Effect of Remimazolam on Emergence Delirium in Children Undergoing Laparoscopic Surgery: A Double-Blinded Randomized Trial.

BACKGROUND: Preventing emergence delirium is a clinical goal for pediatric anesthesia, yet there is no consensus on its prevention. This study investigated the hypothesis that a continuous infusion or a single bolus of remimazolam can reduce the incidence of emergence delirium in children. METHODS: A hundred and twenty children aged 1-6 years old were randomly and equally allocated into three groups: group RC, which received a continuous infusion of remimazolam at 1 mg kg -1 h -1; group RB, which received a single bolus of remimazolam at 0.2 mg kg -1 at the beginning of wound closure; and group C, which received a continuous infusion of saline at 1 mL kg -1 h -1 and single bolus of saline at 0.2 mL kg -1 at the beginning of sutures. The primary outcome was the incidence of emergence delirium assessed by pediatric anesthesia emergence delirium (PAED) scale. Secondary outcomes included the number of rescues propofol administrations in the post-anesthesia care unit (PACU), recovery time, end-tidal sevoflurane concentration when maintaining BIS within the range of 40-60, and adverse events. RESULTS: The incidence of emergence delirium in group RC (5%, vs. group C, risk ratio, 0.14; 95% CI, 0.04 to 0.59; P=0.001) and group RB (7.7%, vs. group C, risk ratio, 0.22; 95% CI, 0.07 to 0.71; P=0.003) was significantly lower compared with group C (32.5%). Propofol was given to 2 patients in each of groups RC and RB to treat delirium and to 10 patients in group C (group RC vs. group C, risk ratio, 0.20; 95% CI, 0.05 to 0.86; P=0.012; group RB vs. group C, risk ratio, 0.21; 95% CI, 0.05 to 0.88; P=0.014). No differences in the recovery time and adverse effects were detected. CONCLUSIONS: Both continuous infusion and single bolus administration of remimazolam can effectively reduce the occurrence of emergence delirium in children.

Patient and Process Outcomes among Pediatric Patients Undergoing Appendectomy during the COVID-19 Pandemic: An International Retrospective Cohort Study.

BACKGROUND: COVID-19 forced healthcare systems to make unprecedented changes in clinical care processes. The authors hypothesized that the COVID-19 pandemic adversely impacted timely access to care, perioperative processes, and clinical outcomes for pediatric patients undergoing primary appendectomy. METHODS: A retrospective, international, multicenter study was conducted using matched cohorts within participating centers of the international PEdiatric Anesthesia COVID-19 Collaborative (PEACOC). Patients younger than 18 yr old were matched using age, American Society of Anesthesiologists Physical Status, and sex. The primary outcome was the difference in hospital length of stay of patients undergoing primary appendectomy during a 2-month period early in the COVID-19 pandemic (April to May 2020) compared with prepandemic (April to May 2019). Secondary outcomes included time to appendectomy and the incidence of complicated appendicitis. RESULTS: A total of 3,351 cases from 28 institutions were available with 1,684 cases in the prepandemic cohort matched to 1,618 in the pandemic cohort. Hospital length of stay was statistically significantly different between the two groups: 29 h (interquartile range: 18 to 79) in the pandemic cohort versus 28 h (interquartile range: 18 to 67) in the prepandemic cohort (adjusted coefficient, 1 [95% CI, 0.39 to 1.61]; P < 0.001), but this difference was small. Eight centers demonstrated a statistically significantly longer hospital length of stay in the pandemic period than in the prepandemic period, while 13 were shorter and 7 did not observe a statistically significant difference. During the pandemic period, there was a greater occurrence of complicated appendicitis, prepandemic 313 (18.6%) versus pandemic 389 (24.1%), an absolute difference of 5.5% (adjusted odds ratio, 1.32 [95% CI, 1.1 to 1.59]; P = 0.003). Preoperative SARS-CoV-2 testing was associated with significantly longer time-to-appendectomy, 720 min (interquartile range: 430 to 1,112) with testing versus 414 min (interquartile range: 231 to 770) without testing, adjusted coefficient, 306 min (95% CI, 241 to 371; P < 0.001), and longer hospital length of stay, 31 h (interquartile range: 20 to 83) with testing versus 24 h (interquartile range: 14 to 68) without testing, adjusted coefficient, 7.0 (95% CI, 2.7 to 11.3; P = 0.002). CONCLUSIONS: For children undergoing appendectomy, the COVID-19 pandemic did not significantly impact hospital length of stay.

Optimal Positioning of Nasopharyngeal Temperature Probes in Infants and Children: A Prospective Cohort Study.

BACKGROUND: The nasopharynx is an easily accessible core-temperature monitoring site, but insufficient or excessive nasopharyngeal probe insertion can underestimate core temperature. Our goal was to estimate optimal nasopharyngeal probe insertion depth as a function of age. METHODS: We enrolled 157 pediatric patients who had noncardiac surgery with endotracheal intubation in 5 groups: (1) newborn to 6 months old, (2) infants 7 months to 1 year old, (3) children 13 to 23 months old, (4) children 2 to 5 years old, and (5) children 6 to 12 years old. A reference esophageal temperature probe was inserted at an appropriate depth based on each patient's height. A nasopharyngeal temperature probe was inserted from the naris at 10 cm in newborn and infants, 15 cm in children aged 1 to 5 years old, and 20 cm in children who were 6 years or older. The study nasopharyngeal probes were withdrawn 1, 2.5, or 2 cm (depending on age) 10 times at 5-minute intervals. Optimal probe insertion distances were defined by limits of agreement (LOAs) between nasopharyngeal and esophageal temperatures <0.5 °C. RESULTS: Optimal nasopharyngeal temperature probe position ranged from 6 to 10 cm in infants up to 6 months old, 7 to 8 cm in infants 7 to 12 months old, 7.5 to 12 cm in children 13 to 23 months old, and 10 to 12 cm in children aged 6 years and older. The 95% LOAs were <0.5 °C for all age categories except the 2- to 5-year-old group where the limits extended from -0.67 °C to 0.52 °C at 9 cm. At the optimal position within each age range, the bias (average nasopharyngeal-to-esophageal temperature difference) was ≤0.1 °C. CONCLUSIONS: Nasopharyngeal thermometers accurately measure core temperature, but only when probes are inserted a proper distance, which varies with age. As with much in pediatrics, nasopharyngeal thermometer insertion depths should be age appropriate.

Continued challenges in pediatric anesthesia during COVID-19 in 2022: An international survey from the pediatric anesthesia COVID-19 collaborative.

INTRODUCTION: This international survey explored the ongoing impact of COVID-19 on pediatric anesthesiology. It assessed COVID-19's impact on the practice of pediatric anesthesiology, staffing, job satisfaction, and retention at the beginning of 2022 and addressed what should be done to ameliorate COVID-19's impact and what initiatives hospitals had implemented. METHODS: This survey focused on five major domains: equipment/medication, vaccination/testing, staffing, burnout, and economic repercussions. Pilot testing for questionnaire clarity was conducted by members of the Pediatric Anesthesia COVID-19 Collaborative. The survey was administered by e-mail to a representative of the 72 collaborative centers. Respondents were instructed to answer based on their institution's practice from February through April of 2022. Descriptive statistics with 95% confidence intervals are reported. RESULTS: Seventy of seventy-two institutions participated in this survey (97% response rate). Fifty-nine (84%) were from the United States, and 11 (16%) included other countries. The majority experienced equipment (68%) and medication (60%) shortages. Many institutions reported staffing shortages in nursing (37%), perioperative staff (27%), and attending anesthesiologists (11%). Sixty-two institutions (89%) indicated burnout was a frequent topic of conversation among pediatric anesthesiologists. Forty-three institutions (61%) reported anesthesiologists leaving current practice and 37 (53%) early retirement. Twenty-eight institutions (40%) canceled elective cases. The major suggestions for improving job retention included improving financial compensation (76%), decreasing clinical time (67%), and increasing flexibility in scheduled clinical time (66%). Only a minority of institutions had implemented the following initiatives: improving financial compensation (19%), increased access to mental health/counseling services (30%), and assistance with child or elder care (7%). At the time of the survey, 34% of institutions had not made any changes. CONCLUSION: Our study found that COVID-19 has continued to impact pediatric anesthesiology. There are major discrepancies between what anesthesiologists believe are important for job satisfaction and faculty retention compared to implemented initiatives. Data from this survey provide insight for institutions and departments for addressing these challenges.

Perioperative outcomes and management in midface advancement surgery: a multicenter observational descriptive study from the Pediatric Craniofacial Collaborative Group.

BACKGROUND/AIMS: The evolution of Le Fort III and Monobloc procedures with utilization of distraction devices has resulted in shortened surgical times, greater facial advancements, and decreased transfusion requirements. The aim of this observational study was to utilize data from the multicenter Pediatric Craniofacial Surgery Perioperative Registry to present and compare patient characteristics and outcomes in children undergoing midface advancement with distraction osteogenesis. METHODS: We queried the Pediatric Craniofacial Surgery Perioperative Registry for children undergoing midface advancement involving distractor application from June 2012 to September 2016. Data extracted included demographics, perioperative management, complications, fluid and transfusion volumes, and length of stay. The extracted patient characteristics and perioperative variables were summarized and compared. RESULTS: The query yielded 72 cases from 11 institutions: 49 children undergoing Le Fort III and 23 undergoing Monobloc procedures. Monobloc patients were younger, weighed less, and more likely to have tracheostomies along with elevated intracranial pressure. Greater transfusion was observed in the Monobloc group for nearly all of the transfusion outcomes evaluated. Median ICU and hospital length of stay were 2 and 3 days longer, respectively, in the Monobloc group. Perioperative complications were not uncommon, occurring in 18% of patients in the Le Fort III group and 30% in the Monobloc group. CONCLUSION: Monobloc procedures were associated with greater transfusion and longer ICU and hospital length of stay. Perioperative complications were more prevalent in the Monobloc group.

Causes for Pauses During Simulated Pediatric Cardiac Arrest.

OBJECTIVES: Pauses in cardiopulmonary resuscitation negatively impact clinical outcomes; however, little is known about the contributing factors. The objective of this study is to determine the frequency, duration, and causes for pauses during cardiac arrest. DESIGN: This is a secondary analysis of video data collected from a prospective multicenter trial. Twenty-six simulated pediatric cardiac arrest scenarios each lasting 12 minutes in duration were analyzed by two independent reviewers to document events surrounding each pause in chest compressions. SETTING: Ten children's hospitals across Canada, the United, and the United Kingdom. SUBJECTS: Resuscitation teams composed of three healthcare providers trained in cardiopulmonary resuscitation. INTERVENTIONS: A simulated pediatric cardiac arrest case in a 5 year old. MEASUREMENTS AND MAIN RESULTS: The frequency, duration, and associated factors for each pause were recorded. Communication was rated using a four-point scale reflecting the team's shared mental model. Two hundred fifty-six pauses were reviewed with a median of 10 pauses per scenario (interquartile range, 7-12). Median pause duration was 5 seconds (interquartile range, 2-9 s), with 91% chest compression fraction per scenario (interquartile range, 88-94%). Only one task occurred during most pauses (66%). The most common tasks were a change of chest compressors (25%), performing pulse check (24%), and performing rhythm check (15%). Forty-nine (19%) of the pauses lasted greater than 10 seconds and were associated with shock delivery (p < 0.001), performing rhythm check (p < 0.001), and performing pulse check (p < 0.001). When a shared mental model was rated high, pauses were significantly shorter (mean difference, 4.2 s; 95% CI, 1.6-6.8 s; p = 0.002). CONCLUSIONS: Pauses in cardiopulmonary resuscitation occurred frequently during simulated pediatric cardiac arrest, with variable duration and underlying causes. A large percentage of pauses were greater than 10 seconds and occurred more frequently than the recommended 2-minute interval. Future efforts should focus on improving team coordination to minimize pause frequency and duration.

Workload of Team Leaders and Team Members During a Simulated Sepsis Scenario.

OBJECTIVES: Crisis resource management principles dictate appropriate distribution of mental and/or physical workload so as not to overwhelm any one team member. Workload during pediatric emergencies is not well studied. The National Aeronautics and Space Administration-Task Load Index is a multidimensional tool designed to assess workload validated in multiple settings. Low workload is defined as less than 40, moderate 40-60, and greater than 60 signify high workloads. Our hypothesis is that workload among both team leaders and team members is moderate to high during a simulated pediatric sepsis scenario and that team leaders would have a higher workload than team members. DESIGN: Multicenter observational study. SETTING: Nine pediatric simulation centers (five United States, three Canada, and one United Kingdom). PATIENTS: Team leaders and team members during a 12-minute pediatric sepsis scenario. INTERVENTIONS: National Aeronautics and Space Administration-Task Load Index. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-seven teams were recruited from nine sites. One hundred twenty-seven team leaders and 253 team members completed the National Aeronautics and Space Administration-Task Load Index. Team leader had significantly higher overall workload than team member (51 ± 11 vs 44 ± 13; p < 0.01). Team leader had higher workloads in all subcategories except in performance where the values were equal and in physical demand where team members were higher than team leaders (29 ± 22 vs 18 ± 16; p < 0.01). The highest category for each group was mental 73 ± 13 for team leader and 60 ± 20 for team member. For team leader, two categories, mental (73 ± 17) and effort (66 ± 16), were high workload, most domains for team member were moderate workload levels. CONCLUSIONS: Team leader and team member are under moderate workloads during a pediatric sepsis scenario with team leader under high workloads (> 60) in the mental demand and effort subscales. Team leader average significantly higher workloads. Consideration of decreasing team leader responsibilities may improve team workload distribution.

The important role of simulation in sedation.

PURPOSE OF REVIEW: This article reviews the development of simulation-based training strategies to educate sedation providers. RECENT FINDINGS: Medical simulation has been utilized to train and evaluate providers in numerous domains related to sedation. Sedation providers come to the patient with a wide range of clinical training and experience and simulation can serve as a platform for achieving a baseline skill level and for periodic retraining. Although widely accepted by participants in simulation training, data demonstrating simulation's efficacy in improving sedation-related clinical outcomes are lacking. SUMMARY: Simulation provides an opportunity for sedation providers to develop deliberative practice, to consider rare or challenging clinical conditions, and to benefit from directed feedback, in a manner that does not put patients in harm's way.

Added benefit of raxibacumab to antibiotic treatment of inhalational anthrax.

Although antibiotics treat bacteremia in inhalational anthrax, pathogenesis is mainly driven by bacterial exotoxins. Raxibacumab, an IgG1 monoclonal antibody, binds the protective antigen (PA) of Bacillus anthracis, thus blocking toxin effects and leading to improved survival in the rabbit and monkey models of inhalational anthrax. To assess raxibacumab's added benefit over levofloxacin (LVX) alone, rabbits surviving to 84 h after a challenge with 200 times the median (50%) lethal dose of B. anthracis spores were randomized to receive 3 daily intragastric LVX doses of 50 mg/kg of body weight, with the first LVX dose administered just prior to administration of a single intravenous dose of placebo or 40 mg/kg raxibacumab. The percentages of animals alive at 28 days following the last LVX dose were compared between the 2 treatment groups using a two-sided likelihood-ratio chi-square test. The 82% survival rate for the LVX-raxibacumab combination was higher than the 65% survival rate for LVX alone (P=0.0874). There were nearly 2-fold fewer deaths for the combination (7 deaths; n=39) than for LVX alone (13 deaths; n=37), and the survival time was prolonged for the combination (P=0.1016). Toxin-neutralizing-activity titers were similar for both treatment groups, suggesting that survivors in both groups were able to mount a toxin-neutralizing immune response. Microscopic findings considered consistent with anthrax were present in animals that died or became moribund on study in both treatment groups, and there were no anthrax-related findings in animals that survived. Overall, raxibacumab provided a meaningful benefit over antibiotic alone when administered late in the disease course.

New Insight into Microbial Iron Oxidation as Revealed by the Proteomic Profile of an Obligate Iron-Oxidizing Chemolithoautotroph.

Microaerophilic, neutrophilic, iron-oxidizing bacteria (FeOB) grow via the oxidation of reduced Fe(II) at or near neutral pH, in the presence of oxygen, making them relevant in numerous environments with elevated Fe(II) concentrations. However, the biochemical mechanisms for Fe(II) oxidation by these neutrophilic FeOB are unknown, and genetic markers for this process are unavailable. In the ocean, microaerophilic microorganisms in the genus Mariprofundus of the class Zetaproteobacteria are the only organisms known to chemolithoautotrophically oxidize Fe and concurrently biomineralize it in the form of twisted stalks of iron oxyhydroxides. The aim of this study was to identify highly expressed proteins associated with the electron transport chain of microaerophilic, neutrophilic FeOB. To this end, Mariprofundus ferrooxydans PV-1 was cultivated, and its proteins were extracted, assayed for redox activity, and analyzed via liquid chromatography-tandem mass spectrometry for identification of peptides. The results indicate that a cytochrome c4, cbb3-type cytochrome oxidase subunits, and an outer membrane cytochrome c were among the most highly expressed proteins and suggest an involvement in the process of aerobic, neutrophilic bacterial Fe oxidation. Proteins associated with alternative complex III, phosphate transport, carbon fixation, and biofilm formation were abundant, consistent with the lifestyle of Mariprofundus.

Emergent robot-to-open conversion - Multidisciplinary simulation training in crisis management.

Anticipating and addressing unexpected intraoperative events and anatomies are some of the most challenging aspects of pediatric urologic practice; uncontrolled hemorrhage is one of the most anxiety provoking and precarious. The increasing application of the robotic platform in pediatric urology adds another layer of complexity as surgeons are not immediately at the patient's bedside. Should hemorrhage occur in robotic cases, clear communication and seamless coordination between members of the operating room team are paramount to optimize patient safety and minimize errors. This is especially important in pediatric cases for which the margin of error is narrow. Non-technical skills, including leadership, decision-making, situational awareness, stress management, and team-communication, become increasingly critical. While many programs have focused on robotic training, few prepare the operating room team and surgical trainees to manage these unforeseen, emergent intraoperative scenarios. This review discusses the role of a multidisciplinary, in situ robot-to-open conversion simulation program in addressing this educational gap, ways to approach establishing these programs, and potential barriers.

Corrigendum: Tracheal intubation in patients with Pierre Robin sequence: development, application, and clinical value based on a 3-dimensional printed simulator.

[This corrects the article DOI: 10.3389/fphys.2023.1292523.].

Comparison of Deep and Moderate Neuromuscular Blockade for Major Laparoscopic Surgery in Children: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Neuromuscular blocking agents are routinely used in laparoscopic surgery to optimize operative conditions. We compared the effect of a deep and moderate neuromuscular blockade (NMB) on surgical conditions and postoperative outcomes in children undergoing major laparoscopic surgery. METHODS: Sixty children aged 2-14 years scheduled to undergo major laparoscopic surgery were randomly allocated to deep (post-tetanic count 1-2 twitches) or moderate (train-of-four 1-2 twitches) NMB groups. The anesthesia was maintained with propofol and remifentanil, and the NMB was maintained with a rocuronium continuous infusion. At the end of the operation, the NMB were antagonized with sugammadex. The intra-abdominal pressure, airway pressure, Leiden Surgical Rating Scale, intraoperative hemodynamics, drug usages, duration of surgery, postoperative recovery time, pain, and complications were compared between the groups. RESULTS: The maximum and mean intra-abdominal pressure, the peak inspiratory pressure, and mean airway pressure were significantly lower in the deep NMB group than in the moderate NMB group (p < 0.001). The Leiden Surgical Rating Scale and the dosage of rocuronium were significantly higher in the deep NMB group than the moderate NMB group (p < 0.001). The intraoperative hemodynamics, duration of surgery, post-operative recovery time, pain, and the incidence rate of complications were not significantly different between the groups (p > 0.05). CONCLUSIONS: A deep NMB provided better operative conditions and similar recovery profiles compared with a moderate NMB as reversed with sugammadex in children undergoing major laparoscopic surgery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR2100053821.

The effect of remimazolam-based total intravenous anesthesia versus sevoflurane-based inhalation anesthesia on emergence delirium in children undergoing tonsillectomy and adenoidectomy: study protocol for a prospective randomized controlled trial.

Background: Remimazolam, a new ultrashort-acting benzodiazepine, is becoming increasingly applied in general anesthesia. This study is designed to investigate the effect of remimazolam-based total intravenous anesthesia and sevoflurane-based inhalation anesthesia on emergence delirium in pediatric tonsillectomy and adenoidectomy. Methods and analysis: This is a monocentric, prospective, randomized, double-blind clinical trial. A total of 90 pediatric patients will be randomized to receive remimazolam-based total intravenous anesthesia (remimazolam group, n = 45) or sevoflurane-based inhalation anesthesia (sevoflurane group, n = 45). The primary outcome will be the incidence of emergence delirium, which will be evaluated using the Pediatric Anesthesia Emergence Delirium (PAED) scale. The secondary outcomes include the extubation time, recovery time, behavior change using the post-hospitalization behavior questionnaire for ambulatory surgery (PHBQ-AS), and adverse events. Ethics and dissemination: This study has been approved by the Institutional Review Board (IRB) of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (2023-K-262-02). Clinical trial registration: ClinicalTrials.gov, identifier NCT06214117.

Comparison of postoperative analgesia and side effects in pediatric laparoscopic surgery with morphine and nalbuphine.

There is currently no consensus on the optimal perioperative pain management strategy involving specific opioids. This study aims to compare the postoperative analgesia, the associated side effects between nalbuphine and morphine in children undergoing laparoscopic surgery. One hundred ninety children were randomly assigned to nalbuphine (0.2 mg/kg) or morphine (0.2 mg/kg). Nalbuphine's analgesic effect was non-inferior to morphine, with similar total rescue analgesic consumption during PACU stay (0.03 ± 0.05mg vs. 0.04 ± 0.06 mg, p > 0.05). Nalbuphine group had a lower incidence of respiratory depression (RR ≤ 10/min) (4.8% vs. 38.6%, p < 0.001), PONV (2.4% vs. 18.1%, p = 0.002), and pruritus (0% vs. 16.9%, p < 0.001) than morphine. Additionally, nalbuphine showed a shorter laryngeal mask airway removal time (13.9 [12.7, 15.1]) compared with morphine (17.0 [15.1, 18.9], p = 0.011). Nalbuphine provides equipotent analgesia with significantly lower incidences of respiratory depression, PONV, and pruritus compared with morphine in pediatric laparoscopic surgery.

Tracheal intubation in patients with Pierre Robin sequence: development, application, and clinical value based on a 3-dimensional printed simulator.

Background: The main clinical manifestations of patients with Pierre Robin sequence (PRS) include micrognathia, the glossoptosis and dyspnoea. The difficulty of tracheal intubation (TI) in such patients is increased. Objective: The purpose of the study was to evaluate the reliability and efficacy of the PRS simulator. Methods: A PRS simulator was developed by using 3-dimensional (3D) printing technology under computer-aided design. A total of 12 anaesthesiologists each trained 5 times for TI on the PRS Training Simulator-1 and recorded the simulation time. After the training, they were randomly divided into three groups with a total of 12 nontrained anaesthesiologists, and the simulation was completed on PRS Simulator-2, 3 and 4. The simulation time was recorded, and the performance was evaluated by three chief anaesthesiologists. Then, all 24 anaesthesiologists completed the questionnaire. Results: A PRS simulator developed by 3D printing was used to simulate the important aspects of TI. The average number of years worked was 6.3 ± 3.1 years, and 66.7% were female. The time for the 12 anaesthesiologists to complete the training gradually decreased (p < 0.01). Compared with the trained anaesthesiologists, the simulation time of TI in the nontrained anaesthesiologists was much longer (all p < 0.01). In addition, the simulation performance of the trained anaesthesiologists was relatively better (all p < 0.01). Conclusion: The reliability and efficacy of the PRS simulator is herein preliminarily validated, and it has potential to become a teaching and training tool for anaesthesiologists.

Management of the Normal and Difficult Pediatric Airway: Unique Challenges in the Time of COVID-19.

Purpose of Review: This review focuses on the challenges faced by acute care healthcare workers in the management of the normal and difficult pediatric airway during the COVID-19 pandemic and how these protocols and practices evolved during the pandemic. The current state of knowledge on timing of surgery and anesthesia is also discussed. Recent Findings: In the early days of the pandemic, information about the SARS-CoV-2 virus and disease process was scarce. Governmental, healthcare, and professional organizations created several guidelines to protect invaluable healthcare workers from the contagious virus while also delivering appropriate care to children with COVID-19. With the emergence of new studies and the deployment of new life-saving COVID-19 vaccines and other therapies, these guidelines evolved. The use of aerosol containment devices such as aerosol boxes and flexible barrier techniques was found to be ineffective in reliably containing virus particles while posing potential harm to both healthcare workers and patients. Also, the definition of aerosol-generating and dispersing medical procedures was vastly broadened. To date, use of appropriate personal protection equipment and COVID-19 vaccination are the most effective ways to protect healthcare workers and safely manage children infected with SARS-CoV-2 who require airway intervention. Summary: Evidence-based public health measures and appropriate personal protective equipment remain the best way to protect both healthcare workers and patients. As the virus and population evolve and COVID-19 vaccines become more widely available, clinicians must be willing to adapt to the emerging evidence of their impact on how safe pediatric perioperative care is delivered.

A Multi-Center Evaluation of the Pharmacokinetics and Safety of Intravenous Ibuprofen in Infants 1-6 Months of Age.

BACKGROUND: Enteral ibuprofen was first approved as a prescription drug in 1974 for the US market. An intravenous (IV) ibuprofen formulation is approved for use in children older than 6 months of age, but there are limited studies specifically evaluating the pharmacokinetics and safety in children 1-6 months of age. AIMS: The primary purpose of this study was to evaluate the pharmacokinetics of IV ibuprofen in infants younger than 6 months of age. The secondary objective was to evaluate the safety of single and repeated doses of IV ibuprofen in infants younger than 6 months of age. METHODS: This was an industry-sponsored multi-center study. Institutional Review Board approval and informed parental consent were obtained prior to enrollment. Hospitalized neonates and infants younger than 6 months of age with fever or expected postoperative pain were eligible. Enrolled patients received 10 mg/kg of IV ibuprofen every 6 h, with up to four doses per day. Patients were randomized to two sparse sampling technique pharmacokinetic sample time groups. Group 1 samples were drawn at 0, 30 min, and 2 h, while group 2 samples were drawn at 0 min, 1, and 4 h after administration. RESULTS: A total of 24 children were enrolled in the study, with 15 male patients and 9 female patients. The median age of the cohort was 4.4 months (range 1.1-5.9 months), and the median weight was 5.9 kg (range 2.3-8.8 kg). The arithmetic mean and standard error for peak plasma ibuprofen concentration was 56.28 ± 2.77 µg/mL. Plasma levels declined rapidly with a mean elimination half-life of 1.30 h. Time to peak ibuprofen effect and concentration were similar when compared with older pediatric patients. Clearance and volume of distribution were also similar to those reported in older pediatric patients. No drug-related adverse events were reported. CONCLUSIONS: The pharmacokinetic and short-term safety profiles of IV ibuprofen in pediatric patients 1-6 months of age are comparable to those in children older than 6 months of age. TRIAL REGISTRATION: Clinicaltrials.gov Trial Registration number and date: NCT02583399-Registered July 2017.

Raxibacumab for the treatment of inhalational anthrax.

BACKGROUND: Inhalational anthrax caused by Bacillus anthracis is associated with high mortality primarily due to toxin-mediated injury. Raxibacumab is a human IgG1lambda monoclonal antibody directed against protective antigen, a component of the anthrax toxin. METHODS: We evaluated the efficacy of raxibacumab as a prophylactic agent and after disease onset in a total of four randomized, placebo-controlled studies conducted in rabbits and monkeys. Animals were exposed to an aerosolized target exposure of B. anthracis spores that was approximately 100 times (in the prophylactic studies) and 200 times (in the therapeutic-intervention studies) the median lethal dose. In the therapeutic-intervention studies, animals were monitored for the onset of symptoms. Animals with detectable protective antigen in serum, a significant increase in temperature, or both received a single intravenous bolus of placebo or raxibacumab at a dose of either 20 mg per kilogram of body weight or 40 mg per kilogram. The primary end point was survival at day 14 (in rabbits) or at day 28 (in monkeys). Safety studies were conducted with intravenous raxibacumab (40 mg per kilogram) in 333 healthy human volunteers. RESULTS: In both rabbits and monkeys, the time to detection of protective antigen correlated with the time to bacteremia (r=0.9, P<0.001). In the therapeutic-intervention studies, the survival rate was significantly higher among rabbits that received raxibacumab at a dose of 40 mg per kilogram (44% [8 of 18]) than among rabbits that received placebo (0% [0 of 18]; P=0.003). Raxibacumab treatment also significantly increased survival in monkeys (64% [9 of 14], vs. 0% [0 of 12] with placebo; P<0.001). In human subjects, intravenous raxibacumab at a dose of 40 mg per kilogram had a half-life of 20 to 22 days and provided a maximum concentration of the drug in excess of levels that are protective in animals. Concentrations of raxibacumab provide a surrogate end point that should be predictive of clinical benefit. CONCLUSIONS: A single dose of raxibacumab improved survival in rabbits and monkeys with symptomatic inhalational anthrax. (ClinicalTrials.gov number, NCT00639678.)