Changes In Minute Ventilation Research Articles

Effects of Voluntary Changes in Minute Ventilation on Microvascular Skin Blood Flow

Effects of Voluntary Changes in Minute Ventilation on Microvascular Skin Blood Flow

Hyperoxic ventilatory response in infants is related to nocturnal hypoxaemia

BackgroundThe carotid bodies primarily serve as oxaemia sensors that affect tidal breathing. Their function has not yet been studied in infants with nocturnal hypoxaemia. This cross-sectional study aimed to characterise the hyperoxic ventilatory response (HVR) in infants and its relationship to nocturnal hypoxaemia.MethodsThe HVR was analysed in term infants aged <24 months with childhood interstitial lung disease (chILD), those with severe recurrent wheezing (wheeze), and nonrespiratory controls. The HVR timing was characterised using hyperoxia response time (HRT1), and HVR magnitude was characterised by the relative change in minute volume between normoxia and 30-s hyperoxia (VE_dH30). Time spent with an arterial haemoglobin oxygen saturation (SpO2) <90% during overnight monitoring (t90) was estimated.ResultsHVR data were available for 23 infants with chILD, 24 wheeze and 14 control infants. A significant decrease in minute volume under 30 s of hyperoxia was observed in all patients. HRT1 was shorter in chILD (5.6±1.2 s) and wheeze (5.9±1.5 s) groups than in the controls (12.6±5.5 s) (ANOVA p<0.001).VE_dH30 was increased in the chILD group (24.3±8.0%) compared with that in the controls (14.7±9.2%) (p=0.003).t90was abnormal in the wheeze (8.0±5.0%) and chILD (32.7±25.8%) groups and higher in the chILD group than in the controls (p<0.001). HRT1 negatively correlated witht90in all groups.ConclusionSignificant differences in HVR timing and magnitude were noted in the chILD, wheeze and control groups. A relationship between nocturnal hypoxaemia and HRT1 was proposed. HVR characterisation may help identify patients with abnormal nocturnalSpO2.

Characterisation of the acute hypoxic response using breathing variability parameters: A pilot study in humans

PurposeWe aimed to investigate respiratory rate variability (RRV) and tidal volume (Vt) variability during exposure to normobaric hypoxia (i.e., reduction in the fraction of inspired oxygen - FiO2), and the association of the changes in RRV and Vt variability with the changes in pulse oxygen saturation (SpO2). MethodsThirty healthy human participants (15 females) were exposed to: (1) 15-min normoxia, (2) 10-min hypoxia simulating 2200 m, (3) 10-min hypoxia simulating 4000 m, (4) 10-min hypoxia simulating 5000 m, (5) 15-min recovery in normoxia. Linear regression modelling was applied with SpO2 (dependent variable) and the changes in RRV and Vt variability (independent variables), controlling for FiO2, age, sex, changes in heart rate (HR), changes in HR variability (HRV), and changes in minute ventilation (VE). ResultsWhen modelling breathing parameter variability as root-mean-square standard deviation (RMSSD), a significant independent association of the changes in RRV with the changes in SpO2 was found (B = −4.3e-04, 95% CI = −8.3e-04/−2.1e-05, p = 0.04). The changes in Vt variability showed no significant association with the changes in SpO2 (B = −1.6, 95% CI = −5.5/2.4, p = 0.42). When modelling parameters variability as SD, a significant independent association of the changes in RRV with the changes in SpO2 was found (B = −8.2e-04, 95% CI = −1.5e-03/−9.4e-05, p = 0.03). The changes in Vt variability showed no significant association with the changes in SpO2 (B=1.4, 95% CI = −5.8/8.6, p = 0.69). ConclusionHigher RRV is independently associated with lower SpO2 during acute hypoxic exposure, while Vt variability parameters are not. Therefore, RRV may be a potentially interesting parameter to characterize individual responses to acute hypoxia.

Stimulation-induced respiratory enhancement in corticothalamic regions.

We aimed to identify corticothalamic areas and electrical stimulation paradigms that optimally enhance breathing. Twenty-nine patients with medically intractable epilepsy were prospectively recruited in an epilepsy monitoring unit while undergoing stereoelectroencephalographic evaluation. Direct electrical stimulation in cortical and thalamic regions was carried out using low (<1 Hz) and high (≥10 Hz) frequencies, and low (<5 mA) and high (≥5 mA) current intensities, with pulse width of .1 ms. Electrocardiography, arterial oxygen saturation (SpO2 ), end-tidal carbon dioxide (ETCO2 ), oronasal airflow, and abdominal and thoracic plethysmography were monitored continuously during stimulations. Airflow signal was used to estimate breathing rate, tidal volume, and minute ventilation (MV) changes during stimulation, compared to baseline. Electrical stimulation increased MV in the amygdala, anterior cingulate, anterior insula, temporal pole, and thalamus, with an average increase in MV of 20.8% ± 28.9% (range = 0.2%-165.6%) in 19 patients. MV changes were associated with SpO2 and ETCO2 changes (p < .001). Effects on respiration were parameter and site dependent. Within amygdala, low-frequency stimulation of the medial region produced 78.49% greater MV change (p < .001) compared to high-frequency stimulation. Longer stimulation produced greater MV changes (an increase of 4.47% in MV for every additional 10 s, p = .04). Stimulation of amygdala, anterior cingulate gyrus, anterior insula, temporal pole, and thalamus, using certain stimulation paradigms, enhances respiration. Among tested paradigms, low-frequency, low-intensity, long-duration stimulation of the medial amygdala is the most effective breathing enhancement stimulation strategy. Such approaches may pave the way for the future development of neuromodulatory techniques that aid rescue from seizure-related apnea, potentially as a targeted sudden unexpected death in epilepsy prevention method.

Hypoxic ventilatory response and respiratory chemosensitivity in differing rat models of female sex hormone loss

Respiratory function is modulated by circulating sex steroids. Specifically, concentrations of circulating 17β-estradiol and progesterone regulate the responsiveness of the respiratory system in adult female rats. Progesterone was first noted to influence breathing following the observation that pregnancy impacted blood gasses. 17β-estradiol is the most abundant and neuroactive form of estrogen, and female respiratory neuroplasticity is dependent on its presence. Circulating sex hormone levels fluctuate across the normal estrus cycle and gradually decline as part of the natural aging process. The specific influences of sex hormones on hypoxic ventilatory response (HVR) and chemosensitivity are slowly emerging in the literature. A developing pattern is that short-term hormone fluctuations, such as estrus cycle, do not appear to significantly change basic respiratory responsiveness. However, less is known about larger hormone shifts, such as those following the loss of gonads or with natural aging. We hypothesized that the loss of sex hormones would differentially impact HVR and chemosensitivity in an ovariectomy (OVX) model versus a naturally aged female rat. Specifically, we theorized that aged rats would demonstrate reduced sensitivity to hypoxia and reduced dynamic range within ventilatory output, as compared to OVX and intact female rats. Three experimental groups of female rats were used: young rats (3 mos old; n=4), young OVX rats (n=5), and aged rats (&gt;24 mos old; n=5). Chemosensitivity was measured during progressive hypoxic challenges at 15%, 12%, and 9% oxygen (O 2 ) using unrestrained barometric plethysmography. Serum samples were taken for measurement of estrogen (E 2 ) and progesterone (P) using ELISA assays. At the highest level of hypoxia (9% O 2 ), all groups exhibited intact chemosensitivity as demonstrated by significant changes in minute ventilation (V E ; &lt; 0.05), V E controlling for metabolism (V E / VCO 2 ; &lt; 0.05), and respiratory neural drive (calculated as the ratio of tidal volume (T V ) to inspiratory time (Ti), controlling for metabolism; T V /T i /VCO 2 ; &lt; 0.05). Further analysis showed that young and OVX groups demonstrated greater sensitivity to hypoxia as compared to the aged group. Using analyses targeting rate of change, the young and OVX groups had a faster rate of change in V E , V E / VCO 2 , and T V /T i /VCO 2 (&lt; 0.05) as the hypoxia intensity increased. ELISA analyses suggest that E 2 , but not P, concentration is significantly correlated with these results (&lt; 0.05). Collectively, these data indicate that aging impacts respiratory function in complex and unique ways that differ from OVX in female rats. This may be significant since OVX is commonly used as a model of age-related physiological changes. University of Minnesota BIRCWH/Women's Health Research Program Seed Grant, National Heart Lungs Brain Institute R01HL146477, Rehabilitation Science Graduate Program, UMN Medical School This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of an asymmetrical high flow nasal cannula interface in hypoxemic patients

BackgroundOptimal noninvasive respiratory support for patients with hypoxemic respiratory failure should minimize work of breathing without increasing the transpulmonary pressure. Recently, an asymmetrical high flow nasal cannula (HFNC) interface (Duet, Fisher & Paykel Healthcare Ltd), in which the caliber of each nasal prong is different, was approved for clinical use. This system might reduce work of breathing by lowering minute ventilation and improving respiratory mechanics.MethodsWe enrolled 10 patients ≥ 18 years of age who were admitted to the Ospedale Maggiore Policlinico ICU in Milan, Italy, and had a PaO2/FiO2 < 300 mmHg during HFNC support with a conventional cannula. We investigated whether the asymmetrical interface, compared to a conventional high flow nasal cannula, reduces minute ventilation and work of breathing. Each patient underwent support with the asymmetrical interface and the conventional interface, applied in a randomized sequence. Each interface was provided at a flow rate of 40 l/min followed by 60 l/min. Patients were continuously monitored with esophageal manometry and electrical impedance tomography.ResultsApplication of the asymmetrical interface resulted in a −13.5 [−19.4 to (−4.5)] % change in minute ventilation at a flow rate of 40 l/min, p = 0.006 and a −19.6 [−28.0 to (−7.5)] % change at 60 l/min, p = 0.002, that occurred despite no change in PaCO2 (35 [33–42] versus 35 [33–43] mmHg at 40 l/min and 35 [32–41] versus 36 [32–43] mmHg at 60 l/min). Correspondingly, the asymmetrical interface lowered the inspiratory esophageal pressure–time product from 163 [118–210] to 140 [84–159] (cmH2O*s)/min at a flow rate of 40 l/min, p = 0.02 and from 142 [123–178] to 117 [90–137] (cmH2O*s)/min at a flow rate of 60 l/min, p = 0.04.The asymmetrical cannula did not have any impact on oxygenation, the dorsal fraction of ventilation, dynamic lung compliance, or end-expiratory lung impedance, suggesting no major effect on PEEP, lung mechanics, or alveolar recruitment.ConclusionsAn asymmetrical HFNC interface reduces minute ventilation and work of breathing in patients with mild-to-moderate hypoxemic respiratory failure supported with a conventional interface. This appears to be primarily driven by increased ventilatory efficiency due to enhanced CO2 clearance from the upper airway.

ELEVATIONS IN END TIDAL CO2 WITH CO2 USE DURING PEDIATRIC ENDOSCOPY WITH AIRWAY PROTECTION: IS THIS PHYSIOLOGICALLY SIGNIFICANT?

Inflation of the gastrointestinal lumen is vital for proper visualization during endoscopy. Air, insufflated via the endoscope, is gradually being replaced with carbon dioxide (CO2) in many centers, with the intention of minimizing post-procedural discomfort due to retained gas. Recent studies suggest that the use of CO2 during pediatric esophagogastroduodenoscopy (EGD) with an unprotected airway is associated with transient elevations in exhaled CO2 (end-tidal CO2, EtCO2), raising safety concerns. One possible explanation for these events is eructation of insufflation gas from the stomach. To distinguish eructated vs absorbed CO2 by sampling EtCO2 from a protected airway with either laryngeal mask airway (LMA) or endotracheal tube (ETT), and to observe for changes in minute ventilation (MV) to exclude hypoventilation events. Double-blinded, randomized clinical trial of CO2 versus air insufflation for EGD with airway protection by either LMA or ETT. Tidal volume, respiratory rate, MV, and EtCO2 were automatically recorded every minute. Cohort demographics were described with descriptive characteristics. Variables including the percent of children with peak, transient EtCO2 ≥ 60mmHg were compared between groups. 195 patients were enrolled for 200 procedures. Transient elevations in EtCO2 of ≥ 60mmHg were more common in the CO2 group, compared to the air group (16% vs. 5%, p=0.02), but were mostly observed with LMA and less with ETT. Post-procedure pain was not different between groups, but flatulence was reported more with air insufflation. (p=0.004). Transient elevations in EtCO2 occur more often with CO2 than with air insufflation during pediatric EGD despite protecting the airway with an LMA or, to a lesser degree, with ETT. These elevations were not associated with changes in MV. Although no adverse clinical effects from CO2 absorption were observed, these findings suggest that caution should be exercised when considering the use of CO2 insufflation, especially since the observed benefits of using this gas were minimal.

S-nitroso-L-cysteine stereoselectively blunts the adverse effects of morphine on breathing and arterial blood gas chemistry while promoting analgesia

S-nitrosothiols exert multiple effects on neural processes in the central and peripheral nervous system. This study shows that intravenous infusion of S-nitroso-L-cysteine (SNO-L-CYS, 1 μmol/kg/min) in anesthetized male Sprague Dawley rats elicits (a) sustained increases in minute ventilation, via increases in frequency of breathing and tidal volume, (b) a decrease in Alveolar-arterial (A-a) gradient, thus improving alveolar gas-exchange, (c) concomitant changes in arterial blood-gas chemistry, such as an increase in pO2 and a decrease in pCO2, (d) a decrease in mean arterial blood pressure (MAP), and (e) an increase in tail-flick (TF) latency (antinociception). Infusion of S-nitroso-D-cysteine (SNO-D-CYS, 1 μmol/kg/min, IV), did not elicit similar responses, except for a sustained decrease in MAP equivalent to that elicited by SNO-L-CYS. A bolus injection of morphine (2 mg/kg, IV) in rats receiving an infusion of vehicle elicited (a) sustained decreases in frequency of breathing tidal volume, and therefore minute ventilation, (b) a sustained decrease in MAP, (c) sustained decreases in pH, pO2 and maximal sO2 with sustained increases in pCO2 and A-a gradient, and (d) a sustained increase in TF latency. In rats receiving SNO-L-CYS infusion, morphine elicited markedly smaller changes in minute ventilation, arterial blood gas chemistry, A-a gradient and MAP. In contrast, the antinociceptive effects of morphine were enhanced in rats receiving the infusion of SNO-L-CYS. The morphine-induced responses in rats receiving SNO-D-CYS infusion were similar to vehicle-infused rats. These data are the first to demonstrate that infusion of an S-nitrosothiol, such as SNO-L-CYS, can stereoselectively ameliorate the adverse effects of morphine on breathing and alveolar gas exchange while promoting antinociception.

The Role of Carotid Body Chemoreceptor Afferents in Mediating Abnormal Ventilation in Acute Lung Injury

Background‐Acute lung injury (ALI) induces inflammation that disrupts the normal alveolar‐capillary endothelial barrier which impairs gas exchange to induce hypoxemia that reflexively increases respiration. Increased respiratory rate (RR) usually develops within a few hours to a few days after ALI. This disorder of acute respiratory failure affects approximately 200,000 new cases each year in the US alone and has high morbidity and mortality. The neural mechanisms underlying the respiratory dysfunction after ALI are not fully understood. The purpose of this study involved investigating the role of carotid body chemoreceptor afferents in mediating abnormal ventilation in ALI.Methods and Results‐ALI was induced in male SD rats (200‐250g) using a single intra‐tracheal injection of bleomycin (Bleo) (day 0) and respiratory variables‐ RR, TV (Tidal Volume), and MV (Minute Ventilation) in response to 10% hypoxia (10% O2, 0% CO2) and 5% hypercapnia (21% O2, 5% CO2) were measured weekly from W1‐W4 using whole‐ body plethysmography (WBP). MV at 21% O2 increased from baseline (W0) to W1 and W2 in bleo treated rats (p≤0.01 compared to saline treated sham rats). Changes in MV were due to a significant increase in RR while TV showed no changes. Chemoreflex was assessed by measuring the absolute difference between 21% O2 and hypoxia (10% O2, 0% CO2) &amp; hypercapnia (21% O2, 5% CO2). Chemoreflex activation is a fundamental protective reflex that maintains oxygen homeostasis. Our data indicated a blunted chemoreflex at W1 and a sensitized chemoreflex in W3‐W4 during hypoxia and hypercapnia. We hypothesized that the blunted chemoreflex in W1 could be due to maximal pre‐activation of chemoreceptors, called the ‘ceiling effect’. To test this possibility, 90% hyperoxia (90% O2, 0% CO2) was given to bleo treated rats to inhibit the chemoreflex and our results showed no changes in RR, suggesting absence of the tonic activity at W1 post‐ALI.Conclusions‐These data suggest that chemoreflex activation in response to hypoxia and hypercapnia is blunted at acute stage of lung injury but became sensitized at the recovery stage.

Breathing variability during propofol/remifentanil procedural sedation with a single additional dose of midazolam or s-ketamine: a prospective observational study

PurposeRegulation of spontaneous breathing is highly complex and may be influenced by drugs administered during the perioperative period. Because of their different pharmacological properties we hypothesized that midazolam and s-ketamine exert different effects on the variability of minute ventilation (MV), tidal volume (TV) and respiratory rate (RR).MethodsPatients undergoing procedural sedation (PSA) with propofol and remifentanil received a single dose of midazolam (1–3 mg, n = 10) or s-ketamine (10–25 mg, n = 10). We used non-invasive impedance-based respiratory volume monitoring to record RR as well as changes in TV and MV. Variability of these three parameters was calculated as coefficients of variation.ResultsTV and MV decreased during PSA to a comparable extent in both groups, whereas there was no significant change in RR. In line with our hypothesis we observed marked differences in breathing variability. The variability of MV (– 47.5% ± 24.8%, p = 0.011), TV (– 42.1% ± 30.2%, p = 0.003), and RR (– 28.5% ± 29.3%, p = 0.011) was significantly reduced in patients receiving midazolam. In contrast, variability remained unchanged in patients receiving s-ketamine (MV + 16% ± 45.2%, p = 0.182; TV +12% ± 47.7%, p = 0.390; RR +39% ± 65.2%, p = 0.129). After termination of PSA breathing variables returned to baseline values.ConclusionsWhile midazolam reduces respiratory variability in spontaneously breathing patients undergoing procedural sedation, s-ketamine preserves variability suggesting different effects on the regulation of spontaneous breathing.

Hypercapnic ventilatory response in epilepsy patients treated with VNS: A case-control study.

Central CO2 chemoreception (CCR), a major chemical drive for breathing, can be quantified with a CO2 re-breathing test to measure the hypercapnic ventilatory response (HCVR). An attenuated HCVR correlates with the severity of respiratory dysfunction after generalized convulsive seizures and is a potential biomarker for sudden unexpected death in epilepsy (SUDEP) risk. Vagus nerve stimulation (VNS) may reduce SUDEP risk, but for unclear reasons the risk remains higher during the first 2 years after implantation. The vagus nerve has widespread connections in the brainstem, including key areas related to CCR. Here we examined whether chronic electrical stimulation of the vagus nerve induces changes in CCR. We compared the HCVR in epilepsy patients with or without an active VNS in a sex- and age-matched case-control study. Eligible subjects were selected from a cohort of patients who previously underwent HCVR testing. The HCVR slope, change in minute ventilation (VE) with respect to change in end tidal (ET) CO2 (∆ VE/ ∆ ETCO2) during the test was calculated for each subject. Key variables were compared between the two groups. Univariate and multivariate analyses were carried out for HCVR slope as dependent variable. A total of 86subjects were in the study. HCVR slope was significantly lower in the cases compared to the controls. Cases had longer duration of epilepsy and higher number of anti-epileptic drugs (AEDs) tried during lifetime. Having active VNS and ETCO2 were associated with a low HCVR slope while high BMI was associated with high HCVR slope in both univariate and multivariate analyses. We found having an active VNS was associated with relatively attenuated HCVR slope. Although duration of epilepsy and number of AEDs tried during lifetime was significantly different between the groups, they were not predictors of HCVR slope in subsequent analysis. Chronic electrical stimulation of the vagus nerve by VNS may be associated with an attenuated CCR [Correction added on 24 November 2021, after first online publication: The preceding sentence has been revised from “Chronic electrical stimulation of VNS nerve by VNS…”]. A larger prospective study may help to establish the time course of this effect in relation to the time of VNS implantation, whether there is a causal relationship, and determine how it affects SUDEP risk.

Mirtazapine reduces susceptibility to hypocapnic central sleep apnea in males with sleep-disordered breathing: a pilot study.

Studies in humans and animal models with spinal cord injury (SCI) have demonstrated that medications targeting serotonin receptors may decrease the susceptibility to central sleep-disordered breathing (SDB). We hypothesized that mirtazapine would decrease the propensity to develop hypocapnic central sleep apnea (CSA) during sleep. We performed a single-blind pilot study on a total of 10 men with SDB (7 with chronic SCI and 3 noninjured) aged 52.0 ± 11.2 yr. Participants were randomly assigned to either mirtazapine (15 mg at bedtime) or a placebo for at least 1 wk, followed by a 7-day washout period before crossing over to the other intervention. Split-night studies included polysomnography and induction of hypocapnic CSA using a noninvasive ventilation (NIV) protocol. The primary outcome was CO2 reserve, defined as the difference between eupneic and end of NIV end-tidal CO2 ([Formula: see text]) preceding induced hypocapneic CSA. Secondary outcomes included controller gain (CG), other ventilatory parameters, and SDB severity. CG was defined as the ratio of change in minute ventilation (V̇e) between control and hypopnea to the change in CO2 during sleep. CO2 reserve was significantly widened on mirtazapine than placebo (-3.8 ± 1.2 vs. -2.0 ± 1.5 mmHg; P = 0.015). CG was significantly decreased on mirtazapine compared with placebo [2.2 ± 0.7 vs. 3.5 ± 1.9 L/(mmHg × min); P = 0.023]. There were no significant differences for other ventilatory parameters assessed or SDB severity between mirtazapine and placebo trials. These findings suggest that the administration of mirtazapine can decrease the susceptibility to central apnea by reducing chemosensitivity and increasing CO2 reserve; however, considering the lack of changes in apnea-hypopnea index (AHI), further research is required to understand the significance of this finding.NEW & NOTEWORTHY To our knowledge, this research study is novel as it is the first study in humans assessing the effect of mirtazapine on CO2 reserve and chemosensitivity in individuals with severe sleep-disordered breathing. This is also the first study to determine the potential therapeutic effects of mirtazapine on sleep parameters in individuals with a spinal cord injury.

Novel Mechanism of Neural Control of Breathing in Acute Lung Injury (ALI)

Increased respiratory rate (RR) usually develops within a few hours to a few days after ALI. However, the neural mechanisms underlying the breathing dysfunction after ALI are not fully understood. The purpose involved investigating the role of chemoreceptor afferents and pulmonary spinal afferents in the control of breathing in ALI. ALI was induced in male SD rats (200-250g) using intra-tracheal injections of bleomycin (Bleo) (day 0) and measured RR, TV (Tidal Volume), and MV (Minute Ventilation) weekly from W1-W4 using whole body plethysmography (WBP). Chemoreflex was assessed by measuring the absolute difference between 21% O2 and hypoxia (10% O2) & hypercapnia (5% CO2 and 7% CO2). MV at 21% O2 increased from baseline to W1 and W2. Changes in MV were due to significant increase in RR while TV showed no changes. Blunted chemoreflex was observed at W1 and W2 during hypoxia and hypercapnia which could be due to maximal pre-activation of chemoreceptors, called ceiling effect. Chemoreflex was inhibited in bleo-rats through 90% O2 (hyperoxia) which showed no changes in RR, suggesting absence of tonic activity. Other experiments included bleomycin on day 0, ablation of TRPV1-positive lung spinal afferents by bilaterally injecting 5μl of RTX (50 μg/ml) into the stellate ganglion (day 3) and measuring lung parameters (day 7). RTX ablation of pulmonary spinal afferents caused a significant reduction in RR in bleo-rats at W1. These data suggest that chemoreflex activation in response to hypoxia and hypercapnia is blunted whereas, pulmonary spinal afferent activation may play a major role in the increased RR in ALI.

The Effects of Laryngoscope Shape and Needle Position on Distal Airway Pressure in Jet Ventilation.

Laryngoscopes and subglottiscopes of multiple shapes and lengths are used in airway surgery to maintain an open airway; protect the trachea; and provide a place to mount the light, evacuator, and ventilation needle. Despite differences in scopes and ventilation needle mounting positions, the same jet pressures are typically used. We hypothesized that different scopes and scope configurations would affect distal airway pressure magnitude and homogeneity. A laboratory investigation of distal airway pressures in a lung modelduring low frequency jet ventilation. A three-dimensional airway model based on the computed tomography scan of a 15-year old healthy male was fabricated with pressure transducers at the fifth airway generation. A laryngoscope and a subglottiscope were each mounted in the model coaxial with the trachea. Parameters including scope depth and needle mounting position were adjusted, and the effects on distal airway pressure were recorded. Changing the scope depth from 1 to 3 cm past the laryngeal inlet had a limited effect on distal airway pressure. Needle mounting angle in the laryngoscope strongly influenced distal airway pressure, with a 7° angle change yielding a 67.5% increase. Compared to a loose needle centered in the trachea 1 cm past the laryngeal inlet, the subglottiscope and laryngoscope showed up to 16% and 150% increases in distal airway pressure, respectively. Different scopes or changes in the configuration, such as the needle angle, strongly influence distal airway pressure. Our findings indicate that different jet pressures are required for different scopes and that a stable needle mount is a critical design consideration to prevent changes in minute ventilation due to needle movement. NA (Basic Research) Laryngoscope, 131:E354-E357, 2021.

Prolonged treadmill running in normobaric hypoxia causes gastrointestinal barrier permeability and elevates circulating levels of pro- and anti-inflammatory cytokines.

This study examined the impact of treadmill running in normobaric hypoxia on gastrointestinal barrier permeability and the systemic inflammatory response. Ten recreationally active participants completed two 1-h bouts of matched-workload treadmill exercise (65% normoxic maximal oxygen consumption) in counterbalanced order. One bout was performed in normoxia (NORM: fraction of inspired oxygen (FIO2) = 20.9%) and the other in normobaric hypoxia (HYP: FIO2 = 13.5%). Minute ventilation, respiratory rate (RR), tidal volume (VT), oxygen consumption, carbon dioxide production, respiratory exchange ratio (RER), and heart rate (HR) were measured with a metabolic cart. Peripheral oxygen saturation (SpO2) was measured with pulse oximetry. Absolute tissue saturation (StO2) was measured with near-infrared spectroscopy. Fatty acid-binding protein (I-FABP) and circulating cytokine concentrations (interleukin (IL)-1Ra, IL-6, IL-10) were assayed from plasma samples that were collected pre-exercise, postexercise, 1 h-postexercise, and 4 h-postexercise. Data were analyzed with 2-way (condition × time) repeated-measures ANOVAs. Newman-Keuls post hoc tests were run where appropriate (p < 0.05). As compared with NORM, 1 h of treadmill exercise in HYP caused greater (p < 0.05) changes in minute ventilation (+30%), RR (+16%), VT (+10%), carbon dioxide production (+18%), RER (+16%), HR (+4%), SpO2 (-16%), and StO2 (-10%). Gut barrier permeability and circulating cytokine concentrations were also greater (p < 0.05) following HYP exercise, where I-FABP was shown increased at postexercise (+68%) and IL-1Ra at 1 h-postexercise (+266%). I-FABP and IL-1Ra did not change (p > 0.05) following NORM exercise. IL-6 and IL-10 increased with exercise in both study conditions but were increased more (p < 0.05) following HYP at postexercise (+705% and +127%, respectively) and 1 h-postexercise (+400% and +128%, respectively). Novelty Normobaric hypoxia caused significant desaturation and increased most cardiopulmonary responses by 10%-30%. Significant gut barrier permeability and increased pro- and anti-inflammatory cytokine concentrations could promote an "open window" in the hours following HYP exercise.

Patients alter power of breathing as the primary response to changes in pressure support ventilation

IntroductionThe patient-ventilator relationship is dynamic as the patient's health fluctuates and the ventilator settings are modified. Spontaneously breathing patients respond to mechanical ventilation by changing their patterns of breathing. This study measured the physiologic response when pressure support (PS) settings were modified during mechanical ventilation. MethodsSubjects were instrumented with a non-invasive pressure, flow, and carbon dioxide airway sensor to estimate tidal volume, respiratory rate, minute ventilation, and end-tidal CO2. Additionally, a catheter was used to measure esophageal pressure and estimate effort exerted during breathing. Respiratory function measurements were obtained while PS settings were adjusted 569 times between 5 and 25 cmH2O. ResultsData was collected on 248 patients. The primary patient response to changes in PS was to adjusting effort (power of breathing) followed by adjusting tidal volume. Changes in respiratory rate were less definite while changes in minute ventilation and end-tidal CO2 appeared unrelated to the change in PS. ConclusionThe data indicates that patients maintain a set minute ventilation by adjusting their breathing rate, volume, and power. The data indicates that the subjects regulate their Ve and PetCO2 by adjusting power of breathing and breathing pattern.

Carbonic anhydrase inhibition and chemoreflex control of breathing: A litmus test for methazolamide as a viable alternative to acetazolamide.

Carbonic anhydrase inhibition and chemoreflex control of breathing: A litmus test for methazolamide as a viable alternative to acetazolamide.

Ventilation Is an Important Confounding Variable When End-Tidal Carbon Dioxide Is Used to Help Guide Cardiopulmonary Resuscitation

Ventilation Is an Important Confounding Variable When End-Tidal Carbon Dioxide Is Used to Help Guide Cardiopulmonary Resuscitation

Use of a novel non-invasive respiratory monitor to study changes in pulmonary ventilation during labor epidural analgesia

Measuring continuous changes in maternal ventilation during labor neuraxial analgesia is technically difficult. Consequently, the magnitude of pulmonary minute ventilation (MV) alterations following labor analgesia remains unknown. We hypothesized that a novel, bio-impedance based non-invasive respiratory monitor would provide this information. Furthermore, we sought to determine if an association between changes in MV and maternal temperature existed. Following calibration with a Haloscale Standard Wright Respirometer, the ExSpiron respiratory volume monitor (RVM) measured MV, respiratory rate (RR), and tidal volume (TV) in 41 term parturients receiving epidural analgesia. Simultaneously, maternal oral temperatures were recorded at pre-specified hourly intervals after epidural analgesia initiation until delivery. Cumulative MV changes were calculated as the integral of MV change over time: MV [Formula: see text], where T represents the time between epidural placement and variable measurement. The association between changes in MV and cumulative MV versus maternal temperature was determined by comparing patients whose temperature did or did not increase by ≥ 0.5°C. After initiation of epidural analgesia, MV decreased by 11.1 ± 27.6% [mean ± SD] at 30min, p = 0.006, and 19.8 ± 26.1% at 2h compared to baseline (12.6 ± 7.3L/min at baseline vs. 15.3 ± 6.3 L/min at 2h, p < 0.001), Minute ventilation remained decreased at 4h by 14.3 ± 31.4% (p = 0.013). The cumulative MV also decreased by 437 ± 852L [mean ± SD], p = 0.009) at 2h and by 795 ± 1431L, p < 0.001) at 4h following epidural analgesia initiation, compared to baseline. The association between changes in cumulative MV and maternal temperature following epidural placement was weak (R < 0.3); however, a decrease in MV at 30 min (p=0.002) and cumulative MV at 2 h (p=0.012) was observed in women whose temperature increased by at least 0.5°C during labor. Our findings suggest that RVM can be a useful noninvasive technology to investigate pulmonary physiology during labor. The association between maternal MV and temperature change during labor analgesia deserves further investigation.Trial Registrationwww.clinicaltrials.gov (NCT02339389).

Cardiopulmonary exercise testing may not predict appropriate implantable cardioverter defibrillator therapies in heart failure patients

Background: The prognostic value of cardiopulmonary exercise testing (CPET) variables for major cardiovascular events in patients with heart failure (HF) is widely established. However, the prognostic value of these variables as predictors of appropriate implantable cardioverter-defibrillator (ICD) therapies has not been sufficiently well addressed. This study aimed to evaluate CPET variables such as peak oxygen uptake (VO2 peak), relationship between change in minute ventilation (VE) and carbon dioxide output (VCO2) during incremental exercise (VE/VCO2 slope) and exercise-related periodic breathing (EPB) as appropriate ICD therapy predictors in HF patients.Methods: We retrospectively assessed 61 HF patients who underwent CPET and had ICD implanted for primary prevention. Patients were followed for 767 ± 601 days. Primary outcome was appropriate ICD-delivered therapy, either anti-tachycardia pacing (ATP) or shock.Results: The sample consisted mostly of male patients (65.6%), with severe ventricular dysfunction (mean left ventricular ejection fraction (LVEF) 27 ± 6%). The primary outcome occurred in 20 patients (32%). There were no significant differences in VO2 peak (17.7 ± 4.1 and 16.9 ± 4.5 mL/kg/min), VE/VCO2 slope (39.7 ± 8.4 and 39.6 ± 10.2) or EPB prevalence (20% and 19.5%) in patients with or without appropriate ICD therapy. According to Cox regression analysis, none of the CPET variables were significant predictors of appropriate ICD therapy.Conclusions: In this cohort study of HF patients, CPET variables did not predict appropriate ICD therapies. Further studies with large number of patients are warranted to address this issue.