Purpose A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed... Show morePurpose A hallmark of acute respiratory distress syndrome (ARDS) is hypoxaemic respiratory failure due to pulmonary vascular hyperpermeability. The tyrosine kinase inhibitor imatinib reversed pulmonary capillary leak in preclinical studies and improved clinical outcomes in hospitalized COVID-19 patients. We investigated the effect of intravenous (IV) imatinib on pulmonary edema in COVID-19 ARDS. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial. Invasively ventilated patients with moderate-to-severe COVID-19 ARDS were randomized to 200 mg IV imatinib or placebo twice daily for a maximum of seven days. The primary outcome was the change in extravascular lung water index (.EVLWi) between days 1 and 4. Secondary outcomes included safety, duration of invasive ventilation, ventilator-free days (VFD) and 28-day mortality. Posthoc analyses were performed in previously identified biological subphenotypes. Results 66 patients were randomized to imatinib (n = 33) or placebo (n = 33). There was no difference in.EVLWi between the groups (0.19 ml/kg, 95% CI - 3.16 to 2.77, p = 0.89). Imatinib treatment did not affect duration of invasive ventilation (p = 0.29), VFD (p = 0.29) or 28-day mortality (p = 0.79). IV imatinib was well-tolerated and appeared safe. In a subgroup of patients characterized by high IL-6, TNFR1 and SP-D levels (n = 20), imatinib significantly decreased EVLWi per treatment day (- 1.17 ml/kg, 95% CI - 1.87 to - 0.44). Conclusions IV imatinib did not reduce pulmonary edema or improve clinical outcomes in invasively ventilated COVID-19 patients. While this trial does not support the use of imatinib in the general COVID-19 ARDS population, imatinib reduced pulmonary edema in a subgroup of patients, underscoring the potential value of predictive enrichment in ARDS trials. Show less
Background: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with... Show moreBackground: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with mortality in critically ill COVID-19 patients. Methods: This was a retrospective cohort study of central venous catheters (CVCs) in critically ill COVID-19 patients. Eligible CVC insertions required an indwelling time of at least 48 hours and were identified using a full-admission electronic health record database. Risk factors were identified using logistic regression. Differences in survival rates at day 28 of follow-up were assessed using a log-rank test and proportional hazard model. Results: In 538 patients, a total of 914 CVCs were included. Prevalence and incidence of suspected catheter-related infection were 7.9% and 9.4 infections per 1,000 catheter indwelling days, respectively. Prone ventilation for more than 5 days was associated with increased risk of suspected catheter-related infection; odds ratio, 5.05 (95% confidence interval 2.12-11.0). Risk of death was significantly higher in patients with suspected catheter-related infection (hazard ratio, 1.78; 95% confidence interval, 1.25-2.53). Conclusions: This study shows that in critically ill patients with COVID-19, prevalence and incidence of suspected catheter-related infection are high, prone ventilation is a risk factor, and mortality is higher in case of catheter-related infection. Show less
Lung ultrasound (LUS) can be used to assess loss of aeration, which is associated with outcome in patients with coronavirus disease 2019 (COVID-19) presenting to the emergency department. We... Show moreLung ultrasound (LUS) can be used to assess loss of aeration, which is associated with outcome in patients with coronavirus disease 2019 (COVID-19) presenting to the emergency department. We hypothesized that LUS scores are associated with outcome in critically ill COVID-19 patients receiving invasive ventilation. This retrospective international multicenter study evaluated patients with COVID-19-related acute respiratory distress syndrome (ARDS) with at least one LUS study within 5 days after invasive mechanical ventilation initiation. The global LUS score was calculated by summing the 12 regional scores (range 0-36). Pleural line abnormalities and subpleural consolidations were also scored. The outcomes were successful liberation from the ventilator and intensive care mortality within 28 days, analyzed with multistate, competing risk proportional hazard models. One hundred thirty-seven patients with COVID-19-related ARDS were included in our study. The global LUS score was associated with successful liberation from mechanical ventilation (hazard ratio [HR]: 0.91 95% confidence interval [CI] 0.87-0.96; P = 0.0007) independently of the ARDS severity, but not with 28 days mortality (HR: 1.03; 95% CI 0.97-1.08; P = 0.36). Subpleural consolidation and pleural line abnormalities did not add to the prognostic value of the global LUS score. Examinations within 24 hours of intubation showed no prognostic value. To conclude, a lower global LUS score 24 hours after invasive ventilation initiation is associated with increased probability of liberation from the mechanical ventilator COVID-19 ARDS patients, independently of the ARDS severity. Show less
In the last decade, ultrasound has found its place in the intensive care unit (ICU). Initially, ultrasound was used primarily to increase the safety and efficacy of line insertion, but currently... Show moreIn the last decade, ultrasound has found its place in the intensive care unit (ICU). Initially, ultrasound was used primarily to increase the safety and efficacy of line insertion, but currently many intensivists use point-of-care ultrasound (POCUS) to aid in making the diagnosis, monitoring therapy, and supporting therapeutic interventions. In this series, we aim to highlight one specific POCUS technique at a time, which we believe will prove to be useful in your clinical practice. This specific article will focus on assessment of right ventricular (RV) size and function, and the application of tricuspid annular plane systolic excursion (TAPSE). RV assessment during focused cardiac ultrasound (FoCUS) depends, currently, on visual evaluation - 'eyeballing' - of the RV size and function and left and right ventricular interaction. However, 'eyeballing' is subjective, depends on experience and may be misleading if done by unexperienced sonographers. Objective measurements of RV size and function are necessary and provide an additional understanding of RV performance. There are different ways to assess the RV objectively. Many of these measurements, however, require a lot of training and are not yet available in portable devices. Evaluation of TAPSE is a validated and reproducible way of evaluating RV function and only requires the utilisation of M-mode or a 2D measurement. TAPSE, assessed in the apical four-chamber view, is sometimes difficult to measure, especially in mechanically ventilated patients. In recent years subcostal variants have been introduced: the subcostal echocardiographic assessment of tricuspid annular kick (SEATAK) and the subcostal-TAPSE (S-TAPSE). These measurements are alternatives when the 'classical' TAPSE cannot reliably be evaluated. Show less
Background The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase... Show moreBackground The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.Methods This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged >= 18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10).Findings Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0.95 [95% CI 0.76-1.20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0.51 [0.27-0.95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0.52 (95% CI 0.26-1.05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1.07 (0.63-1.80; p=0.81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0.0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events.Interpretation The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Show less
This article is part of the point-of-care ultrasound (POCUS) series. During cardiopulmonary resuscitation, bedside ultrasound has important clinical value for confirming a diagnosis, establishing a... Show moreThis article is part of the point-of-care ultrasound (POCUS) series. During cardiopulmonary resuscitation, bedside ultrasound has important clinical value for confirming a diagnosis, establishing a prognosis and in therapeutic decision-making. In this article we provide a practical review on how to implement and apply POCUS during cardiopulmonary resuscitation and discuss its merits and pitfalls. Show less
In the last decade, ultrasound has found its place in the intensive care unit (ICU). Initially, ultrasound was used primarily to increase the safety and efficacy of line insertion, but now many... Show moreIn the last decade, ultrasound has found its place in the intensive care unit (ICU). Initially, ultrasound was used primarily to increase the safety and efficacy of line insertion, but now many intensivists use point-of-care ultrasound (POCUS) to aid in diagnosis, assess therapy and support therapeutic interventions. In this series, we aim to highlight one specific POCUS technique at a time, which we believe will prove to be useful in your clinical practice. Focused cardiac ultrasound (FoCUS) is an important tool for the intensivist and can help in, among other things, diagnosing undifferentiated shock, evaluating the response to therapy and guiding procedures. FoCUS has, until recently, been performed with transthoracic echocardiography (TTE). FoCUS-TTE is, however, not always possible and not without problems. In this issue, we aim to describe the merits and pitfalls of focused transoesophageal echocardiography (FoCUS-TEE) in the ICU. Show less
Background: Lung ultrasound can adequately monitor disease severity in pneumonia and acute respiratory distress syndrome. We hypothesize lung ultrasound can adequately monitor COVID-19 pneumonia in... Show moreBackground: Lung ultrasound can adequately monitor disease severity in pneumonia and acute respiratory distress syndrome. We hypothesize lung ultrasound can adequately monitor COVID-19 pneumonia in critically ill patients.Methods: Adult patients with COVID-19 pneumonia admitted to the intensive care unit of two academic hospitals who underwent a 12-zone lung ultrasound and a chest CT examination were included. Baseline characteristics, and outcomes including composite endpoint death or ICU stay > 30 days were recorded. Lung ultrasound and CT images were quantified as a lung ultrasound score involvement index (LUSI) and CT severity involvement index (CTSI). Primary outcome was the correlation, agreement, and concordance between LUSI and CTSI. Secondary outcome was the association of LUSI and CTSI with the composite endpoints.Results: We included 55 ultrasound examinations in 34 patients, which were 88% were male, with a mean age of 63 years and mean P/F ratio of 151. The correlation between LUSI and CTSI was strong (r = 0.795), with an overall 15% bias, and limits of agreement ranging - 40 to 9.7. Concordance between changes in sequentially measured LUSI and CTSI was 81%. In the univariate model, high involvement on LUSI and CTSI were associated with a composite endpoint. In the multivariate model, LUSI was the only remaining independent predictor.Conclusions: Lung ultrasound can be used as an alternative for chest CT in monitoring COVID-19 pneumonia in critically ill patients as it can quantify pulmonary involvement, register changes over the course of the disease, and predict death or ICU stay > 30 days. Show less
In the last docade ultrasound has found its place in the intensive care unit. Initially, ultrasound was used primarily to increase safety and efficacy of line insertions but now many intensivists... Show moreIn the last docade ultrasound has found its place in the intensive care unit. Initially, ultrasound was used primarily to increase safety and efficacy of line insertions but now many intensivists use point-of-care ultrasound (POCUS) to aid in diagnosis, assessment of therapy and to guide therapeutic interventions. In this series we aim to highlight one specific POCUS technique at a time, which we believe will prove to be useful in clinical practice. Our aim is to provide the reader with a short and practical description of the technique as well as its merits and pitfalls. In this issue we describe the use of the rapid ultrasound in shock (RUSH) protocol to quickly investigate shock in the ICU. Show less
Background: Using ultrasound as a guidance tool during central venous catheter placement has repeatedly been shown to improve procedural safety. More recent evidence has shown its potential as a... Show moreBackground: Using ultrasound as a guidance tool during central venous catheter placement has repeatedly been shown to improve procedural safety. More recent evidence has shown its potential as a diagnostic modality to detect placement-associated complications. A protocol combining these modalities is lacking. This article uses the Indication, Acquisition, Interpretation and Medical decision-making (I-AIM) model, common to other ultrasound protocols, to provide a systematic ultrasound approach to guide central venous catheter placement and assess potential related complications. It is part of a larger series published in this journal.Methods: Relevant articles were found in a thorough search in PubMed using the MeSH terms: "diagnostic imaging" or "ultrasonography" or "sonography" and "central venous catheter" or "central venous cannulation" and "complications" or "placement procedure". Studies conducted on patients younger than 18 years and studies conducted in animals were excluded. Two independent researchers evaluated the articles for relevance and quality. The results of the various studies were used to create the following structured ultrasound approach.Recommended approach: Following the I-AIM model, acquiring the most valuable images is subdivided into patient, probe, picture and protocol considerations. Ultrasound guidance during central venous catheter placement should be conducted in four steps: pre-cannulation, confirming patency, dynamic guidance during insertion, and confirmation of intravenous central venous catheter position. After these steps, ultrasound should be used in the diagnostic evaluation of malposition and iatrogenic pneumothorax.Conclusions: This model provides a comprehensive and ready to use ultrasound approach to guide central venous catheter placement and assess potential placement associated complications. Show less
Background: Over 2 million people worldwide have been infected with severe acute respiratory distress syndrome-coronavirus-2 (SARS CoV-2). Lung ultrasound has been proposed to diagnose and monitor... Show moreBackground: Over 2 million people worldwide have been infected with severe acute respiratory distress syndrome-coronavirus-2 (SARS CoV-2). Lung ultrasound has been proposed to diagnose and monitor it, despite the fact that little is known about the ultrasound appearance due to the novelty of the illness. The aim of this manuscript is to characterise the lung ultrasonographic appearance of critically ill patients with SARS-CoV-2 pneumonia, with particular emphasis on its relationship with the time course of the illness and clinical parameters.Methods: Adult patients from the intensive care unit of two academic hospitals who tested positive for SARS-CoV-2 were included. Images were analysed using internationally recognised techniques which included assessment of the pleura, number of B-lines, pathology in the PLAPS (posterolateral alveolar and/or pleural syndrome) point, bedside lung ultrasound in emergency profiles, and the lung ultrasound score. The primary outcomes were frequencies, percentages and differences in lung ultrasound findings overall and between short (<= 14 days) and long (>14 days) durations of symptoms and their correlation with clinical parameters.Results: In this pilot observational study, 61 patients were included with 76 examinations available for analysis. 26% of patients had no anterior lung abnormalities, while the most prevalent pathological ultrasound findings were thickening of the pleura (42%), >= 3 B-lines per view (38%) and presence of PLAPS (74%). Patients with "long" duration of symptoms presented more frequently with a thickened and irregular pleura (32 (21%) versus 11 (9%)), C-profile (18 (47%) versus 8 (25%)) and pleural effusion (14 (19%) versus 3 (5%)), compared to patients with short duration of symptoms. Lung ultrasound findings did not correlate with arterial oxygen tension/inspiratory oxygen fraction ratio, fluid balance or dynamic compliance.Conclusion: SARS-CoV-2 results in significant, but not specific, ultrasound changes, with decreased lung sliding, thickening of the pleura and a B-profile being the most commonly observed. With time, a thickened and irregular pleura, C-profile and pleural effusion become more common findings. When screening patients, a comprehensive ultrasound protocol might be necessary. Show less
This article is part of the point-of-care ultrasound (POCUS) series. During the Coronavirus Disease 2019 (COVID-19) pandemic, we have been managing large numbers of infected patients whilst... Show moreThis article is part of the point-of-care ultrasound (POCUS) series. During the Coronavirus Disease 2019 (COVID-19) pandemic, we have been managing large numbers of infected patients whilst maintaining high-quality healthcare. In this article we aim to provide a short and practical description on how point-of-care lung ultrasound can be of use to facilitate diagnosis and treatment in critically ill patients diagnosed with COVID-19. Show less
In the last decade ultrasound has found its place in the intensive care unit. Initially ultrasound was used primarily to increase safety and efficacy of line insertion but now many intensivists use... Show moreIn the last decade ultrasound has found its place in the intensive care unit. Initially ultrasound was used primarily to increase safety and efficacy of line insertion but now many intensivists use point-of-care ultrasound (POCUS) to aid in diagnosis, assessment of therapy and therapeutic interventions. In this series we aim to highlight one specific POCUS technique at a time, which we believe will prove to be useful in your clinical practice. In this issue our aim is to provide you with a short and practical description of the measurement of E-point septal separation to identify a severely reduced left ventricular ejection fraction. Show less
Matta, J.E.L.; Kraemer, C.V.E.; Tuinman, P.R.; Westerloo, D.J. van 2019
