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Background: Apnea is common in preterm infants and can be accompanied with severe hypoxic damage. Early assessment of apnea risk can impact the prognosis of preterm infants. We constructed a prediction model to assess apnea risk in premature infants for identifying high-risk groups., Methods: A total of 162 and 324 preterm infants with and without apnea who were admitted to the neonatal intensive care unit of Xiamen University between January 2018 and December 2021 were selected as the case and control groups, respectively. Demographic characteristics, laboratory indicators, complications of the patients, pregnancy-related factors, and perinatal risk factors of the mother were collected retrospectively. The participants were randomly divided into modeling (n = 388) and validation (n = 98) sets in an 8:2 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate logistic regression analyses were used to independently filter variables from the modeling set and build a model. A nomogram was used to visualize models. The calibration and clinical utility of the model was evaluated using consistency index, receiver operating characteristic (ROC) curve, calibration curve, and decision curve, and the model was verified using the validation set., Results: Results of LASSO combined with multivariate logistic regression analysis showed that gestational age at birth, birth length, Apgar score, and neonatal respiratory distress syndrome were predictors of apnea development in preterm infants. The model was presented as a nomogram and the Hosmer-Lemeshow goodness of fit test showed a good model fit (χ 2 =5.192, df=8, P=0.737), with Nagelkerke R 2 of 0.410 and C-index of 0.831. The area under the ROC curve and 95% CI were 0.831 (0.787-0.874) and 0.829 (0.722-0.935), respectively. Delong's test comparing the AUC of the two data sets showed no significant difference (P=0.976). The calibration curve showed good agreement between the predicted and actual observations. The decision curve results showed that the threshold probability range of the model was 0.07-1.00, the net benefit was high, and the constructed clinical prediction model had clinical utility., Conclusions: Our risk prediction model based on gestational age, birth length, Apgar score 10 min post-birth, and neonatal respiratory distress syndrome was validated in many aspects and had good predictive efficacy and clinical utility., (© 2024. The Author(s).)

Objective: This study aimed to establish which anesthetic agents are associated with minimized adverse outcomes during laryngeal mask airway (LMA) insertion., Methods: Databases were searched for randomized controlled trials (RCTs) with American Society of Anesthesiologists I or II adult patients (≥15 years of age) receiving general anesthesia (GA) with an LMA. Propofol only was the comparator to other anesthetics used during LMA insertion. The primary outcome was prolonged apnea, and secondary outcomes were adverse airway events, LMA insertion failure, inadequate depth of anesthesia, and hemodynamic events. A network meta-analysis was conducted to estimate the treatment effects (odds ratios, 95% credible intervals, and surface under the cumulative ranking curve [SUCRA])., Results: A total of 28 anesthetic combinations used on 4695 patients for GA induction and LMA insertion were examined across 53 RCTs. Overall, there was an apnea incidence rate of 33.3% (849 of 2548) with a mean time of 3.74 ± 3.56 minutes (n = 3091). Propofol + dexmedetomidine had the highest overall summed score of SUCRA ranks in reducing adverse outcomes (apnea incidence: SUCRA = 37%, apnea time: SUCRA = 66%, airway adverse event: SUCRA = 67%, insertion failure: SUCRA = 73%, inadequate depth of anesthesia: SUCRA = 84%). In comparison among all propofol combinations, propofol alone ranked lowest for overall summed score of SUCRA in reducing adverse outcomes (apnea incidence: SUCRA = 47%, apnea time: SUCRA = 71%, airway adverse event: SUCRA = 9%, insertion failure: SUCRA = 20%, inadequate depth of anesthesia: SUCRA = 9%)., Conclusion: All anesthetic combinations, other than those with thiopental, reduced adverse outcomes as compared with propofol alone. The combination of propofol and dexmedetomidine infused over 10 minutes ranked as the most effective for reducing adverse outcomes during LMA insertion.

Objective: This study aimed to systematically analyze the existing literature and conduct a meta-analysis on the acute effects of apnea on the hematological response by assessing changes in hemoglobin (Hb) concentration and hematocrit (Hct) values., Methods: Searches in Pubmed, The Cochrane Library, and Web of Science were carried out for studies in which the main intervention was voluntary hypoventilation, and Hb and Hct values were measured. Risk of bias and quality assessments were performed., Results: Nine studies with data from 160 participants were included, involving both subjects experienced in breath-hold sports and physically active subjects unrelated to breath-holding activities. The GRADE scale showed a "high" confidence for Hb concentration, with a mean absolute effect of 0.57 g/dL over control interventions. "Moderate" confidence appeared for Hct, where the mean absolute effect was 2.45% higher over control interventions. Hb concentration increased to a greater extent in the apnea group compared to the control group (MD = 0.57 g/dL [95% CI 0.28, 0.86], Z = 3.81, p = 0.0001) as occurred with Hct (MD = 2.45% [95% CI 0.98, 3.93], Z = 3.26, p = 0.001)., Conclusions: Apnea bouts lead to a significant increase in the concentration of Hb and Hct with a high and moderate quality of evidence, respectively. Further trials on apnea and its application to different settings are needed., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

This study aimed to investigate what factors determine freedivers' maximal static apnea dive time. We correlated some physical/physiological factors with male freedivers' maximum apnea diving duration. Thirty-six experienced male freedivers participated in this study. The divers participated in two days of the experiments. On the first day, apnea diving time, blood oxygen saturation (SpO 2 ), heart rate (HR), blood pressure (BP), stress index, and blood parameters were measured before, during, and after the apnea diving in the pool. On the second day, body composition, lung capacity, resting and maximal oxygen consumption (VO 2 max), and the Wingate anaerobic power were measured in the laboratory. The data were analyzed with Pearson's Correlation using the SPSS 22 program. The correlation coefficient (R) of determination was set at 0.4, and the level of significance was set at p <0.05. There were positive correlations of diving experience, maximum SpO 2 , and lung capacity with the maximum apnea time R>0.4, P<0.05). There were negative correlations of BMI, body fat percentage, body fat mass, minimum SpO 2 , stress index, and total cholesterol with the maximum apnea diving time (R>-0.4, P<0.05). No correlations of age, height, weight, fat-free mass, skeletal muscle mass, HR, BP, blood glucose, beta- hydroxybutyrate, lactate, and hemoglobin levels with the maximum apnea diving time were observed (R<0.4, P>0.05). It is concluded that more experience in freediving, reduced body fat, extended SpO 2 range, and increased lung capacity are the performance predictors and beneficial for freedivers to improve their maximum apnea diving performance., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Background: During stabilisation of preterm infants at birth, a face mask is used to provide respiratory support. However, application of these masks may activate cutaneous stretch receptors of the trigeminal nerve, causing apnoea and bradycardia. This study investigated the amount of force exerted on the face mask during non-invasive ventilation of preterm infants at birth and whether the amount of exerted force is associated with apnoea and bradycardia., Methods: A prospective observational study was performed in preterm infants born <32 weeks of gestation who were stabilised at birth. During the first 10 minutes of respiratory support, we measured breathing and heart rate as well as the amount of force exerted on a face mask using a custom-made pressure sensor placed on top of the face mask., Results: Thirty infants were included (median (IQR) gestational age(GA) 28 +3 (27 +0 -30 +0 ) weeks, birthweight 1104 (878-1275) grams). The median exerted force measured was 297 (198-377) grams, ranging from 0 to 1455 grams. Significantly more force was exerted on the face mask during positive pressure ventilation when compared to CPAP (410 (256-556) vs 286 (190-373) grams, p = 0.009). In a binary logistic regression model, higher forces were associated with an increased risk of apnoea (OR = 1.607 (1.556-1.661), p < 0.001) and bradycardia (OR = 1.140 (1.102-1.180), p < 0.001) during the first 10 minutes of respiratory support at birth., Conclusion: During mask ventilation, the median exerted force on a face mask was 297 grams with a maximum of 1455 grams. Higher exerted forces were associated apnoea and bradycardia during the first 10 minutes of respiratory support at birth., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘K.L.A.M. Kuypers is the recipient of an unrestricted research grant from Fisher & Paykel Healthcare Limited; they had no role or influence in study design nor in the collection, analysis, and interpretation of data, writing of the report and decision to submit the paper for publication.’., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Lumbar puncture is a common invasive procedure performed in newborns for diagnostic and therapeutic purposes. Approximately one in two lumbar punctures fail, resulting in both short- and long-term negative consequences for the clinical management of patients. The most common positions used to perform lumbar puncture are the lateral decubitus and sitting position, and each can impact the success rate and safety of the procedure. However, it is uncertain which position best improves patient outcomes., Objectives: To assess the benefits and harms of the lateral decubitus, sitting, and prone positions for lumbar puncture in newborn infants., Search Methods: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2023., Selection Criteria: We included randomized controlled trials (RCTs) and quasi-RCTs involving newborn infants of postmenstrual age up to 46 weeks and 0 days, undergoing lumbar puncture for any indication, comparing different positions (i.e. lateral decubitus, sitting, and prone position) during the procedure., Data Collection and Analysis: We used standard Cochrane methods. We used the fixed-effect model with risk ratio (RR) and risk difference (RD) for dichotomous data and mean difference (MD) and standardized mean difference (SMD) for continuous data, with their 95% confidence intervals (CI). Our primary outcomes were successful lumbar puncture procedure at the first attempt; total number of lumbar puncture attempts; and episodes of bradycardia. We used GRADE to assess the certainty of evidence for each outcome., Main Results: We included five studies with 1476 participants. Compared to sitting position: lateral decubitus position probably results in little to no difference in successful lumbar puncture procedure at the first attempt (RR 0.99, 95% CI 0.88 to 1.12; RD 0.00, 95% CI -0.06 to 0.05; I 2 = 47% and 46% for RR and RD, respectively; 2 studies, 1249 infants, low-certainty evidence). None of the studies reported the total number of lumbar puncture attempts as specified in this review. Lateral decubitus position likely increases episodes of bradycardia (RR 1.72, 95% CI 1.08 to 2.76; RD 0.03, 95% CI 0.00 to 0.05; number needed to treat for an additional harmful outcome (NNTH) = 33; I 2 = not applicable and 69% for RR and RD, respectively; 3 studies, 1279 infants, moderate-certainty evidence) and oxygen desaturation (RR 2.10, 95% CI 1.42 to 3.08; RD 0.06, 95% CI 0.03 to 0.09; NNTH = 17; I 2 = not applicable and 96% for RR and RD, respectively; 2 studies, 1249 infants, moderate-certainty evidence). Lateral decubitus position results in little to no difference in time to perform the lumbar puncture compared to sitting position (I 2 = not applicable; 2 studies; 1102 infants; high-certainty evidence; in one of the study median and IQR to report time to perform the lumbar puncture were 8 (5-13) and 8 (5-12) in the lateral and sitting position, respectively, I 2 = not applicable; 1 study, 1082 infants; in the other study: mean difference 2.00, 95% CI -4.98 to 8.98; I 2 = not applicable; 1 study, 20 infants). Lateral decubitus position may result in little to no difference in the number of episodes of apnea during the procedure (RR not estimable; RD 0.00, 95% CI -0.03 to 0.03; I 2 = not applicable and 0% for RR and RD, respectively; 2 studies, 197 infants, low-certainty evidence). No studies reported apnea defined as number of infants with one or more episodes during the procedure. Compared to prone position: lateral decubitus position may reduce successful lumbar puncture procedure at first attempt (RR 0.75, 95% CI 0.63 to 0.90; RD -0.21, 95% CI -0.34 to -0.09; number needed to treat for an additional beneficial outcome = 5; I 2 = not applicable; 1 study, 171 infants, low-certainty evidence). None of the studies reported the total number of lumbar puncture attempts or episodes of apnea. Pain intensity during and after the procedure was reported using a non-validated pain scale. None of the studies comparing lateral decubitus versus prone position reported the other critical outcomes of this review., Authors' Conclusions: When compared to sitting position, lateral decubitus position probably results in little to no difference in successful lumbar puncture procedure at first attempt. None of the included studies reported the total number of lumbar puncture attempts as specified in this review. Furthermore, infants in a sitting position likely experience less episodes of bradycardia and oxygen desaturation than in the lateral decubitus, and there may be little to no difference in episodes of apnea. Lateral decubitus position results in little to no difference in time to perform the lumbar puncture compared to sitting position. Pain intensity during and after the procedure was reported using a pain scale that was not included in our prespecified tools for pain assessment due to its high risk of bias. Most study participants were term newborns, thereby limiting the applicability of these results to preterm babies. When compared to prone position, lateral decubitus position may reduce successful lumbar puncture procedure at first attempt. Only one study reported on this comparison and did not evaluate adverse effects. Further research exploring harms and benefits and the effect on patients' pain experience of different positions during lumbar puncture using validated pain scoring tool may increase the level of confidence in our conclusions., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Influenza C virus infection is a common and mild disease in children. Nevertheless, it remains an under-recognized cause of acute respiratory illnesses. Herein, we report the case of a 54-day-old infant who developed an influenza C virus infection and frequent apnea attacks, which could be a risk factor for sudden death and has never been reported earlier., Competing Interests: The authors have no funding o r conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We investigated the relationship between respiratory events experienced before and after hospital discharge and developmental outcomes at 6 months corrected age (CA)., Study Design: Preterm infants born between 28-32 weeks gestational age (GA) were studied at 32-36 weeks postmenstrual age (PMA), 36-40 weeks PMA, 3- and 6-months CA. Percentage total sleep time (%TST) with respiratory events (isolated apneas, sequential apneas and periodic breathing (PB)) at each study was calculated. Stepwise multiple linear regressions determined significant predictors of developmental outcomes at 6 months., Result: %TST with respiratory events at term were significant predictors of language (R 2  = 0.165, β = -0.416) and motor (R 2  = 0.180, β = -0.485) composite scores of the Bayley Scales of Infant Development at 6 months, independent of GA, birth weight and sex., Conclusions: In clinically stable very preterm infants at term equivalent age, time spent having respiratory events, was related to a reduction in language and motor outcomes at 6 months., (© 2023. The Author(s).)

Prevention of arterial oxygen desaturation during anaesthesia with high-flow nasal oxygen (HFNO) has gained greater acceptance for a widening range of procedures. However, during HFNO use there remains the potential for development of significant anaesthesia-associated apnoea or hypoventilation and the possibility of hypercarbia, with harmful cardiovascular or neurological sequelae. The aim of this study was to determine whether any HFNO-related hypercarbia adverse incidents had been reported on webAIRS, an online database of adverse anaesthesia-related incidents. Two relevant reports were identified of complications due to marked hypercarbia during HFNO use to maintain oxygenation. In both reports, HFNO and total intravenous anaesthesia were used during endoscopic procedures through the upper airway. In both, the extent of hypoventilation went undetected during HFNO use. An ensuing cardiac arrest was reported in one report, ascribed to acute hypercarbia-induced exacerbation of the patient's pre-existing pulmonary hypertension. In the other report, hypercarbia led to a prolonged duration of decreased level of consciousness post procedure, requiring ventilatory support. During the search, an additional 11 reports of postoperative hypercarbia-associated sedation were identified, unrelated to HFNO. In these additional reports an extended duration of severe acute hypercarbia led to sedation or loss of consciousness, consistent with the known effects of hypercarbia on consciousness. These 13 reports highlight the potential dangers of unrecognised and untreated hypercarbia, even if adequate oxygenation is maintained., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Yasmin Endlich is the current coordinator of the webAIRS publications group. Martin Culwick is the medical director of the Australian and New Zealand Tripartite Anaesthetic Data Committee. The other authors have no conflicts of interest to declare.

Objective: To evaluate the mechanisms leading to intermittent hypoxemia (IH) episodes in spontaneously breathing extremely premature infants at 32 weeks and 36 weeks postmenstrual age (PMA)., Methods: We studied spontaneously breathing premature infants born at 23-28 weeks of gestational age who presented with IH episodes while on noninvasive respiratory support at 32 or 36 weeks PMA. Daytime recordings of arterial oxygen saturation (SpO 2 ), esophageal pressure, respiratory inductive plethysmography of the abdomen, chest wall, and their sum were obtained during 4 hours at 32 weeks and 36 weeks PMA. IH episodes (SpO 2  <90% for ≥5 seconds) and severe IH episodes (SpO 2  < 80% for ≥5 seconds) were classified as resulting from apnea, active exhalation and breath holding, reduced tidal volume (VT), or reduced respiratory rate (RR) during the preceding 60 seconds., Results: Fifty-one infants with a mean gestational age of 25.9 ± 1.5 weeks and a mean birth weight of 846 ± 185 g were included. Of these, 31 and 41 were included in the analysis at 32 weeks and 36 weeks PMA, respectively. At both 32 weeks and 36 weeks PMA, greater proportions of all IH episodes and severe IH episodes were associated with active exhalation and breath holding than with apnea, reduced RR, or reduced VT. The severity and duration of the IH episodes did not differ between mechanisms., Conclusions: In this group of premature infants, the predominant mechanism associated with daytime IH was active exhalation and breath holding. This etiology is more closely associated with behavioral factors than abnormal respiratory control and can have implications for prevention., Competing Interests: Declaration of Competing Interest Supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health of the Prematurity Related Ventilatory Control (Pre-Vent): Role in Respiratory Outcomes Project (Grants U01 HL133689 and U01 HL133708), the Micah Batchelor Foundation, and the University of Miami Project NewBorn. The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The clinical manifestation of coronavirus disease 2019 (COVID-19) infection in newborns varies from asymptomatic infection to severe illness. Apnea or cyanosis as the earliest symptoms is rarely mentioned. The aim of this study is to describe the characteristics of newborns with COVID-19 infection admitted to the neonatal intensive care unit considering cyanosis or apnea as a form of presentation., Methodology: This is a descriptive observational study with retrospectively collected data. All neonates under 30 days old and preterm infants with corrected gestational age of 44 weeks who had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with a positive antigen or reverse transcriptase polymerase chain reaction (RT-PCR) test and who were attended to between March 2020 and March 2022 were included., Results: During the two years of the study, 410 patients were admitted to the neonatal unit. Twenty-six patients (6.3%) presented with confirmed SARS-CoV-2 infection. The main clinical characteristic at admission was apnea in 55% and cyanosis in 45%. Of the 11 patients admitted with this presentation, eight were diagnosed with COVID-19 acute upper respiratory disease, and three met the definition of COVID-19 bronchiolitis. A large proportion of the patients had a mild infection (65%, n = 17), 31% (n = 8) had a severe infection and only one patient had a critical infection, accounting for 4%., Conclusions: Apnea and cyanosis can be a manifestation of SARS-CoV-2 infection in newborns, which suggests the need to include it in the diagnostic workup as other viral respiratory infections., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Carolina Tamayo-Múnera, Zoila Margarita Insignares Vizcaino, Ana Lucia Torres Millán, Laura Niño-Serna, Carolina Giraldo Alzate, Cesar Augusto Vanegas Diaz, Hernan Dario Herrera Salazar, Sandra Liliana Gómez Tovar, Maria Carolina Caicedo Baez, Eliana López-Barón.)

Background: Lumbar puncture is a common invasive procedure performed in newborns for diagnostic and therapeutic purposes. Approximately one in two lumbar punctures fail, resulting in both short- and long-term negative consequences for the clinical management of patients. The most common positions used to perform lumbar puncture are the lateral decubitus and sitting position, and each can impact the success rate and safety of the procedure. However, it is uncertain which position best improves patient outcomes., Objectives: To assess the benefits and harms of the lateral decubitus, sitting, and prone positions for lumbar puncture in newborn infants., Search Methods: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2023., Selection Criteria: We included randomized controlled trials (RCTs) and quasi-RCTs involving newborn infants of postmenstrual age up to 46 weeks and 0 days, undergoing lumbar puncture for any indication, comparing different positions (i.e. lateral decubitus, sitting, and prone position) during the procedure., Data Collection and Analysis: We used standard Cochrane methods. We used the fixed-effect model with risk ratio (RR) and risk difference (RD) for dichotomous data and mean difference (MD) and standardized mean difference (SMD) for continuous data, with their 95% confidence intervals (CI). Our primary outcomes were successful lumbar puncture procedure at the first attempt; total number of lumbar puncture attempts; and episodes of bradycardia. We used GRADE to assess the certainty of evidence for each outcome., Main Results: We included five studies with 1476 participants. Compared to sitting position: lateral decubitus position may result in little to no difference in successful lumbar puncture procedure at the first attempt (RR 0.93, 95% CI 0.85 to 1.02; RD -0.04, 95% CI -0.09 to 0.01; I 2 = 70% and 72% for RR and RD, respectively; 2 studies, 1249 infants, low-certainty evidence). None of the studies reported the total number of lumbar puncture attempts. Lateral decubitus position likely increases episodes of bradycardia (RR 1.72, 95% CI 1.08 to 2.76; RD 0.03, 95% CI 0.00 to 0.05; number needed to treat for an additional harmful outcome (NNTH) = 33; I 2 = not applicable and 69% for RR and RD, respectively; 3 studies, 1279 infants, moderate-certainty evidence) and oxygen desaturation (RR 2.10, 95% CI 1.42 to 3.08; RD 0.06, 95% CI 0.03 to 0.09; NNTH = 17; I 2 = not applicable and 96% for RR and RD, respectively; 2 studies, 1249 infants, moderate-certainty evidence). The evidence is very uncertain regarding the effect of lateral decubitus position on time to perform the lumbar puncture (MD 2.00, 95% CI -4.98 to 8.98; I 2 = not applicable; 1 study, 20 infants, very low-certainty evidence). Lateral decubitus position may result in little to no difference in the number of episodes of apnea during the procedure (RR not estimable; RD 0.00, 95% CI -0.03 to 0.03; I 2 = not applicable and 0% for RR and RD, respectively; 2 studies, 197 infants, low-certainty evidence). No studies reported apnea defined as number of infants with one or more episodes during the procedure. Compared to prone position: lateral decubitus position may reduce successful lumbar puncture procedure at first attempt (RR 0.75, 95% CI 0.63 to 0.90; RD -0.21, 95% CI -0.34 to -0.09; number needed to treat for an additional beneficial outcome = 5; I 2 = not applicable; 1 study, 171 infants, low-certainty evidence). None of the studies reported the total number of lumbar puncture attempts or episodes of apnea. Pain intensity during and after the procedure was reported using a non-validated pain scale. None of the studies comparing lateral decubitus versus prone position reported the other critical outcomes of this review., Authors' Conclusions: When compared to sitting position, lateral decubitus position may result in little to no difference in successful lumbar puncture procedure at first attempt. None of the included studies reported the total number of lumbar puncture attempts. Furthermore, infants in a lateral decubitus position likely experience more episodes of bradycardia and oxygen desaturation, and there may be little to no difference in episodes of apnea. The evidence is very uncertain regarding time to perform lumbar puncture. Pain intensity during and after the procedure was reported using a pain scale that was not included in our prespecified tools for pain assessment due to its high risk of bias. Most study participants were term newborns, thereby limiting the applicability of these results to preterm babies. When compared to prone position, lateral decubitus position may reduce successful lumbar puncture procedure at first attempt. Only one study reported on this comparison and did not evaluate adverse effects. Further research exploring harms and benefits and the effect on patients' pain experience of different positions during lumbar puncture using validated pain scoring tool may increase the level of confidence in our conclusions., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Study Objective: Investigate a low-cost, nasopharyngeal apnoeic oxygenation technique, establish its efficacy, and compare it to preoxygenation only in an obese population. The study's hypothesis was that nasopharyngeal apnoeic oxygenation at 18 l.min -1 would significantly prolong safe apnoea time compared to preoxygenation alone., Design: Randomised controlled study., Setting: Theatre complex of a resource constrained hospital., Patients: 30 adult, obese (BMI ≥ 35 kg.m -2 ) patients presenting for elective surgery. Patients with limiting cardio-respiratory disease, suspected difficult airway, risk of aspiration, and that were pregnant, were excluded. Patients were allocated by block randomisation in a 1:2 ratio to a preoxygenation-only (No-AO) and an intervention group (NPA-O 2 )., Interventions: All patients were preoxygenated to an Et-O2 > 80%, followed by a standardised induction. The intervention group received oxygen at 18 l.min -1 via the nasopharyngeal catheter intervention. The desaturation process was documented until an SpO 2 of 92% or 600 s was reached., Measurements: Baseline demographic and clinical characteristics were collected. The primary outcome was safe apnoea time, defined as the time taken to desaturate to an SpO 2 of 92%. Secondary outcomes were rate of carbon dioxide accumulation and factors affecting the risk of desaturation., Main Results: The study was conducted in a morbidly obese population (NoAO = 41,1 kg.m -2 ; NPA-O 2  = 42,5 kg.m -2 ). The risk of desaturation was signifantly lower in the intervention group (Hazzard Ratio = 0,072, 95% CI[0,019-0,283]) (Log-Rank test, p < 0.001). The median safe apnoea time was significantly longer in the intervention group (NoAO = 262 s [IQR 190-316]; NPA-O 2  = 600 s [IQR 600-600]) (Mann-Whitney-U test, p < 0.001). The mean rate of CO 2 accumalation was significantly slower in the intervention group (NoAO = 0,47 ± 0,14 kPa.min -1 ; NPA-O 2  = 0,3 ± 0,09 kPa.min -1 ) (t-test, p = 0.003). There were no statistically significant risk factors associated with an increased risk of desaturation found., Conclusions: Nasopharyngeal apnoeic oxygenation at 18 l/min prolongs safe apnoea time, compared to preoxygenation alone, and reduces the risk of desaturation in morbidly obese patients., Clinical Trial Registration: PACTR202202665252087; WC/202004/007., Competing Interests: Declaration of Competing Interest There were no conflict of interest of either authors in the production of this wok. The research was conducted for completion of Degree purposes. There was no funding, grants, stock ownership or patent applications made. There are no academic disclosures to mention., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) is gaining acceptance as a safe method for apneic ventilation and oxygenation during laryngeal procedures, but remains controversial during laser laryngeal surgery (LLS) due to the theoretical risk of airway fire. This study describes our experience with THRIVE during LLS., Study Design: Retrospective cohort study., Setting: Stanford University Hospital, October 15, 2015 to June 1, 2021., Methods: Retrospective chart review of patients ≥18 years who underwent LLS involving the CO 2 or KTP laser with THRIVE as the primary mode of oxygenation., Results: A total of 172 cases were identified. 20.9% were obese (BMI ≥ 30). Most common operative indication was subglottic stenosis. The CO 2 laser was used in 79.1% of cases. Median lowest intraoperative SpO 2 was 96%. 44.7% cases were solely under THRIVE while 16.3% required a single intubation and 19.2% required multiple intubations. Mean apnea time for THRIVE only cases was 32.1 minutes and in cases requiring at least one intubation 24.0 minutes (p < .001). Mean apnea time was significantly lower for patients who were obese (p < .001) or had a diagnosis of hypertension (p = .016). Obese patients and patients with hypertension were 2.03 and 1.43 times more likely to require intraoperative intubation, respectively. There were no intraoperative complications or fires since the institution of our LLS safety protocol., Conclusion: By eliminating the fuel component of the fire triangle, THRIVE can be safely used for continuous delivery of high FiO 2 during LLS, provided adherence to institutional THRIVE-LLS protocols., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Apnoeic oxygenation is the delivery of oxygen during the apnoeic phase preceding intubation. It is used to prevent respiratory complications of endotracheal intubation that have the potential to lead to significant adverse events including dysrhythmia, haemodynamic decompensation, hypoxic brain injury and death. Oxygen delivered by nasal cannulae during the apnoeic phase of intubation (apnoeic oxygenation) may serve as a non-invasive adjunct to endotracheal intubation to decrease the incidence of hypoxaemia, morbidity and mortality., Objectives: To evaluate the benefits and harms of apnoeic oxygenation before intubation in adults in the prehospital, emergency department, intensive care unit and operating theatre environments compared to no apnoeic oxygenation during intubation., Search Methods: We used standard, extensive Cochrane search methods. The latest search date was 4 November 2022., Selection Criteria: We included randomized controlled trials (RCTs) and quasi-RCTs that compared the use of any form of apnoeic oxygenation including high flow and low flow nasal cannulae versus no apnoeic oxygenation during intubation. We defined quasi-randomization as participant allocation to each arm by means that were not truly random, such as alternation, case record number or date of birth. We excluded comparative prospective cohort and comparative retrospective cohort studies, physiological modelling studies and case reports., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were 1. hospital stay and 2. incidence of severe hypoxaemia. Our secondary outcomes were 3. incidence of hypoxaemia, 4. lowest recorded saturation of pulse oximetry (SpO 2 ), 5. intensive care unit (ICU) stay, 6. first pass success rate, 7. adverse events and 8., Mortality: We used GRADE to assess certainty of evidence., Main Results: We included 23 RCTs (2264 participants) in our analyses. Eight studies (729 participants) investigated the use of low-flow (15 L/minute or less), and 15 studies (1535 participants) investigated the use of high-flow (greater than 15 L/minute) oxygen. Settings were varied and included the emergency department (2 studies, 327 participants), ICU (7 studies, 913 participants) and operating theatre (14 studies, 1024 participants). We considered two studies to be at low risk of bias across all domains. None of the studies reported on hospital length of stay. In predominately critically ill people, there may be little to no difference in the incidence of severe hypoxaemia (SpO 2 less than 80%) when using apnoeic oxygenation at any flow rate from the start of apnoea until successful intubation (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.66 to 1.11; P = 0.25, I² = 0%; 15 studies, 1802 participants; low-certainty evidence). There was insufficient evidence of any effect on the incidence of hypoxaemia (SpO 2 less than 93%) (RR 0.58, 95% CI 0.23 to 1.46; P = 0.25, I² = 36%; 3 studies, 489 participants; low-certainty evidence). There may be an improvement in the lowest recorded oxygen saturation, with a mean increase of 1.9% (95% CI 0.75% to 3.05%; P < 0.001, I² = 86%; 15 studies, 1525 participants; low-certainty evidence). There may be a reduction in the duration of ICU stay with the use of apnoeic oxygenation during intubation (mean difference (MD) ‒1.13 days, 95% CI ‒1.51 to ‒0.74; P < 0.0001, I² = 46%; 5 studies, 815 participants; low-certainty evidence). There may be little to no difference in first pass success rate (RR 1.00, 95% CI 0.93 to 1.08; P = 0.79, I² = 0%; 8 studies, 826 participants; moderate-certainty evidence). There may be little to no difference in incidence of adverse events including oral trauma, arrhythmia, aspiration, hypotension, pneumonia and cardiac arrest when apnoeic oxygenation is used. There was insufficient evidence about any effect on mortality (RR 0.84, 95% CI 0.70 to 1.00; P = 0.06, I² = 0%; 6 studies, 1015 participants; low-certainty evidence)., Authors' Conclusions: There was some evidence that oxygenation during the apnoeic phase of intubation may improve the lowest recorded oxygen saturation. However, the differences in oxygen saturation were unlikely to be clinically significant. This did not translate into any measurable effect on the incidence of hypoxaemia or severe hypoxaemia in a group of predominately critically ill people. We were unable to assess the influence on hospital length of stay; however, there was a reduction in ICU stay in the apnoeic oxygenation group. The mechanism for this is unclear as there was little to no difference in first pass success or adverse event rates., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Since a high incidence of mortality and morbidity is induced by preterm birth, it is important to understand how hypoxic ischemic encephalopathy (HIE) in preterm infants alters gut microbiota development., Methods: We analyzed 89 stools from 30 term newborns (NNG), 30 preterm infants without apnea (PG) and 29 preterm infants with definite diagnosis of apnea (PAG) by 16S rRNA gene sequencing in this study., Results: The data showed that species richness and diversity in PG and PAG were significantly lower compared with NNG. This study investigated the difference in bacteria and relative abundance between NNG, PG and PAG. The abundance of Klebsiella and Streptococcus strains were markedly increased, while Clostridium was significantly decreased in PAG compared with PG. The most notable exceptions included Klebsiella pneumoniae and Escherichia coli, which were markedly increased in PG and PAG, and these provide the main bacterial source of dopamine and serotonin production. This study also revealed that Lactobacillus and Bifidobacterium were markedly increased in PG and PAG, and these are the main source of GABA production for bacteria., Conclusion: The present study confirmed that apnea had a uniform effect on species richness and diversity. However, it cannot be established whether the abundance and difference of these bacterial genera and species directly affect the occurrence and development of preterm infants with HIE by secreting intestinal neurotransmitters., Competing Interests: Declaration of competing interest None of the authors have a source of funding or conflict of interest to declare. The funding source had no involvement whatsoever in design, preparation, conduct, writing, or submission of the study., (Copyright © 2023 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Mask ventilation during anaesthesia induction is generally used to provide adequate oxygenation but improper mask ventilation can result in gastric insufflation. It has been reported that oxygen administered by transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) during anaesthesia induction can maintain oxygenation but its effect on gastric insufflation is unknown., Objectives: The primary aim of this study was to evaluate whether THRIVE provided adequate oxygenation without gastric insufflation. The secondary aim was to explore the change in cross-sectional area of the antrum (CSAa) during anaesthesia induction. Other potential risk factors of gastric insufflation were also explored., Design: A prospective, randomised, double-blind study., Setting: Single centre, Department of Anaesthesiology, 1 st Affiliated Hospital, Wenzhou Medical University, China, from May 2022 to September 2022., Patients: A total of 210 patients (age >18 years, ASA classification I to III) scheduled to undergo general anaesthesia were enrolled., Interventions: For induction of general anaesthesia, patients were randomised into two groups: THRIVE and pressure-controlled facemask ventilation (PCFV). The THRIVE group received high-flow nasal oxygen with no additional ventilation. The PCFV group had pressure-controlled positive pressure ventilation from the anaesthesia machine via a tight fitting facemask. Gastric insufflation was detected using real-time ultrasonography. The CSAa was measured from ultrasonography images obtained before anaesthesia induction and at 0, 1, 2 and 3 min after loss of consciousness., Main Outcome Measures: The incidence of gastric insufflation during the period from loss of consciousness until intubation., Results: The THRIVE group had a lower incidence of gastric insufflation during anaesthesia induction than the PCFV group (13.0 vs. 35.3%, odds ratio (OR) = 0.27, 95% confidence interval (CI), 0.14 to 0.56, P  < 0.001). Increase in the CSA after anaesthesia induction was significantly correlated with gastric insufflation (OR = 5.35, 95% CI, 2.90 to 9.89, P  < 0.001). Multivariate logistic regression analysis showed that advancing age (OR = 1.04, 95% CI, 1.01 to 1.07), obstructive sleep apnoea syndrome (OR = 2.43, 95% CI, 1.24 to 4.76), higher Mallampati score (OR = 2.66, 95% CI, 1.21 to 5.85) and PCFV (OR = 4.78, 95% CI, 2.06 to 11.06) were important independent risk factors for gastric insufflation., Conclusion: During anaesthesia induction, the THRIVE technique provided adequate oxygenation with a reduced incidence of gastric insufflation. PCFV, advancing age, obstructive sleep apnoea syndrome and the Mallampati score were found to be independent risk factors for gastric insufflation during anaesthesia induction., Trial Registration: Chinese Clinical Trial Registry ChiCTR200059555., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Improved ablation catheter-tissue contact results in more effective ablation lesions. Respiratory motion causes catheter instability, which impacts durable pulmonary vein isolation (PVI)., Objectives: This study sought to evaluate the safety and efficacy of a novel ablation strategy involving prolonged periods of apneic oxygenation during PVI., Methods: We conducted a multicenter, prospective controlled study of 128 patients (mean age 63 ± 11 years; 37% women) with paroxysmal atrial fibrillation undergoing PVI. Patients underwent PVI under general anesthesia using serial 4-minute runs of apneic oxygenation (apnea group; n = 64) or using standard ventilation settings (control group; n = 64). Procedural data, arterial blood gas samples, catheter position coordinates, and ablation lesion characteristics were collected., Results: Baseline characteristics between the 2 groups were similar. Catheter stability was significantly improved in the apnea group, as reflected by a decreased mean catheter displacement (1.55 ± 0.97 mm vs 2.25 ± 1.13 mm; P < 0.001) and contact force SD (4.9 ± 1.1 g vs 5.2 ± 1.5 g; P = 0.046). The percentage of lesions with a mean catheter displacement >2 mm was significantly lower in the apnea group (22% vs 44%; P < 0.001). Compared with the control group, the total ablation time to achieve PVI was reduced in the apnea group (18.8 ± 6.9 minutes vs 23.4 ± 7.8 minutes; P = 0.001). There were similar rates of first-pass PVI, acute PV reconnections and dormant PV reconnections between the two groups., Conclusions: A novel strategy of performing complete PVI during apneic oxygenation results in improved catheter stability and decreased ablation times without adverse events. (Radiofrequency Ablation of Atrial Fibrillation Under Apnea; NCT04170894)., Competing Interests: Funding Support and Author Disclosures Dr Cheung has received consulting fees from Abbott and Boston Scientific; research support from Boston Scientific; and fellowship grant support from Abbott, Biosense Webster, Boston Scientific, and Medtronic. Dr Patel has received consulting fees from Biosense Webster. Dr Markowitz has received fees from Boston Scientific for serving on a data safety monitoring board. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In preterm infants, spinal anesthesia (SpA) is recognized as an alternative to general anesthesia for inguinal hernia repair (IHR); however, some patients require supplemental anesthesia during surgery. The purpose of this study was to investigate the frequency and impact of supplemental anesthesia on perioperative care and adverse respiratory and hemodynamic events., Methods: A retrospective study of preterm infants undergoing IHR at Heidelberg University Hospital within the first year of life between 2009 and 2018 was carried out., Results: In total, 230 patients (255 surgeries) were investigated. Among 189 procedures completed using SpA 24 patients received supplemental anesthesia. Reasons for supplemental anesthesia included loss of anesthetic effect, returning motor response, and respiratory complications. Compared to SpA alone, no differences were found concerning hemodynamic parameters; however, patients requiring supplemental anesthesia displayed higher rates of postoperative oxygen supplementation and unexpected admission to the intensive care unit. The rate of perioperative apnea was 2.7%. Apneic events exclusively occurred after supplemental anesthesia. Bilateral IHR and duration of surgery were associated with the need for supplemental anesthesia., Conclusion: Whereas SpA might be favorable when compared to general anesthesia for IHR, the data indicate that particular caution is required in patients receiving supplemental anesthesia due to the possible risk for adverse respiratory events., (© 2022. The Author(s).)

We recently demonstrated that the hypoxic ventilatory response (HVR) is facilitated by the AMP-activated protein kinase (AMPK) in catecholaminergic neural networks that likely lie downstream of the carotid bodies within the caudal brainstem. Here, we further subcategorise the neurons involved, by cross-comparison of mice in which the genes encoding the AMPK-α1 (Prkaa1) and AMPK-α2 (Prkaa2) catalytic subunits were deleted in catecholaminergic (TH-Cre) or adrenergic (PNMT-Cre) neurons. As expected, the HVR was markedly attenuated in mice with AMPK-α1/α2 deletion in catecholaminergic neurons, but surprisingly was modestly augmented in mice with AMPK-α1/α2 deletion in adrenergic neurons when compared against a variety of controls (TH-Cre, PNMT-Cre, AMPK-α1/α2 floxed). Moreover, AMPK-α1/α2 deletion in catecholaminergic neurons precipitated marked hypoventilation and apnoea during poikilocapnic hypoxia, relative to controls, while mice with AMPK-α1/α2 deletion in adrenergic neurons entered relative hyperventilation with reduced apnoea frequency and duration. We conclude, therefore, that AMPK-dependent modulation of non-adrenergic networks may facilitate increases in ventilatory drive that shape the classical HVR, whereas AMPK-dependent modulation of adrenergic networks may provide some form of negative feedback or inhibitory input to moderate HVR, which could, for example, protect against hyperventilation-induced hypocapnia and respiratory alkalosis., (© 2022. The Author(s).)

Objectives/hypothesis: This study aimed to analyze the feasibility of transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) during laryngeal microsurgery (LMS) and investigated its efficiency and application according to the location of the lesion., Study Design: Retrospective chart review., Methods: Patients over 20 years of age who underwent LMS without underlying cardiac, pulmonary, or cerebrovascular disease were retrospectively reviewed. Overall, 54 patients with endotracheal intubation (ETI) and 44 patients with THRIVE were included. The operation and anesthesia time, induction and emergence time, oxygen saturation (SpO 2 ), and transcutaneous carbon dioxide (TcCO 2 ) levels were analyzed and compared between the two ventilation methods according to disease subsite., Results: Compared with ETI, patients with THRIVE presented reduced operation time (16.3 ± 9.69 min vs. 21.9 ± 12.0 min), anesthesia time (33.6 ± 11.4 min vs. 45.4 ± 13.9 min), emergence time (6.73 ± 2.49 min vs. 8.52 ± 3.17 min), without significant decreases in SpO 2 but with increased TcCO 2 (10.9 ± 6.12% vs. 7.33 ± 3.86%). Comparing THRIVE to ETI for lesions at the glottis yielded similar findings, which were particularly more significant. However, lesions above the glottis presented no significant difference for any parameters between THRIVE and ETI groups. Lesions involving multiple subsites and prolonged operation time were risk factors for the intraoperative conversion of ventilation method., Conclusion: THRIVE is reliable for maintaining oxygenation during LMS and is efficient in reducing the operation and emergence times, leading to shorter anesthesia time, especially for lesions at the glottis. However, caution is required administering THRIVE, when lesion involves multiple subsites, and when operation time is prolonged., Level of Evidence: 3 Laryngoscope, 132:1061-1068, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

This meta-analysis aimed at investigating the efficacy of high-flow nasal oxygenation (HFNO) against hypoxemia in patients with obesity compared with conventional oxygenation therapy and non-invasive ventilation. Databases were searched from inception to August 2021. Studies involving peri- or post-procedural use of HFNO were included. The primary outcome was risk of hypoxemia, while the secondary outcomes included status of oxygenation and carbon dioxide elimination. Ten randomized controlled trials (RCTs) were included. We found that HFNO prolonged the safe apnea time at induction compared to control group [mean difference (MD) = 73.88 s, p = 0.0004; 2 RCTs] with no difference in risk of peri-procedural hypoxemia [relative risk (RR) = 0.91, p = 0.64; 4 RCTs], minimum SpO2 (MD = 0.09%, p = 0.95; 4 RCTs), PaO2 (MD = - 8.13 mmHg, p = 0.86; 3 RCTs), PaCO2 (MD = - 6.71%, p = 0.2; 2 RCTs), EtCO2 (MD = - 0.28 mmHg, p = 0.8; 4 RCTs) between the two groups. HFNO also did not improve postprocedural PaO2/FiO2 ratio (MD = 41.76, p = 0.58; 2 RCTs) and PaCO2 (MD = - 2.68 mmHg, p = 0.07; 2 RCTs). This meta-analysis demonstrated that the use of HFNO may be associated with a longer safe apnea time without beneficial impact on the risk of hypoxemia, oxygenation, and CO2 elimination in patients with obesity. The limited number of trials warranted further large-scale studies to support our findings., (© 2022. The Author(s).)

Although the amygdala plays an important part in the pathogenesis of anxiety and generation of exteroceptive fear, recent discoveries have challenged the directionality of this brain-behavior relationship with respect to interoceptive fear. Here we highlight several paradoxical findings including: (1) amygdala lesion patients who experience excessive fear and panic following inhalation of carbon dioxide (CO 2 ), (2) clinically anxious patients who have significantly smaller (rather than larger) amygdalae and a pronounced hypersensitivity toward CO 2 , and (3) epilepsy patients who exhibit apnea immediately following stimulation of their amygdala yet have no awareness that their breathing has stopped. The above findings elucidate an entirely novel role for the amygdala in the induction of apnea and inhibition of CO 2 -induced fear. Such a role is plausible given the strong inhibitory connections linking the central nucleus of the amygdala with respiratory and chemoreceptive centers in the brainstem. Based on this anatomical arrangement, we propose a model of Apnea-induced Anxiety (AiA) which predicts that recurring episodes of apnea are being unconsciously elicited by amygdala activation, resulting in transient spikes in CO 2 that provoke fear and anxiety, and lead to characteristic patterns of escape and avoidance behavior in patients spanning the spectrum of anxiety. If this new conception of AiA proves to be true, and activation of the amygdala can repeatedly trigger states of apnea outside of one's awareness, then it remains possible that the chronicity of anxiety disorders is being interoceptively driven by a chemoreceptive system struggling to maintain homeostasis in the midst of these breathless states., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Percutaneous dilation tracheostomy is an aerosol-generating procedure carrying a documented infectious risk during respiratory virus pandemics. For this reason, during the COVID-19 outbreak, surgical tracheostomy was preferred to the percutaneous one, despite the technique related complications increased risk., Methods: We describe a new sequence for percutaneous dilation tracheostomy procedure that could be considered safe both for patients and healthcare personnel. A fiberscope was connected to a video unit to allow bronchoscopy. Guidewire positioning was performed as usual. While the established standard procedure continues with the creation of the stoma without any change in mechanical ventilation, we retracted the bronchoscope until immediately after the access valve in the mount tube, allowing normal ventilation. After 3 minutes of ventilation with 100% oxygen, mechanical ventilation was stopped without disconnecting the circuit. During apnea, the stoma was created by dilating the trachea and the tracheostomy cannula was inserted. Ventilation was then resumed. We evaluated the safeness of the procedure by recording any severe desaturation and by performing serological tests to all personnel., Results: Thirty-six patients (38%) of 96 underwent tracheostomy; 22 (23%) percutaneous dilation tracheostomies with the new approach were performed without any desaturation. All personnel (150 operators) were evaluated for serological testing: 9 (6%) had positive serology but none of them had participated in tracheostomy procedures., Conclusion: This newly described percutaneous dilation tracheostomy technique was not related to severe desaturation events and we did not observe any positive serological test in health workers who performed the tracheostomies., (Copyright © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Competing Interests: AUTHOR DISCLOSURE:Drs Ness, King, Kukreja, and Sundgren have disclosed no financial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.

Background: Hypoxaemia occurs frequently in infants during anaesthetic induction., Objective: We evaluated the effect of positive end-expiratory pressure during anaesthesia induction on nonhypoxic apnoea time in infants., Design: Randomised controlled trial., Setting: Tertiary care children's hospital, single centre, from November 2018 to October 2019., Patients: We included patients under 1 year of age receiving general anaesthesia., Intervention: We assigned infants to a 7 cmH2O or 0 cmH2O positive end-expiratory pressure group. Anaesthesia was induced with 0.02 mg kg-1 atropine, 5 mg kg-1 thiopental sodium and 3 to 5% sevoflurane, and neuromuscular blockade with 0.6 mg kg-1 rocuronium. Thereafter, 100% oxygen was provided via face mask with volume-controlled ventilation of 6 ml kg-1 tidal volume, and either 7 cmH2O or no positive end-expiratory pressure. After 3 min of ventilation, the infants' trachea was intubated but disconnected from the breathing circuit, and ventilation resumed when pulse oximetry reached 95%., Main Outcome Measure: The primary outcome was nonhypoxic apnoea time defined as the time from cessation of ventilation to a pulse oximeter reading of 95%, whereas the secondary outcome was the incidence of significant atelectasis (consolidation score ≥2) assessed by lung ultrasound., Results: Sixty patients were included in the final analysis. Apnoea time in the 7 cmH2O positive end-expiratory pressure group (105.2 s) increased compared with that in the control group (92.1 s) (P = 0.011, mean difference 13.0 s, 95% CI, 3.1 to 22.9 s). Significant atelectasis was observed in all patients without positive end-expiratory pressure and 66.7% of those with 7 cmH2O positive end-expiratory pressure (P = 0.019, 95% CI, 1.7 to 563.1, odds ratio 31.2)., Conclusion: Positive end-expiratory pressure during anaesthesia induction with face mask ventilation increased nonhypoxic apnoea time in infants., Clinical Trial Registration: www.clinicaltrials.gov, NCT03540940., (Copyright © 2020 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

This narrative review provides a broad perspective on immature control of breathing, which is universal in infants born premature. The degree of immaturity and severity of clinical symptoms are inversely correlated with gestational age. This immaturity presents as prolonged apneas with associated bradycardia or desaturation, or brief respiratory pauses, periodic breathing, and intermittent hypoxia. These manifestations are encompassed within the clinical diagnosis of apnea of prematurity, but there is no consensus on minimum criteria required for diagnosis. Common treatment strategies include caffeine and noninvasive respiratory support, but other therapies have also been advocated with varying effectiveness. There is considerable variability in when and how to initiate and discontinue treatment. There are significant knowledge gaps regarding effective strategies to quantify the severity of clinical manifestations of immature breathing, which prevent us from better understanding the long-term potential adverse outcomes, including neurodevelopment and sudden unexpected infant death., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: Application of a face mask may induce apnoea and bradycardia, possibly via the trigeminocardiac reflex (TCR). We aimed to describe rates of apnoea and bradycardia in term and late-preterm infants following facemask application during neonatal stabilisation and compare the effects of first facemask application with subsequent applications., Design: Subgroup analysis of a prospective, randomised trial comparing two face masks., Setting: Single-centre study in the delivery room PATIENTS: Infants>34 weeks gestational age at birth METHODS: Resuscitations were video recorded. Airway flow and pressure were measured using a flow sensor. The effect of first and subsequent facemask applications on spontaneously breathing infants were noted. When available, flow waveforms as well as heart rate (HR) were assessed 20 s before and 30 s after each facemask application., Results: In total, 128 facemask applications were evaluated. In eleven percent of facemask applications infants stopped breathing. The first application was associated with a higher rate of apnoea than subsequent applications (29% vs 8%, OR (95% CI)=4.76 (1.41-16.67), p=0.012). On aggregate, there was no change in median HR over time. In the interventions associated with apnoea, HR dropped by 38bpm [median (IQR) at time of facemask application: 134bpm (134-150) vs 96bpm (94-102) 20 s after application; p=0.25] and recovered within 30 s., Conclusions: Facemask applications in term and late-preterm infants during neonatal stabilisation are associated with apnoea and this effect is more pronounced after the first compared with subsequent applications. Healthcare providers should be aware of the TCR and vigilant when applying a face mask to newborn infants., Trial Registration Number: ACTRN12616000768493., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To assess the clinical picture underlying apparent life-threatening events (ALTEs) occurring in infants with achondroplasia and provide guidance for evaluation after an event., Methods: A population of 477 individuals with achondroplasia was retrospectively reviewed, and information regarding possible ALTEs was recorded in a REDCap database., Results: ALTEs occurred in the first year of life in 18 of 477 individuals (3.8%). Most (14/18, 78%) occurred in the first 6 months of life and presented as episodes of apnoea and/or seizures. Of affected infants, 8/18 (44%) had more than one episode. Many of the initial ALTEs arose while infants were in car seats (11/18, 61%). Assessment following ALTEs most often demonstrated either craniocervical junction concerns and/or seizures, with 12/18 (67%) patients undergoing cervicomedullary decompression and 5/18 (28%) starting on anti-epileptic medications after the event., Conclusion: Although this study is limited in size and was retrospective, it shows that infants with achondroplasia appear to be at high risk for ALTEs. Evaluation after an event should include neuroimaging of the foramen magnum, inpatient hospital observation including respiratory monitoring and electroencephalography, and a car seat challenge., (©2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: Caffeine is an antagonist of the adenosine pathway, which is involved in regulation of breathing. Extracellular concentrations of adenosine are increased in the immediate aftermath of a seizure. Seizure-related overstimulation of adenosine receptors might promote peri-ictal apnea. However, the relation between caffeine consumption and risk of seizure-related respiratory dysfunction in patients with drug-resistant focal epilepsy remains unknown., Methods: We performed a cross-sectional analysis of data collected in patients included in the SAVE study in Lyon's epilepsy monitoring unit at the Adult Epilepsy Department of the Lyon University Hospital between February 2016 and October 2018. The video-electroencephalographic recordings of 156 patients with drug-resistant focal epilepsy included in the study were reviewed to identify those with ≥1 focal seizure (FS), valid pulse oximetry (SpO 2 ) measurement, and information about usual coffee consumption. This latter was collected at inclusion using a standardized self-questionnaire and further classified into four groups: none, rare (≤3 cups/week), moderate (4 cups/week to 3 cups/day), and high (≥4 cups/day). Peri-ictal hypoxemia (PIH) was defined as SpO 2 < 90% for at least 5 s occurring during the ictal period, the post-ictal period, or both., Results: Ninety patients fulfilled inclusion criteria, and 323 seizures were analyzed. Both the level of usual coffee consumption (p = .033) and the level of antiepileptic drug withdrawal (p = .004) were independent risk factors for occurrence of PIH. In comparison with FS in patients with no coffee consumption, risk of PIH was four times lower in FS in patients with moderate consumption (odds ratio [OR] = .25, 95% confidence interval [CI] = .07-.91, p = .036) and six times lower in FS in patients with high coffee consumption (OR = .16, 95% CI = .04-.66, p = .011). However, when PIH occurred, its duration was longer in patients with moderate or high consumption than in those with no coffee consumption (p = .042)., Significance: Coffee consumption may be a protective factor for seizure-related respiratory dysfunction, with a dose-dependent effect., (© 2021 International League Against Epilepsy.)

Chronic opioid consumption is associated with addiction, physical dependence, and tolerance. Tolerance results in dose escalation to maintain the desired opioid effect. Intake of high-dose or potent opioids may cause life-threatening respiratory depression, an effect that may be reduced by tolerance. We performed a pharmacokinetic-pharmacodynamic analysis of the respiratory effects of fentanyl in chronic opioid users and opioid-naïve subjects to quantify tolerance to respiratory depression. Fourteen opioid-naïve individuals and eight chronic opioid users received escalating doses of intravenous fentanyl (opioid-naïve subjects: 75-350 µg/70 kg; chronic users: 250-700 µg/70 kg). Isohypercapnic ventilation was measured and the fentanyl plasma concentration-ventilation data were analyzed using nonlinear mixed-effects modeling. Apneic events occurred in opioid-naïve subjects after a cumulative fentanyl dose (per 70 kg) of 225 (n = 3) and 475 µg (n = 6), and in 7 chronic opioid users after a cumulative dose of 600 (n = 2), 1,100 (n = 2), and 1,800 µg (n = 3). The time course of fentanyl's respiratory depressant effect was characterized using a biophase equilibration model in combination with an inhibitory maximum effect (E max ) model. Differences in tolerance between populations were successfully modeled. The effect-site concentration causing 50% ventilatory depression, was 0.42 ± 0.07 ng/mL in opioid-naïve subjects and 1.82 ± 0.39 ng/mL in chronic opioid users, indicative of a 4.3-fold sensitivity difference. Despite higher tolerance to fentanyl-induced respiratory depression, apnea still occurred in the opioid-tolerant population indicative of the potential danger of high-dose opioids in causing life-threatening respiratory depression in all individuals, opioid-naïve and opioid-tolerant., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Perioperative pulse oximetry hemoglobin saturation (Spo2) measurement is associated with fewer desaturation and hypoxia episodes. However, the sigmoidal nature of oxygen-hemoglobin dissociation limits the accuracy of estimation of the partial pressure of oxygen (Pao2) >80 mm Hg and correspondingly limits the ability to identify when Pao2 >80 mm Hg but falling. We hypothesized that a proxy measurement for oxygen saturation (Oxygen Reserve Index [ORI]) derived from multiwavelength pulse oximetry may allow additional warning time before critical desaturation or hypoxia. To test our hypothesis, we used a Masimo multiwavelength pulse oximeter to compare ORI and Spo2 warning times during apnea in high-risk surgical patients undergoing cardiac surgery., Methods: This institutional review board-approved prospective study (NCT03021473) enrolled American Society of Anesthesiologists physical status III or IV patients scheduled for elective surgery with planned preinduction arterial catheter placement. In addition to standard monitors, an ORI sensor was placed and patients were monitored with a pulse oximeter displaying the ORI, a nondimensional parameter that ranges from 0 to 1. Patients were then preoxygenated until ORI plateaued. Following induction of anesthesia, mask ventilation with 100% oxygen was performed until neuromuscular blockade was established. Endotracheal intubation was accomplished using videolaryngoscopy to confirm placement. The endotracheal tube was not connected to the breathing circuit, and patients were allowed to be apneic. Ventilation was resumed when Spo2 reached 94%. We defined ORI warning time as the time from when the ORI alarm registered (based on the absolute value and the rate of change) until the Spo2 decreased to 94%. We defined the Spo2 warning time as the time for Spo2 to decrease from 97% to 94%. The added warning time provided by ORI was defined as the difference between ORI warning time and Spo2 warning time., Results: Forty subjects were enrolled. Complete data for analysis were available from 37 patients. The ORI alarm registered before Spo2 decreasing to 97% in all patients. Median (interquartile range [IQR]) ORI warning time was 80.4 seconds (59.7-105.9 seconds). Median (IQR) Spo2 warning time was 29.0 seconds (20.5-41.0 seconds). The added warning time provided by ORI was 48.4 seconds (95% confidence interval [CI], 40.4-62.0 seconds; P < .0001)., Conclusions: In adult high-risk surgical patients, ORI provided clinically relevant added warning time of impending desaturation compared to Spo2. This additional time may allow modification of airway management, earlier calls for help, or assistance from other providers. The potential patient safety impact of such monitoring requires further study., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2020 International Anesthesia Research Society.)

Background: Obese patients are at risk for rapid oxygen desaturation during anesthesia induction. Apneic oxygenation with regular flow oxygen insufflation has successfully been used to prolong the duration of safe apnea without desaturation (DAWD) in morbidly obese patients. Using high-flown nasal insufflation of oxygen (HFNI) for apneic oxygenation might further increase the DAWD., Objectives: To compare the duration of safe apnea using high-flown nasal insufflation of oxygen or standard flow oxygen insufflation for apneic oxygenation in a simulated difficult intubation scenario in patients with morbid obesity., Setting: Operating room, University Hospital, Austria., Methods: In a prospective, randomized, clinical trial, patients received standardized preoxygenation and anesthesia induction. Apneic oxygenation was performed using standard nasal prongs (10 L/min) or HFNI (120 L/min) during laryngoscopy. A Cormack-Lehane 3° view was maintained until the oxygen saturation on pulse oximetry (SpO 2 ) dropped ≤95% or for a maximum of 15 minutes. The primary outcome of this study was to compare the duration of safe apnea using HFNI or standard flow oxygen insufflation for apneic oxygenation. In addition, arterial blood gas results, and airway pressures were investigated., Results: In 40 patients with morbid obesity (body mass index [BMI] >40 kg/m 2 ) and the American Society of Anesthesiologists physical classification ≤3 who underwent bariatric surgery, the median duration of safe apnea was 601 (268-900) seconds in the standard group and 537 (399-808) seconds in the HFNI group (P = .698). No differences in arterial blood gas results were observed between the groups. The median airway pressure was 0 (0-0) cm H 2 O in the standard group and 1 (0-2) cm H 2 O in the HFNI group (P = .005)., Conclusion: Compared with standard nasal apneic oxygenation, HFNI did not increase the duration of safe apnea in patients with morbid obesity. A significant but clinically negligible higher airway pressure was observed when using HFNI., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Respiratory insufficiency is a leading cause of death due to drug overdose or neuromuscular disease. We hypothesized that a stimulation paradigm using temporal interference (TI) could restore breathing in such conditions. Following opioid overdose in rats, two high frequency (5000 Hz and 5001 Hz), low amplitude waveforms delivered via intramuscular wires in the neck immediately activated the diaphragm and restored ventilation in phase with waveform offset (1 Hz or 60 breaths/min). Following cervical spinal cord injury (SCI), TI stimulation via dorsally placed epidural electrodes uni- or bilaterally activated the diaphragm depending on current and electrode position. In silico modeling indicated that an interferential signal in the ventral spinal cord predicted the evoked response (left versus right diaphragm) and current-ratio-based steering. We conclude that TI stimulation can activate spinal motor neurons after SCI and prevent fatal apnea during drug overdose by restoring ventilation with minimally invasive electrodes.

Congenital central hypoventilation syndrome (CCHS) represents a rare genetic disorder usually caused by mutations in the homeodomain transcription factor PHOX2B. Some CCHS patients suffer mainly from deficiencies in CO 2 and/or O 2 respiratory chemoreflex, whereas other patients present with full apnea shortly after birth. Our goal was to identify the neuropathological mechanisms of apneic presentations in CCHS. In the developing murine neuroepithelium, Phox2b is expressed in three discrete progenitor domains across the dorsal-ventral axis, with different domains responsible for producing unique autonomic or visceral motor neurons. Restricting the expression of mutant Phox2b to the ventral visceral motor neuron domain induces marked newborn apnea together with a significant loss of visceral motor neurons, RTN ablation, and preBötzinger complex dysfunction. This finding suggests that the observed apnea develops through non-cell autonomous developmental mechanisms. Mutant Phox2b expression in dorsal rhombencephalic neurons did not generate significant respiratory dysfunction, but did result in subtle metabolic thermoregulatory deficiencies. We confirm the expression of a novel murine Phox2b splice variant which shares exons 1 and 2 with the more widely studied Phox2b splice variant, but which differs in exon 3 where most CCHS mutations occur. We also show that mutant Phox2b expression in the visceral motor neuron progenitor domain increases cell proliferation at the expense of visceral motor neuron development. We propose that visceral motor neurons may function as organizers of brainstem respiratory neuron development, and that disruptions in their development result in secondary/non-cell autonomous maldevelopment of key brainstem respiratory neurons., (© 2020 International Society of Neuropathology.)

Objectives: To determine the prevalence of adverse events during apnea testing for determination of death by neurologic criteria using continuous positive airway pressure in children., Design: Single-center retrospective descriptive study., Setting: Academic children's hospital., Patients: Children evaluated for death by neurologic criteria in the PICU from 2013 to 2018., Interventions: None., Measurements and Main Results: For each patient evaluated for death by neurologic criteria, we abstracted the number of apnea tests performed, vital signs and arterial blood gases during apnea testing, and outcome from the medical record. Adverse events were defined as oxygen-hemoglobin desaturation (arterial oxygen saturation < 85%), hypotension, or other significant event (e.g. arrhythmia, cardiac arrest) based on documentation in the medical record. We determined which adverse events resulted in early termination of the apnea test. We used oxygenation index, ventilator variables, and presence of vasopressors to determine preapnea test cardiopulmonary dysfunction. Seventy-two patients (age 7 yr [2.7-13.2 yr]; 48% male) underwent 121 apnea tests. Nine patients (12%) had 13 potential apnea tests deferred due to concern for cardiopulmonary instability as determined by the attending physician. Patients who underwent apnea testing had an oxygenation index of 3.5 (2.5-4.8) and were receiving vasopressors at the time of 108 apnea tests (89%). Hypotension was reported during seven apnea tests (6%) and resulted in the early termination of one apnea test (<1%). No other adverse events were reported. One hundred and twenty apnea tests (99%) were consistent with death by neurologic criteria., Conclusions: Apnea testing following a protocol that uses continuous positive airway pressure for apneic oxygenation has a low rate of adverse events in children meeting prerequisite criteria and determined by a pediatric intensivist to be physiologically appropriate for testing.