Subphenotypes in patients with acute respiratory distress syndrome treated with high-flow oxygen.

BACKGROUND: Acute respiratory distress syndrome (ARDS) subphenotypes differ in outcomes and treatment responses. Subphenotypes in high-flow nasal oxygen (HFNO)-treated ARDS patients have not been investigated. OBJECTIVES: To identify biological subphenotypes in HFNO-treated ARDS patients. METHODS: Secondary analysis of a prospective multicenter observational study including ARDS patients supported with HFNO. Plasma inflammation markers (interleukin [IL]-6, IL-8, and IL-33 and soluble suppression of tumorigenicity-2 [sST2]) and lung epithelial (receptor for advanced glycation end products [RAGE] and surfactant protein D [SP-D]) and endothelial (angiopoietin-2 [Ang-2]) injury were measured. These biomarkers and bicarbonate were used in K-means cluster analysis to identify subphenotypes. Logistic regression was performed on biomarker combinations to predict clustering. We chose the model with the best AUROC and the lowest number of variables. This model was used to describe the HAIS (High-flow ARDS Inflammatory Subphenotype) score. RESULTS: Among 41 HFNO patients, two subphenotypes were identified. Hyperinflammatory subphenotype (n = 17) showed higher biomarker levels than hypoinflammatory (n = 24). Despite similar baseline characteristics, the hyperinflammatory subphenotype had higher 60-day mortality (47 vs 8.3% p = 0.014) and longer ICU length of stay (22.0 days [18.0-30.0] vs 39.5 [25.5-60.0], p = 0.034). The HAIS score, based on IL-8 and sST2, accurately distinguished subphenotypes (AUROC 0.96 [95%CI: 0.90-1.00]). A HAIS score ≥ 7.45 was predictor of hyperinflammatory subphenotype. CONCLUSION: ARDS patients treated with HFNO exhibit two biological subphenotypes that have similar clinical characteristics, but hyperinflammatory patients have worse outcomes. The HAIS score may identify patients with hyperinflammatory subphenotype and might be used for enrichment strategies in future clinical trials.

Use of thoracic ultrasound in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a significant cause of morbidity and mortality in critically ill patients, yet it is often underrecognized. Current imaging techniques, such as CT scan and X-ray, have several limitations, including inter-observer reliability, limited accessibility, radiation and the need for transportation. Ultrasound has become an essential bedside tool in the critical care setting and the emergency room, offering several advantages over traditional imaging techniques. It is nowadays widely used for diagnosis and early management of acute respiratory and circulatory failure. Lung ultrasound (LUS) provides non-invasively valuable information regarding lung aeration, ventilation distribution and respiratory complications in ARDS patients at the bedside. Moreover, a holistic ultrasound approach, combining LUS, echocardiography, and diaphragm ultrasound offers physiological information that could help the clinician to personalize ventilator settings and guide fluid resuscitation in these patients. Ultrasound techniques could also inform about possible causes of weaning failure in difficult-to-wean patients. However, it is uncertain whether clinical decisions based on ultrasound assessment can improve outcomes in ARDS patients and this clinical approach requires further investigation. In this article, we review the use of thoracic ultrasound, including lung and diaphragm examination, for the clinical assessment of patients with ARDS, and discuss its limitations and future perspectives.

Role of ultrasound in acute respiratory failure and in the weaning of mechanical ventilation.

Comprehensive ultrasound assessment has become an essential tool to facilitate the diagnosis and therapeutic management of critically ill patients with acute respiratory failure (ARF). There is evidence supporting the use of ultrasound for the diagnosis of pneumothorax, acute respiratory distress syndrome, cardiogenic pulmonary edema, pneumonia and acute pulmonary thromboembolism, and in patients with COVID-19. In addition, in recent years, the use of ultrasound to evaluate responses to treatment in critically ill patients with ARF has been developed, providing a noninvasive tool for titrating positive end-expiratory pressure, monitoring recruitment maneuvers and response to prone position, as well as for facilitating weaning from mechanical ventilation. The objective of this review is to summarize the basic concepts on the utility of ultrasound in the diagnosis and monitoring of critically ill patients with ARF.

Lung allograft transbronchial cryobiopsy for critical ventilated patients: a randomised trial.

BACKGROUND: Transbronchial lung cryobiopsy is an emerging technique for diagnosing pulmonary rejection. However, no prospective studies of this procedure for critically ill lung transplant recipients who require mechanical ventilation in the intensive care unit (ICU) have been performed. METHODS: From March 2017 to January 2020, we performed a prospective, randomised, comparative study to assess the diagnostic yield, histological quality and safety of transbronchial lung biopsy using biopsy forceps, a 1.9-mm cryoprobe or a 2.4-mm cryoprobe. RESULTS: 89 out of 129 consecutive transbronchial biopsy procedures (forceps group, 28 procedures; 1.9-mm cryoprobe group, 31 procedures; 2.4-mm cryoprobe group, 30 procedures) were randomised. Compared with lung samples from the forceps and 1.9-mm cryoprobe groups, lung samples from the 2.4-mm cryoprobe group allowed the most definitive diagnoses (p<0.01 and p=0.02, respectively), the most diagnoses of acute lung rejection (p<0.01 and p=0.01, respectively) and the most diagnoses of rejection severity (p<0.01 and p<0.01, respectively). These samples were larger (p<0.01 and p=0.04, respectively), had the most adequate alveolar tissue (p<0.01 and p=0.02, respectively), had more vessels per procedure (p<0.01 and p=0.01, respectively) and had no significant crush artefacts. Moderate bleeding was observed in 23% of cases (p=0.01 and p=0.08, respectively). No severe bleeding was observed. CONCLUSIONS: Transbronchial lung biopsy using a 2.4-mm cryoprobe allows the safe collection of lung tissue samples from critically ill lung transplant recipients who require mechanical ventilation in the ICU and has good diagnostic performance.

Lung ultrasound response to awake prone positioning predicts the need for intubation in patients with COVID-19 induced acute hypoxemic respiratory failure: an observational study.

BACKGROUND: Awake prone positioning (APP) reduces the intubation rate in COVID-19 patients treated by high-flow nasal cannula (HFNC). However, the lung aeration response to APP has not been addressed. We aimed to explore the lung aeration response to APP by lung ultrasound (LUS). METHODS: This two-center, prospective, observational study enrolled patients with COVID-19-induced acute hypoxemic respiratory failure treated by HFNC and APP. LUS score was recorded 5-10 min before, 1 h after APP, and 5-10 min after supine in the first APP session within the first three days. The primary outcome was LUS score changes in the first three days. Secondary outcomes included changes in SpO2/FiO2 ratio, respiratory rate and ROX index (SpO2/FiO2/respiratory rate) related to APP, and the rate of treatment success (patients who avoided intubation). RESULTS: Seventy-one patients were enrolled. LUS score decreased from 20 (interquartile range [IQR] 19-24) to 19 (18-21) (p < 0.001) after the first APP session, and to 19 (18-21) (p < 0.001) after three days. Compared to patients with treatment failure (n = 20, 28%), LUS score reduction after the first three days in patients with treatment success (n = 51) was greater (- 2.6 [95% confidence intervals - 3.1 to - 2.0] vs 0 [- 1.2 to 1.2], p = 0.001). A decrease in dorsal LUS score > 1 after the first APP session was associated with decreased risk for intubation (Relative risk 0.25 [0.09-0.69]). APP daily duration was correlated with LUS score reduction in patients with treatment success, especially in dorsal lung zones (r = - 0.76; p < 0.001). CONCLUSIONS: In patients with acute hypoxemic respiratory failure due to COVID-19 and treated by HFNC, APP reduced LUS score. The reduction in dorsal LUS scores after APP was associated with treatment success. The longer duration on APP was correlated with greater lung aeration. Trial registration This study was prospectively registered on clinicaltrials.gov on April 22, 2021. Identification number NCT04855162 .

Echocardiographic assessment of COVID19 sequelae in survivors with elevated cardiac biomarkers.

AIMS: We sought to determine, using advanced echocardiography, the prevalence and type of cardiovascular sequelae after COVID19 infection with marked elevation of cardiovascular biomarkers (CVB), and their prognostic implications. METHODS: All patients admitted from March 1st to May 25th, 2020 to a tertiary referral hospital were included. Those with cardiovascular diseases or dead during admission were excluded. Patients with hs-TnI > 45 ng/L, NT-proBNP>300 pg/mL, and D-dimer >8000 ng/mL were matched with COVID controls (three biomarkers within the normal range) based on intensive care requirements and age, and separately analyzed. RESULTS: From 2025 patients, 80 patients with significantly elevated CVB and 29 controls were finally included. No differences in baseline characteristics were observed among groups, but elevated CVB patients were sicker. Follow-up echocardiograms showed no differences among groups regarding LVEF and only slight differences between groups within the normal range. Hs-TnI patients had lower myocardial work and longitudinal strain. The presence of an abnormal echocardiogram was more frequent in the elevated CVB group compared to controls (23.8 vs 10.3%, P = 0.123) but mainly associated with mild abnormalities in deformation parameters. Management did not change in any case and no major cardiovascular events except deep vein thrombosis occurred after a median follow-up of 7 months. CONCLUSION: Minimal abnormalities in cardiac structure and function are observed in COVID19 survivors without previous cardiovascular diseases who presented a significant CVB rise at admission, with no impact on patient management or short-term prognosis. These results do not support a routine screening program after discharge in this population.

Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study).

BACKGROUND: We aimed to assess the efficacy of a closed-loop oxygen control in critically ill patients with moderate to severe acute hypoxemic respiratory failure (AHRF) treated with high flow nasal oxygen (HFNO). METHODS: In this single-centre, single-blinded, randomized crossover study, adult patients with moderate to severe AHRF who were treated with HFNO (flow rate ≥ 40 L/min with FiO2 ≥ 0.30) were randomly assigned to start with a 4-h period of closed-loop oxygen control or 4-h period of manual oxygen titration, after which each patient was switched to the alternate therapy. The primary outcome was the percentage of time spent in the individualized optimal SpO2 range. RESULTS: Forty-five patients were included. Patients spent more time in the optimal SpO2 range with closed-loop oxygen control compared with manual titrations of oxygen (96.5 [93.5 to 98.9] % vs. 89 [77.4 to 95.9] %; p < 0.0001) (difference estimate, 10.4 (95% confidence interval 5.2 to 17.2). Patients spent less time in the suboptimal range during closed-loop oxygen control, both above and below the cut-offs of the optimal SpO2 range, and less time above the suboptimal range. Fewer number of manual adjustments per hour were needed with closed-loop oxygen control. The number of events of SpO2 < 88% and < 85% were not significantly different between groups. CONCLUSIONS: Closed-loop oxygen control improves oxygen administration in patients with moderate-to-severe AHRF treated with HFNO, increasing the percentage of time in the optimal oxygenation range and decreasing the workload of healthcare personnel. These results are especially relevant in a context of limited oxygen supply and high medical demand, such as the COVID-19 pandemic. Trial registration The HILOOP study was registered at www. CLINICALTRIALS: gov under the identifier NCT04965844 .

Consequences of ICU Readmission After Lung Transplantation: Beyond the Early Postoperative Period / Consecuencias del reingreso en la UCI tras el trasplante de pulmón: más allá del periodo postoperatorio temprano

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Driving Pressure Is a Risk Factor for ARDS in Mechanically Ventilated Subjects Without ARDS.

BACKGROUND: Driving pressure (ΔP) has been described as a risk factor for mortality in patients with ARDS. However, the role of ΔP in the outcome of patients without ARDS and on mechanical ventilation has received less attention. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. METHODS: This was a post hoc analysis of a multicenter, prospective, observational, international study that included subjects who were on mechanical ventilation for > 12 h. Our objective was to evaluate the association between ΔP on the first day of mechanical ventilation with the development of ARDS. To assess the effect of ΔP, a logistic regression analysis was performed when adjusting for other potential risk factors. Validation of the results obtained was performed by using a bootstrap method and by repeating the same analyses at day 2. RESULTS: A total of 1,575 subjects were included, of whom 65 (4.1%) developed ARDS. The ΔP was independently associated with ARDS (odds ratio [OR] 1.12, 95% CI 1.07-1.18 for each cm H2O of ΔP increase, P < .001). The same results were observed at day 2 (OR 1.14, 95% CI 1.07-1.21; P < .001) and after bootstrap validation (OR 1.13, 95% CI 1.04-1.22; P < .001). When taking the prevalence of ARDS in the lowest quartile of ΔP (≤9 cm H2O) as a reference, the subjects with ΔP > 12-15 cm H2O and those with ΔP > 15 cm H2O presented a higher probability of ARDS (OR 3.65, 95% CI 1.32-10.04 [P = .01] and OR 7.31, 95% CI, 2.89-18.50 [P < .001], respectively). CONCLUSIONS: In the subjects without ARDS, a higher level of ΔP on the first day of mechanical ventilation was associated with later development of ARDS. (ClinicalTrials.gov registration NCT02731898.).

To prone or not to prone ARDS patients on ECMO.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .

Hemadsorption as a Treatment Option for Multisystem Inflammatory Syndrome in Children Associated With COVID-19. A Case Report.

Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 is characterized by hypercytokinemia leading to overwhelming inflammation. We describe the use of a hemadsorption device as part of the supportive treatment for cytokine storm.

Pleth variability index may predict preload responsiveness in patients treated with nasal high flow: a physiological study.

The purpose of this study was to determine whether the plethysmographic variability index ("PVi") can predict preload responsiveness in patients with nasal high flow (NHF) (≥30 L/min) with any sign of hypoperfusion. "Preload responsiveness" was defined as a ≥10% increase in stroke volume (SV), measured by transthoracic echocardiography, after passive leg raising. SV and PVi were reassessed in preload responders after receiving a 250-mL fluid challenge. Twenty patients were included and 12 patients (60%) were preload responders. Responders showed higher baseline mean PVi (24% vs. 13%; P = 0.001) and higher mean PVi variation (ΔPVi) after passive leg raising (6.8% vs. -1.7%; P < 0.001). No differences between mean ΔPVi after passive leg raising and mean ΔPVi after fluid challenge were observed (6.8% vs. 7.4%; P = 0.24); and both values were strongly correlated (r = 0.84; P < 0.001). Baseline PVi and ΔPVi after passive leg raising showed excellent diagnostic accuracy identifying preload responders (AUROC 0.92 and 1.00, respectively). Baseline PVi ≥ 16% had a sensitivity of 91.7% and a specificity of 87.5% for detecting preload responders. Similarly, ΔPVi after passive leg raising ≥2% had a 100% of both sensitivity and specificity. Thus, PVi might predict "preload responsiveness" in patients treated with NHF, suggesting that it may guide fluid administration in these patients.NEW & NOTEWORTHY This is the first study that analyzes the use of noninvasive plethysmographic variability index (PVi) for preload assessment in patients treated with nasal high flow (NHF). Its results showed that PVi might identify preload responders. Therefore, PVi may be used in the day-to-day clinical decision-making process in critically ill patients treated with NHF, helping to provide adequate resuscitation volume.

Hemodynamic support in septic shock.

PURPOSE OF REVIEW: The current article reviews recent findings on the monitoring and hemodynamic support of septic shock patients. RECENT FINDINGS: The ultimate goal of hemodynamic resuscitation is to restore tissue oxygenation. A multimodal approach combining global and regional markers of tissue hypoxia seems appropriate to guide resuscitation. Several multicenter clinical trials have provided evidence against an aggressive fluid resuscitation strategy. Fluid administration should be personalized and based on the evidence of fluid responsiveness. Dynamic indices have proven to be highly predictive of responsiveness. Recent data suggest that balanced crystalloids may be associated with less renal failure. When fluid therapy is insufficient, a multimode approach with different types of vasopressors has been suggested as an initial approach. Dobutamine remains the firs inotropic option in patients with persistent hypotension and decrease ventricular systolic function. Calcium sensitizer and phosphodiesterase inhibitors may be considered, but evidence is still limited. Veno-arterial extracorporeal membrane oxygenation may be considered in selected unresponsive patients, particularly with myocardial depression, and in a highly experienced center. SUMMARY: Resuscitation should be personalized and based on global and regional markers of tissue hypoxia as well as the fluid responsiveness indices. The beneficial effect of multimode approach with different types of vasopressors, remains to be determined.

Extracorporeal Membrane Oxygenation Retrieval in Coronavirus Disease 2019: A Case-Series of 19 Patients Supported at a High-Volume Extracorporeal Membrane Oxygenation Center.

OBJECTIVE: To evaluate the performance of the extracorporeal membrane oxygenation retrieval team at a high-volume extracorporeal membrane oxygenation center during the coronavirus disease 2019 pandemic. DESIGN: Observational study including all adult patients with confirmed infection due to severe acute respiratory syndrome coronavirus-2 cannulated at other centers and transported on extracorporeal membrane oxygenation to the ICU of the Vall d'Hebron University Hospital between 15 March and 10 June 2020. SETTING: The ICU (capacity expanded to 200 during the pandemic) of the Vall d'Hebron University Hospital (a 1,100-bed public university hospital in Barcelona), the referral center for extracorporeal respiratory support in Catalonia (7.5 million inhabitants). PATIENTS: Extracorporeal membrane oxygenation was considered if the Pao2/Fio2 ratio less than 80 mm Hg (refractory to prone position) and/or Paco2 greater than 80 mm Hg and pH less than 7.25 for more than 6 hours, and no contraindications for extracorporeal support were present. INTERVENTIONS: Venovenous extracorporeal membrane oxygenation was initiated in the primary center. Then, patients were transferred to the ICU of the Vall d'Hebron University Hospital where they received support until respiratory improvement. After decannulation, patients were discharged for rehabilitation at the primary center. MEASUREMENTS AND MAIN RESULTS: Nineteen patients with severe acute respiratory syndrome coronavirus-2 infection and with a mean Pao2/Fio2 ratio of 71 mm Hg (57-118 mm Hg) despite prone positioning and a mean Paco2 of 70 mm Hg (47-110 mm Hg) were transferred to our center from their primary hospital after cannulation and received venovenous extracorporeal membrane oxygenation support. Prior to cannulation, six patients (31.5%) presented vascular thrombosis, and nine (47.4%) were already receiving anticoagulant therapy. Eighteen transfers were carried out with no significant complications. While on extracorporeal membrane oxygenation, thrombotic events were recorded in nine patients (47.4%) and hemorrhagic events in 13 (68.4%). Thirteen patients (68.4%) were successfully weaned, and 12 (63.1%) were discharged home. CONCLUSIONS: Extracorporeal membrane oxygenation retrieval can rescue young, previously healthy patients with severe coronavirus disease 2019 in whom all the conventional respiratory measures have failed. Thrombotic and hemorrhagic complications are frequent in this cohort.

High-Flow Oxygen with Capping or Suctioning for Tracheostomy Decannulation.

BACKGROUND: When patients with a tracheostomy tube reach a stage in their care at which decannulation appears to be possible, it is common practice to cap the tracheostomy tube for 24 hours to see whether they can breathe on their own. Whether this approach to establishing patient readiness for decannulation leads to better outcomes than one based on the frequency of airway suctioning is unclear. METHODS: In five intensive care units (ICUs), we enrolled conscious, critically ill adults who had a tracheostomy tube; patients were eligible after weaning from mechanical ventilation. In this unblinded trial, patients were randomly assigned either to undergo a 24-hour capping trial plus intermittent high-flow oxygen therapy (control group) or to receive continuous high-flow oxygen therapy with frequency of suctioning being the indicator of readiness for decannulation (intervention group). The primary outcome was the time to decannulation, compared by means of the log-rank test. Secondary outcomes included decannulation failure, weaning failure, respiratory infections, sepsis, multiorgan failure, durations of stay in the ICU and hospital, and deaths in the ICU and hospital. RESULTS: The trial included 330 patients; the mean (±SD) age of the patients was 58.3±15.1 years, and 68.2% of the patients were men. A total of 161 patients were assigned to the control group and 169 to the intervention group. The time to decannulation was shorter in the intervention group than in the control group (median, 6 days [interquartile range, 5 to 7] vs. 13 days [interquartile range, 11 to 14]; absolute difference, 7 days [95% confidence interval, 5 to 9]). The incidence of pneumonia and tracheobronchitis was lower, and the duration of stay in the hospital shorter, in the intervention group than in the control group. Other secondary outcomes were similar in the two groups. CONCLUSIONS: Basing the decision to decannulate on suctioning frequency plus continuous high-flow oxygen therapy rather than on 24-hour capping trials plus intermittent high-flow oxygen therapy reduced the time to decannulation, with no evidence of a between-group difference in the incidence of decannulation failure. (REDECAP ClinicalTrials.gov number, NCT02512744.).