Modified fluid gelatin 4% for perioperative volume replacement in pediatric patients (GPS): Results of a European prospective noninterventional multicenter study.

INTRODUCTION: Modified fluid gelatin 4% is approved for use in children, but there is still a surprising lack of clinical studies including large numbers of pediatric patients. Therefore, we performed a European prospective noninterventional multicenter study to evaluate the use of a modified fluid gelatin 4% in saline (sal-GEL) or an acetate-containing balanced electrolyte solution (bal-GEL) in children undergoing major pediatric surgery. AIMS: The primary aim was to assess the indications and dosing of modified fluid gelatin, and the secondary aim was to assess the safety and efficacy, focusing, in particular, on routinely collected clinical parameters. METHODS: Children aged up to 12 years with ASA risk scores of I-III receiving sal-GEL or bal-GEL were followed perioperatively. Demographic data, surgical procedures performed, anesthesia, hemodynamic and laboratory data, adverse events, and adverse drug reactions were documented using a standardized case report form. RESULTS: 601 children that were investigated at 13 European pediatric centers from May 2015 to March 2020 (sal-GEL 20.1%, bal-GEL 79.9%; mean age 29.1 ± 38.6 (range 0-144) months; body weight 12.1 ± 10.5 (1.4-70) kg) were included in the analysis. The most frequent indications for GEL infusion were hemodynamic instability without bleeding (76.0%), crystalloids alone not being sufficient for hemodynamic stabilization (55.7%), replacement of preoperative deficit (26.0%), and significant bleeding (13.0%). Mean infused GEL volume was 13.0 ± 5.3 (2.4-37.5) ml kg-1 . The total dose was affected by age, with higher doses in younger patients. After gelatin infusion, mean arterial pressure increased (mean change 8.5 ± 7.3 [95% CI: 8 to 9.1] mmHg), and the hemoglobin concentrations decreased significantly (mean change -1.1 ± 1.8 [95% CI: -1.2 to -0.9] g·dL-1 ). Acid-base parameters were more stable with bal-GEL. No serious adverse drug reactions directly related to gelatin (i.e., anaphylactoid reaction, clotting disorders, and renal failure) were observed. CONCLUSION: Moderate doses up to 20 ml kg-1 of modified fluid gelatin were infused most frequently to improve hemodynamic stability in children undergoing major pediatric surgery. The acid-base balance was more stable when gelatin in a balanced electrolyte solution was used instead of saline. No serious adverse drug reactions associated with gelatin were observed.

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE).

BACKGROUND: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. METHODS: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. RESULTS: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04-1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15-1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7-3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64-7.71) and mortality (RR=19.80; 95% CI, 5.87-66.7). CONCLUSIONS: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants. CLINICAL TRIAL REGISTRATION: NCT02350348.

[Anaesthesia Induction in Non-fasting Patients - the Example of Pregnant Women and Children]. / Einleitung von nicht nüchternen Patienten am Beispiel von Schwangeren und Kindern.

Aspiration during anesthesia induction is no triviality, but can lead to serious complications and mortality. The classic technique of rapid sequence induction (RSI) is a fundamental form of anesthesia induction in non-fasting patients to prevent pulmonary aspiration of gastric contents.Pregnant women and children pose a special challenge due to their hypoxia risk; the classical RSI concept "induction - apnea - (cricoid pressure -) intubation" can lead to hypoxia and therefore must be modified in favor of a controlled technique with preservation of oxygenation in this patient group. A controlled procedure with continuous oxygenation as far as possible should be used.The preparation of an RSI involves the careful selection of medicines, equipment and monitoring. An important quality criterion of RSI is the atraumatic airway management in deep anesthesia with profound muscle relaxation without resistance (coughing, choking, pressing) of the patient.

Perioperative fluid management in children: can we sum it all up now?

PURPOSE OF REVIEW: The composition and type of intravenous fluids during paediatric anaesthesia have been subjects of debates for decades. Errors in perioperative fluid management in children may lead to serious complications and a negative outcome. Therefore, in this review, historical and recent developments and recommendations for perioperative fluid management in children are presented, based on physiology and focused on safety and efficacy. RECENT FINDINGS: Optimized fasting times and liberal clear fluid intake until 1 h improve patient comfort and metabolic and haemodynamic condition after induction of anaesthesia. Physiologically composed balanced isotonic electrolyte solutions are safer than hypotonic electrolyte solutions or saline 0.9% to protect young children against the risks of hyponatraemia and hyperchloraemic acidosis. For intraoperative maintenance infusion, addition of 1-2% glucose is sufficient to avoid hypoglycaemia, lipolysis or hyperglycaemia. Modified fluid gelatine or hydroxyethyl starch in balanced electrolyte solution can safely be used to quickly normalize blood volume in case of perioperative circulatory instability and blood loss. SUMMARY: Physiologically composed balanced isotonic electrolyte solutions are beneficial for maintaining homeostasis, shifting the status more towards the normal range in patients with preexisting imbalances and have a wide margin of safety in case of accidental hyperinfusion.

Safe pediatric procedural sedation and analgesia by anesthesiologists for elective procedures: A clinical practice statement from the European Society for Paediatric Anaesthesiology.

The growing number of medical procedures performed in children that require cooperation of patients, lack of movement, anxiolysis or/and analgesia triggers the increased need for procedural sedation. This document presents the consensus statement of the European Society for Paediatric Anaesthesiology about the principles connected with the safe management of procedural sedation and analgesia (PSA) by anaesthesiologists for elective procedures in children. It does not aim to provide a legal statement on how and by whom PSA should be performed. The document highlights that any staff taking part in sedation of children must be appropriately trained with the required competencies and must be able to demonstrate regularly that they have maintained their knowledge, skills and clinical experience. The main goal of creating this document was to reflect the opinions of the community of the paediatric anaesthesiologists in Europe regarding how PSA for paediatric patients should be organized to make it safe.

[Reduction the risk in pediatric anesthesia-what should we know-what should we do]. / Risikominimierung in der Kinderanästhesie ­ was sollten wir wissen ­ was sollten wir tun.

Pediatric anesthesia has always been conjuncted with higher risk than anesthesia for adults (JP Morray; Pediatric Anesthesia 2011;21:722-9). Not only the imminent critical events, but also, caused by recently published data, the theoretical neurotoxicity of anesthetic agents and a potencial negative influence of anesthetics on braindevelopement, are in the spotlight.Concerns about the neurodevelopement and the general warnings from the U.S. Food and Drug Administration (FDA) for anesthesia in young children led to a worldwide discussion about safety in pediatric anesthesia (FDA Safety Anouncement 2017).Beside these theoretical risks, which are based only on animal research, we have to pay much more attention to the widely spread out poor quality of anesthesia in children.The following article should summarize the state of science about the risks and the opportunities to minimize them.

[Drama in the Recovery Unit: Paediatric Emergence Delirium]. / Drama im Aufwachraum: pädiatrisches Emergence-Delir.

The upcoming and ongoing debate on neurotoxicity of anesthetics at a young age put a new spotlight on the emergence delirium of children (paedED). The European Society for Anesthesiology published a consensus guideline on prevention and therapy in 2017 which can be a useful guidance in daily clinical practice. Patient data management systems with their clear documentation concerning pain/therapy of pain and paedED will be valuable tools in order to assess the real incidence of paedED. Differentiating between pain/agitation and paedED migth not always be easy. Age-adapted scores should always be applied. Main focus in the prevention of paedED is the reduction of anxiety. The way this is achieved by the dedicated pediatric anesthesia teams caring for children, e.g. by oral midazolam, clowns, music, smartphone induction, does not matter. Using α2-agonists in the perioperative phase and applying propofol seems to be effective. A quiet supportive environment for recovery adds to a relaxed, stress-free awakening. For the future detecting paedED on normal wards becomes an important issue. This may be achieved by structured interviews or questionnaires assessing postoperative negative behavioural changes at the same time.

Anesthesia and the developing brain: A way forward for laboratory and clinical research.

All commonly used general anesthetics have been shown to cause neurotoxicity in animal models, including nonhuman primates. Opinion, however, remains divided over how cumulative evidence from preclinical and human studies in this field should be interpreted and its translation to current practices in pediatric anesthesia and surgery. A group of international experts in laboratory and clinical sciences recently convened in Genoa, Italy, to evaluate the current state of both laboratory and clinical research and discuss future directions for basic, translational, and clinical studies in this field. This paper describes those discussions and conclusions. A central goal identified was the importance of continuing to pursue laboratory research efforts to better understand the biological pathways underlying anesthesia neurotoxicity. The distinction between basic and translational experimental designs in this field was highlighted, and it was acknowledged that it will be important for future animal research to try to causally link structural changes with long-term cognitive abnormalities. While inherent limitations will continue to affect the ability of even large observational cohorts to determine if anesthesia impacts neurodevelopment or behavioral outcomes, the importance of conducting further large well-designed cohort studies was also emphasized. Adequately powered cohorts could clarify which populations are at increased risk, provide information on environmental and healthcare-related risk modifiers, and guide future interventional trials. If anesthetics cause structural or functional adverse neurological effects in young children, alternative or mitigating strategies need to be considered. While protective or mitigating strategies have been repeatedly studied in animals, there are currently no human data to support alternative anesthetic strategies in clinical practice. Lastly, it was noted that there is still considerable debate over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate the impact of other aspects of perioperative care on neurodevelopment must also be considered.

Choosing Wisely in pediatric anesthesia: An interpretation from the German Scientific Working Group of Paediatric Anaesthesia (WAKKA).

Inspired by the Choosing Wisely initiative, a group of pediatric anesthesiologists representing the German Working Group on Paediatric Anaesthesia (WAKKA) coined and agreed upon 10 concise positive ("dos") or negative ("don'ts") evidence-based recommendations. (i) In infants and children with robust indications for surgical, interventional, or diagnostic procedures, anesthesia or sedation should not be avoided or delayed due to the potential neurotoxicity associated with the exposure to anesthetics. (ii) In children without relevant preexisting illnesses (ie, ASA status I/II) who are scheduled for elective minor or medium-risk surgical procedures, no routine blood tests should be performed. (iii) Parental presence during the induction of anesthesia should be an option for children whenever possible. (iv) Perioperative fasting should be safe and child-friendly with shorter real fasting times and more liberal postoperative drinking and enteral feeding. (v) Perioperative fluid therapy should be safe and effective with physiologically composed balanced electrolyte solutions to maintain a normal extracellular fluid volume; addition of 1%-2.5% glucose to avoid lipolysis, hypoglycemia, and hyperglycemia, and colloids as needed to maintain a normal blood volume. (vi) To achieve safe and successful airway management, the locally accepted airway algorithm and continued teaching and training of basic and alternative techniques of ventilation and endotracheal intubation are required. (vii) Ultrasound and imaging systems (eg, transillumination) should be available for achieving central venous access and challenging peripheral venous and arterial access. (viii) Perioperative disturbances of the patient's homeostasis, such as hypotension, hypocapnia, hypothermia, hypoglycemia, hyponatremia, and severe anemia, should not be ignored and should be prevented or treated immediately. (ix) Pediatric patients with an elevated perioperative risk, eg, preterm and term neonates, infants, and critically ill children, should be treated at institutions where all caregivers have sufficient expertise and continuous clinical exposure to such patients. (x) A strategy for preventing postoperative vomiting, emergence delirium, and acute pain should be a part of every anesthetic procedure.

Perioperative considerations for airway management and drug dosing in obese children.

PURPOSE OF REVIEW: Childhood obesity, a phenomenon that is increasing globally, holds substantial relevance for pediatric anesthesia. In particular, understanding the nuances of airway management and drug dosing in obese children can be daunting. RECENT FINDINGS: Respiratory adverse events and challenges in managing the airway may be anticipated. In addition, drug-dosing strategies for the obese child are complex and poorly understood although recent advances have clarified the optimal dosing for anesthetics in these children. SUMMARY: Theoretical knowledge, practical skills, meticulous risk stratification and optimal drug regimens are crucial to ensure the safe conduct of anesthesia for obese children.

Red blood cell transfusion in perioperative pediatric anesthesia: a survey of current practice in Germany.

BACKGROUND: Little is known about the current practice of the perioperative transfusion of red blood cells (RBCs) in pediatric patients. This study was performed to evaluate the practice of RBC transfusion in German pediatric anesthesia. STUDY DESIGN AND METHODS: An online survey was conducted among members of the German Society of Anesthesiology and Intensive Care. Participants were asked to indicate the hemoglobin (Hb) thresholds for starting RBC transfusion in six cases of different bleeding situations in pediatric anesthesia. Demographics of participants, general knowledge, and application of transfusion rules and guidelines were assessed. RESULTS: We included 1207 of 1396 returned questionnaires. Of the respondents, 89% were qualified specialists and 68% had experience in anesthesia in children aged less than 6 months. The lowest median Hb transfusion threshold was 6 g/dL in a 16-year-old and the highest was 10 g/dL in a premature neonate. Intraoperative Hb thresholds increased for clinically unstable (median difference to clinically stable children, +1 g/dL; p < 0.001) or neonate and premature children (median difference to older children, +1 and +2 g/dL; p < 0.001). The stated Hb threshold ranges were broad, especially in neonates or premature children (interquartile range, neonates 3, premature children 4 g/dL). Of the participants, only 16% had knowledge of a guideline that includes blood transfusion in children. CONCLUSION: Striking variability exists in practice of perioperative pediatric RBC transfusion. A specialized guideline for perioperative blood transfusion in children could be helpful to define and promote optimal pediatric RBC transfusion strategies.

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe.

BACKGROUND: Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. METHODS: The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. FINDINGS: Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0-5·5) with an incidence of respiratory critical events of 3·1% (2·9-3·3). Cardiovascular instability occurred in 1·9% (1·7-2·1), with an immediate poor outcome in 5·4% (3·7-7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86-0·90; p<0·0001), medical history, and physical condition (1·60, 1·40-1·82; p<0·0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0·99, 0·981-0·997; p<0·0048 for respiratory critical events, and 0·98, 0·97-0·99; p=0·0039 for cardiovascular critical events), rather than the type of health institution or providers. INTERPRETATION: This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia. FUNDING: European Society of Anaesthesiology.

An update on the perioperative management of children with upper respiratory tract infections.

PURPOSE OF REVIEW: This review summarizes the current evidence for the management of children with recent upper respiratory tract infections (URTIs). Furthermore, the review includes management guidelines for children with URTIs. RECENT FINDINGS: Good history and clinical examination is sufficient in most children presenting with URTI. Testing for immune markers or preoperative nitric oxide measurement does not add any additional value. Preoperative bronchodilator administration, intravenous induction with propofol, and noninvasive airway management all reduce the occurrence of respiratory adverse events. SUMMARY: Most children can be safely anaesthetized even in the presence of an URTIs if the perioperative anaesthesia management is optimized. In this review article, we have included a management algorithm for children with URTI presenting for elective surgery.

Metamizole for Postoperative Pain Therapy in Infants Younger than 1 Year.

Background Due to possible serious adverse drug reactions (ADRs), the use of metamizole for postoperative pain therapy in infants is a subject of debate. Safety studies with large sample sizes are missing. Aim This prospective multicenter observational study was conducted to evaluate the use of metamizole in infants younger than 1 year undergoing surgery with a particular focus on possible serious ADRs (e.g., hemodynamic, anaphylactic or respiratory reactions, and agranulocytosis). Methods Infants aged up to 1 year (American Society of Anesthesiologists [ASA] I-III) receiving a single dose of metamizole for postoperative pain therapy were enrolled. Patient demographics, main and secondary diagnosis, surgical procedures performed, metamizole dose, hemodynamic data, use of other analgesics and regional blocks, results of pain measurement, and incidence of ADRs were documented using a standardized case report form. Results A total of 316 infants observed at five pediatric centers were included for analysis (age 4.4 ± 3.7 [0.06-12] months). Mean metamizole dose was 17.8 ± 3.1 (9.2-29.8) mg·kg-1. Mean arterial pressure (MAP) remained stable during metamizole infusion (MAP before infusion 45 ± 9.5 [25-95] and after infusion 45 ± 9.2 [25-99] mm Hg). Erythema was observed in one patient (ADRs total: 0.3%, 95% confidence interval: 0.27-0.32). No respiratory adverse events directly related to the metamizole administration and no clinical signs of agranulocytosis were reported. Conclusion Single intravenous doses of metamizole used for prevention or treatment of postoperative pain were safe in more than 300 infants younger than 1 year. The statistical probability of serious ADRs (e.g., hemodynamic, anaphylactic or respiratory reactions) was lower than 1%. The sample size and follow-up were not sufficient to detect agranulocytosis.

Perioperative intravenous fluid therapy in children: guidelines from the Association of the Scientific Medical Societies in Germany.

This consensus- based S1 Guideline for perioperative infusion therapy in children is focused on safety and efficacy. The objective is to maintain or re-establish the child's normal physiological state (normovolemia, normal tissue perfusion, normal metabolic function, normal acid- base- electrolyte status). Therefore, the perioperative fasting times should be as short as possible to prevent patient discomfort, dehydration, and ketoacidosis. A physiologically composed balanced isotonic electrolyte solution (BS) with 1-2.5% glucose is recommended for the intraoperative background infusion to maintain normal glucose concentrations and to avoid hyponatremia, hyperchloremia, and lipolysis. Additional BS without glucose can be used in patients with circulatory instability until the desired effect is achieved. The additional use of colloids (albumin, gelatin, hydroxyethyl starch) is recommended to recover normovolemia and to avoid fluid overload when crystalloids alone are not sufficient and blood products are not indicated. Monitoring should be extended in cases with major surgery, and autotransfusion maneuvers should be performed to assess fluid responsiveness.

[Patient blood management: Does the approach also make sense in children?]. / Patient Blood Management - Ist das Konzept auch bei Kindern sinnvoll?

Patient blood management describes an interdisciplinary concept which aims at rational and adequate use of blood products accompanied by strategies to prevent and treat anemia, to reduce blood loss and to use alternatives to blood transfusion. While patient blood management has been widely implemented in adult medicine, concepts for such measures in the care of children are rare. The basic principles of preoperative evaluation, optimization of blood volume, perioperative minimizing of blood loss and a differentiated use of blood products are effective both in adults and children. There are differences in the physiology of hemoglobin and cardiovascular systems, particularly in the first year of life. It can be difficult to determine impending anemic hypoxia in children, so that indication for transfusion based on standardized hemoglobin threshold values should always be supported by an individual risk-benefit analysis based on clinical assessment.