Factors Influencing Willingness to Participate in Clinical Studies in Pediatric Anesthesia (FILIPPA): A vignette-based, structured interview study.

BACKGROUND: Informed consent is a relevant backdrop for conducting clinical trials, particularly those involving children. While several factors are known to influence the willingness to consent to pediatric anesthesia studies, the influence of study design on consenting behavior is unknown. AIMS: To quantify the impact of study complexity on willingness to consent to pediatric anesthesia studies. METHODS: We conducted a vignette-based interview study by presenting three hypothetical studies to 106 parents or legal guardians whose children were scheduled to undergo anesthesia. These studies differed in level of complexity and included an example of a prospective observational study, a randomized controlled trial, and a phase-II-pharmacological study. Primary outcome was the willingness to consent, using a 5-point Likert scale ranging from "absolutely consent" to "absolutely decline". Secondary outcomes were the effects of child-related (such as sex, age, previous anesthesia, research exposure) and proxy-related factors. RESULTS: Response probabilities for "absolute consent" were 90.9% [95% CI 85.3-96.5] for the observational study, 48.6% [95% CI 38.3-58.9] for the randomized controlled trial, and 32.7% [95% CI 23.9-41.6] for the phase-II-pharmacological study. Response probabilities for "absolutely decline" were 1.6% [95% CI 0.3-2.8], 14.4% [95% CI 8.3-20.5], and 24.7% [95% CI 16.6-32.7], respectively. Significant effects were found for previous research exposure (OR = 0.486 [95% CI 0.256-0.923], p = .027), older age (OR = 0.963 [95% CI 0.927-0.999], p = .045) and the gender of the parent or legal guardian, as mothers were less willing to consent (OR = 0.234 [95% CI 0.107-0.512], p < .001). CONCLUSIONS: Willingness to consent decreased with increasing level of study complexity. When conducting more complex studies, greater efforts need to be made to increase the enrollment of pediatric patients.

The pediatric anesthesiology publication activity and landscape over the past two decades: A longitudinal scientometric analysis.

BACKGROUND: Scientometric analyses characterize the output of research publications using quantitative methods. While it has been reported that the number of publications in anesthesiology has been increasing for years, the global research activity in pediatric anesthesiology and its landscape is largely unknown. AIMS: To examine the activity, developmental dynamics, and collaboration landscape of research publications in pediatric anesthesiology over the past two decades. METHODS: PubMed and WebOfScience were searched for pediatric anesthesiology publications published between 2001 and 2020. The identified publications were exported into a database, matched, curated, and then assigned to one or more countries according to their affiliation field(s). The primary outcome was the publication activity and its growth rate. Secondary outcomes included the geographical distribution, the evolution of international collaborations (as indicated by articles affiliated with more than one country), and the main sources. RESULTS: Thirty-four thousand, three hundred and forty-three pediatric anesthesiology publications were retrieved. The compound annual growth rate over the study period was +7.6%. The highest annual growth rate was +20.6% from 2019 to 2020. Corresponding authors were most often affiliated with USA (32.5%), Germany (5.5%), and China (5.5%). China (+22.9%), Iran (+21.7%), and India (+16.1%) had the highest compound annual growth rates. 6001 (17.5%) articles involved international collaboration, with a compound annual growth rate of +13.1%. The most frequent collaboration was between USA and Canada (716 articles together). The most prominent source was Pediatric Anesthesia (10.0%). CONCLUSIONS: Publication activity in pediatric anesthesiology has increased from 2001 to 2020 and has become more geographically diverse. With the volume of international collaborations even outpacing this growth, it is hoped that this will gradually lead to a larger evidence base in pediatric anesthesia.

Evaluation of the non-invasive Temple Touch Pro temperature monitoring system compared with oesophageal temperature in paediatric anaesthesia (PETER PAN): A prospective observational study.

BACKGROUND: Monitoring peri-operative body temperature in children is currently mainly achieved through invasive devices. The Temple Touch Pro Temperature Monitoring System estimates core temperature noninvasively based on heat flux thermometry. OBJECTIVE: To investigate the agreement of this noninvasive sensor against standard oesophageal core temperature. DESIGN: A prospective observational study. SETTING: University hospital recruiting between April and July 2021. PATIENTS: One hundred children (32 girls) aged 6 years or younger scheduled for noncardiac surgery, resulting in 6766 data pairs. Exclusion criteria were contraindication for the insertion of an oesophageal temperature probe, and procedures in which one of the measurement methods would interfere with the surgical field. MAIN OUTCOME MEASURES: Primary outcome was the agreement analysis by a Bland-Altman comparison with multiple measurements. Posthoc, we performed another agreement analysis after exclusion of a statistically determined equilibration time. Secondary outcomes were the temperature differences over time and subgroup analysis of hypothermic, normothermic and hyperthermic temperature ranges, age, sex and sensor's side by type III analysis of variance. Further, we correlated the sonographically determined depth of the artery with trueness. RESULTS: The mean difference was -0.07°C (95% CI -0.15 to +0.05) with limits of agreement of -1.00 and +0.85°C. After adjusting for an equilibration time of 13 min, the mean difference improved to -0.04°C (95% CI -0.08 to +0.01) with limits of agreement of -0.68 and +0.60°C. Concordance correlation coefficient was 0.83 (95% CI 0.82 to 0.84). Differences between the skin sensor and oesophageal reference increased over time by -0.05°C per hour. Subgroup analysis showed no clinically relevant differences. Depth of artery negatively correlated with trueness by 0.03°C per millimetre. CONCLUSIONS: Although the Temple Touch Pro sensor showed acceptable accuracy after allowing for an equilibration time, it still needs further investigation for routine use in children. This particularly affects accuracy in hypothermic ranges, imprecise positioning and applicability in children with immature or vulnerable skin. TRIAL REGISTRATION: German Clinical Trials Register, identifier: DRKS00024703.

Guedel oropharyngeal airway: The validation of facial landmark-distances to estimate sizing in children - Visualisation by magnetic resonance imaging (GUEDEL-I): A prospective observational study.

OBJECTIVE: To validate the ERC-recommended facial landmark-distance for oropharyngeal airway sizing in children. METHODS: We conducted a prospective observational study in anaesthetised, spontaneously breathing children ≤12 years undergoing cranial MRI. Oropharyngeal airways were inserted following the distance from the maxillary incisors to the mandibular angle. Primary outcome was the rate of properly sized oropharyngeal airways on MRI, defined as the distal end positioned within 10 mm from the epiglottis without contacting it. Secondary outcomes were the occurrence of tongue protrusion, oropharyngeal airways clinical efficacy, and related adverse events. Furthermore, we calculated probabilities for the estimation of proper size when considering five facial landmark-distances and optimal rules based on biometric parameters. RESULTS: In 94 children with a mean (SD) age of 4.7 (±3) years, 47.9% [95%-CI 38%-57.9%] oropharyngeal airways were properly sized, while 23.4% [95%-CI 15.9%-33%] were undersized, and 28.7% [95%-CI 20.5%-38.7%] oversized. Tongue protrusion occurred in 59.1% [95%-CI 38.2%-77.2%] of undersized and 15.6% [95%-CI 7.6%-29.2%] of properly sized oropharyngeal airways. No oropharyngeal airway required replacement. Comparing probabilities for five landmark-distances, "maxillary incisors to the angle of the mandible" proved superior for proper sizing at 41.2% [95%-CI 32%-51.7%]. The best-fit formula was "22.43 + 17.54 × log(weight[kg])" with a probability of 61.7% [95%-CI 51.5%-70.9%]. CONCLUSION: Although the facial landmark-distance "maxillary incisors to the angle of the mandible" does not reliably predict oropharyngeal airway size, no clinical problems have been encountered. Since it can be considered the least inaccurate facial landmark-distance, it can serve as an approximation, but the efficacy of oropharyngeal airways should be evaluated clinically. REGISTERED CLINICAL TRIAL: German Clinical Trials Register; DRKS00025918.

Modeling iatrogenic intraoperative hyperthermia from external warming in children: A pooled analysis from two prospective observational studies.

BACKGROUND: Maintenance of normothermia is an important quality metric in pediatric anesthesia. While inadvertent hypothermia is effectively prevented by forced-air warming, this therapeutic approach can lead to iatrogenic hyperthermia in young children. AIMS: To estimate the influence of external warming by forced air on the development of intraoperative hyperthermia in anesthetized children aged 6 years or younger. METHODS: We pooled data from two previous clinical studies. Primary outcome was the course of core temperature over time analyzed by a quadratic regression model. Secondary outcomes were the incidence of hyperthermia (body core temperature >38°C), the probability of hyperthermia over the duration of warming in relation to age and surface-area-to-weight ratio, respectively, analyzed by multiple logistic regression models. The influence of baseline temperature on hyperthermia was estimated using a Cox proportional hazards model. RESULTS: Two hundred children (55 female) with a median age of 2.1 [1st -3rd quartile 1-4.2] years were analyzed. Mean temperature increased by 0.43°C after 1 h, 0.64°C after 2 h, and reached a peak of 0.66°C at 147 min. Overall, 33 children were hyperthermic at at least one measurement point. The odds ratios of hyperthermia were 1.14 (95%-CI: 1.07-1.22) or 1.13 (95%-CI: 1.06-1.21) for every 10 min of warming therapy in a model with age or surface-area-to weight ratio (ceteris paribus), respectively. Odds ratio was 1.33 (95%-CI: 1.07-1.71) for a decrease of 1 year in age and 1.63 (95%-CI: 0.93-2.83) for an increase of 0.01 in the surface-to-weight-area ratio (ceteris paribus). An increase of 0.1°C in baseline temperature increased the hazard of becoming hyperthermic by a factor of 1.33 (95%-CI: 1.23-1.43). CONCLUSIONS: In children, external warming by forced-air needs to be closely monitored and adjusted in a timely manner to avoid iatrogenic hyperthermia especially during long procedures, in young age, higher surface-area-to-weight ratio, and higher baseline temperature.

[Allocation of single-use drugs in children in global compassionate use programs]. / Allokation von einmalig zu applizierenden Arzneimitteln bei Kindern in globalen Compassionate Use-Programmen.

Definition of the problem: Compassionate use is the use of unapproved drugs in groups of patients suffering from a disease that, in the absence of an alternative treatment option, is life-threatening or leads to severe disability. Physicians are not in charge because access to the drug is only granted by pharmaceutical companies, which comes along with many ethical issues. Launched in 2020, the program of Onasemnogenum abeparvovecum against spinal muscular atrophy in children reached a new dimension. The intent of this drug is to stop the progression of the disease with just a single dose, but the company limited the doses in the program to only 100. The global allocation was by lottery, which was considered a novelty in compassionate use history and therefore widely criticized. This paper investigates alternative allocation principles. Arguments: Each possible principle is accompanied by many aspects that need to be considered with regard to urgency and global distribution. This makes some principles like first-come-first-served seem negligible. Remaining principles are ordered hierarchically to derive an algorithm that can represent an alternative to a lottery. A combination of willingness to participate in research, urgency, and likelihood of success (relative to the availability of supportive treatment options) may be considered in similar cases in future global compassionate use programs with children. Conclusion: Since universal algorithms are difficult to define, allocation criteria should always be discussed by an independent panel of experts. Both the constitution of such a panel and its mandatory consultation are necessary in order to decrease the burden for all those involved and to prevent arbitrariness.

Sex differences in appropriate insertion depth for intraosseous access in adults: An exploratory radiologic single-center study.

BACKGROUND: Intraosseous access is a recommended alternative to venous access in emergencies. For its application, knowledge of the correct insertion depth is indispensable. We aimed to determine sex-specific differences on the appropriate insertion depth for intraosseous access in adults at the insertion sites most frequently used, namely the proximal and distal tibia and the proximal humerus. METHODS: In this exploratory retrospective study, we measured thickness of soft tissue cover, cortex and cancellous bone along the puncture line on magnetic resonance images or computed tomography scans. Inclusion criteria were both sexes, 18-90 years of age and appropriate image quality. Primary outcome was the appropriate insertion depth to reach the cancellous bone for each sex. This was defined as the corridor between (i) the sum of the soft tissue cover and the cortex and (ii) the sum of (i) plus the diameter of the cancellous bone. Secondary outcomes were the differences in thickness of each layer between sexes. RESULTS: In 179 females and males, the appropriate insertion depth was 32.5-45.5 mm and 20.5-42.0 mm in the proximal tibia, 14.5-30.5 mm and 16.5-34.5 mm in the distal tibia, and 27.5-52.5 mm and 26.0-56.5 mm in the proximal humerus. Although females had a thicker soft tissue cover (+6.8 mm [95% CI 3.7-10.1], p < 0.01) in the proximal tibia, extrapolation by correlation analysis showed no clinically relevant difference between the sexes. CONCLUSION: In adults, there are no sex-specific differences in the appropriate insertion depth for intraosseous access in the proximal or distal tibia or in the proximal humerus.

Target insertion depth of nasopharyngeal temperature probes in children: A prospective observational study analyzing magnetic resonance images.

BACKGROUND: Core temperature monitoring is indispensable to prevent children from perioperative thermal perturbations. Although nasopharyngeal measurements are commonly used in anesthesia and considered to reflect core temperature accurately, standardized target depths for probe insertion are unknown in children. AIMS: Our primary goal was to determine a target depth of nasopharyngeal temperature probe insertion in children by measuring distances on magnetic resonance imaging (MRI). Secondary aims were to correlate these measurements with biometric variables and facial landmark-distances to derive formulas estimating target depth. METHODS: We conducted a prospective observational study in children ≤12 years undergoing cranial MRI with anesthesia. We documented patient characteristics and measured the landmark-distances nostril-mandible, nostril-tragus, and philtrum-tragus on patient's faces. On MRI, the target point for the probe tip was considered to be the site of the nasopharyngeal mucosa with the closest proximity to the internal carotid artery. After its determination in the transverse axis and triangulation to the sagittal axis, we measured the distance to the nostril. This distance, defined as target insertion depth, was correlated with the patient characteristics and used for univariate and multiple linear regression analysis. RESULTS: One hundred twenty children with a mean age of 4.5 years were included. The target insertion depth ranged from 61.8 mm in infants to 89.8 mm in 12-year-old children. Height correlated best (ρ = 0.685, 95%-CI: [0.57-0.77]). The best-fit estimation in millimeters, "40.8 + height [cm] × 0.32,″ would lead to a placement in the target position in 67% of cases. A simplified approach by categories of 50-80, 80-110, 110-130, and >130 cm height with target insertion depths of 60, 70, 80, and 85 mm, respectively, achieved similar probabilities. CONCLUSIONS: Height-based formulas could be a valuable proxy for the insertion depth of nasopharyngeal temperature probes. Further clinical trials are necessary to investigate their measurement accuracy.

Working with estimation-formulas to predict nasopharyngeal airway insertion depth in children: Looking at magnetic resonance images - A prospective observational study (WEND:LI-Study).

OBJECTIVE: To determine the accuracy of the recently proposed landmark-method 'nostril-to-tragus minus 10 mm' and compare with ERC-recommended distances for nasopharyngeal airway length sizing in children. METHOD: We conducted a prospective observational study in sedated children < 12 years. Nasopharyngeal airways were inserted following 'nostril-to-tragus minus 10 mm'. Primary outcome was the rate of nasopharyngeal airway tips between soft palate and epiglottis on magnetic resonance imaging (MRI) indicated for medical reasons. An optimal placement was defined when the tip lied within 25-75% of the total soft palate-to-epiglottis distance. Between 0-100% of this distance, placement was still considered acceptable, below 0% too proximal or above 100% too distal. Secondary outcomes were the rate of adverse events, the qualitative positions of airway tips, and the comparison of ́nostril-to-tragus minus 10 mm with the ERC-recommended distances 'nostril-to-angle of the mandible' and 'nostril-to-tragus' with objective MRI measurements. RESULTS: We analysed 92 patients with a mean age of 4.3 years. Nasopharyngeal airways were optimally placed in 37.0% (8.7% too proximal-77.2% acceptable-14.1% too distal). Three qualitative malpositions, but no airway-associated adverse event occurred. Objective measurements on MRI revealed the probability of 40.2% optimally placed nasopharyngeal airways (5.4%-67.4%-27.2%) for 'nostril-to-tragus minus 10 mm', 38.0% (17.4%-58.7%-23.9%) for 'nostril-to-mandible' and 13.0% (0%-28.3%-71.7%) for 'nostril-to-tragus', respectively. CONCLUSION: No landmark-method predicted nasopharyngeal airway position reliably. 'Nostril-to-tragus minus 10 mm' seems the least inaccurate one and could be a valuable approximation until another estimation-formula proves more accurate. During insertion, careful clinical evaluation of airway patency is crucial. REGISTERED CLINICAL TRIAL: German Clinical Trials Register; DRKS00021007.

Perioperative Hypothermia-A Narrative Review.

Unintentional hypothermia (core temperature < 36 °C) is a common side effect in patients undergoing surgery. Several patient-centred and external factors, e.g., drugs, comorbidities, trauma, environmental temperature, type of anaesthesia, as well as extent and duration of surgery, influence core temperature. Perioperative hypothermia has negative effects on coagulation, blood loss and transfusion requirements, metabolization of drugs, surgical site infections, and discharge from the post-anaesthesia care unit. Therefore, active temperature management is required in the pre-, intra-, and postoperative period to diminish the risks of perioperative hypothermia. Temperature measurement should be done with accurate and continuous probes. Perioperative temperature management includes a bundle of warming tools adapted to individual needs and local circumstances. Warming blankets and mattresses as well as the administration of properly warmed infusions via dedicated devices are important for this purpose. Temperature management should follow checklists and be individualized to the patient's requirements and the local possibilities.

Perioperative Hypothermia in Children.

BACKGROUND: First described by paediatric anaesthesiologists, perioperative hypothermia is one of the earliest reported side effects of general anaesthesia. Deviations from normothermia are associated with numerous complications and adverse outcomes, with infants and small children at the highest risk. Nowadays, maintenance of normothermia is an important quality metric in paediatric anaesthesia. METHODS: This review is based on our collection of publications regarding perioperative hypothermia and was supplemented with pertinent publications from a MEDLINE literature search. RESULTS: We provide an overview on perioperative hypothermia in the paediatric patient, including definition, history, incidence, development, monitoring, risk factors, and adverse events, and provide management recommendations for its prevention. We also summarize the side effects and complications of perioperative temperature management. CONCLUSIONS: Perioperative hypothermia is still common in paediatric patients and may be attributed to their vulnerable physiology, but also may result from insufficient perioperative warming. An effective perioperative warming strategy incorporates the maintenance of normothermia during transportation, active warming before induction of anaesthesia, active warming during anaesthesia and surgery, and accurate measurement of core temperature. Perioperative temperature management must also prevent hyperthermia in children.

Intraoperative zero-heat-flux thermometry overestimates esophageal temperature by 0.26 °C: an observational study in 100 infants and young children.

In pediatric anesthesia, deviations from normothermia can lead to many complications, with infants and young children at the highest risk. A measurement method for core temperature must be clinically accurate, precise and should be minimally invasive. Zero-heat-flux (ZHF) temperature measurements have been evaluated in several studies in adults. We assessed the agreement between the 3M Bair Hugger™ temperature measurement sensor (TZHF) and esophageal temperature (TEso) in children up to and including 6 years undergoing surgery with general anesthesia. Data were recorded in 5 min-intervals. We investigated the accuracy of the ZHF sensor overall and in subgroups of different age, ASA classification, and temperature ranges by Bland-Altman comparisons of differences with multiple measurements. Change over time was assessed by a linear mixed model regression. Data were collected in 100 children with a median (1st-3rd quartile) age of 1.7 (1-3.9) years resulting in 1254 data pairs. Compared to TEso (range from 35.3 to 39.3 °C; median 37.2 °C), TZHF resulted in a mean bias of +0.26 °C (95% confidence interval +0.22 to +0.29 °C; 95% limits of agreement -0.11 to +0.62 °C). Lin's concordance correlation coefficient was 0.89. There was no significant or relevant change of temperature over time (0.006 °C per hour measurement interval, p = 0.199) and no relevant differences in the subgroups. Due to the mean bias of +0.26 °C in TZHF, the risk of hypothermia may be underestimated, while the risk of hyperthermia may be overestimated. Nevertheless, because of its high precision, we consider ZHF valuable for intraoperative temperature monitoring in children and infants.