The diagnostic accuracy of lung auscultation in adult patients with acute pulmonary pathologies: a meta-analysis

The stethoscope is used as first line diagnostic tool in assessment of patients with pulmonary symptoms. However, there is much debate about the diagnostic accuracy of this instrument. This meta-analysis aims to evaluate the diagnostic accuracy of lung auscultation for the most common respiratory pathologies. Studies concerning adult patients with respiratory symptoms are included. Main outcomes are pooled estimates of sensitivity and specificity with 95% confidence intervals, likelihood ratios (LRs), area under the curve (AUC) of lung auscultation for different pulmonary pathologies and breath sounds. A meta-regression analysis is performed to reduce observed heterogeneity. For 34 studies the overall pooled sensitivity for lung auscultation is 37% and specificity 89%. LRs and AUC of auscultation for congestive heart failure, pneumonia and obstructive lung diseases are low, LR- and specificity are acceptable. Abnormal breath sounds are highly specific for (hemato)pneumothorax in patients with trauma. Results are limited by significant heterogeneity. Lung auscultation has a low sensitivity in different clinical settings and patient populations, thereby hampering its clinical utility. When better diagnostic modalities are available, they should replace lung auscultation. Only in resource limited settings, with a high prevalence of disease and in experienced hands, lung auscultation has still a role

Complement activation in COVID-19 and targeted therapeutic options: A scoping review

Increasing evidence suggests that activation of the complement system plays a key role in the pathogenesis and disease severity of Coronavirus disease 2019 (COVID-19). We used a systematic approach to create an overview of complement activation in COVID-19 based on histopathological, preclinical, multiomics, observational and clinical interventional studies. A total of 1801 articles from PubMed, EMBASE and Cochrane was screened of which 157 articles were included in this scoping review. Histopathological, preclinical, multiomics and observational studies showed apparent complement activation through all three complement pathways and a correlation with disease severity and mortality. The complement system was targeted at different levels in COVID-19, of which C5 and C5a inhibition seem most promising. Adequately powered, double blind RCTs are necessary in order to further investigate the effect of targeting the complement system in COVID-19

Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients

Abstract Background Vilobelimab, a complement 5a (C5a)-specific monoclonal antibody, reduced mortality in critically ill COVID-19 patients in a phase 3 multicentre, randomized, double-blind, placebo-controlled study. As part of the study, vilobelimab concentrations and C5a levels as well as antidrug antibodies (ADAs) to vilobelimab were analysed. Results From Oct 1, 2020 to Oct 4, 2021, 368 invasively mechanically ventilated COVID-19 patients were randomized: 177 patients were randomly assigned to receive vilobelimab while 191 patients received placebo. Pharmacokinetic sampling was only performed at sites in Western Europe. Blood samples for vilobelimab measurements were available for 93 of 177 (53%) patients in the vilobelimab group and 99 of 191 (52%) patients in the placebo group. On day 8, after three infusions, mean vilobelimab (trough) concentrations ranged from 21,799.3 to 302,972.1 ng/mL (geometric mean 137,881.3 ng/mL). Blood samples for C5a measurements were available for 94 of 177 (53%) patients in the vilobelimab group and 99 of 191 (52%) patients in the placebo group. At screening, C5a levels were highly elevated and comparable between groups. In the vilobelimab group, median C5a levels were 118.3 ng/mL [IQR 71.2–168.2 ng/mL] and in the placebo group, median C5a levels were 104.6 ng/mL [IQR 77.5–156.6 ng/mL]. By day 8, median C5a levels were reduced by 87% in the vilobelimab group (median 14.5 ng/mL [IQR 9.5–21.0 ng/mL], p < 0.001) versus an 11% increase in the placebo group (median 119.2 ng/mL [IQR 85.9–152.1 ng/mL]). Beyond day 8, though plasma sampling was sparse, C5a levels did not reach screening levels in the vilobelimab group while C5a levels remained elevated in the placebo group. Treatment-emergent ADAs were observed in one patient in the vilobelimab group at hospital discharge on day 40 and in one patient in the placebo group at hospital discharge on day 25. Conclusions This analysis shows that vilobelimab efficiently inhibits C5a in critically ill COVID-19 patients. There was no evidence of immunogenicity associated with vilobelimab treatment. Trial registration ClinicalTrials.gov, NCT04333420. Registered 3 April 2020, https://clinicaltrials.gov/ct2/show/NCT0433342

Ultrasound to Detect Central Venous Catheter Placement Associated Complications: A Multicenter Diagnostic Accuracy Study

BACKGROUND: Mechanical complications arising after central venous catheter placement are mostly malposition or pneumothorax. To date, to confirm correct position and detect pneumothorax, chest x-ray film has been the reference standard, while ultrasound might be an accurate alternative. The aim of this study was to evaluate diagnostic accuracy of ultrasound to detect central venous catheter malposition and pneumothorax. METHODS: This was a prospective, multicenter, diagnostic accuracy study conducted at the intensive care unit and postanesthesia care unit. Adult patients who underwent central venous catheterization of the internal jugular vein or subclavian vein were included. Index test consisted of venous, cardiac, and lung ultrasound. Standard reference test was chest x-ray film. Primary outcome was diagnostic accuracy of ultrasound to detect malposition and pneumothorax; for malposition, sensitivity, specificity, and other accuracy parameters were estimated. For pneumothorax, because chest x-ray film is an inaccurate reference standard to diagnose it, agreement and Cohen's κ-coefficient were determined. Secondary outcomes were accuracy of ultrasound to detect clinically relevant complications and feasibility of ultrasound. RESULTS: In total, 758 central venous catheterizations were included. Malposition occurred in 23 (3.3%) out of 688 cases included in the analysis. Ultrasound sensitivity was 0.70 (95% CI, 0.49 to 0.86) and specificity 0.99 (95% CI, 0.98 to 1.00). Pneumothorax occurred in 5 (0.7%) to 11 (1.5%) out of 756 cases according to chest x-ray film and ultrasound, respectively. In 748 out of 756 cases (98.9%), there was agreement between ultrasound and chest x-ray film with a Cohen's κ-coefficient of 0.50 (95% CI, 0.19 to 0.80). CONCLUSIONS: This multicenter study shows that the complication rate of central venous catheterization is low and that ultrasound produces a moderate sensitivity and high specificity to detect malposition. There is moderate agreement with chest x-ray film for pneumothorax. In conclusion, ultrasound is an accurate diagnostic modality to detect malposition and pneumothorax

Ultrasound to detect central venous catheter placement associated complications: A multicenter diagnostic accuracy study

Background: Mechanical complications arising after central venous catheter placement are mostly malposition or pneumothorax. To date, to confirm correct position and detect pneumothorax, chest x-ray film has been the reference standard, while ultrasound might be an accurate alternative. The aim of this study was to evaluate diagnostic accuracy of ultrasound to detect central venous catheter malposition and pneumothorax. Methods: This was a prospective, multicenter, diagnostic accuracy study conducted at the intensive care unit and postanesthesia care unit. Adult patients who underwent central venous catheterization of the internal jugular vein or subclavian vein were included. Index test consisted of venous, cardiac, and lung ultrasound. Standard reference test was chest x-ray film. Primary outcome was diagnostic accuracy of ultrasound to detect malposition and pneumothorax; for malposition, sensitivity, specificity, and other accuracy parameters were estimated. For pneumothorax, because chest x-ray film is an inaccurate reference standard to diagnose it, agreement and Cohen's κ-coefficient were determined. Secondary outcomes were accuracy of ultrasound to detect clinically relevant complications and feasibility of ultrasound. Results: In total, 758 central venous catheterizations were included. Malposition occurred in 23 (3.3%) out of 688 cases included in the analysis. Ultrasound sensitivity was 0.70 (95% CI, 0.49 to 0.86) and specificity 0.99 (95% CI, 0.98 to 1.00). Pneumothorax occurred in 5 (0.7%) to 11 (1.5%) out of 756 cases according to chest x-ray film and ultrasound, respectively. In 748 out of 756 cases (98.9%), there was agreement between ultrasound and chest x-ray film with a Cohen's κ-coefficient of 0.50 (95% CI, 0.19 to 0.80). Conclusions: This multicenter study shows that the complication rate of central venous catheterization is low and that ultrasound produces a moderate sensitivity and high specificity to detect malposition. There is moderate agreement with chest x-ray film for pneumothorax. In conclusion, ultrasound is an accurate diagnostic modality to detect malposition and pneumothorax

Holistic ultrasound to predict extubation failure in clinical practice

BACKGROUND: A weaning trial can be considered a stress test of the cardiorespiratory system; it increases oxygen demand and thus warrants a higher cardiac index and elevated breathing effort. We hypothesized that the combination of easily performed ultrasound measurements of heart, lungs, and diaphragm would yield good diagnostic accuracy to predict extubation failure. METHODS: Adult subjects ventilated for > 72 h with a successful spontaneous breathing trial were included. Ultrasound measurements of heart (left ventricular function), lungs (number of B-lines), and diaphragm thickening fraction were performed during a spontaneous breathing trial. The primary outcomes were sensitivity, specificity, and area under the receiver operating characteristic curve of a holistic ultrasound approach for extubation failure. Re-intubation within 48 h was considered extubation failure. RESULTS: Eighty-three subjects were included, of whom 15 (18%) were re-intubated within 48 h. The sensitivity and specificity of a holistic approach were 100% (78.2–100%) and 7.7% (2.5–17.1%), respectively, with an area under the receiver operating characteristic curve of 0.54. The sensitivity and specificity of diaphragm thickening fraction, using a cutoff value of 72 h who had a successful spontaneous breathing trial, holistic ultrasound was a weak predictor for extubation failure

Holistic Ultrasound to Predict Extubation Failure in Clinical Practice

BACKGROUND: A weaning trial can be considered a stress test of the cardiorespiratory system; it increases oxygen demand and thus warrants a higher cardiac index and elevated breathing effort. We hypothesized that the combination of easily performed ultrasound measurements of heart, lungs, and diaphragm would yield good diagnostic accuracy to predict extubation failure. METHODS: Adult subjects ventilated for > 72 h with a successful spontaneous breathing trial were included. Ultrasound measurements of heart (left ventricular function), lungs (number of B-lines), and diaphragm thickening fraction were performed during a spontaneous breathing trial. The primary outcomes were sensitivity, specificity, and area under the receiver operating characteristic curve of a holistic ultrasound approach for extubation failure. Re-intubation within 48 h was considered extubation failure. RESULTS: Eighty-three subjects were included, of whom 15 (18%) were re-intubated within 48 h. The sensitivity and specificity of a holistic approach were 100% (78.2–100%) and 7.7% (2.5–17.1%), respectively, with an area under the receiver operating characteristic curve of 0.54. The sensitivity and specificity of diaphragm thickening fraction, using a cutoff value of 72 h who had a successful spontaneous breathing trial, holistic ultrasound was a weak predictor for extubation failure

EXpert consensus On Diaphragm UltraSonography in the critically ill (EXODUS): a Delphi consensus statement on the measurement of diaphragm ultrasound-derived parameters in a critical care setting

International audienceBackground Diaphragm ultrasonography is rapidly evolving in both critical care and research. Nevertheless, methodologically robust guidelines on its methodology and acquiring expertise do not, or only partially, exist. Therefore, we set out to provide consensus-based statements towards a universal measurement protocol for diaphragm ultrasonography and establish key areas for research. Methods To formulate a robust expert consensus statement, between November 2020 and May 2021, a two-round, anonymous and online survey-based Delphi study among experts in the field was performed. Based on the literature review, the following domains were chosen: “Anatomy and physiology”, “Transducer Settings”, “Ventilator Impact”, “Learning and expertise”, “Daily practice” and “Future directions”. Agreement of ≥ 68% (≥ 10 panelists) was needed to reach consensus on a question. Results Of 18 panelists invited, 14 agreed to participate in the survey. After two rounds, the survey included 117 questions of which 42 questions were designed to collect arguments and opinions and 75 questions aimed at reaching consensus. Of these, 46 (61%) consensus was reached. In both rounds, the response rate was 100%. Among others, there was agreement on measuring thickness between the pleura and peritoneum, using > 10% decrease in thickness as cut-off for atrophy and using 40 examinations as minimum training to use diaphragm ultrasonography in clinical practice. In addition, key areas for research were established. Conclusion This expert consensus statement presents the first set of consensus-based statements on diaphragm ultrasonography methodology. They serve to ensure high-quality and homogenous measurements in daily clinical practice and in research. In addition, important gaps in current knowledge and thereby key areas for research are established. Trial registration The study was pre-registered on the Open Science Framework with registration digital object identifier https://doi.org/10.17605/OSF.IO/HM8UG