Effects of hyperventilation on repeated breath-holding while in a fasting state: do risks outweigh the benefits?

Breath-holding preceded by either an overnight fast or hyperventilation has been shown to potentiate the risk of a hypoxic blackout. However, no study has explored the combined effects of fasting and hyperventilation on apneic performance and associated physiological responses. Nine nondivers (8 males) attended the laboratory on two separate occasions (≥48 h apart), both after a 12-h overnight fast. During each visit, a hyperoxic rebreathing trial was performed followed by three repeated maximal static apneas preceded by either normal breathing (NORM) or a 30-s hyperventilation (HYPER). Splenic volume, hematology, cardiovascular, and respiratory variables were monitored. There were no interprotocol differences at rest or during hyperoxic rebreathing for any variable (P ≥ 0.09). On nine occasions (8 in HYPER), the subjects reached our safety threshold (oxygen saturation 65%) and were asked to abort their apneas, with the preponderance of these incidents (6 of 9) occurring during the third repetition. Across the sequential attempts, longer apneas were recorded in HYPER [median(range), 220(123-324) s vs. 185(78-296) s, P ≤ 0.001], with involuntary breathing movements occurring later [134(65-234) s vs. 97(42-200) s, P ≤ 0.001] and end-apneic partial end-tidal pressures of oxygen (PETO2) being lower (P ≤ 0.02). During the final repetition, partial end-tidal pressure of carbon dioxide [(PETCO2), 6.53 ± 0.46 kPa vs. 6.01 ± 0.45 kPa, P = 0.005] was lower in HYPER. Over the serial attempts, preapneic tidal volume was gradually elevated [from apnea 1 to 3, by 0.26 ± 0.24 L (HYPER) and 0.28 ± 0.30 L (NORM), P ≤ 0.025], with a correlation noted with preapneic PETCO2 (r = -0.57, P < 0.001) and PETO2 (r = 0.76, P < 0.001), respectively. In a fasted state, preapnea hyperventilation compared with normal breathing leads to longer apneas but may increase the susceptibility to a hypoxic blackout.NEW & NOTEWORTHY This study shows that breath-holds (apneas) preceded by a 12-h overnight fast coupled with a 30-s hyperventilation as opposed to normal breathing may increase the likelihood of a hypoxic blackout through delaying the excitation of hypercapnic ventilatory sensory chemoreflexes. Evidently, this risk is exacerbated over a series of repeated maximal attempts, possibly due to a shift in preapneic gas tensions facilitated by an unintentional increase in tidal volume breathing.

Detecting central apneas using multichannel signals in premature infants.

Objective. Monitoring of apnea of prematurity, performed in neonatal intensive care units by detecting central apneas (CAs) in the respiratory traces, is characterized by a high number of false alarms. A two-step approach consisting of a threshold-based apneic event detection algorithm followed by a machine learning model was recently presented in literature aiming to improve CA detection. However, since this is characterized by high complexity and low precision, we developed a new direct approach that only consists of a detection model based on machine learning directly working with multichannel signals.Approach. The dataset used in this study consisted of 48 h of ECG, chest impedance and peripheral oxygen saturation extracted from 10 premature infants. CAs were labeled by two clinical experts. 47 features were extracted from time series using 30 s moving windows with an overlap of 5 s and evaluated in sets of 4 consecutive moving windows, in a similar way to what was indicated for the two-step approach. An undersampling method was used to reduce imbalance in the training set while aiming at increasing precision. A detection model using logistic regression with elastic net penalty and leave-one-patient-out cross-validation was then tested on the full dataset.Main results. This detection model returned a mean area under the receiver operating characteristic curve value equal to 0.86 and, after the selection of a FPR equal to 0.1 and the use of smoothing, an increased precision (0.50 versus 0.42) at the expense of a decrease in recall (0.70 versus 0.78) compared to the two-step approach around suspected apneic events.Significance. The new direct approach guaranteed correct detections for more than 81% of CAs with lengthL≥ 20 s, which are considered among the most threatening apneic events for premature infants. These results require additional verifications using more extensive datasets but could lead to promising applications in clinical practice.

Apnea Testing Practice to Increase Baseline PaCO2 and Frequency of Blood Gas Analyses.

OBJECTIVE: To study the influence of the initial partial pressure of carbon dioxide (PaCO2) and frequency of blood gas analyses on the positivity rate and safety of apnea testing (AT). DESIGN: A prospective multicenter cohort study. SETTING: Seven teaching hospitals. PARTICIPANTS: A total of 55 patients who underwent AT. INTERVENTIONS: Patients were divided into 2 groups according to their initial PaCO2-the experimental group (≥40 mmHg, 27 patients) and the control group (<40 mmHg, 28 patients). Blood gas analysis was performed at 3, 5, and 8 minutes, and vital signs were taken. AT results and complications were compared between the groups. RESULTS: The initial PaCO2 of the experimental group was 42.8 ± 2.2 mmHg v 36.4 ± 2.9 mmHg in the controls. The AT positivity rate was 100%. The experimental group needed less time to reach the target PaCO2 than the control group (4.07 ± 1.27 minutes v 5.68 ± 2.06 minutes; p = 0.001). Twenty-six patients (96.3%) in the experimental group reached the target PaCO2 in 5 minutes v 17 in the control group (60.7%) (p = 0.001). Seven patients (12.7%) were unable to complete 8-minute disconnection due to hypotension. The experimental group had a slightly lower incidence of hypotension than the control group, but there was no statistical difference (7.4% v 17.9%, p = 0.245). CONCLUSION: Increasing the baseline PaCO2 and doing more blood gas analyses can significantly shorten the time needed for AT and improve the AT positivity rate.

The 2023 American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine Pediatric and Adult Brain Death/Death by Neurologic Criteria Determination Consensus Guidelines: What the Critical Care Team Needs to Know.

Guidelines for brain death/death by neurologic criteria (BD/DNC) determination were revised to provide a consistent and updated approach to BD/DNC evaluation across all ages by the American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and Society of Critical Care Medicine. This article is intended to complement the guidelines and highlight aspects relevant to the critical care community; the actual guidelines should be used to update hospital protocols and dictate clinical practice. Because BD/DNC evaluations are conducted in the ICU, it is essential for members of the critical care community to familiarize themselves with these guidelines. The fundamental concept of BD/DNC has not changed; BD/DNC is permanent loss of function of the brain as a whole, including the brain stem, resulting in coma, brainstem areflexia, and apnea in the setting of an adequate stimulus. The BD/DNC evaluation requires a sufficient observation period to ensure there is no chance of recovery, followed by exclusion of potentially confounding conditions like hypothermia, hypotension, severe metabolic disturbances, or medication effects. Specific guidance is provided for patients who were treated with therapeutic hypothermia or medical or surgical interventions to manage intracranial hypertension. The guidelines outline a structured and meticulous neurologic examination and detail the responses consistent with BD/DNC. A protocol is provided for how to safely perform apnea testing, including modifications needed for patients on extracorporeal membrane oxygenation. Controversial issues such as consent, BD/DNC evaluation in pregnancy, preservation of neuroendocrine function, and primary posterior fossa injuries are addressed. The ultimate goal is to ensure a consistent and accurate approach to BD/DNC evaluation in patients of all ages, fostering public trust in the medical community's ability to determine death. By adhering to these guidelines, critical care clinicians can confidently navigate the challenging aspects of BD/DNC determination.

Breath-holding as model for the evaluation of EEG signal during respiratory distress.

PURPOSE: Research describes the existence of a relationship between cortical activity and the regulation of bulbar respiratory centers through the evaluation of the electroencephalographic (EEG) signal during respiratory challenges. For example, we found evidences of a reduction in the frequency of the EEG (alpha band) in both divers and non-divers during apnea tests. For instance, this reduction was more prominent in divers due to the greater physiological disturbance resulting from longer apnea time. However, little is known about EEG adaptations during tests of maximal apnea, a test that voluntarily stops breathing and induces dyspnea. RESULTS: Through this mini-review, we verified that a protocol of successive apneas triggers a significant increase in the maximum apnea time and we hypothesized that successive maximal apnea test could be a powerful model for the study of cortical activity during respiratory distress. CONCLUSION: Dyspnea is a multifactorial symptom and we believe that performing a successive maximal apnea protocol is possible to understand some factors that determine the sensation of dyspnea through the EEG signal, especially in people not trained in apnea.

Frequent Apnea Attacks in a 1-Month-old Infant With Influenza C Virus Infection.

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.

Apnea or cyanosis as COVID-19 initial presentation in newborns.

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.

Cardiorespiratory monitoring with a wireless and nonadhesive belt measuring diaphragm activity in preterm and term infants: A multicenter non-inferiority study.

INTRODUCTION: We determined if the heart rate (HR) monitoring performance of a wireless and nonadhesive belt is non-inferior compared to standard electrocardiography (ECG). Secondary objective was to explore the belt's respiratory rate (RR) monitoring performance compared to chest impedance (CI). METHOD: In this multicenter non-inferiority trial, preterm and term infants were simultaneously monitored with the belt and conventional ECG/CI for 24 h. HR monitoring performance was estimated with the HR difference and ability to detect cardiac events compared to the ECG, and the incidence of HR-data loss per second. These estimations were statistically compared to prespecified margins to confirm equivalence/non-inferiority. Exploratory RR analyses estimated the RR trend difference and ability to detect apnea/tachypnea compared to CI, and the incidence of RR-data loss per second. RESULTS: Thirty-nine infants were included. HR monitoring with the belt was non-inferior to the ECG with a mean HR difference of 0.03 beats per minute (bpm) (standard error [SE] = 0.02) (95% limits of agreement [LoA]: [-5 to 5] bpm) (p < 0.001). Second, sensitivity and positive predictive value (PPV) for cardiac event detection were 94.0% (SE = 0.5%) and 92.6% (SE = 0.6%), respectively (p ≤ 0.001). Third, the incidence of HR-data loss was 2.1% (SE = 0.4%) per second (p < 0.05). The exploratory analyses of RR showed moderate trend agreement with a mean RR-difference of 3.7 breaths/min (SE = 0.8) (LoA: [-12 to 19] breaths/min), but low sensitivities and PPV's for apnea/tachypnea detection. The incidence of RR-data loss was 2.2% (SE = 0.4%) per second. CONCLUSION: The nonadhesive, wireless belt showed non-inferior HR monitoring and a moderate agreement in RR trend compared to ECG/CI. Future research on apnea/tachypnea detection is required.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange Augments Oxygenation in Children With Juvenile Onset Recurrent Respiratory Papillomatosis During Surgery: A Prospective Randomized Crossover Controlled Trial.

BACKGROUND: Evidence is lacking regarding the efficacy of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) in tubeless anesthesia, especially in pediatric patients. This study aimed to evaluate the use of THRIVE for juvenile onset recurrent respiratory papillomatosis (JORRP) patients. METHODS: Twenty-eight children aged 2 to 12 years with JORRP, abnormal airways, and ASA physical status II-III that presented for surgical treatment under general anesthesia were included in this study. Each patient received 2 interventions in random order, with a 5-minute washout period between treatments: apnea without oxygen supplementation and apnea with THRIVE intervention. The primary outcome apnea time was defined as the duration from withdrawal of intubation to reintubation and resumption of controlled ventilation. The secondary outcomes were the mean transcutaneous carbon dioxide (tc co2 ) increase rate, the minimum pulse oxygen saturation (Sp o2 ) during apnea, and the occurrence of unexpected adverse effects. RESULTS: The median apnea time in the THRIVE period was significantly longer than that in the control period (8.9 [8.6-9.4] vs 3.8 [3.4-4.3] minutes; mean difference [95% confidence interval (CI)], 5.0 [4.4-5.6]; P < .001) for all patients. The rate of CO 2 change in the control period was higher than that in the THRIVE period both for patients aged 2 to 5 years old (6.29 [5.19-7.4] vs 3.22 [2.92-3.76] mm Hg min -1 ; mean difference [95% CI], 3.09 [2.27-3.67]; P < .001) and for patients aged 6 to 12 years old (4.76 [3.7-6.2] vs 3.38 [2.64-4.0] mm Hg min -1 ; mean difference [95% CI], 1.63 [0.75-2.56]; P < .001). The minimum Sp o2 was significantly higher in the THRIVE period than in the control period (mean difference [95% CI], 19.7 [14.8-22.6]; P < .001). CONCLUSIONS: Our findings demonstrate that THRIVE safely increased the apnea time among children with JORRP undergoing surgery and decreased the rate of carbon dioxide increase. THRIVE is clinically recommended as an airway management technique for tubeless anesthesia in apneic children.

Tracheal sound-based apnea detection using hidden Markov model in sedated volunteers and post anesthesia care unit patients.

The current method of apnea detection based on tracheal sounds is limited in certain situations. In this work, the Hidden Markov Model (HMM) algorithm based on segmentation is used to classify the respiratory and non-respiratory states of tracheal sounds, to achieve the purpose of apnea detection. Three groups of tracheal sounds were used, including two groups of data collected in the laboratory and a group of patient data in the post anesthesia care unit (PACU). One was used for model training, and the others (laboratory test group and clinical test group) were used for testing and apnea detection. The trained HMMs were used to segment the tracheal sounds in laboratory test data and clinical test data. Apnea was detected according to the segmentation results and respiratory flow rate/pressure which was the reference signal in two test groups. The sensitivity, specificity, and accuracy were calculated. For the laboratory test data, apnea detection sensitivity, specificity, and accuracy were 96.9%, 95.5%, and 95.7%, respectively. For the clinical test data, apnea detection sensitivity, specificity, and accuracy were 83.1%, 99.0% and 98.6%. Apnea detection based on tracheal sound using HMM is accurate and reliable for sedated volunteers and patients in PACU.

The effect of capnography on the incidence of hypoxia during sedation for EGD and colonoscopy in mildly obese patients: a randomized, controlled study.

BACKGROUND: By continually monitoring end-tidal carbon dioxide concentrations, capnography can detect abnormal ventilation or apnoea early. This randomized, controlled study explored the effect of early intervention with capnography on the incidence of hypoxia in mildly obese patients undergoing sedation for esophagogastroduodenoscopy (EGD) and colonoscopy. METHODS: This is a single-center, randomized, single-blind, parallel-assignment, controlled trial. Mildly obese patients (28 kg/m2 ≤ BMI < 40 kg/m2) undergoing sedation for EGD and colonoscopy were randomly assigned to either the standard or capnography group. Standard cardiopulmonary monitoring equipment was used in both groups, and additional capnography was performed in the capnography group. In the event of inadequate alveolar ventilation during sedation, five interventions were administered in sequence (a-e) : a: increasing oxygen flow (5 L/min); b: a chin lift or jaw thrust maneuver; c: placement of the nasopharyngeal airway and chin lift; d: mask positive-pressure ventilation, and e: ventilator-assisted ventilation with tube insertion. The primary outcome was the incidence of hypoxia (SpO2 < 90%, ≥ 10 s) in each group. The secondary outcomes included the incidence of severe hypoxia (SpO2 ≤ 85%), subclinical respiratory depression (90% ≤ SpO2 < 95%), interventions, minimum SpO2 during operation, patient satisfaction, endoscopist satisfaction, and other adverse events of anesthesia sedation. RESULTS: 228 patients were included (capnography group = 112; standard group = 113; three patients were excluded) in this study. The incidence of hypoxia was significantly lower in the capnography group than in the standard group (13.4% vs. 30.1%, P = 0.002). Subclinical respiratory depression in the capnography group was higher than that of the standard group (30.4% vs. 17.7%, P = 0.026). There was only a 5.4% incidence of severe hypoxia in the capnography group compared with 14.2% in the standard group (P = 0.026). During sedation, 96 and 34 individuals in the capnography and standard groups, respectively, underwent the intervention. There was a statistically significant difference (P < 0.0001) in the number of the last intraoperative intervention between the two groups ( a:47 vs. 1, b:46 vs. 26, c:2 vs. 5, d:1 vs. 2, e:0 vs. 0 ). No significant differences were found between the two groups in terms of minimum SpO2 during operation, patient satisfaction, or endoscopist satisfaction rating. There was no statistically significant difference in adverse events of anesthesia sedation between the two groups. CONCLUSION: Capnography during sedation for EGD and colonoscopy allows for the detection of apnea and altered breathing patterns in mildly obese patients before SpO2 is reduced. Effective intervention measures are given to patients within this time frame, which reduces the incidence of hypoxia and severe hypoxia in patients. TRIAL REGISTRATION: Ethical approval was granted by the Medical Ethics Committee (Chairperson Professor Tian Hui) of Qilu Hospital, Shandong University ((Ke) Lun Audit 2021 (186)) on 15/07/2021. The study was registered ( https://www.chictr.org.cn ) on 23/10/2021(ChiCTR2100052234). Designed and reported using CONSORT statements.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a statistical analysis plan for a randomised controlled trial.

The placement of an endotracheal tube for children with acute or critical illness is a low-frequency and high-risk procedure, associated with high rates of first-attempt failure and adverse events, including hypoxaemia. To reduce the frequency of these adverse events, the provision of oxygen to the patient during the apnoeic phase of intubation has been proposed as a method to prolong the time available for the operator to insert the endotracheal tube, prior to the onset of hypoxaemia. However, there are limited data from randomised controlled trials to validate the efficacy of this technique in children. The technique known as transnasal humidified rapid insufflation ventilatory exchange (THRIVE) uses high oxygen flow rates (approximately 2 L/kg/min) delivered through nasal cannulae during apnoea. It has been shown to at least double the amount of time available for safe intubation in healthy children undergoing elective surgery. The technique and its application in real time have not previously been studied in acutely ill or injured children presenting to the emergency department or admitted to an intensive care unit. The Kids THRIVE trial is a multicentre, international, randomised controlled trial (RCT) in children less than 16 years old undergoing emergent intubation in either the intensive care unit or emergency department of participating hospitals. Participants will be randomised to receive either the THRIVE intervention or standard care (no apnoeic oxygenation) during their intubation. The primary objective of the trial is to determine if the use of THRIVE reduces the frequency of oxygen desaturation and increases the frequency of first-attempt success without hypoxaemia in emergent intubation of children compared with standard practice. The secondary objectives of the study are to assess the impact of the use of THRIVE on the rate of adverse events, length of mechanical ventilation and length of stay in intensive care. In this paper, we describe the detailed statistical analysis plan as an update of the previously published protocol.

Adverse Events During Apnea Testing for the Determination of Death by Neurologic Criteria: A Single-Center, Retrospective Pediatric Cohort.

OBJECTIVES: To report the prevalence of adverse events in children undergoing apnea testing as part of the determination of death by neurologic criteria (DNC). DESIGN: Single-center, retrospective study. SETTING: Academic children's hospital that is a Level I Trauma Center. PATIENTS: All children who underwent apnea testing to determine DNC from July 2013 to June 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We abstracted the medical history, blood gases, ventilator settings, blood pressures, vasoactive infusions, intracranial pressures, chest radiographs, and echocardiograms for all apnea tests as well as any ancillary test. Adverse events were defined as hypotension, hypoxia, pneumothorax, arrhythmia, intracranial hypertension, and cardiac arrest. Fifty-eight patients had 105 apnea tests. Adverse events occurred in 21 of 105 apnea tests (20%), the most common being hypotension (15/105 [14%]) and hypoxia (4/105 [4%]). Five of 21 apnea tests (24%) with adverse events were terminated prematurely (three for hypoxia, one for hypotension, and one for both hypoxia and hypotension) but the patients did not require persistent escalation in care. In the other 16 of 21 apnea tests (76%) with adverse events, clinical changes were transient and managed by titrating vasoactive infusions or completing the apnea test. CONCLUSIONS: In our center, 20% of all apnea tests were associated with adverse events. Only 5% of all apnea tests required premature termination and the remaining 15% were completed and the adverse events resolved with medical care.

Inter-hospital cardiorespiratory telemonitoring of newborns and infants: a wellworking example of a hub and spoke network.

BACKGROUND: Patients who experience cardiorespiratory events usually have to be moved to specialized centers to perform cardiorespiratory studies. To avoid the transfer of these patients to specialized centers, a network has been created based on an interchange system, where the recordings were uploaded in unspecialized centers (spokes) and downloaded by the Sleep Disorders Breathing (SDB) Center (hub) to be analyzed. METHODS: The inter-hospital network was established in November 2008. Initially only 3 non-tertiary hospitals in the Tuscany Region joined the network. Currently, 12 Tuscany hospitals are included. RESULTS: From November 2008 to December 2020, 625 recordings were collected belonging to 422 infants. No recurrent life-threatening episode or infant death occurred in the study population and none of the infants needed to be readmitted or be moved to a tertiary center, except infants who underwent home monitoring. The discharge diagnoses belong to the following categories: apnoea, respiratory problem of the newborn, syncope, gastroesophageal reflux, altered consciousness, transient loss of consciousness and cyanosis. CONCLUSIONS: This study shows that the inter-hospital network is an efficient system that allows accurate and safe management of infants at risk for apnoea, bradycardia, and hypoxemia to remain in unspecialized centers, avoiding unnecessary transfers of patients and over - hospitalizations.