Increased Work Of Breathing Research Articles

PSAT190 Denosumab use for life-threatening hypercalcemia of malignancy in a toddler. A weight base dose

Abstract Introduction Denosumab, an inhibitor of receptor activator of nuclear factor kappa-B ligand, has emerged as an important novel therapy for osteoporosis, hypercalcemia of malignancy (HCM), and other skeletal disorders in adults. While off-label use has been reported in children with these conditions, pediatric data is limited. We report a case of a 35-month old patient who had received Denosumab for management of life-threatening HCM. Case 2-year-old male previously healthy who presented with increase work of breathing, altered mental status, and changes in his voice in the setting of progressive neck swelling over 2-weeks. Initial workup revealed a large mediastinal mass and metabolic anomalies including hypercalcemia (21.6mg/dL), shortened QTc on ECG, and acute kidney injury (AKI) stage 1-2 (eGFR 71 ml/min/1.73m2). Flow cytometry confirmed diagnosis of T-Cell ALL. PTHrP was 8.6pmol/L with a PTH of 7.1Pg/ml and a 25OH vitamin D of 38.9Ng/ml with 1,25OH of 6pg/ml. On admission, patient started maintenance IV fluids, dexamethasone, calcitonin, and denosumab 0.3mg/kg. His calcium normalized by day 2-3 of treatment and eventually started oral calcium supplementation (25mg/kg elemental) with calcitriol to prevent hypocalcemia. Calcium stabilized with the lowest level at 7.6mg/dL on day 7; did not require IV calcium correction during hospitalization and renal function normalized. Patient was discharged on 0.5 mcg of calcitriol daily and 125mg/kg/day of elemental calcium. Discussion HCM develops in less than 1% of pediatric patients with cancer. Most cases are due to systemic parathyroid hormone-related protein, followed by osteolytic metastases leading to inflammatory cytokines locally released and least common via ectopic production of 1,25 dihydroxy vitamin D. HCM is an oncologic emergency. In adults, Denosumab has been used for HCM as a second-line agent after failure to respond to bisphosphonates, or when they are contraindicated. Bisphosphonates have shown to worsen renal function, even in those with normal glomerular filtration. Denosumab has been overall very well tolerated by patients. Initial hypocalcemia that peaks between days 4–10, and rebound hypercalcemia are one of the more feared side effects. Despite Denosumab not been cleared by the kidney, in adult patients with AKI or CKD, they have a higher risk of developing rebound hypercalcemia after receiving the standard 120mg SQ dose; a weight base dose was proposed, 0.3mg/kg for those with renal impairment. The reported dose in pediatrics for HCM has been 120mg, but we decided to do a weight base dose as our patient had AKI at presentation, with increased risk for decompensation once chemotherapy was started. Our patient responded very well to Denosumab with improvement in hypercalcemia, without severe hypocalcemia requiring IV calcium supplementation. Incidentally, to the best of our knowledge, our patient is the youngest patient reported to have received Denosumab for management of HCM. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Diving ergospirometry with suspended weights: breathing- and fin-swimming style matter

PurposeScuba diving is a complex condition including elevated ambient pressure, limited air supply, increased breathing work, and unfamiliar fin-swimming. Earlier approaches to assess diving specific data did not comprehensively address these aspects. We first present an underwater ergospirometry system and then test the hypothesis that both breathing characteristics and fin-swimming style affect the air consumption.Methods/ParticipantsA suspended-weights ergospirometry system was mounted inside a hyperbaric chamber. Ergo group: 25 divers (24.6 ± 4.1 years); three set-ups: dry normobaric cycling (75–225 W), dry cycling at 20 m simulated depth (75–225 W), fin-swimming at 20 m (5–8 kg suspended weights). Style group: 20 other divers (24.6 ± 4.1 years): fin-swimming at 20 m (5–8 kg) with regard to ventilation (dot{V}E) and fin-swimming style.ResultsErgo group: linear heart rate and oxygen uptake (dot{V}O2) increases with both 50 W-bicycle steps and suspended-weights ergometry (r = 0.97). During hyperbaric conditions, dot{V}E was less increased versus normobaric conditions. Style group: the more efficient hip/thigh-oriented style shifted towards the knee/calf-oriented style. dot{V}E and dot{V}O2 were higher in beginners (< 100 dives) versus advanced divers (≥ 100 dives). Significant differences on the 5 kg-step: dot{V}E: 31.5 ± 7.1 l/min vs. 23.7 ± 5.9 l/min and dot{V}O2: 1.6 ± 0.3 l/min vs. 1.2 ± 0.3 l/min. A comparison is presented, in addition to illustrate the impact of differences in breathing characteristics and fin-swimming style.ConclusionsDiving ergospirometry with suspended weights in a hyperbaric chamber allows for comprehensive studies. Little diving experience in terms of breathing characteristics and fin-swimming style significantly increases dot{V}E thereby increasing the risk of running-out-of-air.

The effects of face mask specifications on work of breathing and particle filtration efficiency

The outbreak of the ongoing coronavirus disease 2019 (COVID-19) pandemic has led to the recommended routine use of face masks to reduce exposure risk. In this study, the increase in work of breathing (WOB) imposed by face masks is theoretically studied for both normals and patients with obstructive and restrictive lung diseases at different levels of activity. The results show a significant increase in WOB due to face masks, which is more severe in higher activity levels. The added WOB is considerable during physical activity and may be intolerable for patients with preexisting lung disease and may contribute to inspiratory muscle fatigue and dyspnea. Moreover, in this study, the effects of the physical properties of a fibrous medium, including thickness, porosity, and fiber diameter, are analyzed on the particle filtration efficiency (PFE) and the added WOB. The relations between the physical properties of the fibrous medium and the added WOB and the PFE are shown on some contour plots as a quick and simple tool to select the desired physical properties for a single layer filter to ensure that the added WOB is comfortable while the PFE is sufficiently high.

Pulmonary Effects of Sustained Periods of High-G Acceleration Relevant to Suborbital Spaceflight.

AbstractBACKGROUND: Members of the public will soon be taking commercial suborbital spaceflights with significant Gx (chest-to-back) acceleration potentially reaching up to 6 Gx. Pulmonary physiology is gravity-dependent and is likely to be affected, which may have clinical implications for medically susceptible individuals.METHODS: During 2-min centrifuge exposures ranging up to 6 Gx, 11 healthy subjects were studied using advanced respiratory techniques. These sustained exposures were intended to allow characterization of the underlying pulmonary response and did not replicate actual suborbital G profiles. Regional distribution of ventilation in the lungs was determined using electrical impedance tomography. Neural respiratory drive (from diaphragm electromyography) and work of breathing (from transdiaphragmatic pressures) were obtained via nasoesophageal catheters. Arterial blood gases were measured in a subset of subjects. Measurements were conducted while breathing air and breathing 15 oxygen to simulate anticipated cabin pressurization conditions.RESULTS: Acceleration caused hypoxemia that worsened with increasing magnitude and duration of Gx. Minimum arterial oxygen saturation at 6 Gx was 86 1 breathing air and 79 1 breathing 15 oxygen. With increasing Gx the alveolar-arterial (A-a) oxygen gradient widened progressively and the relative distribution of ventilation reversed from posterior to anterior lung regions with substantial gas-trapping anteriorly. Severe breathlessness accompanied large progressive increases in work of breathing and neural respiratory drive.DISCUSSION: Sustained high-G acceleration at magnitudes relevant to suborbital flight profoundly affects respiratory physiology. These effects may become clinically important in the most medically susceptible passengers, in whom the potential role of centrifuge-based preflight evaluation requires further investigation.Pollock RD, Jolley CJ, Abid N, Couper JH, Estrada-Petrocelli L, Hodkinson PD, Leonhardt S, Mago-Elliott S, Menden T, Rafferty G, Richmond G, Robbins PA, Ritchie GAD, Segal MJ, Stevenson AT, Tank HD, Smith TG. Pulmonary effects of sustained periods of high-G acceleration relevant to suborbital spaceflight. Aerosp Med Hum Perform. 2021; 92(7):633641.

Cardiopulmonary Pathophysiological Aspects in the Context of COVID-19 and Obesity.

Obesity is a significant public health concern associated with high morbidity. Obese patients are at risk of severe COVID-19 infection, and obesity is a high-risk factor for admission to the intensive care unit. We aimed to write a narrative review of cardiac and pulmonary pathophysiological aspects of obese patients in the context of COVID-19 infection. Obesity affects lung volume, with a decrease in expiratory reserve volume, which is associated with a decrease in lung and chest wall compliance, an increase in airway resistance, and an increase in work of breathing. Obesity affects cardiac structure and hemodynamics. Obesity is a risk factor for hypertension and cardiovascular disorders. Moreover, obesity is associated with a low-grade inflammatory state, endothelial dysfunction, hyperinsulinemia, and metabolic disorders. Obesity is associated with severe COVID-19 and invasive mechanical ventilation. These previous cardiopulmonary pathological aspects may explain the clinical severity in obese patients with COVID-19. Obese patients are at risk of severe COVID-19 infection. Understanding cardiorespiratory pathophysiological aspects may help physicians manage patients in hospitals.

Effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of airway secretions in endotracheal tubes: substudy of a randomized clinical trial

BackgroundAccumulated airway secretions in the endotracheal tube increase work of breathing and may favor airway colonization eventually leading to pneumonia. The aim of this preplanned substudy of the ‘Preventive Nebulization of Mucolytic Agents and Bronchodilating Drugs in Intubated and Ventilated Intensive Care Unit Patients trial’ (NEBULAE) was to compare the effect of routine vs on-demand nebulization of acetylcysteine with salbutamol on accumulation of secretions in endotracheal tubes in critically ill patients.ResultsIn this single-center substudy of a national multicenter trial, patients were randomized to a strategy of routine nebulizations of acetylcysteine with salbutamol every 6 h until end of invasive ventilation, or to a strategy with on-demand nebulizations of acetylcysteine or salbutamol applied on strict clinical indications only. The primary endpoint, the maximum reduction in cross-sectional area (CSA) of the endotracheal tube was assessed with high-resolution computed tomography. Endotracheal tubes were collected from 72 patients, 36 from patients randomized to the routine nebulization strategy and 36 of patients randomized to the on-demand nebulization strategy. The maximum cross-sectional area (CSA) of the endotracheal tube was median 12 [6 to 15]% in tubes obtained from patients in the routine nebulization group, not different from median 9 [6 to 14]% in tubes obtained from patients in the on-demand nebulization group (P = 0.33).ConclusionIn adult critically ill patients under invasive ventilation, routine nebulization of mucolytics and bronchodilators did not affect accumulation of airway secretions in the endotracheal tube.Trial registration Clinicaltrials.gov Identifier: NCT02159196

EVALUATION AND MANAGEMENT OF UNILATERAL DIAPHRAGMATIC PARALYSIS IN SYMPTOMATIC CYSTIC FIBROSIS PATIENT

SESSION TITLE: Medical Student/Resident Genetic and Developmental Disorders Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Diaphragmatic paralysis is a condition commonly associated with trauma, neurologic compromise, or systemic disease. Unilateral diaphragmatic paralysis (UDP) is more common than bilateral disease and uncommonly results in respiratory symptoms. However, this case details a presentation of UDP in a 23-year-old CF patient that resulted in progressively worsening lung function necessitating surgical correction. CASE PRESENTATION: TL is a 23 year old male with CF who presented with a 4-week history of worsening dyspnea, productive cough, chest tightness, and decreased exercise capacity. He was hospitalized and started on IV antibiotics. During hospitalization, patient underwent radiology which showed progression of disease via CT, PFT, and BD testing. Patient was discharged home after 6 weeks with a lack of improvement in lung function and given home IV antibiotics. A clinic follow-up appointment was scheduled to assess lung function following home IV. At 4-week follow up he reported worsening shortness of breath and his PFT did not show improvement. Physical exam showed significant increase in work of breathing lying down as compared to sitting upright. Chest X-ray was concerning for significant elevation of right hemi-diaphragm. A repeat chest CT confirmed elevation of right hemi diaphragm with progressive fibrosis. He underwent bronchoscopy and BAL which confirmed patent airways. He underwent sniff testing using flouroscopic guidance which confirmed paralyzed right hemi diaphragm with paradoxical motion. The combined results were felt to be consistent with idiopathic unilateral diaphragmatic paralysis leading to rapid decline in lung function. The patient underwent right thoracotomy and plication of right hemi diaphragm. Patient tolerated surgery well. At 6 weeks follow-up he had significant improvement in his shortness of breath, quality of life and exercise capacity. His PFT recovered to baseline and are now stable. DISCUSSION: UDP is often asymptomatic but underlying heart or lung disease, such as CF, significantly worsens dyspnea in patients with UDP(1). The most common causes of UDP include postsurgical complications, trauma, infection and neurological disease. CF drugs like aminoglycosides, colistin, linezolid and atypical infections can potentially lead to diaphragmatic weakness with significant loss of lung function (2). The work-up for diagnosing diaphragmatic weakness is extremely important, especially in CF, and this case demonstrates the breadth of etiologies that can be investigated. CONCLUSIONS: Diaphragmatic dysfunction is an important and underdiagnosed cause of shortness of breath. It can negatively affect quality of life, indicate disease severity, and be potentially prognostic. Although paralysis can often be due to phrenic nerve dysfunction, this presentation is an example of drug and/or infection-induced paralysis that can lead to significant loss of lung function. Reference #1: Armstrong, J. D. (2012). Dysfunction of the diaphragm [4]. New England Journal of Medicine, 366(21), 2036–2037 Reference #2: Wilcox, P.G., Pardy, R.L. (1989) Diaphragmatic weakness and paralysis. Lung 167, 323–341 DISCLOSURES: Advisory Committee Member relationship with PARI Please note: $1001 - $5000 Added 03/31/2020 by Nauman Chaudary, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Novartis Please note: $1001 - $5000 Added 03/31/2020 by Nauman Chaudary, source=Web Response, value=Consulting fee No relevant relationships by Radu Mitran, source=Web Response

SUN-182 When Insulin Is Not Enough...

Introduction: Multiple factors contribute to hyperglycemia in hospitalized patients, such as underlying medical conditions, pathophysiological stress, and medications. The development of transient insulin resistance is a known cause of hyperglycemia in both diabetic and non-diabetic patients. Rarely, patients can develop extreme insulin resistance, defined as having an insulin requirement of more than 3 units/kg/day. We report a case of extreme insulin resistance in a patient admitted with diabetic ketoacidosis (DKA) mediated by anti-insulin receptor antibodies. Case: 91 y/o F with history of CLL and IDDM (diagnosed three months prior, Last Hemoglobin A1C 14.2%) that was brought to the ED by EMS after being found covered in urine, lethargic and confused. On admission, she was found to be tachycardic, afebrile, normotensive, BMI 28.71. On physical exam she was diaphoretic and altered, but moving all extremities. She showed no findings consistent with acromegaly, hirsutism, red striae, moon-like facies, buffalo hump, or acanthosis nigricans. Initial labs included pronounced leukocytosis of 29.24, potassium of 5.9, glucose of 655, Anion Gap 25, HCO3 4, Beta Hydroxybutyrate 91.55, Lactic Acid 4.1, BUN 33, and a serum Cr of 1.49. UA showed: +30 protein, +80 ketones, Glucose >500, (-) nitrite and leukocyte esterase, & 2+ WBCs. The urine was positive for Bence Jones Protein Lambda Type. Her Kappa/Lambda Ratio was WNLs at 1.42 mg/L. UCx & BCx were negative. Patient was admitted to the ICU with an insulin drip following our hospital’s DKA protocol. After admission, she became hypotensive with increase work of breathing, for which she was intubated and started on vasopressin. On the second day of admission, Endocrinology was consulted due to inability to control blood glucose levels despite maximizing the rate of IV insulin infusion and persistent acidosis. Additional labs revealed a normal TSH, FT4, AM cortisol, IGF-1 27 ng/mL, AM Glucagon, Troponin, CEA and CA-125. Hemoglobin A1C was 8.9%. On the third day of admission, patient’s blood glucose levels persisted in the 400s-500s despite increasing her insulin infusion to 21 units/h and adding 15 units of HumuLIN R/per hour plus Insulin Glargine 40 units twice daily. She received over 900,000 U of insulin in the first 72 hours of hospitalization. In the setting of critical condition without a clear path to recovery, the family decided to pursue palliative care with comfort measures. Patient expired two hours after palliative extubation. Four days after patient expired, the blood work for the antibodies was received. The results were consistent with Negative Islet Cell Antibody, Negative GAD-65 Ab, & Positive Insulin Autoantibody (more than 50 U/ML). Conclusion: This case highlights the importance of considering immune-mediated IR along with other more common causes of IR in hospitalized patients with marked insulin demands.

The Nocturnal Respiratory Rate in COPD Patients of Varying GOLD Severity with/without Nicotine Consumption: Calculation by Means of Breath Sound Analysis

Respiratory rate is an important risk marker and enables early detection of critically ill and vulnerable patients in clinical routine. The aim of this pilot study with 31 patients (COPD severity levels II - IV) was to determine the mean nocturnal respiratory rate based on breath sound recordings and to investigate the dependence of respiratory rate on COPD severity level and smoker status. The mean respiratory rate of the total collective was 19/min. For the COPD-GOLD severity levels, no significant differences in mean respiratory rate could be observed. When nicotine consumption is taken into account, active smokers showed a significantly higher mean respiratory rate of 20.84 ± 4.45/min compared to non-smokers with 17.41 ± 3.14/min (p < 0.05). In addition, active smokers in the study were significantly more frequent among patients with night-time wheezing (60 % vs. 23.8 %). This might suggest that smokers need to perform increased breathing work with increased breathing rate to compensate for oxygen deficiency in bronchial obstruction. The results of the present study show that with the acoustic recording of breath sounds, a reliable representation and calculation of the breath frequency is possible.

Impact of Spontaneous Breathing Trial on Work of Breathing Indices Derived From Esophageal Pressure, Electrical Activity of the Diaphragm, and Oxygen Consumption in Children.

The present study aimed to characterize the behavior of 3 components of respiratory muscle function during mechanical ventilation weaning in children to better understand the respective impact of a spontaneous breathing trial on ventilatory mechanical action (esophageal pressure [Pes], ventilatory demand (electrical activity of the diaphragm [EAdi]), and oxygen consumption. This was a prospective single-center study. All children > 1 months and <18 y old who were intubated and on mechanical ventilation, and who were hospitalized in the pediatric ICU were eligible. Subjects considered as ready to extubate were included. Simultaneous recordings of oxygen consumption, Pes, and EAdi were performed during 3 steps: before, during, and after the spontaneous breathing test. Twenty subjects (median age, 5.5 mo) were included. Half of them were admitted for a respiratory cause. The increase in Pes swings and esophageal pressure-time product during the spontaneous breathing trial was not significant (P = .33 and P = .75, respectively), and a similar trend was observed with peak EAdi (P = .06). Oxygen consumption obtained by indirect calorimetry was stable in the 3 conditions (P = .98). In these children who were critically ill, a spontaneous breathing trial induced a moderate and nonsignificant increase in work of breathing, as reflected by the respiratory drive with EAdi and respiratory mechanics with Pes. However, indirect calorimetry did not seem to be a sensitive tool to assess respiratory muscle function during the weaning phase in children who were on mechanical ventilation, especially when work of breathing was slightly increased.

CON: Persistent Central Sleep Apnea/Hunter-Cheyne-Stokes Breathing, Despite Best Guideline-Based Therapy of Heart Failure With Reduced Ejection Fraction, Is Not a Compensatory Mechanism and Should Be Suppressed.

CON: Persistent Central Sleep Apnea/Hunter-Cheyne-Stokes Breathing, Despite Best Guideline-Based Therapy of Heart Failure With Reduced Ejection Fraction, Is Not a Compensatory Mechanism and Should Be Suppressed.

Respiratory muscular response to obstructive maneuvers in non-invasively ventilated healthy subjects

The hypothesis of this study is that muscular activity measured through surface electromyography (sEMG) is useful to estimate the work of breathing (WOB) and respiratory mechanics. Thirty-two healthy volunteers were non-invasively ventilated, and an airflow resistor was attached to the airway circuit. sEMG signals from diaphragm, intercostal and sternocleidomastoid muscles were processed and compared with WOB changes.The airway resistance was increased from a median of 9.58 to 22.51 cmH2O/L/s adding a resistance of 20 cmH2O/L/s, achieving the lower compliance too. The respiratory mechanics changes implied linear increases in WOB, with Pearson correlation of 88.43% respect to changes in resistance. Muscles increased their activity in agreement with changes of WOB, being higher the increment in diaphragm followed by sternocleidomastoid.The non-invasively monitored respiratory muscles activity allowed evaluating the changes in WOB when it depends on addition of obstructive loads, confirming that it could be used to improve the available respiratory mechanics and WOB monitoring tools.

An unexpected adult onset genetic disease in a former late preterm infant

An 8-week-old, former 35 weeker boy, was admitted to the hospital for increased work of breathing, cough, and stridor. Given his arrival in winter, respiratory viruses were suspected but workup including RSV and influenza returned negative. Instead, his physical examination revealed a significant pectus excavatum, micrognathia, hypospadias, and sacral dimples. He also possessed stridor that was both inspiratory and expiratory, worsening with changes in neck position. Subsequent investigation for intra- and extrathoracic obstruction including tracheomalacia, vascular rings and airway polyps with CT angiogram and esophagram returned negative. ENT was subsequently …

Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model.

Here we examine the organ level toxicology of both carbon black (CB) and silver nanoparticles (AgNP). We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF). C57Bl6/J male mice were intratracheally instilled with saline (control), low (0.05 μg/g) or high (0.5 μg/g) doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D) content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.

Respiratory Sensations in Dynamic Hyperinflation: Physiological and Clinical Applications.

Dynamic hyperinflation is a common cause of dyspnea and functional limitation in patients with emphysema. Dynamic hyperinflation occurs in individuals with air-flow limitation when expiratory time is decreased during periods of relative tachypnea (such as during exercise or agitation, for example). In this setting, patients with emphysema develop lung hyperinflation, impairment of inspiratory respiratory muscles, and an increase in work of breathing. The associated decrease in inspiratory capacity results in the stimulation of several receptors, including chemoreceptors and pulmonary receptors, which signal the brain to increase tidal volume. The inability of the respiratory system to respond to signals of increased demand (eg, by enlarging tidal volume and increasing inspiratory flow) results in a dissociation between afferent and efferent signaling thereby intensifying breathing discomfort, or what clinicians term dyspnea. A thorough understanding of the physiology of dyspnea and pathophysiology of dynamic hyperinflation informs the interventions used to mitigate sensations of dyspnea and the physiologic effects of dynamic hyperinflation, respectively. Pharmacotherapy, pulmonary rehabilitation, breathing techniques, positive airway pressure, and lung volume reduction are well-studied interventions that target pathways to dyspnea in patients with dynamic hyperinflation.

Work of Breathing in Fixed and Pressure Relief Continuous Positive Airway Pressure (C-Flex™): A post hoc Analysis

Background: Expiratory pressure relief continuous positive airway pressure (pressure relief CPAP; C-Flex™) causes increases in inspiratory duty cycle and shortening of expiratory time. It has been suggested that these changes are caused by an increase in work of breathing. Objectives: We studied the effects of C-Flex on work of breathing and intrinsic positive end-expiratory pressure as compared to fixed CPAP. Methods: Work of breathing was analyzed in 24 patients with obstructive sleep apnea during treatment with fixed CPAP and C-Flex with 3 different pressure relief settings in a randomized order during rapid-eye-movement (REM) and non-REM sleep. Work of breathing was assessed on a breath-by-breath basis using a piezoelectric esophageal pressure catheter and a pneumotachograph for measuring airflow. Results: We found there was no increase in inspiratory work of breathing observed using C-Flex compared to fixed CPAP. Instead, we found a linear decrease in inspiratory work of breathing with increasing pressure relief, with a mean difference of 1.22 J/min between CPAP and maximum pressure release (C-Flex 3; 90% of the value with nasal CPAP); however, the decrease was not statistically significant. The decrease in inspiratory work of breathing associated with C-Flex has a significant inverse correlation with BMI. Conclusions: The C-Flex technology does not change work of breathing but shows a tendency towards a reduction of inspiratory work of breathing in patients with a lower BMI using higher C-Flex. The effect is probably caused by diminishing airway resistance generated by the positive end-expiratory pressure. Our findings may lead to additional fields of application of the C-Flex technology, such as chronic obstructive pulmonary disease or muscular dystrophy.

Metabolic Requirement of Septic Shock Patients Before and After Liberation From Mechanical Ventilation.

This study identified the difference in energy expenditure and substrate utilization of patients during and upon liberation from mechanical ventilation. Patients under intensive care who were diagnosed with septic shock and dependent on mechanical ventilation were recruited. Indirect calorimetry measurements were performed during and upon liberation from mechanical ventilation. Thirty-five patients were recruited (20 men and 15 women; mean age, 69 ± 10 years). Measured energy expenditures during ventilation and upon liberation were 2090 ± 489 kcal·d-1 and 1910 ± 579 kcal·d-1, respectively ( P < .05). Energy intake was provided at 1148 ± 495 kcal·d-1 and differed significantly from all measured energy expenditures ( P < .05). Mean carbohydrate utilization was 0.19 ± 0.1 g·min-1 when patients were on mechanical ventilation compared with 0.15 ± 0.09 g·min-1 upon liberation ( P < .05). Mean lipid oxidation was 0.08 ± 0.05 g·min-1 during and 0.09 ± 0.07 g·min-1 upon liberation from mechanical ventilation ( P > .05). Measured energy expenditure was higher during than upon liberation from mechanical ventilation. This could be the increase in work of breathing from the continuous positive pressure support, repeated weaning cycles from mechanical ventilation, and/or the asynchronization between patients' respiration and ventilator support. Future studies should examine whether more appropriately matching energy expenditure with energy intake would promote positive health outcomes.

Pulse Oximetry As A Non-Invasive Method of Predicting Respiratory Compensation During Graded Exercise

Respiratory compensation (ResComp) during exercise is associated with an increase in work of breathing, decrease in economy, and initiation of the slow component of VO2 kinetics. Therefore, ResComp may be ideal for gauging an athlete’s training status. Acute metabolic acidosis at ResComp fosters weaker oxyhemoglobin association, reflected by a dip in arterial oxygen saturation (SaO2). Pulse oximetry, used to measure SaO2, may serve as an inexpensive, non-invasive method to predict ResComp. PURPOSE: The purpose of this study was to explore the validity of using SaO2 as a simple, non-invasive predictor of oxygen consumption (VO2), heart rate (HR), and respiratory exchange ratio (RER) at ResComp using different graded exercise test (GXT) protocols. METHODS: Sixteen active, healthy college students (n=16) performed a GXT to maximum on a motorized treadmill using either a three minute (n=7), one minute (n=4), or thirty second (n=5) graded protocol. Using indirect calorimetry, RespComp was determined separately by the V-slope method (V-slope), the ventilatory threshold method in which an a-linear increase in ventilatory equivalent for O2 corresponded with a decrease in peak end-tidal CO2 (PetCO2), and by detecting an a-linear decrease in SaO2 using pulse oximetry. Mixed-design repeated measures ANOVAs were used to analyze differences in the VO2, HR, and RER at ResComp across the three methods, and three GXT protocols. RESULTS: There were no significant differences in VO2 at ResComp; 3.2 l/min ± 0.9 (V-Slope), 3.2 l/min ± 0.9 (PetCO2), and 3.3 l/min ± 0.9 (SaO2); HR at ResComp; 177.1 bpm ± 6.6 (V-Slope), 177.1 bpm ± 5.3 (PetCO2), and 180.7 bpm ± 4.8 (SaO2); and RER at ResComp; 1.1 ± 0.1 (V-Slope), 1.1 ± 0.1 (PetCO2), and 1.1 ± 0.1(SaO2). There was a significant correlation in VO2 between PetCO2 and SaO2 methods used to determine ResComp (r2 = 0.93, p< 0.01). There were no significant differences among ResComp measurement methods and GXT protocols in predicting ResComp HR (p=.243); VO2 (p=.199); and RER (p=.117). CONCLUSION: Monitoring a drop in SaO2 using pulse oximetry may be a simple, non-invasive method of predicting ResComp, thereby serving as a useful tool for endurance programming and assessment.

Work of Breathing into Snow in the Presence versus Absence of an Artificial Air Pocket Affects Hypoxia and Hypercapnia of a Victim Covered with Avalanche Snow: A Randomized Double Blind Crossover Study.

Presence of an air pocket and its size play an important role in survival of victims buried in the avalanche snow. Even small air pockets facilitate breathing. We hypothesize that the size of the air pocket significantly affects the airflow resistance and work of breathing. The aims of the study are (1) to investigate the effect of the presence of an air pocket on gas exchange and work of breathing in subjects breathing into the simulated avalanche snow and (2) to test whether it is possible to breathe with no air pocket. The prospective interventional double-blinded study involved 12 male volunteers, from which 10 completed the whole protocol. Each volunteer underwent two phases of the experiment in a random order: phase “AP”—breathing into the snow with a one-liter air pocket, and phase “NP”—breathing into the snow with no air pocket. Physiological parameters, fractions of oxygen and carbon dioxide in the airways and work of breathing expressed as pressure-time product were recorded continuously. The main finding of the study is that it is possible to breath in the avalanche snow even with no air pocket (0 L volume), but breathing under this condition is associated with significantly increased work of breathing. The significant differences were initially observed for end-tidal values of the respiratory gases (EtO2 and EtCO2) and peripheral oxygen saturation (SpO2) between AP and NP phases, whereas significant differences in inspiratory fractions occurred much later (for FIO2) or never (for FICO2). The limiting factor in no air pocket conditions is excessive increase in work of breathing that induces increase in metabolism accompanied by higher oxygen consumption and carbon dioxide production. The presence of even a small air pocket reduces significantly the work of breathing.

Impact of nitroglycerin infusion on weaning off hypertensive mechanically ventilated chronic obstructive pulmonary disease patients

IntroductionMechanical ventilation (MV) weaning trial can be compared to a cardiac stress test where spontaneous ventilation is a form of an exercise and therefore hemodynamic compromise can occur during the weaning process in critically ill patients. The combined increase in arterial pressure and heart rate during unsuccessful weaning is quite suggestive of weaning failure of cardiac origin. Assessment and prediction of weaning failure from cardiac origin remain complicated in patients with chronic obstructive pulmonary disease (COPD). Recent data showed that COPD itself is a powerful independent risk factor for cardiovascular morbidity and mortality, suggesting that occult cardiac dysfunction could be frequent in patients with COPD. The immediate transition from positive pressure mechanical ventilation to spontaneous ventilation may generate significant cardiopulmonary alterations that are complex and mainly include the inspiratory fall in intrathoracic pressure, the increase in work of breathing, and the catecholamine discharge that occur during abrupt transfer from mechanical ventilation to spontaneous breathing. Therefore, it could be suggested that a treatment targeting the cardiovascular system decreasing the preload might help the heart to tolerate the critical period of weaning more effectively. MethodsThis study was carried on 60 adult male and female patients admitted to the Critical Care Medicine Departments in the Alexandria Main University Hospital and who fulfilled the diagnosis of acute exacerbation of COPD according to the Global initiative for chronic obstructive lung disease (GOLD) [1], and considered eligible for weaning after at least 24h of invasive mechanical ventilation exhibiting systemic arterial hypertension during the start of spontaneous breathing trial. 30 of them were adult patients and served as the study group (Group I), and the other 30 were age-matched adults who served as the control group (Group II). Each group was subjected to spontaneous breathing trial (SBT) using a T-piece receiving FiO2 the same as during mechanical ventilation. Control group underwent SBT alone while the nitroglycerin group underwent continuous nitroglycerin infusion started at the beginning of the SBT and titrated to maintain normal arterial systolic blood pressure that is; 120–139mmHg). Hemodynamic, oxygenation and respiratory measurements were performed on the start of SBT, and after a 2-h T-piece SBT. ResultsCompared to the start of SBT, systolic arterial blood pressure and mean arterial blood pressure decreased [from (Mean±SD) 150.33±14.26, 112.56±9.37mmHg to 134.33±11.04, 92.78±5.81mmHg, respectively] in the nitroglycerin group, while the opposite occurred in the control group as systolic arterial blood pressure and mean arterial blood pressure increased [from (Mean±SD) 144.67±13.58, 109.78±10.09mmHg to 158.0±19.43, 114.73±10.82mmHg, respectively]. Mixed central venous saturation (ScvO2) decreased significantly in the control group at the end of SBT [from (Mean±SD) 71.90±1.84 to 69.25±2.20%], while in the nitroglycerin group, ScvO2 did not change at the end in comparison to the start of SBT [from (Mean±SD) 71.63±1.75 to 71.12±1.65%]. Nitroglycerin infusion at the start of SBT enabled a successful weaning from mechanical ventilation in 90% of patients in comparison to a successful weaning from mechanical ventilation of only 63.3% in the control group. ConclusionsNitroglycerin infusion might facilitate the weaning off hypertensive COPD patients by alleviating the cardiovascular compromise occurring during liberation from MV.