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.

Improving case duration accuracy of orthopedic surgery using bidirectional encoder representations from Transformers (BERT) on Radiology Reports.

PURPOSE: A major source of inefficiency in the operating room is the mismatch between scheduled versus actual surgical time. The purpose of this study was to demonstrate a proof-of-concept study for predicting case duration by applying natural language processing (NLP) and machine learning that interpret radiology reports for patients undergoing radius fracture repair. METHODS: Logistic regression, random forest, and feedforward neural networks were tested without NLP and with bag-of-words. Another NLP method tested used feedforward neural networks and Bidirectional Encoder Representations from Transformers specifically pre-trained on clinical notes (ClinicalBERT). A total of 201 cases were included. The data were split into 70% training and 30% test sets. The average root mean squared error (RMSE) were calculated (and 95% confidence interval [CI]) from 10-fold cross-validation on the training set. The models were then tested on the test set to determine proportion of times surgical cases would have scheduled accurately if ClinicalBERT was implemented versus historic averages. RESULTS: The average RMSE was lowest using feedforward neural networks using outputs from ClinicalBERT (25.6 min, 95% CI: 21.5-29.7), which was significantly (P < 0.001) lower than the baseline model (39.3 min, 95% CI: 30.9-47.7). Using the feedforward neural network and ClinicalBERT on the test set, the percentage of accurately predicted cases, which was defined by the actual surgical duration within 15% of the predicted surgical duration, increased from 26.8 to 58.9% (P < 0.001). CONCLUSION: This proof-of-concept study demonstrated the successful application of NLP and machine leaning to extract features from unstructured clinical data resulting in improved prediction accuracy for surgical case duration.

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.

Basal Infusion versus Automated Boluses and a Delayed Start Timer for "Continuous" Sciatic Nerve Blocks after Ambulatory Foot and Ankle Surgery: A Randomized Clinical Trial.

BACKGROUND: The common technique using a basal infusion for an ambulatory continuous peripheral nerve blocks frequently results in exhaustion of the local anesthetic reservoir before resolution of surgical pain. This study was designed to improve and prolong analgesia by delaying initiation using an integrated timer and delivering a lower hourly volume of local anesthetic as automated boluses. The hypothesis was that compared with a traditional continuous infusion, ropivacaine administered with automated boluses at a lower dose and 5-h delay would (1) provide at least noninferior analgesia (difference in average pain no greater than 1.7 points) while both techniques were functioning (average pain score day after surgery) and (2) result in a longer duration (dual primary outcomes). METHODS: Participants (n = 70) undergoing foot or ankle surgery with a popliteal-sciatic catheter received an injection of ropivacaine 0.5% with epinephrine (20 ml) and then were randomized to receive ropivacaine (0.2%) either as continuous infusion (6 ml/h) initiated before discharge or as automated boluses (8 ml every 2 h) initiated 5 h after discharge using a timer. Both groups could self-deliver supplemental boluses (4 ml, lockout 30 min); participants and outcome assessors were blinded to randomization. All randomized participants were included in the data analysis. RESULTS: The day after surgery, participants with automated boluses had a median [interquartile range] pain score of 0.0 [0.0 to 3.0] versus 3.0 [1.8 to 4.8] for the continuous infusion group, with an odds ratio of 3.1 (95% CI, 1.23 to 7.84; P = 0.033) adjusting for body mass index. Reservoir exhaustion in the automated boluses group occurred after a median [interquartile range] of 119 h [109 to 125] versus 74 h [57 to 80] for the continuous infusion group (difference of 47 h; 95% CI, 38 to 55; P < 0.001 adjusting for body mass index). CONCLUSIONS: For popliteal-sciatic catheters, replacing a continuous infusion initiated before discharge with automated boluses and a start-delay timer resulted in better analgesia and longer infusion duration.

The association of Serratus Anterior Plane blocks with postoperative opioid use and analgesia following simple lumpectomy: a retrospective cohort analysis.

BACKGROUND: The potential benefit of regional interventions for simple lumpectomy breast cancer surgeries has not been well investigated. Understanding which patients to not offer a regional intervention to can be just as important as knowing which would benefit. It is unclear whether fascial plane blocks, such as serratus anterior plane (SAP) block, should be routinely performed for less extensive breast surgeries. Therefore, our goal in this retrospective cohort study was to evaluate the association of integrating SAP blocks into a standard perioperative multimodal analgesia plan in patients undergoing simple lumpectomies (without node biopsies) with perioperative opioid consumption. As secondary outcomes, we also analyzed postoperative pain scores and post-anesthesia care unit (PACU) length of stay. METHODS: This was a single institution retrospective cohort study (surgical site infiltration only versus SAP block cohorts) assessing the association of SAP blocks to our outcomes of interest. In the adjusted analysis, we created matched cohorts using 1:1 (surgical site infiltration only: SAP block) propensity-score matching using nearest neighbor-matching without replacement. To compare the primary and secondary outcomes in the matched cohorts, we used the Wilcoxon signed rank test. A P-value of < 0.05 was considered statistically significant. RESULTS: There were 419 patients included in the analysis, in which 116 (27.7%) received a SAP block preoperatively in addition to our standard perioperative analgesia plan. In an unadjusted analysis, no differences were seen in perioperative opioid consumption, PACU pain scores, and PACU length of stay. Among the matched cohorts, the median [quartile] perioperative opioid consumption in the surgical site infiltration only versus SAP block cohorts were 10 mg [10, 13.25 mg] and 10 mg [7, 15 mg], respectively (P = 0.16). No differences were seen in the other outcomes. CONCLUSIONS: In this study, we evaluated the impact of SAP blocks on patients undergoing simple lumpectomies, which are relatively less involved breast surgeries. We concluded that routine use of preoperative regional anesthesia is not beneficial for these specific patients. Future studies should focus on identifying patients that would directly benefit from regional interventions.

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.

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.

Evaluation of a new smartphone optical blood pressure application (OptiBP™) in the post-anesthesia care unit: a method comparison study against the non-invasive automatic oscillometric brachial cuff as the reference method.

We compared blood pressure (BP) values obtained with a new optical smartphone application (OptiBP™) with BP values obtained using a non-invasive automatic oscillometric brachial cuff (reference method) during the first 2 h of surveillance in a post-anesthesia care unit in patients after non-cardiac surgery. Three simultaneous BP measurements of both methods were recorded every 30 min over a 2-h period. The agreement between measurements was investigated using Bland-Altman and error grid analyses. We also evaluated the performance of the OptiBP™ using ISO81060-2:2018 standards which requires the mean of the differences ± standard deviation (SD) between both methods to be less than 5 mmHg ± 8 mmHg. Of 120 patients enrolled, 101 patients were included in the statistical analysis. The Bland-Altman analysis demonstrated a mean of the differences ± SD between the test and reference methods of + 1 mmHg ± 7 mmHg for mean arterial pressure (MAP), + 2 mmHg ± 11 mmHg for systolic arterial pressure (SAP), and + 1 mmHg ± 8 mmHg for diastolic arterial pressure (DAP). Error grid analysis showed that the proportions of measurement pairs in risk zones A to E were 90.3% (no risk), 9.7% (low risk), 0% (moderate risk), 0% (significant risk), 0% (dangerous risk) for MAP and 89.9%, 9.1%, 1%, 0%, 0% for SAP. We observed a good agreement between BP values obtained by the OptiBP™ system and BP values obtained with the reference method. The OptiBP™ system fulfilled the AAMI validation requirements for MAP and DAP and error grid analysis indicated that the vast majority of measurement pairs (≥ 99%) were in risk zones A and B.Trial Registration ClinicalTrials.gov Identifier: NCT04262323.

Computer-assisted Individualized Hemodynamic Management Reduces Intraoperative Hypotension in Intermediate- and High-risk Surgery: A Randomized Controlled Trial.

BACKGROUND: Individualized hemodynamic management during surgery relies on accurate titration of vasopressors and fluids. In this context, computer systems have been developed to assist anesthesia providers in delivering these interventions. This study tested the hypothesis that computer-assisted individualized hemodynamic management could reduce intraoperative hypotension in patients undergoing intermediate- to high-risk surgery. METHODS: This single-center, parallel, two-arm, prospective randomized controlled single blinded superiority study included 38 patients undergoing abdominal or orthopedic surgery. All included patients had a radial arterial catheter inserted after anesthesia induction and connected to an uncalibrated pulse contour monitoring device. In the manually adjusted goal-directed therapy group (N = 19), the individualized hemodynamic management consisted of manual titration of norepinephrine infusion to maintain mean arterial pressure within 10% of the patient's baseline value, and mini-fluid challenges to maximize the stroke volume index. In the computer-assisted group (N = 19), the same approach was applied using a closed-loop system for norepinephrine adjustments and a decision-support system for the infusion of mini-fluid challenges (100 ml). The primary outcome was intraoperative hypotension defined as the percentage of intraoperative case time patients spent with a mean arterial pressure of less than 90% of the patient's baseline value, measured during the preoperative screening. Secondary outcome was the incidence of minor postoperative complications. RESULTS: All patients were included in the analysis. Intraoperative hypotension was 1.2% [0.4 to 2.0%] (median [25th to 75th] percentiles) in the computer-assisted group compared to 21.5% [14.5 to 31.8%] in the manually adjusted goal-directed therapy group (difference, -21.1 [95% CI, -15.9 to -27.6%]; P < 0.001). The incidence of minor postoperative complications was not different between groups (42 vs. 58%; P = 0.330). Mean stroke volume index and cardiac index were both significantly higher in the computer-assisted group than in the manually adjusted goal-directed therapy group (P < 0.001). CONCLUSIONS: In patients having intermediate- to high-risk surgery, computer-assisted individualized hemodynamic management significantly reduces intraoperative hypotension compared to a manually controlled goal-directed approach.

Automated closed-loop versus manually controlled norepinephrine infusion in patients undergoing intermediate- to high-risk abdominal surgery: a randomised controlled trial.

BACKGROUND: Hypotension occurs frequently during surgery and may be associated with adverse complications. Vasopressor titration is frequently used to correct hypotension, but requires considerable time and attention, potentially reducing the time available for other clinical duties. To overcome this issue, we have developed a closed-loop vasopressor (CLV) controller to help correct hypotension more efficiently. The aim of this randomised controlled study was to evaluate whether the CLV controller was superior to traditional vasopressor management at minimising hypotension in patients undergoing abdominal surgery. METHODS: Thirty patients scheduled for elective intermediate-to high-risk abdominal surgery were randomised into two groups. In the CLV group, hypotension was corrected automatically via the CLV controller system, which adjusted the rate of a norepinephrine infusion according to MAP values recorded using an advanced haemodynamic device. In the control group, management of hypotension consisted of standard, manual adjustment of the norepinephrine infusion. The primary outcome was the percentage of time that a patient was hypotensive, defined as MAP <90% of their baseline value, during surgery. RESULTS: The percentage of time patients were hypotensive during surgery was 10 times less in the CVL group than in the control group (1.6 [0.9-2.3]% vs 15.4 [9.9-24.3]%; difference: 13 [95% confidence interval: 9-19]; P<0.0001). The CVL group also spent much less time with MAP <65 mm Hg (0.2 [0.0-0.4]% vs 4.5 [1.1-7.9]%; P<0.0001). CONCLUSIONS: In patients undergoing intermediate- to high-risk surgery under general anaesthesia, computer-assisted adjustment of norepinephrine infusion significantly decreases the incidence of hypotension compared with manual control. CLINICAL TRIAL REGISTRATION: NCT04089644.

Intraoperative hypotension during liver transplant surgery is associated with postoperative acute kidney injury: a historical cohort study.

BACKGROUND: Acute kidney injury (AKI) occurs frequently after liver transplant surgery and is associated with significant morbidity and mortality. While the impact of intraoperative hypotension (IOH) on postoperative AKI has been well demonstrated in patients undergoing a wide variety of non-cardiac surgeries, it remains poorly studied in liver transplant surgery. We tested the hypothesis that IOH is associated with AKI following liver transplant surgery. METHODS: This historical cohort study included all patients who underwent liver transplant surgery between 2014 and 2019 except those with a preoperative creatinine > 1.5 mg/dl and/or who had combined transplantation surgery. IOH was defined as any mean arterial pressure (MAP) < 65 mmHg and was classified according to the percentage of case time during which the MAP was < 65 mmHg into three groups, based on the interquartile range of the study cohort: "short" (Quartile 1, < 8.6% of case time), "intermediate" (Quartiles 2-3, 8.6-39.5%) and "long" (Quartile 4, > 39.5%) duration. AKI stages were classified according to a "modified" "Kidney Disease: Improving Global Outcomes" (KDIGO) criteria. Logistic regression modelling was conducted to assess the association between IOH and postoperative AKI. The model was run both as a univariate and with multiple perioperative covariates to test for robustness to confounders. RESULTS: Of the 205 patients who met our inclusion criteria, 117 (57.1%) developed AKI. Fifty-two (25%), 102 (50%) and 51 (25%) patients had short, intermediate and long duration of IOH respectively. In multivariate analysis, IOH was independently associated with an increased risk of AKI (adjusted odds ratio [OR] 1.05; 95%CI 1.02-1.09; P < 0.001). Compared to "short duration" of IOH, "intermediate duration" was associated with a 10-fold increased risk of developing AKI (OR 9.7; 95%CI 4.1-22.7; P < 0.001). "Long duration" was associated with an even greater risk of AKI compared to "short duration" (OR 34.6; 95%CI 11.5-108.6; P < 0.001). CONCLUSIONS: Intraoperative hypotension is independently associated with the development of AKI after liver transplant surgery. The longer the MAP is < 65 mmHg, the higher the risk the patient will develop AKI in the immediate postoperative period, and the greater the likely severity. Anesthesiologists and surgeons must therefore make every effort to avoid IOH during surgery.

Mild increases in plasma creatinine after intermediate to high-risk abdominal surgery are associated with long-term renal injury.

BACKGROUND: The potential relationship between a mild acute kidney injury (AKI) observed in the immediate postoperative period after major surgery and its effect on long term renal function remains poorly defined. According to the "Kidney Disease: Improving Global Outcomes" (KDIGO) classification, a mild injury corresponds to a KIDIGO stage 1, characterized by an increase in creatinine of at least 0.3 mg/dl within a 48-h window or 1.5 to 1.9 times the baseline level within the first week post-surgery. We tested the hypothesis that patients who underwent intermediate-to high-risk abdominal surgery and developed mild AKI in the following days would be at an increased risk of long-term renal injury compared to patients with no postoperative AKI. METHODS: All consecutive adult patients with a plasma creatinine value ≤1.5 mg/dl who underwent intermediate-to high-risk abdominal surgery between 2014 and 2019 and who had at least three recorded creatinine measurements (before surgery, during the first seven postoperative days, and at long-term follow up [6 months-2 years]) were included. AKI was defined using a "modified" (without urine output criteria) KDIGO classification as mild (stage 1 characterised by an increase in creatinine of > 0.3 mg/dl within 48-h or 1.5-1.9 times baseline) or moderate-to-severe (stage 2-3 characterised by increase in creatinine 2 to 3 times baseline or to ≥4.0 mg/dl). The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the same KDIGO initiative criteria. Development of long-term renal injury was compared in patients with and without postoperative AKI. RESULTS: Among the 815 patients included, 109 (13%) had postoperative AKI (81 mild and 28 moderate-to-severe). The median long-term follow-up was 360, 354 and 353 days for the three groups respectively (P = 0.2). Patients who developed mild AKI had a higher risk of long-term renal injury than those who did not (odds ratio 3.1 [95%CI 1.7-5.5]; p < 0.001). In multivariable analysis, mild postoperative AKI was independently associated with an increased risk of developing long-term renal injury (adjusted odds ratio 4.5 [95%CI 1.8-11.4]; p = 0.002). CONCLUSIONS: Mild AKI after intermediate-to high-risk abdominal surgery is associated with a higher risk of long-term renal injury 1 y after surgery.

Anesthetic Management Using Multiple Closed-loop Systems and Delayed Neurocognitive Recovery: A Randomized Controlled Trial.

BACKGROUND: Cognitive changes after anesthesia and surgery represent a significant public health concern. We tested the hypothesis that, in patients 60 yr or older scheduled for noncardiac surgery, automated management of anesthetic depth, cardiac blood flow, and protective lung ventilation using three independent controllers would outperform manual control of these variables. Additionally, as a result of the improved management, patients in the automated group would experience less postoperative neurocognitive impairment compared to patients having standard, manually adjusted anesthesia. METHODS: In this single-center, patient-and-evaluator-blinded, two-arm, parallel, randomized controlled, superiority study, 90 patients having noncardiac surgery under general anesthesia were randomly assigned to one of two groups. In the control group, anesthesia management was performed manually while in the closed-loop group, the titration of anesthesia, analgesia, fluids, and ventilation was performed by three independent controllers. The primary outcome was a change in a cognition score (the 30-item Montreal Cognitive Assessment) from preoperative values to those measures 1 week postsurgery. Secondary outcomes included a battery of neurocognitive tests completed at both 1 week and 3 months postsurgery as well as 30-day postsurgical outcomes. RESULTS: Forty-three controls and 44 closed-loop patients were assessed for the primary outcome. There was a difference in the cognition score compared to baseline in the control group versus the closed-loop group 1 week postsurgery (-1 [-2 to 0] vs. 0 [-1 to 1]; difference 1 [95% CI, 0 to 3], P = 0.033). Patients in the closed-loop group spent less time during surgery with a Bispectral Index less than 40, had less end-tidal hypocapnia, and had a lower fluid balance compared to the control group. CONCLUSIONS: Automated anesthetic management using the combination of three controllers outperforms manual control and may have an impact on delayed neurocognitive recovery. However, given the study design, it is not possible to determine the relative contribution of each controller on the cognition score.

Hydroxyethyl starch for perioperative goal-directed fluid therapy in 2020: a narrative review.

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.

Automated systems for perioperative goal-directed hemodynamic therapy.

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.

Automated Titration of Vasopressor Infusion Using a Closed-loop Controller: In Vivo Feasibility Study Using a Swine Model.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Intraoperative hypotension has been associated with adverse postoperative outcomes.A randomized controlled trial of individualized blood pressure management in patients undergoing major abdominal surgery found reduced postoperative adverse events in patients in the blood pressure management intervention group versus the standard of care group. WHAT THIS ARTICLE TELLS US THAT IS NEW: In this study of pigs with normovolemic hypotension induced by administration of sodium nitroprusside, an automated closed-loop vasopressor administration device was able to maintain mean arterial pressure within 5 mmHg of 80 mmHg for 98% of the intraoperative period. This suggests that norepinephrine can be accurately titrated using an automated infusion device in order to maintain target blood pressure. BACKGROUND: Multiple studies have reported associations between intraoperative hypotension and adverse postoperative complications. One of the most common interventions in the management of hypotension is vasopressor administration. This approach requires careful and frequent vasopressor boluses and/or multiple adjustments of an infusion. The authors recently developed a closed-loop controller that titrates vasopressors to maintain mean arterial pressure (MAP) within set limits. Here, the authors assessed the feasibility and overall performance of this system in a swine model. The authors hypothesized that the closed-loop controller would be able to maintain MAP at a steady, predefined target level of 80 mmHg for greater than 85% of the time. METHODS: The authors randomized 14 healthy anesthetized pigs either to a control group or a closed-loop group. Using infusions of sodium nitroprusside at doses between 65 and 130 µg/min, we induced four normovolemic hypotensive challenges of 30 min each. In the control group, nothing was done to correct hypotension. In the closed-loop group, the system automatically titrated norepinephrine doses to achieve a predetermined MAP of 80 mmHg. The primary objective was study time spent within ±5 mmHg of the MAP target. Secondary objectives were performance error, median performance error, median absolute performance error, wobble, and divergence. RESULTS: The controller maintained MAP within ±5 mmHg of the target for 98 ± 1% (mean ± SD) of the time. In the control group, the MAP was 80 ± 5 mmHg for 14.0 ± 2.8% of the time (P< 0.0001). The MAP in the closed-loop group was above the target range for 1.2 ± 1.2% and below it for 0.5 ± 0.9% of the time. Performance error, median performance error, median absolute performance error, wobble, and divergence were all optimal. CONCLUSIONS: In this experimental model of induced normovolemic hypotensive episodes in pigs, the automated controller titrated norepinephrine infusion to correct hypotension and keep MAP within ±5 mmHg of target for 98% of management time.

Feasibility of closed-loop titration of norepinephrine infusion in patients undergoing moderate- and high-risk surgery.

BACKGROUND: Vasopressor agents are used to prevent intraoperative hypotension and ensure adequate perfusion. Vasopressors are usually administered as intermittent boluses or manually adjusted infusions, but this practice requires considerable time and attention. We have developed a closed-loop vasopressor (CLV) controller to correct hypotension more efficiently. Here, we conducted a proof-of-concept study to assess the feasibility and performance of CLV control in surgical patients. METHODS: Twenty patients scheduled for elective surgical procedures were included in this study. The goal of the CLV system was to maintain MAP within 5 mm Hg of the target MAP by automatically adjusting the rate of a norepinephrine infusion using MAP values recorded continuously from an arterial catheter. The primary outcome was the percentage of time that patients were hypotensive, as defined by a MAP of 5 mm Hg below the chosen target. Secondary outcomes included the total dose of norepinephrine, percentage of time with hypertension (MAP>5 mm Hg of the chosen target), raw percentage "time in target" and Varvel performance criteria. RESULTS: The 20 subjects (median age: 64 years [52-71]; male (35%)) underwent elective surgery lasting 154 min [124-233]. CLV control maintained MAP within ±5 mm Hg of the target for 91.6% (85.6-93.3) of the intraoperative period. Subjects were hypotensive for 2.6% of the intraoperative period (range, 0-8.4%). Additional performance criteria for the controller included mean absolute performance error of 2.9 (0.8) and mean predictive error of 0.5 (1.0). No subjects experienced major complications. CONCLUSIONS: In this proof of concept study, CLV control minimised perioperative hypotension in subjects undergoing moderate- or high-risk surgery. Further studies to demonstrate efficacy are warranted. TRIAL REGISTRY NUMBER: NCT03515161 (ClinicalTrials.gov).

Feasibility of Fully Automated Hypnosis, Analgesia, and Fluid Management Using 2 Independent Closed-Loop Systems During Major Vascular Surgery: A Pilot Study.

Automated titration of intravenous anesthesia and analgesia using processed electroencephalography monitoring is no longer a novel concept. Closed-loop control of fluid administration to provide goal-directed fluid therapy has also been increasingly described. However, simultaneously combining 2 independent closed-loop systems together in patients undergoing major vascular surgery has not been previously detailed. The aim of this pilot study was to evaluate the clinical performance of fully automated hypnosis, analgesia, and fluid management using 2 independent closed-loop controllers in patients undergoing major vascular surgery before implementation within a larger study evaluating true patient outcomes.