Sedation Research in Critically Ill Pediatric Patients: Proposals for Future Study Design From the Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research IV Workshop.

OBJECTIVES: Sedation and analgesia for infants and children requiring mechanical ventilation in the PICU is uniquely challenging due to the wide spectrum of ages, developmental stages, and pathophysiological processes encountered. Studies evaluating the safety and efficacy of sedative and analgesic management in pediatric patients have used heterogeneous methodologies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research (SCEPTER) IV hosted a series of multidisciplinary meetings to establish consensus statements for future clinical study design and implementation as a guide for investigators studying PICU sedation and analgesia. DESIGN: Twenty-five key elements framed as consensus statements were developed in five domains: study design, enrollment, protocol, outcomes and measurement instruments, and future directions. SETTING: A virtual meeting was held on March 2-3, 2022, followed by an in-person meeting in Washington, DC, on June 15-16, 2022. Subsequent iterative online meetings were held to achieve consensus. SUBJECTS: Fifty-one multidisciplinary, international participants from academia, industry, the U.S. Food and Drug Administration, and family members of PICU patients attended the virtual and in-person meetings. Participants were invited based on their background and experience. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Common themes throughout the SCEPTER IV consensus statements included using coordinated multidisciplinary and interprofessional teams to ensure culturally appropriate study design and diverse patient enrollment, obtaining input from PICU survivors and their families, engaging community members, and using developmentally appropriate and validated instruments for assessments of sedation, pain, iatrogenic withdrawal, and ICU delirium. CONCLUSIONS: These SCEPTER IV consensus statements are comprehensive and may assist investigators in the design, enrollment, implementation, and dissemination of studies involving sedation and analgesia of PICU patients requiring mechanical ventilation. Implementation may strengthen the rigor and reproducibility of research studies on PICU sedation and analgesia and facilitate the synthesis of evidence across studies to improve the safety and quality of care for PICU patients.

Evolution of the American College of Surgeons Children's Surgery Verification Program: Implications for optimizing multidisciplinary surgical care of the pediatric patient.

The Children's Surgery Verification Program of the American College of Surgeons began in 2016 based on the standards created by the Task Force for Children's Surgery. This program seeks to improve the surgical care of children by assuring the appropriate resources and robust performance improvement programs at participating centers. Three levels of centers with defined scopes of practice and matching resources are defined. Since its inception more than 50 center have been verified. A specialty hospital program was launched in 2019. The standards for all hospitals were revised in 2021 based on lessons learned. In this article the leaders of the program discuss the development, areas of greatest impact and future directions of the program.

Preventing Home Medication Administration Errors.

Medication administration errors that take place in the home are common, especially when liquid preparations are used and complex medication schedules with multiple medications are involved; children with chronic conditions are disproportionately affected. Parents and other caregivers with low health literacy and/or limited English proficiency are at higher risk for making errors in administering medications to children in their care. Recommended strategies to reduce home medication errors relate to provider prescribing practices; health literacy-informed verbal counseling strategies (eg, teachback and showback) and written patient education materials (eg, pictographic information) for patients and/or caregivers across settings (inpatient, outpatient, emergency care, pharmacy); dosing-tool provision for liquid medication measurement; review of medication lists with patients and/or caregivers (medication reconciliation) that includes prescription and over-the-counter medications, as well as vitamins and supplements; leveraging the medical home; engaging adolescents and their adult caregivers; training of providers; safe disposal of medications; regulations related to medication dosing tools, labeling, packaging, and informational materials; use of electronic health records and other technologies; and research to identify novel ways to support safe home medication administration.

Educational Perspectives: Anesthesia 101: What the Neonatologist Needs to Know About Anesthesiology.

As the complexity of medicine increases, so too do the challenges with multidisciplinary communication and coordinated patient care. Anesthesiology represents a field for which there is no required study for medical students, pediatric residents, or neonatal-perinatal medicine fellows in the United States, so a neonatologist may have never received any formal training in anesthesiology (and vice versa for pediatric anesthesiologists in neonatology). In this review, we address frequently asked questions of neonatologists to anesthesiologists to better frame common issues. These topics include thermal regulation, fluid management, airway management, and the field of regional anesthesiology. Finally, collaborative efforts between the surgical and medical fields, such as the American College of Surgeons Children's Surgery Verification Quality Improvement Program, and the American Academy of Pediatrics NICU Verification Program, are ongoing and robust; these programs represent important opportunities to significantly improve the perioperative care of infants. Our hope is that this summary can serve as a primer and reference for those caring for neonatal patients during any perioperative period, including seasoned neonatologists and those early in their training. It is our further desire that this review will lead to improved communication and collegiality between the specialties.

Population Pharmacokinetics of Intraperitoneal Bupivacaine Using Manual Bolus Atomization Versus Micropump Nebulization and Morphine Requirements in Young Children.

BACKGROUND: Intraperitoneal (IP) administration of local anesthetics is used in adults and children for postoperative analgesia after laparoscopic surgery. Population pharmacokinetics (PK) of IP bupivacaine has not been determined in children. Objectives of this study were (1) to develop a population PK model to compare IP bupivacaine administered via manual bolus atomization and micropump nebulization and (2) to assess postoperative morphine requirements after intraoperative administration. We hypothesized similar PK profiles and morphine requirements for both delivery methods. METHODS: This was a prospective, sequential, observational study. After institutional review board (IRB) approval and written informed parental consent, 67 children 6 months to 6 years of age undergoing robot-assisted laparoscopic urological surgery received IP bupivacaine at the beginning of surgery. Children received a total dose of 1.25 mg/kg bupivacaine, either diluted in 30-mL normal saline via manual bolus atomization over 30 seconds or undiluted bupivacaine 0.5% via micropump nebulization into carbon dioxide (CO2) insufflation tubing over 10-17.4 minutes. Venous blood samples were obtained at 4 time points between 1 and 120 minutes intraoperatively. Samples were analyzed by liquid chromatography with mass spectrometry. PK parameters were calculated using noncompartmental and compartmental analyses. Nonlinear regression modeling was used to estimate PK parameters (primary outcomes) and Mann-Whitney U test for morphine requirements (secondary outcomes). RESULTS: Patient characteristics between the 2 delivery methods were comparable. No clinical signs of neurotoxicity or cardiotoxicity were observed. The range of peak plasma concentrations was 0.39-2.44 µg/mL for the manual bolus atomization versus 0.25-1.07 µg/mL for the micropump nebulization. IP bupivacaine PK was described by a 1-compartment model for both delivery methods. Bupivacaine administration by micropump nebulization resulted in a significantly lower Highest Plasma Drug Concentration (Cmax) and shorter time to reach Cmax (Tmax) (P < .001) compared to manual bolus atomization. Lower plasma concentrations with less interpatient variability were observed and predicted by the PK model for the micropump nebulization (P < .001). Adjusting for age, weight, and sex as covariates, Cmax and area under the curve (AUC) were significantly lower with micropump nebulization (P < .001). Regardless of the delivery method, morphine requirements were low at all time points. There were no differences in cumulative postoperative intravenous/oral morphine requirements between manual bolus atomization and micropump nebulization (0.14 vs 0.17 mg/kg; P = .85) measured up to 24 hours postoperatively. CONCLUSIONS: IP bupivacaine administration by micropump nebulization demonstrated lower plasma concentrations, less interpatient variability, low risk of toxicity, and similar clinical efficacy compared to manual bolus atomization. This is the first population PK study of IP bupivacaine in children, motivating future randomized controlled trials to determine efficacy.

Anesthesia Exposure in Children: Practitioners Respond to the 2016 FDA Drug Safety Communication.

In December 2016, the US Food and Drug Administration (FDA) issued a drug safety warning stating that 11 commonly used anesthetic and sedative medications had potential neurotoxic effects when used in children under the age of 3 years and in pregnant women during the third trimester. A panel presentation at the sixth biennial Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) symposium addressed the FDA announcement in a session entitled "Anesthesia Exposure in Children During Surgical and Non-Surgical Procedures: How Do We Respond to the 2016 FDA Drug Safety Communication?" Panelists included representatives from pediatric anesthesiology, obstetrics, pediatric surgery, and several pediatric surgical subspecialties. Each panelist was asked to address the following questions: How has the FDA labelling change affected your clinical practice including patient discussions, timing, and frequency of procedures? Has your professional society provided any guidelines for this discussion? Has there been any discussion of this topic at your national meetings? The panelists provided important perspectives specific to each specialty, which generated a lively discussion and a detailed response from the Deputy Director of the Division of Anesthesia and Addiction of the FDA describing the FDA procedures that led to this drug safety warning.

Neurotoxicity of Anesthesia in Children: Prevention and Treatment.

PURPOSE OF REVIEW: The purpose of this review is to summarize the current evidence regarding the impact of the exposure to anesthetic and sedative agents on neurodevelopment during the period of rapid brain growth in the first 3 years of life. Though much of the definitive data demonstrating anesthesia-induced neurotoxicity has come from studies in young animals, the focus of this review is on emerging human data. RECENT FINDINGS: In 2016, the first prospective trials investigating the neurodevelopmental impact of early anesthetic exposure (GAS and PANDA studies) were published, both showing no significant impact on IQ from a single brief anesthetic. More recent population cohort analyses have shown varying, but minimal, impacts from early anesthetic exposure on academic performance and IQ, much smaller than that of maternal education and other environmental factors. Animal and human data document that post-anesthetic neurotoxicity is a genuine phenomenon, but its long-term clinical significance is uncertain. Most experts would agree that a single, brief anesthetic likely has no significant impact on neurodevelopment, but it is yet to be determined whether longer exposures or multiple anesthetics are associated with subsequent learning issues. Future research is aimed at determining the mechanisms of neuronal injury from exposure to anesthetic and sedative agents, adjunctive medications that may prevent or ameliorate this injury, and therapeutic approaches such as early intervention that can enhance recovery. While these studies are underway, it is recommended that exposure to anesthetic and sedative agents be minimized in young children and consideration be given to alternative methods of immobilization for nonpainful procedures such as radiologic imaging.

American College of Surgeons Children's Surgery Verification Quality Improvement Program: What Anesthesiologists Need to Know Now.

A task force of pediatric surgical specialists with the support of The American College of Surgeons recently launched a verification program for pediatric surgery, the Children's Surgery Verification quality improvement program, with the goal of improving pediatric surgical, procedural, and perioperative care. Included in this program are specific standards for the delivery of pediatric anesthesia care across a variety of practice settings. We review the background, available evidence, requirements for verification, and verification process and its implications for the practice of pediatric anesthesia across the country. In addition, we have included a special roundtable interview of 3 recently Children's Surgery Verification-verified program directors to provide an up-to-date real-world perspective of this children's surgery quality improvement program.

Hyperkalemia After Laparoscopic Nephrectomy in Patients With Renal Insufficiency: A Case Report.

Laparoscopic surgery is an evolving surgical modality in children, which has been applied to increasingly more complex surgeries and patients, including patients with renal insufficiency. These patients are particularly susceptible to the challenges that laparoscopy imposes on their altered physiology, leading to marked electrolyte disturbances, including metabolic acidosis and hyperkalemia. Hyperkalemia has the potential for marked impairment of cardiac conduction. We report 2 cases where significant, potentially lethal hyperkalemia developed during laparoscopic nephrectomy in adolescents with renal insufficiency. Awareness of this issue, as well as adequate preparation and intraoperative monitoring are essential to preventing this life-threatening complication.

Anaesthetic considerations for surgery in newborns.

Almost 30 years ago, the American Academy of Pediatrics Committee on Fetus and Newborn coauthored a policy statement strongly advocating for the use of anaesthesia in all neonates stating 'local or systemic pharmacologic agents now available permit relatively safe administration of anesthesia or analgesia to neonates undergoing surgical procedures and that such administration is indicated according to the usual guidelines for the administration of anesthesia to high-risk, potentially unstable patients'. With current techniques and advanced monitoring, preterm and full-term infants routinely undergo surgical procedures under general anaesthesia to repair congenital defects that were lethal in years past. Recent research in immature animal models, however, has shown evidence of enhanced neuroapoptosis and other signs of neurotoxicity with all of the currently used anaesthetic agents. There is also increasing concern about the potential adverse effects of perioperative hypotension and hypocapnia on neurocognitive development in infants. This review outlines the most recent animal and human evidence regarding the effects of general anaesthesia and anaesthetic-related haemodynamic changes on the developing brain of newborns.

The American College of Surgeons Children's Surgery Verification and Quality Improvement Program: implications for anesthesiologists.

PURPOSE OF REVIEW: The Task Force for Children's Surgical Care, an ad-hoc multidisciplinary group of invited leaders in pediatric perioperative medicine, was assembled in May 2012 to consider approaches to optimize delivery of children's surgical care in today's competitive national healthcare environment. Over the subsequent 3 years, with support from the American College of Surgeons (ACS) and Children's Hospital Association (CHA), the group established principles regarding perioperative resource standards, quality improvement and safety processes, data collection, and verification that were used to develop an ACS-sponsored Children's Surgery Verification and Quality Improvement Program (ACS CSV). RECENT FINDINGS: The voluntary ACS CSV was officially launched in January 2017 and more than 125 pediatric surgical programs have expressed interest in verification. ACS CSV-verified programs have specific requirements for pediatric anesthesia leadership, resources, and the availability of pediatric anesthesiologists or anesthesiologists with pediatric expertise to care for infants and young children. SUMMARY: The present review outlines the history of the ACS CSV, key elements of the program, and the standards specific to pediatric anesthesiology. As with the pediatric trauma programs initiated more than 40 years ago, this program has the potential to significantly improve surgical care for infants and children in the United States and Canada.

Fifty years of the American Academy of Pediatrics Section on Anesthesiology: a history of our specialty.

The American Academy of Pediatrics Section on Anesthesiology and Pain Medicine celebrated its 50th Anniversary in 2015. The Section was one of the first and only subspecialty organizations in anesthesiology at the time. This special article will focus on the contributions of the Section to the practice of pediatric anesthesiology in the areas of advocacy, education and member contributions. In 1986, the Section created the Robert M. Smith Award to honor those members who had made significant advances in the practice of pediatric anesthesiology. It is named after one of the Section founders, an influential educator, inventor, and researcher in our field. We will focus the latter part of the article on the Robert M. Smith award winners to illustrate the contributions of the Section and its members to the development of the field of pediatric anesthesiology.

Optimal Timing of Surgical Procedures in Pediatric Patients.

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.

Institutional Policy Changes to Prevent Cardiac Toxicity Associated With Bupivacaine Penile Blockade in Infants.

Dorsal penile nerve block is a widely used method of analgesia for infants undergoing penile surgery. Because of its potency, extended duration of action, and lack of vasoconstriction, bupivacaine remains the most commonly used local anesthetic. Rapid systemic absorption of bupivacaine, however, has been associated with profound central nervous system and cardiovascular side effects, including cardiac arrest. As determined by retrospective medical record analysis, the incidence of complications associated with dorsal penile blockade in our institution was 0.075%. This was significantly higher than previously reported prompting a change in institutional policy that has eliminated penile block complications.

Robotic surgery and anesthesia for pediatric urologic procedures.

PURPOSE OF REVIEW: Minimally invasive approaches to pediatric surgery have become increasingly popular over the last 15 years. With the advent of robotically controlled instruments, common pediatric urologic surgeries such as pyeloplasty and ureteral reimplantation, which were previously technically challenging, are now commonly performed laparoscopically. It is important to recognize the unique physiologic considerations with this approach and how to provide safe and effective anesthesia for these procedures. RECENT FINDINGS: Although there are multiple studies in the surgical literature describing robot-assisted laparoscopic approaches for pediatric urologic surgery, there are few articles that describe the anesthetic considerations for this type of surgery in children. As the first pediatric hospital in the USA to obtain a surgical robot in 2001, a consistent, collaborative approach has been developed to care for infants and children undergoing robot-assisted laparoscopic surgery. SUMMARY: Robot-assisted laparoscopic surgery is increasingly utilized for common pediatric urologic surgeries. To provide safe and effective anesthesia for this type of surgery, it is important to have a thorough understanding of the multiple physiologic derangements that occur with robot-assisted laparoscopic surgery in infants and children, the potential complications that can occur with this approach and have a consistent approach to the anesthetic management and postoperative pain control for these procedures.

Critical Elements for the Pediatric Perioperative Anesthesia Environment.

The American Academy of Pediatrics proposes guidance for the pediatric perioperative anesthesia environment. Essential components are identified to optimize the perioperative environment for the anesthetic care of infants and children. Such an environment promotes the safety and well-being of infants and children by reducing the risk of adverse events.

Development, implementation, and initial participant feedback of a pediatric sedation provider course.

BACKGROUND: No standardized educational curriculum exists for pediatric sedation practitioners. We sought to describe the curriculum and implementation of a pediatric sedation provider course and assess learner satisfaction with the course curriculum. DESCRIPTION: The course content was determined by formulating a needs assessment using published sedation guidelines, reports of sedation related adverse events, and a survey of sedation practitioners. Students provided feedback regarding satisfaction with the course immediately following the course and 6 months later. EVALUATION: The course consisted of 5 didactic lectures, 1 small-group session, 6 simulation scenarios, a course syllabus, and a written examination. The course was conducted over 1 day at 3 different locations. Sixty-nine students completed the course and were uniformly satisfied with the course curriculum. CONCLUSIONS: A standardized pediatric sedation provider course was developed for sedation practitioners and consisted of a series of lectures and simulation scenarios. Overall satisfaction with the course was positive.