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Objective: The volemic status of a patient can be determined by measuring mean systemic filling pressure (Pmsf). Pmsf is obtained from the venous return curve, i.e. the relationship between central venous pressure (Pcv) and blood flow. We evaluated the feasibility and precision of Pmsf measurement.Methods: In ten piglets we constructed venous return curves using seven 12 s inspiratory holds transiently increasing Pcv to seven different steady state levels and monitored the resultant blood flow, by pulse contour (COpc) and by flow probes around the pulmonary artery (COr) and aorta (COl). Pmsf is obtained by extrapolation of the venous return curve to zero flow. Measurements were repeated to evaluate the precision of Pmsf.Results: During the inspiratory holds, 133 paired data points were obtained for COr, COl, COpc and Pcv. Bland-Altman analysis showed no difference between COr and COl, but a small significant difference was present between COl and COpc. All Pcv versus flow (COl or COpc) relationships were linear. Mean Pmsf was 10.78 with COl and 10.37 mmHg with COpc. Bland-Altman analysis for Pmsf with COl and with COpc, showed a bias of 0.40  ±  0.48 mmHg. The averaged coefficient of variation for repeated measurement of Pmsf with COl was 6.2% and with COpc 6.1%.Conclusions: During an inspiratory hold pulmonary flow and aortic flow equilibrate. Cardiac output estimates by arterial pulse contour and by a flow probe around the aorta are interchangeable. Therefore, the venous return curve and Pmsf can be estimated accurately by pulse contour methods. [ABSTRACT FROM AUTHOR]

Objective: We present a new physiological model that discriminated between changes in the systemic arterial and venous circulation. To test our model, we studied the effects of dobutamine and hypovolemia in intact pentabarbital-anesthetized piglets.Methods: Aorta pressure (Pao), central venous pressure (Pcv), mean systemic filling pressure (Pmsf) and cardiac output (CO), were measured in 10 piglets, before, during and after dobutamine infusion (6 µg kg⁻¹ min⁻¹), as well as during hypovolemia (-10 mL kg⁻¹), and after fluid resuscitation to normovolemia. Venous (Rv) and total systemic (Rsys) resistance were determined from Pao, Pcv, Pmsf and CO. The quotient of Rv/Rsys was used to determine the predominant location of vascular changes (i.e. vasoconstriction or dilatation on either venous or arterial side).Results: Administration of dobutamine increased heart rate and CO, whereas it decreased Pmsf, Rsys, Rv and Rv/Rsys. The decrease in Rv was significantly greater than Rsys. Pao and Pcv did not change. Hypovolemia decreased CO, Pcv, Pmsf, Rv and Rv/Rsys, but kept Rsys constant and increased heart rate.Conclusions: Hypovolemia and dobutamine differentially alter Pmsf, Rsys, Rv and Rv/Rsys ratio. The increase in CO during dobutamine infusion was attributed to the combined increased cardiac function and decreased Rv. The decrease in CO with hypovolemia was due to a decreased Pmsf but was partly compensated for by a decrease in Rv tending to preserve venous return and thus CO. [ABSTRACT FROM AUTHOR]

Objectives: Cardiac surgery is associated with perioperative complications, some of which might be attributable to hypotension. The Hypotension Prediction Index (HPI), a machine-learning-derived early warning tool for hypotension, has only been evaluated in noncardiac surgery. We investigated whether using HPI with diagnostic guidance reduced hypotension during cardiac surgery and in the ICU., Design: Randomized clinical trial conducted between May 2021 and February 2023., Setting: Single-center study conducted in an academic hospital in the Netherlands., Patients: Adults undergoing elective on-pump coronary artery bypass grafting, with or without single heart valve surgery, were enrolled if a mean arterial pressure (MAP) greater than or equal to 65 mm Hg was targeted during the surgical off-pump phases and ICU stay. After eligibility assessment, 142 of 162 patients approached gave informed consent for participation., Interventions: Patients randomized 1:1 received either diagnostic guidance in addition to standard care if HPI reached greater than or equal to 75 (n = 72) or standard care alone (n = 70)., Measurements and Main Results: The primary outcome was the severity of hypotension, measured as time-weighted average (TWA) of MAP less than 65 mm Hg. Secondary outcomes encompassed hypertension severity and intervention disparities. Of 142 patients randomized, 130 were included in the primary analysis. The HPI group showed 63% reduction in median TWA of hypotension compared with the standard care group, with a median of differences of -0.40 mm Hg (95% CI, -0.65 to -0.27; p < 0.001). In the HPI group, patients spent a median 28 minutes (95% CI, 17-44 min) less in hypotension, with a measurement duration of 322 minutes in the HPI group and 333 minutes in the standard care group. No significant differences were observed in hypertension severity, treatment choice, or fluid, vasopressors, and inotrope amounts., Conclusions: Using HPI combined with diagnostic guidance on top of standard care significantly decreased hypotension severity in elective cardiac surgery patients compared with standard care., Competing Interests: Drs. Schuurmans’s, Rellum’s, Hollmann’s, and Veelo’s institutions received funding from Edwards Lifesciences. Dr. Schuurman’s institution received funding from Hypotension Prediction Index. Dr. Geets disclosed that he is shareholder of Healthplus.ai. Dr. Hollmann serves as Executive Section Editor Pharmacology with Anesthesia and Analgesia, Section Editor Anesthesiology with the Journal of Clinical Medicine, and Editor with Frontiers in Physiology; he received research funding and lecture fees or honorarium for consultancy from B.Braun, Fresenius, Merck & Co., Inc., PAION Pharma GmbH, CSL Behring, Internationl Drug Development Pharma, and Medical Developments. Dr. Eberl received funding from BJA ESAIC Research Grant 2022 (a collaborative initiative between the European Society of Anaesthesiology and Intensive Care [ESAIC] and the British Journal of Anaesthesia [BJA] Charity). Dr. Veelo’s institution received funding from Royal Philips Nederland B.V. Dr. Vlaar acknowledges receiving unrestricted research grants and lecture fees from Edwards Lifesciences and Philips, which were disbursed to the institution. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

The relationship between weather and acute coronary syndrome (ACS) incidence has been the subject of considerable research, with varying conclusions. Harnessing machine learning techniques, our study explores the relationship between meteorological factors and ACS presentations in the emergency department (ED), offering insights into seasonal variations and inter-day fluctuations to optimize patient care and resource allocation. A retrospective cohort analysis was conducted, encompassing ACS presentations to Dutch EDs from 2010 to 2017. Temporal patterns were analyzed using heat-maps and time series plots. Multivariable linear regression (MLR) and Random Forest (RF) regression models were employed to forecast daily ACS presentations with prediction horizons of one, three, seven, and thirty days. Model performance was assessed using the coefficient of determination (R²), Mean Absolute Error (MAE), and Mean Absolute Percentage Error (MAPE). The study included 214,953 ACS presentations, predominantly unstable angina (UA) (94,272; 44%), non-ST-elevated myocardial infarction (NSTEMI) (78,963; 37%), and ST-elevated myocardial infarction (STEMI) (41,718; 19%). A decline in daily ACS admissions over time was observed, with notable inter-day (estimated median difference: 41 (95%CI = 37-43, p = < 0.001) and seasonal variations (estimated median difference: 9 (95%CI 6-12, p = < 0.001). Both MLR and RF models demonstrated similar predictive capabilities, with MLR slightly outperforming RF. The models showed moderate explanatory power for ACS incidence (adjusted R² = 0.66; MAE (MAPE): 7.8 (11%)), with varying performance across subdiagnoses. Prediction of UA incidence resulted in the best-explained variability (adjusted R² = 0.80; MAE (MAPE): 5.3 (19.1%)), followed by NSTEMI and STEMI diagnoses. All models maintained consistent performance over extended prediction horizons. Our findings indicate that ACS presentation exhibits distinctive seasonal changes and inter-day differences, with marked reductions in incidence during the summer months and a distinct peak prevalence on Mondays. The predictive performance of our model was moderate. Nonetheless, we obtained good explanatory power for UA presentations. Our model emerges as a potentially valuable supplementary tool to enhance ED resource allocation or future predictive models predicting ACS incidence in the ED., (© 2024. The Author(s).)

Background: Postoperative infections remain a crucial challenge in health care, resulting in high morbidity, mortality, and costs. Accurate identification and labeling of patients with postoperative bacterial infections is crucial for developing prediction models, validating biomarkers, and implementing surveillance systems in clinical practice., Objective: This scoping review aimed to explore methods for identifying patients with postoperative infections using electronic health record (EHR) data to go beyond the reference standard of manual chart review., Methods: We performed a systematic search strategy across PubMed, Embase, Web of Science (Core Collection), the Cochrane Library, and Emcare (Ovid), targeting studies addressing the prediction and fully automated surveillance (ie, without manual check) of diverse bacterial infections in the postoperative setting. For prediction modeling studies, we assessed the labeling methods used, categorizing them as either manual or automated. We evaluated the different types of EHR data needed for the surveillance and labeling of postoperative infections, as well as the performance of fully automated surveillance systems compared with manual chart review., Results: We identified 75 different methods and definitions used to identify patients with postoperative infections in studies published between 2003 and 2023. Manual labeling was the predominant method in prediction modeling research, 65% (49/75) of the identified methods use structured data, and 45% (34/75) use free text and clinical notes as one of their data sources. Fully automated surveillance systems should be used with caution because the reported positive predictive values are between 0.31 and 0.76., Conclusions: There is currently no evidence to support fully automated labeling and identification of patients with infections based solely on structured EHR data. Future research should focus on defining uniform definitions, as well as prioritizing the development of more scalable, automated methods for infection detection using structured EHR data., (©Siri Lise van der Meijden, Anna M van Boekel, Harry van Goor, Rob GHH Nelissen, Jan W Schoones, Ewout W Steyerberg, Bart F Geerts, Mark GJ de Boer, M Sesmu Arbous. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 10.09.2024.)

Background: Stroke patients admitted to an intensive care unit (ICU) follow a particular survival pattern with a high short-term mortality, but if they survive the first 30 days, a relatively favourable subsequent survival is observed., Objectives: The development and validation of two prognostic models predicting 30-day mortality for ICU patients with ischaemic stroke and for ICU patients with intracerebral haemorrhage (ICH), analysed separately, based on parameters readily available within 24 h after ICU admission, and with comparison with the existing Acute Physiology and Chronic Health Evaluation IV (APACHE-IV) model., Design: Observational cohort study., Setting: All 85 ICUs participating in the Dutch National Intensive Care Evaluation database., Patients: All adult patients with ischaemic stroke or ICH admitted to these ICUs between 2010 and 2019., Main Outcome Measures: Models were developed using logistic regressions and compared with the existing APACHE-IV model. Predictive performance was assessed using ROC curves, calibration plots and Brier scores., Results: We enrolled 14 303 patients with stroke admitted to ICU: 8422 with ischaemic stroke and 5881 with ICH. Thirty-day mortality was 27% in patients with ischaemic stroke and 41% in patients with ICH. Important factors predicting 30-day mortality in both ischaemic stroke and ICH were age, lowest Glasgow Coma Scale (GCS) score in the first 24 h, acute physiological disturbance (measured using the Acute Physiology Score) and the application of mechanical ventilation. Both prognostic models showed high discrimination with an AUC 0.85 [95% confidence interval (CI), 0.84 to 0.87] for patients with ischaemic stroke and 0.85 (0.83 to 0.86) in ICH. Calibration plots and Brier scores indicated an overall good fit and good predictive performance. The APACHE-IV model predicting 30-day mortality showed similar performance with an AUC of 0.86 (95% CI, 0.85 to 0.87) in ischaemic stroke and 0.87 (0.86 to 0.89) in ICH., Conclusion: We developed and validated two prognostic models for patients with ischaemic stroke and ICH separately with a high discrimination and good calibration to predict 30-day mortality within 24 h after ICU admission., Trial Registration: Trial registration: Dutch Trial Registry ( https://www.trialregister.nl/ ); identifier: NTR7438., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology and Intensive Care.)

Background: Diligent fluid management is an instrumental part of Enhanced Recovery After Surgery. However, the effect of a ward regimen to limit intravenous fluid administration on outcome remains unclear. We performed a meta-analysis investigating the effect of a restrictive versus a conventional fluid regimen on complications in patients after non-cardiac surgery in the postoperative period on the clinical ward., Study Design: We performed a systematic search in MEDLINE, Embase, Cochrane Library, and CINAHL databases, from the start of indexing until June 2022, with constraints for English language and adult human study participants. Data were combined using classic methods of meta-analyses and were expressed as weighted pooled risk ratio (RR) or odds ratio (OR) with 95% confidence interval (CI). Quality assessment and risk of bias analyses was performed according to PRISMA guidelines., Results: Seven records, three randomized controlled trials, and four non-randomized studies were included with a total of 883 patients. A restrictive fluid regimen was associated with a reduction in overall complication rate in the RCTs (RR 0.46, 95% CI 0.23 to 0.95; P < .03; I 2  = 35%). This reduction in overall complication rate was not consistent in the non-randomized studies (RR 0.74, 95% CI 0.53 to 1.03; P 0.07; I 2  = 45%). No significant association was found for mortality using a restrictive fluid regimen (RCTs OR 0.51, 95% CI 0.05 to 4.90; P = 0.56; I 2  = 0%, non-randomized studies OR 0.30, 95% CI 0.06 to 1.46; P = 0.14; I 2  = 0%). A restrictive fluid regimen is significantly associated with a reduction in postoperative length of stay in the non-randomized studies (MD - 1.81 days, 95% CI - 3.27 to - 0.35; P = 0.01; I 2  = 0%) but not in the RCTs (MD 0.60 days, 95% CI - 0.75 to 1.95; P = 0.38). Risk of bias was moderate to high. Methodological quality was very low to moderate., Conclusion: This meta-analysis suggests restrictive fluid therapy on the ward may be associated with an effect on postoperative complication rate. However, the quality of evidence was moderate to low, the sample size was small, and the data came from both RCTs and non-randomized studies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Competing Interests: BG is currently CEO and majority shareholder of Healthplus.ai B.V. and subsidiaries. BG has also consulted for and received research grants from Philips NV and Edwards Lifesciences LLC. SvdM works as a data scientist and PhD at Healthplus.ai and LUMC. SvdM owns share options in Healthplus.ai.

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: A decade ago, it became possible to derive mean systemic filling pressure (MSFP) at the bedside using the inspiratory hold maneuver. MSFP has the potential to help guide hemodynamic care, but the estimation is not yet implemented in common clinical practice. In this study, we assessed the ability of MSFP, vascular compliance (Csys), and stressed volume (Vs) to track fluid boluses. Second, we assessed the feasibility of implementation of MSFP in the intensive care unit (ICU). Exploratory, a potential difference in MSFP response between colloids and crystalloids was assessed. Methods: This was a prospective cohort study in adult patients admitted to the ICU after cardiac surgery. The MSFP was determined using 3-4 inspiratory holds with incremental pressures (maximum 35 cm H 2 O) to construct a venous return curve. Two fluid boluses were administered: 100 and 500 ml, enabling to calculate Vs and Csys. Patients were randomized to crystalloid or colloid fluid administration. Trained ICU consultants acted as study supervisors, and protocol deviations were recorded. Results: A total of 20 patients completed the trial. MSFP was able to track the 500 ml bolus ( p < 0.001). In 16 patients (80%), Vs and Csys could be determined. Vs had a median of 2029 ml (IQR 1605-3164), and Csys had a median of 73 ml mmHg -1 (IQR 56-133). A difference in response between crystalloids and colloids was present for the 100 ml fluid bolus ( p = 0.019) and in a post hoc analysis, also for the 500 ml bolus ( p = 0.010). Conclusion: MSFP can be measured at the bedside and provides insights into the hemodynamic status of a patient that are currently missing. The clinical feasibility of Vs and Csys was judged ambiguously based on the lack of required hemodynamic stability. Future studies should address the clinical obstacles found in this study, and less-invasive alternatives to determine MSFP should be further explored. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03139929., Competing Interests: Author BG was employed by Healthplus.ai. The remaining 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 Wijnberge, Jansen, Pinsky, Klanderman, Terwindt, Bosboom, Lemmers, Vlaar, Veelo and Geerts.)

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.

The Hypotension Prediction Index (HPI) is a commercially available machine-learning algorithm that provides warnings for impending hypotension, based on real-time arterial waveform analysis. The HPI was developed with arterial waveform data of surgical and intensive care unit (ICU) patients, but has never been externally validated in the latter group. In this study, we evaluated diagnostic ability of the HPI with invasively collected arterial blood pressure data in 41 patients with COVID-19 admitted to the ICU for mechanical ventilation. Predictive ability was evaluated at HPI thresholds from 0 to 100, at incremental intervals of 5. After exceeding the studied threshold, the next 20 min were screened for positive (mean arterial pressure (MAP) < 65 mmHg for at least 1 min) or negative (absence of MAP < 65 mmHg for at least 1 min) events. Subsequently, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and time to event were determined for every threshold. Almost all patients (93%) experienced at least one hypotensive event. Median number of events was 21 [7-54] and time spent in hypotension was 114 min [20-303]. The optimal threshold was 90, with a sensitivity of 0.91 (95% confidence interval 0.81-0.98), specificity of 0.87 (0.81-0.92), PPV of 0.69 (0.61-0.77), NPV of 0.99 (0.97-1.00), and median time to event of 3.93 min (3.72-4.15). Discrimination ability of the HPI was excellent, with an area under the curve of 0.95 (0.93-0.97). This validation study shows that the HPI correctly predicts hypotension in mechanically ventilated COVID-19 patients in the ICU, and provides a basis for future studies to assess whether hypotension can be reduced in ICU patients using this algorithm., (© 2021. The Author(s).)

Background & Aims: Early oral postoperative nutrition is a proven beneficial element of postoperative care, resulting in improvement in quality of life and a shorter hospital stay. Guidelines state that postoperative oral nutrition can safely be started within the first hours after surgery. However, oral nutrition is mainly investigated starting from postoperative day one (POD1). This pragmatic study assessed whether a food service in the Post Anaesthesia Care Unit (PACU) may reduce postoperative fasting times on postoperative day zero (POD0) early after surgery on this high care unit. The primary outcome was postoperative fasting time in the PACU. Secondary outcomes were postoperative patient experiences and nutritional tolerance., Methods: This pragmatic prospective before-after study, included adult patients with a planned overnight stay in the PACU, and without anticipated postoperative dietary restrictions. A food service was developed, allowing re-uptake of oral nutrition early after surgery, already at POD0. Postoperative fasting time in the PACU was defined as the duration of time between the moment of arrival at the PACU, until first postoperative intake or until 9 a.m. on POD1, when most patients were discharged to the surgical ward. Secondary outcomes such as postoperative patient experiences and nutritional tolerance were scored on POD0 at 8 p.m. and on POD1 at 8 a.m., Results: A total of 235 patients were included, 119 in the pre-implementation (control) and 116 in the post-implementation (intervention) group. Mean postoperative fasting time was reduced by a mean of 6.0 h (95% CI 4.8-7.4, p-value ≤ .001), from 17.5 h in controls to 11.5 h in the intervention group. In the intervention group, 45% of patients had nutritional intake on POD0 (8 p.m.), increasing to 80% of patients on POD1 (8 a.m.), compared to no intake at both time-points in the control group. In the intervention group, average patient satisfaction increased over time. Flatus frequency was higher in the intervention group on POD1 (45% vs. 22%, p-value ≤ .001), while postoperative nausea and/or vomiting, and usage of anti-emetic medication were not different between groups., Conclusions: In a heterogeneous group of adult post-surgical patients with a planned overnight stay in the PACU, implementation of a food service resulted in a significant and clinically relevant reduction of postoperative fasting time, and increased patient satisfaction without compromising nutritional tolerance. Registered at www.isrctn.org with study ID ISRCTN17976930., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Objectives: Transfusion-associated circulatory overload (TACO) is a major cause of severe transfusion-related morbidity. Transfusion of red blood cells (RBCs) has been shown to induce hydrostatic pressure overload. It is unclear which product-specific factors contribute. We set out to determine the effect of autologous RBC transfusion versus saline on pulmonary capillary wedge pressure (PCWP) change., Materials and Methods: In a randomized crossover trial, patients who had undergone coronary bypass surgery were allocated to treatment post-operatively in the intensive care unit with either an initial 300 ml autologous RBC transfusion (salvaged during surgery) or 300 ml saline infusion first, followed by the other. Primary outcome was the difference in PCWP change. Secondary outcome measures were the difference in extra-vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI)., Results: Change in PCWP was not higher after autologous RBC transfusion compared to saline (ΔPCWP 0.3 ± 0.4 vs. 0.1 ± 0.4 mmHg). ΔEVLWI and ΔPVPI were significantly decreased after autologous RBC transfusion compared to saline (ΔEVLWI -1.6 ± 0.6 vs. 0.2 ± 0.4, p = 0.02; ΔPVPI -0.3 ± 0.1 vs. 0.0 ± 0.1, p = 0.01). Haemodynamic variables and colloid osmotic pressure were not different for autologous RBC transfusion versus saline., Conclusion: Transfusion of autologous RBCs did not result in a more profound increase in PCWP compared to saline. RBC transfusion resulted in a decrease of EVLWI and PVPI compared to saline. Our data suggest that transfusing autologous RBCs may lead to less pulmonary oedema compared to saline. Future studies with allogeneic RBCs are needed to investigate other factors that may mediate the increase of PCWP, resulting in TACO., (© 2022 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion related morbidity and mortality. The only treatment is empirical use of furosemide. Our aim was to investigate if furosemide can prevent TACO. A randomized controlled trial was performed using a previously validated two-hit rat model for TACO. Volume incompliance was induced (first hit) in anemic, anesthetized Lewis rats. Rats were randomized to placebo, low-dose (5 mg kg -1 ) or high-dose (15 mg kg -1 ) furosemide-administered prior to transfusion (second-hit) and divided over two doses. Primary outcome was change in left-ventricular end-diastolic pressure (∆LVEDP) pre- compared to post-transfusion. Secondary outcomes included changes in preload, afterload, contractility and systemic vascular resistance, as well as pulmonary outcomes. Furosemide treated animals had a significantly lower ∆LVEDP compared to placebo (p = 0.041), a dose-response effect was observed. ∆LVEDP in placebo was median + 8.7 mmHg (IQR 5.9-11), + 3.9 (2.8-5.6) in the low-dose and 1.9 (- 0.6 to 5.6) in the high-dose group. The effect of furosemide became apparent after 15 min. While urine output was significantly higher in furosemide treated animals (p = 0.03), there were no significant changes in preload, afterload, contractility or systemic vascular resistance. Furosemide rapidly and dose-dependently decreases the rise in hydrostatic pulmonary pressure following transfusion, essential for preventing TACO., (© 2022. The Author(s).)

Intraoperative hypotension is associated with postoperative complications. However, in the majority of surgical patients, blood pressure (BP) is measured intermittently with a non-invasive cuff around the upper arm (NIBP-arm). We hypothesized that NIBP-arm, compared with a non-invasive continuous alternative, would result in missed events and in delayed recognition of hypotensive events. This was a sub-study of a previously published cohort study in adult patients undergoing surgery. The detection of hypotension (mean arterial pressure below 65 mmHg) was compared using two non-invasive methods; intermittent oscillometric NIBP-arm versus continuous NIBP measured with a finger cuff (cNIBP-finger) (Nexfin, Edwards Lifesciences). cNIBP-finger was used as the reference standard. Out of 350 patients, 268 patients (77%) had one or more hypotensive events during surgery. Out of the 286 patients, 72 (27%) had one or more missed hypotensive events. The majority of hypotensive events (92%) were detected with NIBP-arm, but were recognized at a median of 1.2 (0.6-2.2) minutes later. Intermittent BP monitoring resulted in missed hypotensive events and the hypotensive events that were detected were recognized with a delay. This study highlights the advantage of continuous monitoring. Future studies are needed to understand the effect on patient outcomes.

Background and Objectives: Transfusion-associated circulatory overload (TACO) is the primary cause of transfusion-related mortality. Speed and volume of transfusion are major risk factors. The aim of this study was to investigate the interaction of red blood cell (RBC) transfusion speed and volume on the development of TACO., Materials and Methods: A validated model for TACO in anaemic Lewis rats with an acute myocardial infarction was used. The effect on pulmonary hydrostatic pressure of one, two or four units of packed RBCs transfused in either 30 or 60 min was evaluated (3.3-26.6 ml·kg -1 ·hr -1 ). Pulmonary capillary pressure was measured as left ventricular end-diastolic pressure (LVEDP). Cardiac stress biomarkers atrial natriuretic-peptide (ANP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured 1-h post-transfusion., Results: Thirty animals were included (n = 5 per group). Transfusion of RBCs increased LVEDP in a volume-dependent manner (ΔLVEDP [mmHg]: -0.95, +0.50, +6.26, p < 0.001). Fast transfusion increased overall ΔLVEDP by +3.5 mmHg and up to +11.8 mmHg in the four units' group (p = 0.016). Doubling transfusion speed increased ΔLVEDP more than doubling volume in the larger volume groups. No difference in ANP or NT-proBNP were seen in high transfusion volume or groups., Conclusion: Transfusion volume dose-dependently increased LVEDP, with speed of transfusion rapidly elevating LVEDP at higher transfusion volumes. ANP and NT-proBNP were not impacted by transfusion volume or speed in this model. TACO is seen as purely volume overload, however, this study emphasizes that limiting transfusion speed, as a modifiable risk factor, might aid in preventing TACO., (© 2021 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

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.)

Objective: The aim of this survey was to describe existing perioperative care standards and best practices in the Netherlands and Belgium., Design: An online survey was followed up by an in-depth personal interview. The main outcomes were the existing standards of perioperative care for patients undergoing cardiac surgery., Setting: The online survey and subsequent interviews were targeted to one representative in the intensive care unit (ICU), cardiac surgery, and anesthesiology department from each cardiac surgical center in the Netherlands and Belgium., Participants: A representative intensive care physician, cardiac surgeon, and cardiac anesthesiologist., Interventions: None., Measurements and Main Results: The response rate was 60% (71% for the Netherlands, and 44% in Belgium). Agreement across centers was found for discontinuation of proton-pump inhibitors (80%) and avoiding intra- and postoperative (92%) nonsteroidal antiinflammatory drugs. Additionally, 98% of respondents stated that physiotherapy should be started immediately in the ICU. Major divergence was found for elements such as the discontinuation of angiotensin-converting enzyme inhibitors (55%) or the postoperative use of chest support vests (44%)., Conclusions: The authors demonstrated a wide range of different local protocols. Strategies differed among disciplines, hospitals, and countries. This emphasized the need for the implementation of a more universal protocol to further reduce variance and improve recovery practices. This nationwide survey was the first of its kind simultaneously studying best practices for cardiac surgery through the entire care pathway at the advent of Enhanced Recovery After Surgery (ERAS) Cardiac implementation. A multinational randomized controlled trial to test the implementation of an evidence-based ERAS Cardiac protocol is the next step to pave the way for further outcome improvements in this high-risk population., Competing Interests: Conflict of Interest None, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Intraoperative and postoperative hypotension are associated with morbidity and mortality. The Hypotension Prediction (HYPE) trial showed that the Hypotension Prediction Index (HPI) reduced the depth and duration of intraoperative hypotension (IOH), without excess use of intravenous fluid, vasopressor, and/or inotropic therapies. We hypothesised that intraoperative HPI-guided haemodynamic care would reduce the severity of postoperative hypotension in the PACU., Methods: This was a sub-study of the HYPE study, in which 60 adults undergoing elective noncardiac surgery were allocated randomly to intraoperative HPI-guided or standard haemodynamic care. Blood pressure was measured using a radial intra-arterial catheter, which was connected to a FloTracIQ sensor. Hypotension was defined as MAP <65 mm Hg, and a hypotensive event was defined as MAP <65 mm Hg for at least 1 min. The primary outcome was the time-weighted average (TWA) of postoperative hypotension. Secondary outcomes were absolute incidence, area under threshold for hypotension, and percentage of time spent with MAP <65 mm Hg., Results: Overall, 54/60 (90%) subjects (age 64 (8) yr; 44% female) completed the protocol, owing to failure of the FloTracIQ device in 6/60 (10%) patients. Intraoperative HPI-guided care was used in 28 subjects; 26 subjects were randomised to the control group. Postoperative hypotension occurred in 37/54 (68%) subjects. HPI-guided care did not reduce the median duration (TWA) of postoperative hypotension (adjusted median difference, vs standard of care: 0.118; 95% confidence interval [CI], 0-0.332; P=0.112). HPI-guidance reduced the percentage of time with MAP <65 mm Hg by 4.9% (adjusted median difference: -4.9; 95% CI, -11.7 to -0.01; P=0.046)., Conclusions: Intraoperative HPI-guided haemodynamic care did not reduce the TWA of postoperative hypotension., Competing Interests: Declarations of interest The Department of Anaesthesiology of the Amsterdam UMC, location ‘AMC' received financial support for this project from Edwards Lifesciences. DPV, APV, MW, RVI, and BFG received consultancy fees from Edwards Lifesciences. The Hypotension Prediction Index algorithm is proprietary to Edwards Lifesciences LLC. None of the investigators of the Amsterdam UMC have any form of (in)direct ownership in the algorithm, software or hardware of Edwards, and/or subject of this study. Also, no rights or claims to rights exist that might lead to financial gains for any of the authors or the Amsterdam UMC as an institution. BFG and DPV received consultancy fees and research grants from Philips outside the submitted word. MWH is executive section editor Pharmacology with Anesthesia & Analgesia. He received consultancy fees from Eurocept BV and speakers fees from Eurocept and CSL Behring. JS, JMM, BJPS, and LH declare that they have no conflict of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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: Low central venous pressure (low-CVP) is the clinical standard for fluid therapy during major liver surgery. Although goal-directed fluid therapy (GDFT) has been associated with reduced morbidity and mortality in major abdominal surgery, concerns remain on blood loss when applying GDFT in liver surgery. This randomized trial compared outcomes of low-CVP and GDFT during major liver resections., Methods: In this surgeon- and patient-blinded RCT, patients undergoing major open liver resections (≥3 segments) were randomized between low-CVP (n = 20) or GDFT (n = 20). Primary outcome was intraoperative blood loss. Secondary outcomes included the quality of the surgical field (VAS scale 0 (worst)-100 (best)) and major morbidity (≥grade 3 Clavien-Dindo)., Results: During surgery, CVP was 3 ± 2 mmHg in the low-CVP group vs. 7 ± 3 mmHg in the GDFT group (P < 0.001). Blood loss (1425 vs. 1275 mL; P = 0.640) and the rate of major morbidity (40% vs. 50%, P = 0.751), did not differ between low-CVP and GDFT, respectively. The quality of the surgical field was comparable between groups (low-CVP 83% vs. GDFT 80%, P = 0.955)., Conclusion: In major open liver resections, GDFT was not associated with differences in intraoperative blood loss, major morbidity or quality of the surgical field, compared to low-CVP. Larger RCTs are needed to confirm this finding. Registration number: NTR5821 (www.trialregister.nl)., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This review describes the steps and conclusions from the development and validation of an artificial intelligence algorithm (the Hypotension Prediction Index), one of the first machine learning predictive algorithms used in the operating room environment. The algorithm has been demonstrated to reduce intraoperative hypotension in two randomized controlled trials via real-time prediction of upcoming hypotensive events prompting anesthesiologists to act earlier, more often, and differently in managing impending hypotension. However, the algorithm entails no dynamic learning process that evolves from use in clinical patient care, meaning the algorithm is fixed, and furthermore provides no insight into the decisional process that leads to an early warning for intraoperative hypotension, which makes the algorithm a "black box." Many other artificial intelligence machine learning algorithms have these same disadvantages. Clinical validation of such algorithms is relatively new and requires more standardization, as guidelines are lacking or only now start to be drafted. Before adaptation in clinical practice, impact of artificial intelligence algorithms on clinical behavior, outcomes and economic advantages should be studied too., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Intra-operative hypotension is associated with adverse postoperative outcomes. A machine-learning-derived algorithm developed to predict hypotension based on arterial blood pressure (ABP) waveforms significantly reduced intra-operative hypotension. The algorithm calculates the likelihood of hypotension occurring within minutes, expressed as the Hypotension Prediction Index (HPI) which ranges from 0 to 100. Currently, HPI is only available for patients monitored with invasive ABP, which is restricted to high-risk procedures and patients. In this study, the performance of HPI, employing noninvasive continuous ABP measurements, is assessed., Objectives: The first aim was to compare the performance of the HPI algorithm, using noninvasive versus invasive ABP measurements, at a mathematically optimal HPI alarm threshold (Youden index). The second aim was to assess the performance of the algorithm using a HPI alarm threshold of 85 that is currently used in clinical trials. Hypotension was defined as a mean arterial pressure (MAP) below 65 mmHg for at least 1 min. The predictive performance of the algorithm at different HPI alarm thresholds (75 and 95) was studied., Design: Observational cohort study., Setting: Tertiary academic medical centre., Patients: Five hundred and seven adult patients undergoing general surgery., Results: The performance of the algorithm with invasive and noninvasive ABP input was similar. A HPI alarm threshold of 85 showed a median [IQR] time from alarm to hypotension of 2.7 [1.0 to 7.0] min with a sensitivity of 92.7 (95% confidence interval [CI], 91.2 to 94.3), specificity of 87.6 (95% CI, 86.2 to 89.0), positive predictive value of 79.9 (95% CI, 77.7 to 82.1) and negative predictive value of 95.8 (95% CI, 94.9 to 96.7). A HPI alarm threshold of 75 provided a lower positive predictive value but a prolonged time from prediction to actual hypotension., Conclusion: This study demonstrated that the algorithm can be employed using continuous noninvasive ABP waveforms. This opens up the potential to predict and prevent hypotension in a larger patient population., Trial Registration: Clinical trials registration number NCT03533205., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Importance: Quality improvement programs for colorectal cancer surgery have been introduced with benchmarking based on quality indicators, such as mortality. Detailed (pre)operative characteristics may offer relevant information for proper case-mix correction., Objective: To investigate the added value of machine learning to predict quality indicators for colorectal cancer surgery and identify previously unrecognized predictors of 30-day mortality based on a large, nationwide colorectal cancer registry that collected extensive data on comorbidities., Design, Setting, and Participants: All patients who underwent resection for primary colorectal cancer registered in the Dutch ColoRectal Audit between January 1, 2011, and December 31, 2016, were included. Multiple machine learning models (multivariable logistic regression, elastic net regression, support vector machine, random forest, and gradient boosting) were made to predict quality indicators. Model performance was compared with conventionally used scores. Risk factors were identified by logistic regression analyses and Shapley additive explanations (ie, SHAP values). Statistical analysis was performed between March 1 and September 30, 2020., Main Outcomes and Measures: The primary outcome of this cohort study was 30-day mortality. Prediction models were trained on a training set by performing 5-fold cross-validation, and outcomes were measured by the area under the receiver operating characteristic curve on the test set. Machine learning was further used to identify risk factors, measured by odds ratios and SHAP values., Results: This cohort study included 62 501 records, most patients were male (35 116 [56.2%]), were aged 61 to 80 years (41 560 [66.5%]), and had an American Society of Anesthesiology score of II (35 679 [57.1%]). A 30-day mortality rate of 2.7% (n = 1693) was found. The area under the curve of the best machine learning model for 30-day mortality (0.82; 95% CI, 0.79-0.85) was significantly higher than the American Society of Anesthesiology score (0.74; 95% CI, 0.71-0.77; P < .001), Charlson Comorbidity Index (0.66; 95% CI, 0.63-0.70; P < .001), and preoperative score to predict postoperative mortality (0.73; 95% CI, 0.70-0.77; P < .001). Hypertension, myocardial infarction, chronic obstructive pulmonary disease, and asthma were comorbidities with a high risk for increased mortality. Machine learning identified specific risk factors for a complicated course, intensive care unit admission, prolonged hospital stay, and readmission. Laparoscopic surgery was associated with a decreased risk for all adverse outcomes., Conclusions and Relevance: This study found that machine learning methods outperformed conventional scores to predict 30-day mortality after colorectal cancer surgery, identified specific patient groups at risk for adverse outcomes, and provided directions to optimize benchmarking in clinical audits.

Background: Intraoperative hypotension, with varying definitions in literature, may be associated with postoperative complications. The aim of this meta-analysis was to assess the association of intraoperative hypotension with postoperative morbidity and mortality., Methods: MEDLINE, Embase and Cochrane databases were searched for studies published between January 1990 and August 2018. The primary endpoints were postoperative overall morbidity and mortality. Secondary endpoints were postoperative cardiac outcomes, acute kidney injury, stroke, delirium, surgical outcomes and combined outcomes. Subgroup analyses, sensitivity analyses and a meta-regression were performed to test the robustness of the results and to explore heterogeneity., Results: The search identified 2931 studies, of which 29 were included in the meta-analysis, consisting of 130 862 patients. Intraoperative hypotension was associated with an increased risk of morbidity (odds ratio (OR) 2.08, 95 per cent confidence interval 1.56 to 2.77) and mortality (OR 1.94, 1.32 to 2.84). In the secondary analyses, intraoperative hypotension was associated with cardiac complications (OR 2.44, 1.52 to 3.93) and acute kidney injury (OR 2.69, 1.31 to 5.55). Overall heterogeneity was high, with an I2 value of 88 per cent. When hypotension severity, outcome severity and study population variables were added to the meta-regression, heterogeneity was reduced to 50 per cent., Conclusion: Intraoperative hypotension during non-cardiac surgery is associated with postoperative cardiac and renal morbidity, and mortality. A universally accepted standard definition of hypotension would facilitate further research into this topic., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background and Objectives: Colloid osmotic pressure (COP) is a principal determinant of intravascular fluid homeostasis and a pillar of fluid therapy and transfusion. Transfusion-associated circulatory overload (TACO) is a leading complication of transfusion, and COP could be responsible for recruiting additional fluid. Study objective was to measure COP of blood products as well as investigate the effects of product concentration and storage lesion on COP., Materials and Methods: Three units of each product were sampled longitudinally. COP was measured directly as well as the determinants thereof albumin and total protein. Conventional blood products, that is red blood cell (RBC), fresh-frozen plasma (FFP) and platelet concentrates (PLTs), were compared with their concentrated counterparts: volume-reduced RBCs, hyperconcentrated PLTs, and fully and partially reconstituted lyophilized plasma (prLP). Fresh and maximally stored products were measured to determine changes in protein and COP. We calculated potential volume load (PVL) to estimate volume recruited using albumin's water binding per product., Results: Colloid osmotic pressure varies widely between conventional products (RBCs, 1·9; PLTs, 7·5; and FFP, 20·1 mmHg); however, all are hypooncotic compared with human plasma COP (25·4 mmHg). Storage lesion did not increase COP. Concentrating RBCs and PLTs did not increase COP; only prLP showed a supraphysiological COP of 47·3 mm Hg. The PVL of concentrated products was lower than conventional products., Conclusion: Colloid osmotic pressure of conventional products was low. Therefore, third-space fluid recruitment is an unlikely mechanism in TACO. Concentrated products had a lower calculated fluid load and may prevent TACO. Finally, storage did not significantly increase oncotic pressure of blood products., (© 2020 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Objectives: Assessment of all-cause mortality of intracerebral hemorrhage and ischemic stroke patients admitted to the ICU and comparison to the mortality of other critically ill ICU patients classified into six other diagnostic subgroups and the general Dutch population., Design: Observational cohort study., Setting: All ICUs participating in the Dutch National Intensive Care Evaluation database., Patients: All adult patients admitted to these ICUs between 2010 and 2015; patients were followed until February 2017., Interventions: None., Measurements and Main Results: Of all 370,386 included ICU patients, 7,046 (1.9%) were stroke patients, 4,072 with ischemic stroke, and 2,974 with intracerebral hemorrhage. Short-term mortality in ICU-admitted stroke patients was high with 30 days mortality of 31% in ischemic stroke and 42% in intracerebral hemorrhage. In the longer term, the survival curve gradient among ischemic stroke and intracerebral hemorrhage patients stabilized. The gradual alteration of mortality risk after ICU admission was assessed using left-truncation with increasing minimum survival period. ICU-admitted stroke patients who survive the first 30 days after suffering from a stroke had a favorable subsequent survival compared with other diseases necessitating ICU admission such as patients admitted due to sepsis or severe community-acquired pneumonia. After having survived the first 3 months after ICU admission, multivariable Cox regression analyses showed that case-mix adjusted hazard ratios during the follow-up period of up to 3 years were lower in ischemic stroke compared with sepsis (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.36) and severe community-acquired pneumonia (adjusted hazard ratio, 1.57; 95% CI, 1.39-1.77) and in intracerebral hemorrhage patients compared with these groups (adjusted hazard ratio, 1.14; 95% CI, 0.98-1.33 and adjusted hazard ratio, 1.49; 95% CI, 1.28-1.73)., Conclusions: Stroke patients who need intensive care treatment have a high short-term mortality risk, but this alters favorably with increasing duration of survival time after ICU admission in patients with both ischemic stroke and intracerebral hemorrhage, especially compared with other populations of critically ill patients such as sepsis or severe community-acquired pneumonia patients.

Objectives: Previous studies demonstrated that extensive fluid loading and consequently positive fluid balances during sepsis resuscitation are associated with adverse outcome. Yet, the association between fluid balance and mortality after reversal of shock, that is, during deresuscitation, is largely unappreciated. Our objective was to investigate the effects of fluid balance on mortality in the days after septic shock reversal., Design: Retrospective observational cohort study., Setting: ICUs of two university-affiliated hospitals in The Netherlands., Patients: Adult patients admitted with septic shock followed by shock reversal. Reversal of septic shock was defined based on Sepsis-3 criteria as the first day that serum lactate was less than or equal to 2 mmol/L without vasopressor requirement., Interventions: None., Measurements and Main Results: Reversal of septic shock occurred in 636 patients, of whom 20% died in the ICU. Mixed-effects logistic regression modeling, adjusted for possible confounders, showed that fluid balance in the days after reversal of septic shock (until discharge or death) was an independent predictor of ICU mortality: odds ratio 3.18 (1.90-5.32) per 10 mL/kg increase in daily fluid balance. Similar results were found for 30-day, 90-day, hospital, and 1-year mortality: odds ratios 2.09 (1.64-2.67); 1.79 (1.38-2.32); 1.70 (1.40-2.07); and 1.53 (1.17-2.01), respectively. Positive cumulative fluid balances vs. neutral or negative fluid balances on the final day in the ICU were associated with increased ICU, hospital, 30-day, and 90-day mortality: odds ratios 3.46 (2.29-5.23); 3.39 (2.35-4.9); 5.33 (3.51-8.08); and 3.57 (2.49-5.12), respectively. Using restricted cubic splines, we found a dose-response relationship between cumulative fluid balance after shock reversal and ICU mortality., Conclusions: A higher fluid balance in the days after septic shock reversal was associated with increased mortality. This stresses the importance of implementing restrictive and deresuscitative fluid management strategies after initial hemodynamic resuscitation. Prospective interventional studies are needed to confirm our results., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Potentially, mean circulatory filling pressure (Pmcf) could aid hemodynamic management in patients admitted to the intensive care unit (ICU). However, data regarding the normal range for Pmcf do not exist challenging its clinical use. We aimed to define the range for Pmcf for ICU patients and also calculated in what percentage of cases equilibrium between arterial blood pressure (ABP) and central venous pressure (CVP) was reached. In patients in whom no equilibrium was reached, we corrected for arterial-to-venous compliance differences. Finally, we studied the influence of patient characteristics on Pmcf. We hypothesized fluid balance, the use of vasoactive medication, being on mechanical ventilation, and the level of positive end-expiratory pressure would be positively associated with Pmcf. We retrospectively studied a cohort of 311 patients that had cardiac arrest in ICU while having active recording of ABP and CVP 1 min after death. Median Pmcf was 15 mmHg [interquartile range (IQR) 12-18]. ABP and CVP reached an equilibrium state in 52% of the cases. Correction for arterial-to-venous compliances differences resulted in a maximum alteration of 1.3 mmHg in Pmcf. Fluid balance over the last 24 h, the use of vasoactive medication, and being on mechanical ventilation were associated with a higher Pmcf. Median Pmcf was 15 mmHg (IQR 12-18). When ABP remained higher than CVP, correction for arterial-to-venous compliance differences did not result in a clinically relevant alteration of Pmcf. Pmcf was affected by factors known to alter vasomotor tone and effective circulating blood volume. NEW & NOTEWORTHY In a cohort of 311 intensive care unit (ICU) patients, median mean circulatory filling pressure (Pmcf) measured after cardiac arrest was 15 mmHg (interquartile range 12-18). In 48% of cases, arterial blood pressure remained higher than central venous pressure, but correction for arterial-to-venous compliance differences did not result in clinically relevant alterations of Pmcf. Fluid balance, use of vasopressors or inotropes, and being on mechanical ventilation were associated with a higher Pmcf.

Main Outcome: Thirty patients (60%) found it satisfying or very satisfying to communicate their pain with the app. Pain experienced after surgery was scored by patients as 'no': 3 (6%), 'little': 5 (10%), 'bearable': 25 (50%), 'considerable': 13 (26%) and 'severe': 1 (2%). Forty-five patients (90%) were positive about the ease of recording. Forty-five patients (90%) could correctly record their pain with the app. Thirty-eight patients (76%) agreed that in-app notifications to record pain were useful. Two patients (4%) were too ill to use the application. Based on usability feedback, we will redesign the pain intensity wheel and the in-app pain chart to improve clarity for patients to understand the course of their pain., Secondary Outcomes: The median patient recorded pain app score 4.0 (range 0 to 10) and nurse recorded numerical rating scale (NRS) for pain NRS 4.0 (range 0 to 9) were not statistically different (p = 0.06). Forty-two percent from a total of 307 patient pain app scores were ≥ 5 (on a scale from 0 no pain at all to 10 worst imaginable pain). Of these, 83% were recorded as 'bearable' while only in 18% of the recordings patients asked for additional analgesia. The results suggest that self-recording the severity of postoperative pain by patients with a smartphone application could be useful for postoperative pain management. The application was perceived as user-friendly and had high satisfaction rates from both patients and stakeholders. Further research is needed to validate the 11-point numeric and faces pain scale with the current gold standards visual analogue scale (VAS) and NRS for pain., Competing Interests: We have read the journal’s policy and the authors of this manuscript have the following competing interests: Rover A.A.M. van Mierlo is employee at Logicapps the company that built the application commissioned by OLVG. OLVG and Logicapps have no commercial interest in the application. The application is available free of charge for patients. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Importance: Intraoperative hypotension is associated with increased morbidity and mortality. A machine learning-derived early warning system to predict hypotension shortly before it occurs has been developed and validated., Objective: To test whether the clinical application of the early warning system in combination with a hemodynamic diagnostic guidance and treatment protocol reduces intraoperative hypotension., Design, Setting, and Participants: Preliminary unblinded randomized clinical trial performed in a tertiary center in Amsterdam, the Netherlands, among adult patients scheduled for elective noncardiac surgery under general anesthesia and an indication for continuous invasive blood pressure monitoring, who were enrolled between May 2018 and March 2019. Hypotension was defined as a mean arterial pressure (MAP) below 65 mm Hg for at least 1 minute., Interventions: Patients were randomly assigned to receive either the early warning system (n = 34) or standard care (n = 34), with a goal MAP of at least 65 mm Hg in both groups., Main Outcomes and Measures: The primary outcome was time-weighted average of hypotension during surgery, with a unit of measure of millimeters of mercury. This was calculated as the depth of hypotension below a MAP of 65 mm Hg (in millimeters of mercury) × time spent below a MAP of 65 mm Hg (in minutes) divided by total duration of operation (in minutes)., Results: Among 68 randomized patients, 60 (88%) completed the trial (median age, 64 [interquartile range {IQR}, 57-70] years; 26 [43%] women). The median length of surgery was 256 minutes (IQR, 213-430 minutes). The median time-weighted average of hypotension was 0.10 mm Hg (IQR, 0.01-0.43 mm Hg) in the intervention group vs 0.44 mm Hg (IQR, 0.23-0.72 mm Hg) in the control group, for a median difference of 0.38 mm Hg (95% CI, 0.14-0.43 mm Hg; P = .001). The median time of hypotension per patient was 8.0 minutes (IQR, 1.33-26.00 minutes) in the intervention group vs 32.7 minutes (IQR, 11.5-59.7 minutes) in the control group, for a median difference of 16.7 minutes (95% CI, 7.7-31.0 minutes; P < .001). In the intervention group, 0 serious adverse events resulting in death occurred vs 2 (7%) in the control group., Conclusions and Relevance: In this single-center preliminary study of patients undergoing elective noncardiac surgery, the use of a machine learning-derived early warning system compared with standard care resulted in less intraoperative hypotension. Further research with larger study populations in diverse settings is needed to understand the effect on additional patient outcomes and to fully assess safety and generalizability., Trial Registration: ClinicalTrials.gov Identifier: NCT03376347.

Background: During hysteroscopic surgery intravasation of irrigation fluid occurs, leading to potentially dangerous intravascular fluid overload. Currently, intravasation is usually measured volumetrically as fluid deficit. Intravasation could also be calculated using the decrease in hemoglobin or increase in chloride ion concentration, both phenomena known to result from intravasation. We compared the values of intravasation measured volumetrically as fluid deficit versus calculated from the biochemical change in hemoglobin and chloride. We expected that these values would show strong correlation and agreement., Methods: In a retrospective data analysis of 51 patients who underwent hysteroscopic resection of myomas or endometrium a pre and post procedure concentration of haemoglobin and chloride was available. The fluid deficit was plotted against the two versions of calculated intravasation. Furthermore, we put the data into Bland-Altman plots to scrutinize their relationship., Results: The volumetric assessed fluid deficit and both versions of biochemically assessed intravasation, either using the change in hemoglobin or chloride ion concentration, turned out to be three totally different entities with weak correlation. Bland-Altman plots show too wide limits of agreement, and a striking difference between the two methods of calculated intravasation., Conclusion: Our study shows significant differences and poor agreement between volumetric and biochemically assessed intravasation. Based on this study, routinely assessing intravasation by biochemical methods does not have additional benefit compared to the volumetric fluid deficit. It remains unclear which method resembles true intravasation., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Transfusion-associated circulatory overload (TACO) is the predominant complication of transfusion resulting in death. The pathophysiology is poorly understood, but inability to manage volume is associated with TACO, and observational data suggest it is different from simple cardiac overload due to fluids. We developed a two-hit TACO animal model to assess the role of volume incompliance ("first-hit") and studied whether volume overload ("second-hit") by red blood cell (RBC) transfusion is different compared to fluids (Ringer's lactate [RL])., Materials and Methods: Male adult Lewis rats were stratified into a control group (no intervention) or a first hit: either myocardial infarction (MI) or acute kidney injury (AKI). Animals were randomized to a second hit of either RBC transfusion or an equal volume of RL. A clinically relevant difference was defined as an increase in left ventricular end-diastolic pressure (ΔLVEDP) of +4.0 mm Hg between the RBC and RL groups., Results: In control animals (without first hit) LVEDP was not different between infusion groups (Δ + 1.6 mm Hg). LVEDP increased significantly more after RBCs compared to RL in animals with MI (Δ7.4 mm Hg) and AKI (Δ + 5.4 mm Hg), respectively. Volume-incompliant rats matched clinical TACO criteria in 92% of transfused versus 25% of RL-infused animals, with a greater increase in heart rate and significantly higher blood pressure., Conclusion: To our knowledge, this is the first animal model for TACO, showing that a combination of volume incompliance and transfusion is essential for development of circulatory overload. This model allows for further testing of mechanistic factors as well as therapeutic approaches., (© 2019 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

Introduction: Acute respiratory distress syndrome (ARDS) is characterized by acute, diffuse, inflammatory lung injury leading to increased pulmonary vascular permeability, pulmonary oedema and loss of aerated tissue. Previous literature showed that restrictive fluid therapy in ARDS shortens time on mechanical ventilation and length of ICU-stay. However, the effect of intravenous fluid use on mortality remains uncertain. We investigated the relationship between cumulative fluid balance (FB), time on mechanical ventilation and mortality in ARDS patients., Materials and Methods: Retrospective observational study. Patients were divided in four cohorts based on cumulative FB on day 7 of ICU-admission: ≤0 L (Group I); 0-3.5 L (Group II); 3.5-8 L (Group III) and ≥8 L (Group IV). In addition, we used cumulative FB on day 7 as continuum as a predictor of mortality. Primary outcomes were 28-day mortality and ventilator-free days. Secondary outcomes were 90-day mortality and ICU length of stay., Results: Six hundred ARDS patients were included, of whom 156 (26%) died within 28 days. Patients with a higher cumulative FB on day 7 had a longer length of ICU-stay and fewer ventilator-free days on day 28. Furthermore, after adjusting for severity of illness, a higher cumulative FB was associated with 28-day mortality (Group II, adjusted OR (aOR) 2.1 [1.0-4.6], p = 0.045; Group III, aOR 3.3 [1.7-7.2], p = 0.001; Group IV, aOR 7.9 [4.0-16.8], p<0.001). Using restricted cubic splines, a non-linear dose-response relationship between cumulative FB and probability of death at day 28 was found; where a more positive FB predicted mortality and a negative FB showed a trend towards survival., Conclusions: A higher cumulative fluid balance is independently associated with increased risk of death, longer time on mechanical ventilation and longer length of ICU-stay in patients with ARDS. This underlines the importance of implementing restrictive fluid therapy in ARDS patients., Competing Interests: The authors have declared that no competing interests exist.

Background: Intraoperative hypotension is associated with increased morbidity and mortality. Current treatment is mostly reactive. The Hypotension Prediction Index (HPI) algorithm is able to predict hypotension minutes before the blood pressure actually decreases. Internal and external validation of this algorithm has shown good sensitivity and specificity. We hypothesize that the use of this algorithm in combination with a personalized treatment protocol will reduce the time weighted average (TWA) in hypotension during surgery spent in hypotension intraoperatively., Methods/design: We aim to include 100 adult patients undergoing non-cardiac surgery with an anticipated duration of more than 2 h, necessitating the use of an arterial line, and an intraoperatively targeted mean arterial pressure (MAP) of > 65 mmHg. This study is divided into two parts; in phase A baseline TWA data from 40 patients will be collected prospectively. A device (HemoSphere) with HPI software will be connected but fully covered. Phase B is designed as a single-center, randomized controlled trial were 60 patients will be randomized with computer-generated blocks of four, six or eight, with an allocation ratio of 1:1. In the intervention arm the HemoSphere with HPI will be used to guide treatment; in the control arm the HemoSphere with HPI software will be connected but fully covered. The primary outcome is the TWA in hypotension during surgery., Discussion: The aim of this trial is to explore whether the use of a machine-learning algorithm intraoperatively can result in less hypotension. To test this, the treating anesthesiologist will need to change treatment behavior from reactive to proactive., Trial Registration: This trial has been registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov, ID: NCT03376347 . The trial was submitted on 4 November 2017 and accepted for registration on 18 December 2017.

Purpose: Deep neuromuscular blockade (NMB) can improve surgical conditions and possibly pain after low-risk laparoscopic surgery. We hypothesized that targeting a deep level of NMB by a continuous compared with an on-demand infusion of rocuronium could improve surgical conditions in patients undergoing thoraco-laparoscopic esophagectomy., Methods: In this single-centre, randomized-controlled, double-blind trial, patients received either a continuous infusion of rocuronium 0.6 mg·kg -1 ·hr -1 (intervention) or NaCl 0.9% (control). Both surgeon and anesthesiologist were blinded to group assignment and the train-of-four measurements. Open-label rocuronium was given if requested (i.e., on-demand) by the surgeon. At the end of surgery, sugammadex was given if necessary to reverse the NMB. The primary outcome was the quality of surgical conditions during the abdominal phase of the operation as measured by the surgical rating scale (SRS). Secondary outcomes included the thoracic SRS, number of on-demand boluses, intraoperative surgical events, pain scores (up to 12 hr postoperatively), and duration of surgery., Results: The median [interquartile range] abdominal SRS was not different between the intervention (4 [4-5]) and control (4 [4-5]) groups (median difference, 0; 95% confidence interval, 0 to 0; P = 0.45). The thoracic SRS was 4 [4-4] in both groups (P = 0.23). The median number of rocuronium bolus requests was higher in the control group compared with the intervention group (3 [3-6] vs 1 [0-2], respectively; P < 0.01). There were no between-group differences in intraoperative surgical events (P = 0.05), pain scores (overall P > 0.05), or duration of surgery (P = 0.95)., Conclusions: Continuous rocuronium infusion did not improve surgical conditions when boluses of rocuronium were available on-demand. No major benefits in other outcomes were seen., Trial Registration: EUDRACT (2014-002147-18); registered 19 May, 2014 and clinicaltrials.gov (NCT02320734); registered 18 December, 2014.

In cardiac surgical patients it is a complex challenge to find the ideal balance between anticoagulation and hemostasis. Preoperative anemia and perioperative higher transfusion rates are related to increased morbidity and mortality. Patient blood management (PBM) is an evidence based patient specific individualized protocol used in the perioperative setting in order to reduce perioperative bleeding and transfusion rates and to improve patient outcomes. The three pillars of PBM in cardiac surgery consist of optimization of preoperative erythropoiesis and hemostasis, minimizing blood loss, and improving patient specific physiological reserves. This narrative review focuses on the challenges with special emphasis on PBM in the preoperative phase and intraoperative transfusion management and hemostasis in cardiac surgery patients. It is a "must" that PBM is a collaborative effort between anesthesiologists, surgeons, perfusionists, intensivists and transfusion laboratory teams. This review represents an up to date overview over "PBM in cardiac surgery patients"., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

For 30 years, transfusion-associated circulatory overload (TACO) has been recognized as a serious transfusion complication. Currently, TACO is the leading cause of transfusion-related morbidity and mortality worldwide which occurs in 1% to 12% of at-risk populations. Despite an incomplete understanding of the underlying pathophysiology, TACO is defined as a collection of signs and symptoms of acute pulmonary edema due to circulatory overload occurring within 6 to 12 hours of transfusion. In the past decade, large observational cohort studies resulted in better insight into the associated transfusion risk factors leading to the development of TACO. In this clinical review, we critically analyze the pathogenesis of TACO, associated risk factors, clinical presentation, diagnostic modalities, and treatment options to guide clinicians with early detection of this syndrome and intervention to improve clinical outcomes. Future research should focus on better understanding of the pathogenesis to help advance the field of volume kinetics and endothelial barrier function., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Transfusion-associated circulatory overload (TACO) is the leading cause of transfusion-related major morbidity and mortality. Diagnosing TACO is difficult because there are no pathognomonic signs and symptoms. TACO biomarkers may aid in diagnosis, decrease time to treatment, and differentiate from other causes of posttransfusion dyspnea such a transfusion-related acute lung injury., Study Design and Methods: A systematic review of literature was performed in EMBASE, PubMed, the TRIP Database, and the Cochrane Library, from inception to June 2018. All articles discussing diagnostic markers for TACO were included. Non-English articles or conference abstracts were excluded., Results: Twenty articles discussing biomarkers for TACO were included. The majority investigated B-type natriuretic peptide (BNP) and the N-terminal prohormone cleavage fragment of BNP (NT-proBNP), markers of hydrostatic pressure that can be determined within 1 hour. The data indicate that a post/pretransfusion NT-proBNP ratio > 1.5 can aid in the diagnosis of TACO. Posttransfusion levels of BNP less than 300 or NT-proBNP less than 2000 pg/mL, drawn within 24 hours of the reaction, make TACO unlikely. Cut-off levels that exclude TACO are currently unclear. In critically ill patients, the specificity of natriuretic peptides for circulatory overload is poor. Other biomarkers, such as cytokine profiles, cannot discriminate between TACO and transfusion-related acute lung injury., Conclusion: Currently, BNP and NT-proBNP are the primary diagnostic biomarkers researched for TACO. An NT-proBNP ratio greater than 1.5 is supportive of TACO, and low levels of BNP or NT-proBNP can exclude TACO. However, they are unreliable in critically ill patients. Other biomarkers, including cytokines and pulmonary edema fluid-to-serum protein ratio have not yet been sufficiently investigated for clinical use., (© 2018 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

Background: Fluid and pain management during liver surgery (eg, low central venous pressure) is a classic topic of controversy between anesthesiologists and surgeons. Little is known about practices worldwide. The aim of this study was to assess perioperative practices in liver surgery among and between surgeons and anesthesiologists worldwide that could guide the design of future international studies., Methods: An online questionnaire was sent to 22 societies, including 4 international hepatopancreatobiliary societies, the American Society of Anesthesiologists, and 17 other (inter-)national societies., Results: A total of 913 participants (495 surgeons and 418 anesthesiologists) from 66 countries were surveyed. A large heterogeneity in fluid management practices was identified, with 66% using low central venous pressure, 22% goal-directed fluid therapy, and 6% normovolemia. In addition, large heterogeneity was found regarding pain management practices, with 49% using epidural analgesia, 25% patient-controlled analgesia with opioids, and 12% regional techniques. Most participants assume that there is a relation between perioperative pain management and morbidity and mortality (78% of surgeons vs 89% of anesthesiologists; P < .001). Both surgeons and anesthesiologists have the highest expectations for minimally invasive surgery and enhanced recovery pathways for improving outcomes in liver surgery. No clear differences between continents were found., Conclusion: Worldwide there is a large heterogeneity in fluid and pain management practices in liver surgery. This survey identified several areas of interest for future international studies aiming to improve outcomes in liver surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: This study aims at identifying factors that disciplines consider when diagnosing and reporting transfusion-associated circulatory overload ('TACO')., Background: TACO is a clinical diagnosis based mainly on subjective factors. Therefore, TACO could be an underreported complication of blood transfusion., Methods: A survey was conducted among critical care physicians, anaesthesiologists, haematologists, transfusion medicine physicians and haemovigilance officers using case vignettes and a questionnaire. Factors that may affect diagnosing TACO were investigated using conjoint analysis. A positive B-coefficient indicates a positive preference for diagnosing TACO. Participants rated factors influencing reporting TACO on a 0- to 100-point scale., Results: One hundred and seven surveys were returned (62%). Vignettes showed preferences in favour of diagnosing TACO with the onset of symptoms within 2 h [β 0·4(-0·1-1·0)], positive fluid balance [β 0·9(0·4-1·5)] and history of renal failure [β 0·6(0·1-1·2)]. Compared with transfusion of a single unit of red blood cells (RBC), respondents showed a preference for diagnosing TACO following a single unit of solvent/detergent (S/D) plasma or pooled platelet concentrate (PPC) [β 0·3(-0·2-0·7) resp. 0·5(-0·1-1·2)]. Multiple transfusion (6 RBC + 4 S/D plasma) was a strong preference for diagnosing TACO compared to 1 RBC and 1 S/D plasma [β 0·3(-0·8-1·3)]. Respondents did not fully take into account new hypertension and tachycardia when reporting TACO [median 70 (IQR 50-80) resp. 60 (IQR 50-80)]. No differences were observed between disciplines involved., Conclusion: When diagnosing and reporting TACO, physicians and haemovigilance officers do consider known risk factors for TACO. Reporting could be improved by increasing the awareness of haemodynamic variables in future education programmes., (© 2017 British Blood Transfusion Society.)

Objectives: To determine the predictive value of commonly used clinical variables upon ICU admission for long-term all-cause mortality and functional outcome of adult stroke patients admitted to the ICU., Design: Retrospective observational cohort study., Setting: General and neurosurgical ICUs of the University College London Hospitals in North Central London., Patients: All adult ICU patients with a clinical diagnosis of acute stroke admitted between February 2010 and May 2012., Interventions: None., Measurements and Main Results: Demographic and clinical data concerning the first 24 hours after ICU admission were obtained. Patients were followed until February 2016 to assess long-term survival. Functional outcome was determined using the modified Rankin Scale. We evaluated 131 critically ill stroke patients, with a median (interquartile range) age of 70 years (55-78 yr). One-year mortality rate was 52.7%. Surviving patients were followed up over a median (interquartile range) period of 4.3 years (4.0-4.8 yr). The multivariable model that best predicted long-term all-cause mortality indicated that mortality of critically ill stroke patients was predicted by high Acute Physiology and Chronic Health Evaluation II score, impaired consciousness (Glasgow Coma Scale score ≤ 8) as reason for ICU admission, low Glasgow Coma Scale sum score after 24 hours, and absence of brainstem reflexes. Long-term independent functional status occurred in 30.9% of surviving patients and was predicted by low Acute Physiology and Chronic Health Evaluation II score, high Glasgow Coma Scale sum score at ICU admission, and absence of mass effect on CT scan., Conclusions: Mortality in critically ill stroke patients is high and occurs most often shortly after the event. Less than one in three surviving patients is able to function independently after 1 year. This study has identified several clinical variables that predict long-term all-cause mortality and functional outcome among critically ill stroke patients and found that mainly acute physiologic disturbance and absolute values of neurologic clinical assessment are predictive.