The hemodynamic stability of remimazolam compared with propofol in patients undergoing endoscopic submucosal dissection: A randomized trial

In EMR of early gastric cancer (EGC), en bloc resection reduces the risk of residual cancer. Endoscopic submucosal dissection (ESD) now allows en bloc resection of large EGCs. To retrospectively determine whether ESD is more advantageous than EMR for EGCs. EMR (825 lesions, 711 patients) or ESD (195 lesions, 185 patients) was performed. The en bloc resection rate, histologically complete resection rate, operation time, complications, and local recurrence rate were studied in relation to ulceration. Hiroshima University Hospital. Subjects comprised 896 patients in whom 1020 EGCs were resected endoscopically from 1990 to 2004. In cases without ulceration, en bloc and histologically complete resection rates were significantly higher with ESD than with EMR, regardless of tumor size. The frequency of ulceration did not differ significantly between groups. Average operation time was significantly longer for ESD than for EMR, regardless of tumor size. Also, regardless of ulceration, the incidence of intraoperative bleeding was significantly higher with ESD (22.6%) than with EMR (7.6%). Delayed bleeding did not differ. In cases with ulceration, the incidence of perforation was significantly higher with ESD (53.8%) than with EMR (2.9%). Local recurrences were treated by incomplete EMR (en bloc, 2.9%; piecemeal, 4.4%). No patient experienced recurrence after ESD. ESD increased en bloc and histologically complete resection rates and may reduce the local recurrence rate. Increased operation time and complication risks with ESD in comparison with EMR remain problematic. Special measures are necessary for ESD of ulcerated lesions to reduce the rates of perforation and incomplete resection.

A new benzodiazepine derivative, CNS 7056, has been developed to permit a superior sedative profile to current agents, i.e., more predictable fast onset, short duration of sedative action, and rapid recovery profile. This goal has been achieved by rendering the compound susceptible to metabolism via esterases. The authors now report on the profile of CNS 7056 in vitro and in vivo. The affinity of CNS 7056 and its carboxylic acid metabolite, CNS 7054, for benzodiazepine receptors and their selectivity profiles were evaluated using radioligand binding. The activity of CNS 7056 and midazolam at subtypes (alpha1beta2gamma2, alpha2beta2gamma2, alpha3beta2gamma2, alpha5beta2gamma2) of the gamma-aminobutyric acid type A (GABAA) receptor was evaluated using the whole cell patch clamp technique. The activity of CNS 7056 at brain benzodiazepine receptors in vivo was measured in rats using extracellular electrophysiology in the substantia nigra pars reticulata. The sedative profile was measured in rodents using the loss of righting reflex test. CNS 7056 bound to brain benzodiazepine sites with high affinity. The carboxylic acid metabolite, CNS 7054, showed around 300 times lower affinity. CNS 7056 and CNS 7054 (10 mum) showed no affinity for a range of other receptors. CNS 7056 enhanced GABA currents in cells stably transfected with subtypes of the GABAA receptor. CNS 7056, like midazolam and other classic benzodiazepines, did not show clear selectivity between subtypes of the GABAA receptor. CNS 7056 (intravenous) caused a dose-dependent inhibition of substantia nigra pars reticulata neuronal firing and recovery to baseline firing rates was reached rapidly. CNS 7056 (intravenous) induced loss of the righting reflex in rodents. The duration of loss of righting reflex was short (< 10 min) and was inhibited by pretreatment with flumazenil. CNS 7065 is a high-affinity and selective ligand for the benzodiazepine site on the GABAA receptor. CNS 7056 does not show selectivity between GABAA receptor subtypes. CNS 7056 is a potent sedative in rodents with a short duration of action. Inhibition of substantia nigra pars reticulata firing and the inhibition of the effects of CNS 7056 by flumazenil show that it acts at the brain benzodiazepine receptor.

Remimazolam (CNS 7056) is a new ultra-short-acting benzodiazepine for intravenous sedation and anesthesia. Its pharmacokinetics and pharmacodynamics have been reported for bolus administration. This study aimed to investigate the pharmacokinetics and pharmacodynamics of remimazolam after continuous infusion.