Effective doses of cisatracurium in the adult and the elderly.

BACKGROUND: There are few information about the differences of the effective dose (ED) of cisatracurium between the adult and the elderly. We investigated the ED and the onset time of cisatracurium in the adults and the elderly. METHODS: We studied two hundred patients of the adults aged 20 through 64 years and the elderly aged ≥ 65 years, with American Society of Anesthesiologists physical status I or II. Each 100 patients with 20 patients of each dose group, randomly selected from 30, 40, 50, 60 or 70 µg/kg of cisatracurium, were randomly allocated to the adults and the elderly groups. We recorded the 0.1 Hz single twitch responses of the adductor pollicis and the onset times to maximal blockade. The magnitude of muscle relaxation was recorded by using an acceleromyography. The effect of cisatracurium on single twitch was calculated as percent reduction. After converting each drug dose into logarithm and percent reduction of the muscle reduction into probit, the EDs representing the muscle relaxation effects of 5%, 25%, 50%, 75% and 95% were estimated using the linear regression analysis. RESULTS: No significant differences were found in age, weight, height, or body mass index within or between the groups. The ED50 and ED95 of the adult group were 35.39 and 59.58 µg/kg. The ED50 and ED95 of the elderly group were 34.89 and 55.50 µg/kg, respectively. The onset times were 375.4 ± 76.9 seconds in the adult group and 369.1 ± 70.0 seconds in the elderly group. CONCLUSIONS: The ED and the onset time were not significantly different between the adult and the elderly.

Effectiveness of Modal Decomposition for Tapping Atomic Force Microscopy Microcantilevers in Liquid Environment.

The modal decomposition of tapping mode atomic force microscopy microcantilevers in liquid environments was studied experimentally. Microcantilevers with different lengths and stiffnesses and two sample surfaces with different elastic moduli were used in the experiment. The response modes of the microcantilevers were extracted as proper orthogonal modes through proper orthogonal decomposition. Smooth orthogonal decomposition was used to estimate the resonance frequency directly. The effects of the tapping setpoint and the elastic modulus of the sample under test were examined in terms of their multi-mode responses with proper orthogonal modes, proper orthogonal values, smooth orthogonal modes and smooth orthogonal values. Regardless of the stiffness of the microcantilever under test, the first mode was dominant in tapping mode atomic force microscopy under normal operating conditions. However, at lower tapping setpoints, the flexible microcantilever showed modal distortion and noise near the tip when tapping on a hard sample. The stiff microcantilever had a higher mode effect on a soft sample at lower tapping setpoints. Modal decomposition for tapping mode atomic force microscopy can thus be used to estimate the characteristics of samples in liquid environments.

The effect of high concentration of magnesium with ropivacaine, gentamicin, rocuronium, and their combination on neuromuscular blockade.

BACKGROUND: Magnesium, ropivacaine, gentamicin, and rocuronium block neuromuscular (NM) transmission by different mechanisms. Therefore, concurrent administration of these agents may induce prolonged muscle paralysis via synergistic interaction. This study investigated the efficacy and safety of NM block caused by the administration of high concentrations of magnesium in combination with ropivacaine, gentamicin, and rocuronium. METHODS: Eighty-three left phrenic nerve-hemidiaphragms from male SD rats (150-250 g) were hung in Krebs solution. Three consecutive single twitch tension (ST, 0.1 Hz) and one tetanic tension (TT, 50 Hz for 1.9 s) were obtained before drug application and at each new drug concentration. The concentration of MgCl2 and MgSO4 in Krebs solution was increased until an 80 to 90% reduction in ST was reached. To test the effects of combinations of NM agents, a Krebs solution was premixed with MgCl2 alone, MgCl2 and ropivacaine, or MgCl2, ropivacaine, and gentamicin. The concentration of ropivacaine, gentamicin, or rocuronium was then progressively increased until an 80 to 90% reduction in ST was reached. The effective concentrations were estimated with a probit model. RESULTS: The potency of MgCl2 was greater than that of MgSO4, and pretreatment with MgCl2 increased the potency of gentamicin and rocuronium. Unexpectedly, MgCl2 did not potentiate ropivacaine, and the potency of gentamicin and rocuronium failed to show an increase when premixed with 0.5 µM ropivacaine. CONCLUSIONS: The concomitant administration of high concentrations of magnesium and ropivacaine together with clinically relevant concentrations of gentamicin or rocuronium potentiated NM blockade but not with clinically relevant concentrations of ropivacaine.

Do bupivacaine, clindamycin, and gentamicin at their clinical concentrations enhance rocuronium-induced neuromuscular block?

BACKGROUND: Bupivacaine, clindamycin, and gentamicin inhibit neuromuscular (NM) conduction. When they are combined, they may synergistically reduce the effective concentration of each to the therapeutic concentration in augmenting rocuronium-induced NM block. Thus, the aim of this study was to investigate whether combinations of the three drugs, at around their therapeutic concentrations, potentiate rocuronium-induced NM block. METHODS: Fifty-seven left-phrenic nerve hemidiaphragms (Male S-D rats, 150-250 g) were hung in a 20-ml organ bath filled with Krebs solution. Three consecutive single-twitch tensions (0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained. A Krebs solution was premixed with concentration sets of bupivacaine and clindamycin, bupivacaine and gentamicin, or bupivacaine, clindamycin and gentamicin. Then, the concentration of rocuronium was cumulatively increased in the Krebs solution (1, 3, 5, 7, 9, 12, 14, 16, 18, and 20 µM) until an 80% to 90% reduction in single twitch was attained. The effective concentrations for each experiment were determined with the probit model. RESULTS: The combinations of bupivacaine, clindamycin, and gentamicin enhanced rocuronium-induced NM block. When the three drugs were applied simultaneously, their concentrations were reduced to near-therapeutic levels in potentiating the action of rocuronium. CONCLUSIONS: Bupivacaine, clindamycin, and gentamicin blocked NM conduction, and when all three drugs were applied together, they augmented rocuronium-induced NM block at their near-therapeutic concentrations. Clinicians should be aware of the cooperability in NM block between drugs that interrupt NM conduction.

The synergistic effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade.

BACKGROUND: Gentamicin reduces acetylcholine release and clindamycin causes end-plate ion channel blockade. Because of these reasons, two drugs show muscular relaxant effect and potentiate the action of nondepolarizing neuromuscular agents. This study was intended to evaluate the effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade and the interaction between these drugs. METHODS: Male Sprague-Dawley rats' phrenic nerves and diaphragms were installed in a bath containing Krebs solution. They were divided into three study groups. The first group was pre-treated with 0.1 (n = 3), 0.2 (n = 4) or 0.5 (n = 3) mM gentamicin and the tension was measured as the concentration of rocuronium was increased. The second group was experimented by increasing gentamicin on 0.25 (n = 5), 0.5 (n = 6) or 1.0 (n = 6) mM clindamycin. The final group was pre-treated with various combinations of gentamicin and clindamycin. The drug concentration was gradually increased until single twitch tension decreased by around 80%. Effective concentration was calculated using a probit model and interaction indices derived the Loewe additivity. RESULTS: The administration of gentamicin and the combination of gentamicin and clindamycin enhanced rocuronium-induced neuromuscular blockade. At 0.2 and 0.5 mM gentamicin, synergistic interactions with rocuronium were observed. Likewise, at 0.5 and 1.0 mM clindamycin, synergistic interactions with gentamicin appeared. When all three drugs were combined, in the tetanic fade, all the groups except for those administered with 0.01 mM gentamicin and 0.25 mM clindamycin showed synergistic interactions. CONCLUSIONS: This study demonstrate that gentamicin and clindamycin potentiated rocuronium induced neuromuscular blockade. Moreover, it was found that these drugs interacted synergistically.

At therapeutic concentration bupivacaine causes neuromuscular blockade and enhances rocuronium-induced blockade.

BACKGROUND: Partially paralyzed patients may be placed in the risk of pharyngeal dysfunction. Bupivacaine acts as acetylcholine receptor ion channel blocker and may synergistically interact with rocuronium to augment NM blockade. Thus, this study aims to elucidate whether or not, at a therapeutic concentration, bupivacaine by itself may cause NM blockade and reduce an effective concentration of rocuronium. METHODS: Twenty-two left phrenic nerve-hemidiaphragms (Male SD rats, 150-250 g) were hung in Krebs solution. Three consecutive ST, 0.1 Hz and one TT, 50 Hz for 1.9 s were obtained before drug application and at each new drug concentration. A concentration of bupivacaine in Krebs solution (n = 5) was cumulatively increased by way of 0.01, 0.1, 1, (1, 2, 3, 4, 5, 6, 7) × 10 µM. In a Krebs solution, pre-treated with bupivacaine 0 (n = 5), 0.1 (n = 5), 1.0 (n = 5), 10 (n = 2) µM, and then concentrations of rocuronium were cumulatively increased by way of 1, 3, 5, 7, 9, 12, 14, 16, 18, 20 µM. EC for each experiment were determined by a probit. The EC(50)'s of rocuronium were compared using a Student's t-test with Bonferroni's correction. Differences were considered significant when P < 0.05. RESULTS: The potency of bupivacaine for normalized TF was 11.4 (± 1.1) µM. Below 30 µM of bupivacaine, the single twitch potentiation sustained despite the development of tetanic fade and partial inhibition of PTT. Bupivacaine significantly facilitated the NM blockade induced by rocuronium. CONCLUSIONS: Clinicians should be aware that bupivacaine by itself at its therapeutic concentration inhibit NM conduction and enhances rocuronium-induced muscle relaxation.

The antagonistic effect of neostigmine on rocuronium-, clindamycin-, or both-induced neuromuscular blocking in the rat phrenic nerve-hemidiaphragm.

BACKGROUND: Neostigmine augments clindamycin-induced neuromuscular block and antagonizes rocuronium-induced neuromuscular block; however, it remains unclear whether neostigmine enhances the neuromuscular blocking (NMB) that is caused by combinations of rocuronium and clindamycin. The intent of this study was to determine whether neostigmine potentiates the muscle relaxation that is induced by combinations of rocuronium and clindamycin and to estimate whether both clindamycin and rocuronium have synergistic actions on NMB. METHODS: Forty-one left phrenic nerve-hemidiaphragms (from male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Three consecutive single twitches (ST, 0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained for each increase in concentration of rocuronium or clindamycin. The concentrations of rocuronium were cumulatively increased until an 80% to 90% reduction in ST was attained in the Krebs solutions pre-treated with 0 (n = 5), 0.1 (n = 1), 0.25 (n = 1), 0.5 (n = 4), or 1.0 (n = 1) mM clindamycin or with 0 (n = 4), 0.1 (n = 1), 0.5 (n = 5), 1.0 (n = 5), or 2.0 (n = 4) mM clindamycin in combination with 250 nM neostigmine, and so were the concentrations of clindamycin in the Krebs solutions pre-treated with 0 (n = 6) or 250 nM (n = 6) neostigmine. RESULTS: Clindamycin increased the potency of rocuronium for ST and tetanic fade, irrespective of the presence of neostigmine. Neostigmine shifted the concentration-response curve of rocuronium to the right in the presence or absence of clindamycin. The interaction between rocuronium and clindamycin was synergistic when clindamycin concentrations were in excess of 0.5 mM, irrespective of the presence of neostigmine. CONCLUSIONS: Neostigmine may partially antagonize the neuromuscular block that is induced by a combination of clindamycin and rocuronium. Clinicians are advised to be aware that clindamycin synergistically increases the degree of rocuronium-induced neuromuscular block, even when neostigmine is present.

Drug interaction: focusing on response surface models.

Anesthesiologists have been aware of the importance of optimal drug combination long ago and performed many investigations about the combined use of anesthetic agents. There are 3 classes of drug interaction: additive, synergistic, and antagonistic. These definitions of drug interaction suggest that a zero interaction model should exist to be used as a reference in classifying the interaction of drug combinations. The Loewe additivity has been used as a universal reference model for classifying drug interaction. Most anesthetic drugs follow the sigmoid E(max) model (Hill equation); this model will be used for modeling response surface. Among lots of models for drug interaction in the anesthetic area, the Greco model, Machado model, Plummer model, Carter model, Minto model, Fidler model, and Kong model are adequate to be applied to the data of anesthetic drug interaction. A model with a single interaction parameter does not accept an inconsistency in the classes of drug interactions. To solve this problem, some researchers proposed parametric models which have a polynomial interaction function to capture synergy, additivity, and antagonism scattered all over the surface of drug combinations. Inference about truth must be based on an optimal approximating model. Akaike information criterion (AIC) is the most popular approach to choosing the best model among the aforementioned models. Whatever the good qualities of a chosen model, it is uncertain whether the chosen model is the best model. A more robust inference can be extracted from averaging several models that are considered relevant.

Analysis of the rocuronium-vecuronium interaction on tetanic fade based on a generalized response surface model with varying relative potencies.

BACKGROUND: Some studies have shown that rocuronium and vecuronium have additive, or synergistic effects on muscle relaxation based on the Loewe additivity. Therefore, we performed a fit of tetanic fade data to a generalized response surface model with varying relative potencies proposed by Kong and Lee (KLGRS) to evaluate the usefulness of KLGRS for capturing the interspersed drug interactions and to characterize the interaction between the two drugs. METHODS: Left phrenic nerve-hemidiaphragms (Male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Supramaximal electrical stimulation (0.2 ms, rectangular) of 50 Hz for 1.9 s to the phrenic nerve evoked tetanic contractions that were measured with a force transducer. Each preparation was exposed to one of 4 vecuronium concentrations (0.0, 1.5, 2.5, and 3.0 microM), or one of 4 rocuronium concentrations (0.0, 3.0, 4.5, and 5.5 microM). Subsequently the adequate amount of rocuronium was added to a vecuronium bath and that of vecuronium was added to a rocuronium until an 80-90% increase in tetanic fade was achieved. We then fitted the modified KLGRS models to the above data, after which we selected the best model, based on 5 methods for determining goodness of fit. Using this method, we obtained the response surface, as well as contour plots for the response surface (i.e. isoboles), the polynomial function and the interaction index. RESULTS: The model with the constant relative potency ratio and 8 parameters was found to best describe the results, and this model reflected well the characteristics of the raw data. In addition, the two drugs showed a synergistic interaction in almost every area and an antagonistic one in a very narrow area. CONCLUSIONS: KLGRS was found to be a useful method of analyzing data describing interspersed drug interactions. The interaction between rocuronium and vecuronium was found to be synergistic.

Stress-induced cardiomyopathy during ophthalmologic surgery: A case report.

Stress-induced cardiomyopathy or Takotsubo cardiomyopathy is a recently described clinical entity which is associated with a chest pain occurring during a stress, an abnormal ECG and/or an increase in the troponin blood level and a transient left ventricular dysfunction. Transient left ventricular dysfunction generally involves the midsection and the apex of the heart with an akinesis. We reported a case of a 55-year-old female patient who developed a stress-induced cardiomyopathy after local epinephrine use during ophthalmologic surgery.

Calcium and neostigmine antagonize gentamicin, but augment clindamycin-induced tetanic fade in rat phrenic nerve-hemidiaphragm preparations.

PURPOSE: A reduction in acetylcholine release induced by gentamicin may limit neostigmine-induced increases in acetylcholine concentration in the neuromuscular junction. An increase in acetylcholine concentration caused by neostigmine and calcium may enhance the use-dependent ion channel block of the nicotinic acetylcholine receptor caused by clindamycin. The purpose of this study was to determine whether calcium and neostigmine antagonize the neuromuscular blockade caused by gentamicin and augment the blockade caused by clindamycin during both single-twitch (0.1 Hz) and tetanic stimulation (50 Hz for 1.9 s). METHODS: Left phrenic nerve-hemidiaphragm preparations (Male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. The concentration-response curves of gentamicin and clindamycin were obtained. The reversal effects of treatment with 5 mM calcium or 250 nM neostigmine on the effects of 1.5 mM gentamicin, which caused 72% reduction of single twitch, were studied. The effects of calcium or neostigmine on the effects of clindamycin were studied by examining the shift of the concentration-response curve of clindamycin with pretreatments with these agents. The effective concentrations were determined by a probit model. RESULTS: Calcium antagonized the single-twitch depression and tetanic fade caused by gentamicin more effectively than neostigmine. The effective concentration of 50% maximal effect (EC(50)) values of clindamycin for tetanic fade in the presence of 5 mM calcium or 250 nM neostigmine were reduced by approximately 52%. CONCLUSION: Clindamycin and gentamicin interfere with neuromuscular transmission and cause tetanic fade. Neostigmine and calcium antagonized the neuromuscular blockade caused by gentamicin, but augmented that caused by clindamycin.

Surface passivation of CdS/Zn2SiO4 nanocomposites prepared by a wet chemical route.

Highly luminescent CdS/Zn2SiO4 nanocrystals were prepared by a wet chemical method. The effect of surface passivation was observed in photoluminescence measurements of CdS nanocrystals embedded in colloidal nanocrystallite or amorphous Zn2SiO4 matrix. The resultant luminescent emission of as-prepared CdS/Zn2SiO4 nanocomposite thin films displays two distinct components. One is attributed to the band-edge emission and the other is due to the surface defects. The effect of aging on CdS/Zn2SiO4 nanocomposite thin films has been investigated, showing the active role of Zn2SiO4 matrix in modifying the surface states.