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Introduction: Sepsis, a life-threatening syndrome, is often accompanied by tachycardia in spite of hypovolemia and hypotension have been corrected. Recently, relevant studies have shown that sustained tachycardia in sepsis was related to high mortality, and appropriate control of heart rate (HR) could improve prognosis. Ivabradine reduces HR directly without a negative inotropic effect through inhibition of the I f ionic current, which is different from the traditional rate control drug (beta-blockers)., Methods and Analysis: This is a prospective, multicenter, randomized, open label study designed to investigate the effect of heart rate control with ivabradine on hemodynamic in patients with sepsis. Our study will enroll 172 patients with sepsis as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria with sinus rate of 95 bpm or higher despite a hemodynamic optimization. Patients will be randomly assigned to standard treatment group (GS) or ivabradine group (GI, standard treatment for sepsis plus enteral ivabradine). Patients in GI will receive ivabradine to maintain HR between 70 and 94 bpm. The primary outcome is the difference of a reduction in HR below 95 bpm and the effect of ivabradine on hemodynamics between GI and GS group within the first 96 h after randomization. The secondary outcomes include organ function measures, the difference in SOFA score, incidence of adverse events, need for organ support, length of ICU stay, and 28-day overall mortality., Discussion: There are limited studies on ivabradine to control heart rate in patients with sepsis. Our study aims to evaluate whether direct sinus node inhibition can improve hemodynamics, as well as its impact on organ function and prognosis in patients with sepsis, so as to provide evidence for the safe usage in clinical practice., Trial Registration: ClinicalTrials.gov NCT05882708. Registered on May 11, 2023, https://clinicaltrials.gov/ct2/show/NCT05882708 ., (© 2024. The Author(s).)

Introduction: Hemorrhagic shock requires immediate treatment to prevent mortality and organ dysfunction. This study evaluates the efficacy of methylene blue (MB) with blood transfusion (BT) as a potential rescue therapy in acute severe bleeding in pigs., Methods: Thirty animals were randomly assigned to one of six groups following the induction of fixed-pressure hemorrhagic shock, after reaching a mean arterial pressure (MAP) of 55 mmHg - Group 1 (60 BT: BT after 60 minutes), Group 2 (60 MB: MB infusion after 60 minutes), Group 3 (60 MB + BT: MB and BT after 60 minutes), Group 4 (15 MB + BT: MB and BT after 15 minutes), Group 5 (15 BT + 60 MB: BT after 15 minutes and MB infusion after 60 minutes), and Group 6 (15 MB + 60 BT: MB infusion after 15 minutes and BT after 60 minutes). Hemodynamic and blood gas parameters were meticulously recorded, reversal of the shock was considered when MAP reached 90% of the baseline MAP., Results: Except for Group 2, all groups reverted from the shock. However, groups that received MB in combination with BT, specifically Groups 3 and 4, exhibited statistically significant higher ratios of maximum MAP to baseline MAP., Conclusion: Using MB concomitant with BT allowed the reversal of hemorrhagic shock with higher median arterial pressure levels compared to BT alone or applying MB separately from BT. This suggests that simultaneous application of MB and BT could be a more effective strategy for reversing the effects of severe acute bleeding.

Chronic kidney disease (CKD) affects ~10% of the population and cardiovascular disease is its commonest complication. Despite treatment, patient outcomes remain poor and newer therapies are urgently needed. Here, we investigated the systemic and renal effects of apelin in CKD. In a randomized, double-blind, placebo-controlled, crossover study, 24 subjects (12 patients with CKD and 12 matched healthy subjects) received pyroglutamated apelin-13 ([Pyr 1 ]apelin-13, 1 nmol/min and 30 nmol/min) or matched placebo on two separate visits. Systemic and renal hemodynamics were monitored throughout. The co-primary endpoints were change in systemic vascular resistance index and renal blood flow. Secondary endpoints were change in blood pressure, cardiac output, pulse wave velocity, glomerular filtration rate, natriuresis, free water clearance and urinary protein excretion. In both health and CKD, 30 nmol/min [Pyr 1 ]apelin-13 reduced mean arterial pressure by ~4%, systemic vascular resistance by ~12%, and increased cardiac index by ~10%, compared to placebo (p < 0.05 for all). Both doses of [Pyr 1 ]apelin-13 increased renal blood flow by ~15%, natriuresis by ~20% and free water clearance by ~10%, compared to placebo (p < 0.05 for all). In patients with chronic kidney disease only, glomerular filtration rate fell by ~10%, effective filtration fraction by ~5% and proteinuria by ~25% (p < 0.01 for all). Apelin has short-term cardiovascular and renal benefits in CKD. If maintained longer-term, these should improve patient outcomes. Clinical trials of long-acting oral apelin agonists are justified in CKD and other conditions with impaired salt and water balance. Registration number at www.clinicalTrials.gov : NCT03956576. Funded by Kidney Research UK., (© 2024. The Author(s).)

Background: The incidence of cardiovascular complications may be higher in unilateral than bilateral primary aldosteronism (PA). We compared noninvasive hemodynamics after targeted therapy of bilateral vs. unilateral PA., Methods: Adrenal vein sampling was performed, and hemodynamics recorded using radial artery pulse wave analysis and whole-body impedance cardiography (n = 114). In 40 patients (adrenalectomy n = 20, spironolactone-based treatment n = 20), hemodynamic recordings were performed after 33 months of PA treatment., Results: In initial cross-sectional analysis, 51 patients had bilateral and 63 unilateral PA. The mean ages were 50.6 and 54.3 years (P = 0.081), and body mass indexes 30.3 and 30.6 kg/m2 (P = 0.724), respectively. Aortic blood pressure (BP) and cardiac output did not differ between the groups, but left cardiac work was ~10% higher in unilateral PA (P = 0.022). In the follow-up study, initial and final BPs in the aorta were not significantly different, while initial cardiac output (+13%, P = 0.015) and left cardiac work (+17%, P = 0.009) were higher in unilateral than bilateral PA. After median treatment of 33 months, the differences in cardiac load were abolished, and extracellular water volume was reduced by 1.3 and 1.4 l in bilateral vs. unilateral PA, respectively (P = 0.814)., Conclusions: These results suggest that unilateral PA burdens the heart more than bilateral PA, providing a possible explanation for the higher incidence of cardiac complications in unilateral disease. A similar reduction in aldosterone-induced volume excess was obtained with targeted surgical and medical treatment of PA., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.)

Infection-related lipopolysaccharide (LPS) release causes cytokine storm and acute lung injury. Emerging data show that the interleukin 6 (IL-6) inhibitor tocilizumab can improve lung damage in patients with sepsis. This study aimed to investigate the therapeutic effect of tocilizumab on acute lung injury in cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Tocilizumab was administered on post-operative day 21, and LPS was injected intraperitoneally on day 29. Three hours after LPS injection, hemodynamic parameters, biochemistry data, and arterial blood gas analysis were evaluated, along with measurements of IL-6 and tumor necrosis factor-α (TNF-α). Liver and lung histology was examined, and protein levels were analyzed. LPS administration reduced portal pressure, portal venous flow and cardiac index in the BDL rats. In addition, LPS administration induced acute lung injury, hypoxia and elevated TNF-α and IL-6 levels. Pre-treatment with tocilizumab did not affect hemodynamic and biochemistry data, but it ameliorated lung injury and decreased TNF-α, IL-6, and CD68-positive macrophage infiltration. Moreover, tocilizumab administration improved hypoxia and gas exchange in the BDL rats, and downregulated hepatic and pulmonary inflammatory protein expression. In conclusion, LPS administration induced acute lung injury in biliary cirrhotic rats. Pre-treatment with tocilizumab reduces lung damage and hypoxia, possibly by downregulating inflammatory proteins and reducing IL-6, TNF-α and CD68-positive macrophage recruitment in the lung., Competing Interests: Declaration of competing interest The authors would like to acknowledge the Clinical Research Core Laboratory of Taipei Veterans General Hospital for providing the experimental space and facilities. This work was supported by grants from the Taipei Veterans General Hospital (V112D-65-003-MY2-1) and the Szu-Zuan Research Foundation of Internal Medicine (grant nos. 111025), Taipei, Taiwan. The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Epinephrine is the only recommended vasopressor during neonatal cardiopulmonary resuscitation. However, there are concerns about the potential adverse effects of epinephrine, which might hamper efficacy during cardiopulmonary resuscitation. An alternative might be vasopressin, which has a preferable adverse effect profile, however, its optimal dose and route of administration is unknown. We aimed to compare the pharmacodynamics and pharmacokinetics of various vasopressin doses administered via intravenous (IV), intraosseous (IO), endotracheal (ETT), and intranasal (IN) routes in healthy neonatal piglets. Forty-four post-transitional piglets (1-3 days of age) were anesthetized, intubated via a tracheostomy, and randomized to receive vasopressin via intravenous (control), IO, ETT, or IN route. Heart rate (HR), arterial blood pressure, carotid blood flow, and cardiac function (e.g., stroke volume, ejection fraction) were continuously recorded throughout the experiment. Blood was collected prior to drug administration and throughout the observation period for pharmacodynamics and pharmacokinetic analysis. Significant changes in hemodynamic parameters were observed following IO administration of vasopressin while pharmacokinetic parameters were not different between IV and IO vasopressin. Administration of vasopressin via ETT or IN did not change hemodynamic parameters and had significantly lower maximum plasma concentrations and systemic absorption compared to piglets administered IV vasopressin (p < 0.05). The IV and IO routes appear the most effective for vasopressin administration in neonatal piglets, while the ETT and IN routes appear unsuitable for vasopressin administration., (© 2024. The Author(s).)

Background: SELECT was the first global randomised controlled trial of selexipag with standard of care in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension., Methods: SELECT was a multicentre, randomised, double-blind, placebo-controlled, parallel-group, group-sequential, phase 3 study (ClinicalTrials.gov: NCT03689244). Adults aged ≤85 years in World Health Organization Functional Class I-IV, with a 6-min walk distance of 100-450 m, were randomised (1:1) to receive selexipag (200-1600 µg twice daily titration until individual maximum tolerated dose)+standard of care or placebo+standard of care. Patients were recruited into the haemodynamic set (first 91 randomised patients to undergo right heart catheterisation (RHC); week 20) or non-haemodynamic cohort (remaining patients, no RHC required). The primary end-point was percent of baseline pulmonary vascular resistance (PVR; week 20). Safety was also assessed., Results: Of 321 patients screened, 128 were randomised (haemodynamic set n=91 (selexipag n=47; placebo n=44)). In the haemodynamic set, 29 (31.9%) patients had previous pulmonary endarterectomy (PEA), 20 (22.0%) balloon pulmonary angioplasty (BPA), and 14 (15.4%) both PEA and BPA; 28 (30.8%) were inoperable. The independent data monitoring committee recommended to stop the study for futility as no statistically significant difference was observed for the primary end-point (between-treatment geometric least squares mean ratio of PVR: 0.95, 95% CI 0.84-1.07; p=0.412). Adverse events were reported in 63 (98.4%) and 53 (82.8%) patients for selexipag and placebo, respectively., Conclusions: SELECT was discontinued for futility, as no treatment effect on the primary end-point (PVR) was observed. Safety data were consistent with the established safety profile of selexipag, with no new safety signals identified., Competing Interests: Conflict of interest: N.H. Kim has consulted for, received research grants from or spoken for Janssen, Bayer, Merck, United Therapeutics, Enzyvant, Gossamer Bio, Polarean and Pulnovo. R. Channick has consulted for, received research grants from or spoken for Janssen, Bayer, United Therapeutics, Respira, Third Pole, Merck, Aria CV and Gossamer. M. Delcroix reports research grants from Janssen, speaker and consultant fees from Altavant, Acceleron, AOP, Bayer, Ferrer, Gossamer, INARI, Janssen, United Therapeutics and MSD, outside the submitted work, and all paid to her institution; and is holder of a Janssen Chair for Pulmonary Hypertension at KU Leuven. M. Madani has served as a consultant and has received fees from Wexler Surgical, Janssen, Bayer and MSD. J. Pepke-Zaba reports research grants from MSD and consultant fees from Ferrer, Gossamer, Janssen, United Therapeutics and MSD. V. Easton, S. Gesang and D. Richard are employees of Johnson & Johnson and own shares in the company. J.I. Borissoff is an employee of Johnson & Johnson. H-A. Ghofrani reports consultancy fees from Gossamer Bio, Inc., Aerovate, Altavant, Bayer AG, Attgeno, Janssen/Actelion, MSD/Acceleron, Pfizer, Liquidia, Morphic and Keros, payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer AG, Janssen/Actelion, Gossamer Bio, Keros and MSD/Acceleron, participation on a data safety monitoring board or advisory board with Aerovate, Altavant, Bayer AG, Attgeno, Janssen/Actelion, Insmed, MSD/Acceleron and Pfizer; H-A. Ghofrani's spouse is an employee of Liquidia., (Copyright ©The authors 2024.)

To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p < 0.05). Moreover, the amount of fluid requirements decreased significantly in the 6 h following HSA infusion [8.7 ml/kg (SD 9.6) vs. 15.1 ml/kg (SD 13.6) in the previous 6 h (p < 0.05)]. Serum levels of sodium and chloride increased after the infusion, reaching their peak concentration after one hour (143 mEq/L (SD 3.5) and 109.7 mEq/L (SD 6) respectively). HSA-related metabolic acidosis or acute kidney injury were not observed in this study. Hypertonic saline albumin is safe and effective when infused at a dose of 5 ml/kg in critically ill children. However, further research is required to confirm our findings., (© 2024. The Author(s).)

Background: The optimal strategy in prosthetic heart valve thrombosis (PVT) remains controversial, with no randomized trials and conflicting observational data. We performed a systematic review and meta-analysis of evidence comparing systemic thrombolysis and cardiac surgery in PVT., Methods and Results: We searched PubMed, the Cochrane Library, and Embase for studies on treatment strategies in patients with left-sided PVT since 2000. The primary outcome was death, and the secondary outcomes were major bleeding and thromboembolism during follow-up (International Prospective Register of Systematic Reviews No. CRD42022384092). We identified 2298 studies, of which 16 were included, comprising 1389 patients with PVT (mean age, 50.4±9.3 years; 60.0% women). Among them, 67.2% were New York Heart Association stage III/IV at admission. Overall, 48.1% were treated with systemic thrombolysis and 51.9% with cardiac surgery. The mortality rate was 10.8% in the thrombolysis group and 15.3% in the surgery group. The pooled risk difference for death with systemic thrombolysis was 1.13 (exact CI, 0.74-1.79; ζ 2 =0.89; P <0.001) versus cardiac surgery. Rates of both transient ischemic attack and non-central nervous system embolism were higher in the thrombolysis group ( P =0.002 and P =0.02, respectively). Treatment success, major bleeding, and stroke were similar between groups. Sensitivity analysis including studies that used low-dose or slow-infusion thrombolysis showed that the mortality rate was lower, and treatment success was higher, in patients referred to systemic thrombolysis, with similar rates of other secondary outcomes., Conclusions: There is evidence to suggest that thrombolysis might be the preferred option for the management of PVT without cardiogenic shock, pending future randomized controlled trials or larger observational studies.

Objectives: Compare hemodynamics between 4% albumin and Ringer's acetate., Design: Exploratory analysis of the double-blind randomized ALBumin In Cardiac Surgery trial., Setting: Single-center study in Helsinki University Hospital., Participants: We included 1,386 on-pump cardiac surgical patients., Intervention: We used 4% albumin or Ringer's acetate administration for cardiopulmonary bypass priming, volume replacement intraoperatively and 24 hours postoperatively., Measurements and Main Results: Hypotension (time-weighted average mean arterial pressure of <65 mmHg) and hyperlactatemia (time-weighted average blood lactate of >2 mmol/L) incidences were compared between trial groups in the operating room (OR), and early (0-6 hours) and late (6-24 hours) postoperatively. Associations of hypotension and hyperlactatemia with the ALBumin In Cardiac Surgery primary outcome (≥1 major adverse event [MAE]) were studied. In these time intervals, hypotension occurred in 118, 48, and 17 patients, and hyperlactatemia in 313, 131, and 83 patients. Hypotension and hyperlactatemia associated with MAE occurrence. Hypotension did not differ between the groups (albumin vs Ringer's: OR, 8.8% vs 8.5%; early postoperatively, 2.7% vs 4.2%; late postoperatively, 1.2% vs 1.3%; all p > 0.05). In the albumin group, hyperlactatemia was less frequent late postoperatively (2.9% vs 9.1%; p < 0.001), but not earlier (OR, 22.4% vs 23.6%; early postoperatively, 7.9% vs 11.0%; both p > 0.025 after Bonferroni-Holm correction)., Conclusions: In on-pump cardiac surgery, hypotension and hyperlactatemia are associated with the occurrence of ≥1 MAE. Compared with Ringer's acetate, albumin did not decrease hypotension and decreased hyperlactatemia only late postoperatively. Albumin's modest hemodynamic effect is concordant with the finding of no difference in MAEs between albumin and Ringer's acetate in the ALBumin In Cardiac Surgery trial., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hanna Vlasov reports that Prothya Biosolutions Ltd (former Sanquin Plasma Products) Amsterdam, The Netherlands, supported financially the ALBICS trial., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To compare the efficacy of low vs conventional dose intravenous paracetamol in early closure of haemodynamically significant patent ductus arteriosus within 7 days of life., Methods: Preterm infants (<32 weeks of gestation) having echocardiographic evidence of hsPDA were given low dose (15 mg/kg initially followed by 7.5 mg/kg every 6 hourly) vs conventional dose (15 mg/kg every 6 hourly) for 5-7 days., Results: In total, 56 infants (28 in each group) were enrolled. Ductal closure was achieved in 96% infants in the low-dose group and 100% infants in the conventional group (P = 1.00). Secondary outcomes, including ductal reopening and need for the second course of medical treatment (21% vs 3.5%, P = 0.1), median duration of hospital stay [30 (15, 43.5) vs 27 (18.5,45), P = 0.64], cumulative oxygen requirement [17.5 (7, 25) vs 14 (8.5, 25), P = 0.89], mortality (10.7% vs 25%, P = 0.29) and other morbidities, were comparable in both the groups. Median paracetamol levels were comparable in both the groups [53.4 μg/L (47, 2,70) vs 62.5 (55.6, 81.2), P = 0.67]., Conclusion: Low-dose paracetamol was non-inferior to conventional dose paracetamol for early ductal closure in preterm infants., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Remimazolam is a recently marketed ultrashort-acting benzodiazepine. This drug is considered safe and effective during general anesthesia; however, limited information is available about its effects on patients undergoing cardiac surgery. Therefore, the present study was conducted to evaluate the efficacy and hemodynamic stability of a bolus administration of remimazolam during anesthesia induction in patients undergoing cardiac surgery., Methods: Patients undergoing elective cardiac surgery were randomly assigned to any 1 of the following 3 groups: anesthesia induction with a continuous infusion of remimazolam 6 mg/kg/h (continuous group), a single-bolus injection of remimazolam 0.1 mg/kg (bolus 0.1 group), or a single-bolus injection of remimazolam 0.2 mg/kg (bolus 0.2 group). Time to loss of responsiveness, defined as modified Observer's Assessment of Alertness/Sedation Scale <3, and changes in hemodynamic status during anesthetic induction were measured., Results: Times to loss of responsiveness were 137 ± 20, 71 ± 35, and 48 ± 9 seconds in the continuous, bolus 0.1, and bolus 0.2 groups, respectively. The greatest mean difference was observed between the continuous and bolus 0.2 groups (89.0, 95% confidence interval [CI], 79.1-98.9), followed by the continuous and bolus 0.1 groups (65.8, 95% CI, 46.9-84.7), and lastly between the bolus 0.2 and bolus 0.1 groups (23.2, 95% CI, 6.6-39.8). No significant differences were found in terms of arterial blood pressures and heart rates of the patients., Conclusions: A single-bolus injection of remimazolam provided efficient anesthetic induction in patients undergoing cardiac surgery. A 0.2 mg/kg bolus injection of remimazolam resulted in the shortest time to loss of responsiveness among the 3 groups, without significantly altering the hemodynamic parameters. Therefore, this dosing can be considered a favorable anesthetic induction method for patients undergoing cardiac surgery., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

General Anaesthesia (GA) is accompanied by a marked decrease in sympathetic outflow and thus loss of vasomotor control of cardiac preload. The use of vasoconstriction during GA has mainly focused on maintaining blood pressure. Phenylephrine (PE) is a pure α1-agonist without inotropic effects widely used to correct intraoperative hypotension. The potential of PE for augmenting cardiac stroke volume (SV) and -output (CO) by venous recruitment is controversial and no human studies have explored the effects of PE in preload dependent circulation using indicator dilution technique. We hypothesized that PE-infusion in patients with cardiac stroke volume limited by reduced preload would restore preload and thus augment SV and CO. 20 patients undergoing GA for gastrointestinal surgery were monitored with arterial catheter and LiDCO unity monitor. Upon stable haemodynamics after induction patients were placed in head-up tilt (HUT). All patients became preload responsive as verified by a stroke volume variation (SVV) of > 12%. PE-infusion was then started at 15-20mikrg/min and adjusted until preload was restored (SVV < 12%). Li-dilution cardiac output (CO) was initially measured after induction (baseline), again with HUT in the preload responsive phase, and finally when preload was restored with infusion of PE.At baseline SVV was 10 ± 3% (mean ± st.dev.), CI was 2,6 ± 0,4 L/min*m 2 , and SVI 43 ± 7mL/m 2 . With HUT SVV was 19 ± 4%, CI was 2,2 ± 0,4 L/min*m 2 , SVI 35 ± 7mL/m 2 . During PE-infusion SVV was reduced to 6 ± 3%, CI increased to 2,6 ± 0,5 L/min*m 2 , and SVI increased to 49 ± 11mL/m 2 . All differences p < 0,001. In conclusion: Infusion of phenylephrine during preload dependency increased venous return abolishing preload dependency as evaluated by SVV and increased cardiac stroke volume and -output as measured by indicator-dilution technique. (ClinicalTrials.gov NCT05193097)., (© 2024. The Author(s).)

Study Objective: The mid-point transverse process to pleura block (MTPB) is a new variant of thoracic paravertebral block (TPVB). This study aimed to compare TPVB and MTPB with respect to intraoperative attenuation of the hemodynamic stress response to surgery and postoperative analgesia in pediatric open heart surgery with midline sternotomy., Design: A single-center, randomized, controlled, double-blind, non-inferiority study., Setting: Tertiary care children's university hospital., Patients: We recruited 83 children aged 2-12 years of both sexes with American Society of Anesthesiologists (ASA) physical status class II who were scheduled for elective open cardiac surgeries with midline sternotomy for the repair of simple noncyanotic congenital heart defects., Interventions: Eligible participants were randomized into either the TPVB or MTPB groups at a ratio of 1:1. In the TPVB group, patients were bilaterally injected with 0.4 ml/kg of 0.25% bupivacaine in the paravertebral space at T4 and T5. In the MTPB group, patients were bilaterally injected with 0.4 ml/kg of 0.25% bupivacaine mid-transverse process and pleura just posterior to superior costotransverse ligament at the level of T4 and T5., Measurements: The primary outcome was the hemodynamic responses to sternotomy incision, including heart rate (HR) and invasive mean arterial pressure (MAP), recorded before and after the induction of anesthesia, after skin incision, after sternotomy, 15 min after cardiopulmonary bypass (CPB), and after the closure of the sternum. The secondary outcomes were time needed to perform the bilateral block, intraoperative fentanyl consumption, postoperative fentanyl consumption, modified objective pain score (MOPS) measured at 1, 2, 6, 12, 18, and 24 h after extubation, extubation time, intensive care unit (ICU) discharge time, and the incidence of non-surgical complications (postoperative pruritus, postoperative vomiting, pneumothorax, hematoma or local anesthetic toxicity)., Main Results: There were no significant differences in HR and MAP in the TPVB group compared with the MTPB group at the following time points: baseline, after induction, after skin incision, after sternotomy, 15 min after CPB, and after sternal closure. Intergroup comparisons of HR and MAP did not reveal significant differences between the groups. The median (IQR) time needed to perform bilateral MTPB (7[6-8] min) was significantly (p < 0.001) shorter than that of TPVB (12[10-13] min). Intraoperative fentanyl consumption and fentanyl consumption in the first postoperative 24 h after extubation were similar in the TPVB and MTPB groups (4[2-4] vs 4[2-4] and 4.66 ± 0.649 vs 4.88 ± 1.082 μg/kg), respectively. Extubation time and ICU discharge time were comparable in the TPVB and MTPB groups (2[1-3] vs 2[1-3] h and 21.2 ± 2.5 vs 20.8 ± 2.6 h), respectively. Measurements of MOPS pain scores at 1, 2, 6, 12, 18, and 24 h after extubation were similar in both groups. The incidence of nonsurgical complications was similar in both groups., Conclusions: MTPB is non-inferior to TPVB in attenuating the intraoperative hemodynamic stress response to noxious surgical stimuli and in reducing perioperative opioid consumption, extubation time, and ICU discharge time. Moreover, MTPB is technically easier than TPVB and requires less time to perform. Clinical trial registration number The clinical trial registration was prospectively performed at the Pan African Clinical Trials Registry (PACTR202204901612169, approval date 01/04/2022, URL https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=22602)., Competing Interests: Declaration of competing interest There is no conflict of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The need for safe anesthetic agents with minimal side effects has led to the development of remimazolam, a new benzodiazepine designed to be an alternative to the commonly used drug propofol, which has significant hemodynamic effects. This study aims to compare the hemodynamic effects of remimazolam with propofol during general anesthesia., Evidence Acquisition: A systematic search was conducted in Embase, Web of Science, Cochrane Library, Scopus, and PubMed databases on 13/02/2023, following the recommendations of Cochrane Handbook and the PRISMA statement. The measure of association used was Risk Ratio (RR) or standardized mean difference, with 95% confidence intervals (CI) and 95% Prediction intervals (PI). An additional search was conducted on 04/09/2023. A Trial Sequential Analysis and a GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence table were conducted based on the editor's recommendation., Evidence Synthesis: After applying eligibility criteria and removing duplicates, 16 randomized clinical trials comprising 1951 patients were included in the meta-analysis. Significant associations favoring remimazolam over propofol were observed in the following aspects: intraoperative hypotension events (RR=0.47; 95% CI=0.41 to 0.54; 95% PI=0.40 to 0.55); frequency of vasoactive drug administration (RR=0.54; 95% CI=0.46 to 0.64; 95% PI=0.41 to 0.74); intraoperative bradycardia (RR=0.39; 95% CI=0.27 to 0.57; 95% PI=0.26 to 0.66); mean arterial pressure at induction (MD=7.77; 95% CI=6.00 to 9.55; 95% PI=4.39 to 11.15); heart rate at induction (MD=6.40; 95% CI=4.07 to 8.73; 95% PI=0.33 to 12.48); and heart rate at intubation (MD=6.06; 95% CI=2.33 to 9.78; 95% PI=-5.59 to 17.71)., Conclusions: This study provides evidence that remimazolam induces fewer cardiorespiratory depressant effects and has a more favorable side effect profile compared to propofol during general anaesthesia.

Background: Cervical spinal cord injury usually results in cardiorespiratory dysfunctions due to interruptions of the bulbospinal pathways innervating the cervical phrenic motoneurons and thoracic sympathetic preganglionic neurons., Purpose: The present study aimed to evaluate the therapeutic effects of adrenergic agents on systemic and spinal hemodynamics during acute cervical spinal cord injury., Study Design: In vivo animal study., Methods: The cardiorespiratory function and spinal cord blood flow and oxygenation level were monitored in response to cervical spinal cord contusion and intravenous infusion of three types of adrenergic agents (phenylephrine, dobutamine, and norepinephrine)., Results: Cervical spinal cord contusion resulted in immediate reduction of respiratory airflow, arterial blood pressure, and spinal cord blood flow. The arterial blood pressure and spinal cord blood flow remained lower than the preinjury value in contused animals infused with saline at 60 min postinjury. Infusion of phenylephrine (500, 1000, and 2000 μg/kg) and norepinephrine (125, 250, and 500 μg/kg) significantly increased the arterial blood pressure, while only norepinephrine augmented the spinal cord blood flow. Conversely, dobutamine (1000 and 2000 μg/kg) reduced both arterial blood pressure and spinal cord blood flow. Notably, administration of adrenergic agents tended to increase spinal cord hemorrhage in contused animals., Conclusions: Infusion of norepinephrine can effectively maintain the blood pressure and improve spinal cord blood flow during acute spinal cord injury., Clinical Significance: Norepinephrine may be a superior medicine for hemodynamic management; however, the potential hemorrhage should be considered when utilizing the vasopressor to regulate systemic and spinal hemodynamics at the acute injured stage., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this quality improvement initiative, we aimed to increase provider adherence with palivizumab administration guidelines for hospitalized infants with hemodynamically significant congenital heart disease. We included 470 infants over four respiratory syncytial virus (RSV) seasons from 11/2017 to 03/2021 (baseline season: 11/2017-03/2018). Interventions included the following: education, including palivizumab in the sign-out template, identifying a pharmacy expert, and a text alert (seasons 1 and 2: 11/2018-03/2020) that was replaced by an electronic health record (EHR) best practice alert (BPA) in season 3 (11/2020-03/2021). The text alert and BPA prompted providers to add "Need for RSV immunoprophylaxis" to the EHR problem list. The outcome metric was the percentage of eligible patients administered palivizumab prior to discharge. The process metric was the percentage of eligible patients with "Need for RSV immunoprophylaxis" on the EHR problem list. The balancing metric was the percentage of palivizumab doses administered to ineligible patients. A statistical process control P-chart was used to analyze the outcome metric. The mean percentage of eligible patients who received palivizumab prior to hospital discharge increased significantly from 70.1% (82/117) to 90.0% (86/96) in season 1 and to 97.9% (140/143) in season 3. Palivizumab guideline adherence was as high or higher for those with "Need for RSV immunoprophylaxis" on the problem list than for those without it in most time periods. The percentage of inappropriate palivizumab doses decreased from 5.7% (n = 5) at baseline to 4.4% (n = 4) in season 1 and 0.0% (n = 0) in season 3. Through this initiative, we improved adherence with palivizumab administration guidelines for eligible infants prior to hospital discharge., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Compared with the use of ultrasound for noninvasive monitoring of the anesthetic sodium pentobarbital versus tribromoethanol in an animal model of renal ischemia-reperfusion injury in rats., Methods: Adult rats were randomly assigned to a renal ischemia-reperfusion injury model, and preoperative anesthetics were administered as either sodium pentobarbital or tribromoethanol. Color Doppler ultrasound and spectral Doppler ultrasound were used to detect changes in respiratory rate and heart rate during and after the surgery, as well as measure renal hemodynamic parameters including peak systolic velocity, end-diastolic velocity, and resistance index., Results: The frequency of changes in respiration and heart rate was significantly higher in the sodium pentobarbital anesthesia group compared to the tribromoethanol anesthesia group. The peak systolic velocity and end-diastolic velocity values in the sodium pentobarbital anesthesia group were significantly lower than those in the tribromoethanol group. However, the resistance index in the sodium pentobarbital group was higher than that in the tribromoethanol group., Conclusion: Ultrasound can be used to dynamically monitor the effects of anesthesia during the experiment, including changes in respiratory rate and heart rate, as well as semi-quantitatively monitor hemodynamic changes in the kidneys, which indirectly reflects whole-body hemodynamic changes in rats., (© 2024 Wiley Periodicals LLC.)

Objective: The use of vasopressin as an adjunctive therapy in pulmonary hypertension associated with refractory systemic hypotension has increased. The objective of our study is to describe its effects on term infants., Study Design: Retrospective observational study. Setting in a referral level IV neonatal intensive care unit from a middle-income region. The patients are term neonates admitted to our NICU who required vasopressin due to severe Pulmonary Hypertension and refractory hypotension during a 49-month period (December 2019 and December 2023)., Results: We identified 68 term infants, all in mechanical ventilation, receiving inhaled nitric oxide (iNO), and a phased protocol management for hypotension. Vasopressin was a started at a mean of 2 days with a mean duration of 80 h. Regarding hemodynamic outcome: diastolic, systolic, and median systemic pressure significantly increased during the first 4 h of treatment, as well as arterial pH and urine output. Accordingly, lactate and Vasoactive Inotropic Score (VIS) score decreased after 4 and 8 h, respectively, after vasopressin was started. Regarding oxygenation markers: oxygen requirements and mean airway pressure decreased significantly (and therefore the oxygenation index decreased in concordance) after 4 h of vasopressin. Echocardiographic indices of pulmonary hypertension progressively improved after vasopressin infusion with a significant decrease of tricuspid ingurgitation velocities and the rate of right-to- left ductal shunt through the ductus arteriosus. In the same way, left and right ventricular output increased after the initiation of vasopressin., Conclusion: This study showed that the use of vasopressin in neonates with persistent pulmonary hypertension was associated with a rapid and significant improvement in oxygenation and hemodynamic markers of perfusion, including blood pressure. Its effects begin early during the first hours of treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

After Fontan operation, decreased venous capacitance and venoconstriction are adaptive mechanisms to maintain venous return and cardiac output. The consequent higher venous pressure may adversely impact end-organ function, exercise capacity and result in worse clinical outcomes. This pilot study evaluated the safety and effect of isosorbide dinitrate (ISDN), a venodilator, on exercise capacity, peripheral venous pressure (PVP), and liver stiffness in patients with Fontan circulation. In this prospective single-arm trial, 15 individuals with Fontan circulation were evaluated at baseline and after 4 weeks of therapeutic treatment with ISDN. Primary aims were to assess the safety of ISDN and the effect on maximal exercise. We also aimed to evaluate the effect of ISDN on ultrasound-assessed liver stiffness, markers of submaximal exercise, and PVP at rest and peak exercise. Repeated measures t-tests were used to assess change in variables of interest in response to ISDN. Mean age was 23.5 ± 9.2 years (range 11.2-39.0 years), and 10/15 (67%) were male. There was no statistically significant change in peak VO 2 (1401 ± 428 to 1428 ± 436 mL/min, p = 0.128), but VO 2 at the anaerobic threshold increased (1087 ± 313 to 1115 ± 302 mL/min, p = 0.03). ISDN was also associated with a lower peak exercise PVP (22.5 ± 4.5 to 20.6 ± 3.0 mmHg, p = 0.015). Liver stiffness was lower with ISDN, though the difference was not statistically significant (2.3 ± 0.4 to 2.1 ± 0.5 m/s, p = 0.079). Of the patients completing the trial, mild headache was common (67%), but there were no major adverse events. Treatment with ISDN for 4 weeks is well-tolerated in patients with a Fontan circulation. ISDN is associated with an increase in VO 2 at anaerobic threshold, lower peak PVP, and a trend toward lower liver stiffness. Larger, longer duration studies will be necessary to define the impact of ISDN on clinical outcomes in the Fontan circulation.Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT04297241., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Septic shock is now the leading cause of mortality in intensive care units (ICUs). Refractory septic shock requires high doses of vasopressors. Some previous studies have revealed that methylene blue could improve hypotension status and help reduce the dosage of catecholamines. This study aims to investigate the clinical effect of methylene blue in septic shock and explore whether it can increase arterial pressure and reduce the usage of vasopressors., Methods: This study is a multicenter, randomized, placebo-controlled trial planning to include 100 refractory septic shock patients. The protocol is to administer a bolus of 2 mg/kg methylene blue intravenously followed by a continuous infusion of 0.5 mg/kg/h for 48 h. The primary outcome is the total dose of vasopressor required in refractory septic shock in the first 48 h. Secondary outcomes include other hemodynamic parameters, oxygen metabolism indexes, tissue perfusion indexes, major organ function indexes, and certain plasma cytokines and other factors., Discussion: This protocol aims to evaluate the safety and efficacy of methylene blue as adjuvant therapy for refractory septic shock. The main outcome measure will be vasopressor requirements and hemodynamic parameters. Additionally, bedside ultrasonography, blood gases, and cytokines will be assessed to evaluate perfusion, respiratory, and metabolic effects. The results are intended to provide evidence on the safety and efficacy of methylene blue in refractory septic shock, guiding clinical decision-making., Trial Registration: This clinical trial has been registered at ChiCTR ( https://www.chictr.org.cn/ ) on March 16, 2023. ChiCTR registration number: ChiCTR2300069430., (© 2024. The Author(s).)

Competing Interests: The authors report no conflicts of interest in this communication.

Background: Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. This study tested the hypothesis that Dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF., Methods: In this secondary analysis from the CAMEO-DAPA trial (Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction Trial), 37 patients with HFpEF (mean age 68 ± 9 years, women 65%) underwent invasive hemodynamic exercise testing with simultaneous echocardiography at baseline and following treatment for 24 weeks with Dapagliflozin or placebo. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated from hemodynamic indices fit to a comprehensive cardiovascular model., Results: There was no statistically significant effect of Dapagliflozin on resting BP, but Dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mm Hg [95% CI, -33.9 to -3.7] P =0.016). Reduction in BP was related to improved exertional total arterial compliance (ETD, 0.06 mL/mm Hg/m 2 [95% CI, 0.003-0.11] P =0.039) and aortic root characteristic impedance (ETD, -2.6 mm Hg/mL*sec [95% CI: -5.1 to -0.03] P =0.048), with no significant effect on systemic vascular resistance. Dapagliflozin reduced estimated stressed blood volume at rest and during peak exercise (ETD, -292 mm Hg [95% CI, -530 to -53] P =0.018), and improved venous capacitance evidenced by a decline in ratio of estimated stressed blood volume to total blood volume (ETD, -7.3% [95% CI, -13.3 to -1.3] P =0.020). Each of these effects of Dapagliflozin at peak exercise were also observed during matched 20W exercise intensity. Improvements in total arterial compliance and estimated stressed blood volume were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in estimated stressed blood volume during exercise (r=0.40, P =0.019). Decreases in BP were correlated with reduction in pulmonary capillary wedge pressure during exercise (r=0.56, P <0.001)., Conclusions: In patients with HFpEF, treatment with Dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with sodium-glucose cotransporter-2 inhibitors in HFpEF., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04730947., Competing Interests: Dr Borlaug receives research support from the National Institutes of Health (NIH) and the United States Department of Defense, as well as research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, and Tenax Therapeutics. Dr Borlaug has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations, and is named inventor (US Patent no. 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure, Dr Chirinos has recently consulted for Bayer, Fukuda-Denshi, Bristol-Myers Squibb, JNJ, Edwards Life Sciences, Merck, and NGM Biopharmaceuticals. He received University of Pennsylvania research grants from National Institutes of Health, Fukuda-Denshi, Bristol-Myers Squibb, Microsoft and Abbott. He is named as inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of HFpEF and for the use of biomarkers in heart failure. He has received research device loans from Atcor Medical, Fukuda-Denshi, Unex, Uscom, NDD Medical Technologies, Microsoft and MicroVision Medical. B. Pourmussa has no relevant disclosures.

BACKGROUND Awake endotracheal intubation (AEI) involves the placement of an endotracheal tube in patients who can maintain spontaneous respirations. This retrospective study aimed to compare sedation with remimazolam during AEI with that of dexmedetomidine in patients who underwent scoliosis correction surgery. MATERIAL AND METHODS This is a retrospective study based on data from 98 patients who had AEI procedures between January and December 2023. The remimazolam group included 55 patients, and the dexmedetomidine group included 43 patients. Remimazolam 0.05 mg/kg was injected 1 min before intubation, while dexmedetomidine 1 ug/kg was pumped 10 min before intubation. Evaluations of AEI, hemodynamics, and respiratory adverse events were then compared between the 2 groups. RESULTS There was no significant difference in demographic data between the groups. After administrating sedation, dexmedetomidine led to a larger reduction of mean arterial pressure (MAP) and heart rate (HR) than did remimazolam (11.30±1.86 vs 8.33±2.28 mmHg, P<0.001; 12.28±2.50 vs 2.85±1.82 beats/min, P<0.001). When conducting intubation, the increase of MAP in the remimazolam group was lower than that in the dexmedetomidine group (7.40±2.81 vs 9.26±5.08 mmHg, P=0.024), while the difference in HR change was not significant (7.53±5.41 vs 8.37±5.31 beats/min, P=0.441). When combined with local anesthesia, the success rate of AEI, time of AEI procedure, attempt times, increase of MAP during intubation, depth of sedation, and respiratory adverse events were comparable between the groups (P>0.05). CONCLUSIONS With local anesthesia, remimazolam and dexmedetomidine sedation can facilitate AEI for patients with scoliosis. However, remimazolam is associated with more stable hemodynamics.

Objective: Uncooperative behavior in pediatric dentistry is one of the most common manifestations of dental anxiety. Managing anxious patients can be attained by moderate sedation. This study aimed to compare the effect of sedation by dexmedetomidine-ketamine combination (DEX-KET) versus dexmedetomidine (DEX) on behavior of uncooperative pediatric dental patients., Methodology: In total, 56 uncooperative healthy children (3-5 years old) requiring dental treatment were divided randomly into two groups: Group I (study group), which received buccal dexmedetomidine (2 μg/kg) and ketamine (2 mg/kg), and Group II (control group), which received only buccal dexmedetomidine (4 μg/kg). Drugs effects were assessed in terms of hemodynamic parameters, patient's drug acceptance, child behavior, postoperative effect of sedation, amnesic effect, incidence of adverse events, as well as procedural induced stress measured by salivary secretory immunoglobulin A (s-IgA)., Results: Hemodynamic results did not reveal a statistically significant difference between the two study groups (P>0.05). There was a significant difference in patient's acceptance to sedative drug between both groups, favoring DEX (p=0.005). Children who received DEX-KET showed significantly better behavior than those who received DEX for local anesthesia (p=0.017) and during operative procedure (p=0.037). Adverse events, post-operative and amnesic effects of drugs were comparable in both groups (p>0.05). Moreover, the mean difference in the salivary s-IgA levels between initial and final value was not statistically significant between both groups (p=0.556)., Conclusion: Both DEX-KET combination and DEX alone are effective in providing hemodynamic stability. DEX-KET combination significantly improved the behavior of sedated children compared to DEX alone but the drug acceptance was decreased in the DEX-KET group. Both regimens did not have a negative effect on postoperative behavior of children and had comparable amnesic effect with no significant adverse events. Salivary s-IgA is not considered a potential stress biomarker in sedated children.

Background: Electronic cigarettes have gained popularity as a nicotine delivery system, which has been recommended by some as an aid to help people quit traditional smoking. The potential long-term effects of vaping on the cardiovascular system, as well as how their effects compare with those from standard cigarettes, are not well understood. The intrinsic frequency (IF) method is a systems approach for analysis of left ventricle and arterial function. Recent clinical studies have demonstrated the diagnostic and prognostic value of IF. Here, we aim to determine whether the novel IF metrics derived from carotid pressure waveforms can detect effects of nicotine (delivered by chronic exposure to electronic cigarette vapor or traditional cigarette smoke) on the cardiovascular system., Methods and Results: One hundred seventeen healthy adult male and female rats were exposed to purified air (control), electronic cigarette vapor without nicotine, electronic cigarette vapor with nicotine, and traditional nicotine-rich cigarette smoke, after which hemodynamics were comprehensively evaluated. IF metrics were computed from invasive carotid pressure waveforms. Standard cigarettes significantly increased the first IF (indicating left ventricle contractile dysfunction). Electronic cigarettes with nicotine significantly reduced the second IF (indicating adverse effects on vascular function). No significant difference was seen in the IF metrics between controls and electronic cigarettes without nicotine. Exposure to electronic cigarettes with nicotine significantly increased the total IF variation (suggesting adverse effects on left ventricle-arterial coupling and its optimal state), when compared with electronic cigarettes without nicotine., Conclusions: Our IF results suggest that nicotine-containing electronic cigarettes adversely affect vascular function and left ventricle-arterial coupling, whereas standard cigarettes have an adverse effect on left ventricle function.

Systemic arterial hypertension is accompanied by autonomic impairments that, if not contained, promotes cardiac functional and morphological damages. Pyridostigmine bromide (PYR) treatment results in positive effects on autonomic control and beneficial cardiac remodeling. These findings were also observed after aerobic physical training (APT). However, little is known about PYR effects on left ventricular contractility, mainly when it is combined with APT. We aimed to investigate the effects of chronic acetylcholinesterase inhibition on cardiac autonomic tone balance, coronary bed reactivity, and left ventricular contractility in spontaneously hypertensive rats (SHR) submitted to APT. Male SHR (18 weeks) were divided into two groups (N = 16): untrained and submitted to APT for 14 weeks (18th to 32nd week). Half of each group was treated with PYR (15 mg/kg/day) for two weeks (31st to 32nd week). The experimental protocol consisted of recording hemodynamic parameters, double autonomic blockade with atropine and propranolol, and assessment of coronary bed reactivity and ventricular contractility in isolated hearts using the Langendorff technique. PYR and APT reduced blood pressure, heart rate, and sympathetic influence on the heart. The Langendorff technique showed that APT increased coronary perfusion pressure and left ventricle contractility in response to coronary flow and β-agonist administration. However, treatment with PYR annulled the effects of APT. In conclusion, although chronic treatment with PYR reduces cardiac sympathetic tonic influence, it does not favor coronary bed reactivity and cardiac contractility gains. PYR treatment in the trained SHR group nullified the coronary vascular reactivity and cardiac contractility gains., (© 2024. The Author(s).)

Background: To analyze the effects of different anesthesia depths on perioperative heart rate variability and hemodynamics in middle-aged and elderly patients undergoing general anesthesia, and to provide a basis for clinical application., Methods: A total of 111 patients with gastric cancer who were treated with epidural anesthesia combined with general anesthesia were selected as the study subjects, and the patients were randomly divided into group A, group B and group C. The bispectral index (BIS) was maintained by adjusting the infusion speed of anesthetics, the BIS of group A was maintained at 50 ~ 59, the BIS of group B was maintained at 40 ~ 49, and the BIS of group C was maintained at 30 ~ 39. The high-frequency power (HFP), low-frequency power (LFP), total power (TP), mean arterial pressure (MAP), heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were measured before anesthesia induction (T1), immediately after intubation (T2), 3 min after intubation (T3), and 6 min after extubation (T4). The cognitive function of the patients was evaluated before and 48 h after surgery., Results: The HFP, LFP/HFP, TP, HR, DBP and SBP between the three groups at T1 ~ T3 are significantly difference from each other (P < 0.05). There were significant differences in spontaneous breathing recovery time, eye opening time and extubation time among group A, B and C groups, and group B had the lowest spontaneous breathing recovery time, eye opening time and extubation time (P < 0.05). There was no significant difference in the incidence of adverse reactions during anesthesia between the three groups. The cognitive function score of group B was significantly higher than that of group A and group C (P < 0.05)., Conclusions: BIS maintenance of 40 ~ 49 has little effect on perioperative heart rate variability and hemodynamics in middle-aged and elderly patients undergoing general anesthesia, which is helpful for postoperative recovery., (© 2024. The Author(s).)

Dual endothelin-1 (ET-1) and angiotensin II (AngII) receptor antagonism with sparsentan has strong antiproteinuric actions via multiple potential mechanisms that are more pronounced, or additive, compared with current standard of care using angiotensin receptor blockers (ARBs). Considering the many actions of ET-1 and AngII on multiple cell types, this study aimed to determine glomeruloprotective mechanisms of sparsentan compared to the ARB losartan by direct visualization of its effects in the intact kidney in focal segmental glomerulosclerosis (FSGS) using intravital multiphoton microscopy. In both healthy and FSGS models, sparsentan treatment increased afferent/efferent arteriole diameters; increased or preserved blood flow and single-nephron glomerular filtration rate; attenuated acute ET-1 and AngII-induced increases in podocyte calcium; reduced proteinuria; preserved podocyte number; increased both endothelial and renin lineage cells and clones in vasculature, glomeruli, and tubules; restored glomerular endothelial glycocalyx; and attenuated mitochondrial stress and immune cell homing. These effects were either not observed or of smaller magnitude with losartan. The pleiotropic nephroprotective effects of sparsentan included improved hemodynamics, podocyte and endothelial cell functions, and tissue repair. Compared with losartan, sparsentan was more effective in the sustained preservation of kidney structure and function, which underscores the importance of the ET-1 component in FSGS pathogenesis and therapy.

Background: To investigate the protective effect and mechanism of Ghrelin on Doxorubicin (Dox) hydrochloride induced heart failure (HF) and myocardial injury in rats., Methods: 45 rats were randomly divided into control group, HF group and Ghrelin group. Dox hydrochloride was injected intraperitoneally to establish the model of HF in rats of HF group and Ghrelin group. Rats in the Ghrelin group were given intraperitoneal injection of Ghrelin twice a day, and rats in the HF group and control group were given equal volume of normal saline for a total of 6 weeks. The changes of echocardiography, cardiac hemodynamics, myocardial histology and plasma inflammatory factors were observed., Results: After the Ghrelin intervention, compared with the HF group, the left ventricular end-diastolic diameter (LVDD) and left ventricular end-systolic diameter (LVSD) in the Ghrelin group was markedly reduced (P < 0.05), and left ventricular ejection fraction (LVEF) was significantly increased (P < 0.05). Compared with HF group, the left ventricular systolic pressure (LVSP), maximum rate of increase in left ventricular pressure (+ dP/dtmax) and maximum rate of decrease in left ventricular pressure (- dP/dtmax) of Ghrelin group was remarkedly increased (P < 0.05), left ventricular diastolic pressure (LVDP) decreased (P < 0.05). In the Ghrelin group, the degree and extent of cardiomyocyte degeneration and necrosis were remarkedly reduced compared with the HF group. The levels of TNF-α and iNOS in Ghrelin group were notably lower than those in HF group (P < 0.05), the IL-10 level increased markedly (P < 0.05)., Conclusion: Ghrelin may reduce Dox-induced myocardial injury and improve cardiac function in rats by regulating inflammation and oxidative stress., (© 2024. The Author(s).)

In experiments on Wistar rats, the effect of a new selective JNK inhibitor tryptanthrin oxime (TR-Ox) on parameters of systemic hemodynamics, cardiohemodynamics, and post-infarction fibrosis was studied 4 months after acute myocardial ischemia (1 h) followed by reperfusion. TR-Ox was administered intraperitoneally at a dose of 12 mg/kg 20 min before reperfusion, and then once a day for the next 4 days. Administration of TR-Ox to animals in the acute phase of myocardial infarction contributed to more complete preservation of myocardial viability in the delayed period: a relative increase of muscle elements proportion in the scar, a decrease in the formation of connective tissue areas with complete and >50% replacement of the myocardium, and deceleration of fibrotic scarring in myocardium areas distant from the focus of injury, resulting in improved systolic and diastolic myocardial function. Four months after myocardial infarction, significant improvement in systemic hemodynamics and cardiohemodynamics parameters was observed in the group treated with TR-Ox: stroke volume, cardiac output, left ventricular systolic pressure, maximum rates of left ventricle pressure rise and fall significantly increased and the left ventricle end-diastolic pressure decreased in comparison with the corresponding parameters in the control group., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

The effect of intraperitoneal injection of LPS (pyrogenal, 100 μg/kg) on the asymmetry of the right-left hemodynamic balance of microcirculation (MCR) was studied in 10 male Wistar rats. Synchronous measurements of the MCR parameters of the outer surface of the symmetrical areas of the tail base were carried out by laser Doppler flowmetry. The coefficients of asymmetry of the regression relationships between changes in perfusion of each of the observation sides and the initial perfusion values of both the eponymous and opposite observation sides, as well as the mean values and coefficients of perfusion variation of the studied areas, were analyzed. Injection of pyrogenal changed parameters of the asymmetry of the right-left hemodynamic balance of MCR in comparison with the initial values. One hour after the injection of pyrogenal, the contribution of the left MCR bed to the right-left hemodynamic balance increased, and the right one decreased. At the same time, the value of the perfusion variation coefficient decreased on the left and increased on the right. The shift of the hemodynamic balance towards the left MCR bed led to significant increase in blood supply to the left MCR pool after pyrogenal injection. The results of the studies indicate a stress type of reaction of the animal body to the injected drug., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In pediatric critical care, vasoactive/inotropic support is widely used in patients with heart failure, but it remains controversial because the influence of multiple medications and the interplay between their inotropic and vasoactive effects on a given patient are hard to predict. Robust evidence supporting their use and quantifying their effects in this group of patients is scarce., Study Question: The aim of this study was to characterize the effect of vasoactive medications on various cardiovascular parameters in pediatric patient with decreased ejection fraction., Study Design: Clinical-data based physiologic simulator study., Measure and Outcomes: We used a physics-based computer simulator for quantifying the response of cardiovascular parameters to the administration of various types of vasoactive/inotropic medications in pediatric patients with decreased ejection fraction. The simulator allowed us to study the impact of increasing medication dosage and the simultaneous administration of some vasoactive agents. Correlation and linear regression analyses yielded the quantified effects on the vasoactive/inotropic support., Results: Cardiac output and systemic venous saturation significantly increased with the administration of dobutamine and milrinone in isolation, and combination of milrinone with dobutamine, dopamine, or epinephrine. Both parameters decreased with the administration of epinephrine and norepinephrine in isolation. No significant change in these hemodynamic parameters was observed with the administration of dopamine in isolation., Conclusions: Milrinone and dobutamine were the only vasoactive medications that, when used in isolation, improved systemic oxygen delivery. Milrinone in combination with dobutamine, dopamine, or epinephrine also increased systemic oxygen delivery. The induced increment on afterload can negatively affect systemic oxygen delivery., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the role of dexmedetomidine in potentiating the local anaesthetic efficacy of a low dose of bupivacaine when used as an adjuvant., Study Design: A prospective, double-blind, randomised study. Place and Duration of the Study: Department of Anaesthesia, Sindh Institute of Urology and Transplantation, Karachi, Pakistan, from July 2021 to February 2022., Methodology: One hundred and eight patients of ASA physical class I-III undergoing transurethral resection of the prostate (TURP) under sub-arachnoid block (SAB) were enroled and distributed into two equal groups. Group BUPIPURE (BP) was given 7.5 mg of pure 0.5% hyperbaric bupivacain whereas group BUPIDEX (BD) was given 6 mg of 0.5% hyperbaric bupivacain with 3 μg dexmedetomidine intrathecally. The effects in Both groups were compared using chi-square and unpaired t-tests. A significance level of p <0.05 was used to evaluate the statistical significance., Results: Both groups demonstrated a steady decrease in mean heart rate (mean HR 98.9-62.7 per minute as compared to 79.1-59.4 per minute in groups BP and BD, respectively), however, no patient reached to HR <50/min. Group BP had a higher HR variability than group BD. The two groups' median peak sensory levels were similar. However, a statistically significant difference was revealed in the time taken for 2-segment regression (87.5 ± 11.3 min vs. 115.5 ± 6.2 min p <0.001 in BP and BD), as well as the time to reach T10 sensory level (13.56 ± 2.5 min vs. 10.9 ± 3.0 min p <0.001)., Conclusion: In patients having TURP, intrathecal dexmedetomidine combined with low-dose bupivacaine results in a quicker start, extended sensory and motor block, and a decreased need for rescue analgesics., Key Words: Adjuvants, Dexmedetomidine, Spinal anaesthesia, Transurethral Resection of Prostate.

Heart failure is a leading cause of morbidity and mortality 1,2 . Elevated intracardiac pressures and myocyte stretch in heart failure trigger the release of counter-regulatory natriuretic peptides, which act through their receptor (NPR1) to affect vasodilation, diuresis and natriuresis, lowering venous pressures and relieving venous congestion 3-8 . Recombinant natriuretic peptide infusions were developed to treat heart failure but have been limited by a short duration of effect 9,10 . Here we report that in a human genetic analysis of over 700,000 individuals, lifelong exposure to coding variants of the NPR1 gene is associated with changes in blood pressure and risk of heart failure. We describe the development of REGN5381, an investigational monoclonal agonist antibody that targets the membrane-bound guanylate cyclase receptor NPR1. REGN5381, an allosteric agonist of NPR1, induces an active-like receptor conformation that results in haemodynamic effects preferentially on venous vasculature, including reductions in systolic blood pressure and venous pressure in animal models. In healthy human volunteers, REGN5381 produced the expected haemodynamic effects, reflecting reductions in venous pressures, without obvious changes in diuresis and natriuresis. These data support the development of REGN5381 for long-lasting and selective lowering of venous pressures that drive symptomatology in patients with heart failure., (© 2024. The Author(s).)

Background: The efficacy of combination empiric antibiotic therapy for all intensive care unit (ICU) patients with community-acquired sepsis is a subject of ongoing debate in the era of increasing antibiotic resistance. This study was conducted to evaluate the patterns of antibiotic usage and microbial resistance in sepsis patients admitted to the ICU with both hemodynamically stable (HS) and unstable states and to analyze their clinical outcomes. Methods: In this observational study, patients aged 18 years and above who received antibiotics upon admission and had a culture report were included. These patients were categorized into the following groups: HS and hemodynamically unstable (HU), single or combined antibiotics group (more than one antibiotic used empirically to cover one or more groups of organisms), culture-positive and culture-negative group. The microbiological isolates were grouped according to their identified resistance patterns. The outcome parameters involved assessing the differences in empiric antibiotics use upon admission and microbial resistance with hemodynamic stability and investigating any associations with ICU and hospital outcomes. Results: The study included a total of 2675 patients, of which 70.3% were in the HS group, and 29.7% in the HU group. The use of combination antibiotics was significantly higher ( p  < 0 .0001) across all groups. Carbapenems were used more frequently in the single antibiotic group ( p  < 0 .001). The culture was positive in 27.8% ( n   =  747) of patients. A significantly higher number of patients in the HU group ( p  < 0 .001) were found to have carbapenem-resistant and multidrug-resistant organisms. The ICU and hospital mortality rates were significantly higher in the HU group ( p  < 0 .001), the culture-positive group with resistance ( p  < 0 .001), and the HS patients who received combination antibiotics. Conclusion: The usage of combination antibiotics, coupled with the presence of resistant organisms, emerged as an important variable in predicting ICU and hospital mortality rates in cases of community-acquired sepsis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cardiovascular trials have revealed the positive impact of GLP-1 receptor agonists (GLP-1 RAs) on cardiovascular outcomes in type 2 diabetes (T2D). However, the specific effects of endogenous GLP-1 on arterial stiffness and renal function remain understudied. This study aimed to explore the influence of endogenous GLP-1 response post-bariatric surgery on arterial stiffness and renal haemodynamic., Methods: Thirty individuals with morbid obesity and without T2D, scheduled for Roux-en-Y Gastric Bypass (RYGB), were included. Clinical parameters, 3-hour oral glucose tolerance test (OGTT) with serial sampling for glycaemia, GLP-1 and insulin, carotid-femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient (carotid-DC) and renal resistive index (RRI) measurements were conducted pre-surgery and 1-year post-surgery. Participants were categorized into high-response and low-response groups based on their post-surgery increase in GLP-1 (median increase of 104% and 1%, respectively, pre- vs. post-surgery)., Results: Post-surgery, high-response group demonstrated a greater reduction in cf-PWV (p = .033) and a greater increase (p = .043) in carotid DC compared to low-response group. These enhancements were observed independently of weight loss or blood pressure changes. High-response group exhibited a reduction in RRI (p = .034), although this association was influenced by improvement in pulse pressure. Finally, a multivariate stepwise regression analysis indicated that the percentage increase of GLP1, Δ-GLP1 (AUC) %, was the best predictor of percentage decrease in cf-PWV (p = .014)., Conclusions: Elevated endogenous GLP-1 response following RYGB was associated with improved arterial stiffness and renal resistances, suggesting potential cardio-renal benefits. The findings underscore the potential role of endogenous GLP-1 in influencing vascular and renal haemodynamics independent of traditional weight loss., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Understanding of the mechanisms contributing to the increased maternal susceptibility for major adverse cardiovascular events in the postpartum period remains poor. Accordingly, this study tested the hypothesis that the balance between coronary blood flow and myocardial metabolism is compromised during the puerperium period (35-45 days post-delivery) in swine. Systemic and coronary hemodynamic responses were assessed in anesthetized, open-chest control (nonpregnant) and puerperium/postpartum swine at baseline and in response to intravenous infusion of dobutamine (1-30 μg/kg/min). Blood pressure and heart rate were lower in postpartum swine at baseline and in response to dobutamine (P < 0.05). Coronary blood flow and myocardial oxygen delivery were significantly diminished at baseline in postpartum swine (P < 0.001), which corresponded with ∼35% reduction in myocardial oxygen consumption (MVO 2 ) (P < 0.001). Postpartum swine displayed enhanced retrograde coronary flow, larger cardiomyocyte area (P < 0.01) and marked capillary rarefaction (P < 0.01). The relationship between coronary blood flow and heart rate (P < 0.05) or MVO 2 (P < 0.001) was significantly diminished in postpartum swine as dobutamine increased MVO 2 up to ∼135% in both groups. This reduction in myocardial perfusion was associated with decreases in myocardial lactate uptake (P < 0.001), increases in coronary venous PCO 2 (P < 0.01) and decreased coronary venous pH (P < 0.01). These findings suggest an impaired balance between coronary blood flow and myocardial metabolism could contribute to the increased incidence of maternal myocardial ischemia and premature death in the postpartum period., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

In the vasculature, nitric oxide (NO) is produced in the endothelium by endothelial nitric oxide synthase (eNOS) and is critical for the regulation of blood flow and blood pressure. Blood flow may also be regulated by the formation of nitrite-derived NO catalyzed by hemoproteins under hypoxic conditions. We sought to investigate whether nitrite administration may affect tissue perfusion and systemic hemodynamics in WT and eNOS knockout mice. We found that global eNOS KO mice show decreased tissue perfusion compared to WT mice by using laser speckle contrast imaging. To study both the acute and long-term effects of sodium nitrite (0, 0.1, 1, and 10 mg/kg) on peripheral blood flow and systemic blood pressure, a bolus of nitrite was delivered intraperitoneally every 24 h over 4 consecutive days. We found that nitrite administration resulted in a dose-dependent and acute increase in peripheral blood flow in eNOS KO mice but had no effects in WT mice. The nitrite induced changes in tissue perfusion were transient, as determined by intraindividual comparisons of tissue perfusion 24-h after injection. Accordingly, 10 mg/kg sodium nitrite acutely decreased blood pressure in eNOS KO mice but not in WT mice as determined by invasive Millar catheterization. Interestingly, we found the vasodilatory effects of nitrite to be inversely correlated to baseline tissue perfusion. These results demonstrate the nitrite acutely recovers hypoperfusion and hypertension in global eNOS KO mice and suggest the vasodilatory actions of nitrite are dependent upon tissue hypoperfusion., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The attenuation of glomerular hyperfiltration is posited to be a principal mechanism underlying the kidney protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in diabetic kidney disease. Notably, the impact of SGLT2 inhibitors on kidney hemodynamic function has been posited to vary between type 1 and type 2 diabetes. The study by Wada et al. documents that in an animal model of type 2 diabetes, SGLT2 inhibitors mitigate glomerular hyperfiltration predominantly through afferent arteriolar constriction, a process mediated by the adenosine/A1 receptor pathway. This observation is consistent with mechanisms identified in type 1 diabetes, arguing for similar methods in type 1 and 2 diabetes., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest Dr. Chawla is currently the chief medical officer of Silver Creek Pharmaceuticals. Previously, Dr. Chawla was CMO at La Jolla Pharmaceutical Company, where he holds patent equity as an inventor on patents for “Angiotensin II Alone Or In Combination For The Treatment Of Hypotension” (US Patent 9,220,745, US Patent Application 14/941301). Dr. Ince is the CSO of Active Medical BV, Leiden, The Netherlands, a company that provides devices (OxyCam), software (MicroTools), education (Microcirculation Academy), and services related to clinical microcirculation. All other authors declare that they have no conflict of interest.

Objective: To evaluate the propofol-sparing and hemodynamic effects of guaifenesin administered for co-induction of anesthesia in sheep., Study Design: Prospective, blinded, two-way crossover experimental study., Animals: Thirteen healthy adult female sheep., Methods: Anesthesia was induced without premedication with intravenous (IV) guaifenesin 5% at 100 mg kg -1 (GGE) or an equivalent volume of physiologic saline (SAL), followed by IV propofol at a controlled rate (1 mg kg -1 min -1 ). Heart rate (HR), respiratory rate and oscillometric noninvasive arterial blood pressure (NIBP) were recorded at baseline after co-induction administration, following endotracheal intubation and every 2 minutes thereafter for 10 minutes. Propofol doses required to achieve intubation after each co-induction treatment were compared by independent Student's t-test. Values of p < 0.05 were considered statistically significant., Results: The propofol dose required (mean ± standard deviation) to achieve intubation was significantly lower (p = 0.001) in the GGE treatment (3.40 ± 0.74 mg kg -1 ) than in the SAL treatment (5.94 ± 1.09 mg kg -1 ). HR was increased after anesthetic induction compared with baseline in both treatments. HR was generally lower in the GGE treatment than in the SAL treatment. NIBP did not vary between GGE and SAL treatments., Conclusions and Clinical Relevance: Guaifenesin, when administered as a co-induction agent with propofol in sheep, reduces propofol dose requirements and maintains hemodynamic variables within a clinically acceptable range., (Published by Elsevier Ltd.)

Background: The intraoperative autonomic neural blockade (ANB) was found safe and effective in controlling pain and associated symptoms and reducing analgesic consumption after laparoscopic sleeve gastrectomy (LSG). This study evaluated whether ANB performed at the outset of LSG reduces anesthetic consumption and promotes hemodynamic stability., Methods: This prospective, double-blinded, randomized trial involved patients undergoing LSG in 2 high-volume institutions. Patients were randomized to receive ANB either at the onset or the end of the procedure. The primary outcome measure was the consumption of remifentanil and sevoflurane. Secondary outcomes included Aldrete scale score differences in the recovery room and hemodynamic stability during the surgery., Results: In total, 80 patients (40 in the ANB at the onset group and 40 in the control group) were included for analysis. The consumption of remifentanil was significantly lower in the onset group compared to the control group (mean difference -0.04 mcg/kg/min, 95% confidence interval [CI], -0.06 to -0.02; P < .0001). There were no differences in the Aldrete scale scores between the 2 groups. Mean heart rate (HR) and mean arterial pressure (MAP) were also significantly less during surgery in the ANB at the onset group. No complications related to the ANB occurred., Conclusions: Performing ANB at the onset of LSG is a safe and effective approach that reduces remifentanil consumption and promotes hemodynamic stability during the procedure. This technique holds promise for optimizing anesthesia management in LSG and other minimally invasive surgeries., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society.)

The mechanisms responsible for glomerular hemodynamic regulation with sodium-glucose co-transporter 2 (SGLT2) inhibitors in kidney disease due to type 2 diabetes remain unclear. Therefore, we investigated changes in glomerular hemodynamic function using an animal model of type 2 diabetes, treated with an SGLT2 inhibitor alone or in combination with a renin-angiotensin-aldosterone system inhibitor using male Zucker lean (ZL) and Zucker diabetic fatty (ZDF) rats. Afferent and efferent arteriolar diameter and single-nephron glomerular filtration rate (SNGFR) were evaluated in ZDF rats measured at 0, 30, 60, 90, and 120 minutes after the administration of a SGLT2 inhibitor (luseogliflozin). Additionally, we assessed these changes under the administration of the adenosine A1 receptor (A1aR) antagonist (8-cyclopentyl-1,3-dipropylxanthine), along with coadministration of luseogliflozin and an angiotensin II receptor blocker (ARB), telmisartan. ZDF rats had significantly increased SNGFR, and afferent and efferent arteriolar diameters compared to ZL rats, indicating glomerular hyperfiltration. Administration of luseogliflozin significantly reduced afferent vasodilatation and glomerular hyperfiltration, with no impact on efferent arteriolar diameter. Urinary adenosine levels were increased significantly in the SGLT2 inhibitor group compared to the vehicle group. A1aR antagonism blocked the effect of luseogliflozin on kidney function. Co-administration of the SGLT2 inhibitor and ARB decreased the abnormal expansion of glomerular afferent arterioles, whereas the efferent arteriolar diameter was not affected. Thus, regulation of afferent arteriolar vascular tone via the A1aR pathway is associated with glomerular hyperfiltration in type 2 diabetic kidney disease., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this preliminary study was to investigate the similarities and differences in cortical activation patterns during the swallowing of water, acetic acid solution and salt solution in healthy adults using functional near-infrared spectroscopy (fNIRS)., Methods: Eighteen right-handed healthy adults were recruited and fNIRS was used to measure changes in concentrations of oxygenated hemoglobin (HbO 2 ) and deoxygenated hemoglobin (HbR) in 35 channels during the swallowing of water, acetic acid solution and salt solution. The task-based experiment used a block-design in which participants alternated between resting blocks of 30 s and task blocks (swallowing water, acetic acid solution, or salt solution) of 30 s, repeated six times. Participants remained still during the resting blocks and performed a swallowing action every 6 s during the task blocks. Data preprocessing was conducted using NirSpark software and statistical analyses were performed using either one-sample or paired t -tests to compare differences in cortical activation in healthy participants between swallowing a water and acetic acid solution, as well as swallowing a water and salt solution., Results: Compared to the resting state, nine brain regions, including primary somatosensory cortex (S1), primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), Wernicke's area, premotor cortex (PMC), supplementary motor area (SMA), inferior frontal cortex (IFC), orbitofrontal cortex (OFC) and frontopolar area, were commonly activated during the process of swallowing water, acetic acid solution, and salt solution. The DLPFC, Broca's area, PMC and SMA showed higher activation levels during the swallowing of acetic acid solution when compared to swallowing water, with statistically significant differences ( p < 0.05). The frontopolar area and OFC exhibited higher activation during the swallowing of salt solution when compared to water, also with statistically significant differences ( p < 0.05)., Conclusions: Multiple brain regions were activated during the swallowing of water, acetic acid solution and salt solution in healthy adults. Moreover, swallowing acetic acid solution leads to stronger activation of DLPFC, Broca's area, PMC and SMA, while swallowing salt solution leads to stronger activation of the frontopolar area and OFC., (© 2024 The Author(s). Published by IMR Press.)

Competing Interests: The authors report no financial support and potential conflicts of interest for this communication.

Background: Dexmedetomidine has acceptable clinical utility for inducing sedation during flexible bronchoscopy. Reducing its dose may not only ameliorate its cardiovascular side effects, but also maintain its clinical usefulness., Methods: Patients between 18 and 65 years were randomized to either dexmedetomidine (0.75 µg/kg) or the midazolam-fentanyl group (0.035 mg/kg midazolam and 25 mcg fentanyl). The primary outcome measure was the composite score. Other parameters noted were: oxygen saturation, hemodynamic variables, Modified Ramsay Sedation Score, Numerical Rating Scale (NRS) for pain intensity and distress, Visual Analog Scale score for cough, rescue medication doses, ease of doing bronchoscopy, and patient response 24 hours after bronchoscopy., Results: In each arm, 31 patients were enrolled. The composite score at the nasopharynx was in the ideal category in 26 patients in dexmedetomidine and 21 in the midazolam-fentanyl group (P=0.007). At the tracheal level, the corresponding values were 24 and 16 (P=0.056). There was no significant difference between the 2 groups regarding the secondary outcome measures except hemodynamic parameters. The mean heart rate in the dexmedetomidine and midazolam-fentanyl groups, respectively, was as follows: at 10 minutes after start of FB (90.10±14.575, 104.35±18.48; P=0.001), at the end of FB (98.39±18.70, 105.94±17.45; P=0.016), and at 10 minutes after end of FB (89.84±12.02, 93.90±13.74; P=0.022). No patient developed bradycardia. Two patients (P=0.491) in the dexmedetomidine group developed hypotension., Conclusion: Low-dose dexmedetomidine (0.75 μg/kg single dose) appears to lead to a better composite score compared with the midazolam-fentanyl combination., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to investigate the effects of combining remimazolam with estazolam on hemodynamics and pain levels after laparoscopic gastrointestinal surgery., Methods: A total of 184 patients who underwent laparoscopic gastrointestinal surgery were enrolled in this double-blind randomized controlled trial. The patients were divided into four groups: Study Group 1(Remimazolam), Study Group 2(Estazolam), Study Group 3(Remimazolam + Estazolam), and Control Group. Anesthesia induction included intravenous injection of remimazolam and estazolam in the study groups, while the control group received normal saline. Hemodynamic parameters, stress responses, anxiety levels, and pain intensity were assessed at various time points., Results: The results showed that the combination of remimazolam and estazolam significantly improved hemodynamic parameters compared to the control group. Study Group 3 exhibited the lowest anxiety levels and stress responses among all groups. Furthermore, Study Group 3 had the lowest pain intensity scores at different postoperative time points., Conclusion: The combination of remimazolam and estazolam effectively stabilized hemodynamics, reduced anxiety levels, and alleviated pain intensity after laparoscopic gastrointestinal surgery. These findings suggest that this combination therapy has the potential to improve surgical outcomes and patient comfort., (© 2024. The Author(s).)

Background: Tracheal intubation may cause significant hemodynamic responses. Many drugs have been shown to be effective in modifying these cardiovascular responses, including remifentanil, fentanyl, sufentanil, and alfentanil. However, the 90% effect-site concentration (EC90) of remifentanil required to control cardiovascular responses to tracheal intubation when combined with ciprofol remains unclear. The purpose of this study was to determine the EC90 of remifentanil inhibiting cardiovascular responses to tracheal intubation during anesthesia induction with ciprofol using biased-coin design up-and-down sequential method (BC-UDM)., Methods: This is a prospective sequential allocation dose-finding study. American Society of Anesthesiologists physical status (ASA) I-II elective surgical patients receiving target-controlled infusion (TCI) of remifentanil effect-site concentration (Ce), followed by ciprofol and rocuronium for anesthesia, were enrolled. The cardiovascular response to tracheal intubation was defined as positive when mean arterial pressure (MAP) or heart rate (HR) is 15% higher than the baseline value. Using the BC-UDM, the Ce of remifentanil was determined based on the cardiovascular response to tracheal intubation of the previous patient. The EC90 and 90% confidence intervals (90% CIs) were estimated by R-Foundation centered isotonic regression and the pooled adjacent violators algorithm with bootstrapping., Discussion: The results of this study sought to demonstrate EC90 of remifentanil blunting sympathetic responses to tracheal intubation during anesthesia index (Ai)-guided ciprofol anesthesia using BCD-UDM. It may help to minimize the cardiovascular responses to tracheal intubation., Trial Registration: Chinese Clinical Trial Registry ChiCTR2300078275. Registered on December 3, 2023., (© 2024. The Author(s).)

Surfactant administration significantly improves respiratory outcomes in preterm infants with respiratory distress syndrome (RDS). However, surfactant administration may lead to hemodynamic alterations, particularly in the heart, affecting the patent ductus arteriosus (PDA), the consequences of which are not fully understood. This prospective observational study took place in an Indian neonatal care unit from July 2019 to November 2020, enrolling preterm neonates (26-34 weeks' gestation) with RDS needing non-invasive positive pressure ventilation. They were divided into two groups: those who received surfactant while on respiratory support and those who did not. All newborns in the study had an initial echocardiogram within 24 h to detect PDA flow. Subsequent echocardiograms were conducted between 48 and 72 h or earlier based on symptoms. Of 220 infants requiring respiratory support, 84 were enrolled, with 42 in each group. While demographic variables were similar, the surfactant group had a lower median gestational age (29.0 vs. 31.0 weeks). In the surfactant group, a significantly higher percentage of neonates had hemodynamically significant PDA (hsPDA) compared to the non-surfactant group (54.76% vs. 26.19%, P-value = .008). Multiple logistic regression found no significant association between gestation, birth weight, or shock and hsPDA occurrence. Pulmonary hemorrhage occurred more often in the surfactant group. Bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) > grade 2, and necrotizing enterocolitis (NEC) ≥ grade 2 did not differ significantly between the groups. Surfactant therapy via the less invasive surfactant administration technique was associated with a higher incidence of hsPDA. While surfactant is crucial for neonatal respiratory care, its potential hemodynamic effects, including hsPDA, should be considered., (© The Author(s) [2024]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)