Minute Ventilation Research Articles

Ageing-related modification of sleep and breathing in orexin-knockout narcoleptic mice.

Narcolepsy type-1 (NT1) is a lifelong sleep disease, characterised by impairment of the orexinergic system, with a typical onset during adolescence and young adulthood. Since the wake-sleep cycle physiologically changes with ageing, this study aims to compare sleep patterns between orexin-knockout (KO) and wild type (WT) control mice at different ages. Four groups of age-matched female KO and WT mice (16 weeks of age: 8 KO-YO and 9 WT-YO mice; 87 weeks of age: 13 KO-OLD and 12 WT-OLD mice) were implanted with electrodes for discriminating wakefulness, rapid-eye-movement sleep (REMS), and non-REMS (NREMS). Mice were recorded for 48 h in their home cages and for 7 more hours into a plethysmographic chamber to characterise their sleep-breathing pattern. Regardless of orexin deficiency, OLD mice spent less time awake and had fragmentation of this behavioural state showing more bouts of shorter length than YO mice. OLD mice also had more NREMS bouts and less frequent NREMS apneas than YO mice. Regardless of age, KO mice showed cataplexy-like episodes and shorter REMS latency than WT controls and had a faster breathing rate and an increased minute ventilation during REMS. KO mice also had more wakefulness, NREMS and REMS bouts, and a shorter mean length of wakefulness bouts than WT controls. Our experiment indicated that the lack of orexins as well as ageing importantly modulate the sleep and breathing phenotype in mice. The narcoleptic phenotype caused by orexin deficiency in female mice was substantially preserved with ageing.

Workload and spirometry associated with untethered swimming in horses

BackgroundSwimming has been used empirically for rehabilitation and conditioning of horses. However, due to challenges imposed by recording physiological parameters in water, the intensity of free swimming effort is unknown.ObjectivesMeasure the physiological workload associated with untethered swimming in horses.Five fit Arabian endurance horses were assessed while swimming in a 100 m-long indoor pool. Horses were equipped with a modified ergospirometry facemask to measure oxygen consumption (V̇O2) and ventilatory parameters (inspired/expired volumes, VI, VE; peak inspiratory/expiratory flows, PkVI, PkVE; respiratory frequency, Rf; minute ventilation, VE; inspiratory/expiratory durations and ratios, tI, tE, tI/ttot, tE/ttot); and an underwater electrocardiogram that recorded heart rate (HR). Postexercise venous blood lactate and ammonia concentrations were measured. Data are reported as median (interquartile ranges).ResultsHorses showed bradypnea (12 breaths/min (10–16)) for the first 30 s of swimming. V̇O2 during swimming was 43.2 ml/(kg.min) (36.0–56.6). Ventilatory parameters were: VI = 16.7 L (15.3–21.8), VE = 14.7 L (12.4–18.9), PkVI = 47.8 L/s (45.8–56.5), PkVE = 55.8 L/s (38.3–72.5), Rf = 31.4 breaths/min (20.0–33.8), VE = 522.9 L/min (414.7–580.0), tI = 0.5 s (0.5–0.6), tE = 1.2 s (1.1–1.6), tI/ttot = 0.3 (0.2–0.4), tE/ttot = 0.7 (0.6–0.8). Expiratory flow tracings showed marked oscillations that coincided with a vibrating expiratory sound. HR was 178.0 bpm (148.5–182.0), lactate = 1.5 mmol/L (1.0–1.9) and ammonia = 41.0 µmol/L (36.5–43.5).ConclusionsFree (untethered) swimming represents a submaximal, primarily aerobic exercise in horses. The breathing pattern during swimming is unique, with a relatively longer apneic period at the beginning of the exercise and an inspiratory time less than half that of expiration.

Mapping responses to focal injections of bicuculline in the lateral parafacial region identifies core regions for maximal generation of active expiration

The lateral parafacial area (pFL) is a crucial region involved in respiratory control, particularly in generating active expiration through an expiratory oscillatory network. Active expiration involves rhythmic abdominal (ABD) muscle contractions during late-expiration, increasing ventilation during elevated respiratory demands. The precise anatomical location of the expiratory oscillator within the ventral medulla’s rostro-caudal axis is debated. While some studies point to the caudal tip of the facial nucleus (VIIc) as the oscillator’s core, others suggest more rostral areas. Our study employed bicuculline (a γ-aminobutyric acid type A [GABA-A] receptor antagonist) injections at various pFL sites (–0.2 mm to +0.8 mm from VIIc) to investigate the impact of GABAergic disinhibition on respiration. These injections consistently elicited ABD recruitment, but the response strength varied along the rostro-caudal zone. Remarkably, the most robust and enduring changes in tidal volume, minute ventilation, and combined respiratory responses occurred at more rostral pFL locations (+0.6/+0.8 mm from VIIc). Multivariate analysis of the respiratory cycle further differentiated between locations, revealing the core site for active expiration generation with this experimental approach. Our study advances our understanding of neural mechanisms governing active expiration and emphasizes the significance of investigating the rostral pFL region.

Mapping responses to focal injections of bicuculline in the lateral parafacial region identifies core regions for maximal generation of active expiration.

The lateral parafacial area (pFL) is a crucial region involved in respiratory control, particularly in generating active expiration through an expiratory oscillatory network. Active expiration involves rhythmic abdominal (ABD) muscle contractions during late-expiration, increasing ventilation during elevated respiratory demands. The precise anatomical location of the expiratory oscillator within the ventral medulla's rostro-caudal axis is debated. While some studies point to the caudal tip of the facial nucleus (VIIc) as the oscillator's core, others suggest more rostral areas. Our study employed bicuculline (a γ-aminobutyric acid type A [GABA-A] receptor antagonist) injections at various pFL sites (-0.2 mm to +0.8 mm from VIIc) to investigate the impact of GABAergic disinhibition on respiration. These injections consistently elicited ABD recruitment, but the response strength varied along the rostro-caudal zone. Remarkably, the most robust and enduring changes in tidal volume, minute ventilation, and combined respiratory responses occurred at more rostral pFL locations (+0.6/+0.8 mm from VIIc). Multivariate analysis of the respiratory cycle further differentiated between locations, revealing the core site for active expiration generation with this experimental approach. Our study advances our understanding of neural mechanisms governing active expiration and emphasizes the significance of investigating the rostral pFL region.

Energetics and Basic Stroke Kinematics of Swimming With Different Styles of Wetsuits.

Lim, B, Villalobos, A, Mercer, JA, and Crocker, GH. Energetics and basic stroke kinematics of swimming with different styles of wetsuits. J Strength Cond Res XX(X): 000-000, 2024-This study investigated the physiological responses and basic stroke kinematics while wearing different styles of wetsuits during submaximal intensity front-crawl swimming. Fourteen subjects (6 men and 8 women) completed a swimming-graded exercise test to determine maximal aerobic capacity (V̇O2max) and four 4-minute submaximal front-crawl swims at a pace that elicited 80% of V̇O2max with different wetsuits: regular swimsuit (no wetsuit [NWS]), buoyancy shorts (BS), sleeveless wetsuit (SLW), and full-sleeve wetsuit (FSW). The rate of oxygen consumption (V̇O2), rate of carbon dioxide production (V̇CO2), minute ventilation (V̇E), heart rate (HR), respiratory exchange ratio, and cost of swimming (CS) were determined as the average for the last minute of each trial. The rating of perceived exertion was assessed after each swimming bout. In addition, stroke length and index were determined from swimming pace and stroke rate. V̇O2, V̇CO2, V̇E, HR, and CS differed significantly among wetsuit conditions (p < 0.01). Respiratory exchange ratio and rating of perceived exertion also varied by wetsuit conditions (p < 0.05). However, stroke rate, length, and index were not significantly different across wetsuit conditions (p > 0.05). No differences existed between SLW and FSW for any dependent variable (p > 0.05). Results from this study suggest that swimming at the same pace without a wetsuit is the least economical, and both SLW and FSW are most and equally economical without significant kinematic changes. In addition, BS could be beneficial during training and racing in terms of less physiological demands than a regular swimsuit but not as economical as the SLW or FSW.

Effect of Arm-Ergometry Versus Treadmill Supervised Exercise on Cardiorespiratory Fitness and Walking Distances in Patients With Peripheral Artery Disease: The ARMEX Randomized Clinical Trial.

To compare arm-ergometry and treadmill supervised exercise training on cardiorespiratory fitness and walking distances in patients with peripheral artery disease (PAD). ARMEX was a single-center, single-blinded, parallel group, non-inferiority trial enrolling symptomatic patients with PAD. Patients were randomized (1:1 ratio) to a 12-wk arm-ergometry (AEx) or standard treadmill (TEx) supervised exercise training protocol. The powered primary end point was the change in peak oxygen uptake (VO2) at 12 wk, measured on a treadmill cardiopulmonary exercise test (CPX). Secondary outcomes included changes in VO2 at the first ventilatory threshold (VT-1), ventilatory efficiency (ratio of minute ventilation [VE] to carbon dioxide production [VCO2], VE/VCO2), walking distances by CPX and 6-min walking test (6MWT), and self-reported walking limitations. Fifty-six patients (66±8yr; 88% male) were randomized (AEx, n =28; TEx, n =28). At 12 wk, VO2peak change was not significantly different between groups (0.75 mL/kg/min; 95% CI, -0.94 to 2.44; P=.378), despite a significant increase only in AEx. VO2 at VT-1 improved in both groups without between-group differences, and VE/VCO2 slope improved more in AEx. The TEx attained greater improvements in walking distance by CPX (121.08 m; 95% CI, 24.49-217.66; P=.015) and 6MWT (25.08 m; 95% CI, 5.87-44.29; P=.012) and self-perceived walking distance. Arm-ergometry was noninferior to standard treadmill training for VO2peak, and treadmill training was associated with greater improvements in walking distance. Our data support the use of treadmill as a first-line choice in patients with PAD to enhance walking capacity, but arm-ergometry could be an option in selected patients.

Absolute values of regional ventilation-perfusion mismatch in patients with ARDS monitored by electrical impedance tomography and the role of dead space and shunt compensation

BackgroundAssessment of regional ventilation/perfusion (V′/Q) mismatch using electrical impedance tomography (EIT) represents a promising advancement for personalized management of the acute respiratory distress syndrome (ARDS). However, accuracy is still hindered by the need for invasive monitoring to calibrate ventilation and perfusion. Here, we propose a non-invasive correction that uses only EIT data and characterized patients with more pronounced compensation of V′/Q mismatch.MethodsWe enrolled twenty-one ARDS patients on controlled mechanical ventilation. Cardiac output was measured invasively, and ventilation and perfusion were assessed by EIT. Relative V′/Q maps by EIT were calibrated to absolute values using the minute ventilation to invasive cardiac output (MV/CO) ratio (V′/Q-ABS), left unadjusted (V′/Q-REL), or corrected by MV/CO ratio derived from EIT data (V′/Q-CORR). The ratio between ventilation to dependent regions and perfusion reaching shunted units (VD′\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{V}}_{{\ ext{D}}}^{\\prime }$$\\end{document}/QSHUNT) was calculated as an index of more effective hypoxic pulmonary vasoconstriction. The ratio between perfusion to non-dependent regions and ventilation to dead space units (QND/VDS′\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{V}}_{{{\ ext{DS}}}}^{\\prime }$$\\end{document}) was calculated as an index of hypocapnic pneumoconstriction.ResultsOur calibration factor correlated with invasive MV/CO (r = 0.65, p < 0.001), showed good accuracy and no apparent bias. Compared to V′/Q-ABS, V′/Q-REL maps overestimated ventilation (p = 0.013) and perfusion (p = 0.002) to low V′/Q units and underestimated ventilation (p = 0.011) and perfusion (p = 0.008) to high V′/Q units. The heterogeneity of ventilation and perfusion reaching different V′/Q compartments was underestimated. V′/Q-CORR maps eliminated all these differences with V′/Q-ABS (p > 0.05). Higher VD′/QSHUNT\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$V_{D}^{\\prime } /Q_{SHUNT}$$\\end{document} correlated with higher PaO2/FiO2 (r = 0.49, p = 0.025) and lower shunt fraction (ρ = − 0.59, p = 0.005). Higher QND/VDS′\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$Q_{ND} /V_{DS}^{\\prime }$$\\end{document} correlated with lower PEEP (ρ = − 0.62, p = 0.003) and plateau pressure (ρ = − 0.59, p = 0.005). Lower values of both indexes were associated with less ventilator-free days (p = 0.05 and p = 0.03, respectively).ConclusionsRegional V′/Q maps calibrated with a non-invasive EIT-only method closely approximate the ones obtained with invasive monitoring. Higher efficiency of shunt compensation improves oxygenation while compensation of dead space is less needed at lower airway pressure. Patients with more effective compensation mechanisms could have better outcomes.

Effect of Inspiratory Muscle-Loaded Exercise Training on Ventilatory Response and Intercostal Muscle Deoxygenation During Incremental Cycling Exercise

ABSTRACT Purpose: This study evaluated the effects of exercise training (ET) and inspiratory muscle-loaded exercise training (IMLET) on ventilatory response and intercostal muscle deoxygenation levels during incremental cycling exercise. Methods: Twenty-one male participants were randomly divided into IMLET (n = 10) or ET (n = 11) groups. All participants underwent a 4-week cycling exercise training at 60% peak oxygen uptake. IMLET loaded 50% of maximal inspiratory pressure (PImax). Respiratory muscle strength test, respiratory muscle endurance test (RMET), resting hypoxic ventilatory responsiveness (HVR) test, and incremental cycling test were performed pre- and post-training. Results: The extent of improvement in the PImax was significantly greater in the IMLET group (24%) than in the ET group (8%) (p = .018), and an extended RMET time was observed in the IMLET group (p < .001). Minute ventilation ( V ˙ E ) during exercise was unchanged in both groups before and after training, but tidal volume during exercise increased in the IMLET group. The increase in the exercise intensity threshold for muscle deoxygenation was similar in both groups (p < .001). HVR remained unchanged in both groups post-training. The exercise duration for the incremental exercise until reaching fatigue increased by 7.9% after ET and 6.9% after IMLET (p < .001). Conclusion: The 4-week IMLET improved respiratory muscle strength and endurance but did not alter HVR. Respiratory muscle deoxygenation was alleviated by exercise training, with a limited impact of inspiratory load training.

The Ventilatory Changes of Pediatric Peroral Endoscopic Myotomy Patients.

Peroral endoscopic myotomy (POEM) has proven to be a successful treatment method for achalasia in both adult and pediatric patients. Yet, there is a lack of evidence for anaesthetic management of pediatric patients who underwent POEM procedure. In this study, we aim to present perioperative and postoperative management strategies for pediatric patients with achalasia from in anaesthesia aspect. Medical records were reviewed for 16 pediatric patients at a single center who underwent POEM procedure for achalasia between 2017 and 2020. Patients' data regarding demographics, preoperative diet, body mass index, perioperative monitoring and vitals, airway management, anaesthesia maintenance, mechanical ventilation settings duration of recovery, length of stay, pain management and adverse events were evaluated. The study cohort included 7 female and 9 male patients with a mean age of 5.5 years. Anaesthesia maintenance was provided with 0.8-1.2 minimum alveolar concentration sevoflurane in a 40-60% O2-air mixture, Remifentanil infusion and bolus doses of Rocuronium. The median age was 3 years for patients ventilated in pressure controlled ventilation mode and 10 years in volume controlled ventilation mode. Respiration rate and minute ventilation were adjusted to maintain end tidal carbon dioxide (ETCO2) below 45 mmHg. Needle decompression was applied for 14 patients (87.5%) for treatment of capnoperitoneum. The mean procedure duration and recovery room duration were 66 (±22.9) minutes and 62 (±21) minutes, respectively. Postoperative pain management is provided with paracetamol and tramadol in total 8 patients (50%). There was no adverse event during postoperative period and all patients discharged in a mean time of 3 days. POEM has demonstrated encouraging outcomes in terms of safety and effectiveness in pediatric patients. Due to challenging nature of the pediatric patients, it is important to acknowledge that the procedure requires specialized anaesthesia management. Management of perioperative complications of increased ETCO2 requires understanding the physiologic results of pneumo-mediastinum and pneumo-peritoneum. Beside the known anaesthetic management strategies, a tailored approach should be adopted for each patient. Further investigations should be conducted to develop standardized management.

Stabilization, respiratory care and survival of extremely low birth weight infants transferred on the first day of life.

To assess stabilization, respiratory care and survival of extremely low birth weight (ELBW, <1000 g at birth) infants requiring emergency transfer to tertiary NICUs on the first day of life. Retrospective cohort study of 55 ELBW infants transported by a dedicated neonatal transport service over a 65-month period. Ventilator data were downloaded computationally. 95% of infants were intubated and received surfactant prior to transfer. Median expired tidal volume was 5.0 mL/kg (interquartile range: 4.6-6.2 mL/kg). Infants ventilated with SIPPV had significantly higher mean airway pressure and minute ventilation, but similar FiO2 compared to babies on SIMV. Blood gases showed significant improvement during transport. 55% of infants survived to discharge from NICU. Most ELBW infants transferred on the first day of life require mechanical ventilation and can be ventilated with 5 mL/kg tidal volume.

Assessment of Energy Consumption Patterns and Validation of Predictive Equations among ICU Patients at Muhimbili National Hospital in Dar es Salaam, Tanzania

Background: Nutritional support in critically-ill patients is one of the most important parameters guarding the prognosis and influencing morbidity and mortality in these patients, owing to that fact, accurate measurement of the resting energy expenditure using Indirect calorimetry is recommended by guidelines as a gold standard. But due to lack of resources and other technicalities predictive equations are conveniently used as surrogates. Aims: This study was intended to examine the extent of malnutrition, poor nutrition support practices and to validate the common used predictive equations in critically-ill patients in our setting. Methodology: A hospital-based descriptive cross-sectional study was conducted on consecutively sampled 110 mechanically ventilated ICU patients at Muhimbili National Hospital Mloganzila. Anthropometric measurements, duration of stay in ICU, Temperature and Minute Volumes were recorded so as to estimate resting energy expenditure, REE from different predictive equations. Using Indirect Calorimetry Module patient’s REE was measured and recorded then a statistical data analyzed using SPSS software version 23. Results: The prevalence of poor nutritional support was 69%; underfeeding and overfeeding were observed in 41.8% and 27.3% of all participants respectively. Prevalence of malnutrition was 51.8%; underweight and overweight were found to be in 29.1% and 22.7% of all participants respectively. The accuracy of predictive equation in ±10% difference was 30%, 45.5%, 46.4% and 68.2% in HB, MSJ, ESPEN and PENN respectively. Conclusion and Recommendation: Malnutrition and Poor Nutritional support are common problems in ICU. Predictive equations have poor accuracy and validity in comparison to indirect calorimetry. Penn State Equation was the most accurate and with the highest agreement with IC.

Cardiorespiratory failure induced by inhalation of aerosolized fentanyl in anesthetized rats

Intravenous rapid injection of fentanyl causes respiratory depression (severe apneas), leading to sudden death, which constitutes the deadliest drug reaction among overdoses of synthetic opioids. Here we asked whether acute inhalation of overdose fentanyl would also result in similar respiratory failure and death. The anesthetized and spontaneously breathing rats with tracheal cannulation were exposed to aerosolized fentanyl at 100 mg/m3 (FNTH) or 30 mg/m3 (FNTL) for 10 min. Minute ventilation (VE), electromyography (EMG) of the internal and external intercostal muscles and thyroarytenoid muscles (EMGII, EMGEI, and EMGTA), heart rate and arterial blood pressure were recorded. During the exposure, FNTH and FNTL immediately triggered bradypnea (40 % reduction, p < 0.05) with TE prolonged and then gradually decreased VE by 40 % (P < 0.05) after a brief VE recovery. The initial TE prolongation (apneas) were characterized by the cessation of EMGEI activity with enhanced tonic discharges of EMGTA and EMGII. After termination of the exposure, the cardiorespiratory responses to FNTL returned to the baseline values 30 min later, while those to FNTH were greatly exacerbated (P < 0.05), leading to ventilatory and cardiac arrest occurred 16.4 ± 4.7 min and 19.3 ± 4.5 min respectively after the onset of FNTH. The ventilatory arrest was featured by cessation of both EMGEI and EMGII and augmentation of tonic EMGTA. Our results suggest that acute exposure to an overdose of fentanyl aerosol leads to death through initially inducing a brief central and upper airway obstructive apnea as well as chest wall rigidity followed by gradual severe hypoventilation, bradycardia and hypotension, and eventual cardiorespiratory arrest in anesthetized rats.

Balloon pulmonary angioplasty for chronic thromboembolic pulmonary disease without pulmonary hypertension.

Balloon pulmonary angioplasty (BPA) is beneficial for patients with chronic thromboembolic pulmonary disease (CTEPD) with pulmonary hypertension (PH). However, the clinical benefit of BPA for the patients with CTEPD without PH remains unknown. In this study, we aimed to evaluate the efficacy, safety, and long-term outcomes of BPA in patients with CTEPD without PH. We retrospectively analyzed the data from 84 CTEPD patients with mean pulmonary artery pressure (mPAP) < 25 mmHg and 39 CTEPD patients with mPAP ≤ 20 mmHg (without PH). Among the 39 patients with CTEPD without PH, 14 underwent BPA (BPA-treated group), and the remaining 25 received no treatment (untreated group). In the patients with CTEPD without PH, BPA led to improvements in symptoms, pulmonary vascular resistance (3.6 ± 1.6 to 2.6 ± 1.1 Wood units, p < 0.001), peak oxygen consumption (16.1 ± 4.0 to 18.8 ± 4.3 mL/kg/min, p = 0.033), minute ventilation versus carbon dioxide production slope (41.4 ± 12.2 to 35.1 ± 6.7, p = 0.026), and mPAP/cardiac output slope (7.0 ± 2.6 to 4.4 ± 2.0 mmHg/L/min, p = 0.004) and facilitated the discontinuation of home oxygenation therapy, with no serious complications. Kaplan-Meier analysis showed no significant difference in all-cause mortality between the untreated and BPA-treated groups. BPA may be a safe treatment option for the patients with CTEPD without PH that can alleviate symptoms, improve exercise capacity, and facilitate weaning from home oxygen therapy. Further prospective randomized trials are needed to confirm these findings.

복식 호흡과 노래 부르기를 통한 호흡 기능 개선 영향도 분석

The objective of this study is to analyse the effects of diaphragmatic breathing and singing interventions on respiratory functions in women over 30 and to demonstrate their utility. The subjects were 46 women in their 20s from S University in C City, Chungnam, who had not yet exhibited the typical respiratory decline associated with age. A total of 12 subjects were randomly selected from this group and assigned to the control group. The experimental group comprised nine women over the age of 30, with the exception of three individuals who did not meet the established criteria for participation. All participants underwent five types of respiratory function tests using a diagnostic with the objective of assessing, assessing expiratory vital capacity, expiratory reserve volume, inspiratory reserve volume, minute ventilation, and tidal volume. The experimental group participated in a 12-session program, or comprising diaphragmatic breathing and singing for 60 minutes three times a week over four weeks. Comparing the results of respiratory function tests in the experimental group before and after the intervention, expiratory vital capacity increased by 4.5% from 2.87L to 3.00L, expiratory reserve increased by 27.5% from 0.91L to 1.16L, and minute ventilation increased by 16.7% from 7.00L/min to 8.17L/min. Consequently, this study confirms the effectiveness of diaphragmatic breathing and singing in enhancing respiratory functions and their utility in improving respiratory health. Future research could expand these findings by incorporating dance movements into an integrated approach for respiratory function improvement and psychotherapy.

The Ventilatory Ratio as a Predictor of Successful Weaning from a Veno-Venous Extracorporeal Membrane Oxygenator.

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a critical intervention for patients with severe lung failure, especially acute respiratory distress syndrome (ARDS). The weaning process from ECMO relies largely on expert opinion due to a lack of evidence-based guidelines. The ventilatory ratio (VR), which correlates with dead space and mortality in ARDS, is calculated as [minute ventilation (mL/min) x arterial pCO2 (mmHg)]/[predicted body weight × 100 × 37.5]. Objectives: The aim of this study was to determine whether the VR alone can serve as a reliable predictor of safe or unsafe liberation from VV-ECMO in critically ill patients. Methods: A multicenter retrospective analysis was conducted, involving ARDS patients undergoing VV-ECMO weaning at Massachusetts General Hospital (January 2016 - December 2020) and at the University Hospital Aachen (January 2012-December 2021). Safe liberation was defined as no need for ECMO recannulation within 48 h after decannulation. Clinical parameters were obtained for both centers at the same time point: 30 min after the start of the SGOT (sweep gas off trial). Results: Of the patients studied, 83.3% (70/84) were successfully weaned from VV-ECMO. The VR emerged as a significant predictor of unsafe liberation (OR per unit increase: 0.38; CI: 0.17-0.81; p = 0.01). Patients who could not be safely liberated had longer ICU and hospital stays, with a trend towards higher mortality (38% vs. 13%; p = 0.05). Conclusions: The VR may be a valuable predictor for safe liberation from VV-ECMO in ARDS patients, with higher VR values associated with an elevated risk of unsuccessful weaning and adverse clinical outcomes.

Tropine exacerbates the ventilatory depressant actions of fentanyl in freely-moving rats.

Our lab is investigating the efficacy profiles of tropine analogs against opioid-induced respiratory depression. The companion manuscript reports that the cell-permeant tropeine, tropine ester (Ibutropin), produces a rapid and sustained reversal of the deleterious actions of fentanyl on breathing, alveolar-arterial (A-a) gradient (i.e., index of alveolar gas exchange), and arterial blood-gas (ABG) chemistry in freely-moving male Sprague Dawley rats, while not compromising fentanyl analgesia. We report here that in contrast to Ibutropin, the injection of the parent molecule, tropine (200μmol/kg, IV), worsens the adverse actions of fentanyl (75μg/kg, IV) on ventilatory parameters (e.g., frequency of breathing, tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives), A-a gradient, ABG chemistry (e.g., pH, pCO2, pO2, and sO2), and sedation (i.e., the righting reflex), while not affecting fentanyl antinociception (i.e., the tail-flick latency) in freely-moving male Sprague Dawley rats. These data suggest that tropine augments opioid receptor-induced signaling events that mediate the actions of fentanyl on breathing and alveolar gas exchange. The opposite effects of Ibutropin and tropine may result from the ability of Ibutropin to readily enter peripheral and central cells. Of direct relevance is that tropine, resulting from the hydrolysis of Ibutropin, would combat the Ibutropin-induced reversal of the adverse effects of fentanyl. Because numerous drug classes, such as cocaine, atropine, and neuromuscular blocking drugs contain a tropine moiety, it is possible that their hydrolysis to tropine has unexpected/unintended consequences. Indeed, others have found that tropine exerts the same behavioral profile as cocaine upon central administration. Together, these data add valuable information about the pharmacological properties of tropine.

Association of dead space fraction to mortality in patients with COVID-19-related ARDS: A historical cohort observational study

ObjectiveTo assess the correlation of dead space fraction (VD/VT) measured through time capnography, corrected minute volume (CMV) and ventilation ratio (VR) with clinical outcomes in COVID-19 patients requiring invasive mechanical ventilation. DesignObservational study of a historical cohort. SettingUniversity hospital in Medellin, Colombia. ParticipantsPatients aged 15 and above with a confirmed COVID-19 diagnosis admitted to the ICU and requiring mechanical ventilation. InterventionsMeasurement of VD/VT, CMV, and VR in COVID-19 patients. Main variables of interestVD/VT, CMV, VR, demographic data, oxygenation indices and ventilatory parameters. ResultsDuring the study period, 1047 COVID-19 patients on mechanical ventilation were analyzed, of whom 446 (42%) died. Deceased patients exhibited a higher prevalence of advanced age and obesity, elevated Charlson index, higher APACHE II and SOFA scores, as well as an increase in VD/VT ratio (0.27 in survivors and 0.31 in deceased) and minute ventilation volume on the first day of mechanical ventilation. The multivariate analysis revealed independent associations to in-hospital mortality, higher VD/VT (HR 1.24; 95%CI 1.003–1.525; p = 0.046), age (HR 1.024; 95%CI 1.014–1.034; p < 0.001), and SOFA score at onset (HR: 1.036; 95%CI: 1.001–1.07; p = 0.017). ConclusionsVD/VT demonstrated an association with mortality in COVID-19 patients with ARDS on mechanical ventilation. These findings suggest that VD/VT measurement may serve as a severity marker for the disease.

Diamedica Draw-over Vaporiser: bench testing the UK Defence Anaesthesia System in the deployed environment

IntroductionThe Diamedica Draw-over Vaporiser 2 (DDV2) is the sevoflurane vaporiser used by the UK Defence Medical Services to provide deployed volatile general anaesthesia. The Defence Anaesthesia System employs the DDV2...

Prognostic utility of cardiopulmonary exercise testing with simultaneous exercise echocardiography in heart failure with preserved ejection fraction.

Cardiopulmonary exercise testing (CPET) combined with exercise echocardiography (CPETecho) allows simultaneous assessments of cardiac, pulmonary, and ventilation in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to determine whether simultaneous assessment of CPET variables could provide additive predictive value over exercise stress echocardiography in patients with dyspnoea. CPETecho was performed in 443 patients with suspected HFpEF (240 HFpEF and 203 controls without HF). Patients with HFpEF were divided based on peak oxygen consumption (VO2, ≥10 or <10 ml/min/kg) or the slope of minute ventilation to carbon dioxide production (VE vs. VCO2 slope ≥45.0 or <45.0). The primary endpoint was defined as a composite of all-cause mortality, HF hospitalization, unplanned hospital visits requiring intravenous diuretics, or intensification of oral diuretics. During a median follow-up of 399 days, the composite outcome occurred in 57 patients. E/e' ratio during peak exercise was associated with adverse outcomes. Patients with HFpEF and lower peak VO2 had increased risks of the composite event (hazard ratio [HR] 5.05, 95% confidence interval [CI] 2.65-9.62, p < 0.0001 vs. controls; HR 3.14, 95% CI 1.69-5.84, p = 0.0003 vs. HFpEF with higher peak VO2). Elevated VE versus VCO2 slope was also associated with adverse events in HFpEF. The addition of either the presence of abnormal peak VO2 or VE versus VCO2 slope increased the predictive ability over the model based on age, sex, atrial fibrillation, left atrial volume index, and exercise E/e' (p < 0.05). These data provide new insights into the role of CPETecho in patients with HFpEF.

Time-restricted feeding reveals a role for neural respiratory clocks in optimizing daily ventilatory-metabolic coupling in mice.

The master circadian clock, located in the suprachiasmatic nuclei (SCN), organizes the daily rhythm in minute ventilation (VE). However, the extent that the daily rhythm in VE is secondary to SCN-imposed O2 and CO2 cycles (i.e., metabolic rate), or driven by other clock mechanisms, remains unknown. Here, we experimentally shifted metabolic rate using time-restricted feeding (without affecting light-induced synchronization of the SCN) to determine the influence of metabolic rate in orchestrating the daily VE rhythm. Mice eating predominantly at night exhibited robust daily rhythms in O2 consumption (VO2), CO2 production (VCO2), and VE with similar peak times (~ZT18) that were consistent with SCN organization. However, feeding mice exclusively during the day separated the relative timing of metabolic and ventilatory rhythms, resulting in a ~8.5-hr advance in VCO2, and a disruption of the VE rhythm, suggesting opposing circadian and metabolic influences on VE. To determine if the molecular clock of cells involved in the neural control of breathing contribute to the daily VE rhythm, we examined VE in mice lacking BMAL1 in Phox2b-expressing respiratory cells (i.e., BKOP mice). The ventilatory and metabolic rhythms of predominantly night-fed BKOP mice did not differ from wild-type mice. However, in contrast to wild-type mice, exclusive day feeding of BKOP mice led to an unfettered daily VE rhythm with a peak time aligning closely with the daily VCO2 rhythm. Taken together, these results indicate that both daily VCO2 changes and intrinsic circadian time-keeping within Phox2b respiratory cells are predominant orchestrators of the daily rhythm in ventilation.