Perioperative Fluid and Vasopressor Therapy in 2050: From Experimental Medicine to Personalization Through Automation.

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.

The Urethral Perfusion Index During Off-Pump Coronary Artery Bypass Surgery: An Observational Study.

OBJECTIVES: The IKORUS system (Vygon, Écouen, France) allows continuous monitoring of the urethral perfusion index (uPI) using a photoplethysmographic sensor mounted near the base of the balloon of a dedicated urinary catheter. We aimed to test the hypothesis that the uPI decreases during off-pump coronary artery bypass (OPCAB) surgery and to investigate the relationship between the uPI and macrocirculatory variables. DESIGN: Prospective observational study. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PARTICIPANTS: Twenty patients having OPCAB surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was changes in the uPI during OPCAB surgery. We additionally investigated associations between the uPI and cardiac output, mean arterial pressure, heart rate, and point-of-care variables. Twenty patients with 24,137 uPI measurements were included. Overall, there was a high interindividual variability in the uPI. Compared with the preparation phase (during which the median [interquartile range] uPI was 7.7 [5.6-12.0]), the uPI decreased by 14% (95% CI 13%-15%) during the bypass grafting phase, by 35% (95% CI 34%-36%) during the cardiac positioning phase, and by 7% (95% CI 6%-9%) during hemostasis. There was no clinically important association between uPI and either cardiac output, mean arterial pressure, or heart rate. CONCLUSIONS: The uPI decreases during OPCAB surgery, specifically during the cardiac positioning phase. There was no clinically important association between uPI and either cardiac output, mean arterial pressure, or heart rate. It, therefore, remains to be determined whether intraoperative uPI decreases are clinically important, reflect alterations in intra-abdominal tissue perfusion that are not reflected by systemic macrohemodynamics, and can help clinicians guide therapeutic interventions.

Closing the loop: automation in anesthesiology is coming.

Anesthesiology and intensive care medicine provide fertile ground for innovation in automation, but to date we have only achieved preliminary studies in closed-loop intravenous drug administration. Anesthesiologists have yet to implement these tools on a large scale despite clear evidence that they outperform manual titration. Closed-loops continuously assess a predefined variable as input into a controller and then attempt to establish equilibrium by administering a treatment as output. The aim is to decrease the error between the closed-loop controller's input and output. In this editorial we consider the available intravenous anesthesia closed-loop systems, try to clarify why they have not yet been implemented on a large scale, see what they offer, and propose the future steps towards automation in anesthesia.

Closed-loop anesthesia: foundations and applications in contemporary perioperative medicine.

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.

Control of mean arterial pressure using a closed-loop system for norepinephrine infusion in severe brain injury patients: the COMAT randomized controlled trial.

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.

Tight control of mean arterial pressure using a closed loop system for norepinephrine infusion after high-risk abdominal surgery: a randomized controlled trial.

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: IQR25-75: 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.

Intraoperative blood pressure: could less be more?

Retrospective observational studies have reported a significant association between intraoperative hypotension and postoperative morbidity. However, association does not imply causation, and whether preventing intraoperative hypotension can improve patient outcome remains to be demonstrated. In this issue of the British Journal of Anaesthesia, D'Amico and colleagues meta-analysed 10 prospective randomised trials comparing low (≤60 mm Hg) and higher mean arterial pressure targets during anaesthesia and surgery. They did not observe an increase in postoperative morbidity and mortality in the low target group. In contrast, they reported a statistically significant (but not clinically relevant) reduction in postoperative cardiac arrhythmia and hospital length of stay when targeting mean arterial pressure ≤60 mm Hg. These findings suggest that during most surgical cases, intraoperative hypotension is a marker of the severity, frailty, or both rather than a mediator of postoperative complications.

Diagnostic accuracy of the peripheral venous pressure variation induced by an alveolar recruitment maneuver to predict fluid responsiveness during high-risk abdominal surgery.

BACKGROUND: In patients undergoing high-risk surgery, it is recommended to titrate fluid administration using stroke volume or a dynamic variable of fluid responsiveness (FR). However, this strategy usually requires the use of a hemodynamic monitor and/or an arterial catheter. Recently, it has been shown that variations of central venous pressure (ΔCVP) during an alveolar recruitment maneuver (ARM) can predict FR and that there is a correlation between CVP and peripheral venous pressure (PVP). This prospective study tested the hypothesis that variations of PVP (ΔPVP) induced by an ARM could predict FR. METHODS: We studied 60 consecutive patients scheduled for high-risk abdominal surgery, excluding those with preoperative cardiac arrhythmias or right ventricular dysfunction. All patients had a peripheral venous catheter, a central venous catheter and a radial arterial catheter linked to a pulse contour monitoring device. PVP was always measured via an 18-gauge catheter inserted at the antecubital fossa. Then an ARM consisting of a standardized gas insufflation to reach a plateau of 30 cmH2O for 30 s was performed before skin incision. Invasive mean arterial pressure (MAP), pulse pressure, heart rate, CVP, PVP, pulse pressure variation (PPV), and stroke volume index (SVI) were recorded before ARM (T1), at the end of ARM (T2), before volume expansion (T3), and one minute after volume expansion (T4). Receiver-operating curves (ROC) analysis with the corresponding grey zone approach were performed to assess the ability of ∆PVP (index test) to predict FR, defined as an ≥ 10% increase in SVI following the administration of a 4 ml/kg balanced crystalloid solution over 5 min. RESULTS: ∆PVP during ARM predicted FR with an area under the ROC curve of 0.76 (95%CI, 0.63 to 0.86). The optimal threshold determined by the Youden Index was a ∆PVP value of 5 mmHg (95%CI, 4 to 6) with a sensitivity of 66% (95%CI, 47 to 81) and a specificity of 82% (95%CI, 63 to 94). The AUC's for predicting FR were not different between ΔPVP, ΔCVP, and PPV. CONCLUSION: During high-risk abdominal surgery, ∆PVP induced by an ARM can moderately predict FR. Nevertheless, other hemodynamic variables did not perform better.

Perioperative clinical practice in liver transplantation: a cross-sectional survey.

PURPOSE: The objective of this study was to describe some components of the perioperative practice in liver transplantation as reported by clinicians. METHODS: We conducted a cross-sectional clinical practice survey using an online instrument containing questions on selected themes related to the perioperative care of liver transplant recipients. We sent email invitations to Canadian anesthesiologists, Canadian surgeons, and French anesthesiologists specialized in liver transplantation. We used five-point Likert-type scales (from "never" to "always") and numerical or categorical answers. Results are presented as medians or proportions. RESULTS: We obtained answers from 130 participants (estimated response rate of 71% in Canada and 26% in France). Respondents reported rarely using transesophageal echocardiography routinely but often using it for hemodynamic instability, often using an intraoperative goal-directed hemodynamic management strategy, and never using a phlebotomy (medians from ordinal scales). Fifty-nine percent of respondents reported using a restrictive fluid management strategy to manage hemodynamic instability during the dissection phase. Forty-two percent and 15% of respondents reported using viscoelastic tests to guide intraoperative and postoperative transfusions, respectively. Fifty-four percent of respondents reported not pre-emptively treating preoperative coagulations disturbances, and 91% reported treating them intraoperatively only when bleeding was significant. Most respondents (48-64%) did not have an opinion on the maximal graft ischemic times. Forty-seven percent of respondents reported that a piggyback technique was the preferred vena cava anastomosis approach. CONCLUSION: Different interventions were reported to be used regarding most components of perioperative care in liver transplantation. Our results suggest that significant equipoise exists on the optimal perioperative management of this population.

RéSUMé: OBJECTIF: L'objectif de cette étude était de décrire certaines composantes de la pratique périopératoire en transplantation hépatique telles que rapportées par les cliniciens. MéTHODE: Nous avons mené un sondage transversal sur la pratique clinique à l'aide d'un instrument en ligne comportant des questions sur des thèmes sélectionnés liés aux soins périopératoires des receveurs de greffe du foie. Nous avons envoyé des invitations par courriel à des anesthésiologistes canadiens, des chirurgiens canadiens et des anesthésiologistes français spécialisés en transplantation hépatique. Nous avons utilisé des échelles de type Likert à cinq points (de « jamais ¼ à « toujours ¼) et des réponses numériques ou catégorielles. Les résultats sont présentés sous forme de médianes ou de proportions. RéSULTATS: Nous avons obtenu des réponses de 130 participants (taux de réponse estimé à 71 % au Canada et à 26 % en France). Les répondants ont déclaré utiliser rarement l'échocardiographie transœsophagienne de routine, mais l'utiliser fréquemment pour l'instabilité hémodynamique, souvent en utilisant une stratégie de prise en charge hémodynamique peropératoire axée sur les objectifs, et jamais en utilisant une phlébotomie (médianes des échelles ordinales). Cinquante-neuf pour cent des répondants ont déclaré utiliser une stratégie restrictive de gestion liquidienne pour prendre en charge l'instabilité hémodynamique pendant la phase de dissection. Quarante-deux pour cent et 15 % des répondants ont déclaré utiliser des tests viscoélastiques pour guider les transfusions peropératoires et postopératoires, respectivement. Cinquante-quatre pour cent des répondants ont déclaré ne pas traiter préventivement les troubles préopératoires de la coagulation, et 91 % ont déclaré les traiter en peropératoire uniquement lorsque les saignements étaient importants. La plupart des répondants (48-64 %) n'avaient pas d'opinion sur les temps ischémiques maximaux du greffon. Quarante-sept pour cent des répondants ont déclaré qu'une technique de 'piggyback' (anastomose latéroterminale) était l'approche préférée pour l'anastomose de la veine cave. CONCLUSION: Différentes interventions ont été signalées pour la plupart des composantes des soins périopératoires dans la transplantation hépatique. Nos résultats suggèrent qu'il existe une incertitude significative concernant la prise en charge périopératoire optimale de cette population.

Control of Postoperative Hypotension Using a Closed-Loop System for Norepinephrine Infusion in Patients After Cardiac Surgery: A Randomized Trial.

BACKGROUND: Vasopressors are a cornerstone for the management of vasodilatory hypotension. Vasopressor infusions are currently adjusted manually to achieve a predefined arterial pressure target. We have developed a closed-loop vasopressor (CLV) controller to help correct hypotension more efficiently during the perioperative period. We tested the hypothesis that patients managed using such a system postcardiac surgery would present less hypotension compared to patients receiving standard management. METHODS: A total of 40 patients admitted to the intensive care unit (ICU) after cardiac surgery were randomized into 2 groups for a 2-hour study period. In all patients, the objective was to maintain mean arterial pressure (MAP) between 65 and 75 mm Hg using norepinephrine. In the CLV group, the norepinephrine infusion was controlled via the CLV system; in the control group, it was adjusted manually by the ICU nurse. Fluid administration was standardized in both groups using an assisted fluid management system linked to an advanced hemodynamic monitoring system. The primary outcome was the percentage of time patients were hypotensive, defined as MAP <65 mm Hg, during the study period. RESULTS: Over the 2-hour study period, the percentage of time with hypotension was significantly lower in the CLV group than that in the control group (1.4% [0.9-2.3] vs 12.5% [9.9-24.3]; location difference, -9.8% [95% CI, -5.4 to -15.9]; P < .001). The percentage of time with MAP between 65 and 75 mm Hg was also greater in the CLV group (95% [89-96] vs 66% [59-77]; location difference, 27.6% [95% CI, 34.3-19.0]; P < .001). The percentage of time with an MAP >75 mm Hg (and norepinephrine still being infused) was also significantly lower in patients in the CLV group than that in the control group (3.2% [1.9-5.4] vs 20.6% [8.9-32.5]; location difference, -17% [95% CI, -10 to -24]; P < .001).The number of norepinephrine infusion rate modifications over the study period was greater in the CLV group than that in the control group (581 [548-597] vs 13 [11-14]; location difference, 568 [578-538]; P < .001). No adverse event occurred during the study period in both groups. CONCLUSIONS: Closed-loop control of norepinephrine infusion significantly decreases postoperative hypotension compared to manual control in patients admitted to the ICU after cardiac surgery.

Evaluation of a novel optical smartphone blood pressure application: a method comparison study against invasive arterial blood pressure monitoring in intensive care unit patients.

BACKGROUND: Arterial hypertension is a worldwide public health problem. While it is currently diagnosed and monitored non-invasively using the oscillometric method, having the ability to measure blood pressure (BP) using a smartphone application could provide more widespread access to hypertension screening and monitoring. In this observational study in intensive care unit patients, we compared blood pressure values obtained using a new optical smartphone application (OptiBP™; test method) with arterial BP values obtained using a radial artery catheter (reference method) in order to help validate the technology. METHODS: We simultaneously measured three BP values every hour for five consecutive hours on two consecutive days using both the smartphone and arterial methods. Bland-Altman and error grid analyses were used for agreement analysis between both approaches. The performance of the smartphone application was investigated using the Association for the Advancement of Medical Instrumentation (AAMI) and the International Organization for Standardization (ISO) definitions, which require the bias ± SD between two technologies to be below 5 ± 8 mmHg. RESULTS: Among the 30 recruited patients, 22 patients had adequate OptiBP™ values and were thus analyzed. In the other 8 patients, no BP could be measured due to inadequate signals. The Bland-Altman analysis revealed a mean of the differences ± SD between both methods of 0.9 ± 7 mmHg for mean arterial pressure (MAP), 0.2 ± 14 mmHg for systolic arterial pressure (SAP), and 1.1 ± 6 mmHg for diastolic arterial pressure (DAP). Error grid analysis demonstrated that the proportions of measurement pairs in risk zones A to E were 88.8% (no risk), 10% (low risk), 1% (moderate risk), 0% (significant risk), and 0% (dangerous risk) for MAP and 88.4%, 8.6%, 3%, 0%, 0%, respectively, for SAP. CONCLUSIONS: This method comparison study revealed good agreement between BP values obtained using the OptiBP™ and those done invasively. The OptiBP™ fulfills the AAMI/ISO universal standards for MAP and DAP (but not SAP). Error grid showed that the most measurements (≥ 97%) were in risk zones A and B. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT04728477.

Assessing the discriminative ability of the respiratory exchange ratio to detect hyperlactatemia during intermediate-to-high risk abdominal surgery.

BACKGROUND: A mismatch between oxygen delivery (DO2) and consumption (VO2) 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 DO2 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 DO2 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 DO2/VO2 mismatch as suggested by the subsequent presence of hyperlactatemia.

Incidental finding of elevated pulmonary arterial pressures during liver transplantation and postoperative pulmonary complications.

BACKGROUND: In patients with end stage liver disease (ESLD) scheduled for liver transplantation (LT), an intraoperative incidental finding of elevated mean pulmonary arterial pressure (mPAP) may be observed. Its association with patient outcome has not been evaluated. We aimed to estimate the effects of an incidental finding of a mPAP > 20 mmHg during LT on the incidence of pulmonary complications. METHODS: We examined all patients who underwent a LT at Paul-Brousse hospital between January 1,2015 and December 31,2020. Those who received: a LT due to acute liver failure, a combined transplantation, or a retransplantation were excluded, as well as patients for whom known porto-pulmonary hypertension was treated before the LT or patients who underwent a LT for other etiologies than ESLD. Using right sided pulmonary artery catheterization measurements made following anesthesia induction, the study cohort was divided into two groups using a mPAP cutoff of 20 mmHg. The primary outcome was a composite of pulmonary complications. Univariate and multivariable logistic regression analyses were performed to identify variables associated with the primary outcome. Sensitivity analyses of multivariable models were also conducted with other mPAP cutoffs (mPAP ≥ 25 mmHg and ≥ 35 mmHg) and even with mPAP as a continuous variable. RESULTS: Of 942 patients who underwent a LT, 659 met our inclusion criteria. Among them, 446 patients (67.7%) presented with an elevated mPAP (mPAP of 26.4 ± 5.9 mmHg). When adjusted for confounding factors, an elevated mPAP was not associated with a higher risk of pulmonary complications (adjusted OR: 1.16; 95%CI 0.8-1.7), nor with 90 days-mortality or any other complications. In our sensitivity analyses, we observed a lower prevalence of elevated mPAP when increasing thresholds (235 patients (35.7%) had an elevated mPAP when defined as ≥ 25 mmHg and 41 patients (6.2%) had an elevated mPAP when defined as ≥ 35 mmHg). We did not observe consistent association between a mPAP ≥ 25 mmHg or a mPAP ≥ 35 mmHg and our outcomes. CONCLUSION: Incidental finding of elevated mPAP was highly prevalent during LT, but it was not associated with a higher risk of postoperative complications.

Intraoperative measurement of the respiratory exchange ratio predicts postoperative complications after liver transplantation.

BACKGROUND: During surgery, any mismatch between oxygen delivery (DO2) and consumption (VO2) can promote the development of postoperative complications. The respiratory exchange ratio (RER), defined as the ratio of carbon dioxide (CO2) production (VCO2) to VO2, may be a useful noninvasive tool for detecting inadequate DO2. 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 DO2/VO2 relationship, including arterial lactate, mixed venous oxygen saturation, and veno-arterial difference in the partial pressure of carbon dioxide (VAPCO2gap), 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 DO2/VO2 relationship (arterial lactate, SvO2, and VAPCO2gap) 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.

Postoperative Pulmonary Complications After Cardiac Surgery: The VENICE International Cohort Study.

OBJECTIVE: Postoperative pulmonary complications (PPC) remain a main issue after cardiac surgery. The objective was to report the incidence and identify risk factors of PPC after cardiac surgery. DESIGN: An international multicenter prospective study (42 international centers in 9 countries). PARTICIPANTS: A total of 707 adult patients who underwent cardiac surgery under cardiopulmonary bypass. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: During a study period of 2 weeks, the investigators included all patients in their respective centers and screened for PPCs. PPC was defined as the occurrence of at least 1 pulmonary complication among the following: atelectasis, pleural effusion, respiratory failure, respiratory infection, pneumothorax, bronchospasm, or aspiration pneumonitis. Among 676 analyzed patients, 373 patients presented with a PPC (55%). The presence of PPC was significantly associated with a longer intensive care length of stay and hospital length of stay. One hundred ninety (64%) patients were not intraoperatively ventilated during cardiopulmonary bypass. Ventilation settings were similar regarding tidal volume, respiratory rate, inspired oxygen. In the regression model, age, the Euroscore II, chronic obstructive pulmonary disease, preoxygenation modality, intraoperative positive end-expiratory pressure, the absence of pre- cardiopulmonary bypass ventilation, the absence of lung recruitment, and the neuromuscular blockade were associated with PPC occurrence. CONCLUSION: Both individual risk factors and ventilatory settings were shown to explain the high level of PPCs. These findings require further investigations to assess a bundle strategy for optimal ventilation strategy to decrease PPC incidence.

Impact of conventional vs. goal-directed fluid therapy on urethral tissue perfusion in patients undergoing liver surgery: A pilot randomised controlled trial.

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 ±â€Š9 vs. 33 ±â€Š7 and 3.5 ±â€Š0.7 vs. 2.4 ±â€Š0.4, respectively; P < 0.001). Although CVP was higher in the GDFT group (9.3 ±â€Š2.5 vs. 6.5 ±â€Š2.9 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.

In-silico analysis of closed-loop vasopressor control of phenylephrine versus norepinephrine.

We have previously demonstrated in in-silico, pre-clinical animal models, and finally human clinical studies the ability of a novel closed-loop vasopressor titration system to manage norepinephrine infusion rates to keep mean arterial blood pressure in a very tight range, reduce hypotension time and severity, and reduce overtreatment. We hypothesized that the same controller could, with modification for pharmacologic differences, suitably titrate a lower-potency longer duration of action agent like phenylephrine. Using the same physiologic simulation model as was used previously for in-silico testing of our controller for norepinephrine, we first updated the model to include a new vasopressor agent modeled after phenylephrine. A series of simulation tests patterned after our previous norepinephrine study was then conducted, this time using phenylephrine for management, in order to both test the system with the new agent and allow for comparisons between the two. Hundreds of simulation trials were conducted across a range of patient and environmental variances. The controller performance was characterized based on time in target, time above and below target, coefficient of variation, and using Varvel's criteria. The controller kept the simulated patients' MAP in target for 94% of management time in the simple scenarios and more than 85% of time in the most challenging scenarios. Varvel criteria were all under 1% error for expected pharmacologic responses and were consistent with those established for norepinephrine in our previous studies. The controller was able to acceptably titrate phenylephrine in this simulated patient model consistent with performance previously seen for norepinephrine after adjusting for the anticipated differences between the two agents.

Current trends in anesthetic depth and antinociception monitoring: an international survey.

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 Chi2 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.

Detection of arterial pressure waveform error using machine learning trained algorithms.

In critically ill and high-risk surgical room patients, an invasive arterial catheter is often inserted to continuously measure arterial pressure (AP). The arterial waveform pressure measurement, however, may be compromised by damping or inappropriate reference placement of the pressure transducer. Clinicians, decision support systems, or closed-loop applications that rely on such information would benefit from the ability to detect error from the waveform alone. In the present study we hypothesized that machine-learning trained algorithms could discriminate three types of transducer error from accurate monitoring with receiver operator characteristic (ROC) curve areas greater than 0.9. After obtaining written consent, patient arterial line waveform data was collected in the operating room in real-time during routine surgery requiring arterial pressure monitoring. Three deliberate error conditions were introduced during monitoring: Damping, Transducer High, and Transducer Low. The waveforms were split up into 10 s clips that were featurized. The data was also either calibrated against the patient's own baseline or left uncalibrated. The data was then split into training and validation sets, and machine-learning algorithms were run in a Monte-Carlo fashion on the training data with variable sized training sets and hyperparameters. The algorithms with the highest balanced accuracy were pruned, then the highest performing algorithm in the training set for each error state (High, Low, Damped) for both calibrated and uncalibrated data was finally tested against the validation set and the ROC and precision-recall curve area-under the curve (AUC) calculated. 38 patients were enrolled in the study with a mean age of 52 ± 15 years. A total of 40 h of monitoring time was recorded with approximately 120,000 heart beats featurized. For all error states, ROC AUCs for algorithm performance on classification of the state were greater than 0.9; when using patient-specific calibrated data AUCs were 0.94, 0.95, and 0.99 for the transducer low, transducer high, and damped conditions respectively. Machine-learning trained algorithms were able to discriminate arterial line transducer error states from the waveform alone with a high degree of accuracy.

Evaluation of a novel mobile phone application for blood pressure monitoring: a proof of concept study.

To provide information about the clinical relevance of blood pressure (BP) measurement differences between a new smartphone application (OptiBP™) and the reference method (automated oscillometric technique) using a noninvasive brachial cuff in patients admitted to the emergency department. We simultaneously recorded three BP measurements using both the reference method and the novel OptiBP™ (test method), except when the inter-arm difference was > 10 mmHg BP. Each OptiBP™ measurement required 1-min and the subsequent reference method values were compared to the values obtained with OptiBP™ using a Bland-Altman analysis and error grid analysis. Among the 110 patients recruited, OptiBP™ BP values could be collected on 61 patients (55%) and were included in the statistical analysis. The mean of differences (95% limits of agreement) between the reference method and the test method were - 0.1(- 22.5 to 22.4 mmHg) for systolic arterial pressure (SAP), - 0.1(- 12.9 to 12.7 mmHg) for diastolic arterial pressure (DAP) and - 0.3(- 18.1 to 17.4 mmHg) for mean arterial pressure (MAP). The proportions of measurements in risk zones A-E were 86.9%, 13.1%, 0%, 0%, and 0% for MAP and 89.3%, 10.7%, 0%, 0%, and 0% for SAP. In this pilot study conducted in stable and awake patients admitted to the emergency department, the absolute agreement between the OptiBP™ and the reference method was moderate. However, when BP measurements were made immediately after an initial calibration, error grid analysis showed that 100% of measurement differences between the OptiBP™ and reference method were categorized as no- or low-risk treatment decisions for all patients.Trial Registration: ClinicalTrials.gov Identifier: NCT04121624.