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 30 min, p = 0.006, and 19.8 ± 26.1% at 2 h compared to baseline (12.6 ± 7.3 L/min at baseline vs. 15.3 ± 6.3 L/min at 2 h, p < 0.001), Minute ventilation remained decreased at 4 h by 14.3 ± 31.4% (p = 0.013). The cumulative MV also decreased by 437 ± 852 L [mean ± SD], p = 0.009) at 2 h and by 795 ± 1431 L, p < 0.001) at 4 h 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).

The Evaluation of a Noninvasive Respiratory Volume Monitor in Pediatric Patients Undergoing General Anesthesia.

BACKGROUND: Pediatric patients following surgery are at risk for respiratory compromise such as hypoventilation and hypoxemia depending on their age, comorbidities, and type of surgery. Quantitative measurement of ventilation in nonintubated infants/children is a difficult and inexact undertaking. Current respiratory assessment in nonintubated patients relies on oximetry data, respiratory rate (RR) monitors, and subjective clinical assessment, but there is no objective measure of respiratory parameters that could be utilized to predict early respiratory compromise. New advances in technology and digital signal processing have led to the development of an impedance-based respiratory volume monitor (RVM, ExSpiron, Respiratory Motion, Inc, Waltham, MA). The RVM has been shown to provide accurate real-time, continuous, noninvasive measurements of tidal volume (TV), minute ventilation (MV), and RR in adult patients.In this prospective observational study, our primary aim was to determine whether the RVM accurately measures TV, RR, and MV in pediatric patients. METHODS: A total of 72 pediatric patients (27 females, 45 males), ASA I to III, undergoing general anesthesia with endotracheal intubation were enrolled. After endotracheal intubation, continuous data of MV, TV, and RR were recorded from the RVM and an in-line monitoring spirometer (NM3 monitor, Phillips Healthcare). RVM and NM3 measurements of MV, TV, and RR were compared during a 10-minute period prior to the incision ("Presurgery") and a 10-minute period after the end of surgery ("Postsurgery"). Relative errors were calculated over 1-minute segment within each 10-minute period. Bias, precision, and accuracy were calculated using Bland-Altman analyses and paired-difference equivalence tests were performed. RESULTS: Combined across the Presurgery and Postsurgery periods, the RVM's mean measurement bias (RVM - NM3 measurement) for MV was -3.8% (95% limits of agreement) (±1.96 SD): (-19.9% to 12.2%), for TV it was -4.9 (-21.0% to 11.3%), and for RR it was 1.1% (-4.1% to 6.2%). The mean measurement accuracies for MV, TV, and RR were 11.9%, 12.0%, and 4.2% (0.6 breaths/min), respectively. Note that lower accuracy numbers correspond to more accurate RVM measurements. The equivalence tests rejected the null hypothesis that the RVM and NM3 have different mean values and conclude with 90% power that the measurements of MV, TV, and RR from the RVM and NM3 are equivalent within ±10%. CONCLUSIONS: Our data indicate acceptable agreement between RVM and NM3 measurements in pediatric mechanically-ventilated patients. Future studies assessing the capability of the RVM to detect respiratory compromise in other clinical settings are needed.

The relationship between minute ventilation and end tidal CO2 in intubated and spontaneously breathing patients undergoing procedural sedation.

BACKGROUND: Monitoring respiratory status using end tidal CO2 (EtCO2), which reliably reflects arterial PaCO2 in intubated patients under general anesthesia, has often proven both inaccurate and inadequate when monitoring non-intubated and spontaneously breathing patients. This is particularly important in patients undergoing procedural sedation (e.g., endoscopy, colonoscopy). This can be undertaken in the operating theater, but is also often delivered outside the operating room by non-anesthesia providers. In this study we evaluated the ability for conventional EtCO2 monitoring to reflect changes in ventilation in non-intubated surgical patients undergoing monitored anesthesia care and compared and contrasted these findings to both intubated patients under general anesthesia and spontaneously breathing volunteers. METHODS: Minute Ventilation (MV), tidal volume (TV), and respiratory rate (RR) were continuously collected from an impedance-based Respiratory Volume Monitor (RVM) simultaneously with capnography data in 160 patients from three patient groups: non-intubated surgical patients managed using spinal anesthesia and Procedural Sedation (n = 58); intubated surgical patients under General Anesthesia (n = 54); and spontaneously breathing Awake Volunteers (n = 48). EtCO2 instrument sensitivity was calculated for each patient as the slope of a Deming regression between corresponding measurements of EtCO2 and MV and expressed as angle from the x-axis (θ). All data are presented as mean ± SD unless otherwise indicated. RESULTS: While, as expected, EtCO2 and MV measurements were negatively correlated in most patients, we found gross systematic differences across the three cohorts. In the General Anesthesia patients, small changes in MV resulted in large changes in EtCO2 (high sensitivity, θ = -83.6 ± 9.9°). In contrast, in the Awake Volunteers patients, large changes in MV resulted in insignificant changes in EtCO2 (low sensitivity, θ = -24.7 ± 19.7°, p < 0.0001 vs General Anesthesia). In the Procedural Sedation patients, EtCO2 sensitivity showed a bimodal distribution, with an approximately even split between patients showing high EtCO2 instrument sensitivity, similar to those under General Anesthesia, and patients with low EtCO2 instrument sensitivity, similar to the Awake Volunteers. CONCLUSIONS: When monitoring non-intubated patients undergoing procedural sedation, EtCO2 often provides inadequate instrument sensitivity when detecting changes in ventilation. This suggests that augmenting standard patient care with EtCO2 monitoring is a less than optimal solution for detecting changes in respiratory status in non-intubated patients. Instead, adding direct monitoring of MV with an RVM may be preferable for continuous assessment of adequacy of ventilation in non-intubated patients.

Modeling variability in air pollution-related health damages from individual airport emissions.

In this study, we modeled concentrations of fine particulate matter (PM2.5) and ozone (O3) attributable to precursor emissions from individual airports in the United States, developing airport-specific health damage functions (deaths per 1000t of precursor emissions) and physically-interpretable regression models to explain variability in these functions. We applied the Community Multiscale Air Quality model using the Decoupled Direct Method to isolate PM2.5- or O3-related contributions from precursor pollutants emitted by 66 individual airports. We linked airport- and pollutant-specific concentrations with population data and literature-based concentration-response functions to create health damage functions. Deaths per 1000t of primary PM2.5 emissions ranged from 3 to 160 across airports, with variability explained by population patterns within 500km of the airport. Deaths per 1000t of precursors for secondary PM2.5 varied across airports from 0.1 to 2.7 for NOx, 0.06 to 2.9 for SO2, and 0.06 to 11 for VOCs, with variability explained by population patterns and ambient concentrations influencing particle formation. Deaths per 1000t of O3 precursors ranged from -0.004 to 1.0 for NOx and 0.03 to 1.5 for VOCs, with strong seasonality and influence of ambient concentrations. Our findings reinforce the importance of location- and source-specific health damage functions in design of health-maximizing emissions control policies.

A Comparison of Measurements of Change in Respiratory Status in Spontaneously Breathing Volunteers by the ExSpiron Noninvasive Respiratory Volume Monitor Versus the Capnostream Capnometer.

BACKGROUND: Current respiratory monitoring technologies such as pulse oximetry and capnography have been insufficient to identify early signs of respiratory compromise in nonintubated patients. Pulse oximetry, when used appropriately, will alert the caregiver to an episode of dangerous hypoxemia. However, desaturation lags significantly behind hypoventilation and alarm fatigue due to false alarms poses an additional problem. Capnography, which measures end-tidal CO2 (EtCO2) and respiratory rate (RR), has not been universally used for nonintubated patients for multiple reasons, including the inability to reliably relate EtCO2 to the level of impending respiratory compromise and lack of patient compliance. Serious complications related to respiratory compromise continue to occur as evidenced by the Anesthesiology 2015 Closed Claims Report. The Anesthesia Patient Safety Foundation has stressed the need to improve monitoring modalities so that "no patient will be harmed by opioid-induced respiratory depression." A recently available, Food and Drug Administration-approved noninvasive respiratory volume monitor (RVM) can continuously and accurately monitor actual ventilation metrics: tidal volume, RR, and minute ventilation (MV). We designed this study to compare the capabilities of capnography versus the RVM to detect changes in respiratory metrics. METHODS: Forty-eight volunteer subjects completed the study. RVM measurements (MV and RR) were collected simultaneously with capnography (EtCO2 and RR) using 2 sampling methods (nasal scoop cannula and snorkel mouthpiece with in-line EtCO2 sensor). For each sampling method, each subject performed 6 breathing trials at 3 different prescribed RRs (slow [5 min], normal [12.6 ± 0.6 min], and fast [25 min]). All data are presented as mean ± SEM unless otherwise indicated. RESULTS: Following transitions in prescribed RRs, the RVM reached a new steady state value of MV in 37.7 ± 1.4 seconds while EtCO2 changes were notably slower, often failing to reach a new asymptote before a 2.5-minute threshold. RRs as measured by RVM and capnography during steady breathing were strongly correlated (R = 0.98 ± 0.01, bias = Capnograph-based RR - RVM-based RR = 0.21 ± 1.24 [SD] min). As expected, changes in MV were negatively correlated with changes in EtCO2. However, large changes in MV following transitions in prescribed RR resulted in relatively small changes in EtCO2 (instrument sensitivity = ΔEtCO2/ΔMV = -0.71 ± 0.11 and -0.55 ± 0.11 mm Hg per 1 L/min for nasal and in-line sampling, respectively). Nasal cannula EtCO2 measurements were on average 4 mm Hg lower than in-line measurements. CONCLUSIONS: RVM measurements of MV change more rapidly and by a greater degree than capnography in response to respiratory changes in nonintubated patients. Earlier detection could enable earlier intervention that could potentially reduce frequency and severity of complications due to respiratory depression.

Spatial distribution of airway wall displacements during breathing and bronchoconstriction measured by ultrasound elastography using finite element image registration.

With every breath, the airways within the lungs are strained. This periodic stretching is thought to play an important role in determining airway caliber in health and disease. Particularly, deep breaths can mitigate excessive airway narrowing in healthy subjects, but this beneficial effect is absent in asthmatics, perhaps due to an inability to stretch the airway smooth muscle (ASM) embedded within an airway wall. The heterogeneous composition throughout an airway wall likely modulates the strain felt by the ASM but the magnitude of ASM strain is difficult to measure directly. In this study, we optimized a finite element image registration method to measure the spatial distribution of displacements and strains throughout an airway wall during pressure inflation within the physiological breathing range before and after induced narrowing with acetylcholine (ACh). The method was shown to be repeatable, and displacements estimated from different image sequences of the same deformation agreed to within 5.3µm (0.77%). We found the magnitude and spatial distribution of displacements were radially and longitudinally heterogeneous. The region in the middle layer of the airway experienced the largest radial strain due to a transmural pressure (Ptm) increase simulating tidal breathing and a deep inspiration (DI), while the region containing the ASM (i.e., closest to the lumen) strained least. During induced narrowing with ACh, we observed temporal longitudinal heterogeneity of the airway wall. After constriction, the displacements and strain are much smaller than the relaxed airway and the pattern of strains changed, suggesting the airway stiffened heterogeneously.

Can breathing-like pressure oscillations reverse or prevent narrowing of small intact airways?

Periodic length fluctuations of airway smooth muscle during breathing are thought to modulate airway responsiveness in vivo. Recent animal and human intact airway studies have shown that pressure fluctuations simulating breathing can only marginally reverse airway narrowing and are ineffective at protecting against future narrowing. However, these previous studies were performed on relatively large (>5 mm diameter) airways, which are inherently stiffer than smaller airways for which a preponderance of airway constriction in asthma likely occurs. The goal of this study was to determine the effectiveness of breathing-like transmural pressure oscillations to reverse induced narrowing and/or protect against future narrowing of smaller, more compliant intact airways. We constricted smaller (luminal diameter = 2.92 ± 0.29 mm) intact airway segments twice with ACh (10(-6) M), once while applying tidal-like pressure oscillations (5-15 cmH2O) before, during, and after inducing constriction (Pre + Post) and again while only imposing the tidal-like pressure oscillation after induced constriction (Post Only). Smaller airways were 128% more compliant than previously studied larger airways. This increased compliance translated into 196% more strain and 76% greater recovery (41 vs. 23%) because of tidal-like pressure oscillations. Larger pressure oscillations (5-25 cmH2O) caused more recovery (77.5 ± 16.5%). However, pressure oscillations applied before and during constriction resulted in the same steady-state diameter as when pressure oscillations were only applied after constriction. These data show that reduced straining of the airways before a challenge likely does not contribute to the emergence of airway hyperreactivity observed in asthma but may serve to sustain a given level of constriction.

Tidal stretches differently regulate the contractile and cytoskeletal elements in intact airways.

Recent reports suggest that tidal stretches do not cause significant and sustainable dilation of constricted intact airways ex vivo. To better understand the underlying mechanisms, we aimed to map the physiological stretch-induced molecular changes related to cytoskeletal (CSK) structure and contractile force generation through integrin receptors. Using ultrasound, we measured airway constriction in isolated intact airways during 90 minutes of static transmural pressure (Ptm) of 7.5 cmH2O or dynamic variations between Ptm of 5 and 10 cmH20 mimicking breathing. Integrin and focal adhesion kinase activity increased during Ptm oscillations which was further amplified during constriction. While Ptm oscillations reduced ß-actin and F-actin formation implying lower CSK stiffness, it did not affect tubulin. However, constriction was amplified when the microtubule structure was disassembled. Without constriction, α-smooth muscle actin (ASMA) level was higher and smooth muscle myosin heavy chain 2 was lower during Ptm oscillations. Alternatively, during constriction, overall molecular motor activity was enhanced by Ptm oscillations, but ASMA level became lower. Thus, ASMA and motor protein levels change in opposite directions due to stretch and contraction maintaining similar airway constriction levels during static and dynamic Ptm. We conclude that physiological Ptm variations affect cellular processes in intact airways with constriction determined by the balance among contractile and CSK molecules and structure.

Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?

Fluctuating forces imposed on the airway smooth muscle due to breathing are believed to regulate hyperresponsiveness in vivo. However, recent animal and human isolated airway studies have shown that typical breathing-sized transmural pressure (Ptm) oscillations around a fixed mean are ineffective at mitigating airway constriction. To help understand this discrepancy, we hypothesized that Ptm oscillations capable of producing the same degree of bronchodilation as observed in airway smooth muscle strip studies requires imposition of strains larger than those expected to occur in vivo. First, we applied increasingly larger amplitude Ptm oscillations to a statically constricted airway from a Ptm simulating normal functional residual capacity of 5 cmH2O. Tidal-like oscillations (5-10 cmH2O) imposed 4.9 ± 2.0% strain and resulted in 11.6 ± 4.8% recovery, while Ptm oscillations simulating a deep inspiration at every breath (5-30 cmH2O) achieved 62.9 ± 12.1% recovery. These same Ptm oscillations were then applied starting from a Ptm = 1 cmH2O, resulting in approximately double the strain for each oscillation amplitude. When extreme strains were imposed, we observed full recovery. On combining the two data sets, we found a linear relationship between strain and resultant recovery. Finally, we compared the impact of Ptm oscillations before and after constriction to Ptm oscillations applied only after constriction and found that both loading conditions had a similar effect on narrowing. We conclude that, while sufficiently large strains applied to the airway wall are capable of producing substantial bronchodilation, the Ptm oscillations necessary to achieve those strains are not expected to occur in vivo.

Factors determining airway caliber in asthma.

Airway hyperresponsiveness is a hallmark of asthma in which airways narrow excessively in response to an agonist, resulting in difficulty in breathing. Constriction of the smooth muscle that spirals around the airways is the principle cause of airway narrowing during an asthma attack. It is likely that several mechanisms are involved in the development of a hyperresponsive airway in asthma. In this review, we focus on the structural and functional aspects that govern the narrowing of a single airway within a lung, then we review the current understanding of how these factors become altered in a way that leads to the airway hyperresponsiveness observed in asthma. We first examine airway caliber as a simple equilibrium of forces favoring narrowing and the forces opposing this narrowing. We then review the role that the dynamic forces of tidal breathing and deep inspirations have across all length scales of the respiratory system; we describe an intriguing inconsistency that has arisen from these data. Finally, we examine the interaction between airway remodeling and inflammation and their roles in health and disease.