Platelet Transfusion before CVC Placement in Patients with Thrombocytopenia.

BACKGROUND: Transfusion guidelines regarding platelet-count thresholds before the placement of a central venous catheter (CVC) offer conflicting recommendations because of a lack of good-quality evidence. The routine use of ultrasound guidance has decreased CVC-related bleeding complications. METHODS: In a multicenter, randomized, controlled, noninferiority trial, we randomly assigned patients with severe thrombocytopenia (platelet count, 10,000 to 50,000 per cubic millimeter) who were being treated on the hematology ward or in the intensive care unit to receive either one unit of prophylactic platelet transfusion or no platelet transfusion before ultrasound-guided CVC placement. The primary outcome was catheter-related bleeding of grade 2 to 4; a key secondary outcome was grade 3 or 4 bleeding. The noninferiority margin was an upper boundary of the 90% confidence interval of 3.5 for the relative risk. RESULTS: We included 373 episodes of CVC placement involving 338 patients in the per-protocol primary analysis. Catheter-related bleeding of grade 2 to 4 occurred in 9 of 188 patients (4.8%) in the transfusion group and in 22 of 185 patients (11.9%) in the no-transfusion group (relative risk, 2.45; 90% confidence interval [CI], 1.27 to 4.70). Catheter-related bleeding of grade 3 or 4 occurred in 4 of 188 patients (2.1%) in the transfusion group and in 9 of 185 patients (4.9%) in the no-transfusion group (relative risk, 2.43; 95% CI, 0.75 to 7.93). A total of 15 adverse events were observed; of these events, 13 (all grade 3 catheter-related bleeding [4 in the transfusion group and 9 in the no-transfusion group]) were categorized as serious. The net savings of withholding prophylactic platelet transfusion before CVC placement was $410 per catheter placement. CONCLUSIONS: The withholding of prophylactic platelet transfusion before CVC placement in patients with a platelet count of 10,000 to 50,000 per cubic millimeter did not meet the predefined margin for noninferiority and resulted in more CVC-related bleeding events than prophylactic platelet transfusion. (Funded by ZonMw; PACER Dutch Trial Register number, NL5534.).

Use of Lung Ultrasound in the New Definitions of Acute Respiratory Distress Syndrome Increases the Occurrence Rate of Acute Respiratory Distress Syndrome.

OBJECTIVES: To assess the effect of incorporating bilateral abnormalities as detected by lung ultrasound (LUS) in the Kigali modification and the New Global definition of acute respiratory distress syndrome (ARDS) on the occurrence rate of ARDS. DESIGN: Post hoc analysis of a previously published prospective cohort study. SETTING: An academic mixed medical-surgical ICU. PATIENTS: The original study included critically ill adults with any opacity on chest radiography in whom subsequent LUS was performed. Patients with ARDS according to the Berlin definition, COVID-19 patients and patients with major thorax trauma were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: LUS was performed within 24 hours of chest radiography and the presence of unilateral and bilateral abnormalities on LUS and chest radiograph (opacities) was scored. Subsequently, the Kigali modification and the New Global definition of ARDS were applied by two independent researchers on the patients with newly found bilateral opacities. Of 120 patients, 116 were included in this post hoc analysis. Thirty-three patients had bilateral opacities on LUS and unilateral opacities on chest radiograph. Fourteen of these patients had ARDS according to the Kigali modification and 12 had ARDS according to the New Global definition. The detected LUS patterns were significantly different between patients with and without ARDS ( p = 0.004). An A-profile with a positive PosteroLateral Alveolar and/or Pleural Syndrome was most prevalent in patients without ARDS, whereas heterogeneous and mixed A, B, and C patterns were most prevalent in patients with ARDS. CONCLUSION: The addition of bilateral abnormalities as detected by LUS to the Kigali modification and the New Global definition increases the occurrence rate of the ARDS. The nomenclature for LUS needs to be better defined as LUS patterns differ between patients with and without ARDS. Incorporating well-defined LUS criteria can increase specificity and sensitivity of new ARDS definitions.

Setting positive end-expiratory pressure: lung and diaphragm ultrasound.

PURPOSE OF REVIEW: The purpose of this review is to summarize the role of lung ultrasound and diaphragm ultrasound in guiding ventilator settings with an emphasis on positive end-expiratory pressure (PEEP). Recent advances for using ultrasound to assess the effects of PEEP on the lungs and diaphragm are discussed. RECENT FINDINGS: Lung ultrasound can accurately diagnose the cause of acute respiratory failure, including acute respiratory distress syndrome and can identify focal and nonfocal lung morphology in these patients. This is essential in determining optimal ventilator strategy and PEEP level. Assessment of the effect of PEEP on lung recruitment using lung ultrasound is promising, especially in the perioperative setting. Diaphragm ultrasound can monitor the effects of PEEP on the diaphragm, but this needs further validation. In patients with an acute exacerbation of chronic obstructive pulmonary disease, diaphragm ultrasound can be used to predict noninvasive ventilation failure. Lung and diaphragm ultrasound can be used to predict weaning outcome and accurately diagnose the cause of weaning failure. SUMMARY: Lung and diaphragm ultrasound are useful for diagnosing the cause of respiratory failure and subsequently setting the ventilator including PEEP. Effects of PEEP on lung and diaphragm can be monitored using ultrasound.

Lung ultrasound and ARDS: global collaboration is the way to go.

We would like to extend our gratitude to Dr. da Hora Passos et al. for their interest in our recently published review and meta-analysis in Critical Care. In this response, we will elaborate on the points raised by the authors. We agree with the authors that LUS, like any other diagnostic technique, is valuable and safe only when utilized by trained operators. The authors expressed uncertainty regarding the sensitivity of LUS in detecting mild ARDS or ARDS at an early stage. This variance in sensitivity is more likely due to diversity in diagnostic thresholds. We advocate for global collaboration among LUS experts to align LUS methodologies and strengthen the evidence supporting LUS in the diagnosis of ARDS and its morphological subphenotypes.

Diagnostic accuracy of lung ultrasound in diagnosis of ARDS and identification of focal or non-focal ARDS subphenotypes: a systematic review and meta-analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory condition with high mortality rates, accounting for 10% of all intensive care unit admissions. Lung ultrasound (LUS) as diagnostic tool for acute respiratory failure has garnered widespread recognition and was recently incorporated into the updated definitions of ARDS. This raised the hypothesis that LUS is a reliable method for diagnosing ARDS. OBJECTIVES: We aimed to establish the accuracy of LUS for ARDS diagnosis and classification of focal versus non-focal ARDS subphenotypes. METHODS: This systematic review and meta-analysis used a systematic search strategy, which was applied to PubMed, EMBASE and cochrane databases. Studies investigating the diagnostic accuracy of LUS compared to thoracic CT or chest radiography (CXR) in ARDS diagnosis or focal versus non-focal subphenotypes in adult patients were included. Quality of studies was evaluated using the QUADAS-2 tool. Statistical analyses were performed using "Mada" in Rstudio, version 4.0.3. Sensitivity and specificity with 95% confidence interval of each separate study were summarized in a Forest plot. RESULTS: The search resulted in 2648 unique records. After selection, 11 reports were included, involving 2075 patients and 598 ARDS cases (29%). Nine studies reported on ARDS diagnosis and two reported on focal versus non-focal ARDS subphenotypes classification. Meta-analysis showed a pooled sensitivity of 0.631 (95% CI 0.450-0.782) and pooled specificity of 0.942 (95% CI 0.856-0.978) of LUS for ARDS diagnosis. In two studies, LUS could accurately differentiate between focal versus non-focal ARDS subphenotypes. Insufficient data was available to perform a meta-analysis. CONCLUSION: This review confirms the hypothesis that LUS is a reliable method for diagnosing ARDS in adult patients. For the classification of focal or non-focal subphenotypes, LUS showed promising results, but more research is needed.

The effect of liver surgery and fluid strategy on renin activity and aldosterone and anti-diuretic hormone levels: a secondary analysis of the GALILEO trial.

BACKGROUND: It is unknown whether liver surgery leads to increased RAAS activity and anti-diuretic hormone (ADH) levels and subsequent fluid accumulation. Furthermore, it is unknown whether the peri-operative fluid strategy changes this effect. METHODS: This is a pre-planned post hoc analysis of a randomised controlled trial which compared restrictive (n = 20) versus liberal fluid strategy (n = 20) in patients undergoing liver surgery. Primary outcomes for the current study were the difference in hormone levels after anaesthesia induction and after liver resection. Fluid overload was defined as a ≥10% increase in weight. RESULTS: Renin activity (6 [2.1-15.5] vs. 12 [4.6-33.5]) and ADH levels (6.0 [1.7-16.3] vs. 3.8 [1.6-14.7]) did not differ significantly before and after resection. However, aldosterone levels were significantly higher after resection (0.30 [0.17-0.49] vs. 0.69 [0.31-1.21] ). Renin activity and aldosterone levels did not differ between the groups. ADH was significantly higher in the restrictive strategy group (1.6 [1.1-2.1] vs 5.9 [3.8-16.0]). No differences in hormone levels were found in patients with and without fluid overload. DISCUSSION: Aldosterone levels increased after liver surgery but renin activity and ADH levels did not. ADH levels were higher in the restrictive group. Development of post-operative fluid overload was not associated with RAAS activity or ADH levels.

Development, feasibility testing, and preliminary evaluation of the Communication with an Artificial airway Tool (CAT): Results of the Crit-CAT pilot study.

BACKGROUND: A purpose-built outcome measure for assessing communication effectiveness in patients with an artificial airway is needed. OBJECTIVES: The objective of this study was to develop the Communication with an Artificial airway Tool (CAT) and to test the feasibility and to preliminary evaluate the clinical metrics of the tool. METHODS: Eligible patients with an artificial airway in the Intensive Care Unit were enrolled in the pilot study (Crit-CAT). The CAT was administered at least twice before and after the communication intervention. Item correlation analysis was performed. Participant and family member acceptability ratings and feedback were solicited. A qualitative thematic analysis was undertaken. RESULTS: Fifteen patients with a mean age of 53 years (standard deviation [SD]: 19.26) were included. The clinician-reported scale was administered on 50 attempts (100%) with a mean completion time of 4.5 (SD: 0.77) minutes. The patient-reported scale was administered on 46 out of 49 attempts (94%) and took a mean of 1.5 (SD: 0.39) minutes to complete. The CAT was feasible for use in the Intensive Care Unit, with patients with either an endotracheal or tracheostomy tube, whilst receiving invasive mechanical ventilation or not, and while using either verbal or nonverbal modes of communication. Preliminary establishment of responsiveness, validity, and reliability was made. The tool was acceptable to participants and their family members. CONCLUSION: The clinician-reported and patient-reported components of the study were feasible for use. The CAT has the potential to enable quantifiable comparison of communication interventions for patients with an artificial airway. Future research is required to determine external validity and reliability.

The Impact of Thoracic Ultrasound on Clinical Management of Critically Ill Patients (UltraMan): An International Prospective Observational Study.

OBJECTIVES: To investigate the impact of thoracic ultrasound (TUS) examinations on clinical management in adult ICU patients. DESIGN: A prospective international observational study. SETTING: Four centers in The Netherlands and Italy. PATIENTS: Adult ICU patients (> 18 yr) that received a clinically indicated lung ultrasound examination. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinicians performing TUS completed a pre- and post-examination case report form. Patient characteristics, TUS, and resulting clinical effects were recorded. First, change of management, defined as a TUS-induced change in clinical impression leading to a change in treatment plan, was reported. Second, execution of intended management changes within 8 hours was verified. Third, change in fluid balance after 8 hours was calculated. A total of 725 TUS performed by 111 operators across 534 patients (mean age 63 ± 15.0, 70% male) were included. Almost half of TUS caused a change in clinical impression, which resulted in change of management in 39% of cases. The remainder of TUS confirmed the clinical impression, while a minority (4%) did not contribute. Eighty-nine percent of management changes indicated by TUS were executed within 8 hours. TUS examinations that led to a change in fluid management also led to distinct and appropriate changes in patient's fluid balance. CONCLUSIONS: In this international observational study in adult ICU patients, use of TUS had a major impact on clinical management. These results provide grounds for future randomized controlled trials to determine if TUS-induced changes in decision-making also lead to improved health outcomes.

Performance of Noninvasive Airway Occlusion Maneuvers to Assess Lung Stress and Diaphragm Effort in Mechanically Ventilated Critically Ill Patients.

BACKGROUND: Monitoring and controlling lung stress and diaphragm effort has been hypothesized to limit lung injury and diaphragm injury. The occluded inspiratory airway pressure (Pocc) and the airway occlusion pressure at 100 ms (P0.1) have been used as noninvasive methods to assess lung stress and respiratory muscle effort, but comparative performance of these measures and their correlation to diaphragm effort is unknown. The authors hypothesized that Pocc and P0.1 correlate with diaphragm effort and lung stress and would have strong discriminative performance in identifying extremes of lung stress and diaphragm effort. METHODS: Change in transdiaphragmatic pressure and transpulmonary pressure was obtained with double-balloon nasogastric catheters in critically ill patients (n = 38). Pocc and P0.1 were measured every 1 to 3 h. Correlations between Pocc and P0.1 with change in transdiaphragmatic pressure and transpulmonary pressure were computed from patients from the first cohort. Accuracy of Pocc and P0.1 to identify patients with extremes of lung stress (change in transpulmonary pressure > 20 cm H2O) and diaphragm effort (change in transdiaphragmatic pressure < 3 cm H2O and >12 cm H2O) in the preceding hour was assessed with area under receiver operating characteristic curves. Cutoffs were validated in patients from the second cohort (n = 13). RESULTS: Pocc and P0.1 correlate with change in transpulmonary pressure (R2 = 0.62 and 0.51, respectively) and change in transdiaphragmatic pressure (R2 = 0.53 and 0.22, respectively). Area under receiver operating characteristic curves to detect high lung stress is 0.90 (0.86 to 0.94) for Pocc and 0.88 (0.84 to 0.92) for P0.1. Area under receiver operating characteristic curves to detect low diaphragm effort is 0.97 (0.87 to 1.00) for Pocc and 0.93 (0.81 to 0.99) for P0.1. Area under receiver operating characteristic curves to detect high diaphragm effort is 0.86 (0.81 to 0.91) for Pocc and 0.73 (0.66 to 0.79) for P0.1. Performance was similar in the external dataset. CONCLUSIONS: Pocc and P0.1 correlate with lung stress and diaphragm effort in the preceding hour. Diagnostic performance of Pocc and P0.1 to detect extremes in these parameters is reasonable to excellent. Pocc is more accurate in detecting high diaphragm effort.

Efficacy and safety of intravenous imatinib in COVID-19 ARDS: a randomized, double-blind, placebo-controlled clinical trial.

PURPOSE: 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. Trial registration NCT04794088 , registered 11 March 2021. European Clinical Trials Database (EudraCT number: 2020-005447-23).

Bosutinib prevents vascular leakage by reducing focal adhesion turnover and reinforcing junctional integrity.

Endothelial barrier dysfunction leads to edema and vascular leak, causing high morbidity and mortality. Previously, Abl kinase inhibition has been shown to protect against vascular leak. Using the distinct inhibitory profiles of clinically available Abl kinase inhibitors, we aimed to provide a mechanistic basis for novel treatment strategies against vascular leakage syndromes. We found that the inhibitor bosutinib most potently protected against inflammation-induced endothelial barrier disruption. In vivo, bosutinib prevented lipopolysaccharide (LPS)-induced alveolar protein extravasation in an acute lung injury mice model. Mechanistically, mitogen-activated protein 4 kinase 4 (MAP4K4) was identified as important novel mediator of endothelial permeability, which signaled via ezrin, radixin and moesin proteins to increase turnover of integrin-based focal adhesions. The combined inhibition of MAP4K4 and Abl-related gene (Arg, also known as ABL2) by bosutinib preserved adherens junction integrity and reduced turnover of focal adhesions, which synergistically act to stabilize the endothelial barrier during inflammation. We conclude that MAP4K4 is an important regulator of endothelial barrier integrity, increasing focal adhesion turnover and disruption of cell-cell junctions during inflammation. Because it inhibits both Arg and MAP4K4, use of the clinically available drug bosutinib might form a viable strategy against vascular leakage syndromes.

Extended Lung Ultrasound to Differentiate Between Pneumonia and Atelectasis in Critically Ill Patients: A Diagnostic Accuracy Study.

OBJECTIVES: To determine the diagnostic accuracy of extended lung ultrasonographic assessment, including evaluation of dynamic air bronchograms and color Doppler imaging to differentiate pneumonia and atelectasis in patients with consolidation on chest radiograph. Compare this approach to the Simplified Clinical Pulmonary Infection Score, Lung Ultrasound Clinical Pulmonary Infection Score, and the Bedside Lung Ultrasound in Emergency protocol. DESIGN: Prospective diagnostic accuracy study. SETTING: Adult ICU applying selective digestive decontamination. PATIENTS: Adult patients that underwent a chest radiograph for any indication at any time during admission. Patients with acute respiratory distress syndrome, coronavirus disease 2019, severe thoracic trauma, and infectious isolation measures were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Lung ultrasound was performed within 24 hours of chest radiograph. Consolidated tissue was assessed for presence of dynamic air bronchograms and with color Doppler imaging for presence of flow. Clinical data were recorded after ultrasonographic assessment. The primary outcome was diagnostic accuracy of dynamic air bronchogram and color Doppler imaging alone and within a decision tree to differentiate pneumonia from atelectasis. Of 120 patients included, 51 (42.5%) were diagnosed with pneumonia. The dynamic air bronchogram had a 45% (95% CI, 31-60%) sensitivity and 99% (95% CI, 92-100%) specificity. Color Doppler imaging had a 90% (95% CI, 79-97%) sensitivity and 68% (95% CI, 56-79%) specificity. The combined decision tree had an 86% (95% CI, 74-94%) sensitivity and an 86% (95% CI, 75-93%) specificity. The Bedside Lung Ultrasound in Emergency protocol had a 100% (95% CI, 93-100%) sensitivity and 0% (95% CI, 0-5%) specificity, while the Simplified Clinical Pulmonary Infection Score and Lung Ultrasound Clinical Pulmonary Infection Score had a 41% (95% CI, 28-56%) sensitivity, 84% (95% CI, 73-92%) specificity and 68% (95% CI, 54-81%) sensitivity, 81% (95% CI, 70-90%) specificity, respectively. CONCLUSIONS: In critically ill patients with pulmonary consolidation on chest radiograph, an extended lung ultrasound protocol is an accurate and directly bedside available tool to differentiate pneumonia from atelectasis. It outperforms standard lung ultrasound and clinical scores.

Lung- and Diaphragm-Protective Ventilation by Titrating Inspiratory Support to Diaphragm Effort: A Randomized Clinical Trial.

OBJECTIVES: Lung- and diaphragm-protective ventilation is a novel concept that aims to limit the detrimental effects of mechanical ventilation on the diaphragm while remaining within limits of lung-protective ventilation. The premise is that low breathing effort under mechanical ventilation causes diaphragm atrophy, whereas excessive breathing effort induces diaphragm and lung injury. In a proof-of-concept study, we aimed to assess whether titration of inspiratory support based on diaphragm effort increases the time that patients have effort in a predefined "diaphragm-protective" range, without compromising lung-protective ventilation. DESIGN: Randomized clinical trial. SETTING: Mixed medical-surgical ICU in a tertiary academic hospital in the Netherlands. PATIENTS: Patients (n = 40) with respiratory failure ventilated in a partially-supported mode. INTERVENTIONS: In the intervention group, inspiratory support was titrated hourly to obtain transdiaphragmatic pressure swings in the predefined "diaphragm-protective" range (3-12 cm H2O). The control group received standard-of-care. MEASUREMENTS AND MAIN RESULTS: Transdiaphragmatic pressure, transpulmonary pressure, and tidal volume were monitored continuously for 24 hours in both groups. In the intervention group, more breaths were within "diaphragm-protective" range compared with the control group (median 81%; interquartile range [64-86%] vs 35% [16-60%], respectively; p < 0.001). Dynamic transpulmonary pressures (20.5 ± 7.1 vs 18.5 ± 7.0 cm H2O; p = 0.321) and tidal volumes (7.56 ± 1.47 vs 7.54 ± 1.22 mL/kg; p = 0.961) were not different in the intervention and control group, respectively. CONCLUSIONS: Titration of inspiratory support based on patient breathing effort greatly increased the time that patients had diaphragm effort in the predefined "diaphragm-protective" range without compromising tidal volumes and transpulmonary pressures. This study provides a strong rationale for further studies powered on patient-centered outcomes.

Lung Ultrasound Signs to Diagnose and Discriminate Interstitial Syndromes in ICU Patients: A Diagnostic Accuracy Study in Two Cohorts.

OBJECTIVES: To determine the diagnostic accuracy of lung ultrasound signs for both the diagnosis of interstitial syndrome and for the discrimination of noncardiogenic interstitial syndrome (NCIS) from cardiogenic pulmonary edema (CPE) in a mixed ICU population. DESIGN: A prospective diagnostic accuracy study with derivation and validation cohorts. SETTING: Three academic mixed ICUs in the Netherlands. PATIENTS: Consecutive adult ICU patients that received a lung ultrasound examination. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULT: The reference standard was the diagnosis of interstitial syndrome (NCIS or CPE) or noninterstitial syndromes (other pulmonary diagnoses and no pulmonary diagnoses) based on full post-hoc clinical chart review except lung ultrasound. The index test was a lung ultrasound examination performed and scored by a researcher blinded to clinical information. A total of 101 patients were included in the derivation and 122 in validation cohort. In the derivation cohort, patients with interstitial syndrome ( n = 56) were reliably discriminated from other patients based on the presence of a B-pattern (defined as greater than or equal to 3 B-lines in one frame) with an accuracy of 94.7% (sensitivity, 90.9%; specificity, 91.1%). For discrimination of NCIS ( n = 29) from CPE ( n = 27), the presence of bilateral pleural line abnormalities (at least two: fragmented, thickened or irregular) had the highest diagnostic accuracy (94.6%; sensitivity, 89.3%; specificity, 100%). A diagnostic algorithm (Bedside Lung Ultrasound for Interstitial Syndrome Hierarchy protocol) using B-pattern and bilateral pleural abnormalities had an accuracy of 0.86 (95% CI, 0.77-0.95) for diagnosis and discrimination of interstitial syndromes. In the validation cohort, which included 122 patients with interstitial syndrome, bilateral pleural line abnormalities discriminated NCIS ( n = 98) from CPE ( n = 24) with a sensitivity of 31% (95% CI, 21-40%) and a specificity of 100% (95% CI, 86-100%). CONCLUSIONS: Lung ultrasound can diagnose and discriminate interstitial syndromes in ICU patients with moderate-to-good accuracy. Pleural line abnormalities are highly specific for NCIS, but sensitivity is limited.

Incidence of transfusion-related acute lung injury temporally associated with solvent/detergent plasma use in the ICU: A retrospective before and after implementation study.

BACKGROUND: Transfusion-related acute lung injury (TRALI) is a severe complication of plasma transfusion, though the use of solvent/detergent pooled plasma (SDP) has nearly eliminated reported TRALI cases. The goal of this study was to investigate the incidence of TRALI in intensive care units (ICU) following the replacement of quarantined fresh frozen plasma (qFFP) by SDP. STUDY DESIGN AND METHODS: A retrospective multicenter observational before-after cohort study was performed during two 6-month periods, before (April-October 2014) and after the introduction of SDP (April-October 2015), accounting for a washout period. A full chart review was performed for patients who received ≥1 plasma units and developed hypoxemia within 24 h. RESULTS: During the study period, 8944 patients were admitted to the ICU. Exactly 1171 quarantine fresh frozen plasma (qFFP) units were transfused in 376 patients, and respectively, 2008 SDP units to 396 patients after implementation. Ten TRALI cases occurred during the qFFP and nine cases occurred during the SDP period, in which plasma was transfused. The incidence was 0.85% (CI95%: 0.33%-1.4%) per unit qFFP and 0.45% (CI95%: 0.21%-0.79%, p = 0.221) per SDP unit. One instance of TRALI occurred after a single SDP unit. Mortality was 70% for patients developing TRALI in the ICU compared with 22% in patients receiving at least one plasma transfusion. CONCLUSION: Implementation of SDP lowered the incidence of TRALI in which plasma products were implicated, though not significantly. Clinically diagnosed TRALI can still occur following SDP transfusion. Developing TRALI in the ICU was associated with high mortality rates, therefore, clinicians should remain vigilant.

Association between early cumulative fluid balance and successful liberation from invasive ventilation in COVID-19 ARDS patients - insights from the PRoVENT-COVID study: a national, multicenter, observational cohort analysis.

BACKGROUND: Increasing evidence indicates the potential benefits of restricted fluid management in critically ill patients. Evidence lacks on the optimal fluid management strategy for invasively ventilated COVID-19 patients. We hypothesized that the cumulative fluid balance would affect the successful liberation of invasive ventilation in COVID-19 patients with acute respiratory distress syndrome (ARDS). METHODS: We analyzed data from the multicenter observational 'PRactice of VENTilation in COVID-19 patients' study. Patients with confirmed COVID-19 and ARDS who required invasive ventilation during the first 3 months of the international outbreak (March 1, 2020, to June 2020) across 22 hospitals in the Netherlands were included. The primary outcome was successful liberation of invasive ventilation, modeled as a function of day 3 cumulative fluid balance using Cox proportional hazards models, using the crude and the adjusted association. Sensitivity analyses without missing data and modeling ARDS severity were performed. RESULTS: Among 650 patients, three groups were identified. Patients in the higher, intermediate, and lower groups had a median cumulative fluid balance of 1.98 L (1.27-7.72 L), 0.78 L (0.26-1.27 L), and - 0.35 L (- 6.52-0.26 L), respectively. Higher day 3 cumulative fluid balance was significantly associated with a lower probability of successful ventilation liberation (adjusted hazard ratio 0.86, 95% CI 0.77-0.95, P = 0.0047). Sensitivity analyses showed similar results. CONCLUSIONS: In a cohort of invasively ventilated patients with COVID-19 and ARDS, a higher cumulative fluid balance was associated with a longer ventilation duration, indicating that restricted fluid management in these patients may be beneficial. Trial registration Clinicaltrials.gov ( NCT04346342 ); Date of registration: April 15, 2020.

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.

BACKGROUND: 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 .

Incidence and risk factors of deep vein thrombosis after extracorporeal life support.

BACKGROUND: Deep vein thrombosis (DVT) after decannulation of extracorporeal life support (ECLS) is not uncommon. Moreover, the impact of anticoagulation and potential risk factors is unclear. Furthermore, it is unclear if cannula-associated DVT is more common in ECLS patients compared to critically ill patients without ECLS. METHODS: All adult patients who were successfully weaned from ECLS and were screened for DVT following decannulation were included in this observational cohort study. The incidence of post-ECLS-DVT was assessed and the cannula-associated DVT rate was compared with that of patients without ECLS after central venous catheter (CVC) removal. The correlation between the level of anticoagulation, risk factors, and post-ECLS-DVT was determined. RESULTS: We included 30 ECLS patients and 53 non-ECLS patients. DVT was found in 15 patients (50%) of which 10 patients had a DVT in a cannulated vein. No correlation between the level of anticoagulation and DVT was found. V-V ECLS mode was the only independent risk factor for post-ECLS-DVT (OR 5.5; 95%CI 1.16-26.41). We found no difference between the ECLS and non-ECLS cohorts regarding cannula-associated DVT rate (33% vs. 32%). CONCLUSION: Post-ECLS-DVT is a common finding that occurs in half of all patients supported with ECLS. The incidence of cannula-associated DVT was equal to CVC-associated DVT in critically ill patients without ECLS. V-V ECLS was an independent risk factor for post-ECLS-DVT.

Changes in Respiratory Muscle Thickness during Mechanical Ventilation: Focus on Expiratory Muscles.

BACKGROUND: The lateral abdominal wall muscles are recruited with active expiration, as may occur with high breathing effort, inspiratory muscle weakness, or pulmonary hyperinflation. The effects of critical illness and mechanical ventilation on these muscles are unknown. This study aimed to assess the reproducibility of expiratory muscle (i.e., lateral abdominal wall muscles and rectus abdominis muscle) ultrasound and the impact of tidal volume on expiratory muscle thickness, to evaluate changes in expiratory muscle thickness during mechanical ventilation, and to compare this to changes in diaphragm thickness. METHODS: Two raters assessed the interrater and intrarater reproducibility of expiratory muscle ultrasound (n = 30) and the effect of delivered tidal volume on expiratory muscle thickness (n = 10). Changes in the thickness of the expiratory muscles and the diaphragm were assessed in 77 patients with at least two serial ultrasound measurements in the first week of mechanical ventilation. RESULTS: The reproducibility of the measurements was excellent (interrater intraclass correlation coefficient: 0.994 [95% CI, 0.987 to 0.997]; intrarater intraclass correlation coefficient: 0.992 [95% CI, 0.957 to 0.998]). Expiratory muscle thickness decreased by 3.0 ± 1.7% (mean ± SD) with tidal volumes of 481 ± 64 ml (P < 0.001). The thickness of the expiratory muscles remained stable in 51 of 77 (66%), decreased in 17 of 77 (22%), and increased in 9 of 77 (12%) patients. Reduced thickness resulted from loss of muscular tissue, whereas increased thickness mainly resulted from increased interparietal fasciae thickness. Changes in thickness of the expiratory muscles were not associated with changes in the thickness of the diaphragm (R2 = 0.013; P = 0.332). CONCLUSIONS: Thickness measurement of the expiratory muscles by ultrasound has excellent reproducibility. Changes in the thickness of the expiratory muscles occurred in 34% of patients and were unrelated to changes in diaphragm thickness. Increased expiratory muscle thickness resulted from increased thickness of the fasciae.

Weaning the patient: between protocols and physiology.

PURPOSE OF REVIEW: Ventilator weaning forms an integral part in critical care medicine and strategies to shorten duration are rapidly evolving alongside our knowledge of the relevant physiological processes. The purpose of the current review is to discuss new physiological and clinical insights in ventilator weaning that help us to fasten liberation from mechanical ventilation. RECENT FINDINGS: Several new concepts have been introduced in the field of ventilator weaning in the past 2 years. Approaches to shorten the time until ventilator liberation include frequent spontaneous breathing trials, early noninvasive mechanical ventilation to shorten invasive ventilation time, novel ventilatory modes, such as neurally adjusted ventilatory assist and drugs to enhance the contractile efficiency of respiratory muscles. Equally important, ultrasound has been shown to be a versatile tool to monitor physiological changes of the cardiorespiratory system during weaning and steer targeted interventions to improve extubation outcome. SUMMARY: A thorough understanding of the physiological adaptations during withdrawal of positive pressure ventilation is extremely important for clinicians in the ICU. We summarize and discuss novel insights in this field.