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Background: Improvements in oxygenation and lung mechanics with prone position (PP) in patients with acute respiratory distress syndrome (ARDS) are inconstant. The objectives of the study were (i) to identify baseline variables, including the recruitment-to-inflation ratio (R/I), associated with a positive response to PP in terms of oxygenation (improvement of the ratio of arterial oxygen partial pressure over the inspired oxygen fraction (PaO2/FiO2) ≥ 20 mmHg) and lung mechanics; (ii) to evaluate whether the response to the previous PP session is associated with the response to the next session. Methods: In this prospective, observational, single-center study in patients who underwent PP for ARDS due to COVID-19, respiratory variables were assessed just before PP and at the end of the session. Respiratory variables included mechanical ventilation settings and respiratory mechanics variables, including R/I, an estimate of the potential for lung recruitment compared to lung overinflation. Results: In 50 patients, 201 PP sessions lasting 19 ± 3 h were evaluated. Neuromuscular blockades were used in 116 (58%) sessions. The PaO2/FiO2 ratio increased from 109 ± 31 mmHg to 165 ± 65 mmHg, with an increase ≥ 20 mmHg in 142 (71%) sessions. In a mixed effect logistic regression, only pre-PP PaO2/FiO2 (OR 1.12 (95% CI [1.01–1.24])/every decrease of 10 mmHg, p = 0.034) in a first model and improvement in oxygenation at the previous PP session (OR 3.69 (95% CI [1.27–10.72]), p = 0.017) in a second model were associated with an improvement in oxygenation with PP. The R/I ratio (n = 156 sessions) was 0.53 (0.30–0.76), separating lower- and higher-recruiters. Whereas PaO2/FiO2 improved to the same level in both subgroups, driving pressure and respiratory system compliance improved only in higher-recruiters (from 14 ± 4 to 12 ± 4 cmH2O, p = 0.027, and from 34 ± 11 to 38 ± 13 mL/cmH2O, respectively, p = 0.014). Conclusions: A lower PaO2/FiO2 at baseline and a positive O2-response at the previous PP session are associated with a PP-induced improvement in oxygenation. In higher-recruiters, lung mechanics improved along with oxygenation. Benefits of PP could thus be greater in these patients. [ABSTRACT FROM AUTHOR]

This narrative review delves into the intricate interplay between the lungs and the kidneys, with a focus on elucidating the pathogenesis of diseases influenced by immunological factors, acid–base regulation, and blood gas disturbances, as well as assessing the effects of various therapeutic modalities on these interactions. Key disorders, such as anti-glomerular basement membrane (anti-GBM) disease, the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and Anti-neutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV), are also examined to shed light on their underlying mechanisms. This review also explores the relationship between acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), emphasizing how inflammatory mediators can lead to systemic damage and impact multiple organs. In ARDS, fluid overload exacerbates pulmonary edema, while imbalances in blood volume, such as hypovolemia or hypervolemia, can precipitate renal dysfunction. The review highlights how mechanical ventilation strategies can compromise renal blood flow, trigger systemic inflammation, and induce hemodynamic and neurohormonal alterations, all contributing to lung and kidney damage. The impact of extracorporeal membrane oxygenation (ECMO) on lung–kidney interactions is evaluated, highlighting its role in severe respiratory failure and its renal implications. Emerging therapies, such as mesenchymal stem cells and extracellular vesicles, are discussed as promising avenues to mitigate organ damage and enhance outcomes in critically ill patients. Overall, this review offers a nuanced exploration of lung–kidney dynamics, bridging historical insights with contemporary perspectives. It underscores the clinical significance of these interactions in critically ill patients and advocates for integrated management approaches to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Factor XII (FXII) is the zymogen of the plasma protease FXIIa that activates the intrinsic coagulation pathway and the kallikrein kinin-system. The role of FXII in inflammation has been obscure. Here, we report a single-domain antibody (nanobody, Nb) fused to the Fc region of a human immunoglobulin (Nb-Fc) that recognizes FXII in a conformation-dependent manner and interferes with FXIIa formation. Nb-Fc treatment inhibited arterial thrombosis in male mice without affecting hemostasis. In a mouse model of extracorporeal membrane oxygenation (ECMO), FXII inhibition or knockout reduced thrombus deposition on oxygenator membranes and systemic microvascular thrombi. ECMO increased circulating levels of D-dimer, alkaline phosphatase, creatinine and TNF-α and triggered microvascular neutrophil adherence, platelet aggregation and their interaction, which were substantially attenuated by FXII blockade. Both Nb-Fc treatment and FXII knockout markedly ameliorated immune complex-induced local vasculitis and anti-neutrophil cytoplasmic antibody-induced systemic vasculitis, consistent with selectively suppressed neutrophil migration. In human blood microfluidic analysis, Nb-Fc treatment prevented collagen-induced fibrin deposition and neutrophil adhesion/activation. Thus, FXII is an important mediator of inflammatory responses in vasculitis and ECMO, and Nb-Fc provides a promising approach to alleviate thrombo-inflammatory disorders. Thrombosis and inflammation coexist in many diseases, however, there is lack of treatments targeting both pathologies. This study reports a novel antibody against blood factor XII, which bears a promise to treat broad thrombo-inflammatory disorder. [ABSTRACT FROM AUTHOR]

The use of extracorporeal membrane oxygenation (ECMO) has grown rapidly, driven by the COVID-19 pandemic. Despite its widespread adoption, neurological complications pose a significant risk, impacting both mortality and survivors' quality of life. Detecting these complications is challenging due to sedation and the heterogeneous nature of ECMO-associated neurological injury. Still, consensus of neurologic monitoring during ECMO is lacking since utilization and effectiveness of current neuromonitoring methods are limited. Especially in view of the heterogeneous nature of neurological injury during ECMO support an easily acquirable biomarker tracing neuronal damage independently from the underlying pathomechanism would be favorable. In a single-center prospective study on 34 severe acute respiratory distress syndrome (ARDS) patients undergoing ECMO, we explored the potential of serum neurofilament light chain levels (NfL) as a biomarker for neurological complications and its predictive power towards the overall outcome of ECMO patients. Individuals experiencing neurological complications (41%) demonstrated a notable rise in NfL levels (Tbaseline median 92.95 pg/ml; T24h median 132 pg/ml (IQR 88.6–924 pg/ml), p = 0.008; T7d median 248 pg/ml (IQR 157–1090 pg/ml), p = 0.001). Moreover, under ECMO therapy, these patients exhibited markedly elevated concentrations compared to those without neurological complications (T24h median 70.75 pg/ml (IQR 22.2–290 pg/ml), p = 0.023; T7d median 128 pg/ml (IQR 51.8–244 pg/ml), p = 0.002). There was no significant difference in the NfL dynamics between surviving patients and those who died during or shortly after ECMO therapy. While NfL indicates neuro-axonal damage during intensive care with ECMO therapy, we could not identify any correlation between survival outcome and the levels of NfL, indicating that NfL may not serve as a prognostic marker for survival. Nevertheless, additional studies involving a larger patient cohort are required. [ABSTRACT FROM AUTHOR]

In this work, the interactions between nitric oxide (NO)/nitrogen dioxide (NO2) and the polymer materials of a gas exchanger system used in an extracorporeal membrane oxygenation (ECMO) setting are characterized. FTIR-ATR, XPS, and SEM were used to analyze the effects of the gas treatment. The polymer materials used in the gas exchanger system consisted of polymethylpentene (PMP) hollow fiber membranes, inlet/outlet caps made of methyl methacrylate acrylonitrile butadiene styrene (MABS), casting material consisting of polyurethane (PU), and the gas hoses made of polyvinyl chloride (PVC). Gas treatment with NO and NO2 was conducted, with exposure times ranging from 30 min to 10 days. The gas concentrations range from 80 to 1000 ppm in the case of NO2 and a maximum of 10,000 ppm in the case of NO. The formation of nitro and nitrate ester groups and nitric acid (HNO3) adsorption on the polymers' surface was observed using FTIR-ATR and XPS. The investigations showed that these effects depend on exposure time and gas concentration. The alterations persisted over more extended periods. The XPS measurements showed that the reaction only occurred exclusively on the surface of the polymers. The recorded SEM images showed no macroscopic changes in the surface structures of the polymers. [ABSTRACT FROM AUTHOR]

Purpose: Patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) frequently develop arterial hyperoxaemia, which may be harmful. However, lower oxygen saturation targets may also lead to harmful episodes of hypoxaemia. Methods: In this registry-embedded, multicentre trial, we randomly assigned adult patients receiving VA-ECMO in an intensive care unit (ICU) to either a conservative (target SaO2 92–96%) or to a liberal oxygen strategy (target SaO2 97–100%) through controlled oxygen administration via the ventilator and ECMO gas blender. The primary outcome was the number of ICU-free days to day 28. Secondary outcomes included ICU-free days to day 60, mortality, ECMO and ventilation duration, ICU and hospital lengths of stay, and functional outcomes at 6 months. Results: From September 2019 through June 2023, 934 patients who received VA-ECMO were reported to the EXCEL registry, of whom 300 (192 cardiogenic shock, 108 refractory cardiac arrest) were recruited. We randomised 149 to a conservative and 151 to a liberal oxygen strategy. The median number of ICU-free days to day 28 was similar in both groups (conservative: 0 days [interquartile range (IQR) 0–13.7] versus liberal: 0 days [IQR 0–13.7], median treatment effect: 0 days [95% confidence interval (CI) – 3.1 to 3.1]). Mortality at day 28 (59/159 [39.6%] vs 59/151 [39.1%]) and at day 60 (64/149 [43%] vs 62/151 [41.1%] were similar in conservative and liberal groups, as were all other secondary outcomes and adverse events. The conservative group experienced 44 (29.5%) major protocol deviations compared to 2 (1.3%) in the liberal oxygen group (P < 0.001). Conclusions: In adults receiving VA-ECMO in ICU, a conservative compared to a liberal oxygen strategy, did not affect the number of ICU-free days to day 28. [ABSTRACT FROM AUTHOR]

Purpose: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is an integral part of the management algorithm of patients with severe respiratory failure refractory to evidence-based conventional treatments. Right ventricular injury (RVI) pertaining to abnormalities in the dimensions and/or function of the right ventricle (RV) in the context of VV-ECMO significantly influences mortality. However, in the absence of a universally accepted RVI definition and evidence-based guidance for the management of RVI in this very high-risk patient cohort, variations in clinical practice continue to exist. Methods: Following a systematic search of the literature, an international Steering Committee consisting of eight healthcare professionals involved in the management of patients receiving ECMO identified domains and knowledge gaps pertaining to RVI definition and management where the evidence is limited or ambiguous. Using a Delphi process, an international panel of 52 Experts developed Expert position statements in those areas. The process also conferred RV-centric overarching open questions for future research. Consensus was defined as achieved when 70% or more of the Experts agreed or disagreed on a Likert-scale statement or when 80% or more of the Experts agreed on a particular option in multiple‐choice questions. Results: The Delphi process was conducted through four rounds and consensus was achieved on 31 (89%) of 35 statements from which 24 Expert position statements were derived. Expert position statements provided recommendations for RVI nomenclature in the setting of VV-ECMO, a multi-modal diagnostic approach to RVI, the timing and parameters of diagnostic echocardiography, and VV-ECMO settings during RVI assessment and management. Consensus was not reached on RV-protective driving pressure thresholds or the effect of prone positioning on patient-centric outcomes. Conclusion: The proposed definition of RVI in the context of VV-ECMO needs to be validated through a systematic aggregation of data across studies. Until further evidence emerges, the Expert position statements can guide informed decision-making in the management of these patients. [ABSTRACT FROM AUTHOR]

This article discusses the importance of protecting the diaphragm during invasive mechanical ventilation. Diaphragm dysfunction is a common issue in mechanically ventilated patients and can be caused by various factors. The article outlines a stepwise approach to diaphragm protection, including monitoring diaphragmatic effort, minimizing the duration of diaphragm inactivity, avoiding excessive respiratory drive and effort, maintaining patient-ventilator synchrony, and following evidence-based weaning strategies. It is important to note that the impact of diaphragm-protective ventilation on outcomes has not been established and further clinical trials are needed. [Extracted from the article]

Extracorporeal life support systems (ECLS) are life-sustaining measures for severe cardiovascular diseases, serving as bridging treatment either until cardiovascular function is restored or alternative treatment, such as heart transplantation or the implantation of permanent ventricular assist devices is performed. Given the insufficient evidence and frequent urgency of implantation without initial patient consent, the ethical challenges and psychological burden for patients, relatives and the interprofessional intensive care team are significant. As with any treatment, an appropriate therapeutic goal for ECLS treatment based on the indications and patient informed consent is mandatory. In order to integrate the necessary ethical considerations into everyday clinical practice, a structured algorithm for handling ECLS is proposed here, which takes ethical aspects into due account. [ABSTRACT FROM AUTHOR]

Background: The South Korean government implemented a multidisciplinary nutritional support team (NST) system to focus on the proper evaluation and supply of nutritional status in hospitalized patients who are at a higher risk of malnutrition. Methods: This nationwide population-based cohort study included patients diagnosed with sepsis who were admitted to hospitals from 2016 to 2020. The NST should consist of four professional personnel (physicians, full-time nurses, full-time pharmacists, and full-time clinical dietitians). The NST group included patients with sepsis admitted to a hospital with an NST system, whereas the non-NST group included patients with sepsis admitted to a hospital without an NST system. Results: A total of 323,841 patients with sepsis were included in the final analysis, and 120,274 (37.1%) admitted to a hospital with an NST system were included in the NST group. In the multivariable Cox regression analysis, the NST group showed a 15% lower 90-day mortality than the non-NST group (hazard ratio [HR]:0.85, 95% confidence interval [CI]:0.83, 0.86; P < 0.001). The NST group shows 11% lower 1-year all-cause mortality than the non-NST group (HR:0.89, 95% CI:0.87, 0.90; P < 0.001). In subgroup analyses, a more evident association of the NST group with lower 90-day mortality was shown in the intensive care unit admission group and age ≥65 years old group. Conclusions: Multidisciplinary NST intervention is associated with improved survival outcomes in patients with sepsis. Moreover, this association was more evident in patients with sepsis aged ≥65 years old who were admitted to the ICU. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) remains a significant challenge in critical care, with high mortality rates despite advancements in treatment. Venovenous extracorporeal membrane oxygenation (VV-ECMO) is employed as salvage therapy for refractory cases. However, some patients may continue to experience persistent severe hypoxemia despite being treated with VV-ECMO. To achieve this, moderate hypothermia and short-acting selective β1-blockers have been proposed. Methods: Using a swine model of severe ARDS treated with VV-ECMO, this study investigated the efficacy of moderate hypothermia or β-blockade in improving arterial oxygen saturation (SaO2) three hours after VV-ECMO initiation. Primary endpoints included the ratio of VV-ECMO flow to cardiac output and arterial oxygen saturation before VV-ECMO start (H0) and three hours after ECMO start (H3). Secondary safety criteria encompassed hemodynamics and oxygenation parameters. Results: Twenty-two male pigs were randomized into three groups: control (n = 6), hypothermia (n = 9) and β-blockade (n = 7). At H0, all groups demonstrated similar hemodynamic and respiratory parameters. Both moderate hypothermia and β-blockade groups exhibited a significant increase in the ratio of VV-ECMO flow to cardiac output at H3, resulting in improved SaO2. At H3, despite a decrease in oxygen delivery and consumption in the intervention groups compared to the control group, oxygen extraction ratios across groups remained unchanged and lactate levels were normal. Conclusions: In a swine model of severe ARDS treated with VV-ECMO, both moderate hypothermia and β-blockade led to an increase in the ratio of VV-ECMO flow to cardiac output resulting in improved arterial oxygen saturation without any impact on tissue perfusion. [ABSTRACT FROM AUTHOR]

Background: A combination of prone positioning (PP) and venovenous extracorporeal membrane oxygenation (VV-ECMO) is safe, feasible, and associated with potentially improved survival for severe acute respiratory distress syndrome (ARDS). However, whether ARDS patients, especially non-COVID-19 patients, placed in PP before VV-ECMO should continue PP after a VV-ECMO connection is unknown. This study aimed to test the hypothesis that early use of PP during VV-ECMO could increase the proportion of patients successfully weaned from ECMO support in severe ARDS patients who received PP before ECMO. Methods: In this prospective observational study, patients with severe ARDS who were treated with VV-ECMO were divided into two groups: the prone group and the supine group, based on whether early PP was combined with VV-ECMO. The proportion of patients successfully weaned from VV-ECMO and 60-day mortality were analyzed before and after propensity score matching. Results: A total of 165 patients were enrolled, 50 in the prone and 115 in the supine group. Thirty-two (64%) and 61 (53%) patients were successfully weaned from ECMO in the prone and the supine groups, respectively. The proportion of patients successfully weaned from VV-ECMO in the prone group tended to be higher, albeit not statistically significant. During PP, there was a significant increase in partial pressure of arterial oxygen (PaO2) without a change in ventilator or ECMO settings. Tidal impedance shifted significantly to the dorsal region, and lung ultrasound scores significantly decreased in the anterior and posterior regions. Forty-five propensity score-matched patients were included in each group. In this matched sample, the prone group had a higher proportion of patients successfully weaned from VV-ECMO (64.4% vs. 42.2%; P = 0.035) and lower 60-day mortality (37.8% vs. 60.0%; P = 0.035). Conclusions: Patients with severe ARDS placed in PP before VV-ECMO should continue PP after VV-ECMO support. This approach could increase the probability of successful weaning from VV-ECMO. Trial Registration: ClinicalTrials.Gov: NCT04139733. Registered 23 October 2019. [ABSTRACT FROM AUTHOR]

Background: Mortality for patients receiving extracorporeal membrane oxygenation (ECMO) for COVID-19 increased over the course of the pandemic. We investigated the association between immunomodulators and mortality for patients receiving ECMO for COVID-19. Methods: We retrospectively analysed the Extracorporeal Life Support Organisation registry from 1 January, 2020, through 31 December, 2021, to compare the outcomes of patients who received no immunomodulators, only corticosteroids, only other immunomodulators (selective interleukin blockers, janus-kinase inhibitors, convalescent plasma, and intravenous immunoglobulin), and a combination of corticosteroids and other immunomodulators administered either before or during ECMO. We used Cox regression models to estimate survival time until 90 days. We estimated the propensity score of receiving different immunomodulators using multinomial regression, and incorporated these scores into the regression models. Results: We included 7181 patients in the final analysis; 6169 patients received immunomodulators either before or during ECMO. The 90-day survival was 58.1% (95%-CI 55.1–61.2%) for patients receiving no immunomodulators, 50.7% (95%-CI 49.0–52.5%) for those receiving only corticosteroids, 62.2% (95%-CI 57.4–67.0%) for those receiving other immunomodulators, and 48.5% (95%-CI 46.7–50.4%) for those receiving corticosteroids and other immunomodulators. Compared to patients without immunomodulators, patients receiving either corticosteroids alone (HR: 1.13, 95%-CI 1.01–1.28) or with other immunomodulators (HR: 1.21, 95%-CI: 1.07–1.54) had significantly shorter survival time, while patients receiving only other immunomodulators had significantly longer survival time (HR: 0.79, 95%-CI: 0.66–0.96). The receipt of immunomodulators (across all three groups) was associated with an increase in secondary infections. Conclusions: In this cohort study, we found that immunomodulators, in particular corticosteroids, were associated with significantly higher mortality amongst patients receiving ECMO for COVID-19, after adjusting for potential confounding variables and propensity score. In addition, patients receiving corticosteroids with or without other immunomodulators had longer ECMO runs, which has potential implications for resource allocation. While residual confounding likely remains, further studies are required to evaluate the timing of immunomodulators and better understand the possible mechanisms behind this association, including secondary infections. [ABSTRACT FROM AUTHOR]

Background: Obesity causes significant difficulties in successful extracorporeal membrane oxygenation (ECMO) support and may interfere with patient outcomes. During the COVID-19 pandemic, we experienced an increased number of obese patients supported with ECMO in our intensive care unit due to severe illness in this population. Methods: We designed a single-center retrospective study to identify prognostic factors for 180-day survival in obese critical COVID-19 patients receiving venovenous ECMO (VV-ECMO). We included adult critical COVID-19 patients on VV-ECMO, who were obese and overweight (according to the World Health Organization) and admitted to a tertiary hospital's intensive care unit from April 1, 2020, to May 31, 2022. Univariate logistic regression analysis was performed to assess differences in 180-day mortality. Results: Forty-one patients were included. The median age was 55 (IQR 45–60) years, and 70.7% of the patients were male. The median body mass index (BMI) was 36 (IQR 31–42.5) kg/m2; 39% of patients had a BMI ≥ 40 kg/m2. The participants had 3 (IQR 1.5–4) days of mechanical ventilation prior to ECMO, and 63.4% were weaned from VV-ECMO support after a median of 19 (IQR 10–34) days. The median ICU length of stay was 31.9 (IQR 17.5–44.5) days. The duration of mechanical ventilation was 30 (IQR 19–49.5) days. The 180-day mortality rate was 41.5%. Univariate logistic regression analysis revealed that a higher BMI was associated with greater 180-day survival (OR 1.157 [1.038–1.291], p = 0.009). Younger age, female sex, less invasive ventilation time before ECMO, and fewer complications at the time of ECMO cannulation were associated with greater 180-day survival [OR 0.858 (0.774–0.953), p 0.004; OR 0.074 (0.008–0.650), p 0.019; OR 0.612 (0.401–0.933), p 0.022; OR 0.13 (0.03–0.740), p 0.022), respectively]. Conclusion: In this retrospective cohort of critical COVID-19 obese adult patients supported by VV-ECMO, a higher BMI, younger age, and female sex were associated with greater 180-day survival. A shorter invasive ventilation time before ECMO and fewer complications at ECMO cannulation were also associated with increased survival. [ABSTRACT FROM AUTHOR]

Purpose: Nowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration. Methods: Data collection was carried out until November 2023 by search of electronic databases including PubMed, Google Scholar, Scopus, and Web of Science. GRADE system has been used to determine the quality of evidence and strength of recommendations for each albumin indication. Results: A total of 165 relevant studies were included in this review. Fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis, have a moderate to high quality of evidence and a strong recommendation for administering albumin. Moreover, albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia has a low to moderate quality of evidence and weak recommendation to use. Also, in modest volume paracentesis, severe hyponatremia in cirrhosis has a low to moderate quality of evidence and a weak recommendation. Conclusion: Albumin administration is most indicated in management of cirrhosis complications. Fluid resuscitation or treatment of severe and refractory edema, especially in patients with hypoalbuminemia and not responding to other treatments, is another rational use for albumin. Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin. [ABSTRACT FROM AUTHOR]

Background: Impaired cerebral autoregulation (CA) is one of several proposed mechanisms of acute brain injury in patients supported by extracorporeal membrane oxygenation (ECMO). The primary aim of this study was to determine the feasibility of continuous CA monitoring in adult ECMO patients. Our secondary aims were to describe changes in cerebral oximetry index (COx) and other metrics of CA over time and in relation to functional neurologic outcomes. Methods: This is a single-center prospective observational study. We measured COx, a surrogate measurement of cerebral blood flow measured by near-infrared spectroscopy, which is an index of CA derived from the moving correlation between mean arterial pressure (MAP) and slow waves of regional cerebral oxygen saturation. A COx value that approaches 1 indicates impaired CA. Using COx, we determined the optimal MAP (MAPOPT) and lower and upper limits of autoregulation for individual patients. These measurements were examined in relation to modified Rankin Scale (mRS) scores. Results: Fifteen patients (median age 57 years [interquartile range 47–69]) with 150 autoregulation measurements were included for analysis. Eleven were on veno-arterial ECMO (VA-ECMO), and four were on veno-venous ECMO (VV-ECMO). Mean COx was higher on postcannulation day 1 than on day 2 (0.2 vs. 0.09, p < 0.01), indicating improved CA over time. COx was higher in VA-ECMO patients than in VV-ECMO patients (0.12 vs. 0.06, p = 0.04). Median MAPOPT for the entire cohort was highly variable, ranging from 55 to 110 mm Hg. Patients with mRS scores 0–3 (good outcome) at 3 and 6 months spent less time outside MAPOPT compared with patients with mRS scores 4–6 (poor outcome) (74% vs. 82%, p = 0.01). The percentage of time when observed MAP was outside the limits of autoregulation was higher on postcannulation day 1 than on day 2 (18.2% vs. 3.3%, p < 0.01). Conclusions: In ECMO patients, it is feasible to monitor CA continuously at the bedside. CA improved over time, most significantly between postcannulation days 1 and 2. CA was more impaired in VA-ECMO patients than in VV-ECMO patients. Spending less time outside MAPOPT may be associated with achieving a good neurologic outcome. [ABSTRACT FROM AUTHOR]

Background: Central nervous system (CNS) injury following initiation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) is common. An acute decrease in partial pressure of arterial carbon dioxide (PaCO2) following VV-ECMO initiation has been suggested as an etiological factor, but the challenges of diagnosing CNS injuries has made discerning a relationship between PaCO2 and CNS injury difficult. Methods: We conducted a prospective cohort study of adult patients undergoing VV-ECMO for acute respiratory failure. Arterial blood gas measurements were obtained prior to initiation of VV-ECMO, and at every 2–4 h for the first 24 h. Neuroimaging was conducted within the first 7–14 days in patients who were suspected of having neurological injury or unable to be examined because of sedation. We collected blood biospecimens to measure brain biomarkers [neurofilament light (NF-L); glial fibrillary acidic protein (GFAP); and phosphorylated-tau 181] in the first 7 days following initiation of VV-ECMO. We assessed the relationship between both PaCO2 over the first 24 h and brain biomarkers with CNS injury using mixed methods linear regression. Finally, we explored the effects of absolute change of PaCO2 on serum levels of neurological biomarkers by separate mixed methods linear regression for each biomarker using three PaCO2 exposures hypothesized to result in CNS injury. Results: In our cohort, 12 of 59 (20%) patients had overt CNS injury identified on head computed tomography. The PaCO2 decrease with VV-ECMO initiation was steeper in patients who developed a CNS injury (− 0.32%, 95% confidence interval − 0.25 to − 0.39) compared with those without (− 0.18%, 95% confidence interval − 0.14 to − 0.21, P interaction < 0.001). The mean concentration of NF-L increased over time and was higher in those with a CNS injury (464 [739]) compared with those without (127 [257]; P = 0.001). GFAP was higher in those with a CNS injury (4278 [11,653] pg/ml) compared with those without (116 [108] pg/ml; P < 0.001). The mean NF-L, GFAP, and tau over time in patients stratified by the three thresholds of absolute change of PaCO2 showed no differences and had no significant interaction for time. Conclusions: Although rapid decreases in PaCO2 following initiation of VV-ECMO were slightly greater in patients who had CNS injuries versus those without, data overlap and absence of relationships between PaCO2 and brain biomarkers suggests other pathophysiologic variables are likely at play. [ABSTRACT FROM AUTHOR]

The prone position is an immediately available and easily implemented procedure that was introduced more than 50 years ago as a method for improvement of gas exchange in patients with acute respiratory distress syndrome (ARDS). In the meantime, a survival advantage could also be shown in patients with severe ARDS, which led to the recommendation of the prone position for treatment of severe ARDS by expert consensus and specialist society guidelines. The continuing coronavirus disease 2019 (COVID-19) pandemic moved the prone position to the forefront of medicine, including the widespread implementation of the prone position for awake, spontaneously breathing nonintubated patients with acute hypoxemic respiratory insufficiency. The survival advantage is possible due to a reduction of the ventilator-associated lung damage. In this article, the physiological effects, data on clinical results, practical considerations and open questions with respect to the prone position are discussed. [ABSTRACT FROM AUTHOR]

The primary objective of this study was to determine whether or not hemodynamic parameters and laboratory values at the time of admission to the pediatric cardiac intensive care unit after the Norwood operation were associated with a composite outcome of either need for extracorporeal membrane oxygenation or inpatient mortality. This was a single-center retrospective study of infants with functionally univentricular hearts admitted to intensive care after the Norwood procedure from January 2011 to January 2020. Data were obtained at a single point (after a Norwood procedure) and then compared between two subsets of patients based on the presence or not of the composite outcome of interest. In univariate and multiple regression analyses, a series of receiver operator curves were generated to assess the relationship between the variables of interest and the composite outcome. Eight (7.6%) experienced the composite outcome out of a total of 104 patients. Those who experienced the composite endpoint had significantly higher oxygen extraction ratio (0.43 vs. 0.31, p = 0.01), lower systemic blood flow (2.5 L/min versus 3.1 L/min, p = 0.01), and higher systemic vascular resistance (20.2 indexed woods units versus 14.8 indexed woods units, p = 0.01). Those with systemic blood flow of less than 2.5 L/min/m2 had a 17% risk of experiencing the composite endpoint AUC = 0.79. Those with systemic vascular resistance of greater than 19 indexed woods units had a 22% risk of experiencing the composite endpoint AUC 0.80. Systemic blood flow and systemic vascular resistance are independently associated with this composite outcome. [ABSTRACT FROM AUTHOR]

Purpose: Skin pigmentation influences peripheral oxygen saturation (SpO2) compared to arterial saturation of oxygen (SaO2). Occult hypoxemia (SaO2 ≤ 88% with SpO2 ≥ 92%) is associated with increased in-hospital mortality in venovenous-extracorporeal membrane oxygenation (VV-ECMO) patients. We hypothesized VV-ECMO cannulation, in addition to race/ethnicity, accentuates the SpO2-SaO2 discrepancy due to significant hemolysis. Methods: Adults (≥ 18 years) supported with VV-ECMO with concurrently measured SpO2 and SaO2 measurements from over 500 centers in the Extracorporeal Life Support Organization Registry (1/2018–5/2023) were included. Multivariable logistic regressions were performed to examine whether race/ethnicity was associated with occult hypoxemia in pre-ECMO and on-ECMO SpO2-SaO2 calculations. Results: Of 13,171 VV-ECMO patients, there were 7772 (59%) White, 2114 (16%) Hispanic, 1777 (14%) Black, and 1508 (11%) Asian patients. The frequency of on-ECMO occult hypoxemia was 2.0% (N = 233). Occult hypoxemia was more common in Black and Hispanic patients versus White patients (3.1% versus 1.7%, P < 0.001 and 2.5% versus 1.7%, P = 0.025, respectively). In multivariable logistic regression, Black patients were at higher risk of pre-ECMO occult hypoxemia versus White patients (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI] = 1.18–2.02, P = 0.001). For on-ECMO occult hypoxemia, Black patients (aOR = 1.79, 95% CI = 1.16–2.75, P = 0.008) and Hispanic patients (aOR = 1.71, 95% CI = 1.15–2.55, P = 0.008) had higher risk versus White patients. Higher pump flow rates (aOR = 1.29, 95% CI = 1.08–1.55, P = 0.005) and on-ECMO 24-h lactate (aOR = 1.06, 95% CI = 1.03–1.10, P < 0.001) significantly increased the risk of on-ECMO occult hypoxemia. Conclusion: SaO2 should be carefully monitored if using SpO2 during ECMO support for Black and Hispanic patients especially for those with high pump flow and lactate values at risk for occult hypoxemia. [ABSTRACT FROM AUTHOR]

Background: Neurological complications are common in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) support. We used machine learning (ML) algorithms to identify predictors for neurological outcomes for these patients. Methods: All demographic, clinical, and circuit-related variables were extracted for adults with VV-ECMO support at a tertiary care center from 2016 to 2022. The primary outcome was good neurological outcome (GNO) at discharge defined as a modified Rankin Scale of 0–3. Results: Of 99 total VV-ECMO patients (median age = 48 years; 65% male), 37% had a GNO. The best performing ML model achieved an area under the receiver operating characteristic curve of 0.87. Feature importance analysis identified down-trending gas/sweep/blender flow, FiO2, and pump speed as the most salient features for predicting GNO. Conclusion: Utilizing pre- as well as post-initiation variables, ML identified on-ECMO physiologic and pulmonary conditions that best predicted neurological outcomes. [ABSTRACT FROM AUTHOR]

The article discusses the relationship between acute kidney injury (AKI) and acute respiratory distress syndrome (ARDS) in critically ill patients. The study analyzed data from 10 randomized controlled trials conducted in the United States between 1996 and 2018. The authors found that AKI occurred in approximately 43.7% of patients with ARDS, with a higher incidence of AKI stage 3 and acute kidney disease (AKD) in patients with more severe AKI. The study also found that AKI was associated with higher mortality rates at 28 and 90 days. However, the study has some limitations, including the lack of consideration for certain variables and the heterogeneity of ARDS and AKI subphenotypes. Further research is needed to better understand the relationship between AKI and ARDS and to identify strategies for improving outcomes. [Extracted from the article]

This article discusses the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) as a treatment for acute myocardial infarction-related cardiogenic shock (AMI-CS). The article highlights that while there has been a significant increase in the use of VA-ECMO, there is a lack of evidence from randomized controlled trials (RCTs) to support its effectiveness. The article presents the findings of several RCTs and a meta-analysis, which suggest that routine VA-ECMO does not significantly reduce mortality in AMI-CS patients. The article also discusses the safety concerns associated with VA-ECMO, such as bleeding and peripheral ischemic complications. The limitations of the current evidence and the need for further research to identify specific patient subgroups that may benefit from VA-ECMO are also discussed. Overall, the article concludes that routine immediate VA-ECMO is not beneficial for the majority of AMI-CS patients, and further research is needed to determine its effectiveness in specific situations. [Extracted from the article]

Background: There is good evidence describing pharmacy workforce and service provision in general critical care units. However, no data exist from adult extracorporeal membrane oxygenation (ECMO) centres. Aim: To describe workforce characteristics, pharmacy service provision, and pharmaceutical care activities in critical care units (CCUs) providing an adult ECMO service in the United Kingdom (UK) and compare to national staffing standards for CCUs. Method: We conducted a multicentre, cross-sectional electronic survey inviting one pharmacy professional response per UK ECMO centre. We collated information on workforce, service provision, and pharmaceutical care activities provided by pharmacy teams in adult CCUs with an ECMO service. Results: The survey response rate was 90.9%: representatives of 10/11 tertiary hospitals providing ECMO services responded. Median critical care pharmacist to critical care bed was 1:12.1 (IQR: 1:9.4–1:14.9). Most centres (90.0%) did not meet national standards for pharmacy professionals to critical care bed staffing ratios for weekday services. Total critical care beds covered by the critical care pharmacy team varied across the UK: median (IQR) – 45 (37–80) beds. Two centres funded pharmacist time for ECMO activity, and one centre funded a pharmacy technician post. Median peak ECMO activity was 4 ECMO patients in a single day (IQR: 3–5). Most respondents reported reduced pharmacy service at weekends compared to weekday, with limited on-site support. Conclusion: Most responding ECMO centres in the UK reported pharmacy staffing ratios below nationally agreed critical care standards. There was high variability in clinical pharmacy services to ECMO patients over 7 days. [ABSTRACT FROM AUTHOR]

Background: The survival benefit of venovenous extracorporeal membrane oxygenation (VV-ECMO) in adult patients with severe acute respiratory distress syndrome (ARDS) remains controversial. This study aimed to investigate the efficiency and potential prognostic factors of VV-ECMO for severe ARDS in adults by evaluating our institutional experience and results. Materials and methods: This research studied ARDS patients receiving VV-ECMO between June 2011 and May 2023. The inclusion criteria were PaO2/FiO2 < 100 mmHg at FiO2 of 1.0. Retrospective data was analyzed to identify factors associated with successful ECMO weaning and hospital discharge survival. Results: A total of 18 patients were included in this study, with 7 cases (38.9%) successfully weaned from ECMO and 5 cases (27.8%) surviving hospital discharge. The overall complication rate was 77.8%. After treatment with VV ECMO, there were statistically significant improvements in both PaO2 and PaCO2 (P < 0.05). Patients in the successful weaning group had a lower pTB value, less accumulative volume of sodium bicarbonate during ECMO, and lower accumulative volume of intravenous immunoglobulin in the hospital compared to the unsuccessful weaning group (all P < 0.05). Furthermore, compared to the non-survivors, the survivors had less severe acidosis, higher mean arterial pressure before ECMO, a lower level of pCr, and a lower pTB value during ECMO (all P < 0.05). Conclusion: ECMO can effectively promote oxygenation and carbon dioxide (CO2) removal in patients with severe ARDS. Early initiation of ECMO with appropriate management could benefit in reducing comorbidities and mortality. [ABSTRACT FROM AUTHOR]

Background: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterized by the proliferation of Langerhans cells along the small airways, which causes nodular and cystic changes in the lung parenchyma. Lung transplantation can be a life-saving option for patients with severe respiratory failure or pulmonary hypertension. Herein, we present a case of successful lung transplantation in a patient with PLCH who developed unusually large thrombi in the central pulmonary artery. Case presentation: A 47-year-old woman with 16-year history of PLCH with rapidly developing respiratory failure was admitted to our hospital for the evaluation of a lung transplant. Enhanced computed tomography revealed large thrombi in dilated central pulmonary arteries. Right heart catheterization revealed severe pulmonary hypertension, with a mean pulmonary artery pressure of 48 mmHg. The thrombi shrank markedly after 3 months of anticoagulation therapy. However, the respiratory status of the patient did not improve. We performed bilateral living-donor lobar lung transplantation with thrombectomy under extracorporeal membrane oxygenation for the remaining thrombi in the main pulmonary arteries. The dilated main pulmonary arteries of the recipient required direct plication for size mismatch. The patient survived in good condition for more than 2 years with no recurrence of thrombosis. Conclusion: Preoperative anticoagulation therapy for massive thrombi in the pulmonary arteries was effective and led to safe lung transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Patients on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support are at a high risk of hemorrhagic complications, including upper gastrointestinal bleeding (UGIB). The objective of this study was to evaluate the incidence and impact of this complication in V-A ECMO patients. Materials and methods: A retrospective single-center study (2013–2017) was conducted on V-A ECMO patients, excluding those who died within 24 h. All patients with suspected UGIB underwent esophagogastroduodenoscopy (EGD) and were analyzed and compared to the remainder of the cohort, from the initiation of ECMO until 5 days after explantation. Results: A total of 150 V-A ECMO cases (65 after cardiac surgery and 85 due to medical etiology) were included. 90% of the patients received prophylactic proton pump inhibitor therapy and enteral nutrition. Thirty-one patients underwent EGD for suspected UGIB, with 16 confirmed cases of UGIB. The incidence was 10.7%, with a median occurrence at 10 [7–17] days. There were no significant differences in clinical or biological characteristics on the day of EGD. However, patients with UGIB had significant increases in packed red blood cells and fresh frozen plasma needs, mechanical ventilation duration and V-A ECMO duration, as well as in length of intensive care unit and hospital stays. There was no significant difference in mortality. The only independent risk factor of UGIB was a history of peptic ulcer (OR = 7.32; 95% CI [1.07–50.01], p = 0.042). Conclusion: UGIB occurred in at least 1 out of 10 cases of V-A ECMO patients, with significant consequences on healthcare resources. Enteral nutrition and proton pump inhibitor prophylaxis did not appear to protect V-A ECMO patients. Further studies should assess their real benefits in these patients with high risk of hemorrhage. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) and cardiac dysfunction are established comorbidities of congenital diaphragmatic hernia (CDH). However, there is very little data focusing on arterial hypertension in CDH. This study aims to investigate the incidence of arterial hypertension in neonates with CDH at hospital discharge. Archived clinical data of 167 CDH infants who received surgical repair of the diaphragmatic defect and survived for > 60 days were retrospectively analyzed. Blood pressure (BP) values were averaged for the last 7 days before discharge and compared to standard BP values for sex, age, and height provided by the AHA in 2004. BP values reaching or extending the 95th percentile were defined as arterial hypertension. The use of antihypertensive medication was analyzed at discharge and during hospitalization. Arterial hypertension at discharge was observed in 19 of 167 infants (11.3%) of which 12 (63%) were not receiving antihypertensive medication. Eighty patients (47.9%) received antihypertensive medication at any point during hospitalization and 28.9% of 152 survivors (n = 44) received antihypertensive medication at discharge, although in 45.5% (n = 20) of patients receiving antihypertensive medication, the indication for antihypertensive medication was myocardial hypertrophy or frequency control. BP was significantly higher in ECMO compared to non-ECMO patients, despite a similar incidence of arterial hypertension in both groups (13.8% vs. 10.1%, p = 0.473). Non-isolated CDH, formula feeding, and minimal creatinine in the first week of life were significantly associated with arterial hypertension on univariate analysis. Following multivariate analysis, only minimal creatinine remained independently associated with arterial hypertension. Conclusion: This study demonstrates a moderately high incidence of arterial hypertension in CDH infants at discharge and an independent association of creatinine values with arterial hypertension. Physicians should be aware of this risk and include regular BP measurements and test of renal function in CDH care and follow-up. What is Known: • Due to decreasing mortality, morbidity is increasing in surviving CDH patients. • Pulmonary hypertension and cardiac dysfunction are well-known cardiovascular comorbidities of CDH. What is New: • There is a moderately high incidence of arterial hypertension in CDH infants at discharge even in a population with frequent treatment with antihypertensive medication. • A more complicated hospital course (ECMO, higher degree of PH, larger defect size) was associated with a higher risk for arterial hypertension. [ABSTRACT FROM AUTHOR]

Purpose: To review possible risk factors for permanent delayed-onset, progressive sensorineural hearing loss (SNHL) in the paediatric population to recommend follow-up protocols for early detection. Methods: PRISMA-compliant systematic review was performed, including observational studies on the paediatric population up to 16 years old who have passed the newborn hearing screening programme (NHSP), investigating the development of late-onset, progressive SNHL. Electronic searches were performed through Medline, Embase, Cochrane, and Emcare. Results: 37 studies were included. 21 showed an association between late-onset SNHL and congenital cytomegalovirus (cCMV) infection (age at hearing loss diagnosis 0.75 to 204 months, mean 45.6 ± 43.9), while 16 between late-onset SNHL and other congenital or perinatal factors, namely Neonatal Intensive Care Unit (NICU) stay, prematurity, neonatal respiratory failure, mechanical ventilation, extracorporeal membrane oxygenation (ECMO) support, hypocapnia, hypoxia, alkalosis, seizure activity, congenital diaphragmatic hernia (CDH), inner ear malformation, and gene mutations (age at hearing loss diagnosis 2.5 to 156 months, mean 38.7 ± 40.7). Conclusions: cCMV infection may cause late-onset SNHL, which can be missed on standard NHSP. There is, therefore, evidence to support universal screening programmes to enable detection in even asymptomatic neonates. Ongoing audiological follow-up for all children with cCMV is advisable, to enable timely treatment. In the paediatric population presenting conditions such as NICU stay > 5 days, prematurity ≤ 34 weeks gestation, severe neonatal respiratory failure, mechanical ventilation, ECMO support, and CDH surgery, an audiological follow-up from 3 months of age up to at least 3–4 years of age, and at least annually, should be recommended. [ABSTRACT FROM AUTHOR]

Purpose: Severe acute respiratory distress syndrome (ARDS) with PaO2/FiO2 < 80 mmHg is a life-threatening condition. The optimal management strategy is unclear. The aim of this meta-analysis was to compare the effects of low tidal volumes (Vt), moderate Vt, prone ventilation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on mortality in severe ARDS. Methods: We performed a frequentist network meta-analysis of randomised controlled trials (RCTs) with participants who had severe ARDS and met eligibility criteria for VV-ECMO or had PaO2/FiO2 < 80 mmHg. We applied the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to discern the relative effect of interventions on mortality and the certainty of the evidence. Results: Ten RCTs including 812 participants with severe ARDS were eligible. VV-ECMO reduces mortality compared to low Vt (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.59–0.99, moderate certainty) and compared to moderate Vt (RR 0.75, 95% CI 0.57–0.98, low certainty). Prone ventilation reduces mortality compared to moderate Vt (RR 0.78, 95% CI 0.66–0.93, high certainty) and compared to low Vt (RR 0.81, 95% CI 0.63–1.02, moderate certainty). We found no difference in the network comparison of VV-ECMO compared to prone ventilation (RR 0.95, 95% CI 0.72–1.26), but inferences were based solely on indirect comparisons with very low certainty due to very wide confidence intervals. Conclusions: In adults with ARDS and severe hypoxia, both VV-ECMO (low to moderate certainty evidence) and prone ventilation (moderate to high certainty evidence) improve mortality relative to low and moderate Vt strategies. The impact of VV-ECMO versus prone ventilation remains uncertain. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) plays a crucial role in managing heart and respiratory failure. However, it is associated with complications such as bleeding, acute renal failure, neurological issues, and thrombosis. Cerebral venous sinuses thrombosis (CVST) is a rare condition that primarily affects young females, especially those of childbearing age. CVST can result from multiple factors, both congenital and acquired, such as pregnancy, dehydration, oral contraceptives, and the postpartum period. The most common and nonspecific symptom is headache. Notably, the occurrence of CVST during ECMO has not been documented in adult patients. In this case report, we present the case of a 29-year-old lactating mother who was admitted to our hospital with complaints and clinical features indicative of community-acquired pneumonia. Despite conventional treatment, her oxygen requirement increased; therefore, she was placed on veno-venous ECMO (VV ECMO). Her condition gradually improved, and she was extubated while still on ECMO support (Awake ECMO). However, a day later of successful weaning from ECMO, she reported blurred vision and proptosis. Magnetic resonance imaging (MRI) and MR venography (MRV) of the brain showed features suggestive of CVST. She was promptly treated with anticoagulation and later discharged with minimal residual complications. This paper emphasizes the importance of early clinical recognition and treatment with anticoagulants in cases of CVST during ECMO for improved outcomes. [ABSTRACT FROM AUTHOR]

In recent years the number of patients treated in intensive care units by extracorporeal membrane oxygenation (ECMO) due to severe respiratory failure or cardiogenic shock has steadily increased [1]. Consequently, the number of invasive procedures and operations in these patients has also increased. A fundamental understanding of these systems and the clinical indications is therefore helpful for the practicing (non-cardiac) surgeon. This review article focuses on peripheral ECMO procedures: venovenous (V-V) ECMO for patients with respiratory failure and venoarterial (V-A) ECMO for circulatory support in cardiogenic shock. [ABSTRACT FROM AUTHOR]

This article discusses the need to revise the Uniform Determination of Death Act (UDDA) due to concerns raised by experts. These concerns include the need for consent for brain death evaluation and managing objections to it. Other concerns involve the evaluation of neuroendocrine function and the lack of clarity in medical standards. The drafting committee of the Uniform Law Commission (ULC) has paused its work on revising the UDDA due to a lack of consensus. However, there are still opportunities to address these issues through other pathways, such as state legislatures or federal regulations. [Extracted from the article]

This study determined whether compared to conventional mechanical ventilation (MV), extracorporeal membrane oxygenation (ECMO) is associated with decreased hospital mortality or fibrotic changes in patients with COVID-19 acute respiratory distress syndrome. A cohort of 72 patients treated with ECMO and 390 with conventional MV were analyzed (February 2020–December 2021). A target trial was emulated comparing the treatment strategies of initiating ECMO vs no ECMO within 7 days of MV in patients with a PaO2/FiO2 < 80 or a PaCO2 ≥ 60 mmHg. A total of 222 patients met the eligibility criteria for the emulated trial, among whom 42 initiated ECMO. ECMO was associated with a lower risk of hospital mortality (hazard ratio [HR], 0.56; 95% confidence interval [CI] 0.36–0.96). The risk was lower in patients who were younger (age < 70 years), had less comorbidities (Charlson comorbidity index < 2), underwent prone positioning before ECMO, and had driving pressures ≥ 15 cmH2O at inclusion. Furthermore, ECMO was associated with a lower risk of fibrotic changes (HR, 0.30; 95% CI 0.11–0.70). However, the finding was limited due to relatively small number of patients and differences in observability between the ECMO and conventional MV groups. [ABSTRACT FROM AUTHOR]

Background: A notable increase in severe cases of COVID-19, with significant hospitalizations due to the emergence and spread of JN.1 was observed worldwide in late 2023 and early 2024. However, no clinical data are available regarding critically-ill JN.1 COVID-19 infected patients. Methods: The current study is a substudy of the SEVARVIR prospective multicenter observational cohort study. Patients admitted to any of the 40 participating ICUs between November 17, 2022, and January 22, 2024, were eligible for inclusion in the SEVARVIR cohort study (NCT05162508) if they met the following inclusion criteria: age ≥ 18 years, SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction (RT-PCR) in nasopharyngeal swab samples, ICU admission for acute respiratory failure. The primary clinical endpoint of the study was day-28 mortality. Evaluation of the association between day-28 mortality and sublineage group was conducted by performing an exploratory multivariable logistic regression model, after systematically adjusting for predefined prognostic factors previously shown to be important confounders (i.e. obesity, immunosuppression, age and SOFA score) computing odds ratios (OR) along with their corresponding 95% confidence intervals (95% CI). Results: During the study period (November 2022–January 2024) 56 JN.1- and 126 XBB-infected patients were prospectively enrolled in 40 French intensive care units. JN.1-infected patients were more likely to be obese (35.7% vs 20.8%; p = 0.033) and less frequently immunosuppressed than others (20.4% vs 41.4%; p = 0.010). JN.1-infected patients required invasive mechanical ventilation support in 29.1%, 87.5% of them received dexamethasone, 14.5% tocilizumab and none received monoclonal antibodies. Only one JN-1 infected patient (1.8%) required extracorporeal membrane oxygenation support during ICU stay (vs 0/126 in the XBB group; p = 0.30). Day-28 mortality of JN.1-infected patients was 14.6%, not significantly different from that of XBB-infected patients (22.0%; p = 0.28). In univariable logistic regression analysis and in multivariable analysis adjusting for confounders defined a priori, we found no statistically significant association between JN.1 infection and day-28 mortality (adjusted OR 1.06 95% CI (0.17;1.42); p = 0.19). There was no significant between group difference regarding duration of stay in the ICU (6.0 [3.5;11.0] vs 7.0 [4.0;14.0] days; p = 0.21). Conclusions: Critically-ill patients with Omicron JN.1 infection showed a different clinical phenotype than patients infected with the earlier XBB sublineage, including more frequent obesity and less immunosuppression. Compared with XBB, JN.1 infection was not associated with higher day-28 mortality. [ABSTRACT FROM AUTHOR]

Mechanical circulatory support (MCS) devices, including veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, have been widely used for patients with cardiogenic shock (CS). However, hemodynamics with each device and combination therapy is not thoroughly understood. We aimed to elucidate the hemodynamics with MCS using a pulsatile flow model. Hemodynamics with Impella CP, VA-ECMO, and a combination of Impella CP and VA-ECMO were assessed based on the pressure and flow under support with each device and the pressure–volume loop of the ventricle model. The Impella CP device with CS status resulted in an increase in aortic pressure and a decrease in end-diastolic volume and end-diastolic pressure (EDP). VA-ECMO support resulted in increased afterload, leading to a significant increase in aortic pressure with an increase in end-systolic volume and EDP and decreasing venous reservoir pressure. The combination of Impella CP and VA-ECMO led to left ventricular unloading, regardless of increase in afterload. Hemodynamic support with Impella and VA-ECMO should be a promising combination for patients with severe CS. [ABSTRACT FROM AUTHOR]

Refractory out-of-hospital cardiac arrest (OHCA) has a very poor prognosis, with survival rates at around 10%. Extracorporeal membrane oxygenation (ECMO) for patients in refractory arrest, known as ECPR, aims to provide perfusion to the patient whilst the underlying cause of arrest can be addressed. ECPR use has increased substantially, with varying survival rates to hospital discharge. The best outcomes for ECPR occur when the time from cardiac arrest to implementation of ECPR is minimised. To reduce this time, systems must be in place to identify the correct patient, expedite transfer to hospital, facilitate rapid cannulation and ECMO circuit flows. We describe the process of activation of ECPR, patient selection, and the steps that emergency department clinicians can utilise to facilitate timely cannulation to ensure the best outcomes for patients in refractory cardiac arrest. With these processes in place our survival to hospital discharge for OHCA patients is 35%, with most patients having a good neurological function. [ABSTRACT FROM AUTHOR]

Background and objectives: Despite being clinically utilized for the treatment of infections, the limited therapeutic range of polymyxin B (PMB), along with considerable interpatient variability in its pharmacokinetics and frequent occurrence of acute kidney injury, has significantly hindered its widespread utilization. Recent research on the population pharmacokinetics of PMB has provided valuable insights. This study aims to review relevant literature to establish a theoretical foundation for individualized clinical management. Methods: Follow PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, Pop-PK studies of PMB were searched in PubMed and EMBASE database systems from the inception of the database until March 2023. Result: To date, a total of 22 population-based studies have been conducted, encompassing 756 subjects across six different countries. The recruited population in these studies consisted of critically infected individuals with multidrug-resistant bacteria, patients with varying renal functions, those with cystic fibrosis, kidney or lung transplant recipients, patients undergoing extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy (CRRT), as well as individuals with obesity or pediatric populations. Among these studies, seven employed a one-compartmental model, with the range of typical clearance (CL) and volume (Vc) being 1.18–2.5L /h and 12.09–47.2 L, respectively. Fifteen studies employed a two-compartmental model, with the ranges of the clearance (CL) and volume of the central compartment (Vc), the volume of the peripheral compartment (Vp), and the intercompartment clearance (Q) were 1.27–8.65 L/h, 5.47–38.6 L, 4.52–174.69 L, and 1.34–24.3 L/h, respectively. Primary covariates identified in these studies included creatinine clearance and body weight, while other covariates considered were CRRT, albumin, age, and SOFA scores. Internal evaluation was conducted in 19 studies, with only one study being externally validated using an independent external dataset. Conclusion: We conclude that small sample sizes, lack of multicentre collaboration, and patient homogeneity are the primary reasons for the discrepancies in the results of the current studies. In addition, most of the studies limited in the internal evaluation, which confined the implementation of model-informed precision dosing strategies. [ABSTRACT FROM AUTHOR]

Background: Pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease progression. Comorbidities, such as chronic arterial hypertension, diabetes mellitus, advanced maternal age and high body mass index, may predispose to severe disease. The management of pregnant COVID-19 patients on the intensive care unit (ICU) is challenging and requires careful consideration of maternal, fetal and ethical issues. Objective: Description and discussion of intensive care treatment strategies and perinatal anesthesiological management in patients with COVID-19 acute respiratory distress syndrome (CARDS). Material and methods: We analyzed the demographic data, maternal medical history, clinical intensive care management, complications, indications and management of extracorporeal membrane oxygenation (ECMO) and infant survival of all pregnant patients treated for severe CARDS in the anesthesiological ICU of a German university hospital between March and November 2021. Results: The cohort included 9 patients with a mean age of 30.3 years (range 26–40 years). The gestational age ranged from 21 + 3 weeks to 37 + 2 weeks. None of the patients had been vaccinated against SARS-CoV‑2. Of the nine patients seven were immigrants and communication was hampered by inadequate Central European language skills. Of the patients five had a PaO2/FiO2 index < 150 mm Hg despite escalated invasive ventilation (FiO2 > 0.9 and a positive end-expiratory pressure [PEEP] of 14 mbar) and were therefore treated with repeated prolonged prone positioning maneuvers (5–14 prone positions for 16 h each, a total of 47 prone positioning treatments) and 2 required treatment with inhaled nitric oxide and venovenous ECMO. The most common complications were bacterial superinfection of the lungs, urinary tract infection and delirium. All the women and five neonates survived. All newborns were delivered by cesarean section, two patients were discharged home with an intact pregnancy and two intrauterine fetal deaths were observed. None of the newborns tested positive for SARS-CoV‑2 at birth. Conclusion: High survival rates are possible in pregnant patients with CARDS. The peripartum management of pregnant women with CARDS requires close interdisciplinary collaboration and should prioritize maternal survival in early pregnancy. In our experience, prolonged prone positioning, an essential evidence-based cornerstone in the treatment of ARDS, can also be safely used in advanced stages of pregnancy. Inhaled nitric oxide (iNO) and ECMO should be considered as life-saving treatment options for carefully selected patients. For cesarean section, neuraxial anesthesia can be safely performed in patients with mild CARDS if well planned but the therapeutic anticoagulation recommended for COVID-19 may increase the risk of bleeding complications, making general anesthesia a more viable alternative, especially in severe disease. [ABSTRACT FROM AUTHOR]

To evaluate EEG monitoring during neonatal ECMO and to identify any correlations between seizure detection to abnormal neuroimaging. Eight-year, service evaluation of neonates who received at least one continuous EEG (cEEG) whilst on ECMO at Great Ormond Street Hospital. Pearson's chi-square test and multivariate logistic regression analysis were used to assess clinical and EEG variables association with seizures and neuroimaging findings. Fifty-seven neonates were studied; 57 cEEG recordings were reviewed. The incidence of seizures was 33% (19/57); of these 74% (14/19) were electrographic-only. The incidence of status epilepticus was 42%, (8/19 with 6 neonates having electrographic-only status and 2 electro-clinical status. Seizures were detected within an hour of recording in 84%, (16/19). The overall mortality rate was 39% (22/57). Seizure detection was strongly associated with female gender (OR 4.8, 95% CI: 1.1–20.4, p = 0.03), abnormal EEG background activity (OR 2.8, 95% CI: 1.1–7.4, p = 0.03) and abnormal EEG focal features (OR 23.6, 95% CI: 5.4–103.9, p = 0.001). There was a strong association between the presence of seizures and abnormal neuroimaging findings (OR 10.9, 95% CI: 2.8–41.9, p = 0.001). Neonates were highly likely to have abnormal neuroimaging findings in the presence of severely abnormal background EEG (OR 9.5, 95% CI 1.7–52.02, p = 0.01) and focal EEG abnormalities (OR 6.35, 95% CI 1.97–20.5, p = 0.002) Conclusion: The study highlights the importance of cEEG in neonates undergoing ECMO. An association between seizure detection and abnormal neuroimaging findings was described. What is Known: • Patients on ECMO are at a higher risk of seiures. • Continuous EEG monitoring is recommended by the ACNS for high risk and ECMO patients. What is New: • In this cohort, neonates with sezirues were 11 times more likely of having abnromal neuroimaging findings. • Neonates with burst suppressed or suppressed EEG background were 9.5 times more likely to have abnormal neuroimaging findings. What does this study add? • This study reports a 33% incidence of neonatal seizures during ECMO. • Neonates with seizures were 11 times more likely to have an abnormal brain scan. • The study captures the real-time approach of EEG monitoring. • Recommended cEEG monitoring should last at least 24 h for ECMO patients. • This is the first study to assess this in neonates only. [ABSTRACT FROM AUTHOR]

Background: Recirculation is a common problem in venovenous extracorporeal membrane oxygenation (VV ECMO) and may limit the effect of ECMO treatment due to less efficient blood oxygenation or unfavorable ECMO and ventilator settings. The impact of hypovolemia and positive end expiratory pressure (PEEP) on recirculation is unclear and poorly described in guidelines, despite clinical importance. The aim of this study was to investigate how hypovolemia, autotransfusion and PEEP affect recirculation in comparison to ECMO cannula distance and circuit flow. Methods: In anesthetized and mechanically ventilated pigs (n = 6) on VV ECMO, we measured recirculation fraction (RF), changes in recirculation fraction (∆RF), hemodynamics and ECMO circuit pressures during alterations in PEEP (5 cmH2O vs 15 cmH2O), ECMO flow (3.5 L/min vs 5.0 L/min), cannula distance (10–14 cm vs 20–26 cm intravascular distance), hypovolemia (1000 mL blood loss) and autotransfusion (1000 mL blood transfusion). Results: Recirculation increased during hypovolemia (median ∆RF 43%), high PEEP (∆RF 28% and 12% with long and short cannula distance, respectively), high ECMO flow (∆RF 49% and 28% with long and short cannula distance, respectively) and with short cannula distance (∆RF 16%). Recirculation decreased after autotransfusion (∆RF − 45%). Conclusions: In the present animal study, hypovolemia, PEEP and autotransfusion were important determinants of recirculation. The alterations were comparable to other well-known factors, such as ECMO circuit flow and intravascular cannula distance. Interestingly, hypovolemia increased recirculation without significant change in ECMO drainage pressure, whereas high PEEP increased recirculation with less negative ECMO drainage pressure. Autotransfusion decreased recirculation. The findings are interesting for clinical studies. [ABSTRACT FROM AUTHOR]

Background: In refractory cardiogenic shock, temporary mechanical support (tMCS) may be crucial for maintaining tissue perfusion and oxygen delivery. tMCS can serve as a bridge-to-decision to assess eligibility for left ventricular assist device (LVAD) implantation or heart transplantation, or as a bridge-to-recovery. ECPELLA is a novel tMCS configuration combining venoarterial extracorporeal membrane oxygenation with Impella. The present study presents the clinical parameters, outcomes, and complications of patients supported with ECPELLA. Methods: All patients supported with ECPELLA at University Medical Centre Utrecht between December 2020 and August 2023 were included. The primary outcome was 30-day mortality, and secondary outcomes were LVAD implantation/heart transplantation and safety outcomes. Results: Twenty patients with an average age of 51 years, and of whom 70% were males, were included. Causes of cardiogenic shock were acute heart failure (due to acute coronary syndrome, myocarditis, or after cardiac surgery) or chronic heart failure, respectively 70 and 30% of cases. The median duration of ECPELLA support was 164 h (interquartile range 98–210). In 50% of cases, a permanent LVAD was implanted. Cardiac recovery within 30 days was seen in 30% of cases and 30-day mortality rate was 20%. ECPELLA support was associated with major bleeding (40%), haemolysis (25%), vascular complications (30%), kidney failure requiring replacement therapy (50%), and Impella failure requiring extraction (15%). Conclusion: ECPELLA can be successfully used as a bridge to LVAD implantation or as a bridge-to-recovery in patients with refractory cardiogenic shock. Despite a significant number of complications, 30-day mortality was lower than observed in previous cohorts. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation (ECMO) not only significantly improves survival rates in severely ill neonates but also is associated with long-term neurodevelopmental issues. To systematically review the available literature on the neurodevelopmental outcomes of neonates and infants who have undergone ECMO treatment, with a focus on motor deficits, cognitive impairments, sensory impairments, and developmental delays. This review aims to understand the incidence, prevalence, and risk factors for these problems and to explore current nursing care and management strategies. Data sources: A comprehensive literature search was performed across PubMed, EMBASE, and Web of Science using a wide array of keywords and phrases pertaining to ECMO, neonates, infants, and various facets of neurodevelopment. The initial screening involved reviewing titles and abstracts to exclude irrelevant articles, followed by a full-text assessment of potentially relevant literature. The quality of each study was evaluated based on its research methodology and statistical analysis. Moreover, citation searches were conducted to identify potentially overlooked studies. Although the focus was primarily on neonatal ECMO, studies involving children and adults were also included due to the limited availability of neonate-specific literature. Results: About 50% of neonates post-ECMO treatment exhibit varying degrees of brain injury, particularly in the frontal and temporoparietal white matter regions, often accompanied by neurological complications. Seizures occur in 18%–23% of neonates within the first 24 hours, and bleeding events occur in 27%–60% of ECMO procedures, with up to 33% potentially experiencing ischemic strokes. Although some studies suggest that ECMO may negatively impact hearing and visual development, other studies have found no significant differences; hence, the influence of ECMO remains unclear. In terms of cognitive, language, and intellectual development, ECMO treatment may be associated with potential developmental delays, including lower composite scores in cognitive and motor functions, as well as potential language and learning difficulties. These studies emphasize the importance of early detection and intervention of potential developmental issues in ECMO survivors, possibly necessitating the implementation of a multidisciplinary follow-up plan that includes regular neuromotor and psychological evaluations. Overall, further multicenter, large-sample, long-term follow-up studies are needed to determine the impact of ECMO on these developmental aspects. Conclusions: The impact of ECMO on an infant's nervous system still requires further investigation with larger sample sizes for validation. Fine-tuned management, comprehensive nursing care, appropriate patient selection, proactive monitoring, nutritional support, and early rehabilitation may potentially contribute to improving the long-term outcomes for these infants. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend the use of mechanical circulatory support (MCS) for patients with cardiogenic shock that is refractory to medical therapy. Bleeding is the most common complication of MCS. Transarterial embolization (TAE) is often performed to treat this complication, because it is a less invasive hemostatic procedure. However, the TAE option needs to be carefully considered during MCS, as the access route may be limited during MCS. Case presentation: A man in his 70 s was diagnosed with acute myocardial infarction and underwent percutaneous coronary intervention via venoarterial extracorporeal membrane oxygenation (VA-ECMO) and Impella. During treatment in the intensive care unit, he suffered damage to a branch of the internal thoracic artery during a cardiac drainage procedure, which was subsequently treated via emergency TAE. An ECMO return cannula and an Impella sheath were inserted into the patient's right and left femoral arteries, respectively. An approach from the left brachial artery was selected, and the left internal thoracic artery was embolized. Subsequently, the patient required re-intervention to treat re-bleeding from another artery. Because it was difficult to target the target artery from the brachial one, owing to interference from the Impella catheter, the ECMO circuit near the return cannula was punctured and a guiding sheath was inserted. The ECMO flow and the patient's blood pressure decreased following placement of this guiding sheath. We were thus able to maintain the patient's blood pressure by increasing the infusion fluids and Impella flow, and embolize the target artery using a gelatin sponge to achieve hemostasis. Conclusion: When TAE is difficult to perform during MCS using an approach from the upper extremities, a lower extremity approach with a sheath inserted into the ECMO circuit may represent a viable alternative. [ABSTRACT FROM AUTHOR]

In Germany, a comprehensive reimbursement policy for extracorporeal membrane oxygenation (ECMO) results in the highest per capita use worldwide, although benefits remain controversial. Public ECMO data is unstructured and poorly accessible to healthcare professionals, researchers, and policymakers. In addition, there are no uniform policies for ECMO allocation which confronts medical personnel with ethical considerations during health crises such as respiratory virus outbreaks.Retrospective information on adult and pediatric ECMO support performed in German hospitals was extracted from publicly available reimbursement data and hospital quality reports and processed to create the web-based ECMO Dashboard built on Open-Source software. Patient-level and hospital-level data were merged resulting in a solid base for ECMO use analysis and ECMO demand forecasting with high spatial granularity at the level of 413 county and city districts in Germany.The ECMO Dashboard (https://www.ecmo-dash.de/), an innovative visual platform, presents the retrospective utilization patterns of ECMO support in Germany. It features interactive maps, comprehensive charts, and tables, providing insights at the hospital, district, and national levels. This tool also highlights the high prevalence of ECMO support in Germany and emphasizes districts with ECMO surplus – where patients from other regions are treated, or deficit – origins from which ECMO patients are transferred to other regions. The dashboard will evolve iteratively to provide stakeholders with vital information for informed and transparent resource allocation and decision-making.Accessible public routine data could support evidence-informed, forward-looking resource management policies, which are urgently needed to increase the quality and prepare the critical care infrastructure for future pandemics. [ABSTRACT FROM AUTHOR]

In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100β, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRβ, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments. [ABSTRACT FROM AUTHOR]

This cross-sectional study, conducted between January 2020 and July 2023, aimed to assess the knowledge, attitude, and post-traumatic stress symptoms (PTSS) among parents with children undergoing extracorporeal membrane oxygenation (ECMO) treatment. Out of 201 valid questionnaires collected, the median knowledge score was 3.00, the mean attitude score was 27.00 ± 3.20, and the mean PTSS score was 3.50 ± 1.54. Logistic regression identified associations between PTSS and parents with lower education levels, particularly junior high school and high school/technical secondary school education, as well as those occupied as housewives. Structural equation modeling highlighted direct effects, such as the impact of residence on education, education on employment status, and associations between knowledge, attitude, PTSS, employment status, monthly income, and parental demographics. The findings indicated inadequate knowledge and suboptimal attitudes among parents, especially those with lower education levels, emphasizing the need for educational resources. Furthermore, addressing parental PTSS through psychosocial support and screening was deemed essential, providing valuable insights for tailored interventions in this context. [ABSTRACT FROM AUTHOR]

Thrombus formation in extracorporeal membrane oxygenation (ECMO) remains a major concern as it can lead to fatal outcomes. To the best of our knowledge, there is no standard non-invasive method for quantitatively measuring thrombi. This study's purpose was to verify thrombus detection in an ECMO circuit using novel, non-invasive ultrasonic sensors in real-time, utilizing the fact that the ultrasonic velocity in a thrombus is known to be higher than that in the blood. Ultrasonic sensors with a customized chamber, an ultrasonic pulse-receiver, and a digital storage oscilloscope (DSO) were used to set up the measuring unit. The customized chamber was connected to an ECMO circuit primed with porcine blood. Thrombi formed from static porcine blood were placed in the circuit and ultrasonic signals were extracted from the oscilloscope at various ECMO flow rates of 1–4 L/min. The ultrasonic signal changes were successfully detected at each flow rate on the DSO. The ultrasonic pulse signal shifted leftward when a thrombus passed between the two ultrasonic sensors and was easily detected on the DSO screen. This novel real-time non-invasive thrombus detection method may enable the early detection of floating thrombi in the ECMO system and early management of ECMO thrombi. [ABSTRACT FROM AUTHOR]

Background: Point-of-care ultrasound (POCUS) has become a mainstay in the evaluation of critically ill patients in the intensive care unit (ICU). ECMO patients are susceptible to complications during prolonged ICU stay, including cannula malposition, which has deleterious consequences. Although the literature surrounding utility of ultrasound on ECMO patients is expansive, direct comparison between radiographic imaging versus ultrasound for identification of cannula malposition is lacking. Case presentation: The authors identified four patients with cannula malposition discovered through POCUS that was missed on routine radiographic imaging. Identification and correction of malposition changed their ECMO course. Conclusion: This case series is the first in literature demonstrating that ultrasound may be superior to radiographic images for ECMO cannula malposition. Further investigation into this subject is warranted. [ABSTRACT FROM AUTHOR]