No abstract available.
Electroencephalography ; Flumazenil* ; Status Epilepticus*

We investigated the usefulness of the method of producing sedation with midazolam and reversing with antagonist flumazenil in upper gastrointestinal endoscopy. Twenty-five adult outpatients underwent diagnostic upper gastrointestinal endoscopy 3 min after having an intravenous injection of 5 mg of midazolam for sedation, and received 0.25 mg of flumazenil intravenously 5 min after the removal of the endoscope. Blood pressure, heart rate, and percutaneous arterial oxygen saturation (SpO2) were measured, recorded, and compared at nine points : 1 min before midazolam injection, 2 min after midazolam injection, 1, 3, and 5 min after the insertion of the endoscope, 1 and 3 min after the removal of the endoscope, 1 min after flumazenil injection, and their awakening time at which they are easily able to respond to verbal commands. Fifteen minntes after their awakening, we asked those patients about their memory during the endoscopy and evaluated their pain with the Visual Analogue Scale (VAS). A significant decrease in systolic blood pressure was noted 2 min after midazolam injection. But the systolic blood pressure measured 1 min after the insertion of the endoscope significantly increased when compared with the level 2 min after midazolam injection. Then it gradually started decreasing. Although the systolic blood pressures 1 min after flumazenil injection and at their awakening time increased slightly, the levels were significantly lower than those 1 min before midazolam injection. The heart rate increased to the maximum 1 min after the insertion of the endoscope. Then it gradually started decreasing. The heart rates 1 min after flumazenil injection and at their awakening time decreased significantly when compared with those 1 min after the insertion of the endoscope. SpO2 significantly decreased from 97.6±1.6% 1 min before midazolam injection to 95.7±2.5% 2 min after midazolam injection and remained depressing around 95% during the endoscopy. However, SpO2 recovered 96.6±2.0% at their awakening time. Two patients had a vague memory but all the rest had no memory recollection at all of what happened during the examination. VAS was 20 mm for one patient and 0 mm for another patient. We showed the clinical usefulness of the method of antagonizing with flumazenil after upper gastrointestinal endoscopy performed on patients given an i.v. injection of midazolam, because this method might provide a minimal circulatory change due to some protection against hemodynamics stress in response to manipulation of the endoscope, anterograde amnesia, and disappearance of pain. However, we should take care of respiratory depression of the patient during endoscopy.
Minute of time ; Midazolam ; Injections ; Flumazenil ; Awake

Prolonged oversedation occurs frequently in postoperative care units, and sometimes delays transfer to normal units. Flumazenil is a known reversal drug for benzodiazepines, and is used to reverse the oversedation caused by benzodiazepines. However, we found that flumazenil was effective in a case of sevoflurane induced oversedation. A prolonged oversedation of 90 minutes occurred after sevoflurane anesthesia without benzodiazepine at a postoperative care unit. Immediately after an intravenous injection of flumazenil, the patient fully awoke and was oriented.
Anesthesia* ; Benzodiazepines ; Flumazenil* ; Humans ; Injections, Intravenous ; Postoperative Care

PURPOSE: Radiotracers that bind to the central benzodiazepine receptor are useful for the investigation of various neurological and psychiatric diseases. [C-11]Flumazenil, a benzodiazepine antagonist, is the most widely used radioligand for central benzodiazepine receptor imaging by PET. We synthesized 3-(2-[F- 18]fluoro)flumazenil, a new fluorine-18 (t1/2=110 min) labeled analogue of benzodiazepine receptor imaging agent, and evaluated in vivo for biodistribution in mice. MATERIALS AND METHODS: Flumazenil (Ro 15-1788) was synthesized by a modification of the reported method. Precursor of 3-(2-[F-18]fluoro)flumazenil, the tosylated flumazenil derivative was prepared by the tosylation of the ethyl ester by ditosylethane. [F-18] labeling of tosyl substitued flumazenil precursor was performed by adding F-18 ion at 85 degree C in the hot cell for 20 min. The reaction mixture was trapped by C18 cartridge, washed with 10% ethanol, and eluted by 40% ethanol. Bidistribution in mice was determined after intravenous injection. RESULTS: The total chemical yield of tosylated flumazenil derivative was ~40%. The efficiency of labeling 3-(2-[F-18]fluoro)flumazenil was 66% with a total synthesis time of 50 min. Brain uptakes of 3-(2-[F-18]fluoro)flumazenil at 10, 30, 60 min after injection, were 2.5+/-0.37, 2.2+/-0.26, 2.1+/-0.11 and blood activities were 3.7+/-0.43, 3.3+/-0.07, 3.3+/-0.09%ID/g, respectively. CONCLUSION: We synthesized a tosylated flumazenil derivative which was successfully labeled with no-carrier-added F-18 by nucleophilic substitution.
Animals ; Benzodiazepines* ; Brain ; Ethanol ; Flumazenil* ; Injections, Intravenous ; Mice ; Receptors, GABA-A*

PURPOSE: Flutamide (4-nitro-3-t-trifluoromethyl-isobutyranilide) is an androgen-receptor antagonist with typical antiandrogenic effect, used to treat androgen-dependent disorders such as prostate cancer. However, some reports noted that flutamide has direct effects to neuronal cells. It has been shown to retard the development of electrical kindling in rats. METHODS: We used the chemoconvulsant 4-aminopyridine (4-AP) and picrotoxin (PTX) in the in vitro hippocampal slice model to determine of flutamide for the suppression of epileptiform discharges. Extracellular field potential recordings were obtained from the CA3 pyramidal layer of hippocampus. RESULTS: The concentration of 30 and 100 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 57.8% and 66.8% each compared with the 4-AP only slices. In 100 micrometer PTX, 10 and 30 micrometer flutamide suppressed the whole mean number of epileptiform discharges to 56.6% and 82.5% each. Intermixed with flumazenil, the anticonvulsant effect of flutamide was decreased. CONCLUSIONS: Flutamide suppressed epileptiform discharges induced by 4-AP and PTX in vitro seizure model. It suggests that flutamide influence to anti-epileptic activity by benzodiazepine site of the GABAA receptor.
4-Aminopyridine ; Benzodiazepines ; Flumazenil ; Flutamide ; Neurons ; Picrotoxin ; Prostatic Neoplasms ; Seizures

The effects of lorazepam on cerebral function, metabolism, and hemodynamics were studied in eight dogs receiving a general anesthesia with isoflurane(0.5 vo1%)-50% nitrous oxide-oxy-gen. The effects of benzodiazepine antaronist, flumazenil, were also examined. Lorazepam(0.5 mg/kg) administration did decrease mean arterial pressure(MAP) and herat rate(HR). It did significantly decrease cerebral blood flow(CBF)(measured by posterior sagittal sinus outflow method) by 25% of control value(68+/-l3 vs. 51+/-12ml/100gm/min, meanSD) and cereberal metabolic rate for oxygen(CMRO ) by 17% (3.96+/-1.04 vs. 3.30+/-0.92ml/l00gm/min, mean+/-SD). Electroencephalogram(EEG) converted to high amplitude, predominantly theta and delta activity. Intracranial pressure(ICP) increased markedly. Following flumazenil(0.06 mg/kg) administration, HR recovered completely to control level but MAP increased only at 5 min. compared to pre-flumazenil value and returned to pre-flumazenil level. CBF recovered to control level for 15 min. and deereased after 30 min. compared to control level but higher than pre-flumazenil level about 9-15%. CMRO recovered completely to control leveL EEG changed to an awake pattern after fluamzenil administration. It is concluded that lorarepam decreased cerebral function and metabolism and depressed hemodynamic fuction. Benzodiazepine antag- onist, flumazenil, was effective in reversing cerebral and hemodynamic effects, may be in dose related manner.
Anesthesia, General ; Animals ; Benzodiazepines ; Dogs* ; Electroencephalography ; Flumazenil* ; Hemodynamics ; Lorazepam* ; Metabolism

Endoscopy is increasingly performed with the patient under conscious sedation in many countries. The majority of patients can be adequately and safely sedated during routine upper endoscopy and colonoscopy with a combination of a benzodiazepine and opioid. Midazolam is a water-soluble benzodiazepine that is characterized by a rapid onset of action and a shorter duration compared with that of the other drugs of the same class. The major side effect of midazolam is respiratory depression, which can be reversed by flumazenil, a benzodiazepine-specific antagonist. Propofol is a lipid-soluble agent that has the advantages of a more rapid onset of action and a shorter recovery time compared to that of midazolam. However, it should be used with caution since it can lead to hypotension and respiratory depression. Propofol can be safely and effectively administered by nonanesthesiology physicians and nurses provided that they have received adequate training. Two models have been proposed for the administration of propofol by endoscopists: nurse-administered propofol sedation (NAPS) and combination propofol (propofol plus other agents) sedation. In order to modify the pharmacological disadvantages of propofol, fospropofol sodium, a water-soluble prodrug of propofol, has recently been developed. In addition, new delivery systems have been devised: patient-controlled sedation and computer-assisted personalized sedation, in which the computer continuously monitors the patient's condition and adjusts the dose of propofol accordingly. Endoscopists must have a thorough understanding of the medications used for endoscopic sedation and they must acquire the skills necessary for the treatment of cardiopulmonary complications. Therefore, it is necessary to develop a practice guideline pertaining to endoscopic sedation and also training programs for physicians and nurses in Korea.
Benzodiazepines ; Colonoscopy ; Conscious Sedation ; Endoscopy ; Flumazenil ; Humans ; Hypotension ; Korea ; Midazolam ; Propofol ; Respiratory Insufficiency ; Sodium

We report a case of profound amnesia, anterograde and retrograde, in a patient, who had been premedicated with midazolam and underwent a posterior fusion of the cervical spine under inhalation anesthesia. The patient's memory was restored immediately after intravenous injections of the benzodiazepine antagonist flumazenil.
Amnesia ; Amnesia, Anterograde ; Amnesia, Retrograde* ; Anesthesia, Inhalation ; Benzodiazepines ; Flumazenil* ; Humans ; Injections, Intravenous ; Memory ; Midazolam* ; Spine

BACKGROUND/AIMS: Paradoxical reaction after midazolam administration is relatively uncommon and can obstruct the performance of ERCP. But it can not be predicted before drug administration. We investigate the difference in occurrence of paradoxical reaction according to personal characteristics and clinical status of patients. METHODS: During 155 ERCP procedures, we injected midazolam and meperidine intravenously for conscious sedation until deep sleep occurred. Among 155 patients, 108 patients did not showed paradoxical reaction (group I) and 47 patients (30.3%) showed gross behavioral disturbance and/or agitation (group II). Paradoxical agitation was seen in 9 (7.1%) procedures. RESULTS: Type A-like personality (p=0.002), sleep-talking habit (p=0.026) and presence of pain at the beginning of ERCP (p=0.036) and during ERCP (p=0.021) were seen more frequently in group II. Duration of ERCP was longer (p=0.034) and dosage of midazolam was larger (p=0.009) in group II. In multivariate analysis, having sleep-talking (OR, 5.5), type A-like personality (OR 3.9) and dosage of midazolam (OR 1.3) were risk factors of paradoxical reaction. CONCLUSIONS: Paradoxical agitation after midazolam administration was uncommon and can be managed with flumazenil. Paradoxical reaction can be predicted more often in patients with type A-like personality, sleep-talking habit, complaining pain before ERCP, and in patients injected large dosage of midazolam.
Cholangiopancreatography, Endoscopic Retrograde* ; Conscious Sedation* ; Dihydroergotamine ; Flumazenil ; Humans ; Meperidine ; Midazolam* ; Multivariate Analysis ; Risk Factors

BACKGROUND/AIMS: Appropriate sedation during endoscopy can significantly reduce the discomfort experienced by a patient when the procedure is performed; however, it is associated with several potential risks. Very few reports describe sedation-related adverse events occurring during endoscopy. Our study evaluated the current status of sedation-related adverse events during a diagnostic upper endoscopy. MATERIALS AND METHODS: We reviewed medical records of 5,564 cases of diagnostic upper endoscopy performed using midazolam for sedation at the Ewha Womans University, Mokdong Hospital, between January 2015 and March 2016. RESULTS: Among the 5,564 cases, sedation-related adverse events were reported in 56 cases (1.0%). Among these 56 patients, 30 patients (53.6.%) were men and 26 patients (46.4%) were women. Mean age of the patients was 63.7±15.4 years. The most common adverse event reported was hypoxia, which was observed in 37 patients (0.7%). Other adverse events included sedation failure (18 patients, 0.3%) and delayed discharge from the recovery room due to delayed recovery of consciousness (one patient, 0.02%). Among patients presenting with hypoxia, 35 patients recovered after administration of intravenous flumazenil and oxygen via nasal prongs. Administration of oxygen alone helped recovery in 2 patients. All patients recovered uneventfully with no mortalities registered. CONCLUSIONS: Our study showed that the use of sedative midazolam is relatively safe during an upper endoscopy. The rate of occurrence of adverse events was very low, and no fatal adverse events were observed. However, close observation and continuous monitoring is an essential component of safe sedation during endoscopy.
Anoxia ; Conscious Sedation ; Consciousness ; Endoscopy* ; Female ; Flumazenil ; Humans ; Male ; Medical Records ; Midazolam ; Mortality ; Oxygen ; Recovery Room