Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Prospective Randomized Pilot Trial on the Effects of Mild Hypercapnia on Cerebral Oxygen Saturation in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting.

OBJECTIVE AND DESIGN: A single-center prospective randomized controlled study was conducted to assess the effect of targeted mild hypercapnia (TMH) on cerebral oxygen saturation (rSO2) in patients undergoing off-pump coronary artery bypass grafting (CABG). SETTING AND PARTICIPANTS: A prospective randomized controlled study involving 100 patients undergoing off-pump CABG at U. N. Mehta Hospital, Ahmedabad, Gujarat, India. INTERVENTION: Patients were randomized to either the TMH (PaCO2 45-55 mmHg) or the targeted normocapnia (TN; PaCO2 35-45 mmHg) group, containing 50 patients in each group. MEASUREMENTS: Monitoring of rSO2, heart rate, mean arterial pressure (MAP), PaCO2, and peripheral oxygen saturation was done at baseline, after induction, after left internal mammary artery harvesting, at each grafting (distal and proximal), after protamine, and after shifting to the intensive care unit. The standardized minimental-state examination (SMMSE) was performed preoperatively and at 8, 12, and 24 hours postextubation. Data were analyzed using an independent sample t test. RESULTS: The TMH group had higher MAP during grafting (p < 0.001) and higher rSO2 on both sides during distal and proximal grafting (p < 0.001) and after protamine (p < 0.05), as compared to the TN group. Compared to preoperative values, SMMSE scores in the TN group were significantly lower at 12 and 24 hours postextubation (p < 0.001). CONCLUSION: TMH during grafting increased the cerebral blood flow and rSO2 when hemodynamic instability was very common. It has a protective role on the brain and helps maintain cognition postoperatively.

Carotid body chemosensitivity is not attenuated during cold water diving.

Tonic carotid body (CB) activity is reduced during exposure to cold and hyperoxia. We tested the hypotheses that cold water diving lowers CB chemosensitivity and augments CO2 retention more than thermoneutral diving. Thirteen subjects [age: 26 ± 4 yr; body mass index (BMI): 26 ± 2 kg/m2) completed two 4-h head-out water immersion protocols in a hyperbaric chamber (1.6 ATA) in cold (15°C) and thermoneutral (25°C) water. CB chemosensitivity was assessed with brief hypercapnic ventilatory response ([Formula: see text]) and hypoxic ventilatory response ([Formula: see text]) tests before dive, 80 and 160 min into the dive (D80 and D160, respectively), and immediately after and 60 min after dive. Data are reported as an absolute mean (SD) change from predive. End-tidal CO2 pressure increased during both the thermoneutral water dive [D160: +2 (3) mmHg; P = 0.02] and the cold water dive [D160: +1 (2) mmHg; P = 0.03]. Ventilation increased during the cold water dive [D80: 4.13 (4.38) and D160: 7.75 (5.23) L·min-1; both P < 0.01] and was greater than the thermoneutral water dive at both time points (both P < 0.01). [Formula: see text] was unchanged during the dive (P = 0.24) and was not different between conditions (P = 0.23). [Formula: see text] decreased during the thermoneutral water dive [D80: -3.45 (3.61) and D160: -2.76 (4.04) L·min·mmHg-1; P < 0.01 and P = 0.03, respectively] but not the cold water dive. However, [Formula: see text] was not different between conditions (P = 0.17). In conclusion, CB chemosensitivity was not attenuated during the cold stress diving condition and does not appear to contribute to changes in ventilation or CO2 retention.

Adrenergically induced translocation of red blood cell ß-adrenergic sodium-proton exchangers has ecological relevance for hypoxic and hypercapnic white seabass.

White seabass (Atractoscion nobilis) increasingly experience periods of low oxygen (O2; hypoxia) and high carbon dioxide (CO2, hypercapnia) due to climate change and eutrophication of the coastal waters of California. Hemoglobin (Hb) is the principal O2 carrier in the blood and in many teleost fishes Hb-O2 binding is compromised at low pH; however, the red blood cells (RBC) of some species regulate intracellular pH with adrenergically stimulated sodium-proton-exchangers (ß-NHEs). We hypothesized that RBC ß-NHEs in white seabass are an important mechanism that can protect the blood O2-carrying capacity during hypoxia and hypercapnia. We determined the O2-binding characteristics of white seabass blood, the cellular and subcellular response of RBCs to adrenergic stimulation, and quantified the protective effect of ß-NHE activity on Hb-O2 saturation. White seabass had typical teleost Hb characteristics, with a moderate O2 affinity (Po2 at half-saturation; P50 2.9 kPa) that was highly pH-sensitive (Bohr coefficient -0.92; Root effect 52%). Novel findings from super-resolution microscopy revealed ß-NHE protein in vesicle-like structures and its translocation into the membrane after adrenergic stimulation. Microscopy data were corroborated by molecular and phylogenetic results and a functional characterization of ß-NHE activity. The activation of RBC ß-NHEs increased Hb-O2 saturation by ∼8% in normoxic hypercapnia and by up to ∼20% in hypoxic normocapnia. Our results provide novel insight into the cellular mechanism of adrenergic RBC stimulation within an ecologically relevant context. ß-NHE activity in white seabass has great potential to protect arterial O2 transport during hypoxia and hypercapnia but is less effective during combinations of these stressors.

Effect of Permissive Mild Hypercapnia on Cerebral Vasoreactivity in Infants: A Randomized Controlled Crossover Trial.

BACKGROUND: Mechanical ventilation interferes with cerebral perfusion via changes in intrathoracic pressure and/or as a consequence of alterations in CO2. Cerebral vascular vasoreactivity is dependent on CO2, and hypocapnia can potentially lead to vasoconstriction and subsequent decrease in cerebral blood flow. Thus, we aimed at characterizing whether protective ventilation with mild permissive hypercapnia improves cerebral perfusion in infants. METHODS: Following ethical approval and parental consent, 19 infants were included in this crossover study and randomly assigned to 2 groups for which the initial ventilation parameters were set to achieve an end-tidal carbon dioxide (Etco2) of 6.5 kPa (group H: mild hypercapnia, n = 8) or 5.5 kPa (group N: normocapnia, n = 11). The threshold was then reversed before going back to the initial set value of normo- or hypercapnia. At each step, hemodynamic, respiratory, and near-infrared spectroscopy (NIRS)-derived parameters, including tissue oxygenation index (TOI) and tissue hemoglobin index (THI), concentration of deoxygenated hemoglobin (HHb) and oxygenated hemoglobin (O2Hb), were collected. Concomitantly, sevoflurane maintenance concentration, ventilatory (driving pressure) and hemodynamic parameters, as mean arterial pressure (MAP), were recorded. RESULTS: Targeting an Etco2 of 5.5 kPa resulted in significantly higher mean driving pressure than an Etco2 of 6.5 kPa (P < .01) with no difference between the groups in end-tidal sevoflurane, MAP, and heart rate. A large scatter was observed in NIRS-derived parameters, with no evidence for difference in Etco2 changes between or within groups. A mild decrease with time was observed in THI and MAP in infants randomly assigned to group N (P < .036 and P < .017, respectively). When pooling all groups together, a significant correlation was found between the changes in MAP and TOI (r = 0.481, P < .001). CONCLUSIONS: Allowing permissive mild hypercapnia during mechanical ventilation of infants led to lower driving pressure and comparable hemodynamic, respiratory, and cerebral oxygenation parameters than during normocapnia. Whereas a large scatter in NIRS-derived parameters was observed at all levels of Etco2, the correlation between TOI and MAP suggests that arterial pressure is an important component of cerebral oxygenation at mild hypercapnia.

Very low blood flow carbon dioxide removal system is not effective in a chronic obstructive pulmonary disease exacerbation setting.

Extracorporeal carbon dioxide removal (ECCO2 R) is a low blood flow veno-venous extracorporeal membrane oxygenation technique that provides artificial blood CO2 removal. Recently, a new ECCO2 R system (PrismaLung), providing very low blood flow has been commercialized. The aim of this study is to report its use in severe chronic obstructive pulmonary disease (COPD) patients needing an ECCO2 R therapy. Six severe COPD patients with acute exacerbation leading to refractory hypercapnic respiratory acidosis were treated with ECCO2 R therapy. Two different systems were used: a PrismaLung system and a conventional ECCO2 R device. The maximum blood flow provided by PrismaLung was significantly lower than that with the conventional ECCO2 R system. In three patients initially treated with PrismaLung, there were no improvements in pH, PaCO2 , or RR. Thus, the therapy was switched to a conventional ECCO2 R system in these three patients, and three others were treated from the outset by the conventional ECCO2 R system, providing significant improvement in pH, PaCO2 , and RR. The present retrospective study describes the first use of PrismaLung in severe COPD patients with acute exacerbation. When compared with a higher blood flow ECCO2 R system, our results show that this novel, very low-flow device is not able to remove sufficient CO2 , normalize pH or decrease respiratory rate.

Coagulation dysfunction in patients with AECOPD and its relation to infection and hypercapnia.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have coagulation abnormalities. However, the factors that lead to coagulation dysfunction in acute exacerbation of COPD (AECOPD) remain insufficiently explored. This study aimed to investigate the factors affecting coagulation status in patients with COPD and their influence on thrombosis. METHODS: Data of COPD patients, including 135 cases in acute exacerbation stage and 44 cases in stable stage from Nov 2016 to Nov 2019 in our hospital, were collected. Healthy people (n = 135) were enrolled as the controls. The coagulation parameters, blood gas indexes and blood routine examination results were collected and analyzed. RESULTS: White blood count (WBC), neutrophil count, neutrophil percentage (N%), platelet (PLT), prothrombin time (PT), international normalized ratio (INR), fibrinogen (FIB), and activated partial thromboplastin time (APTT) increased, plasma thrombin time (TT) decreased in AECOPD group compared with the control group. In AECOPD group, PT, APTT, and FIB were positively correlated with neutrophils and C-reaction protein levels. PT was positively correlated with PCO2 and negatively with pH. Thrombosis was observed in five acute exacerbation and three stable stage COPD patients. CONCLUSIONS: Patients with AECOPD presented abnormal coagulation status, which was correlated to infection and hypercapnia and might be potentially the risk factor of thrombosis.

Impacts of prolonged sitting with mild hypercapnia on vascular and autonomic function in healthy recreationally active adults.

Prolonged sitting, which is known to impair peripheral vascular function, often occurs in spaces (e.g., offices) with mild hypercapnic atmospheres. However, the effects of prolonged sitting in hypercapnic conditions on vascular function are unknown. Therefore, the purpose of this study was to investigate the effects of prolonged sitting in mild hypercapnic conditions on vascular and autonomic function in humans. Twelve healthy young adults participated in two experimental visits that consisted of sitting for 2.5 h in a control condition [normal atmospheric conditions sitting (PSIT)] or a mild hypercapnic condition (HCAP; CO2 = 1,500 ppm). During each visit, heart rate variability (HRV), blood pressure (BP), pulse wave velocity (PWV), augmentation index (AIx), brachial and popliteal artery flow-mediated dilation (FMD), and near-infrared spectroscopy (NIRS) were assessed before and after prolonged sitting. Sitting significantly decreased AIx in both groups (P < 0.05). Brachial and popliteal FMD were reduced with sitting (P < 0.05), and the reduction in popliteal FMD was amplified by HCAP (P < 0.05). Baseline microvascular oxygenation was decreased following sitting in both groups (P < 0.05). However, microvascular reoxygenation upon cuff release was slower only in HCAP (P < 0.05). HRV, HR, BP, and PWV did not significantly change with sitting in either group (P > 0.05). We conclude that prolonged sitting attenuated both brachial and popliteal endothelial function and was associated with perturbed microcirculation. Additionally, mild hypercapnic conditions further impaired peripheral endothelial and microvascular function. Together, these findings suggest that prolonged sitting is accompanied by a host of deleterious effects on the vasculature, which are exacerbated by mild hypercapnia.NEW & NOTEWORTHY The results of this study reveal that prolonged sitting attenuates endothelial function and microvascular function. Additionally, prolonged sitting with mild hypercapnia, which is similar to everyday environments, further exacerbates peripheral endothelial function and microvascular function.

Sex differences in integrated neurocardiovascular control of blood pressure following acute intermittent hypercapnic hypoxia.

Repetitive hypoxic apneas, similar to those observed in sleep apnea, result in resetting of the sympathetic baroreflex to higher blood pressures (BP). This baroreflex resetting is associated with hypertension in preclinical models of sleep apnea (intermittent hypoxia, IH); however, the majority of understanding comes from males. There are data to suggest that female rats exposed to IH do not develop high BP. Clinical data further support sex differences in the development of hypertension in sleep apnea, but mechanistic data are lacking. Here we examined sex-related differences in the effect of IH on sympathetic control of BP in humans. We hypothesized that after acute IH we would observe a rise in muscle sympathetic nerve activity (MSNA) and arterial BP in young men (n = 30) that would be absent in young women (n = 19). BP and MSNA were measured during normoxic rest before and after 30 min of IH. Baroreflex sensitivity (modified Oxford) was evaluated before and after IH. A rise in mean BP following IH was observed in men (+2.0 ± 0.7 mmHg, P = 0.03), whereas no change was observed in women (-2.7 ± 1.2 mmHg, P = 0.11). The elevation in MSNA following IH was not different between groups (4.7 ± 1.1 vs. 3.8 ± 1.2 bursts/min, P = 0.65). Sympathetic baroreflex sensitivity did not change after IH in either group (P > 0.05). Our results support sex-related differences in the effect of IH on neurovascular control of BP and show that any BP-raising effects of IH are absent in young women. These data enhance our understanding of sex-specific mechanisms that may contribute to BP changes in sleep apnea.

Evaluation of time courses of agreement between minutely obtained transcutaneous blood gas data and the gold standard arterial data from spontaneously breathing Asian adults, and various subgroup analyses.

BACKGROUND: Usual clinical practice for arterial blood gas analysis (BGA) in conscious patients involves a one-time arterial puncture to be performed after a resting period of 20-30 min. The aim of this study was to evaluate the use of transcutaneous BGA for estimating this gold standard arterial BGA. METHODS: Spontaneously breathing Asian adults (healthy volunteers and respiratory patients) were enrolled (n = 295). Transcutaneous PO2 (PtcO2) and PCO2 (PtcCO2) were monitored using a transcutaneous monitor (TCM4, Radiometer Medical AsP, Denmark) with sensors placed on the chest, forearm, earlobe or forehead. Transcutaneous BGA at 1-min intervals was compared with arterial BGA at 30 min. Reasonable steps to find severe hypercapnia with PaCO2 > 50 mmHg were evaluated. RESULTS: Sensors on the chest and forearm were equally preferred and used because of small biases (n = 272). The average PCO2 bias was close to 0 mmHg at 4 min, and was almost constant (4-5 mmHg) with PtcCO2 being higher than PaCO2 at ≥8 min. The limit of agreement for PCO2 narrowed over time: ± 13.6 mmHg at 4 min, ± 7.5 mmHg at 12-13 min, and ± 6.3 mmHg at 30 min. The limit of agreement for PO2 also narrowed over time (± 23.1 mmHg at 30 min). Subgroup analyses showed that the PaCO2 and PaO2 levels, gender, and younger age significantly affected the biases. All hypercapnia subjects with PaCO2 > 50 mmHg (n = 13) showed PtcCO2 ≥ 50 mmHg for until 12 min. CONCLUSIONS: Although PtcCO2 is useful, it cannot completely replace PaCO2 because PCO2 occasionally showed large bias. On the other hand, the prediction of PaO2 using PtcO2 was unrealistic in Asian adults. PtcCO2 ≥ 50 mmHg for until 12 min can be used as a screening tool for severe hypercapnia with PaCO2 > 50 mmHg.

High flow nasal cannula in acute hypercapnic exacerbation of chronic obstructive pulmonary disease: an emerging utility.

High flow nasal cannula (HFNC) provides warmed and humidified air with flow rates up to 60 liters/min with relatively fixed oxygen content (FiO2). It has been extensively evaluated for hypoxemic respiratory failure and has been used in mild acute respiratory distress syndrome, pre-intubation, bronchoscopy and pediatric obstructive sleep apnea. Recent data has suggested a role in stable hypercapnic chronic obstructive pulmonary disease (COPD) and even in acute exacerbations, though, the use has not been advocated by any guidelines yet. We present a case of acute hypercapnic exacerbation of COPD, intolerant to non-invasive ventilation, showing response and improvement on use of HFNC. This case highlights this potential mechanisms and prospects for the same.

Exogenous vasopressin dose-dependently modulates gastric microcirculatory oxygenation in dogs via V1A receptor.

BACKGROUND: Hypercapnia improves gastric microcirculatory oxygenation (µHbO2) and increases vasopressin plasma levels, whereas V1A receptor blockade abolishes the increase of µHbO2. The aim of this study was to evaluate the effect of exogenous vasopressin (AVP) in increasing doses on microcirculatory perfusion and oxygenation and systemic hemodynamic variables. Furthermore, we evaluated the role of the vasopressin V1A receptor in mediating the effects. METHODS: In repetitive experiments, six anesthetized dogs received a selective vasopressin V1A receptor inhibitor ([Pmp1, Tyr (Me)2]-Arg8-Vasopressin) or sodium chloride (control groups). Thereafter, a continuous infusion of AVP was started with dose escalation every 30 min (0.001 ng/kg/min-1 ng/kg/min). Microcirculatory variables of the oral and gastric mucosa were measured with reflectance spectrometry, laser Doppler flowmetry, and incident dark field imaging. Transpulmonary thermodilution was used to measure systemic hemodynamic variables. AVP plasma concentrations were measured during baseline conditions and 30 min after each dose escalation. RESULTS: During control conditions, gastric µHbO2 did not change during the course of experiments. Infusion of 0.001 ng/kg/min and 0.01 ng/kg/min AVP increased gastric µHbO2 to 87 ± 4% and 87 ± 6%, respectively, compared to baseline values (80 ± 7%), whereas application of 1 ng/kg/min AVP strongly reduced gastric µHbO2 (59 ± 16%). V1A receptor blockade prior to AVP treatment abolished these effects on µHbO2. AVP dose-dependently enhanced systemic vascular resistance (SVR) and decreased cardiac output (CO). After prior V1A receptor blockade, SVR was reduced and CO increased (0.1 ng/kg/min + 1 ng/kg/min AVP). CONCLUSIONS: Exogenous AVP dose-dependently modulates gastric µHbO2, with an increased µHbO2 with ultra-low dose AVP. The effects of AVP on µHbO2 are abolished by V1A receptor inhibition. These effects are independent of a modulation of systemic hemodynamic variables.

Role of venous blood gases in hypercapnic respiratory failure chronic obstructive pulmonary disease patients presenting to the emergency department.

BACKGROUND: Many patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have type 2 respiratory failure (T2RF). Often arterial blood gases are not performed and correlation with venous blood gases (VBG) is controversial. The venous pH and bicarbonate (HCO3 ) are useful, but VBG pCO2 (PvCO2 ) is considered too unpredictable. AIM: To examine the utility of VBG in this cohort of patients. METHODS: A prospective study of AECOPD patients with T2RF presenting to the emergency department was performed. Patients being considered for non-invasive ventilation and who required an arterial blood gas were invited to participate. A subsequent VBG was also taken, and Bland-Altman plots were used for analysis. RESULTS: Sixty-three patients were included in this study. The limits of agreement for pH and HCO3 were narrow. Wider limits of agreement with a systematic bias of 7.7 mmHg were noted with pCO2 . CONCLUSIONS: The utility of VBG pH and HCO3 was again demonstrated. VBG pCO2 in this cohort of patients may have a role in the assessment of patients with AECOPD. Further study is needed on the possible role of VBG in the management of such patients with T2RF particularly those using non-invasive ventilation.

Hyperacute Hemodynamic Effects of BiPAP Noninvasive Ventilation in Patients With Acute Heart Failure and Left Ventricular Systolic Dysfunction in Emergency Department.

BACKGROUND: Acute heart failure (AHF) is one of the leading causes of admission to emergency department (ED); severe hypoxemic AHF may be treated with noninvasive ventilation (NIV). Despite the demonstrated clinical efficacy of NIV in relieving symptoms of AHF, less is known about the hyperacute effects of bilevel positive airway pressure (BiPAP) ventilation on hemodynamics of patients admitted to ED for AHF. We therefore aimed to assess the effect of BiPAP ventilation on principal hemodynamic, respiratory, pulse oximetry, and microcirculation indexes in patients admitted to ED for AHF, needing NIV. METHODS: Twenty consecutive patients admitted to ED for AHF and left ventricular systolic dysfunction, needing NIV, were enrolled in the study; all patients were treated with NIV in BiPAP mode. The following parameters were measured at admission to ED (T0, baseline before treatment), 3 hours after admission and initiation of BiPAP NIV (T1), and after 6 hours (T2): arterial blood oxygenation (pH, partial pressure of oxygen in the alveoli/fraction of inspired oxygen ratio, Paco2, lactate concentration, HCO3-), hemodynamics (tricuspid annular plane systolic excursion, transpulmonary gradient, transaortic gradient, inferior vena cava diameter, brain natriuretic peptide [BNP] levels), microcirculation perfusion (end-tidal CO2 [etco2], peripheral venous oxygen saturation [SpvO2]). RESULTS: All evaluated indexes significantly improved over time (analysis of variance, P < .001 in quite all cases.). CONCLUSIONS: The BiPAP NIV may rapidly ameliorate several hemodynamic, arterial blood gas, and microcirculation indexes in patients with AHF and left ventricular systolic dysfunction.

Efficient CO2 removal using extracorporeal lung and renal assist device.

We developed a novel system comprising acid infusion, membrane lung, and a continuous renal replacement therapy console for efficient CO2 removal at a low blood flow. To evaluate the new system, we used an ex vivo experimental model using swine blood. A liter of aliquoted blood adjusted to pH 7.25 and pCO2 65 mm Hg was mixed with acid (0, 10, or 20 mL of lactic or hydrochloric acid [1 mol/L]) and was immediately delivered to the system in a single pass. We collected blood samples at each point of the circuit and calculated the amount of CO2 eliminated by the membrane lung. The new system removed 13.2 ± 0.8, 32.0 ± 2.1, and 51.6 ± 3.7 mL/min of CO2 (with 0, 10, and 20 mEq/L of lactic acid) and 21.2 ± 1.2, 27.3 ± 0.3, and 42.0 ± 1.3 mL/min (with 0, 10, and 20 mEq/L of hydrochloric acid), respectively. The levels of lactate and Cl- ions for acid-base equilibrium were restored after continuous hemodiafiltration. Thus, the amount of CO2 eliminated by the membrane lung was 3.9 times higher with lactic acid and 2.0 times higher with hydrochloric acid compared with non-acid controls. In conclusion, this easy-to-setup CO2 removal system was safe, effective, and removed CO2 at a low blood flow.

Evaluation of Cerebrovascular Reactivity in Subjects with and without Obstructive Sleep Apnea.

BACKGROUND: Both obstructive sleep apnea (OSA) and altered cerebrovascular reactivity (CVR) are associated with increased stroke risk. Nevertheless, the incidence of abnormal CVR in patients with OSA is uncertain due to the high variability in the way CVR is measured both within and between studies. We hypothesized that a standardized CVR with a consistent vasoactive stimulus and cerebral blood flow (CBF) measure would be reduced in patients with severe OSA compared with healthy controls. METHODS: This was a prospective study in which subjects with and without OSA were administered a standardized hypercapnic stimulus, and CBF was monitored by blood oxygen level-dependent magnetic resonance signal changes, a high space and time resolved surrogate for CBF. RESULTS: Twenty-four subjects with OSA (mean age 45.9 years, apnea-hypopnea index [AHI] 26.8 per hour) and 6 control subjects (mean age 42.8 years, AHI 2.4 per hour) were included. Compared with controls, subjects with OSA had a significantly greater whole brain (.1565 versus .1094, P = .013), gray matter (.2077 versus .1423, P = .009), and white matter (.1109 versus .0768, P = .024) CVR, respectively. CONCLUSIONS: Contrary to expectations, subjects with OSA had greater CVR compared with control subjects.

Measurement of Cerebrovascular Reactivity as Blood Oxygen Level-Dependent Magnetic Resonance Imaging Signal Response to a Hypercapnic Stimulus in Mechanically Ventilated Patients.

BACKGROUND: Impaired cerebrovascular reactivity (CVR) is an important prognostic marker of stroke. Most measures of CVR lack (1) a reproducible vasoactive stimulus and (2) a high time and spatial resolution measure of cerebral blood flow (CBF), particularly for mechanically ventilated patients. The aim of our study was to investigate the feasibility of measuring CVR using sequential gas delivery circuit and gas blender for precise targeting of end-tidal PCO2 (PetCO2), and blood oxygen level-dependent magnetic resonance imaging (BOLD-MRI) signal as a surrogate of CBF, in mechanically ventilated patients. METHODS: Four patients with known moyamoya disease requiring preoperative CVR measurements under general anesthesia were studied. All patients had standard anesthesia induction and maintenance with intravenous propofol and rocuronium. Patients were intubated and manually ventilated with a self-inflating bag connected to a sequential breathing circuit. A computer-controlled gas blender supplied the gas mixture in proportions to attain target PetCO2. BOLD-MRI was performed at 3.0 Tesla magnet. Changes in signal per change in PetCO2 were calculated, and their magnitude color-coded and mapped onto the anatomic scan to form CVR maps. RESULTS: CVR studies were successfully performed on all patients, and the CVR values were lower in both gray and white matter bilaterally when compared with healthy volunteers. In addition, CVR maps in 3 patients showed intracerebral steal phenomenon in spite of having had cerebral revascularization procedures, indicating that they are still at risk of cerebral ischemia. CONCLUSIONS: BOLD-MRI CVR studies are feasible in mechanically ventilated patients anesthetized with propofol.

Effect of prolonged inspiratory time on gas exchange during robot-assisted laparoscopic urologic surgery.

BACKGROUND: Gas exchange disturbance may develop during urologic robotic laparoscopic surgery with the patient in a steep Trendelenburg position. This study investigated whether prolonged inspiratory time could mitigate gas exchange disturbances including hypercapnia. METHODS: In this randomized cross-over trial, 32 patients scheduled for robot-assisted urologic surgery were randomized to receive an inspiratory to expiratory time ratio (I:E) of 1:1 for the first hour of pneumoperitoneum followed by 1:2 for last period of surgery (group A, n = 17) or I:E of 1:2 followed by 1:1 (group B, n = 15). Arterial blood gas analysis, airway pressure and hemodynamic variables were assessed at four time points (T1: 10 min after induction of general anesthesia, T2: 1 h after the initiation of pneumoperitoneum, T3: 1 h after T2 and T4: at skin closure). The carry over effect of initial I:E was also evaluated over the next hour through arterial blood gas analysis. RESULTS: There was a significant decrease in partial pressure of oxygen in arterial blood (PaO2) for both groups at T2 and T3 compared to T1 but in group B the PaO2 at T4 was not decreased from the baseline. Partial pressure of carbon dioxide in arterial blood (PaCO2) increased with I:E of 1:2 but did not significantly increase with I:E of 1:1; however, there were no differences in PaO2 and PaCO2 between the groups. CONCLUSION: Decreased oxygenation by pneumoperitoneum was improved and PaCO2 did not increase after 1 h of I:E of 1:1; however, the effect of equal ratio ventilation longer than 1 h remains to be determined. There was no carryover effect of the two different I:E ratios.

Arterial CO2 Fluctuations Modulate Neuronal Rhythmicity: Implications for MEG and fMRI Studies of Resting-State Networks.

UNLABELLED: A fast emerging technique for studying human resting state networks (RSNs) is based on spontaneous temporal fluctuations in neuronal oscillatory power, as measured by magnetoencephalography. However, it has been demonstrated recently that this power is sensitive to modulations in arterial CO2 concentration. Arterial CO2 can be modulated by natural fluctuations in breathing pattern, as might typically occur during the acquisition of an RSN experiment. Here, we demonstrate for the first time the fine-scale dependence of neuronal oscillatory power on arterial CO2 concentration, showing that reductions in alpha, beta, and gamma power are observed with even very mild levels of hypercapnia (increased arterial CO2). We use a graded hypercapnia paradigm and participant feedback to rule out a sensory cause, suggesting a predominantly physiological origin. Furthermore, we demonstrate that natural fluctuations in arterial CO2, without administration of inspired CO2, are of a sufficient level to influence neuronal oscillatory power significantly in the delta-, alpha-, beta-, and gamma-frequency bands. A more thorough understanding of the relationship between physiological factors and cortical rhythmicity is required. In light of these findings, existing results, paradigms, and analysis techniques for the study of resting-state brain data should be revisited. SIGNIFICANCE STATEMENT: In this study, we show for the first time that neuronal oscillatory power is intimately linked to arterial CO2 concentration down to the fine-scale modulations that occur during spontaneous breathing. We extend these results to demonstrate a correlation between neuronal oscillatory power and spontaneous arterial CO2 fluctuations in awake humans at rest. This work identifies a need for studies investigating resting-state networks in the human brain to measure and account for the impact of spontaneous changes in arterial CO2 on the neuronal signals of interest. Changes in breathing pattern that are time locked to task performance could also lead to confounding effects on neuronal oscillatory power when considering the electrophysiological response to functional stimulation.

Nitric oxide-sensitive guanylyl cyclase signaling affects CO2-dependent but not pressure-dependent regulation of cerebral blood flow.

Cerebrovascular CO2 reactivity is affected by nitric oxide (NO). We tested the hypothesis that sildenafil selectively potentiates NO-cGMP signaling, which affects CO2 reactivity. Fourteen healthy males (34 ± 2 yr) were enrolled in the study. Blood pressure (BP), ECG, velocity of cerebral blood flow (CBF; measured by transcranial Doppler), and end-tidal CO2 (EtCO2) were assessed at baseline (CO2 ~39 mmHg), during hyperventilation (CO2 ~24 mmHg), during hypercapnia (CO2 ~46 mmHg), during boluses of phenylephrine (25-200 µg), and during graded head-up tilting (HUT). Measurements were repeated 1 h after 100 mg sildenafil were taken. Results showed that sildenafil did not affect resting BP, heart rate, CBF peak and mean velocities, estimated regional cerebrovascular resistance (eCVR; mean BP/mean CBF), breath/min, and EtCO2: 117 ± 2/67 ± 3 mmHg, 69 ± 3 beats/min, 84 ± 5 and 57 ± 4 cm/s, 1.56 ± 0.1 mmHg·cm-1·s-1, 14 ± 0.5 breaths/min, and 39 ± 0.9 mmHg, respectively. Sildenafil increased and decreased the hypercapnia induced in CBF and eCVR, respectively. Sildenafil also attenuated the decrease in peak velocity of CBF, 25 ± 2 vs. 20 ± 2% (P < 0.05) and increased the eCVR, 2.5 ± 0.2 vs. 2 ± 0.2% (P < 0.03) during hyperventilation. Sildenafil did not affect CBF despite significant increases in the eCVRs that were elicited by phenylephrine and HUT. This investigation suggests that sildenafil, which potentiates the NO-cGMP signaling, seems to affect the cerebrovascular CO2 reactivity without affecting the static and dynamic pressure-dependent mechanisms of cerebrovascular autoregulation.