The alveolus: Our current knowledge of how the gas exchange unit of the lung is constructed and repaired.

The mammalian lung completes its last step of development, alveologenesis, to generate sufficient surface area for gas exchange. In this process, multiple cell types that include alveolar epithelial cells, endothelial cells, and fibroblasts undergo coordinated cell proliferation, cell migration and/or contraction, cell shape changes, and cell-cell and cell-matrix interactions to produce the gas exchange unit: the alveolus. Full functioning of alveoli also involves immune cells and the lymphatic and autonomic nervous system. With the advent of lineage tracing, conditional gene inactivation, transcriptome analysis, live imaging, and lung organoids, our molecular understanding of alveologenesis has advanced significantly. In this review, we summarize the current knowledge of the constituents of the alveolus and the molecular pathways that control alveolar formation. We also discuss how insight into alveolar formation may inform us of alveolar repair/regeneration mechanisms following lung injury and the pathogenic processes that lead to loss of alveoli or tissue fibrosis.

Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: a systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis to evaluate the impact of extracorporeal carbon dioxide removal (ECCO2R) on gas exchange and respiratory settings in critically ill adults with respiratory failure. METHODS: We conducted a comprehensive database search, including observational studies and randomized controlled trials (RCTs) from January 2000 to March 2022, targeting adult ICU patients undergoing ECCO2R. Primary outcomes were changes in gas exchange and ventilator settings 24 h after ECCO2R initiation, estimated as mean of differences, or proportions for adverse events (AEs); with subgroup analyses for disease indication and technology. Across RCTs, we assessed mortality, length of stay, ventilation days, and AEs as mean differences or odds ratios. RESULTS: A total of 49 studies encompassing 1672 patients were included. ECCO2R was associated with a significant decrease in PaCO2, plateau pressure, and tidal volume and an increase in pH across all patient groups, at an overall 19% adverse event rate. In ARDS and lung transplant patients, the PaO2/FiO2 ratio increased significantly while ventilator settings were variable. "Higher extraction" systems reduced PaCO2 and respiratory rate more efficiently. The three available RCTs did not demonstrate an effect on mortality, but a significantly longer ICU and hospital stay associated with ECCO2R. CONCLUSIONS: ECCO2R effectively reduces PaCO2 and acidosis allowing for less invasive ventilation. "Higher extraction" systems may be more efficient to achieve this goal. However, as RCTs have not shown a mortality benefit but increase AEs, ECCO2R's effects on clinical outcome remain unclear. Future studies should target patient groups that may benefit from ECCO2R. PROSPERO Registration No: CRD 42020154110 (on January 24, 2021).

Comparative effects of variable versus conventional volume-controlled one-lung ventilation on gas exchange and respiratory system mechanics in thoracic surgery patients: A randomized controlled clinical trial.

BACKGROUND: Mechanical ventilation with variable tidal volumes (V-VCV) has the potential to improve lung function during general anesthesia. We tested the hypothesis that V-VCV compared to conventional volume-controlled ventilation (C-VCV) would improve intraoperative arterial oxygenation and respiratory system mechanics in patients undergoing thoracic surgery under one-lung ventilation (OLV). METHODS: Patients were randomized to V-VCV (n = 39) or C-VCV (n = 39). During OLV tidal volume of 5 mL/kg predicted body weight (PBW) was used. Both groups were ventilated with a positive end-expiratory pressure (PEEP) of 5 cm H2O, inspiration to expiration ratio (I:E) of 1:1 (during OLV) and 1:2 during two-lung ventilation, the respiratory rate (RR) titrated to arterial pH, inspiratory peak-pressure ≤ 40 cm H2O and an inspiratory oxygen fraction of 1.0. RESULTS: Seventy-five out of 78 Patients completed the trial and were analyzed (dropouts were excluded). The partial pressure of arterial oxygen (PaO2) 20 min after the start of OLV did not differ among groups (V-VCV: 25.8 ± 14.6 kPa vs C-VCV: 27.2 ± 15.3 kPa; mean difference [95% CI]: 1.3 [-8.2, 5.5], P = 0.700). Furthermore, intraoperative gas exchange, intraoperative adverse events, need for rescue maneuvers due to desaturation and hypercapnia, incidence of postoperative pulmonary and extra-pulmonary complications, and hospital free days at day 30 after surgery did not differ between groups. CONCLUSIONS: In thoracic surgery patients under OLV, V-VCV did not improve oxygenation or respiratory system mechanics compared to C-VCV. Ethical Committee: EK 420092019. TRIAL REGISTRATION: at the German Clinical Trials Register: DRKS00022202 (16.06.2020).

The Effect of Recruitment Maneuver on Static Lung Compliance in Patients Undergoing General Anesthesia for Laparoscopic Cholecystectomy: A Single-Centre Prospective Clinical Intervention Study.

Background and Objectives: The aim of this study was to examine whether the use of an alveolar recruitment maneuver (RM) leads to a significant increase in static lung compliance (Cstat) and an improvement in gas exchange in patients undergoing laparoscopic cholecystectomy. Material and Methods: A clinical prospective intervention study was conducted. Patients were divided into two groups according to their body mass index (BMI): normal-weight (group I) and pre-obese and obese grade I (group II). Lung mechanics were monitored (Cstat, dynamic compliance-Cdin, peak pressure-Ppeak, plateau pressure-Pplat, driving pressure-DP) alongside gas exchange, and hemodynamic changes (heart rate-HR, mean arterial pressure-MAP) at six time points: T1 (induction of anesthesia), T2 (formation of pneumoperitoneum), T3 (RM with a PEEP of 5 cm H2O), T4 (RM with a PEEP of 7 cm H2O), T5 (desufflation), and T6 (RM at the end). The RM was performed by increasing the peak pressure by +5 cm of H2O at an equal inspiration-to-expiration ratio (I/E = 1:1) and applying a PEEP of 5 and 7 cm of H2O. Results: Out of 96 patients, 33 belonged to group I and 63 to group II. An increase in Cstat values occurred after all three RMs. At each time point, the Cstat value was measured higher in group I than in group II. A higher increase in Cstat was observed in group II after the second and third RM. Cstat values were higher at the end of the surgical procedure compared to values after the induction of anesthesia. The RM led to a significant increase in PaO2 in both groups without changes in HR or MAP. Conclusions: During laparoscopic cholecystectomy, the application of RM leads to a significant increase in Cstat and an improvement in gas exchange. The prevention of atelectasis during anesthesia should be initiated immediately after the induction of anesthesia, using protective mechanical ventilation and RM.

Effects of positive end-expiratory pressure on regional cerebral oxygen saturation in elderly patients undergoing thoracic surgery during one-lung ventilation: a randomized crossover-controlled trial.

BACKGROUND: A significant reduction in regional cerebral oxygen saturation (rSO2) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO2, pulmonary oxygenation, and hemodynamics during OLV. METHODS: Forty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP-0 cmH2O, 5 cmH2O, and 10 cmH2O. The primary endpoint was rSO2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables. RESULTS: After exclusion, thirty-six patients (36.11% female; age range: 60-76 year) were assigned to six groups (n = 6 in each group). The rSO2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO2) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p < 0.001) and OLV(5) (difference, -3.139 mmHg; [95% CI, -4.110 to -2.167 mmHg]; p < 0.001) than at OLV(10). CONCLUSIONS: PEEP with 10 cmH2O makes rSO2 decrease compared with 0 cmH2O. Applying PEEP with 5 cmH2O during OLV in elderly patients can improve oxygenation and maintain high rSO2 levels, without significantly increasing peak airway pressure compared to not using PEEP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200060112 on 19 May 2022.

Hemodynamic, ventilatory and gas exchange responses to exercise using a cycle ergometer and the incremental shuttle walk test in pregnant women.

BACKGROUND: Cardiovascular disease, including hypertension, in pregnant women is a leading cause of morbidity and mortality globally. The development of reference intervals for cardiovascular responses using exercising testing to measure oxygen utilisation (V̇O2) with cardiopulmonary exercise testing (CPET), and distances walked using the incremental shuttle walk test (ISWT), may be promising methods to assess and stratify pregnant women regarding their risk of adverse pregnancy outcomes, to encourage exercise during pregnancy, and to improve exercise prescriptions during pregnancy. We aimed to determine the reference intervals for V̇O2 at rest, anaerobic threshold (AT), and submaximal exercise using CPET, and the reference interval for the ISWT, to develop a correlation equitation that predicts submaximal V̇O2 from the distance walked in the ISWT, and to explore the relationship between hemoglobin (Hb) and ferritin concentration and V̇O2 at AT in women in second trimester. METHODS: After prospective IRB approval (HREC 15/23) and clinical trials registration (ANZCTR ACTRN12615000964516), and informed written consent, we conducted CPET and the ISWT according to international guidelines in a university associated tertiary referral obstetric and adult medicine hospital, in healthy pregnant women in second trimester (14 to 27 gestational weeks). Hemoglobin and ferritin concentrations were recorded from pathology results in the participants' medical records at the time of exercise testing. Adverse events were recorded. RESULTS: About 90 participants undertook CPET, 28 of which also completed the ISWT. The mean ± SD age and body mass index (BMI) were 32 ± 3.2 years, and 25 ± 2.7 kg/m2. Median (IQR) gestation was 23 (22-24) weeks. One in 4 women were 24 weeks or greater gestation. The reference intervals for V̇O2 at rest, AT, and submaximal exercise were 2.9 to 5.3, 8.1 to 20.7, and 14.1 to 30.5 mL/kg/min respectively. The reference interval for the ISWT was 218 to 1058 meters. The correlation equation to predict submaximal V̇O2 from the distance walked in the ISWT was submaximal V̇O2 (mL/kg/min) = 0.012*distance walked in ISWT (m) + 14.7 (95%CI slope 0.005-0.070, Pearson r = 0.5426 95%CI 0.2126-0.7615, P = .0029). Hemoglobin concentration was positively correlated with V̇O2 at AT (AT V̇O2 (mL/kg/min) = 0.08*Hb (g/L) + 4.9 (95%CI slope 0.0791-0.143, Pearson r = 0.2538 95%CI 0.049-0.438, P = .016). There was no linear association between ferritin and submaximal V̇O2 (Pearson r = 0.431 P = .697). There were no maternal or fetal complications. CONCLUSIONS: CPET and ISWT are safe and feasible in women in second trimester including those at or beyond 24 weeks gestation. We have established the reference interval for V̇O2 at rest, AT, and submaximal exercise by CPET, the reference interval for the distance walked for the ISWT, and a correlation equation to predict submaximal V̇O2 for use in clinical practice and research. Hemoglobin rather than ferritin is likely correlated with exercise capacity in pregnancy suggesting vigilance to correct lower hemoglobin levels may positively impact maternal health. CLINICAL TRIALS REGISTRY: The study was prospectively registered with the Australian and New Zealand Clinical Date of registration - 15/9/2015; Date of initial participant enrolment - 4/11/2015; Clinical trial identification number; ACTRN12615000964516; URL of the registration site - https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369216.

Toward 3D printed microfluidic artificial lungs for respiratory support.

Microfluidic artificial lungs (µALs) are a new class of membrane oxygenators. Compared to traditional hollow-fiber oxygenators, µALs closely mimic the alveolar microenvironment due to their size-scale and promise improved gas exchange efficiency, hemocompatibility, biomimetic blood flow networks, and physiologically relevant blood vessel pressures and shear stresses. Clinical translation of µALs has been stalled by restrictive microfabrication techniques that limit potential artificial lung geometries, overall device size, and throughput. To address these limitations, a high-resolution Asiga MAX X27 UV digital light processing (DLP) 3D printer and custom photopolymerizable polydimethylsiloxane (PDMS) resin were used to rapidly manufacture small-scale µALs via vat photopolymerization (VPP). Devices were designed in SOLIDWORKS with 500 blood channels and 252 gas channels, where gas and blood flow channels were oriented orthogonally and separated by membranes on the top and bottom, permitting two-sided gas exchange. Successful devices were post-processed to remove uncured resin from microchannels and assembled with external tubing in preparation for gas exchange performance testing with ovine whole blood. 3D printed channel dimensions were 172 µm-tall × 320 µm-wide, with 62 µm-thick membranes and 124 µm-wide support columns. Measured outlet blood oxygen saturation (SO2) agreed with theoretical models and rated flow of the device was 1 mL min-1. Blood side pressure drop was 1.58 mmHg at rated flow. This work presents the highest density of 3D printed microchannels in a single device, one of the highest CO2 transfer efficiencies of any artificial lung to date, and a promising approach to translate µALs one step closer to the clinic.

The pulmonary physiology of exercise.

The pulmonary system is the first and last "line of defense" in terms of maintaining blood gas homeostasis during exercise. Our review provides the reader with an overview of how the pulmonary system responds to acute exercise. We undertook this endeavor to provide a companion article to "Cardiovascular Response to Exercise," which was published in Advances in Physiological Education. Together, these articles provide the readers with a solid foundation of the cardiopulmonary response to acute exercise in healthy individuals. The intended audience of this review is level undergraduate or graduate students and/or instructors for such classes. By intention, we intend this to be used as an educational resource and seek to provide illustrative examples to reinforce topics as well as highlight uncertainty to encourage the reader to think "beyond the textbook." Our treatment of the topic presents "classic" concepts along with new information on the pulmonary physiology of healthy aging.NEW & NOTEWORTHY Our narrative review is written with the student of the pulmonary physiology of exercise in mind, be it a senior undergraduate or graduate student or those simply refreshing their knowledge. We also aim to provide examples where the reader can incorporate real scenarios.

Haemodynamic changes during prone versus supine position in patients with COVID-19 acute respiratory distress syndrome.

BACKGROUND: Prone positioning improves oxygenation in patients with acute respiratory distress syndrome (ARDS) secondary to COVID-19. However, its haemodynamic effects are poorly understood. OBJECTIVES: The objective of this study was to investigate the acute haemodynamic changes associated with prone position in mechanically ventilated patients with COVID-19 ARDS. The primary objective was to describe changes in cardiac index with prone position. The secondary objectives were to describe changes in mean arterial pressure, FiO2, PaO2/FiO2 ratio, and oxygen delivery (DO2) with prone position. METHODS: We performed this cohort-embedded study in an Australian intensive care unit, between September and November 2021. We included adult patients with severe COVID-19 ARDS, requiring mechanical ventilation and prone positioning for respiratory failure. We placed patients in the prone position for 16 h per session. Using pulse contour technology, we collected haemodynamic data every 5 min for 2 h in the supine position and for 2 h in the prone position consecutively. RESULTS: We studied 18 patients. Cardiac index, stroke volume index, and mean arterial pressure increased significantly in the prone position compared to supine position. The mean cardiac index was higher in the prone group than in the supine group by 0.44 L/min/m2 (95% confidence interval, 0.24 to 0.63) (P < 0.001). FiO2 requirement decreased significantly in the prone position (P < 0.001), with a significant increase in PaO2/FiO2 ratio (P < 0.001). DO2 also increased significantly in the prone position, from a median DO2 of 597 mls O2/min (interquartile range, 504 to 931) in the supine position to 743 mls O2/min (interquartile range, 604 to 1075) in the prone position (P < 0.001). CONCLUSION: Prone position increased the cardiac index, mean arterial pressure, and DO2 in invasively ventilated patients with COVID-19 ARDS. These changes may contribute to improved tissue oxygenation and improved outcomes observed in trials of prone positioning.

Signal Variability Comparative Analysis of Healthy Early- and Late-Pubertal Children during Cardiopulmonary Exercise Testing.

PURPOSE: The kinetics of physiological responses to exercise have traditionally been characterized by estimating exponential equation parameters using iterative best-fit techniques of heart rate (HR) and gas exchange (respiratory rate, oxygen uptake (V̇O 2 ), carbon dioxide output, and ventilation). In this study, we present a novel approach to characterizing the maturation of physiological responses to exercise in children by accounting for response uncertainty and variability. METHODS: Thirty-seven early-pubertal (17 females, 20 males) and 44 late-pubertal (25 females, 19 males) participants performed three multiple brief exercise bouts (MBEB). MBEB consisted of ten 2-min bouts of cycle ergometry at constant work rate interspersed by 1-min rest. Exercise intensity was categorized as low, moderate, or high, corresponding to 40%, 60%, and 80% of peak work rate, and performed in random order on 3 separate days. We evaluated sample entropy (SampEn), approximate entropy, detrended fluctuation analysis, and average absolute local variability of HR and gas exchange. RESULTS: SampEn of HR and gas-exchange responses to MBEB was greater in early- compared with late-pubertal participants (e.g., V̇O 2 early-pubertal vs late-pubertal, 1.70 ± 0.023 vs 1.41 ± 0.027; P = 2.97 × 10 -14 ), and decreased as MBEB intensity increased (e.g., 0.37 ± 0.01 HR for low-intensity compared with 0.21 ± 0.014 for high intensity, P = 3.56 × 10 -17 ). Females tended to have higher SampEn than males (e.g., 1.61 ± 0.025 V̇O 2 for females vs 1.46 ± 0.031 for males, P = 1.28 × 10 -4 ). Average absolute local variability was higher in younger participants for both gas exchange and HR (e.g., early-pubertal vs late-pubertal V̇O 2 , 17.48 % ± 0.56% vs 10.24 % ± 0.34%; P = 1.18 × 10 -21 ). CONCLUSIONS: The greater entropy in signal response to a known, quantifiable exercise perturbation in the younger children might represent maturation-dependent, enhanced competition among physiological controlling mechanisms that originate at the autonomic, subconscious, and cognitive levels.

Accuracy of respiratory gas variables, substrate, and energy use from 15 CPET systems during simulated and human exercise.

PURPOSE: Various systems are available for cardiopulmonary exercise testing (CPET), but their accuracy remains largely unexplored. We evaluate the accuracy of 15 popular CPET systems to assess respiratory variables, substrate use, and energy expenditure during simulated exercise. Cross-comparisons were also performed during human cycling experiments (i.e., verification of simulation findings), and between-session reliability was assessed for a subset of systems. METHODS: A metabolic simulator was used to simulate breath-by-breath gas exchange, and the values measured by each system (minute ventilation [V̇E], breathing frequency [BF], oxygen uptake [V̇O2 ], carbon dioxide production [V̇CO2 ], respiratory exchange ratio [RER], energy from carbs and fats, and total energy expenditure) were compared to the simulated values to assess the accuracy. The following manufacturers (system) were assessed: COSMED (Quark CPET, K5), Cortex (MetaLyzer 3B, MetaMax 3B), Vyaire (Vyntus CPX, Oxycon Pro), Maastricht Instruments (Omnical), MGC Diagnostics (Ergocard Clinical, Ergocard Pro, Ultima), Ganshorn/Schiller (PowerCube Ergo), Geratherm (Ergostik), VO2master (VO2masterPro), PNOE (PNOE), and Calibre Biometrics (Calibre). RESULTS: Absolute percentage errors during the simulations ranged from 1.15%-44.3% for V̇E, 1.05-3.79% for BF, 1.10%-13.3% for V̇O2 , 1.07%-18.3% for V̇CO2 , 0.62%-14.8% for RER, 5.52%-99.0% for Kcal from carbs, 5.13%-133% for Kcal from fats, and 0.59%-12.1% for total energy expenditure. Between-session variation ranged from 0.86%-21.0% for V̇O2 and 1.14%-20.2% for V̇CO2 , respectively. CONCLUSION: The error of respiratory gas variables, substrate, and energy use differed substantially between systems, with only a few systems demonstrating a consistent acceptable error. We extensively discuss the implications of our findings for clinicians, researchers and other CPET users.

Causes of Hypoxemia in COVID-19 Acute Respiratory Distress Syndrome: A Combined Multiple Inert Gas Elimination Technique and Dual-energy Computed Tomography Study.

BACKGROUND: Despite the fervent scientific effort, a state-of-the art assessment of the different causes of hypoxemia (shunt, ventilation-perfusion mismatch, and diffusion limitation) in COVID-19 acute respiratory distress syndrome (ARDS) is currently lacking. In this study, the authors hypothesized a multifactorial genesis of hypoxemia and aimed to measure the relative contribution of each of the different mechanism and their relationship with the distribution of tissue and blood within the lung. METHODS: In this cross-sectional study, the authors prospectively enrolled 10 patients with COVID-19 ARDS who had been intubated for less than 7 days. The multiple inert gas elimination technique (MIGET) and a dual-energy computed tomography (DECT) were performed and quantitatively analyzed for both tissue and blood volume. Variables related to the respiratory mechanics and invasive hemodynamics (PiCCO [Getinge, Sweden]) were also recorded. RESULTS: The sample (51 ± 15 yr; Pao2/Fio2, 172 ± 86 mmHg) had a mortality of 50%. The MIGET showed a shunt of 25 ± 16% and a dead space of 53 ± 11%. Ventilation and perfusion were mismatched (LogSD, Q, 0.86 ± 0.33). Unexpectedly, evidence of diffusion limitation or postpulmonary shunting was also found. In the well aerated regions, the blood volume was in excess compared to the tissue, while the opposite happened in the atelectasis. Shunt was proportional to the blood volume of the atelectasis (R2 = 0.70, P = 0.003). V˙A/Q˙T mismatch was correlated with the blood volume of the poorly aerated tissue (R2 = 0.54, P = 0.016). The overperfusion coefficient was related to Pao2/Fio2 (R2 = 0.66, P = 0.002), excess tissue mass (R2 = 0.84, P < 0.001), and Etco2/Paco2 (R2 = 0.63, P = 0.004). CONCLUSIONS: These data support the hypothesis of a highly multifactorial genesis of hypoxemia. Moreover, recent evidence from post-mortem studies (i.e., opening of intrapulmonary bronchopulmonary anastomosis) may explain the findings regarding the postpulmonary shunting. The hyperperfusion might be related to the disease severity.

The algorithm used for the calculation of gas exchange affects the estimation of O2 uptake kinetics at the onset of moderate-intensity exercise.

At the start of a moderate-intensity square-wave exercise, after a short delay, breath-by-breath O2 uptake at the mouth is approximated to a mono-exponential function, whose time constant is considered matched to that of the O2 uptake of the working muscles. We compared the kinetic parameters obtained from the breath-by-breath gas exchange data yielded by the 'Independent-breath' algorithm (IND), which accounts for the changes in lung gas stores, with those obtained with the classical 'Expiration-only' algorithm (EXP). The two algorithms were applied on the same flow and gas fraction traces acquired on 10 healthy volunteers, performing 10 times the same moderate-intensity exercise transition. Repeated O2 uptake responses were stacked together and the kinetic parameters of a mono-exponential function were estimated by non-linear regression, removing the data pertaining to 1-s progressively longer initial periods (ΔTr ). Independently of ΔTr , the mean response time (time constant + time delay) obtained for the IND data was faster compared to the EXP data (∼43 s vs. ∼47 s, P < 0.001), essentially because of shorter time delays. Between ΔTr  = 16 s and ΔTr  = 29s, the time constants of the IND data decreased (30.7 s vs. 28.0 s, P < 0.05; drop = 10%), but less than those of the EXP data (32.2 s vs. 26.2 s, P < 0.001; drop = 23%); with the same ΔTr , the time constants of the two algorithms' data were not different (P > 0.07). The different decrease in the time constant, together with the different mean response time, suggests that the data yielded by the two algorithms provide a different picture of the phenomena occurring at the beginning of the exercise.

Neuromuscular blockade and oxygenation changes during prone positioning in COVID-19.

PURPOSE: Neuromuscular blockers (NMBs) are often used during prone positioning to facilitate mechanical ventilation in COVID-19 related ARDS. However, their impact on oxygenation is uncertain. METHODS: Multi-centre observational study of invasively ventilated COVID-19 ARDS adults treated with prone positioning. We collected data on baseline characteristics, prone positioning, NMB use and patient outcome. We assessed arterial blood gas data during supine and prone positioning and after return to the supine position. RESULTS: We studied 548 prone episodes in 220 patients (mean age 54 years, 61% male) of whom 164 (75%) received NMBs. Mean PaO2:FiO2 (P/F ratio) during the first prone episode with NMBs reached 208 ± 63 mmHg compared with 161 ± 66 mmHg without NMBs (Δmean = 47 ± 5 mmHg) for an absolute increase from baseline of 76 ± 56 mmHg versus 55 ± 56 mmHg (padj < 0.001). The mean P/F ratio on return to the supine position was 190 ± 63 mmHg in the NMB group versus 141 ± 64 mmHg in the non-NMB group for an absolute increase from baseline of 59 ± 58 mmHg versus 34 ± 56 mmHg (padj < 0.001). CONCLUSION: During prone positioning, NMB is associated with increased oxygenation compared to non-NMB therapy, with a sustained effect on return to the supine position. These findings may help guide the use of NMB during prone positioning in COVID-19 ARDS.

The effect of high-flow nasal oxygen flow rate on gas exchange in apnoeic patients: a randomised controlled trial.

High-flow nasal oxygen can be administered at induction of anaesthesia for the purposes of pre-oxygenation and apnoeic oxygenation. This intervention is claimed to enhance carbon dioxide elimination during apnoea, but the extent to which this occurs remains poorly quantified. The optimal nasal oxygen flow rate for gas exchange is also unknown. In this study, 114 patients received pre-oxygenation with high-flow nasal oxygen at 50 l.min-1. At the onset of apnoea, patients were allocated randomly to receive one of three nasal oxygen flow rates: 0 l.min-1; 70 l.min-1; or 120 l.min-1. After 4 minutes of apnoea, all oxygen delivery was ceased, tracheal intubation was performed, and oxygen delivery was recommenced when SpO2 was 92%. Mean (SD) PaCO2 rise during the first minute of apnoea was 1.39 (0.39) kPa, 1.41 (0.29) kPa, and 1.26 (0.38) kPa in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.16. During the second, third and fourth minutes of apnoea, mean (SD) rates of rise in PaCO2 were 0.34 (0.08) kPa.min-1, 0.36 (0.06) kPa.min-1 and 0.37 (0.07) kPa.min-1 in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, respectively; p = 0.17. After 4 minutes of apnoea, median (IQR [range]) arterial oxygen partial pressures in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups were 24.5 (18.6-31.4 [12.3-48.3]) kPa; 36.6 (28.1-43.8 [9.8-56.9]) kPa; and 37.6 (26.5-45.4 [11.0-56.6]) kPa, respectively; p < 0.001. Median (IQR [range]) times to desaturate to 92% after the onset of apnoea in the 0 l.min-1, 70 l.min-1 and 120 l.min-1 groups, were 412 (347-509 [190-796]) s; 533 (467-641 [192-958]) s; and 531 (462-681 [326-1007]) s, respectively; p < 0.001. In conclusion, the rate of carbon dioxide accumulation in arterial blood did not differ significantly between apnoeic patients who received high-flow nasal oxygen and those who did not.