Comparison of an automatic analysis and a manual analysis of conjunctival microcirculation in a sheep model of haemorrhagic shock

Life-threatening diseases of critically ill patients are known to derange microcirculation. Automatic analysis of microcirculation would provide a bedside diagnostic tool for microcirculatory disorders and allow immediate therapeutic decisions based upon microcirculation analysis

Cost-Effectiveness of Propofol (Diprivan) Versus Inhalational Anesthetics to Maintain General Anesthesia in Noncardiac Surgery in the United States.

Abstract Objectives It is not known whether using propofol total intravenous anaesthesia (TIVA) to reduce incidence of postoperative nausea and vomiting (PONV) is cost-effective. We assessed the economic impact of propofol TIVA versus inhalational anesthesia in adult patients for ambulatory and inpatient procedures relevant to the US healthcare system. Methods Two models simulate individual patient pathways through inpatient and ambulatory surgery with propofol TIVA or inhalational anesthesia with economic inputs from studies on adult surgical US patients. Efficacy inputs were obtained from a meta-analysis of randomized controlled trials. Probabilistic and deterministic sensitivity analyses assessed the robustness of the model estimates. Results Lower PONV rate, shorter stay in the post-anesthesia care unit, and reduced need for rescue antiemetics offset the higher costs for anesthetics, analgesics, and muscle relaxants with propofol TIVA and reduced cost by 11.41 ± 10.73 USD per patient in the inpatient model and 11.25 ± 9.81 USD in the ambulatory patient model. Sensitivity analyses demonstrated strong robustness of the results. Conclusions Maintenance of general anesthesia with propofol was cost-saving compared to inhalational anesthesia in both inpatient and ambulatory surgical settings in the United States. These economic results support current guideline recommendations, which endorse propofol TIVA to reduce PONV risk and enhance postoperative recovery

A framework for qualitative communications using big packet protocol

In the current Internet architecture, a packet is a minimal or fundamental unit upon which different actions such as classification, forwarding, or discarding are performed by the network nodes. When faced with constrained or poor network conditions, a packet is subjected to undesirable drops and re-transmissions, resulting in unpredictable delays and subsequent traffic overheads in the network. Alternately, we introduce qualitative communication services which allow partial, yet timely, delivery of a packet instead of dropping it entirely. These services allow breaking down packet payloads into smaller units (called chunks), enabling much finer granularity of bandwidth utilization. We propose Packet Wash as anew operation in forwarding nodes to support qualitative services. Upon packet error or network congestion, the forwarding node selectively removes some chunk(s) from the payload based on the relationship among the chunks or the individual signiicance level of each chunk. We also present a qualitative communication framework as well as a Packet Wash directive implemented in a newly evolved data plane technology, called Big Packet Protocol (BPP)

A Framework for Qualitative Communications Using Big Packet Protocol

In the current Internet architecture, a packet is a minimal or fundamental unit upon which different actions such as classification,forwarding, or discarding are performed by the network nodes.When faced with constrained or poor network conditions, a packet is subjected to undesirable drops and re-transmissions, resulting in unpredictable delays and subsequent traffic overheads in the network. Alternately, we introduce qualitative communication services which allow partial, yet timely, delivery of a packet instead of dropping it entirely. These services allow breaking down packet payloads into smaller units (called chunks), enabling much finer granularity of bandwidth utilization. We propose Packet Wash as a new operation in forwarding nodes to support qualitative services. Upon packet error or network congestion, the forwarding node selectively removes some chunk(s)from the payload based on the relationship among the chunks or the individual significance level of each chunk. We also present a qualitative communication framework as well as a Packet Wash directive implemented in a newly evolved data plane technology,called Big Packet Protocol (BPP)Comment: Accepted in NEAT workshop, ACM SIGCOMM, August 2019, Beijing, Chin

Development of Extended Unimpaired Streamflow Records in the Saluda Basin, South Carolina

This paper presents the steps involved and the methodologies employed in the first phase of the South Carolina Surface Water Assessment - development of extended and unimpaired streamflow estimates based on USGS gage data in the Saluda basin. Streamflow data are first adjusted to remove effects of anthropogenic impairments. Adjustments are made for reservoirs, withdrawals, and discharges based on available documentation. Where documentation is insufficient, hindcasting methods are used. The resulting datasets are called unimpaired flows (UIFs). The UIFs are then extended in time from 1925, the starting date of the first continuous stream discharge data available in the basin, through 2013. Candidate reference gages for each short-record gage are selected based on a qualitative assessment. Area ratio and Maintenance of Variance Extension (Hirsch, 1982) methods are applied. Statistical and graphical evaluation of the extension results is followed by composition of extended UIFs

Serum S-100B adds incremental value for the prediction of symptomatic intracranial hemorrhage and brain edema after acute ischemic stroke

Brain edema; Intracranial hemorrhage; Serum biomarkerEdema cerebral; Hemorragia intracraneal; Biomarcador séricoEdema cerebral; Hemorràgia intracranial; Biomarcador sèricBackground: Early identification of patients developing symptomatic intracranial hemorrhage and symptomatic brain edema after acute ischemic stroke is essential for clinical decision-making. Astroglial protein S-100B is a marker of blood-brain barrier disruption, which plays an important role in the formation of intracranial hemorrhage and brain edema. In this study, we assessed the prognostic value of serum S-100B for the development of these complications. Methods: Serum S-100B levels were measured within 24 h from symptom onset in 1749 consecutive acute ischemic stroke patients from the prospective, observational, multicenter BIOSIGNAL cohort study (mean age 72.0 years, 58.3% male). To determine symptomatic intracranial hemorrhage or symptomatic brain edema, follow-up neuroimaging was performed in all patients receiving reperfusion therapy or experiencing clinical worsening with an NIHSS increase of ⩾4. Results: Forty six patients (2.6%) developed symptomatic intracranial hemorrhage and 90 patients (5.2%) developed symptomatic brain edema. After adjustment for established risk factors, log10S-100B levels remained independently associated with both symptomatic intracranial hemorrhage (OR 3.41, 95% CI 1.7–6.9, p = 0.001) and symptomatic brain edema (OR 4.08, 95% CI 2.3–7.1, p < 0.001) in multivariable logistic regression models. Adding S-100B to the clinical prediction model increased the AUC from 0.72 to 0.75 (p = 0.001) for symptomatic intracranial hemorrhage and from 0.78 to 0.81 (p < 0.0001) for symptomatic brain edema. Conclusions: Serum S-100B levels measured within 24 h after symptom onset are independently associated with the development of symptomatic intracranial hemorrhage and symptomatic brain edema in acute ischemic stroke patients. Thus, S-100B may be useful for early risk-stratification regarding stroke complications.This study was supported with research grants from the Swiss National Science Foundation (142422), the Swiss Heart Foundation, the Göhner Foundation and the Swiss Seaside Foundation

Role of selective V2-receptor-antagonism in septic shock: a randomized, controlled, experimental study

ABSTRACT : INTRODUCTION : V2-receptor (V2R) stimulation potentially aggravates sepsis-induced vasodilation, fluid accumulation and microvascular thrombosis. Therefore, the present study was performed to determine the effects of a first-line therapy with the selective V2R-antagonist (Propionyl1-D-Tyr(Et)2-Val4-Abu6-Arg8,9)-Vasopressin on cardiopulmonary hemodynamics and organ function vs. the mixed V1aR/V2R-agonist arginine vasopressin (AVP) or placebo in an established ovine model of septic shock. METHODS : After the onset of septic shock, chronically instrumented sheep were randomly assigned to receive first-line treatment with the selective V2R-antagonist (1 g/kg per hour), AVP (0.05 g/kg per hour), or normal saline (placebo, each n = 7). In all groups, open-label norepinephrine was additionally titrated up to 1 g/kg per minute to maintain mean arterial pressure at 70 ± 5 mmHg, if necessary. RESULTS : Compared to AVP- and placebo-treated animals, the selective V2R-antagonist stabilized cardiopulmonary hemodynamics (mean arterial and pulmonary artery pressure, cardiac index) as effectively and increased intravascular volume as suggested by higher cardiac filling pressures. Furthermore, left ventricular stroke work index was higher in the V2R-antagonist group than in the AVP group. Notably, metabolic (pH, base excess, lactate concentrations), liver (transaminases, bilirubin) and renal (creatinine and blood urea nitrogen plasma levels, urinary output, creatinine clearance) dysfunctions were attenuated by the V2R-antagonist when compared with AVP and placebo. The onset of septic shock was associated with an increase in AVP plasma levels as compared to baseline in all groups. Whereas AVP plasma levels remained constant in the placebo group, infusion of AVP increased AVP plasma levels up to 149 ± 21 pg/mL. Notably, treatment with the selective V2R-antagonist led to a significant decrease of AVP plasma levels as compared to shock time (P < 0.001) and to both other groups (P < 0.05 vs. placebo; P < 0.001 vs. AVP). Immunohistochemical analyses of lung tissue revealed higher hemeoxygenase-1 (vs. placebo) and lower 3-nitrotyrosine concentrations (vs. AVP) in the V2R-antagonist group. In addition, the selective V2R-antagonist slightly prolonged survival (14 ± 1 hour) when compared to AVP (11 ± 1 hour, P = 0.007) and placebo (11 ± 1 hour, P = 0.025). CONCLUSIONS : Selective V2R-antagonism may represent an innovative therapeutic approach to attenuate multiple organ dysfunction in early septic shock

Microvascular Effects of Heart Rate Control With Esmolol in Patients With Septic Shock: A Pilot Study*

none14β-blocker therapy may control heart rate and attenuate the deleterious effects of β-stimulating catecholamines in septic shock. However, their negative chronotropy and inotropy may potentially lead to an inappropriately low cardiac output, with a subsequent compromise of microvascular blood flow. The purpose of the present pilot study was to investigate the effects of reducing heart rate to less than 95 beats per minute in patients with septic shock using the β-1 adrenoceptor blocker, esmolol, with specific focus on systemic hemodynamics and the microcirculation.Prospective, observational clinical study.Multidisciplinary ICU at a university hospital.After 24 hours of initial hemodynamic optimization, 25 septic shock patients with a heart rate greater than or equal to 95 beats per minute and requiring norepinephrine to maintain mean arterial pressure greater than or equal to 65 mm Hg received a titrated esmolol infusion to maintain heart rate less than 95 beats per minute. Sublingual microcirculatory blood flow was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 24 hours after esmolol administration. Heart rates targeted between 80 and 94 beats per minute were achieved in all patients. Whereas cardiac index decreased (4.0 [3.5; 5.3] vs 3.1 [2.6; 3.9] L/min/m; p < 0.001), stroke volume remained unchanged (34 [37; 47] vs 40 [31; 46] mL/beat/m; p = 0.32). Microcirculatory blood flow in small vessels increased (2.8 [2.6; 3.0] vs 3.0 [3.0; 3.0]; p = 0.002), while the heterogeneity index decreased (median 0.06 [interquartile range 0; 0.21] vs 0 [0; 0]; p = 0.002). PaO2 and pH increased while PaCO2 decreased (all p < 0.05). Of note, norepinephrine requirements were significantly reduced by selective β-1 blocker therapy (0.53 [0.29; 0.96] vs 0.41 [0.22; 0.79] µg/kg/min; p = 0.03).This pilot study demonstrated that heart rate control by a titrated esmolol infusion in septic shock patients was associated with maintenance of stroke volume, preserved microvascular blood flow, and a reduction in norepinephrine requirements.A. Morelli;A. Donati;C. Ertmer;S. Rehberg;T. Kampmeier;A. Orecchioni;A. D'Egidio;V. Cecchini;G. Landoni;P. Pietropaoli;M. Westphal;M. Venditti;A. Mebazaa;M. SingerA., Morelli; Donati, Abele; C., Ertmer; S., Rehberg; T., Kampmeier; A., Orecchioni; A., D'Egidio; V., Cecchini; G., Landoni; P., Pietropaoli; M., Westphal; M., Venditti; A., Mebazaa; M., Singe

Renal Ischemia/Reperfusion Injury in Soluble Epoxide Hydrolase-Deficient Mice

Aim 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) are cytochrome P450 (CYP)-dependent eicosanoids that play opposite roles in the regulation of vascular tone, inflammation, and apoptosis. 20-HETE aggravates, whereas EETs ameliorate ischemia/reperfusion (I/R)-induced organ damage. EETs are rapidly metabolized to dihydroxyeicosatrienoic acids (DHETs) by the soluble epoxide hydrolase (sEH). We hypothesized that sEH gene (EPHX2) deletion would increase endogenous EET levels and thereby protect against I/R-induced acute kidney injury (AKI). Methods Kidney damage was evaluated in male wildtype (WT) and sEH-knockout (KO)-mice that underwent 22-min renal ischemia followed by two days of reperfusion. CYP-eicosanoids were analyzed by liquid chromatography tandem mass spectrometry. Results Contrary to our initial hypothesis, renal function declined more severely in sEH-KO mice as indicated by higher serum creatinine and urea levels. The sEH-KO-mice also featured stronger tubular lesion scores, tubular apoptosis, and inflammatory cell infiltration. Plasma and renal EET/DHET-ratios were higher in sEH-KO than WT mice, thus confirming the expected metabolic consequences of sEH deficiency. However, CYP-eicosanoid profiling also revealed that renal, but not plasma and hepatic, 20-HETE levels were significantly increased in sEH-KO compared to WT mice. In line with this finding, renal expression of Cyp4a12a, the murine 20-HETE-generating CYP-enzyme, was up-regulated both at the mRNA and protein level, and Cyp4a12a immunostaining was more intense in the renal arterioles of sEH-KO compared with WT mice. Conclusion These results indicate that the potential beneficial effects of reducing EET degradation were obliterated by a thus far unknown mechanism leading to kidney-specific up- regulation of 20-HETE formation in sEH-KO-mice

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock.

none15ABSTRACT: INTRODUCTION: The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20\% in the microvascular flow index of small vessels among groups. METHODS: The design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 μg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization. RESULTS: TP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 μg/kg/minute (0.29 to 1.04) vs. 0.16 μg/kg/minute (0.03 to 0.37) for TP and 0.40 μg/kg/minute (0.20 to 1.05) vs. 0.23 μg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7\% (2.6 to 19.8) for TP, 8.9\% (0.0 to 17.8) for AVP, and 6.9\% (3.5 to 10.1) for placebo (P < 0.05 vs. baseline for each comparison), as well as perfused vessel density 18.6\% (8.6 to 36.9) for TP, 20.2\% (-3.0 to 37.2) for AVP, and 11.4\% (-3.0 to 19.4) for placebo (P < 0.05 vs. baseline for each comparison). CONCLUSIONS: The present study suggests that to achieve a MAP of 65 to 75 mmHg in septic patients treated with NE, the addition of continuously infused low-dose TP or AVP does not affect sublingual microcirculatory blood flow. In addition, our results suggest that microcirculatory flow abnormalities are mainly related to other factors (for example, volume status, timing, hemodynamics and progression of the disease) rather than to the vasopressor per se. TRIAL REGISTRATION: ClinicalTrial.gov NCT00995839.A. Morelli;A. Donati;C. Ertmer;S. Rehberg;T. Kampmeier;A. Orecchioni;A. D. Russo;A. D'Egidio;G. Landoni;M. R. Lombrano;L. Botticelli;A. Valentini;A. Zangrillo;P. Pietropaoli;M. WestphalA., Morelli; Donati, Abele; C., Ertmer; S., Rehberg; T., Kampmeier; A., Orecchioni; A. D., Russo; A., D'Egidio; G., Landoni; M. R., Lombrano; L., Botticelli; A., Valentini; A., Zangrillo; P., Pietropaoli; M., Westpha