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.

Incidence of Post-Operative Complications and Factors Influencing Their Occurrence in Patients with Sickle Cell Disease in a Low-Income Country: A Case Study of Cameroon.

This study aimed to analyse post-operative complications and possible factors influencing their occurrence in the management of patients with sickle cell disease in a low-income country. We prospectively collected data regarding the management of patients with sickle cell disease requiring anesthesia for surgery in 11 Cameroonian hospitals from 1 May 2019 to 30 April 2021. The data were analysed using descriptive statistics and a binary logistic regression was used to determine the dependence between the variables. A total of 124 patients with sickle cell disease were enrolled; 64 were male and 60 female, giving a sex ratio of 0.93. The rate of post-operative complications was 23.4% (29/124) and the death rate was 3.2% (4/124). The female subjects had more complications than the male subjects p < 0.05. The number of vaso-occlusive crises experienced per year showed a significant impact on the occurrence of post-operative complications p < 0.05. Laparoscopic surgery had fewer post-operative complications 5/46 (10.9%) than laparotomy 14/43 (32.5%). The surgical technique for the abdominal procedures had a significant impact on the occurrence of post-operative complications p < 0.05. The type of surgery (p = 0.198) and the anaesthesia technique (p = 0.225) did not show a significant impact on the occurrence of post-operative complications. Particular attention should be paid to female patients with sickle cell disease as they are more likely to experience post-operative complications, as well as to the frequency of vaso-occlusive crises, which are also predictive of post-operative complications. Opting for laparoscopic surgery whenever possible would help to reduce post-operative complications.

Long-Term Outcome After Venoarterial Extracorporeal Membrane Oxygenation as Bridge to Left Ventricular Assist Device Preceding Heart Transplantation.

OBJECTIVES: To determine if venoarterial extracorporeal membrane oxygenation (VA ECMO) as a bridge to left ventricular assist device (LVAD) in heart transplant (HT) candidates (ie, double bridge to HT) was associated with increased morbidity and mortality when compared to LVAD bridging to HT (ie, single bridge to HT). DESIGN: A retrospective analysis of patients undergoing LVAD support from 2011 to 2020. A Kaplan-Meier survival curve and Cox-Mantel hazard ratios (HR) were calculated during LVAD support and after HT. Postoperative complications were collected. SETTING: University Hospital Erasme. PARTICIPANTS: HT candidates requiring LVAD. INTERVENTIONS: VA ECMO bridging to LVAD (ECMO-LVAD group [n = 24]) versus LVAD (LVAD group [n = 64]). MEASUREMENTS AND MAIN RESULTS: Eighty-eight patients underwent HeartWare LVAD (HVAD, Medtronic) placement. Survival to hospital discharge and during the entire study period were lower in the ECMO-LVAD group (66.7% v 92.2%; p = 0.0027, and 37.5% v 62.5%; p = 0.035, respectively). Overall HR of death was 2.46 (95% confidence interval [CI]: 1.13-5.37; p = 0.005) in the ECMO-LVAD group and remained elevated throughout their time on LVAD support (HR 3.24 [95% CI: 1.15-9.14]; p = 0.0036). However, in patients who underwent HT (n = 50), mortality was similar between groups (HR 1.33 [95% CI: 0.33-5.31]; p = 0.66). Postoperative complications were more frequent in the ECMO-LVAD group (infection = 83.3% v 51.6%, p = 0.007; renal replacement therapy = 45.8% v 9.4%, p = 0.0001; post-LVAD ECMO = 25.0% v 1.6%; p = 0.0003). CONCLUSIONS: VA ECMO as a bridge to LVAD support before HT was associated with increased morbidity and mortality during LVAD support. However, in patients who underwent HT, outcomes were similar regardless of VA ECMO bridging.

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.

Pharmacodynamics of rocuronium in sickle cell patients.

BACKGROUND: Sickle cell disease is the most widespread genetic disease in the world. The chronic organ damage due to this disease could lead to variability of responses to the anaesthetic drugs. We analysed the pharmacodynamics response of rocuronium to sickle cell patients. METHODS: We observed and compared the onset time and clinical duration (time to recovery first twitch) of 0.6 mg kg-1 of rocuronium using a TOFscan® monitor, as well as the time before the first incremental dose (time to recovery second twitch), in a group of 22 homozygous sickle cell patients and a group of 23 controls, all programmed for laparoscopic surgical procedures. RESULTS: The onset time of rocuronium was longer in sickle cell patients [mean ± SD (extremes)], [6.3 ± 2.1 (1.8-10) min] than in the control group [2.5 ± 0.6 (1.4-3.5) min] (P < 0.01). The clinical duration was shorter in sickle cell patients [19.2 ± 7.1 (13-41) min] when compared to the control group [28.9 ± 6.9 (21-48) min] (P < 0.01). The time before the first incremental dose was shorter in the sickle cell patients group [27.7 ± 7.9 (19-49) min] compared to the control group [39.9 ± 8.7 (30-56) min] (P < 0.01). CONCLUSION: The onset time of rocuronium was significantly longer with a shorter duration of action in patients with sickle cell disease versus the general population.

Early Hyperdynamic Sepsis Alters Coronary Blood Flow Regulation in Porcine Fecal Peritonitis.

Background: Sepsis is a common condition known to impair blood flow regulation and microcirculation, which can ultimately lead to organ dysfunction but such contribution of the coronary circulation remains to be clarified. We investigated coronary blood flow regulatory mechanisms, including autoregulation, metabolic regulation, and endothelial vasodilatory response, in an experimental porcine model of early hyperdynamic sepsis. Methods: Fourteen pigs were randomized to sham (n = 7) or fecal peritonitis-induced sepsis (n = 7) procedures. At baseline, 6 and 12 h after peritonitis induction, the animals underwent general and coronary hemodynamic evaluation, including determination of autoregulatory breakpoint pressure and adenosine-induced maximal coronary vasodilation for coronary flow reserve and hyperemic microvascular resistance calculation. Endothelial-derived vasodilatory response was assessed both in vivo and ex vivo using bradykinin. Coronary arteries were sampled for pathobiological evaluation. Results: Sepsis resulted in a right shift of the autoregulatory breakpoint pressure, decreased coronary blood flow reserve and increased hyperemic microvascular resistance from the 6th h after peritonitis induction. In vivo and ex vivo endothelial vasomotor function was preserved. Sepsis increased coronary arteries expressions of nitric oxide synthases, prostaglandin I2 receptor, and prostaglandin F2α receptor. Conclusion: Autoregulation and metabolic blood flow regulation were both impaired in the coronary circulation during experimental hyperdynamic sepsis, although endothelial vasodilatory response was preserved.

The Practices of Anaesthesiologists in the Management of Patients with Sickle Cell Disease: Empirical Evidence from Cameroon.

Patients with sickle cell disease are more likely to undergo surgery during their lifetime, especially given the numerous complications they may develop. There is a paucity of data concerning the management of patients with sickle cell disease by anaesthesiologists, especially in Africa. This study aimed to describe the practices of anaesthesiologists in Cameroon concerning the perioperative management of patients with sickle cell disease. A cross-sectional study was carried out over four months and involved 35 out 47 anaesthesiologists working in hospitals across the country, who were invited to fill a data collection form after giving their informed consent. The data were analysed using descriptive statistics and a binary logistic regression model. Among the 35 anaesthesiologists included in the study, most (29 (82.9%)) had managed patients with sickle cell disease for both emergency and elective surgical procedures. Most of them had never asked for a haematology consultation before surgery. Most participants (26 (74.3%)) admitted to having carried out simple blood transfusions, while 4 (11.4%) carried out exchange transfusions. The haemoglobin thresholds for transfusion varied from one practitioner to another, between <6 g/dL and <9 g/dL. Only 6 (17.1%) anaesthesiologists had a treatment guideline for the management of patients with sickle cell disease in the hospitals where they practiced. Only 9 (25.7%) prescribed a search for irregular agglutinins. The percentage of haemoglobin S before surgery was always available for 5 (14.3%) of the participants. The coefficient (0.06) of the occurrence of a haematology consultation before surgery had a significant influence on the probability of management of post-operative complications (coefficient 0.06, 10% level of probability). This study highlights the fact that practices in the perioperative management of patients with sickle cell disease in Cameroon vary greatly from one anaesthesiologist to another. We disclosed major differences in the current recommendations, which support the fact that even in Sub-Saharan countries, guidelines applicable to the local settings should be published.

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.

Earlier and lower dose administration of sugammadex: A randomised placebo-controlled trial.

BACKGROUND: Sugammadex allows for rapid reversal of muscle relaxation after the use of rocuronium or vecuronium. The lowest recommended dose is 2 mg kg-1 intravenously when there are two twitches during the train-of-four stimulation. OBJECTIVE: To study the efficacy and risks of a lower dose of sugammadex administered earlier. DESIGN: Monocentric randomised controlled double-blind study. SETTING: Academic hospital. PATIENTS: Eighty patients were enrolled and randomised in 8 groups of 10 patients, 56 were finally evaluated. INTERVENTIONS: Patients were distributed in two clusters constituting four groups each. In the first cluster, injections were administered after the return of one twitch with the train-of-four (TOF1). In the second cluster, injections were delivered after the return of two twitches with the TOF (TOF2). We created four groups in each cluster for different dosages: placebo, 0.5, 1 or 2 mg kg-1. MAIN OUTCOME MEASURES: Time between the injection of sugammadex and full recovery (TOF ratio > 0.9) that is expressed in minutes. RESULTS: Fifty-six successive patients were assessed between February and August 2018. The difference to TOF greater than 0.9 was not statistically significant between groups with the same dose administered at different times (F value = 0.001, P value = 0.975). There was a significant difference between groups with a different dosage administered at the same time (F ratio = 28.34; P value <0.0001). Concerning the time to TOF greater than 0.9 from the time point of TOF1, the timing of the dosages were statistically significant using log rank test (P < 0.0001). No patient presented a reparalysis. CONCLUSION: No difference between injecting sugammadex at TOF1 or TOF2 was found regarding time to full recovery. Difference regarding sugammadex quantity was found and compatible with other studies. TRIAL REGISTRATION: clinicaltrials.gov: 'BRIDION_ERASME', EudraCT: 2017-005074-19.

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.

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.

An intact animal model for the assessment of coronary blood flow regulation "Coronary blood flow regulation".

Coronary blood flow adapts to metabolic demand ("metabolic regulation") and remains relatively constant over a range of pressure changes ("autoregulation"). Coronary metabolic regulation and autoregulation are usually studied separately. We developed an intact animal experimental model to explore both regulatory mechanisms of coronary blood flow. Coronary pressure and flow-velocities were measured in four anesthetized and closed-chest pigs using an intracoronary Doppler wire. Metabolic regulation was assessed by coronary flow reserve defined as the ratio between the maximally vasodilated and the basal flow, with hyperemia achieved using intracoronary administration of adenosine (90 µg) or bradykinin (10-6  M) as endothelium-independent and -dependent vasodilators respectively. For both vasodilators, we found a healthy coronary flow reserve ≥ 3.0 at baseline, which was maintained at 2.9 ± 0.2 after a 6-hr period. Autoregulation was assessed by the lower breakpoint of coronary pressure-flow relationships, with gradual decrease in coronary pressure through the inflation of an intracoronary balloon. We found a lower limit of autoregulation between 42 and 55 mmHg, which was stable during a 6-hr period. We conclude that this intact animal model is adequate for the study of pharmacological interventions on the coronary circulation in health and disease, and as such suitable for preclinical drug studies.

Intravenous lidocaine to prevent endothelial dysfunction after major abdominal surgery: a randomized controlled pilot trial.

BACKGROUND: Major abdominal surgery is associated with endothelial glycocalyx disruption. The anti-inflammatory effects of lidocaine were recently associated with endothelial barrier protection. METHODS: This was a single-centre, parallel group, randomized, controlled, double blind, pilot trial. Forty adult patients scheduled for major abdominal surgery were included between December 2016 and March 2017 in the setting of a University Hospital in Brussels (Belgium); reasons for non-inclusion were planned liver resection and conditions associated to increased risk of local anesthetics systemic toxicity. Patients were randomized to receive either lidocaine by continuous intravenous administration or an equivalent volume of 0.9% saline. The primary endpoint was the postoperative syndecan-1 concentration (difference between groups). Near-infrared spectroscopy of the thenar eminence in association with the vascular occlusion test, and contemporary analysis of flow-mediated dilation of the brachial artery were the secondary outcomes, along with haemodynamic data. Blood samples and data were collected before surgery (T0), and at 1-3 h (T1) and 24 h (T2) post-surgery. RESULTS: Syndecan-1 concentration increased significantly post-surgery (P < 0.001), but without any difference between groups. The near-infrared spectroscopy-derived and flow-mediated dilation-derived variables showed minor changes unrelated to group assignment. Compared with the placebo group, the intervention group had a significantly lower peri-operative mean arterial pressure and cardiac index, despite equally conducted goal-directed haemodynamic management. Postoperative lactate concentrations were similar between groups. CONCLUSIONS: Lidocaine failed to have any effect on endothelial function. Since in comparisons to other types of clinical situations, syndecan-1 was only slightly upregulated, endothelial dysfunction after major abdominal surgery might be overestimated. TRIAL REGISTRATION: « ISRCTN Registry ¼ identifier: ISRCTN63417725. Date: 15/06/2020. Retrospectively registered.

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.

Brain Aging and Anesthesia.

Herein, the authors review the neuroanatomical and the neurophysiological aspects of the normal aging evolution based on the recent literature and briefly describe the difference between physiological and pathological brain aging, with consideration of the currently recommended anesthesia management of older patients. The population of elderly patients is growing drastically with advances in medicine that have prolonged the life span. One of the direct consequence has been a significant increase in the request for anesthesia care for older patients despite the type of surgery (cardiac vs noncardiac and mainly orthopedic). Because the brain of this category of patients undergoes a specific triple influence (immune, metabolic, and inflammatory), some particular physiological, anatomical, and structural modifications must be taken into account because they expose these patients more specifically to postoperative cognitive disturbances. To prevent type of adverse outcome, a better knowledge and understanding of these neurosciences must be promoted. The strategies developed to prevent such adverse outcomes include the determination and detection of significant at-risk patients and improvement in the titration of anesthesia to reduce exposure of anesthesia to these patients through an adapted anesthesia-induced unconsciousness that avoids, as much as possible, the risk of toxic overdose with an overly deep brain depression. To accomplish this, the unprocessed electroencephalogram (EEG) and its spectrogram may represent a significant improvement in monitoring, first by allowing for the rapid recognition of repetitive or persistent EEG suppression by the on-line reading of the raw EEG trace and second by allowing for the accurate determination of the adequate anesthetic-induced state, obtained in general in this category of patients by substantially lowered doses of anesthetic agents. This represents a new methodology for anesthesia titration that is adjusted on a more case-by-case basis and is related to the physiology of individual patients. A better understanding of aging-induced brain transformations remains the key regarding the improvement of the anesthetic management of the always growing population of elderly patients. The promotion of the unprocessed EEG may represent the best method of preventing the risk of anesthetic toxicity, including postoperative cognitive dysfunctions.

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.

Monitoring of pulse pressure variation using a new smartphone application (Capstesia) versus stroke volume variation using an uncalibrated pulse wave analysis monitor: a clinical decision making study during major abdominal surgery.

Pulse pressure variation (PPV) and stroke volume variation (SVV) can be used to assess fluid status in the operating room but usually require dedicated advanced hemodynamic monitors. Recently, a smartphone application (Capstesia™), which automatically calculates PPV from a picture of the invasive arterial pressure waveform from any monitor screen (PPVCAP), has been developed. The purpose of this study was to compare PPVCAP with SVV from an uncalibrated pulse wave analysis monitor (SVVPC). In 40 patients undergoing major abdominal surgery, we compared PPVCAP with SVVPC at post-induction, pre-incision, post-incision, end of surgery, and during every hypotensive episode (mean arterial pressure < 65 mmHg). We classified PPVCAP and SVVPC into three categories reflecting the thresholds used for the decision to administer fluids: no fluid administration (PPV and SVV < 9%), gray zone (PPV and SVV 9-13%), and fluid administration (PPV and SVV > 13%). The agreement between SVVPC and PPVCAP for these three categories was measured by the number of concordant paired measurements divided by the total number of paired measurements and Cohen's kappa coefficient. In the 549 pairs of PPV-SVV data obtained, the overall agreement of PPVCAP with SVVPC was 79%, and the kappa coefficient was moderate (0.55). The highest agreement and kappa coefficient value were observed after the induction of anesthesia before surgical incision. PPVCAP and SVVPC would have resulted in completely opposite clinical decisions regarding fluid administration in 1% of the cases. In this clinical decision making study in patients undergoing major abdominal surgery, we observed a moderate agreement between PPVCAP and SVVPC with regard to categories used to guide fluid administration. Trial Registration: Clinical Trials.gov (NCT03137901).

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 .