Adverse Events In Pediatric Patients Research Articles

Thromboelastography-guided Intraoperative Platelet Transfusion in Pediatric Heart Surgery

BackgroundPostoperative bleeding is associated with significant resource use and is an important contributor to other major adverse events in pediatric patients undergoing complex cardiac surgical procedures. Thromboelastography (TEG; TEG 6S, Haemonetics) can guide perioperative blood product transfusions to reduce the risk of postoperative bleeding. This study validated the use of a previously developed TEG 6S maximum amplitude (TEG-MA)–based platelet transfusion calculator used during cardiac surgical procedures to minimize the risk of postoperative bleeding. MethodsIn this single-center retrospective study of pediatric patients (aged ≤18 years) who underwent cardiac surgical procedures requiring cardiopulmonary bypass at Boston Children’s Hospital (Boston, MA) (N = 1000), the volume of platelet transfusion administered at surgical team discretion was compared with the platelet calculator–recommended platelet transfusion volume by using linear regression analysis. Associations between the adequacy of perioperative platelet transfusion and postoperative bleeding or thrombotic complications within the first 24 hours postoperatively (bleeding) and until hospital discharge (thrombosis) were evaluated by logistic regression analysis. ResultsLower TEG-MA (≤45 mm) measurements after transfusion were associated with a higher risk for postoperative bleeding (odds ratio, 4.4; 95% CI, 2.6-7.4; P < .01 [significant P value <.05]). The platelet transfusion calculator–recommended platelet transfusion volume (on the basis of TEG-MA measured at the time of rewarming) demonstrated moderate correlation with the measured TEG-MA value after platelet transfusion (Pearson r = 0.7). Intraoperative volumes of platelet transfusion that failed to increase a postoperative TEG-MA of at least 45 mm significantly increased the risk for postoperative bleeding in the first 24 hours after surgical procedures (odds ratio, 3.2; 95% CI, 1.9-5.4; P < .01 [significant P value <.05]). The posttransfusion TEG-MA was not independently associated with thrombosis. ConclusionsCustomizing perioperative platelet transfusion therapy by using quantitative diagnostic tests can help reduce postoperative bleeding complications.

Impact of varied anesthesia maintenance strategies on postoperative respiratory complications in pediatric patients undergoing tonsillectomy and adenoidectomy (AmPRAEC study): study protocol for a multicenter randomized, double-blind clinical trial

BackgroundPostoperative respiratory adverse events are the most common perioperative complications in pediatric anesthesia, particularly prevalent in children undergoing tonsillectomy and adenoidectomy, with an incidence rate as high as 50%. The choice of anesthetic induction regimen directly influences the incidence of respiratory adverse events during the induction period. However, this effect seems to have minimal impact on postoperative outcomes. The occurrence rate of postoperative respiratory adverse events is likely more closely associated with the anesthetic maintenance phase, yet this relationship remains uncertain at present.MethodsThe objective of this study was to assess the impact of different anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients undergoing tonsillectomy and adenoidectomy. The AmPRAEC study is a multicenter, randomized, double-blind controlled trial. A total of 717 pediatric patients were recruited from 12 medical centers and randomly assigned to three groups: group A (intravenous maintenance group, receiving propofol infusion); group B (intravenous-inhalational combination group, maintained with 1% sevoflurane combined with propofol); and group C (inhalational maintenance group, maintained with 2–3% sevoflurane inhalation). The primary outcome measure was the incidence rate of postoperative respiratory adverse events.DiscussionThis clinical trial aims to elucidate the impact of various anesthetic maintenance regimens on postoperative respiratory adverse events in pediatric patients. The outcomes of this study are anticipated to facilitate anesthesiologists in devising more comprehensive perioperative management strategies, enhancing comfort, and improving the clinical outcomes for this patient population.Trial registrationChinese Clinical Trial Registry (http://www.chictr.org.cn) ChiCTR2300074803. Registered on August 16, 2023.

ERCP-Related adverse events in pediatric patients: a 10-years single-site review.

This retrospective analysis aimed to assess the feasibility and safety of endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients by examining ERCP-related adverse events (AEs) occurring over a decade at a single center. Pediatric patients under 18years old who underwent ERCP at the Second Hospital of Hebei Medical University from 1/2013 to 11/2023 were included. ERCP-related AEs were defined according to ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Clinical data of patients experiencing ERCP-related AEs were obtained from electronic medical records for analysis. Over the past decade, a total of 76 pediatric patients underwent 113 ERCP procedures, including 26 patients who underwent repeat ERCP, totaling 63 procedures. There were 32 males and 44 females, with a median age of 13years (range 3years and 5months-17years and 9months). Among all ERCP procedures, 14 (12.4%) were diagnostic and 99 (87.6%) were therapeutic, with a 100% success rate. 16 cases (14.2%) of ERCP-related AEs, all post-ERCP pancreatitis (PEP), were observed, while no other AEs defined by ESGE such as bleeding, perforation, cholangitis, cholecystitis, or sedation-related events were noted. Additionally, 23 cases (20.4%) of ERCP-related AEs not included in the ESGE definition were observed, including post-ERCP abdominal pain in 20 cases (17.7%), post-ERCP nausea and vomiting in 2 cases (1.8%), and unplanned reoperation in 1 case (0.9%). In the 26 cases of pediatric patients who underwent repeat ERCP, we observed that AEs occurred in 15 cases (57.7%) during their initial ERCP, which was much higher than the overall average level. Post-ERCP abdominal pain and PEP are the most common ERCP-related AEs in pediatric patients, while severe AEs such as bleeding and perforation are rare. The incidence of AEs after initial ERCP in pediatric patients who received repeat ERCP is higher than the overall average level. Based on our center's experience, we believe that ERCP can be safely performed in children over 3years old with biliary and pancreatic diseases and obtain reliable clinical benefits. However, active monitoring and management of ERCP-related AEs are essential to improve the clinical outcomes of pediatric ERCP.

The Use of Narco SS Score in Predicting Adverse Events in Children Undergoing Major Elective Abdominal Surgery at The University Teaching Hospital, Lusaka, Zambia.

The neurological, airway, respiratory, cardiovascular and other, with a subscore of surgical severity (NARCO-SS) is a scoring system which assesses the presence of systemic disease and the risk the operation poses to the patient. A number of patients that undergo major abdominal surgery suffer adverse events. The aim of the study was to determine the reliability of NARCO-SS in predicting peri-operative adverse events and to determine the risk factors for peri-operative adverse events in paediatric patients undergoing elective abdominal surgery. Prospective cohort study. Consecutively sampled patients from December 2019 to December 2020 were used. Patients scheduled for elective abdominal surgery were scored pre-operatively and end points were; when an adverse event occurred or up to day 30. Analysis of the reliability of the tool, bivariate and multivariate logistics regression was done. One hundred and nineteen patients were enrolled and 49% of them had adverse events. Both bivariate and multivariate analyses showed no significant association between the NARCO-SS score and the occurrence of adverse events. The area under the receiver operating characteristics curve (area under the curve) of the NARCO-SS for adverse events was 0.518; there was a significant correlation between high scores and mortality. Longer duration of surgery and complex surgery were the risk factors for adverse events. The NARCO-SS score was found to be a poor predictor of adverse events with a fair inter-rater reliability as a scoring tool. Future research could evaluate a modification of neurological and airway categories.

Long term follow-up of patients with patent ductus arteriosus after transcatheter closure.

To investigate the concurrent, long-term, and future adverse events and assess the trend of adverse events in pediatric patients with patent ductus arteriosus (PDA) after transcatheter closure. A total of 1590 patients underwent transcatheter PDA closure were enrolled, including 465 patients (median age = 22 months) in the training group and 1125 patients in the validation group. Logistic regression analysis was used to assess independent risk factors associated with concurrent adverse events after closure. The chi-square test was used to evaluate the 5-year follow-up trend. Multivariable logistic regression analysis indicated that low age, female, and high pulmonary end diameter were independent risk factors for concurrent adverse events after closure. For patients without concurrent adverse events and for those who with concurrent adverse events but return to normal, the Chi-square test showed no abnormal results at the 5-year follow-up. Furthermore, the follow-up data of the validation group were not significantly different from those of the training group. The value of long-term follow-up of children may be limited for those who did not have a concurrent adverse event after closure nor for those who had a concurrent adverse event after closure but returned to normal during the 5-year follow-up period. Follow-up monitoring of adverse events tended to be recommended in pediatric patients with PDA after transcatheter closure. However, follow-up in these pediatric patients is expensive and there is a risk of sedation for echocardiography examination frequently. ·Patients who had no concurrent adverse events after closure did not show any abnormality at 5-year follow-up. ·Most of the patients who had concurrent adverse events after closure returned to normal at 5-year follow-up. The value of long-term follow-up may be limited for the above patients after transcatheter PDA closure.

The Effects of Intraoperative Methadone on Postoperative Pain Control in Pediatric Patients: A Scoping Review.

Inadequate perioperative pain control has deleterious effects on children's development and can lead to heightened pain experiences and the avoidance of future medical procedures. Reports of perioperative use of methadone in children are increasing, as it has a favorable pharmacodynamic profile; however, the effectiveness of methadone in reducing postoperative pain has not been established. We, therefore, aimed to provide a scoping review of the literature comparing the effect of intraoperative methadone versus other opioids on postoperative opioid consumption, pain scores, and adverse events in pediatric patients. We identified studies in PubMed, Scopus, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to January 2023. Postoperative opioid consumption, pain scores, and adverse events were extracted for analysis. We screened 1864 studies, of which 83 studies were selected for full-text review. Five studies were included in the final analysis. Postoperative opioid consumption was decreased overall in children who received methadone compared to those who did not. The majority of studies indicated that methadone was superior to other opioids in reported pain scores, while the frequency of adverse events was similar between the groups. Although the data reviewed highlight a potential benefit of intraoperative methadone in pediatric patients, 4 of the 5 studies had serious methodological concerns. Thus, we cannot make strong recommendations for the regular use of methadone in the perioperative setting at this time. Our results highlight the need for large, well-designed randomized trials to fully evaluate the safety and efficacy of intraoperative methadone in diverse pediatric surgical populations.

OR1-3 | A Multicenter Predictive Model for Clinically Meaningful Adverse Events in Pediatric Patients Undergoing Transcatheter Pulmonary Vein Interventions

OR1-3 | A Multicenter Predictive Model for Clinically Meaningful Adverse Events in Pediatric Patients Undergoing Transcatheter Pulmonary Vein Interventions

Consensus recommendations on management of selumetinib-associated adverse events in pediatric patients with neurofibromatosis type 1 and plexiform neurofibromas.

Selumetinib is the first approved treatment for pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN) in the EU and US, as well as in multiple other countries. Evidence for the management of selumetinib-associated adverse events (AEs) is mostly limited to clinical trials and expanded-access programs. We gathered a panel of European healthcare practitioners with clinical experience prescribing selumetinib and/or managing pediatric patients with NF1-PN to provide recommendations on the prevention and management of AEs. A modified Delphi approach was used to develop the recommendations among the group of experts. Initial statements were developed from a literature review of current management recommendations and regulatory reports. The panel refined the statements and rated the extent to which they agreed with them in 2 sessions and a follow-up survey. The panel comprised 2 pediatric neuro-oncologists, 1 pediatric oncologist, 1 pediatrician, 1 neuropediatrician, 1 oncologist, 1 neurologist, 2 psychologists, and 1 dermatologist. The experts agreed on the relative frequency and impact of AEs potentially associated with selumetinib. Consensus-level agreement was reached for 36 statements regarding the prevention and management of AEs potentially associated with selumetinib. Experts recommended treatments for AEs based on their experience. The development of a variety of consensus statements indicates expert agreement on best practices for the prevention and management of AEs potentially associated with selumetinib in pediatric patients with NF1-PN. These events are generally manageable and should be considered alongside treatment benefit. Information sharing is warranted as further experience is gained.

Modeling the Relationship Between Diastolic Phenotype and Outcomes in Pediatric Hypertrophic Cardiomyopathy

Pediatric hypertrophic cardiomyopathy (HCM) is associated with adverse events. The contribution of diastolic dysfunction to adverse events is poorly understood. The aim of this study was to explore the association between diastolic phenotype and outcomes in pediatric patients with HCM. Children <18years of age with diagnosed with HCM were included. Diastolic function parameters were measured from the first echocardiogram at the time of diagnosis, including Doppler flow velocities, tissue Doppler velocities, and left atrial volume and function. Using principal-component analysis, key features in echocardiographic parameters were identified. The principal components were regressed to freedom from major adverse cardiac events (MACE), defined as implantable cardioverter-defibrillator insertion, myectomy, aborted sudden cardiac death, transplantation, need for mechanical circulatory support, and death. Variables that estimate left ventricular filling pressures were highly collinear and associated with MACE (hazard ratio, 0.86; 95% CI, 0.75-1.00), though this was no longer significant after controlling for left ventricular thickness and genetic variation. Left atrial size parameters adjusted for body surface area were independently associated with outcomes in the covariate-adjusted model (hazard ratio, 0.69; 95% CI, 0.5-0.94). The covariate-adjusted model had an Akaike information criterion of 213, an adjusted R2 value of 0.78, and a concordance index of 0.82 for association with MACE. Echocardiographic parameters of diastolic dysfunction were associated with MACE in this population study, in combination with the severity of left ventricular hypertrophy and genetic variation. Left atrial size parameters adjusted for body surface area were independently associated with adverse events. Additional study of diastolic function parameters adjusted for patient size could facilitate the prediction of adverse events in pediatric patients with HCM.

Identifying risk factors of anti-TNF induced skin lesions and other adverse events in paediatric patients with inflammatory bowel disease.

While higher infliximab (IFX) trough concentrations (TCs) are associated with better outcomes in patients with inflammatory bowel disease (IBD), they could pose a risk for adverse events (AEs), including IFX-induced skin lesions. Therefore, we studied correlations between IFX TCs and occurrence of AEs in paediatric IBD patients. In this single-centre study, all children with Crohn's disease (CD) and ulcerative colitis (UC) receiving IFX maintenance therapy who underwent proactive drug monitoring between March 2015 and August 2022 were included. IFX doses/intervals/TCs and patient characteristics were systematically registered, as well as AEs and skin lesions appearance. A total of 109 patients (72 CD and 37 UC) contributed 2913 IFX TCs. During a median follow-up of 3.0 [1.5-4.5] years, we observed 684 AEs in 101 patients and 49 skin lesions in 35 patients. There was no significant difference (p = .467) in median TCs between patients with and without skin lesions. However, higher median IFX doses were associated with an increased hazard rate of skin lesions [HR 1.084 (1.024-1.148), p = .005], in addition to female sex [2.210 (1.187-5.310), p = .016] and diagnosis of CD [1.695 (1.241-1.877), p = .011]. Considering IFX therapeutic TC cut-offs of 5.0 and 9.0 µg/mL, there was no significant difference in AE rate (p = .749 and p = .833, respectively). Also, no significant association between IFX doses and AE rate (p = .159). Increasing the IFX dose to achieve therapeutic TCs may not increase the overall risk of AEs in paediatric IBD patients. However, concerns arise regarding the risk of skin lesions, especially in female CD patients.

Analysis of Allergic Transfusion Reactions at a Children's Tertiary Care Center

Background: Transfusion reaction adverse events are a relatively rare occurrence in the United States. This is due to specific blood safety measures such as appropriate collection, preparation, testing, storage, and distribution of blood components as well as appropriate monitoring of patients receiving these transfusions. Several years of data have been collected by our institution's blood bank. Through our analysis, we have been able to describe the rate of transfusion- associated adverse events in pediatric patients at Children's Hospital of Michigan from 2018-2022. Objectives: The aim of this retrospective chart review was to assess the rate of allergic blood transfusion complications and reactions among pediatric patients at Children's Hospital of Michigan in Detroit, Michigan. Materials and Methods: An institution-based retrospective chart review was conducted for a total of 43,210 transfusions over a span of five years from 2018-2022. Results: There were a total of 43,210 transfusions. A total of 26,669 of these products were red blood cell (RBC) transfusions, 10,447 were platelets, 4,392 were plasma, and 1,702 were cryoprecipitate (combined plasma and cryoprecipitate was 6,094). A reported reaction was encountered in 176 of the 43,210 transfusions. These reported reactions were part of the patients' underlying diseases. A true acute transfusion reaction (ATR) was encountered in 116 of the 43,210 transfusions. Of the 116 transfusions, 66 (56.9%) were classified as allergic reactions. About 61% of those reactions were skin manifestations (urticaria, itching), 9% were respiratory symptoms (dyspnea, tachypnea), and the remaining 30% were both skin and respiratory symptoms. Of the total amount of RBC transfusions, 35 (0.131%) resulted in an allergic reaction. Similarly, 19 (0.182%) platelet and 12 (0.197%) plasma transfusions resulted in ATRs. ATRs were most associated with plasma, followed by platelets and RBC transfusions. Combining all transfusions received, these represented a total of 66 (0.153%) allergic transfusion reactions. These results are demonstrated in Figure 1. Conclusion: ATRs were observed in 0.268% of total transfusions (allergic reactions (0.153%) and other reactions (0.115%)) that occurred over the course of five years at our institution. This is about 1 in 655 blood components transfused that was associated with an allergic reaction (more commonly with plasma &amp;gt; platelets &amp;gt; packed RBCs). The rate of allergic reactions is less than what was reported by National Blood Collection and Utilization Survey 2017 (0.282%). This rate is also less than what is reported for children (0.53%) and adults (0.26%) in a meta-analysis (Wang Y, Sun W, Wang X, et al. Comparison of transfusion reactions in children and adults: A systematic review and meta-analysis. Pediatr Blood Cancer. 2022;69(9):e29842.). These lower rates could be secondary to changes in blood processing and under-reporting.

The impact of pediatric intensivists on the management of pediatric diabetic ketoacidosis in pediatric intensive care units

IntroductionThe impact of pediatric intensivists on managing pediatric patients with diabetic ketoacidosis (DKA) remains unknown. This study aimed to evaluate the impact of pediatric intensivists on outcomes in pediatric intensive care units (PICUs).MethodsThis was a two-institution retrospective study of patients with DKA admitted to the PICU between 2012 and 2023. Pediatric patients (< 19 years of age) were included if they met the moderate to severe DKA criteria on PICU admission. The patients were subsequently divided into two groups based on the presence or absence of a pediatric intensivist. The primary outcome was the PICU length of stay (LOS). Secondary outcomes were adverse events during DKA treatment, hospital LOS, and mortality.ResultsFifty-two patients admitted to the PICU with a median age of 13.00 years (range, 0–18 years) were included; 32 (61.54%) were female. Patients managed by pediatric intensivists had significantly shorter PICU LOS (2.52 vs. 3.69 days, p < 0.05). Also, adverse events during DKA treatment were significantly decreased in the high-intensity group compared to the low-intensity group (12.50% vs. 50.00%, p < 0.05).ConclusionsHigh-intensity ICU staffing was associated with shorter PICU LOS and lower adverse events in pediatric patients with DKA. Our results suggest that dedicated pediatric intensivists can improve outcomes of critically ill pediatric patients with DKA.

Association between preoperative respiratory symptoms and perioperative respiratory adverse events in pediatric patients with positive viral testing

Study objectiveTo determine the association between the presence of upper respiratory tract viral infection symptoms and occurrence of perioperative respiratory adverse events (PRAE) in children with positive viral screening, and to analyze the risk of PRAE in children with SARS-CoV-2 compared to non-SARS-CoV-2 infection. DesignA prospective cohort study. SettingA tertiary, freestanding pediatric hospital in Dallas, Texas. PatientsChildren <18 years of age with positive respiratory viral testing who underwent general anesthesia. InterventionMeasurement of incidence of PRAE and severe adverse events during the first 7 postoperative days. MeasurementsThe primary outcome was a composite of PRAE: oxygen saturation < 90% for >5 min, supplemental oxygen for >2 h after anesthesia, laryngospasm, and bronchospasm. The secondary outcome was severe adverse events: high flow nasal cannula >6 l of oxygen per minute, admission to the ICU for escalation of respiratory support post-anesthetic, acute respiratory distress syndrome, postoperative pneumonia, cardiovascular arrest, extracorporeal life support, and death. Main resultsIn this convenience sample of 196 children, 83 were symptomatic and 113 were asymptomatic. The risk of PRAE was similar in children with active viral symptoms and asymptomatic children (risk difference: −1.9%; 95% CI: −10.9, 7.9%), but higher among children with documented fever within 48 h of the anesthetic (risk difference: 20.8%; 95% CI: 5.3, 39.7%). The multivariable adjusted odds ratio of PRAE was 0.68 (95% CI: 0.25, 1.85) for symptomatic compared to asymptomatic patients, and 0.46 (95% CI: 0.14, 1.44) for patients with SARS-CoV-2 compared to non-SARS-CoV-2 infection. ConclusionsThere was no significant difference in the incidence of PRAE between symptomatic and asymptomatic children with laboratory confirmed viral respiratory infection, and between children with the Omicron variant of SARS-CoV-2 compared to non-SARS-CoV-2 respiratory viruses. However, the risk was increased in children with recent fever.

A Predictive Model of Major Postoperative Respiratory Adverse Events in Pediatric Patients Undergoing Rigid Bronchoscopy for Exploration and Foreign Body Removal.

Background: No nomogram has been established to predict the incidence of major postoperative respiratory adverse events (mPRAEs) in children undergoing rigid bronchoscopy for airway foreign bodies (AFB) removal and exploration of the airway, though some studies have confirmed the risk factors. Methods: 1214 pediatric patients (≤3 years old) undergoing rigid bronchoscopy for AFB from June 2014 to December 2020 were enrolled in this study. The primary outcome was the occurrence of mPRAEs, including laryngospasm and bronchospasm. Following that, a nomogram prediction model for the mPRAEs was developed. Results: The incidence of mPRAEs was 84 (6.9%) among 1214 subjects. American Society of Anesthesiologists physical status (ASA-PS), intraoperative desaturation (SpO2 < 90%), procedural duration and ventilatory approach were all independent risk factors of mPRAEs. The area under the receiver operating characteristic curve (AUC) value of the nomogram for predicting mPRAEs was 0.815 (95% CI: 0.770-0.861), and the average AUC for ten-fold cross-validation was 0.799. These nomograms were well calibrated by Hosmer-Lemshow (p = 0.607). Decision curve analysis showed that the nomogram prediction model is effective in clinical settings. Conclusions: Combining ASA-PS, intraoperative desaturation, procedural duration, and ventilatory approach, the nomogram model is adequate for predicting the risk of developing mPRAEs, followed by rigid bronchoscopy for AFB removal and exploration.

Henoch-Schönlein purpura in a 6-year-old boy after initial COVID-19 vaccination

The COVID-19 pandemic has significantly impacted global health, and the widespread immunization of adults against SARS-CoV-2 has played a pivotal role in altering the course of the disease. While COVID-19 vaccine adverse events are generally uncommon and mild, the recent vaccination of the pediatric population has emphasized the need for vigilance and reporting of potential side effects. In this case report, we present a 6-year-old boy who developed Henoch-Schönlein purpura following the administration of the first dose of Pfizer-BioNTech BNT16B2b2 mRNA COVID-19 vaccine, making it the earliest reported case of such an adverse event. Our report highlights the importance of continued monitoring and reporting of adverse events in pediatric patients receiving the COVID-19 vaccine, as well as the need for prompt diagnosis and management of potential vaccine-related complications.

TRLS-07. GLOBAL POST-MARKETING SURVEILLANCE DATA FROM PEDIATRIC AND ADULT PATIENTS WITH CENTRAL NERVOUS SYSTEM MALIGNANCIES TREATED WITH TUMOR TREATING FIELDS (TTFIELDS) THERAPY BETWEEN 2011–2022

Abstract BACKGROUND TTFields are electric fields that exert physical forces to disrupt cellular processes critical for cancer cell viability and tumor progression. TTFields therapy is approved for adults with recurrent (r) and newly diagnosed (nd) glioblastoma (GBM), based on the phase 3 EF-11 (TTFields 200 kHz) and EF-14 studies (TTFields therapy 200 kHz + temozolomide), respectively, which showed clinical benefit without increase in systemic adverse events (AEs). Pediatric patients were not included in the EF-11 and EF-14 studies. Here, we present pediatric safety data from an updated global post-marketing surveillance (PMS) analysis of patients with brain tumors treated with TTFields therapy, over an 11-year timeframe. METHODS Unsolicited PMS data from patients with brain tumors who received TTFields therapy from October 2011-March 2022 in North America, Europe, Middle East, Africa, and Japan were included. AEs were categorized using MedDRA version 25.1. RESULTS Overall, 25,898 patients were included. Diagnoses were ndGBM (68%), rGBM (26%), anaplastic astrocytoma/oligodendroglioma (4%) and other (2%). Two-thirds of patients were male. The analysis included 93 (0.4%) pediatric/adolescent patients (&amp;lt;18 years). In pediatric patients, 62% experienced ≥1 AE, with 53% related to TTFields therapy; these values were comparable with the overall population (73% and 56%, respectively). The most common treatment-related AEs in pediatric patients were: skin reaction (39%), heat sensation (14%), and headache (12%); and in the overall population were: skin reaction (43%), electric sensation (14%), and heat sensation (12%). CONCLUSIONS This long-term, global, real-world data analysis, including pediatric patients with brain tumors, demonstrates a tolerable safety profile of TTFields therapy, consistent with pivotal clinical studies. There were no major differences in AEs between pediatric and adult patients and no new safety signals identified in the pediatric population. Consistent with the overall dataset, most AEs in pediatric patients were localized mild–moderate skin events, which are typically easily managed.

Effect of Tulobuterol Patch Versus Placebo on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomies: A Randomized Controlled Trial.

Perioperative respiratory adverse events are common in children. We aimed to evaluate the effect of the transdermal β-2 agonist, tulobuterol, compared with that of placebo on the incidence of perioperative respiratory adverse events in pediatric patients undergoing tonsillectomy. In this triple-blinded (patient, anesthesia provider, and outcome assessor) randomized controlled trial, 188 patients were randomly allocated to receive tulobuterol or a placebo. The tulobuterol groups received a tulobuterol patch (1 mg) masked with a bandage, whereas the placebo only received the bandage. The assigned bandage was applied to the patients 8 to 10 hours before the surgery. The primary outcome was the occurrence of any perioperative respiratory adverse events: oxygen desaturation <95%, airway obstruction, laryngospasm, bronchospasm, severe coughing, or stridor. The outcomes were evaluated using the average relative effect test, which estimates the effect of individual components of a composite outcome and then averages effects across components. A total of 88 and 94 patients who received tulobuterol and placebo, respectively, were analyzed. The incidence of any perioperative respiratory adverse event was lower with tulobuterol (n = 13/88; 14.7%) than that with the placebo (n = 40/94; 42.5%), with an estimated average relative risk (95% confidence interval) across components of 0.35 (0.20-0.60; P < .001). The symptoms of airway obstruction were lower with tulobuterol (n = 8/88; 9.0%) than that with the placebo (n = 32/94; 34.0%), with relative risk (95% CI) of 0.31 (0.17-0.56; P < .001). The occurrence of severe coughing was lower with tulobuterol (n = 1/88; 1.1%) than that with the placebo (n = 8/94; 8.5%), with relative risk (95% CI) of 0.15 (0.03-0.68; P = .014). In preschool children undergoing tonsillectomy, the preoperative application of a tulobuterol patch could decrease the occurrence of perioperative respiratory adverse events. Further studies are needed to elucidate the effect of the tulobuterol patch in a broad spectrum of pediatric anesthesia.

Pediatric Population Pharmacokinetic Modeling and Exposure-Response Analysis of Ambrisentan in Pulmonary Arterial Hypertension and Comparison With Adult Data.

This study aimed to develop a population pharmacokinetic (PK) model of ambrisentan in pediatric patients (8 to <18 years) with pulmonary arterial hypertension (PAH) and compare pediatric ambrisentan systemic exposure with previously reported adult data. Association of ambrisentan exposure with efficacy (6-minute walking distance) and safety (adverse events) were exploratory analyses. A population PK model was developed using pediatric PK data. Steady-state systemic exposure metrics were estimated for the pediatric population and compared with previously reported data in adult patients with PAH and healthy subjects. No covariates had a significant effect on PK parameters; therefore, the final covariate model was the same as the base model. The pediatric population PK model was a 2-compartment model including the effect of body weight (allometric scaling),first-order absorption and elimination, and absorption lag time. Steady-state ambrisentan exposure was similar between the pediatric and adult population when accounting for body weight differences. Geometric mean area under the concentration-time curve at steady state in pediatric patients receiving ambrisentan low dose was 3% lower than in the adult population (and similar in both populations receiving high dose). Geometric mean maximum plasma concentration at steady state in pediatric patients receiving low and high doses was 11% and 18% higher, respectively, than in the adult population. There was no apparent association in the pediatric or adult population between ambrisentan exposure and change in 6-minute walking distance or incidence of ambrisentan-related adverse events in pediatric patients. The similar ambrisentan exposure and exposure-response profiles observed in pediatric and adult populations with PAH suggests appropriateness of body-weight-based dosing in the pediatric population with PAH.

Perioperative Respiratory-Adverse Events Following General Anesthesia Among Pediatric Patients After COVID-19.

The perianesthetic morbidity, mortality risk and anesthesia-associated risk after preoperative coronavirus disease 2019 (COVID-19) omicron variant in pediatric patients have not been fully demonstrated. We examined the association between preoperative COVID-19 omicron diagnosis and the incidence of overall perioperative adverse events in pediatric patients who received general anesthesia. This retrospective study included patients aged < 18 years who received general anesthesia between February 1 and June 10, 2022, in a single tertiary pediatric hospital. They were divided into two groups; patients in a COVID-19 group were matched to patients in a non-COVID-19 group during the omicron-predominant period in Korea. Data on patient characteristics, anesthesia records, post-anesthesia records, COVID-19-related history, symptoms, and mortality were collected. The primary outcomes were the overall perioperative adverse events, including perioperative respiratory adverse events (PRAEs), escalation of care, and mortality. In total, 992 patients were included in the data analysis (n = 496, COVID-19; n = 496, non-COVID-19) after matching. The overall incidence of perioperative adverse events was significantly higher in the COVID-19 group than in the non-COVID-19 group (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.89-1.94). The difference was significant for PRAEs (OR, 2.00; 95% CI, 1.96-2.02) but not in escalation of care or mortality. The most pronounced difference between the two groups was observed in instances of high peak inspiratory pressure ≥ 25 cmH2O during the intraoperative period (OR, 11.0; 95% CI, 10.5-11.4). Compared with the non-COVID-19 group, the risk of overall perioperative adverse events was higher in the COVID-19 group diagnosed 0-2 weeks before anesthesia (OR, 6.5; 95% CI, 2.1-20.4) or symptomatic on the anesthesia day (OR, 6.4; 95% CI, 3.30-12.4). Pediatric patients with the preoperative COVID-19 omicron variant had increased risk of PRAEs. Patients within 2 weeks after COVID-19 or those with symptoms had a higher risk of PRAEs.

Intravenous acetaminophen for postoperative pain control after open abdominal and thoracic surgery in pediatric patients: a systematic review and meta-analysis.

Pediatric opioid exposure increases short- and long-term adverse events (AE). The addition of intravenous acetaminophen (IVA) to pediatric pain regimes to may reduce opioids but is not well studied postoperatively. Our objective was to quantify the impact of IVA on postoperative pain, opioid use, and AEs in pediatric patients after major abdominal and thoracic surgery. Medline, Embase, CINAHL, Web of Science, and Cochrane Library were searched systematically for randomized controlled trials (RCTs) comparing IVA to other modalities. Five RCTs enrolling 443 patients with an average age of 2.12years (± 2.81) were included. Trials comparing IVA with opioids to opioids alone were meta-analyzed. Low to very low-quality evidence demonstrated equivalent pain scores between the groups (-0.23, 95% CI -0.88 to 0.40, p 0.47) and a reduction in opioid consumption (-1.95 morphine equivalents/kg/48h, 95% CI -3.95 to 0.05, p 0.06) and minor AEs (relative risk 0.39, 95% CI 0.11 to 1.43, p 0.15). We conclude that the addition of IVA to opioid-based regimes in pediatric patients may reduce opioid use and minor AEs without increasing postoperative pain. Given the certainty of evidence, further research featuring patient-important outcomes and prolonged follow-up is necessary to confirm these findings.