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Introduction: The sharpened Romberg test (SRT) is a physical maneuver that has been used to identify ataxia in individuals in resource-limited settings. Previous research has suggested that performance on balance testing may be affected by hypocapnia. In this study, we sought to determine whether acute hyperventilation-induced hypocapnia affects performance on the SRT at 501 meters above sea level., Methods: We recruited 22 healthy subjects. Each subject performed a baseline SRT. Subjects were then asked to hyperventilate to the point of hypocapnia, confirmed by measurement with a capnometer. Subjects were then asked to re-perform SRT. The primary endpoint was time to loss of balance, measured as time-to-stepout., Results: Time-to-stepout (TTS) on SRT at baseline had a mean ± standard deviation of 101 ± 117 s. In the hypocapnic condition, TTS was reduced to 48 ± 68 s. TTS normalized to 121 ± 132 s after recovery to normal capnic levels. Time-to-stepout was found to be significantly shorter in the hypocapnic measurement compared to the baseline measurement ( P  = .0128). Statistical analysis was conducted using one-tailed, paired sample T-tests using a P -value of < .05., Conclusions: Our study found a statistically and clinically significant reduction in performance on a balance test (SRT) when exposed to acute hyperventilation-induced hypocapnia compared to a eucapnic control. Our results suggest that acute hypocapnia may contribute to neurological dysfunction independently of hypobaric hypoxia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs. Stepanek and Pradhan are inventors on USPTO patent number 11529492 (methods and materials for treating hypocapnia).

Purpose: Carbon dioxide (CO 2 ) is a potent cerebral vasomotor agent. Despite reduction in CO 2 levels (hypocapnia) being described in several acute diseases, there is no clear data on baseline CO 2 values in acute stroke. The aim of the study was to systematically assess CO 2 levels in acute stroke., Material and Methods: Four online databases, Web of Science, MEDLINE, EMBASE and CENTRAL, were searched for articles that described either partial pressure of arterial CO 2 (PaCO 2 ) and end-tidal CO 2 (EtCO 2 ) in acute stroke., Results: After screening, based on predefined inclusion and exclusion criteria, 20 studies were retained. There were 5 studies in intracerebral hemorrhage and 15 in ischemic stroke, totalling 660 stroke participants. Acute stroke was associated with a significant decrease in CO 2 levels compared to controls. Cerebral haemodynamic studies using transcranial Doppler ultrasonography demonstrated a significant reduction in cerebral blood flow velocities and cerebral autoregulation in acute stroke patients., Conclusion: The evidence from this review suggests that acute stroke patients are significantly more likely than controls to be hypocapnic, supporting the value of routine CO 2 assessment in the acute stroke setting. Further studies are required in order to evaluate the clinical impact of these findings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Intermittent hypoxia, reoxygenation, and hypercapnia or hypocapnia occur in both adults and children during untreated apnoea and hypopnoea, along with changes in cerebral blood flow and sleep fragmentation. These effects can result in cognitive deficits with functional effects on work and school efficiency. The assessment of how obstructive sleep apnoea affects cognition depends on the specificity and sensitivity of the tests, which are rarely developed specifically for obstructive sleep apnoea. In this Review, we discuss both the neural adaptive and maladaptive processes in response to hypoxaemia. The net result on cognitive and emotional performance depends on the stage of this dynamic process, effects on other body systems, cognitive reserve, and idiosyncratic susceptibility. We also explore the contribution of fragmented sleep, and the disruption of sleep structure, with focus on the effect at different times in the development of disease. This Review will address the gap in the underlying pathophysiology of new clinical and translational findings, and argue their contribution to the inherent complexity of the association between obstructive sleep apnoea and the brain., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We report the case of an 80-year-old woman with symptomatic postural hypoxaemia caused by a right-to-left shunt through a patent foramen ovale. The hypoxaemia was enhanced by the supine position and disappeared in upright position. Potential mechanisms underlying postural variations of the shunt seemed to be similar to those describe in platypnea-orthodeoxia syndrome. Patient became asymptomatic after shunt resolution., (Copyright © 2013. Published by Elsevier SAS.)

A computerized decision support system is described to predict the changes in the cerebral blood flow (CBF) of mechanically ventilated infants in response to different ventilatory settings. A CBF controller was developed and combined with a mathematical model of the infant's respiratory system to simulate the effects of ventilatory settings on the infant's CBF. The performance of the system was examined under various ventilatory treatments and the results were compared with available experimental data. The comparisons showed good agreement between the simulation results and experimental data for preterm infants. These included the results obtained under conditions of hypoventilation, hyperventilation, hypoxia, and hyperoxia. The presented decision support system has the potential to be used as an aide to the intensivist in choosing appropriate ventilation treatments for infants to prevent the untoward consequences of hazardous changes in CBF in mechanically ventilated infants such as hypoxic-ischemic brain injuries., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

This study examined the effect of anxiety on cerebral blood flow at different levels of pCO2 in healthy participants (N=29). Three types of breathing were used to manipulate pCO2 in a within-subject threat-of-shock paradigm: spontaneous breathing, CO2-inhalation and hyperventilation resulting in normo-, hyper- and hypocapnia. Transcranial Doppler ultrasonography was used to measure CBF velocity (CBFv) in the right middle cerebral artery, while breathing behavior and end-tidal pCO2 were monitored. During normocapnia, elevated anxiety was clearly associated with increased CBFv. Consistent with the cerebral vasoconstrictive and vasodilating effects of, respectively, hypo- and hypercapnia, we observed a positive linear association between CBFv and pCO2. The slope of this association became steeper with increasing anxiety, indicating that anxiety enhances the sensitivity of CBFv to changes in pCO2. The findings may elucidate conflicting findings in the literature and are relevant for brain imaging relying on regional cerebral blood flow., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Anaesthetic-induced developmental neurotoxicity (AIDN) has been clearly established in laboratory animal models. The possibility of neurotoxicity during uneventful anaesthetic procedures in human neonates or infants has led to serious questions about the safety of paediatric anaesthesia. However, the applicability of animal data to clinical anaesthesia practice remains uncertain. The spectre of cerebral injury due to cerebral hypoperfusion, metabolic derangements, coexisting disease, and surgery itself further muddles the picture. Given the potential magnitude of the public health importance of this issue, the clinician should be cognisant of the literature and ongoing investigations on AIDN, and raise awareness of the risks of both surgery and anaesthesia.

Background/aims: Previous studies proved that vasodilation, caused by hypercapnia or acetazolamide, does not inhibit the visually evoked flow velocity changes in the posterior cerebral arteries. Our aim was to determine whether vasoconstriction induced by hypocapnia affects the neurovascular coupling., Methods: By using a visual cortex stimulation paradigm, visually evoked flow velocity changes were detected by transcranial Doppler sonography in both posterior cerebral arteries of fourteen young healthy adults. The control measurement was followed by the examination under hyperventilation. Visual-evoked-potentials were also recorded during the control and hyperventilation phases., Results: The breathing frequency increased from 16 ± 2 to 37 ± 3/min during hyperventilation, resulting in a decrease of the end-tidal CO(2) from 37 ± 3 to 25 ± 3 mm Hg and decrease of resting peak systolic flow velocity from 58 ± 11 to 48 ± 11 cm/s (p<0.01). To allow comparisons between volunteers, relative flow velocity was calculated in relation to baseline. Repeated measures analysis of variance revealed significant difference between the relative flow velocity time courses during hyper- and normoventilation (p<0.001). The maximum changes of visually evoked relative flow velocities were 26 ± 7% and 12 ± 5% during normoventilation and hyperventilation, respectively (p<0.01). Visual-evoked-potentials did not differ in the control and hyperventilation phases., Conclusion: The significantly lower visually evoked flow velocity changes but preserved visual-evoked-potential during hyperventilation indicates that the hypocapnia induced vasoconstriction significantly inhibits the neuronal activity evoked flow response., (Copyright © 2011 Elsevier B.V. All rights reserved.)

There is a large body of experimental evidence showing benefits of deliberate mild hypothermia (33-35 degrees C) on the injured brain as well as an improvement of neurological outcome after cardiac arrest in humans. However, the clinical evidence of any benefit of hypothermia following stroke, brain trauma and neonatal asphyxia is still lacking. Controversial results have been published in patients with brain trauma or neonatal asphyxia. Hypothermia can reduce the elevation of intracranial pressure, through mechanisms not completely understood. Hypothermia-induced hypocapnia should have a role on the reduction of intracranial pressure. The temperature target is unknown but no additional benefit was found below 34 degrees C. The duration of deliberate hypothermia for the treatment of elevated intracranial pressure might be at least 48 hours, and the subsequent rewarming period must be very slow to prevent adverse effects.

Lung injury in ventilated premature infants occurs primarily through the mechanism of volutrauma, often due to the combination of high tidal volumes in association with a high end-inspiratory volume and occasionally end-expiratory alveolar collapse. Tolerating a higher level of arterial partial pressure of carbon dioxide (PaCO2) is considered as 'permissive hypercapnia' and when combined with the use of low tidal volumes may reduce volutrauma and lead to improved pulmonary outcomes. Permissive hypercapnia may also protect against hypocapnia-induced brain hypoperfusion and subsequent periventricular leukomalacia. However, extreme hypercapnia may be associated with an increased risk of intracranial hemorrhage. It may therefore be important to avoid large fluctuations in PaCO2 values. Recent randomized clinical trials in preterm infants have demonstrated that mild permissive hypercapnia is safe, but clinical benefits are modest. The optimal PaCO2 goal in clinical practice has not been determined, and the available evidence does not currently support a general recommendation for permissive hypercapnia in preterm infants.

Background: Hyperventilation, with the resulting hypocapnia, reduces cerebral blood flow and causes slowing of the EEG activity. However, neuronal oscillating properties including the thalamocortical network during hyperventilation have not been elucidated. To assess these features provoked by hyperventilation, the present study examined quadratic phase coupling features by means of bicoherence analysis., Methods: Twenty-two patients were anaesthetized using sevoflurane 1.5% combined with remifentanil or epidural anaesthesia. After a stable normocapnic period, hypocapnia was induced by hyperventilation, and the raw EEG signals were collected. Bispectral analysis (bicoherence) and power spectrum analysis were performed before and after hypocapnia., Results: Mean (sd) peak bicoherence in the delta- area increased from 35.6 (10.9)% during normocapnia to 43.8 (10.9)% during hypocapnia (P<0.05), whereas mean (sd) peak bicoherence in the alpha area decreased from 42.8 (14.4)% during normocapnia to 37.5 (12.3)% during hypocapnia (P<0.05). Normalized power in the delta- frequencies on the power spectrum increased from 60.2 (13.1)% to 72.5 (12.7)% (P<0.05). Bispectral index and spectral edge frequency changed from 45.9 (7.0) to 40.1 (5.6) (P<0.05) and from 15.0 (2.3) to 14.0 (2.5) Hz (P<0.05), respectively. No significant differences in these values were observed between the two types of anaesthesia., Conclusions: Hypocapnia enlarged bicoherence growth in the delta- frequency range, suggesting the contribution of subcortical oscillating mechanisms in regulating EEG during hyperventilation.

We have used a novel neurophysiological technique in the NeuroScope system in combination with conventional electroencephalography (EEG) to monitor both brainstem and cortical activity simultaneously in real-time in a girl with Rett syndrome. The presenting clinical features in our patient were severe sleep disturbances, irregular breathing in the awake state dominated by Valsalva's type of breathing followed by tachypnoea and very frequent attacks of seizures and vacant spells. Our novel neurophysiological data showed that the patient was a Forceful Breather according to the breathing categories in Rett syndrome. She had frequent abnormal spontaneous brainstem activation (ASBA) preceded by severe attacks of hypocapnoea, which was caused by a combination of Valsalva's type of breathing and tachypnoea and all these together were responsible for the seizures and non-epileptic vacant spells. The ASBA was not detectable in conventional EEG and there were no epileptiform changes in the EEG during the seizures and vacant spells caused by the hypocapnic attacks, therefore these were pseudo-seizures. The record of brainstem activity confirmed that these were autonomic events, a kind of "brainstem epilepsy". We successfully treated the sleep disturbance with Pipamperone, a 5-hydroxytryptophan antagonist of receptor type 2 and we prevented the severe hypocapnoea during Valsalva's type of breathing and during tachypnoea using carbogen (a mixture of 5% carbon dioxide and 95% oxygen), which we gave by inhalation. Our treatment drastically reduced the autonomic events, promoted whole night sleep and significantly improved the quality of life in our patient. She can now participate in normal family activity which was previously impossible before treatment.

Objectives: To assess whether head-up tilt-induced hyperventilation is seen more often in patients with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS) as compared to healthy subjects or those with familial Mediterranean fever (FMF)., Patients and Methods: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n = 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one PETCO2 measurement of 25 or less was accepted as hyperventilation., Results: Hypocapnia was diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n = 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80). Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients., Conclusions: Hyperventilation appears to be the major abnormal response to postural challenge in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events. Our study does not support an essential role for hypocapnia in NMS or in postural symptoms associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and nonspecific dizziness, capnography should be a part of the evaluation of patients with such conditions.

There is some evidence that breathing retraining may be beneficial for patients with asthma, but the mechanism behind this benefit is still unknown. One hypothesis is that individuals can be trained to raise carbon dioxide levels and thereby reverse the bronchoconstrictive effects of hypocapnia and utilize the bronchodilatory effects of hypercapnia. This theory presupposes that individuals with asthma have lower carbon dioxide levels than the healthy population. This article reviews the available evidence supporting the hypothesis and concludes that although attractive, there is currently insufficient evidence to attribute the benefits of breathing retraining to this mechanism.

Phosphodiesterase inhibitors, such as pentoxifylline and aminophylline, may reduce inflammatory cytokine-induced endothelial permeability. We tested the hypothesis that aminophylline treatment may ameliorate the pulmonary and extrapulmonary effects of endotoxemia in a rat model. In anesthetized rats, a tracheotomy was performed along with catheterization of a femoral vein and artery. Anesthesia, fluid balance, and normothermia were maintained throughout the 6-h experiment. A stable hemodynamic and gas-exchange baseline was established at which time the rats were randomly divided into three groups. Group I received aminophylline (1mg/kg) over 30 min followed by 0.5mg/kg/h. Group II received a single dose of endotoxin (4 mg/kg) while Group III received both aminophylline and endotoxin as described for Groups I and II, respectively. Gas-exchange profiles, mean arterial blood pressure, and heart rate were determined every 2h. At hour 6, the rats were euthanized and lung, kidney, and heart tissue were removed for determination of water content. As our control group, we utilized data from our previously published study involving an identical surgical procedure with normal saline. Endotoxemia produced characteristic respiratory and hemodynamic signs of sepsis including hypotension, hyperventilation, tachycardia, and renal and pulmonary edema. Aminophylline treatment failed to prevent these endotoxemia-induced respiratory and hemodynamic manifestations of sepsis, but significantly improved the acid-base imbalance that developed during surgical procedures in saline-treated control rats. Further studies are warranted to determine potentially beneficial doses of aminophylline and resulting theophylline serum concentrations under such septic conditions.

Plasma endothelin elevations have been associated with cerebrovascular pathology. Mechanisms of stimulation, however, are unknown. Therefore, in healthy subjects a marked physiological cerebrovascular response was experimentally provoked by hypercapnia, hypocapnia, and alternating capneic conditions. During these challenges plasma immunoreactive-endothelin-1 (ir-ET-1) concentrations were determined using a radioimmunassay. Physiological effects were continuously recorded for pCO(2), cerebral blood flow velocity, pulse frequency, and arterial blood pressure. No alterations in plasma ET-1 levels were found upon any of the cerebrovascular stimuli. We conclude that massive cerebrovascular challenges in healthy individuals do not lead to high circulating ET-1 levels.

Objective: To confirm the hypothesis that the ventilatory response to hypoxia (VRH) may be abolished by hypocapnia., Methods: We studied four healthy subjects during intermittent positive-pressure ventilation delivered through a nasal mask (nIPPV). Delivered minute ventilation (Ed) was progressively increased to lower end-tidal carbon dioxide pressure (PETCO(2)) below the apneic threshold. Then, at different hypocapnic levels, nitrogen was added to induce falls in oxygen saturation, a hypoxic run (N(2) run). For each N(2) run, the reappearance of a diaphragmatic muscle activity and/or an increase in effective minute ventilation (E) and/or deformations in mask-pressure tracings were considered as a VRH, whereas unchanged tracings signified absence of a VRH. For the N(2) runs eliciting a VRH, the threshold response to hypoxia (TRh) was defined as the transcutaneous oxygen saturation level that corresponds to the beginning of the ventilatory changes., Results: Thirty-seven N(2) runs were performed (7 N(2) runs during wakefulness and 30 N(2) runs during sleep). For severe hypocapnia (PETCO(2) of 27.1 +/- 5.2 mm Hg), no VRH was noted, whereas a VRH was observed for N(2) runs performed at significantly higher PETCO(2) levels (PETCO(2) of 34.0 +/- 2.1 mm Hg, p < 0.001). Deep oxygen desaturation (up to 64%) never elicited a VRH when the PETCO(2) level was < 29.3 mm Hg, which was considered the carbon dioxide inhibition threshold. For the 16 N(2) runs inducing a VRH, no correlations were found between PETCO(2) and TRh and between TRh and both Ed and E., Conclusion: During nIPPV, VRH is highly dependent on the carbon dioxide level and can be definitely abolished for severe hypocapnia.

Background: Gastroenterologic symptoms are common in the postural tachycardia syndrome (POTS), and postprandial worsening of orthostatic symptoms often occurs. We, therefore, investigated splanchnic-mesenteric vasoregulation in POTS., Subjects and Methods: Eleven patients with POTS (one man, 10 women, 29.4 +/- 7.7 (S.D.) years) and 10 controls (two men, eight women, 27.9 +/- 5.6 years) participated in this study. The protocol included 5 min of 70 degrees head-up tilt (HUT) before and after a liquid meal, as well as 1.5 min of hyperventilation. Blood pressure (BP), heart rate (HR), endtidal CO2, and cardiovascular indices derived from thoracic electrical bioimpedance were continuously monitored. Superior mesenteric artery (SMA) blood flow was measured by real time Doppler ultrasound and analyzed off-line. Cross-sectional area of SMA (SMA-area) and time-averaged velocity (SMA-TAV) were measured; SMA blood flow (SMA-BF) and vascular resistance (SMA-VR) were derived., Results: The following significant results were found: at supine rest, the POTS group had higher HR, BP, SMA-TAV and SMA-BF and a lower SMA-VR than the control group. HUT resulted in a reduction of pulse pressure, CO2 level, SMA-area, SMA-TAV and SMA-VF and increment of HR and SMA-VR in both groups. The POTS group underwent greater increment of HR and greater reduction of CO2 than controls. Hyperventilation induced increment of HR and cardiac index (CI) and reduction of SMA-VR in controls; no significant change occurred in POTS. The test meal induced increments of HR, CI, SMA-area, SMA-TAV and SMA-VF and reduction of SMA-VR in patients and controls for both supine rest and HUT., Conclusion: The main novel observations of increased resting SMA-BF, SMA-TAV supine, and reduced SMA-VR when compared with controls support the notion that there is excessive splanchnic capacity (pooling) at rest in POTS.

To clarify a possible origin of 'respiratory like' rhythmic activities observed in in vitro brainstem preparation, the phrenic (Phr) and cranial nerve (XII or IX) inspiratory activities were analyzed in halothane-anesthetized, vagotomized and artificially ventilated newborn (2--6 days after birth) and young adult rats (30--50 days) during altered chemical stimuli and prolonged asphyxia at 25 degrees C. The newborn rat showed regular rhythmic inspiratory discharges of short duration, and their responses to CO(2) and hypoxia did not differ from those seen in adult rats. In the newborn rat the Phr and cranial nerve inspiratory discharges increased first, then respiratory frequency decreased and finally ceased completely for approximately 1--2 min during asphyxia. Thereafter, 'secondary' rhythmic inspiratory activity emerged at a slower rate with decremental inspiratory discharge profile, which persisted for a period more than 40 min of asphyxia. A normal respiratory activity recovered after resumption of artificial ventilation. Though young adult rats exhibited similar sequential changes in respiratory activity during asphyxia, the 'secondary' rhythmic activity persisted for a period of several min only. The pattern of 'secondary' respiratory activity corresponded well with that of rhythmic activities seen in the isolated medullary block preparation of newborn rat. 'Respiratory like' activity found in isolated medullary preparations of newborn animals may arise from a mechanism that generates 'secondary' (or so called 'gasping' type) rhythmic inspiratory activity during prolonged asphyxia in in vivo preparations.

The purpose of this study was to determine the relationship between the increase in local cerebral blood flow during neuronal activation (evoked LCBF) and the baseline flow level. We measured the hemodynamics in alpha-chloralose-anesthetized rats using laser-Doppler flowmetry during somatosensory stimulation under the hypocapnic, normocapnic and hypercapnic conditions. The baseline levels of LCBF and red blood cell (RBC) velocity under hypocapnia (PaCO(2)=26.4+/-1.1 mmHg) were, respectively, 10 and 11% lower than those under normocapnia (PaCO(2)=34.2+/-1.4 mmHg) (P<0.01). The evoked response magnitude of LCBF and RBC velocity under hypocapnia were, respectively, 22 and 18% lower than those under normocapnia. There was no significant difference in the baseline level and evoked response magnitude of RBC concentration. On the other hand, the baseline levels of LCBF, RBC velocity and RBC concentration under hypercapnia (PaCO(2)=73.4+/-13.3 mmHg) were, respectively, 47, 24 and 14% higher than those under normocapnia (PaCO(2)=34.7+/-2.5 mmHg) (P<0.01). The evoked response magnitude of LCBF, RBC velocity and RBC concentration under hypercapnia were, respectively, 96, 82 and 62% greater than those under normocapnia. After normalization with respect to each baseline level, there was no significant difference in normalized evoked response magnitude of LCBF, RBC velocity and RBC concentration, either between hypocapnic and normocapnic conditions or between hypercapnic and normocapnic conditions, indicating that evoked LCBF is proportional to the baseline flow. These results suggest that the amount of evoked LCBF is not determined by the demand for metabolic substrates.

We have studied the effects of acute changes in acid-base status and hypoxia on the cardiotoxic effects of intracoronary injection of ropivacaine in anaesthetized dogs. The effects of intracoronary ropivacaine were compared when ropivacaine was administered during eucapnia and during each of another nine states in random order: hypocapnia, hypercapnia, hypoxia, metabolic alkalosis, metabolic acidosis, combined metabolic acidosis and hypocapnia, combined metabolic alkalosis and hypercapnia, combined hypoxia and hypercapnia, and combined metabolic acidosis and hypoxia. Hypocapnic alkalosis consistently reduced the cardiotoxic effects of intracoronary ropivacaine (P < 0.01). Our findings indicate that induction of hypocapnic alkalosis may provide a useful adjunct to standard resuscitative measure after inadvertent administration of amide local anaesthetic agents.

Hyperoxia can improve oxygen delivery in patients exposed to hypocapnia for neurosurgical procedures but this effect may be modified by regional differences in the degree of hypocapnic vasoconstriction. Using functional magnet resonance imaging (fMRI), we have investigated the influence of hyperoxia on blood flow and blood oxygenation in the primary visual cortex in hypocapnic volunteers. Consecutive fMRI measurements were performed in 10 awake, male volunteers during hypocapnia (mean PE'CO2 3.3 (SD 0.1) kPa) and normocapnia (PE'CO2 5.3 (0.1) kPa) at FIO2 values of 0.21 and 1.0, respectively. Hypocapnia significantly reduced the pixel count in the primary visual cortex (median 169 (quartiles 34-246) vs 21 (0-40) pixels at an FIO2 of 0.21). Additional hyperoxia had no influence on this reduction in pixel count (16 (0-28) pixels at FIO2 1.0 vs 21 (0-40) pixels at FIO2 0.21). Hyperoxia did not influence hypocapnic vasoconstriction in the primary visual cortex. These data suggest that in the primary visual cortex, administration of oxygen alone may not be sufficient to improve oxygen delivery under hypocapnic conditions.

Objective: To assess in children with a transcranial Doppler the effect on cerebral blood flow velocities of desflurane, whose cerebral vasodilator effects have been studied in animals and in adults with intracranial lesions., Study Design: Prospective clinical study., Patients: Ten healthy children, mean age: 3.4 yr, ASA physical class 1, undergoing minor urologic surgery, were included in this study., Method: Induction was obtained with atropine 10 micrograms.kg-1, fentanyl 3 micrograms.kg-1 and propofol 3 mg.kg-1. Endotracheal intubation was facilitated by atracurium 0.3 mg.kg-1. Mechanical ventilation, with a 50% air/oxygen mixture was adjusted to achieve an end-tidal CO2 (PETCO2) level of 38 +/- 2 mmHg. Monitoring included measurement of mean arterial blood pressure (MAP), heart rate, PETCO2, SpO2 and end-tidal desflurane concentrations (FETDes). Mean blood flow velocities (Vmean) were measured in the middle cerebral artery using a bi-directional 2 MHz TCD system (EME-TC 2000 S). A first TCD measurement followed intubation (T1). Thereafter, desflurane was adjusted to 1 MAC. Six other TCDs were recorded each minute until FETDes reached the inspired fraction (T2-T7). Thereafter, CO2 reactivity was assessed with a hypocapnia test, induced by hyperventilation. Measures were done at T8 (PETCO2: 33 +/- 1 mmHg), T9 (PETCO2: 29 +/- 1 mmHg), and T10 (initial PETCO2: 38 +/- 1 mmHg). All these measurements were made before starting surgery. Analysis of variance (ANOVA) was used to analyse the data (P < 0.05 was considered as significant)., Results: The Vmean and heart rate increased significantly with increasing concentrations of desflurane (Vmean from 68 +/- 27 to 106 +/- 30 cm.s-1 and heart rate from 109 +/- 17 to 136 +/- 15 b.min-1 between T1 and T7). During hypocapnia, Vmean decreased to 68 +/- 23 cm.s-1 at T9, and returned to normal values with PETCO2 at 38 mmHg at T10. SpO2 remained unchanged. Mean arterial pressure was stable from T1 to T7, but decreased significantly at T9 and T10., Conclusion: Desflurane elicits a dose-dependent increase in cerebral blood flow velocities and heart rate, but does not change mean arterial pressure, suggesting that its cerebrovascular action is independent of its systemic vascular action. CO2 reactivity is maintained at one MAC. The results in children are similar to those seen in adults.

Cheyne-Stokes respiration (CSR) is a form of sleep-disordered breathing seen in approximately 40% of congestive heart failure patients with a left ventricular ejection fraction of < 40%. It is characterized by a crescendo-decrescendo alteration in tidal volume separated by periods of apnea or hypopnea. Sleep is generally disrupted, often with frequent nocturnal arousals. Clinical features include excessive daytime sleepiness, paroxysmal nocturnal dyspnea, insomnia, and snoring. Proposed mechanisms include the following: (1) an increased CNS sensitivity to changes in arterial PCO2 and PO2 (increased central controller gain); (2) a decrease in total body stores of CO2 and O2 with resulting instability in arterial blood gas tensions in response to changes in ventilation (underdamping); and (3) an increased circulatory time. In addition, hyperventilation induced hypocapnia seems to be an important determinant for the development of CSR. Mortality appears to be increased in patients with CSR compared to control subjects with a similar degree of left ventricular dysfunction. Therapeutic options include medically maximizing cardiac function, nocturnal oxygen therapy, and nasal continuous positive airway pressure. The role that other therapeutic modalities, such as inhaled CO2 and acetazolamide, might have in the treatment of CSR associated with congestive heart failure has yet to be determined.

Background/aims: Normally, cerebral blood flow responds to changes in the arterial carbon dioxide tension (PaCO2) but not to changes in mean arterial pressure, commonly referred to as the cerebral CO2-reactivity and autoregulation. In patients with fulminant hepatic failure and in the rat with thioacetamide-induced liver failure, autoregulation is absent, presumably due to cerebral vasoparalysis. Since also CO2-reactivity may then be compromised, it was studied in patients with fulminant hepatic failure and rats with thioacetamide-induced liver failure., Methods: In ten patients (median age 32 (range 20-48) years)) and in ten age-matched volunteers, cerebral perfusion was elevated by transcranial Doppler assessed mean flow velocity (V(mean)) in the middle cerebral artery during hypo- and hyper-capnia. In six rats with liver failure and in six control rats, cerebral blood flow was measured repeatedly by the intracarotid 133 Xenon injection technique., Results: In the patients and volunteers, PaCO2 was lowered from 33 (23-44) to 28 (23-39) mmHg by hypocapnia and raised to 40 (34-48) mmHg by hypercapnia or 5% CO2 inhalation. During hypocapnia, the CO2-reactivity did not differ significantly between patients and volunteers, 4.0 (1.1-7.4) vs. 3.0 (1.7-5.0)% mmHg(-1), while it was reduced during hypercapnia in the patients, 2.2 (1.8-5.2) vs. 4.6 (3.0-8.0)% mmHg(-1) (p < 0.05). In the rats, PaCO2 was reduced from 39 (37-40) to 30 (29-31) mmHg and then raised to 51 (41-55) mmHg. During hypocapnia, CO2-reactivity was similar in rats with liver failure and in control rats, 2.3 vs 2.7% mmhg(21), respectively. In all rats with liver failure CO2-reactivity was abolished during hypercapnia, while it was 1.5% mmHg(-1) in the control rats (p < 0.01)., Conclusions: The finding that cerebral CO2 reactivity is reduced in hypercapnia, while it is preserved in hypocapnia, suggests that gradual dilation of the cerebral resistance vessels develops in fulminant hepatic failure and connects previous morphological studies with changes in the regulation of cerebral blood flow, i.e. impaired cerebral autoregulation and blunted CO2-reactivity.

Shifts in scalp-recorded direct current (DC) potential were studied in relation to the changes in end-tidal partial CO2 (PACO2) or O2 (PAO2) of the expired gas either during hyperventilation (HV), hypoventilation (HYPO) or inhalation of high CO2 content air during HV or HYPO in 10 healthy subjects. The DC potential was obtained through a chopper stabilized type of DC amplifier from Cz referred to linked earlobes. Each session was comprised of 3 min control, 3 min experimental and 5 min recovery periods. HV induced a negative shift of the DC potential of 765.5 +/- 203.0 microV (mean +/- SEM). Inhalation of 6% CO2 air during HYPO induced a positive shift of the DC potential of 280.6 +/- 62.8 microV (mean +/- SEM). The magnitude of the DC potential shifts was linearly dependent on the changes in the end-tidal PACO2 (r = 0.78, P < 0.0001). There was no change in the cephalic inter-electrodes impedance during each experimental session. The results suggest that the scalp-recorded DC potentials reflect the changes in cortical excitability associated with the PACO2 level.

Deliberate hypocapnia during the anaesthetic management of the patient undergoing craniotomy has become an accepted standard of care. However there has been a resurgence of interest, in how hypocapnia should be applied in intra- and extra-operative settings. There are three possible therapeutic effects of hypocapnia, namely, (a) reduction of brain bulk through a reduction in cerebral blood volume, with a decrease cerebral blood flow; (b) developing an "inverse steal" by redistribution of blood from normal to ischaemic regions and (c) acting to offset cerebral acidosis by increasing pH in the extracellular space. In anaesthetic intraoperative practice, hypocapnia is used as a specific treatment of, or prophylaxis against, intracranial hypertension during induction of anaesthesia and the period before dural exposure. More commonly, hypocapnia is used for intraoperative brain relaxation (intracranial pressure = 0). Severe hypocapnia (< 20 mmHg) may result in cerebral production of lactate; however no studies have shown that a Paco2 in the range of 23-28 mmHg has deleterious effects. Recent studies in head-injured patients suggest that routine long-term hyperventilation, without an objective index of cerebral flow/metabolism coupling, may place the brain at risk for adverse outcome. The few data available for intraoperative management suggest that Paco2 figures of 30-35 mmHg result in acceptable operating conditions. Unless otherwise specifically indicated by surgical conditions or cerebral flow/metabolism coupling (e.g. jugular O2 saturation), routine application of profound (Paco2 < 28-30 mmHg) hyperventilation should probably be avoided and its use needs reevaluation.

In physiological conditions, the regulation of acid-base balance in brain maintains a noteworthy stability of cerebral pH. During systemic metabolic acid-base imbalances cerebral pH is well controlled as the blood/brain barrier is slowly and poorly permeable to electrolytes (HCO3- and H+). Cerebral pH is regulated by a modulation of the respiratory drive, triggered by the early alterations of interstitial fluid pH, close to medullary chemoreceptors. As blood/brain barrier is highly permeable to Co2, CSF pH is corrected in a few hours, even in case of severe metabolic acidosis and alkalosis. Conversely, during ventilatory acidosis and alkalosis the cerebral pH varies in the same direction and in the same range than blood pH. Therefore, the brain is better protected against metabolic than ventilatory acid-base imbalances. Ventilatory acidosis and alkalosis are able to impair cerebral blood flow and brain activity through interstitial pH alterations. During respiratory acidosis, [HCO3-] increases in extracellular fluids to control cerebral pH by two main ways: a carbonic anhydrase activation at the blood/brain and blood/CSF barriers level and an increase in chloride shift in glial cells (HCO3- exchanged for Cl-). During respiratory alkalosis, [HCO3-] decreases in extracellular fluids by the opposite changes in HCO3- transport and by an increase in lactic acid synthesis by cerebral cells. The treatment of metabolic acidosis with bicarbonates may induce a cerebral acidosis and worsen a cerebral oedema during ketoacidosis. Moderate hypocapnia carried out to treat intracranial hypertension is mainly effective when cerebral blood flow is high and vascular CO2 reactivity maintained. Hypocapnia may restore an altered cerebral blood flow autoregulation. Instrumental hypocapnia requires a control of cerebral perfusion pressure and cerebral arteriovenous difference for oxygen, to select patients for whom this kind of treatment may be of benefit, to choose the optimal level of hypocapnia and to avoid any deleterious effect. If hypocapnia is maintained over several days, an adaptation of CSF pH may limit the therapeutic effect on the cerebral blood flow and the intracranial pressure.

The effects of chronic respiratory alkalosis on divalent ion homeostasis have not been reported in any species. We studied four normal male subjects during a four-day control period (residence at 500 m), during six days of chronic respiratory alkalosis induced by hypobaric hypoxia (residence at 3450 m), followed by a six-day eucapnic recovery period (500 m) under metabolic balance conditions. Chronic respiratory alkalosis (delta PaCO2, -8.4 mm Hg, delta[H+] -3.2 nmol/liter) resulted in a sustained decrement in plasma ionized calcium concentration (delta[IoCa++]p, -0.10 mmol/liter, P less than 0.05) and a sustained increment in plasma phosphate concentration (delta[PO4]p, +0.14 mmol/liter, P less than 0.005) associated with increased fractional excretion of Ca++ (+0.5%, P less than 0.005), decreased phosphate clearance (-6.1 ml/min, P less than 0.025) and decreased excretion of nephrogenous cAMP (-1.5 nmol/100 ml GFR, P less than 0.0025). Urinary phosphate excretion decreased by 15.4 mmol/24 hr on day 1 of chronic respiratory alkalosis (P less than 0.0025), but returned to control values by day 6 despite hyperphosphatemia. Serum intact [PTH] did not change. Sustained hypomagnesuria (-0.8 mmol/24 hr, P less than 0.05) occurred during chronic respiratory alkalosis and was accounted for, at least in part, by decreased fractional excretion of Mg++ (-0.7%, P less than 0.05) in the absence of change in plasma magnesium concentration. Serum 1,25(OH)2D levels were unchanged by chronic respiratory alkalosis. In conclusion, the decrease in nephrogenous cAMP generation despite unchanged serum intact PTH concentration suggests that chronic respiratory alkalosis results in impaired renal responsiveness to PTH as manifested by alterations in PTH-dependent renal calcium and phosphate transport.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the role of cerebral hypoxia as a causative factor in the alteration of the qEEG during hyperventilation, qEEG changes caused by progressive hypocapnia were compared with qEEG changes due to progressive normobaric hypoxia in two parallel groups of 12 and 10 healthy male subjects (age 20-27 years), respectively. In the first group, qEEG records were obtained before and during hyperventilation to pCO2 levels of 4.0, 3.0 and 2.0 kPa. In the second group, the qEEG samples were taken before and during hypoxia with hemoglobin oxygen saturations of 80, 70 and 60%. In both groups, blood flow velocity in the middle cerebral artery was also recorded. Hyperventilation caused an exponential increase in slow activity and a decrease in alpha power. No shift in the alpha mean frequency and alpha peak frequency was observed, except with the pCO2 level of 4.0 kPa, which caused an increase in both variables. Hypoxia with a hemoglobin oxygen saturation of 60% caused a much less pronounced increase in slow activity. No change in total power in the alpha band was found, but both the alpha peak frequency and alpha mean frequency decreased. Lesser degrees of hypoxia caused only minimal EEG changes. Blood flow velocity was decreased by hyperventilation but increased by hypoxia. It is concluded that the EEG changes observed during hyperventilation must mainly or totally be attributed to factors other than cerebral hypoxia.