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Purpose: The use of arterial partial pressure of carbon dioxide (PaCO2) as a target intervention to manage elevated intracranial pressure (ICP) and its effect on clinical outcomes remain unclear. We aimed to describe targets for PaCO2 in acute brain injured (ABI) patients and assess the occurrence of abnormal PaCO2 values during the first week in the intensive care unit (ICU). The secondary aim was to assess the association of PaCO2 with in-hospital mortality. Methods: We carried out a secondary analysis of a multicenter prospective observational study involving adult invasively ventilated patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), or ischemic stroke (IS). PaCO2 was collected on day 1, 3, and 7 from ICU admission. Normocapnia was defined as PaCO2 > 35 and to 45 mmHg; mild hypocapnia as 32–35 mmHg; severe hypocapnia as 26–31 mmHg, forced hypocapnia as < 26 mmHg, and hypercapnia as > 45 mmHg. Results: 1476 patients (65.9% male, mean age 52 ± 18 years) were included. On ICU admission, 804 (54.5%) patients were normocapnic (incidence 1.37 episodes per person/day during ICU stay), and 125 (8.5%) and 334 (22.6%) were mild or severe hypocapnic (0.52 and 0.25 episodes/day). Forced hypocapnia and hypercapnia were used in 40 (2.7%) and 173 (11.7%) patients. PaCO2 had a U-shape relationship with in-hospital mortality with only severe hypocapnia and hypercapnia being associated with increased probability of in-hospital mortality (omnibus p value = 0.0009). Important differences were observed across different subgroups of ABI patients. Conclusions: Normocapnia and mild hypocapnia are common in ABI patients and do not affect patients' outcome. Extreme derangements of PaCO2 values were significantly associated with increased in-hospital mortality.

Breath-hold diving or freediving exposes the body to stressors such as low oxygen and high carbon dioxide levels in the blood, increased hydrostatic pressure, and cold. The reduction in blood oxygen levels is considered a primary factor for loss of consciousness while diving. This is known as hypoxic blackout. My thesis aimed to enhance the understanding of the factors that lead to hypoxic blackout in serial freediving. This includes studying the physiological mechanisms that protect the body against hypoxia and exploring how hyperventilation affects those mechanisms, with a specific focus on repetitive dives. The protective mechanisms, splenic contraction (Studies I, II) and diving bradycardia (Studies II and IV), were tested in experimental conditions. The effect of hyperventilation on simulated serial dives (Study II) was investigated, and a strategy to identify actual hyperventilation during diving was developed and explored (Study III). A static apnea test allowing identification of individuals at particular risk for blackout was developed (Study IV). The results showed that hypoxia-induced splenic contraction occurs rapidly enough to be protective in long-duration breath-holds (Study I). Serial simulated dives, preceded by short-term hyperventilation, lead to longer apnea duration and progressive oxygen desaturation (Study II). Despite the more severe desaturation resulting from hyperventilation, these consecutive apneas do not show an augmented diving response or splenic contraction. Hyperventilation was also observed when divers intended to avoid it (Studies II, III, and IV). Therefore, the possibility of estimating hyperventilation from the signal of a force sensor attached to a chest belt was explored (Study III). A stronger diving bradycardia and a bigger spleen were found to be protective against hypoxia and are related to slower oxygen desaturation (Study IV). The main conclusion is that oxygenation is impaired by the accumulation of an oxygen debt wh, Vid tidpunkten för disputationen var följande delarbeten opublicerade: delarbete 3 inskickat under granskning, delarbete 4 manuskript.At the time of the doctoral defence the following papers were unpublished: paper 3 in review, paper 4 in manuscript.

Background Acid–base status in full-term pregnant women is characterised by hypocapnic alkalosis. Whether this respiratory alkalosis is primary or consequent to changes in CSF electrolytes is not clear. Methods We enrolled third-trimester pregnant women (pregnant group) and healthy, non-pregnant women of childbearing age (controls) undergoing spinal anaesthesia for Caesarean delivery and elective surgery, respectively. Electrolytes, strong ion difference (SID), partial pressure of carbon dioxide (), and pH were measured in simultaneously collected CSF and arterial blood samples. Results All pregnant women (20) were hypocapnic, whilst only four (30%) of the controls (13) had an arterial <4.7 kPa (P<0.001). The incidence of hypocapnic alkalosis was higher in the pregnant group (65% vs 8%; P=0.001). The CSF-to-plasma Pco2 difference was significantly higher in pregnant women (1.5 [0.3] vs 1.0 [0.4] kPa; P<0.001), mainly because of a decrease in arterial Pco2 (3.9 [0.3] vs 4.9 [0.5] kPa; P<0.001). Similarly, the CSF-to-plasma difference in SID was less negative in pregnant women (–7.8 [1.4] vs –11.4 [2.3] mM; P<0.001), mainly because of a decreased arterial SID (31.5 [1.2] vs 36.1 [1.9] mM; P<0.001). The major determinant of the reduced plasma SID of pregnant women was a relative increase in plasma chloride compared with sodium. Conclusions Primary hypocapnic alkalosis characterises third-trimester pregnant women leading to chronic acid–base adaptations of CSF and plasma. The compensatory SID reduction, mainly sustained by an increase in chloride concentration, is more pronounced in plasma than in CSF, as the decrease in Pco2 is more marked in this compartment.

Transcription Factor 4 (TCF4) has been associated with autism, schizophrenia, and other neuropsychiatric disorders. However, how pathological TCF4 mutations affect the human neural tissue is poorly understood. Here, we derive neural progenitor cells, neurons, and brain organoids from skin fibroblasts obtained from children with Pitt-Hopkins Syndrome carrying clinically relevant mutations in TCF4. We show that neural progenitors bearing these mutations have reduced proliferation and impaired capacity to differentiate into neurons. We identify a mechanism through which TCF4 loss-of-function leads to decreased Wnt signaling and then to diminished expression of SOX genes, culminating in reduced progenitor proliferation in vitro. Moreover, we show reduced cortical neuron content and impaired electrical activity in the patient-derived organoids, phenotypes that were rescued after correction of TCF4 expression or by pharmacological modulation of Wnt signaling. This work delineates pathological mechanisms in neural cells harboring TCF4 mutations and provides a potential target for therapeutic strategies for genetic disorders associated with this gene.

The hyperventilation provocation test (HPTest) is a diagnostic tool for idiopathic hyperventilation syndrome (HVS), encountered in some long-COVID patients. However, interpretation of the HPTest remains unclear regarding the relevant PETCO2 values to focus on and whether subjective symptoms should be considered. This study aimed to re-evaluate objective HPTest results for diagnosing HVS by determining accurate PETCO2 kinetics in two groups of patients previously screened via the Nijmegen questionnaire (NQ)., SCOPUS: ar.j, info:eu-repo/semantics/published

PURPOSE: To describe the management of arterial partial pressure of carbon dioxide (PaCO2) in severe traumatic brain-injured (TBI) patients, and the optimal target of PaCO2 in patients with high intracranial pressure (ICP). METHODS: Secondary analysis of CENTER-TBI, a multicentre, prospective, observational, cohort study. The primary aim was to describe current practice in PaCO2 management during the first week of intensive care unit (ICU) after TBI, focusing on the lowest PaCO2 values. We also assessed PaCO2 management in patients with and without ICP monitoring (ICPm), and with and without intracranial hypertension. We evaluated the effect of profound hyperventilation (defined as PaCO2 < 30 mmHg) on long-term outcome. RESULTS: We included 1100 patients, with a total of 11,791 measurements of PaCO2 (5931 lowest and 5860 highest daily values). The mean (± SD) PaCO2 was 38.9 (± 5.2) mmHg, and the mean minimum PaCO2 was 35.2 (± 5.3) mmHg. Mean daily minimum PaCO2 values were significantly lower in the ICPm group (34.5 vs 36.7 mmHg, p < 0.001). Daily PaCO2 nadir was lower in patients with intracranial hypertension (33.8 vs 35.7 mmHg, p < 0.001). Considerable heterogeneity was observed between centers. Management in a centre using profound hyperventilation (HV) more frequently was not associated with increased 6 months mortality (OR = 1.06, 95% CI = 0.77-1.45, p value = 0.7166), or unfavourable neurological outcome (OR 1.12, 95% CI = 0.90-1.38, p value = 0.3138). CONCLUSIONS: Ventilation is manipulated differently among centers and in response to intracranial dynamics. PaCO2 tends to be lower in patients with ICP monitoring, especially if ICP is increased. Being in a centre which more frequently uses profound hyperventilation does not affect patient outcomes.

The overall aim of this thesis is to describe variation in management of TBI patients among European ICUs, and to assess the quality and effectiveness of some components of ICU care for TBI patients.

Purpose To describe the management of arterial partial pressure of carbon dioxide (PaCO2) in severe traumatic brain-injured (TBI) patients, and the optimal target of PaCO2 in patients with high intracranial pressure (ICP). Methods Secondary analysis of CENTER-TBI, a multicentre, prospective, observational, cohort study. The primary aim was to describe current practice in PaCO2 management during the first week of intensive care unit (ICU) after TBI, focusing on the lowest PaCO2 values. We also assessed PaCO2 management in patients with and without ICP monitoring (ICPm), and with and without intracranial hypertension. We evaluated the effect of profound hyperventilation (defined as PaCO2 < 30 mmHg) on long-term outcome. Results We included 1100 patients, with a total of 11,791 measurements of PaCO2 (5931 lowest and 5860 highest daily values). The mean (+/- SD) PaCO2 was 38.9 (+/- 5.2) mmHg, and the mean minimum PaCO2 was 35.2 (+/- 5.3) mmHg. Mean daily minimum PaCO2 values were significantly lower in the ICPm group (34.5 vs 36.7 mmHg, p < 0.001). Daily PaCO2 nadir was lower in patients with intracranial hypertension (33.8 vs 35.7 mmHg, p < 0.001). Considerable heterogeneity was observed between centers. Management in a centre using profound hyperventilation (HV) more frequently was not associated with increased 6 months mortality (OR = 1.06, 95% CI = 0.77-1.45, p value = 0.7166), or unfavourable neurological outcome (OR 1.12, 95% CI = 0.90-1.38, p value = 0.3138). Conclusions Ventilation is manipulated differently among centers and in response to intracranial dynamics. PaCO2 tends to be lower in patients with ICP monitoring, especially if ICP is increased. Being in a centre which more frequently uses profound hyperventilation does not affect patient outcomes.

PURPOSE: To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs). METHODS: We studied high TIL treatments (metabolic suppression, hypothermia (< 35 °C), intensive hyperventilation (PaCO2 < 4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended (GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP. RESULTS: 313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.26). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE ≥ 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR 1.4, 95% CI [1.0-2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome. CONCLUSION: Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies. TAKE HOME MESSAGE: Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a step

The human transcription factor 4 gene (TCF4) encodes a helix-loop-helix transcription factor widely expressed throughout the body and during neural development. Mutations in TCF4 cause a devastating autism spectrum disorder known as Pitt-Hopkins syndrome, characterized by a range of aberrant phenotypes including severe intellectual disability, absence of speech, delayed cognitive and motor development, and dysmorphic features. Moreover, polymorphisms in TCF4 have been associated with schizophrenia and other psychiatric and neurological conditions. Details about how TCF4 genetic variants are linked to these diseases and the role of TCF4 during neural development are only now beginning to emerge. Here, we provide a comprehensive review of the functions of TCF4 and its protein products at both the cellular and organismic levels, as well as a description of pathophysiological mechanisms associated with this gene.

PURPOSE: To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs). METHODS: We studied high TIL treatments (metabolic suppression, hypothermia (< 35 °C), intensive hyperventilation (PaCO2 < 4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended (GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP. RESULTS: 313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.26). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE ≥ 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR 1.4, 95% CI [1.0-2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome. CONCLUSION: Substantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies. TAKE HOME MESSAGE: Substantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a step

Hyperventilation is a commonly used therapy to treat intracranial hypertension (ICTH) in traumatic brain injury patients (TBI). Hyperventilation promotes hypocapnia, which causes vasoconstriction in the cerebral arterioles and thus reduces cerebral blood flow and, to a lesser extent, cerebral blood volume effectively, decreasing temporarily intracranial pressure. However, hyperventilation can have serious systemic and cerebral deleterious effects, such as ventilator-induced lung injury or cerebral ischemia. The routine use of this therapy is therefore not recommended. Conversely, in specific conditions, such as refractory ICHT and imminent brain herniation, it can be an effective life-saving rescue therapy. The aim of this review is to describe the impact of hyperventilation on extra-cerebral organs and cerebral hemodynamics or metabolism, as well as to discuss the side effects and how to implement it to manage TBI patients., SCOPUS: re.j, info:eu-repo/semantics/published

Key points: The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO2–[H+] washout-induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO2 affinity for haemoglobin. Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation. We then quantified ventilation, cerebral perfusion/metabolism, arterial/internal jugular vein blood gases and oxidant/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production/accumulation contributes to the hyperoxia-induced hyperventilation in humans. Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion. Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production/accumulation and reduced brain CO2–[H+] washout. Abstract: The hypothetical mechanism for the increase in ventilation ((Formula presented.)) in response to hyperoxia (HX) includes central chemoreceptor stimulation via reduced CO2–[H+] washout. Nonetheless, hyperoxia disturbs redox homeostasis and raises the hypothesis that excessive brain reactive oxygen species (ROS) production/accumulation may increase the sensitivity to CO2 or even solely activate the central chemoreceptors, resulting in hyperventilation. To determine the mechanism behind the HX-evoked increase in (Formula presented.), 10 healthy men (24 ± 4 years) underwent 10 min trials of HX under saline and ascorbic acid infusion. (Formula presented.)

Hyperventilation is a double-edged sword strategy for controlling intracranial volumes and therefore reducing intracranial pressure (ICP) after acute brain damage. The effect is linked to the induced local alkalosis producing a reduction in cerebral blood flow (CBF). Although this effect is short-lasting, hyperventilation carries a potential risk of cerebral ischemia. Although all patients with severe traumatic brain injury (TBI) are mechanically ventilated, the target for the partial pressure of carbon dioxide in arterial blood (PaCO2) remains poorly defined and there is insufficient evidence to support any recommendation. A target PaCO2 of ≈36–40 mmHg has been reported by clinicians and suggested by consensus statements. In presence of raised ICP, this is usually lowered to ≈30–35 mmHg. In this chapter, starting from physiological concepts, we will review the evidence around PaCO2 management in TBI and will present some data on current practice of the use of hyperventilation in TBI. We observed considerable variability in CO2 management between centers in Europe. Further research is needed to identify optimal ventilatory strategies in the management of severe TBI.

OBJECTIVE: Hyperventilation is a controversial treatment in traumatic brain injury (TBI). Prophylactic severe hyperventilation below 3.3 kPa/25 mm Hg) is generally avoided, due to the risk of cerebral ischemia. Mild hyperventilation (arterial pCO2 within 4.0-4.5 kPa/30-34 mm Hg) in cases of intracranial hypertension is commonly used, but its safety and benefits are not fully elucidated. The aim of this study was to evaluate the use of mild hyperventilation and its relation to, cerebral energy metabolism, pressure autoregulation and clinical outcome in TBI. METHOD: This retrospective study was based on 120 patients with severe TBI treated at the neurointensive care unit, Uppsala university hospital, Sweden, 2008-2018. Data from cerebral microdialysis (glucose, pyruvate and lactate), arterial pCO2 and pressure reactivity index (PRx55-15) were analyzed for the first three days post-injury. RESULTS: Mild hyperventilation 4.0-4.5 kPa (30-34 mm Hg) was more frequently used early and the patients were gradually normoventilated. Low pCO2 was associated with slightly higher intracranial pressure and slightly lower cerebral perfusion pressure (p-value < 0.01). There was no univariate correlation between low pCO2 and worse cerebral energy metabolism. Multiple linear regression analysis showed that mild hyperventilation was associated with lower PRx55-15 day 2 (p-value = 0.03), suggesting better pressure autoregulation. Younger age and lower ICP were also associated with lower PRx55-15. CONCLUSIONS: These findings support the notion that mild hyperventilation is safe and may improve cerebrovascular reactivity.

Aim Current resuscitation guidelines recommend waveform capnography as an indirect indicator of perfusion during cardiopulmonary resuscitation (CPR). Chest compressions (CCs) and ventilations during CPR have opposing effects on the exhaled carbon dioxide (CO2) concentration, which need to be better characterized. The purpose of this study was to model the impact of ventilations in the exhaled CO2 measured from capnograms collected during out-of-hospital cardiac arrest (OHCA) resuscitation. Methods We retrospectively analyzed OHCA monitor-defibrillator files with concurrent capnogram, compression depth, transthoracic impedance and ECG signals. Segments with CC pauses, two or more ventilations, and with no pulse-generating rhythm were selected. Thus, only ventilations should have caused the decrease in CO2 concentration. The variation in the exhaled CO2 concentration with each ventilation was modeled with an exponential decay function using non-linear-least-squares curve fitting. Results Out of the original 1002 OHCA dataset (one per patient), 377 episodes had the required signals, and 196 segments from 96 patients met the inclusion criteria. Airway type was endotracheal tube in 64.8% of the segments, supraglottic King LT-D (TM) in 30.1%, and unknown in 5.1%. Median (IQR) decay factor of the exhaled CO2 concentration was 10.0% (7.8 - 12.9) with R-2 = 0.98(0.95 - 0.99). Differences in decay factor with airway type were not statistically significant (p = 0.17). From these results, we propose a model for estimating the contribution of CCs to the end-tidal CO2 level between consecutive ventilations and for estimating the end-tidal CO2 variation as a function of ventilation rate. Conclusion We have modeled the decrease in exhaled CO2 concentration with ventilations during chest compression pauses in CPR. This finding allowed us to hypothesize a mathematical model for explaining the effect of chest compressions on ETCO2 compensating for the influence of ventilation rate dur

BackgroundAcute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety.MethodsThe Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy.ResultsThe panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy.ConclusionThe available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in

Resting-state functional MRI has shown potential for detecting changes in cerebral blood oxygen level-dependent signal in patients with epilepsy, even in the absence of epileptiform activity. Furthermore, it has been suggested that coefficient of variation mapping of fast functional MRI signal may provide a powerful tool for the identification of intrinsic brain pulsations in neurological diseases such as dementia, stroke and epilepsy. In this study, we used fast functional MRI sequence (magnetic resonance encephalography) to acquire ten whole-brain images per second. We used the functional MRI data to compare physiological brain pulsations between healthy controls (n- 102) and patients with epilepsy (n =33) and furthermore to drug-naive seizure patients (n= 9). Analyses were performed by calculating coefficient of variation and spectral power in full band and filtered sub-bands. Brain pulsations in the respiratory-related frequency sub-band (0.11-0.51 Hz) were significantly (P<0.05) increased in patients with epilepsy, with an increase in both signal variance and power. At the individual level, over 80% of medicated and drug-naive seizure patients exhibited areas of abnormal brain signal power that correlated well with the known clinical diagnosis, while none of the controls showed signs of abnormality with the same threshold. The differences were most apparent in the basal brain structures, respiratory centres of brain stem, midbrain and temporal lobes. Notably, full-band, very low frequency (0.01-0.1 Hz) and cardiovascular (0.81.76 Hz) brain pulses showed no differences between groups. This study extends and confirms our previous results of abnormal fast functional MRI signal variance in epilepsy patients. Only respiratory-related brain pulsations were clearly increased with no changes in either physiological cardiorespiratory rates or head motion between the subjects. The regional alterations in brain pulsations suggest that mechanisms driving the cerebros

Partial amniotic carbon dioxide insufflation (PACI) involves insufflating the amniotic sac with carbon dioxide (CO2) and, in some cases, draining some of the amniotic fluid. The creation of a gaseous intra-amniotic compartment improves visualization, even in the presence of limited bleeding, and creates the work space required for complex fetoscopic procedures. Clinically, PACI is mostly used to perform fetoscopic myelomeningocele (MMC) repair, enabling a minimally invasive alternative to open fetal surgery. However, evidence of the fetal safety of PACI is limited. Previous animal experiments in sheep demonstrate that PACI induces fetal hypercapnia and acidosis with largely unknown short and longer term implications. In this review, we examine the literature for the physiological effects of intrauterine insufflation pressure, duration, humidity, and the role of maternal hyperventilation on fetal physiology and well-being.Copyright © 2018 John Wiley & Sons, Ltd.

Introduction and objective: With this paper, we pretend to explain the characteristics and the field of application of two clinical explorations used in the patient with suspected vestibular pathology, the hyperventilation maneuver and the Valsalva maneuver. Methodology: Narrative review. Results: Through different neurophysiological mechanisms, hyperventilation can induce nystagmus in cases of vestibular asymmetry, both peripheral and central. The Valsalva maneuver may also trigger nystagmus and vertigo because of direct transmission of internal ear pressure in cases of perilymphatic fistula, anomalies of the cranio-cervical junction (Arnold-Chiari malformation), and other ossicles, oval window and saccule pathologies. Discussion and conclusions: Both the hyperventilation test and the Valsalva maneuver should be included in the battery of tests for patients with vestibular pathology to, depending on the results obtained, anatomically locate the site of the lesion and justify the use of imaging techniques., Introducción y objetivo: Con este trabajo pretendemos explicar las características y el campo de aplicación de dos exploraciones clínicas utilizadas en el paciente con sospecha de patología vestibular, la maniobra de hiperventilación y la de Valsalva. Metodología: Revisión narrativa. Resultados: A través de diferentes mecanismos neurofisiológicos, la hiperventilación puede inducir un nistagmo en casos de asimetría vestibular, tanto de causa periférica como central. Por su parte, la maniobra de Valsalva puede también desencadenar nistagmo y vértigo, consecuencia de la transmisión directa de la presión al oído interno en casos de fístula perilinfática, anomalías de la unión craneocervical (malformación de Arnold-Chiari) y otras alteraciones de los osículos, de la ventana oval y del sáculo. Discusión y conclusiones: Tanto el test de hiperventilación como el de la maniobra de Valsalva deberían incluirse en la batería diagnóstica de pacientes con patología vestibular para, en función de los resultados obtenidos, ubicar anatómicamente el sitio de la lesión y justificar el uso de técnicas de imagen.

Purpose: To evaluate EEG differences among syndromes in genetic generalized epilepsy based on quantified data. Method(s): Twenty-four-hour ambulatory EEGs were recorded in consecutive patients diagnosed with genetic generalized epilepsy. All epileptiform EEG abnormalities were quantified into density scores (total duration of epileptiform discharges per hour). One-way analysis of variance was conducted to find out differences in EEG density scores among the syndromes. Generalized linear mixed models were also fitted to explore the association between the proportion of "pure" generalized spike-wave paroxysms and fragments (without intervening polyspikes/polyspike-waves) and the syndromes. Result(s): In total, 6,923 epileptiform discharges were analyzed from 105 abnormal EEGs. In the analysis of variance, six EEG variables were significantly different among syndromes: total spike density (P = 0.001), total polyspike and polyspike-wave density (P = 0.049), generalized spike-wave-only density (P , 0.001), generalized paroxysm density (P , 0.001), generalized paroxysm duration mean (P = 0.018), and generalized paroxysm duration maximum (P = 0.009). The density of epileptiform discharges and the paroxysm durations were the highest in juvenile absence epilepsy followed by juvenile myoclonic epilepsy, childhood absence epilepsy, and generalized epilepsy with tonic-clonic seizures only. Generalized linear mixed models revealed that "pure" generalized spike-wave discharges (without intervening polyspikes/polyspike waves) tended to be more frequent in absence epilepsies, although the difference was not statistically significant (P = 0.21). Conclusion(s): The findings of this study suggest that the density and duration of epileptiform discharges can help differentiate among genetic generalized epilepsy syndromes.Copyright © 2016 by the American Clinical Neurophysiology Society.

Genetic generalized epilepsy (GGE) consists of several syndromes diagnosed and classified on the basis of clinical features and electroencephalographic (EEG) abnormalities. The main EEG feature of GGE is bilateral, synchronous, symmetric, and generalized spike-wave complex. Other classic EEG abnormalities are polyspikes, epileptiform K-complexes and sleep spindles, polyspike-wave discharges, occipital intermittent rhythmic delta activity, eye-closure sensitivity, fixation-off sensitivity, and photoparoxysmal response. However, admixed with typical changes, atypical epileptiform discharges are also commonly seen in GGE. There are circadian variations of generalized epileptiform discharges. Sleep, sleep deprivation, hyperventilation, intermittent photic stimulation, eye closure, and fixation-off are often used as activation techniques to increase the diagnostic yield of EEG recordings. Reflex seizure-related EEG abnormalities can be elicited by the use of triggers such as cognitive tasks and pattern stimulation during the EEG recording in selected patients. Distinct electrographic abnormalities to help classification can be identified among different electroclinical syndromes.Copyright © 2017 Seneviratne, Cook and D'Souza.

To investigate the effect of different breathing patterns (spontaneous breathing as a control, hyperventilation and forced exhalation) on biochemical, cardiorespiratory and performance variables following a specific tennis test. Methods: Thirteen trained nationally ranked male tennis participated in this study. In three different sessions the players performed a passing-shot drill test, only modifying the breathing pattern (hyperventilation, forced exhalation or spontaneous breathing) during the recovery periods in randomized and counterbalance manner. Results: No differences were found between the three tests in biochemical variables (pH: F2,12=0.118, P=0.890; pCO2: F2,24=1.24, P=0.307; [HCO3-]: F2,24=3.257, P=0.056; [La-] F2,24=0.179, P=0.838) except for the base excess (BE; F2,24=4.339, P=0.025). On the other hand, ventilation and breathing frequency were different among the test (VE: F2,24=23.134, P<0.001; BF: F2,24=74.633, P<0.001, respectively), while VO2 and heart rate were similar (VO2: F2,24=0.031, P=0.9691; HR: F2,24=1.213, P=0.315, respectively). Finally, no relevant differences were observed for the performance variables, being the mean speed stroke, maximum speed stroke and precision stroke similar between the three tests (F2,36=0.043, P=0.958; F2,36=0.007, P=0.993; F2,36=0.435, P=0.651, respectively). Conclusion: It seems that the performance during a submaximal specific tennis drill is not influenced by the breathing pattern used during recoveries. Therefore, altering breathing pattern does not seem a good strategy to modify the acid-base status or performance during a tennis trial., Investigar el efecto de los diferentes patrones respiratorios (respiración espontánea como control, hiperventilación y espiración forzada) sobre variables bioquímicas, cardiorrespiratorias y de rendimiento tras una prueba específica de tenis. Métodos: Trece tenistas, varones, bien entrenados y clasificados a nivel nacional participaron en este estudio. En tres sesiones diferentes, los jugadores realizaron un simulacro de entrenamiento de carrera lateral, modificando únicamente el patrón respiratorio (hiperventilación, espiración forzada o respiración espontánea) durante los períodos de recuperación de forma aleatoria y contrabalanceada. Resultados: No se encontraron diferencias entre las tres pruebas en variables bioquímicas (pH: F2,12=0.118, P=0.890; pCO2: F2,24=1.24, P=0.307;[HCO3-]: F2,24=3.257, P=0.056;[La-] F2,24=0.179, P=0.838) excepto para el exceso de base (BE; F2,24=4.339, P=0.025). Por otra parte, la ventilación y la frecuencia respiratoria fueron diferentes entre las pruebas (VE: F2,24=23.134, P<0.001; BF: F2,24=74.633, P<0.001, respectivamente), mientras que VO2 y frecuencia cardíaca fueron similares (VO2: F2,24=0.031, P=0.9691; HR: F2,24=1.213, P=0.315, respectivamente). Finalmente, no se observaron diferencias relevantes para las variables de rendimiento, siendo la carrera media, la carrera máxima y la carrera de precisión similares entre las tres pruebas (F2,36=0.043, P=0.958; F2,36=0.007, P=0.993; F2,36=0.435, P=0.651, respectivamente). Conclusión: Parece que el rendimiento durante un entrenamiento de tenis submáximo específico no se ve influenciado por el patrón de respiración utilizado durante las recuperaciones. Por lo tanto, alterar el patrón de respiración no parece una buena estrategia para modificar el estado ácido-base durante la práctica del tenis.

During traumatic brain injury, intracranial hypertension (ICH) can become a life-threatening condition if it is not managed quickly and adequately. Physicians use therapeutic hyperventilation to reduce elevated intracranial pressure (ICP) by manipulating autoregulatory functions connected to cerebrovascular CO2 reactivity. Inducing hypocapnia via hyperventilation reduces the partial pressure of arterial carbon dioxide (PaCO2), which incites vasoconstriction in the cerebral resistance arterioles. This constriction decrease cerebral blood flow, which reduces cerebral blood volume and, ultimately, decreases the patient’s ICP. The effects of therapeutic hyperventilation (HV) are transient, but the risks accompanying these changes in cerebral and systemic physiology must be carefully considered before the treatment can be deemed advisable. The most prominent criticism of this approach is the cited possibility of developing cerebral ischemia and tissue hypoxia. While it is true that certain measures, such as cerebral oxygenation monitoring, are needed to mitigate these dangerous conditions, using available evidence of potential poor outcomes associated with HV as justification to dismiss the implementation of therapeutic HV is debatable and remains a controversial subject among physicians. This review highlights various issues surrounding the use of HV as a means of controlling posttraumatic ICH, including indications for treatment, potential risks, and benefits, and a discussion of what techniques can be implemented to avoid adverse complications.

Pitt-Hopkins syndrome is a neurodevelopmental disorder characterized by severe intellectual disability and a distinctive facial gestalt. It is caused by haploinsufficiency of the TCF4 gene. The TCF4 protein has different functional domains, with the NLS (nuclear localization signal) domain coded by exons 7–8 and the bHLH (basic Helix-Loop-Helix) domain coded by exon 18. Several alternatively spliced TCF4 variants have been described, allowing for translation of variable protein isoforms. Typical PTHS patients have impairment of at least the bHLH domain. To which extent impairment of the remaining domains contributes to the final phenotype is not clear. There is recent evidence that certain loss-of-function variants disrupting TCF4 are associated with mild ID, but not with typical PTHS. We describe a frameshift-causing partial gene deletion encompassing exons 4–6 of TCF4 in an adult patient with mild ID and nonspecific facial dysmorphisms but without the typical features of PTHS, and a c.520C > T nonsense variant within exon 8 in a child presenting with a severe phenotype largely mimicking PTHS, but lacking the typical facial dysmorphism. Investigation on mRNA, along with literature review, led us to suggest a preliminary phenotypic map of loss-of-function variants affecting TCF4. An intragenic phenotypic map of loss-of-function variants in TCF4 is suggested here for the first time: variants within exons 1–4 and exons 4–6 give rise to a recurrent phenotype with mild ID not in the spectrum of Pitt-Hopkins syndrome (biallelic preservation of both the NLS and bHLH domains); variants within exons 7–8 cause a severe phenotype resembling PTHS but in absence of the typical facial dysmorphism (impairment limited to the NLS domain); variants within exons 9–19 cause typical Pitt-Hopkins syndrome (impairment of at least the bHLH domain). Understanding the TCF4 molecular syndromology can allow for proper nosology in the current era of whole genomic investigatio

Aim:The rates of chest compressions (CCs) and ventilations are both important metrics to monitor the quality of cardiopulmonary resuscitation (CPR). Capnography permits monitoring ventilation, but the CCs provided during CPR corrupt the capnogram and compromise the accuracy of automatic ventilation detectors. The aim of this study was to evaluate the feasibility of an automatic algorithm based on the capnogram to detect ventilations and provide feedback on ventilation rate during CPR, specifically addressing intervals where CCs are delivered. Methods:The dataset used to develop and test the algorithm contained in-hospital and out-of-hospital cardiac arrest episodes. The method relies on adaptive thresholding to detect ventilations in the first derivative of the capnogram. The performance of the detector was reported in terms of sensitivity (SE) and Positive Predictive Value (PPV). The overall performance was reported in terms of the rate error and errors in the hyperventilation alarms. Results were given separately for the intervals with CCs. Results: A total of 83 episodes were considered, resulting in 4880 min and 46,740 ventilations (8741 during CCs). The method showed an overall SE/PPV above 99% and 97% respectively, even in intervals with CCs. The error for the ventilation rate was below 1.8 min−1 in any group, and >99% of the ventilation alarms were correctly detected. Conclusion: A method to provide accurate feedback on ventilation rate using only the capnogram is proposed. Its accuracy was proven even in intervals where canpography signal was severely corrupted by CCs. This algorithm could be integrated into monitor/defibrillators to provide reliable feedback on ventilation rate during CPR.

Purpose Effort sense has been suggested to be involved in the hyperventilatory response during intense exercise (IE). However, the mechanism by which effort sense induces an increase in ventilation during IE has not been fully elucidated. The aim of this study was to determine the relationship between effort-mediated ventilatory response and corticospinal excitability of lower limb muscle during IE. Eight subjects performed 3 min of cycling exercise at 75-85 % of maximum workload twice (IE1st and IE2nd). IE2nd was performed after 60 min of resting recovery following 45 min of submaximal cycling exercise at the workload corresponding to ventilatory threshold. Vastus lateralis muscle response to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs), effort sense of legs (ESL, Borg 0-10 scale), and ventilatory response were measured during the two IEs. The slope of ventilation (l/min) against CO2 output (l/min) during IE2nd (28.0 +/- 5.6) was significantly greater than that (25.1 +/- 5.5) during IE1st. Mean ESL during IE was significantly higher in IE2nd (5.25 +/- 0.89) than in IE1st (4.67 +/- 0.62). Mean MEP (normalized to maximal M-wave) during IE was significantly lower in IE2nd (66 +/- 22 %) than in IE1st (77 +/- 24 %). The difference in mean ESL between the two IEs was significantly (p < 0.05, r = -0.82) correlated with the difference in mean MEP between the two IEs. The findings suggest that effort-mediated hyperventilatory response to IE may be associated with a decrease in corticospinal excitability of exercising muscle.

Purpose Effort sense has been suggested to be involved in the hyperventilatory response during intense exercise (IE). However, the mechanism by which effort sense induces an increase in ventilation during IE has not been fully elucidated. The aim of this study was to determine the relationship between effort-mediated ventilatory response and corticospinal excitability of lower limb muscle during IE. Eight subjects performed 3 min of cycling exercise at 75-85 % of maximum workload twice (IE1st and IE2nd). IE2nd was performed after 60 min of resting recovery following 45 min of submaximal cycling exercise at the workload corresponding to ventilatory threshold. Vastus lateralis muscle response to transcranial magnetic stimulation of the motor cortex (motor evoked potentials, MEPs), effort sense of legs (ESL, Borg 0-10 scale), and ventilatory response were measured during the two IEs. The slope of ventilation (l/min) against CO2 output (l/min) during IE2nd (28.0 +/- 5.6) was significantly greater than that (25.1 +/- 5.5) during IE1st. Mean ESL during IE was significantly higher in IE2nd (5.25 +/- 0.89) than in IE1st (4.67 +/- 0.62). Mean MEP (normalized to maximal M-wave) during IE was significantly lower in IE2nd (66 +/- 22 %) than in IE1st (77 +/- 24 %). The difference in mean ESL between the two IEs was significantly (p < 0.05, r = -0.82) correlated with the difference in mean MEP between the two IEs. The findings suggest that effort-mediated hyperventilatory response to IE may be associated with a decrease in corticospinal excitability of exercising muscle.

In sepsis, higher PaCO2 levels are associated with impaired dynamic cerebral autoregulation (dCA), which may expose the brain to hypo- and hyperperfusion during acute fluctuations in blood pressure. We hypothesised that short-term mechanical hyperventilation would dCA in critically ill patients with sepsis. Seven mechanically ventilated septic patients were included. We assessed dCA before and after 30 min of mechanical hyperventilation. Transfer function analysis of spontaneous oscillations in transcranial Doppler-based middle cerebral artery blood flow velocity (MCAv) and invasive mean arterial blood pressure was used to assess dCA. Mechanical enhance hyperventilation reduced the median PaCO2 from 5.3 (IQR, 5.0-6.5) to 4.7 (IQR, 4.2-5.1) kPa (p < 0.05). This was associated with a reduction in the median MCAv from 57 (IQR, 33-68) to 32 (IQR, 21-40) cm sec(-1) (p < 0.05). Apart from a small increase in gain in the low frequency range (2.32 [IQR 1.80-2.41] vs. 2.59 (2.40-4.64) cm mmHg(-1) sec(-1); p < 0.05), this was not associated with any enhancement in dCA. In conclusion, cerebral CO2 vasoreactivity was found to be preserved in septic patients; nevertheless, and in contrast to our working hypothesis, short-term mechanical hyperventilation did not enhance dCA.

In athletes, a secure diagnosis of exercise-induced bronchoconstriction (EIB) is dependent on objective testing. Evaluating spirometric indices of airflow before and following an exercise bout is intuitively the optimal means for the diagnosis; however, this approach is recognized as having several key limitations. Accordingly, alternative indirect bronchoprovocation tests have been recommended as surrogate means for obtaining a diagnosis of EIB. Of these tests, it is often argued that the eucapnic voluntary hyperpnea (EVH) challenge represents the ‘gold standard’. This article provides a state-of-the-art review of EVH, including an overview of the test methodology and its interpretation. We also address the performance of EVH against the other functional and clinical approaches commonly adopted for the diagnosis of EIB. The published evidence supports a key role for EVH in the diagnostic algorithm for EIB testing in athletes. However, its wide sensitivity and specificity and poor repeatability preclude EVH from being termed a ‘gold standard’ test for EIB.

Oxygen administration is thought to suppress periodic breathing (PB) by reducing carotid body activity, and yet earlier experiments in neonates have shown that PB incidence may be increased following the application of hyperoxia. To clarify this paradox, we studied the changes in the pattern of PB that occur following administration of oxygen in a lamb model of PB. PB was induced in eleven of seventeen anaesthetized lambs following passive hyper-ventilation with air. When oxygen was administered during PB, the pattern was first enhanced, as evidenced by a sudden decrease in the ratio of the ventilatory duration to the apnoeic pause duration, and then suppressed, as evidenced by a progressive return to stable breathing which was associated with an increase in minute ventilation. Five of the six lambs that did not show PB following passive hyperventilation with air could be made to do so if oxygen was substituted for air as the inspired gas following passive hyperventilation. Five of the eleven lambs that showed PB following hyperventilation with air responded to the application of oxygen during PB by switching to a gross form of episodic breathing consisting of long apnoeic pauses followed by equally long periods of breathing during which minute ventilation fell progressively with time. 5 We conclude that when applied against a background of arterial hypoxaemia, oxygen has a destabilizing influence on ventilation in that (a) it accentuates the unstable breathing that occurs during PB, (b) it induces PB in lambs that exhibited stable breathing in air, and (c) it may precipitate episodic breathing.Copyright © 1997 The Physiological Society.

Purpose of review The purpose of this study is to review the recent literature describing how to assess and treat postcardiac arrest syndrome associated haemodynamics and manage oxygenation and ventilation derangements. Recent findings Postcardiac arrest syndrome is a well described entity that includes systemic ischemia-reperfusion response, myocardial dysfunction and neurologic dysfunction. Continued resuscitation in the hours to days following return of spontaneous circulation (ROSC) is important to increase the likelihood of long-term survival and neurological recovery. Post-ROSC hypotension is common and associated with worse outcome. Myocardial dysfunction peaks in the first 24h following ROSC and in survivors resolves over the next few days. Hyperoxemia (pao 2 >300mmHg) and hypoxemia (pao 2 <60mmHg) are associated with worse outcomes and hyperventilation may exacerbate cerebral ischemic injury by decreasing cerebral oxygenation. Summary Patients who are successfully resuscitated from cardiac arrest often have hypotension and myocardial dysfunction. Careful attention to haemodynamic and ventilator management targeting normal blood pressure, normoxemia and normocapnia may help to avoid secondary organ injury and potentially improve outcomes., SCOPUS: re.j, info:eu-repo/semantics/published

Several anaesthetics are able to induce a burst-suppression (B-S) pattern in the electroencephalogram (EEG) during deep levels of anaesthesia. A burst-suppression pattern consists of alternating high amplitude bursts and periods of suppressed background activity. All monitors measuring the adequacy of anaesthesia recognize the EEG B-S as one criterion. A better understanding of EEG burst-suppression is important in understanding the mechanisms of anaesthesia. The aim of the study was to acquire a more comprehensive understanding of the function of neural pathways during deep anaesthesia. The thesis is comprised of four prospective clinical studies with EEG recordings from 64 patients, and of one experimental study of a porcine model of epilepsy with EEG registrations together with BOLD fMRI during isoflurane anaesthesia (II). In study I, somatosensory cortical evoked responses to median nerve stimulation were studied under sevoflurane anaesthesia at EEG B-S levels. In study III, The EEGs of three Parkinson’s patients were observed to describe the characteristics of B-S during propofol anaesthesia using scalp electrodes and depth electrodes in the subthalamic nucleus. In study IV, EEG topography was observed in 20 healthy children under anaesthesia mask induction with sevoflurane. Twenty male patients were randomized to either controlled hyperventilation or spontaneous breathing groups for anaesthesia mask induction with sevoflurane in study V. EEG alterations in relation to haemodynamic responses were examined in studies IV and V. Somatosensory information reached the cortex even during deep anaesthesia at EEG burst-suppression level. Further processing of these impulses in the cortex was suppressed. The EEG slow wave oscillations were synchronous over the entire cerebral cortex, while spindles and sharp waves were produced by the sensorimotor cortex. The development of focal epileptic activity could be detected as a BOLD signal increase, which preceded the, Tiivistelmä Useat anestesia-aineet pystyvät aiheuttamaan aivosähkökäyrän (EEG) purskevaimentuman syvän anestesian aikana. Purskevaimentuma koostuu EEG:n suuriamplitudisten purskeiden sekä vaimentuneen taustatoiminnan vaihtelusta. Kaikkien anestesian syvyyttä mittaavien valvontalaitteiden toiminta perustuu osaltaan EEG:n purskevaimentuman tunnistamiseen. Tämän ilmiön parempi tunteminen on tärkeää anestesiamekanismien ymmärtämiseksi. Tutkimuksen päämääränä oli saada kattavampi käsitys hermoratojen toiminnasta syvässä anestesiassa. Väitöskirjatyö koostuu neljästä prospektiivisesta yhteensä 64 potilaan EEG-rekisteröinnit sisältävästä tutkimuksesta sekä yhdestä kokeellisen epilepsiatutkimuksen koe-eläintyöstä, jossa porsailla käytettiin isofluraanianestesiassa sekä EEG-rekisteröintejä sekä että magneettikuvantamista (fMRI) samanaikaisesti (II). Ensimmäisessä osatyössä tutkittiin keskihermon stimulaation aiheuttamia somatosensorisia herätepotentiaaleja aivokuorella EEG:n purskevaimentumatasolla sevofluraanianestesian aikana. Kolmannessa osatyössä selvitettiin propofolianestesian aiheuttamaa EEG:n purskevaimentumaa kolmelta Parkinsonin tautia sairastavalta potilaalta käyttäen sekä pintaelektrodien että subtalamisen aivotumakkeen syväelektrodien rekisteröintejä. Neljännessä osatyössä tutkittiin EEG:n topografiaa 20:llä terveeellä lapsella indusoimalla anestesia sevofluraanilla. Kaksikymmentä miespotilasta nukutettiin sevofluraanilla ja heidät satunnaistettiin joko kontrolloidun hyperventilaation tai spontaanin hengityksen ryhmiin osatyössä V. EEG-muutoksia sekä niiden yhteyttä verenkiertovasteisiin selviteltiin molemmissa osatöissä IV ja V. Omasta kehosta tuleviin tuntoärsykkeisiin liittyvä somatosensorinen informaatio saavutti aivokuoren myös syvässä EEG:n purskevaimentumatasoisessa anestesiassa. Impulssien jatkokäsittely aivokuorella oli kuitenkin estynyt. EEG:n hidasaaltotoiminta oli synkronista koko aivokuoren alueella, sen sijaan unisukkulat ja terävät aallot paikantui

Purpose: Acid–base disturbances were investigated in patients with cirrhosis in relation to hemodynamic derangement to analyze the hyperventilatory effects and the metabolic compensation. Methods: A total of 66 patients with cirrhosis and 44 controls were investigated during a hemodynamic study. Results: Hyperventilatory hypocapnia was present in all patients with cirrhosis and progressed from Child class A to C (P<0.01). Arterial pH increased significantly from class A to C (P<0.001) and was correlated inversely to the mean arterial blood pressure (r=–0.30, P<0.02), systemic vascular resistance (r=–0.25, P<0.05), indocyanine green clearance (r=–0.37, P<0.005), and serum sodium (r=–0.38, P<0.002). Metabolic compensation was shown by a reduced standard base excess in all patients (P<0.001). Standard base excess contained elements related to changes in serum albumin, water dilution, and effects of unidentified ions (all P<0.001). A significant hepatic component in the acid–base disturbances could not be identified. Conclusion: Hypocapnic alkalosis is related to disease severity and hyperdynamic systemic circulation in patients with cirrhosis. The metabolic compensation includes alterations in serum albumin and water retention that may result in a delicate acid–base balance in these patients., PURPOSE: Acid-base disturbances were investigated in patients with cirrhosis in relation to hemodynamic derangement to analyze the hyperventilatory effects and the metabolic compensation.METHODS: A total of 66 patients with cirrhosis and 44 controls were investigated during a hemodynamic study.RESULTS: Hyperventilatory hypocapnia was present in all patients with cirrhosis and progressed from Child class A to C (P<0.01). Arterial pH increased significantly from class A to C (P<0.001) and was correlated inversely to the mean arterial blood pressure (r=-0.30, P<0.02), systemic vascular resistance (r=-0.25, P<0.05), indocyanine green clearance (r=-0.37, P<0.005), and serum sodium (r=-0.38, P<0.002). Metabolic compensation was shown by a reduced standard base excess in all patients (P<0.001). Standard base excess contained elements related to changes in serum albumin, water dilution, and effects of unidentified ions (all P<0.001). A significant hepatic component in the acid-base disturbances could not be identified.CONCLUSION: Hypocapnic alkalosis is related to disease severity and hyperdynamic systemic circulation in patients with cirrhosis. The metabolic compensation includes alterations in serum albumin and water retention that may result in a delicate acid-base balance in these patients.

Based upon the results obtained from these studies, we can draw the following conclusions: 1) Airway hyperresponsiveness developed in Ova-sensitized mice was less pronounced in TRPV1-null mice, indicating an important role of TRPV1. 2) An increase in airway temperature within the normal physiological range triggered bronchoconstriction in sensitized rats, but not in control rats. Chronic airway inflammation in sensitized animals is likely a major contributing factor in causing this response. 3) transient increase in airway resistance was generated immediately after hyperventilation with warm humid air in patients with mild asthma, but the same warm humid air challenge failed to cause any bronchoconstriction in healthy subjects. Furthermore, this bronchoconstriction is likely generated by the increase in airway temperature because hyperventilation with humidified air at room temperature did not generate any change in airway resistance in the same patients. These studies, once completed, should provide important and novel information for: 1) documenting the pulmonary stresses induced by hyperthermia in healthy individuals and in patients with sensitized airways; 2) understanding the mechanism underlying the hyperthermia-induced pulmonary dysfunction; and 3) detecting the susceptibility to heat stress in soldiers with underestimated or overlooked airway hypersensitivity such as in airway allergy or mild asthma., The original document contains color images.

Chronic stress is among the most common diagnoses in Sweden, most commonly in the form of exhaustion syndrome (ICD-10 classification - F43.8). The majority of patients with this syndrome also have disturbed breathing (hyperventilation). The aim of this study was to investigate the association between hyperventilation and exhaustion syndrome. Thirty patients with exhaustion syndrome and 14 healthy subjects were evaluated with the Nijmegen Symptom Questionnaire (NQ). The participants completed questionnaires about exhaustion, mental state, sleep disturbance, pain and quality of life. The evaluation was repeated 4 weeks later, after half of the patients and healthy subjects had engaged in a therapy method called 'Grounding', a physical exercise inspired by African dance. The patients reported significantly higher levels of hyperventilation as compared to the healthy subjects. All patients' average score on NQ was 26.57 +/- 10.98, while that of the healthy subjects was 15.14 +/- 7.89 (t = -3.48, df = 42, p < 0.001). The NQ scores correlated strongly with two measures of exhaustion (Karolinska Exhaustion Scale KES r = 0.772, p < 0.01; Shirom Melamed Burnout Measure SMBM r = 0.565, p < 0.01), mental status [Hospital Anxiety and Depression Score (HADS) depression r = 0.414, p < 0.01; HADS anxiety r = 0.627, p < 0.01], sleep disturbances (r = -0.514, p < 0.01), pain (r = -.370, p < 0.05) and poor well-being (Medical Outcomes Survey Short Form 36 questionnaire-SR Health r = -0.529, p < 0.05). In the logistic regression analysis, the variance in the scores from NQ were explained to a high degree (R-2 = 0.752) by scores in KES and HADS. The brief Grounding training contributed to a near significant reduction in hyperventilation (F = 2.521, p < 0.124) and to significant reductions in exhaustion scores and scores of depression and anxiety. The conclusion is that hyperventilation is common in exhaustion syndrome patients and that it can be reduced by sy

The upper airway is often modeled as a classical Starling resistor, featuring a constant inspiratory airflow, or plateau, over a range of downstream pressures. However, airflow tracings from clinical sleep studies often show an initial peak before the plateau. To conform to the Starling model, the initial peak must be of small magnitude or dismissed as a transient. We developed a method to simulate fast or slow inspirations through the human upper airway, to test the hypothesis that this initial peak is a transient. Eight subjects [4 obstructive sleep apnea (OSA), 4 controls] slept in an "iron lung" and wore a nasal mask connected to a continuous/bilevel positive airway pressure machine. Downstream pressure was measured using an epiglottic catheter. During non-rapid eye movement (NREM) sleep, subjects were hyperventilated to produce a central apnea, then extrathoracic pressure was decreased slowly (∼2-4 s) or abruptly (<0.5 s) to lower downstream pressure and create inspiratory airflow. Pressure-flow curves were constructed for flow-limited breaths, and slow vs. fast reductions in downstream pressure were compared. All subjects exhibited an initial peak and then a decrease in flow with more negative pressures, demonstrating negative effort dependence (NED). The rate of change in downstream pressure did not affect the peak to plateau airflow ratio: %NED 22 ± 13% (slow) vs. 20 ± 5% (fast), P = not significant. We conclude that the initial peak in inspiratory airflow is not a transient but rather a distinct mechanical property of the upper airway. In contrast to the classical Starling resistor model, the upper airway exhibits marked NED in some subjects.

This review summarizes evidence in humans for an association between hyperventilation (HV)-induced hypocapnia and a reduction in cerebral perfusion leading to syncope defined as transient loss of consciousness (TLOC). The cerebral vasculature is sensitive to changes in both the arterial carbon dioxide (PaCO2) and oxygen (PaO2) partial pressures so that hypercapnia/hypoxia increases and hypocapnia/hyperoxia reduces global cerebral blood flow. Cerebral hypoperfusion and TLOC have been associated with hypocapnia related to HV. Notwithstanding pronounced cerebrovascular effects of PaCO2 the contribution of a low PaCO2 to the early postural reduction in middle cerebral artery blood velocity is transient. HV together with postural stress does not reduce cerebral perfusion to such an extent that TLOC develops. However when HV is combined with cardiovascular stressors like cold immersion or reduced cardiac output brain perfusion becomes jeopardized. Whether, in patients with cardiovascular disease and/or defect, cerebral blood flow cerebral control HV-induced hypocapnia elicits cerebral hypoperfusion, leading to TLOC, remains to be established.

Based upon the results obtained from these studies, we can draw the following conclusions: 1) Airway hyperresponsiveness developed in Ova-sensitized mice was less pronounced in TRPV1-null mice, indicating an important role of TRPV1. 2) An increase in airway temperature within the normal physiological range triggered bronchoconstriction in sensitized rats, but not in control rats. Chronic airway inflammation in sensitized animals is likely a major contributing factor in causing this response. 3) transient increase in airway resistance was generated immediately after hyperventilation with warm humid air in patients with mild asthma, but the same warm humid air challenge failed to cause any bronchoconstriction in healthy subjects. Furthermore, this bronchoconstriction is likely generated by the increase in airway temperature because hyperventilation with humidified air at room temperature did not generate any change in airway resistance in the same patients. These studies, once completed, should provide important and novel information for: 1) documenting the pulmonary stresses induced by hyperthermia in healthy individuals and in patients with sensitized airways; 2) understanding the mechanism underlying the hyperthermia-induced pulmonary dysfunction; and 3) detecting the susceptibility to heat stress in soldiers with underestimated or overlooked airway hypersensitivity such as in airway allergy or mild asthma., The original document contains color images.

Chronic stress is among the most common diagnoses in Sweden, most commonly in the form of exhaustion syndrome (ICD-10 classification - F43.8). The majority of patients with this syndrome also have disturbed breathing (hyperventilation). The aim of this study was to investigate the association between hyperventilation and exhaustion syndrome. Thirty patients with exhaustion syndrome and 14 healthy subjects were evaluated with the Nijmegen Symptom Questionnaire (NQ). The participants completed questionnaires about exhaustion, mental state, sleep disturbance, pain and quality of life. The evaluation was repeated 4 weeks later, after half of the patients and healthy subjects had engaged in a therapy method called 'Grounding', a physical exercise inspired by African dance. The patients reported significantly higher levels of hyperventilation as compared to the healthy subjects. All patients' average score on NQ was 26.57 ± 10.98, while that of the healthy subjects was 15.14 ± 7.89 (t = -3.48, df = 42, p < 0.001). The NQ scores correlated strongly with two measures of exhaustion (Karolinska Exhaustion Scale KES r = 0.772, p < 0.01; Shirom Melamed Burnout Measure SMBM r = 0.565, p < 0.01), mental status [Hospital Anxiety and Depression Score (HADS) depression r = 0.414, p < 0.01; HADS anxiety r = 0.627, p < 0.01], sleep disturbances (r = -0.514, p < 0.01), pain (r = -.370, p < 0.05) and poor well-being (Medical Outcomes Survey Short Form 36 questionnaire- SR Health r = -0.529, p < 0.05). In the logistic regression analysis, the variance in the scores from NQ were explained to a high degree (R(2) = 0.752) by scores in KES and HADS. The brief Grounding training contributed to a near significant reduction in hyperventilation (F = 2.521, p < 0.124) and to significant reductions in exhaustion scores and scores of depression and anxiety. The conclusion is that hyperventilation is common in exhaustion syndrome patients and that it can be reduced by sys

The purpose of the present study was to explore the effects of Holorenic Breathwork (HrnB), a prolonged, voluntary hyperventilation procedure, on certain personality properties, meaning of life and levels of distress. A total of 62 subjects, aged 18-35 years, were compared using a repeated measures design. The experimental group (N=31) participated for the first timein a workshop where the hyperventilation procedure was used. Measures were taken before and after the workshop (one week and one month later). The control group subjects (N=31) did not receive any alternative treatment. The tests used were the Symptom Checklist-90-Revised(SCL-R-90), the Purpose in Life Test (PLT) and the Temperament and Character Inventory (TCI-R). In the experimental group, there was a significant reduction in the Global Severity Index of the SCL-R-90, and a significant increase in the meaning of life (PLT), Self-directedness, Cooperativeness and Self-transcendence (TCI-R) one week and one month after the workshop, El presente estudio tiene como objetivo principal explorar los efectos de la Respiración Holorénica(RHrn) en el nivel de malestar subjetivo, percepción del sentido de la vida y ciertas características de la personalidad. La Respiración Holorénicaes una técnica voluntaria y prolongada de hiperventilación. Se compararon un total de 62 sujetos, de entre 18-35 años, usando un diseño de medidas repetidas. El grupo experimental (N=31) participó por primera vez en un taller en el que se empleaba la técnica de hiperventilación. El grupo control (N=31) no recibió ningún tratamiento alternativo. Los instrumentos empleados fueron el Inventario de Síntomas-Revisado (SCL-R-90), el Purpose in Life Test (PLT) y el Inventario de Temperamento yCarácter-Revisado (TCI-R). Los resultados del estudio mostraron una reducción significativa en el Índice de Severidad Global del SCL-R-)0, y un aumento significativo en el sentido de la vida (PLT), Autodirección, Cooperación y Autotrascendencia (TCI-R), una semana y un mes después del taller

Based upon the results obtained from these studies, we can draw the following conclusions: 1) Airway hyperresponsiveness developed in Ova-sensitized mice was less pronounced in TRPV1-null mice, indicating an important role of TRPV1. 2) An increase in airway temperature within the normal physiological range triggered bronchoconstriction in sensitized rats, but not in control rats. Chronic airway inflammation in sensitized animals is likely a major contributing factor in causing this response. 3) transient increase in airway resistance was generated immediately after hyperventilation with warm humid air in patients with mild asthma, but the same warm humid air challenge failed to cause any bronchoconstriction in healthy subjects. Furthermore, this bronchoconstriction is likely generated by the increase in airway temperature because hyperventilation with humidified air at room temperature did not generate any change in airway resistance in the same patients. These studies, once completed, should provide important and novel information for: 1) documenting the pulmonary stresses induced by hyperthermia in healthy individuals and in patients with sensitized airways; 2) understanding the mechanism underlying the hyperthermia- induced pulmonary dysfunction; and 3) detecting the susceptibility to heat stress in soldiers with underestimated or overlooked airway hypersensitivity such as in airway allergy or mild asthma., The original document contains color images.

Purpose: To systematically study the semiology of psychogenic nonepileptic seizures (PNES) captured by video-electroencephalography (EEG) monitoring (VEM) and categorize the typical patterns observed. Method(s): VEM records of patients who underwent evaluation from January 2002 to June 2007 were reviewed to identify those who had PNES with or without a background of epilepsy. The semiology of each event was visually analyzed and entered into a statistical database. Type of movement, anatomic distribution, synchrony, symmetry, onset, offset, course, duration, vocalization, hyperventilation, eye movements, and responsiveness were evaluated. PNES were classified into distinct groups according to the predominant motor manifestation. Result(s): A total of 330 PNES from 61 patients were studied. Based on semiology, six different types of PNES were observed as follows: (1) rhythmic motor PNES characterized by rhythmic tremor or rigor-like movements (46.7%); (2) hypermotor PNES characterized by violent movements (3.3%); (3) complex motor PNES characterized by complex movements such as flexion, extension, abduction, adduction, rotation, with or without clonic-like and myoclonic-like components of varying combinations and anatomic distribution (10%); (4) dialeptic PNES characterized by unresponsiveness without motor manifestations (11.2%); (5) nonepileptic auras characterized by subjective sensations without any external manifestations, marked in the VEM records as "seizure button presses" (23.6%); and (6) mixed PNES where combinations of above seizure types were seen (5.2%). In a given patient, all the seizures belonged to a single type of PNES in 82% of cases. Discussion(s): PNES can be classified into six stereotypic categories. Contrary to common belief, PNES demonstrates stereotypy both within and across patients. © 2010 International League Against Epilepsy.

Based upon the results obtained from these studies, we can draw the following conclusions: 1) Airway hyperresponsiveness developed in Ova-sensitized mice was less pronounced in TRPV1-null mice, indicating an important role of TRPV1. 2) An increase in airway temperature within the normal physiological range triggered bronchoconstriction in sensitized rats, but not in control rats. Chronic airway inflammation in sensitized animals is likely a major contributing factor in causing this response. 3) transient increase in airway resistance was generated immediately after hyperventilation with warm humid air in patients with mild asthma, but the same warm humid air challenge failed to cause any bronchoconstriction in healthy subjects. Furthermore, this bronchoconstriction is likely generated by the increase in airway temperature because hyperventilation with humidified air at room temperature did not generate any change in airway resistance in the same patients. These studies, once completed, should provide important and novel information for: 1) documenting the pulmonary stresses induced by hyperthermia in healthy individuals and in patients with sensitized airways; 2) understanding the mechanism underlying the hyperthermia-induced pulmonary dysfunction; and 3) detecting the susceptibility to heat stress in soldiers with underestimated or overlooked airway hypersensitivity such as in airway allergy or mild asthma., The original document contains color images.

Idiopathic generalized epilepsy (IGE) is classified into several subsyndromes based on clinical and electroencephalography (EEG) features. The EEG signature of IGE is bisynchronous, symmetric, and generalized spike-wave complex; although focal, irregular, and so called "fragments" of discharges are not uncommon. Other characteristic EEG features include polyspikes, polyspike-wave discharges, occipital intermittent rhythmic delta activity, and photoparoxysmal response. Both human and animal data suggest involvement of the thalamus and the cortex in the generation of spike-wave discharges in IGE. Circadian variations of generalized epileptiform discharges are well described, and these can be useful in diagnostic confirmation. Those discharges tend to occur more often after awakening and during cyclic alternating pattern phase-A of non-rapid eye movement sleep. Activation procedures such as hyperventilation, intermittent photic stimulation, eye closure, and fixation-off are useful techniques to increase the yield of both interictal and ictal EEG abnormalities. Although not in routine use, specific triggers such as pattern stimulation and cognitive tasks may also be of value in eliciting rare reflex seizure-related EEG abnormalities. Variations of EEG abnormalities are evident between different electroclinical syndromes. EEG is also affected by certain external as well as internal factors, which should be borne in mind when interpreting EEG studies in IGE. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

We attempted to elucidate effects of hyperventilation in experimental pulmonary air-embolism of dogs. Pulmonary air embolism was produced by air infusion 0.1 ml/kg/min. for 10 minuten (0.1 ml/kg) via inserted pulmonary artery catheter ; endotracheal anesthetized dogs with fentanyl and vecuronium bromide under mechanical ventilation. We measured hemodynamic variables and pH, blood gas (arterial, mixed venous blood) at baseline, post-air infusion and after recovered pulmonary artery pressure (PAP). In addition PAP recovery-times were counted. As results, PAP recovery-times in hyperventilation group (pH=7.50, PaCO₂=25 mmHg) were attenuated significantly compared with normoventilation (control) group (pH=7.40, PaCO₂=40 mmHg) ; these values were 14.2±5.2 min. versus 17.8±6.0 min. (n=8, p<0.05). On the threshould air volume of paradoxical air-embolism, we confirmed air bubbles in the left atrium and/or aorta with using transesophageal echocardiography and recognized 0.75±0.27 ml/kg (hyperventilation group), and 0.83±0.26 ml/kg (control) respectively ; there were no significant differences related to the ventilation-modus. We concluded that recovery-time of elevated pulmonary artery pressure was attenuated with induced hyperventilation in the experimental air embolism, but that hyperventilation revealed no beneficial effects on the threshold air volume of paradoxical air-embolism.