IMPORTANCEIn patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. OBJECTIVE To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. INTERVENTIONS Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). MAIN OUTCOMES AND MEASURESThe primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. RESULTS Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device.CONCLUSIONS AND RELEVANCE Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference.

Key points• Any unusual cardiovascular or neurological signs, including outright cardiac arrest, after local anaesthetic (LA) administration should raise suspicion of local anaesthetic systemic toxicity (LAST).• The risk of LAST is influenced by patient factors, the site and conduct of the block, and the LA type and dose.• There are pre-, intra-, and post-procedure measures to reduce the risk of LAST.

Background and Objectives: The bronchoscopic microsample (BMS) probe allows direct epithelial lining fluid (ELF) level measurement without saline lavage. We investigated whether cytokine levels in ELF from a BMS differed from those obtained by bronchoalveolar lavage (BAL) in stable and acute lung disease. Methods: In a single-centre, prospective observational cohort study of 45 patients, a sequential BMS probe procedure and BAL were performed on patients with stable chronic obstructive lung disease, interstitial lung disease, acute lung injury (ALI), burns-related inhalational injury or controls. ELF samples were assayed for IL-1β, IL-6, IL-8, TNF-α and G-CSF. Results: Both bronchoscopic microsampling and BAL showed significantly higher cytokine levels in the ELF from patients with ALI and burns-related inhalational injury than from those with chronic stable lung disease. The BMS method detected cytokine levels approximately 20- to 80-fold higher than the corresponding BAL (uncorrected for dilution). The ratio of BMS and BAL cytokine levels was as follows: the ratio for IL-1β [mean 55, 95% confidence interval (CI) 34-88] was higher than that for IL-6 (mean 16, 95% CI 10-23, p = 0.015) and IL-8 (mean 13, 95% CI -5 to 36, p = 0.03). The ratio for G-CSF (mean 43, 95% CI 24-75) was higher than that for IL-6 (mean 16, 95% CI 10-23, p = 0.008). Conclusions: The BMS probe safely collects ELF with higher equivalent inflammatory cytokine concentrations than via BAL from patients with both acute and chronic lung disease and can be an alternative to saline BAL. Variations in cytokine concentrations between BMS and BAL and sampling-site differences warrant further study.

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Common causes of death in COVID-19 due to SARS-CoV-2 include thromboembolic disease, cytokine storm and adult respiratory distress syndrome (ARDS). Our aim was to develop a system for early detection of disease pattern in the emergency department (ED) that would enhance opportunities for personalised accelerated care to prevent disease progression. A single Trust’s COVID-19 response control command was established, and a reporting team with bioinformaticians was deployed to develop a real-time traffic light system to support clinical and operational teams. An attempt was made to identify predictive elements for thromboembolism, cytokine storm and ARDS based on physiological measurements and blood tests, and to communicate to clinicians managing the patient, initially via single consultants. The input variables were age, sex, and first recorded blood pressure, respiratory rate, temperature, heart rate, indices of oxygenation and C-reactive protein. Early admissions were used to refine the predictors used in the traffic lights. Of 923 consecutive patients who tested COVID-19 positive, 592 (64%) flagged at risk for thromboembolism, 241/923 (26%) for cytokine storm and 361/923 (39%) for ARDS. Thromboembolism and cytokine storm flags were met in the ED for 342 (37.1%) patients. Of the 318 (34.5%) patients receiving thromboembolism flags, 49 (5.3% of all patients) were for suspected thromboembolism, 103 (11.1%) were high-risk and 166 (18.0%) were medium-risk. Of the 89 (9.6%) who received a cytokine storm flag from the ED, 18 (2.0% of all patients) were for suspected cytokine storm, 13 (1.4%) were high-risk and 58 (6.3%) were medium-risk. Males were more likely to receive a specific traffic light flag. In conclusion, ED predictors were used to identify high proportions of COVID-19 admissions at risk of clinical deterioration due to severity of disease, enabling accelerated care targeted to those more likely to benefit. Larger prospective studies are encouraged.