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Preterm and term neonate pain assessment in neonatal intensive care units is vitally important because of the prevalence of procedural and postoperative pain. Of the 40 plus tools available, a few should be chosen for different populations and contexts (2 have been validated in premature infants). Preterm neonates do not display pain behaviors and physiologic indicators as reliably and specifically as full-term infants, and are vulnerable to long-term sequelae of painful experiences. Brain-oriented approaches may become available in the future; meanwhile, neonatal pain assessment tools must be taught, implemented, and their use optimized for consistent, reproducible, safe, and effective treatment.

Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo‐controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patients with acute postoperative pain assessed pharmacokinetics (PK) and safety, in addition to efficacy and pharmacodynamics of repeated doses administered over 24 hours. Neonate and infant patients (

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 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.

Clinical trials to test the safety and efficacy of analgesics across all pediatric age cohorts are needed to avoid inappropriate extrapolation of adult data to children. However, the selection of acute pain models and trial design attributes to maximize assay sensitivity, by pediatric age cohort, remains problematic. Acute pain models used for drug treatment trials in adults are not directly applicable to the pediatric age cohorts-neonates, infants, toddlers, children, and adolescents. Developmental maturation of metabolic enzymes in infants and children must be taken into consideration when designing trials to test analgesic treatments for acute pain. Assessment tools based on the levels of cognitive maturation and behavioral repertoire must be selected as outcome measures. Models and designs of clinical trials of analgesic medications used in the treatment of acute pain in neonates, infants, toddlers, children, and adolescents were reviewed and discussed at an Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) Pediatric Pain Research Consortium consensus meeting. Based on extensive reviews and continuing discussions, the authors recommend a number of acute pain clinical trial models and design attributes that have the potential to improve the study of analgesic medications in pediatric populations. Recommendations are also provided regarding additional research needed to support the use of other acute pain models across pediatric age cohorts.

Opioids are still widely used in the management of severe acute and chronic pain in children. However, there are increased concerns related to both the acute side effects and chronic problems, which include the potential for abuse and addiction. A thorough knowledge of the mechanism of action of opioids is critical to the understanding of the pathogenesis of the various opioid-related side effects and facilitates appropriate prophylactic and therapeutic interventions to mitigate the incidence and severity of the same. In addition, the use of multimodal therapy, when possible, helps reduce the amount of opioid needed for pain relief and, thereby, decreases the incidence and severity of side effects. Opioids prescribed for home administration after discharge must be accompanied by family education about safe administration, storage, and disposal of medication.

Clinical researchers studying the long-term neurocognitive effects of anesthetic and sedative agents on children continue to struggle with identifying a phenotype for anesthetic neurotoxicity, the window of vulnerability, and the toxicity threshold in terms of concentration and duration. The Sixth Biennial Pediatric Anesthesia Neurodevelopment Assessment (PANDA) symposium at Columbia University included a moderated poster presentation session where 4 investigators presented their latest contributions to the landscape of clinical anesthetic neurotoxicity research. A lack of standardization in the design of clinical studies in terms of age at exposure, duration and type of exposure, and outcome measures assessed were highlighted by all the investigators. Suggestions for the future direction of clinical trials included the implementation of more consistent study parameters and the employment of standardized neurocognitive testing and imaging before and after exposure to general anesthesia. Presentations covered a broad range of topics including the valid translation of preclinical studies to human subjects, the quantification of real-world exposures to anesthetic and sedative medications, and possible alternatives to these exposures.

OBJECTIVES Opioid pharmacotherapy is the cornerstone of postoperative analgesia. Despite its effectiveness, it has a variety of potential adverse effects. Therefore, a multimodal approach with non-opioid analgesics would be optimal. The aim of this study was to determine if intravenous (IV) acetaminophen would reduce opioid requirements and improve clinical outcomes in children after surgery. METHODS A single-center, randomized, double-blind study was conducted in 57 children (10–18 years old) undergoing posterior spine fusion surgery between July 2011 to May 2014. All subjects received either acetaminophen or placebo at the end of surgery, followed by repeated doses every 6 hours for a total of 8 doses. RESULTS In the first 24 postoperative hours, the average opioid consumption was lower for the active group compared with the placebo group (p = 0.02). The total unadjusted time to patient controlled analgesia (PCA) discontinuation was also longer in the placebo group than the active group (90 hours vs. 73 hours, p = 0.02); however, this was not statistically significant after normalizing for body weight. Additionally, time to first solid intake was longer without the use of acetaminophen (69 hours vs. 49 hours, p = 0.01). CONCLUSIONS Postoperative use of IV acetaminophen was associated with earlier time to diet advancement and discontinuation of IV analgesics and may result in lower opioid consumption.

SummaryBackground Recent articles in both scholarly journals and the lay press about the topic of anesthetic related neurotoxicity have increased the awareness and discussion of this topic with parents and other pediatric medical specialties (i.e., surgeons, radiologists, and pediatricians). Aim The purpose of the present study was to survey how a subset of pediatric anesthesia departments in the US have responded to the issue of anesthetic related neurotoxicity in terms of clinical practice, training and communication with other medical specialties, and the frequency and timing of discussions with families. Methods A survey consisting of 22 questions was sent to PALC (Pediatric Anesthesia Leadership Council) & PAPDA (Pediatric Anesthesia Program Directors Association) via SurveyMonkey. The survey was divided into sections on Anesthesia Faculty/Trainees, Parents and Non-Anesthesia Providers. Responses to the survey were solicited via email to PALC and PAPDA, and then followed up with reminders to individual emails using the mailing lists of both organizations. Results The results of this survey demonstrate that pediatric anesthesia programs around the US do not have a consistent approach in managing the topic of anesthesia-related neurotoxicity with pediatric anesthesiologists, anesthesiology residents, pediatric anesthesiology fellows and their non-anesthesia medical and surgical colleagues, as well as the discussion of this topic with parents. Conclusion A significant need exists to provide information to other pediatric professionals and parents. A consistent message from all providers that includes what is known, and indeed more importantly what is not known may be a useful approach.

Background:Postoperative apnea is a complication in young infants. Awake regional anesthesia (RA) may reduce the risk; however, the evidence is weak. The General Anesthesia compared to Spinal anesthesia study is a randomized, controlled trial designed to assess the influence of general anesthesia (GA) on neurodevelopment. A secondary aim is to compare rates of apnea after anesthesia.Methods:Infants aged 60 weeks or younger, postmenstrual age scheduled for inguinal herniorrhaphy, were randomized to RA or GA. Exclusion criteria included risk factors for adverse neurodevelopmental outcome and infants born less than 26 weeks gestation. The primary outcome of this analysis was any observed apnea up to 12 h postoperatively. Apnea assessment was unblinded.Results:Three hundred sixty-three patients were assigned to RA and 359 to GA. Overall, the incidence of apnea (0 to 12 h) was similar between arms (3% in RA and 4% in GA arms; odds ratio [OR], 0.63; 95% CI, 0.31 to 1.30, P = 0.2133); however, the incidence of early apnea (0 to 30 min) was lower in the RA arm (1 vs. 3%; OR, 0.20; 95% CI, 0.05 to 0.91; P = 0.0367). The incidence of late apnea (30 min to 12 h) was 2% in both RA and GA arms (OR, 1.17; 95% CI, 0.41 to 3.33; P = 0.7688). The strongest predictor of apnea was prematurity (OR, 21.87; 95% CI, 4.38 to 109.24), and 96% of infants with apnea were premature.Conclusions:RA in infants undergoing inguinal herniorrhaphy reduces apnea in the early postoperative period. Cardiorespiratory monitoring should be used for all ex-premature infants.

Context Appropriate use of opioids is essential to manage moderate-to-severe pain in children safely and effectively, yet published guidance regarding opioid treatment for pediatric patients is limited, potentially resulting in excessive variation in opioid use in pediatric patients across hospitals in the U.S. Objectives The aim was to evaluate hospital variation in opioid use in pediatric inpatients. Methods Using data from the Pediatric Health Information System and the Premier Perspective Database regarding all pediatric inpatients in 626 hospitals, we examined hospital variation in opioid use and the length of opioid use, adjusting for patient demographic and clinical characteristics and for hospital type (children's vs. general) and hospital patient volume, using multilevel generalized linear regression modeling. Results Overall, 41.2% of all pediatric hospitalizations were exposed to opioids. Among the exposed patients, the mean length of exposure was 4.6 days. Exposure proportion and exposure length varied substantially across hospitals, even after accounting for patient demographic and clinical characteristics, hospital type and hospital patient volume, especially among terminal hospitalizations. For patients discharged alive vs. died, the adjusted exposure percentage for each hospital ranged from 0.7% to 99.1% (interquartile range [IQR]: 35.3%–59.9%) vs. 0.1% to 100.0% (IQR: 29.2%–66.2%), respectively, and the adjusted exposure length ranged from 1.0 to 8.4 days (IQR: 2.2–2.7 days) vs. 0.9 to 35.2 days (IQR: 4.0–7.4 days). Conclusion The substantial hospital-level variation in opioid use in pediatric inpatients suggests room for improvement in clinical practice.

Background Pectus excavatum is the most common congenital chest wall deformity. The Nuss procedure is frequently used for surgical correction and this technique has been associated with severe and prolonged post-operative pain. At the present time, the optimal analgesic strategy for managing patients following this procedure has not been determined. Methods A web-based survey was sent to representatives from 108 primarily pediatric hospitals in North America, Europe, Asia and Australia. One individual per institution was contacted to complete the survey on behalf of their department. Results Survey response rate was 54% and 55 institutions reported using the Nuss procedure for correction of pectus excavatum. Annual case volume is less than or equal to 25 cases in 57% of institutions, and the most common age of patients is 14 to 17 years old. A clinical protocol for patient post-operative pain management is used in 45% of institutions. Thoracic epidural is utilized as a primary analgesic modality by 91% of institutions. Concomitant use of intravenous patient-controlled analgesia is reported by 27% of institutions. Nine respondents (16%) reported that they had recently stopped performing epidurals because of surgeon preference. Referral of one or more patients annually for chronic pain management was reported in 22% of surveys. Conclusions Post-operative pain management following the Nuss procedure is variable and poorly characterized. Clinical trials or large observational registries comparing the safety and efficacy of primary modalities and long-term outcomes are needed to enable evidence-based decision-making for the management of these patients.

Although the role of regional anesthesia in pediatric patients has been increasing over the last few years, there are only a few small case series that describe the use of ambulatory continuous peripheral nerve blocks (CPNBs) in this patient population. In this report, we describe our experience with the use of ambulatory CPNBs in 1285 children.Data were collected for consecutive children who had a CPNB placed between January 2005 and December 2011 at The Children's Hospital of Philadelphia from the departmental regional anesthesia database. Data collected included demographics, the site of catheter placement and technique of nerve block, presence of sensory/motor blockade, use of perioperative opioids, and any complications related to CPNBs.Continuous infusions of local anesthetics were administered via the catheters in 1285 outpatients. The mean duration of the CPNB was 50.7 ± 14.4 hours (mean ± SD). Among patients discharged home with the CPNBs, 969 (75.4%) of the patients required either no supplemental opioids or oral opioids only on an "as needed" basis in the postoperative period (confidence interval, 73.0%-77.8%). Two patients were readmitted for IV pain management after they were discharged home with the CPNB catheters. No neurological deficit related to the CPNBs was identified in any of the patients at their 6-month follow-up with the orthopedic surgeon (confidence interval, 0%-0.29%).This audit of 1285 children shows ambulatory CPNBs can provide postoperative analgesia and may reduce the need for inpatient parenteral opioid therapy.

The Pediatric Anesthesia Neuro Development Assessment (PANDA) team at the Anesthesiology Department at Columbia University Medical Center held its fifth biennial symposium to discuss issues regarding potential neurotoxicity of anesthetic agents in pediatric patients. Overall optimal surgical timing as well as a "critical window" for surgery on a specialty specific basis are areas of focus for the American Academy of Pediatrics Surgical Advisory Panel. An ad hoc panel of pediatric surgical experts representing general surgery, urology, neurosurgery, and ophthalmology was assembled for this meeting and provided a dialogue focused on the benefits of early intervention versus potential anesthetic risk, addressing parental concerns, and the need for continued interdisciplinary collaboration in this area.

BACKGROUND: Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) is associated with significant pain and prolonged hospitalization. There is evidence that early mobilization and multimodal analgesia can accelerate functional recovery and reduced length of stay (LOS). Using these principles, we implemented a quality improvement initiative to enable earlier functional recovery in our AIS–PSF population. METHODS: We designed and implemented a standardized rapid recovery pathway (RRP) with evidence-based management recommendations for children aged 10 to 21 years undergoing PSF for AIS. Our primary outcome, functional recovery, was assessed using statistical process control charts for LOS and average daily pain scores. Our process measures were medication adherence and order set utilization. The balancing measure was 30-day readmission rate. RESULTS: We included 322 patients from January 1, 2011 to June 30, 2015 with 134 (42%) serving as historical controls, 104 (32%) representing our transition population, and 84 (26%) serving as our RRP population. Baseline average LOS was 5.7 days and decreased to 4 days after RRP implementation. Average daily pain scores remained stable with improvement on postoperative day 0 (3.8 vs 4.9 days) and 1 (3.8 vs 5 days) after RRP implementation. In the second quarter of 2015, gabapentin (91%) and ketorolac (95%) use became routine and order set utilization was 100%. Readmission rates did not increase as a result of this pathway. CONCLUSIONS: Implementation of a standardized RRP with multimodal pain management and early mobilization strategies resulted in reduced LOS without an increase in reported pain scores or readmissions.

The Pediatric Anesthesia NeuroDevelopment Assessment research group at Columbia University Medical Center Department of Anesthesiology has conducted biannual national Symposia since 2008 to evaluate study data and invigorate continued thinking about unresolved issues of pediatric anesthesia neurotoxicities. The third Symposium extended the dialogue between pediatric anesthesiologists and surgeons in panel presentations and discussions by four surgical specialists. This paper reports the prevailing opinions expressed by a pediatric general surgeon, urologist, plastic surgeon and ophthalmologist and explores factors related to delayed operative intervention, need for multiple procedures, and parental concerns.

Analgesic trials pose unique scientific, ethical, and practical challenges in pediatrics. Participants in a scientific workshop sponsored by the US Food and Drug Administration developed consensus on aspects of pediatric analgesic clinical trial design. The standard parallel-placebo analgesic trial design commonly used for adults has ethical and practical difficulties in pediatrics, due to the likelihood of subjects experiencing pain for extended periods of time. Immediate-rescue designs using opioid-sparing, rather than pain scores, as a primary outcome measure have been successfully used in pediatric analgesic efficacy trials. These designs maintain some of the scientific benefits of blinding, with some ethical and practical advantages over traditional designs. Preferred outcome measures were recommended for each age group. Acute pain trials are feasible for children undergoing surgery. Pharmacodynamic responses to opioids, local anesthetics, acetaminophen, and nonsteroidal antiinflammatory drugs appear substantially mature by age 2 years. There is currently no clear evidence for analgesic efficacy of acetaminophen or nonsteroidal antiinflammatory drugs in neonates or infants younger than 3 months of age. Small sample designs, including cross-over trials and N of 1 trials, for particular pediatric chronic pain conditions and for studies of pain and irritability in pediatric palliative care should be considered. Pediatric analgesic trials can be improved by using innovative study designs and outcome measures specific for children. Multicenter consortia will help to facilitate adequately powered pediatric analgesic trials.

Summary Objective/Aims: To assess current practices in the management of children undergoing craniofacial surgery and identify areas of significant practice variability with the intent to direct future research. Background: The perioperative management of infants and children undergoing craniofacial reconstruction surgery can be challenging because of the routine occurrence of significant blood loss with associated morbidity. A variety of techniques have been described to improve the care for these children. It is presently unknown to what extent these practices are currently employed. Methods: A web-based survey was sent to representatives from 102 institutions. One individual per institution was surveyed to prevent larger institutions from being over-represented in the results. Results: Requests to complete the survey were sent to 102 institutions; 48 surveys were completed. The survey was composed of two parts: management of infants undergoing strip craniectomies, and management of children undergoing major craniofacial reconstruction. Conclusions: Significant variability exists in the management of children undergoing these procedures; further study is required to determine the optimal management strategies. Clinical trials assessing the utility of central venous pressure and other hemodynamic monitoring modalities would enable evidence-based decision-making for monitoring in these children. The development of institutional transfusion thresholds should be encouraged, as there exists a body of evidence supporting their efficacy and safety.

Summary Prenatally diagnosed sacrococcygeal teratomas (SCT) have higher mortality rates than those diagnosed in the neonatal period. Natural history of SCT varies, and management depends on pathophysiology. Treatment may be minimally invasive or require open surgery. Intervention may take place in the prenatal period, or it may occur within minutes to days after birth. Optimal care requires close follow up and communication between members of a multidisciplinary team. We present a case of prenatally diagnosed SCT and address the evaluation, anesthetic considerations, and mechanisms needed to care for this high risk population.

This is an audit of the continuous peripheral nerve blockade (CPNB) program that was implemented at our institution to provide postoperative analgesia after orthopedic procedures in children.We reviewed the departmental regional anesthesia registry and the medical records of consecutive children who received CPNB for postoperative analgesia at The Children's Hospital of Philadelphia between February 2003 and July 2006. Patients were prospectively followed until cessation of the effects of CPNB and/or resolution of any related complications. Data collected contemporaneously included presence of sensory and motor blockade, pain scores in inpatients, opioid administration, and complications related to CPNB.A total of 226 peripheral nerve catheters were placed in 217 patients. One hundred eight patients (112 catheters) were discharged home with CPNB. The ages ranged from 4 to 18 yr (13.7 +/- 3.4). Local anesthetic solution (0.125% bupivacaine [n = 164], 0.1% ropivacaine [n = 12], or 0.15% ropivacaine [n = 27]) was infused at an initial rate of 2-12 mL/h based on patients' weights and locations of catheters. The mean duration of local anesthetic infusion was 48.4 +/- 29.3 h (range 0-160 h). The percentage of patients who did not require any opioids in the first 8, 24, and 48 h after surgery was 56%, 26%, and 21%, respectively. The incidence of nausea and vomiting was 14% (13% in outpatients, 15% in inpatients). Complications were noted in 2.8% of patients. Three patients had prolonged numbness (24 h) that resolved spontaneously; one developed superficial cellulitis that resolved with a course of antibiotics; one had difficulty removing the catheter at home and one developed tinnitus 24 h after starting CPNB that resolved quickly after clamping of the catheter followed by removal.It is feasible to implement a CPNB program to provide an alternative method of inpatient and outpatient postoperative analgesia after orthopedic surgery in children when appropriate expertise is available. Patient and family education along with frequent follow-up are crucial to detect and address adverse events promptly.

Pruritus occurs frequently following opioid use, particularly after neuraxial administration. Although not life threatening, pruritus is discomforting and may decrease patient satisfaction. Even though the mechanism of opioid-induced pruritus is not yet fully understood, there is increasing evidence of the important role played by micro opioid receptors. Animal experiments pointing to the role of the micro opioid receptor and the efficacy of micro opioid receptor antagonists for opioid adverse effect prophylaxis and treatment have been replicated in several studies. Serotonin and dopamine D(2) receptors, prostaglandins and spinal inhibitory pathways may also be involved in the genesis of pruritus. Several pharmacological agents have been used both for the treatment of established pruritus and in its prevention. Of these, micro opioid receptor antagonists have been most consistent in terms of attenuating opioid-induced pruritus but present problems in dose and administration. Other drugs, including mixed opioid receptor agonist-antagonists, serotonin 5-HT(3) receptor antagonists, propofol, NSAIDs and D(2) receptor antagonists, have also been demonstrated to be useful. This review summarises the current understanding of the mechanisms causing opioid-induced pruritus and the pharmacological therapies available to prevent and/or manage this disorder.

Summary Introduction Continuous thoracic epidural analgesia is useful in the management of infants following thoracotomy. Concerns about drug accumulation and toxicity limit the amount of amide local anesthetics that can be delivered. Continuous epidural infusions of the ester local anesthetic chloroprocaine result in little drug accumulation allowing for higher infusion rates. We retrospectively compared patients managed with 1.5% 2- chloroprocaine or 0.1% ropivacaine epidural infusions to determine if the increased infusion rate resulted in similar or improved analgesia. Methods This retrospective cohort comparison consisted of full term infants 6 months or younger who underwent thoracotomy for congenital lung lesion resection. Patients were included if they were managed with either a 1.5% 2-chloroprocaine (Group C) (n = 26) or 0.1% ropivacaine (Group R) (n = 28) infusion administered through a caudally placed thoracic epidural catheter. The primary outcome was morphine administration at 0–24 h. Results Patients were similar in age, weight, length of stay, epidural location and duration. There was weak evidence for a difference in morphine use in the first 24 h in Group C compared to Group R (P = 0.08) but no difference 24–48 h. Group C was more commonly managed with ketorolac at 0–24 h (P = 0.03) and 24–48 h (P =

Context Although patient-controlled analgesia (PCA) is an effective pain control modality, there is a lack of large studies on PCA safety in pediatric patients. Objectives This study compared the delivery of morphine either via intravenous route (morphine IV) or via PCA device (morphine PCA) on risk of cardiopulmonary resuscitation (CPR) and mechanical ventilation (MV) using a large administrative database. Methods We assembled a retrospective cohort of pediatric inpatients between five and 21 years old in 42 children's hospitals between 2007 and 2011 from the Pediatric Health Information System database. After propensity score matching, we created matched cohorts of morphine PCA and morphine IV patients, in both surgical and nonsurgical samples, who were similar on demographic, clinical, and hospital-level factors. We examined if PCA administration was associated with greater likelihood of CPR or MV up to two days after drug administration. Results Surgical and nonsurgical patients administered morphine PCA generally had lower odds of having MV on the baseline day and up to two days after PCA exposure, although these estimates were not statistically significant. Similarly, PCA exposure was associated with about 20%–44% lower odds of same day CPR in both surgical and nonsurgical patients, with a slightly greater reduction in the odds of CPR in the surgical patients. Conclusion In this large pediatric inpatient population, morphine administered via PCA device for surgical and nonsurgical pain was not associated with an increased risk of receiving CPR or MV, and was associated with slightly better safety outcomes than intravenous morphine.

The administration of epidural opioids, though effective for producing analgesia, has severe side effects in most patients. It is unknown whether clonidine can effectively replace opioids and cause fewer side effects. We compared, in this randomized trial, the incidence of vomiting and pruritus as well as the analgesic profile of three different combinations of bupivacaine, fentanyl, and clonidine administered epidurally in patients undergoing the Nuss procedure: bupivacaine + fentanyl, bupivacaine + clonidine, bupivacaine + fentanyl + clonidine. The incidence of side effects was significantly less in the bupivacaine + clonidine group (33%) compared with the bupivacaine + fentanyl (92%) and bupivacaine + fentanyl + clonidine (73%) groups (P = 0.004). Quality of postoperative analgesia was similar in the three groups. No significant complications were observed. In conclusion, clonidine is an effective and safe alternative to epidural opioids.

Recent advances in neurobiology and clinical medicine have established that the fetus and newborn may experience acute, established, and chronic pain. They respond to such noxious stimuli by a series of complex biochemical, physiologic, and behavioral alterations. Studies have concluded that controlling pain experience is beneficial with respect to short-term and perhaps long-term outcomes. Yet, pain-control measures are adopted infrequently because of unresolved scientific issues and lack of appreciation for the need for control of pain and its long-term sequelae during the critical phases of neurologic maturation in the preterm and term newborn. The neonatal pain-control group, as part of the Newborn Drug Development Initiative (NDDI) Workshop I, addressed these concerns. The specific issues addressed were (1) management of pain associated with invasive procedures, (2) provision of sedation and analgesia during mechanical ventilation, and (3) mitigation of pain and stress responses during and after surgery in the newborn infant. The cross-cutting themes addressed within each category included (1) clinical-trial designs, (2) drug prioritization, (3) ethical constraints, (4) gaps in our knowledge, and (5) future research needs. This article provides a summary of the discussions and deliberations. Full-length articles on procedural pain, sedation and analgesia for ventilated infants, perioperative pain, and study designs for neonatal pain research were published in Clinical Therapeutics (June 2005).

Objective: The purpose of this article is to summarize the clinical, methodologic, and ethical considerations for researchers interested in designing future trials in neonatal analgesia and anesthesia, hopefully stimulating additional research in this field.Methods: The MEDLINE, PubMed, EMBASE, and Cochrane register databases were searched using subject headings related to infant, newborn, neonate, analgesia, anesthesia, ethics, and study design. Cross-references and personal files were searched manually. Studies reporting original data or review articles related to these topics were assessed and critically evaluated by experts for each topical area. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were abstracted and synthesized in a systematic manner and refined by group members. Data synthesis and results were reviewed by a panel of independent experts and presented to a wider audience including clinicians, scientists, regulatory personnel, and industry representatives at the Newborn Drug Development Initiative workshop. Recommendations were revised after extensive discussions at the workshop and between committee members.Results: Designing clinical trials to investigate novel or currently available approaches for analgesia and anesthesia in neonates requires consideration of salient study designs and ethical issues. Conditions requiring treatment include pain/stress resulting from invasive procedures, surgical operations, inflammatory conditions, and routine neonatal intensive care. Study design considerations must define the inclusion and exclusion criteria, a rationale for stratification, the confounding effects of comorbid conditions, and other clinical factors. Significant ethical issues include the constraints of studying neonates, obtaining informed consent, making risk-benefit assessments, defining compensation or rewards for participation, safety considerations, the use of placebo controls, and the variability among institutional review boards in interpreting federal guidelines on human research. For optimal study design, investigators must formulate well-defined study questions, choose appropriate trial designs, estimate drug efficacy, calculate sample size, determine the duration of the studies, identify pharmacokinetic and pharmacodynamic parameters, and avoid drug-drug interactions. Specific outcome measures may include scoring on pain assessment scales, various biomarkers and their patterns of response, process outcomes (eg, length of stay, time to extubation), intermediate or long-term outcomes, and safety parameters.Conclusions: Much more research is needed in this field to formulate a scientifically sound, evidence-based, and clinically useful framework for management of anesthesia and analgesia in neonates. Newer study designs and additional ethical dilemmas may be defined with accumulating data in this field. Copyright (c) 2005 Excerpta Medica, Inc.

Background: Historically, the use of anesthetics and analgesics in neonates and infants has been based on extrapolations from studies performed in adults and older children. Over the past 20 years, there has been a growing body of research on the clinical pharmacology and clinical outcomes of these agents in neonates and infants. Objective: This article summarizes clinical pharmacology and clinical outcomes studies of opioids, opioid antagonists, sedative-hypnotics, nonsteroidal anti-inflammatory drugs and acetaminophen, and local anesthetics in neonates and infants to highlight gaps in the available knowledge, review some concerns about study design, and identify drugs that should receive high priority for future study. Methods: Relevant studies were identified through a search of MEDLINE and a review of textbooks, conference proceedings, and abstracts. The available literature was subjected to expert committee-based review. Conclusions: There is a growing body of information on analgesic and anesthetic pharmacokinetics, pharmacodynamics, and clinical outcomes in neonates and infants, permitting safe and effective use in some clinical settings. Major gaps in knowledge persist, however. Future research may involve a combination of clinical trials and preclinical studies in suitable infant animal surrogate models.

The author has reviewed recent developments in preoperative assessment and testing, emphasizing issues that are of greatest concern in pediatric patients. Attention to these areas during the process of preoperative preparation and appropriate communication of conditions that may contribute to increased peri-operative risk will provide greater predictability for families, surgeons, and operating room staff. This predictability is an important component to improved patient or family satisfaction and operating room efficiency.

The application of sedation/analgesia in paediatric patients is rapidly expanding as less invasive, non-operative techniques of diagnosis and treatment are applied to the paediatric population. Medical providers who are asked to provide sedation may include radiologists, paediatricians, nurses and emergency physicians, as well as anaesthesiologists and intensive care physicians. At the same time, the range of drugs used in these settings has expanded considerably. As there is no single drug fulfilling the criteria for the ideal sedative (rapid-onset, rapid recovery, no adverse effects, immobility appropriate to procedure being performed), multiple drugs may be used in combination. It is imperative that practitioners using drugs for sedation/analgesia in children be aware of the adverse effect profile(s) of these drugs, both individually and in combination. The purpose of this review is to describe the adverse effects of sedative and reversal agents currently used in paediatric sedation/analgesia.

Fetal IM injection of fentanyl is frequently performed during ex utero intrapartum therapy (EXIT procedure). We quantified the concentration of fentanyl in umbilical vein blood. Thirteen samples from 13 subjects were analyzed. Medians and ranges are reported as follows. Weight of the newborn at delivery was 3000 g (2020-3715 g). The dose of fentanyl was 60 μg (45-65 μg). The time between IM administration of fentanyl and collection of the sample was 37 minutes (5-86 minutes). Fentanyl was detected in all of the samples, with a median serum concentration of 14.0 ng/mL (4.3-64.0 ng/mL).

Although former preterm birth infants are at risk for postoperative apnea after surgery, it is unclear whether the same is true of full-term birth infants. We evaluated the incidence of apnea in 60 full-term neonates and infants undergoing pyloromyotomy both before and after anesthesia. All subjects were randomized to a remifentanil- or halothane-based anesthetic. Apnea was defined by the presence of prolonged apnea (>15 s) or frequent brief apnea, as observed on the pneumocardiogram. Apnea occurred before surgery in 27% of subjects and after surgery in 16% of subjects, with no significant difference between subjects randomized to remifentanil or halothane anesthesia. This apnea was primarily central in origin, occurred throughout the recording epochs, and was associated with severe desaturation in some instances. Of the subjects with normal preoperative pneumocardiograms, new onset postoperative apnea occurred in 3 (23%) of 13 subjects who received halothane-based anesthetics versus 0 (0%) of 22 subjects who received remifentanil-based anesthetics (P = 0.04). Thus, postoperative apnea can follow anesthesia in otherwise healthy full-term infants after pyloromyotomy and is occasionally severe with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.

Pyloric stenosis is sometimes associated with hemodynamic instability and postoperative apnea. In this multicenter study we examined the hemodynamic response and recovery profile of remifentanil and compared it with that of halothane in infants undergoing pyloromyotomy. After atropine, propofol, and succinylcholine administration and tracheal intubation, patients were randomized (2:1 ratio) to receive either remifentanil with nitrous oxide and oxygen or halothane with nitrous oxide and oxygen as the maintenance anesthetic. Pre- and postoperative pneumograms were done and evaluated by an observer blinded to the study. Intraoperative hemodynamic data and postanesthesia care unit (PACU) discharge times, PACU recovery scores, pain medications, and adverse events (vomiting, bradycardia, dysrhythmia, and hypoxemia) were recorded by the study's research nurse. There were no significant differences in patient age or weight between the two groups. There were no significant differences in hemodynamic values between the two groups at the various intraoperative stress points. The extubation times, PACU discharge times, pain medications, and adverse events were similar for both groups. No patient anesthetized with remifentanil who had a normal preoperative pneumogram had an abnormal postoperative pneumogram, whereas three patients with a normal preoperative pneumogram who were anesthetized with halothane had abnormal pneumograms after.The use of ultra-short-acting opioids may be an appropriate technique for infants less than 2 mo old when tracheal extubation after surgery is anticipated.

Recent developments in perioperative practice, emphasizing issues that are of greatest concern in pediatric patients, are reviewed in this article. Many areas bear further evaluation in the evolving field of perioperative medicine: Effective techniques of psychologic preparation for children and their parents in an era in which the family rarely encounters the hospital environment before the day of surgery Application of newer intraoperative anesthetics, such as new narcotics and muscle relaxants, to shorten PACU and pediatric ICU stay while maintaining safety and comfort Critical evaluation of current methods of pain management to optimize comfort, while minimizing cost of such management in an increasingly cost-conscious health care environment The recent advent of a process for credentialing pediatric anesthesia fellowship programs, which requires a research component, bodes well for the prospect of finding answers to some of these questions.

Accurate pain assessment in preterm and term neonates in the neonatal intensive care unit (NICU) is of vital importance because of the high prevalence of painful experiences in this population, including both daily procedural pain and postoperative pain. Over 40 tools have been developed to assess pain in neonates, and each NICU should choose a limited number of pain assessment tools for different populations and contexts. Only two pain assessment tools have a metric adjustment to account for differences of pain assessment in prematurity. Preterm neonates do not display behavior and physiologic indicators of pain as reliably and specifically as full term infants, and preterm infants are vulnerable to long term sequelae of painful experiences. "Brain-oriented" approaches for more objective measurement of pain in neonates may become available in the future. In the meantime, neonatal pain assessment tools need to be taught, implemented, and their ongoing use optimized to form a consistent, reproducible basis for the safe and effective treatment of neonatal pain.

a) To determine the need for intensive monitoring on the first operative night of surgery in children undergoing adenotonsillectomy for mild obstructive sleep apnea; b) to examine the effect of narcotics on postoperative obstructive sleep apnea.Randomized, prospective study.University hospital.Children, ranging in age between 1 and 18 yrs, presented to the Pediatric Otolaryngology Clinic for adenotonsillectomy for mild obstructive sleep apnea defined as from one to 15 obstructive apnea events per hour on preoperative polysomnogram.Patients were assigned to receive either a narcotic- or a halothane-based anesthetic for adenotonsillectomy. A postoperative polysomnogram was performed in the pediatric intensive care unit on the first operative night.Eighteen patients were recruited, 15 of whom met inclusion criteria: nine patients received a halothane-based anesthetic and six patients received a fentanyl-based anesthetic. When the data were analyzed by pooling both groups, the differences between pre- and postoperative sleep studies demonstrated a reduction in the number of obstructive events and less severe oxygen desaturations on the operative night. Total sleep time between the two sleep studies decreased from 371 +/- 13 to 304 +/- 14 mins. The number of obstructive apnea events/hr decreased as well. The lowest oxygen saturation measured during rapid eye movement sleep was 78 +/- 5% preoperatively and 92 +/- 1% postoperatively.Our data suggest that children without underlying medical conditions, neuromotor diseases, or carniofacial abnormalities, 1 to 18 yrs of age, who suffer from mild obstructive sleep apnea, have improvements documented by polysomnography on the night of surgery following adenotonsillectomy and do not necessarily need to be monitored intensively. These findings were not significantly affected by the choice of intraoperative anesthetic.

Background Understanding the clinical pharmacology of the antifibrinolytic epsilon-aminocaproic acid (EACA) is necessary for rational drug administration in children. The aim of this study is to determine the pharmacokinetics (PKs) of EACA in infants aged 6–24 months undergoing craniofacial reconstruction surgery. Methods Cohorts of six infants were enrolled sequentially to one of the three escalating loading dose–continuous i.v. infusion (CIVI) regimens: 25 mg kg−1, 10 mg kg−1 h−1; 50 mg kg−1, 20 mg kg−1 h−1; 100 mg kg−1, 40 mg kg−1 h−1. Plasma EACA concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry assay. A population non-linear mixed effects modelling approach was used to characterize EACA PKs. Results Population PK parameters of EACA were estimated using a two-compartment disposition model with weight expressed as an allometric covariate and an age effect. The typical patient in this study had an age of 38.71 weeks and a weight of 8.82 kg. PK parameters for this typical patient were: pre-/postoperative plasma drug clearance of 32 ml min−1 (3.6 ml kg−1 min−1), inter-compartmental clearance of 42.4 ml min−1 (4.8 ml min−1 kg−1), central volume of distribution of 1.27 litre (0.14 litre kg−1), and peripheral volume of distribution of 2.53 litre (0.29 litre kg−1). Intra-operative clearance and central volume of distribution were 89% and 80% of the pre-/postoperative value, respectively. Conclusions EACA clearance increased with weight and age. The dependence of clearance on body weight supports weight-based dosing. Based on this study, a loading dose of 100 mg kg−1 followed by a CIVI of 40 mg kg−1 h−1 is appropriate to maintain target plasma EACA concentrations in children aged 6–24 months undergoing these procedures.

Importance Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand. Objective To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood. Design, Setting, and Participants Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data. Exposures A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months. Main Outcomes and Measures The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior. Results Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = −0.2 (95% CI, −2.6 to 2.9); performance = 0.5 (95% CI, −2.7 to 3.7); and verbal = −0.5 (95% CI, −3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior. Conclusions and Relevance Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.