Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Airway dimensions from fetal life to adolescence-A literature overview

BACKGROUND Data on airway dimensions in pediatric patients are important for proper selection of pediatric airway equipment such as endotracheal tubes, double-lumen tubes, bronchial blockers, or stents. The aim of the present work was to provide a synopsis of the available data on pediatric airway dimensions. METHODS A systematic literature search was carried out in the PubMed database, Scopus, Embase, Web of Science, Prisma, and Google Scholar and secondarily completed by a reference search. Based on inclusion and exclusion criteria, a final selection of 109 studies with data on pediatric airway dimensions published from 1923 to 2018 were further analyzed. RESULTS Six different airway measurement methods were identified. They included anatomical examinations, chest X-ray, computed tomography, magnetic resonance tomography, bronchoscopy, and ultrasound. Anatomical studies were more abundant compared to other methods. Data provided were very heterogeneously presented and powered. In addition, due to different study conditions, they are hardly comparable. Among all, anatomical and computer tomography studies are thought to provide the most reliable data. Ultrasound is an upcoming technique to estimate airway parameters of fetus and premature infants. There was, in general, a lack of comprehensive studies providing a complete range of airway dimensions in larger groups of patients from birth to adolescence. CONCLUSIONS This work revealed a large heterogeneity of studies providing data on pediatric airway dimensions, making it impossible to compare, or assemble them to normograms for clinical use. Comprehensive studies in large population of children are needed to provide full range nomograms on pediatric airway dimensions

Effect of Lanz Pressure Regulating Valve on Self-sealing Mechanism and Air Leakage Across the Tracheal Tube Cuffs in a Benchtop Model

Background: The aim of the present study was to investigate the effect of the Lanz system on air sealing by self-inflation in high volume-low pressure (HVLP) tube cuffs. Methods: In vitro tracheal air sealing was studied in HVLP tracheal tube cuffs (internal diameter [ID] 8.0 mm) made from polyurethane ([PU] Seal Guard tracheal tube, Covidien, Athlone, Ireland) and from polyvinylchloride ([PVC] HiLo tracheal tube, Covidien) with and without Lanz pressure regulating valve. Tube cuffs were placed in a vertical 22 mm ID artificial trachea and inflated to 5, 10, 15, 20, 25, or 30 cm H(2)O cuff pressures. Pressure control ventilation with peak inspiratory pressures (PIPs) of 20 or 25 cm H(2)O was applied and air leakage was assessed spirometrically as the ratio of expiratory to inspiratory tidal volumes. Nonparametric Mann-Whitney test was applied to compare the air leakage with and without Lanz system for both cuff types at each cuff pressure and PIP (P < .05). Results: The PVC tube cuffs with Lanz system resulted in significant air leakage at both 20 and 25 cm H(2)O PIP as compared to those without the Lanz system, especially at cuff pressures lower than the preset PIP (P < .05). Although PU tube cuffs with Lanz system showed reduced air sealing when compared with cuffs without Lanz, the difference was not statistically significant. Conclusion: Cuff pressure compensation with the Lanz system during cyclic respiratory pressure changes interferes with the self-sealing mechanism in HVLP tube cuffs at cuff pressures lower than PIP level. This results in larger air leak across tube cuffs particularly in tube cuffs made from PVC

Insertion of cuff inflation line into pediatric tracheal tubes related to oral and nasal tracheal intubation depth

BACKGROUND In clinical practice, the cuff inflation line of cuffed pediatric tracheal tubes often interferes with securing tracheal tubes. METHODS The insertion site of the cuff inflation lines and the lengths of four different brands and nine sizes of commonly used cuffed pediatric tracheal tubes were measured and compared in vitro with oral and nasotracheal intubation depths as calculated by different formulas for pediatric patients aged from birth to 16 years. Motoyama's recommendation was used for age-related size selection of cuffed pediatric tracheal tubes. RESULTS The proportion of the distance from the tracheal tube tip to the insertion site of the cuff inflation line varied considerably between the tracheal tubes (Microcuff: 48.5-60.7%; Parker: 48.7-73.2%; Ruesch: 59.1-77.8%; and Shiley: 46.0-60.3%). Using different formulas for oral or nasotracheal intubation depth, the insertion site of the cuff inflation line was placed within the oral or nasal cavity or within an area 1 cm beyond the teeth or the nostrils in almost all tracheal tubes tested. Positioning the insertion site 2 cm from the proximal end of the tracheal tubes resulted in a cuff line-free tube area of ≥1 cm in all orally and almost in all nasally inserted tracheal tubes, considering maximum recommended tracheal intubation depths. CONCLUSION The cuff inflation line in almost all commonly used cuffed pediatric tracheal tubes interferes with securing the tracheal tube due to its insertion site into the tracheal tube. This potentially carries the risk of kinking, obstruction, or damage to the cuff inflation line with ensuing failure to deflate or inflate the cuff. The proposed position of the insertion of the cuff inflation line 2 cm from the proximal end of the tracheal tube would ensure a 1-cm-wide cuff line-free circular area beyond the oral or nasal cavity in nearly all assessed tracheal tube sizes

Cuffed pediatric endotracheal tubes-Outer cuff diameters compared to age-related airway dimensions

BACKGROUND Reliable sealing of the pediatric airway requires appropriately sized tracheal tube cuffs. The aim of this study was to compare residual cuff diameters of pediatric tracheal tubes with pediatric airway dimensions. METHODS Cuff diameters of five different brands of locally marketed pediatric cuffed tracheal tubes with internal diameters of 3.0-7.0 mm were measured at a cuff pressure of 20 cm H$_{2}$ O and compared with cuff diameters indicated by their manufacturers. The latter values were compared to tracheal dimensions using the Motoyama and Khine formulas for cuffed tracheal tube size selection. RESULTS There is considerable heterogeneity in cuff diameters among pediatric tracheal tube brands, except for two brands from different manufacturers (Halyard and Parker Medical) which were identically designed. Cuffs made from polyurethane revealed fewer differences (91%-118%) between measured and manufacturer-indicated values for outer cuff diameters than did those made from polyvinylchloride (91%-146%). Particularly in smaller sized tracheal tubes, cuffs did not reach 100% of the tracheal lateral diameter, while others were oversized in larger tracheal tubes, independent of the two formulas used for cuffed tracheal tube size selection. Cuff diameters indicated by the manufacturer corresponded to 86%-188% of the median and 68%-157% of the maximum mid-tracheal lateral diameter of the corresponding upper age range. CONCLUSION Our findings show that many of the cuff diameters of currently marketed tracheal tube brands lack an age-related anatomical rationale. A proposal for age-related anatomically based cuff diameters is provided for both recommendations for cuffed tracheal tube size selection in children

Inflation volume-balloon diameter and inflation pressure-balloon diameter characteristics of commonly used bronchial blocker balloons for single-lung ventilation in children

BACKGROUND Balloon-tipped bronchial blocker catheters are widely used in pediatric thoracic anesthesia to establish single-lung ventilation. In clinical practice, their balloons demonstrate sudden expansion when inflated with air. In addition, there are concerns related to the high inflation pressures required to expand the balloons. METHODS This in vitro study assessed inflation volume- and inflation pressure-balloon diameter characteristics of the Fogarty arterial embolectomy catheters and Arndt endobronchial blockers. Balloon diameters were photographically assessed during unrestricted volume- and pressure-guided inflation, using air up to the maximum allowed inflation volume as indicated by the manufacturers. Inflation pressures required to open the blocker balloons and inflation pressures needed to expand them to maximum indicated diameter were measured. RESULTS Volume-guided inflation demonstrated a late acute rise in diameter in Fogarty blocker balloons, whereas in the Arndt endobronchial blocker balloons almost linear inflation volume-to-diameter characteristics were observed. Pressure-guided inflation on the other hand demonstrated low-volume, high-pressure characteristics in the Fogarty blocker balloons, with inflation pressures required to expand the balloons to maximum diameters ranging from (mean (SD)) 636 (75) to 947 (152) cmH$_{2}$ O. The inflation pressures required to open the Fogarty blocker balloons were even >1000 cmH$_{2}$ O. Inflation pressures required to expand the 5 F, 7 F, and 9 F Arndt endobronchial blocker balloons to maximum indicated diameter were much lower, namely at 218 (15), 252 (28), and 163 (8) cmH$_{2}$ O. CONCLUSION Based on these study findings, the balloons of Fogarty arterial embolectomy catheters represent high-pressure devices and do not permit stepwise controlled bronchial blockage. The Arndt endobronchial blockers have some advantages over the Fogarty blocker devices, but also represent high-pressure equipment and must be used with caution and limited duration. Manufacturers are asked to design pediatric endobronchial blocker catheters with truly high-volume, low-pressure balloons in accordance to age-related pediatric airway dimensions

Pediatric airway dimensions-A summary and presentation of existing data

BACKGROUND Age-related pediatric airway dimension reference values for cricoid, tracheal, and bronchial diameters as well as tracheal and bronchial lengths are essential for distinguishing normal from pathological airway findings and for manufacturing and selecting appropriately sized airway equipment. AIM The aim of this work was to summarize and present existing pediatric airway dimension data for the larynx, trachea, and main stem bronchi from fetus to adolescence. METHODS A systematic literature search was carried out using PubMed, Scopus, Embase, and Google Scholar. Publications containing original data on pediatric airway dimensions as mean or median in tabular form and spanning narrow age groups of 1 or 2 years were included in our study. Original data such as diameters, lengths, and cross-sectional areas of trachea, cricoid, left and right main bronchi in fetuses and children were collected and presented as figures. RESULTS Pediatric airway dimension data were gathered and compiled from 15 studies fulfilling the inclusion criteria. Data were obtained from different measurement methods such as autopsy, chest X-ray, computed tomography, magnetic resonance imaging, rigid and flexible bronchoscopy as well as ultrasound examinations. There was considerable variation among age-related data due to biologic heterogeneity, different presentation of data, different definitions, and various measurement techniques. CONCLUSION This investigation revealed heterogeneous data on pediatric airway dimensions, making it impossible to compile them into standard reference values for airway dimensions. New studies with structured and standardized measurements and data presentation in large populations of children are required to provide more valid pediatric airway dimension data

Simulated dimensional compatibility of uncuffed and cuffed tracheal tubes for selective endobronchial intubation in children

Background: Cuffed tracheal tubes have recently been recommended for selective endobronchial intubation to establish single-lung ventilation even in smaller children. This implies that, compared with uncuffed tracheal tubes, the cuffed tracheal tubes selected will be smaller and therefore have a shorter length. We hypothesized that cuffed tracheal tubes might be of insufficient length for selective endobronchial intubation if the tube cuff were fully immersed in the left or right mainstem bronchus. Methods: The distance from the proximal end of the tracheal tube to the upper border of the cuff in cuffed tracheal tubes and to the upper margin of the Murphy eye in uncuffed tracheal tubes, respectively, was assessed in sizes 3.0-7.0 mm internal diameter. The raw data sets of two previously performed studies obtained from 337 children aged from birth to 16 years, including the distances "teeth to tracheal tube tip" and "tracheal tube tip to carina," were used to calculate age-, weight-, and height-related data for the distance from "teeth to carina." Tracheal tube dimensions were compared with age-related distances from "teeth to carina," applying published recommendations for the selection of uncuffed and cuffed tracheal tubes for selective endobronchial intubation in children. Results: The differences between the length of the age-related tracheal tube and the tracheal tube insertion length required to guarantee full insertion of the tracheal tube cuff or the Murphy eye within the mainstem bronchus ranged from -3.5 to 52.6 mm in cuffed tracheal tubes and from 42.3 to 83.3 mm in uncuffed tracheal tubes. Conclusions: For many age groups of patients requiring selective endobronchial intubation, the lengths of cuffed tracheal tubes, in contrast to those of uncuffed tracheal tubes, were revealed to be critically short for safe taping outside the oral cavity with the cuff placed completely within the right or left mainstem bronchus