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Background: INTELLiVENT-Adaptive Support Ventilation (ASV) is a closed-loop ventilation mode that uses capnography to adjust tidal volume (VT) and respiratory rate according to a user-set end-tidal CO2 (etCO2) target range. We compared sidestream versus mainstream capnography with this ventilation mode with respect to the quality of breathing in patients after cardiac surgery., Methods: Single-center, single-blinded, non-inferiority, randomized clinical trial in adult patients scheduled for elective cardiac surgery that were expected to receive at least two hours of postoperative ventilation in the ICU. Patients were randomized 1:1 to closed-loop ventilation with sidestream or mainstream capnography. Each breath was classified into a zone based on the measured VT, maximum airway pressure, etCO2 and pulse oximetry. The primary outcome was the proportion of breaths spent in a predefined 'optimal' zone of ventilation during the first three hours of postoperative ventilation, with a non-inferiority margin for the difference in the proportions set at -20%. Secondary endpoints included the proportion of breaths in predefined 'acceptable' and 'critical' zones of ventilation, and the proportion of breaths with hypoxemia., Results: Of 80 randomized subjects, 78 were included in the intention-to-treat analysis. We could not confirm the non-inferiority of closed-loop ventilation using sidestream with respect to the proportion of breaths in the 'optimal' zone (mean ratio 0.87 [0.77 to ∞]; P = 0.116 for non-inferiority). The proportion of breaths with hypoxemia was higher in the sidestream capnography group versus the mainstream capnography group., Conclusions: We could not confirm that INTELLiVENT-ASV using sidestream capnography is non-inferior to INTELLiVENT-ASV using mainstream capnography with respect to the quality of breathing in subjects receiving postoperative ventilation after cardiac surgery., Trial Registration: NCT04599491 (clinicaltrials.gov)., Competing Interests: MJS was a part–time employee of Hamilton Medical AG, Bonaduz, Switzerland, where he was the team leader of the department of research and new technologies from January 2022 to January 2023. The other authors have no conflicts of interest., (Copyright: © 2023 Nijbroek et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high morbidity and mortality. Our study aimed to gain insights into patient characteristics, outcomes and treatment strategies in CS patients. Patients with CS who underwent percutaneous coronary intervention (PCI) between 2017 and 2021 were identified in a nationwide registry. Data on medical history, laboratory values, angiographic features and outcomes were retrospectively assessed. A total of 2328 patients with a mean age of 66 years and of whom 73% were male, were included. Mortality at 30 days was 39% for the entire cohort. Non-survivors presented with a lower mean blood pressure and increased heart rate, blood lactate and blood glucose levels ( p -value for all <0.001). Also, an increased prevalence of diabetes, multivessel coronary artery disease and a prior coronary event were found. Of all patients, 24% received mechanical circulatory support, of which the majority was via intra-aortic balloon pumps (IABPs). Furthermore, 79% of patients were treated with at least one vasoactive agent, and multivessel PCI was performed in 28%. In conclusion, a large set of hemodynamic, biochemical and patient-related characteristics was identified to be associated with mortality. Interestingly, multivessel PCI and IABPs were frequently applied despite a lack of evidence.

Introduction: Hypotension is common during cardiac surgery and often persists postoperatively in the intensive care unit (ICU). Still, treatment is mainly reactive, causing a delay in its management. The Hypotension Prediction Index (HPI) can predict hypotension with high accuracy. Using the HPI combined with a guidance protocol resulted in a significant reduction in the severity of hypotension in four non-cardiac surgery trials. This randomised trial aims to evaluate the effectiveness of the HPI in combination with a diagnostic guidance protocol on reducing the occurrence and severity of hypotension during coronary artery bypass grafting (CABG) surgery and subsequent ICU admission., Methods and Analysis: This is a single-centre, randomised clinical trial in adult patients undergoing elective on-pump CABG surgery with a target mean arterial pressure of 65 mm Hg. One hundred and thirty patients will be randomly allocated in a 1:1 ratio to either the intervention or control group. In both groups, a HemoSphere patient monitor with embedded HPI software will be connected to the arterial line. In the intervention group, HPI values of 75 or above will initiate the diagnostic guidance protocol, both intraoperatively and postoperatively in the ICU during mechanical ventilation. In the control group, the HemoSphere patient monitor will be covered and silenced. The primary outcome is the time-weighted average of hypotension during the combined study phases., Ethics and Dissemination: The medical research ethics committee and the institutional review board of the Amsterdam UMC, location AMC, the Netherlands, approved the trial protocol (NL76236.018.21). No publication restrictions apply, and the study results will be disseminated through a peer-reviewed journal., Trial Registration Number: The Netherlands Trial Register (NL9449), ClinicalTrials.gov (NCT05821647)., Competing Interests: Competing interests: The Departments of Anaesthesiology and Intensive Care of the Amsterdam UMC, location AMC, receive financial support from Edwards Lifesciences to perform this study. Alexander P.J. Vlaar reports receipt of unrestricted research grants and lecture fees from Edwards Lifesciences and Philips paid to the institution. Denise P. Veelo reports receipt of research grants from Philips as well as consultancy, lecture, and travel expenses fees from Edwards Lifesciences. Bart F. Geerts reports receipt of research grants from Edwards Lifesciences and Philips and additional consultancy fees from Philips. Finally, Markus Hollmann reports receipt of a research grant from the Dutch healthcare financing organization ZonMW paid to the institution, consulting fees from Commonwealth Serum Laboratories (CSL) Behring and Interventional Drug Development (IDD) Pharma, and he serves as an executive section editor for Anesthesia Analgesia, section editor for Journal of Clinical Medicine, and editor for Frontiers in Physiology. The other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The majority of patients admitted to the intensive care unit (ICU) experience severe hypotension which is associated with increased morbidity and mortality. At present, prospective studies examining the incidence and severity of hypotension using continuous waveforms are missing. Methods: This study is a prospective observational cohort study in a mixed surgical and non-surgical ICU population. All patients over 18 years were included and continuous arterial pressure waveforms data were collected. Mean arterial pressure (MAP) below 65 mmHg for at least 10 s was defined as hypotension and a MAP below 45 mmHg as severe hypotension. The primary outcome was the incidence of hypotension. Secondary outcomes were the severity of hypotension expressed in time-weighted average (TWA), factors associated with hypotension, the number and duration of hypotensive events. Results: 499 patients were included. The incidence of hypotension (MAP < 65 mmHg) was 75% (376 out of 499) and 9% (46 out of 499) experienced severe hypotension. Median TWA was 0.3 mmHg [0−1.0]. Associated clinical factors were age, male sex, BMI and cardiogenic shock. There were 5 (1−12) events per patients with a median of 52 min (5−170). Conclusions: In a mixed surgical and non-surgical ICU population the incidence of hypotension is remarkably high.

Background: Deep vein thrombosis (DVT) after decannulation of extracorporeal life support (ECLS) is not uncommon. Moreover, the impact of anticoagulation and potential risk factors is unclear. Furthermore, it is unclear if cannula-associated DVT is more common in ECLS patients compared to critically ill patients without ECLS., Methods: All adult patients who were successfully weaned from ECLS and were screened for DVT following decannulation were included in this observational cohort study. The incidence of post-ECLS-DVT was assessed and the cannula-associated DVT rate was compared with that of patients without ECLS after central venous catheter (CVC) removal. The correlation between the level of anticoagulation, risk factors, and post-ECLS-DVT was determined., Results: We included 30 ECLS patients and 53 non-ECLS patients. DVT was found in 15 patients (50%) of which 10 patients had a DVT in a cannulated vein. No correlation between the level of anticoagulation and DVT was found. V-V ECLS mode was the only independent risk factor for post-ECLS-DVT (OR 5.5; 95%CI 1.16-26.41). We found no difference between the ECLS and non-ECLS cohorts regarding cannula-associated DVT rate (33% vs. 32%)., Conclusion: Post-ECLS-DVT is a common finding that occurs in half of all patients supported with ECLS. The incidence of cannula-associated DVT was equal to CVC-associated DVT in critically ill patients without ECLS. V-V ECLS was an independent risk factor for post-ECLS-DVT., (© 2022 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: The objective of the study was to determine the association between right ventricular (RV) myocardial performance index (MPI) and successful liberation from the ventilator and death within 28 days., Methods: Post hoc analysis of 2 ventilation studies in invasively ventilated patients not having ARDS. RV-MPI was collected through transthoracic echocardiography within 24-48 h from the start of invasive ventilation according to the study protocols. RV-MPI ≤ 0.54 was considered normal. The primary endpoint was successful liberation from the ventilator < 28 days; the secondary endpoint was 28-day mortality., Results: A total of 81 patients underwent transthoracic echocardiography at median 30 (24-42) h after the start of ventilation-in 73 (90%) patients, the RV-MPI could be collected. A total of 56 (77%) patients were successfully liberated from the ventilator < 28 days; A total of 22 (30%) patients had died before or at day 28. A total of 18 (25%) patients had an abnormal RV-MPI. RV-MPI was neither associated with successful liberation from the ventilator within 28 days [HR, 2.2 (95% CI 0.47-10.6); p = 0.31] nor with 28-day mortality [HR, 1.56 (95% CI 0.07-34.27) ; p = 0.7]., Conclusion: In invasively ventilated critically ill patients without ARDS, an abnormal RV-MPI indicative of RV dysfunction was not associated with time to liberation from invasive ventilation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pierrakos, Geke Algera, Simonis, Cherpanath, Lagrand, Paulus, Bos and Schultz.)

The aim of this study was to investigate whether lower PEEP (positive end-expiratory pressure) had beneficial effects on myocardial function among intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) compared to higher PEEP. In this pre-planned substudy of a randomized controlled trial (RELAx), comparing lower to higher PEEP, 44 patients underwent transthoracic echocardiography. The exclusion criteria were known poor left ventricular function and severe shock requiring high dosages of norepinephrine. To create contrast, we also excluded patients who received PEEP between 2 cmH2O and 7 cmH2O in the two randomization arms of the study. The primary outcome was the right ventricular myocardial performance index (MPI), a measure of systolic and diastolic function. The secondary outcomes included systolic and diastolic function parameters. A total of 20 patients were ventilated with lower PEEP (mean ± SD, 0 ± 1 cmH2O), and 24 patients, with higher PEEP (8 ± 1 cmH2O) (mean difference, -8 cmH2O; 95% CI: -8.1 to -7.9 cmH2O; p = 0.01). The tidal volume size was low in both groups (median (IQR), 7.2 (6.3 to 8.1) versus 7.0 (5.3 to 9.1) ml/kg PBW; p = 0.97). The median right ventricular MPI was 0.32 (IQR, 0.26 to 0.39) in the lower-PEEP group versus 0.38 (0.32 to 0.41) in the higher-PEEP group; the median difference was -0.03; 95% CI: -0.11 to 0.03; p = 0.33. The other systolic and diastolic parameters were similar. In patients without ARDS ventilated with a low tidal volume, a lower PEEP had no beneficial effects on the right ventricular MPI.

Introduction: Hypotension in the ICU is common, yet management is challenging and variable. Insight in management by ICU physicians and nurses may improve patient care and guide future hypotension treatment trials and guidelines., Methods: We conducted an international survey among ICU personnel to provide insight in monitoring, management, and perceived consequences of hypotension., Results: Out of 1464 respondents, 1197 (81.7%) were included (928 physicians (77.5%) and 269 nurses (22.5%)). The majority indicated that hypotension is underdiagnosed (55.4%) and largely preventable (58.8%). Nurses are primarily in charge of monitoring changes in blood pressure, physicians are in charge of hypotension treatment. Balanced crystalloids, dobutamine, norepinephrine, and Trendelenburg position were the most frequently reported fluid, inotrope, vasopressor, and positional maneuver used to treat hypotension. Reported complications believed to be related to hypotension were AKI and myocardial injury. Most ICUs do not have a specific hypotension treatment guideline or protocol (70.6%), but the majority would like to have one in the future (58.1%)., Conclusions: Both physicians and nurses report that hypotension in ICU patients is underdiagnosed, preventable, and believe that hypotension influences morbidity. Hypotension management is generally not protocolized, but the majority of respondents would like to have a specific hypotension management protocol., Competing Interests: Declaration of Competing Interest TWLS received research grants and honoraria from Edwards Lifesciences (Irvine, CA, USA) and Masimo Inc. (Irvine, CA, USA) for consulting and lecturing and from Pulsion Medical Systems SE (Feldkirchen, Germany) for lecturing (all payments made to institution). DPV reported receipt of personal fees and other from Edwards Lifesciences (Irvine, CA, USA) as well as consultancy fees and research grants from Philips (Eindhoven, the Netherlands) and Hemologic (Amersfoort, the Netherlands). APJV reported receipt of grants from Edwards Lifesciences (Irvine, CA, USA) and Philips (Eindhoven, the Netherlands). WHV, JS, JS, SR, TGVC, WKL, PT, PWGE, PRT, JB, BFG, and FP declare that they have no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation., Design: Mixed method approach combining multicenter retrospective study and survey., Setting: Sixteen ICUs worldwide., Patients: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019., Interventions: None., Measurements and Main Results: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients., Conclusions: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation., Competing Interests: Dr. Lorusso’s institution received funding from Medtronic, Livanova, Eurosets, and Getinge. Dr. Dos Reis Miranda’s institution received funding from Xenios. Dr. Donker receives speaker fees from Getinge-Maquet and Xenios NovaLung Fresenius and research cooperation with Getinge-Maquet and Xenios NovaLung Fresenius. Dr. Broman received funding from Eurosets and Xenios. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Aims: To assess differences in long-term outcome and functional status of patients with cardiogenic shock (CS) treated by percutaneous mechanical circulatory support (pMCS) and intra-aortic balloon pump (IABP)., Methods and Results: Long-term follow-up of the multicentre, randomized IMPRESS in Severe Shock trial (NTR3450) was performed 5-year after initial randomization. Between 2012 and 2015, a total of 48 patients with severe CS from acute myocardial infarction (AMI) with ST-segment elevation undergoing immediate revascularization were randomized to pMCS by Impella CP (n = 24) or IABP (n = 24). For the 5-year assessment, all-cause mortality, functional status, and occurrence of major adverse cardiac and cerebrovascular event (MACCE) were assessed. MACCE consisted of death, myocardial re-infarction, repeat percutaneous coronary intervention, coronary artery bypass grafting, and stroke. Five-year mortality was 50% (n = 12/24) in pMCS patients and 63% (n = 15/24) in IABP patients (relative risk 0.87, 95% confidence interval 0.47-1.59, P = 0.65). MACCE occurred in 12/24 (50%) of the pMCS patients vs. 19/24 (79%) of the IABP patients (P = 0.07). All survivors except for one were in New York Heart Association Class I/II [pMCS n = 10 (91%) and IABP n = 7 (100%), P = 1.00] and none of the patients had residual angina. There were no differences in left ventricular ejection fraction between the groups (pMCS 52 ± 11% vs. IABP 48 ± 10%, P = 0.53)., Conclusions: In this explorative randomized trial of patients with severe CS after AMI, there was no difference in long-term 5-year mortality between pMCS and IABP-treated patients, supporting previously published short-term data and in accordance with other long-term CS trials., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: Although hypotension in ICU patients is associated with adverse outcome, currently used definitions are unknown and no universally accepted definition exists., Methods: We conducted an international, peer-reviewed survey among ICU physicians and nurses to provide insight in currently used definitions, estimations of incidence, and duration of hypotension., Results: Out of 1394 respondents (1055 physicians (76%) and 339 nurses (24%)), 1207 (82%) completed the questionnaire. In all patient categories, hypotension definitions were predominantly based on an absolute MAP of 65 mmHg, except for the neuro(trauma) category (75 mmHg, p < 0.001), without differences between answers from physicians and nurses. Hypotension incidence was estimated at 55%, and time per day spent in hypotension at 15%, both with nurses reporting higher percentages than physicians (estimated mean difference 5%, p = 0.01; and 4%, p < 0.001)., Conclusions: An absolute MAP threshold of 65 mmHg is most frequently used to define hypotension in ICU patients. In neuro(trauma) patients a higher threshold was reported. The majority of ICU patients are estimated to endure hypotension during their ICU admission for a considerable amount of time, with nurses reporting a higher estimated incidence and time spent in hypotension than physicians., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: To examine whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) improves survival of patients with acute pulmonary embolism (PE)., Methods: Following the PRISMA guidelines, a systematic search was conducted up to August 2019 of the databases: PubMed/MEDLINE, EMBASE and Cochrane. All studies reporting the survival of adult patients with acute PE treated with VA-ECMO and including four patients or more were included. Exclusion criteria were: correspondences, reviews and studies in absence of a full text, written in other languages than English or Dutch, or dating before 1980. Short-term (hospital or 30-day) survival data were pooled and presented with relative risks (RR) and 95% confidence intervals (95% CI). Also, the following pre-defined factors were evaluated for their association with survival in VA-ECMO treated patients: age > 60 years, male sex, pre-ECMO cardiac arrest, surgical embolectomy, catheter directed therapy, systemic thrombolysis, and VA-ECMO as single therapy., Results: A total of 29 observational studies were included (N = 1947 patients: VA-ECMO N = 1138 and control N = 809). There was no difference in short-term survival between VA-ECMO treated patients and control patients (RR 0.91, 95% CI 0.71-1.16). In acute PE patients undergoing VA-ECMO, age > 60 years was associated with lower survival (RR 0.72, 95% CI 0.52-0.99), surgical embolectomy was associated with higher survival (RR 1.96, 95% CI 1.39-2.76) and pre-ECMO cardiac arrest showed a trend toward lower survival (RR 0.88, 95% CI 0.77-1.01). The other evaluated factors were not associated with a difference in survival., Conclusions: At present, there is insufficient evidence that VA-ECMO treatment improves short-term survival of acute PE patients. Low quality evidence suggest that VA-ECMO patients aged ≤60 years or who received SE have higher survival rates. Considering the limited evidence derived from the present data, this study emphasizes the need for prospective studies., Protocol Registration: PROSPERO CRD42019120370., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

It is important to gain more insight into the cardiogenic shock (CS) population, as currently, little is known on how to improve outcomes. Therefore, we assessed clinical outcome in acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI) with and without CS at admission. Furthermore, the incidence of CS and predictors for mortality in CS patients were evaluated. The Netherlands Heart Registration (NHR) is a nationwide registry on all cardiac interventions. We used NHR data of ACS patients treated with PCI between 2015 and 2019. Among 75,407 ACS patients treated with PCI, 3028 patients (4.1%) were identified with CS, respectively 4.3%, 3.9%, 3.5%, and 4.3% per year. Factors associated with mortality in CS were age (HR 1.02, 95%CI 1.02-1.03), eGFR (HR 0.98, 95%CI 0.98-0.99), diabetes mellitus (DM) (HR 1.25, 95%CI 1.08-1.45), multivessel disease (HR 1.22, 95%CI 1.06-1.39), prior myocardial infarction (MI) (HR 1.24, 95%CI 1.06-1.45), and out-of-hospital cardiac arrest (OHCA) (HR 1.71, 95%CI 1.50-1.94). In conclusion, in this Dutch nationwide registry-based study of ACS patients treated by PCI, the incidence of CS was 4.1% over the 4-year study period. Predictors for mortality in CS were higher age, renal insufficiency, presence of DM, multivessel disease, prior MI, and OHCA.

We describe the practice of ventilation and mortality rates in invasively ventilated normal-weight (18.5 ≤ BMI ≤ 24.9 kg/m 2 ), overweight (25.0 ≤ BMI ≤ 29.9 kg/m 2 ), and obese (BMI > 30 kg/m 2 ) COVID-19 ARDS patients in a national, multicenter observational study, performed at 22 intensive care units in the Netherlands. The primary outcome was a combination of ventilation variables and parameters over the first four calendar days of ventilation, including tidal volume, positive end-expiratory pressure (PEEP), respiratory system compliance, and driving pressure in normal-weight, overweight, and obese patients. Secondary outcomes included the use of adjunctive treatments for refractory hypoxaemia and mortality rates. Between 1 March 2020 and 1 June 2020, 1122 patients were included in the study: 244 (21.3%) normal-weight patients, 531 (47.3%) overweight patients, and 324 (28.8%) obese patients. Most patients received a tidal volume < 8 mL/kg PBW; only on the first day was the tidal volume higher in obese patients. PEEP and driving pressure were higher, and compliance of the respiratory system was lower in obese patients on all four days. Adjunctive therapies for refractory hypoxemia were used equally in the three BMI groups. Adjusted mortality rates were not different between BMI categories. The findings of this study suggest that lung-protective ventilation with a lower tidal volume and prone positioning is similarly feasible in normal-weight, overweight, and obese patients with ARDS related to COVID-19. A patient's BMI should not be used in decisions to forgo or proceed with invasive ventilation.

Background: Mechanical ventilation can induce or even worsen lung injury, at least in part via overdistension caused by too large volumes or too high pressures. The complement system has been suggested to play a causative role in ventilator-induced lung injury., Aims and Methods: This was a single-center prospective study investigating associations between pulmonary levels of complement activation products and two ventilator settings, tidal volume (V T ) and driving pressure (ΔP), in critically ill patients under invasive ventilation. A miniature bronchoalveolar lavage (BAL) was performed for determination of pulmonary levels of C5a, C3b/c, and C4b/c. The primary endpoint was the correlation between BAL fluid (BALF) levels of C5a and V T and ΔP. Levels of complement activation products were also compared between patients with and without ARDS or with and without pneumonia., Results: Seventy-two patients were included. Median time from start of invasive ventilation till BAL was 27 [19 to 34] hours. Median V T and ΔP before BAL were 6.7 [IQR 6.1 to 7.6] ml/kg predicted bodyweight (PBW) and 15 [IQR 11 to 18] cm H 2 O, respectively. BALF levels of C5a, C3b/c and C4b/c were neither different between patients with or without ARDS, nor between patients with or without pneumonia. BALF levels of C5a, and also C3b/c and C4b/c, did not correlate with V T and ΔP. Median BALF levels of C5a, C3b/c, and C4b/c, and the effects of V T and ΔP on those levels, were not different between patients with or without ARDS, and in patients with or without pneumonia., Conclusion: In this cohort of critically ill patients under invasive ventilation, pulmonary levels of complement activation products were independent of the size of V T and the level of ΔP. The associations were not different for patients with ARDS or with pneumonia. Pulmonary complement activation does not seem to play a major role in VILI, and not even in lung injury per se, in critically ill patients under invasive ventilation.

Background: In selected patients with an acute myocardial infarction (AMI) complicated by Cardiogenic shock (CS), mechanical circulatory support with Impella may be beneficial, although conclusive evidence is still lacking. Nevertheless, it has been suggested that Impella initiation prior to primary PCI might improve survival., Objective: To investigate the effect pre-PCI versus immediate post-PCI Impella initiation on short term mortality., Methods: A prospective, single center, observational study, was performed including all patients with STEMI complicated by CS, treated with primary PCI and Impella. Thirty day mortality was compared between patients with Impella initiation pre-PCI and immediately post-PCI., Results: A total of 88 patients were included. In the pre-PCI group (n = 21), admission heart rate was lower (84 versus 94 bpm, p = 0.04) and no IABP was implanted before Impella initiation, versus 17.9% in post-PCI group (n = 67), p = 0.04. Total 30-day all-cause mortality was 58%, and was lower in pre-PCI group, 47.6% versus 61.2% in the post-PCI group, however not statistically significant (HR 0.7, 95% CI 0.3-1.3, p = 0.21). Thirty-day cardiac mortality was significantly lower in the pre-PCI group, 19% versus 44.7% in the post-PCI group (HR 0.3, 95% CI 0.09-0.96, p = 0.042)., Conclusion: Pre-PCI Impella initiation in AMICS patients was not associated with a statistically significant difference in 30-day all-cause mortality, compared to post-PCI Impella initiation., Competing Interests: The authors have declared that no competing interests exist.

Lung ultrasound (LUS) is a non-invasive bedside method used to quantify extravascular lung water (EVLW). To evaluate the methodology and diagnostic accuracy of LUS in studies assessing EVLW in intensive care unit patients, PubMed and Embase were searched for studies comparing LUS with imaging modalities. In 14 relevant studies a wide variety of equipment used and training of examiners were noted. Four scoring systems were reported: (i) a binary score (the presence of three or more B-lines); (ii) a categorical score; (iii) a numerical score; (iv) a quantitative LUS score using software. The diagnostic accuracy of LUS varied: sensitivity ranged from 50%-98%, specificity from 76%-100% and r² from 0.20-0.91. Methodology and diagnostic accuracy varies substantially in published reports. Further research is needed to correlate methodological factors with diagnostic accuracy. Hospitals should standardize LUS methodology. Consensus is needed to harmonize LUS methodology for lung water assessment., (Copyright © 2020 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Vasopressors and inotropes are routinely used in acute myocardial infarction (AMI) related cardiogenic shock (CS) to improve hemodynamics. We aimed to investigate the effect of routinely used vasopressor and inotropes on mortality in AMI related CS. A systematic search of MEDLINE, EMBASE and CENTRAL was performed up to 20 February 2019. Randomized and observational studies reporting mortality of AMI related CS patients were included. At least one group should have received the vasopressor/inotrope compared with a control group not exposed to the vasopressor/inotrope. Exclusion criteria were case reports, correspondence and studies including only post-cardiac surgery patients. In total, 19 studies (6 RCTs) were included, comprising 2478 CS patients. The overall quality of evidence was graded low. Treatment with adrenaline, noradrenaline, vasopressin, milrinone, levosimendan, dobutamine or dopamine was not associated with a difference in mortality between therapy and control group. We found a trend toward better outcome with levosimendan, compared with control (RR 0.69, 95% CI 0.47-1.00). In conclusion, we found insufficient evidence that routinely used vasopressors and inotropes are associated with reduced mortality in patients with AMI related CS. Considering the limited evidence, this study emphasizes the need for randomized trials with appropriate endpoints and methodology.

Background: Mechanical ventilation with low tidal volumes has the potential to mitigate ventilation-induced lung injury, yet the clinical effect of tidal volume size on myocardial function has not been clarified. This cross-sectional study investigated whether low tidal volume ventilation has beneficial effects on myocardial systolic and diastolic function compared to intermediate tidal volume ventilation., Methods: Forty-two mechanically ventilated patients without acute respiratory distress syndrome (ARDS) underwent transthoracic echocardiography after more than 24 h of mechanical ventilation according to the Protective Ventilation in Patients without ARDS (PReVENT) trial comparing a low versus intermediate tidal volume strategy. The primary outcome was left ventricular and right ventricular myocardial performance index as measure for combined systolic and diastolic function, with lower values indicating better myocardial function and a right ventricular myocardial performance index greater than 0.54 regarded as the abnormality threshold. Secondary outcomes included specific systolic and diastolic parameters., Results: One patient was excluded due to insufficient acoustic windows, leaving 21 patients receiving low tidal volumes with a tidal volume size (mean ± SD) of 6.5 ± 1.8 ml/kg predicted body weight, while 20 patients were subjected to intermediate tidal volumes receiving a tidal volume size of 9.5 ± 1.6 ml/kg predicted body weight (mean difference, -3.0 ml/kg; 95% CI, -4.1 to -2.0; P < 0.001). Right ventricular dysfunction was reduced in the low tidal volume group compared to the intermediate tidal volume group (myocardial performance index, 0.41 ± 0.13 vs. 0.64 ± 0.15; mean difference, -0.23; 95% CI, -0.32 to -0.14; P < 0.001) as was left ventricular dysfunction (myocardial performance index, 0.50 ± 0.17 vs. 0.63 ± 0.19; mean difference, -0.13; 95% CI, -0.24 to -0.01; P = 0.030). Similarly, most systolic parameters were superior in the low tidal volume group compared to the intermediate tidal volume group, yet diastolic parameters did not differ between both groups., Conclusions: In patients without ARDS, intermediate tidal volume ventilation decreased left ventricular and right ventricular systolic function compared to low tidal volume ventilation, although without an effect on diastolic function.

Background: Impaired microvascular perfusion is central to the development of coma and lactic acidosis in severe falciparum malaria. Refractory hypotension is rare on admission but develops frequently in fatal cases. We assessed cardiac function and volume status in severe falciparum malaria and its prognostic significance., Methods: Patients with severe (N = 101) or acute uncomplicated falciparum malaria (N = 83) were recruited from 2 hospitals in India and Bangladesh, and healthy participants (N = 44) underwent echocardiography., Results: Patients with severe malaria had 38% shorter left ventricular (LV) filling times and 25% shorter LV ejection times than healthy participants because of tachycardia; however, stroke volume, LV internal diameter in diastole (LVIDd), and LV internal diameter in systole (LVIDs) indices were similar. A low endocardial fraction shortening (eFS) was present in 17% (9 of 52) of severe malaria patients. Adjusting for preload and afterload, eFS was similar in health and severe malaria. Fatal cases had smaller baseline LVIDd and LVIDs indices, more collapsible inferior vena cavae (IVC), and higher heart rates than survivors. The LVIDs and IVC collapsibility were independent predictors for mortality, together with base excess and Glasgow Coma Scale., Conclusions: Patients with severe malaria have rapid ejection of a normal stroke volume. Fatal cases had features of relative hypovolemia and reduced cardiac index reserve., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Short-term mechanical circulatory support devices are increasingly used in cardiogenic shock after acute myocardial infarction. As no randomised evidence is available, the choice between high-output Impella or extra-corporeal membrane oxygenation (ECMO) is still a matter of debate. Real-life data are necessary to assess adverse outcomes and to help guide the treatment decision between the different devices. The purpose of this study was to compare characteristics and clinical outcomes of Impella CP/5.0 with ECMO support in patients with cardiogenic shock from myocardial infarction., Methods: A retrospective, two-centre study was performed on all cardiogenic shock from myocardial infarction patients with Impella CP/5.0 or ECMO support, from 2006 until 2018. The primary outcome was 30-day mortality. Potential baseline imbalance between the groups was adjusted using inverse probability treatment weighting, and survival analysis was performed with an adjusted log-rank test. Secondarily, the occurrence of device-related complications (limb ischaemia, access site-related bleeding, access site-related infection) was evaluated., Results: A total of 128 patients were included (Impella, N =90; ECMO, N =38). The 30-day mortality was similar for both groups (53% vs. 49%, P =0.30), also after adjustment for potential baseline imbalance between the groups (weighted log-rank P =0.16). Patients with Impella support had significantly fewer device-related complications than patients treated with ECMO (respectively, 17% vs. 40%, P <0.01)., Conclusions: Patients treated with Impella CP/5.0 or ECMO for cardiogenic shock after myocardial infarction did not differ in 30-day mortality. More device-related complications occurred with ECMO compared to Impella support.

Background: The complement system has frequently been suggested to play a role in the pathophysiology of acute respiratory distress syndrome (ARDS). The current study explored the association between pulmonary depositions of a complement activation product and the clinical diagnosis of ARDS., Methods: Lung tissue material from autopsied critically ill patients who died whilst on invasively mechanical ventilation was collected and stained for complement C3d. The diagnosis of ARDS was by the Berlin Definition. Lung injury scores (LIS) and driving pressures were calculated, 48 and 24 h prior to death. A pathologist who remained blinded for the clinical data scored the extent of C3d depositions, using a C3d deposition score (a minimum and maximum score of 0 and 24), and of diffuse alveolar damage (DAD). The primary analysis focused on the association between the C3d deposition score and the clinical diagnosis of ARDS. Secondary analyses focused on associations between the C3d deposition score and the presence of diffuse alveolar damage (DAD) in histopathology, and LIS and driving pressures in the last 2 days before death., Results: Of 36 patients of whom autopsy material was available, 12 were diagnosed as having had ARDS. In all patients, C3d depositions were found in various parts of the lungs, and to a different extent. Notably, C3d deposition scores were similar for patients with ARDS and those without ARDS (4.5 [3.3-6.8] vs. 5.0 [4.0-6.0]; not significant). C3d deposition scores were also independent from the presence or absence of DAD, and correlations between C3d scores and LIS and driving pressures prior to death were poor., Conclusion: Pulmonary C3d depositions are found in the lungs of all deceased ICU patients, independent of the diagnosis of ARDS. The presence of complement C3d was not associated with the presence of DAD on histopathology and had a poor correlation with ventilation characteristics prior to death.

Background: Semi-quantification of lung aeration by ultrasound helps to assess presence and extent of pulmonary pathologies, including the acute respiratory distress syndrome (ARDS). It is uncertain which lung regions add most to the diagnostic accuracy for ARDS of the frequently used global lung ultrasound (LUS) score. We aimed to compare the diagnostic accuracy of the global versus those of regional LUS scores in invasively ventilated intensive care unit patients., Methods: This was a post-hoc analysis of a single-center observational study in the mixed medical-surgical intensive care unit of a university-affiliated hospital in the Netherlands. Consecutive patients, aged ≥ 18 years, and are expected to receive invasive ventilation for > 24 h underwent a LUS examination within the first 2 days of ventilation. The Berlin Definition was used to diagnose ARDS, and to classify ARDS severity. From the 12-region LUS examinations, the global score (minimum 0 to maximum 36) and 3 regional scores (the 'anterior,' 'lateral,' and 'posterior' score, minimum 0 to maximum 12) were computed. The area under the receiver operating characteristic (AUROC) curve was calculated and the best cutoff for ARDS discrimination was determined for all scores., Results: The study enrolled 152 patients; 35 patients had ARDS. The global score was higher in patients with ARDS compared to patients without ARDS (median 19 [15-23] vs. 5 [3-9]; P < 0.001). The posterior score was the main contributor to the global score, and was the only score that increased significantly with ARDS severity. However, the posterior score performed worse than the global score in diagnosing ARDS, and it had a positive predictive value of only 50 (41-59)% when using the optimal cutoff. The combined anterolateral score performed as good as the global score (AUROC of 0.91 [0.85-0.97] vs. 0.91 [0.86-0.95])., Conclusions: While the posterior score increases with ARDS severity, its diagnostic accuracy for ARDS is hampered due to an unfavorable signal-to-noise ratio. An 8-region 'anterolateral' score performs as well as the global score and may prove useful to exclude ARDS in invasively ventilated ICU patients.

Aims: Mortality in cardiogenic shock patients remains high. Short-term mechanical circulatory support with Impella can be used to support the circulation in these patients, but data from randomised controlled studies and 'real-world' data are sparse. The aim is to describe real-life data on outcomes and complications of our 12 years of clinical experience with Impella in patients with cardiogenic shock after acute myocardial infarction and to identify predictors of 6-month mortality., Methods: We describe a single-centre registry from October 2004 to December 2016 including all patients treated with Impella for cardiogenic shock after acute myocardial infarction. We report outcomes and complications and identify predictors of 6-month mortality., Results: Our overall clinical experience consists of 250 patients treated with Impella 2.5, Impella CP or Impella 5.0. A total of 172 patients received Impella therapy for cardiogenic shock, of which 112 patients had cardiogenic shock after acute myocardial infarction. The mean age was 60.1±10.6 years, mean arterial pressure was 67 (56-77) mmHg, lactate was 6.2 (3.6-9.7) mmol/L, 87.5% were mechanically ventilated and 59.6% had a cardiac arrest before Impella placement. Overall 30-day mortality was 56.2% and 6-month mortality was 60.7%. Complications consisted of device-related vascular complications (17.0%), non-device-related bleeding (12.5%), haemolysis (7.1%) and stroke (3.6%). In a multivariate analysis, pH before Impella placement is a predictor of 6-month mortality., Conclusions: Our registry shows that Impella treatment in cardiogenic shock after acute myocardial infarction is feasible, although mortality rates remain high and complications occur.

In the present report, we describe 2 cases of endocarditis after MitraClip (Abbott Vascular, Santa Clara, CA) procedures. In both patients, successful bailout surgical treatment was performed despite a high-risk constellation due to significant comorbidities. These cases highlight that surgical treatment may still be an option in patients initially declined for surgical therapy and that endocarditis after MitraClip procedure might be an underrecognized complication., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

In Table 1 of this article, the numerical data were correct but the graphic part was imprecise.

Background: Despite advances in treatment, mortality in acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains high. Short-term mechanical circulatory support devices acutely improve hemodynamic conditions., Objectives: The aim of this study was to determine whether a new percutaneous mechanical circulatory support (pMCS) device (Impella CP, Abiomed, Danvers, Massachusetts) decreases 30-day mortality when compared with an intra-aortic balloon pump (IABP) in patients with severe shock complicating AMI., Methods: In a randomized, prospective, open-label, multicenter trial, 48 patients with severe CS complicating AMI were assigned to pMCS (n = 24) or IABP (n = 24). Severe CS was defined as systolic blood pressure <90 mm Hg or the need for inotropic or vasoactive medication and the requirement for mechanical ventilation. The primary endpoint was 30-day all-cause mortality., Results: At 30 days, mortality in patients treated with either IABP or pMCS was similar (50% and 46%, respectively; hazard ratio with pMCS: 0.96; 95% confidence interval: 0.42 to 2.18; p = 0.92). At 6 months, mortality rates for both pMCS and IABP were 50% (hazard ratio: 1.04; 95% confidence interval: 0.47 to 2.32; p = 0.923)., Conclusions: In this explorative randomized controlled trial involving mechanically ventilated patients with CS after AMI, routine treatment with pMCS was not associated with reduced 30-day mortality compared with IABP. (IMPRESS in Severe Shock; NTR3450)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Veno-arterial extracorporeal life support (ECLS) is increasingly used in patients during cardiac arrest and cardiogenic shock, to support both cardiac and pulmonary function. We performed a systematic review and meta-analysis of cohort studies comparing mortality in patients treated with and without ECLS support in the setting of refractory cardiac arrest and cardiogenic shock complicating acute myocardial infarction., Methods: We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed updated to December 2015. Thirteen studies were included of which nine included cardiac arrest patients (n = 3098) and four included patients with cardiogenic shock after acute myocardial infarction (n = 235). Data were pooled by a Mantel-Haenzel random effects model and heterogeneity was examined by the I 2 statistic., Results: In cardiac arrest, the use of ECLS was associated with an absolute increase of 30 days survival of 13 % compared with patients in which ECLS was not used [95 % CI 6-20 %; p < 0.001; number needed to treat (NNT) 7.7] and a higher rate of favourable neurological outcome at 30 days (absolute risk difference 14 %; 95 % CI 7-20 %; p < 0.0001; NNT 7.1). Propensity matched analysis, including 5 studies and 438 patients (219 in both groups), showed similar results. In cardiogenic shock, ECLS showed a 33 % higher 30-day survival compared with IABP (95 % CI, 14-52 %; p < 0.001; NNT 13) but no difference when compared with TandemHeart/Impella (-3 %; 95 % CI -21 to 14 %; p = 0.70; NNH 33)., Conclusions: In cardiac arrest, the use of ECLS was associated with an increased survival rate as well as an increase in favourable neurological outcome. In the setting of cardiogenic shock there was an increased survival with ECLS compared with IABP., Competing Interests: Compliance with ethical standards Conflicts of interest J.P.S. Henriques reports research grants outside the submitted work. The other authors do not declare any conflicts of interest.

Aim: Besides supportive care, the only recommended treatment for comatose patients after cardiac arrest is target temperature management. Helium reduces ischaemic injury in animal models, and might ameliorate neurological injury in patients after cardiac arrest. As no studies exist on the use of helium in patients after cardiac arrest we investigated whether this is safe and feasible., Methods: The study was an open-label single arm intervention study in a mixed-bed academic intensive care unit. We included 25 patients admitted after circulatory arrest, with a presenting rhythm of ventricular fibrillation or pulseless tachycardia, return of spontaneous circulation within 30min and who were treated with hypothermia. Helium was administrated in a 1:1 mix with oxygen for 3h. A safety committee reviewed all ventilation problems, complications and causes of mortality., Results: Helium ventilation was started 4:59±0:52 (mean±SD)h after circulatory arrest. In one patient, helium ventilation was discontinued prematurely due to oxygenation problems. This was caused by pre-existing pulmonary oedema, and imposed limitations to PEEP and FiO2 by the study protocol, rather than the use of helium ventilation. Sixteen (64%) patients had a favourable neurological outcome., Conclusions: We found that helium ventilation is feasible and can be used safely in patients treated with hypothermia after cardiac arrest. No adverse events related to the use of helium occurred during the three hours of administration., (Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.)

Objectives: The use of intracardiac assist devices is expanding, and correct position of these devices is required for optimal functioning. The aortic valve is an important landmark for positioning of those devices. It would be of great value if the device position could be easily monitored on plain supine chest radiograph in the ICU. We introduce a ratio-based tool for determination of the aortic valve location on plain supine chest radiograph images, which can be used to evaluate intracardiac device position., Design: Retrospective observational study., Setting: Large academic medical center., Patients: Patients admitted to the ICU and supported by an intracardiac assist device., Interventions: We developed a ratio to determine the aortic valve location on supine chest radiograph images. This ratio is used to assess the position of a cardiac assist device and is compared with echocardiographic findings., Measurements and Main Results: Supine anterior-posterior chest radiographs of patients with an aortic valve prosthesis (n = 473) were analyzed to determine the location of the aortic valve. We calculated several ratios with the potential to determine the position of the aortic valve. The aortic valve location ratio, defined as the distance between the carina and the aortic valve, divided by the thoracic width, was found to be the best performing ratio. The aortic valve location ratio determines the location of the aortic valve caudal to the carina, at a distance of 0.25 ± 0.05 times the thoracic width for male patients and 0.28 ± 0.05 times the thoracic width for female patients. The aortic valve location ratio was validated using CT images of patients with angina pectoris without known valvular disease (n = 95). There was a good correlation between cardiac device position (Impella) assessed with the aortic valve location ratio and with echocardiography (n = 53)., Conclusions: The aortic valve location ratio enables accurate and reproducible localization of the aortic valve on supine chest radiograph. This tool is easily applicable and can be used for assessment of cardiac device position in patients on the ICU.

We present a female patient with severe acute respiratory distress syndrome (ARDS) necessitating intubation and mechanical ventilation on the intensive care unit (ICU). High ventilatory pressures were needed because of hypoxia and severe hypercapnia with respiratory acidosis, resulting in right ventricular dysfunction with impaired haemodynamic stability. A veno-venous extracorporeal CO2 removal (ECCO2R) circuit was initiated, effectively eliminating carbon dioxide while improving oxygenation and enabling a reduction in applied ventilatory pressures. We noted a marked improvement of right ventricular function with restoration of haemodynamic stability. Within one week, the patient was weaned from both ECCO2R and mechanical ventilation. Besides providing adequate gas exchange, extracorporeal assist devices may be helpful in ameliorating right ventricular dysfunction during ARDS., (© The Author(s) 2015.)

Objectives: To examine the effect of positive end-expiratory pressure (PEEP) on right ventricular stroke volume variation (SVV), with possible implications for the number and timing of pulmonary artery catheter thermodilution measurements., Design: Prospective, clinical pilot study., Setting: Academic medical center., Participants: Patients who underwent volume-controlled mechanical ventilation and had a pulmonary artery catheter., Intervention: PEEP was increased from 5-to-10 cmH2O and from 10-to-15 cmH2O with 10-minute intervals, with similar decreases in PEEP, from 15-to-10 cmH2O and 10-to-5 cmH2O., Measurements and Main Results: In 15 patients, right ventricular parameters were measured using thermodilution at 10% intervals of the ventilatory cycle at each PEEP level with a rapid-response thermistor. Mean right ventricular stroke volume and end-diastolic volume declined during incremental PEEP and normalized on return to 5 cmH2O PEEP (p = 0.01 and p = 0.001, respectively). Right ventricular SVV remained unaltered by changes in PEEP (p = 0.26), regardless of incremental PEEP (p = 0.15) or decreased PEEP (p = 0.12). The coefficients of variation in the ventilatory cycle of all other thermodilution-derived right ventricular parameters also were unaffected by changes in PEEP., Conclusions: This study showed that increases in PEEP did not affect right ventricular SVV in critically ill patients undergoing mechanical ventilation despite reductions in mean right ventricular stroke volume and end-diastolic volume. This could be explained by cyclic counteracting changes in right ventricular preloading and afterloading during the ventilatory cycle, independent of PEEP. Changes in PEEP did not affect the number and timing of pulmonary artery catheter thermodilution measurements., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Passive leg raising creates a reversible increase in venous return allowing for the prediction of fluid responsiveness. However, the amount of venous return may vary in various clinical settings potentially affecting the diagnostic performance of passive leg raising. Therefore we performed a systematic meta-analysis determining the diagnostic performance of passive leg raising in different clinical settings with exploration of patient characteristics, measurement techniques, and outcome variables., Data Sources: PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and citation tracking of relevant articles., Study Selection: Clinical trials were selected when passive leg raising was performed in combination with a fluid challenge as gold standard to define fluid responders and non-responders., Data Extraction: Trials were included if data were reported allowing the extraction of sensitivity, specificity, and area under the receiver operating characteristic curve., Data Synthesis: Twenty-three studies with a total of 1,013 patients and 1,034 fluid challenges were included. The analysis demonstrated a pooled sensitivity of 86% (95% CI, 79-92), pooled specificity of 92% (95% CI, 88-96), and a summary area under the receiver operating characteristic curve of 0.95 (95% CI, 0.92-0.98). Mode of ventilation, type of fluid used, passive leg raising starting position, and measurement technique did not affect the diagnostic performance of passive leg raising. The use of changes in pulse pressure on passive leg raising showed a lower diagnostic performance when compared with passive leg raising-induced changes in flow variables, such as cardiac output or its direct derivatives (sensitivity of 58% [95% CI, 44-70] and specificity of 83% [95% CI, 68-92] vs sensitivity of 85% [95% CI, 78-90] and specificity of 92% [95% CI, 87-94], respectively; p < 0.001)., Conclusions: Passive leg raising retains a high diagnostic performance in various clinical settings and patient groups. The predictive value of a change in pulse pressure on passive leg raising is inferior to a passive leg raising-induced change in a flow variable.

Cardiac abnormalities after subarachnoid hemorrhage (SAH) such as electrocardiographic changes, echocardiographic wall motion abnormalities, and elevated troponin levels are independently associated with a poor prognosis. They are caused by catecholaminergic stress coinciding with influx of inflammatory cells into the heart. These abnormalities could be a sign of a myocarditis, potentially giving insight in pathophysiology and treatment options. These inflammatory cells are insufficiently characterized, and it is unknown whether myocarditis is associated with SAH. Myocardium of 25 patients who died of SAH and 18 controls was stained with antibodies identifying macrophages (CD68), lymphocytes (CD45), and neutrophil granulocytes (myeloperoxidase). Myocytolysis was visualized using complement staining (C3d). CD31 was used to identify putative thrombi. We used Mann-Whitney U testing for analysis. In the myocardium of SAH patients, the amount of myeloperoxidase-positive (P < .005), CD45-positive (P < .0005), and CD68-positive (P < .0005) cells was significantly higher compared to controls. Thrombi in intramyocardial arteries were found in 22 SAH patients and 1 control. Myocytolysis was found in 6 SAH patients but not in controls. Myocarditis, consisting of an influx of neutrophil granulocytes, lymphocytes, and macrophages, coinciding with myocytolysis and thrombi in intramyocardial arteries, occurs in patients with SAH but not in controls. These findings might explain the cardiac abnormalities after SAH and may have implications for treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: High tidal volume ventilation has shown to cause ventilator-induced lung injury (VILI), possibly contributing to concomitant extrapulmonary organ dysfunction. The present study examined whether left ventricular (LV) function is dependent on tidal volume size and whether this effect is augmented during lipopolysaccharide(LPS)-induced lung injury., Methods: Twenty male Wistar rats were sedated, paralyzed and then randomized in four groups receiving mechanical ventilation with tidal volumes of 6 ml/kg or 19 ml/kg with or without intrapulmonary administration of LPS. A conductance catheter was placed in the left ventricle to generate pressure-volume loops, which were also obtained within a few seconds of vena cava occlusion to obtain relatively load-independent LV systolic and diastolic function parameters. The end-systolic elastance / effective arterial elastance (Ees/Ea) ratio was used as the primary parameter of LV systolic function with the end-diastolic elastance (Eed) as primary LV diastolic function., Results: Ees/Ea decreased over time in rats receiving LPS (p = 0.045) and high tidal volume ventilation (p = 0.007), with a lower Ees/Ea in the rats with high tidal volume ventilation plus LPS compared to the other groups (p < 0.001). Eed increased over time in all groups except for the rats receiving low tidal volume ventilation without LPS (p = 0.223). A significant interaction (p < 0.001) was found between tidal ventilation and LPS for Ees/Ea and Eed, and all rats receiving high tidal volume ventilation plus LPS died before the end of the experiment., Conclusions: Low tidal volume ventilation ameliorated LV systolic and diastolic dysfunction while preventing death following LPS-induced lung injury in mechanically ventilated rats. Our data advocates the use of low tidal volumes, not only to avoid VILI, but to avert ventilator-induced myocardial dysfunction as well.

Mechanical ventilation has the potential to cause lung injury, and the role of complement activation herein is uncertain. We hypothesized that inhibition of the complement cascade by administration of plasma-derived human C1-esterase inhibitor (C1-INH) prevents ventilation-induced pulmonary complement activation, and as such attenuates lung inflammation and lung injury in a rat model of Streptococcus pneumoniae pneumonia. Forty hours after intratracheal challenge with S. pneumoniae causing pneumonia rats were subjected to ventilation with lower tidal volumes and positive end-expiratory pressure (PEEP) or high tidal volumes without PEEP, after an intravenous bolus of C1-INH (200 U/kg) or placebo (saline). After 4 h of ventilation blood, broncho-alveolar lavage fluid and lung tissue were collected. Non-ventilated rats with S. pneumoniae pneumonia served as controls. While ventilation with lower tidal volumes and PEEP slightly amplified pneumonia-induced complement activation in the lungs, ventilation with higher tidal volumes without PEEP augmented local complement activation more strongly. Systemic pre-treatment with C1-INH, however, failed to alter ventilation-induced complement activation with both ventilation strategies. In accordance, lung inflammation and lung injury were not affected by pre-treatment with C1-INH, neither in rats ventilated with lower tidal volumes and PEEP, nor rats ventilated with high tidal volumes without PEEP. Ventilation augments pulmonary complement activation in a rat model of S. pneumoniae pneumonia. Systemic administration of C1-INH, however, does not attenuate ventilation-induced complement activation, lung inflammation, and lung injury.

Aim: To investigate the effects of inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock., Methods and Results: Thirty patients with cardiogenic shock were included. Patients received dobutamine, enoximone, or norepinephrine. We performed hemodynamic measurements at baseline and after titration of the inotropic agent until cardiac index (CI) ≥ 2.5 L.min-1.m(-2) or mixed-venous oxygen saturation (SvO2) ≥ 70% (dobutamine or enoximone), and mean arterial pressure (MAP) ≥ 70 mmHg (norepinephrine). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD). All patients reached predefined therapeutic targets. The inotropes did not significantly change delta-T. Dobutamine did not change PCD. Enoximone increased PCD (9.1 [8.9-10.2] vs. 11.4 [8.4-13.9] mm.mm(-2); p<0.05), and norepinephrine tended to decrease PCD (9.8 [8.5-11.9] vs. 8.8 [8.2-9.6] mm.mm-2, p = 0.08). Fifteen patients (50%) died within 30 days after admission. Patients who had low final PCD (≤ 10.3 mm.mm-2; 64%) were more likely to die than patients who had preserved PCD (>10.3 mm.mm(-2); mortality 72% vs. 17%, p = 0.003)., Conclusion: This study demonstrates the effects of commonly used inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Despite hemodynamic optimization, tissue perfusion was not sufficiently restored in most patients. In these patients, mortality was high. Interventions directed at improving microcirculation may eventually help bridging the gap between improved hemodynamics and dismal patient outcome in cardiogenic shock.

1. The present study examined the relationship between centrally measured stroke volume variation (SVV) and peripherally derived pulse pressure variation (PPV) in the setting of increased total arterial compliance (CA rt ). 2. Ten male Wistar rats were anaesthetized, paralysed and mechanically ventilated before being randomized to receive intrapulmonary lipopolysaccharide (LPS) or no LPS. Pulse pressure (PP) was derived from the left carotid artery, whereas stroke volume (SV) was measured directly in the left ventricle. Values of SVV and PPV were calculated over three breaths. Balloon inflation of a catheter positioned in the inferior vena cava was used, for a maximum of 30 s, to decrease preload while the SVV and PPV measurements were repeated. Values of CA rt were calculated as SV/PP. 3. Intrapulmonary LPS increased CA rt and SV. Values of SVV and PPV increased in both LPS-treated and untreated rats during balloon inflation. There was a correlation between SVV and PPV in untreated rats before (r = 0.55; P = 0.005) and during (r = 0.69; P < 0.001) occlusion of the vena cava. There was no such correlation in LPS-treated rats either before (r = -0.08; P = 0.70) or during (r = 0.36; P = 0.08) vena cava occlusion. 4. In conclusion, under normovolaemic and hypovolaemic conditions, PPV does not reflect SVV during an increase in CA rt following LPS-induced pneumonia in mechanically ventilated rats. Our data caution against their interchangeability in human sepsis., (© 2013 Wiley Publishing Asia Pty Ltd.)

Introduction. Helium is a noble gas with low density and increased carbon dioxide (CO2) diffusion capacity. This allows lower driving pressures in mechanical ventilation and increased CO2 diffusion. We hypothesized that heliox facilitates ventilation in patients during lung-protective mechanical ventilation using low tidal volumes. Methods. This is an observational cohort substudy of a single arm intervention study. Twenty-four ICU patients were included, who were admitted after a cardiac arrest and mechanically ventilated for 3 hours with heliox (50% helium; 50% oxygen). A fixed protective ventilation protocol (6 mL/kg) was used, with prospective observation for changes in lung mechanics and gas exchange. Statistics was by Bonferroni post-hoc correction with statistical significance set at P < 0.017. Results. During heliox ventilation, respiratory rate decreased (25 ± 4 versus 23 ± 5 breaths min(-1), P = 0.010). Minute volume ventilation showed a trend to decrease compared to baseline (11.1 ± 1.9 versus 9.9 ± 2.1 L min(-1), P = 0.026), while reducing PaCO2 levels (5.0 ± 0.6 versus 4.5 ± 0.6 kPa, P = 0.011) and peak pressures (21.1 ± 3.3 versus 19.8 ± 3.2 cm H2O, P = 0.024). Conclusions. Heliox improved CO2 elimination while allowing reduced minute volume ventilation in adult patients during protective mechanical ventilation.

Predicting fluid responsiveness, the response of stroke volume to fluid loading, is a relatively novel concept that aims to optimise circulation, and as such organ perfusion, while avoiding futile and potentially deleterious fluid administrations in critically ill patients. Dynamic parameters have shown to be superior in predicting the response to fluid loading compared with static cardiac filling pressures. However, in routine clinical practice the conditions necessary for dynamic parameters to predict fluid responsiveness are frequently not met. Passive leg raising as a means to alter biventricular preload in combination with subsequent measurement of the change in stroke volume can provide a fast and accurate way to guide fluid management in a broad population of critically ill patients.

Background: Little is known about the clinical impact of arrhythmias after surgery for congenital heart disease (CHD) in adults. Therefore, we investigated the prevalence of in-hospital arrhythmias after CHD surgery and their impact on clinical outcome., Methods: This was a multicenter retrospective study and included adults who underwent congenital cardiac surgery between January 2009 and December 2011. Clinical events were defined as all cause mortality, heart failure (HF) requiring medical treatment, thrombo-embolic event, major infections and permanent pacemaker (PM) implantation., Results: Overall, 419 patients were included (mean age 38 ± 14 years, 55% male). Arrhythmias occurred in 134 patients (32%) and included supraventricular tachycardia (SVT, n = 100), bradycardias (n = 47) and ventricular tachycardia (VT, n = 19). In multivariate analysis age ≥40 years at surgery (OR 2.48, 95% Cl 1.40-4.60, P = 0.003), NYHA class ≥ II (OR 2.42, 95% Cl 1.18-4.67, P = 0.009), significant subpulmonary AV-valve regurgitation (OR 2.84, 95% Cl 1.19-6.72, P = 0.018), coronary bypass time (OR 1.35/60 minute increase, 95% Cl 1.06-1.82, P = 0.019) and CK-MB (OR 1.05 per 10 U/L increase, 95% Cl 1.01-1.09, P = 0.021) were associated with in-hospital arrhythmias. Overall, 58 clinical events occurred in 55 patients (13%) and included in the majority of the cases permanent PM implantation (5%), HF (4%) and death (2%). In-hospital arrhythmias were independently associated with clinical events (OR 7.80, 95% CI 2.41-25.54, P = 0.001)., Conclusion: Arrhythmias are highly prevalent after congenital heart surgery in adults and are associated with worse clinical outcome. Older and symptomatic patients with significant valvular heart disease at baseline are at risk of in-hospital arrhythmias., (© 2013.)

Aim: Postcardiotomy cardiogenic shock (PCCS) is associated with high mortality rates, despite full conventional treatment. Although the results of treatment with surgically implantable ventricular assist devices have been encouraging, the invasiveness of this treatment limits its applicability. Several less invasive devices have been developed, including the Impella system. The objective of this study was to describe our three-center experience with the Impella 5.0 device in the setting of PCCS., Methods: From January 2004 through December 2010, a total of 46 patients were diagnosed with treatment-refractory PCCS and treated with the Impella 5.0 percutaneous left ventricular assist device at three european heart centers. Baseline and follow-up characteristics were collected retrospectively and entered into a dedicated database., Results: Within the study cohort of 46 patients, mean logistic and additive EuroSCORES were 24 ± 19 and 10 ± 4. The majority of patients underwent coronary artery bypass grafting (48%) or combined surgery (33%). Half of all patients had been treated with an intra-aortic balloon pump before 5.0-implantation, 1 patient had been treated with an Impella 2.5 device. All patients were on mechanical ventilation and intravenous inotropes. The Kaplan-Meier estimate of overall 30-day survival was 39.5%., Conclusion: Thirty-day survival rates for patients with PCCS, refractory to aggressive conventional treatment and treated with the Impella 5.0 device, are comparable to those reported in studies evaluating surgically implantable VADs, whereas the Impella system is much less invasive. Therefore, mechanical circulatory support with the Impella 5.0 device is a suitable treatment modality for patients with severe PCCS.