Surge of Sympathetic Activity during Hyperventilation at the End of Apnea for Patients with Obstructive Sleep Apnea.

Background and Objectives: The mechanisms connecting obstructive sleep apnea (OSA) and cardiovascular disease are multifactorial, involving intermittent hypoxia, hypercapnia, and sympathetic activation. The aim of this study was to explore the oscillations of sympathetic activity during the sleep apnea episodes throughout the entire night in patients with OSA. Materials and Methods: The participants received whole-night polysomnography (PSG), and electrocardiogram (EKG) data from the PSG were collected for heart rate variability (HRV) analysis. HRV measurements were conducted in the time and frequency domains. The root mean square of successive differences between normal heartbeats (RMSSD), which reflects parasympathetic activity, and the ratio of the absolute power of the low-frequency band (0.04-0.15 Hz) to the absolute power of the high-frequency band (0.015-0.4 Hz) (LF/HF ratio), which indicates sympathetic activity, were computed. Results: A total of 43 participants (35 men and 8 women) were included in the analysis. The mean age of the participants was 44.1 ± 11.3 years old, and the mean BMI was 28.6 ± 5.4 kg/m2. The sleep apnea episodes throughout the entire night in patients with OSA were selected randomly and occurred most frequently during the non-REM stages (39, 90.7%). The selected sleep apnea episodes typically exhibited multiple apneas, often interrupted by snoring respiration and followed by hyperventilation at the end of the episode (HE). Our findings indicate that the centers of the 5 min HRV window for the lowest and highest LF/HF ratios, at 111.8 ± 88.2 and 117.4 ± 88.6 min after sleep onset, respectively, showed a statistically significant difference (p < 0.001). Similarly, the ratios of the lowest and highest LF/HF, at 0.82 ± 0.56 and 3.53 ± 2.94, respectively, exhibited a statistically significant difference (p < 0.001). Conclusions: In the current study, the selected sleep apnea episodes throughout the entire night in patients with OSA occurred primarily during the non-REM stages. Additionally, we observed that sympathetic activity reached its peak in the window that includes hyperventilation at the end stage of apnea, potentially posing a cardiovascular risk. However, additional studies are needed to validate these results.

Association between the presence of an advanced airway and ventilation rate during pediatric CPR: A report from the Videography in Pediatric Resuscitation (VIPER) collaborative.

OBJECTIVE: To determine the association between presence of an advanced airway during pediatric cardiopulmonary resuscitation (CPR) and ventilation rates. METHODS: Prospective observational study, January 2017 to June 2020. Patients ≤18 years receiving CC for ≥2 minutes were enrolled. Ventilation rate and type of airway (advanced airway (AA), either endotracheal tube (ETT) or supraglottic airway (SGA); or natural airway (NA)) were collected from video review and analyzed in 'CPR segments' (periods of CPR by individual providers). Ventilation rate (breaths per minute, bpm) was calculated for each segment; hyperventilation was defined as >12 bpm according to 2015 American Heart Association guidelines. Univariate analysis between airway type was done by χ2 testing. Multivariate regression was used to determine the association between the presence of AA with hyperventilation while controlling for within-patient covariance. RESULTS: 779 CPR segments from 94 CPR event were analyzed. The mean ventilation rate per CPR segment across all events was 22 bpm (±16 bpm)). Mean ventilation rates were higher with AA, either ETT (24 ± 17 bpm) or SGA (34 ± 19 bpm), than with NA (17 ± 14, p < 0.001). Hyperventilation occurred more often with AA in place (ETT: 68%; SGA: 96%; NA: 43%; p < 0.001). The presence of AA was independently associated with hyperventilation (AOR 9.3, 95% CI 4.3-20.1). CONCLUSIONS: During pediatric CPR, hyperventilation occurs more often with an AA in place than during CPR with NA. Future research should focus on respiratory physiology during pediatric CPR to determine optimal ventilation rate(s) during pediatric cardiac arrest.

Methods for calculating ventilation rates during resuscitation from out-of-hospital cardiac arrest.

OBJECTIVE: Ventilation control is important during resuscitation from out-of-hospital cardiac arrest (OHCA). We compared different methods for calculating ventilation rates (VR) during OHCA. METHODS: We analyzed data from the Pragmatic Airway Resuscitation Trial, identifying ventilations through capnogram recordings. We determined VR by: 1) counting the number of breaths within a time epoch ("counted" VR), and 2) calculating the mean of the inverse of measured time between breaths within a time epoch ("measured" VR). We repeated the VR estimates using different time epochs (10, 20, 30, 60 sec). We defined hypo- and hyperventilation as VR <6 and >12 breaths/min, respectively. We assessed differences in estimated hypo- and hyperventilation with each VR measurement technique. RESULTS: Of 3,004 patients, data were available for 1,010. With the counted method, total hypoventilation increased with longer time epochs ([10-s epoch: 75 sec hypoventilation] to [60-s epoch: 97 sec hypoventilation]). However, with the measured method, total hypoventilation decreased with longer time epochs ([10-s epoch: 223 sec hypoventilation] to [60-s epoch: 150 sec hypoventilation]). With the counted method, the total duration of hyperventilation decreased with longer time epochs ([10-s epochs: 35 sec hyperventilation] to [60-s epoch: 0 sec hyperventilation]). With the measured method, total hyperventilation decreased with longer time epochs ([10-s epoch: 78 sec hyperventilation] to [60-s epoch: 0 sec hyperventilation]). Differences between the measured and counted estimates were smallest with a 60-s time epoch. CONCLUSIONS: Quantifications of hypo- and hyperventilation vary with the applied measurement methods. Measurement methods are important when characterizing ventilation rates in OHCA.

Improving Ventilation Rates During Pediatric Cardiopulmonary Resuscitation.

BACKGROUND: Excessive ventilation at rates of 30 breaths per minute (bpm) or more during cardiopulmonary resuscitation (CPR) decreases venous return and coronary perfusion pressure, leading to lower survival rates in animal models. A review of our institution's pediatric CPR data revealed that patients frequently received excessive ventilation. METHODS: We designed a multifaceted quality improvement program to decrease the incidence of clinically significant hyperventilation (≥30 bpm) during pediatric CPR. The program consisted of provider education, CPR ventilation tools (ventilation reminder cards, ventilation metronome), and individual CPR team member feedback. CPR events were reviewed pre- and postintervention. The first 10 minutes of each CPR event were divided into 20 second epochs, and the ventilation rate in each epoch was measured via end-tidal carbon dioxide waveform. Individual epochs were classified as within the target ventilation range (<30 bpm) or clinically significant hyperventilation (≥30 bpm). The proportion of epochs with clinically significant hyperventilation, as well as median ventilation rates, were analyzed in the pre- and postintervention periods. RESULTS: In the preintervention period (37 events, 699 epochs), 51% of CPR epochs had ventilation rates ≥30 bpm. In the postintervention period (24 events, 426 epochs), the proportion of CPR epochs with clinically significant hyperventilation decreased to 29% (P < .001). Median respiratory rates decreased from 30 bpm (interquartile range 21-36) preintervention to 21 bpm (interquartile range 12-30) postintervention (P < .001). CONCLUSIONS: A quality improvement initiative grounded in improved provider education, CPR team member feedback, and tools focused on CPR ventilation rates was effective at reducing rates of clinically significant hyperventilation during pediatric CPR.

Airway strategy and ventilation rates in the pragmatic airway resuscitation trial.

BACKGROUND: We sought to describe ventilation rates during out-of-hospital cardiac arrest (OHCA) resuscitation and their associations with airway management strategy and outcomes. METHODS: We analyzed continuous end-tidal carbon dioxide capnography data from adult OHCA enrolled in the Pragmatic Airway Resuscitation Trial (PART). Using automated signal processing techniques, we determined continuous ventilation rates for consecutive 10-second epochs after airway insertion. We defined hypoventilation as a ventilation rate < 6 breaths/min. We defined hyperventilation as a ventilation rate > 12 breaths/min. We compared differences in total and percentage post-airway hyper- and hypoventilation between airway interventions (laryngeal tube (LT) vs. endotracheal intubation (ETI)). We also determined associations between hypo-/hyperventilation and OHCA outcomes (ROSC, 72-hour survival, hospital survival, hospital survival with favorable neurologic status). RESULTS: Adequate post-airway capnography were available for 1,010 (LT n = 714, ETI n = 296) of 3,004 patients. Median ventilation rates were: LT 8.0 (IQR 6.5-9.6) breaths/min, ETI 7.9 (6.5-9.7) breaths/min. Total duration and percentage of post-airway time with hypoventilation were similar between LT and ETI: median 1.8 vs. 1.7 minutes, p = 0.94; median 10.5% vs. 11.5%, p = 0.60. Total duration and percentage of post-airway time with hyperventilation were similar between LT and ETI: median 0.4 vs. 0.4 minutes, p = 0.91; median 2.1% vs. 1.9%, p = 0.99. Hypo- and hyperventilation exhibited limited associations with OHCA outcomes. CONCLUSION: In the PART Trial, EMS personnel delivered post-airway ventilations at rates satisfying international guidelines, with only limited hypo- or hyperventilation. Hypo- and hyperventilation durations did not differ between airway management strategy and exhibited uncertain associations with OCHA outcomes.

Central Neurogenic Hyperventilation and Hyperlactatemia After Resection of a Fourth Ventricle Tumor: A Case Report.

We report a rare case of central neurogenic hyperventilation (CNH) and hyperlactatemia after resection of a fourth ventricle tumor. Our management consisted of close monitoring and exclusion of alternate causes of hyperventilation and hyperlactatemia. We hypothesize that a localized increase in tissue lactate, related to tumor metabolism, may have triggered CNH in our patient through stimulation of the brainstem respiratory centers. CNH should be considered during the differential diagnosis of perioperative hyperventilation with respiratory alkalosis in patients with posterior fossa tumors. Hyperlactatemia can trigger compensatory hyperventilation but will not result in alkalosis.

OTUB1 regulates lung development, adult lung tissue homeostasis, and respiratory control.

OTUB1 is one of the most highly expressed deubiquitinases, counter-regulating the two most abundant ubiquitin chain types. OTUB1 expression is linked to the development and progression of lung cancer and idiopathic pulmonary fibrosis in humans. However, the physiological function of OTUB1 is unknown. Here, we show that constitutive whole-body Otub1 deletion in mice leads to perinatal lethality by asphyxiation. Analysis of (single-cell) RNA sequencing and proteome data demonstrated that OTUB1 is expressed in all lung cell types with a particularly high expression during late-stage lung development (E16.5, E18.5). At E18.5, the lungs of animals with Otub1 deletion presented with increased cell proliferation that decreased saccular air space and prevented inhalation. Flow cytometry-based analysis of E18.5 lung tissue revealed that Otub1 deletion increased proliferation of major lung parenchymal and mesenchymal/other non-hematopoietic cell types. Adult mice with conditional whole-body Otub1 deletion (wbOtub1del/del ) also displayed increased lung cell proliferation in addition to hyperventilation and failure to adapt the respiratory pattern to hypoxia. On the molecular level, Otub1 deletion enhanced mTOR signaling in embryonic and adult lung tissues. Based on these results, we propose that OTUB1 is a negative regulator of mTOR signaling with essential functions for lung cell proliferation, lung development, adult lung tissue homeostasis, and respiratory regulation.

Respiratory rehabilitation for Covid-19 related persistent dyspnoea: A one-year experience.

BACKGROUND: Growing consideration is emerging regarding the burden of persisting sequelae after SARS-CoV-2 infection. Out-patients exhibiting long Covid may benefit from ambulatory rehabilitation which is, to date, poorly documented. METHODS: A longitudinal follow-up over a one-year period was conducted in two ambulatory rehabilitation structures in order to describe the characteristics of real-life patients referred with Covid-19 sequelae and their evolution over the course of rehabilitation. RESULTS: 39 consecutive patients were included from April 1st, 2020 to April 1st, 2021. Patients were middle-aged (48 ± 15yr), without comorbidities, and mostly mild to moderate SARS-CoV-2 infection (25(64%) not requiring hospitalisation). Rehabilitation referral was considered with a median delay of 73[34-178] days after disease onset. Most prevalent symptoms were dyspnoea (n = 35(90%)) and fatigue (n = 30(77%)). Hyperventilation syndrome was highly frequent (n = 12(34%)). 29(74%) patients presented with prolonged functional sequelae, which was associated with younger age (43 ± 14 vs. 50 ± 10yr; p = 0.002), greater prevalence of hyperventilation syndrome (n = 12(41%) vs. 0(0%); p = 0.255) and poorer quality of life (VQ-11; 31 ± 10 vs. 23 ± 9; p = 0.030). Over the course of rehabilitation, exertional dyspnoea, 6-min walking distance, 3-min sit-to-stand test, hyperventilation syndrome prevalence and quality of life significantly improved. CONCLUSION: Hyperventilation is frequent in long Covid and may explain persistent dyspnoea as well as altered quality of life. Our data support screening of hyperventilation syndrome and functional impairment in mild Covid-19 out-patients as both of these components may improve with ambulatory rehabilitation.

Seguridad en procedimientos dermatológicos: anafilaxia, reacción vasovagal e hiperventilación / Safety in Dermatologic Procedures: Anaphylaxis, Vasovagal Reaction, and Hyperventilation

En el presente artículo de la serie «Seguridad en procedimientos dermatológicos» se aborda el diagnóstico, prevención, manejo y tratamiento de tres situaciones. Primeramente, se aborda la anafilaxia: una situación infrecuente, grave y potencialmente mortal, que requiere una identificación ágil para un manejo urgente coordinado por parte de médicos especialistas en anestesiología. En segundo lugar, la reacción vasovagal, que es la complicación médica más frecuente durante la cirugía dermatológica (una de cada 160 intervenciones), con una evolución habitualmente benigna autorresolutiva, pero que, en individuos muy sensibles, puede provocar una parada cardiaca por asistolia. En tercer y último lugar, el síndrome de hiperventilación aguda, que es una respuesta anómala de determinados individuos a un evento estresante, con un incremento de la ventilación que excede la demanda metabólica. En los tres casos se incluyen recomendaciones que se plasman de forma práctica y somera (AU)

This article, part of a the series on safety in dermatologic procedures, covers the diagnosis, prevention, management, and treatment of 3 situations or conditions. The first condition we address is anaphylaxis, an uncommon but severe and potentially fatal reaction that must be recognized quickly so that urgent management coordinated with an anesthesiologist can commence. The second is the vasovagal reaction, which is the most common complication in dermatologic surgery. This event, which occurs in 1 out of every 160 procedures, usually follows a benign course and resolves on its own. However, in patients susceptible to vasovagal reactions, syncope may lead to asystole and cardiac arrest. The third is acute hyperventilation syndrome, which is an anomalous anxiety-related increase in breathing rate beyond metabolic requirements. Brief practical recommendations for managing all 3 events are included (AU)

Effects of hyperventilation with face mask on brain network in patients with epilepsy.

OBJECTIVES: During the ongoing pandemic of COVID-19, wearing face masks was recommended, including patients with epilepsy doing the hyperventilation (HV) test during electroencephalogram (EEG) examination somewhere. However, evidence was still limited about the effect of HV with face mask on cortical excitability of patients with epilepsy. The motivation of this work is to make use of the graph theory of EEG to characterize the cortical excitability of patients with epilepsy when they did HV under the condition wearing a surgical face mask. METHODS: We recruited 19 patients with epilepsy and 17 normal controls. All of participants completed two HV experiments, including HV with face mask (HV+) and HV without a mask (HV). The interval was 30 min and the sequence was random. Each experiment consisted of three segments: resting EEG, EEG of HV, and EEG of post-HV. EEG were recorded successively during each experiment. Participants were asked to evaluate the discomfort degree using a questionnaire when every HV is completed. RESULTS: All of the participants felt more uncomfortable after HV + . Moreover, not only HV decreased small-worldness index in patients with epilepsy, but also HV + significantly increased the clustering coefficient in patients with epilepsy. Importantly, the three-way of Mask*HV*Epilepsy showed interaction in the clustering coefficient in the delta band, as well as in the path length and the small-worldness index in the theta band. CONCLUSIONS: The results of this study indicated that patients with epilepsy showed the increased excitability of brain network during HV + . We should pay more attention to the adverse effect on brain network excitability caused by HV + in patients with epilepsy. In the clinical practice under the COVID-19 pandemic, it is important that the wearing face mask remain cautious for the individuals with epilepsy when they carried out HV behavior such as exercise (e.g., running, etc.).

Paroxysmal dyspnea in Parkinson's disease: Respiratory dyskinesias and autonomic hyperventilation are not the same.

Respiratory complaints are not uncommon in patients with Parkinson's disease (PD). While many are explained by pulmonary and cardiovascular problems unrelated to PD, secondary effects of PD, such as kyphoscoliosis, respiratory muscle rigidity, repeated pneumonias, or side effects of medication such as dyskinesias, there is a small group of patients with paroxysmal dyspnea for whom neither anxiety or other explanation has been found. This Point of View was written to call attention to this neglected, uncommon, but very distressing symptom.

[The psychological burden of asthma]. / Le fardeau psychologique de l'asthme.

The experience of living with asthma varies between patients. In some cases, the psychological experience can take a central place and determine the course of asthma. Asthmatic disease can be complicated by adaption disorders that hamper the treatment, or genuine anxiety and depressive disorders that require the intervention of mental health specialists. Even more, the psychological experience can influence the intensity and frequency of the physical symptoms themselves, for example when asthma is associated with a hyperventilation syndrome worsening the functional impact and complicating the treatment. In this article, we underline the significance of the psychological experience through several clinical vignettes of patients suffering from asthma. In particular, we discuss the role of denial, or conversely identification with the status of being a patient, and the importance of the emotional experience associated with the symptoms of asthma. We highlight the relevance of therapeutic education programs as well as cognitive-behavioral therapies and psycho-corporal techniques, such as relaxation, for the psychological care of asthmatic disease. Finally, we detail how to better recognize a hyperventilation syndrome associated with asthma, how it can be approached with the patient and the treatment options. Through these examples, we illustrate the relevance of a comprehensive approach that integrates the psychological experience into the care of asthmatic disease.

Central neurogenic hyperventilation secondary to suspected metastatic renal cell carcinoma.

Central neurogenic hyperventilation (CNH) is a neurogenic disorder rarely described within Emergency Medicine literature. CNH is a primary cause of hyperventilation, most commonly due to primary central nervous system neoplasms. Patient presentation varies based on the underlying cause, and may present with a sole chief complaint of dyspnea. We present a case of an adult male with a history of deep vein thrombosis, anticoagulated on apixaban, and extensively metastatic renal cell carcinoma who presented with a two-week history of dyspnea. Evaluation in the emergency department showed a primary respiratory alkalosis with a compensatory metabolic acidosis. Diagnostic work-up failed to reveal a cardiac, pulmonary, metabolic, or toxic cause. During the emergency department course, the patient became dysarthric and altered, at which point, computed tomography scan of the head revealed a pontine hemorrhage. The hemorrhage was stabilized with prothrombin complex concentrate, but the patient's dyspnea and mental status deteriorated throughout the course of his hospitalization. While the cause of the patient's hemorrhage was not elucidated, given the patient's widely metastatic disease, it was presumed to be secondary to metastasis. Our case highlights both a unique cause of a rare disorder of hyperventilation, and a diagnostic challenge to the emergency medicine provider. It is important to consider central causes of hyperventilation in patients with dyspnea and neurologic symptoms.

Comparative analysis between available challenge tests in the hyperventilation syndrome.

BACKGROUND: The hyperventilation syndrome (HVS) is characterized by somatic/ psychological symptoms due to sustained hypocapnia and respiratory alkalosis without any organic disease. OBJECTIVE: The purpose of this study was to compare ventilatory parameters and symptoms reproducibility during the hyperventilation provocation test (HVPT) and cardiopulmonary exercise test (CPET) as diagnostic tools in patients with HVS, and to identify the most frequent etiologies of the HVS by a systematic assessment. METHODS: After exclusion of organic causes, 59 patients with HVS according to Nijmegen's questionnaire (NQ) score ≥23 with associated hypocapnia (PaCO2/PETCO2<35 mm Hg) were studied. RESULTS: The most frequent comorbidities of HVS were anxiety and asthma (respectively 95% and 73% of patients). All patients described ≥3 symptoms of NQ during the HVPT vs 14% of patients during the CPET (p<0.01). For similar maximal ventilation (61 L/min during HVPT vs 60 L/min during CPET), the median level of PETCO2 decreased from 30 mmHg at baseline to 15 mmHg during hyperventilation and increased from 31 mmHg at baseline to 34 mmHg at peak exercise (all p<0.01). No significant difference for the ventilatory parameters was found between patients with HVS (n = 16) and patients with HVS + asthma (n = 43). CONCLUSIONS: In term of symptoms reproducibility, HVPT is a better diagnostic tool than CPET for HVS. An important proportion of patients with HVS has an atypical asthma previously misdiagnosed. The exercise-induced hyperventilation did not induce abnormal reduction in PETCO2, suggesting that the exercise could be a therapeutic tool in HVS.

Caffeine Exacerbates Hyperventilation and Reductions in Cerebral Blood Flow in Physically Fit Men Exercising in the Heat.

INTRODUCTION: Caffeine is an exercise performance enhancer widely used by individuals engaged in training or competition under heat-stressed conditions. Caffeine ingestion during exercise in the heat is believed to be safe because it does not greatly affect body temperature responses, heart rate, or body fluid status. However, it remains unknown whether caffeine affects hyperthermia-induced hyperventilation or reductions in the cerebral blood flow index. We tested the hypothesis that under conditions inducing severe hyperthermia, caffeine exacerbates hyperthermia-induced hyperventilation and reduces the cerebral blood flow index during exercise. METHODS: Using a randomized, single-blind, crossover design, 12 physically active healthy young men (23 ± 2 yr) consumed a moderate dose of caffeine (5 mg·kg-1) or placebo in the heat (37°C). Approximately 60 min after the ingestion, they cycled for ~45 min at a workload equal to ~55% of their predetermined peak oxygen uptake (moderate intensity) until their core temperature increased to 2.0°C above its preexercise baseline level. RESULTS: In both trials, ventilation increased and the cerebral blood flow index assessed by middle cerebral artery mean blood velocity decreased as core temperature rose during exercise (P < 0.05), indicating that hyperthermia-induced hyperventilation and lowering of the cerebral blood flow occurred. When core temperature was elevated by 1.5°C or more (P < 0.05), ventilation was higher and the cerebral blood flow was lower throughout the caffeine trial than the placebo trial (P < 0.05). CONCLUSIONS: A moderate dose of caffeine exacerbates hyperthermia-induced hyperventilation and reductions in the cerebral blood flow index during exercise in the heat with severe hyperthermia.