Processed electroencephalography-guided general anesthesia and norepinephrine requirements: A randomized trial in patients having vascular surgery.

STUDY OBJECTIVE: Processed electroencephalography (pEEG) may help clinicians optimize depth of general anesthesia. Avoiding excessive depth of anesthesia may reduce intraoperative hypotension and the need for vasopressors. We tested the hypothesis that pEEG-guided - compared to non-pEEG-guided - general anesthesia reduces the amount of norepinephrine needed to keep intraoperative mean arterial pressure above 65 mmHg in patients having vascular surgery. DESIGN: Randomized controlled clinical trial. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PATIENTS: 110 patients having vascular surgery. INTERVENTIONS: pEEG-guided general anesthesia. MEASUREMENTS: Our primary endpoint was the average norepinephrine infusion rate from the beginning of induction of anesthesia until the end of surgery. MAIN RESULT: 96 patients were analyzed. The mean ± standard deviation average norepinephrine infusion rate was 0.08 ± 0.04 µg kg-1 min-1 in patients assigned to pEEG-guided and 0.12 ± 0.09 µg kg-1 min-1 in patients assigned to non-pEEG-guided general anesthesia (mean difference 0.04 µg kg-1 min-1, 95% confidence interval 0.01 to 0.07 µg kg-1 min-1, p = 0.004). Patients assigned to pEEG-guided versus non-pEEG-guided general anesthesia, had a median time-weighted minimum alveolar concentration of 0.7 (0.6, 0.8) versus 0.8 (0.7, 0.8) (p = 0.006) and a median percentage of time Patient State Index was <25 of 12 (1, 41) % versus 23 (3, 49) % (p = 0.279). CONCLUSION: pEEG-guided - compared to non-pEEG-guided - general anesthesia reduced the amount of norepinephrine needed to keep mean arterial pressure above 65 mmHg by about a third in patients having vascular surgery. Whether reduced intraoperative norepinephrine requirements resulting from pEEG-guided general anesthesia translate into improved patient-centered outcomes remains to be determined in larger trials.

Evaluation of the early use of norepinephrine in major abdominal surgery on medical and surgical postoperative complications: study protocol for a randomised controlled trial (EPON STUDY).

BACKGROUND: Post-induction anaesthesia often promotes intraoperative hypotension (IOH) that can worsen postoperative outcomes. This study aims to assess the benefit of norepinephrine versus ephedrine at the induction of anaesthesia to prevent postoperative complications following major abdominal surgery by preventing IOH. METHODS AND ANALYSIS: The EPON STUDY is a prospective single-centre randomised controlled trial with the planned inclusion of 500 patients scheduled for major abdominal surgery at the Amiens University Hospital. The inclusion criteria are patients aged over 50 years weighing more than 50 kg with an American Society of Anesthesiologists physical status score of ≥2 undergoing major abdominal surgery under general anaesthesia. Patients are allocated either to the intervention group (n=250) or the standard group (n=250). In the intervention group, the prevention of post-induction IOH is performed with norepinephrine (dilution to 0.016 mg/mL) using an electric syringe pump at a rate of 0.48 mg/h (30 mL/h) from the start of anaesthesia and then titrated to achieve the haemodynamic target. In the control group, the prevention of post-induction IOH is performed with manual titration of ephedrine, with a maximal dose of 30 mg, followed by perfusion with norepinephrine. In both groups, the haemodynamic target to maintain is a mean arterial pressure (MAP) of 65 mm Hg or 70 mm Hg for patients with a medical history of hypertension. An intention-to-treat analysis will be performed. The primary outcome is the Clavien-Dindo score assessed up to 30 days postoperatively. The secondary endpoints are the length of hospital stay and length of stay in an intensive care unit/postoperative care unit; postoperative renal function; postoperative cardiovascular, respiratory, neurological, haematological and infectious complications at 1 month; and volume of intraoperative vascular filling and mortality at 1 month. ETHICS AND DISSEMINATION: Ethical approval was obtained from the committee of protection of the persons of Ile de France in May 2021 (number 21 05 41). The authors will be involved in disseminating the research findings (through attending conferences and co-authoring papers). The results of the study will be disseminated via peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT05276596.

Adverse Events of Peripherally Administered Norepinephrine During Surgery: A Prospective Multicenter Study.

BACKGROUND: Perioperative treatment of hypotension by intravenous administration of norepinephrine in a peripheral vein can lead to adverse events, for example, tissue necrosis. However, the incidence and severity of adverse events during perioperative administration are unknown. METHODS: This was a prospective observational study conducted at 3 Swedish hospitals from 2019 to 2022. A total of 1004 patients undergoing surgery, who met the criteria for perioperative peripheral norepinephrine administration, were included. The infusion site was inspected regularly. If swelling or paleness of skin was detected, the infusion site was changed to a different peripheral line. Systolic blood pressure and pulse frequency were monitored during the infusion time and defined as adverse events at >220 mm Hg and <40 beats•min -1 . In case of adverse events, patients were observed for up to 48 hours. The primary outcome was prevalence of extravasation, defined as swelling around the infusion site. Secondary outcomes were all types of adverse events and associations between predefined clinical variables and risk of adverse events. RESULTS: We observed 2.3% (95% confidence interval [CI], 1.4%-3.2%) extravasation of infusion and 0.9% (95% CI, 0.4%-1.7%) bradycardia. No cases of tissue necrosis or severe hypertension were detected. All adverse events had dissipated spontaneously within 48 hours. Proximal catheter placement was associated with more adverse events. CONCLUSIONS: Extravasation of peripherally administrated norepinephrine in the perioperative period occurred at similar rates as in previous studies in critically ill patients. In our setting, where we regularly inspected the infusion site and shifted site in case of swelling or paleness of skin, we observed no case of severe adverse events. Given that severe adverse events were absent, the potential benefit of this preventive approach requires confirmation in a larger population.

Low-Concentration Norepinephrine Infusion for Major Surgery: A Safety and Feasibility Pilot Randomized Controlled Trial.

BACKGROUND: Prevention of hypotension during the intra- and postoperative period is an important goal. Peripheral administration of low-concentration norepinephrine may be a safe and effective strategy to reduce the risk of hypotension. METHODS: We conducted a 2-center, randomized pilot feasibility trial, with a target of 60 adult patients undergoing major noncardiac surgery. We randomized patients to receive a peripheral low-concentration (10 µg/mL) norepinephrine or placebo (saline 0.9%) infusion. The study drug infusion was titrated to achieve a minimum systolic blood pressure target, preselected within 10% of baseline value and within the range limit 100 to 120 mm Hg during surgery and for up to 4 or 24 hours postoperatively. RESULTS: We achieved a high consent rate (84%), successful study drug administration throughout surgery (98% of patients) and absence of unblinding. There were no important study drug-related adverse events. The average intraoperative systolic blood pressure was 120 ± 12.6 mm Hg in the norepinephrine group and 115 ± 14.9 mm Hg in the placebo group. The mean difference between the intraoperative systolic blood pressure achieved less the preselected minimum systolic blood pressure target was 10.0 ± 12.7 mm Hg in the norepinephrine group and 2.9 ± 14.7 mm Hg in the placebo group; difference in means, 7.1 (95% confidence interval, 0.2-14.0) mm Hg. CONCLUSIONS: A future large trial evaluating the effectiveness and safety of peripheral administration of low-concentration norepinephrine during the perioperative period is feasible, and likely to achieve a minimum systolic blood pressure threshold.

Effects of Sodium Thiosulfate During Resuscitation From Trauma-and-Hemorrhage in Cystathionine Gamma Lyase (CSE) Knockout Mice.

BACKGROUND: Sodium thiosulfate (Na2S2O3) is a clinically established drug with antioxidant and sulphide-releasing properties. Na2S2O3 mediated neuro- and cardioprotective effects in ischemia/reperfusion models and anti-inflammatory effects in LPS-induced acute lung injury. Moreover, Na2S2O3 improved lung function during resuscitation from hemorrhagic shock in swine with pre-existing atherosclerosis, characterized by decreased expression of cystathionine γ-lyase (CSE), a major source of hydrogen sulfide (H2S) synthesis in the vasculature. Based on these findings, we investigated the effects of Na2S2O3 administration during resuscitation from trauma-and-hemorrhage in mice under conditions of whole body CSE deficit. METHODS: After blast wave-induced blunt chest trauma and surgical instrumentation, CSE knockout (CSE-/-) mice underwent 1 h of hemorrhagic shock (MAP 35 ±â€Š5 mm Hg). At the beginning of resuscitation comprising retransfusion, norepinephrine support and lung-protective mechanical ventilation, animals received either i.v. Na2S2O3 (0.45 mg g-1, n = 12) or vehicle (saline, n = 13). Hemodynamics, acid-base status, metabolism using stable isotopes, and visceral organ function were assessed. Blood and organs were collected for analysis of cytokines, mitochondrial respiratory capacity, and immunoblotting. RESULTS: Na2S2O3 treatment improved arterial paO2 (P = 0.03) coinciding with higher lung tissue glucocorticoid receptor expression. Norepinephrine requirements were lower in the Na2S2O3 group (P < 0.05), which was associated with lower endogenous glucose production and higher urine output. Na2S2O3 significantly increased renal tissue IκBα and heme oxygenase-1 expression, whereas it lowered kidney IL-6 and MCP-1 levels. CONCLUSION: Na2S2O3 exerted beneficial effects during resuscitation of murine trauma-and-hemorrhage in CSE-/- mice, confirming and extending the previously described organ-protective and anti-inflammatory properties of Na2S2O3. The findings make Na2S2O3 a potentially promising therapeutic option in the context of impaired CSE activity and/or reduced endogenous H2S availability.

[Staphylococcal scalded skin syndrom: a case report]. / Syndrome de Lyell staphylococcique: à propos d'un cas.

Staphylococcal scalded skin syndrom is a bullous dermatosis induced by exfoliating staphylococcal exotoxins. Children are most often affected. We report the case of a 6-month-old infant who had angina in the few days before leading up to bullous erythroderma and whose skin biopsy showed characteristic appearance of staphylococcal scalded skin syndrom. The development was rapidly unfavourable and the infant died in a refractory septic shock chart, despite the introduction of norepinephrine and anti-SAMR antibiotic therapy. The term staphylococcal scalded skin syndrome (SSSS) was separated from the toxic or allergic epidermal necrolysis by Lyell into the opposite anatomical aspect of these two entities: in scalded skin syndrome, Skin detachment is done by cleavage of the superficial part of the epidermis at the granular layer, while in toxic Lyell syndrome, the cleavage sits deeper at the level of the mucous body.

Obesity protects against sepsis-induced and norepinephrine-induced white adipose tissue browning.

Sepsis is a dysregulated systemic response to infection and can lead to organ damage and death. Obesity is a significant problem worldwide and affects outcomes from sepsis. Our laboratory demonstrated that white adipose tissue (WAT) undergoes browning during sepsis, a process whereby WAT adopts a brown adipose tissue phenotype. However, this browning process was not observed in obese mice during sepsis. White adipose tissue browning is detrimental in patients with burn injury and cancer. We hypothesize that norepinephrine (NE) induces WAT browning in nonobese mice but not in obese mice similarly to sepsis-induced WAT browning. Six-week-old C57BL/6 male mice were randomized to a high-fat diet or normal diet. After 6-7 wk of feeding, polymicrobial sepsis was induced by cecal ligation and puncture (CLP). Norepinephrine was administered intraperitoneally via osmotic minipumps for 18 h or 72 h (no CLP) at which time tissue and plasma were harvested. Controls were mice that underwent CLP (no NE) with 18-h harvest. A separate group of mice underwent pretreatment with NE or vehicle infusion for 72 h, CLP was performed, and at 18 h had tissue and plasma harvested. Sepsis resulted in significant weight loss in both nonobese and obese mice. NE treatment alone caused weight loss in obese mice. Septic nonobese mice had higher uncoupling protein-1 (UCP1) expression compared with control and obese septic mice. NE treatment increased UCP1 expression in nonobese, but not obese mice. NE-treated obese septic mice had lower lung myeloperoxidase (MPO) activity, alanine aminotransferase (ALT), aspartate aminotransferase (AST), TNFα, and IL-6 levels compared with NE-treated nonobese septic mice. Obesity protects mice from septic-induced and NE-induced WAT browning.NEW & NOTEWORTHY White adipose tissue browning is detrimental in patients with burn injury and cancer. WAT browning occurs in nonobese mice and can be induced by ß receptor norepinephrine infusion, but obese mice are resistant to sepsis-induced and norepinephrine-induced WAT browning. We propose that the lack of WAT browning and unchanged inflammatory cytokine response may contribute to the protection of obese mice from sepsis.

Effect of remimazolam induction on hemodynamics in patients undergoing valve replacement surgery: A randomized, double-blind, controlled trial.

BACKGROUND: The stability of hemodynamics during anesthesia induction in patients undergoing valve replacement surgery is particularly important. Remimazolam is a new type of benzodiazepine drug, with supposed advantages of rapid induction, rapid recovery, stable hemodynamics, and mild respiratory inhibition. AIM: To evaluate the effect of remimazolam anesthesia induction on hemodynamics in patients undergoing valve replacement surgery. METHODS: This randomized, double-blind, controlled trial enrolled consecutive patients undergoing mitral valve replacement (MVR)/aortic valve replacement (AVR)/double-valve replacement (DVR) surgery on cardiopulmonary bypass (CPB). The study was conducted according to the Consolidated Standards of Reporting Trials statement. Participants were randomly assigned to receive either remimazolam or propofol induction of 30 patients each. All patients, data collectors, and data analyzers were blinded to the group allocation. The primary outcomes were the fluctuations in hemodynamic parameters (the difference of maximum or minimum heart rate to baseline, ▲HR, the difference of maximum or minimum mean arterial pressure to baseline, ▲MAP), the occurrence of cardiovascular events (hypotension, severe bradycardia), and the cumulative norepinephrine doses used per patient, averaged per group during induction. The secondary outcomes were hemodynamic parameters (heart rate, HR, mean arterial pressure, MAP, bispectral index, BIS, plasma lactic acid, Lac, and blood glucose, Glu values). RESULTS: A total of 60 patients with heart valve replacement were included in the final analysis, with 30 patients in each group. The ▲MAP was significantly lower in the remimazolam group than in the propofol group during induction (p < .05). The incidences of hypotension and the cumulative norepinephrine doses used per patient, averaged per group during induction were significantly lower in the remimazolam group than in the propofol group (p < .05). CONCLUSION: Remimazolam may be safe and effective for induction and may as an alternative to propofol during anesthesia induction in patients undergoing valve replacement surgery.

Percutaneous hepatic melphalan perfusion: Single center experience of procedural characteristics, hemodynamic response, complications, and postoperative recovery.

BACKGROUND: Percutaneous hepatic melphalan perfusion (PHMP) for the selective treatment of hepatic metastases is known to be associated with procedural hypotension and coagulation disorders. Studies on anesthetic management, perioperative course, complications, and postoperative recovery in the intensive care unit (ICU) have not been published. METHODS: In a retrospective observational study, we analyzed consecutive patients who were admitted for PHMP over a 6-year period (2016-2021). Analyses included demographic, treatment, and outcome data with regard to short-term complications until ICU discharge. RESULTS: Fifty-three PHMP procedures of 16 patients were analyzed. In all of the cases, procedure-related hypotension required the median (range) highest noradrenaline infusion rate of 0.5 (0.17-2.1) µg kg min-1 and fluid resuscitation volume of 5 (3-14) liters. Eighty-four PHMP-related complications were observed in 33 cases (62%), of which 9 cases (27%) involved grade III and IV complications. Complications included airway constriction (requiring difficult airway management), vascular catheterization issues (which resulted in the premature termination of PHMP, as well as to the postponement of PHMP and to the performance of endovascular bleeding control after PHMP), and renal failure that required hemodialysis. Discharge from the ICU was possible after one day in most cases (n = 45; 85%); however, in 12 cases (23%), prolonged mechanical ventilation was required. There were no procedure-related fatalities. CONCLUSIONS: PHMP is frequently associated with challenging cardiovascular conditions and complications that require profound anesthetic skills. For safety reasons, PHMP should only be performed in specialized centers that provide high-level hospital infrastructures and interdisciplinary expertise.

Prophylactic Norepinephrine Infusion Reduces Postoperative Complications and Hospitalization Time in Elderly Patients Undergoing Posterior Lumbar Spinal Fusion.

This single-center prospective randomized controlled trial explores the effect of prophylactic norepinephrine infusion on the incidence of complications and hospitalization time in elderly patients (60-85 years old) undergoing posterior lumbar spinal fusion. In total, 129 elderly patients were randomized into two groups: a group that received norepinephrine during general anesthesia and a control group not receiving norepinephrine. The primary outcomes were in-hospital complications and 90-day postoperative complications and hospitalization time. The results show that in-hospital complications occurred in 24 of 60 patients (40%) in the control group versus 11 of 60 patients (18.3%) in the norepinephrine group (RR, 2.182; 95% CI, 1.177-4.045; P = 0.015). Cardiac events occurred significantly more frequently in the control than in the norepinephrine group. Total number of patients experiencing complications within 90 days postoperatively was lower in the norepinephrine (11 of 60; 18.3%) than in the control group (26 of 60; 43.3%; RR, 2.364; 95% CI, 1.288-4.339; P = 0.005). The median length of hospital stay was 17 days (11-27) in the control group and 15 days (10- 23) in the norepinephrine group (P = 0.01). The secondary outcomes were serum levels of syndecan-1, hyaluronic acid, heparan sulfate, and brain natriuretic peptide. Logistic regression analysis is used to describe the relationship between selected independent variables and in-hospital complications. Intraoperative total fluid, crystalloid, and colloid volumes were significantly higher in the control than in the norepinephrine group. The patients in the norepinephrine group had a higher MAP but a lower heart rate than those in the control group after the induction of anesthesia and intraoperatively. Syndecan-1, hyaluronic acid, and heparan sulfate serum levels showed a different course in the two groups. In conclusion, prophylactic norepinephrine infusion during posterior lumbar spinal fusion is preferable for elderly patients undergoing lumbar spinal fusion under general anesthesia. It can reduce postoperative complications and hospitalization time by reducing the injury to the vascular endothelium. This trial is registered with Clinical Trial Registration http://www.chictr.org.cn/showproj.aspx?proj=33660, identifier ChiCTR-1900021309.

Clinical features and outcome of septic shock in dogs: 37 Cases (2008-2015).

OBJECTIVES: To describe patient characteristics of dogs with septic shock, investigate markers of disease severity, and assess treatment impact on outcome. DESIGN: Retrospective study. SETTING: Single center, university veterinary teaching intensive care unit. ANIMALS: Thirty-seven dogs with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mean number of organ dysfunction was 3.24 ± 1.0, and included cardiovascular (100%), respiratory (73%), hematologic (68%), renal (49%), and hepatic (32%) dysfunction. The gastrointestinal tract was the most common source of sepsis. Mean blood pressure prior to resuscitation was 50 ± 8 mm Hg. All dogs were given IV fluids before vasopressor therapy with a mean rate of 12.1 ± 11.0 mL/kg/h. All dogs were given antimicrobials, administered within a mean of 4.3 ± 5.7 hours after diagnosis. Dopamine or norepinephrine was administered IV, respectively in 51.3% and 37.8% of dogs, with a mean duration of hypotension of 2.6 ± 3.0 hours. Mortality rate was 81.1%. Survivors were more likely to have a feeding tube (P = 0.007) and to have gastrointestinal sepsis (P = 0.012), and less likely to have respiratory dysfunction (P < 0.001). APPLEFull scores (P = 0.014) and time to antimicrobial therapy (P = 0.047) were identified as predictors of mortality. Treatment bundles consisting of 7 interventions that may improve outcomes in people with septic shock were evaluated. Survivors received 4.1 ± 1.3 interventions, whereas nonsurvivors received 2.4 ± 1.4 (P = 0.003). CONCLUSIONS: Septic shock in dogs confers a guarded prognosis. Early antimicrobial therapy and the utilization of treatment bundles may increase survivability in dogs with septic shock. More research is warranted to investigate the impact of specific interventions on survival.

Hepatic Arterial Blood Flow Modulation in Patients with Hepatocellular Carcinoma: A Pilot Study of the Influence of Intraarterial Norepinephrine Assessed with CT Perfusion.

PURPOSE: This pilot study aims to evaluate the effect of hepatic intraarterial norepinephrine injection in vasculature modulation for hepatocellular carcinoma (HCC) tumors. MATERIALS AND METHODS: This is a single-center prospective study of patients with HCC with proven single-lobe tumors > 3 cm. Eight patients were included, with a mean age of 63 y ± 8. All patients had Barcelona Clinic Liver Cancer stage B HCC and an Eastern Cooperative Oncology Group performance status of 0. Mean tumor size was 6.1 cm ± 1.8; all tumors were hypervascular. Patients underwent CT hepatic perfusion before and after injection of 24 µg of norepinephrine intraarterially (4 µg/mL; total 6 mL injected at a rate of 1 mL/s). Color-coded perfusion maps were used to assess the effects of local therapy on hepatic perfusion values. Tumor-to-liver ratio (TLR) was calculated from the ratio of tumor perfusion to background liver perfusion value. RESULTS: Seven of 8 patents had significant (P = .04) absolute increase in tumor perfusion vs background liver, varying from incremental (-2 mL/min/100 mL) to 290 mL/min/100 mL. There was a nonsignificant increase in TLR from 2.7 ± 1.3 to 2.9 ± 1.4 after norepinephrine injection (P = .8). Mean peak time to maximal increase in tumor perfusion after injection was 6.1 s (range, 4.5-9.1 s). Norepinephrine injection was well tolerated without major adverse events. CONCLUSIONS: Norepinephrine causes increased blood flow toward HCC tumors, but with a corresponding smaller increase in blood flow to noncancerous liver tissue, with no observed systemic side effects.

Should we change our approach to resuscitating victims of femoral fracture? A clinical experience in a busy trauma hospital in Shiraz, Iran.

PURPOSE: Traumatic hemorrhagic shock is a life-threatening event worldwide. Severe brain trauma accompanying femoral fractures can trigger inflammatory responses in the body and increase pre-inflammatory cytokines such as TNF-α, IL-1. The primary treatment in these cases is hydration with crystalloids, which has both benefits and complications. The purpose of this study was to investigate the effects of fluid therapy on the hemodynamics, coagulation profiles, and blood gases in such patients. METHODS: In this cross-sectional study, patients were divided into two groups: femoral fracture group and non-femoral group. The hemodynamic status, coagulation profile, and blood gases of patients in both groups were evaluated upon arrival at the hospital and again 2 h later. Data were analyzed by t-test and ANOVA with repeated data and paired samples t-test. RESULTS: A total of 681 trauma patients (605 men and 76 women) participated in this study, including 69 (86.3%) men and 11 (13.8%) women in femoral fracture group and 536 men (89.2%) and 65 women (10.8%) in non-femoral group. The laboratory parameters were evaluated in response to the equal amount of crystalloid fluid given upon arrival and 2 h later. Blood gases decreased in the fracture group despite fluid therapy (p < 0.003), and the coagulation profile worsened although the change was not statistically significant. CONCLUSION: The treatment of multiple-trauma patients with femoral bone fractures should be more concerned with the need for the infusion of vasopressors such as norepinephrine. If there is evidence of clinical shock, excessive crystalloid infusion (limited to 1 L) should be avoided, and blood and blood products should be started as soon as possible.

Do Elderly Patients With Diastolic Dysfunction Require Higher Doses of Norepinephrine During General Anesthesia for Noncardiac Surgeries? A Prospective Observational Study.

BACKGROUND: Diastolic dysfunction is a risk factor for postoperative major cardiovascular events. During anesthesia, patients with diastolic dysfunction might experience impaired hemodynamic function and worsening of diastolic function, which in turn, might be associated with a higher incidence of postoperative complications.We aimed to investigate whether patients with diastolic dysfunction require higher doses of norepinephrine during general anesthesia. Furthermore, we aimed to examine the association between the grade of diastolic dysfunction and the E/e' ratio during anesthesia. A high E/e' ratio corresponds to elevated filling pressures and is an important measure of impaired diastolic function. METHODS: We conducted a prospective observational cohort study at a German university hospital from February 2017 to September 2018. Patients aged ≥60 years and undergoing general anesthesia (ie, propofol and sevoflurane) for elective noncardiac surgery were enrolled. Exclusion: mitral valve disease, atrial fibrillation, and implanted mechanical device.The primary outcome parameter was the administered dose of norepinephrine within 30 minutes after anesthesia induction (µg·kg-1 30 min-1). The secondary outcome parameter was the change of Doppler echocardiographic E/e' from ECHO1 (baseline) to ECHO2 (anesthesia). Linear models and linear mixed models were used for statistical evaluation. RESULTS: A total of 247 patients were enrolled, and 200 patients (75 female) were included in the final analysis. Diastolic dysfunction at baseline was not associated with a higher dose of norepinephrine during anesthesia (P = .6953). The grade of diastolic dysfunction at baseline was associated with a decrease of the E/e' ratio during anesthesia (P < .001). CONCLUSIONS: We did not find evidence for an association between diastolic dysfunction and impaired hemodynamic function, as expressed by high vasopressor support during anesthesia. Additionally, our findings suggest that diastolic function, as expressed by the E/e' ratio, does not worsen during anesthesia.

Automated closed-loop versus manually controlled norepinephrine infusion in patients undergoing intermediate- to high-risk abdominal surgery: a randomised controlled trial.

BACKGROUND: Hypotension occurs frequently during surgery and may be associated with adverse complications. Vasopressor titration is frequently used to correct hypotension, but requires considerable time and attention, potentially reducing the time available for other clinical duties. To overcome this issue, we have developed a closed-loop vasopressor (CLV) controller to help correct hypotension more efficiently. The aim of this randomised controlled study was to evaluate whether the CLV controller was superior to traditional vasopressor management at minimising hypotension in patients undergoing abdominal surgery. METHODS: Thirty patients scheduled for elective intermediate-to high-risk abdominal surgery were randomised into two groups. In the CLV group, hypotension was corrected automatically via the CLV controller system, which adjusted the rate of a norepinephrine infusion according to MAP values recorded using an advanced haemodynamic device. In the control group, management of hypotension consisted of standard, manual adjustment of the norepinephrine infusion. The primary outcome was the percentage of time that a patient was hypotensive, defined as MAP <90% of their baseline value, during surgery. RESULTS: The percentage of time patients were hypotensive during surgery was 10 times less in the CVL group than in the control group (1.6 [0.9-2.3]% vs 15.4 [9.9-24.3]%; difference: 13 [95% confidence interval: 9-19]; P<0.0001). The CVL group also spent much less time with MAP <65 mm Hg (0.2 [0.0-0.4]% vs 4.5 [1.1-7.9]%; P<0.0001). CONCLUSIONS: In patients undergoing intermediate- to high-risk surgery under general anaesthesia, computer-assisted adjustment of norepinephrine infusion significantly decreases the incidence of hypotension compared with manual control. CLINICAL TRIAL REGISTRATION: NCT04089644.

Terlipressin relieves intestinal and renal injuries induced by acute mesenteric ischemia via PI3K/Akt pathway.

Background: To date, the effect of vasopressin on organ damages after acute mesenteric ischemia (MI) remains poorly understood. Aims: To investigate the effect of terlipressin, a selective vasopressin V1 receptor agonist, versus norepinephrine on the intestinal and renal injuries after acute MI, and to explore the underlying mechanism of terlipressin. Methods: Acute MI model was produced by clamping the superior mesenteric artery for 1 hour. Immediately after unclamping, terlipressin or norepinephrine was intravenously administered for 2 hours. Meanwhile, in vitro, RAW264.7 cells were treated with lipopolysaccharide or lipopolysaccharide+terlipressin. In addition, wortmannin was used to determine the role of phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) pathway in the potential impacts of terlipressin. Results: MI led to severe hypotension, caused notable intestinal and renal impairments and resulted in high mortality, which were markedly improved by terlipressin or norepinephrine. Terlipressin increased mean arterial pressure, decreased intestinal epithelial cell apoptosis, inhibited the generation of M1 macrophage in intestinal and renal tissues, and hindered the release of inflammatory cytokines after MI. Moreover, in cultured macrophages, terlipressin reduced the mRNA level of specific M1 markers and the release of inflammatory cytokines caused by lipopolysaccharide challenge. Wortmannin decreased the expression of PI3K and Akt induced by terlipressin in cells and in tissues, and abolished the above protective effects conferred by terlipressin. Conclusions: Terlipressin or norepinephrine could effectively improve organ damages and mortality after acute MI. Terlipressin elevates blood pressure and inhibits intestinal epithelial apoptosis and macrophage M1 polarization via the PI3K/Akt pathway.

Specific Fluorescent Probe Based on "Protect-Deprotect" To Visualize the Norepinephrine Signaling Pathway and Drug Intervention Tracers.

In recent years, increased social pressure and other factors have led to a surge in the number of people suffering from depression: studies show that quite a few people will experience major depression in their lifetime. Currently, it is widely believed that the internal cause of major depression is reduced levels of norepinephrine (NE) in brain tissue. Norepinephrine is very similar in structure and chemical properties to the other two catecholamine neurotransmitters, epinephrine (EP) and dopamine (DA). These three neurotransmitters are synthesized sequentially through enzymatic reactions in the biological system. Therefore, design of a norepinephrine-specific fluorescent probe is very challenging. In this work, we utilized a "protect-deprotect" strategy: longer emission wavelength cyanine containing water-soluble sulfonate was protected by a carbonic ester linking departing group thiophenol; the ß-hydroxy ethyl amine moiety of norepinephrine may react with the carbonic ester via nucleophilic substitution and intramolecular nucleophilic cyclization to release the fluorophore. The process realized the specific red fluorescence detection of norepinephrine. Imaging of the norepinephrine nerve signal transduction stimulated by potassium ion was studied. More importantly, real-time fluorescence imaging of norepinephrine levels in the brain of rats stimulated by antidepressant drugs was studied for the first time.

Prevention of hypotension during elective cesarean section with a fixed-rate norepinephrine infusion versus a fixed-rate phenylephrine infusion. Α double-blinded randomized controlled trial.

BACKGROUND: Spinal anesthesia for cesarean section can be complicated by hypotension, with untoward effects for both the mother and fetus. Frequently used phenylephrine can lead to baroreceptor-mediated reflex bradycardia. The aim of the present study was to compare a fixed-rate prophylactic norepinephrine infusion to a fixed-rate prophylactic phenylephrine infusion during elective cesarean section under combined spinal-epidural anesthesia. MATERIALS AND METHODS: Eighty-two parturients were randomized to either norepinephrine 4 µg/min or phenylephrine 50 µg/min fixed-rate infusions, starting simultaneously with the administration of the subarachnoid solution. The primary endpoint was the incidence of maternal bradycardia. Maternal hemodynamics at specific timepoints, the incidence of hypotension or hypertension, the requirement for ephedrine or atropine bolus administration as well as the acid-base status and Apgar score of the neonate were recorded. RESULTS: The incidence of bradycardia as well as the requirement for atropine administration was lower in the norepinephrine group (4.8% vs. 31.7%, p = 0.004 and 2.4% vs. 24.3%, p = 0.01, respectively). Fetal pH, and fetal blood glucose concentration were higher in the norepinephrine group (p = 0.027 and 0.019, respectively). No difference in the occurrence of hypotension, hypertension, in the requirement for bolus vasoconstrictive medication or in Apgar scores was demonstrated. CONCLUSIONS: A fixed-rate infusion of norepinephrine is as effective in the management of hypotension during regional anesthesia for cesarean section as a fixed-rate infusion of phenylephrine, with the avoidance of phenylephrine-induced bradycardia. The more favourable neonatal acid-base profile of noradrenaline might be due to better maintenance of placental blood flow in the noradrenaline group due to its beta action, while the higher fetal glucose concentration in the same group might result from a catecholamine-stimulated glucose metabolism increase and a ß-receptor mediated insulin decrease.

The effect of epinephrine for the treatment of spinal-hypotension: comparison with norepinephrine and phenylephrine, clinical trial / O efeito de epinefrina, norepinefrina e fenilefrina no tratamento da hipotensão pós-raquianestesia: estudo clínico comparativo

Abstract Background and objectives: Limited data are present on safety and efficiency of epinephrine for the prophylaxis and treatment of spinal-hypotension. This study was conducted to compare the effect of epinephrine with norepinephrine and phenylephrine on the treatment of spinal-hypotension and ephedrine requirement during cesarean delivery. Methods: One hundred and sixty parturients with uncomplicated pregnancies undergoing elective cesarean delivery under spinal anesthesia were recruited. They were allocated randomly to receive norepinephrine 5 µg.mL−1 (n = 40), epinephrine 5 µg.mL−1 (n = 40), phenylephrine 100 µg.mL−1 (n = 40) or 0.9% saline infusions (n = 40) immediately after induction of spinal anesthesia. Whenever systolic blood pressure drops to less than 80% of baseline, 5 mg of intravenous ephedrine was administered as rescue vasopressor. The incidence of hypotension, total number of hypotension episodes, the number of patients requiring ephedrine, the mean amount of ephedrine consumption and side effects were recorded. Results: There was no statistically significant difference in incidence of maternal hypotension between groups. The number of patients requiring ephedrine was significantly greater in group saline than in group phenylephrine (p< 0.001). However, it was similar between phenylephrine, norepinephrine, and epinephrine groups. The mean ephedrine consumption was significantly higher in group saline than in norepinephrine, epinephrine, phenylephrine groups (p= 0.001). Conclusion: There is no statistically significant difference in incidence of hypotension and ephedrine consumption during spinal anesthesia for cesarean delivery with the use of epinephrine when compared to norepinephrine or phenylephrine. Epinephrine can be considered an alternative agent for management of spinal hypotension.

Resumo Justificativa e objetivos: Existem dados limitados sobre segurança e eficiência da epinefrina na profilaxia e tratamento da hipotensão arterial associada à raquianestesia. O presente estudo foi realizado para comparar o efeito da epinefrina com norepinefrina e fenilefrina no tratamento da hipotensão após raquianestesia e necessidade de efedrina durante o parto cesáreo. Método: Foram recrutadas 160 parturientes com gestações não complicadas, submetidas a cesariana eletiva sob raquianestesia. Elas foram alocadas aleatoriamente para receber norepinefrina 5 µg.mL-1 (n = 40), epinefrina 5 µg.mL-1 (n = 40), fenilefrina 100 µg.mL-1 (n = 40) ou infusão de solução fisiológica NaCl a 0,9% (n = 40) imediatamente após a indução da raquianestesia. Sempre que houvesse redução da pressão arterial sistólica para valor inferior a 80% da linha de base, 5 mg de efedrina iv eram administrados como vasopressor de resgate. A incidência de hipotensão, o número total de episódios de hipotensão, o número de pacientes que necessitaram de efedrina, o consumo médio de efedrina e os efeitos colaterais foram registrados. Resultados: Não houve diferença estatisticamente significante na incidência de hipotensão materna entre os grupos. O número de pacientes que necessitaram de efedrina foi significantemente maior no grupo solução fisiológica do que no grupo fenilefrina (p< 0,001). No entanto, foi semelhante entre os grupos fenilefrina, norepinefrina e epinefrina. O consumo médio de efedrina foi significantemente maior no grupo solução fisiológica do que nos grupos norepinefrina, epinefrina e fenilefrina (p = 0,001). Conclusão: Não houve diferença estatisticamente significante na incidência de hipotensão e consumo de efedrina durante raquianestesia para parto cesáreo com uso de epinefrina quando comparada à norepinefrina ou fenilefrina. A epinefrina pode ser considerada como agente alternativo para o tratamento da hipotensão após raquianestesia.