Hypotension Prediction Index Software to Prevent Intraoperative Hypotension during Major Non-Cardiac Surgery: Protocol for a European Multicenter Prospective Observational Registry (EU-HYPROTECT)

Intraoperative hypotension is common in patients having non-cardiac surgery and associated with postoperative acute myocardial injury, acute kidney injury, and mortality. Avoiding intraoperative hypotension is a complex task for anesthesiologists. Using artificial intelligence to predict hypotension from clinical and hemodynamic data is an innovative and intriguing approach. The AcumenTM Hypotension Prediction Index (HPI) software (Edwards Lifesciences; Irvine, CA, USA) was developed using artificial intelligence-specifically machine learning-and predicts hypotension from blood pressure waveform features. We aimed to describe the incidence, duration, severity, and causes of intraoperative hypotension when using HPI monitoring in patients having elective major non-cardiac surgery

Hypotension prediction index software to prevent intraoperative hypotension during major non-cardiac surgery: protocol for a european multicenter prospective observational registry (EU-HYPROTECT)

Background: Intraoperative hypotension is common in patients having non-cardiac surgery and associated with postoperative acute myocardial injury, acute kidney injury, and mortality. Avoiding intraoperative hypotension is a complex task for anesthesiologists. Using artificial intelligence to predict hypotension from clinical and hemodynamic data is an innovative and intriguing approach. The AcumenTM Hypotension Prediction Index (HPI) software (Edwards Lifesciences; Irvine, CA, USA) was developed using artificial intelligence-specifically machine learning-and predicts hypotension from blood pressure waveform features. We aimed to describe the incidence, duration, severity, and causes of intraoperative hypotension when using HPI monitoring in patients having elective major non-cardiac surgery. Methods: We built up a European, multicenter, prospective, observational registry including at least 700 evaluable patients from five European countries. The registry includes consenting adults (?18 years) who were scheduled for elective major non-cardiac surgery under general anesthesia that was expected to last at least 120 min and in whom arterial catheter placement and HPI monitoring was planned. The major objectives are to quantify and characterize intraoperative hypotension (defined as a mean arterial pressure [MAP] < 65 mmHg) when using HPI monitoring. This includes the time-weighted average (TWA) MAP < 65 mmHg, area under a MAP of 65 mmHg, the number of episodes of a MAP < 65 mmHg, the proportion of patients with at least one episode (1 min or more) of a MAP < 65 mmHg, and the absolute maximum decrease below a MAP of 65 mmHg. In addition, we will assess causes of intraoperative hypotension and investigate associations between intraoperative hypotension and postoperative outcomes. Discussion: There are only sparse data on the effect of using HPI monitoring on intraoperative hypotension in patients having elective major non-cardiac surgery. Therefore, we built up a European, multicenter, prospective, observational registry to describe the incidence, duration, severity, and causes of intraoperative hypotension when using HPI monitoring in patients having elective major non-cardiac surgery.Funding: Edwards Lifesciences SA, Department of Critical Care, Route de l’Etraz 70, 1260 Nyon, Switzerland funded the study and acts as the legal sponsor. The sponsor/funder had an active role in the design of the study. The collection, analysis, and interpretation of the data will be a collaborative effort of all investigators, who will also write the manuscript. Acknowledgments: We acknowledge the support of all participating patients and their physicians. We also acknowledge the tremendous contribution of the staff at Edwards Lifesciences, especially Edward Hembrow, Tim van den Boom, Anne Halfmann, Pierre Sibileau, Barbara Plasschaert, Volker Haag, Giulia Torricella and Alessia Longo. We further appreciate the excellent project management secured by Daniel Greinert, Marie Zielinksi and Claudia Lüske at the Institute for Pharmacology and Preventive Medicine (Cloppenburg, Germany). Data are captured using the s4trials software provided by Software for Trials Europe GmbH (Berlin, Germany)

The ICEBERG: A score and visual representation to track the severity of traumatic brain injury: Design principles and preliminary results

International audienceBACKGROUND Establishing neurological prognoses in traumatic brain injury (TBI) patients remains challenging. To help physicians in the early management of severe TBI, we have designed a visual score (ICEBERG score) including multimodal monitoring and treatment-related criteria. We evaluated the ICEBERG scores among patients with severe TBI to predict the 28-day mortality and long-term disability (Extended Glasgow Outcome Scale score at 3 years). In addition, we made a preliminary assessment of the nurses and doctors on the uptake and reception to the use of the ICEBERG visual tool. METHODS This study was part of a larger prospective cohort study of 207 patients with severe TBI in the Parisian region (PariS-TBI study). The ICEBERG score included six variables from multimodal monitoring and treatment-related criteria: cerebral perfusion pressure, intracranial pressure, body temperature, sedation depth, arterial partial pressure of CO2, and blood osmolarity. The primary outcome measures included the ICEBERG score and its relationship with hospital mortality and Extended Glasgow Outcome Score. RESULTS The hospital mortality was 21% (45/207). The ICEBERG score baseline value and changes during the 72nd first hours were more strongly associated with TBI prognosis than the ICEBERG parameters measured individually. Interestingly, when the clinical and computed tomography parameters at admission were combined with the ICEBERG score at 48 hours using a multimodal approach, the predictive value was significantly increased (area under the curve = 0.92). Furthermore, comparing the ICEBERG visual representation with the traditional numerical readout revealed that changes in patient vitals were more promptly detected using ICEBERG representation (p < 0.05). CONCLUSION The ICEBERG score could represent a simple and effective method to describe severity in TBI patients, where a high score is associated with increased mortality and disability. In addition, ICEBERG representation could enhance the recognition of unmet therapeutic goals and dynamic evolution of the patient's condition. These preliminary results must be confirmed in a prospective manner. LEVEL OF EVIDENCE Diagnostic Tests or Criteria; Level III

Blood pressure measurement during cesarean delivery: Evaluation of a beat-to-beat noninvasive device (NexfinTM)

International audienceABSTRACT: 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. Copyrigh

Repurposing EEG monitoring of general anaesthesia for building biomarkers of brain ageing: An exploratory study

Background: EEG is a common tool for monitoring anaesthetic depth but is rarely reused at large for biomedical research. This study sets out to explore repurposing of EEG during anaesthesia to learn biomarkers of brain ageing. Methods: We focused on brain age estimation as an example. Using machine learning, we reanalysed 4-electrodes EEG of 323 patients under propofol and sevoflurane. We included spatio-spectral features from stable anaesthesia for EEG-based age prediction applying recently published reference methods. Anaesthesia was considered stable when 95% of the total power was below a frequency between 8Hz and 13Hz. Results: We considered moderate-risk patients (ASA <= 2) with propofol anaesthesia to explore predictive EEG signatures. Average alpha-band power (8-13Hz) was informative about age. Yet, state-of-the-art prediction performance was achieved by analysing the entire power spectrum from all electrodes (MAE = 8.2y, R2 = 0.65). Clinical exploration revealed that brain age was systematically linked with intra-operative burst suppression-commonly associated with agerelated postoperative cognitive issues. Surprisingly, the brain age was negatively correlated with burst suppression in high-risk patients (ASA = 3), pointing at unknown confounding effects. Secondary analyses revealed that brain-age EEG signatures were specific to propofol anaesthesia, reflected by limited prediction performance under sevoflurane and poor cross-drug generalisation. Conclusions: EEG from general anaesthesia may enable state-of-the-art brain age prediction. Yet, differences between anaesthetic drugs can impact the effectiveness of repurposing EEG from anaesthesia. To unleash the dormant potential of repurposing EEG-monitoring for clinical and health research, collecting larger datasets with precisely documented drug dosage will be key enabling factors

Repurposing electroencephalogram monitoring of general anaesthesia for building biomarkers of brain ageing: an exploratory study

Background: Electroencephalography (EEG) is increasingly used for monitoring the depth of general anaesthesia, but EEG data from general anaesthesia monitoring are rarely reused for research. Here, we explored repurposing EEG monitoring from general anaesthesia for brain-age modelling using machine learning. We hypothesised that brain age estimated from EEG during general anaesthesia is associated with perioperative risk. Methods: We reanalysed four-electrode EEGs of 323 patients under stable propofol or sevoflurane anaesthesia to study four EEG signatures (95% of EEG power <8–13 Hz) for age prediction: total power, alpha-band power (8–13 Hz), power spectrum, and spatial patterns in frequency bands. We constructed age-prediction models from EEGs of a healthy reference group (ASA 1 or 2) during propofol anaesthesia. Although all signatures were informative, state-of-the-art age-prediction performance was unlocked by parsing spatial patterns across electrodes along the entire power spectrum (mean absolute error=8.2 yr; R2=0.65). Results: Clinical exploration in ASA 1 or 2 patients revealed that brain age was positively correlated with intraoperative burst suppression, a risk factor for general anaesthesia complications. Surprisingly, brain age was negatively correlated with burst suppression in patients with higher ASA scores, suggesting hidden confounders. Secondary analyses revealed that age-related EEG signatures were specific to propofol anaesthesia, reflected by limited model generalisation to anaesthesia maintained with sevoflurane. Conclusions: Although EEG from general anaesthesia may enable state-of-the-art age prediction, differences between anaesthetic drugs can impact the effectiveness and validity of brain-age models. To unleash the dormant potential of EEG monitoring for clinical research, larger datasets from heterogeneous populations with precisely documented drug dosage will be essential

Intraoperative Implications of the Recipients' Disease for Double-Lung Transplantation

International audienceObjectives: To compare intraoperative patterns among patients based on their primary pulmonary disease (cystic fibrosis [CF], chronic obstructive pulmonary disease [COPD]/emphysema [CE], and pulmonary fibrosis [PF]) during double- lung transplantation. The following 3 major outcomes were reported: blood transfusion, extracorporeal membrane oxygenation (ECMO) management, and the possibility of immediate extubation at the end of surgery. Design: Retrospective analysis of a prospectively maintained database, including donor and recipient characteristics and intraoperative variables. Setting: Foch Hospital, Suresnes, France (academic center performing 60-80 lung transplantations per year). Participants: Patients who underwent double- lung transplantation from 2012–2019. Patients with retransplantation, multiorgan transplantation, or surgery performed with cardiopulmonary bypass were excluded. Interventions: None. Measurements and Main Results: Two hundred forty-six patients had CF, 117 had CE, and 66 had PF. No patient had primary pulmonary arterial hypertension. Blood transfusion was higher in the CF group than in the other 2 groups (red blood cells [p < 0.001], fresh frozen plasma [p = 0.004]). The CF and CE groups were characterized by a lower intraoperative requirement of ECMO (p = 0.002), and the PF group more frequently required postoperative ECMO (p < 0.001). CF and CE patients were more frequently extubated in the operating room than were PF patients (37.4%, 50.4%, and 13.6%, respectively; p < 0.001). Conclusions: Intraoperative outcomes differed depending on the initial pathology. Such differences should be taken into account in specific clinical studies and in intraoperative management protocols

Use of pragmatic and explanatory trial designs in acute care research: lessons from COVID-19

International audienceUnique challenges arise when conducting trials to evaluate therapies already in common clinical use, including difficulty enrolling patients owing to widespread open-label use of trial therapies and the need for large sample sizes to detect small but clinically meaningful treatment effects. Despite numerous successes in trials evaluating novel interventions such as vaccines, traditional explanatory trials have struggled to provide definitive answers to time-sensitive questions for acutely ill patients with COVID-19. Pragmatic trials, which can increase efficiency by allowing some or all trial procedures to be embedded into clinical care, are increasingly proposed as a means to evaluate therapies that are in common clinical use. In this Personal View, we use two concurrently conducted COVID-19 trials of hydroxychloroquine (the US ORCHID trial and the UK RECOVERY trial) to contrast the effects of explanatory and pragmatic trial designs on trial conduct, trial results, and the care of patients managed outside of clinical trials. In view of the potential advantages and disadvantages of explanatory and pragmatic trial designs, we make recommendations for their optimal use in the evaluation of therapies in the acute care setting

Contemporary strategies to improve clinical trial design for critical care research: insights from the First Critical Care Clinical Trialists Workshop.

BACKGROUND: Conducting research in critically-ill patient populations is challenging, and most randomized trials of critically-ill patients have not achieved pre-specified statistical thresholds to conclude that the intervention being investigated was beneficial. METHODS: In 2019, a diverse group of patient representatives, regulators from the USA and European Union, federal grant managers, industry representatives, clinical trialists, epidemiologists, and clinicians convened the First Critical Care Clinical Trialists (3CT) Workshop to discuss challenges and opportunities in conducting and assessing critical care trials. Herein, we present the advantages and disadvantages of available methodologies for clinical trial design, conduct, and analysis, and a series of recommendations to potentially improve future trials in critical care. CONCLUSION: The 3CT Workshop participants identified opportunities to improve critical care trials using strategies to optimize sample size calculations, account for patient and disease heterogeneity, increase the efficiency of trial conduct, maximize the use of trial data, and to refine and standardize the collection of patient-centered and patient-informed outcome measures beyond mortality

The subset of patients with acute heart failure able to secrete relaxin-2 at pregnancy concentrations could have a longer survival: a pilot study

<p><b>Objective:</b> To investigate how many patients with acute heart failure (AHF) hypersecrete relaxin-2 concentrations similar to those of pregnant women and determine their long-term outcome.</p> <p><b>Methods:</b> In consecutive AHF patients relaxin-2 was quantified by ELISA sandwich method. Patients were divided into pregnancy-like group (PLG, relaxin-2 ≥ 500 pg/mL) and control group (CG, relaxin-2 < 500 pg/mL). The primary outcome was all-cause death during follow-up. Secondary endpoints were prolonged hospitalisation (>10 days), combined endpoint (death, rehospitalisation, ED revisit) 30 days after discharge, and 30-day, one-year and three-year death rates.</p> <p><b>Results</b>: We included 814 patients [81 (SD = 9) years; 53.0% women] followed during 1.9 (SD 2.8) years; 517 (63.5%) died. Twenty patients (2.5%) formed the PLG (median relaxin-2 = 1459 pg/mL; IQR = 1722) and 794 the CG (median = 26; IQR = 44). There was no interaction with variables included on adjustment (age, sex, ischaemic cardiomyopathy, NT-proBNP, glycaemia, and sodium). PLG patients did not have better short-term secondary endpoints, but did show a significantly lower three-year mortality [OR_adjusted = 0.17 (0.05–0.5), <i>p</i> = 0.003].</p> <p><b>Conclusions:</b> The small proportion of AHF patients achieving relaxin-2 concentrations similar to those observed in pregnancy may survive longer.</p