Design of a pharmacokinetic/pharmacodynamic model for administration of low dose peripheral norepinephrine during general anaesthesia.

AIMS: Intraoperative hypotension is a risk factor for kidney, heart and cognitive postoperative complications. Literature suggests that the use of low-dose peripheral norepinephrine (NOR) reduces organ dysfunction, yet its administration remains unstandardized. In this work we develop a pharmacokinetic (PK)/pharmacodynamic (PD) model of NOR and its effect on mean arterial pressure (MAP). METHODS: From June 2018 to December 2021, we included patients scheduled for elective neurosurgery and requiring vasopressors for intraoperative hypotension management at Lariboisière Hospital, Paris. Low doses of NOR were administered peripherally, and successive arterial blood samples were collected to track its plasmatic concentration. We used a compartmental modelling approach for NOR PK. We developed and compared 2 models for NOR PD on MAP. Model comparison was done using Bayes information criteria. The resulting PK/PD model parameters were fitted over the entire population and linked to age, weight, height and sex. RESULTS: We included 29 patients (age 52 [46-64] years, 69% female). NOR median time to peak effect on MAP was 74 [53-94] s. After bolus administration, MAP increased by 24% (15-31%). A 2-comparment model with depot best captured NOR PK. NOR PD effect on MAP was well represented by both Emax and Windkessel models, with better results for the former. We found that age, height and weight as well as history of smoking and hypertension were correlated with model parameters. CONCLUSION: We have developed a PK/PD model to accurately track norepinephrine plasma concentration and its effect on MAP over time, which could serve for target-controlled infusion.

Trending Ability of End-Tidal Capnography Monitoring During Mechanical Ventilation to Track Changes in Arterial Partial Pressure of Carbon Dioxide in Critically Ill Patients With Acute Brain Injury: A Monocenter Retrospective Study.

BACKGROUND: Changes in arterial partial pressure of carbon dioxide (Pa co2 ) may alter cerebral perfusion in critically ill patients with acute brain injury. Consequently, international guidelines recommend normocapnia in mechanically ventilated patients with acute brain injury. The measurement of end-tidal capnography (Et co2 ) allows its approximation. Our objective was to report the agreement between trends in Et co2 and Pa co2 during mechanical ventilation in patients with acute brain injury. METHODS: Retrospective monocenter study was conducted for 2 years. Critically ill patients with acute brain injury who required mechanical ventilation with continuous Et co2 monitoring and with 2 or more arterial gas were included. The agreement was evaluated according to the Bland and Altman analysis for repeated measurements with calculation of bias, and upper and lower limits of agreement. The directional concordance rate of changes between Et co2 and Pa co2 was evaluated with a 4-quadrant plot. A polar plot analysis was performed using the Critchley methods. RESULTS: We analyzed the data of 255 patients with a total of 3923 paired ΔEt co2 and ΔPa co2 (9 values per patient in median). Mean bias by Bland and Altman analysis was -8.1 (95 CI, -7.9 to -8.3) mm Hg. The directional concordance rate between Et co2 and Pa co2 was 55.8%. The mean radial bias by polar plot analysis was -4.4° (95% CI, -5.5 to -3.3) with radial limit of agreement (LOA) of ±62.8° with radial LOA 95% CI of ±1.9°. CONCLUSIONS: Our results question the performance of trending ability of Et co2 to track changes in Pa co2 in a population of critically ill patients with acute brain injury. Changes in Et co2 largely failed to follow changes in Pa co2 in both direction (ie, low concordance rate) and magnitude (ie, large radial LOA). These results need to be confirmed in prospective studies to minimize the risk of bias.

Association of sleep and anaesthesia EEG biomarkers with preoperative MoCA score: A pilot study.

INTRODUCTION: Preoperative cognitive impairments increase the risk of postoperative complications. The electroencephalogram (EEG) could provide information on cognitive vulnerability. The feasibility and clinical relevance of sleep EEG (EEGsleep ) compared to intraoperative EEG (EEGintraop ) in cognitive risk stratification remains to be explored. We investigated similarities between EEGsleep and EEGintraop vis-a-vis preoperative cognitive impairments. METHODS: Pilot study including 27 patients (63 year old [53.5, 70.0]) to whom Montreal cognitive assessment (MoCA) and EEGsleep were administered 1 day before a propofol-based general anaesthesia, in addition to EEGintraop acquisition from depth-of-anaesthesia monitors. Sleep spindles on EEGsleep and intraoperative alpha-band power on EEGintraop were particularly explored. RESULTS: In total, 11 (41%) patients had a MoCA <25 points. These patients had a significantly lower sleep spindle power on EEGsleep (25 vs. 40 µv2 /Hz, p = .035) and had a weaker intraoperative alpha-band power on EEGintraop (85 vs. 150 µv2 /Hz, p = .001) compared to patients with normal MoCA. Correlation between sleep spindle and intraoperative alpha-band power was positive and significant (r = 0.544, p = .003). CONCLUSION: Preoperative cognitive impairment appears to be detectable by both EEGsleep and EEGintraop . Preoperative sleep EEG to assess perioperative cognitive risk is feasible but more data are needed to demonstrate its benefit compared to intraoperative EEG.

Micro- and macrocirculatory effects of norepinephrine on anaesthesia-induced hypotension: a prospective preliminary study.

BACKGROUND: Intraoperative arterial hypotension (IOH) leads to increased postoperative morbidity. Norepinephrine is often use to treat IOH. The question regarding the mode of administration in either a bolus or continuous infusion remains unanswered. The aim of the present study was to describe and compare the effects on macrocirculation and microcirculation of a bolus and a continuous infusion of norepinephrine to treat IOH. METHODS: We conducted a prospective observational study with adult patients who underwent neurosurgery. Patients with invasive arterial blood pressure and cardiac output (CO) monitoring were screened for inclusion. All patients underwent microcirculation monitoring by video-capillaroscopy, laser doppler, near-infrared spectroscopy technology, and tissular CO2. In case of IOH, the patient could receive either a bolus of 10 µg or a continuous infusion of 200 µg/h of norepinephrine. Time analysis for comparison between bolus and continuous infusion were at peak of MAP. The primary outcome was MFI by videocapillaroscopy. RESULTS: Thirty-five patients were included, with 41 boluses and 33 continuous infusion. Bolus and continuous infusion induced an maximal increase in mean arterial pressure of +30[20-45] and +23[12-34] %, respectively (P=0,07). For macrocirculatory parameters, continuous infusion was associated with a smaller decrease in CO and stroke volume (p<0.05). For microcirculatory parameters, microvascular flow index (-0,1 vs. + 0,3, p=0,03), perfusion index (-12 vs. +12%, p=0,008), total vessel density (-0,2 vs. +2,3 mm2/mm2, p=0,002), showed significant opposite variations with bolus and continuous infusion, respectively. CONCLUSIONS: These results on macro and microcirculation enlighten the potential benefits of a continuous infusion of norepinephrine rather than a bolus to treat anaesthesia-induced hypotension. TRIAL REGISTRATION: (NOR-PHARM: 1-17-42 Clinical Trials: NCT03454204), 05/03/2018.

Estimation of cardiac output variations induced by hemodynamic interventions using multi-beat analysis of arterial waveform: a comparative off-line study with transesophageal Doppler method during non-cardiac surgery.

Multi-beat analysis (MBA) of the radial arterial pressure (AP) waveform is a new method that may improve cardiac output (CO) estimation via modelling of the confounding arterial wave reflection. We evaluated the precision and accuracy using the trending ability of the MBA method to estimate absolute CO and variations (ΔCO) during hemodynamic challenges. We reviewed the hemodynamic challenges (fluid challenge or vasopressors) performed when intra-operative hypotension occurred during non-cardiac surgery. The CO was calculated offline using transesophageal Doppler (TED) waveform (COTED) or via application of the MBA algorithm onto the AP waveform (COMBA) before and after hemodynamic challenges. We evaluated the precision and the accuracy according to the Bland & Altman method. We also assessed the trending ability of the MBA by evaluating the percentage of concordance with 15% exclusion zone between ΔCOMBA and ΔCOTED. A non-inferiority margin was set at 87.5%. Among the 58 patients included, 23 (40%) received at least 1 fluid challenge, and 46 (81%) received at least 1 bolus of vasopressors. Before treatment, the COTED was 5.3 (IQR [4.1-8.1]) l min-1, and the COMBA was 4.1 (IQR [3-5.4]) l min-1. The agreement between COTED and COMBA was poor with a 70% percentage error. The bias and lower and upper limits of agreement between COTED and COMBA were 0.9 (CI95 = 0.82 to 1.07) l min-1, -2.8 (CI95 = -2.71 to-2.96) l min-1 and 4.7 (CI95 = 4.61 to 4.86) l min-1, respectively. After hemodynamic challenge, the percentage of concordance (PC) with 15% exclusion zone for ΔCO was 93 (CI97.5 = 90 to 97)%. In this retrospective offline analysis, the accuracy, limits of agreements and percentage error between TED and MBA for the absolute estimation of CO were poor, but the MBA could adequately track induced CO variations measured by TED. The MBA needs further evaluation in prospective studies to confirm those results in clinical practice conditions.

Velocity-pressure loops can estimate intrinsic and pharmacologically induced changes in cardiac afterload during non-cardiac surgery. An observational study.

PURPOSE: Continuous measurement of aortic pressure and aortic flow velocity signals in the operating theatre allows us to draw velocity-pressure (Vel-Pre) loops. The global afterload angle (GALA), derived from the Vel-Pre loops, has been linked to cardiac afterload indicators. As age is the major determinant of constitutive arterial stiffness, we aimed to describe (1) the evolution of the GALA according to age in a large cohort of anesthetized patients and (2) GALA variations induced by haemodynamic interventions. METHODS: We included patients for whom continuous monitoring of arterial pressure and cardiac output were indicated. Fluid challenges or vasopressors were administered to treat intra-operative hypotension. The primary endpoint was the comparison of the GALA values between young and old patients. The secondary endpoint was the difference in the GALA values before and after haemodynamic interventions. RESULTS: We included 133 anaesthetized patients: 66 old and 67 young patients. At baseline, the GALA was higher in the old patients than in young patients (38 ± 6 vs. 25 ± 4 degrees; p < 0.001). The GALA was positively associated with age (p < 0.001), but the mean arterial pressure (MAP) and cardiac output were not. The GALA did not change after volume expansion, regardless of the fluid response, but it did increase after vasopressor administration. Furthermore, while a vasopressor bolus led to a similar increase in MAP, phenylephrine induced a more substantial increase in the GALA than noradrenaline (+ 12 ± 5° vs. + 8 ± 5°; p = 0.01). CONCLUSION: In non-cardiac surgery, the GALA seems to be associated with both intrinsic rigidity (reflected by age) and pharmacologically induced vasoconstriction changes (by vasopressors). In addition, the GALA can discriminate the differential effects of phenylephrine and noradrenaline. These results should be confirmed in a prospective, ideally randomized, trial.

Real-time estimation of mean arterial blood pressure based on photoplethysmography dicrotic notch and perfusion index. A pilot study.

Hypotension during general anesthesia is associated with poor outcome. Continuous monitoring of mean blood pressure (MAP) during anesthesia is useful and needs to be reliable and minimally invasive. Conventional cuff measurements can lead to delays due to its discontinuous nature. It has been shown that there is a relationship between MAP and photoplethysmography (PPG) parameters like the dicrotic notch and perfusion index (PI). The objective of the study was to continuously estimate MAP from PPG. Pulse wave analysis based on PPG was implemented using either notch relative amplitude (MAPNRA), notch absolute amplitude (MAPNAA) or PI (MAPPI) to estimate MAP from PPG waveform features during general anesthesia. Estimated MAP values were compared to brachial cuff MAP (MAPcuff) and to radial invasive MAP (MAPinv). Forty-six patients were analyzed for a total of 235 h. Compared to MAPcuff, mean bias and limits of agreement were 1 mmHg (- 26 to +29), - 1 mmHg (- 10 to +8) and - 3 mmHg (- 21 to +13) for MAPNRA, MAPNAA and MAPPI respectively. Compared to MAPinv, mean absolute error (MAE) was 20 mmHg [10 to 39], 11 mmHg [5 to 18] and 16 mmHg [9 to 24] for MAP derived from MAPNRA, MAPNAA and MAPPI respectively. When calibrated every 5 min, MAPNAA showed a MAE of 6 mmHg [5 to 9]. MAPNAA provides the best estimates with respect to brachial cuff MAP and invasive MAP. Regular calibration allows to reduce drift over time. Beat to beat estimation of MAP during general anesthesia from the PPG appears possible with an acceptable average error.

Impact of hypotension on cerebral perfusion during general anesthesia induction: A prospective observational study in adults.

INTRODUCTION: During anesthesia, decreases in mean arterial pressure (MAP) are common but the impact on possible cerebral hypoperfusion remains a matter of debate. We evaluated cerebral perfusion in patients with or without cardiovascular comorbidities (Hi-risk vs Lo-risk) during induction of general anesthesia and during hypotensive episodes. METHODS: Patients scheduled for neuroradiology procedure using standardized target-controlled Propofol-Remifentanil infusion were prospectively included. Monitoring included Transcranial Doppler (TCD) measuring mean blood velocity of the middle cerebral artery (Vm), Bispectral Index with burst suppression ratio (SR) and cerebral Near-Infrared Spectroscopy (NIRS). Hypotensive episodes were treated with a 10 µg bolus of Norepinephrine. RESULTS: Eighty-one patients were included, 37 Hi-risk and 44 Lo-risk. During induction of anesthesia, MAP and Vm decreased in all patients, with greater changes observed in Hi-risk patients compared to Lo-risk patients (-34 [38-29]% vs -17 [25-8]%, P < .001 and -39 [45-29]% vs -28 [34-19]%, P < .01 respectively). In Hi-risk patients, the MAP-decrease correlated with the Vm-decrease (r = .48, P < .01), and was associated with more frequent occurrences of SR (21 vs 5 patients, P < .01 for Hi-risk vs Lo-risk). For the MAP-increase induced by norepinephrine, the Vm-increase was greater in Hi-risk than in Lo-risk patients (+15 [8-21]% vs +4 [1-11]%, P < .01). During induction and norepinephrine boluses, NIRS values did not follow acute changes of Vm. CONCLUSION: Our results showed that Hi-risk patients had a higher decrease in MAP and Vm, and a higher occurrence of SR during induction of anesthesia than Lo-risk patients. Correction of MAP with norepinephrine increased Vm mainly in Hi-rik patients.

Anesthesia management for low-grade glioma awake surgery: a European Low-Grade Glioma Network survey.

BACKGROUND: Awake surgery has become a key treatment of diffuse low-grade gliomas (DLGG) and is divided in three main phases: opening, tumor resection - during which the patient needs to be fully awake - and closure. The anesthetic management of awake neurosurgery is a challenge, and there are currently no guidelines. OBJECTIVE: The objective of the survey was to explore differences and commonalities regarding the anesthetic management of awake DLGG surgery within the European Low-Grade Glioma Network (ELGGN) centers. METHODS: A form that contained 14 questions about the anesthetic management was sent to 28 centers in May 2015. RESULTS: Twenty centers responded. During the opening and closing non-awake periods, 56% of teams chose general anesthesia with mechanical ventilation for at least one period (asleep-awake-asleep, SAS protocol), and 44% monitored anesthesia care including sedation without mechanical ventilation (MAC protocol). In case of SAS, all the teams chose intravenous anesthesia, 82% used laryngeal mask instead of endotracheal intubation during the opening sequence, and 71% during closure. Local and regional anesthesia was practiced by all the teams. The most frequently reported cause of pain was dural and cerebral vessels manipulation (77%). Pain management was mostly based on paracetamol (70%) and remifentanil (55%). CONCLUSION: Our survey showed that there was an equivalent proportion of centers using SAS or MAC protocols in the anesthetic management of awake surgery in ELGGN centers. The advantages and disadvantages of each anesthesia protocol were reviewed.

Noninvasive continuous detection of arterial hypotension during induction of anaesthesia using a photoplethysmographic signal: proof of concept.

BACKGROUND: During general anaesthesia, intraoperative hypotension (IOH), defined as a mean arterial pressure (MAP) reduction of > 20%, is frequent and may lead to complications. Pulse oximetry is mandatory in the operating room, making the photoplethysmographic signal and parameters, such as relative dicrotic notch height (Dicpleth) or perfusion index (PI), readily available. The purpose of this study was to investigate whether relative variations of Dicpleth and PI could detect IOH during anaesthesia induction, and to follow their variations during vasopressor boluses. METHODS: MAP, Dicpleth, and PI were monitored at 1-min intervals during target control induction of anaesthesia with propofol and remifentanil in 61 subjects. Vasopressor infusion (norepinephrine or phenylephrine) was performed when hypotension occurred according to the decision of the physician. RESULTS: The delta in Dicpleth and PI accurately detected IOH, with areas under the receiver operating characteristic curves (AUC) of 0.86 and 0.83, respectively. The optimal thresholds were -19% (sensitivity 79%; specificity 84%) and 51% (sensitivity 82%; specificity 74%) for ΔDicpleth and ΔPI, respectively. There was no difference between the ROC of ΔDicpleth and ΔPI (P=0.22). Combining both ΔDicpleth and ΔPI further improved the hypotension detection power (AUC=0.91) with a sensitivity and specificity of 84%. MAP variations were correlated with ΔDicpleth and ΔPI during vasopressor infusion (r=0.73 and -0.62, respectively; P<0.001). CONCLUSIONS: The relative variation in Dicpleth and PI derived from the photoplethysmographic signal can be used as a non invasive, continuous, and simple tool to detect intraoperative hypotension, and to track the vascular response to vasoconstrictor drugs during induction of general anaesthesia. CLINICAL TRIAL REGISTRATION: NCT03756935.

Propofol/Remifentanil Anesthesia Might Not Alter the Middle Cerebral Artery Diameter by Digital Subtraction Angiography.

INTRODUCTION: Transcranial Doppler (TCD) of the middle cerebral artery (MCA) enables the measurement of the mean blood velocity (MCAVm) and the estimation of the cerebral blood flow (CBF), provided that no significant changes occur in the MCA diameter (MCADiam). Previous studies described a decrease in the MCAVm associated with the induction of total intravenous anesthesia (TIVA) by propofol and remifentanil. This decrease in blood velocity might be interpreted as a decrease in the CBF only where the MCADiam is not modified across TCD examinations. METHODS: In this observational study, we measured the MCADiam of 24 subjects (almost exclusively females) on digital subtraction angiography under awake and TIVA conditions. RESULTS: Across the two phases, we observed a decrease in the mean arterial blood pressure (from 84 ± 9 to 71 ± 6 mmHg; p < 0.001) and heart rate (76 ± 10 vs. 65 ± 8 beats/min; p < 0.001), and a concomitant decrease in the MCAVm (61 vs. 42 cm/s; p < 0.001). In contrast, the MCADiam did not vary in association with TIVA (2.3 ± 0.2 vs. 2.3 ± 0.2 mm; p = 0.52). CONCLUSIONS: Those results suggested that in this population, no significant changes in the MCADiam are associated with TIVA.

Controlling the Quality Factor of a Single Acoustic Nanoresonator by Tuning its Morphology.

The mechanical vibrations of individual gold nanodisks nanopatterned on a sapphire substrate are investigated using ultrafast time-resolved optical spectroscopy. The number and characteristics of the detected acoustic modes are found to vary with nanodisk geometry. In particular, their quality factors strongly depend on nanodisk aspect ratio (i.e., diameter over height ratio), reaching a maximal value of ≈70, higher than those previously measured for substrate-supported nano-objects. The peculiarities of the detected acoustic vibrations are confirmed by finite-element simulations, and interpreted as the result of substrate-induced hybridization between the vibrational modes of a nanodisk. The present findings demonstrate novel possibilities for engineering the vibrational modes of nano-objects.

Evaluation of cardiac output variations with the peripheral pulse pressure to mean arterial pressure ratio.

Cardiac output (CO) optimisation during surgery reduces post-operative morbidity. Various methods based on pulse pressure analysis have been developed to overcome difficulties to measure accurate CO variations in standard anaesthetic settings. Several of these methods include, among other parameters, the ratio of pulse pressure to mean arterial pressure (PP/MAP). The aim of this study was to evaluate whether the ratio of radial pulse pressure to mean arterial pressure (ΔPPrad/MAP) could track CO variations (ΔCO) induced by various therapeutic interventions such as fluid infusions and vasopressors boluses [phenylephrine (PE), norepinephrine (NA) or ephedrine (EP)] in the operating room. Trans-oesophageal Doppler signal and pressure waveforms were recorded in patients undergoing neurosurgery. CO and PPrad/MAP were recorded before and after fluid challenges, PE, NA and EP bolus infusions as medically required during their anaesthesia. One hundred and three patients (mean age: 52 ± 12 years old, 38 men) have been included with a total of 636 sets of measurement. During fluids challenges (n = 188), a positive correlation was found between ΔPPrad/MAP and ΔCO (r = 0.22, p = 0.003). After PE (n = 256) and NA (n = 121) boluses, ΔPPrad/MAP positively tracked ΔCO (r = 0.53 and 0.41 respectively, p < 0.001). By contrast, there was no relation between ΔPPrad/MAP and ΔCO after EP boluses (r = 0.10, p = 0.39). ΔPPrad/MAP tracked ΔCO variations during PE and NA vasopressor challenges. However, after positive fluid challenge or EP boluses, ΔPPrad/MAP was not as performant to track ΔCO which could make the use of this ratio difficult in current clinical practice.

Mechanical Vibrations of Atomically Defined Metal Clusters: From Nano- to Molecular-Size Oscillators.

Acoustic vibrations of small nanoparticles are still ruled by continuum mechanics laws down to diameters of a few nanometers. The elastic behavior at lower sizes (<1-2 nm), where nanoparticles become molecular clusters made by few tens to few atoms, is still little explored. The question remains to which extent the transition from small continuous-mass solids to discrete-atom molecular clusters affects their specific low-frequency vibrational modes, whose period is classically expected to linearly scale with diameter. Here, we investigate experimentally by ultrafast time-resolved optical spectroscopy the acoustic response of atomically defined ligand-protected metal clusters Au n(SR) m with a number n of atoms ranging from 10 to 102 (0.5-1.5 nm diameter range). Two periods, corresponding to fundamental breathing- and quadrupolar-like acoustic modes, are detected, with the latter scaling linearly with cluster diameters and the former taking a constant value. Theoretical calculations based on density functional theory (DFT) predict in the case of bare clusters vibrational periods scaling with size down to diatomic molecules. For ligand-protected clusters, they show a pronounced effect of the ligand molecules on the breathing-like mode vibrational period at the origin of its constant value. This deviation from classical elasticity predictions results from mechanical mass-loading effects due to the protecting layer. This study shows that clusters characteristic vibrational frequencies are compatible with extrapolation of continuum mechanics model down to few atoms, which is in agreement with DFT computations.

Beat-by-beat assessment of cardiac afterload using descending aortic velocity-pressure loop during general anesthesia: a pilot study.

INTRODUCTION: Continuous cardiac afterload evaluation could represent a useful tool during general anesthesia (GA) to titrate vasopressor effect. Using beat to beat descending aortic pressure(P)/flow velocity(U) loop obtained from esophageal Doppler and femoral pressure signals might allow to track afterload changes. Methods We defined three angles characterizing the PU loop (alpha, beta and Global After-Load Angle (GALA)). Augmentation index (AIx) and total arterial compliance (Ctot) were measured via radial tonometry. Peripheral Vascular Resistances (PVR) were also calculated. Twenty patients were recruited and classified into low and high cardiovascular (CV) risk group. Vasopressors were administered, when baseline mean arterial pressure (MAP) fell by 20%. Results We studied 118 pairs of pre/post bolus measurements. At baseline, patients in the lower CV risk group had higher cardiac output (6.1 ± 1.7 vs 4.2 ± 0.6 L min; p = 0.005), higher Ctot (2.7 ± 1.0 vs 2.0 ± 0.4 ml/mmHg, p = 0.033), lower AIx and PVR (13 ± 10 vs 32 ± 11% and 1011 ± 318 vs 1390 ± 327 dyn s/cm5; p < 0.001 and p = 0.016, respectively) and lower GALA (41 ± 15 vs 68 ± 6°; p < 0.001). GALA was the only PU Loop parameter associated with Ctot, AIx and PVR. After vasopressors, MAP increase was associated with a decrease in Ctot, an increase in AIx and PVR and an increase in alpha, beta and GALA (p < 0.001 for all). Changes in GALA and Ctot after vasopressors were strongly associated (p = 0.004). Conclusions PU Loop assessment from routine invasive hemodynamic optimization management during GA and especially GALA parameter could monitor cardiac afterload continuously in anesthetized patients, and may help clinicians to titrate vasopressor therapy.

Velocity-pressure loops for continuous assessment of ventricular afterload: influence of pressure measurement site.

VPloop, the graphical representation of pressure versus velocity, and its characteristic angles, GALA and ß, can be used to monitor cardiac afterload during anesthesia. Ideally VPloop should be measured from pressure and velocity obtained at the same arterial location but standard of care usually provide either radial or femoral pressure waveforms. The purpose of this study was to look at the influence of arterial sites and the use of a transfer function (TF) on VPloop and its related angles. Invasive pressure signals were recorded in 25 patients undergoing neuroradiology intervention under general anesthesia with transesophageal flow velocity monitoring. Pressures were recorded in the descending thoracic aorta, abdominal aorta, femoral and radial arteries. We compared GALA and ß from VPloops generated from each location and in high and low risk patients. GALA was similar in the central locations (55°[49-63], 52°[47-61] and 54°[45-62] from descending thoracic to femoral artery, median[interquartile], p = 0.10), while there was a difference in ß angle (16°[4-27] to 8°[3-15], p < 0.0001). GALA and ß obtained from radial waveforms were different (39°[31-47] compared to 46°[36-54] and 6°[2-14] compared to 16°[4-27] for GALA and ß angles respectively, p < 0.001) which was corrected by the use of a TF (45°[32-55] and 17°[5-28], p = ns). GALA and ß are underestimated when measured with a radial catheter. Using pressure waveforms from femoral locations alters VPloops, GALA and ß in a smaller extend. The use of a TF on radial pressure allows to correctly plot VPloops and their characteristic angles for routine clinical use.

Impact of extended monitoring-guided intensive care on outcome after severe traumatic brain injury: A prospective multicentre cohort study (PariS-TBI study).

OBJECTIVE: We evaluated whether an integrated monitoring with systemic and specific monitoring affect mortality and disability in adults with severe traumatic brain injury (sTBI). METHODS: Adults with severeTBI (Glasgow Coma Scale [GCS] ≤ 8) admitted alive in intensive care units (ICUs) were prospectively included. Primary endpoints were in-hospital 30-day mortality and extended Glasgow outcome score (GOSE) at 3 years. Association with the intensity of monitoring and outcome was studied by comparing a high level of monitoring (HLM) (systemic and ≥3 specific monitoring) and low level of monitoring (LLM) (systemic and 0-2 specific monitoring) and using inverse probability weighting procedure. RESULTS: 476 patients were included and IPW was used to improve the balance between the two groups of treatments (HLM/LMM). Overall hospital mortality (at 30 days) was 43%, being significantly lower in HLM than LLM group (27% vs. 53%: RR, 1.63: 95% CI: 1.23-2.15). The 14-day hospital mortality was also lower in the HLM group than expected, based upon the CRASH prediction model (35%). At 3 years, disability was not significantly different between the monitoring groups. CONCLUSIONS: After adjustment, HLM group improved short-term mortality but did not show any improvement in the 3-year outcome compared with LLM.

Fano Interference in the Optical Absorption of an Individual Gold-Silver Nanodimer.

Fano resonances are central features in the responses of many systems including atoms, molecules, and nanomaterials. They arise as a consequence of interferences between two channels, most frequently associated with two system modes. In plasmonic materials, Fano interferences between optical modes have been shown, experimentally and theoretically, to induce narrow features in their scattering spectra. By investigating individual silver-gold heterodimers, we first experimentally demonstrate that Fano interference is also a key effect in the optical absorption of plasmonic nano-objects, in agreement with theoretical predictions. Conversely to previously investigated systems, the two interacting modes at the origin of absorptive Fano effect are mostly localized on either one or the other dimer component. Experimental results were obtained by selectively monitoring the optical absorption of one dimer component using a two-color nonlinear time-resolved technique. This also opens the way to full optical far-field noncontact investigations of charge or energy exchanges between nano-objects with a spatial resolution much smaller than the optical wavelength.