Genetic variants in eleven central and peripheral chemoreceptor genes in sudden infant death syndrome.

BACKGROUND: Sudden infant death syndrome (SIDS) is still one of the leading causes of postnatal infant death in developed countries. The occurrence of SIDS is described by a multifactorial etiology that involves the respiratory control system including chemoreception. It is still unclear whether genetic variants in genes involved in respiratory chemoreception might play a role in SIDS. METHODS: The exome data of 155 SIDS cases were screened for variants within 11 genes described in chemoreception. Pathogenicity of variants was assigned based on the assessment of variant types and in silico protein predictions according to the current recommendations of the American College of Medical Genetics and Genomics. RESULTS: Potential pathogenic variants in genes encoding proteins involved in respiratory chemoreception could be identified in 5 (3%) SIDS cases. Two of the variants (R137S/A188S) were found in the KNCJ16 gene, which encodes for the potassium channel Kir5.1, presumably involved in central chemoreception. Electrophysiologic analysis of these KCNJ16 variants revealed a loss-of-function for the R137S variant but no obvious impairment for the A188S variant. CONCLUSIONS: Genetic variants in genes involved in respiratory chemoreception may be a risk factor in a fraction of SIDS cases and may thereby contribute to the multifactorial etiology of SIDS. IMPACT: What is the key message of your article? Gene variants encoding proteins involved in respiratory chemoreception may play a role in a minority of SIDS cases. What does it add to the existing literature? Although impaired respiratory chemoreception has been suggested as an important risk factor for SIDS, genetic variants in single genes seem to play a minor role. What is the impact? This study supports previous findings, which indicate that genetic variants in single genes involved in respiratory control do not have a dominant role in SIDS.

Cuffed versus uncuffed tracheal tubes in a rabbit training model for establishing an emergency front-of-neck airway in infants: a prospective trial.

BACKGROUND: There is a paucity of evidence regarding the optimal type of tracheal tube to be advanced over a Frova catheter when performing a 'bougie' emergency front-of-neck airway (eFONA) technique in infants during a 'cannot intubate, cannot oxygenate' situation. METHODS: A prospective non-inferiority trial in a rabbit cadaver surgical tracheotomy model to assess the performance of the eFONA technique with an uncuffed 3.5 mm ID tracheal tube vs a cuffed 3.0 mm ID tracheal tube. Queried outcomes include success rate, performance time, and severe secondary airway injuries among tracheal tube types. RESULTS: In 60 tracheostomies performed by 30 participants, the overall success rate was 98%. Performance time was independent from tracheal tube choice (uncuffed: 61 s [95% confidence interval (CI), 52-76], cuffed: 64 s [95% CI, 55-79]; P = 0.82). No tracheal tube type was preferred in terms of usability by participants. The cuffed tracheal tube required increased force to be advanced over the Frova catheter and was associated with a risk ratio of 2.5 (95% CI, 0.53-11.9; number needed to harm, 10) for severe secondary airway injuries when compared with the uncuffed tracheal tube. CONCLUSION: In performing eFONA in the rabbit cadaver model, an ID 3.5 uncuffed is non-inferior to an ID 3.0 cuffed tracheal tube regarding performance time and preference by the operator. Greater force application to advance the cuffed tube over the Frova catheter and more severe airway injuries may argue for the standardised performance of the eFONA technique with a uncuffed tracheal tube in infants.

Dimensional compatibility of currently available equipment for cricothyroidotomy and adult airway anatomy: an in vitro analysis.

BACKGROUND: There are scant data on the dimensional compatibility of cricothyroidotomy equipment and related airway anatomy. We compared the dimensional design of devices for cricothyroidotomy with anatomical airway data for adult patients. METHODS: For all available cricothyroidotomy equipment the outer diameter was recorded from manufacturer information or, if not available, measured using a sliding calliper. Outer diameters were compared with recently published mean (standard deviation [sd]) values for the height of the cricothyroid membrane obtained from computed tomography, separately for males (7.9 [2.2] mm) and for females (5.9 [1.7] mm). RESULTS: Twenty-one cricothyroidotomy sets (10 uncuffed, 11 cuffed) with 15 differently designed devices were included. Inner diameters of the tubes ranged from 3.5 to 6.0 mm and outer diameters from 5.0 to 11.7 mm. The outer diameter of the 15 different tubes was found to be greater than the mean membrane height of the adult male cricothyroid membrane in eight devices and greater than the mean membrane height for female adults in 10 devices. Considering the lower range of cricothyroid membrane height, 12 tube outer diameters would be too large for male adults and all 15 for female adults in this range. CONCLUSION: The outer diameter of many devices currently marketed for cricothyroidotomy are oversized for adult airway anatomy, particularly for females. For emergency front-of-neck access through the cricothyroid membrane, anatomical data suggest that cricothyroidotomy devices with outer tube diameters of <7 mm for male and <6 mm for female adult patients should be preferred.

Rabbit training model for establishing an emergency front of neck airway in children.

BACKGROUND: A 'cannot intubate, cannot oxygenate' (CICO) situation is rare in paediatric anaesthesia, but can always occur in children under certain emergency situations. There is a paucity of literature on specific procedures for securing an emergency invasive airway in children younger than 6 yr. A modified emergency front of neck access (eFONA) technique using a rabbit cadaver model was developed to teach invasive airway protection in a CICO situation in children. METHODS: After watching an instructional video of our eFONA technique (tracheotomy, intubation with Frova catheter over which a tracheal tube is inserted), 29 anaesthesiologists performed two separate attempts on rabbit cadavers. The primary outcome was the success rate and the performance time overall and in subgroups of trained and untrained participants. RESULTS: The overall success rate across 58 tracheotomies was 95% and the median performance time was 67 s (95% confidence interval [CI], 56-76). Performance time decreased from the first to the second attempt from 72 s (95% CI, 57-81) to 61 s (95% CI, 50-81). Performance time was 59 s (95% CI, 49-79) for untrained participants and 72 s (95% CI, 62-81) for trained participants. Clinical experience and age of the participants was not correlated with performance time, whereas the length of the tracheotomy incision showed a significant correlation (P=0.006). CONCLUSION: This eFONA training model for children facilitates rapid skill acquisition under realistic anatomical conditions to perform an emergency invasive airway in children younger than 2 yr.

How Accurate Are Pediatric Emergency Tapes? A Comparison of 4 Emergency Tapes With Different Length-Based Weight Categorization.

OBJECTIVE: Pediatric emergency tapes have been developed to support paramedics and emergency physicians when dosing drugs and selecting medical equipment in pediatric emergency situations. The aim of this study was to compare the accuracy of 4 pediatric emergency tapes to correctly estimate patient's weight based on a large population of patients. METHODS: Patients undergoing general anesthesia between January 2012 and March 2015 with documented age, sex, body weight, and length were identified from the electronic anesthesia patient data management system of the Department of Anaesthesia, University Children's Hospital, Zurich, Switzerland. Weight estimation by means of the Broselow-Tape, the Pädiatrisches Notfalllineal, the Paulino System, and the Kinder-Sicher were compared with true patient's weight. Percentages of estimated body weight within a ±10% and ±20% interval were calculated. Data are median (interquartile range) or count (percent); statistical calculations were done with McNemar and Bonferroni correction. RESULTS: A total of 3307 patients were identified with complete data sets, 1930 (58.4%) were male, median age was 4.1 years (1.1-8.2 years), median length 101.0 cm (74.0-126.0 cm) and median patient weight 15.8 kg (9.2-25.0 kg). The proportion weight estimation within the ±10% and the ±20% interval was the highest in the Broselow-Tape with 54.0% and 81.5% (P < 0.001 and P = 0.003), followed by the Pädiatrisches Notfalllineal (50.5% and 79.8%), Paulino System (49.9% and 78.0%) and Kinder-Sicher (48.2% and 77.5%). CONCLUSIONS: The overall accuracy of all 4 emergency tapes tested is poor and including a larger number of weight categories does not necessarily increase accuracy. Other strategies have to be developed to improve weight estimation in pediatric emergency situations.

Frequency distribution of modified Cormack-Lehane views-A retrospective audit of tracheal intubation in children with normal airways.

BACKGROUND: Paediatric patients with an unanticipated poor grade of laryngoscopic view during tracheal intubation represent a challenging situation potentially associated with increased morbidity and mortality. The aim of this study was to investigate the frequency of modified Cormack-Lehane (MCL) views and to elucidate variables for poor views in a large collective of children without anticipated airway difficulties. METHODS: The departmental anaesthesia patient database was searched for patients who had undergone general anaesthesia with tracheal intubation between January 2007 and March 2017. Inclusion criteria were age from birth to 17.99 years, general anaesthesia with tracheal intubation using direct laryngoscopy, no history, symptoms or signs of a difficult airway and the best obtained MCL view documented in the database. Patient- and anaesthesia-related variables associated with a poor view (MCL IIb, III and IV) were elucidated using a logistic regression model. RESULTS: In all, 22 965 patients were included; of these, 17 593 were observed only once. The prevalence of the first observed MCL views I, IIa, IIb, III and IV was 90.6%, 8.5%, 0.86%, 0.05% and 0%, respectively. The logistic regression model indicates that age and gender are the most important variables associated with MCL views IIb and III in the model. The probability for MCL views IIb/III decreases across the first 5-7 years before increasing again. CONCLUSIONS: The incidence of a poor grade of laryngoscopic view was found to be very low in children with a normal airway. They mainly occurred in infants and adolescent patients and were more common in male patients.

Neurological excitation in a 6-week-old male infant after morphine overdose.

While respiratory depression is a known complication of morphine overdose, the neuro-excitatory side effect of the morphine metabolite morphine-3-glucuronide is less widely known. Here, we report the case of an infant with neurological excitation after morphine overdose. The neuro-excitation in this infant was probably induced by an elevated morphine-3-glucuronide concentration.

Pediatric airway dimensions-A summary and presentation of existing data.

BACKGROUND: Age-related pediatric airway dimension reference values for cricoid, tracheal, and bronchial diameters as well as tracheal and bronchial lengths are essential for distinguishing normal from pathological airway findings and for manufacturing and selecting appropriately sized airway equipment. AIM: The aim of this work was to summarize and present existing pediatric airway dimension data for the larynx, trachea, and main stem bronchi from fetus to adolescence. METHODS: A systematic literature search was carried out using PubMed, Scopus, Embase, and Google Scholar. Publications containing original data on pediatric airway dimensions as mean or median in tabular form and spanning narrow age groups of 1 or 2 years were included in our study. Original data such as diameters, lengths, and cross-sectional areas of trachea, cricoid, left and right main bronchi in fetuses and children were collected and presented as figures. RESULTS: Pediatric airway dimension data were gathered and compiled from 15 studies fulfilling the inclusion criteria. Data were obtained from different measurement methods such as autopsy, chest X-ray, computed tomography, magnetic resonance imaging, rigid and flexible bronchoscopy as well as ultrasound examinations. There was considerable variation among age-related data due to biologic heterogeneity, different presentation of data, different definitions, and various measurement techniques. CONCLUSION: This investigation revealed heterogeneous data on pediatric airway dimensions, making it impossible to compile them into standard reference values for airway dimensions. New studies with structured and standardized measurements and data presentation in large populations of children are required to provide more valid pediatric airway dimension data.

Factors associated with intravenous lidocaine in pediatric patients undergoing laparoscopic appendectomy - a retrospective, single-centre experience.

BACKGROUND: Due to its potential beneficial effects, intra- and postoperative application of intravenous lidocaine has become increasingly accepted over the last couple of years, e.g. in patients undergoing laparoscopic surgical procedures. Based on its beneficial properties, lidocaine was introduced to the standard of care for all pediatric laparoscopic procedures in our institution in mid-2016. In contrast to adult care, scarce data is available regarding the use of perioperative intravenous lidocaine administration in children undergoing laparoscopic procedures, such as an appendectomy. METHODS: Retrospective analysis of all pediatric patients undergoing laparoscopic appendectomy at the University Children's Hospital Zurich in 2016. Perioperative data, as recorded in the electronic patient data management system, were evaluated for any signs of systemic lidocaine toxicity (neurological and cardiovascular), behavioral deterioration, as well as for hemodynamic instability. Additionally, the incidence of postoperative nausea and vomiting, administration of pain rescue medication, time to hospital discharge and to first bowel movement, as well as any postoperative complications were recorded. Starting on 01/07/2016, all patients undergoing laparoscopic surgery received intravenous lidocaine (1.5 mg/kg body weight (BW) bolus after induction of anesthesia followed by continuous infusion of 1.5 mg/kgBW/h). These patients were then compared to children without lidocaine administration who had undergone laparoscopic appendectomy between 01/01/2016 and 30/06/2016. RESULTS: Data of 116 patients was analyzed. Of these, 60 patients received lidocaine. No signs of systemic toxicity, neurologic impairment or circulatory disturbances were noted in any of these patients. A (non-significant) difference in the incidence of emergence delirium was observed (0 cases in the lidocaine group vs. 4 cases in the control group, p = 0.05). CONCLUSION: This retrospective analysis did not reveal any adverse effects in pediatric patients receiving intravenous lidocaine for laparoscopic appendectomy under general anesthesia. However, further trials investigating beneficial effects as well as pharmacokinetic properties of intravenous lidocaine in children are required.

Work of breathing for cuffed and uncuffed pediatric endotracheal tubes in an in vitro lung model setting.

BACKGROUND: Over the last decade, cuffed endotracheal tubes are increasingly used in pediatric anesthesia and also in pediatric intensive care. However, the smaller inner diameter of cuffed endotracheal tubes and, implicitly, the increased endotracheal tube resistance is still a matter of debate. AIMS: This in vitro study investigated work of breathing and inspiratory airway pressures in cuffed and uncuffed endotracheal tubes and the impact of pressure support ventilation and automatic tube compensation. METHODS: In 5 simulated neonatal and pediatric lung models, the Active Servo Lung 5000 and an intensive care ventilator were used to quantify the differences in work of breathing under spontaneous breathing (with and without pressure support ventilation and automatic tube compensation) between cuffed and uncuffed endotracheal tubes. Additionally, differences in inspiratory airway pressures, measured either proximal or distal of the endotracheal tube, between cuffed and uncuffed endotracheal tubes under mechanical ventilation were investigated. RESULTS: Work of breathing was overall 10.27% [95% confidence interval 9.01-11.94] higher with cuffed than with uncuffed endotracheal tubes and was dramatically reduced by 34.19% [95% confidence interval 31.61-35.25] with the application of pressure support. Automatic tube compensation almost diminished work of breathing differences between the 2 endotracheal tube types in nearly all pediatric lung models. Peak inspiratory and mean airway pressures measured at the proximal endotracheal tube end revealed significantly higher values in cuffed than in uncuffed endotracheal tubes. However, these differences measured at the distal end of the endotracheal tube became minimal. CONCLUSION: This in vitro study confirmed significant differences in work of breathing and inspiratory pressures between cuffed and uncuffed endotracheal tubes. Work of breathing, however, is almost neutralized by pressure support ventilation with automatic tube compensation and distal inspiratory airway pressures that, from a clinical perspective, are not significantly increased.

Favourable neurological outcome following paediatric out-of-hospital cardiac arrest: a retrospective observational study.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) in children is rare and can potentially result in severe neurological impairment. Our study aimed to identify characteristics of and factors associated with favourable neurological outcome following the resuscitation of children by the Swiss helicopter emergency medical service. MATERIALS AND METHODS: This retrospective observational study screened the Swiss Air-Ambulance electronic database from 01-01-2011 to 31-12-2021. We included all primary missions for patients ≤ 16 years with OHCA. The primary outcome was favourable neurological outcome after 30 days (cerebral performance categories (CPC) 1 and 2). Multivariable linear regression identified potential factors associated with favourable outcome (odd ratio - OR). RESULTS: Having screened 110,331 missions, we identified 296 children with OHCA, which we included in the analysis. Patients were 5.0 [1.0; 12.0] years old and 61.5% (n = 182) male. More than two-thirds had a non-traumatic OHCA (67.2%, n = 199), while 32.8% (n = 97) had a traumatic OHCA. Thirty days after the event, 24.0% (n = 71) of patients were alive, 18.9% (n = 56) with a favourable neurological outcome (CPC 1 n = 46, CPC 2 n = 10). Bystander cardiopulmonary resuscitation (OR 10.34; 95%CI 2.29-51.42; p = 0.002) and non-traumatic aetiology (OR 11.07 2.38-51.42; p = 0.002) were the factors most strongly associated with favourable outcome. Factors associated with an unfavourable neurological outcome were initial asystole (OR 0.12; 95%CI 0.04-0.39; p < 0.001), administration of adrenaline (OR 0.14; 95%CI 0.05-0.39; p < 0.001) and ongoing chest compression at HEMS arrival (OR 0.17; 95%CI 0.04-0.65; p = 0.010). CONCLUSION: In this study, 18.9% of paediatric OHCA patients survived with a favourable neurologic outcome 30 days after treatment by the Swiss helicopter emergency medical service. Immediate bystander cardiopulmonary resuscitation and non-traumatic OHCA aetiology were the factors most strongly associated with a favourable neurological outcome. These results underline the importance of effective bystander and first-responder rescue as the foundation for subsequent professional treatment of children in cardiac arrest.

Perioperative targeted temperature management of severely burned patients by means of an oesophageal temperature probe.

BACKGROUND: Hypothermia in severely burned patients is associated with a significant increase in morbidity and mortality. The use of an oesophageal heat exchanger tube (EHT) can improve perioperative body temperatures in severely burned patients. The aim of this study was to investigate the intraoperative warming effect of oesophageal heat transfer in severe burn patients. METHODS: Single-centre retrospective study performed at the Burns Centre of the University Hospital Zurich. Between January 2020 and May 2021 perioperative temperature management with EHT was explored in burned patients with a total body surface area (TBSA) larger than 30%. Data from patients, who received perioperative temperature management by EHT, were compared to data from the same patients during interventions performed under standard temperature management matching for length and type of intervention. RESULTS: A total of 30 interventions (15 with and 15 without EHT) in 10 patients were analysed. Patient were 38 [26-48] years of age, presented with severe burns covering a median of 50 [42-64] % TBSA and were characterized by an ABSI of 10 [8-12] points. When receiving EHT management patients experienced warming at 0.07 °C per minute (4.2 °C/h) compared to a temperature loss of - 0.03 °C per minute (1.8 °C/h) when only receiving standard temperature management (p < 0.0001). No adverse or serious adverse events were reported. CONCLUSION: The use of an oesophageal heat transfer device was effective and safe in providing perioperative warming to severely burned patients when compared to a standard temperature management protocol. By employing an EHT as primary temperature management device perioperative hypothermia in severely burned patients can possibly be averted, potentially leading to reduced hypothermia-associated complications.

Association between Intraoperative Blood Transfusion, Regional Anesthesia and Outcome after Pediatric Tumor Surgery for Nephroblastoma.

BACKGROUND: Recent data suggest that anesthesiologic interventions-e.g., the choice of the anesthetic regimen or the administration of blood products-might play a major role in determining outcome after tumor surgery. In contrast to adult patients, only limited data are available regarding the potential association of anesthesia and outcome in pediatric cancer patients. METHODS: A retrospective multicenter study assessing data from pediatric patients (0-18 years of age) undergoing surgery for nephroblastoma between 2004 and 2018 was conducted at three academic centers in Europe. Overall and recurrence-free survival were the primary outcomes of the study and were evaluated for a potential impact of intraoperative administration of erythrocyte concentrates, the use of regional anesthesia and the choice of the anesthetic regimen. The length of stay on the intensive care unit, the time to hospital discharge after surgery and blood neutrophil-to-lymphocyte ratio were defined as secondary outcomes. RESULTS: In total, data from 65 patients were analyzed. Intraoperative administration of erythrocyte concentrates was associated with a reduction in recurrence-free survival (hazard ratio (HR) 7.59, 95% confidence interval (CI) 1.36-42.2, p = 0.004), whereas overall survival (HR 5.37, 95% CI 0.42-68.4, p = 0.124) was not affected. The use of regional anesthesia and the choice of anesthetic used for maintenance of anesthesia did not demonstrate an effect on the primary outcomes. It was, however, associated with fewer ICU transfers, a shortened time to discharge and a decreased postoperative neutrophil-to-lymphocyte ratio. CONCLUSIONS: The current study provides the first evidence for a possible association between blood transfusion as well as anesthesiologic interventions and outcome after pediatric cancer surgery.

More Than 500 Kids Could Be Saved Each Year! Ten Consensus Actions to Improve Quality of Pediatric Resuscitation in DACH-Countries (Austria, Germany, and Switzerland).

• Quality and outcome of pediatric resuscitation often does not achieve recommended goals. • Quality improvement initiatives with the aim of better survival rates and decreased morbidity of resuscitated children are urgently needed. • These initiatives should include an action framework for a comprehensive, fundamental, and interprofessional reorientation of clinical and organizational structures concerning resuscitation and post-resuscitation care of children. • The authors of this DACH position statement suggest the implementation of 10 evidence-based actions (for out-of-hospital and in-house cardiac arrests) that should improve survival rates and decrease morbidity of resuscitated children with better neurological outcome and quality of life.

Abnormal respiration under hyperoxia in TASK-1/3 potassium channel double knockout mice.

Despite intensive research, the exact function of TASK potassium channels in central and peripheral chemoreception is still under debate. In this study, we investigated the respiration of unrestrained TASK-3 (TASK-3-/-) and TASK-1/TASK-3 double knockout (TASK-1/3-/-) adult male mice in vivo using a plethysmographic device. Ventilation parameters of TASK-3-/- mice were normal under control condition (21% O2) and upon hypoxia and hypercapnia they displayed the physiological increase of ventilation. TASK-1/3-/- mice showed increased ventilation under control conditions. This increase of ventilation was caused by increased tidal volumes (VT), a phenomenon similarly observed in TASK-1-/- mice. Under acute hypoxia, TASK-1/3-/- mice displayed the physiological increase of the minute volume. Interestingly, this increase was not related to an increase of the respiratory frequency (fR), as observed in wild-type mice, but was caused by a strong increase of VT. This particular respiratory phenotype is reminiscent of the respiratory phenotype of carotid body-denervated rodents in the compensated state. Acute hypercapnia (5% CO2) stimulated ventilation in TASK-1/3-/- and wild-type mice to a similar extent; however, at higher CO2 concentrations (>5% CO2) the stimulation of ventilation was more pronounced in TASK-1/3-/- mice. At hyperoxia (100% O2), TASK-1-/-, TASK-3-/- and wild-type mice showed the physiological small decrease of ventilation. In sharp contrast, TASK-1/3-/- mice exhibited an abnormal increase of ventilation under hyperoxia. In summary, these measurements showed a grossly normal respiration of TASK-3-/- mice and a respiratory phenotype of TASK-1/3-/- mice that was characterized by a markedly enhanced tidal volume, similar to the one observed in TASK-1-/- mice. The abnormal hyperoxia response, exclusively found in TASK-1/3-/- double mutant mice, indicates that both TASK-1 and TASK-3 are essential for the hyperoxia-induced hypoventilation. The peculiar respiratory phenotype of TASK-1/3 knockout mice is reminiscent of the respiration of animals with long-term carotid body dysfunction. Taken together, TASK-1 and TASK-3 appear to serve specific and distinct roles in the complex processes underlying chemoreception and respiratory control.