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.

Hyperventilation testing in the diagnosis of vasospastic angina: A clinical review and meta-analysis.

BACKGROUND: Given the limited access to invasive vasospastic reactivity testing in Western Countries, there is a need to further develop alternative non-invasive diagnostic methods for vasospastic angina (VSA). Hyperventilation testing (HVT) is defined as a class IIa recommendation to diagnose VSA by the Japanese Society of Cardiology. METHODS: In this systematic review and meta-analysis reported according to the PRISMA statement, we review the mechanisms, methods, modalities and diagnostic accuracy of non-invasive HVT for the diagnostic of VSA. RESULTS: A total of 106 articles published between 1980 and 2022 about VSA and HVT were included in the systematic review, among which 16 were included in the meta-analysis for diagnostic accuracy. Twelve electrocardiogram-HVT studies including 804 patients showed a pooled sensitivity of 54% (95% confidence intervals [CI]; 30%-76%) and a pooled specificity of 99% (95% CI; 88%-100%). Four transthoracic echocardiography-HVT studies including 197 patients revealed a pooled sensitivity of 90% (95% CI; 82%-94%) and a pooled specificity of 98% (95% CI; 86%-100%). Six myocardial perfusion imaging-HVT studies including 112 patients yielded a pooled sensitivity of 95% (95% CI; 63%-100%) and a pooled specificity of 78% (95% CI; 19%-98%). Non-invasive HVT resulted in a low rate of adverse events, ventricular arrhythmias being the most frequently reported, and were resolved with the administration of nitroglycerin. CONCLUSIONS: Non-invasive HVT offers a safe alternative with high diagnostic accuracy to diagnose VSA in patients with otherwise undiagnosed causes of chest pain.

Acetazolamide as an effective treatment for pilomotor seizures in autoimmune encephalitis.

Pilomotor seizures are strongly associated with autoimmune encephalitis (AE), particularly anti-LGI1 encephalitis. The carbonic anhydrase inhibitor acetazolamide may have special efficacy for treating AE-associated pilomotor seizures. Six patients with AE (five anti-LGI1, one seronegative) and temporal lobe pilomotor seizures (five with seizures inducible by hyperventilation) were treated with acetazolamide, administered in a cycling (2-days-ON, 4-days-OFF) regimen to offset tolerance. Seizures were assessed during epilepsy monitoring unit (EMU) recordings in four inpatients (one of whom also maintained an outpatient seizure diary chronicling 1203 seizures over 1079 days); two outpatients self-reported seizure frequencies. The extended diary revealed an inverse correlation between acetazolamide and proportion of seizures/day: 6%, 2% (days 1, 2 ON); 3%, 13%, 31%, 45% (days 1, 2, 3, 4 OFF). This patient later developed focal status epilepticus upon wean of antiseizure medications during a seropositive AE relapse that was remarkably aborted with acetazolamide monotherapy. The other three EMU patients averaged .56 seizures/day ON, and 3.81 seizures/day OFF (p = .004). The two outpatients reported seizure reductions from 3-5/day to 2/week, and 15-20/day to none, respectively, after initiation of cycling acetazolamide. Likely related to cerebral CO2/pH sensitivity, acetazolamide can be unusually effective in controlling pilomotor seizures in AE, chronically or in acute settings.

Breathing control training for functional seizures: A multi-site, open-label pilot study.

There are no well-validated treatments for functional seizures. While specialist psychotherapy is usually recommended, the evidence for its benefit is qualified, and it can be difficult to obtain. Given the association between hyperventilation and functional seizures we explored an alternative modality, breathing control training, in a multi-site open label pilot trial. Participants with functional seizures over the age of 16 received an hour of breathing training from a respiratory physiotherapist, with a half-hour booster session a month later. Seizure frequency and Nijmegen scores (a measure of hyperventilation) were reported at baseline and follow-up, 3-4 months later. Eighteen subjects were recruited, and 10 completed follow-up. Seven of these 10 had improved seizure frequency, and 3 did not (Wilcoxon signed rank test, p = 0.09), with seizure frequency correlating with Nijmegen score (Spearman's rank correlation = 0.75, p = 0.034). The intervention was well tolerated, with no adverse events reported. These preliminary results support a potentially new approach to treating functional seizures that should prove cost-effective and acceptable, though require confirmation by a randomised controlled trial.

Persisting exercise ventilatory inefficiency in subjects recovering from COVID-19. Longitudinal data analysis 34 months post-discharge.

BACKGROUND: SARS-CoV-2 infection has raised concerns about long-term health repercussions. Exercise ventilatory inefficiency (EVin) has emerged as a notable long-term sequela, potentially impacting respiratory and cardiovascular health. This study aims to assess the long-term presence of EVin after 34 months and its association with cardiorespiratory health in post-COVID patients. METHODS: In a longitudinal study on 32 selected post-COVID subjects, we performed two cardiopulmonary exercise tests (CPETs) at 6 months (T0) and 34 months (T1) after hospital discharge. The study sought to explore the long-term persistence of EVin and its correlation with respiratory and cardiovascular responses during exercise. Measurements included also V̇O2peak, end-tidal pressure of CO2 (PETCO2) levels, oxygen uptake efficiency slope (OUES) and other cardiorespiratory parameters, with statistical significance set at p < 0.05. The presence of EVin at both T0 and T1 defines a persisting EVin (pEVin). RESULTS: Out of the cohort, five subjects (16%) have pEVin at 34 months. Subjects with pEVin, compared to those with ventilatory efficiency (Evef) have lower values of PETCO2 throughout exercise, showing hyperventilation. Evef subjects demonstrated selective improvements in DLCO and oxygen pulse, suggesting a recovery in cardiorespiratory function over time. In contrast, those with pEvin did not exhibit these improvements. Notably, significant correlations were found between hyperventilation (measured by PETCO2), oxygen pulse and OUES, indicating the potential prognostic value of OUES and Evin in post-COVID follow-ups. CONCLUSIONS: The study highlights the clinical importance of long-term follow-up for post-COVID patients, as a significant group exhibit persistent EVin, which correlates with altered and potentially unfavorable cardiovascular responses to exercise. These findings advocate for the continued investigation into the long-term health impacts of COVID-19, especially regarding persistent ventilatory inefficiencies and their implications on patient health outcomes.

Short-term mild hyperventilation on intracranial pressure, cerebral autoregulation, and oxygenation in acute brain injury patients: a prospective observational study.

Current guidelines suggest a target of partial pressure of carbon dioxide (PaCO2) of 32-35 mmHg (mild hypocapnia) as tier 2 for the management of intracranial hypertension. However, the effects of mild hyperventilation on cerebrovascular dynamics are not completely elucidated. The aim of this study is to evaluate the changes of intracranial pressure (ICP), cerebral autoregulation (measured through pressure reactivity index, PRx), and regional cerebral oxygenation (rSO2) parameters before and after induction of mild hyperventilation. Single center, observational study including patients with acute brain injury (ABI) admitted to the intensive care unit undergoing multimodal neuromonitoring and requiring titration of PaCO2 values to mild hypocapnia as tier 2 for the management of intracranial hypertension. Twenty-five patients were included in this study (40% female), median age 64.7 years (Interquartile Range, IQR = 45.9-73.2). Median Glasgow Coma Scale was 6 (IQR = 3-11). After mild hyperventilation, PaCO2 values decreased (from 42 (39-44) to 34 (32-34) mmHg, p < 0.0001), ICP and PRx significantly decreased (from 25.4 (24.1-26.4) to 17.5 (16-21.2) mmHg, p < 0.0001, and from 0.32 (0.1-0.52) to 0.12 (-0.03-0.23), p < 0.0001). rSO2 was statistically but not clinically significantly reduced (from 60% (56-64) to 59% (54-61), p < 0.0001), but the arterial component of rSO2 (ΔO2Hbi, changes in concentration of oxygenated hemoglobin of the total rSO2) decreased from 3.83 (3-6.2) µM.cm to 1.6 (0.5-3.1) µM.cm, p = 0.0001. Mild hyperventilation can reduce ICP and improve cerebral autoregulation, with minimal clinical effects on cerebral oxygenation. However, the arterial component of rSO2 was importantly reduced. Multimodal neuromonitoring is essential when titrating PaCO2 values for ICP management.

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.

[Dyspnea in post-COVID-19 patients: A review].

New coronavirus infection may lead to long-term consequences, particularly to post-COVID syndrome, one of the most common manifestations of which is dyspnea. Post-COVID-19 shortness of breath may persist from one to several months and even years that results in low quality of life of patients. The review highlights possible risk factors and causes of dyspnea in post-COVID period such as lung damage, cardiovascular pathology, hyperventilation syndrome, dysfunction of the autonomic nervous system, detraining, anemia, etc. The authors present data about COVID-19-associated causes of dyspnea and severity of acute COVID-19. The review emphasizes the importance of a multidisciplinary approach to the diagnosis and treatment of patients with shortness of breath in post-COVID-19 period.

Exercise ventilatory response after COVID-19: comparison between ambulatory and hospitalized patients.

Inefficient ventilatory response during cardiopulmonary exercise testing (CPET) has been suggested as a cause of post-COVID-19 dyspnea. It has been described in hospitalized patients (HOSP) with lung parenchymal sequelae but also after mild infection in ambulatory patients (AMBU). We hypothesize that AMBU and HOSP have different ventilatory responses to exercise, due to different etiologies. We analyzed CPET realized between July 2020 and May 2022 of patients with persisting respiratory symptoms 3 mo after COVID-19. Chest computed tomography (CT) scan, pulmonary function tests, quality of life, and respiratory questionnaires were collected. CPET data were specifically explored as a function of ventilation (V̇e) and time. Seventy-nine consecutive patients were included (42 AMBU and 37 HOSP, median: 54 [44-60] yr old, 57% female). Patients were hospitalized for a median of 20 [8-34] days, with pneumonia (41%) or acute respiratory distress syndrome (ARDS; 30%). Among HOSP, 12(32%) patients had abnormal values for spirometry and 18(51%) for carbon monoxide diffusing capacity (P < 0.001). CPET showed no differences between AMBU and HOSP in peak absolute O2 uptake (V̇o2) (1.59 [1.22-2.11] mL·min-1; P = 0.65). Tidal volume (VT) as a function of V̇e, was lower in AMBU than in HOSP (P < 0.01) toward the end of exercise. The slope of the V̇e-CO2 production was higher than normal in both groups (30.9 [26.1-34.3]; P = 0.96). In conclusion, the severity of COVID-19 did not influence the exercise capacity, but AMBU demonstrated a less efficient ventilatory response to exercise as compared with HOSP. CPET with exploration of data as a function of V̇e and throughout the exercise better unveil ventilatory inefficiency.NEW & NOTEWORTHY We evaluated the exercise ventilatory response in patients with persisting dyspnea after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. We found that despite similar peak power and peak absolute O2 uptake, tidal volume as a function of ventilation was lower in ambulatory than in hospitalized patients toward the end of exercise, reflecting ventilatory inefficiency. We call for evaluation of minute ventilation with the exploration of data throughout the exercise and not only peak data to better unveil ventilatory inefficiency.

Hypocapnia attenuates local skin thermal perception to innocuous warm and cool stimuli in normothermic resting humans.

When one is exposed to a stressful situation in their daily life, a common response is hyperventilation. Although the physiological significance of stress-induced hyperventilation remains uncertain, this response may blunt perception of the stress-inducing stimulus. This study examined the effects of voluntary hyperventilation and resultant hypocapnia on the local skin thermal detection threshold in normothermic resting humans. Local skin thermal detection thresholds were measured in 15 young adults (three females) under three breathing conditions: 1) spontaneous breathing (Control trial), 2) voluntary hypocapnic hyperventilation (HH trial), and 3) voluntary normocapnic hyperventilation (NH trial). Local skin thermal detection thresholds were measured using thermostimulators containing a Peltier element that were attached to the forearm and forehead. The temperature of the probe was initially equilibrated to the skin temperature, then gradually increased or decreased at a constant rate (±0.1 °C/s) until the participants felt warmth or coolness. The difference between the initial skin temperature and the local skin temperature at which the participant noticed warmth/coolness was assessed as an index of the local skin warm/cool detection threshold. Local detection of warm and cool stimuli did not differ between the Control and NH trials, but it was blunted in the HH trial as compared with the Control and NH trials, except for detection of warm stimuli on the forearm. These findings suggest that hyperventilation-induced hypocapnia, not hyperventilation per se, attenuates local skin thermal perception, though changes in responses to warm stimuli may not be clearly perceived at some skin areas (e.g., forearm).

Sodium bicarbonate reduces ventilation without altering core temperature threshold or sensitivity of hyperthermia-induced hyperventilation in exercising humans.

Hyperthermia stimulates ventilation (hyperthermia-induced hyperventilation). In exercising humans, once the core temperature reaches ∼37°C, minute ventilation (V̇e) increases linearly with rising core temperature, and the slope of the relation between V̇e and core temperature reflects the sensitivity of the response. We previously reported that sodium bicarbonate ingestion reduces V̇e during prolonged exercise in the heat without affecting the sensitivity of hyperthermia-induced hyperventilation. Here, we hypothesized that reductions in V̇e associated with sodium bicarbonate ingestion reflect elevation of the core temperature threshold for hyperthermia-induced hyperventilation. Thirteen healthy young males ingested sodium bicarbonate (0.3 g/kg body wt) (NaHCO3 trial) or sodium chloride (0.208 g/kg body wt) (NaCl trial), after which they performed a cycle exercise at 50% of peak oxygen uptake in the heat (35°C and 50% relative humidity) following a pre-cooling. The pre-cooling enabled detection of an esophageal temperature (Tes: an index of core temperature) threshold for hyperthermia-induced hyperventilation. The Tes thresholds for increases in V̇e were similar between the two trials (P = 0.514). The slopes relating V̇E to Tes also did not differ between trials (P = 0.131). However, V̇e was lower in the NaHCO3 than in the NaCl trial in the range of Tes = 36.8-38.4°C (P = 0.007, main effect of trial). These results suggest that sodium bicarbonate ingestion does not alter the core temperature threshold or sensitivity of hyperthermia-induced hyperventilation during prolonged exercise in the heat; instead, it downshifts the exercise hyperpnea.

Fear conditioning as a pathogenic mechanism in the postural tachycardia syndrome.

Despite its increasing recognition and extensive research, there is no unifying hypothesis on the pathophysiology of the postural tachycardia syndrome. In this cross-sectional study, we examined the role of fear conditioning and its association with tachycardia and cerebral hypoperfusion on standing in 28 patients with postural tachycardia syndrome (31 ± 12 years old, 25 females) and 21 matched controls. We found that patients had higher somatic vigilance (P = 0.0167) and more anxiety (P < 0.0001). They also had a more pronounced anticipatory tachycardia right before assuming the upright position in a tilt-table test (P = 0.015), a physiological indicator of fear conditioning to orthostasis. While standing, patients had faster heart rate (P < 0.001), higher plasma catecholamine levels (P = 0.020), lower end-tidal CO2 (P = 0.005) and reduced middle cerebral artery blood flow velocity (P = 0.002). Multi-linear logistic regression modelling showed that both epinephrine secretion and excessive somatic vigilance predicted the magnitude of the tachycardia and the hyperventilation. These findings suggest that the postural tachycardia syndrome is a functional disorder in which standing may acquire a frightful quality, so that even when experienced alone it may elicit a fearful conditioned response. Heightened somatic anxiety is associated with and may predispose to a fear-conditioned hyperadrenergic state when standing. Our results have therapeutic implications.

A case of Pitt-Hopkins syndrome: psychopharmacological approach for anxiety, insomnia, and agitation.

Pitt-Hopkins syndrome (PTHS) is a rare genetic disorder resulting from TCF4 gene mutations which is characterized by dysmorphic facial features, psychomotor delay, intellectual disability, breathing anomalies, and seizures. Psychiatric conditions are occasionally seen. We present the case report of a seven-year-old PTHS patient with anxiety, insomnia, and agitation. We discuss the psychopharmacological intervention options for this patient. The present case study reports on a 7-year-old female with PTHS, autism spectrum disorder (ASD), and intellectual disability. She had insomnia, crying spells and agitation complaints. For anxiety symptoms and agitation, risperidone, fluoxetine, and clonazepam treatment were given by the neurologist which caused behavioral disinhibition, paroxysmal agitation and no benefit. After admission to our hospital, aripiprazole and hydroxyzine were prescribed for anxiety and ASD-related irritability. She showed a minimal improvement but hyperventilation attacks were still ongoing. Hydroxyzine was stopped, and quetiapine was given to eliminate sleep disturbance. Her sleep period went up to eleven hours. For the anxiety symptoms, escitalopram was prescribed. She showed improvements in sleep, diminished hyperactivity and decreased frequency of abnormal breathing spells. Also, enhancement of social communication skills like increased eye contact and response to her name was observed. Patients with genetic syndromes may have various psychiatric complaints. Psychopharmacological interventions should be administered carefully for the side effects.

Hyperventilation syndrome in children with asthma.

BACKGROUND: Hyperventilation syndrome (HVS) may be associated with asthma. In the absence of a gold standard diagnosis for children, its impact on asthma has been rarely assessed. OBJECTIVE: To assess the impact of HVS on the symptoms and lung function of children with asthma and determine the diagnostic value of the Nijmegen questionnaire in comparison to a hyperventilation test (HVT). METHODS: Data from asthmatic children followed in the department of Pediatric Pulmonology of Necker Hospital and explored for HVS were retrospectively analyzed. HVS was diagnosed by a positive HVT. Asthma exacerbations, control and lung function were assessed in children with or without a positive HVT. The sensitivity and specificity of the Nijmegen questionnaire were determined relative to the positivity of a HVT. The Nijmegen questionnaire threshold was ≥23. RESULTS: Data from 112 asthmatic children, median age 13.9 years [11.6-16], were analyzed. Twenty-eight children (25%) had mild or moderate asthma and 84 (75%) severe asthma. The HVT was performed on 108 children and was negative for 34 (31.5%) and positive for 74 (68.5%). The number of asthma exacerbations in the past 12 months, Asthma Control Test (ACT) score, and lung function did not differ between children with a positive HVT and a negative HVT. The Nijmegen questionnaire was administered to 103 children. Its sensitivity was 56.3% and specificity 56.3%. CONCLUSION: The symptoms and lung function of adolescents with asthma are not affected by the presence of HVS. The sensitivity and specificity of the Nijmegen questionnaire are low.

Arterial to end-tidal CO2 gradients during isocapnic hyperventilation.

Isocapnic hyperventilation (ICHV) is occasionally used to maintain the end-expired CO2 partial pressure (PETCO2) when the inspired CO2 (PICO2) rises. Whether maintaining PETCO2 with ICHV during an increase of the PICO2 also maintains arterial PCO2 (PaCO2) remains poorly documented. 12 ASA PS I-II subjects undergoing a robot-assisted radical prostatectomy (RARP) (n = 11) or cystectomy (n = 1) under general endotracheal anesthesia with sevoflurane in O2/air (40% inspired O2) were enrolled. PICO2 was sequentially increased from 0 to 0.5, 1.0, 1.5 and 2% by adding CO2 to the inspiratory limb of the circle system, while increasing ventilation to a target PETCO2 of 4.7-4.9% by adjusting respiratory rate during controlled mechanical ventilation. Pa-ETCO2 gradients were determined after a 15 min equilibration period at each PICO2 level and compared using ANOVA. Mean (standard deviation) age, height, and weight were 66 (6) years, 171 (6) cm, and 75 (8) kg, respectively. Capnograms were normal and hemodynamic parameters remained stable. PETCO2 could be maintained within 4.7-4.9% in all subjects at all times except in 1 subject with 1.5% PICO2 and 5 subjects with 2.0% PICO2; data from the one subject in whom both 1.5 and 2.0% PICO2 resulted in PETCO2 > 5.1% were excluded from analysis. Pa-ETCO2 gradients did not change when PICO2 increased. The effect of a modest rise of PICO2 up to 1.5% on PETCO2 during RARP can be readily overcome by increasing ventilation without altering the Pa-ETCO2 gradients. At higher PICO2, airway pressures may become a limiting factor, which requires further study.

Arterial Blood Gases in Normal Subjects at 2240 Meters Above Sea Level: Impact of Age, Gender, and Body Mass Index.

Background: The values of arterial blood gases (ABG) change with altitude above sea level; empirical verification is essential because ventilatory acclimatization varies with ethnicity and a population's adaptation. Objective: The aim of the study was to describe ABG in a healthy population residing at 2,240 meters above sea level, to identify the mean level of alveolar ventilation (PaCO2), and to know whether a progressive increase in PaCO2 occurs with age and the impact of increasing body mass index (BMI). Methods: We conducted a cross-sectional study in a referral center for respiratory diseases in Mexico City. Associations among variables with correlation coefficient and regression models of PaO2, SaO2, and P(A-a)O2 as dependent variables as a function of age, BMI, minute ventilation, or breathing frequency were explored. Results: Two hundred and seventeen healthy subjects were evaluated with a mean age of 40 ± 15 years, mean of the PaO2 was 71 ± 6 mmHg, SaO2 94% ± 1.6%, PaCO2 30.2 ± 3.4 mmHg, HCO3 20 ± 2 mmol/L, BE-2.9 ± 1.9 mmol/L, and the value of pH was 7.43 ± 0.02. In a linear regression, the main results were PaO2 = 77.5-0.16*age (p < 0.0001) and with aging P(A-a)O2 tended to increase 0.12 mmHg/year. PaCO2 in women increased with age by 0.075 mmHg/year (p = 0.0012, PaCO2 =26.3 + 0.075*age). SaO2 and PaO2 decreased significantly in women with higher BMI 0.14% and 0.52 mmHg per kg/m2, (p = 0.004 and 0.002 respectively). Conclusion: Mean PaCO2 was 30.7 mmHg, implying a mean alveolar ventilation of around 30% above that at sea level.

[Dyspnea «sine materia¼]. / La dyspnée «sine materia¼.

Dyspnea is a symptom of respiratory discomfort commonly encountered in clinical practice which, in most of the cases, relates to a cardiopulmonary or a metabolic disorder. Its genesis is complex and results from numerous interactions within cortical and limbic brain areas following intero- and nociceptive stimuli. The term dyspnea «sine materia¼ points to a state where no clear underlying cardiopulmonary or metabolic pathology has been identified and we include here the hyperventilation syndrome and the physical deconditioning. Treatment of dyspnea «sine materia¼ is based on behavioural psychotherapy and on reathtletisation programme in case of physical deconditioning.

La dyspnée est un symptôme d'inconfort respiratoire extrêmement courant en médecine qui traduit, le plus souvent, un désordre cardiorespiratoire ou métabolique. Sa genèse est complexe et résulte de l'intégration, au niveau du cortex et du système limbique, de messages intéro- et nociceptifs. Par dyspnée «sine materia¼, nous entendons ici une dyspnée sans pathologie cardiorespiratoire ou métabolique sous-jacente avérée et nous y incluons celle du syndrome d'hyperventilation et du déconditionnement physique. La prise en charge de la dyspnée «sine materia¼ et, notamment, celle du syndrome d'hyperventilation repose sur la psychothérapie comportementale et la gestion du déconditionnement physique par des programmes de réathlétisation.

Associations between psychological and respiratory distress in post-deployment Veterans.

Since September 11, 2001, over 2.7 million United States service members have deployed to South-West Asia and the Middle East and have been exposed to environmental hazards and psychological trauma. Many of these service members have returned with medical and psychological illnesses, some of which have proved complex and resistant to treatment. One notable constellation of symptoms is post-deployment respiratory illness, which has become a focus of research and policy efforts. The present study sought to examine the impact of post-deployment psychological distress on respiratory symptom severity. Data were obtained from the Veterans Affairs Airborne Hazards and Open Burn Pit Registry (AHOBPR) health surveillance database (N =107,403). Psychological factors were compared against common organic and environmental predictors of post-deployment respiratory distress. Psychological distress following deployment was a stronger predictor of 12-month shortness of breath severity than general respiratory pathology or level of exposure to environmental hazards, controlling for gender, age, race, and tobacco use. Additionally, psychological distress was a better predictor of shortness of breath severity than documented respiratory illnesses including asthma, chronic obstructive pulmonary disease, and chronic bronchitis. Implications and directions for future research are discussed, as well as potential alterations to existing treatment and health surveillance paradigms.

Contribution of the carotid body to thermally mediated hyperventilation in humans.

Humans hyperventilate under heat and cold strain. This hyperventilatory response has detrimental consequences including acid-base dysregulation, dyspnoea, decreased cerebral blood flow and accelerated brain heating. The ventilatory response to hypoxia is exaggerated under whole-body heating and cooling, indicating that altered carotid body function might contribute to thermally mediated hyperventilation. To address whether the carotid body might contribute to heat- and cold-induced hyperventilation, we indirectly measured carotid body tonic activity via hyperoxia, and carotid body sensitivity via hypoxia, under graded heat and cold strain in 13 healthy participants in a repeated-measures design. We hypothesised that carotid body tonic activity and sensitivity would be elevated in a dose-dependent manner under graded heat and cold strain, thereby supporting its role in driving thermally mediated hyperventilation. Carotid body tonic activity was increased in a dose-dependent manner with heating, reaching 175% above baseline (P < 0.0005), and carotid body suppression with hyperoxia removed all of the heat-induced increase in ventilation (P = 0.9297). Core cooling increased carotid body activity by up to 250% (P < 0.0001), but maximal values were reached with mild cooling and thereafter plateaued. Carotid body sensitivity to hypoxia was profoundly increased by up to 180% with heat stress (P = 0.0097), whereas cooling had no detectable effect on hypoxic sensitivity. In summary, cold stress increased carotid body tonic activity and this effect was saturated with mild cooling, whereas heating had clear dose-dependent effects on carotid body tonic activity and sensitivity. These dose-dependent effects with heat strain indicate that the carotid body probably plays a primary role in driving heat-induced hyperventilation. KEY POINTS: Humans over-breathe (hyperventilate) when under heat and cold stress, and though this has detrimental physiological repercussions, the mechanisms underlying this response are unknown. The carotid body, a small organ that is responsible for driving hyperventilation in hypoxia, was assessed under incremental heat and cold strain. The carotid body drive to breathe, as indirectly assessed by transient hyperoxia, increased in a dose-dependent manner with heating, reaching 175% above baseline; cold stress similarly increased the carotid body drive to breathe, but did not show dose-dependency. Carotid body sensitivity, as indirectly assessed by hypoxic ventilatory responses, was profoundly increased by 70-180% with mild and severe heat strain, whereas cooling had no detectable effect. Carotid body hyperactivity and hypersensitivity are two interrelated mechanisms that probably underlie the increased drive to breathe with heat strain, whereas carotid body hyperactivity during mild cooling may play a subsidiary role in cold-induced hyperventilation.

Optimising alkalinisation and its effect on QRS narrowing in tricyclic antidepressant poisoning.

AIMS: The objectives were to determine the effect of NaHCO3 and/or mechanical ventilation on the biochemical profile and serum alkalinisation in tricyclic antidepressant (TCA) poisoning and investigate the impact of effective alkalinisation therapy on the QRS interval in TCA poisoning. METHODS: This was a retrospective review of TCA poisonings from three Australian toxicology units and a poisons information centre (Jan 2013 to Jan 2019). We included patients with TCA toxicity who ingested>10 mg/kg or had clinically significant toxicities consistent with TCA poisoning, and analysed patients' clinical, electrocardiogram and biochemical data. RESULTS: Of 210 patients, 84 received NaHCO3 and ventilation (dual therapy), 12 NaHCO3 , 46 ventilation and 68 supportive care treatment. When compared with single/supportive groups, patients who received dual therapy had taken a significantly higher median dose of TCA (1.5 g vs1.3 g, P < .001), a longer median maximum QRS interval (124 ms, interquartile ranges [IQR] 108-138 vs106 ms, IQR 98-115, P < .001) and were more likely to have seizures (14% vs3%, P = .006) and arrhythmias (17% vs1%, P < .001). The dual therapy group demonstrated greater increases in serum pH (median 0.11, IQR 0.04-0.17) compared to the single/supportive therapy group (median 0.03, IQR -0.01-0.09, p < .001). A greater proportion of patients reached the target pH 7.45-7.55 in the dual therapy group (59%) compared to the single/supportive therapy group (10%) (P < .001). For each 100 mmol bolus of NaHCO3 given, the median increase in serum sodium was 2.5 mmol/L (IQR 1.5-4.0). QRS narrowing occurred twice as quickly in the dual therapy vs single/supportive therapy group. CONCLUSIONS: A combination of NaHCO3 and mechanical ventilation was most effective in achieving serum alkalinisation and was associated with a more rapid narrowing of the QRS interval. We advise that the maximal dose of NaHCO3 should be <400 mmol (6 mmol/kg).