Respiratory function and symptoms after acute COVID-19 infection in children and adolescents

Introduction/Aim: Significant long-term effects on both symptomatology and respiratory function have been recognised in adult populations after COVID-19 infection, termed 'Long COVID'. These have caused loss of productivity and increased need for healthcare services. This study aimed to measure symptoms and lung function in children and adolescents after acute COVID-19 infection Methods: Between June 1 and 31 October 2021 there were 144 children admitted to hospital across the Sydney Children's Hospital Network, Australia. Of these, 63 children were referred to the respiratory clinic with symptoms of ongoing cough, shortness of breath and fatigue, 3-6 months post COVID infection. 20 of these children performed reliable lung function. For these children, body plethysmography and double diffusion testing were performed within 3-6 months of their infection. The Liverpool respiratory questionnaire and PROMIS paediatric sleep questionnaires were also administered. Result(s): Of the 20 patients tested, 7 had COVID pneumonitis requiring hospitalisation during the acute illness. 6 of the 20 patients had significant persistent symptoms as measured by the Liverpool respiratory questionnaire, while none of the children had any significant sleep symptoms. All children had preserved spirometry within normal limits. Of note, 2 children with persistent respiratory symptoms had DLNO/DLCO ratio >1.15, suggesting pulmonary vascular disease. The same two children who had elevated DLNO / DLCO had high ventilator equivalents on CPET testing suggesting increased physiological dead space ventilation. Despite this, their peak aerobic capacity was within normal limits. There were no significant differences between the alpha and delta cohorts or between children treated at home vs those requiring hospitalisation during their infection. Conclusion(s): COVID-19 may cause long-lasting effects in children. In this cohort, all children maintained spirometry results within normal limits despite significant symptoms impacting daily activities. Double diffusion testing may shed some light on lung changes leading to persistent symptomatology after COVID infection.

Association between pulmonary extravascular water, dead space, and clinical outcome in intubated patients with COVID ARDS

Introduction: The aim of this study was to determine whether there is an association between extravascular lung water index (EVLWi) and physiological respiratory dead space (VDphys/VT) and to determine if these factors are associated with the possibility to being discharged alive on day 28. Method(s): We analyzed a prospective cohort of patients with COVID ARDS supported with invasive mechanical ventilation (IMV) admitted in our ICU who were monitored with volumetric capnography and transpulmonary thermodilution (TPTD). First day TDTP and VDphys/VT were considered. Bohr-Enghoff formula was used to obtain VDphys/ VT. This protocol was approved by the local IRB and informed consent was waived. Result(s): 31 patients with matched TPTD and VDphys/VT during the first 24 h were analyzed in who EVLWi correlated with VDphys/VT (r = 0.599 p = 0.002), however, EVLWi did not associated with PaFi. Patients with EVLWi > 10 ml/kg had higher APACHE II and VDphys/VT. These patients had a lower cumulative incidence to be discharged alive on day 28 with aHR 7.3 [1.4-39.1] p = 0.02 (adjusted by APACHE II and VDphys/VT, Fig. 1A). Remarkably, patients with EVLWi > 10 ml/ kg + VDphys/VT > 57% had worse outcome compared to those who had EVLWi > 10 ml/kg + VDphys/VT < 57% (25% vs 75%, p = 0.032, Fig. 1B). Conclusion(s): In patients with COVID ARDS supported with IMV, VDphys/VT give prognostic data additional to EVLWi.

Effectiveness of the Air-Filled Technique to Reduce the Dead Space in Syringes and Needles during ChAdox1-n CoV Vaccine Administration.

In the current study, we calculated the vaccine volume and amount of dead space in a syringe and needle during ChAdox1-n CoV vaccine administration using the air-filled technique. The aim is to reduce the dead space in syringes and needles in order to administer up to 12 doses per vial. The hypothetical situation uses a vial with a similar size as the ChAdox1-n CoV vial. We used distilled water (6.5 mL) to fill the same volume as five vials of ChAdox1-n CoV. When 0.48 mL of distilled water is drawn according to the number on the side of the barrel, an additional 0.10 mL of air can be used in the dead space of the distilled water in the syringe and needle for 60 doses, which can be divided into an average of 0.5 mL per dose. ChAdox1-n CoV was administered using a 1-mL syringe and 25G needle into 12 doses using this air-filled technique. The volume of the recipient vaccine will increase by 20% and save on the budget for low dead space syringes (LDS).

Is COVID-19 different from other causes of acute respiratory distress syndrome?

Coronavirus disease 2019 (COVID-19) pneumonia can lead to acute hypoxemic respiratory failure. When mechanical ventilation is needed, almost all patients with COVID-19 pneumonia meet the criteria for acute respiratory distress syndrome (ARDS). The question of the specificities of COVID-19-associated ARDS compared to other causes of ARDS is of utmost importance, as it may justify changes in ventilatory strategies. This review aims to describe the pathophysiology of COVID-19-associated ARDS and discusses whether specific ventilatory strategies are required in these patients.

Blockchain-based digital trust mechanism: a use case of cloud manufacturing of LDS syringes for COVID-19 vaccination

Trust is essential in the digital world. It is a critical task to build digital trust for the ongoing digital engineering transformation. Aiming at developing a blockchain-based digital trust mechanism for Cloud Manufacturing or Manufacturing-as-a-Service (MaaS), in this paper, we use the manufacturing of low dead space (LDS) medical syringes through Cloud Manufacturing as a motivating scenario to develop a basic framework. To meet the need of optimally saving COVID-19 vaccine doses to save more lives, the medical device manufacturing community needs to make a swift move to meet the surged need for LDS syringes. Cloud Manufacturing is a form of emerging Digital Manufacturing facilitated with Cloud/Edge Computing, the Internet of Things, and other digital technologies. Cloud manufacturing allows quickly establishing a digital virtual enterprise that pools together various manufacturing resources worldwide to meet the surged needs of products and save cost and time. Trusting the product quality and safety is a significant challenge when using Cloud Manufacturing to manufacture the products. This paper proposes a schema of blockchain-based digital trust mechanisms with examples of using Cloud Manufacturing of medical LDS syringes for the urgent needs of catering COVID-19 vaccination. © 2023 - The authors. Published by IOS Press.

Evaluation of covid-19 lung involvement effect on exercise capacity in the 3rd and 6th months

Objective: Since Covid-19 was detected in December 2019, it has become evident that it causes different clinical courses. However, the long-term effect of acute severity of disease on systems is still unclear, particularly on exercise capacity. The aim of this study is to evaluate the effect of covid-19 lung involvement on the patients' exercise capacity with cardiopulmonary exercise test (CPET) in the post-covid 3rd and 6th months. Material-Methods: This is a prospective observational study. Between March 2021 and october 2021 76 patients,39 of these with covid-19 lung involvement, who are directed our exercise test laboratory enrolled to the study. All patients underwent pulmonary function and diffusion tests, 6-minute walking test and cpet. Result(s): A total of 76 patients, 31 females and 45 males, were evaluated. While Covid-19 patients with lung involvement were older than without lung involvement (49+/-14 vs 33+/-10, respectively, p=0.0001), body mass index was high in without lung involvement (26+/-4 vs 28+/-4, respectively, p=0.02). D-dimer and fibrinojen were high in lung involvement group (351+/-59 vs 134+/-21, 323+/-75 vs 230+/-43, p=0.002, p=0.0001, respectively). In third and sixth monts there was no differrence peak oygen consumption (VO2) between the groups (p=0.08). Of note, the results of the CPET revealed that lung-involvement group had low ventilatory efficiency (low breathing reserve (BR), and high physiological dead space/tidal volume ratio, VD/VT) (p=0.002, p=0.009, respectively) Conclusion(s): Our study showed that the effect of covid-19 lung involvement to restrict exercise capacity continues at 6 months.

Dead space ventilation-related indices: bedside tools to evaluate the ventilation and perfusion relationship in patients with acute respiratory distress syndrome.

Cumulative evidence has demonstrated that the ventilatory ratio closely correlates with mortality in acute respiratory distress syndrome (ARDS), and a primary feature in coronavirus disease 2019 (COVID-19)-ARDS is increased dead space that has been reported recently. Thus, new attention has been given to this group of dead space ventilation-related indices, such as physiological dead space fraction, ventilatory ratio, and end-tidal-to-arterial PCO2 ratio, which, albeit distinctive, are all global indices with which to assess the relationship between ventilation and perfusion. These parameters have already been applied to positive end expiratory pressure titration, prediction of responses to the prone position and the field of extracorporeal life support for patients suffering from ARDS. Dead space ventilation-related indices remain hampered by several deflects; notwithstanding, for this catastrophic syndrome, they may facilitate better stratifications and identifications of subphenotypes, thereby providing therapy tailored to individual needs.

Persistent P Plateau Pressure Elevation Versus Sporadic: Which Is a Better Indicator of Mortality?

INTRODUCTION: ARDS net trial recommends keeping low tidal volumes (6-8 cc/IBW) and plateau pressures less than 30 cm H20. However, it is not well studied if sporadic elevation or continuous elevation of plateau pressures results in poor outcomes. We hypothesize that persistent elevation of p plat for >24 hrs. or > 6 times (measured 4 hrs. apart) continuously is associated with increased mortality. METHOD(S): Retrospective chart review of patients admitted with COVID-19 during the surge of August to September 2021 at Houston Methodist Baytown hospital. Inclusion Criteria- COVID-19 patients with respiratory failure, ards and intubated. Plateau pressures are recorded every 4 hrs. Data obtained from EPIC ICU flowsheet. Persistent elevation was defined as all the plateau pressures measured for > 24 hrs. and are continuously elevated. Exclusion criteria - patients admitted to ICU with cardiac arrest, patients who are covid negative and covid positive, but no ARDS are excluded. Tidal volume recorded is when the first highest p plateau pressure was documented. Descriptive statistics and t-tests were used to interpret the results. RESULT(S): Out of a total of 48 patients, only 12 patients survived, and 36 patients died. Mortality rate- 75%. Survivors vs. non survivors average Age(y) 42 vs.55 (p< 0.05), Tidal volume 5.98 ml/PBW vs.6.03 ml/PBW (p=0.105), Normal elastance 4.06 vs. 4.07(p=0.44), Delta P 22 vs.23(p=0.27) and ventilatory ratio 84 vs. 98(p< 0.05) were calculated during maximum plateau pressures. In patients with continuous p plat >30, 29 (85%) patients died and 5 (15%) survived. OR- 5.8 (P< 0.05). Out of the 5 patients that survived 2 went on ECMO. Intermittent p plat elevation was noted in 11 out of 14 patients who did not have continuous p plat elevation. CONCLUSION(S): Ventilatory ratio, a simple index of impaired ventilation and physiological dead space was higher in nonsurvivors compared with survivors. Continuous p plat elevation for more than 24 hrs. that is resistant to intervention might be an indirect indicator of worsening lung ventilation and increasing mortality. Rather than a single-time daily measurement of variables like delta P or p plateau pressure multiple measurements and trends might be helpful to prognosticate patients that might have poor outcomes and indicate worsening lung function.

Physiological response to prone positioning in intubated adults with COVID-19 acute respiratory distress syndrome: a retrospective study.

BACKGROUND: COVID-19 related acute respiratory distress syndrome (ARDS) has specific characteristics compared to ARDS in other populations. Proning is recommended by analogy with other forms of ARDS, but few data are available regarding its physiological effects in this population. This study aimed to assess the effects of proning on oxygenation parameters (PaO2/FiO2 and alveolo-arterial gradient (Aa-gradient)), blood gas analysis, ventilatory ratio (VR), respiratory system compliance (CRS) and estimated dead space fraction (VD/VT HB). We also looked for variables associated with treatment failure. METHODS: Retrospective monocentric study of intubated COVID-19 ARDS patients managed with an early intubation, low to moderate positive end-expiratory pressure and early proning strategy hospitalized from March 6 to April 30 2020. Blood gas analysis, PaO2/FiO2, Aa-gradient, VR, CRS and VD/VT HB were compared before and at the end of each proning session with paired t-tests or Wilcoxon tests (p < 0.05 considered as significant). Proportions were assessed using Fischer exact test or Chi square test. RESULTS: Forty-two patients were included for a total of 191 proning sessions, median duration of 16 (5-36) hours. Considering all sessions, PaO2/FiO2 increased (180 [148-210] vs 107 [90-129] mmHg, p < 0.001) and Aa-gradient decreased (127 [92-176] vs 275 [211-334] mmHg, p < 0.001) with proning. CRS (36.2 [30.0-41.8] vs 32.2 [27.5-40.9] ml/cmH2O, p = 0.003), VR (2.4 [2.0-2.9] vs 2.3 [1.9-2.8], p = 0.028) and VD/VT HB (0.72 [0.67-0.76] vs 0.71 [0.65-0.76], p = 0.022) slightly increased. Considering the first proning session, PaO2/FiO2 increased (186 [165-215] vs 104 [94-126] mmHg, p < 0.001) and Aa-gradient decreased (121 [89-160] vs 276 [238-321] mmHg, p < 0.001), while CRS, VR and VD/VT HB were unchanged. Similar variations were observed during the subsequent proning sessions. Among the patients who experienced treatment failure (defined as ICU death or need for extracorporeal membrane oxygenation), fewer expressed a positive response in terms of oxygenation (defined as increase of more than 20% in PaO2/FiO2) to the first proning (67 vs 97%, p = 0.020). CONCLUSION: Proning in COVID-19 ARDS intubated patients led to an increase in PaO2/FiO2 and a decrease in Aa-gradient if we consider all the sessions together, the first one or the 4 subsequent sessions independently. When considering all sessions, CRS increased and VR and VD/VT HB only slightly increased.

Correlation between increased D-dimer in blood with dead space in patients with COVID-19 and acute respiratory distress syndrome

Introduction: Since December 2019, a number of cases of CoV2/COVID-19 severe acute respiratory syndrome (SARS) pneumonia in Wuhan China have been identified as a cause of acute respiratory failure and have spread around the world at high speed. Due to the large number of cases and the need to better understand this condition, tools are required to grade the intensity and vital prognosis of patients. The objective of this study is to determine the relationship between the dead space measured by volumetric capnography or ventilatory ratio and the increase in D-dimer levels in patients diagnosed with COVID-19 pneumonia and who meet the Berlin criteria for Acute Respiratory Distress Syndrome (ARDS). Materials and methods: A single-centre observational study of a prospective cohort on the use of D-dimer and the correlation with dead space. Adults older than 18 years with a diagnosis of pneumonia due to COVID-19 and ARDS hospitalized in the intensive care units of Hospital Santa Clara in Bogotá, Colombia, from August 2020 to July 2021 were included. Results: The study included 67 patients, all with a confirmed SARS-CoV-2 diagnosis, no association was found between D-dimer and dead space on day 1 and 3 of hospitalization in the ICU. Conclusions: D-dimer was not correlated with increased dead space in our study and was not associated with relevant outcomes in patients with ARDS. © 2022 Asociación Colombiana de Medicina Crítica y Cuidado lntensivo

Altered lung physiology in two cohorts after COVID-19 infection as assessed by computed cardiopulmonography.

The longer-term effects of COVID-19 on lung physiology remain poorly understood. Here, a new technique, computed cardiopulmonography (CCP), was used to study two COVID-19 cohorts (MCOVID and C-MORE-LP) at both ∼6 and ∼12 mo after infection. CCP is comprised of two components. The first is collection of highly precise, highly time-resolved measurements of gas exchange with a purpose-built molecular flow sensor based around laser absorption spectroscopy. The second component is estimation of physiological parameters by fitting a cardiopulmonary model to the data set. The measurement protocol involved 7 min of breathing air followed by 5 min of breathing pure O₂. One hundred seventy-eight participants were studied, with 97 returning for a repeat assessment. One hundred twenty-six arterial blood gas samples were drawn from MCOVID participants. For participants who had required intensive care and/or invasive mechanical ventilation, there was a significant increase in anatomical dead space of ∼30 mL and a significant increase in alveolar-to-arterial Po₂ gradient of ∼0.9 kPa relative to control participants. Those who had been hospitalized had reductions in functional residual capacity of ∼15%. Irrespectively of COVID-19 severity, participants who had had COVID-19 demonstrated a modest increase in ventilation inhomogeneity, broadly equivalent to that associated with 15 yr of aging. This study illustrates the capability of CCP to study aspects of lung function not so easily addressed through standard clinical lung function tests. However, without measurements before infection, it is not possible to conclude whether the findings relate to the effects of COVID-19 or whether they constitute risk factors for more serious disease.NEW & NOTEWORTHY This study used a novel technique, computed cardiopulmonography, to study the lungs of patients who have had COVID-19. Depending on severity of infection, there were increases in anatomical dead space, reductions in absolute lung volumes, and increases in ventilation inhomogeneity broadly equivalent to those associated with 15 yr of aging. However, without measurements taken before infection, it is unclear whether the changes result from COVID-19 infection or are risk factors for more severe disease.

Breathing pattern, accessory respiratory muscles work, and gas exchange evaluation for prediction of NIV failure in moderate-to-severe COVID-19-associated ARDS after deterioration of respiratory failure outside ICU: the COVID-NIV observational study.

BACKGROUND: Data on the efficacy of non-invasive ventilation (NIV) after progression of respiratory failure in patients who have already received oxygen therapy, or CPAP outside ICU is limited. The study aimed to find predictors of NIV failure based on breathing pattern, gas exchange, and accessory respiratory muscles evaluation in patients who progressed to moderate-to-severe COVID-19 ARDS. METHODS: This was a prospective observational study in patients with moderate-to-severe COVID-19-ARDS on NIV (n = 80) admitted to COVID-ICU of Sechenov University. The combined success rate for conventional oxygen and CPAP outside ICU was 78.6% (440 of 560 patients). The primary endpoints were intubation rate and mortality. We measured respiratory rate, exhaled tidal volume (Vte), mean peak inspiratory flow (PIF), inspiratory time (Ti), PaO2, SpO2, end-tidal carbon dioxide (PETCO2), and Patrick score, and calculated ROX index, PaO2/FiO2, ventilatory ratio, and alveolar dead space (Vdalv/Vt) on Days 1, 3, 5, 7, 10, and 14. For all significant differences between NIV success and failure groups in measured data, we performed ROC analysis. RESULTS: NIV failure rate in ICU after deterioration of respiratory failure outside ICU was 71.3% (n = 57). Patients with the subsequent NIV failure were older at inclusion, more frail, had longer duration of disease before ICU admission, and higher rate of CPAP use outside ICU. ROC-analysis revealed that the following respiratory parameters after 48 h of NIV can serve as a predictors for NIV failure in moderate-to-severe COVID-19-associated ARDS: PaO2/FiO2 < 112 mmHg (AUROC 0.90 (0.93-0.97), p < 0.0001); PETCO2 < 19.5 mmHg (AUROC 0.84 (0.73-0.94), p < 0.0001); VDalv/VT > 0.43 (AUROC 0.78 (0.68-0.90), p < 0.0001); ROX-index < 5.02 (AUROC 0.89 (0.81-0.97), p < 0.0001); Patrick score > 2 points (AUROC 0.87 (0.78-0.96), p = 0.006). CONCLUSION: In patients who progressed to moderate-to-severe COVID-19-ARDS probability of NIV success rate was about 1/3. Prediction of the NIV failure can be made after 48 h based on ROX index < 5.02, PaO2/FiO2 < 112 mmHg, PETCO2 < 19.5 mmHg, and Patrick score > = 2. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667923 , registered on 16/12/2020.

A portable system for CO2and pressure monitoring inside the dead space of face masks

This paper presents a portable system designed to monitor physical and chemical quantities inside the dead space of face masks that are commonly used to prevent the diffusion of SARS-CoV-2 infection. The system is a 'side stream' analyzer that continuously samples the gas inside the gap between the mask and the user mouth and provides, in real time, the temporal evolution of CO2 concentration, differential pressure and temperature. These quantities are related to the mask behaviour in term of breath resistance, CO2 accumulation and overheating that, in turn, can cause physiological side effects and a feeling of discomfort. These effects become more relevant when the masks are employed during physical activities, such as team sports, and for this reason the system has been designed to have a reduced weight and dimensions as well as a reduced invasiveness of the sampling line. The paper also proposes a measurement procedure for the evaluation of the CO2 inspired volume in real conditions during the physical activity. At the current stage, the proposed procedure is only able to provide qualitative measurements, but it can work in real conditions and it does not require bulky and expensive facilities as the ones required by the actual international standards for the certification of respiratory protective devices. © 2022 IEEE.

Early prolonged prone position in noninvasively ventilated patients with SARS-CoV-2-related moderate-to-severe hypoxemic respiratory failure: clinical outcomes and mechanisms for treatment response in the PRO-NIV study.

BACKGROUND: Whether prone position (PP) improves clinical outcomes in COVID-19 pneumonia treated with noninvasive ventilation (NIV) is unknown. We evaluated the effect of early PP on 28-day NIV failure, intubation and death in noninvasively ventilated patients with moderate-to-severe acute hypoxemic respiratory failure due to COVID-19 pneumonia and explored physiological mechanisms underlying treatment response. METHODS: In this controlled non-randomized trial, 81 consecutive prospectively enrolled patients with COVID-19 pneumonia and moderate-to-severe (paO2/FiO2 ratio < 200) acute hypoxemic respiratory failure treated with early PP + NIV during Dec 2020-May 2021were compared with 162 consecutive patients with COVID-19 pneumonia matched for age, mortality risk, severity of illness and paO2/FiO2 ratio at admission, treated with conventional (supine) NIV during Apr 2020-Dec 2020 at HUMANITAS Gradenigo Subintensive Care Unit, after propensity score adjustment for multiple baseline and treatment-related variables to limit confounding. Lung ultrasonography (LUS) was performed at baseline and at day 5. Ventilatory parameters, physiological dead space indices (DSIs) and circulating inflammatory and procoagulative biomarkers were monitored during the initial 7 days. RESULTS: In the intention-to-treat analysis. NIV failure occurred in 14 (17%) of PP patients versus 70 (43%) of controls [HR = 0.32, 95% CI 0.21-0.50; p < 0.0001]; intubation in 8 (11%) of PP patients versus 44 (30%) of controls [HR = 0.31, 95% CI 0.18-0.55; p = 0.0012], death in 10 (12%) of PP patients versus 59 (36%) of controls [HR = 0.27, 95% CI 0.17-0.44; p < 0.0001]. The effect remained significant within different categories of severity of hypoxemia (paO2/FiO2 < 100 or paO2/FiO2 100-199 at admission). Adverse events were rare and evenly distributed. Compared with controls, PP therapy was associated with improved oxygenation and DSIs, reduced global LUS severity indices largely through enhanced reaeration of dorso-lateral lung regions, and an earlier decline in inflammatory markers and D-dimer. In multivariate analysis, day 1 CO2 response outperformed O2 response as a predictor of LUS changes, NIV failure, intubation and death. CONCLUSION: Early prolonged PP is safe and is associated with lower NIV failure, intubation and death rates in noninvasively ventilated patients with COVID-19-related moderate-to-severe hypoxemic respiratory failure. Early dead space reduction and reaeration of dorso-lateral lung regions predicted clinical outcomes in our study population. CLINICAL TRIAL REGISTRATION: ISRCTN23016116 . Retrospectively registered on May 1, 2021.

Understanding dead space in giraffes, and its application to critically ill COVID-19 patients

Giraffes have long been a subject of study for scientists due to the physiological anomaly their anatomical design can present. The study of the species helps aid in understanding of clinically relevant processes. The long trachea of a giraffe presents the dilemma of exaggerated dead space;however, this physiological problem is surmounted by a narrow trachea when compared to mammals of similar size, thus decreasing potential dead space. As COVID-19 patients in the hospital and ICU can develop COVID-19 associated acute respiratory distress syndrome, limiting excess dead space in COVID-19 patients is favorable. Removing additional tubing for a patient with an endotracheal tube in a ventilator circuit could help lower the patient's PaCO2 and raise their pH.

Increased respiratory dead space could associate with coagulation activation and poor outcomes in COVID-19 ARDS.

PURPOSE: To determine whether VDPhys/VT is associated with coagulation activation and outcomes. MATERIALS AND METHODS: We enrolled patients with COVID-19 pneumonia who were supported by invasive mechanical ventilation and were monitored using volumetric capnography. Measurements were performed during the first 24 h of mechanical ventilation. The primary endpoint was the likelihood of being discharge alive on day 28. RESULTS: Sixty patients were enrolled, of which 25 (42%) had high VDPhys/VT (>57%). Patients with high vs. low VDPhys/VT had higher APACHE II (10[8-13] vs. 8[6-9] points, p = 0.002), lower static compliance of the respiratory system (35[24-46] mL/cmH2O vs. 42[37-45] mL/cmH2O, p = 0.005), and higher D-dimer levels (1246[1050-1594] ng FEU/mL vs. 792[538-1159] ng FEU/mL, p = 0.001), without differences in P/F ratio (157[112-226] vs. 168[136-226], p = 0.719). Additionally, D-dimer levels correlated with VDPhys/VT (r = 0.530, p < 0.001), but not with the P/F ratio (r = -0.103, p = 0.433). Patients with high VDPhys/VT were less likely to be discharged alive on day 28 (32% vs. 71%, aHR = 3.393[1.161-9.915], p = 0.026). CONCLUSIONS: In critically ill COVID-19 patients, increased VDPhys/VT was associated with high D-dimer levels and a lower likelihood of being discharged alive. Dichotomic VDPhys/VT could help identify a high-risk subgroup of patients neglected by the P/F ratio.

The Impact of Ubiquitous Face Masks and Filtering Face Piece Application During Rest, Work and Exercise on Gas Exchange, Pulmonary Function and Physical Performance: A Systematic Review with Meta-analysis.

BACKGROUND: Protection against airborne infection is currently, due to the COVID-19-associated restrictions, ubiquitously applied during public transport use, work and leisure time. Increased carbon dioxide re-inhalation and breathing resistance may result thereof and, in turn, may negatively impact metabolism and performance. OBJECTIVES: To deduce the impact of the surgical mask and filtering face piece type 2 (FFP2) or N95 respirator application on gas exchange (pulse-derived oxygen saturation (SpO2), carbon dioxide partial pressure (PCO2), carbon dioxide exhalation (VCO2) and oxygen uptake (VO2)), pulmonary function (respiratory rate and ventilation) and physical performance (heart rate HR, peak power output Wpeak). METHODS: Systematic review with meta-analysis. Literature available in Medline/Pubmed, the Cochrane Library and the Web of Knowledge with the last search on the 6th of May 2021. Eligibility criteria: Randomised controlled parallel group or crossover trials (RCT), full-text availability, comparison of the acute effects of ≥ 1 intervention (surgical mask or FFP2/N95 application) to a control/comparator condition (i.e. no mask wearing). Participants were required to be healthy humans and > 16 years of age without conditions or illnesses influencing pulmonary function or metabolism. Risk of bias was rated using the crossover extension of the Cochrane risk of bias assessment tool II. Standardised mean differences (SMD, Hedges' g) with 95% confidence intervals (CI) were calculated, overall and for subgroups based on mask and exercise type, as pooled effect size estimators in our random-effects meta-analysis. RESULTS: Of the 1499 records retrieved, 14 RCTs (all crossover trials, high risk of bias) with 25 independent intervention arms (effect sizes per outcome) on 246 participants were included. Masks led to a decrease in SpO2 during vigorous intensity exercise (6 effect sizes; SMD = - 0.40 [95% CI: - 0.70, - 0.09], mostly attributed to FFP2/N95) and to a SpO2-increase during rest (5 effect sizes; SMD = 0.34 [95% CI: 0.04, 0.64]); no general effect of mask wearing on SpO2 occurred (21 effect sizes, SMD = 0.34 [95% CI: 0.04, 0.64]). Wearing a mask led to a general oxygen uptake decrease (5 effect sizes, SMD = - 0.44 [95% CI: - 0.75, - 0.14]), to slower respiratory rates (15 effect sizes, SMD = - 0.25 [95% CI: - 0.44, - 0.06]) and to a decreased ventilation (11 effect sizes, SMD = - 0.43 [95% CI: - 0.74, - 0.12]). Heart rate (25 effect sizes; SMD = 0.05 [95% CI: - 0.09, 0.19]), Wpeak (9 effect sizes; SMD = - 0.12 [95% CI: - 0.39, 0.15]), PCO2 (11 effect sizes; SMD = 0.07 [95% CI: - 0.14, 0.29]) and VCO2 (4 effect sizes, SMD = - 0.30 [95% CI: - 0.71, 0.10]) were not different to the control, either in total or dependent on mask type or physical activity status. CONCLUSION: The number of crossover-RCT studies was low and the designs displayed a high risk of bias. The within-mask- and -intensity-homogeneous effects on gas exchange kinetics indicated larger detrimental effects during exhausting physical activities. Pulse-derived oxygen saturation was increased during rest when a mask was applied, whereas wearing a mask during exhausting exercise led to decreased oxygen saturation. Breathing frequency and ventilation adaptations were not related to exercise intensity. FFP2/N95 and, to a lesser extent, surgical mask application negatively impacted the capacity for gas exchange and pulmonary function but not the peak physical performance. Registration: Prospero registration number: CRD42021244634.

Quantification of COVID-19 Vaccine Needle and Syringe Dead Space Volumes.

INTRODUCTION:  The COVID-19 pandemic taught many lessons regarding vaccine manufacturing, transportation, and delivery. Throughout the vaccination campaign, different vaccination sites reported that six or seven doses of the Pfizer/BioNTech COVID-19 vaccine could be reliably withdrawn from each multidose vial. This discrepancy was hypothesized to be caused by the differences in needle and syringe dead space volumes with differing supplies utilized at each site, but independent data regarding these volumes are lacking; therefore, we sought to objectively evaluate the volume of dead space for supplies commonly used for immunizations. MATERIALS AND METHODS: Available needles and syringes of different brands and specifications that could be used for administering vaccines were gathered. Each needle and/or syringe was weighed with a scientific, calibrated scale upon removal from the manufacturer's packaging and then filled with distilled water to simulate standard vaccine preparation. The water was then expelled, simulating vaccination, and then reweighed on the same scientific scale. The difference between the two weights was secondary to the water remaining within the needle or syringe after the simulated use, which was equivalent to the dead space volume. RESULTS: Manufacturer design, gauge, needle length, and syringe volume separately correlate with volume differences. Intuitively, the needles and syringes with the most dead space were consistently the 1.5-inch needles and the larger volume syringes, regardless of the manufacturer. CONCLUSION: The withdrawal of individual vaccine doses from a multidose vial inevitably results in vaccine volume loss due to the dead space of needles and syringes. As such, reliably obtaining seven doses of the Pfizer/BioNTech COVID-19 vaccine is improbable without utilizing specialized low dead space supplies.

Impact of Airway Humidification Strategy in Mechanically Ventilated COVID-19 Patients.

BACKGROUND: Humidification of inspiratory gases is mandatory in all mechanically ventilated patients in ICUs, either with heated humidifiers (HHs) or with heat and moisture exchangers (HMEs). In patients with COVID-19, the choice of the humidification device may have relevant impact on patients' management as demonstrated in recent studies. We reported data from 2 ICUs using either HME or HH. METHODS: Data from patients with COVID-19 requiring invasive mechanical ventilation during the first wave in 2 ICUs in Québec City were reviewed. In one ICU, HMEs were used, whereas heated-wire HHs were used in the other ICU. We compared ventilator settings and arterial blood gases at day one after adjustment of ventilator settings. Episodes of endotracheal tube occlusions (ETOs) or subocclusions and a strategy to limit the risk of under-humidification were reported. On a bench test, we measured humidity with psychrometry with HH at different ambient temperature and evaluated the relation with heater plate temperature. RESULTS: We reported data from 20 subjects positive for SARS-Cov-2, including 6 in the ICU using HME and 14 in the ICU using HH. In the HME group, PaCO2 was higher (48 vs 42 mm Hg) despite higher minute ventilation (171 vs 145 mL/kg/min predicted body weight [PBW]). We also reported 3 ETOs occurring in the ICU using HH. The hygrometric bench study reported a strong correlation between heater plate temperatures of the HH and humidity delivered. After implementation of measures to avoid under-humidification, including heater plate temperature monitoring, no more ETOs occurred. CONCLUSIONS: The choice of the humidification device used in subjects with COVID-19 had a relevant impact on ventilation efficiency (increased CO2 removal with lower dead space) and on complications related to low humidity, including ETOs that may be present with heated-wire HHs when used with high ambient temperatures.