[Efficacy and safety of sugammadex (Org 25969) in reversing deep neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.

The effect of lidocaine on cholinergic neurotransmission in an identified reconstructed synapse.

BACKGROUND: The presynaptic effect of lidocaine on cholinergic synaptic transmission is unclear because of the difficulty in identifying presynaptic neurons and the complexity of the central nervous system in vivo. To clarify the effect of lidocaine on cholinergic synapse, we reconstructed a cultured soma-soma chemical synapse model consisting of two identified visceral dorsal 4 (VD4) and left pedal e-1 (LPeD1) neurons from the snail, Lymnaea stagnalis, in vitro, and used it to determine how lidocaine affects cholinergic synaptic transmission. METHODS: The response to acetylcholine and excitatory postsynaptic potential (EPSP) amplitude was recorded in the reconstructed chemical synaptic transmission model composed of VD4 and LPeD1 neurons. The currents for acetylcholine measurements were made under voltage-clamp in the presynaptic VD4 and postsynaptic LPeD1 neurons. RESULTS: Lidocaine inhibited both EPSP and the response for acetylcholine of the postsynaptic neuron. EPSP amplitude was reduced in a voltage-dependent manner in the presynaptic neuron, and lidocaine induced a hyperpolarization shift of the voltage-dependent inactivation curves of EPSP amplitude. CONCLUSIONS: Lidocaine inhibits cholinergic synaptic transmission with a voltage-dependent inactivation of EPSP amplitude through the membrane potential depolarization of presynaptic neurons.

[A patient undergoing surgery for gastric cancer four weeks after insertion of a drug-eluting coronary stent].

We report a patient who underwent gastrectomy four weeks after a coronary stent insertion. A 79-year-old man suffering from unstable angina was transferred to our hospital and a sirolimus-eluting coronary stent was inserted into his right coronary artery. The day after receiving the coronary stent, the patient began vomitting bloody gastric fluid. Endoscopic findings showed Borrmann type 3 gastric cancer and a distal partial gastrectomy was scheduled four weeks after stent insertion. One week before the operation, the patient's aspirin and ticlopidine regimen was replaced with heparin injection, which was then discontinued twelve hours before the operation. After confirmation that his activated coagulation time was normalized, an epidural catheter was inserted and anesthesia was induced with midazolam 3.0 mg, fentanyl 0.1 mg and vecuronium 7.0 mg. Then propofol administration was began with a simulated blood concentration of 2 microg x ml(-1). Anesthesia was maintained using propofol infusions and intermittent epidural injections of local anesthetics. Hypotension was treated using an infusion of dopamine. The surgery was successfully performed and the patient was intensively monitored in the ICU. Heparin was restarted three days after the operation, and replaced with antiplatelet therapy five days after the operation. Six months after his gastrectomy, the patient underwent a right colon resection for invasive carcinoma. No complication, such as stent thrombosis or bleeding, occurred during the perioperative period.

Effects of landiolol on the cardiovascular response during tracheal extubation.

The objective of this study was to investigate the effect of landiolol on the cardiovascular responses to emergence from anesthesia and tracheal extubation. Fifty-nine patients without cardiovascular disorders who were scheduled for tympanoplasty were randomly allocated to receive a loading dose of landiolol at 0.125 mg x kg(-1) x min(-1) for 1 min, followed by an infusion at 0.01 mg x kg(-1) x min(-1) (group L1), 0.02 mg x kg(-1) x min(-1) (group L2), 0.03 mg x kg(-1) x min(-1) (group L3), or 0.04 mg x kg(-1) x min(-1) (group L4). At the end of surgery, sevoflurane and nitrous oxide were discontinued, and landiolol was started. The mean arterial pressure (MAP), heart rate (HR), and rate pressure product (RPP) in the four groups were compared before anesthesia induction, just after extubation, 5 min after extubation, 10 min after extubation, and at discharge from the operating room. Just after extubation compared with the baseline, the MAP increased significantly in all groups; the HR increased in groups L1 and L2; and the RPP increased in all groups, except for group L4. Continuous administration of landiolol, at 0.03 or 0.04 mg x kg(-1) x min(-1), may prevent the increases in HR and RPP, respectively, that occur at the emergence from anesthesia and tracheal extubation.

Lidocaine increases intracellular sodium concentration through a Na+-H+ exchanger in an identified Lymnaea neuron.

BACKGROUND: The intracellular sodium concentration ([Na(+)]in) is related to neuron excitability. For [Na(+)]in, a Na(+)-H(+) exchanger plays an important role, which is affected by intracellular pH ([pH]in). However, the effect of lidocaine on [pH]in and a Na(+)-H(+) exchanger is unclear. We used neuron from Lymnaea stagnalis to determine how lidocaine affects [pH]in, Na(+)-H(+) exchanger, and [Na(+)]in. METHODS: Intracellular sodium imaging by sodium-binding benzofuran isophthalate and intracellular pH imaging by 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein were used to measure [Na(+)]in and [pH]in. Measurements for [Na(+)]in were made in normal, Na(+) free saline, with modified extracellular pH, and a Na(+)-H(+) exchanger antagonist [(5-N-ethyl-N-isopropyl amiloride, N-methylisopropylamiloride, and 5-(N,N-hexamethylene)-amiloride) pretreatment trials. Furthermore, [Na(+)]in and [pH]in were recorded simultaneously. From 0.1 to 10 mM, lidocaine, mepivacaine, bupivacaine, prilocaine, and QX-314 were evaluated. RESULTS: Lidocaine, mepivacaine, and prilocaine increased the [Na(+)]in in a dose-dependent manner. In contrast, QX-314 did not change the [Na(+)]in at each dose. In the Na(+) free saline or in the presence of each Na(+)-H(+) exchanger antagonist, lidocaine failed to increase [Na(+)]in. Lidocaine, mepivacaine, and prilocaine induced a significant decrease in [pH]in below baseline with an increase in [Na(+)]in. In contrast, QX-314 did not change the [pH]in. These results demonstrated that lidocaine increases [Na(+)]in through Na(+)-H(+) exchanger activated by intracellular acidification, which is induced by the proton trapping of lidocaine. This [Na(+)]in increase and [pH]in change induces cell toxicity. CONCLUSION: Lidocaine increases the [Na(+)] through a Na(+)-H(+) exchanger by proton trapping.

[Burst spikes induced by lidocaine in the ganglion of Lymnaea stagnalis].

BACKGROUND: To investigate the burst spikes (BS) induced by lidocaine in the ganglion of Lymnaea stagnalis, we used a multielectrode dish for extracellular recording in many points simultaneously. METHODS: Ganglion of Lymnaea stagnalis was placed in the multielectrode dish that has 64 planar microelectrodes. After the basal electrophysiological recordings of neuronal activity in the ganglion, the lidocaine concentrations were increased from 1 to 1,000 microg x ml(-1). RESULTS: A sequence of changes was observed. The initial stage was represented before first BS. Second stage was during first BS (lidocaine concentrations were between 18 +/- 3 and 105 +/- 69 microg x ml(-1)). Third stage was the period before the second BS. The fourth stage was during second BS (lidocaine concentrations were more than 670 +/- 254 microg x ml(-1)). Basic unit frequency of firing were 83 +/- 33% at first stage, 91 +/- 280% at second stage, 77 +/- 29% at third stage, and 50 +/- 41% at fourth stage (P < 0.05) compared to control (100%). CONCLUSIONS: The results of this study showed that the lidocaine induced BS with low and high lidocaine concentrations have different mechanisms in the central nervous system of Lymnaea stagnalis.

[Plasma levobupivacaine concentrations following epidural administration of levobupivacaine conjugated with or without maltosyl-beta-cyclodextrin].

BACKGROUND: To investigate the pharmacokinetics of complexation of levobupivacaine with maltosyl-beta-cyclodextrin, the plasma concentrations of levobupivacaine were measured following epidural administration of levobupivacaine conjugated with maltosyl-beta-cyclodextrin or levobupivacaine alone in a rabbit model. METHODS: Rabbits were randomly divided into two groups, levobupivacaine (1%) group (n = 6) and levobupivacaine (1%) conjugated with maltosyl-beta-cyclodextrin (100 mM) group (n = 6). One ml of each solution was randomly injected through an epidural catheter placed at L5-6. The plasma levobupivacaine concentrations were measured before and 5, 10, 15, 30, 60, 120, 240, 360, and 480 min after injection. RESULTS: The plasma levobupivacaine concentrations were significantly higher in the levobupivacaine conjugated with maltosyl-beta-cyclodextrin group than in levobupivacaine group at 5 min (1,465 +/- 311, 1,033 +/- 347 ng x ml(-1)), 10 min (1,068 +/- 237, 731 +/- 191), and 15 min (958 +/- 311, 605 +/- 118). There were no differences in area under the curve (1,551 +/- 387, 1,176 +/- 154 ng x hr x ml(-1)) and elimination half life (100 +/- 54, 78 +/- 37 min) between the two groups. CONCLUSIONS: The results of this study indicated that the absorption of levobupivacaine conjugated with maltosyl-beta-cyclodextrin from the epidural space and the elimination from the blood were similar to plain levobupivacaine.

Increase in intracellular Ca2+ concentration is not the only cause of lidocaine-induced cell damage in the cultured neurons of Lymnaea stagnalis.

PURPOSE: To determine whether the increase in intracellular Ca2+ concentration induced by lidocaine produces neurotoxicity, we compared morphological changes and Ca2+ concentrations, using fura-2 imaging, in the cultured neurons of Lymnaea stagnalis. METHODS: We used BAPTA-AM, a Ca2+ chelator, to prevent the increase in the intracellular Ca2+ concentration, and Calcimycin A23187, a Ca2+ ionophore, to identify the relationship between increased intracellular Ca(2+) concentrations and neuronal damage without lidocaine. Morphological changes were confirmed using trypan blue to stain the cells. RESULTS: Increasing the dose of lidocaine increased the intracellular Ca2+ concentration; however, there was no morphological damage to the cells in lidocaine at 3 x 10(-3) M. Lidocaine at 3 x 10(-2) M increased the intracellular Ca2+ concentration in both saline (from 238 +/- 63 to 1038 +/- 156 nM) and Ca2+-free medium (from 211 +/- 97 to 1046 +/- 169 nM) and produced morphological damage and shrinkage, with the formation of a rugged surface. With the addition of BAPTA-AM, lidocaine at 3 x 10(-2) M moderately increased the intracellular Ca2+ concentration (from 150 +/- 97 to 428 +/- 246 nM) and produced morphological damage. These morphologically changed cells were stained dark blue with trypan blue dye. The Ca2+ ionophore increased the intracellular Ca2+ concentration (from 277 +/- 191 to 1323 +/- 67 nM) and decreased it to 186 +/- 109 nM at 60 min. Morphological damage was not observed during the 60 min, but became apparent a few hours later. CONCLUSION: These results indicated that the increase in intracellular Ca2+ concentration is not the only cause of lidocaine-induced cell damage.

Lidocaine excites both pre- and postsynaptic neurons of reconstructed respiratory pattern generator in Lymnaea stagnalis.

Lidocaine causes both inhibition and excitation in the central nervous system, including the respiratory pattern. The excitation induced by an excessive dose of local anesthetic is thought to be the result of an initial blockade of an inhibitory pathway in the cerebral cortex. To clarify the effect of lidocaine on the pre- and postsynaptic neurons of an inhibitory synapse, a cultured soma-soma respiratory pattern generator model consisting of two neurons from the snail Lymnaea stagnalis were reconstructed in vitro. First we investigated the effects of lidocaine on single presynaptic (RPeD1) or postsynaptic (VD4) neurons. While RPeD1 and VD4 were simultaneously recorded, the number of action potentials, the membrane potential, and the wavelength of the action potential were compared before and after lidocaine (0.01, 0.1, and 1 mM) administration. Lidocaine increased the number of action potentials and the wavelength of a single action potential, and it depolarized the resting membrane potential in both RPeD1 and VD4 neurons in a dose-dependent manner. Furthermore, lidocaine decreased outward potassium currents. In soma-soma pairs, RPeD1 excitation and VD4 suppression occurred in 0.01 mM lidocaine, whereas both RPeD1 and VD4 neurons were excited by 0.1 and 1 mM lidocaine. In conclusion, lidocaine causes a reduction in synaptic transmission and general neuronal excitation in both presynaptic and postsynaptic neurons.

[Combined spinal and epidural anesthesia for cesarean section: a retrospective study with 0.5% hyperbaric bupivacaine].

BACKGROUND: We investigated retrospectively the relationship between the intrathecal dose of 0.5% hyperbaric bupivacaine and the use of 2% mepivacaine through an epidural catheter. METHODS: Forty-nine patients undergoing cesarean section with combined spinal and epidural anesthesia (CSEA) were analyzed. They were divided into two groups; with (CSEA group) and without additional epidural injection group (spinal group). RESULTS: In the CSEA group (24 patients received 1.2 +/- 0.4 ml of 0.5% hyperbaric bupivacaine), 5-10 ml of 2% mepivacaine were required to achieve the adequate surgical anesthesia. In the spinal group (25 patients received 1.6 +/- 0.3 ml of 0.5% hyperbaric bupivacaine), cesarean section was performed without additional mepivacaine before delivery. The analgesic level and the amount of fluid infusion were similar in the two groups. However, 20% of patients in the spinal group showed hypotension (systolic blood pressure below 80 mmHg), although no patients in the CSEA group developed hypotension. The amount of ephedrine used before delivery was significantly larger in the spinal group (8.9 +/- 7.7 mg) than in the CSEA group (3.9 +/- 4.3 mg). CONCLUSIONS: Spinal anesthesia induced by 1.2 ml of 0.5% hyperbaric bupivacaine with sequential epidural block induced by 5-10 ml of 2% mepivacaine caused no hypotension during cesarean section.

Lidocaine increases intracellular sodium concentration through voltage-dependent sodium channels in an identified lymnaea neuron.

BACKGROUND: The local anesthetic lidocaine affects neuronal excitability in the central nervous system; however, the mechanisms of such action remain unclear. The intracellular sodium concentration ([Na]i) and sodium currents (INa) are related to membrane potential and excitability. Using an identifiable respiratory pacemaker neuron from Lymnaea stagnalis, the authors sought to determine whether lidocaine changes [Na]i and membrane potential and whether INa is related to these changes. METHODS: Intracellular recording and sodium imaging were used simultaneously to measure membrane potentials and [Na]i, respectively. Measurements for [Na]i were made in normal, high-Na, and Na-free salines, with membrane hyperpolarization, and with tetrodotoxin pretreatment trials. Furthermore, changes of INa were measured by whole cell patch clamp configuration. RESULTS: Lidocaine increased [Na]i in a dose-dependent manner concurrent with a depolarization of the membrane potential. In the presence of high-Na saline, [Na]i increased and the membrane potential was depolarized; the addition of lidocaine further increased [Na]i, and the membrane potential was further depolarized. In Na-free saline or in the presence of tetrodotoxin, lidocaine did not change [Na]i. Similarly, hyperpolarization of the membrane by current injections also prevented the lidocaine-induced increase of [Na]i. In the patch clamp configuration, membrane depolarization by lidocaine led to an inward sodium influx. A persistent reduction in membrane potential, resulting from lidocaine, brings the cell within the window current of INa where sodium channel activation occurs. CONCLUSION: Lidocaine increases intracellular sodium concentration and promotes excitation through voltage-dependent sodium channels by altering membrane potential in the respiratory pacemaker neuron.

[Airway obstruction in a patient using a cuff button-like silicone cannula for tracheal stoma].

We described a case of postoperative airway obstruction in a patient using a cuff button-like silicone cannula for tracheal stoma. A 59-year-old woman with rheumatoid arthritis, was admitted to the hospital for total knee arthroplasty. She had been managed by a long-term tracheostomy for rheumatic cricoarytenoid arthritis. Preoperative examination revealed no cardiopulmonary compromise. The surgery was performed under combined spinal-epidural anesthesia without any respiratory problems. Fifteen hours after surgery, she complained of dyspnea. Her oxygen saturation by pulse oximeter was 22-28%. We immediately removed the silicone cannula and inserted a tracheostomy tube. Her condition was dramatically improved next few minutes after the insertion. There were no dyskinesia and neurological disorders. We considered that airway obstruction occurred with the inadequate position of the cuff button-like silicone cannula, attached to the posterior wall of the trachea, sputum augmenting the obstruction.

Procaine and mepivacaine have less toxicity in vitro than other clinically used local anesthetics.

UNLABELLED: The neurotoxicity of local anesthetics can be demonstrated in vitro by the collapse of growth cones and neurites in cultured neurons. We compared the neurotoxicity of procaine, mepivacaine, ropivacaine, bupivacaine, lidocaine, tetracaine, and dibucaine by using cultured neurons from the freshwater snail Lymnaea stagnalis. A solution of local anesthetics was added to the culture dish to make final concentrations ranging from 1 x 10(-6) to 2 x 10(-2) M. Morphological changes in the growth cones and neurites were observed and graded 1 (moderate) or 2 (severe). The median concentrations yielding a score of 1 were 5 x 10(-4) M for procaine, 5 x 10(-4) M for mepivacaine, 2 x 10(-4) M for ropivacaine, 2 x 10(-4) M for bupivacaine, 1 x 10(-4) M for lidocaine, 5 x 10(-5) M for tetracaine, and 2 x 10(-5) M for dibucaine. Statistically significant differences (P < 0.05) were observed between mepivacaine and ropivacaine, bupivacaine and lidocaine, lidocaine and tetracaine, and tetracaine and dibucaine. The order of neurotoxicity was procaine = mepivacaine < ropivacaine = bupivacaine < lidocaine < tetracaine < dibucaine. Although lidocaine is more toxic than bupivacaine and ropivacaine, mepivacaine, which has a similar pharmacological effect to lidocaine, has the least-adverse effects on cone growth among clinically used local anesthetics. IMPLICATIONS: Systematic comparison was assessed morphologically in growth cones and neurites exposed to seven local anesthetics. The order of neurotoxicity was procaine = mepivacaine < ropivacaine = bupivacaine < lidocaine < tetracaine < dibucaine. Although lidocaine is more toxic than bupivacaine and ropivacaine, mepivacaine, which has a similar pharmacological effect to lidocaine, is the safest among clinically used local anesthetics.

Endomorphins suppress nociception-induced c-Fos and Zif/268 expression in the rat spinal dorsal horn.

We evaluated the potency of endomorphin-1 and -2 as endogenous ligands on c-Fos and Zif/268 expression in the spinal dorsal horn by formalin injection to the rat hind paw. Endomorphin-1, -2, or morphine was administered intrathecally or intracerebroventricularly 5 min before formalin injection (5%, 100 microl). All drugs produced marked reductions of formalin-induced c-Fos and Zif/268 immunoreactivity in laminae I and II, and laminae V and VI in the rat lumbar spinal cord. The reductions of Zif/268 expression by endomorphins were greater than those by morphine, while the reductions of c-Fos expression by endomorphins were smaller than those by morphine. These effects of endomorphins were attenuated by pretreatment with naloxone. These results indicate that endomorphin-1 and -2 act as endogenous ligands of mu-opioid receptor in neurons of the spinal dorsal horn and suppress the processing of nociceptive information in the central nervous system.

Effects of vagal nerves or vagosympathetic trunks stimulation on the hemodynamics during spinal anesthesia in cats.

PURPOSE: To clarify the sudden onset of profound bradycardia or hypotension during spinal anesthesia, we stimulated vagal nerves (VN) or vagosympathetic trunks (VST) to examine the effects on the autonomic nervous system during spinal anesthesia with different degrees of cardiac sympathetic nerve block. METHODS: Cats were anesthetized and mechanically ventilated. The left stellate ganglion was exposed to record cardiac sympathetic nerve activity (CSNA). Systolic and diastolic blood pressures (BP), heart rate (HR), and CSNA were measured before and after intrathecal injections of 0.2, 0.5 and 1.0 ml of 1% lidocaine. After each intrathecal injection of lidocaine, bilateral VST (n=5, group A) or VN (n=5, group B) were stimulated and measurements were repeated. ]RESULTS: After 1.0 ml intrathecal injection of 1% lidocaine, CSNA was blocked completely, and BP and HR were decreased. In group A, BP were unchanged following VST stimulation while in group B, BP decreased approximately 30% by VN stimulation from the pre-stimulation levels after 0.2, 0.5, and 1.0 ml injection of 1% lidocaine, respectively. HR decreased further, approximately 35% in group A and 50% in group B, by each stimulation from the prestimulation levels after 0.2, 0.5, and 1.0 ml injection of 1% lidocaine. CONCLUSION: These results suggest that hypotension and bradycardia during a high level of spinal anesthesia are due to the block of CSNA, and vagal reflex may produce profound hypotension and bradycardia especially in high spinal anesthesia.