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Background: It remains unclear whether opioid-free anesthesia (OFA), when compared to opioid-sparing anesthesia (OSA), reduces postoperative opioid consumption while still providing adequate pain control. We thus tested the hypothesis that patients having an OFA strategy during laparoscopic colectomy would require less postoperative opioids when compared to an OSA strategy., Methods: This single-center, prospective randomized controlled superiority trial, randomly allocated consecutive patients undergoing laparoscopic colectomy to receive either sevoflurane-dexmedetomidine anesthesia with a continuous infusion of lidocaine and ketamine (OFA group) or sevoflurane-sufentanil boluses anesthesia with a continuous infusion of lidocaine (OSA group). Both groups received multimodal antinociception with boluses of dexamethasone, lidocaine, and ketamine during anesthesia induction, as well as acetaminophen, ketoprofen, and nefopam before the end of the surgery. OFA patients also received a dose of magnesium sulfate during induction. The primary outcome was cumulative opioid consumption at 48 h after surgery, expressed in oral morphine equivalents (OME). Secondary exploratory outcomes were pain scores, opioid-related adverse events, and patient quality of life (WHODAS score)., Results: Of the 160 randomized patients, 155 were included in a modified intention-to-treat analysis. Median [Q1-Q3] OME consumption at 48 h after surgery did not differ between groups (9 [0-30] mg for OFA vs. 14 [0-30] mg for OSA; p = 0.861). Key secondary outcomes were not different between groups except a three time higher incidence of bradycardia in the OFA group., Conclusions: In patients undergoing laparoscopic colectomy with a multimodal antinociception protocol, OFA, when compared to OSA, did not decrease postoperative opioid consumption., Clinical Trial Registry and Number: NCT05031234., Competing Interests: Declaration of competing interest Alexandre Joosten is consultant for Edwards Lifesciences, Irvine, CA, USA. Sean Coekelenbergh has received honoraria for presentations from Medtronic, Medasense, and Med—Storm. The other authors have no conflicts of interest to declare., (Copyright © 2024 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: Fluid therapy during major hepatic resection aims at minimizing fluids during the dissection phase to reduce central venous pressure, retrograde liver blood flow, and venous bleeding. This strategy, however, may lead to hyperlactatemia. The Acumen assisted fluid management system uses novel decision support software, the algorithm of which helps clinicians optimize fluid therapy. The study tested the hypothesis that using this decision support system could decrease arterial lactate at the end of major hepatic resection when compared to a more restrictive fluid strategy., Methods: This two-arm, prospective, randomized controlled, assessor- and patient-blinded superiority study included consecutive patients undergoing major liver surgery equipped with an arterial catheter linked to an uncalibrated stroke volume monitor. In the decision support group, fluid therapy was guided throughout the entire procedure using the assisted fluid management software. In the restrictive fluid group, clinicians were recommended to restrict fluid infusion to 1 to 2 ml · kg-1 · h-1 until the completion of hepatectomy. They then administered fluids based on advanced hemodynamic variables. Noradrenaline was titrated in all patients to maintain a mean arterial pressure greater than 65 mmHg. The primary outcome was arterial lactate level upon completion of surgery (i.e., skin closure)., Results: A total of 90 patients were enrolled over a 7-month period. The primary outcome was lower in the decision support group than in the restrictive group (median [quartile 1 to quartile 3], 2.5 [1.9 to 3.7] mmol · l-1vs. 4.6 [3.1 to 5.4] mmol · l-1; median difference, -2.1; 95% CI, -2.7 to -1.2; P < 0.001). Among secondary exploratory outcomes, there was no difference in blood loss (median [quartile 1 to quartile 3], 450 [300 to 600] ml vs. 500 [300 to 800] ml; P = 0.727), although central venous pressure was higher in the decision support group (mean ± SD of 7.7 ± 2.0 mmHg vs. 6.6 ± 1.1 mmHg; P < 0.002)., Conclusions: Patients managed using a clinical decision support system to guide fluid administration during major hepatic resection had a lower arterial lactate concentration at the end of surgery when compared to a more restrictive fluid strategy. Future trials are necessary to make conclusive recommendations that will change clinical practice., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: Implementation of goal-directed fluid therapy (GDFT) protocols remains low. Protocol compliance among anesthesiologists tends to be suboptimal owing to the high workload and the attention required for implementation. The assisted fluid management (AFM) system is a novel decision support tool designed to help clinicians apply GDFT protocols. This system predicts fluid responsiveness better than anesthesia practitioners do and achieves higher stroke volume (SV) and cardiac index values during surgery. We tested the hypothesis that an AFM-guided GDFT strategy would also be associated with better sublingual microvascular flow compared to a standard GDFT strategy., Methods: This bicenter, parallel, 2-arm, prospective, randomized controlled, patient and assessor-blinded, superiority study considered for inclusion all consecutive patients undergoing high-risk abdominal surgery who required an arterial catheter and uncalibrated SV monitoring. Patients having standard GDFT received manual titration of fluid challenges to optimize SV while patients having an AFM-guided GDFT strategy received fluid challenges based on recommendations from the AFM software. In all patients, fluid challenges were standardized and titrated per 250 mL and vasopressors were administered to maintain a mean arterial pressure >70 mm Hg. The primary outcome (average of each patient's intraoperative microvascular flow index (MFI) across 4 intraoperative time points) was analyzed using a Mann-Whitney U test and the treatment effect was estimated with a median difference between groups with a 95% confidence interval estimated using the bootstrap percentile method (with 1000 replications). Secondary outcomes included SV, cardiac index, total amount of fluid, other microcirculatory variables, and postoperative lactate., Results: A total of 86 patients were enrolled over a 7-month period. The primary outcome was significantly higher in patients with AFM (median [Q1-Q3]: 2.89 [2.84-2.94]) versus those having standard GDFT (2.59 [2.38-2.78] points, median difference 0.30; 95% confidence interval [CI], 0.19-0.49; P < .001). Cardiac index and SVI were higher (3.2 ± 0.5 vs 2.7 ± 0.7 l.min-1.m-2; P = .001 and 42 [35-47] vs 36 [32-43] mL.m-2; P = .018) and arterial lactate concentration was lower at the end of the surgery in patients having AFM-guided GDFT (2.1 [1.5-3.1] vs 2.9 [2.1-3.9] mmol.L-1; P = .026) than patients having standard GDFT strategy. Patients having AFM received a higher fluid volume but 3 times less norepinephrine than those receiving standard GDFT (P < .001)., Conclusions: Use of an AFM-guided GDFT strategy resulted in higher sublingual microvascular flow during surgery compared to use of a standard GDFT strategy. Future trials are necessary to make conclusive recommendations that will change clinical practice., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

A closed-loop automatically controls a variable using the principle of feedback. Automation within anesthesia typically aims to improve the stability of a controlled variable and reduce workload associated with simple repetitive tasks. This approach attempts to limit errors due to distractions or fatigue while simultaneously increasing compliance to evidence based perioperative protocols. The ultimate goal is to use these advantages over manual care to improve patient outcome. For more than twenty years, clinical studies in anesthesia have demonstrated the superiority of closed-loop systems compared to manual control for stabilizing a single variable, reducing practitioner workload, and safely administering therapies. This research has focused on various closed-loops that coupled inputs and outputs such as the processed electroencephalogram with propofol, blood pressure with vasopressors, and dynamic predictors of fluid responsiveness with fluid therapy. Recently, multiple simultaneous independent closed-loop systems have been tested in practice and one study has demonstrated a clinical benefit on postoperative cognitive dysfunction. Despite their advantages, these tools still require that a well-trained practitioner maintains situation awareness, understands how closed-loop systems react to each variable, and is ready to retake control if the closed-loop systems fail. In the future, multiple input multiple output closed-loop systems will control anesthetic, fluid and vasopressor titration and may perhaps integrate other key systems, such as the anesthesia machine. Human supervision will nonetheless always be indispensable as situation awareness, communication, and prediction of events remain irreplaceable human factors., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The efficacy and safety of opioid-free anaesthesia during bariatric surgery remain debated, particularly when administering multimodal analgesia. As multimodal analgesia has become the standard of care in many centres, we aimed to determine if such a strategy coupled with either dexmedetomidine (opioid-free anaesthesia) or remifentanil with a morphine transition (opioid-based anaesthesia), would reduce postoperative morphine requirements and opioid-related adverse events., Methods: In this prospective double-blind study, 172 class III obese patients having laparoscopic gastric bypass surgery were randomly allocated to receive either sevoflurane-dexmedetomidine anaesthesia with a continuous infusion of lidocaine and ketamine (opioid-free group) or sevoflurane-remifentanil anaesthesia with a morphine transition (opioid-based group). Both groups received at anaesthesia induction a bolus of magnesium, lidocaine, ketamine, paracetamol, diclofenac, and dexamethasone. The primary outcome was 24-h postoperative morphine consumption. Secondary outcomes included postoperative quality of recovery (QoR40), incidence of hypoxaemia, bradycardia, and postoperative nausea and vomiting (PONV)., Results: Eighty-six patients were recruited in each group (predominantly women, 70% had obstructive sleep apnoea). There was no significant difference in postoperative morphine consumption (median [inter-quartile range]: 16 [13-26] vs 15 [10-24] mg, P =0.183). The QoR40 up to postoperative day 30 did not differ between groups, but PONV was less frequent in the opioid-free group (37% vs 59%, P =0.005). Hypoxaemia and bradycardia were not different between groups., Conclusions: During bariatric surgery, a multimodal opioid-free anaesthesia technique did not decrease postoperative morphine consumption when compared with a multimodal opioid-based strategy. Quality of recovery did not differ between groups although the incidence of PONV was less in the opioid-free group., Clinical Trial Registration: NCT05004519., (© 2024 The Author(s).)

Intensive care unit (ICU) nurses frequently manually titrate norepinephrine to maintain a predefined mean arterial pressure (MAP) target after high-risk surgery. However, achieving this task is often suboptimal. We have developed a closed-loop vasopressor (CLV) controller to better maintain MAP within a narrow range. After ethical committee approval, fifty-three patients admitted to the ICU following high-risk abdominal surgery were randomized to CLV or manual norepinephrine titration. In both groups, the aim was to maintain MAP in the predefined target of 80-90 mmHg. Fluid administration was standardized in the two groups using an advanced hemodynamic monitoring device. The primary outcome of our study was the percentage of time patients were in the MAP target. Over the 2-hour study period, the percentage of time with MAP in target was greater in the CLV group than in the control group (median: IQR 25-75 : 80 [68-88]% vs. 42 [22-65]%), difference 37.2, 95% CI (23.0-49.2); p < 0.001). Percentage time with MAP under 80 mmHg (1 [0-5]% vs. 26 [16-75]%, p < 0.001) and MAP under 65 mmHg (0 [0-0]% vs. 0 [0-4]%, p = 0.017) were both lower in the CLV group than in the control group. The percentage of time with a MAP > 90 mmHg was not statistically different between groups. In patients admitted to the ICU after high-risk abdominal surgery, closed-loop control of norepinephrine infusion better maintained a MAP target of 80 to 90 mmHg and significantly decreased postoperative hypotensive when compared to manual norepinephrine titration., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Intravenous (IV) fluids and vasopressor agents are key components of hemodynamic management. Since their introduction, their use in the perioperative setting has continued to evolve, and we are now on the brink of automated administration. IV fluid therapy was first described in Scotland during the 1832 cholera epidemic, when pioneers in medicine saved critically ill patients dying from hypovolemic shock. However, widespread use of IV fluids only began in the 20th century. Epinephrine was discovered and purified in the United States at the end of the 19th century, but its short half-life limited its implementation into patient care. Advances in venous access, including the introduction of the central venous catheter, and the ability to administer continuous infusions of fluids and vasopressors rather than just boluses, facilitated the use of fluids and adrenergic agents. With the advent of advanced hemodynamic monitoring, most notably the pulmonary artery catheter, the role of fluids and vasopressors in the maintenance of tissue oxygenation through adequate cardiac output and perfusion pressure became more clearly established, and hemodynamic goals could be established to better titrate fluid and vasopressor therapy. Less invasive hemodynamic monitoring techniques, using echography, pulse contour analysis, and heart-lung interactions, have facilitated hemodynamic monitoring at the bedside. Most recently, advances have been made in closed-loop fluid and vasopressor therapy, which apply computer assistance to interpret hemodynamic variables and therapy. Development and increased use of artificial intelligence will likely represent a major step toward fully automated hemodynamic management in the perioperative environment in the near future. In this narrative review, we discuss the key events in experimental medicine that have led to the current status of fluid and vasopressor therapies and describe the potential benefits that future automation has to offer., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 International Anesthesia Research Society.)

Brain injury patients require precise blood pressure (BP) management to maintain cerebral perfusion pressure (CPP) and avoid intracranial hypertension. Nurses have many tasks and norepinephrine titration has been shown to be suboptimal. This can lead to limited BP control in patients that are in critical need of cerebral perfusion optimization. We have designed a closed-loop vasopressor (CLV) system capable of maintaining mean arterial pressure (MAP) in a narrow range and we aimed to assess its performance when treating severe brain injury patients. Within the first 48 h of intensive care unit (ICU) admission, 18 patients with a severe brain injury underwent either CLV or manual norepinephrine titration. In both groups, the objective was to maintain MAP in target (within ± 5 mmHg of a predefined target MAP) to achieve optimal CPP. Fluid administration was standardized in the two groups. The primary objective was the percentage of time patients were in target. Secondary outcomes included time spent over and under target. Over the four-hour study period, the mean percentage of time with MAP in target was greater in the CLV group than in the control group (95.8 ± 2.2% vs. 42.5 ± 27.0%, p < 0.001). Severe undershooting, defined as MAP < 10 mmHg of target value was lower in the CLV group (0.2 ± 0.3% vs. 7.4 ± 14.2%, p < 0.001) as was severe overshooting defined as MAP > 10 mmHg of target (0.0 ± 0.0% vs. 22.0 ± 29.0%, p < 0.001). The CLV system can maintain MAP in target better than nurses caring for severe brain injury patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Liver transplantation (LT) remains a potentially haemorrhagic procedure whose perioperative bleeding and transfusion could be better monitored using point-of-care devices. Quantra ® is a device based on sonorheometry to assess whole blood clot formation. Our aims were to describe Quantra ® parameters during LT and to study their correlations with standard laboratory parameters, and to determine Quantra ® cut-off values for thrombocytopenia, hypofibrinogenemia and coagulation factors' deficit., Methods: In 34 patients undergoing LT, blood samples were collected before surgical incision, 15 min after the beginning of the anhepatic phase, and 15 min after arterial revascularization of the graft., Results: Clotting time (CT) was well correlated with prothrombin (PT) ratio and activated partial thromboplastin time (aPTT) ratio. Platelet contribution to clot stiffness (PCS) was correlated with platelets (ρ = 0.82, p < 0.001) and fibrinogen contribution clot stiffness (FCS) with fibrinogen (Fg) (ρ = 0.74, p < 0.001). CT predicted a PT ratio < 30% with an area under the curve (AUC) of 0.93 (95% CI 0.87-0.98; p < 0.001). PCS predicted a platelet count < 50 G/L with an AUC of 0.87 (95% CI 0.76-0.98, p < 0.001). FCS predicted a Fg < 1.0, 1.2 or 1.5 g/L, with an AUC of 0.86 (95% CI 0.77-094, p < 0.001), 0.82 (95% CI 0.74-0.91, p < 0.001) and 0.88 (95% CI 0.82-0.95, p < 0.001), respectively., Conclusion: Quantra ® provides a rapid assessment of haemostasis during LT.

Introduction: Mobile health diagnostics have demonstrated effectiveness in detecting and managing chronic diseases. This method comparison study aims to assess the accuracy and precision of the previously evaluated OptiBP™ technology over a four-week study period. This device uses optical signals recorded by placing a patient's fingertip on a smartphone's camera to estimate blood pressure (BP). Methods: In adult participants without cardiac arrhythmias and minimal interarm blood pressure difference (systolic arterial pressure (SAP) < 15 mmHg or diastolic arterial pressure (DAP) < 10 mmHg), three pairs of 30 s BP measurements with the OptiBP™ (test method) were simultaneously compared using three pairs of measurements with the non-invasive oscillometric brachial cuff (reference method) on the opposite arm over a period of four consecutive weeks at a rate of two measurements per week (one in the morning and one in the afternoon). The agreement of BP values between the two technologies was analyzed using Bland-Altman and error grid analyses. The performance of the smartphone application was investigated using the International Organization for Standardization (ISO) definitions, which require the bias ± standard deviation (SD) between two technologies to be lower than 5 ± 8 mmHg. Results: Among the 65 eligible volunteers, 53 participants had adequate OptiBP™ BP values. In 12 patients, no OptiBP™ BP could be measured due to inadequate signals. Only nine participants had known chronic arterial hypertension and 76% of those patients were treated. The mean bias ± SD between both technologies was -1.4 mmHg ± 10.1 mmHg for systolic arterial pressure (SAP), 0.2 mmHg ± 6.5 mmHg for diastolic arterial pressure (DAP) and -0.5 mmHg ± 6.9 mmHg for mean arterial pressure (MAP). Error grid analyses indicated that 100% of the pairs of BP measurements were located in zones A (no risk) and B (low risk). Conclusions: In a cohort of volunteers, we observed an acceptable agreement between BP values obtained with the OptiBP TM and those obtained with the reference method over a four-week period. The OptiBP TM fulfills the ISO standards for MAP and DAP (but not SAP). The error grid analyses showed that 100% measurements were located in risk zones A and B. Despite the need for some technological improvements, this application may become an important tool to measure BP in the future.

Background: Computational modeling of physiology has become a routine element in the development, evaluation, and safety testing of many types of medical devices. Members of the Food and Drug Administration have recently published a manuscript detailing the development, validation, and sensitivity testing of a computational model for blood volume, cardiac stroke volume, and blood pressure, noting that such a model might be useful in the development of closed-loop fluid administration systems. In the present study, we have expanded on this model to include the pharmacologic effect of sodium nitroprusside and calibrated the model against our previous experimental animal model data., Methods: Beginning with the model elements in the original publication, we added six new parameters to control the effect of sodium nitroprusside: two for the onset time and clearance rates, two for the stroke volume effect (which includes venodilation as a "hidden" element), and two for the direct effect on arterial blood pressure. Using this new model, we then calibrated the predictive performance against previously collected animal study data using nitroprusside infusions to simulate shock with the primary emphasis on MAP. Root-mean-squared error (RMSE) was calculated, and the performance was compared to the performance of the model in the original study., Results: RMSE of model-predicted MAP to actual MAP was lower than that reported in the original model, but higher for SV and CO. The individually fit models showed lower RMSE than using the population average values for parameters, suggesting the fitting process was effective in identifying improved parameters. Use of partially fit models after removal of the lowest variance population parameters showed a very minor decrement in improvement over the fully fit models., Conclusion: The new model added the clinical effects of SNP and was successfully calibrated against experimental data with an RMSE of <10% for mean arterial pressure. Model-predicted MAP showed an error similar to that seen in the original base model when using fluid shifts, heart rate, and drug dose as model inputs.

Background: Liver transplant patients who develop hyperlactatemia are at increased risk of postoperative morbidity and short-term mortality, but there are few data on longer-term outcomes. We therefore investigated if arterial lactate concentration obtained immediately after surgery, at the time of admission to the intensive care unit (ICU), was associated with 1-year mortality., Methods: In this retrospective cohort study, all patients who underwent liver transplant surgery from a deceased donor between September 2013 and December 2019 were screened for inclusion. Patients who underwent combined transplantation surgery and those with a history of previous liver transplantation (ie, redo surgery) were not included. Logistic regression modeling included univariate and multivariate analyses. Receiver operating characteristic curves and areas under the curves were calculated. Lactate thresholds and association with outcome were analyzed for specificity, sensitivity, and Youden's index., Results: Of 226 patients included, 18.4% died within 1 year of liver transplantation. Immediate postoperative lactate concentration was independently associated with 1-year mortality with an adjusted odds ratio of 1.35 (95% CI 1.16-1.59; P < .001) per mmol/L increase in lactate and an area under the curve of 0.80 (95% CI 0.72-0.87; P < .001). A lactate concentration of 2.25 mmol/L (cutoff determined using Youden's index) was associated with increased 1-year mortality with a sensitivity of 0.71 and a specificity of 0.72., Conclusions: Increased arterial lactate concentration on admission to the intensive care unit immediately after orthotopic liver transplantation is independently associated with increased 1-year mortality., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: During surgery, any mismatch between oxygen delivery (DO 2 ) and consumption (VO 2 ) can promote the development of postoperative complications. The respiratory exchange ratio (RER), defined as the ratio of carbon dioxide (CO 2 ) production (VCO 2 ) to VO 2 , may be a useful noninvasive tool for detecting inadequate DO 2 . The primary objective of this study was to test the hypothesis that RER measured during liver transplantation may predict postoperative morbidity. Secondary objectives were to assess the ability of other variables used to assess the DO 2 /VO 2 relationship, including arterial lactate, mixed venous oxygen saturation, and veno-arterial difference in the partial pressure of carbon dioxide (VAPCO 2 gap), to predict postoperative complications., Methods: This retrospective study included consecutive adult patients who underwent liver transplantation for end stage liver disease from June 27th, 2020, to September 5th, 2021. Patients with acute liver failure were excluded. All patients were routinely equipped with a pulmonary artery catheter. The primary analysis was a receiver operating characteristic (ROC) curve constructed to investigate the discriminative ability of the mean RER measured during surgery to predict postoperative complications. RER was calculated at five standardized time points during the surgery, at the same time as measurement of blood lactate levels and arterial and mixed venous blood gases, which were compared as a secondary analysis., Results: Of the 115 patients included, 57 developed at least one postoperative complication. The mean RER (median [25-75] percentiles) during surgery was significantly higher in patients with complications than in those without (1.04[0.96-1.12] vs 0.88[0.84-0.94]; p < 0.001). The area under the ROC curve was 0.87 (95%CI: 0.80-0.93; p < 0.001) with a RER value (Youden index) of 0.92 giving a sensitivity of 91% and a specificity of 74% for predicting the occurrence of postoperative complications. The RER outperformed all other measured variables assessing the DO 2 /VO 2 relationship (arterial lactate, SvO 2 , and VAPCO 2 gap) in predicting postoperative complications., Conclusion: During liver transplantation, the RER can reliably predict postoperative complications. Implementing this measure intraoperatively may provide a warning for physicians of impending complications and justify more aggressive optimization of oxygen delivery. Further studies are required to determine whether correcting the RER is feasible and could reduce the incidence of complications., (© 2022. The Author(s).)

Background: Inadequate antinociception can cause haemodynamic instability. The nociception level (NOL) index measures response to noxious stimuli, but its capacity to predict optimal antinociception is unknown., Objective: To determine if NOL index change to a tetanic stimulus in cardiac and noncardiac surgery patients could predict the required remifentanil concentration for haemodynamic stability at skin incision., Design: A prospective two-phase cohort study., Setting: University hospital., Patients: Patients undergoing remifentanil-propofol target controlled infusion (TCI) anaesthesia., Interventions: During the calibration phase, investigators evaluated the tetanic stimulus induced NOL index change under standardised TCI remifentanil-propofol anaesthesia during a no-touch period [bispectral index (BIS) between 40 and 60, NOL index under 15]. If the NOL index change was 20 or greater following tetanic stimulation, investigators repeated the tetanus at higher remifentanil concentrations until the response was blunted. Surgeons incised the skin at this remifentanil concentration. The investigators derived a prediction model and in the validation phase calculated, using the NOL response to a single tetanus, the required incision remifentanil concentration for the start of surgery., Main Outcome: Haemodynamic stability at incision [i.e. maximum heart rate (HR) < 20% increase from baseline, minimum HR (40 bpm) and mean arterial pressure (MAP) ± <20% of baseline]., Results: During the calibration phase, no patient had hypertension. Two patients had a HR increase slightly greater than 20% (25.4 and 26.7%) within the first 2 min of surgery, but neither of these two patients had a HR above 76 bpm. Two patients were slightly hypotensive after incision (MAP 64 and 73 mmHg). During the validation phase, neither tachycardia nor hypotension occurred, but MAP increased to 21.5% above baseline for one patient., Conclusion: During a no-touch period in patients under steady-state general anaesthesia [propofol effect site concentration (Ce) required for BIS between 40 and 60], the NOL index response to a tetanic stimulus under remifentanil antinociception can be used to personalise remifentanil Ce for the start of surgery and ensure stable haemodynamics., Trial Registration: ClinicalTrials.gov: NCT03324269., (Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Current trends in anesthetic depth (i.e., hypnosis) and antinociception monitoring are unclear. We thus aimed to determine contemporary perspectives on monitoring these components of anesthesia during general anesthesia. Participants received and responded anonymously to an internet-based international survey supported by the European Society of Anaesthesiology and Intensive Care. Comparisons, when applicable, were carried out using Chi 2 analysis or Fischer's exact test. A total of 564 respondents, predominantly from Europe (80.1%), participated. There was a strong participation from Belgium (11.5%). A majority (70.9%) of anesthetists considered hypnotic monitoring important on most occasions to always. In contrast, a majority (62.6%) never or only occasionally considered antinociception monitoring important. This difference in the perceived importance of anesthetic depth versus antinociception monitoring was significant (p < 0.0001). A majority of respondents (70.1%) believed that guiding hypnosis and antinociception using these monitors would improve patient care on most occasions to always. Nonetheless, a substantial number of participants were unsure if hypnotic (23%) or antinociception (32%) monitoring were recommended and there was a lack of knowledge (58%) of any published algorithms to titrate hypnotic and/or antinociceptive drugs based on the information provided by the monitors. In conclusion, current trends in European academic centers prioritize anesthesia depth over antinociception monitoring. Despite an agreement among respondents that applying strategies that optimize anesthetic depth and antinociception could improve outcome, there remains a lack of knowledge of appropriate algorithms. Future studies and recommendations should focus on clarifying goal-directed anesthetic strategies and determine their impact on perioperative patient outcome., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Vasopressor infusions are essential in treating and preventing intraoperative hypotension. Closed-loop vasopressor therapy outperforms clinicians when the target is set at a mean arterial pressure (MAP) baseline, but little is known on the performance metrics of closed-loop vasopressor infusions when systolic arterial pressure (SAP) is the controlled variable. Methods: Patients undergoing intermediate- to high-risk abdominal surgery were included in this prospective cohort feasibility study. All patients received norepinephrine infusion through a computer controlled closed-loop system that targeted SAP at 130 mmHg. The primary objective was to determine the percent of case time in hypotension or under target defined as SAP below 10% of the target (SAP < 117 mmHg). Secondary objectives were the percent of case time “above target” (SAP > 10% of the target or >143 mmHg) and “in target” (within 10% of the SAP target or SAP between 117 and 143 mmHg). Results: A total of 12 patients were included. The closed-loop system infused norepinephrine for a median of 94.6% (25−75th percentile: 90.0−98.0%) of case time. The percentage of case time in hypotension or under target was only 1.8% (0.9−3.6%). The percentages of case time “above target” and “in target” were 4.7% (3.2−7.5%) and 92.4% (90.1−96.3%), respectively. Conclusions: This closed-loop vasopressor system minimizes intraoperative hypotension and maintains SAP within 10% of the target range for >90% of the case time in patients undergoing intermediate- to high-risk abdominal surgery.

Background: A mismatch between oxygen delivery (DO 2 ) and consumption (VO 2 ) is associated with increased perioperative morbidity and mortality. Hyperlactatemia is often used as an early screening tool, but this non-continuous measurement requires intermittent arterial line sampling. Having a non-invasive tool to rapidly detect inadequate DO 2 is of great clinical relevance. The respiratory exchange ratio (RER) can be easily measured in all intubated patients and has been shown to predict postoperative complications. We therefore aimed to assess the discriminative ability of the RER to detect an inadequate DO 2 as reflected by hyperlactatemia in patients having intermediate-to-high risk abdominal surgery., Methods: This historical cohort study included all consecutive patients who underwent intermediate-to-high risk surgery from January 1st, 2014, to April 30th, 2019 except those who did not have RER and/or arterial lactate measured. Blood lactate levels were measured routinely at the beginning and end of surgery and RER was calculated at the same moment as the blood gas sampling. The present study tested the hypothesis that RER measured at the end of surgery could detect hyperlactatemia at that time. A receiver operating characteristic (ROC) curve was constructed to assess if RER calculated at the end of the surgery could detect hyperlactatemia. The chosen RER threshold corresponded to the highest value of the sum of the specificity and the sensitivity (Youden Index)., Results: Among the 996 patients available in our study cohort, 941 were included and analyzed. The area under the ROC curve was 0.73 (95% CI: 0.70 to 0.76; p < 0.001), with a RER threshold of 0.75, allowing to discriminate a lactate > 1.5 mmol/L with a sensitivity of 87.5% and a specificity of 49.5%., Conclusion: In mechanically ventilated patients undergoing intermediate to high-risk abdominal surgery, the RER had moderate discriminative abilities to detect hyperlactatemia. Increased values should prompt clinicians to investigate for the presence of hyperlactatemia and treat any potential causes of DO 2 /VO 2 mismatch as suggested by the subsequent presence of hyperlactatemia., (© 2022. The Author(s).)

Objectives: To determine if venoarterial extracorporeal membrane oxygenation (VA ECMO) as a bridge to left ventricular assist device (LVAD) in heart transplant (HT) candidates (ie, double bridge to HT) was associated with increased morbidity and mortality when compared to LVAD bridging to HT (ie, single bridge to HT)., Design: A retrospective analysis of patients undergoing LVAD support from 2011 to 2020. A Kaplan-Meier survival curve and Cox-Mantel hazard ratios (HR) were calculated during LVAD support and after HT. Postoperative complications were collected., Setting: University Hospital Erasme., Participants: HT candidates requiring LVAD., Interventions: VA ECMO bridging to LVAD (ECMO-LVAD group [n = 24]) versus LVAD (LVAD group [n = 64])., Measurements and Main Results: Eighty-eight patients underwent HeartWare LVAD (HVAD, Medtronic) placement. Survival to hospital discharge and during the entire study period were lower in the ECMO-LVAD group (66.7% v 92.2%; p = 0.0027, and 37.5% v 62.5%; p = 0.035, respectively). Overall HR of death was 2.46 (95% confidence interval [CI]: 1.13-5.37; p = 0.005) in the ECMO-LVAD group and remained elevated throughout their time on LVAD support (HR 3.24 [95% CI: 1.15-9.14]; p = 0.0036). However, in patients who underwent HT (n = 50), mortality was similar between groups (HR 1.33 [95% CI: 0.33-5.31]; p = 0.66). Postoperative complications were more frequent in the ECMO-LVAD group (infection = 83.3% v 51.6%, p = 0.007; renal replacement therapy = 45.8% v 9.4%, p = 0.0001; post-LVAD ECMO = 25.0% v 1.6%; p = 0.0003)., Conclusions: VA ECMO as a bridge to LVAD support before HT was associated with increased morbidity and mortality during LVAD support. However, in patients who underwent HT, outcomes were similar regardless of VA ECMO bridging., Competing Interests: Declaration of Competing Interest Sean Coeckelenbergh received honoraria from Medtronic, outside the submitted context of the work. Fabio Taccone received honoraria from Eurosets, outside the submitted context of the submitted work. The other authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Although fluid administration is a key strategy to optimise haemodynamic status and tissue perfusion, optimal fluid administration during liver surgery remains controversial., Objective: To test the hypothesis that a goal-directed fluid therapy (GDFT) strategy, when compared with a conventional fluid strategy, would better optimise systemic blood flow and lead to improved urethral tissue perfusion (a new variable to assess peripheral blood flow), without increasing blood loss., Design: Single-centre prospective randomised controlled superiority study., Setting: Erasme Hospital., Patients: Patients undergoing liver surgery., Intervention: Forty patients were randomised into two groups: all received a basal crystalloid infusion (maximum 2 ml kg-1 h-1). In the conventional fluid group, the goal was to maintain central venous pressure (CVP) as low as possible during the dissection phase by giving minimal additional fluid, while in the posttransection phase, anaesthetists were free to compensate for any presumed fluid deficit. In the GDFT group, patients received in addition to the basal infusion, multiple minifluid challenges of crystalloid to maintain stroke volume (SV) variation less than 13%. Noradrenaline infusion was titrated to keep mean arterial pressure more than 65 mmHg in all patients., Main Outcome Measure: The mean intra-operative urethral perfusion index., Results: The mean urethral perfusion index was significantly higher in the GDFT group than in the conventional fluid group (8.70 [5.72 to 13.10] vs. 6.05 [4.95 to 8.75], P = 0.046). SV index (ml m-2) and cardiac index (l min-1 m-2) were higher in the GDFT group (48 ± 9 vs. 33 ± 7 and 3.5 ± 0.7 vs. 2.4 ± 0.4, respectively; P < 0.001). Although CVP was higher in the GDFT group (9.3 ± 2.5 vs. 6.5 ± 2.9 mmHg; P = 0.003), intra-operative blood loss was not significantly different in the two groups., Conclusion: In patients undergoing liver surgery, a GDFT strategy resulted in a higher mean urethral perfusion index than did a conventional fluid strategy and did not increase blood loss despite higher CVP., Trial Registration: NCT04092608., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: The effect of dexmedetomidine on Nociception Level Index-guided (Medasense, Israel) antinociception to reduce intra-operative opioid requirements has not been previously investigated., Objective: We aimed to determine if low-dose dexmedetomidine would reduce remifentanil requirements during Nociception Level Index-guided antinociception without increasing complications associated with dexmedetomidine., Design: Double-blind randomised controlled trial., Setting: Two university teaching hospitals in Brussels, Belgium., Patients: American Society of Anesthesiologists 1 and 2 patients (n = 58) undergoing maxillofacial or cervicofacial surgery under propofol--remifentanil target-controlled infusion anaesthesia., Interventions: A 30 min infusion of dexmedetomidine, or equal volume of 0.9% NaCl, was infused at 1.2 μg kg-1 h-1 immediately preceding induction and then decreased to 0.6 μg kg-1 h-1 until 30 min before ending surgery. Nociception Level Index and frontal electroencephalogram guided the remifentanil and propofol infusions, respectively., Main Outcomes: The primary outcome was the remifentanil requirement. Other outcomes included the propofol requirement, cardiovascular status and postoperative outcome., Results: Mean ± SD remifentanil (3.96 ± 1.95 vs. 4.42 ± 2.04 ng ml-1; P = 0.0024) and propofol (2.78 ± 1.36 vs. 3.06 ± 1.29 μg ml-1; P = 0.0046) TCI effect site concentrations were lower in the dexmedetomidine group at 30 min postincision and remained lower throughout surgery. When remifentanil (0.133 ± 0.085 vs. 0.198 ± 0.086 μg kg-1 min-1; P = 0.0074) and propofol (5.7 ± 2.72 vs. 7.4 ± 2.80 mg kg-1 h-1; P = 0.0228) requirements are represented as infusion rates, this effect became statistically significant at 2 h postincision., Conclusion: In ASA 1 and 2 patients receiving Nociception Level Index-guided antinociception, dexmedetomidine decreases intra-operative remifentanil requirements. Combined frontal electroencephalogram and Nociception Level Index monitoring can measure dexmedetomidine's hypnotic and opioid-sparing effects during remifentanil-propofol target-controlled infusion anaesthesia., Trial Registrations: Clinicaltrials.gov: NCT03912740, EudraCT: 2018-004512-22., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Perioperative fluid management - including the type, dose, and timing of administration -directly affects patient outcome after major surgery. The objective of fluid administration is to optimize intravascular fluid status to maintain adequate tissue perfusion. There is continuing controversy around the perioperative use of crystalloid versus colloid fluids. Unfortunately, the importance of fluid volume, which significantly influences the benefit-to-risk ratio of each chosen solution, has often been overlooked in this debate., Main Text: The volume of fluid administered during the perioperative period can influence the incidence and severity of postoperative complications. Regrettably, there is still huge variability in fluid administration practices, both intra-and inter-individual, among clinicians. Goal-directed fluid therapy (GDFT), aimed at optimizing flow-related variables, has been demonstrated to have some clinical benefit and has been recommended by multiple professional societies. However, this approach has failed to achieve widespread adoption. A closed-loop fluid administration system designed to assist anesthesia providers in consistently applying GDFT strategies has recently been developed and tested. Such an approach may change the crystalloid versus colloid debate. Because colloid solutions have a more profound effect on intravascular volume and longer plasma persistence, their use in this more "controlled" context could be associated with a lower fluid balance, and potentially improved patient outcome. Additionally, most studies that have assessed the impact of a GDFT strategy on the outcome of high-risk surgical patients have used hydroxyethyl starch (HES) solutions in their protocols. Some of these studies have demonstrated beneficial effects, while none of them has reported severe complications., Conclusions: The type and volume of fluid used for perioperative management need to be individualized according to the patient's hemodynamic status and clinical condition. The amount of fluid given should be guided by well-defined physiologic targets. Compliance with a predefined hemodynamic protocol may be optimized by using a computerized system. The type of fluid should also be individualized, as should any drug therapy, with careful consideration of timing and dose. It is our perspective that HES solutions remain a valid option for fluid therapy in the perioperative context because of their effects on blood volume and their reasonable benefit/risk profile.

Perioperative goal-directed hemodynamic therapy (GDHT) has evolved from invasive "supra-physiological" maximization of oxygen delivery to minimally or even noninvasively guided automated stroke volume optimization. Over the past four decades, investigators have simultaneously developed novel monitors, updated strategies, and automated technologies to improve GDHT. Decision support technology, which proposes an intervention based on the patient's real time physiologic status, was an important step towards automation. Closed-loop systems have now been created to both increase GDHT compliance and decrease physician workload. These automated systems offer an elegant approach to optimize cardiac output and end-organ perfusion during the perioperative period. Most notably, automated preload optimization guided by dynamic indicators of fluid responsiveness has shown its feasibility, safety, and impact. Making the leap into fully automated GDHT has been accomplished on a small scale, but there are considerable challenges that must be surpassed before integrating all hemodynamic components into an automated system during general anesthesia. In this review, we will discuss the evolution and potential future of automated GDHT during the perioperative period.

Perioperative complications related to obstructive sleep apnea still occur despite the use of partial pressure end-tidal CO 2 [Formula: see text] and pulse oximetry. Airway obstruction can complicate propofol sedation and a novel monitor combining mandibular movement analysis with capnography may facilitate its detection. Patients scheduled for sleep endoscopy were recruited and monitored with standard monitoring, [Formula: see text] and Jaw Activity (JAWAC) mandibular movement sensors. A post hoc analysis investigated airway obstruction prediction using a Respiratory Effort Sequential Detection Algorithm (RESDA) based on [Formula: see text] and mandibular movement signals. 21 patients were recruited and 54 episodes of airway obstruction occurred. RESDA detected obstructive apnea [mean ± SD (median)] 29 ± 29 (21) s, p < 0.0001, before [Formula: see text] alone. This prolonged the time between obstructive apnea detection and decrease to 90% oxygen saturation 64 ± 38 (54) versus 38 ± 20 (35) s, p < 0.0001. It predicted airway obstruction with a sensitivity and specificity of 81% and 93%, respectively. The RESDA algorithm, which is based on the combination of capnography with mandibular movement assessment of respiratory effort, can more rapidly alarm anesthetists of airway obstruction during propofol sedation than [Formula: see text] alone. However, [Formula: see text] pulse oximetry, and clinical monitoring are still required.Trial Registry numbers: ClinicalTrial.gov (NCT02909309) https://clinicaltrials.gov/ct2/show/NCT02909309 .

Objective: Hypotension, defined as a mean arterial pressure of maximum 70 mmHg, is associated with significant morbidity and mortality. The objective of this study was to determine in initially non-critical hypotensive adult patients the proportion of sepsis and if septic patients had different outcome and clinical factors than non-septic patients., Methods: This retrospective observational study was conducted over a year on adult hypotensive emergency department patients initially considered by triage as non-critical. Patients were separated into three groups: hypotensive septic patients (HSP), hypotensive non-septic infected patients (HNSIP), and other hypotensive patients (OHP). Clinical scores, signs, length of stay (LOS), and mortality were compared using analysis of variance for continuous variables and chi-square analysis for categorical variables., Results: There were 136 (35.5%) septic patients, 37 (9.7%) with non-septic infection, and 210 (54.8%) with another cause of hypotension. Overall in-hospital mortality was 12.0% and total mortality was greater in HSP than in HNSIP (20.6% vs. 5.4%, p = 0.031) or OHP (20.6 vs. 7.6%, p < 0.001). LOS was greater for HSP when compared to HNSIP (median(IQR): 9(6-17) vs. 6(1-13), p = 0.004) and OHP (median(IQR): 9(6-17) vs. 3(1-8) days, p < 0.0001)., Conclusion: Sepsis in a priori non-critical hypotensive adult patients, when compared with other causes of hypotension, is associated with significantly higher mortality and increased LOS. Patients that present to the emergency department and have a MAP of 70mmHg or less must be rigorously evaluated and have consistent follow-up., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Advances in noninvasive hemodynamic monitoring systems allow delivery of goal-directed fluid therapy and could therefore be used in less-invasive surgical procedures. In this randomized controlled trial, we compared closed-loop-assisted goal-directed fluid therapy using a noninvasive cardiac output (Clearsight system) monitor (personalized approach) to a protocolized fluid therapy approach in 40 patients undergoing moderate-risk laparoscopic abdominal surgery. Cardiac output and stroke volume variations were not significantly different in both groups and remained within predefined target values >90% of the study time. Personalized fluid therapy does not seem to offer any hemodynamic advantage over a protocolized approach in this population.

Background: Goal-directed fluid therapy (GDFT) based on dynamic indicators of fluid responsiveness has been shown to decrease postoperative complications and hospital length of stay (LOS) in patients undergoing major abdominal surgery. The usefulness of this approach still needs to be clarified in low-to-moderate risk abdominal surgery. Both pulse-pressure variation (PPV) and pleth variability index (PVI) can be used to guide GDFT strategies. The objective of this prospective randomized controlled trial was to determine if the use of PVI guided GDFT, when compared to PPV guided GDFT, would lead to similar hospital LOS in patients undergoing low-to-moderate risk surgery. Secondary outcomes included amount of fluid administered and incidence of postoperative complications., Methods: Patients were randomized into either PVI or PPV guided GDFT groups. Both received a baseline 2 ml kg - 1  h - 1 Lactated Ringer infusion. Additional fluid boluses consisted of 250 mL of colloid that was infused over a 10 min period if PVI was > 15% or PPV was > 13% for at least five minutes. The primary outcome was to determine if hospital LOS, which was defined as the number of days from surgery up to the day the surgeon authorized hospital discharge, was equivalent between the two groups., Results: A total of 76 patients were included and they were randomized into two groups of 38 patients. Baseline characteristics were similar in both groups. Both PVI and PPV guided GDFT strategies were equivalent for the primary outcome of LOS (median [interquartile range]) (days) 2.5 [2.0-3.3] vs. 3.0 [2.0-5.0], p = 0.230, respectively. Fluids infused, postoperative complications, and all other outcomes were not different between groups., Conclusion: In patients undergoing low-to-moderate risk abdominal surgery, PVI seems to guide GDFT similarly to PPV in regards to hospital LOS, amount of fluid, and incidence of postoperative complications. However, in low-risk patients undergoing these surgical procedures optimizing stroke volume may have limited impact on outcome., Trial Registration: ClinicalTrials.gov Identifier: NCT02908256 , September 2016, retrospectively registered.

Background: Goal-directed fluid therapy (GDFT) has been associated with improved patient outcomes. However, implementation of GDFT protocols remains low despite growing published evidence and the recommendations of multiple regulatory bodies in Europe. We developed a closed-loop-assisted GDFT management system linked to a pulse contour monitor to assist anaesthesiologists in applying GDFT., Objective: To assess the impact of our closed-loop system in patients undergoing major abdominal surgery in an academic hospital without a GDFT programme., Design: A case-control study with propensity matching., Setting: Operating rooms, Erasme Hospital, Brussels., Patients: All patients who underwent elective open major abdominal surgery between January 2013 and December 2016., Intervention: Implementation of our closed-loop-assisted GDFT in April 2015., Methods: A total of 104 patients managed with closed-loop-assisted GDFT were paired with a historical cohort of 104 consecutive non-GDFT patients. The historical control group consisted of patients treated before the implementation of the closed-loop-system, and who did not receive GDFT. In the closed-loop group, the system delivered a baseline crystalloid infusion of 3 ml kg h and additional 100 ml fluid boluses of either a crystalloid or colloid for haemodynamic optimisation., Main Outcome Measures: The primary outcome was intra-operative net fluid balance. Secondary outcomes were composite major postoperative complications, composite minor postoperative complications and hospital length of stay (LOS)., Results: Baseline characteristics were similar in both groups. Patients in the closed-loop group had a lower net intra-operative fluid balance compared with the historical group (median interquartile range [IQR] 2.9 [1.6 to 4.4] vs. 6.2 [4.0 to 8.3] ml kg h; P < 0.001). Incidences of major and minor postoperative complications were lower (17 vs. 32%, P = 0.015 and 31 vs. 45%, P = 0.032, respectively) and hospital LOS shorter [median (IQR) 10 (6 to 15) vs. 12 (9 to 18) days, P = 0.022] in the closed-loop group., Conclusion: Implementation of our closed-loop-assisted GDFT strategy resulted in a reduction in intra-operative net fluid balance, which was associated with reduced postoperative complications and shorter hospital LOS., Trial Registration Number: NCT02978430.