Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0027497 (nausea)
23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Flumazenil, a benzodiazepine antagonist, reverses the residual central nervous system effects of benzodiazepines. In this US double-blind, multicenter study, the efficacy of flumazenil was compared with that of placebo in antagonizing the effects of midazolam, a benzodiazepine used to induce intravenous conscious sedation. The mean dose of flumazenil was 0.7 mg, administered intravenously. At 5 minutes posttreatment, 82% of 131 flumazenil-treated patients, compared with 15% of 65 placebo-treated patients, demonstrated complete reversal of sedation. In 85% of patients who responded to flumazenil, this reversal of sedation was maintained throughout the 180-minute observation period. Psychomotor performance returned to prestudy levels 5 minutes posttreatment in 87% of the flumazenil-treated patients, compared with 28% of the placebo-treated patients. At the doses administered, flumazenil was less effective in reversing midazolam-induced amnesia, with only 60% of patients demonstrating partial recovery of memory. It was, nevertheless, more effective than placebo. Flumazenil was well tolerated. Dizziness (10%) and nausea (9%) were the most frequently reported adverse effects. Results of this study demonstrate that flumazenil antagonizes the central nervous system effects of midazolam after intravenous conscious sedation.
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PMID:Reversal of central nervous system effects by flumazenil after intravenous conscious sedation with midazolam: report of a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group I. 128 95

The efficacy and safety of flumazenil in antagonizing the central effects of the benzodiazepine midazolam was demonstrated in patients in whom conscious sedation was induced with midazolam plus an opioid (fentanyl, meperidine, or morphine). In a double-blind, multicenter study, 240 patients were administered flumazenil postoperatively at an average intravenous dose of 0.7 mg (7 ml) and 114 patients were administered an average dose of 9 ml placebo. Complete reversal of sedation was observed in 80% of flumazenil-treated patients and 30% of placebo-treated patients 5 minutes posttreatment. In 87% of patients who responded to flumazenil, the level of alertness was maintained throughout the 180-minute observation period. Midazolam-impaired psychomotor performance returned to normal 5 minutes posttreatment in 80% of the flumazenil-treated patients and 28% of the placebo-treated patients. Flumazenil was less effective in reversing midazolam-induced amnesia, with only 70% of flumazenil-treated patients (and 15% of placebo-treated patients) able to recall the picture shown them at the 5-minute assessment, and fewer patients able to recall pictures shown at later times. Flumazenil was well tolerated, although adverse effects were reported slightly more often than in the placebo group. The most frequent adverse events in both groups were dizziness and nausea. Vital signs were not affected.
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PMID:Reversal of central benzodiazepine effects by intravenous flumazenil after conscious sedation with midazolam and opioids: a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group II. 128 96

The efficacy and safety of a new benzodiazepine antagonist, flumazenil, were assessed in a double-blind multicenter study. Flumazenil (mean dose, 0.76 mg) or placebo (mean dose, 8.9 ml) was administered intravenously to 130 and 67 patients, respectively, who had been given diazepam in conjunction with an opioid (fentanyl, meperidine, or morphine) for the induction and maintenance of intravenous conscious sedation for diagnostic or therapeutic surgical procedures. The group assessable for efficacy comprised 122 patients treated with flumazenil and 64 patients given placebo. After 5 minutes, 80/115 (70%) flumazenil-treated patients, compared with 21/63 (33%) placebo-treated patients, were completely awake and alert, as indicated by a score of 5 on the Observer's Assessment of Alertness/Sedation Scale. Ninety-five percent of patients in each group who attained a score of 5 at the 5-minute assessment showed no loss of alertness throughout the 180-minute assessment period. Flumazenil-treated patients also performed significantly better on the Finger-to-Nose Test and the recall of pictures shown at the 5-minute assessment. Flumazenil was well tolerated, with no serious adverse effects reported. Thirty-nine (30%) of flumazenil-treated patients, compared with 17 (25%) of placebo-treated patients had one or more drug-related adverse experiences. The most common adverse effects were nausea and vomiting in the flumazenil group and nausea and injection-site pain in the placebo group. Flumazenil was found to promptly reverse sedation induced by diazepam in the presence of opioids.
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PMID:Reversal of central benzodiazepine effects by flumazenil after intravenous conscious sedation with diazepam and opioids: report of a double-blind multicenter study. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group II. 128 98

A double-blind clinical trial was conducted to evaluate the efficacy and safety of flumazenil, a benzodiazepine antagonist, in 146 hospitalized patients, who had had general anesthesia induced by midazolam and a long-acting opioid. Ninety-eight patients received flumazenil and 48 received placebo. Administered postoperatively at a mean intravenous dose of 0.84 mg (range: 0.2 mg to 1 mg), flumazenil reversed benzodiazepine-induced sedation to a greater extent than did placebo. At 5 minutes posttreatment, 61 (76%) of 80 flumazenil-treated patients and 7 (18%) of 40 placebo-treated patients had attained a score of 4 or 5 on the Observer's Assessment of Alertness/Sedation Scale, indicating that they were drowsy or fully awake and alert. This level of arousal was maintained for the full 180-minute posttreatment assessment period in 79% of flumazenil-treated patients. Between-group differences in mean change from baseline in level of alertness were statistically significant (P < 0.01) until 60 minutes posttreatment, when the spontaneous recovery of placebo-treated patients resulted in declining intergroup differences. The global efficacy rating (based on the physician's general impression of the effectiveness of the reversal of sedation 5 minutes after test drug administration) was good or excellent in 64 (80%) of the 80 flumazenil-treated patients and 5 (13%) of the 40 placebo-treated patients evaluated. Flumazenil, compared with placebo, was not associated with an increased frequency of operative-site pain, and no serious adverse effects of this benzodiazepine antagonist were reported. The most frequent adverse experiences in both treatment groups were nausea, shivering, and operative-site pain. Vomiting, dizziness, and injection-site reactions were also reported in > or = 5% of patients treated with flumazenil.
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PMID:Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia and use of a long-acting opioid in hospitalized patients: report of a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Hospitalized Patients Study Group II. 128

Flumazenil was studied in a double-blind multicenter trial to confirm its efficacy and safety in antagonizing the central effects of benzodiazepines after general anesthesia (midazolam, short-acting narcotic, nitrous oxide) with muscle relaxants and selected potent volatile anesthetics as needed. One hundred seventy-two outpatients were randomly assigned to receive either flumazenil or placebo titrated to the point of reversal of sedation or a maximum dose of 1 mg of flumazenil or 10 ml of placebo. The test drug was given intravenously (0.2 mg flumazenil or 2 ml placebo) at 1-minute intervals. Tests of alertness, psychomotor function, and memory were conducted prestudy and at baseline before the administration of flumazenil and at 5-, 15-, 30-, 60-, 120-, and 180-minute intervals after administration. The changes from prestudy or baseline scores were analyzed to compare differences between treatment groups. Seventy-five percent of the 105 flumazenil-treated patients and 14% of the 55 placebo-treated patients who met the qualifications for efficacy evaluations obtained a criterion level of response as measured by the Observer's Assessment of Alertness/Sedation Scale. Most (76%) patients who were alert at 5 minutes maintained their level of wakefulness throughout the 180-minute observation period. All 172 patients were included in evaluations of safety. Fifty percent of 113 flumazenil-treated patients and 31% of 59 placebo-treated patients reported one or more adverse experiences. The most frequently reported were nausea, vomiting, and dizziness. Only 6 adverse effects in the flumazenil group and 1 in the placebo group were considered severe; the remainder were mild or moderate. None were considered serious or potentially serious. Postoperative administration of flumazenil (mean dose, 0.85 mg) safely provided a prompt, controlled reversal of the sedative and psychomotor effects of midazolam in most patients.
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PMID:Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia in outpatients premedicated with an opioid and a muscle relaxant: report of a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Outpatients Study Group II. 128 1

Flumazenil, a specific benzodiazepine antagonist, was evaluated as adjunctive therapy in the management of benzodiazepine overdose. Thirteen emergency departments enrolled 326 patients in this double-blind, placebo-controlled trial; 162 patients were randomly allocated to receive flumazenil (maximum dose, 30 ml, providing 3 mg of flumazenil), and 164 were allocated to receive placebo (maximum dose, 30 ml). A successful response was the attainment of a score of 1 or 2 on the Clinical Global Impression Scale (CGIS), denoting a very much improved or much improved status, 10 minutes after the start of intravenous administration of the test drug. Among those patients whose drug screen revealed the presence of benzodiazepines, 75 (77%) of 97 patients given flumazenil and 13 (16%) of 83 given placebo attained such a response. The mean CGIS score at 10 minutes for benzodiazepine-positive patients treated with flumazenil was 1.95 versus 3.58 for those given placebo. As determined by the Neurobehavioral Assessment Scale, 61% of patients who initially responded became resedated; in these patients, the effect of flumazenil lasted a median of 90 minutes. At the investigator's discretion, patients who did not achieve a criterion response in the double-blind trial could receive open-label flumazenil, titrated as in the double-blind phase. Among the benzodiazepine-positive patients, 9 (53%) of 17 patients from the flumazenil group responded to the additional flumazenil, and 58 (81%) of patients previously given placebo responded. Safety was assessed in all 326 patients given the test drug. The most frequent adverse experiences after the administration of flumazenil were agitation (7%), vomiting (7%), abnormal crying (4%), and nausea (4%); these effects were observed with a lower frequency in the placebo group. Serious adverse experiences were reported in 4 patients; these included seizures and cardiac arrhythmias. Of the 3 patients with seizures, 2 had ingested large doses of cyclic antidepressants in addition to the benzodiazepine. The toxicology screen for 1 of the 2 showed 1900 ng/ml of amoxapine and 900 ng/ml of nortriptyline; the toxicology screen for the other, who also had ventricular tachycardia, showed 1928 ng/ml of loxapine and 301 ng/ml of amoxapine. The results of this study confirm published reports of the efficacy of flumazenil in reversing benzodiazepine-induced sedation in patients with benzodiazepine overdose. This was accomplished irrespective of the presence of coingested drugs. Flumazenil is not recommended for patients with serious cyclic antidepressant poisoning or those who use benzodiazepines therapeutically to control seizure disorders. When used as recommended, however, flumazenil has been shown to have an acceptable safety level.
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PMID:Treatment of benzodiazepine overdose with flumazenil. The Flumazenil in Benzodiazepine Intoxication Multicenter Study Group. 128 3

The degree of sedation and amnesia, subjective assessment of awakening and side effects after intravenous injection of 3-4 mg midazolam and 1 mg flumazenil or placebo were studied directly after colonoscopy, and on the first and the eight day. A total of 91 patients were studied; 45 patients were given flumazenil and 46 patients a placebo. Five minutes after injection of the test drugs all 45 patients given flumazenil but only 38 patients given the placebo were alert (p = 0.006). All three response criteria (for sedation, amnesia and subjective assessment of awakening) were fulfilled by 84.4% of the patients given flumazenil and 45.7% of the patients given the placebo (p = 0.0002). Thirty minutes after injection of the test drugs dizziness, nausea, and fatigue were found in 3 patients given flumazenil and in 10 patients given placebo. One day after colonoscopy 9 of 45 patients (20%) given midazolam and flumazenil complained of fatigue and 9 of 46 patients (19.5%) given midazolam and placebo. Eight days (+/- 1 day) later two patients in each group complained of headache, nausea and fatigue. No patient developed phlebitis at the injection site. Flumazenil seems to be a safe and efficient drug for reversing the sedative effect of midazolam, premedication after colonoscopy. However, resedation due to the effects of midazolam may occur. Flumazenil thus permits administration of a higher dose of midazolam without prolongation of the surveillance time. Improved exploitation of time, space and nursing resources is thus possible without jeopardizing patient safety, although caution is necessary since patients may not be fit to resume all normal activities.
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PMID:A randomised controlled trial to evaluate the effects of flumazenil after midazolam premedication in outpatients undergoing colonoscopy. 177 38

Flumazenil (Anexate), a new benzodiazepine antagonist, was administered in doses of 0.2-0.4 mg to 40 patients for reversing the sedative effects of midazolam used as the sole induction agent in doses of 0.15-0.25 mg x kg-1 for short operations with a mean duration of 35 +/- 10 min. Five min after flumazenil was given, 33 patients (82.5%) were fully conscious, while 38 patients (95%) were able to converse 30 min after administration. Flumazenil was very well tolerated in almost all cases, the only side effects being mild confusion in 3 patients and nausea in 3 other cases.
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PMID:Flumazenil in reversal of the central effects of midazolam used as induction agent in general anesthesia. 250 91

Flumazenil (Ro 15-1788) proved to be a very efficacious competitive antagonist of benzodiazepines that reliably counteracts their pharmacological actions within 1-2 min as could be demonstrated in clinical and EEG studies. In general, a total dose of 0.3-0.8 mg will be sufficient in clinical practice, avoiding side effects like nausea, tremor, sweating, or transient anxiety that could be observed when higher dosages were administered. Its therapeutic range is very high as could be demonstrated in experimental animal in which up to 8.000-fold the clinical dose was administered. The total volume of distribution (Vdes) amounts to nearly 1.000 ml/kg BW and the total clearance exceeds 1.200 ml/min, resulting in a biological half-life of less than 60 min. According to the benzodiazepine dosage and the rapid plasma concentration decline of flumazenil, in some cases a resedation could be observed. Hence, a careful observation of the antagonised patient on the ward is mandatory for 1.5-2 h, even if at first sight the antagonization seemed successful and the patient fully awake and cooperative. In anaesthesia, indications to administer flumazenil are adverse drug reactions and prolonged recovery after adequate benzodiazepine dosage. In intensive care medicine, the antagonist may be used in the treatment of benzodiazepine overdose as well as in the differential diagnosis of a coma of unknown origin. Additionally, the antagonist may be administered to interrupt benzodiazepine sedation e.g. for neurological examination.
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PMID:[Antagonism of the effects of benzodiazepines using flumazenil (Ro 15-1788)]. 289 85

We studied the timing and side effects of flumazenil treatment for 10 healthy volunteers and 46 dental outpatients who received intravenous sedation with midazolam. For the volunteers, vital signs were monitored before and after intravenous injection of midazolam and flumazenil. In addition, grip strength, signs and symptoms, and performance on the Romberg's test and addition tests were evaluated 30 min and 60 min after midazolam injection as well as after flumazenil injection. There were no significant changes in vital signs before, immediately after, or 50 min after injection of flumazenil, the latter time corresponding to the half-life of the drug. Thus, awakening from sedation was associated with no effects on the cardiovascular or respiratory systems. Distinct effects of flumazenil were demonstrated by the Romberg's test and the assessment of sedation status. Flumazenil had no effect on the outcome of the addition test. For the outpatients, sedation status and signs and symptoms were studied in patients undergoing procedures lasting 30 min or less (group S) and those undergoing procedures lasting 31 to 60 min (group L). Three patients in group S and one in group L had signs and symptoms of resedation. After treatment with flumazenil, abnormalities such as excitability and nausea were reported by only two patients in group L. One patient in group S had drowsiness that did not resolve after injection of flumazenil and continued until the following day. Our results indicate that flumazenil should be given at least 60 min after intravenous sedation with midazolam in dental outpatients. Moreover, caution should be exercised with regard to the potential side effects of flumazenil.
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PMID:Timing and side effects of flumazenil for dental outpatients receiving intravenous sedation with midazolam. 948 56


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