Short-term outcomes in infants following general anesthesia with low-dose sevoflurane/dexmedetomidine/remifentanil versus standard dose sevoflurane (The TREX trial).

BACKGROUND: The TREX (Trial Remifentanil DEXmedetomidine) trial aimed to determine if, in children < 2 years old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia (LD-SEVO) is superior to standard dose sevoflurane (STD-SEVO) anesthesia in terms of global cognitive function at 3 years of age. The aim of the present secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms. METHODS: This Phase III randomized active controlled, parallel group, assessor blinded, multicenter, superiority trial was performed in 20 centers in Australia, Italy, and the United States. Four hundred and fifty-five infants <2 years of age expected to undergo general anesthesia for at least 2 hours were enrolled. They were randomized between LD-SEVO and STD-SEVO. The short-term perioperative outcomes noted above were compared between these two groups. RESULTS: There was less hypotension (risk difference -11.6%, 95% confidence interval (CI) -18.9% to -4.3%) and more bradycardia (risk difference 18.2%, 95% CI 8.8% to 27.7%) in the LD-SEVO compared to the STD-SEVO arm. There were more patients with episodes of light anesthesia (89 vs. 4), and protocol abandonments (1 vs. 0) in the LD-SEVO arm. Time from eye-opening to Post Anesthesia Care Unit (PACU) discharge was similar in both arms, as were morbidity and mortality. One patient in each arm suffered a life-threatening event but neither suffered long-term sequelae. CONCLUSIONS: These early postoperative results suggest that in children less than 2 years of age receiving greater than 2 hours of general anesthesia, the low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia technique and the standard sevoflurane anesthesia technique are broadly clinically similar, with no clear evidence to support choosing one technique over the other.

The pediatric DAV-expert algorithm: A GAVeCeLT/GAVePed consensus for the choice of the most appropriate venous access device in children.

In pediatric patients, the choice of the venous access device currently relies upon the operator's experience and preference and on the local availability of specific resources and technologies. Though, considering the limited options for venous access in children if compared to adults, such clinical choice has a great critical relevance and should preferably be based on the best available evidence. Though some algorithms have been published over the last 5 years, none of them seems fully satisfactory and useful in clinical practice. Thus, the GAVePed-which is the pediatric interest group of the most important Italian group on venous access, GAVeCeLT-has developed a national consensus about the choice of the venous access device in children. After a systematic review of the available evidence, the panel of the consensus (which included Italian experts with documented competence in this area) has provided structured recommendations answering 10 key questions regarding the choice of venous access both in emergency and in elective situations, both in the hospitalized and in the non-hospitalized child. Only statements reaching a complete agreement were included in the final recommendations. All recommendations were also structured as a simple visual algorithm, so as to be easily translated into clinical practice.

Emergency front-of-neck access in pediatric anesthesia: A narrative review.

BACKGROUND AND OBJECTIVES: Children undergoing airway management during general anesthesia may experience airway complications resulting in a rare but life-threatening situation known as "Can't Intubate, Can't Oxygenate". This situation requires immediate recognition, advanced airway management, and ultimately emergency front-of-neck access. The absence of standardized procedures, lack of readily available equipment, inadequate knowledge, and training often lead to failed emergency front-of-neck access, resulting in catastrophic outcomes. In this narrative review, we examined the latest evidence on emergency front-of-neck access in children. METHODS: A comprehensive literature was performed the use of emergency front-of-neck access (eFONA) in infants and children. RESULTS: Eighty-six papers were deemed relevant by abstract. Finally, eight studies regarding the eFONA technique and simulations in animal models were included. For all articles, their primary and secondary outcomes, their specific animal model, the experimental design, the target participants, and the equipment were reported. CONCLUSION: Based on the available evidence, we propose a general approach to the eFONA technique and a guide for implementing local protocols and training. Additionally, we introduce the application of innovative tools such as 3D models, ultrasound, and artificial intelligence, which can improve the precision, safety, and training of this rare but critical procedure.

Clear rules for clear fluids fasting in children.

Preoperative fasting guidelines published in 2022 by the European Society of Anaesthesiology and Intensive Care represent a paradigm shift in the preoperative preparation of children undergoing general anaesthesia. Schmitz and colleagues report the results from a multi-institutional prospective cohort study to determine if application of the recent guidelines increased the risk of regurgitation and pulmonary aspiration. This study provides support for the concept of reducing real fasting times by allowing clear fluids until 1 h before induction of anaesthesia. Although the study cohort was large, further prospective multicentre studies with even greater sample sizes are warranted to provide definitive evidence for the safety of the new fasting rules.

Apnoeic oxygenation during paediatric tracheal intubation: a systematic review and meta-analysis.

BACKGROUND: Supplemental oxygen administration by apnoeic oxygenation during laryngoscopy for tracheal intubation is intended to prolong safe apnoea time, reduce the risk of hypoxaemia, and increase the success rate of first-attempt tracheal intubation under general anaesthesia. This systematic review examined the efficacy and effectiveness of apnoeic oxygenation during tracheal intubation in children. METHODS: This systematic review and meta-analysis included randomised controlled trials and non-randomised studies in paediatric patients requiring tracheal intubation, evaluating apnoeic oxygenation by any method compared with patients without apnoeic oxygenation. Searched databases were MEDLINE, Embase, Cochrane Library, CINAHL, ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), Scopus, and Web of Science from inception to March 22, 2023. Data extraction and risk of bias assessment followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) recommendation. RESULTS: After initial selection of 40 708 articles, 15 studies summarising 9802 children were included (10 randomised controlled trials, four pre-post studies, one prospective observational study) published between 1988 and 2023. Eight randomised controlled trials were included for meta-analysis (n=1070 children; 803 from operating theatres, 267 from neonatal intensive care units). Apnoeic oxygenation increased intubation first-pass success with no physiological instability (risk ratio [RR] 1.27, 95% confidence interval [CI] 1.03-1.57, P=0.04, I2=0), higher oxygen saturation during intubation (mean difference 3.6%, 95% CI 0.8-6.5%, P=0.02, I2=63%), and decreased incidence of hypoxaemia (RR 0.24, 95% CI 0.17-0.33, P<0.01, I2=51%) compared with no supplementary oxygen administration. CONCLUSION: This systematic review with meta-analysis confirms that apnoeic oxygenation during tracheal intubation of children significantly increases first-pass intubation success rate. Furthermore, apnoeic oxygenation enables stable physiological conditions by maintaining oxygen saturation within the normal range. CLINICAL TRIAL REGISTRATION: Protocol registered prospectively on PROSPERO (registration number: CRD42022369000) on December 2, 2022.

Airway management in neonates and infants: European Society of Anaesthesiology and Intensive Care and British Journal of Anaesthesia joint guidelines.

Airway management is required during general anaesthesia and is essential for life-threatening conditions such as cardiopulmonary resuscitation. Evidence from recent trials indicates a high incidence of critical events during airway management, especially in neonates or infants. It is important to define the optimal techniques and strategies for airway management in these groups. In this joint European Society of Anaesthesiology and Intensive Care (ESAIC) and British Journal of Anaesthesia (BJA) guideline on airway management in neonates and infants, we present aggregated and evidence-based recommendations to assist clinicians in providing safe and effective medical care. We identified seven main areas of interest for airway management: i) preoperative assessment and preparation; ii) medications; iii) techniques and algorithms; iv) identification and treatment of difficult airways; v) confirmation of tracheal intubation; vi) tracheal extubation, and vii) human factors. Based on these areas, Population, Intervention, Comparison, Outcomes (PICO) questions were derived that guided a structured literature search. GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to formulate the recommendations based on those studies included with consideration of their methodological quality (strong '1' or weak '2' recommendation with high 'A', medium 'B' or low 'C' quality of evidence). In summary, we recommend: 1. Use medical history and physical examination to predict difficult airway management (1C). 2. Ensure adequate level of sedation or general anaesthesia during airway management (1B). 3. Administer neuromuscular blocker before tracheal intubation when spontaneous breathing is not necessary (1C). 4. Use a videolaryngoscope with an age-adapted standard blade as first choice for tracheal intubation (1B). 5. Apply apnoeic oxygenation during tracheal intubation in neonates (1B). 6. Consider a supraglottic airway for rescue oxygenation and ventilation when tracheal intubation fails (1B). 7. Limit the number of tracheal intubation attempts (1C). 8. Use a stylet to reinforce and preshape tracheal tubes when hyperangulated videolaryngoscope blades are used and when the larynx is anatomically anterior (1C). 9. Verify intubation is successful with clinical assessment and end-tidal CO2 waveform (1C). 10. Apply high-flow nasal oxygenation, continuous positive airway pressure or nasal intermittent positive pressure ventilation for postextubation respiratory support, when appropriate (1B).

Emergency front-of-neck access in infants: A pragmatic crossover randomized control trial comparing two approaches on a simulated rabbit model.

BACKGROUND: Rapid-sequence tracheotomy and scalpel-bougie tracheotomy are two published approaches for establishing emergency front-of-neck access in infants. It is unknown whether there is a difference in performance times and success rates between the two approaches. AIMS: The aim of this cross-over randomized control trial study was to investigate whether the two approaches were equivalent for establishing tracheal access in rabbit cadavers. The underlying hypothesis was that the time to achieve the tracheal access is the same with both techniques. METHODS: Between May and September 2022, thirty physicians (pediatric anesthesiologists and intensivists) were randomized to perform front-of-neck access using one and then the other technique: rapid-sequence tracheotomy and scalpel-bougie tracheotomy. After watching training videos, each technique was practiced four times followed by a final tracheotomy during which study measurements were obtained. Based on existing data, an equivalence margin was set at ∆ = ±10 s for the duration of the procedure. The primary outcome was defined as the duration until tracheal tube placement was achieved successfully. Secondary outcomes included success rate, structural injuries, and subjective participant self-evaluation. RESULTS: The median duration of the scalpel-bougie tracheotomy was 48 s (95% CI: 37-57), while the duration of the rapid-sequence tracheotomy was 59 s (95% CI: 49-66, p = .07). The difference in the median duration between the two approaches was 11 s (95% CI: -4.9 to 29). The overall success rate was 93.3% (95% CI: 83.8%-98.2%). The scalpel-bougie tracheotomy resulted in significantly fewer damaged tracheal rings and was preferred among participants. CONCLUSIONS: The scalpel-bougie tracheotomy was slightly faster than the rapid-sequence tracheotomy and favored by participants, with fewer tracheal injuries. Therefore, we propose the scalpel-bougie tracheostomy as a rescue approach favoring the similarity to the adult approach for small children. The use of a comparable equipment kit for both children and adults facilitates standardization, performance, and logistics. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05499273.

Airway management in neonates and infants: European Society of Anaesthesiology and Intensive Care and British Journal of Anaesthesia joint guidelines.

Airway management is required during general anaesthesia and is essential for life-threatening conditions such as cardiopulmonary resuscitation. Evidence from recent trials indicates a high incidence of critical events during airway management, especially in neonates or infants. It is important to define the optimal techniques and strategies for airway management in these groups. In this joint European Society of Anaesthesiology and Intensive Care (ESAIC) and British Journal of Anaesthesia (BJA) guideline on airway management in neonates and infants, we present aggregated and evidence-based recommendations to assist clinicians in providing safe and effective medical care. We identified seven main areas of interest for airway management: i) preoperative assessment and preparation; ii) medications; iii) techniques and algorithms; iv) identification and treatment of difficult airways; v) confirmation of tracheal intubation; vi) tracheal extubation, and vii) human factors. Based on these areas, Population, Intervention, Comparison, Outcomes (PICO) questions were derived that guided a structured literature search. GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to formulate the recommendations based on those studies included with consideration of their methodological quality (strong '1' or weak '2' recommendation with high 'A', medium 'B' or low 'C' quality of evidence). In summary, we recommend: 1. Use medical history and physical examination to predict difficult airway management (1С). 2. Ensure adequate level of sedation or general anaesthesia during airway management (1B). 3. Administer neuromuscular blocker before tracheal intubation when spontaneous breathing is not necessary (1С). 4. Use a videolaryngoscope with an age-adapted standard blade as first choice for tracheal intubation (1B). 5. Apply apnoeic oxygenation during tracheal intubation in neonates (1B). 6. Consider a supraglottic airway for rescue oxygenation and ventilation when tracheal intubation fails (1B). 7. Limit the number of tracheal intubation attempts (1C). 8. Use a stylet to reinforce and preshape tracheal tubes when hyperangulated videolaryngoscope blades are used and when the larynx is anatomically anterior (1C). 9. Verify intubation is successful with clinical assessment and end-tidal CO 2 waveform (1C). 10. Apply high-flow nasal oxygenation, continuous positive airway pressure or nasal intermittent positive pressure ventilation for postextubation respiratory support, when appropriate (1B).

Perioperative anaesthetic management and short-term outcome of neonatal repair of oesophageal atresia with or without tracheo-oesophageal fistula in Europe: A sub-analysis of the neonate and children audit of anaesthesia practice in Europe (NECTARINE) prospective multicenter observational study.

BACKGROUND: Oesophageal atresia with or without a tracheo-oesophageal fistula is a congenital abnormality that usually requires surgical repair within the first days of life. OBJECTIVE: Description of the perioperative anaesthetic management and outcomes of neonates undergoing surgery for oesophageal atresia with or without a tracheo-oesophageal fistula, included in the 'neonate and children audit of anaesthesia practice in Europe' (NECTARINE) database. DESIGN: Sub-analyses of prospective observational NECTARINE study. SETTING: European multicentre study. PATIENTS: Neonates who underwent surgery for oesophageal atresia with or without a tracheo-oesophageal fistula in the NECTARINE cohort were selected. MAIN OUTCOME MEASURES: Incidence rates with 95% confidence intervals were calculated for peri-operative clinical events which required a predetermined intervention, postoperative complications, and mortality. RESULTS: One hundred and three neonates undergoing a first surgical intervention for oesophageal atresia with or without a tracheo-oesophageal fistula repair were identified. Their median gestational age was 38 weeks with a median birth weight of 2840 [interquartile range 2150 to 3150] grams. Invasive monitoring was used in 66% of the procedures. The incidence of perioperative clinical events was 69% (95% confidence interval 59 to 77%), of 30-day postoperative complications 47% (95% confidence interval 38 to 57%) and the 30- and 90 days mortality rates were 2.1% and 2.6%, respectively. CONCLUSION: Oesophageal atresia with or without a tracheo-oesophageal fistula repair in neonates is associated with a high number of perioperative interventions in response to clinical events, a high incidence of postoperative complications, and a substantial mortality rate.

Characteristics and neurological survival following intraoperative cardiac arrest in a Swiss University Hospital: a 7-year retrospective observational cohort study.

Introduction: Little is known about intraoperative cardiac arrest during anesthesia care. In particular, data on characteristics of cardiac arrest and neurological survival are scarce. Methods: We conducted a single-center retrospective observational study evaluating anesthetic procedures from January 2015 until December 2021. We included patients with an intraoperative cardiac arrest and excluded cardiac arrest outside of the operating room. The primary outcome was the return of spontaneous circulation (ROSC). Secondary outcomes were sustained ROSC over 20 min, 30-day survival, and favorable neurological outcome according to Clinical Performance Category (CPC) 1 and 2. Results: We screened 228,712 anesthetic procedures, 195 of which met inclusion criteria and were analyzed. The incidence of intraoperative cardiac arrest was 90 (CI 95% 78-103) in 100,000 procedures. The median age was 70.5 [60.0; 79.4] years, and two-thirds of patients (n = 135; 69.2%) were male. Most of these patients with cardiac arrest had ASA physical status IV (n = 83; 42.6%) or V (n = 47; 24.1%). Cardiac arrest occurred more frequently (n = 104; 53.1%) during emergency procedures than elective ones (n = 92; 46.9%). Initial rhythm was pre-dominantly non-shockable with pulseless electrical activity mostly. Most patients (n = 163/195, 83.6%; CI 95 77.6-88.5%) had at least one instance of ROSC. Sustained ROSC over 20 min was achieved in most patients with ROSC (n = 147/163; 90.2%). Of the 163 patients with ROSC, 111 (68.1%, CI 95 60.4-75.2%) remained alive after 30 days, and most (n = 90/111; 84.9%) had favorable neurological survival (CPC 1 and 2). Conclusion: Intraoperative cardiac arrest is rare but is more likely in older patients, patients with ASA physical status ≥IV, cardiac and vascular surgery, and emergency procedures. Patients often present with pulseless electrical activity as the initial rhythm. ROSC can be achieved in most patients. Over half of the patients are alive after 30 days, most with favorable neurological outcomes, if treated immediately.

Practical and societal implications of the potential anesthesia-induced neurotoxicity: The safetots perspective.

Key elements for safe and high-quality care in pediatric anesthesia are personal and institutional competence, perioperative maintenance of physiological homeostasis, prevention, prompt recognition, and appropriate treatment of critical situations as well as the reassurance of the parents and respecting the children's rights. Training in pediatric anesthesia should take place within the framework of harmonized curricular structures. International quality assessment and improvement projects should be encouraged and supported by collaborations. Healthy communication and providing information in a balanced way to the public and all stakeholders is an important task for pediatric anesthesia societies and individuals. The Safetots.org initiative was established to emphasize the role of the conduct of anesthesia to prevent harm, promote quality in the perioperative period, and provide safe and high-quality clinical care. This initiative considers that the prevention of complications and other well-known risk factors of perioperative care, as well as the quality of anesthesia management, have a far more important impact on outcomes following anesthesia and surgery than anesthetic drugs themselves.

Preventing difficult facemask ventilation in children: all is well that starts well.

Difficult facemask ventilation at induction of general anaesthesia can trigger hypoxaemia and inadequate ventilation if not immediately identified and adequately treated. For this reason, identification of predisposing conditions before induction of anaesthesia and causes of poor facemask ventilation are critical to avoid the subsequent complications. In a recently published secondary analysis of the Paediatric Difficult Intubation (PeDI) registry, the incidence and risk factors for difficult facemask ventilation in children with difficult tracheal intubation was described, as highlighted in the editorial.

Morbidity and mortality after anesthesia in early life in Italy. A subgroup analysis of the NECTARINE Trial.

BACKGROUND: Recent literature on neonatal anesthesia focuses on the importance of keeping physiology within the ranges of normality to improve the long-term neurological outcome. The Neonate and Children audit of Anesthesia pRactice IN Europe (NECTARINE) showed a derangement of one or more than one physiological parameters during anesthesia needing a medical intervention in 35.2% of 6592 anesthesia procedure performed in infants up to 60 weeks postmenstrual age. METHODS: Subanalysis of the Italian NECTARINE cohort providing a snapshot of anesthesia management, incidence of clinical events requiring intervention during anesthesia, and morbidity and mortality at 30 and 90 days. Secondary aim was to compare outcomes between Italy and Europe. RESULTS: Twenty-three Italian centers recruited 501 patients (63% male, 37% female) undergoing 611 procedures (441 surgical and 170 non-surgical) with a mean gestational age at birth of 38 weeks. Events requiring a medical intervention during anesthesia occurred in 177 cases (28.9%), lower than those reported in Europe (35.3%). The majority of events concerned episodes of cardiovascular instability, most commonly due to hypotension. The incidence of mortality at 30 days was 2.7%, consistent with the European incidence. CONCLUSIONS: Anesthetizing neonates is challenging. It is crucial that neonatal anesthesia practice is performed in specialized centers to maximize the potential positive outcome. We recommend a certification of quality for Institutions providing care for very young patients.

A machine-learning approach for decision support and risk stratification of pediatric perioperative patients based on the APRICOT dataset.

BACKGROUND: Pediatric anesthesia has evolved to a high level of patient safety, yet a small chance remains for serious perioperative complications, even in those traditionally considered at low risk. In practice, prediction of at-risk patients currently relies on the American Society of Anesthesiologists Physical Status (ASA-PS) score, despite reported inconsistencies with this method. AIMS: The goal of this study was to develop predictive models that can classify children as low risk for anesthesia at the time of surgical booking and after anesthetic assessment on the procedure day. METHODS: Our dataset was derived from APRICOT, a prospective observational cohort study conducted by 261 European institutions in 2014 and 2015. We included only the first procedure, ASA-PS classification I to III, and perioperative adverse events not classified as drug errors, reducing the total number of records to 30 325 with an adverse event rate of 4.43%. From this dataset, a stratified train:test split of 70:30 was used to develop predictive machine learning algorithms that could identify children in ASA-PS class I to III at low risk for severe perioperative critical events that included respiratory, cardiac, allergic, and neurological complications. RESULTS: Our selected models achieved accuracies of >0.9, areas under the receiver operating curve of 0.6-0.7, and negative predictive values >95%. Gradient boosting models were the best performing for both the booking phase and the day-of-surgery phase. CONCLUSIONS: This work demonstrates that prediction of patients at low risk of critical PAEs can be made on an individual, rather than population-based, level by using machine learning. Our approach yielded two models that accommodate wide clinical variability and, with further development, are potentially generalizable to many surgical centers.

Cardiac autonomic control in Rett syndrome: Insights from heart rate variability analysis.

Rett syndrome (RTT) is a rare and severe neurological disorder mainly affecting females, usually linked to methyl-CpG-binding protein 2 (MECP2) gene mutations. Manifestations of RTT typically include loss of purposeful hand skills, gait and motor abnormalities, loss of spoken language, stereotypic hand movements, epilepsy, and autonomic dysfunction. Patients with RTT have a higher incidence of sudden death than the general population. Literature data indicate an uncoupling between measures of breathing and heart rate control that could offer insight into the mechanisms that lead to greater vulnerability to sudden death. Understanding the neural mechanisms of autonomic dysfunction and its correlation with sudden death is essential for patient care. Experimental evidence for increased sympathetic or reduced vagal modulation to the heart has spurred efforts to develop quantitative markers of cardiac autonomic profile. Heart rate variability (HRV) has emerged as a valuable non-invasive test to estimate the modulation of sympathetic and parasympathetic branches of the autonomic nervous system (ANS) to the heart. This review aims to provide an overview of the current knowledge on autonomic dysfunction and, in particular, to assess whether HRV parameters can help unravel patterns of cardiac autonomic dysregulation in patients with RTT. Literature data show reduced global HRV (total spectral power and R-R mean) and a shifted sympatho-vagal balance toward sympathetic predominance and vagal withdrawal in patients with RTT compared to controls. In addition, correlations between HRV and genotype and phenotype features or neurochemical changes were investigated. The data reported in this review suggest an important impairment in sympatho-vagal balance, supporting possible future research scenarios, targeting ANS.

Outcomes in pediatric anesthesia: towards a universal language.

PURPOSE OF REVIEW: The identification of valid, well defined and relevant outcomes is fundamental to provide a reliable and replicable measure that can be used to improve quality of clinical care and research output. The purpose of this review is to provide an update on what the pediatric anesthesia research community is pursuing on standardized and validated outcomes. RECENT FINDINGS: Several initiatives by different research groups have been established during the last years. They all aim to find validated outcomes using the standardized methodology of COMET ( https://www.comet-initiative.org/ ). These initiatives focus on clinical and research outcomes on the field of anesthesia, perioperative medicine, pain and sedation in pediatric age. SUMMARY: Clinical outcomes are measurements of changes in health, function or quality of life and they help evaluating quality of care. In order for them to be relevant in quantifying quality improvement, they need to be well defined, standardized and consistent across trials. A great effort from researchers has been made towards the identification of set of outcomes with these features.