Reduction of the rocuronium-induced withdrawal reflex by MR13A10A, a generic rocuronium with a novel solution: A randomized, controlled study.

BACKGROUND: Rocuronium induces venous pain and the withdrawal reflex during injection. MR13A10A, generic rocuronium with a novel solution, reduced the injection-induced withdrawal reflex in rodents. We hypothesized that MR13A10A would reduce the frequency and severity of injection-induced withdrawal reflexes compared with original rocuronium during clinical anesthesia induction. METHODS: This prospective, open (but assessor-blinded), randomized, controlled study was conducted at a single academic hospital. The assessor was blinded to the study condition in order to minimize observer bias. Participants were allocated to either MR13A10A or traditional formula groups by a blocked stratified randomization method. Participants in the MR13A10A group received MR13A10A, whereas the original rocuronium group received the same amount of original rocuronium. The primary outcome was presence of the withdrawal reflex after rocuronium injection. Severity of the withdrawal reflex, changes in blood pressure and heart rate, and the train of four (TOF) ratio were measured as secondary outcomes. The withdrawal reflex was assessed using a video recording in a blinded manner. RESULTS: Of the 149 participants, 76 were allocated to the MR13A10A group and 73 to the original rocuronium group. The frequency of the withdrawal reflex was significantly lower with MR13A10A compared with original rocuronium (19.7% and 54.8% for MR13A10A and original rocuronium groups, respectively, p<0.001). The odds ratio adjusted for cannulation site, cannula size, induction agent and age was 6.27 (95% CI, 2.87, 13.73 p<0.001). Original rocuronium was an independent factor related to a higher post-treatment heart rate. The proportions of TOF ratios = 0 were similar between the two groups. CONCLUSION: The frequency and severity of the withdrawal reflex after injection were significantly reduced by using MR13A10A. MR13A10A might contribute to safe and less invasive anesthesia management.

The effect of various dilute administration of rocuronium bromide on both vascular pain and pharmacologic onset: a randomized controlled trial.

BACKGROUND: Rocuronium bromide (RB) is known to cause vascular pain. Although there have been a few reports that diluted administration causes less vascular pain, there have been no studies investigating diluted administration and the onset time of muscle relaxation. Therefore, we examined the influence of diluted administration of RB on the onset time of muscle relaxation and vascular pain. METHODS: 39 patients were randomly assigned to three groups: RB stock solution 10 mg/ml (Group 1), two-fold dilution 5 mg/ml (Group 2), or three-fold dilution 3.3 mg/ml (Group 3). After the largest vein of the forearm was secured, anesthesia was induced by propofol and 0.6 mg/kg of RB was administered. The evaluation method devised by Shevchenko et al. was used to evaluate the degree of vascular pain. The time from RB administration until the maximum blocking of T1 by TOF stimulation was measured. RESULTS: There was no significant difference in escape behaviors of vascular pain among the three groups, and the onset time of muscle relaxation was significantly slower in Group 3 than in Group 1 (p = 0.033). CONCLUSION: Our results suggested that it is unnecessary to dilute RB before administration if a large vein in the forearm is used. TRIAL REGISTRATION: UMINCTR Registration number UMIN000026737 . Registered 29 Mar 2017.

Simultaneous quantification of propofol, ketamine and rocuronium in just 10 µL plasma using liquid chromatography coupled with quadrupole mass spectrometry and its pilot application to a pharmacokinetic study in rats.

The combination of propofol, ketamine and rocuronium can be used for anesthesia of ventilated rats. However, reliable pharmacokinetic models of these drugs have yet to be developed in rats, and consequently optimal infusion strategies are also unknown. Development of pharmacokinetic models requires repeated measurements of drug concentrations. In small animals, samples must be tiny to avoid excessing blood extraction. We therefore developed a drug assay system using high-performance liquid chromatography coupled with quadrupole mass spectrometry that simultaneously determines the concentration of all three drugs in just 10 µL rat plasma. We established a plasma extraction protocol, using acetonitrile as the precipitating reagent. Calibration curves were linear with R2 = 0.99 for each drug. Mean recovery from plasma was 91-93% for propofol, 89-93% for ketamine and 90-92% for rocuronium. The assay proved to be accurate for propofol 4.1-8.3%, ketamine 1.9-7.8% and rocuronium -3.6-4.7% relative error. The assay was also precise; the intra-day precisions were propofol 2.0-4.0%, ketamine 2.7-2.9% and rocuronium 2.9-3.3% relative standard deviation. Finally, the method was successfully applied to measurement the three drugs in rat plasma samples. Mean plasma concentrations with standard deviations were propofol 2.0 µg/mL ±0.5%, ketamine 3.9 µg/mL ±1.0% and rocuronium 3.2 µg/mL ±0.8% during ventilation.

Screen printed potentiometric sensor for therapeutic monitoring of rocuronium at the point of care.

Rocuronium bromide (ROC) is currently regarded as the 'gold-standard' in emergency medicine and anesthesia. Globally, millions of human beings are daily administered ROC at emergency settings where it is favored among all the neuromuscular blockers, particularly succinylcholine, for both its fast onset of action and short duration. However, it has been reported that 45% of patients in the post-anesthesia care unit are susceptible to residual postoperative paralysis, undesired ventilator effects and incomplete recovery after ROC administration. From an analytical chemistry perspective, direct determination of ROC is a difficult approach due to the complexity in isolation from biological specimens as well as the lack of a sensitive detection techniques and detectable chromophore. This contribution describes the development of a calix[6]arene-based screen-printed electrode (SPE) that is capable of ROC detection in biological samples at the point of care. This fabricated SPE (sensor 1) exhibited superior performance characteristics (slope, LOD and life time) with respect to an ionophore-free liquid-contact electrode, LCE, (sensor 2). The proposed SPE showed a linear response over a concentration from 1 µM to 10 mM, with a Nernstian slope of 57.9 mV/decade and a detection limit of 0.39 µM. Moreover, this sensor showed a considerable selectivity towards ROC in presence of the anticipated interfering ions. To investigate the ability of the SPE to detect ROC in real biological specimens, ROC has been spiked at a concentration comparable to its anticipated level in human plasma (Cmax~ 40 µM) and the proposed SPE displayed an excellent platform for therapeutic drug monitoring (TDM) of ROC with respect to UV-spectrophotometry and LC/MS. Finally, the developed SPE was used for the determination of ROC in its commercial pharmaceutical formulation.