Takashi Mori

Systemic vascular resistance has an impact on the reliability of the Vigileo-FloTrac system in measuring cardiac output and tracking cardiac output changes

BACKGROUND The aim of this study was to examine the ability of the Vigileo-FloTrac system to measure cardiac output (CO) and track changes in CO induced by increased vasomotor tone, under different states of systemic vascular resistance (SVR). METHODS Forty patients undergoing cardiac surgery were enrolled. Haemodynamic variables including CO measured by the Vigileo-FloTrac system (version 3.02) (APCO), CO measured by a pulmonary artery catheter (ICO), and SVR index (SVRI) were recorded before (T1) and 2 min after (T2) phenylephrine administration (100 μg). Bland and Altman analysis was used to compare ICO and APCO at T1. We used four-quadrant plots and polar plots to compare the trending abilities between ICO and APCO. Patients were divided into three groups according to the SVRI value at T1, with low (<1200 dyn cm(-5) m(2)), normal (1200-2500 dyn cm(-5) m(2)), and high (>2500 dyn cm(-5) m(2)) SVRI states. RESULTS A total of 155 paired data were collected. The adjusted percentage error was 46.3%, 26.4%, and 61.4%, and the concordance rate between ΔICO and ΔAPCO was 67.5%, 28.8%, and 7.7% in the low, normal, and high SVRI state, respectively. The polar plot analysis showed that the mean angular bias was -22.3°, -46.0°, and -3.51°, and the radial limits of agreement were 70°, 85°, and 87°, in the low, normal, and high SVRI state, respectively. CONCLUSIONS These results indicate that the reliability of the Vigileo-FloTrac system to measure CO and track changes in CO induced by phenylephrine administration was not clinically acceptable.

Advance of age decreases the minimum alveolar concentrations of isoflurane and sevoflurane for maintaining bispectral index below 50

BACKGROUND We investigated age-related differences in the minimum alveolar concentration (MAC) of isoflurane and sevoflurane for maintaining bispectral index (BIS) below 50 (MAC(BIS50)). METHODS One hundred and twenty young (<or=40 yr), middle-aged (41-69 yr), and elderly (>or=70 yr) patients were randomly allocated to one of the six groups. Anaesthesia was induced with isoflurane or sevoflurane in oxygen. After tracheal intubation, we arbitrarily started maintenance of anaesthesia in each group with end-tidal isoflurane and sevoflurane concentrations of 0.8 and 1.2 vol%, respectively. After 10 min at predetermined end-tidal isoflurane or sevoflurane concentrations, BIS was measured for 1 min. MAC(BIS50) of isoflurane or sevoflurane for each group was determined by up-down methodology. RESULTS MAC(BIS50) of isoflurane in young, middle-aged, and elderly patients was 0.82% end-tidal (95% confidence intervals 0.76-0.88), 0.67% (0.61-0.73), and 0.56% (0.51-0.61), respectively, and that of sevoflurane in young, middle-aged, and elderly patients was 1.28% (1.24-1.32), 0.97% (0.89-1.05), and 0.87% (0.84-0.90), respectively. For both isoflurane and sevoflurane, the MAC(BIS50) was significantly higher (P=0.002 and 0.001, respectively) in young patients and significantly lower (P=0.02 for both) in elderly patients than those in middle-aged patients. CONCLUSIONS Advance in age significantly decreased the concentrations of isoflurane and sevoflurane required to maintain BIS below 50. BIS correctly reflected age-associated decrease of end-tidal concentrations of isoflurane and sevoflurane required for maintaining adequate depth of anaesthesia during resting state.

The effects of general anesthetics on P2X7 and P2Y receptors in a rat microglial cell line.

BACKGROUND: Microglial cells play important roles in coordinating the inflammatory brain responses to hypoxia and trauma. Ionotropic P2X receptors and metabotropic P2Y receptors (P2YRs) expressed in microglia can be activated by extracellular adenosine triphosphate (ATP) derived from damaged cells or astrocytes, and participate in the signaling pathways evoked in brain insult. Although several inhaled and IV anesthetics produce neuroprotective effects through neuronal mechanisms, little is known about how general anesthetics modulate microglial responses in the pathological state. We examined the effects of various general anesthetics on purinergic responses in a rat microglial cell line. METHODS: Currents were consistently activated by applications of ATP via a U-tube system under the whole-cell configuration. ATP-induced nondesensitizing currents observed after several applications of ATP exhibited characteristics of P2X7 receptors. The P2YRs-mediated mobilization of intracellular Ca2+ was measured using a Ca2+-sensitive fluorescent dye (fura-2). RESULTS: Inhaled anesthetics (sevoflurane, isoflurane, and halothane) at doses three times as high as minimum alveolar concentrations had no effect on the P2X7Rs-mediated currents. IV anesthetics (ketamine, propofol, and thiopental) enhanced the P2X7Rs-mediated currents reversibly. The potencies for activation of P2X7Rs were not correlated with the octanol/buffer partition coefficients. Thiopental, at low concentrations, slightly inhibited the P2X7Rs-mediated currents, suggesting its dual actions on P2X7Rs. The P2YRs-mediated mobilization of intracellular Ca2+ was not affected by any of the general anesthetics tested. CONCLUSIONS: Our results suggest that IV anesthetics, particularly thiopental and propofol, may modulate microglial functions through P2X7Rs in pathological conditions.

Systemic dexmedetomidine augments inhibitory synaptic transmission in the superficial dorsal horn through activation of descending noradrenergic control: An in vivo patch-clamp analysis of analgesic mechanisms

Summary A novel analgesic mechanism of systemic dexmedetomidine (&agr;2‐agonist) revealed by in vivo patch‐clamp analysis: paradoxical activation of descending noradrenergic system enhances spinal inhibitory synaptic transmission. ABSTRACT &agr;2‐Adrenoceptors are widely distributed throughout the central nervous system (CNS) and the systemic administration of &agr;2‐agonists such as dexmedetomidine produces clinically useful, centrally mediated sedation and analgesia; however, these same actions also limit the utility of these agents (ie, unwanted sedative actions). Despite a wealth of data on cellular and synaptic actions of &agr;2‐agonists in vitro, it is not known which neuronal circuits are modulated in vivo to produce the analgesic effect. To address this issue, we made in vivo recordings of membrane currents and synaptic activities in superficial spinal dorsal horn neurons and examined their responses to systemic dexmedetomidine. We found that dexmedetomidine at doses that produce analgesia (<10 &mgr;g/kg) enhanced inhibitory postsynaptic transmission within the superficial dorsal horn without altering excitatory synaptic transmission or evoking direct postsynaptic membrane currents. In contrast, higher doses of dexmedetomidine (>10 &mgr;g/kg) induced outward currents by a direct postsynaptic action. The dexmedetomidine‐mediated inhibitory postsynaptic current facilitation was not mimicked by spinal application of dexmedetomidine and was absent in spinalized rats, suggesting that it acts at a supraspinal site. Furthermore, it was inhibited by spinal application of the &agr;1‐antagonist prazosin. In the brainstem, low doses of systemic dexmedetomidine produced an excitation of locus coeruleus neurons. These results suggest that systemic &agr;2‐adrenoceptor stimulation may facilitate inhibitory synaptic responses in the superficial dorsal horn to produce analgesia mediated by activation of the pontospinal noradrenergic inhibitory system. This novel mechanism may provide new targets for intervention, perhaps allowing analgesic actions to be dissociated from excessive sedation.

Intrathecal gabapentin and clonidine synergistically inhibit allodynia in spinal nerve-ligated rats

AIMS The objective of this study was to elucidate the interaction between intrathecally administered gabapentin and clonidine on neuropathic pain associated with allodynia in the spinal nerve ligation model in the rat. MAIN METHODS Thresholds for hind paw responses to mechanical stimuli were determined by delivering von Frey filaments to the plantar surface. The left L5 spinal nerve was ligated and a fine catheter was intrathecally implanted at the L3-4 interspace under sevoflurane anesthesia. After confirmation of the established allodynia, gabapentin at 10, 30, 60 and 100μg or clonidine at 5, 15, 30 and 50μg was injected as a monotherapy in conscious rats through the intrathecal catheter to obtain the dose-response curve of %MPE (maximum possible effect) of the antiallodynic effect and its ED(50). Gabapentin and clonidine were concomitantly administered in a fixed-dose ratio proportional to the predetermined ED(50) of these drugs, thereby obtaining a dose-response curve for the drug combination and its ED(50). The profile of the interaction between these drugs was analyzed using an isobolographic analysis. KEY FINDINGS The ED(50) for gabapentin and clonidine were 57.3±4.0 and 20.2±1.0μg, respectively (mean±SEM). However, the co-administration of gabapentin and clonidine at a ratio of 20:7 contributed to a much smaller experimental ED(50) values (gabapentin 10.1±1.1μg, and clonidine 3.6±0.3μg) compared with their theoretical ED(50)s on the additive line in the isobologram. SIGNIFICANCE In the L5 spinal nerve-ligated rats, the intrathecal co-administration of gabapentin and clonidine exerted a synergistic action on the mechanical antiallodynic effect.

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.

Inhibition of voltage-gated proton channels by local anaesthetics in GMI-R1 rat microglia.

Non‐technical summary  Lidocaine and bupivacaine are the most commonly used local anaesthetics in clinical practices such as neuraxial anaesthesia and local infiltration. They are known to suppress phagocytosis and the production of reactive oxygen species in immune cells. Voltage‐gated proton channels are abundantly expressed in immune cells, including microglia, and play crucial roles in sustaining phagocytosis. We show that both lidocaine and bupivacaine increase the intracellular pH of microglia by their weak base properties and, consequently, inhibit proton channels. This is a novel mechanism underlying actions of local anaesthetics. Our results also indicate that the proton channel is a useful tool for monitoring the behaviours of lidocaine and bupivacaine across the cellular membrane.

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.

The Effects of Epidural Morphine on Cardiac and Renal Sympathetic Nerve Activity in α-Chloralose-anesthetized Cats

BACKGROUND Epidural morphine yields postoperative pain relief and hemodynamic stability. However, the effects of epidural morphine on sympathetic tone are unclear. This study was designed to elucidate the effects of epidural morphine on cardiac (CSNA) and renal (RSNA) sympathetic nerve activity by direct measurement in anesthetized cats. METHODS Thirty mongrel cats anesthetized with alpha-chloralose were randomly assigned to one of the following five groups: control (0.2 ml/kg thoracic epidural normal saline; n=5); thoracic epidural morphine (n=9); lumbar epidural morphine (n=6); vagotomized, sinoaortic denervated, thoracic epidural morphine (n=5); or intravenous morphine (n=5). Mean arterial pressure (MAP), heart rate (HR), CSNA, and RSNA were measured 0, 15, 30, 60, 90, and 120 min after saline or morphine (200 microg/kg) administration and 15 min after reversal with 200 microg naloxone given intravenously. RESULTS In the control group, no changes in measured variables were found after either thoracic epidural saline or intravenous naloxone. Thoracic and lumbar epidural morphine both significantly reduced MAP, HR, CSNA, and RSNA 30 through 120 min after morphine administration (P < 0.05). These changes were reversed by intravenous naloxone. Changes after thoracic epidural morphine administration in vagotomized, baroreceptor-denervated cats were similar to those in intact cats. Intravenous morphine produced no significant changes except for a decrease in MAP, which was reversed by intravenous naloxone. CONCLUSION In contrast to intravenous morphine, thoracic and lumbar epidural morphine both inhibited cardiac and renal sympathetic nerve activity and consequently reduced MAP and HR in alpha-chloralose anesthetized cats.