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Background: Due to their invasiveness, arterial lines are not typically used in routine monitoring, despite their superior responsiveness in hemodynamic monitoring and detecting intraoperative hypotension. To address this issue, noninvasive, continuous arterial pressure monitoring is necessary. We developed a deep-learning model that reconstructs continuous mean arterial pressure (MAP) using the photoplethysmograhy (PPG) signal and compared it to the arterial line gold standard., Methods: We analyzed high-frequency PPG signals from 117 patients in neuroradiology and digestive surgery with a median of 2201 (interquartile range [IQR], 788-4775) measurements per patient. We compared models with different combinations of convolutional and recurrent layers using as inputs for our neural network high-frequency PPG and derived features including dicrotic notch relative amplitude, perfusion index, and heart rate. Mean absolute error (MAE) was used as performance metrics. Explainability of the deep-learning model was reconstructed with Grad-CAM, a visualization technique using saliency maps to highlight the parts of an input that are significant for a deep-learning model decision-making process., Results: An MAP baseline model, which consisted only of standard cuff measures, reached an MAE of 6.1 (± 14.5) mm Hg. In contrast, the deep-learning model achieved an MAE of 3.5 (± 4.4) mm Hg on the external test set (a 42.6% improvement). This model also achieved the narrowest confidence intervals and met international standards used within the community (grade A). The saliency map revealed that the deep-learning model primarily extracts information near the dicrotic notch region., Conclusions: Our deep-learning model noninvasively estimates arterial pressure with high accuracy. This model may show potential as a decision-support tool in operating-room settings, particularly in scenarios where invasive blood pressure monitoring is unavailable., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 International Anesthesia Research Society.)

Background: This analysis provides details on baseline and changes in quality of life (QoL) and its components as measured by EQ-5D-5L questionnaire, as well as association with objective outcomes, applying high-intensity heart failure (HF) care in patients with acute HF., Methods: In STRONG-HF trial (Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by NT-proBNP Testing, of Heart Failure Therapies) patients with acute HF were randomized just before discharge to either usual care or a high-intensity care strategy of guideline-directed medical therapy up-titration. Patients ranked their state of health on the EQ-5D visual analog scale score ranging from 0 (the worst imaginable health) to 100 (the best imaginable health) at baseline and at 90 days follow-up., Results: In 1072 patients with acute HF with available assessment of QoL (539/533 patients assigned high-intensity care/usual care) the mean baseline EQ-visual analog scale score was 59.2 (SD, 15.1) with no difference between the treatment groups. Patients with lower baseline EQ-visual analog scale (meaning worse QoL) were more likely to be women, self-reported Black and non-European ( P <0.001). The strongest independent predictors of a greater improvement in QoL were younger age ( P <0.001), no HF hospitalization in the previous year ( P <0.001), lower NYHA class before hospital admission ( P <0.001) and high-intensity care treatment (mean difference, 4.2 [95% CI, 2.5-5.8]; P <0.001). No statistically significant heterogeneity in the benefits of high-intensity care was seen across patient subgroups of different ages, with left ventricular ejection fraction above or below 40%, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and systolic blood pressure above or below the median value. The treatment effect on the primary end point did not vary significantly across baseline EQ-visual analog scale ( P interaction =0.87)., Conclusions: Early up-titration of guideline-directed medical therapy significantly improves all dimensions of QoL in patients with HF and improves prognosis regardless of baseline self-assessed health status. The likelihood of achieving optimal doses of HF medications does not depend on baseline QoL., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03412201., Competing Interests: Disclosures Dr Mebazaa has received grants from Roche Diagnostics, Abbott Laboratories, 4TEEN4, and Windtree Therapeutics; honoraria for lectures from Roche Diagnostics, Bayer, and MSD; is a consultant for Corteria Pharmaceuticals, S-form Pharma, FIRE-1, Implicity, 4TEEN4, and Adrenomed; and is coinventor of a patent on combination therapy for patients having acute or persistent dyspnoea. Drs Davison, Barros, Novosadova, Takagi, Cotter, and C. Edwards are employees of Momentum Research, which has received grants for research from Abbott Laboratories, Amgen, Celyad, Cirius Therapeutics, Corteria Pharmaceuticals, Heart Initiative, Sanofi, Windtree Therapeutics, and XyloCor Therapeutics. Drs Davison and Cotter are directors of Heart Initiative a nonprofit organization. Dr Adamo has received speaker fees from Abbott Vascular and Medtronic. Dr Čelutkienė has received personal fees from Novartis, AstraZeneca, Boehringer Ingelheim, Roche Diagnostics, and Pfizer. Dr Cohen-Solal has received honoraria for lectures or consultancy from AstraZeneca, Novartis, Vifor, Bayer, Merck, Sanofi, Abbott, and Boehringer Ingelheim. Dr Chioncel received grants from Servier. Dr Damasceno works for the Faculty of Medicine, Eduardo Mondlane University (Maputo, Mozambique), which received research grants from the Heart Initiative for their participation in this study. Dr Diaz has received supporting fees for coordination of STRONG-HF trial activities. Dr Filippatos has received lecture fees or was a committee member for trials and registries sponsored by Bayer, Vifor, Boehringer Ingelheim, Medtronic, Servier and Amgen. Dr Pagnesi has received personal fees from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim and Vifor Pharma. Dr Pang has received grants or research contracts from American Heart Association, Roche, Siemens, Ortho Diagnostics, Abbott, Beckman Coulter, and Siemens; consulting fees from Roche; honoraria from WebMD; and he has financial interest in The Heart Course. Dr Sliwa has received grants from Medtronic, Servier, and Amylam and honoraria from MSD, Novartis, and Sanofi. Dr Lam is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Novo Nordisk and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Alleviant Medical, Allysta Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CardioRenal, CPC Clinical Research, Eli Lilly, Impulse Dynamics, Intellia Therapeutics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Quidel Corporation, Radcliffe Group Ltd, Recardio Inc, ReCor Medical, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as cofounder and nonexecutive director of Us2.ai. Dr Voors has received consultancy fees or research support from AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Myocardia, Merck, Novartis, Novo Nordisk, and Roche Diagnostics. All other authors declare no conflicts.

Background: Preoperative abnormal cognitive status is a risk factor for postoperative complications yet remains underdiagnosed. During propofol general anesthesia, intraoperative electroencephalography (EEG) variables, such as alpha band power (α-BP), correlate with cognitive status. This relationship under sevoflurane is unclear. We investigated whether EEG biomarkers of poor cognitive status found under propofol could be extended to sevoflurane., Methods: In this monocentric prospective observational study, 106 patients with intraoperative EEG monitoring were included (propofol/sevoflurane = 55/51). We administered the Montreal Cognitive Assessment (MoCA) scale to identify abnormal cognition (low MoCA) 1 day before intervention. EEG variables included delta to beta frequency band powers. Results were adjusted to age and drug dosage. We assessed depth of anesthesia (DoA) using the spectral edge frequency (SEF 95 ) and maintained it within (8-13) Hz., Results: The difference in α-BP between low and normal MoCA patients was significantly larger among propofol patients (propofol: 4.3 ± 4.8 dB versus sevoflurane: 1.5 ± 3.4 dB, P = .022). SEF 95 and age were not statistically different between sevoflurane and propofol groups. After adjusting to age and dose, low α-BP was significantly associated with low MoCA under propofol (odds ratio [OR] [confidence interval {CI}] = 0.39 [0.16-0.94], P = .034), but not under sevoflurane, where theta-band power was significantly associated with low MoCA (OR [CI] = 0.31 [0.13-0.73], P = .007)., Conclusions: We suggest that intraoperative EEG biomarkers of abnormal cognition differ between propofol and sevoflurane under general anesthesia., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)

Background: Long-term outcomes of patients with severe stroke remain poorly documented. We aimed to characterize one-year outcomes of patients with stroke requiring mechanical ventilation in the intensive care unit (ICU)., Methods: We conducted a prospective multicenter cohort study in 33 ICUs in France (2017-2019) on patients with consecutive strokes requiring mechanical ventilation for at least 24 hours. Outcomes were collected via telephone interviews by an independent research assistant. The primary end point was poor functional outcome, defined by a modified Rankin Scale score of 4 to 6 at 1 year. Multivariable mixed models investigated variables associated with the primary end point. Secondary end points included quality of life, activities of daily living, and anxiety and depression in 1-year survivors., Results: Among the 364 patients included, 244 patients (66.5% [95% CI, 61.7%-71.3%]) had a poor functional outcome, including 190 deaths (52.2%). After adjustment for non-neurological organ failure, age ≥70 years (odds ratio [OR], 2.38 [95% CI, 1.26-4.49]), Charlson comorbidity index ≥2 (OR, 2.01 [95% CI, 1.16-3.49]), a score on the Glasgow Coma Scale <8 at ICU admission (OR, 3.43 [95% CI, 1.98-5.96]), stroke subtype (intracerebral hemorrhage: OR, 2.44 [95% CI, 1.29-4.63] versus ischemic stroke: OR, 2.06 [95% CI, 1.06-4.00] versus subarachnoid hemorrhage: reference) remained independently associated with poor functional outcome. In contrast, a time between stroke diagnosis and initiation of mechanical ventilation >1 day was protective (OR, 0.56 [95% CI, 0.33-0.94]). A sensitivity analysis conducted after exclusion of patients with early decisions of withholding/withdrawal of care yielded similar results. We observed persistent physical and psychological problems at 1 year in >50% of survivors., Conclusions: In patients with severe stroke requiring mechanical ventilation, several ICU admission variables may inform caregivers, patients, and their families on post-ICU trajectories and functional outcomes. The burden of persistent sequelae at 1 year reinforces the need for a personalized, multi-disciplinary, prolonged follow-up of these patients after ICU discharge., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03335995., Competing Interests: Disclosures Dr Sonneville reports grants from the French Ministry of Health, outside the submitted work. Dr Mazighi reports compensation from Novo Nordisk for consultant services; compensation from Boerhinger-Ingelheim for consultant services; and compensation from Acticor Biotech for consultant services. Dr Cortier reports employment by Foch. Dr Geri reports compensation from BARD for consultant services. Dr Demoule reports compensation from Agence Européenne Informatique for other services; compensation from Fisher and Paykel Healthcare Limited for other services; compensation from Baxter Healthcare for other services; compensation from Lowenstein for other services; compensation from Getinge for other services; travel support from Lowenstein; compensation from AstraZeneca for other services; compensation from Lungpacer for other services; compensation from Liberate Medical for other services; compensation from Respinor for other services; and compensation from Mindray DS USA Inc. for other services. Dr Timsit reports grants from Merck; compensation from BD Biosciences for consultant services; and grants from Pfizer. The other authors report no conflicts.

Objective: To perform a retrospective root-cause analysis of postoperative death after CRS and HIPEC procedures., Background: The combination of CRS and HIPEC is an effective therapeutic strategy to treat peritoneal surface malignancies, however it is associated with significant postoperative mortality., Methods: All patients treated with a combination of CRS and HIPEC between January 2009 and December 2018 in 22 French centers and died in the hospital, were retrospectively analyzed. Perioperative data of the 101 patients were collected by a local senior surgeon with a sole junior surgeon. Three independent experts investigated the typical root cause of death and provided conclusions on whether postoperative death was preventable (PREV group) or not (NON-PREV group). A typical root cause of preventable postoperative death was classified on a cause-and-effect diagram., Results: Of the 5562 CRS+HIPEC procedures performed, 101 in-hospital deaths (1.8%) were identified, of which a total of 18 patients of 70 years old and above and 20 patients with ASA score of 3. Etiology of peritoneal disease was mainly colorectal. A total of 54 patients (53%) were classified in the PREV group and 47 patients (47%) in the NON-PREV group. The results of the study show that in the PREV group, WHO performance status 1-2 was more frequent and the Median Peritoneal Cancer Index was higher compared with those of the NON-PREV group. The cause of death in the PREV group was classified as: (i) preoperatively for debatable indication (59%), (ii) intraoperatively (30%) and (iii) postoperatively in 17 patients (31%). A multifactorial cause of death was found in 11 patients (20%)., Conclusion: More than half of the postoperative deaths after combined CRS and HIPEC may be preventable, mainly by following guidelines regarding preoperative selection of the patients and adequate intraoperative decisions., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Although clinical presentation of coronavirus disease 2019 has been extensively described, immune response to severe acute respiratory syndrome coronavirus 2 remains yet not fully understood. Similarities with bacterial sepsis were observed; however, few studies specifically addressed differences of immune response between both conditions. Here, we report a longitudinal analysis of the immune response in coronavirus disease 2019 patients, its correlation with outcome, and comparison between severe coronavirus disease 2019 patients and septic patients., Design: Longitudinal, retrospective observational study., Setting: Tertiary-care hospital during the first 2020 coronavirus disease 2019 outbreak in France., Patients: All successive patients with confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the emergency department, medical ward, and ICU with at least one available immunophenotyping performed during hospital stay., Measurements and Main Results: Between March and April 2020, 247 patients with coronavirus disease 2019 were included and compared with a historical cohort of 108 severe septic patients. Nonsevere coronavirus disease 2019 patients (n = 153) presented normal or slightly altered immune profiles. Severe coronavirus disease 2019 (n = 94) immune profile differed from sepsis. Coronavirus disease 2019 exhibited profound and prolonged lymphopenia (mostly on CD3, CD4, CD8, and NK cells), neutrophilia, and human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation. Surprisingly, coronavirus disease 2019 patients presented a unique profile of B cells expansion, basophilia, and eosinophilia. Lymphopenia, human leukocyte antigen D receptor expression on CD14+ monocytes down-regulation, and neutrophilia were associated with a worsened outcome, whereas basophilia and eosinophilia were associated with survival. Circulating immune cell kinetics differed between severe coronavirus disease 2019 and sepsis, lack of correction of immune alterations in coronavirus disease 2019 patients during the first 2 weeks of ICU admission was associated with death and nosocomial infections., Conclusions: Circulating immune cells profile differs between mild and severe coronavirus disease 2019 patients. Severe coronavirus disease 2019 is associated with a unique immune profile as compared with sepsis. Several immune features are associated with outcome. Thus, immune monitoring of coronavirus disease 2019 might be of help for patient management., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Abstract: Early detection of arterial hypotension during cesarean delivery under spinal anesthesia is important. This study aims to compare the validity of NexfinTM as beat-to-beat noninvasive blood pressure monitoring with conventional intermittent oscillometric measurement of blood pressure during elective cesarean delivery.This open prospective observational bicentric study was performed between January 2013 and December 2015. We simultaneously recorded arterial blood pressure with both techniques in pregnant women undergoing elective cesarean delivery under spinal anesthesia. The primary outcome was a Bland-Altman analysis of systolic blood pressure measurement comparing NexfinTM and a conventional method. The secondary outcomes were the time to detect the first relevant hypotensive episode and the comparison of both devices using a four-quadrant graph.One hundred and seventy-four parturients completed the study, and 2640 pairs of systolic blood pressure measurements were analyzed. Bias was -10 mmHg with upper and lower limits of agreement of -61 and +41 mmHg. In 73.9% of the cases, the two techniques provided the same information (normotension or hypotension), but the conventional method missed 20.8% of measurements, with NexfinTM detecting 16.2% more hypotensive measurements. The median [25-75 percentiles] duration to detect the first hypotensive measurement was 331 [206-480] seconds for NexfinTM and 440 [300-500] s for intermittent oscillometry (P < .001).The agreement between NexfinTM and an intermittent method for the measurement of systolic blood pressure was not in an acceptable range during cesarean delivery, although NexfinTM may detect hypotension earlier than the standard method.Trial registration: Clinicaltrials.gov identifier: NCT01732133; November 22, 2012., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Interest in developing and using novel biomarkers in critical care and perioperative medicine is increasing. Biomarkers studies are often presented with flaws in the statistical analysis that preclude them from providing a scientifically valid and clinically relevant message for clinicians. To improve scientific rigor, the proper application and reporting of traditional and emerging statistical methods (e.g., machine learning) of biomarker studies is required. This Readers' Toolbox article aims to be a starting point to nonexpert readers and investigators to understand traditional and emerging research methods to assess biomarkers in critical care and perioperative medicine., (Copyright © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.)

Little is known about respecting the recommended range of bispectral index (BIS) in practice. This exploratory retrospective analysis of 138 robotic surgical patients having received total intravenous anesthesia shows that BIS was between 40 and 60 during 61.3% ± 25.2% (mean ± standard deviation [SD]) of maintenance, >60 during 3.1% ± 5.5%, and <40 during 35.7% ± 26.9%. Burst suppression was present during 17.8% ± 22.2%. Female sex is associated with increased periods of BIS <40 (P = .002) as is body mass index (BMI) <26 (P = .012). Increased age is associated with increase in burst suppression (P = .005). A larger study is required to confirm the role of patients' factors on the number of periods of low BIS.

Background: Global afterload angle (GALA) is a parameter derived from velocity-pressure loop (VP Loop), for continuous assessment of cardiac afterload in the operating room. It has been validated with invasive measure of central pressure. The aim of this study was to evaluate the feasibility of noninvasive VP Loop obtained with central pressure measured with two different noninvasive tonometers., Methods: A prospective, observational, monocentric study was conducted in 51 patients under general anesthesia. Invasive central pressure (cPINV) was measured with a fulfilled intravascular catheter, and noninvasive central pressure signals were obtained with two applanation tonometry devices: radial artery tonometry (cPSHYG: Sphygmocor tonometer) and carotid tonometry (cPCOMP: Complior tonometer). Three VP Loops were built: VP LoopINV, VP LoopSPHYG and VP LoopCOMP. Patients were separated according to cardiovascular risk factors., Results: In the 51 patients under general anesthesia, cPSHYG was adequately obtained in 48 patients (89%) but, compared to cPINV, SBP was underestimated (-4 ± 6 mmHg, P < 0.0001), augmentation index (AIXSPHYG) and a GALASPHYG were overestimated (+13 ± 19%, P = 0.0077 and +4 ± 8°, P = 0.0024, respectively) with large limit of agreement (LOA) (-21 to 47% and -13 to 21° for AIXSPHYG and GALASPHYG, respectively). With the Complior, the failure rate of measurement for cPCOMP was 41%. SBP was similar (3 ± 17 mmHg, P = 0.32), AIXCOMP was underestimated (-11 ± 19%, P = 0.0046) and GALACOMP was similar but with large LOA (-50 to 26% and -20 to 18° for AIXCOMP and GALACOMP, respectively)., Conclusion: In anesthetized patient, the reliability of noninvasive central pressure monitoring by tonometry seems too limited to monitor cardiac afterload with VP Loop.

Background: Acute hypotensive episodes (AHE), defined as a drop in the mean arterial pressure (MAP) <65 mm Hg lasting at least 5 consecutive minutes, are among the most critical events in the intensive care unit (ICU). They are known to be associated with adverse outcome in critically ill patients. AHE prediction is of prime interest because it could allow for treatment adjustment to predict or shorten AHE., Methods: The Super Learner (SL) algorithm is an ensemble machine-learning algorithm that we specifically trained to predict an AHE 10 minutes in advance. Potential predictors included age, sex, type of care unit, severity scores, and time-evolving characteristics such as mechanical ventilation, vasopressors, or sedation medication as well as features extracted from physiological signals: heart rate, pulse oximetry, and arterial blood pressure. The algorithm was trained on the Medical Information Mart for Intensive Care dataset (MIMIC II) database. Internal validation was based on the area under the receiver operating characteristic curve (AUROC) and the Brier score (BS). External validation was performed using an external dataset from Lariboisière hospital, Paris, France., Results: Among 1151 patients included, 826 (72%) patients had at least 1 AHE during their ICU stay. Using 1 single random period per patient, the SL algorithm with Haar wavelets transform preprocessing was associated with an AUROC of 0.929 (95% confidence interval [CI], 0.899-0.958) and a BS of 0.08. Using all available periods for each patient, SL with Haar wavelets transform preprocessing was associated with an AUROC of 0.890 (95% CI, 0.886-0.895) and a BS of 0.11. In the external validation cohort, the AUROC reached 0.884 (95% CI, 0.775-0.993) with 1 random period per patient and 0.889 (0.768-1) with all available periods and BSs <0.1., Conclusions: The SL algorithm exhibits good performance for the prediction of an AHE 10 minutes ahead of time. It allows an efficient, robust, and rapid evaluation of the risk of hypotension that opens the way to routine use.

Objectives: Adrenomedullin has vascular properties and elevated plasma adrenomedullin levels were detected in sepsis. We assessed, in septic and nonseptic ICU patients, the relation between circulating adrenomedullin, the need for organ support and mortality, using an assay of bioactive adrenomedullin., Design: Prospective multicenter observational cohort study., Setting: Data from the French and euRopean Outcome reGistry in ICUs study., Patients: Consecutive patients admitted to intensive care with a requirement for invasive mechanical ventilation and/or vasoactive drug support for more than 24 hours following ICU admission and discharged from ICU were included., Interventions: Clinical and biological parameters were collected at baseline, including bioactive-adrenomedullin. Status of ICU survivors was assess until 1 year after discharge. The main outcome was the need for organ support, including renal replacement therapy and/or for inotrope(s) and/or vasopressor(s). Secondary endpoints were the ICU length of stay and the 28-day all-cause mortality., Measurements and Main Results: Median plasma bioactive adrenomedullin (n = 2,003) was 66.6 pg/mL (34.6-136.4 pg/mL) and the median Simplified Acute Physiology Score II score 49 (36-63). Renal replacement therapy was needed in 23% and inotropes(s) and/or vasopressor(s) in 77% of studied patients. ICU length of stay was 13 days (7-21 d) and mortality at 28 days was 22 %. Elevated bioactive adrenomedullin independently predicted 1) the need for organ support (odds ratio, 4.02; 95% CI, 3.08-5.25) in ICU patients whether admitted for septic or nonseptic causes and 2) the need for renal replacement therapy (odds ratio, 4.89; 3.83-6.28), and for inotrope(s) and/or vasopressor(s) (odds ratio, 3.64; 2.84-4.69), even in patients who were not on those supports at baseline. Elevated bioactive adrenomedullin was also associated with a prolonged length of stay (odds ratio, 1.85; 1.49-2.29) and, after adjustment for Simplified Acute Physiology Score II, with mortality (odds ratio, 2.31; 1.83-2.92)., Conclusions: Early measurement of bioactive adrenomedullin is a strong predictor of the need of organ support and of short-term mortality in critically ill patients.

Objectives: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge., Design: Ancillary investigation of a prospective observational study., Setting: Twenty-one ICUs with 1-year follow-up., Patients: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included., Interventions: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors., Measurements and Main Results: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease)., Conclusions: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

Background: Bleeding modifies the surgeon's view of the field during transsphenoidal endoscopic pituitary surgery. Since ventilation can alter venous return, we compared the effect of volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) on intraoperative bleeding., Methods: Eighty-six patients were randomized to VCV or PCV in this single blinded study; comparisons concerned 42 in the PCV group and 43 in the VCV group., Results: Intraoperative bleeding, the primary endpoint, did not differ between groups whether analysis focused on 7 levels of the score, from minimal bleeding to bleeding with significant change in the conduct of surgical procedure (P = .89) or on a stratification into 3 categories, mild, moderate, and major (P = .47). Median [interquartile range] peak airway pressure was lower in the PCV group (13.5 [12.5-15] vs 16.3 [14.4-19.1] cm H2O, P < .001) while mean airway pressures were similar (P = .08). Means ± SD of tidal volumes were lower in the VCV group when expressed as absolute values (470.6 ± 84 vs 434.7 ± 71.7 ml, P = .05) or as tidal volume/theoretical ideal weight ratio (6.7 [6.5-7] vs 7.2 [6.9-7.9], P < .001). The 2 groups were similar for postoperative complications and number of patients cured., Conclusion: In conclusion, ventilation mode does not influence intraoperative bleeding during transsphenoidal pituitary surgery., Trial Registration: Clinicaltrials.gov identifier: NCT01891838; July 3, 2013.

Background: Thoracic epidural analgesia is associated with a high rate of postoperative urine retention (POUR). Auriculotherapy can reduce visceral dysfunction and can be helpful in anesthesiology and pain control. The aim of this study was to test the efficacy of preoperative auriculotherapy to decrease the occurrence of POUR., Methods: This single-center, double-blinded, 2-arm randomized study was performed between January 2015 and May 2016 in a tertiary care university hospital. Male patients scheduled for an elective lung surgical procedure under combined general anesthesia and thoracic epidural analgesia were included. Auriculotherapy (A group) was performed once the patient was under general anesthesia with 5 semi-permanent needles inserted in both ears at the "Shen Men" "bladder", "pelvic parasympathetic", "anterior hypothalamus", and "frontal lobe" points. Five small round patches of adhesive pads were positioned bilaterally at the same points in the control group (C group). The main outcome measure was the requirement for bladder catheterization during the day and the first night following surgery., Results: Fifty-three patients were randomized and 25 analyzed in each group. Requirement for bladder catheterization was different between groups: 24 C group patients (96%) and 18 A group patients (72%) (P = .049, Fisher exact test; Odds Ratio = 0.11 [0.01-0.95]. The number of patients needed to treat with auriculotherapy to avoid 1 case of bladder catheterization was 4. No adverse effect was observed due to auriculotherapy., Conclusion: This study demonstrates that auriculotherapy is a safe and useful technique reducing POUR in thoracotomy patients benefiting from thoracic epidural analgesia., Trial Registration: Clinicaltrials.gov identifier: NCT02290054 (November 13, 2014).

Research is ongoing to find a noninvasive method of monitoring, which can predict fluid responsiveness in patients undergoing kidney transplantation.To compare the responses to fluid challenges with the Pleth Variability Index, a noninvasive dynamic index derived from plethysmographic variability (Radical 7 pulse oximeter; Masimo Corporation, Irvine, CA), and the esophageal Doppler, the criterion standard.Observational study.University hospital; study from May 2011 and May 2012.Forty-eight patients with end-renal function were included and 44 analyzed. Patients with cardiac failure were not eligible.Fluid challenges were administered during maintenance of general anesthesia but before skin incision and repeated if the patient was deemed to be a "responder" (increase in stroke volume ≥10%).The primary endpoint was to assess if the Pleth Variability Index is an accurate predictor of fluid responsiveness.Among 76 fluid challenges, 38 were considered as positive (increase in stroke volume measured by Doppler ≥10%). Pleth Variability Index was similar at baseline between responders and nonresponder patients. Fluid challenges were associated with a significant decrease in Pleth Variability Index in overall cases (12 [8-14] vs 10 [6-17], P = .050), but it was not able to discriminate between responders (12 [8-15] vs 10 [5-15], P = .650) and nonresponders (11 [6-16] vs 8 [5-14], P = .047). The area under the Receiver Operating Characteristic curve for Pleth Variability Index was 0.49 (0.36-0.62).Pleth Variability Index is not an accurate predictor of fluid responsiveness during kidney transplantation.

Objectives: Mortality in cardiogenic shock complicating acute coronary syndrome is high, and objective risk stratification is needed for rational use of advanced therapies such as mechanical circulatory support. Traditionally, clinical variables have been used to judge risk in cardiogenic shock. The aim of this study was to assess the added value of serial measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide to clinical parameters for risk stratification in cardiogenic shock., Design: CardShock (www.clinicaltrials.gov NCT01374867) is a prospective European multinational study of cardiogenic shock. The main study introduced CardShock risk score, which is calculated from seven clinical variables at baseline, and was associated with short-term mortality., Setting: Nine tertiary care university hospitals., Patients: Patients with cardiogenic shock caused by acute coronary syndrome (n=145)., Interventions: In this substudy, plasma samples from the study patients were analyzed at eight time points during the ICU or cardiac care unit stay. Additional prognostic value of the biomarkers was assessed with incremental discrimination improvement., Measurements and Main Results: The combination of soluble ST2 and amino-terminal pro-B-type natriuretic peptide showed excellent discrimination for 30-day mortality (area under the curve, 0.77 at 12 hr up to 0.93 at 5-10 d after cardiogenic shock onset). At 12 hours, patients with both biomarkers elevated (soluble ST2, ≥ 500 ng/mL and amino-terminal pro-B-type natriuretic peptide, ≥ 4,500 ng/L) had higher 30-day mortality (79%) compared to those with one or neither biomarkers elevated (31% or 10%, respectively; p < 0.001). Combined measurement of soluble ST2 and amino-terminal pro-B-type natriuretic peptide at 12 hours added value to CardShock risk score, correctly reclassifying 11% of patients., Conclusions: The combination of results for soluble ST2 and amino-terminal pro-B-type natriuretic peptide provides early risk assessment beyond clinical variables in patients with acute coronary syndrome-related cardiogenic shock and may help therapeutic decision making in these patients.

Background: Previous reports have brought specific attention to the relationship between oxygenation of the patient and the accuracy of noninvasive measurement of hemoglobin (Hb) using an optical sensor. This study aimed to assess prospectively the relationship between fraction of inspired oxygen (FIO2) and the bias of the measurement of Hb by the use of 2 different noninvasive monitors compared with the classic invasive technique., Methods: Forty-four patients were included prospectively. In each individual, Hb level was determined noninvasively by monitor Pronto-7™ (Masimo Corporation, Irvine, CA) and by monitor NBM-200MP™ (OrSense Ltd, Petah-Tikva, Israel), with the probe placed on 2 fingers on the same hand of the patient. Three measures were performed, first under breathing air and 2 others when fraction of expired oxygen rose to 50% ± 5% and to 90 ± 5%. Simultaneously, a nurse collected a venous blood sample, which was sent immediately to the hematology laboratory for Hb measurement. The main outcome measurement was the mean bias between noninvasive and invasive measurements., Results: Results show no change in median bias [interquartile range] with FIO2 for Pronto-7 (from 1.1 g/dL [0.0-2.0] in FIO2 21% to 1.0 g/dL [0.2-1.5] in FIO2 100%), but increasingly negative median bias with increasing FIO2 for NBM-200MP (from -0.3 g/dL [-1.3 to 0.3] in FIO2 21% to -0.8 g/dL [-1.5 to -0.1] in FIO2 100%, P = .04)., Discussion: This study showed that noninvasive measurement of Hb could be influenced by inspired fraction of oxygen when the monitor NBM-200MP is used.

Background: Brain natriuretic peptide (BNP) serum concentration has been shown to be a preoperative predictor of postoperative outcome in high risk surgery. Whether it is able to predict early post-liver transplantation (LT) mortality in cirrhotic patients is unanswered., Methods: Prospective monocenter observational study including all consecutive patients who received LT for cirrhosis and for whom a preoperative BNP serum dosage was available between January 2011 and December 2014., Results: During the period, 207 cirrhotic patients among 525 LT were studied. The ICU and 180-day mortality rates were, respectively, 6% and 8%. Pre-LT BNP concentration, adjusted on model of end-stage liver disease (MELD) score, was an independent factor of ICU and 180-day mortality rates (for each 50 pg/mL increase; hazard ratio, 1035 [1.022-1.049]; P < 0.001 and 1.035 [1.014-1057]; P = 0.001). According to the receiver operator characteristic curve with an accuracy of 0.79 (0.66-0.93), the optimal cutoff value of pre-LT BNP serum level to predict ICU mortality was 155 pg/mL with a negative predictive value of 99%. All patients with MELD score exceeding 25 and pre-LT serum BNP level less than 155 pg/mL survived, whereas patients combining MELD score exceeding 25 and pre-LT BNP concentration exceeding 155 pg/mL had a 27% ICU mortality rate (P = 0.03)., Conclusions: In cirrhotic patients, pre-LT BNP serum level was an independent predictor of post-LT ICU mortality. With its excellent negative predictive value, the use of this biomarker in combination with MELD score could be useful to better predict post-LT early outcome.

Red blood cell distribution width (RDW) may serve as an integrative marker of pathological processes that portend worse prognosis in heart failure (HF). The prognostic value of RDW variation (ΔRDW) during hospitalization for acute heart failure (AHF) has yet to be studied.We retrospectively analyzed 2 independent cohorts: Centro Hospitalar do Porto (derivation cohort) and Lariboisière hospital (validation cohort). In the derivation cohort a total of 170 patients (age 76.2 ± 10.3 years) were included and in the validation cohort 332 patients were included (age 76.4 ± 12.2 years). In the derivation cohort the primary composite outcome of HF admission and/or cardiovascular death occurred in 78 (45.9%) patients during the 180-day follow-up period.Discharge RDW and ΔRDW were both increased when hemoglobin levels were lower; peripheral edema was also associated with increased discharge RDW (all P < 0.05). Discharge RDW value was significantly associated with adverse events: RDW > 15% at discharge was associated with a 2-fold increase in event rate, HR = 1.95 (1.05-3.62), P = 0.04, while a ΔRDW >0 also had a strong association with outcome, HR = 2.47 (1.35-4.51), P = 0.003. The addition of both discharge RDW > 15% and ΔRDW > 0 to hemoconcentration was associated with a significant improvement in the net reclassification index, NRI = 18.3 (4.3-43.7), P = 0.012. Overlapping results were found in the validation cohort.As validated in 2 independent AHF cohorts, an in-hospital RDW enlargement and an elevated RDW at discharge are associated with increased rates of mid-term events. RDW variables improve the risk stratification of these patients on top of well-established prognostic markers., Competing Interests: All remaining authors have no conflicts of interest to disclose.

Cardiovascular disease (CVD) is the main cause of death in systemic lupus erythematosus (SLE) patients. We aimed to determine whether overweight (defined as a body mass index [BMI] > 25 kg/m(2)) contributed to subclinical atherosclerosis in SLE patients at low risk for CVD according to traditional factors. Wall thickness of the internal carotid artery (ICWT) measured at the carotid bulb and carotid plaques were assessed in 49 SLE patients asymptomatic for CVD and 49 controls matched on Framingham score. Factors associated to ICWT were identified and multivariate analysis was performed.SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (mean 1.9 ± 3.5 in SLE vs 1.8 ± 3.2% in controls, P = 0.37). ICWT (P < 0.001) and number of patients with carotid plaques (P = 0.015) were, however, higher in SLE patients as compared to controls. In multivariable analysis, SLE was an independent risk for a carotid atherosclerosis (OR [95% confidence interval, CI]: 3.53 [1.36-9.14]; P = 0.009). Older age, higher BMI, and higher Framingham score were associated with atherosclerosis in SLE patients in univariate analysis. In multivariate analysis, only the association with overweight remained significant (OR [95% CI]: 4.13 [1.02-16.75]; P = 0.047). Overweight is a major contributor to atherosclerosis in SLE patients at apparent low risk for CVD.

Background: NeuroSENSE is a depth of anesthesia monitor that uses automated electroencephalogram quantification. The Wavelet-based Anesthetic Value for Central Nervous System (WAVCNS) index calculated by this monitor is based on wavelet analysis of a normalized electroencephalogram signal in the γ-frequency band. The aim of this study was to determine the extent of disagreement between the Bispectral Index (BIS) and the WAVCNS index during propofol-based and sevoflurane-based maintenance of general anesthesia in a routine surgical population., Methods: Patients undergoing elective surgery were enrolled in the study and randomly assigned to receive either propofol or sevoflurane for the maintenance of anesthesia and remifentanil in both groups. Anesthesiologists were blinded to monitors in both groups. Discordance between the 2 monitors was assessed by the count of discrepancy in recommendation (DR) (type 1 defined as one parameter <40 and the other >60, or type 2 defined as BIS and WAVCNS values on different sides of a threshold [40 or 60]) and also by the proportion of agreement (P0) between WAVCNS and BIS, obtained every 5 seconds, in 3 categories of index (<40, 40-60, and >60)., Results: The analyzed data set consisted of 22 patients (36,872 data pairs) in the propofol group and 24 patients (32,826 data pairs) in the sevoflurane group. The type 1 DR rarely occurred in both the groups (<1%); however, the median (interquartile range) type 2 DR was significantly more frequent in the propofol group (20.6% [7.0-36.9] vs 4.5% [2.3-12.4]; P = 0.0005). The median difference in P0 was 11.53% (95% confidence interval, 0.57-21.32). Major disagreement between WAVCNS index and BIS was related to the weight of burst suppression pattern for the index calculation., Conclusions: Disagreement between BIS and NeuroSENSE during the maintenance of general anesthesia was worse in the propofol group than that in the sevoflurane groups. The disagreement increases during deep anesthesia or in the occurrence of burst suppression.

Background: Many patients in the intensive care unit are unable to communicate verbally. Accurately predicting whether such patients will exhibit painful behaviors during noxious procedures and assessing the adequacy of analgesia during those procedures is a challenge. In addition to observational pain assessment tools such as the Behavioral Pain Scale, physiologic indicators such as the pupillary response have been proposed. The pupil is innervated by both divisions of the autonomic nervous system and is affected by pain and analgesic medications. We evaluated the pupillary response to a light stimulus before noxious procedures as a method to predict pain during the procedure., Methods: We correlated different aspects of the pupillary light reflex with established strategies for pain assessment to evaluate the adequacy of analgesia before surgical dressing changes performed in the intensive care unit in patients with cellulitis associated with mediastinitis or not., Results: We found that a percentage of variation in pupil size >19% predicted the presence of pain as assessed by a Behavioral Pain Scale score of >3 with a sensitivity of 100% (95% confidence interval, 100%-100%) and a specificity of 77% (95% confidence interval, 54%-100%)., Conclusions: In patients unable to communicate verbally, pupillometry may potentially guide caregivers to adjust analgesia before noxious procedures.

Purpose of Review: The purpose of the present work was to review the literature on the role of biomarkers for the diagnosis, the risk stratification, and the management of circulatory failure., Recent Findings: Recent research has highlighted how biomarkers could guide physicians in making proper diagnosis of the cause of the circulatory failure, assessing the consequence in terms of organ injury and function, refining prognosis prediction and stratification of patients, and guiding treatments, in patients with cardiovascular failure., Summary: Because of the tight association between circulatory and renal failure, we put a special emphasis on cardiovascular [B-type natriuretic peptide (BNP), Nt-proBNP, troponin, QSOX-1, sST-2, mid-regional pro-atrial natriuretic peptide] and renal biomarkers (neutrophil gelatinase-associated lipocalin, cystatin C, liver-type fatty acid-binding protein, kidney injury molecule-1, insulin-like growth factor-binding protein-7, tissue inhibitor of metalloproteinase-2). We also discuss nonspecific biomarkers (pro-ADM, glycemia, MicroRNA, chromogramin A) in this setting. We discuss the potential interest and limits, from diagnosis to prognosis reclassification, of cutting-edge new biomarkers, but also widely available and inexpensive biomarkers, in the particular setting of circulatory failure.

Background: Postpartum hemorrhage is the leading cause of maternal death worldwide. Recent data from trauma patients and patients with hemorrhagic shock have suggested that an increased fresh frozen plasma:red blood cell (FFP:RBC) ratio may be of benefit in massive bleeding. We addressed this issue in cases of severe postpartum hemorrhage., Methods: We reviewed data from all patients diagnosed with severe postpartum hemorrhage during a 4-year period (2006-2009). Patients who were treated with sulprostone and required transfusion within 6 hours of delivery were included in the study and were divided into 2 groups according to their response to sulprostone: bleeding controlled with sulprostone alone (sulprostone group) and bleeding requiring an additional advanced interventional procedure including arterial angiographic embolization and/or surgical procedures (arterial ligation, B-Lynch suture, or hysterectomy; intervention group). The requirement or no requirement for advanced procedures constituted the primary end point of the study. Propensity scoring was used to assess the effect of a high FFP:RBC ratio on bleeding control., Results: Among 12,226 deliveries during the study period, 142 (1.1%) were complicated by severe postpartum hemorrhage. Bleeding was controlled with sulprostone alone in 90 patients (63%). Advanced interventional procedures were required for 52 patients (37%). Forty-one patients were transfused with both RBCs and FFP. The FFP:RBC ratio increased over the study period (P < 0.001), from 1:1.8 at the start to 1:1.1 at the end of the study period. After propensity score modeling (inverse probability of treatment weighting), a high FFP:RBC ratio was associated with lower odds for advanced interventional procedures (odds ratio [95% confidence interval], 1.25 [1.07-1.47]; P = 0.008). There were no deaths, severe organ dysfunction, or other complications as a consequence of severe postpartum hemorrhage., Conclusions: In this retrospective study, a higher FFP:RBC ratio was associated with a lower requirement for advanced interventional procedures in the setting of postpartum hemorrhage. The benefits of transfusion using a higher FFP:RBC ratio should be confirmed by randomized-controlled trials.

Purpose of Review: To review the contemporary management of patients with pulmonary hypertension in critical care., Recent Findings: The normal mean pulmonary artery pressure (mPAP) at rest is 14±3  mmHg and pulmonary hypertension is considered when mPAP is greater than or equal to 25  mmHg at rest. The classification of pulmonary hypertension has been redefined recently and updated in 2009 and could help to guide the management of patients with pulmonary hypertension in critical care. The management of pulmonary hypertension in ICU is based on expert opinion. Among the diagnostic and monitoring tools available, echocardiography provides useful information noninvasively, although pulmonary artery catheter must be used in case of complicated situations. Calcium sensitizers, a new class of inotrope, have inotropic effects and induce dilatation of the pulmonary, systemic, and coronary vasculature and thus could be useful in case of right ventricular failure (RVF), particularly in patients with acute respiratory distress syndrome (ARDS). By increasing the pulmonary vasodilator response to inhaled nitric oxide and preventing the rebound pulmonary vasoconstriction which occurs following cessation of nitric oxide breathing, selective type 5 isoform of phosphodiesterase inhibitors could be useful in critically ill patients., Summary: This article reviews recent and key findings on the management of pulmonary hypertension in critically ill patients.

Acute angle closure glaucoma is a rare complication of general anesthesia. However, in case of delayed diagnosis, it may lead to blindness. We present a case of bilateral acute angle closure glaucoma after cervical spine surgery under general anesthesia in a hypermetropic patient. In this case, the most likely trigger was the use of ephedrine, but nefopam administration and the prone surgical position are discussed as additional potential factors.