Efficacy of Atracurium-Vecuronium Combination in Patients Undergoing Laparoscopic Surgery: A Randomized Controlled Study.

INTRODUCTION: Deep neuromuscular blockade (d-NMB) is an essential requirement for carboperitoneum during laparoscopy surgery. However, sustaining d-NMB till the completion of surgery delays the reversal of the residual block. Therefore, there is a merit in exploring the effect of synergistic vecuronium-atracurium combination on the duration-of-action of d-NMB during "laparoscopic" surgery when we compare intubating bolus non-depolarizers (atracurium, vecuronium) administered alone. This study aims to evaluate whether the synergistic effect atracurium-vecuronium combination increases duration-of-action of d-NMB "laparoscopic" surgery settings. METHODS: Forty-eight patients (18-60 years, American Society of Anesthesiologists physical status- II/III, either sex) undergoing laparoscopic cholecystectomy were randomly allocated to receive vecuronium (vecuronium group, n = 16) or atracurium (atracurium group, n = 16) or vecuroniumatr-acurium combination (vecuronium-atracurium combination group, n = 16) and analyzed for the effects on the duration-of-action (primary objective); onset-of-action, reversibility, and quality of intubating conditions (secondary objectives) profile of neuromuscular blockade in patients undergoing laparoscopic cholecystectomy. RESULTS: Duration-of-action of neuromuscular blockade was significantly longer in patients who received atracurium-vecuronium combination (53.9 ± 9.7 minutes) versus atracurium-alone (41.1 ± 3.8 minutes) or vecuronium-alone (43.5 ± 9.2 minutes) (P = 0.000). No difference was found for the time to onset-of-action (vecuronium [198.1 ± 34.9 seconds], atracurium [188.5 ± 50.6 seconds], or atracurium-vecuronium combination [196.3 ± 46.3 seconds] [P = 0.829]); time for the reversal of muscle relaxation effect (vecuronium [559.9 ± 216.2 seconds], atracurium [584.7 ± 258.3 seconds], and atracurium-vecuronium combination [555.0 ± 205.4 seconds] [P = 0.925]); and quality-of-intubating conditions (vecuronium group [9.6 ± 1.3]; atracurium group [10.0 ± 0.0]; atracurium-vecuronium group [10.0 ± 0.0] [P = 0.182]). CONCLUSION: The synergistic effect of the atracurium-vecuronium combination leads to an increased duration-of-action of d-NMB during laparoscopic cholecystectomy without impacting onset-of-action, quality of intubating conditions, and reversal of muscle relaxant effect.

Sugammadex, the Guardian of Deep Muscle Relaxation During Conventional and Robot-Assisted Laparoscopic Surgery: A Narrative Review.

High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the prognosis of patients undergoing conventional and robot-assisted laparoscopic surgery. The application of deep neuromuscular blockade during the operation is reported to lower the intra-abdominal pressure and improve patients' outcome. However, concern lies in the risks of postoperative residual muscular paralysis with the use of deep neuromuscular blockade. Sugammadex, a specific antagonist for aminosteroids muscle relaxants, can effectively and rapidly reverse rocuronium and vecuronium induced neuromuscular blockade of different depths. Thus, sugammadex allows the ability to safeguard the application of deep neuromuscular blockade in laparoscopic operations and helps to alleviate the adverse complications associated with pneumoperitoneum. Here, we review the application of deep neuromuscular blockade in different laparoscopic surgeries and discuss the benefits and possible risks of sugammadex administration in the reversal of deep neuromuscular blockade in these operations.

Entamoeba histolytica L220 induces the in vitro activation of macrophages and neutrophils and is modulated by neurotransmitters.

The neuroimmunoregulation of inflammation has been well characterized. Entamoeba histolytica provokes an inflammatory response in the host in which macrophages and neutrophils are the first line of defense. The aim of this study was to analyze the effect of the 220 kDa lectin of Entamoeba histolytica on stimulation of human macrophages and neutrophils, especially the secretion of cytokines and the relation of these to neurotransmitters. Human cells were interacted with L220, epinephrine, nicotine, esmolol and vecuronium bromide. The concentrations of IL-1ß, IFN-γ, TNF-α and IL-10 were determined by ELISA at, 4 h of interaction. L220 has a cytokine stimulating function of macrophages and neutrophils for secretion of IL-1ß, and IL-10 only by macrophages, which was modulated by the effect of vecuronium on cholinergic receptors in this immune cells.

Comparison of Different Muscle-Relaxant Anesthetics on Growth, Migration and Invasion of Gastric Cancer Cells.

BACKGROUND/AIM: Muscle relaxants, also known as neuromuscular blocking agents, can block nerve impulses to the muscles and are always used in surgery for general anesthesia. However, the effect of muscle-relaxant anesthetics on cell activity in gastric cancer is currently unknown. The present study aimed to examine and compare the role of three different muscle-relaxant anesthetics in gastric cancer cells. MATERIALS AND METHODS: Gastric cancer cells (SGC7901 and BGC 823) were treated with a different dose of muscle-relaxant anesthetics, Rocuronium bromide (Rb), Vecuronium bromide (Vb) and Cisatracurium Besilate (CB). Using in vitro models, the effects on gastric cancer cell invasion, growth and migration of various anesthetics were subsequently investigated. RESULTS: We found that Rb increased the growth, invasion and migration of gastric cancer cells SGC7901 and BGC823. However, Vb and CB, as relatively mitigative anesthetics, did not significantly affect gastric cancer cell malignant phenotype at their regular blood concentration. CONCLUSION: Our results are important in selecting the type and dose of anesthetic used for surgery of gastric cancer patients. An understanding of the effect of muscle-relaxant anesthetics and their impact on tumor metastasis is critical, since it provides insight into the appropriate anesthetic strategy that could improve long-term survival in some patients with gastric cancer.

Influences of cisatracurium besylate and vecuronium bromide on muscle relaxant effects and electromyography of tracheal intubation under general anesthesia.

OBJECTIVE: To observe the influences of atracurium besylate and vecuronium bromide on muscle relaxant effects and electromyography of patients with tracheal intubation under general anesthesia in thyroid surgery. PATIENTS AND METHODS: 120 patients treated with thyroid surgery were randomly divided into group A and group V. Patients in group A were administered with cisatracurium besylate combined with propofol and fentanyl for induction of tracheal intubation under general anesthesia. Patients in group V were administered with 0.10 mg/kg vecuronium bromide combined with propofol and fentanyl for induction of tracheal intubation under general anesthesia. Then, the amplitude in electromyography was observed 30-70 min after I.V. muscle relaxant medicine to record the time for patients to reach 0% TW convulsion in abductor pollicis muscle and to observe the muscle relaxant effects. RESULTS: There was no statistical difference in the time to reach 0% TW in two groups (p>0.05). After 30 min of injection of muscle relaxants, EMG positive rate and TW value in group A were significantly higher than those in group V (p<0.05). After 50-70 min of injection of muscle relaxants, EMG positive rate of patients in two groups was up to 100%, and EMG amplitude in group A was significantly higher than that in group V (p<0.05). The time of taking muscle relaxant effects in group A was significantly faster than that in group V (p<0.05), while the recovery time of autonomous respiration and the time of autonomous body activity in group A were slightly lower than those in group V (p>0.05). There was no statistical difference in the time of eye-opening of both groups (p>0.05). MAP and HR of patients in both groups showed no statistical difference before and after injection (p>0.05). CONCLUSIONS: Average EMG amplitude and the positive rate of effective EMG amplitude of cisatracurium besylate are all higher than those of vecuronium bromide. With faster effects and shorter action time, cisatracurium besylate is more suitable in thyroid surgery IONM (intraoperative neurophysiological monitoring).

Neuromuscular blockade and inspiratory breath hold during stereotactic body radiation therapy for treatment of heart base tumors in four dogs.

CASE DESCRIPTION 4 dogs were examined because of pleural effusion and ventricular tachycardia, coughing and supraventricular tachycardia, appendicular osteosarcoma, and syncopal episodes. CLINICAL FINDINGS In all 4 dogs, a heart base tumor was identified by means of thoracic CT. TREATMENT AND OUTCOME In all 4 dogs, the heart base tumors were treated by means of stereotactic body radiation therapy. Dogs were anesthetized, and neuromuscular blockade was achieved with atracurium or vecuronium. A circle rebreathing system with 15 m (50 feet) of anesthetic tubing coursing through the vault wall was used to connect the patient to the anesthesia machine, which was located in the control room. After a brief period of hyperventilation, an inspiratory breath was held at 20 cm H2O for the duration of beam delivery. Each beam delivery lasted between 30 and 100 seconds. Immediately following the breath hold, assisted ventilation was resumed. Mean treatment delivery time for each patient was 26 minutes; mean total anesthesia time was 89 minutes. All patients recovered without complications. There was no evidence of hemoglobin desaturation or hypercapnia during the anesthetic procedure. CLINICAL RELEVANCE The technique allowed for control of the respiration cycle from outside the radiation vault and a short overall treatment time. No adverse effects were encountered. This procedure should be considered when delivering radiation to structures within the thoracic cavity.

The effects of intravenous anesthetics on QT interval during anesthetic induction with sevoflurane.

PURPOSE: Sevoflurane is known to prolong the QT interval. This study aimed to determine the effect of the interaction between intravenous anesthetics and sevoflurane on the QT interval. METHODS: The study included 48 patients who underwent lumbar spine surgery. Patients received 3 µg/kg fentanyl and were then randomly allocated to either Group T, in which they received 5 mg/kg thiamylal, or Group P, in which they received 1.5 mg/kg propofol, at 2 min after administration of fentanyl injection for anesthetic induction. Vecuronium (1.5 mg/kg) and sevoflurane (3 % inhaled concentration) were administered immediately after loss of consciousness and tracheal intubation was performed 3 min after vecuronium injection. Heart rate (HR), mean arterial pressure (MAP), bispectral index score (BIS), and the heart rate-corrected QT (QTc) interval on a 12-lead electrocardiogram were recorded immediately before fentanyl administration (T1), 2 min after fentanyl injection (T2), immediately before intubation (T3), and 2 min after intubation (T4). RESULTS: There were no significant differences between the two groups in baseline patient characteristics. BIS and MAP significantly decreased after anesthesia induction in both groups. At T3, MAP in Group T was higher than in Group P, while HR had reduced in both groups. The QTc interval was prolonged after anesthesia induction in Group T, but did not change at any time point in Group P. The QTc interval after anesthesia induction in Group T was longer than in Group P. CONCLUSION: We concluded that an injection of propofol could counteract QTc interval prolongation associated with sevoflurane anesthesia induction.

Sonographic optic nerve sheath diameter as a surrogate measure for intracranial pressure in anesthetized patients in the Trendelenburg position.

BACKGROUND: It remains to be elucidated whether the Trendelenburg position increases intracranial pressure (ICP). ICP can be evaluated by measuring the sonographic optic nerve sheath diameter (ONSD). We investigated the effect of the isolated Trendelenburg position on ONSD in patients undergoing robot-assisted laparoscopic radical prostatectomy. Additionally, we evaluated the effect of the Trendelenburg position combined with pneumoperitoneum on ONSD. METHODS: Twenty-one patients scheduled for robot-assisted laparoscopic radical prostatectomy were enrolled. Sonographic ONSDs and hemodynamic parameters were measured at specific time points: in the supine position after induction of anesthesia, 3 min after the steep Trendelenburg position (35° incline), 3 min after the steep Trendelenburg position combined with pneumoperitoneum, and in the supine position after desufflation of the pneumoperitoneum. RESULTS: The ONSD 3 min after the steep Trendelenburg position was significantly higher than that of the supine position after induction of anesthesia (5.1 ± 0.3 mm vs. 4.5 ± 0.4 mm). In addition, the ONSD 3 min after the steep Trendelenburg position combined with pneumoperitoneum was higher than that of the supine position after induction of anesthesia (4.9 ± 0.4 mm vs. 4.5 ± 0.4 mm). The ONSD in the supine position after desufflation of the pneumoperitoneum was similar to that in the supine position after induction of anesthesia. CONCLUSIONS: Use of the isolated steep Trendelenburg position, for even a short duration, increased the sonographic ONSD, providing a better understanding of the effect of only a transient steep Trendelenburg position on ONSD as a surrogate measure for ICP.

Biophysical study on the interaction of an anesthetic, vecuronium bromide with human serum albumin using spectroscopic and calorimetric methods.

The interactions between an anesthetic, vecuronium bromide (VB) and human serum albumin (HSA) have been investigated systematically by steady-state/time-resolved fluorescence, circular dichroism (CD), UV-vis absorption, Fourier transform infrared spectroscopy (FTIR), mass spectroscopy and differential scanning calorimetry (DSC) methods under physiological conditions. The fluorescence quenching observed is attributed to the formation of a complex between HSA and VB, and the reverse temperature effect of the fluorescence quenching has been found and discussed. Fluorescence analysis has proved that there is one classical binding site on HSA for VB with a relative weak binding constant of 1.07 × 10(4)M(-1) at 298 K. The primary binding pattern is determined by hydrogen bonding or van der Waals forces occurring in site I of HSA with ΔG°=-2.30 × 10(4)J mol(-1), ΔS°=-233 J mol(-1)K(-1) and ΔH°=-9.23 × 10(4)J mol(-1) at 298 K. VB could slightly change the secondary structure and induce unfolding of the polypeptides of protein. The DSC results provide quantitative information on the effect of VB on the stability of serum albumin. It is shown that VB can efficiently bind with HSA and be transported to the focuses needed.

Denervation stage differentially influences resistance to neuromuscular blockers in rat gastrocnemius.

BACKGROUND: Muscle denervation was common in clinical surgery patients, which was mostly caused by trauma, paraplegia, and other factors. Denervated muscle in patients could lead to significant differential reaction to neuromuscle blockers due to the time of denervation and affected muscle area. We tested the hypothesis that resistance to non-depolarizing muscle relaxants (NDMRs) changes with time, and is related to the expression of immature and total acetylcholine receptors (AChRs). MATERIALS AND METHODS: The study evaluated the effect change of neuromuscular blockers in tibial nerve transected rat model. To determine 50% effective dose of NDMRs and succinycholine at 1, 7, 14, 28, and 35 days after denervation, action potential amplitude was monitorted by intracellular recording method. The messenger DNA that encodes the AChR-γ and AChR-ε subunits and the protein of the -γ and -ε subunits were quantified in the gastrocnemius by reverse transcription-polymerase chain reaction and western blotting respectively. Receptor number and pharmacodynamic changes was analyzed by correlation and regression analysis. RESULTS: Increased AChR-γ correlated with total AChRs, suggesting that the up-regulated AChRs may contain the immature isoform. The 50% effective dose of vecuronium and atracurium increased 1.2- to 1.5-fold at all time periods and correlated significantly with AChRs and AChR-γ. CONCLUSIONS: After denervation, resistance to NDMRs occurred earlier, was more marked from 14 days, and changes in resistance to NDMRs in skeletal muscle after nerve injury is dependent on the level of expression of immature and total AChRs. Denervation time should be of concern when such patients undergo surgery.

Effects of reduction of inspired oxygen fraction or application of positive end-expiratory pressure after an alveolar recruitment maneuver on respiratory mechanics, gas exchange, and lung aeration in dogs during anesthesia and neuromuscular blockade.

OBJECTIVE: To evaluate the effectiveness of reduction of inspired oxygen fraction (Fio(2)) or application of positive end-expiratory pressure (PEEP) after an alveolar recruitment maneuver (ARM) in minimizing anesthesia-induced atelectasis in dogs. ANIMALS: 30 healthy female dogs. PROCEDURES: During anesthesia and neuromuscular blockade, dogs were mechanically ventilated under baseline conditions (tidal volume, 12 mL/kg; inspiratory-to-expiratory ratio, 1:2; Fio(2), 1; and zero end-expiratory pressure [ZEEP]). After 40 minutes, lungs were inflated (airway pressure, 40 cm H(2)O) for 20 seconds. Dogs were then exposed to baseline conditions (ZEEP100 group), baseline conditions with Fio(2) reduced to 0.4 (ZEEP40 group), or baseline conditions with PEEP at 5 cm H(2)O (PEEP100 group; 10 dogs/group). For each dog, arterial blood gas variables and respiratory system mechanics were evaluated and CT scans of the thorax were obtained before and at 5 (T5) and 30 (T30) minutes after the ARM. RESULTS: Compared with pre-ARM findings, atelectasis decreased and Pao(2):Fio(2) ratio increased at T5 in all groups. At T30, atelectasis and oxygenation returned to pre-ARM findings in the ZEEP100 group but remained similar to T5 findings in the other groups. At T5 and T30, lung static compliance in the PEEP100 group was higher than values in the other groups. CONCLUSIONS AND CLINICAL RELEVANCE: Application of airway pressure of 40 cm H(2)O for 20 seconds followed by Fio(2) reduction to 0.4 or ventilation with PEEP (5 cm H(2)O) was effective in diminishing anesthesia-induced atelectasis and maintaining lung function in dogs, compared with the effects of mechanical ventilation providing an Fio(2) of 1.

Evaluation of cyclodextrin (sugammadex) for reversal of intense neuromuscular block of rocuronium and vecuronium, experimental and clinical studies.

This study evaluated and explored time course, efficacy, relation, safety, changes in heart rate, and blood pressure after a bolus dose of sugammadex or neostigmine for reversal of a prolonged rocuronium and vecuronium induced neuromuscular block. A total of 60 patients of both sexes, 'ASA' grade I, II and all were scheduled for elective surgery of 30-45 minutes duration. Informed oral consent was obtained from all patients to participate in this study. The results showed statistically significant progressive decrease of heart rate and blood pressure at 2, 5 and 10 minutes when compared to their basal values before anesthesia, then it starts to gain its normal value at 5 and 10 minutes, regardless the dose of sugammadex (effect of anesthesia). Also, heart rate and blood pressure showed statistically non-significant variance between groups of sugammadex when compared at any time of the study with the neostigmine groups (i.e. no effect of the dose on heart rate).

Observations of the potency and duration of vecuronium in isoflurane-anesthetized horses.

OBJECTIVE: To evaluate the potency and duration of three subparalyzing doses of vecuronium (VEC) in isoflurane-anesthetized horses. STUDY DESIGN: Prospective experimental study. ANIMALS: Thirteen healthy adult horses undergoing arthroscopic surgery. METHODS: During isoflurane anesthesia, horses received one of three doses of vecuronium (25, 50, or 100 µg kg(-1)). Neuromuscular transmission was monitored with acceleromyography (AMG) with train-of-four (TOF) stimulation of the radial nerve. Maximal depression of the first twitch (T1), and onset time were recorded for each dose. Recovery time to a TOF ratio >90% was also evaluated. RESULTS: Vecuronium 25 µg kg(-1) produced no observable T1 depression in four horses. VEC 50 µg kg(-1) (n = 5) produced a maximal T1 depression of [median (min, max)] 41 (20, 71) % in four horses, and no neuromuscular block was seen in the fifth. VEC 100 µg kg(-1) was given to four horses and produced a T1 depression of 73 (64, 78) %. Of the four horses in which VEC 50 µg kg(-1) produced a measurable neuromuscular block, three recovered spontaneously 43 (40, 52) minutes after VEC administration; a fourth subject received edrophonium to reverse residual block at the end of the surgery. Spontaneous recovery after VEC 100 µg kg(-1) occurred by 112 minutes in one horse, and had to be facilitated by edrophonium in the remaining three horses, more than 2 hours after VEC had been given. CONCLUSIONS AND CLINICAL RELEVANCE: A dose of 100 µg kg(-1) VEC in isoflurane anesthetized horses failed to produce complete paralysis. The partial neuromuscular block lasted at least 2 hours after this dose had been administered. Edrophonium was required to reverse the neuromuscular block in three of four horses. It is likely that more than 100 µg kg(-1) VEC would be necessary for complete neuromuscular blockade in horses, and that this dose will last >2 hours.

SUGAMADEX: novos horizontes para a reversão do bloqueio neuromuscular / SUGAMMADEX: new horizons for the reversal of neuromuscular blockade

O sugamadex é uma droga nova e revolucionária desenvolvida como antagonista seletivo dos agentes bloqueadores neuromusculares (ABNM) esteroides (rocurônio > vecurônio ¼ pancurônio). O medicamento é uma y-ciclodextrina modificada e hidrossolúvel que forma um composto estável com o ABNM na razão de 1:1. Ele se liga ao ABNM livre no plasma, criando um gradiente de concentração que desloca o ABNM dos receptores nicotínicos na junção neuromuscular, levando à reversão completa e duradoura do BNM. O sugamadex não se liga às proteínas ou a qualquer outro receptor no organismo, o que lhe confere ótimo perfil de tolerância. O sugamadex pode ser usado na reversão do BNM profundo, promovendo recuperação mais rápida em relação à succinilcolina. Seu emprego pode diminuir a necessidade de monitorização do BNM, a incidência de bloqueio residual e ainda evitar os efeitos adversos causados pelos anticolinesterásicos e anticolinérgicos. Entretanto, também há limitações em relação à utilização 00 sugamadex. Ele impede o uso dos AB- NMs esteroides durante 24 horas, caso seja necessário novo BNM, e pode aumentar o risco do emprego desnecessário e indiscriminado dos ABNMs. Além disso, faltam dados da sua utilização em alguns grupos populacionais e de seu uso em larga escala. Por fim, deve-se considerar também o fator econômico, visto que se trata de uma droga nova e de valor ainda elevado no mercado...

Sugammadex is a novel and unique compaund designed as a selective antaganist ot steroidal neuromuscular blaeking agents (NMBA) (rocuronium>vecuronium¼pancuronium). The drug is a modified water-saluble y-cyclodextrin that forms a stable complex at a 1:1 ratio with the NMBA. It combines with the NMBA creating a concentration gradient favoring the movement ot the NMBA from the nicotine receptors ot the neuromuscular junction leading to the complete and lasting reversal af the neuromuscular blockade (NMB). Sugamadex does not bind to plasma proteins or any other receptors system in the body what provides him a great tolerance profile. Sugamadex can be used in the reversal af deep neuromuscular blockade with a faster recovery time in relation to succinylcholine. Its use can diminish the necessity af monitoring af the NMB, the incidence ot residual blockade and still prevent the adverse effects caused by the antiecholinesterase and anticholinergic drugs. However, there are limitatians regarding the use af Sugammadex. It hinders the use ot the steroidal NMBA during 24 hours if a new NMB must be restablished and it can increase the risk ot unnecessary and indiscriminate use af the NMBA. Mareaver, there is a laek ot data regarding the its use in some population groups and in large scale. Final/y, the economic factor must be also considered, since it is a new drug with a still raised value in market...

Presynaptic facilitatory adenosine A2A receptors mediate fade induced by neuromuscular relaxants that exhibit anticholinesterase activity.

1. Pancuronium, cisatracurium and vecuronium are antinicotinic agents that, in contrast with d-tubocurarine and hexamethonium, exhibit anticholinesterase activity. Pancuronium-, cisatracurium- and vecuronium-induced fade results from blockade of facilitatory nicotinic receptors on motor nerves, but fade produced by such agents also depends on the presynaptic activation of inhibitory muscarinic M2 receptors by acetylcholine released from motor nerve terminals and activation of inhibitory adenosine A1 receptors by adenosine released from motor nerves and muscles. The participation of presynaptic facilitatory A2A receptors in fade caused by pancuronium, cisatracurium and vecuronium has not yet been investigated. In the present study, we determined the effects of ZM241385, an antagonist of presynaptic facilitatory A2A receptors, on fade produced by these neuromuscular relaxants in the rat phrenic nerve-diaphragm (PND) preparation. 2. The muscles were stimulated indirectly at 75±3Hz to induce a sustained tetanizing muscular contraction. The lowest concentration at which each antinicotinic agent produced fade without modifying initial tetanic tension (presynaptic action) was determined. 3. d-Tubocurarine-induced fade occurred only at 55 nmol/L, a concentration that also reduced maximal tetanic tension (post-synaptic action). At 10 nmol/L, ZM 241385 alone did not produce fade, but it did attenuate pancuronium (0.32 µmol/L)-, cisatracurium (0.32 µmol/L)- and vecuronium (0.36 µmol/L)-induced fade. 4. The fade induced by the 'pure' antinicotinic agents d-tubocurarine (55 nmol/L) and hexamethonium (413 µmol/L) was not altered by 10 nmol/L ZM 241385, indicating that presynaptic adenosine A2A receptors play a significant role in the fade produced by antinicotinic agents when such agents have anticholinesterase activity.

Assessment of the potential for displacement interactions with sugammadex: a pharmacokinetic-pharmacodynamic modelling approach.

BACKGROUND: Sugammadex is a γ-cyclodextrin that binds with high affinity to the neuromuscular blocking agents (NMBAs) rocuronium (bromide) and vecuronium (bromide) by encapsulation. Cyclodextrins are known to form inclusion complexes with other compounds. OBJECTIVES: We utilized a previously developed pharmacokinetic-pharmacodynamic model to identify potential clinically relevant displacement interactions with sugammadex. The potential for sugammadex to capture other drug molecules, thereby reducing their efficacy, is not discussed here. METHODS: Isothermal titration calorimetry (ITC) was used to determine the binding affinity (estimated by association rate constant [k(ass)]) between sugammadex and 300 commonly prescribed drugs. The screening included drugs commonly used in or shortly after anaesthesia, commonly prescribed drugs such as antidepressants and cardiovascular drugs, drugs (both steroidal and nonsteroidal) acting on steroidal receptors (such as the corticosteroids hydrocortisone, prednisolone and dexamethasone), and the selective estrogen receptor modulator toremifene. The model took into account the population pharmacokinetic-pharmacodynamic relationships of sugammadex, rocuronium and vecuronium, the binding affinities of the NMBAs and other compounds as determined by ITC, and the relationship between the free concentration of NMBA with sugammadex in the presence of a third complexed compound. Using the model, the critical concentrations of a concomitantly administered compound required to result in a train-of-four (TOF) ratio of <0.9, indicating reoccurrence of neuromuscular blockade, for each plasma concentration of sugammadex and NMBA were calculated. For compounds with a k(ass) value of ≥ 2.5 × 104 mol/L likely to be administered during sugammadex reversal, the combinations of k(ass) and maximum plasma drug concentration (C(max)) were entered into a graph, consisting of a critical line established using a conservative approach, and those compounds above this critical line potentially resulting in a TOF ratio <0.9 were subsequently identified. Clinical validation was performed in a post hoc analysis of data from ten sugammadex studies, in which the impact of various drugs administered perioperatively on neuromuscular recovery was assessed for up to 1 hour after sugammadex administration. RESULTS: ITC analysis demonstrated that the binding affinity of rocuronium and vecuronium for sugammadex was very high, with k(ass) values of 1.79 × 107 mol/L and 5.72 × 106 mol/L, respectively. Only three compounds (flucloxacillin, fusidic acid and toremifene) were found to have critical combinations of k(ass) and C(max), and thus the potential for displacement. Sugammadex was administered to 600 patients for reversal of rocuronium- or vecuronium-induced blockade in the ten analysed studies, in which 21 co-administered drugs were selected for analysis. No reoccurrence of blockade occurred in any patient. CONCLUSION: Of 300 drugs screened, only three (flucloxacillin, fusidic acid and toremifene) were found to have potential for a displacement interaction with sugammadex, which might potentially be noticed as a delay in recovery of the TOF ratio to 0.9. A clinical study found no evidence of a clinically relevant displacement interaction of flucloxacillin with sugammadex; these findings confirm the highly conservative nature of the modelling and simulation assumptions in the present study.

[The relationship between the intraoperative hypothermia and the residual neuromuscular of single intubation dose of vecuronium].

OBJECTIVE: To study the relationship between the intraoperative hypothermia and the residual neuromuscular of single intubation dose of vecuronium. METHODS: The designed patients were from July to December in 2009. There are 36 male and 44 female cases. Their age was 19 to 59 years. The induction and sustaining are routine method. There were no additional muscle relaxant. Intraoperative nasopharyngeal temperature (T) < 36°C for the intraoperative hypothermia (LBT group) or non-intraoperative hypothermia group (NBT group). The patients turn back the PACU with tracheal intubation. Measured TOFr immediately after extubation. RESULTS: The incidence of residual neuromuscular single intubation dose of vecuronium was 28.7%. The incidence of postoperative residual neuromuscular was 43.2% (16/37) in the LBT group. The incidence of postoperative residual neuromuscular was 16.3% (7/43) in the NBT group. LBT group compared with the NBT group the incidence of postoperative residual neuromuscular was significant differences (P < 0.05). CONCLUSION: The incidence of residual neuromuscular increases. When patients in the surgery exist low body temperature.

Rocuronium and vecuronium do not affect mandibular bone marrow and masseter muscular blood flow in rabbits.

PURPOSE: The goal of this study was to investigate the effect of rocuronium and vecuronium continuous infusion on oral tissue blood flow in rabbits. MATERIALS AND METHODS: We used 8 male Japan White rabbits. The infusion rates of rocuronium were 7, 14, and 28 microg kg(-1) min(-1) for 20 minutes, in this order. After rocuronium was discontinued and body movement confirmed, continuous infusion of vecuronium was started. The infusion rates of vecuronium were 1.6, 3.2, and 6.4 microg kg(-1) min(-1) for 20 minutes, in this order. Observed variables were systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, common carotid artery blood flow, tongue mucosal blood flow, oxygen partial pressure of the mandibular bone marrow, and oxygen partial pressure of the masseter muscle. RESULTS: Heart rate in both groups tended to decrease depending on the infusion rate. Common carotid artery blood flow in the rocuronium group was increased depending on the infusion rate. Tongue mucosal blood flow in the vecuronium group was decreased depending on the infusion rate. There were no differences in diastolic blood pressure, mean arterial pressure, oxygen partial pressure of the mandibular bone marrow, and oxygen partial pressure of the masseter muscle between the 2 groups. Systolic blood pressure in both groups showed no major change. CONCLUSION: Rocuronium and vecuronium did not change mandibular bone marrow and masseter muscular blood flows. Vecuronium decreased tongue mucosal blood flow depending on the infusion rate.

The post-tetanic count during vecuronium-induced neuromuscular blockade in halothane-anaesthetized dogs.

OBJECTIVE: To evaluate the post-tetanic count (PTC) for predicting the return of reversible neuromuscular blockade at the n. facialis-m. nasolabialis (nF-mNL) and n. ulnaris-mm. carpi flexorii (nU-mCF) nerve-muscle units (NMUs) during profound vecuronium neuromuscular blockade in halothane-anaesthetized dogs. STUDY DESIGN: Randomized, prospective, experimental study. ANIMALS: Twenty-five dogs (seven male 18 female) undergoing surgery; mean age: 4.8 years; mean body weight 22 kg. METHODS: Thirty minutes after acepromazine (0.05 mg kg(-1)) and morphine (0.5 mg kg(-1)) pre-medication, anaesthesia was induced with intravenous (IV) thiopental and maintained with halothane, N(2)O and O(2). The lungs were mechanically ventilated and end-tidal halothane concentration (Fe'(HAL)) maintained at 1.04%. Neuromuscular transmission was monitored using the train-of-four count (TOFC) at one nF-mNL and both nU-mCF units. Vecuronium (50 microg kg(-1) IV) was injected after 15 minutes constant Fe'(HAL). When the first twitch (T1) at both nU-mCF units had disappeared (t = 0) one (randomly allocated) ulnar nerve was stimulated every 5 minutes using PTC; TOF stimulation continued at the other sites. The PTC was plotted against the interval between recording time and T1's reappearance at the other NMUs. RESULTS: At t = 0, the mean PTC in the contralateral nU-mCF unit was 18 (range 0-20). Mean PTC was a minimum at t = 5, rising to the maximum (20) at 25 minutes. Six dogs were vecuronium-resistant as monitored by PTC. Excluding data from these revealed a strong negative relationship between ulnar PTC and the time taken for T1's return at the facial (r = -0.7018; p < 0.00001) and contralateral ulnar (r = -0.8409; p < 0.00001) NMUs. CONCLUSION AND CLINICAL RELEVANCE: Post-tetanic count monitoring beginning >5 minutes after the TOFC at nU-mCF = 0 provided a reliable estimate of T1's return at ulnar and facial NMUs.