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This study assesses the effect of carotid sinus blockade applied with a local anesthetic on hemodynamic parameters during carotid endarterectomy (CEA) operations performed under general anesthesia. The medical records of patients who underwent CEA under general anesthesia between January 2020 and December 2022, were retrospectively reviewed. It was recorded whether the patients received carotid sinus block with 2 mL of 2% prilocaine. Intraoperative and 48-hour postoperative hemodynamic data were examined in the patients included in the study. A total of 129 patients were evaluated in the study, with 70 patients who received carotid sinus blockade (Group I) and 59 patients who did not receive blockade (Group II) during CEA. The comparison of heart rate variability immediately before clamping, immediately after clamping, and at 5, 10, and 20 minutes post-clamping indicated a significantly greater reduction in Group II compared to Group I (P < .05). In the postoperative period, the total dose of glyceryl trinitrate administered was 40.8 ± 31.9 mg in Group I and 53 ± 17.2 mg in Group II, showing a statistically significant difference (P = .001). Additionally, blood pressure measurements during this period were significantly higher in Group II than in Group I (P < .05). While the application of a local anesthetic during CEA appears to provide better intraoperative heart rate and postoperative blood pressure control, attributing these results solely to local anesthesia may not be entirely accurate. Hemodynamic instability observed during and after CEA is influenced by various factors., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To compare seizure-related, hemodynamic, and recovery outcomes when using remimazolam for ECT with those of other anesthetics, specifically propofol and etomidate., Methods: A total of 49 patients who underwent 405 ECT treatment sessions under general anesthesia were retrospectively analyzed. Remimazolam, propofol, and etomidate were used for 93, 138, and 174 ECT sessions, respectively. The primary outcome was durations of motor and electroencephalogram (EEG) seizure activity, whereas secondary outcomes included hemodynamics (ie, mean arterial pressure [MAP] and heart rate [HR] at various time points from induction to postanesthesia care unit [PACU] discharge), antihypertensive drugs administration after electrical stimulus, and recovery profiles (ie, length of PACU stay and incidence of postictal confusion)., Results: Durations of motor and EEG seizures were shorter for remimazolam than etomidate (motor, P < 0.001; EEG, P = 0.003) but similar compared with propofol (motor, P = 0.191; EEG, P = 0.850). During seizure, remimazolam showed a comparable MAP and HR to etomidate (MAP: P = 0.806; HR: P = 0.116). The antihypertensive drug use was lowest for remimazolam (6.8%), followed by propofol (35.6%) and etomidate (65.6%), and the mean length of PACU stay was comparable for remimazolam (19.7 min), propofol (22.8 min), and etomidate (24.5 min). The occurrence of postictal confusion did not differ among the 3 agents ( P > 0.050)., Conclusions: Remimazolam is a promising anesthetic option for ECT because of its comparable seizure profiles, stable hemodynamics, and comparable PACU stay when compared with propofol and etomidate without additional adverse events., Competing Interests: Insun Park and Jung-Hee Ryu have received a grant from Seoul National University Bundang Hospital. The authors other have no conflicts of interest or financial disclosures to report., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Traditional general anesthesia in elderly lung cancer patients undergoing pulmonary lobectomy may lead to hemodynamic fluctuations and postoperative complications. To optimize anesthesia efficacy, this study explores the application of combined anesthesia (general anesthesia combined with thoracic paravertebral block) in such surgeries. We evaluated the improvement of pulmonary oxygenation function, hemodynamic stability, and respiratory compliance in elderly lung cancer patients undergoing pulmonary lobectomy with combined anesthesia. This retrospective study analyzed 100 elderly lung cancer patients who underwent pulmonary lobectomy at our hospital from February 2020 to December 2023. Patients were divided into 2 groups: the control group received general anesthesia, while the treatment group received combined anesthesia (general anesthesia plus thoracic paravertebral block). By comparing intraoperative hemodynamic parameters, postoperative pulmonary oxygenation function, respiratory compliance, cognitive function, sleep quality, and postoperative complication rates between the 2 groups, we assessed the application efficacy of combined anesthesia. Compared to the control group, the treatment group exhibited better hemodynamic stability intraoperatively, significantly improved postoperative pulmonary oxygenation function and respiratory compliance. Additionally, patients in the treatment group showed faster recovery of cognitive function, better sleep quality, and a relatively lower incidence of postoperative complications. Combined anesthesia demonstrates unique advantages in pulmonary lobectomy for elderly lung cancer patients, optimizing intraoperative hemodynamic stability, promoting postoperative pulmonary function recovery, accelerating cognitive function recovery, improving sleep quality, and potentially reducing the risk of postoperative complications. This finding provides a new effective strategy for anesthesia management in elderly lung cancer patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, 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.)

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.

Abstract: The effects of the calcium sensitizer levosimendan on hemodynamics and survival in guinea pigs intoxicated with the calcium blockers verapamil or diltiazem were evaluated in a randomized controlled study. One hundred four animals were randomized to be intoxicated with either verapamil (2.0 mg/kg) or diltiazem (4.5 mg/kg) and thereafter further randomized into 6 groups which received either saline (control), 3 different regimes of levosimendan, calcium chloride, and levosimendan combined with calcium chloride. The hemodynamics and survival of the animals were followed for 60 minutes after intoxication.The negative inotropic effect of calcium blockers was seen as a decrease by over 70% of the positive derivative of the left ventricular pressure. This was reversed by levosimendan. Moreover, both verapamil and diltiazem-induced marked hypotension (-69% and -63% of the baseline value, respectively) which was also reversed by levosimendan. The combined levosimendan and calcium chloride treatment had a synergistic effect in reversing verapamil or diltiazem-induced deterioration in hemodynamics.Both verapamil and diltiazem intoxications decreased the survival rate of guinea pigs to 13%. Levosimendan addition improved survival dose-dependently up to a survival rate of 75% and 88% in the verapamil and diltiazem groups, respectively. Low dose of levosimendan combined with calcium chloride improved survival in verapamil and diltiazem group to 88% and 100%, respectively.In conclusion, the administration of levosimendan improved hemodynamics and survival in calcium channel blocker intoxicated guinea pigs. The synergistic effect of levosimendan and calcium chloride suggests that this combination could be an effective antidote in calcium channel blocker intoxications., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

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.)

Background: Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachycardia in small case series of patients with refractory ventricular tachyarrhythmias and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear, and its use after myocardial infarction is limited by concerns for potential right ventricular dysfunction., Methods: Myocardial infarction was created in Yorkshire pigs (N=22) by left anterior descending coronary artery occlusion. Approximately, six weeks after myocardial infarction, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. Right and left ventricular hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity and intrinsic cardiac neural activity, and ventricular effective refractory periods and slope of restitution (S max ) were assessed before and after TEA. Ventricular tachyarrhythmia inducibility was assessed by programmed electrical stimulation., Results: TEA reduced inducibility of ventricular tachyarrhythmias by 70%. TEA did not affect right ventricular-systolic pressure or contractility, although left ventricular-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular effective refractory periods prolonged significantly at critical sites of arrhythmogenesis, and S max was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both baroreflex sensitivity and intrinsic cardiac neural activity., Conclusions: TEA does not compromise right ventricular function in infarcted hearts. Its antiarrhythmic mechanisms are mediated by increases in ventricular effective refractory period and ARIs, decreases in S max , and reductions in border zone electrophysiological heterogeneities. TEA improves parasympathetic function, which may independently underlie some of its observed antiarrhythmic mechanisms. This study provides novel insights into the antiarrhythmic mechanisms of TEA while highlighting its applicability to the clinical setting., Competing Interests: M. Vaseghi has patents related to neuromodulation at the University of California, Los Angeles, and has performed educational consulting for Biosense Webster, Medtronic, and Recor, Inc, and has shares in NeuCures and Anumana, Inc. The other authors report no conflicts.

Abstract: Combat casualty care can be complicated by transport times exceeding the "golden hour," with intervention and resuscitation limited to what the medic can carry. Pharmaceutical albumin comes highly saturated with nonesterified fatty acids (NEFAs). We recently showed that treatment with 25% bovine serum albumin (BSA) loaded with oleic acid, but not NEFA-free BSA, improved survival for hours after severe hemorrhage and often eliminated the need for resuscitation in rats. However, it was unknown whether pharmaceutical albumin, derived from human sources and loaded with caprylic acid (CA), would have the same benefits. We compared adjunct treatment with oleic acid-saturated BSA, CA-saturated BSA, pharmaceutical human serum albumin, or a no-albumin control in a similar rat hemorrhagic shock model to determine whether the three NEFA-albumin groups provided the same benefits relative to control. We found almost no significant differences among the NEFA-albumin groups in any measure. Mortality in controls was too low to allow for detection of improvement in survival, but NEFA-albumin groups had significantly improved hemodynamics, lactate clearance, and greatly reduced fluid requirements compared with controls. Contrary to expectations of "dehydration," 25% albumins shifted little additional fluid into the vasculature. Rather, they restored protein to the autotransfusion fluid. Nonesterified fatty acids-albumin did not worsen lung permeability, but we observed a loss of circulating protein suggesting it may have increased overall vascular permeability. Our findings suggest that, though imperfect, 25% human serum albumin could be a solution for resuscitation in austere conditions requiring prolonged field care., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Background: Acute aortic regurgitation is life-threatening with few nonsurgical options for immediate stabilization. We propose Trans-Aortic Balloon to Ease Regurgitation Applying Counter-Pulsation (TABERNACL), a simple, on-table temporary valve using commercially available equipment to temporize acute severe aortic regurgitation., Methods: We hypothesize that an appropriately sized commercial balloon dilatation catheter-straddling the aortic annulus and connected to a counterpulsation console-can serve as a temporizing valve to restore hemodynamic stability in acute aortic regurgitation. We performed benchtop testing of valvuloplasty, angioplasty, and sizing balloons as counterpulsation balloons. TABERNACL was assessed in vivo in a porcine model of acute aortic regurgitation (n=8). We also tested a static undersized, continuously inflated transvalvular balloon as a spacer intended physically to obstruct the regurgitant orifice., Results: Benchtop testing identified that Tyshak II and PTS sizing (NuMed Braun) balloon catheters performed adequately as temporary valves (ie, complete inflation and deflation with each cycle) and resisted fatigue, in contrast to others. When TABERNACL was used in the acute severe regurgitation animals, there was immediate hemodynamic improvement, with a significant 35% increase in diastolic aortic pressure by 16 mm Hg ([95% CI, 7-25] P =0.0056), 34% reduction in left ventricular end-diastolic pressure by -7 mm Hg ([95% CI, -10 to -5] P =0.0006), improvement in the aortic diastolic index by 0.28 ([95% CI, 0.18-0.39] P =0.0009), and reversal of electrocardiographic myocardial ischemia. As an alternative, static balloon inflation across the aortic valve stabilized regurgitation hemodynamics at the expense of a new aortic gradient and caused excessive ectopy from balloon movement in the left ventricular outflow tract., Conclusions: TABERNACL improves hemodynamics and reduces coronary ischemia by electrocardiography in animals with acute severe aortic regurgitation. TABERNACL valves obstruct the diastolic regurgitant orifice without systolic obstruction. This may prove a lifesaving bridge to definitive valve replacement therapy., Competing Interests: Disclosures Dr Rogers reports consulting from Edwards Lifesciences, Medtronic, Boston Scientific, and Transmural Systems; is on the advisory board at Medtronic and Boston Scientific; reports equity interest in Transmural Systems; and reports intellectual property (coinventor on patents), assigned to the National Institutes of Health (NIH), for transcatheter electrosurgery devices. Dr Khan reports educational grants from Abbott, Boston Scientific, Edwards Lifesciences, and Philips; is a proctor at Edwards Lifesciences and Medtronic; reports equity interest in Transmural Systems; and reports intellectual property (coinventor on patents), assigned to NIH, for transcatheter electrosurgery devices. The other authors report no conflicts.

Introduction: Septic shock is a lethal disease responsible for a large proportion of deaths in the Intensive Care Unit (ICU), even with therapy centered on fluid resuscitation, use of vasopressors and empirical antibiotic therapy applied within the first hour of diagnosis. Considering the multifactorial pathophysiology of septic shock and the mechanism of action of vasopressors, some patients may not respond adequately, which can lead to the maintenance of vasodilatation, hypotension and increased morbidity, and mortality. This protocol aims to verify whether the use of methylene blue in septic patients with an early diagnosis can contribute to an earlier resolution of a shock compared to standard treatment., Methods and Analysis: This is a study protocol for a single-center randomized clinical trial design in an ICU of a tertiary university hospital. In this study, we intend to include 64 patients aged between 18 and 80 years with a diagnosis of septic shock, of any etiology, with up to 72 hours of evolution after volume restoration, using norepinephrine at a dose ≥0.2 μg/kg/min and vasopressin at a dose of 0.04 IU/min. After the initial approach, we will randomize patients into two groups, standard care, and standard care plus methylene blue. The sample size was calculated in order to show 30% differences in septic shock resolution between groups. The Research Ethics Committee approved the study, and all patients included will sign an informed consent form (Clinical registration: RBR-96584w4)., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: Cerebral small vessel disease-a major cause of stroke and dementia-is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide mononitrate (ISMN) and cilostazol, alone or in combination, improved magnetic resonance imaging-measured cerebrovascular function in patients with lacunar ischemic stroke., Methods: Participants were randomized to ISMN alone, cilostazol alone, both ISMN and cilostazol, or no medication. Participants underwent structural, cerebrovascular reactivity (to 6% carbon dioxide) and phase-contrast pulsatility magnetic resonance imaging at baseline and after 8 weeks of medication., Results: Of 27 participants (mean age, 68±7.7; 44% female), 22 completed cerebrovascular reactivity and pulsatility imaging with complete datasets. White matter cerebrovascular reactivity increased in the ISMN (β=0.021%/mm Hg [95% CI, 0.003-0.040]) and cilostazol (β=0.035%/mm Hg [95% CI, 0.014-0.056]) monotherapy groups and in those taking any versus no medication (β=0.021%/mm Hg [95% CI, 0.005-0.037])., Conclusions: While limited by small sample size, we demonstrate that measuring cerebrovascular function with magnetic resonance imaging is feasible in clinical trials and that ISMN and cilostazol may improve cerebrovascular function. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02481323. URL: www.isrctn.com; Unique identifier: ISRCTN12580546. URL: www.clinicaltrialsregister.eu; Unique identifier: EudraCT 2015-001953-33.

Abstract: Infusions of levosimendan delivered in ambulatory/outpatient settings have been shown to improve quality of life and reduce hospitalizations in patients with advanced heart failure (HF). The aim of this pilot study was to evaluate the effects of ambulatory infusion of levosimendan on echocardiographic markers of perfusion, congestion, and cardiovascular efficiency. Thirty patients with diagnosed advanced HF underwent ambulatorial infusion of levosimendan at a total dose of 6.25 mg as a part of a repetitive biweekly treatment strategy with the inotrope. Standardized transthoracic echocardiography and Doppler examinations, were performed 1 hour before and 48 hours after completion of ambulatory infusion. At 48 hours after ambulatory infusion of levosimendan, a significant increase in the stroke volume (37.47 ± 12.38 mL/beat vs. 45.47 ± 14.48 mL/beat; P < 0.05) and cardiac output (2.64 ± 0.66 L/min vs. 3.26 ± 0.57 L/min; P < 0.05) occurred. Significant postreductions versus prereductions were also recorded in left atrial pressure (27.37 ± 6.62 mm Hg vs. 22.82 ± 4.17 mm Hg; P < 0.01), mean pulmonary artery pressure (27.69 ± 4.64 mm Hg vs. 23.24 ± 5.32; P < 0.01), and inferior vena cava diameter (23.81 ± 7.63 mm vs. 18.53 ± 4.82 mm; P < 0.01). Significant improvements were noted in the resting cardiac power output (0.46 ± 0.15 watt vs. 0.53 ± 0.22 watt; P < 0.01) and the resting cardiac power index (0.24 ± 0.08 watt/m2 vs. 0.28 ± 0.11 watt/m2; P < 0.01). In outpatients with advanced HF, infusion of levosimendan was associated with hemodynamic responses that may contribute to the clinical benefit previously reported in such patients., Competing Interests: P. Pollesello is a full-time employee of Orion Pharma, where levosimendan was discovered and developed. The remaining authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure., Design: Randomized blinded study (animal model)., Setting: University animal research facility., Subjects: Twenty-four adult male "New Zealand White" rabbits., Interventions: Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period., Measurements and Main Results: Pupillary reactivity (primary outcome), levels of S100β protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100β protein levels (189 ± 42 vs 412 ± 63 pg/mL, p < 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p > 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ± 2 vs 29 ± 3 mm Hg; p < 0.05], higher cardiac output [108 ± 4 vs 58 ± 9 mL/min; p < 0.05], higher left ventricle surface shortening fraction [38% ± 3% vs 19% ± 3%; p < 0.05], and lower left ventricular end-diastolic pressure [3 ± 1 vs 8 ± 2 mm Hg; p < 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ± 3 mL/kg; p < 0.01) due to lower diuresis., Conclusions: Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated., Methods: This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus., Results: Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min-1 · m-2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of -1.5 (-2 to -1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of -0.03 (-0.07 to 0.02) mmHg, P = 0.229)., Conclusions: There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Abstract: Paracetamol (PAR) is the most common over-the-counter drug recommended by physicians for treatment of pain and fever during gestation. This drug is not teratogenic, being considered safe for fetus; however, PAR crosses the blood-placental barrier. Considering that, the present study aimed to evaluate the vascular and metabolic safety of PAR exposure during intrauterine and neonatal development in adult male and female-exposed offspring. Wistar female rats were gavaged, with PAR (350 mg/kg/d), from gestational day 6-21 or from gestational day 6 until postnatal day 21. Control dams received water by gavage at the same periods. The male and female offspring were evaluated at adulthood (80 days of life). The thoracic aorta reactivity to acetylcholine, sodium nitroprusside, and phenylephrine was evaluated in male and female adult offspring. It was observed that aortic relaxation was similar between the PAR and control offspring. In addition, the contraction to phenylephrine was similar between the groups. Further, the insulin sensitivity, adipose tissue deposition and blood pressure were not different between PAR and control adult offspring. These results suggest that the protocol of PAR exposure used in the present study did not program vascular and metabolic alterations that would contribute to the development of cardiometabolic diseases in adult life, being safe for the exposed offspring., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Intraoperative hypotension is a common event, and a recent study suggests that maintenance of blood pressure may reduce complications. The splanchnic circulation provides a reservoir of blood that can be mobilized during hemorrhage; hence, intestinal microcirculation is sensitive to volume changes. The aim of this study was to assess the impact of hemorrhage on intestinal microcirculation and hemodynamics, and the effects of phenylephrine on these parameters., Methods: Eight anesthetized, mechanically ventilated Yorkshire/Landrace crossbreed pigs were studied. Graded hemorrhage was performed with the removal of 20% of blood volume in 5% increments. Hemodynamic and intestinal microcirculatory measurements were performed at each stage with side-stream dark field microscopy, following which mean arterial pressure (MAP) was corrected with phenylephrine to baseline values and measurements repeated. A repeated measurement 1-way analysis of variance (ANOVA) was used to compared changes from baseline measurements., Results: The mean baseline microcirculation score was 42 (standard deviation [SD] = 5). A 5% hemorrhage decreased the microcirculation score by a mean difference of 19 (95% confidence interval [CI], 12-27; P < .0001), and an additional 5% hemorrhage further reduced the microcirculation score by a mean difference of 12 (95% CI, 4-19; P = .0001). Subsequent hemorrhage or administration of phenylephrine did not significantly change the microcirculation scores except when phenylephrine was administered at the 15% hemorrhage stage, which increased the microcirculation score by a mean difference of 7 (95% CI, 1-13; P = .003). All hemodynamic variables were returned to baseline values following hemorrhage by the phenylephrine infusion., Conclusions: Intestinal microcirculatory flow is reduced early in hemorrhage and is uncorrected by phenylephrine infusion. Hemodynamic changes associated with hemorrhage are corrected by phenylephrine and do not reflect microcirculatory flow status., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Background: PDE1 (phosphodiesterase type 1) hydrolyzes cyclic adenosine and guanosine monophosphate. ITI-214 is a highly selective PDE1 inhibitor that induces arterial vasodilation and positive inotropy in larger mammals. Here, we assessed pharmacokinetics, hemodynamics, and tolerability of single-dose ITI-214 in humans with stable heart failure with reduced ejection fraction., Methods: Patients with heart failure with reduced ejection fraction were randomized 3:1 to 10, 30, or 90 mg ITI-214 single oral dose or placebo (n=9/group). Vital signs and electrocardiography were monitored predose to 5 hours postdose and transthoracic echoDoppler cardiography predose and 2-hours postdose., Results: Patient age averaged 54 years; 42% female, and 60% Black. Mean systolic blood pressure decreased 3 to 8 mm Hg ( P <0.001) and heart rate increased 5 to 9 bpm ( P ≤0.001 for 10, 30 mg doses, RM-ANCOVA). After 4 hours, neither blood pressure or heart rate significantly differed among cohorts (supine or standing). ITI-214 increased mean left ventricular power index, a relatively load-insensitive inotropic index, by 0.143 Watts/mL 2 ·10 4 ( P =0.03, a +41% rise; 5-71 CI) and cardiac output by 0.83 L/min ( P =0.002, +31%, 13-49 CI) both at the 30 mg dose. Systemic vascular resistance declined with 30 mg (-564 dynes·s/cm- 5 , P <0.001) and 90 mg (-370, P =0.016). Diastolic changes were minimal, and no parameters were significantly altered with placebo. ITI-214 was well-tolerated. Five patients had mild-moderate hypotension or orthostatic hypotension recorded adverse events. There were no significant changes in arrhythmia outcome and no serious adverse events., Conclusions: Single-dose ITI-214 is well-tolerated and confers inodilator effects in humans with heart failure with reduced ejection fraction. Further investigations of its therapeutic utility are warranted. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03387215.

Abstract: Inotropes and inopressors are often first-line treatment in patients with cardiogenic shock. We summarize the pharmacology, indications, and contraindications of dobutamine, milrinone, dopamine, norepinephrine, epinephrine, and levosimendan. We also review the data on the use of these medications for acute decompensated heart failure and cardiogenic shock in this article., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Erectile dysfunction is a common entity in clinical practice. Primary erectile dysfunction, not related to vasculopathy or psychiatric disorder, can be readily treated with phosphodiesterase inhibitors. These drugs have many physiologic effects that can alter a patient's hemodynamic profile considerably, especially in the presence of concomitant structural heart disease, specifically valvular heart disease. Although some contraindications to the use of PDE5 inhibitors in patients with cardiovascular disease are defined, the effect of these drugs in the presence of valvular heart disease is not well documented. The purpose of this review is to analyze the data regarding the safety of PDE5 inhibitors in patients with valvular heart disease., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Laryngeal microsurgery (LMS) causes hemodynamic instability and postoperative agitation, cough, pain, nausea, and vomiting. Moreover, because of a short operation time, it is associated with challenging anesthetic management. The aim of this study was to compare the usefulness of continuous administration of dexmedetomidine and remifentanil in inducing general anesthesia in patients undergoing LMS., Methods: This is a prospective randomized control design. Continuous intravenous infusion of dexmedetomidine (group D) or remifentanil (group R) was administered from 10 minutes before the induction of anesthesia to the end of surgery. In both groups, 1.5 mg/kg propofol and 0.5 mg/kg rocuronium were administered for the induction of anesthesia, and desflurane were titrated during the measurement of the bispectral index. We recorded hemodynamic data, recovery time, grade of cough, pain score, and analgesic requirements during the perioperative period., Results: 61 patients were finally analyzed (30 for group D, 31 for group R). The incidence of moderate to severe postoperative sore throat was higher in group R than in group D (42% vs 10%, P = .008), and the quantity of rescue fentanyl used in post-anesthesia care unit was significantly higher in group R than in group D (23.2 ± 24.7 mg vs 3.3 ± 8.6 mg; P < .001); however, the time required for eye opening was significantly longer in group D than in group R (599.4 ± 177.9 seconds vs 493.5 ± 103.6 seconds; P = .006). The proportion of patients with no cough or single cough during extubation was comparable between the 2 groups (group D vs group R: 73% vs 70%) as was the incidence of hemodynamic instability., Conclusion: Although there was a transient delay in emergence time, dexmedetomidine reduced postoperative opioid use and the incidence of sore throat. Dexmedetomidine may be used as an alternative agent to opioids in patients undergoing LMS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Riociguat is a novel soluble guanylate cyclase stimulator, and has been widely used for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (CTEPH). Some studies found that riociguat had better effects on CTEPH and proved to be safe, but the results were not utterly consistent. Therefore, the purpose of this study was to comprehensively evaluate the efficacy and safety of riociguat in the treatment of CTEPH., Methods: Randomized controlled trials on riociguat for the treatment of CTEPH were searched through such electronic databases as PubMed, Embase, Cochrane Library, Web of Science, China national knowledge internet, and Wanfang. The outcomes included exercise capacity, pulmonary hemodynamics, and side effects. The fixed-effects or random-effects models were used to analyze the pooled data, and heterogeneity was assessed by the I2 test., Results: Four studies involving 520 patients were included in this meta-analysis. Compared with the placebo group, riociguat significantly improved the hemodynamic indexes and increased 6-min walking distance (P < .0001, standardized mean difference (SMD) = -0.24, 95%CI -0.35 to -0.12; P < .00001, SMD = 0.52, 95%CI 0.33 to 0.71), and decreased the Borg dyspnea score (P = .002, SMD = -0.31, 95%CI -0.51 to -0.12). In addition, riociguat could also significantly reduce the living with pulmonary hypertension scores and increase the EQ-5D scores (P = .01, SMD=-0.23, 95%CI -0.42 to -0.05; P < .00001, SMD = 0.47, 95%CI 0.27 to 0.66), but there was no significant difference in the change level of N-terminal pro-hormone B-type natriuretic peptide in patients with riociguat (P = .20, SMD = -0.24, 95%CI -0.61 to -0.13). The common adverse events of riociguat were dyspepsia and peripheral edema, and no other serious adverse reactions were observed., Conclusions: We confirmed that riociguat had better therapeutic effects in improving the hemodynamic parameters and exercise capacity in patients with CTEPH without inducing serious adverse events. This will provide a reasonable medication regimen for the treatment of CTEPH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Checkpoint kinase 1 (CHK1) plays a broad role in regulating the cell cycle process and is involved in the pathogenesis of various malignant tumors. Preclinical and animal studies have shown that CHK1 inhibitors can enhance the cytotoxic effects of radiotherapy and chemotherapy. Currently, CHK1 inhibitors are actively tested in clinical trials. Nonspecific adverse cerebral cardiovascular events were reported after CHK1 inhibitor use; these events need to be monitored and managed carefully during the clinical application of CHK1 inhibitors. To get a better understanding of these, noteworthy adverse cardiovascular events, we systemically searched the PubMed, Cochrane databases, and clinicaltrials.gov, for relevant clinical trials and case reports. A total of 19 studies were identified and included in this review. Among the reported cerebral cardiovascular events, the most common is incident abnormal blood pressure fluctuations (n = 35), followed by incident QTcF prolongation (n = 15), arrhythmia (n = 13, 3 atrial fibrillation and 10 bradycardia), thromboembolic events (n = 9, 6 pulmonary embolisms, 2 stroke, and 1 cerebrovascular event), cardiac troponin T elevation (n = 2), and ischemic chest pain (n = 2). Besides, the estimated incidence for overall cardiovascular events based on the available data is 0.292 (95% confidence interval: 0.096-0.488). CHK1 inhibitors administered in tumor patients on top of conventional therapies can not only enhance the antitumor effects, but also induce adverse cerebral cardiovascular events. It is, therefore, of importance to carefully monitor and manage the CHK1 inhibitor-induced adverse effects on the cerebral cardiovascular system while applying CHK1 inhibitors to tumor patients., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Buccal dexmedetomidine (DEX) produces adequate preoperative sedation and anxiolysis when used as a premedication. Formulating the drug as a gel decreases oral losses and improves the absorption of buccal DEX. We compared pharmacokinetic and pharmacodynamic properties of 3 doses of buccal DEX gel formulated in our pharmaceutical laboratory for sedative premedication in women undergoing modified radical mastectomy for breast cancer., Methods: Thirty-six patients enrolled in 3 groups (n = 12) to receive buccal DEX gel 30 minutes before surgery at 0.5 µg/kg (DEX 0.5 group), 0.75 µg/kg (DEX 0.75 group), or 1 µg/kg (DEX 1 group). Assessments included plasma concentrations of DEX, and pharmacokinetic variables calculated with noncompartmental methods, sedative, hemodynamic and analgesic effects, and adverse effects., Results: The median time to reach peak serum concentration of DEX (Tmax) was significantly shorter in patients who received 1 µg/kg (60 minutes) compared with those who received 0.5 µg/kg (120 minutes; P = .003) and 0.75 µg/kg (120 minutes; P = .004). The median (first quartile-third quartile) peak concentration of DEX (maximum plasma concentration [Cmax]) in plasma was 0.35 ng/mL (0.31-0.49), 0.37 ng/mL (0.34-0.40), and 0.54 ng/mL (0.45-0.61) in DEX 0.5, DEX 0.75, and DEX 1 groups (P = .082). The 3 doses did not produce preoperative sedation. The 1 µg/kg buccal DEX gel produced early postoperative sedation and lower intraoperative and postoperative heart rate values. Postoperative analgesia was evident in the 3 doses in a dose-dependent manner with no adverse effects., Conclusions: Provided that it is administered 60-120 minutes before surgery, sublingual administration of DEX formulated as an oral-mucosal gel may provide a safe and practical means of sedative premedication in adults., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Background: The anesthetic management of supratentorial craniotomy (CR) necessitates tight intraoperative hemodynamic control. This type of surgery may also be associated with substantial postoperative pain. We aimed at evaluating the influence of regional scalp block (SB) on hemodynamic stability during the noxious events of supratentorial craniotomies and total intravenous anesthesia, its influence on intraoperative anesthetic agents' consumption, and its effect on postoperative pain control., Methods: Sixty patients scheduled for elective CR were prospectively enrolled. Patient, anesthesiologist, and neurosurgeon were blind to the random performance of SB with either levobupivacaine 0.33% (intervention group [group SB], n = 30) or the same volume of saline (control group [group CO], placebo group, n = 30). General anesthesia was induced and maintained using target-controlled infusions of remifentanil and propofol that were adjusted according to hemodynamic parameters and state entropy of the electroencephalogram (SE), respectively. Mean arterial blood pressure (MAP), heart rate (HR), SE, and propofol and remifentanil effect-site concentrations (Ce) were recorded at the time of scalp block performance (Baseline), and 0, 1, 3, and 5 minutes after skull-pin fixation (SP), skin incision (SI), CR, and dura-mater incision (DM). Morphine consumption and postoperative pain intensity (0-10 visual analog scale [VAS]) were recorded 1, 3, 6, 24, and 48 hours after surgery. Propofol and remifentanil overall infusion rates were also recorded. Data were analyzed using 2-tailed Student unpaired t tests, 2-way mixed-design analysis of variance (ANOVA), and Tukey's honestly significant difference (HSD) tests for post hoc comparisons as appropriate., Results: Demographics and length of anesthetic procedure of group CO and SB were comparable. SP, SI, and CR were associated with a significantly higher MAP in group CO than in group SB, at least at one of the time points of recording surrounding those noxious events. This was not the case at DM. Similarly, HR was significantly higher in group CO than in group SB during SP and SI, at least at 1 of the points of recording, but not during CR and DM. Propofol and remifentanil Ce and overall infusion rates were significantly higher in group CO than in group SB, except for propofol Ce during SP. Postoperative pain VAS and cumulative morphine consumption were significantly higher in group CO than in group SB., Conclusions: In supratentorial craniotomies, SB improves hemodynamic control during noxious events and provides adequate and prolonged postoperative pain control as compared to placebo., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2020 International Anesthesia Research Society.)

Objective: Chronic hemolysis is a hallmark of sickle cell disease (SCD) and a driver of vasculopathy; however, the mechanisms contributing to hemolysis remain incompletely understood. Although XO (xanthine oxidase) activity has been shown to be elevated in SCD, its role remains unknown. XO binds endothelium and generates oxidants as a byproduct of hypoxanthine and xanthine catabolism. We hypothesized that XO inhibition decreases oxidant production leading to less hemolysis. Approach and Results: Wild-type mice were bone marrow transplanted with control (AA) or sickle (SS) Townes bone marrow. After 12 weeks, mice were treated with 10 mg/kg per day of febuxostat (Uloric), Food and Drug Administration-approved XO inhibitor, for 10 weeks. Hematologic analysis demonstrated increased hematocrit, cellular hemoglobin, and red blood cells, with no change in reticulocyte percentage. Significant decreases in cell-free hemoglobin and increases in haptoglobin suggest XO inhibition decreased hemolysis. Myographic studies demonstrated improved pulmonary vascular dilation and blunted constriction, indicating improved pulmonary vasoreactivity, whereas pulmonary pressure and cardiac function were unaffected. The role of hepatic XO in SCD was evaluated by bone marrow transplanting hepatocyte-specific XO knockout mice with SS Townes bone marrow. However, hepatocyte-specific XO knockout, which results in >50% diminution in circulating XO, did not affect hemolysis levels or vascular function, suggesting hepatocyte-derived elevation of circulating XO is not the driver of hemolysis in SCD., Conclusions: Ten weeks of febuxostat treatment significantly decreased hemolysis and improved pulmonary vasoreactivity in a mouse model of SCD. Although hepatic XO accounts for >50% of circulating XO, it is not the source of XO driving hemolysis in SCD.

Background: This study aimed to investigate the effects of dexmedetomidine (Dex) on hemodynamics and organ protection in congenital heart disease (CHD) children who underwent open-heart surgery under cryogenic cardiopulmonary bypass., Methods: Ninety children were randomly allocated to group C (0.9% saline 0.2 μg/kg/hour), group D1 (Dex 0.2 μg/kg/hour), and group D2 (Dex 0.4 μg/kg/hour) (n = 30 per group). All participants received fentanyl, propofol and 1% sevoflurane for anesthesia induction. Hemodynamic data were measured from T0 (before the induction) to T7 (30 minutes after extubation). The difference of arterial internal jugular vein bulbar oxygen difference and cerebral oxygen extraction ratio were calculated according to Fick formula. Enzyme-linked immunosorbent assay was performed to detect the serum myocardial, brain and kidney injury markers. The incidence of acute kidney injury (AKI) was calculated by serum creatinine level. Tracheal extubation time, postoperative pain score and emergence agitation score were also recorded., Results: Compared with group C, group D1, and D2 exhibited reduction in hemodynamic parameters, myocardial and brain injury indicators, and tracheal extubation time. There were no significant differences in blood urea nitrogen and neutrophil gelatinase-associated lipocalin or incidence of AKI among the 3 groups. Besides, the incidence of tachycardia, nausea, vomiting and moderate agitation, and the FLACC scale in group D1 and D2 were lower than those in group C. Moreover, Dex 0.4 g/kg/hour could further reduce the dosage of fentanyl and dopamine compared with Dex 0.2 g/kg/hour., Conclusions: Dex anesthesia can effectively maintain hemodynamic stability and diminish organ injuries in CHD children., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose of Review: Many forms of acute and chronic disease are linked to changes in renal blood flow, perfusion, vascular density and hypoxia, but there are no readily available methods to assess these parameters in clinical practice. Dynamic contrast enhanced ultrasound (DCE-US) is a method that provides quantitative assessments of organ perfusion without ionising radiation or risk of nephrotoxicity. It can be performed at the bedside and is suitable for repeated measurements. The purpose of this review is to provide updates from recent publications on the utility of DCE-US in the diagnosis or assessment of renal disease, excluding the evaluation of benign or malignant renal masses., Recent Findings: DCE-US has been applied in clinical studies of acute kidney injury (AKI), renal transplantation, chronic kidney disease (CKD), diabetic kidney disease and to determine acute effects of pharmacological agents on renal haemodynamics. DCE-US can detect changes in renal perfusion across these clinical scenarios and can differentiate healthy controls from those with CKD. In sepsis, reduced DCE-US measures of perfusion may indicate those at increased risk of developing AKI, but this requires confirmation in larger studies as there can be wide individual variation in perfusion measures in acutely unwell patients. Recent studies in transplantation have not provided robust evidence to show that DCE-US can differentiate between different causes of graft dysfunction, although it may show more promise as a prognostic indicator of graft function 1 year after transplant. DCE-US can detect acute haemodynamic changes in response to medication that correlate with changes in renal plasma flow as measured by para-aminohippurate clearance., Summary: DCE-US shows promise and has a number of advantages that make it suitable for the assessment of patients with various forms of kidney disease. However, further research is required to evidence its reproducibility and utility before clinical use can be advocated.

Our study aimed to investigate the effect of intravenous thrombolysis with alteplase and edaravone on cerebral hemodynamics and T lymphocyte level in patients harboring acute cerebral infarction.There involved a total of 118 patients with acute cerebral infarction from November 2017 to May 2019 in our hospital were randomly divided into 2 groups: the observation group (59 patients were treated with intravenous thrombolysis with alteplase combined with edaravone) and the control group (59 patients were treated with intravenous thrombolysis of alteplase). The clinical effect, neurological function, cerebral hemodynamic index, T lymphocyte level, oxygen free radical scavenging level and oxidative stress index of the 2 groups were observed and compared.Before the treatment, there were no significant differences in neurological function, cerebral hemodynamic indexes, T-lymphocyte level, oxygen free radical scavenging level and oxidative stress indexes between the 2 groups (P > .05). After the treatment, the neurological function, cerebral hemodynamic indexes, T-lymphocyte level, oxygen free radical scavenging level and oxidative stress indexes of the 2 groups were significantly improved. In addition, the observation group exerted greater beneficial effect in terms of the clinical effect, neurologic function, cerebral hemodynamic index, T lymphocyte level, oxygen free radical scavenging level and oxidative stress index than those of the control group (P < .05).The intravenous thrombolysis with alteplase and edaravone is effective in the treatment of acute cerebral infarction, which also provides better results in terms of improving the clinical efficacy and prognosis of patients and might be an alternative option for clinical practice.

Background: The goal of this study was to comprehensively evaluate the analgesic and antiemetic effects of adjuvant dexmedetomidine (DEX) for breast cancer surgery using a meta-analysis., Methods: Electronic databases were searched to collect the studies that performed randomized controlled trials. The effect size was estimated by odd ratio (OR) or standardized mean difference (SMD). Statistical analysis was performed using the STATA 13.0 software., Results: Twelve published studies involving 396 DEX treatment patients and 395 patients with control treatment were included. Pooled analysis showed that the use of DEX significantly prolonged the time to first request of analgesia (SMD = 1.67), decreased the postoperative requirement for tramadol (SMD = -0.65) and morphine (total: SMD = -2.23; patient-controlled analgesia: SMD = -1.45) as well as intraoperative requirement for fentanyl (SMD = -1.60), and lower the pain score at 1 (SMD = -0.30), 2 (SMD = -1.45), 4 (SMD = -2.36), 6 (SMD = -0.63), 8 (SMD = -2.47), 12 (SMD = -0.81), 24 (SMD = -1.78), 36 (SMD = -0.92), and 48 (SMD = -0.80) hours postoperatively compared with the control group. Furthermore, the risks to develop postoperative nausea/vomiting (PONV) (OR = 0.38) and vomiting (OR = 0.54) were significantly decreased in the DEX group compared with the control group. The pain relief at early time point (2, 6, 12, 24 hours postoperatively) and the decrease in the incidence of PONV were especially obvious for the general anesthesia subgroup (P < .05) relative to local anesthesia subgroup (P >.05)., Conclusion: DEX may be a favorable anesthetic adjuvant in breast cancer surgery, which could lower postoperative pain and the risk to develop PONV. DEX should be combined especially for the patients undergoing general anesthesia.

Ischemic preconditioning and postconditioning are strong measures preserving the heart against ischemia-reperfusion injury in experimental setting but are too invasive and impractical for clinical routine. The cardioprotective effects of ischemic preconditioning and postconditioning can be imitated pharmacologically, for example, with the phosphodiesterase inhibitors sildenafil and milrinone. We hypothesize that sildenafil-induced preconditioning is concentration dependent and further that a combined treatment of "nonprotective" versus "protective" concentrations of sildenafil and milrinone leads to a significant infarct size reduction. Experiments were performed on isolated hearts of male Wistar rats, randomized into 12 groups, mounted onto a Langendorff system, and perfused with Krebs-Henseleit buffer. All hearts underwent 33 minutes ischemia and 60 minutes of reperfusion. For determination of a concentration-dependent effect of sildenafil, hearts were perfused with increasing concentrations of sildenafil (0.1-1 µM) over 10 minutes before ischemia. In a second series of experiments, hearts were treated with 0.3 µM sildenafil or 1 µM milrinone as the "protective" concentrations. A higher concentration of respective drugs did not further reduce infarct size. In addition, a combination of "protective" and "nonprotective" concentrations of sildenafil and milrinone was applied. Sildenafil and milrinone in lower concentrations led to significant infarct size reduction, whereas combining both substances in cardioprotective concentrations did not enhance this effect. Sildenafil in a concentration of 0.3 µM induces myocardial protection. Furthermore, treatment with sildenafil and milrinone in lower concentrations had an equally strong cardioprotective effect regarding infarct size reduction compared with the administration of "protective" concentrations.

Background: Dexmedetomidine is only approved for use in humans as an intravenous medication. An oral formulation may broaden the use and benefits of dexmedetomidine to numerous care settings. The authors hypothesized that oral dexmedetomidine (300 mcg to 700 mcg) would result in plasma concentrations consistent with sedation while maintaining hemodynamic stability., Methods: The authors performed a single-site, open-label, phase I dose-escalation study of a solid oral dosage formulation of dexmedetomidine in healthy volunteers (n = 5, 300 mcg; followed by n = 5, 500 mcg; followed by n = 5, 700 mcg). The primary study outcome was hemodynamic stability defined as lack of hypertension, hypotension, or bradycardia. The authors assessed this outcome by analyzing raw hemodynamic data. Plasma dexmedetomidine concentrations were determined by liquid chromatograph-tandem mass spectrometry. Nonlinear mixed effect models were used for pharmacokinetic and pharmacodynamic analyses., Results: Oral dexmedetomidine was associated with plasma concentration-dependent decreases in heart rate and mean arterial pressure. All but one subject in the 500-mcg group met our criteria for hemodynamic stability. The plasma concentration profile was adequately described by a 2-compartment, weight allometric, first-order absorption, first-order elimination pharmacokinetic model. The standardized estimated parameters for an individual of 70 kg was V1 = 35.6 [95% CI, 23.8 to 52.8] l; V2 = 54.7 [34.2 to 81.7] l; CL = 0.56 [0.49 to 0.64] l/min; and F = 7.2 [4.7 to 14.4]%. Linear models with effect sites adequately described the decreases in mean arterial pressure and heart rate associated with oral dexmedetomidine administration. However, only the 700-mcg group reached plasma concentrations that have previously been associated with sedation (>0.2 ng/ml)., Conclusions: Oral administration of dexmedetomidine in doses between 300 and 700 mcg was associated with decreases in heart rate and mean arterial pressure. Despite low oral absorption, the 700-mcg dose scheme reached clinically relevant concentrations for possible use as a sleep-enhancing medication., (Copyright © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.)

Objective: This study is aims to compare the anesthetic safety of propofol combined with etomidate for painless gastroscopy., Methods: Three hundred patients undergoing painless gastroscopy were randomly assigned to P, PE1, and PE2 groups. Patients were anesthetized with propofol (P group) or propofol combined with etomidate (volume ratio 1: 1, PE1 group; volume ratio 2: 1, PE2 group). The hemodynamics and adverse reactions were observed. The sleep quality satisfaction and nature of dreams were recorded., Results: Compared with pre-anesthesia, the mean arterial pressure and heart rate of the 3 groups were significantly slower during the examination and at the end of the examination. PE1 group had a higher incidence of muscle spasm, body moving, choking, and deglutition. The incidence of hypoxemia and injection pain was higher in P group. P and PE2 group had higher sleep quality satisfaction and dream incidence after awaking. However, there was no difference in the nature of dreams among 3 groups., Conclusion: Our data indicate that the combination of 10 ml 1.0% propofol and 5 ml 0.2% etomidate for painless gastroscopy reduces adverse reactions while not affecting the patients respiratory function. Moreover, it is safe and effective, which is worthy of clinical application and promotion.

Introduction: Coronavirus disease-2019 (COVID-19) outbreak has spread around the world. However, the dynamic course of critically ill COVID-19 has not been described thoroughly., Patients and Methods: We retrospectively analyzed 195 critically ill COVID-19 patients in Hubei province, China, between January 5, 2020 and April 3, 2020. Epidemiologic data, clinical features, treatments, and outcomes were collected and analyzed., Results: Most critically ill patients were older with higher Acute Physiology and Chronic Health Evaluation II scores. After critical illness onset, a total of 181 (92.8%) patients received ventilation support, of which 84 (43.1%) received noninvasive and 97 (49.7%) received invasive mechanic ventilation (IMV). Among the 97 patients with IMV, 28 (28.9%) received prone ventilation, 57 (58.8%) received neuromuscular blocked therapy, and 22 (11.3%) received tracheostomy due to prolonged ventilator use. Early hypoxemia, subsequent hypercapnia, pulmonary hypertension, and finally pulmonary fibrosis were notable in the clinical course of acute respiratory distress syndrome (ARDS). Eighty-nine (45.6%) patients presented with shock. Acute kidney injury (29.7%) and secondary infection (28.2%) were also notable. The overall mortality of critically ill patients at day 28 was 42.1%. Intensive care unit (ICU) mortality was around 33%, as 16 patients died prior to ICU admission. A low PaO2/FiO2 ratio was an independent risk factor for death. High viral load was observed in most non-survivors., Conclusion: ARDS and shock were notable in the critical illness of COVID-19. Ventilation support and hemodynamic support were the cornerstones for critical care. High viral load was associated with death of critically ill COVID-19 patients.

This study aimed at analyzing the clinical profile of real-world patients with heart failure with reduced ejection fraction (HFrEF) and evaluating the safety and efficacy of sacubitril/valsartan among Asian patients in daily practice. We conducted a single-center prospective observational cohort study of HFrEF patients treated with sacubitril/valsartan from September 2017 to September 2018 with a follow-up of 6 months. The mean (SD) age of the 110 patients enrolled was 59.7 ± 13.3, 85 (77.3%) were men and 41 (37.3%) had ischemic cardiomyopathy. Thirty-one (27.2%) patients with low systolic blood pressure initiated sacubitril/valsartan on a tiny dose of 12/13 mg. Despite the low mean daily dose achieved in real world mainly because of hypotension, left ventricular ejection fraction increased significantly from 35.4 ± 8.9% at baseline to 43.0 ± 12.2% after 6-month follow-up (P < 0.001). We also observed a significant improvement in a 6-minute walk test (6-MWT) distance and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration reduction. No severe adverse event was recorded. Low dose sacubitril/valsartan induces beneficial cardiac reverse remodeling and improves clinical functional performance in real-world HFrEF patients without severe adverse effect. A tiny initial dose may enhance tolerability and reduce discontinuation rate by minimizing hypotension events in patients with low systolic blood pressure. These data further support using low-dose sacubitril/valsartan among eligible patients with HFrEF in Asia.

Background: Percutaneous compression of the trigeminal ganglion (PCTG) has been used to treat trigeminal neuralgia since 1983. A PCTG-related trigeminocardiac reflex (TCR) can induce dramatic hemodynamic disturbances. This study investigates the effects of depth of propofol anesthesia on hemodynamic changes during PCTG., Materials and Methods: A total of 120 patients who underwent PTCG for trigeminal neuralgia were randomly assigned to control group-intravenous saline pretreatment before PCTG puncture and anesthesia targeted to bispectral index (BIS) 40 to 60 throughout, and study group-intravenous propofol 1 to 2 mg/kg pretreatment to deepen anesthesia to BIS<40 before PCTG. Mean arterial pressure, heart rate (HR), cardiac output, system vascular resistance, and BIS were measured at 9 time points during the procedure, and the incidence of the TCR was observed at T5 and T6., Results: BIS was lower in the study group compared with the control after pretreatment with propofol or saline, respectively. Compared with the control group, mean arterial pressure was lower in the study group at several points during the procedure, but there was no difference in HR between the 2 groups at any point. Cardiac output was higher and system vascular resistance lower in the study compared with the control group. In the control group, 42 (70.0%) and 52 (86.7%) of patients developed a TCR at the 2 points, and 37 (67.1%) and 45 (75.0%) in the study group. There was no difference in the incidence of TCR between the 2 groups., Conclusion: Increasing the depth of propofol anesthesia partially attenuated PTCG-related elevation of blood pressure but did not modify the abrupt reduction in HR.

Background: Hydrogen gas (H2) inhalation during hemorrhage stabilizes post-resuscitation hemodynamics, improving short-term survival in a rat hemorrhagic shock and resuscitation (HS/R) model. However, the underlying molecular mechanism of H2 in HS/R is unclear. Endothelial glycocalyx (EG) damage causes hemodynamic failure associated with HS/R. In this study, we tested the hypothesis that H2 alleviates oxidative stress by suppressing xanthine oxidoreductase (XOR) and/or preventing tumor necrosis factor-alfa (TNF-α)-mediated syndecan-1 shedding during EG damage., Methods: HS/R was induced in rats by reducing mean arterial pressure (MAP) to 35 mm Hg for 60 min followed by resuscitation. Rats inhaled oxygen or H2 + oxygen after achieving shock either in the presence or absence of an XOR inhibitor (XOR-I) for both the groups. In a second test, rats received oxygen alone or antitumor necrosis factor (TNF)-α monoclonal antibody with oxygen or H2. Two hours after resuscitation, XOR activity, purine metabolites, cytokines, syndecan-1 were measured and survival rates were assessed 6 h after resuscitation., Results: H2 and XOR-I both suppressed MAP reduction and improved survival rates. H2 did not affect XOR activity and the therapeutic effects of XOR-I and H2 were additive. H2 suppressed plasma TNF-α and syndecan-1 expression; however, no additional H2 therapeutic effect was observed in the presence of anti-TNF-α monoclonal antibody., Conclusions: H2 inhalation after shock stabilized hemodynamics and improved survival rates in an HS/R model independent of XOR. The therapeutic action of H2 was partially mediated by inhibition of TNF-α-dependent syndecan-1 shedding.

Background: Bleeding during rhinoplasty leads to many undesirable effects, such as loss of vision in the surgery area, complications during the procedure, and postoperative complications. The most important effect that increases bleeding is hemodynamic changes during surgery. Considering that osteotomy is the most challenging process in rhinoplasty, this study aimed to examine the hemodynamic changes during osteotomy and changes in the depth of anesthesia., Methods: A total of 50 patients, aged 18 to 65 years with an ASA (American Society of Anesthesiology) score of 1 and 2, who underwent osteotomy during rhinoplasty under general anesthesia, were examined retrospectively. After routine monitoring, the patients underwent general anesthesia induction and endotracheal intubation. Before the surgery, they received remifentanil 1 μg/kg as an intravenous bolus followed by 0.5 μg/(kg·min) as intravenous infusion until the end of the surgery. The hemodynamic parameters and depth of anesthesia [bispectral index (BIS) values] of the patients were examined before anesthesia, 10 minutes before osteotomy, during osteotomy, and 10 minutes after osteotomy., Results: A significant difference was found in heart rate (beats/min), systolic and diastolic blood pressures (mm Hg), and BIS values of the patients measured before, during, and after osteotomy (P < 0.001). The heart rate, systolic and diastolic blood pressures, and BIS values were significantly higher during osteotomy. Until the 10th minute after osteotomy, all 4 parameters nearly reached the values measured before osteotomy., Conclusions: Osteotomy directly affects hemodynamic parameters and depth of anesthesia. Hence, it is of utmost importance that the analgesic need and depth of anesthesia are adequately monitored and adjusted during osteotomy. By suppressing hemodynamic stress responses, the amount of bleeding can be reduced, thus increasing the surgical success and the patient's comfort.

The aim of this study was to assess the knowledge of nursing teams that care for hospitalized adolescents undergoing glucocorticoid infusion and to develop an educational protocol for nursing care during pulse therapy. This descriptive, exploratory study with a qualitative approach was developed in a unit specializing in adolescent health at a university hospital in the state of Rio de Janeiro, Brazil. The instrument used for data collection was a semistructured interview conducted in a private room on the unit. The main results indicated that nursing knowledge was focused on the need to evaluate hemodynamic parameters, the care required during infusion therapy, and the complications resulting from the treatment. Educational material was developed to support a holistic view of the adolescent undergoing pulse therapy. Based on information received from the nursing team, it was determined that, although the team performed all the technical aspects of the infusion procedure well, their care did not address specific needs of the adolescent patient, guidance on infection prevention, or hemodynamic evaluation. After evaluating the nursing team's experience, knowledge, and perceptions, the researchers were able to develop appropriate protocols to guide care for hospitalized adolescents undergoing glucocorticoid infusion therapy.

Coagulation management is the leading challenge during extracorporeal life support (ECLS) due to shear stress and foreign-surface-induced coagulation disturbance during circulation. A nonadhesive, liquid-infused coating called tethered liquid perfluorocarbon (TLP) was developed to prevent adhesion of blood on medical materials. We investigated the novel application of TLP to commercial ECLS circuits compared with standard heparin-coated circuits in vivo in anesthetized swine for 6 hours veno-venous ECLS (1 L/min blood flow) without systemic anticoagulation (n = 3/group). We hypothesized that TLP coating permits heparin-free circulation without untoward effects while reducing thrombus deposition compared with controls. Vital signs, respiration, gas transfer, coagulation, and histology were assessed. Scanning electron microscopy (SEM), elemental mapping, and digital imaging were used to assess thrombus deposition after circulation. There were no group differences in vitals, gas exchange, coagulation, and histology. In both groups, ECLS enabled a decrease in minute volume and end-tidal CO2, with concomitant increase in pH (p < 0.05). Scanning electron microscopy and digital imaging revealed significant thrombus on heparin-coated membranes, which was reduced or absent on TLP-coated materials. Tethered liquid perfluorocarbon permitted heparin-free ECLS without altering device performance and prevented thrombus deposition versus immobilized heparin. Pending multiday in vivo testing, TLP is a promising biomaterial solution to eliminate anticoagulation requirements during ECLS.

Objectives: Tracheal intubation in critically ill children with shock poses a risk of hemodynamic compromise. Ketamine has been considered the drug of choice for induction in these patients, but limited data exist. We investigated whether the administration of ketamine for tracheal intubation in critically ill children with or without shock was associated with fewer adverse hemodynamic events compared with other induction agents. We also investigated if there was a dose dependence for any association between ketamine use and adverse hemodynamic events., Design: We performed a retrospective analysis using prospectively collected observational data from the National Emergency Airway Registry for Children database from 2013 to 2017., Setting: Forty international PICUs participating in the National Emergency Airway Registry for Children., Patients: Critically ill children 0-17 years old who underwent tracheal intubation in a PICU., Interventions: None., Measurements and Main Results: The association between ketamine exposure as an induction agent and the occurrence of adverse hemodynamic events during tracheal intubation including dysrhythmia, hypotension, and cardiac arrest was evaluated. We used multivariable logistic regression to account for patient, provider, and practice factors with robust SEs to account for clustering by sites. Of 10,750 tracheal intubations, 32.0% (n = 3,436) included ketamine as an induction agent. The most common diagnoses associated with ketamine use were sepsis and/or shock (49.7%). After adjusting for potential confounders and sites, ketamine use was associated with fewer hemodynamic tracheal intubation associated adverse events compared with other agents (adjusted odds ratio, 0.74; 95% CI, 0.58-0.95). The interaction term between ketamine use and indication for shock was not significant (p = 0.11), indicating ketamine effect to prevent hemodynamic adverse events is consistent in children with or without shock., Conclusions: Ketamine use for tracheal intubation is associated with fewer hemodynamic tracheal intubation-associated adverse events.

Background: This study will specifically investigate the effect of butylphthalide on hemodynamics in patients with watershed stroke (WS)., Methods: We will search the following databases from their inceptions to the March 1, 2020: Cochrane Library, MEDLINE, EMBASE, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and China National Knowledge Infrastructure. All relevant randomized controlled trials on exploring the effect of butylphthalide on hemodynamics in patients with WS will be considered for inclusion. No language limitation will be imposed to this study. All study quality will be checked using Cochrane risk of bias tool. RevMan 5.3 software will be utilized for data analysis., Results: This study will summarize the latest evidence to investigate the effect of butylphthalide on hemodynamics in patients with WS., Conclusion: Findings from this study will provide theoretical basis of butylphthalide on hemodynamics in patients with WS for clinician and future research., Dissemination and Ethics: This study is carried out based on the published data, thus, no ethical approval is required. We will submit this study to a peer-reviewed journal for publication., Systematic Review Registration: INPLASY 202030006.

Background: Intra-arterial nimodipine (IaN) is used in the management of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). The impact of IaN therapy on regional cerebral oxygen saturation (rScO2) assessed by near infra-red spectroscopy, and dynamic cardiac indices, is currently unknown. This study assessed the effect of IaN on rScO2 and systemic hemodynamic indices during IaN therapy for cerebral vasospasm after aSAH., Methods: This prospective cohort study was conducted in 20 patients over sixteen month period after ethics committee approval and informed consent. Patients with angiographic evidence of vasospasm received IaN 3mg over 30 minutes in the spastic vessels. Data regarding rScO2 heart rate (HR), mean blood pressure (MBP) cardiac index (CI), stroke volume index (SVI), stroke volume variation (SVV), and total peripheral resistance index (TPRI) were collected during IaN treatment. The primary outcome measure was change in rScO2 after IaN therapy., Results: There was no significant change from baseline in ipsilateral and contralateral rScO2 after IaN administration (mean difference [MD], 0.2; 95% confidence interval [CI], -2.1 to 1.6; P=0.804, and 1.3; -1.1 to 3.8; P=0.276, respectively). There was a significant decrease in MBP and TPRI (MD, -12.4; 95% CI, -6.6 to -18.2; P<0.001, and -674.3; -374.9 to -973.7; P<0.001, respectively) and increase in SVI and CI (MD, 7.5; 95% CI, 14.4 to 0.6; P=0.035 and 0.7; 0.9 to 0.4; P<0.001, respectively) after IaN therapy. HR and SVV were unchanged., Conclusions: IaN for aSAH-related cerebral vasospasm did not improve rScO2 but was associated with significant systemic hemodynamic effects, including a decrease in MBP and TPRI. These hemodynamic changes might offset any potential effects of IaN to improve rScO2.

Objectives: We investigated whether the vasopressin-analog, terlipressin induces systemic vasoconstriction and pulmonary vasodilation in a porcine model of acute pulmonary embolism., Design: Controlled, animal study., Setting: Tertiary medical center research laboratory., Subjects: Female pigs (n = 12, Cross of Land Race, Duroc, and Yorkshire ~ 60 kg)., Interventions: Acute pulmonary embolism was induced by administration of three large autologous emboli. Animals then received four increasing doses of either terlipressin (n = 6) or vehicle (n = 6)., Measurements and Main Results: Effects were evaluated in vivo at baseline, after pulmonary embolism and after each dose by invasive hemodynamic measures, transesophageal echocardiography, and blood analysis. Isolated pulmonary arteries were evaluated ex vivo in a myograph. Pulmonary embolism caused a four-fold increase in pulmonary vascular resistance (p < 0.0001) and a two-fold increase in mean pulmonary arterial pressure (p < 0.0001) compared with baseline. Terlipressin increased mean systemic blood pressure (28 ± 5 mm Hg; p < 0.0001) and systemic vascular resistance (1,320 ± 143 dynes; p < 0.0001) compared with vehicle. In the pulmonary circulation, terlipressin decreased mean pulmonary arterial pressure (-6.5 ± 1.8 mm Hg; p = 0.005) and tended to decrease pulmonary vascular resistance (-83 ± 33 dynes; p = 0.07). Terlipressin decreased cardiac output (-2.5 ± 0.5 L/min; p < 0.0001) and increased plasma lactate (2.7 ± 0.2 mmol/L; p < 0.0001), possibly indicating systemic hypoperfusion. A biomarker of cerebral ischemia, S100b, remained unchanged, suggesting preserved cerebral perfusion (0.17 ± 0.11 µg/L; p = 0.51). Ex vivo, terlipressin relaxed pulmonary and constricted mesenteric arteries., Conclusions: Terlipressin caused systemic vasoconstriction and pulmonary vasodilation in a porcine in vivo model of acute pulmonary embolism and vasorelaxation in isolated pulmonary arteries. Despite positive vascular effects, cardiac output declined and plasma lactate increased probably due to a predominantly systemic vasoconstrictor effect of terlipressin. These findings should warrant careful translation to the clinical setting and does not suggest routine use in acute pulmonary embolism.