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.

Predicting personalised remifentanil effect site concentration for surgical incision using the nociception level index: A prospective calibration and validation study.

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.

Effect of dexmedetomidine on Nociception Level Index-guided remifentanil antinociception: A randomised controlled trial.

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 ±â€ŠSD remifentanil (3.96 ±â€Š1.95 vs. 4.42 ±â€Š2.04 ng ml-1; P = 0.0024) and propofol (2.78 ±â€Š1.36 vs. 3.06 ±â€Š1.29 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 ±â€Š0.085 vs. 0.198 ±â€Š0.086 µg kg-1 min-1; P = 0.0074) and propofol (5.7 ±â€Š2.72 vs. 7.4 ±â€Š2.80 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.

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.

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.

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.

Ability of a New Smartphone Pulse Pressure Variation and Cardiac Output Application to Predict Fluid Responsiveness in Patients Undergoing Cardiac Surgery.

BACKGROUND: Pulse pressure variation (PPV) can be used to predict fluid responsiveness in anesthetized patients receiving controlled mechanical ventilation but usually requires dedicated advanced monitoring. Capstesia (Galenic App, Vitoria-Gasteiz, Spain) is a novel smartphone application that calculates PPV and cardiac output (CO) from a picture of the invasive arterial pressure waveform obtained from any monitor screen. The primary objective was to compare the ability of PPV obtained using the Capstesia (PPVCAP) and PPV obtained using a pulse contour analysis monitor (PPVPC) to predict fluid responsiveness. A secondary objective was to assess the agreement and the trending of CO values obtained with the Capstesia (COCAP) against those obtained with the transpulmonary bolus thermodilution method (COTD). METHODS: We studied 57 mechanically ventilated patients (tidal volume 8 mL/kg, positive end-expiratory pressure 5 mm Hg, respiratory rate adjusted to keep end tidal carbon dioxide [32-36] mm Hg) undergoing elective coronary artery bypass grafting. COTD, COCAP, PPVCAP, and PPVPC were measured before and after infusion of 5 mL/kg of a colloid solution. Fluid responsiveness was defined as an increase in COTD of >10% from baseline. The ability of PPVCAP and PPVPC to predict fluid responsiveness was analyzed using the area under the receiver-operating characteristic curve (AUROC), the agreement between COCAP and COTD using a Bland-Altman analysis and the trending ability of COCAP compared to COTD after volume expansion using a 4-quadrant plot analysis. RESULTS: Twenty-eight patients were studied before surgical incision and 29 after sternal closure. There was no significant difference in the ability of PPVCAP and PPVPC to predict fluid responsiveness (AUROC 0.74 [95% CI, 0.60-0.84] vs 0.68 [0.54-0.80]; P = .30). A PPVCAP >8.6% predicted fluid responsiveness with a sensitivity of 73% (95% CI, 0.54-0.92) and a specificity of 74% (95% CI, 0.55-0.90), whereas a PPVPC >9.5% predicted fluid responsiveness with a sensitivity of 62% (95% CI, 0.42-0.88) and a specificity of 74% (95% CI, 0.48-0.90). When measured before surgery, PPV predicted fluid responsiveness (AUROC PPVCAP = 0.818 [P = .0001]; PPVPC = 0.794 [P = .0007]) but not when measured after surgery (AUROC PPVCAP = 0.645 [P = .19]; PPVPC = 0.552 [P = .63]). A Bland-Altman analysis of COCAP and COTD showed a mean bias of 0.3 L/min (limits of agreement: -2.8 to 3.3 L/min) and a percentage error of 60%. The concordance rate, corresponding to the proportion of CO values that changed in the same direction with the 2 methods, was poor (71%, 95% CI, 66-77). CONCLUSIONS: In patients undergoing cardiac surgery, PPVCAP and PPVPC both weakly predict fluid responsiveness. However, COCAP is not a good substitute for COTD and cannot be used to assess fluid responsiveness.

Gradual withdrawal of remifentanil delays initial post-operative analgesic demand after thyroid surgery; double-blinded, randomized controlled trial.

BACKGROUND: Mismanagement of remifentanil leads to severe side effects such as opioid-induced tolerance and hyperalgesia. Recently studies revealed an alternative withdrawal method to limit these side effects. A gradual withdrawal of remifentanil seems to be associated with less pain. The hypothesis of this double-blinded, randomized controlled trial was that a gradual withdrawal of remifentanil would be associated with less immediate post-operative pain compared to after an abrupt discontinuation of remifentanil in patients who underwent thyroid surgery. METHODS: This double-blinded, randomized controlled trial was conducted in a tertiary level hospital in Brussels (Belgium) from April until August 2017. 34 patients undergoing thyroid surgery were randomized and 29 patients completed the study. After randomization, patients undergoing thyroid surgery were allocated to two groups: one with an abrupt discontinuation of remifentanil after surgery and one with a gradual withdrawal of remifentanil after surgery. The primary outcome was the initial post-operative demand of analgesic medication. RESULTS: Gradual withdrawal of remifentanil was associated with a delayed initial post-operative demand of analgesic medication (P = 0.006). The first morphine bolus was given after 76.3 +/- 89.0 min in the group with a gradual withdrawal of remifentanil versus after 9.0 +/- 13.5 min in the group with an abrupt discontinuation of remifentanil. However, overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) were similar in both groups (P > 0.05). CONCLUSION: Though overall morphine consumption, numeric rating scale scores, Ramsay Sedation Scale scores, and quality of recovery scores (QoR-40) are not altered, a gradual withdrawal of remifentanil after thyroid surgery is safe and associated with a delayed initial post-operative demand of analgesic drugs. The withdrawal process does, however, require vigilance and training. TRIAL REGISTRATION: Clinicaltrials.gov NCT03110653 (PI: Luc Barvais; date of registration: 03/31/2017).

Synchronized mandibular movement and capnography: a novel approach to obstructive airway detection during procedural sedation-a post hoc analysis of a prospective study.

Perioperative complications related to obstructive sleep apnea still occur despite the use of partial pressure end-tidal CO2[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 .

Two different methods to assess sympathetic tone during general anesthesia lead to different findings.

Noxious stimulation influences the autonomic nervous system activity. Sympathetic tone monitoring is currently used to assess the adequacy of the balance between nociception and anti-nociception during general anesthesia. The Surgical Plethysmographic Index (SPI) and the EBMi software (Custos©) are commercial devices that use different algorithms to measure it. We aimed at determining whether those devices provide similar information during routine surgical procedures under general anesthesia. Data acquired during a previously published study in patients undergoing surgery under general anesthesia were retrospectively analyzed and passed through the EBMi software. The occurrence of EBMi alarms of increased sympathetic tone was compared to the occurrence of SPI values ≥ 60, a commonly recommended intraoperative SPI threshold. Trends in classical parameters of sympathetic tone during the 5 min preceding a SPI ≥ 60, namely blood pressure, heart rate, and plethysmographic pulse amplitude were assessed. SPI ≥ 60 episodes (n = 307) were more frequent than EBMi alerts (n = 240). Approximately 70% of EBMi alerts occurred during periods where the SPI was below 60. Among all episodes of SPI ≥ 60, absence of any EBMi alerts was much more frequent than the inverse. A majority, but not all SPI ≥ 60 episodes were consistently preceded by an increase in heart rate and/or a decrease in pulse amplitude. Blood pressure did not significantly change before SPI ≥ 60. Longer SPI ≥ 60 episodes were associated with lower anti-nociception anesthetic regimen. Different methods of sympathetic tone assessment during general anesthesia provide conflicting information. Prospective studies should be undertaken to clarify the clinical indications of both techniques.

Implementation of closed-loop-assisted intra-operative goal-directed fluid therapy during major abdominal surgery: A case-control study with propensity matching.

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.

Placebo versus low-dose ketamine infusion in addition to remifentanil target-controlled infusion for conscious sedation during oocyte retrieval: A double-blinded, randomised controlled trial.

BACKGROUND: Currently, there is no gold standard for monitored anaesthesia care during oocyte retrieval. OBJECTIVE: In our institution, the standard is a conscious sedation technique using a target-controlled infusion (TCI) of remifentanil, titrated to maintain a visual analogue pain score less than 30 mm. This protocol is well accepted by patients but is associated with frequent episodes of respiratory depression. The main objective of this study was to evaluate whether the addition of a continuous intravenous infusion of ketamine could reduce these episodes. DESIGN: Controlled, randomised, prospective, double-blinded study. SETTING: The current study was conducted in a tertiary-level hospital in Brussels (Belgium) from December 2013 to June 2014. PATIENTS: Of the 132 women undergoing oocyte retrieval included, 121 completed the study. INTERVENTION: After randomisation, patients received either a ketamine infusion (40 µg kg min over 5 min followed by 2.5 µg kg min) or a 0.9% saline infusion in addition to the variable remifentanil TCI. MAIN OUTCOME MEASURES: The primary outcome was the number of respiratory depression episodes. Effect site target remifentanil concentrations, side effects, pain score, patient satisfaction and incidence of pregnancy were also recorded. RESULTS: No significant difference in the incidence of respiratory events was noted (pulse oximetry oxygen saturation < 95% was 49% in the ketamine group and 63% in the control group; P = 0.121). No patient required ventilatory support. In the ketamine group, visual analogue pain score and remifentanil concentrations were significantly reduced, but the latter remained above 2 ng ml. Postoperative nausea was less frequent in the ketamine group, 4 versus 15% (P = 0.038). The addition of ketamine did not influence length of stay nor patient satisfaction. CONCLUSION: The addition of low plasma levels of ketamine to a TCI remifentanil conscious sedation technique did not decrease the incidence nor the severity of respiratory depression. Continuous monitoring of capnography and oxygen saturation is always required. TRIAL REGISTRATION: EUDRACT number 2013-003040-23.

Crystalloid versus Colloid for Intraoperative Goal-directed Fluid Therapy Using a Closed-loop System: A Randomized, Double-blinded, Controlled Trial in Major Abdominal Surgery.

BACKGROUND: The type of fluid and volume regimen given intraoperatively both can impact patient outcome after major surgery. This two-arm, parallel, randomized controlled, double-blind, bi-center superiority study tested the hypothesis that when using closed-loop assisted goal-directed fluid therapy, balanced colloids are associated with fewer postoperative complications compared to balanced crystalloids in patients having major elective abdominal surgery. METHODS: One hundred and sixty patients were enrolled in the protocol. All patients had maintenance-balanced crystalloid administration of 3 ml · kg · h. A closed-loop system delivered additional 100-ml fluid boluses (patients were randomized to receive either a balanced-crystalloid or colloid solution) according to a predefined goal-directed strategy, using a stroke volume and stroke volume variation monitor. All patients were included in the analysis. The primary outcome was the Post-Operative Morbidity Survey score, a nine-domain scale, at day 2 postsurgery. Secondary outcomes included all postoperative complications. RESULTS: Patients randomized in the colloid group had a lower Post-Operative Morbidity Survey score (median [interquartile range] of 2 [1 to 3] vs. 3 [1 to 4], difference -1 [95% CI, -1 to 0]; P < 0.001) and a lower incidence of postoperative complications. Total volume of fluid administered intraoperatively and net fluid balance were significantly lower in the colloid group. CONCLUSIONS: Under our study conditions, a colloid-based goal-directed fluid therapy was associated with fewer postoperative complications than a crystalloid one. This beneficial effect may be related to a lower intraoperative fluid balance when a balanced colloid was used. However, given the study design, the mechanism for the difference cannot be determined with certainty.

Standardised noxious stimulation-guided individual adjustment of remifentanil target-controlled infusion to prevent haemodynamic responses to laryngoscopy and surgical incision: A randomised controlled trial.

BACKGROUND: The surgical plethysmographic index (SPI) is one of the available indexes of the nociception-antinociception (NAN) balance. Individually adjusting the NAN balance to prevent somatic responses to noxious stimulation remains a challenge. OBJECTIVES: To assess whether guiding remifentanil administration according to the SPI response to a calibrated noxious stimulus (NANCAL) can blunt the haemodynamic response to tracheal intubation and surgical incision. DESIGN: Randomised multicentre study. SETTING: Two Belgian university hospitals from January 2014 to April 2015. PATIENTS: After ethic review board approval and informed consent, 48 American Society of Anesthesiologists I or II adult patients scheduled for surgery under general anaesthesia were enrolled. INTERVENTIONS: Patients were randomly assigned to a SPI group, where remifentanil effect-site concentration was adjusted according to NANCAL, or a control group, where it was fixed at 4 ng ml. Propofol concentration was always adjusted to maintain the bispectral index close to 40. NANCAL consisted of a 100 Hz, 60 mA electrical tetanic stimulation during 30 s at the wrist before tracheal intubation and before surgical incision. MAIN OUTCOME MEASURES: The primary endpoint was the efficacy of the NANCAL-guided remifentanil administration to prevent the haemodynamic response to tracheal intubation and surgical incision. The secondary aim was to compare the ability of SPI, analgesia nociception index, pupil diameter and mean arterial pressure response to NANCAL to predict the haemodynamic response to tracheal intubation and surgical incision. RESULTS: Our SPI response to NANCAL-based correcting scheme for remifentanil administration was not superior to a fixed remifentanil concentration at blunting the haemodynamic response to tracheal intubation or surgical incision. Among all tested NAN balance indices, only mean arterial pressure had significant predictive ability with regard to the haemodynamic response to surgical incision. CONCLUSION: Further research is needed to define the best NANCAL stimulus and the best remifentanil correcting scheme to help individualised tailoring of antinociception for each specific subpopulation of surgical patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT: 02884310; https://clinicaltrials.gov/ct2/show/NCT02884310.

Comparison of the ability of esCCO and Volume View to measure trends in cardiac output in patients undergoing cardiac surgery.

BACKGROUND: Cardiac output (CO) is a physiological variable that should be monitored during cardiac surgery. The purpose of this study was to assess the trending ability of two CO monitors, esCCO (Nihon Kohden™, Tokyo, Japan) and Volume View (VV) (Edwards Lifesciences, Irvine, USA). METHODS: A total of 19 patients were included in the study. Before cardiopulmonary bypass (CPB), CO was measured simultaneously using both esCCO and VV devices before and after three CO-modifying manoeuvres (passive leg raise [PLR], the end expiratory occlusion test [EEOT] and positive end expiratory pressure [PEEP] at 10 cm H2O). Five CO values for esCCO and three for VV were averaged and compared during a one-minute period of time before and after each manoeuvre. RESULTS: A total of 114 paired readings were collected. Median CO values were 4.3 L min⁻¹ (IQR: 3.8; 5.2) and 3.8 L min⁻¹ (IQR: 3.5; 4.5) for esCCO and VV, respectively. The precision error was 1.4% (95% CI:1.0-1.7) for esCCO and 2.2% (95% CI: 1.8-2.7) for VV. The bias between esCCO and VV values was normally distributed (P = 0.0596). Between esCCO and VV, the mean bias was +0.6 L min⁻¹ with a Limit of Agreement (LOA) of -1.8 L min⁻¹ and +3.0 L min⁻¹. The concordance rate was 43% (95% CI: 29-58) between esCCO and VV. CONCLUSION: Both single and trended measurements of CO using esCCO and VV were not in agreement. This large discrepancy leads one to the conclusion that any outcome study conducted with one of these devices cannot be applied to the other.

Fully Automated Anesthesia and Fluid Management Using Multiple Physiologic Closed-Loop Systems in a Patient Undergoing High-Risk Surgery.

Automated delivery of anesthesia guided by processed electroencephalogram monitoring using a closed-loop system is no longer a novel concept. However, combining multiple independent physiologic closed-loop systems together has never been documented before. The purpose of this case report was to evaluate the feasibility of automated anesthesia and fluid management based on a combination of physiological variables (bispectral index, stroke volume, and stroke volume variations) using 2 independent closed-loop systems.

Tranexamic acid decreases the magnitude of platelet dysfunction in aspirin-free patients undergoing cardiac surgery with cardiopulmonary bypass: a pilot study.

This study sought to compare the effect of tranexamic acid (TXA) administration on cardiopulmonary bypass-induced platelet dysfunction in patients who received preoperative aspirin or not. We performed a prospective, randomized, double-blind pilot study, including patients undergoing elective cardiac surgery with cardiopulmonary bypass (CPB). Patients without aspirin interruption were enrolled in the 'group ASPIRIN' (n = 18) and those who had never been treated with aspirin were included in the 'group NO ASPIRIN' (n = 10). Patients were then randomized to receive either TXA or the same infusion of normal saline. Multiple electrode aggregometry was used to assess platelet function at the different time points throughout the surgery: baseline, post-TXA loading dose, aortic unclamping (End CPB), and 5 min after protamine (Protamine). Compared to those included in the group NO ASPIRIN, patients included in the group ASPIRIN presented a decreased baseline platelet function measured by ASP test (P < 0.01) and collagen test (P < 0.01). In the group NO ASPIRIN, treatment group (TXA vs. placebo) significantly influenced the results for ADP test (P < 0.01), thrombin receptor-activating peptide test (P = 0.01), and ASP test (P = 0.01). We observed that TXA improved platelet function, as measured using multiple electrode aggregometry on ADP test, thrombin receptor-activating peptide test, and ASP test, at the end of CPB (P < 0.05). TXA might decrease the magnitude of platelet dysfunction in aspirin-free patients undergoing cardiac surgery. Further studies are needed to confirm these results and assess a potential relationship with clinical endpoints.