrospective study cohort was assembled from children born in Olmsted County, Minnesota, from 1996 to 2000 (inclusive). Propensity matching selected children exposed and not exposed to general anesthesia before age 3 yr. Outcomes ascertained via medical and school records included learning disabilities, attention-deficit/hyperactivity disorder, and group-administered ability and achievement tests. Analysis methods included proportional hazard regression models and mixed linear models. Results For the 116 multiply exposed, 457 singly exposed, and 463 unexposed children analyzed, multiple, but not single, exposures were associated with an increased frequency of both learning disabilities and attention-deficit/hyperactivity disorder (hazard ratio for learning disabilities = 2.17 [95% CI, 1.32 to 3.59], unexposed as reference). Multiple exposures were associated with decreases in both cognitive ability and academic achievement. Single exposures were associated with modest decreases in reading and language achievement but not cognitive ability. Conclusions These findings in children anesthetized with modern techniques largely confirm those found in an older birth cohort and provide additional evidence that children with multiple exposures are more likely to develop adverse outcomes related to learning and attention. Although a robust association was observed, these data do not determine whether anesthesia per se is causal.

Summary Background Malignant hyperthermia (MH) is a rare anesthetic pharmacogenetic disorder that can be difficult to detect in its earliest phases. Prompt treatment is known to improve outcomes. The modern anesthesia information management systems (AIMS) collect enormous amounts of data. However, data lack context and are not able to provide real-time guidance. Utilizing our AIMS, we developed the capacity to incorporate decision support. Aims We describe the creation and evaluation of a real-time detection tool for MH. Methods Cases of MH from 2003 to 2013 were retrospectively reviewed to confirm the diagnosis of MH and to calculate a MH clinical grading scale score. The index cases were utilized to develop four electronic data Rules, based on endtidal CO2 (ETCO2) and temperature criteria. The Rules were then applied retrospectively to the index cases and to a full cohort of general operating room (OR) patients from January 2012 to June 2012. If criteria for possible MH was met, the detection tool generated an alert on the monitor at the patient's bedside. Results We identified seven patients with confirmed MH with MH Scores ranging from 28 to 70. Using four data Rules, all of our seven index cases were captured and generated an appropriate alert. Median time from MH computer alert time to dantrolene administration time among our index cases was 23 min (IQR 17–77). There were 938 false-positive alerts for possible MH (1.8%) when the Rules were applied to a general OR cohort of 51 579 total cases from January 2012 to June 2012. Conclusions We demonstrated a real-time MH detection tool based on established physiologic criteria that is sensitive enough to capture cases suspicious for MH, while limiting false positives to prevent alarm fatigue. This has the potential to notify the provider of possible MH such that treatment may be rapidly initiated.

There is increasing evidence that exposure of developing brains in animals, including nonhuman primates, to commonly-utilized anesthetic agents may cause adverse effects on cognition and behavior. In this paper, we summarize our methodology for a population-based, propensity-matched study to evaluate possible anesthesia-related sequelae in preschool children when evaluated in elementary or high school. A cohort of all children born in Olmsted County, Minnesota between the years 1994 and 2007 who are currently local residents has been identified. Existing medical records are being used to identify all episodes of exposure to general anesthesia prior to the age of 3 years (i.e., prior to their 3rd birthday). Children with multiple, single, and no anesthesia exposure are sampled for testing between the ages of 8 and 12 years or 15 and 19 years during the period 2012-2016. To match children in different exposure groups as closely as possible, sampling is guided by propensity-matching for the likelihood of receiving anesthesia. Selected children are invited to participate in a single 4-hour session of neuropsychological testing, including the National Center for Toxicological Research-Operant Test Battery, which has been used to study anesthetic neurotoxicity in nonhuman primates. The results of this testing will be compared among children with different anesthetic exposure histories. The expected products of this research will be a detailed phenotype of possible anesthetic-associated neurotoxicity in humans, utilizing a robust patient database and neuropsychological testing battery, and the first comparison of effects of anesthetic exposure in children and nonhuman primates performing nearly identical behavioral tasks.

Aim The minimally-invasive Nuss procedure has become the preferred technique for pectus excavatum repair. This procedure is still associated with significant postoperative pain, and an optimal pain-management strategy is yet to be determined. The purpose of this study was to compare the efficacy of patient-controlled analgesia (PCA) to thoracic epidural analgesia (TEA). Patients and Methods We retrospectively reviewed 112 charts from a single paediatric centre. Patients were grouped according to pain-management strategy: 90 patients received a PCA, and 22 patients received TEA. Outcomes included length of hospitalization and daily pain scores, operating room time and duration of Foley catheterization. Results Demographic data were similar between the two groups. The daily pain scores were not statistically different between the groups. Length of hospitalization was similar (PCA: 4.6 days, epidural: 4.3 days, P = 0.33). The PCA group required less operating room time (2:44 vs 2:58, P = 0.04) and shorter Foley catheter duration (2.1 days vs 2.5 days, P = 0.04). Conclusion In our patient population, TEA for the Nuss procedure does not offer an advantage over PCA-centred analgesia in terms of subjective daily pain scores or length of hospital stay. The potential risks of TEA need to be carefully considered in this patient population.

There is now more than a decade of mounting animal data that anesthetic drugs can cause apoptosis during a critical period of brain development and that this correlates with later behavioral disturbances. Initial articles examining the effects of early anesthesia on human infants have recently been published. Prospective studies are underway.Several retrospective studies in humans have been published over the last year using different methodologies. Although most raise some concern that anesthetic use in infants and young children may be problematic, all have inherent limitations in methodology that prevent clinicians from drawing firm conclusions regarding the risk of anesthesia on brain development in humans.Although the evidence from animal studies is clear and continuing to mount that anesthetic drugs given at the right time and in sufficiently high and prolonged doses do cause increased neuronal apoptosis and later problems with learning, evidence in humans that this is of clinical concern is both weak and mixed. Additional studies are ongoing to try to better define the risk.

Background Anesthetics administered to immature brains may cause histopathological changes and long-term behavioral abnormalities. The association between perinatal exposure to anesthetics during Cesarean delivery (CD) and development of learning disabilities (LD) was determined in a population-based birth cohort. Methods The educational and medical records of all children born to mothers residing in five townships of Olmsted County, Minnesota from 1976-1982 and remaining in the community at age 5 were reviewed to identify those with LDs. Cox proportional hazards regression was used to compare rates of LD between children delivered vaginally and via CD (with general or regional anesthesia). Results Of the 5,320 children in this cohort, 497 were delivered via CD (under general anesthesia n = 193, and regional anesthesia n = 304). The incidence of LD depended on mode of delivery (P = 0.050, adjusted for sex, birth weight, gestational age, exposure to anesthesia before age 4 yr, and maternal education). LD risk was similar in children delivered by vagina or CD with general anesthesia, but was reduced in children receiving CD with regional anesthesia (hazard ratio = 0.64, 95% confidence interval 0.44 to 0.92; P = 0.017 for comparison of CD under regional anesthesia compared to vaginal delivery). Conclusion Children exposed to general or regional anesthesia during CD are not more likely to develop LD compared to children delivered vaginally, suggesting that brief perinatal exposure to anesthetic drugs does not adversely affect long-term neurodevelopmental outcomes. The risk of LD may be lower in children delivered by CD whose mothers received regional anesthesia.

Background Anesthetic drugs administered to immature animals may cause neurohistopathologic changes and alterations in behavior. We studied association between anesthetic exposure prior to age 4 and the development of reading, written language and math learning disabilities (LD).

Summary Background: Laryngospasm is a common and often serious adverse respiratory event encountered during anesthetic care of children. We examined, in a case control design, the risk factors for laryngospasm in children. Material and Methods: The records of 130 children identified as having experienced laryngospasm under general anesthesia were examined. Cases were identified from those prospectively entered into the Mayo Clinic performance improvement database between January 1, 1996 and December 31, 2005. Potential demographic, patient, surgical and anesthetic related risk factors were determined in a 1 : 2 case–control study. Results: No individual demographic factors were found to be significantly associated with risk for laryngospasm. However, multivariate analysis demonstrated significant associations between laryngospasm and intercurrent upper respiratory infection (OR 2.03 P = 0.022) and the presence of an airway anomaly (OR = 3.35, P = 0.030). Among those experiencing laryngospasm during maintenance or emergence, the use of a laryngeal mask airway was strongly associated even when adjusted for the presence of upper respiratory infection and airway anomaly (P = 0.019). Ten patients experienced postoperatively one or more complications whereas only three complications were observed among controls (P = 0.008). No child required cardiopulmonary resuscitation and there were no deaths in either study cohort. Conclusions: In our pediatric population, the risk of laryngospasm was increased in children with upper respiratory tract infection or an airway anomaly. The use of laryngeal mask airway was found to be associated with laryngospasm even when adjusted for the presence of upper respiratory tract infection and airway anomaly.

Chronic pain in children and adolescents can be difficult for a single provider to manage in a busy clinical setting. Part of this difficulty is that pediatric chronic pain not only impacts the child but also the families of these children. In this review article, we discuss etiology and pathophysiology of chronic pain, along with variables that impact the severity of chronic pain and functional loss. We review diagnosis and management of selected chronic pain conditions in pediatric patients, including headache, low back pain, hypermobility, chronic fatigue, postural orthostatic tachycardia syndrome, abdominal pain, fibromyalgia, and complex regional pain syndrome. For each condition, we create a road map that contains therapy prescriptions, exercise recommendations, and variables that may influence pain severity. Potential medications for these pain conditions and associated symptoms are reviewed. A multidisciplinary approach for managing children with these conditions, including pediatric pain rehabilitation programs, is emphasized. Lastly, we discuss psychological factors and interventions for pediatric chronic pain and potential complementary and alternative natural products and interventions.

Background: Tachyphylaxis to sciatic nerve blockade in rats correlates with hyperalgesia. Spinal inhibition of nitric oxide synthase with NGnitro-L-arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Given systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in preventing tachyphylaxis therefore may be mediated at spinal sites. We compared systemic versus intrathecal potency of L-NAME in modulating tachyphylaxis to sciatic nerve block. Methods: Rats were prepared with intrathecal catheters. Three sequential sciatic nerve blocks were placed. Duration of block of thermal nocifensive, proprioceptive and motor responses was recorded. We compared spinal versus systemic dose–response to L-NAME, and examined effects of intrathecal arginine on tachyphylaxis. An additional group of rats underwent testing after T10 spinal cord transection. In these rats duration of sciatic nerve block was assessed by determining the heat-induced flexion withdrawal reflex. Results:L-NAME was 25-fold more potent in preventing tachyphylaxis given intrathecally than intraperitoneally. Intrathecal arginine augmented tachyphylaxis. Spinalized rats exhibited tachyphylaxis to sciatic block. Conclusion: The increased potency of intrathecal versus systemic L-NAME suggests a spinal site of action in inhibiting tachyphylaxis. Descending pathways are not necessary for the development of tachyphylaxis since it occurs even after T10 spinal cord transection. Thus tachyphylaxis, like hyperalgesia, is mediated at least in part by a spinal site of action.

Local anesthetics (Table 1) are drugs that block the transmission of the action potential along the nerve axon. The mechanism of action is typically a blockade of the sodium channel, preventing depolarization of the nerve. A general rule is that larger-diameter fibers require a higher concentration of local anesthetic for block than do smaller-diameter fibers, so the smallest, nonmyelinated, C fibers are most easily blocked, whereas the thicker, myelinated nerves are more difficult to block. In myelinated nerves, the depolarization leaps between the nodes of Ranvier, however, speeding conduction. Interruption of the signal can be accomplished by completely blocking depolarization at three consecutive nodes or by partial block attenuating conduction at several adjacent nodes. The latter can be accomplished using a lower concentration and higher volume. Local anesthetics have a low affinity for the resting sodium channel and a hgh affinity for the open channel, so nerve fibers that are actively firing

Most infants at risk for neonatal abstinence syndrome have opioid plus another drug exposure; polypharmacy is the rule rather than the exception. Scales for evaluation of neonatal abstinence syndrome are primarily based for opioid withdrawal. A standard protocol to treat neonatal abstinence syndrome has not been developed. Institute nonpharmacologic strategies for all neonates at risk. The American Academy of Pediatrics recommends mechanism-directed therapy (treat opioid withdrawal with an opioid) as the first-line therapy. Second-line medications are currently under evaluation.

A model of local anesthetic tachyphylaxis was developed in our group previously using repeated sciatic nerve blocks in rats. In this model, thermal hyperalgesia accelerated tachyphylaxis, and the noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, MK-801, prevented both hyperalgesia and tachyphylaxis. Nitric oxide is thought to be a second messenger for NMDA pathways in the spinal cord, and appears to be involved in spinal mechanisms of hyperalgesia. We hypothesized that nitric oxide synthase inhibitors would also inhibit the development of tachyphylaxis. Repeated rat sciatic nerve blocks were placed by percutaneous injection of 2-chloroprocaine. Block duration was tested by measuring hot-plate latency at 56 degrees C. Two hours before the first nerve block, rats received intraperitoneal injections with saline or one of six concentrations of NG-nitro-L-arginine methyl ester (L-NAME) in a randomized, blinded pattern. Control rats developed tachyphylaxis as seen previously: the duration of the third block was 30% that of the first. L-NAME inhibited the development of tachyphylaxis in a dose-dependent manner; tachyphylaxis was inhibited by 50% using L-NAME at 0.2mg/kg and completely abolished by 50 mg/kg. Nitric oxide pathways may be involved in the development of tachyphylaxis to local anesthetic nerve block.

Background Previous work showed that incorporation of dexamethasone (0.05 weight/weight percentage) into bupivacaine microspheres prolonged blockade by eight to 13 times compared with that produced by bupivacaine microspheres alone. The determinants of dexamethasone's block-prolonging effect were examined and reported here. Methods Polylactic-co-glycolic acid polymer microspheres (65/35) with 75 weight/weight percentage bupivacaine were prepared. Microspheres were injected adjacent to the rat sciatic nerve, and sensory and motor blockade were assessed. A procedure was developed to test drugs for block-prolonging ability in vivo by placing test drugs in the injection fluid along with a suspension of bupivacaine microspheres. Results Dexamethasone alone in suspension did not produce blockade, nor did it prolong blockade induced by aqueous bupivacaine. Bupivacaine microspheres (150 mg drug/kg rat weight) produced blockade for 6 to 10 h. Dexamethasone in the suspending solution of microspheres prolonged block by up to five times. Glucocorticoids prolonged block in proportion to glucocorticoid/antiinflammatory potency. The corticosteroid antagonist cortexolone inhibited dexamethasone's blockade-prolonging action. Durations of blockade with or without dexamethasone were unaltered by hydroxyurea-induced neutrophil depletion. Microspheres were extracted from rats at time points ranging from 7 h to 7 days, and residual microsphere dry weight and bupivacaine content were similar in groups of rats injected with either bupivacaine microspheres or bupivacaine microspheres containing dexamethasone, respectively. Conclusions Glucocorticoids prolong blockade from bupivacaine microspheres. The mechanism appears unrelated to the kinetics of bupivacaine release in vivo.

Exposure to general anesthesia at an early age has been associated with adverse neurodevelopmental outcomes in both animal and human studies, but some of these studies employed anesthetic agents that are no longer in clinical use. In this manuscript, we describe the methods used to construct a new population-based study cohort to study the association between early anesthetic exposure and subsequent neurodevelopmental outcomes. A birth cohort of all children born in Olmsted County, MN from January 1, 1996 to December 31, 2000 was identified. For each, school enrollment status in the Independent School District (ISD) 535 at age 5 or 6 and all episodes of anesthetic exposure before age 3 were identified. A study cohort was created by matching children enrolled in ISD 535 based on the propensity of receiving general anesthesia. Three analyses were performed to characterize the study cohort by comparing the birth and parental information, comorbidities, and socioeconomic status. The first analysis compared the characteristics of birth cohort children who were and were not enrolled in ISD 535. The second analysis evaluated the success of the propensity matching schemes in creating groups of children that were similar in measured characteristics except for anesthesia exposure. The third analysis compared the characteristics of children with anesthesia exposures who were and were not included in the final cohort based on propensity matching. Results of these analyses demonstrate only slight differences among the comparison groups, and therefore these are unlikely to compromise our future analysis of anesthetic exposure and neurodevelopmental outcomes.

We reviewed cases to determine whether suspected or confirmed epidural infection was associated with epidural analgesia for 1620 infants, children, and adolescents treated over a 6-yr period at Children's Hospital, Boston. Postoperative patients (1458/1620) received epidural infusions for a median of 2 days (range, 0-8 days). No postoperative patient had an epidural abscess. One 10-yr-old with terminal malignancy received thoracic epidural analgesia via two successive catheters over a 4-wk period. She had Candida colonization of the epidural space along with necrotic epidural tumor. A second oncology patient and two patients with reflex sympathetic dystrophy were evaluated for epidural abscess, but none was found. We conclude that the risk of epidural infection is quite low in pediatric postoperative patients receiving short-term catheterization. Use of prolonged epidural analgesia in the management of chronic pain in children requires careful monitoring of warning signs of infection.

BACKGROUND: Annually, millions of children are exposed to anesthetic agents that cause apoptotic neurodegeneration in immature animals. To explore the possible significance of these findings in children, we investigated the association between exposure to anesthesia and subsequent (1) learning disabilities (LDs), (2) receipt of an individualized education program for an emotional/behavior disorder (IEP-EBD), and (3) scores of group-administered achievement tests. METHODS: This was a matched cohort study in which children (N = 8548) born between January 1, 1976, and December 31, 1982, in Rochester, Minnesota, were the source of cases and controls. Those exposed to anesthesia (n = 350) before the age of 2 were matched to unexposed controls (n = 700) on the basis of known risk factors for LDs. Multivariable analysis adjusted for the burden of illness, and outcomes including LDs, receipt of an IEP-EBD, and the results of group-administered tests of cognition and achievement were outcomes. RESULTS: Exposure to multiple, but not single, anesthetic/surgery significantly increased the risk of developing LDs (hazard ratio: 2.12 [95% confidence interval: 1.26–3.54]), even when accounting for health status. A similar pattern was observed for decrements in group-administered tests of achievement and cognition. However, exposure did not affect the rate of children receiving an individualized education program. CONCLUSIONS: Repeated exposure to anesthesia and surgery before the age of 2 was a significant independent risk factor for the later development of LDs but not the need for educational interventions related to emotion/behavior. We cannot exclude the possibility that multiple exposures to anesthesia/surgery at an early age may adversely affect human neurodevelopment with lasting consequence.

To study the association between exposure to procedures performed under general anesthesia before age 2 years and development of attention-deficit/hyperactivity disorder (ADHD).Study patients included all children born between January 1, 1976, and December 31, 1982, in Rochester, MN, who remained in Rochester after age 5. Cases of ADHD diagnosed before age 19 years were identified by applying stringent research criteria. Cox proportional hazards regression assessed exposure to procedures requiring general anesthesia (none, 1, 2 or more) as a predictor of ADHD using a stratified analysis with strata based on a propensity score including comorbid health conditions.Among the 5357 children analyzed, 341 ADHD cases were identified (estimated cumulative incidence, 7.6%; 95% confidence interval [CI], 6.8%-8.4%). For children with no postnatal exposure to procedures requiring anesthesia before the age of 2 years, the cumulative incidence of ADHD at age 19 years was 7.3% (95% CI, 6.5%-8.1%). For single and 2 or more exposures, the estimates were 10.7% ( 95% CI, 6.8%-14.4%) and 17.9% ( 95% CI, 7.2%-27.4%), respectively. After adjusting for gestational age, sex, birth weight, and comorbid health conditions, exposure to multiple (hazard ratio, 1.95; 95% CI, 1.03-3.71), but not single (hazard ratio,1.18; 95% CI, 0.79-1.77), procedures requiring general anesthesia was associated with an increased risk for ADHD.Children repeatedly exposed to procedures requiring general anesthesia before age 2 years are at increased risk for the later development of ADHD even after adjusting for comorbidities.

In prior work, children born to mothers who received neuraxial anesthesia for cesarean delivery had a lower incidence of subsequent learning disabilities compared with vaginal delivery. The authors speculated that neuraxial anesthesia may reduce stress responses to delivery, which could affect subsequent neurodevelopmental outcomes. To further explore this possibility, we examined the association between the use of neuraxial labor analgesia and development of childhood learning disabilities in a population-based birth cohort of children delivered vaginally.The educational and medical records of all children born to mothers residing in the area of 5 townships of Olmsted County, Minnesota from 1976 to 1982 and remaining in the community at age 5 years were reviewed to identify those with learning disabilities. Cox proportional hazards regression was used to compare the incidence of learning disabilities between children delivered vaginally with and without neuraxial labor analgesia, including analyses adjusted for factors of either potential clinical relevance or that differed between the 2 groups in univariate analysis.Of the study cohort, 4684 mothers delivered children vaginally, with 1495 receiving neuraxial labor analgesia. The presence of childhood learning disabilities in the cohort was not associated with use of labor neuraxial analgesia (adjusted hazard ratio, 1.05; 95%confidence interval, 0.85-1.31; P = 0.63).The use of neuraxial analgesia during labor and vaginal delivery was not independently associated with learning disabilities diagnosed before age 19 years. Future studies are needed to evaluate potential mechanisms of the previous finding indicating that the incidence of learning disabilities is lower in children born to mothers via cesarean delivery under neuraxial anesthesia compared with vaginal delivery.

We report on the experience with our first seventy patients who had reflex sympathetic dystrophy and were less than eighteen years old (average age, 12.5 years). In our series, the patients were predominantly girls (male to female ratio, 11:59) and the lower extremity was involved most often (sixty-one of the seventy patients). The average time from the initial injury to the diagnosis was one year, which indicates that the syndrome remains under-recognized in patients in this age-group. Conservative treatment with physical therapy, transcutaneous electrical nerve stimulation, psychological therapies including cognitive-behavioral management and relaxation training, and tricyclic anti-depressants was effective in improving the average scores for pain and function for forty patients. Sympathetic blocks were helpful for twenty-eight of thirty-seven patients. Thirty-eight of the seventy patients in the series continued to have some degree of residual pain and dysfunction. Reflex sympathetic dystrophy in children differs in presentation and clinical course from the syndrome in adults. It is best treated in a multidisciplinary fashion.

Day surgery is a common source of signifi cant pain for children. A combination of opioids, NSAIDs, and regional anesthetic techniques are available to provide comfort post-operatively. Regardless of what is provided in the hospital or surgery center, the patients will need pain care at home. Awareness of the techniques available to children in the operating room can help the primary care physician counsel parents to help them better advocate for their child when they arrive for surgery. Knowing the probable pitfalls in postoperative care that can occur at home can help the parents keep ahead of the pain, and avoid unnecessary complications. The preoperative visit is an excellent time in which to educate the family for the day of surgery.

This review summarizes current information about diagnosis and treatment of complex regional pain syndrome (CRPS) in children. Although it has been widely held that CRPS in children is intrinsically different from adults, there appear to be relatively few differences. However, there is a marked preponderance of lower extremity cases in children. Historically, psychological factors have been invoked to explain the genesis and persistence of CRPS in children, but the evidence is not compelling. Treatment outcome studies are limited but indicate that children generally respond to a primary focus on physical therapy. Multidisciplinary treatment reports are particularly encouraging. The general perception that children have a milder course may relate to the potentially greater willingness of children to actively participate in appropriately targeted treatment rather than to innate differences in the disease process itself. Recurrence rates appear higher than in adults, but response to reinitiation of treatment seems to proceed efficiently. Clinical judgment dictates the extent of medication or interventional therapy added to the treatment to facilitate rehabilitation. In many ways, the approach to the treatment of children mirrors that of adults, with perhaps greater restraint in the use of medications and invasive procedures. The rehabilitation of children with CRPS, like that of adults with CRPS, needs further rigorous investigation.

In order to examine whether repeated sciatic nerve blocks showed tachyphylaxis and continuity of sciatic nerve with spinal cord affected development of tachyphylaxis when assayed in vivo by duration of depression compound action potentials (CAP), rats were anesthetized with halothane, ventilated, monitored and supported with stable hemodynamics and temperature. Posterior tibial nerve distally and sciatic nerve in thigh were exposed, placed on bipolar silver electrodes for stimulation and recording respectively. Three sequential sciatic nerve blocks were performed between these electrodes using 0.15 ml of 3% chloroprocaine. Nine rats were chosen to observe the effects of repeated sciatic nerve blocks on CAP. In another 18 rats, a second investigator exposed the sciatic nerve near its origin at spinal cord and randomly performed nerve cut and sham (n=9), and closed the incision blinding the electrophysiologic investigator. The results showed that electrical stimulated tibial nerve induced sciatic nerve Aalpha/beta, Adelta, C fiber mediated CAP waves. CAP amplitudes were remained stable during whole experimental procedure. CAP amplitudes were decreased completely with 3% chloroprocaine blocked sciatic nerve and recovered fully. The duration of CAP depression were reduced with repeated blocks. There were no selective blocked effects on Aalpha/beta, Adelta, C fiber mediated CAP. With sciatic nerve cut proximally, there was no statistical significant tachyphylaxis with 3% chloroprocaine repeated blocked sciatic nerve, and the duration of first and third blocked Adelta fiber mediated CAP was 108+/-20 and 92+/-14 min respectively (P>0.05). In normal rats the duration of first and third blocked Adelta fiber mediated CAP was 110+/-20 and 75+/-16 min respectively (P

Einige Studien haben gezeigt, dass Lidocain Laryngospasmen bei anasthesierten Kindern reduzieren kann. Allerdings wurde diese Schlussfolgerung aufgrund der Power besagter Studien durchaus infrage gestellt. Erb und Kollegen aus dem Kinderhospital der Universitat Basel konzipierten daher zur Wirkung des Lidocains bei Larygnospasmen eine Studie.

The work by Bartels et al., 2009 that any association between early exposure to anesthetic agents and the subsequent development of learning disabilities is potentially related to comorbidity rather than anesthetic exposure per se is discussed. The study by Bartels has provided valuable information; however, a degree of caution needs to be used in the interpretation and application of these results.

OBJECTIVE: To determine the incidence of side effects with the short-term use of intravenously administered ketorolac in children and the overall cost savings with a unit dosing system. STUDY DESIGN: We prospectively examined the incidence of complications arising from the intravenous administration of ketorolac to 1747 children (14,810 doses) during a 3-year, 3-month period and assessed cost savings resulting from dividing 60 mg syringes into 7.5, 15, 30, and 60 mg unit doses. Complications were recorded prospectively into a computerized database. Estimated drug costs to the pharmacy were calculated on the basis of the total numbers of each drug fraction administered, with allowance for 10% wastage as a result of drug expiration. RESULTS: Side effects occurring with ketorolac administration were rare. Four patients (0.2%) had hypersensitivity reactions to the drug, two of them possibly on the basis of latex allergy. Two patients (0.1%) had renal complications but were subsequently found to have underlying causes that could account for their renal symptoms. One patient (0.05%) had massive gastrointestinal bleeding in the postoperative period. With fractionation of 60 mg syringes, total drug cost to the pharmacy was $34,786, rather than the $86,639 that would have been spent had a single syringe been used for each dose. CONCLUSION: Ketorolac proved safe for short-term intravenous use in children more than 1 year of age when patients with known contraindications to the use of nonsteroidal antiinflammatory drugs were excluded. A considerable reduction in drug costs can be achieved with fractionation of premixed syringes into unit doses. (J PEDIATR 1996;129:292-6)

BACKGROUND Tachyphylaxis to local anesthetics has been shown to be promoted by longer interanalgesic intervals between injections. We hypothesized that thermal hyperalgesia also would accelerate the development of tachyphylaxis. The n-methyl-D-aspartate antagonist ((+)-5 methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine, or dizocilpine) (MK-801) has been shown to prevent thermal hyperalgesia. We therefore also hypothesized that MK-801 would prevent tachyphylaxis. METHODS Catheters were surgically implanted in rats along the sciatic nerve. After recovery and conditioning to the testing paradigm, they received repeated injections of lidocaine or 2-chloroprocaine followed by motor block testing with or without hot-plate testing at 48, 52, or 56 degrees C. In other experiments, MK-801 or saline was administered by intraperitoneal injection before sciatic nerve local anesthetic injection and sensory and motor testing. RESULTS Rats receiving repeated lidocaine or 2-chloroprocaine injections, when repeatedly subjected to hot-plate testing at 56 degrees C, developed thermal hyperalgesia and tachyphylaxis to motor and sensory blockade. Rats receiving either no hot-plate exposure or hot-plate exposure at 48 degrees C developed no tachyphylaxis or hyperalgesia. Rats tested at 52 degrees C developed milder hyperalgesia and developed tachyphylaxis more slowly than did rats tested at 56 degrees C. Control experiments excluded artifacts due to circadian rhythm, injection volume, and learning. Rats pretreated with MK-801 showed no tachyphylaxis over a series of three injections. CONCLUSIONS Thermal hyperalgesia accelerates the development of tachyphylaxis to rat sciatic nerve blockade, and MK-801 prevents tachyphylaxis in this model. n-Methyl-D-aspartate receptor antagonists may have future clinical utility in increasing the duration of effectiveness of prolonged local anesthetic administration.

Hurler syndrome (mucopolysaccharidosis storage disease, Type I-H) is an inherited progressive metabolic disorder. Micrognathia, a very short neck, and restricted motion at the temporomandibular joint may combine to make direct laryngoscopy difficult or impossible. We now report a case of successful fiberoptic intubation in a 12-y-old child with Hurler syndrome with severe upper-airway obstruction. Even though the intubation was successful, postintubation pulmonary edema occurred

Verslag wordt uitgebracht van onze ervaring met 70 patienten met sympathische reflexdystrofie van minder dan achttien jaar oud (gemiddelde leeftijd 12,5 jaar). Onze patientengroep bestond overwegend uit meisjes (jongen- meisje verhouding 11:59) en de onderste extremiteit was het meest

Perdeuterated spin label (DSL) analogs of NAD+, with the spin label attached at either the C8 or N6 position of the adenine ring, have been employed in an EPR investigation of models for negative cooperativity of coenzyme binding to tetrameric glyceraldehyde-3-phosphate dehydrogenase and conformational changes of the DSL-NAD+-enzyme complex during the catalytic reaction. C8-DSL-NAD+ and N6-DSL-NAD+ showed 80 and 45% of the activity of the native NAD+, respectively. Therefore, these spin-labeled compounds are very efficacious for investigations of the motional dynamics and catalytic mechanism of this dehydrogenase. Perdeuterated spin labels enhanced spectral sensitivity and resolution thereby enabling the simultaneous detection of spin-labeled NAD+ in three conditions: (1) DSL-NAD+ freely tumbling in the presence of, but not bound to, glyceraldehyde-3-phosphate dehydrogenase, (2) DSL-NAD+ tightly bound to enzyme subunits remote (58A) from other NAD+ binding sites, and (3) DSL-NAD+ bound to adjacent monomers and exhibiting electron dipolar interactions (8–9Aor 12–13A, depending on the analog). Determinations of relative amounts of DSL-NAD+ in these three environments and measurements of the binding constants, K1−K4, permitted characterization of the mathematical model describing the negative cooperativity in the binding of four NAD+ to glyceraldehyde-3-phosphate dehydrogenase. For enzyme crystallized from rabbit muscle, EPR results were found to be consistent with the ligand-induced sequential model and inconsistent with the pre-existing asymmetry models. The electron dipolar interaction observed between spin labels bound to two adjacent glyceraldehyde-3-phosphate dehydrogenase monomers (8–9 or 12–13A) related by the R-axis provided a sensitive probe of conformational changes of the enzyme-DSL-NAD+ complex. When glyceraldehyde-3-phosphate was covalently bound to the active site cysteine-149, an increase in electron dipolar interaction was observed. This increase was consistent with a closer approximation of spin labels produced by steric interactions between the phosphoglyceryl residue and DSL-NAD+. Coenzyme reduction (DSL-NADH) or inactivation of the dehydrogenase by car☐ymethylation of the active site cysteine-149 did not produce changes in the dipolar interactions or spatial separation of the spin labels attached to the adenine moiety of the NAD+. However, coenzyme reduction or car☐ymethylation did alter the stoichiometry of binding and caused the release of approximately one loosely bound DSL-NAD+ from the enzyme. These findings suggest that ionic charge interactions are important in coenzyme binding at the active site.