[Simple Formula to Predict Residual Amount of Continuously Infused Rocuronium in the Body].

BACKGROUND: When antagonism is performed using sugammadex after continuous infusion of rocuronium, if the total amount of residual rocuronium can be esti- mated prior to performing antagonism, antagonism without excess or deficiency of sugammadex will be made possible. We therefore prepared a simple formula to predict residual amount of rocuronium in the body, which can be easily applied in clinical setting, and veri- fied it using Tivatrainer©. METHODS: 1. Pharmacokinetics of rocuronium was simulated, using a 3-compartment model. The following assumptions were made to derive the simple for- mula : when rocuronium is continuously infused to reach the steady state plasma concentration, an equal concentration in each compartment is reached. Only the amounts of rocuronium infused to the central com- partment and rocuronium excreted from there are thus considered, and these two amounts are in balance. For pharmacokinetic parameters, we referred to V. Saldien, Anesth Analg 2003 ; 97 : 44-9. 2. The prepared simple formula was verified using Tivatrainero. We considered a model in which initial boluses of 0.3, 0.6, 0.9, and 1.2 mg · kg(-1) were adminis- tered, and continuous infusion began at 30 minutes at the rate of 0.2, 0.3, 0.4, 0.5, 0.6, and 0.8 mg - kg-1 - hr-1. Patients with body weight of 50, 60, 70, and 80 kg were investigated. RESULTS: 1. The derived simple formula was as fol- lows : Q=0.74 X R Q Total residual amount of rocuronium (mg) R Dose per hour (mg · hr(-1)) 2. The predicted value of the total residual amount obtained from the simple formula was consistent with the value predicted by Tivatrainer© with a high preci- sion within the error of 1.4%. Convergence time until the stable state was reached varied depending on the condition. However, it took approximately 150 minutes after the beginning of continuous infusion.for the error between values predicted by the simple formula and Tivatrainer© to stabilize within 5 mg. CONCLUSIONS: We prepared a simple formula to esti- mate the total residual amount of rocuronium at a steady state. The value predicted by the simple for- mula agreed with the value predicted by Tivatrainer) with a high precision.

[Bilateral transversus abdominis plane block using catheterization for a patient with severe cardiac dysfunction and chronic kidney failure: a case report].

The transversus abdominis plane (TAP) block is a newly described technique introducing a local anesthetic agent between the internal oblique and the transversus abdominis muscles of the abdominal wall, which is safer and more reliable analgesia in recent years by ultrasound technique. We report the perioperative management of transversus abdominis plane block with catheterization for a patient with severe cardiac dysfunction and chronic kidney failure, who underwent bilateral inguinal hernioplasty. A bilateral TAP block was first performed with 0.5% ropivacaine 20 ml under ultrasonographic visualization on right side, and after sixty-minutes the other side injection was performed through the indwelling catheter. During the operation, the patient received a target-controlled infusion of 0.4-0.6 microg x ml(-1) propofol. The perioperative courses were uneventful and there was no adverse effect including central nervous system (CNS) symptoms.

In vitro surfactant mitigation of gas bubble contact-induced endothelial cell death.

Interactions of gas embolism bubbles with endothelial cells, as can occur during decompression events or other forms of intravascular gas entry, are poorly characterized. Endothelial cells respond to microbubble contact via mechanotransduction responses that can lead to cell death or aberrant cellular function. Cultured bovine aortic endothelial cells were individually contacted with microbubbles. Cells were loaded with fluorescent dyes indicating calcium- and nitric oxide-signaling and cell viability. A surfactant, Pluronic F-127, and/or albumin were added to the culture media. Control experiments utilized calcium-free media as well as probe-poking in place of microbubble contact. We acquired fluorescence microscopy time-lapse images of cell responses to bubble and probe contact and determined contact effects on cell signaling and cell death. Calcium influx was essential for cell death to occur with bubble contact. Bubble contact stimulated extracellular calcium entry without altering nitric oxide levels unless cell death was provoked. Cell responses were independent of bubble contact duration lasting either one or 30 seconds. Microbubble contact provoked cell death over seven times more frequently than micropipette poking. Albumin and the surfactant each attenuated the calcium response to bubble contact and also reduced the lethality of microbubble contact by 67.4% and 76.0%, respectively, when used alone, and by 91.2% when used together. This suggests that surface interactions between the bubble or probe interface and plasma- and cell surface-borne macromolecules differentially modulate the mechanism of calcium trafficking such that microbubble contact more substantially induces cell death or aberrant cellular function. The surfactant findings provide a cytoprotective approach to mitigate this form of mechanical injury.

Preoperative elevated FDP may predict severe intraoperative hypotension after dural opening during decompressive craniectomy of traumatic brain injury.

PURPOSE: Coagulation disorder and intraoperative hypotension are representative complications of traumatic brain injury which cause worse perioperative outcome. The aim of this study was to survey the relation of coagulation disorder and intraoperative hypotension (IH) during decompressive craniectomy. METHOD: Patients who underwent emergency decompressive craniectomy due to traumatic brain injury were retrospectively surveyed. The relation between preoperative coagulation date and intraoperative hypotension (systolic blood pressure < 60 mmHg after dural opening) was analyzed. RESULTS: Of 41 patients screened, 12 patients (27.9%) developed IH. Fibrinogen degradation products (314 vs 64.4 µg/mL; p = 0.01) were significantly higher in the IH group. In contrast, fibrinogen (181 vs 239 mg/dL; p = 0.01) was significantly lower in the IH group. Reduction rate of sBRP before and after dural opening (%) was higher in IH group than in non-IH group (49.1 vs 27.6%: p = 0.001). CONCLUSIONS: Preoperative elevated FDP may predict IH after dural opening during traumatic decompressive craniectomy.

A guest molecule-host cavity fitting algorithm to mine PDB for small molecule targets.

Inhaled anesthetic molecule occupancy of a protein internal cavity depends in part on the volumes of the guest molecule and the host site. Current algorithms to determine volume and surface area of cavities in proteins whose structures have been determined and cataloged make no allowance for shape or small degrees of shape adjustment to accommodate a guest. We developed an algorithm to determine spheroid dimensions matching cavity volume and surface area and applied it to screen the cavities of 6,658 nonredundant structures stored in the Protein Data Bank (PDB) for potential targets of halothane (2-bromo-2-chloro-1,1,1-trifluoroethane). Our algorithm determined sizes of prolate and oblate spheroids matching dimensions of each cavity found. If those spheroids could accommodate halothane (radius 2.91 A) as a guest, we determined the packing coefficient. 394,766 total cavities were identified. Of 58,681 cavities satisfying the fit criteria for halothane, 11,902 cavities had packing coefficients in the range of 0.46-0.64. This represents 20.3% of cavities large enough to hold halothane, 3.0% of all cavities processed, and found in 2,432 protein structures. Our algorithm incorporates shape dependence to screen guest-host relationships for potential small molecule occupancy of protein cavities. Proteins with large numbers of such cavities are more likely to be functionally altered by halothane.

Effect of xenon on catecholamine and hemodynamic responses to surgical noxious stimulation in humans.

STUDY OBJECTIVE: To determine the effect of xenon in combination anesthesia with sevoflurane on the catecholamine and hemodynamic responses to surgical noxious stimulation in humans. DESIGN: Randomized study. SETTING: A university hospital. PATIENTS: This study involved 32 female ASA physical status I and II patients, age 20-58 years, scheduled for abdominal hysterectomy. INTERVENTIONS: Patients were randomly divided into 4 groups: group X50-S1.5, 50% xenon and 1.5% sevoflurane; group X70-S1.5, 70% xenon and 1.5% sevoflurane; group G70-S1.5, 70% nitrous oxide and 1.5% sevoflurane; and group S2.8, 2.8% sevoflurane. No premedication was administered to the patients, and anesthesia was induced by administration of sevoflurane in oxygen and 0.10 to 0.15 mg/kg of vecuronium. After tracheal intubation, the combination of anesthetics was started, and skin incision was performed after equilibration for more than 15 minutes. MEASUREMENTS: Systolic blood pressure and heart rate (HR) were recorded, and the plasma concentrations of norepinephrine, epinephrine (E), and dopamine were measured 0, 2.5, 5, 7.5, 10, 12.5, and 15 minutes after skin incision. MAIN RESULTS: The maximal increase in the E concentration and the values of the area under the curve for E were significantly smaller in the X50-S1.5 and X70-S1.5 groups compared with that in the S2.8 group (P<0.05). At 1 minute after incision, the HR in X50-S1.5 was significantly lower than those in G70-S1.5 and S2.8 groups and the HR in X70-S1.5 was lower than that in S2.8 group (P<0.01). The systolic blood pressure in S2.8 group at 1 minute was significantly higher than those of other groups (P<0.01). CONCLUSION: Combination anesthesia using xenon and sevoflurane suppresses the plasma E concentration and hemodynamic response after skin incision more effectively than sevoflurane anesthesia alone.

Compound A concentration in the circle absorber system during low-flow sevoflurane anesthesia: comparison of Drägersorb Free, Amsorb, and Sodasorb II.

STUDY OBJECTIVE: To determine compound A concentrations in a low-flow circuit containing Drägersorb Free (Dräger, Lübeck, Germany), Amsorb (Armstrong, Coleraine, Northern Ireland), and Sodasorb II (W. R. Grace, Lexington, MA). DESIGN: Randomized study. SETTING: Hamamatsu University Hospital. PATIENTS: 24 ASA physical status I and II patients scheduled for general anesthesia greater than 3 hours' duration. INTERVENTIONS: Patients were allocated to three groups of eight patients each to receive either using either Drägersorb Free, Amsorb, or Sodasorb II. Immediately before anesthesia induction, 1 kg of fresh absorbent was placed in the anesthesia canister. Anesthesia was maintained with sevoflurane (end-tidal concentration 1% to 3%) in oxygen and nitrous oxide (FIO(2) > 0.3) at a total flow of 1 L/min. MEASUREMENTS: Inspiratory compound A concentration in the circuit was measured once every hour. MAIN RESULTS: Maximum compound A concentrations for Drägersorb Free, Amsorb, and Sodasorb II were 2.4 +/- 0.8 (mean +/- SD) ppm, 3.1 +/- 0.5 ppm, and 28.0 +/- 10.0 ppm (p < 0.01 vs. Drägersorb Free and Amsorb). Concentrations with Drägersorb Free and Amsorb remained at less than 4 ppm throughout the study. CONCLUSIONS: Because compound A concentrations in the circuit with Drägersorb Free and Amsorb were negligible, sevoflurane can be used at a fresh gas flow of 1 L/min with these two absorbents.

Dose- and time-dependent liquid sclerosant effects on endothelial cell death.

BACKGROUND: Intravenous sclerotherapy solutions can induce endothelial cell death. OBJECTIVE: The objective was to determine the relationship between sclerosant concentration and minimum contact time required for in endothelial cell death. METHODS: Cultured bovine aortic endothelial cells were exposed to a broad range of concentrations of two liquid sclerosants, polidocanol and sodium tetradecyl sulfate. Fluorescence microscopy was used to study cells using dyes specifically indicating changes in intracellular calcium levels, nitric oxide production, and loss of cell membrane integrity after sclerosant exposure. Fluorescence intensity measurements were used to identify the timing of cell death. RESULTS: Calcium signaling and nitric oxide pathways were activated by the administration of the sclerosants and were followed by cell death. The time to the activation and the cell death was dependent on the concentration of sclerosants. At 0.3% polidocanol or 0.1% sodium tetradecyl sulfate, cell death occurred within 15 minutes. At less than 0.003% polidocanol and at 0.005% sodium tetradecyl sulfate, cells remained alive after 60 minutes. CONCLUSION: Both sclerosants rapidly led to cell death at sufficiently high concentrations. At low sclerosant concentrations, cell viability was maintained beyond the recording time of the experiment. The timing of endothelial cell death is predictable based on sclerosant concentration during exposure.

Microvascular embolization following polidocanol microfoam sclerosant administration.

BACKGROUND: Intravenous microfoam sclerotherapy solutions can potentially cause cerebrovascular arterial embolization. OBJECTIVE: To determine the relationship between polidocanol microfoam formulation and arteriolar embolization bubble lodging and clearance in vivo. METHODS: Three polidocanol microfoams (one made by the double-syringe method using air and two Varisolve (Provensis, Inc., West Conshohocken, PA, USA) formulations using different physiologic gas mixtures composed primarily of oxygen and carbon dioxide and dispensed from a proprietary canister mechanism) were mixed with venous blood and injected into the rat cremaster arterial microcirculation. Bubble dimensions and dynamics were recorded using intravital microscopy. RESULTS: Bubble entry frequency, size, and dynamics depended on microfoam formulation. Air-based bubbles (2.72 1.38 nL; n = 21) lodged, obliterating blood flow. Varisolve bubbles (0.20 0.02 nL; n = 2 and 0.53 0.27 nL; n = 27 for the two gas compositions) entered but either did not lodge or cleared within seconds. Bubble size and number were different among these microfoams. CONCLUSIONS: Both Varisolve formulations produced smaller embolism bubbles than occurred with air-based microfoam. Rapid clearance of Varisolve bubbles suggests that they are so small that they do not have adequate surface area available for significant binding interactions with arteriolar endothelium. Larger air-based bubbles obstruct arteriolar vessels and block blood flow.

Amsorb Plus and Drägersorb Free, two new-generation carbon dioxide absorbents that produce a low compound A concentration while providing sufficient CO2 absorption capacity in simulated sevoflurane anesthesia.

PURPOSE: The properties of two new-generation CO(2) absorbents, Amsorb Plus (Armstrong Medical, Coleraine, UK) and Drägersorb Free (Drager, Lubeck, Germany), were compared with those of Amsorb (Armstrong Medical) and Sodasorb II (W.R. Grace, Lexington, MA, USA). METHODS: The concentration of compound A produced by each absorbent was determined in a low-flow circuit containing sevoflurane, and the CO(2) absorption capacity of the absorbent was measured. The circuit contained 1000 g of each absorbent and had a fresh gas (O(2)) flow rate of 1 l.min(-1) containing 2% sevoflurane. CO(2) was delivered to the circuit at a flow rate of 200 ml.min(-1). RESULTS: The maximum concentrations of compound A were 2.2 +/- 0.0, 2.3 +/- 0.3, 2.2 +/- 0.2, and 23.5 +/- 1.5 ppm (mean +/- SD) for Amsorb Plus, Drägersorb Free, Amsorb, and Sodasorb II, respectively. The maximum concentration of compound A for Sodasorb II was significantly higher than those for the other absorbents (P < 0.01). The CO(2) absorption capacities (time taken to reach an inspiratory CO(2) level of 2 mmHg) were 1023 +/- 48, 1074 +/- 36, 767 +/- 41, and 1084 +/- 54 min, respectively, and the capacity of Amsorb was significantly lower than that of the other absorbents (P < 0.01). CONCLUSION: The new-generation carbon dioxide absorbents, Amsorb Plus and Drägersorb Free, produce a low concentration of compound A in the circuit while showing sufficient CO(2) absorption capacity.