Tokuhiro Yamada

Landiolol has a less potent negative inotropic effect than esmolol in isolated rabbit hearts

PurposeWe compared the negative chronotropic and inotropic effects of landiolol and esmolol, two clinically available short-acting β1-blockers with high β1-selectivity, using whole isolated rabbit heart preparations.MethodsTachycardia was induced by continuous perfusion of 10−7 M isoproterenol, and we used concentrations of landiolol or esmolol in ascending steps (1 · 10−6, 3 · 10−6, 1 · 10−5, 3 · 10−5, and 1 · 10−4 M). Heart rate (HR), left ventricular developed pressure (LVDP), the maximal rates of left ventricular force development (LVdP/dtmax), and myocardial oxygen consumption (MVO2) were measured and compared.ResultsBoth landiolol and esmolol produced dosedependent decreases in HR, LVDP, LVdP/dtmax, and MVO2. The HR lowering effects of the two agents were comparable. At concentrations of 3 · 10−5 and 1 · 10−4 M, esmolol produced more profound depression of LVDP (47 ± 26 and 12 ± 11 mmHg, respectively; mean ± SD) and reduction of LVdP/dtmax (650 ± 287 and 120 ± 103 mmHg·s−1) than landiolol (68 ± 20 and 64 ± 20 mmHg, and 897 ± 236 and 852 ± 240 mmHg·s−1, respectively). At the same concentrations, esmolol caused more profound reduction in MVO2 (40 ± 11 and 35 ± 10 μl·min−1 · g−1) than landiolol (50 ± 8 and 48 ± 8 μl·min−1 · g−1), respectively.ConclusionOur results indicate that in the isolated rabbit heart, landiolol and esmolol had equipotent negative chronotropic effects, however, landiolol had a less potent negative inotropic effect than esmolol.

Pleth variability index predicts hypotension during anesthesia induction.

Background: The pleth variability index (PVI) is a new algorithm used for automatic estimation of respiratory variations in pulse oximeter waveform amplitude, which might predict fluid responsiveness. Because anesthesia‐induced hypotension may be partly related to patient volume status, we speculated that pre‐anesthesia PVI would be able to identify high‐risk patients for significant blood pressure decrease during anesthesia induction.

Improved Performance of the Fourth-Generation FloTrac/Vigileo System for Tracking Cardiac Output Changes

OBJECTIVES The aims of this study were to compare cardiac output (CO) measured by the new fourth-generation FloTrac™/Vigileo™ system (Version 4.00) (COFVS) with that measured by a pulmonary artery catheter (COREF), and to investigate the ability of COFVS to track CO changes induced by increased peripheral resistance. DESIGN Prospective study. SETTING University Hospital. PARTICIPANTS Twenty-three patients undergoing cardiac surgery. INTERVENTIONS Phenylephrine (100 µg) was administered. MEASUREMENTS AND MAIN RESULTS Hemodynamic variables, including CO(REF) and CO(FVS), were measured before and after phenylephrine administration. Bland-Altman analysis was used to assess the discrepancy between CO(REF) and CO(FVS). Four-quadrant plot and polar-plot analyses were utilized to evaluate the trending ability of CO(FVS) against CO(REF) after phenylephrine boluses. One hundred thirty-six hemodynamic interventions were performed. The bias shown by the Bland-Altman analysis was-0.66 L/min, and the percentage error was 55.4%. The bias was significantly correlated with the systemic vascular resistance index (SVRI) before phenylephrine administration (p<0.001, r(2) = 0.420). The concordance rate determined by four-quadrant plot analysis and the angular concordance rate calculated using polar-plot analysis were 87.0% and 83.0%, respectively. Additionally, this trending ability was not affected by SVRI state. CONCLUSIONS The trending ability of the new fourth-generation FloTrac™/Vigileo™ system after increased vasomotor tone was greatly improved compared with previous versions; however, the discrepancy of the new system in CO measurement was not clinically acceptable, as in previous versions. For clinical application in critically ill patients, this vasomotor tone-dependent disagreement must be decreased.

Relationship between noradrenaline release in the locus coeruleus and antiallodynic efficacy of analgesics in rats with painful diabetic neuropathy.

AIMS In animal models of neuropathic pain, the noradrenergic descending pain inhibitory pathways from the locus coeruleus (LC) may be suppressed. However, no study has investigated the correlation between noradrenaline (NA) release in the LC and efficacy of analgesics in rats with painful diabetic neuropathy. Using microdialysis and analysis of mechanical hypersensitivity, we investigated the correlation between NA release in the LC and efficacy of morphine, tramadol, and clomipramine in rats with diabetic mellitus (DM). MAIN METHODS In freely moving rats, basal NA concentrations in LC perfusate were quantitated 72 to 96 h after microdialysis probe implantation. Following intravenous administration of each drug, NA concentrations were expressed as a percentage of basal values. We concurrently measured the threshold to elicit a paw withdrawal response every 20 min for 80 min. KEY FINDINGS NA concentrations in the LC perfusate were significantly higher in the tramadol and clomipramine groups compared to the morphine group. Naloxone administration did not significantly affect NA concentrations. In the morphine group, NA release in the LC was not significantly correlated with the pain threshold. In contrast, in the tramadol and clomipramine groups, NA release in the LC was significantly correlated with the pain threshold. The correlation coefficient was higher in the clomipramine group than in the tramadol group. SIGNIFICANCE Our results suggest that the descending noradrenergic pathway can play an important role in analgesia for DM neuropathy and that there is a significant correlation between NA release in the LC and the efficacy of tramadol and clomipramine.

The Vigileo-FloTracTM System: Arterial Waveform Analysis for Measuring Cardiac Output and Predicting Fluid Responsiveness: A Clinical Review

Surgical mortality rates range from 0.4% to 4%, with the occurrence of perioperative complications ranging from 3% to 17%. 2–5 These perioperative complications typically lead to an increase in the “unnecessary” days of hospitalization after surgery. Therefore, identifying high-risk patients and developing strategies aimed at decreasing perioperative complications are issues of great importance for anesthesiologists. Various interventions aimed at improving surgical outcomes have been examined by previous studies, including goal-directed therapy (GDT), 6–10 glycemic control, 11,12 and neuraxial blockade. 13–15 In a recent review, it has been suggested that interventions such as hemodynamic optimization, oxygen, glycemic control, and neuraxial anesthesia might decrease perioperative mortality. 16 Inadequate tissue perfusion has been indicated to be the strongest intraoperative predictor of perioperative complications. 17 For high-risk surgical patients, the main cause of perioperative mortality is more often related to inadequate tissue perfusion than to cardiac events. 18 Perioperative hemodynamic management can lead successfully to the optimization of cardiac output and ensure adequate oxygen delivery to the tissues; this has been shown to improve postoperative outcomes and reduce the length of the hospital stay. 7,10,19–23 In several studies that focused on cardiac output optimization, a cardiac output monitor was used to bring the patient to the plateau of the Frank-Starling curve. A pulmonary artery catheter (PAC) with intermittent thermodilution has been used as a clinical standard for cardiac output measurement. However, the use of invasive cardiac output monitoring has decreased, and, consequently, there has been an increased use of minimally invasive monitoring techniques in operating rooms and intensive care units (ICU). The term, “minimally invasive monitoring,” indicates any monitoring technique that is less invasive than, PAC; currently, minimally invasive monitoring techniques include the Vigileo-FloTrac TM system, PiCCO TM monitor, LiDCO TM system, transesophageal echocardiography, and pressure recording analytic method (PRAM). 24 The Vigileo-FloTrac TM system (Edwards LifeSciences, Irvine, CA) requires a proprietary transducer, which is attached to a standard radial or femoral arterial catheter and is connected to the Vigileo TM monitor. The Vigileo-FloTrac TM system requires no external calibration. For estimation of the cardiac output, the standard deviation (SD) of pulse pressure sampled in 20 seconds is related to normal stroke volume (SV) based on the patients’ demographic data (height, weight, age, and gender). Further, it also is correlated with a database that contains information regarding cardiac output measured using a PAC in various clinical settings. Vascular resistance and compliance are estimated by arterial waveform analysis. In the last 5 years, these cardiac output measurement algorithms have been improved repeatedly after conflicting data from early validation studies. Further software improvements have addressed the problem of limited accuracy under low systemic vascular resistance (SVR) states, and recent data have shown improvements in cardiac output measurement under these specific conditions. However, the accuracy of this system after acute SVR changes remains an issue of major concern. Some studies have raised questions about the validity of the data provided by the Vigileo-FloTrac TM system. 25,26 Therefore, the authors performed a review about the reliability of this system. The aim of this review was to provide data regarding the ability of the Vigileo-FloTrac TM system to measure cardiac output and track changes in cardiac output after hemodynamic interventions as well as to assess the reliability of stroke volume variation (SVV) measured by this system.

Discrepancy between superior vena cava oxygen saturation and mixed venous oxygen saturation can predict postoperative complications in cardiac surgery patients.

OBJECTIVE To determine if increases in discrepancy between ScvO2 and SvO2 (ScvO2 - SvO2 = ΔSO2) during surgery in cardiac surgery patients can predict postoperative complications. DESIGN Prospective, observational study. SETTING University hospital. PARTICIPANTS One hundred two patients undergoing cardiac surgery were enrolled. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Central venous oxygen saturation (ScvO2) and mixed venous oxygen saturation (SvO2) values during surgery automatically were collected. The average value of ΔSO2 for every minute was calculated. The area under the receiver operating characteristic curve for prolonged postoperative ICU stay (≥3 days) was 0.745 for ΔSO2, which was significantly different from those of ScvO2 and SvO2 (p<0.05) (ScvO2; 0.584, SvO2; 0.598). The optimal threshold value of ΔSO2 to predict prolonged ICU stay (≥3 days) was 12% (sensitivity: 72.0%, specificity: 76.9%). Postoperative ICU duration, ventilation time, and hospital stay were significantly longer in Group D patients (intraoperative maximum ΔSO2 ≥12%) than those in Group N patients (intraoperative maximum ΔSO2<12%). As for postoperative complications, the number of patients with postoperative use of intra-aortic balloon pumping, delirium, respiratory failure requiring tracheotomy, and severe complications was significantly higher in Group D patients. Multivariate logistic regression models were used to evaluate the independent effects of perioperative variables on the risk of developing prolonged ventilation (>24 hours) and prolonged ICU stay (≥3 days). A discrepancy in intraoperative ΔSO2 was an independent risk factor for prolonged postoperative ventilation and ICU stay. CONCLUSION The discrepancy between ScvO2 and SvO2 during cardiac surgery is an independent risk factor of postoperative complications such as prolonged ICU stay and ventilation time.

Effects of inhaled nitric oxide on platelet‐activating factor‐induced pulmonary hypertension in dogs

Background: Platelet‐activating factor (PAF), a lipid mediator released during endotoxin shock, induces pulmonary hypertension, systemic hypotension and cardiac dysfunction. In this study, we compared the effect of inhaled nitric oxide (NO) on PAF‐induced pulmonary hypertension and NO metabolism with that on pulmonary hypertension induced by a stable thromboxane A2 mimetic, U46619. Since PAF‐induced hypotension might be mediated by NO, the effect of inhaled NO combined with an intravenously administered NO synthase inhibitor, NG‐nitro‐L‐arginine (L‐NNA), on PAF‐induced hemodynamic change was also investigated.

The utility of intra-operative three-dimensional transoesophageal echocardiography for dynamic measurement of stroke volume

Measurement of left ventricular stroke volume and cardiac output is very important for managing haemodynamically unstable or critically ill patients. The aims of this study were to compare stroke volume measured by three‐dimensional transoesophageal echocardiography with stroke volume measured using a pulmonary artery catheter, and to examine the ability of three‐dimensional transoesophageal echocardiography to track stroke volume changes induced by haemodynamic interventions. This study included 40 cardiac surgery patients. Haemodynamic variables were measured before and 2 min after haemodynamic interventions, which consisted of phenylephrine 100 μg or ephedrine 5 mg. We used Bland–Altman analysis to assess the agreement between the stroke volume measured by three‐dimensional transoesophageal echocardiography and by the pulmonary artery catheter. Polar‐plot and 4‐quadrant plot analyses were used to assess the trending ability of three‐dimensional transoesophageal echocardiography compared with the pulmonary artery catheter. Bias and percentage error were −1.2 ml and 20%, respectively. The concordance rate in the 4‐quadrant analysis after phenylephrine and ephedrine administration was 75% and 84%, respectively. In the polar‐plot analysis, the angular concordance rate was 66% and 73% after phenylephrine and ephedrine administration, respectively. Three‐dimensional transoesophageal echocardiography was clinically acceptable for measuring stroke volume; however, it was not sufficiently reliable for tracking stroke volume changes after haemodynamic interventions.

Evaluation of a delivery system and monitors for ventilator administration of nitric oxide

The aim of this study was to compare nitric oxide (NO) and nitrogen dioxide (NO2) measurements obtained by chemiluminescence and electrochemical monitors using a delivery system for ventilator administration of NO. The formation of NO2 in this system and the efficacy of a soda-lime absorber to scavenge NO2 from inspiratory gas were also evaluated. Various concentrations of NO without and with soda lime were administered to a model lung via a Servo ventilator 900C with controlled ventilation by setting mass-flow regulators to maintain desired concentrations of NO in 80% O2. Close correlations were found between NO concentrations, as well as NO2 concentrations, measured using electrochemical monitors (TM100; 1002, PACII) and a chemiluminescence monitor (CLA-510SS). Soda-lime removed NO2 almost completely during administration of 0–25 p.p.m. NO, although a high concentration of NO2 appeared in the breathing circuit without soda lime. Four hundred grams of soda lime continued to absorb NO2 effectively during long-term administration of inhaled NO.These findings suggest that electrochemical monitoring is accurate and clinically useful for measurements of NO and NO2 concentrations, and that low doses of inhaled NO can be administered safely and reliably with the NO delivery system using a soda-lime absorber and mass-flow regulators.

Echocardiographic parameters predicting acute hemodynamically significant mitral regurgitation during transfemoral transcatheter aortic valve replacement

Alteration in mitral valve morphology resulting from retrograde stiff wire entanglement sometimes causes hemodynamically significant acute mitral regurgitation (MR) during transfemoral transcatheter aortic valve replacement (TAVR). Little is known about the echocardiographic parameters related to hemodynamically significant acute MR.