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.

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.

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.

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.

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.

Loss to Follow-Up and Social Background in an Inception Cohort of Patients With Severe Traumatic Brain Injury: Results From the PariS-TBI Study.

OBJECTIVES: To assess determinants of loss to follow-up (FU) at 2 time points of an inception traumatic brain injury (TBI) cohort. DESIGN AND PARTICIPANTS: The PariS-TBI study consecutively included 504 adults with severe TBI on the accident scene (76% male, mean age 42 years, mean Glasgow Coma Scale 5). No exclusion criteria were used. MAIN MEASURE: Loss to FU at 1 and 4 years was defined among survivors as having no outcome data other than survival status. RESULTS: Among 257 1-year survivors, 118 (47%) were lost to FU at 1 year and 98 (40%) at 4 years. Main reasons for loss to FU were impossibility to achieve contact (109 at 1 year, 52 at 4 years) and refusal to participate (respectively 5 and 24). At 1 year, individuals not working preinjury or with nonaccidental traumas were more often lost to FU in univariate and multivariable analyses. At 4 years, loss to FU was significantly associated with preinjury alcohol abuse and unemployment. Relationship with injury severity was not significant. CONCLUSIONS: Socially disadvantaged persons are underrepresented in TBI outcome research. It could result in overestimation of outcome and biased estimates of sociodemographic characteristics' effects. These persons, particularly unemployed individuals, require special attention in clinical practice.

Reversal of neutrophil-to-lymphocyte count ratio in early versus late death from septic shock.

INTRODUCTION: Septic shock is one of the most frequent causes of admission to the intensive care unit (ICU) and is associated with a poor prognosis. Early and late death in septic shock should be distinguished because they may involve different underlying mechanisms. In various conditions, the neutrophil-to-lymphocyte count ratio (NLCR) has been described as an easily measurable parameter to express injury severity. In the present study, we investigated whether the timing of death was related to a particular NLCR. METHODS: We conducted a prospective, single-center, observational study that included consecutive septic shock patients. Severity scores, early (before day 5) or late (on or after day 5 of septic shock onset) ICU mortality, and daily leukocyte counts were collected during the ICU stay. We assessed the association between leukocyte counts at admission and their evolution during the first 5 days with early or late death. The association between patient characteristics (including cell counts) and prognosis was estimated using Cox proportional cause-specific hazards models. RESULTS: The study included 130 patients who were diagnosed with abdominal (n = 99) or extra-abdominal (n = 31) septic shock. The median (interquartile range) NLCR was 12.5 (6.5-21.2) in survivors and 6.2 (3.7-12.6) in nonsurvivors (p = 0.001). The NLCR at admission was significantly lower in patients who died before day 5 than in survivors (5 [3.5-11.6] versus 12.5 [6.5-21.2], respectively; p = 0.01). From day 1 to day 5, an increased NLCR related to an increase in neutrophil count and a decrease in lymphocyte count was associated with late death (+34.8 % [-8.2 to 305.4] versus -20 % [-57.4 to 45.9]; p = 0.003). Those results were present in patients with abdominal origin sepsis as well as in those with extra-abdominal sepsis, who were analyzed separately. CONCLUSIONS: In the present study, a reversed NLCR evolution was observed according to the timing of death. Septic shock patients at risk of early death had a low NLCR at admission, although late death was associated with an increased NLCR during the first 5 days.

Subarachnoid hemorrhage induces an early and reversible cardiac injury associated with catecholamine release: one-week follow-up study.

INTRODUCTION: The occurrence of cardiac dysfunction is common after subarachnoid hemorrhage (SAH) and was hypothesized to be related to the release of endogenous catecholamines. The aim of this prospective study was to evaluate the relationship between endogenous catecholamine and cardiac dysfunction at the onset and during the first week after SAH. METHODS: Forty consecutive patients admitted for acute SAH without known heart disease were included. Catecholamine plasma concentrations and transthoracic echocardiography (TTE) were documented on admission, on day 1 (D1), and day 7 (D7). RESULTS: At baseline, 24 patients had a World Federation of Neurosurgical Societies score (WFNS) of one or two; the remaining 16 had a WFNS between three and five. Twenty patients showed signs of cardiac dysfunction on admission, including six with left ventricle (LV) systolodiastolic dysfunction and 14 with pure LV diastolic dysfunction. On admission, norepinephrine, epinephrine, dopamine, B-type Natriuretic Peptide (BNP) and Troponin Ic (cTnI) plasmatic levels were higher in patients with the higher WFNS score and in patients with altered cardiac function (all P <0.05). Among patients with cardiac injury, heart function was restored within one week in 13 patients, while seven showed persistent LV diastolic dysfunction (P = 0.002). Plasma BNP, cTnI, and catecholamine levels exerted a decrease towards normal values between D1 and D7. CONCLUSION: Our findings show that cardiac dysfunction seen early after SAH was associated with both a rapid and sustained endogenous catecholamine release and WFNS score. SAH-induced cardiac dysfunction was regressive over the first week and paralleled the normalization of catecholamine concentration.

Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study.

INTRODUCTION: The role of systemic hemodynamics in the pathogenesis of septic acute kidney injury (AKI) has received little attention. The purpose of this study was to investigate the association between systemic hemodynamics and new or persistent of AKI in severe sepsis. METHODS: A retrospective study between 2006 and 2010 was performed in a surgical ICU in a teaching hospital. AKI was defined as development (new AKI) or persistent AKI during the five days following admission based on the Acute Kidney Injury Network (AKIN) criteria. We studied the association between the following hemodynamic targets within 24 hours of admission and AKI: central venous pressure (CVP), cardiac output (CO), mean arterial pressure (MAP), diastolic arterial pressure (DAP), central venous oxygen saturation (ScvO2) or mixed venous oxygen saturation (SvO2). RESULTS: This study included 137 ICU septic patients. Of these, 69 had new or persistent AKI. AKI patients had a higher Simplified Acute Physiology Score (SAPS II) (57 (46 to 67) vs. 45 (33 to 52), P < 0.001) and higher mortality (38% vs. 15%, P = 0.003) than those with no AKI or improving AKI. MAP, ScvO2 and CO were not significantly different between groups. Patients with AKI had lower DAP and higher CVP (P = 0.0003). The CVP value was associated with the risk of developing new or persistent AKI even after adjustment for fluid balance and positive end-expiratory pressure (PEEP) level (OR = 1.22 (1.08 to 1.39), P = 0.002). A linear relationship between CVP and the risk of new or persistent AKI was observed. CONCLUSIONS: We observed no association between most systemic hemodynamic parameters and AKI in septic patients. Association between elevated CVP and AKI suggests a role of venous congestion in the development of AKI. The paradigm that targeting high CVP may reduce occurrence of AKI should probably be revised. Furthermore, DAP should be considered as a potential important hemodynamic target for the kidney.

Local and systemic innate immune response to secondary human peritonitis.

INTRODUCTION: Our aim was to describe inflammatory cytokines response in the peritoneum and plasma of patients with peritonitis. We also tested the hypothesis that scenarios associated with worse outcome would result in different cytokine release patterns. Therefore, we compared cytokine responses according to the occurrence of septic shock, mortality, type of peritonitis and peritoneal microbiology. METHODS: Peritoneal and plasma cytokines (interleukin (IL) 1, tumor necrosis factor α (TNFα), IL-6, IL-10, and interferon γ (IFNγ)) were measured in 66 patients with secondary peritonitis. RESULTS: The concentration ratio between peritoneal fluid and plasma cytokines varied from 5 (2 to 21) (IFNγ) to 1310 (145 to 3888) (IL-1). There was no correlation between plasma and peritoneal fluid concentration of any cytokine. In the plasma, TNFα, IL-6, IFNγ and IL-10 were higher in patients with shock versus no shock and in nonsurvivors versus survivors (P ≤0.03). There was no differential plasma release for any cytokine between community-acquired and postoperative peritonitis. The presence of anaerobes or Enterococcus species in peritoneal fluid was associated with higher plasma TNFα: 50 (37 to 106) versus 38 (29 to 66) and 45 (36 to 87) versus 39 (27 to 67) pg/ml, respectively (P = 0.02). In the peritoneal compartment, occurrence of shock did not result in any difference in peritoneal cytokines. Peritoneal IL-10 was higher in patients who survived (1505 (450 to 3130) versus 102 (9 to 710) pg/ml; P = 0.04). The presence of anaerobes and Enterococcus species was associated with higher peritoneal IFNγ: 2 (1 to 6) versus 10 (5 to 28) and 7 (2 to 39) versus 2 (1 to 6), P = 0.01 and 0.05, respectively). CONCLUSIONS: Peritonitis triggers an acute systemic and peritoneal innate immune response with a simultaneous release of pro and anti-inflammatory cytokines. Higher levels of all cytokines were observed in the plasma of patients with the most severe conditions (shock, non-survivors), but this difference was not reflected in their peritoneal fluid. There was always a large gradient in cytokine concentration between peritoneal and plasma compartments highlighting the importance of compartmentalization of innate immune response in peritonitis.

Impact of impaired cerebral blood flow autoregulation on electroencephalogram signals in adults undergoing propofol anaesthesia: a pilot study.

Background: Cerebral autoregulation actively maintains cerebral blood flow over a range of MAPs. During general anaesthesia, this mechanism may not compensate for reductions in MAP leading to brain hypoperfusion. Cerebral autoregulation can be assessed using the mean flow index derived from Doppler measurements of average blood velocity in the middle cerebral artery, but this is impractical for routine monitoring within the operating room. Here, we investigate the possibility of using the EEG as a proxy measure for a loss of cerebral autoregulation, determined by the mean flow index. Methods: Thirty-six patients (57.5 [44.25; 66.5] yr; 38.9% women, non-emergency neuroradiology surgery) anaesthetised using propofol were prospectively studied. Continuous recordings of MAP, average blood velocity in the middle cerebral artery, EEG, and regional cerebral oxygen saturation were made. Poor cerebral autoregulation was defined as a mean flow index greater than 0.3. Results: Eighteen patients had preserved cerebral autoregulation, and 18 had altered cerebral autoregulation. The two groups had similar ages, MAPs, and average blood velocities in the middle cerebral artery. Patients with altered cerebral autoregulation exhibited a significantly slower alpha peak frequency (9.4 [9.0, 9.9] Hz vs 10.5 [10.1, 10.9] Hz, P<0.001), which persisted after adjusting for age, norepinephrine infusion rate, and ASA class (odds ratio=0.038 [confidence interval, 0.004, 0.409]; P=0.007). Conclusion: In this pilot study, we found that loss of cerebral autoregulation was associated with a slower alpha peak frequency, independent of age. This work suggests that impaired cerebral autoregulation could be monitored in the operating room using the existing EEG setup. Clinical trial registration: NCT03769142.

The ICEBERG: A score and visual representation to track the severity of traumatic brain injury: Design principles and preliminary results.

BACKGROUND: Establishing neurological prognoses in traumatic brain injury (TBI) patients remains challenging. To help physicians in the early management of severe TBI, we have designed a visual score (ICEBERG score) including multimodal monitoring and treatment-related criteria. We evaluated the ICEBERG scores among patients with severe TBI to predict the 28-day mortality and long-term disability (Extended Glasgow Outcome Scale score at 3 years). In addition, we made a preliminary assessment of the nurses and doctors on the uptake and reception to the use of the ICEBERG visual tool. METHODS: This study was part of a larger prospective cohort study of 207 patients with severe TBI in the Parisian region (PariS-TBI study). The ICEBERG score included six variables from multimodal monitoring and treatment-related criteria: cerebral perfusion pressure, intracranial pressure, body temperature, sedation depth, arterial partial pressure of CO 2 , and blood osmolarity. The primary outcome measures included the ICEBERG score and its relationship with hospital mortality and Extended Glasgow Outcome Score. RESULTS: The hospital mortality was 21% (45/207). The ICEBERG score baseline value and changes during the 72nd first hours were more strongly associated with TBI prognosis than the ICEBERG parameters measured individually. Interestingly, when the clinical and computed tomography parameters at admission were combined with the ICEBERG score at 48 hours using a multimodal approach, the predictive value was significantly increased (area under the curve = 0.92). Furthermore, comparing the ICEBERG visual representation with the traditional numerical readout revealed that changes in patient vitals were more promptly detected using ICEBERG representation ( p < 0.05). CONCLUSION: The ICEBERG score could represent a simple and effective method to describe severity in TBI patients, where a high score is associated with increased mortality and disability. In addition, ICEBERG representation could enhance the recognition of unmet therapeutic goals and dynamic evolution of the patient's condition. These preliminary results must be confirmed in a prospective manner. LEVEL OF EVIDENCE: Diagnostic Tests or Criteria; Level III.

Arterial catheter-related bloodstream infections: results of an 8-year survey in a surgical intensive care unit.

OBJECTIVES: To determine whether a policy based on provisional replacement of catheters every 5 days had an impact on the incidence of arterial catheter-related bloodstream infections in a population of adult surgical intensive care unit patients. DESIGN: Prepost study in which all patients with an arterial catheter who were admitted between 1997 and 2004 were observed. Scheduled replacement of arterial catheters every 5 days during period A (before 2000) was compared to nonscheduled replacement during period B (after 2000). SETTING: A 20-bed surgical intensive care unit at a French university hospital. PATIENTS: All intensive care unit patients requiring an arterial catheter. INTERVENTIONS: Modification to the catheter maintenance policies between period A and period B. MEASUREMENTS AND MAIN RESULTS: A total of 1,672 consecutive patients were included, and 3,247 arterial catheters were analyzed, yielding an average number of 1.9 (sd, 1.7) arterial catheters per patient. The rate of colonization (14.2% before 2000 vs. 16.4% after 2000; p = .10) and the incidence density of arterial catheter colonization (31.32 [95% confidence interval] 27.07-36.25 per 1,000 catheter-days before 2000 vs. 29.79 [95% confidence interval, 26.72-33.21] per 1,000 catheter-days after 2000; p = .11) did not differ significantly between the two periods. However, the rate of arterial catheter-related bloodstream infections (1.4% before 2000 vs. 0.6% after 2000; p = .01) and the arterial catheter-related bloodstream infections incidence density (3.13 [95% confidence interval, 1.97-4.97] before 2000 vs. 1.01 [95% confidence interval, 0.56-1.82] per 1,000 catheter-days after 2000; p < .0001) was significantly higher before 2000. CONCLUSION: Discontinuation of scheduled replacement of arterial catheters every 5 days did not increase the risk of colonization but decreased the risk of bloodstream infections.

Value of Early Circulating Tumor Cells Dynamics to Estimate Docetaxel Benefit in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients.

Circulating tumor cell (CTC) enumeration and changes following treatment have been demonstrated to be superior to PSA response in determining mCRPC outcome in patients receiving AR signaling inhibitors but not taxanes. We carried out a pooled analysis of two prospective studies in mCRPC patients treated with docetaxel. CTCs were measured at baseline and 3-6 weeks post treatment initiation. Cox regression models were constructed to compare 6-month radiographical progression-free survival (rPFS), CTCs and PSA changes predicting outcome. Among the subjects, 80 and 52 patients had evaluable baseline and post-treatment CTC counts, respectively. A significant association of higher baseline CTC count with worse overall survival (OS), PFS and time to PSA progression (TTPP) was observed. While CTC response at 3-6 weeks (CTC conversion (from ≥5 to <5 CTCs), CTC30 (≥30% decline in CTC) or CTC0 (decline to 0 CTC)) and 6-month rPFS were significantly associated with OS (all p < 0.005), the association was not significant for PSA30 or PSA50 response. CTC and PSA response were discordant in over 50% of cases, with outcome driven by CTC response in these patients. The c-index values for OS were superior for early CTC changes compared to PSA response endpoints, and similar to 6-month rPFS. Early CTC declines were good predictors of improved outcomes in mCRPC patients treated with docetaxel in this small study, offering a superior and/or earlier estimation of docetaxel benefit in comparison to PSA or rPFS that merits further confirmation in larger studies.