Administration Of Flumazenil Research Articles

Evaluation of alfaxalone and midazolam with or without flumazenil reversal in Egyptian fruit bats (Rousettus aegyptiacus)

ObjectivesTo evaluate alfaxalone–midazolam anesthesia in Egyptian fruit bats (Rousettus aegyptiacus) and the effect of flumazenil administration on recovery time and quality. Study designRandomized, blinded, crossover and controlled, experimental trial. AnimalsA total of 10 male Egyptian fruit bats. MethodsBats were anesthetized with alfaxalone (15 mg kg−1) and midazolam (2 mg kg−1) administered subcutaneously. During anesthesia, vital signs, muscle tone and reflexes were monitored every 10 minutes. Flumazenil (0.3 mg kg−1) or saline at an equal volume was administered subcutaneously 60 minutes after anesthetic administration. Time to induction, time to first movement and recovery time (flying) were measured. Quality of induction, anesthesia and recovery were assessed on a 1–3 scale (1, poor; 2, good; 3, excellent). ResultsTime to induction was 4.2 ± 1.9 minutes (mean ± standard deviation), with median quality score of 2 (range, 1–3). Anesthesia quality score was 3 (1–3). During anesthesia, heart rate and respiratory frequency decreased significantly and penis relaxation, indicating muscle tone, increased significantly. Administration of flumazenil significantly reduced mean recovery time compared with saline (10 ± 5 versus 45 ± 17 minutes, respectively), and significantly improved the quality of recovery [2.5 (2–3) versus 1 (1–2), respectively]. Conclusions and clinical relevanceAlfaxalone–midazolam anesthesia resulted in good induction, muscle relaxation and sufficient anesthesia to perform routine diagnostic and therapeutic procedures for approximately 40 minutes. Reversal of midazolam with flumazenil is recommended, resulting in quicker and better recovery.

The effects of flumazenil on ventilatory and recovery characteristics in horses following midazolam-ketamine induction and isoflurane anaesthesia.

Flumazenil antagonises the actions of benzodiazepines. There has been no prior research specifically investigating this anaesthetic reversal agent for horses. To determine the effects of flumazenil administration in horses on (a) ventilatory parameters after midazolam-ketamine induction and maintenance with isoflurane in oxygen and on (b) the characteristics of recovery from general anaesthesia. Blinded, randomised, crossover experiment. Six horses were randomly assigned to receive high-dose flumazenil (Fhigh , 20µg/kg), low-dose flumazenil (Flow , 10µg/kg) and saline (control). Cardioventilatory parameters were monitored. After 90minutes of isoflurane anaesthesia, a bolus of Fhigh , Flow or saline was administered i.v. The horses were recovered using head and tail rope assistance. The times to first movement, to achievement of sternal recumbency, to the first attempt to stand and the total recovery time were determined. The recovery quality was evaluated using a 115-point recovery scoring system. The cardioventilatory parameters and recovery times were analysed using mixed-effects regression analyses. Intraclass correlation (ICC) analysis was used to evaluate the recovery scores. A Mann-Whitney U test assessed the relationship between recovery score and flumazenil administration. A significant difference with flumazenil administration was found for SpO2 , mean arterial pressure, I:E ratio, minute volume of ventilation (MV) and peak inspiratory pressure. There was a significant difference with flumazenil administration for the time to sternal recumbency, the time to the first attempt to rise and the total recovery time. There was no significant difference in total recovery score with flumazenil administration. Plasma levels of midazolam and flumazenil were not obtained. Flumazenil has a dose-dependent effect on MV and recovery time, which may make it useful in cases for which a prolonged anaesthetic recovery is undesirable.

Subcutaneous tiletamine-zolazepam immobilization and effect of flumazenil reversal in African pygmy hedgehogs (Atelerix albiventris)

African pygmy hedgehogs ( Atelerix albiventris ) are popular zoological companion animals that routinely require chemical immobilization for veterinary care. The objective of this randomized, blinded, cross-over study was to evaluate the efficacy of low and high dosages of subcutaneous (SC) tiletamine-zolazepam for sedation and the efficacy of flumazenil for recovery in African pygmy hedgehogs. Twelve adult hedgehogs (7 males, 5 females) were administered tiletamine-zolazepam at 10 mg/kg (T10) or 30 mg/kg (T30) SC. Physiologic variables, reflexes and behaviors were monitored to evaluate quality of immobilization. Forty-five minutes after tiletamine-zolazepam injection, hedgehogs were administered flumazenil or an equivalent volume of saline SC. Baseline daily food intake was measured and then recorded daily for 6 days following sedation trials. Median (interquartile range [IQR]) time to onset of first effects for T10 and T30 was 2.9 minutes (2.5–5.3 minutes) and 2 minutes (1.4–2.9 minutes), respectively. Eighty-three percent of T10 and 100% of T30 hedgehogs lost righting reflex. The median (IQR) duration righting reflex was lost for T10 was 32.5 minutes (23.8–37.5 minutes) and it was lost for 47.5 minutes (36.25–63.75 minutes) for T30. Jaw tone was reduced in the majority of animals for both dosages but never lost. Heart and respiratory rate for both treatments remained within normal limits. Hedgehogs became rapidly hypothermic after induction. Flumazenil administration did not have a statistically significant effect on recovery time, but mean recovery times were 18 minutes faster for T10 hedgehogs administered flumazenil. There were no statistically significant differences in food intake within or between dosages of tiletamine-zolazepam at any time point for hedgehogs administered saline or flumazenil; however, mean food intake over the 6 days following T10 administration was 16 g/kg more for hedgehogs administered flumazenil. SC tiletamine-zolazepam at 10 and 30 mg/kg produces dose-dependent heavy sedation to light anesthesia in hedgehogs. Subjectively, while both dosages provided a sufficient depth of immobilization to permit a physical examination and noninvasive procedures like blood collection or diagnostic imaging, some jaw tone was maintained precluding endotracheal intubation. T30 provided a deeper level of immobilization than T10 but longer recovery times. Flumazenil administration did not have a statistically significant effect on recovery but recovery times were noticeably faster following SC flumazenil in hedgehogs sedated with T10. For hedgehogs immobilized with T10, mean food intake was greater when flumazenil was administered. Tiletamine-zolazepam provides an injectable option for immobilization of hedgehogs.

The GABAA-Benzodiazepine Receptor Antagonist Flumazenil Abolishes the Anxiolytic Effects of the Active Constituents of Crocus sativus L. Crocins in Rats.

Anxiety is a chronic severe psychiatric disorder. Crocins are among the various bioactive components of the plant Crocus sativus L. (Iridaceae) and their implication in anxiety is well-documented. However, which is the mechanism of action underlying the anti-anxiety effects of crocins remains unknown. In this context, it has been suggested that these beneficial effects might be ascribed to the agonistic properties of these bioactive ingredients of saffron on the GABA type A receptor. The current experimentation was undertaken to clarify this issue in the rat. For this research project, the light/dark and the open field tests were used. A single injection of crocins (50 mg/kg, i.p., 60 min before testing) induces an anti-anxiety-like effect revealed either in the light-dark or open field tests. Acute administration of the GABAA-benzodiazepine receptor antagonist flumazenil (10 mg/kg, i.p., 30 min before testing) abolished the above mentioned anxiolytic effects of crocins. The current findings suggest a functional interaction between crocins and the GABAA receptor allosteric modulator flumazenil on anxiety.

EVALUATION OF TWO DOSES OF BUTORPHANOL-MEDETOMIDINE-MIDAZOLAM FOR THE IMMOBILIZATION OF WILD VERSUS CAPTIVE BLACK-FOOTED CATS (FELIS NIGRIPES).

The efficacy, safety, physiologic effects, and reversibility of butorphanol-medetomidine-midazolam (BMM) immobilization were evaluated in black-footed cats (Felis nigripes) and compared between captive and wild animals. Nine captive and 14 wild black-footed cats were hand injected into an accessible hind limb muscle group with the BMM combination. The captive cats (captive group) received a lower dose of the combination (butorphanol, 0.25 ± 0.03 mg/kg; medetomidine, 0.06 ± 0.01 mg/kg; midazolam, 0.13 ± 0.02 mg/kg), whereas the wild cats received a higher dose (butorphanol, 0.53 ± 0.11 mg/kg, medetomidine, 0.13 ± 0.03 mg/kg, midazolam, 0.27 ± 0.05 mg/kg). Two capture methods were required to restrain the wild cats; previously collared cats were tracked and excavated out of their burrows during daylight hours (excavated group), whereas uncollared cats were randomly located using spotlights and pursued by a vehicle at night (pursued group). Inductions were rapid and no spontaneous arousals occurred. Mean arterial blood pressure in all cats was within normal limits for domestic cats. Initial rectal temperatures varied greatly among the groups, but decreased in all groups as the immobilization progressed. In the pursued animals, heart rates and respiratory rates were initially elevated. All cats had moderate hypoxemia, hypocapnia, and metabolic acidosis. Intramuscular administration of naltrexone, atipamezole, and flumazenil resulted in rapid, uncomplicated recoveries. BMM is thus a safe, effective immobilizing drug combination for both captive and wild black-footed cats, but higher doses are required in wild animals. The capture methods exerted a greater influence on the physiology of the immobilized animals than did the doses of the drugs used. Although this drug combination can be used safely to immobilize black-footed cats, supplemental oxygen should always be available for use, especially in pursued animals due to hypoxia.

Protective effect of flumazenil infusion in severe acute benzodiazepine toxicity: a pilot randomized trial.

We aimed to investigate the efficacy of flumazenil infusion in the maintenance of arousal and prevention of development of complications in severe benzodiazepine poisoning. Sixty severely poisoned patients (intubated due to loss of consciousness) intoxicated by sole benzodiazepines referred to Loghman Hakim hospital between May 2018 and August 2019 were considered to be included in the current study. All were evaluated for possible contraindications of flumazenil administration. If there were no contraindications, we continued supportive care in one group and supportive care plus flumazenil infusion in the second group. Following response to the stat dose of flumazenil, complications, hospital stay, and outcome were compared between these two groups. A total of 60 benzodiazepine-poisoned patients aged between 16 and 84 years old (37 males and 23 females) were enrolled. There was no statistically significant difference between these two groups regarding the period of hospital stay. Need for intubation significantly decreased in the infusion group. None of the patients experienced seizure or dysrhythmia. One patient died in the control group which received only a stat dose of flumazenil. Administration of flumazenil is safe in benzodiazepine-poisoned patients with appropriate indications. Flumazenil infusion can significantly decrease the need for intubation and subsequent ICU admission. Even though flumazenil is an expensive antidote, its administration may decrease the need for ICU beds in the setting of acute poisoning.

Design, synthesis, and pharmacological evaluation of novel 1,2,4-triazol-3-amine derivatives as potential agonists of GABAA subtype receptors with anticonvulsant and hypnotic effects

In the current study, a series of novel 1,2,4-triazol-3-amine derivatives were designed, synthesized, and biologically evaluated in vivo for their anticonvulsant and hypnotic effects in the pentylenetetrazole (PTZ)-induced seizures, maximal electroshock (MES)-induced seizures, and pentobarbital-induced sleeping tests. Furthermore, the possible side effects of the most potent compounds on the memory, motor coordination, and muscle strength were evaluated in passive avoidance, rotarod, and grip strength tests, respectively. The designed compounds with the main benzodiazepine pharmacophores including aromatic ring and proton accepting group completely mimiced the structure of zolpidem as an α1-selective agonist of GABAA receptor. Compounds 5c (ED50 ≈ 52.5 mg/kg) and 5 g (ED50 ≈ 16.5 mg/kg) in the PTZ test were the most potent compounds among the designed compounds. In the MES test, the observed ED50s for compounds 5c and 5 g were reduced to around 11.8 mg/kg and 10.5 mg/kg, respectively. The considerable hypnotic effect in a dose-dependent manner was observed following the administration of newly synthesized compounds. In all experiments administration of flumazenil as an antagonist of benzodiazepines receptor fully antagonized observed effects which indicated the involvement of GABAA receptors. Since there was no negative effect on memory, motor coordination, and muscle strength following the administration of compounds 5c and 5g as the most potent compounds, it could be concluded that the novel compounds most likely act through α1-containing GABAA receptors and possess no affinity for α5-containing receptors. The newly designed compounds could be considered as leading compounds in synthesizing novel GABAA receptor agonists with minimum side effects.

Postoperative expressive aphasia associated with intravenous midazolam administration: a 5-year retrospective case-control study.

ObjectivesThis study aimed to investigate the epidemiology of intravenous midazolam-induced postoperative expressive aphasia (EA).MethodsThe incidence rate, risk ratio, and contributing factors to intravenous midazolam-induced postoperative EA were analyzed retrospectively in 6756 orthopedic patients. A telephone interview was conducted with patients with EA after surgery.ResultsPatients were allocated to either the midazolam group (n = 6178) or no-midazolam group (n = 578). Twelve patients developed EA in the midazolam group, with an incidence of 0.19%, and no patient developed EA in the no-midazolam group. The mean age of EA patients was 70 years, and 92% were women. Among them, 75% received general anesthesia, and the mean dose of midazolam was 1.8 mg. EA was reversed in nine of 12 (75%) patients within 4 minutes of flumazenil administration, and >60 minutes were required to reverse EA in the other three patients (25%).ConclusionIntravenous midazolam administration for preoperative sedation caused transient EA in 0.19% of patients, especially elderly women who received general anesthesia, and EA could be reversed by flumazenil.

Evaluation of subcutaneous administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius).

To evaluate SC administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). 12 healthy juvenile ball pythons. In a randomized crossover study, each snake was administered a combination of alfaxalone (5 mg/kg [2.3 mg/lb]) and midazolam (0.5 mg/kg [0.23 mg/lb]) and a combination of dexmedetomidine (0.05 mg/kg [0.023 mg/lb]) and midazolam (0.5 mg/kg), SC, with a washout period of at least 7 days between protocols. Respiratory and heart rates and various reflexes and behaviors were assessed and compared between protocols. Forty-five minutes after protocol administration, sedation was reversed by SC administration of flumazenil (0.05 mg/kg) alone or in combination with atipamezole (0.5 mg/kg; dexmedetomidine-midazolam protocol only). Because of difficulties with visual assessment of respiratory effort after sedative administration, the experiment was repeated for a subset of 3 ball pythons, with plethysmography used to assess respiration. Both protocols induced a similar level of moderate sedation with no adverse effects aside from transient apnea. Cardiopulmonary depression was more profound, but time to recovery after reversal was significantly shorter, for the dexmedetomidine-midazolam protocol than for the alfaxalone-midazolam protocol. Plethysmographic findings were consistent with visual observations and suggested that snakes compensated for a decrease in respiratory rate by increasing tidal volume amplitude. Results indicated that both protocols induced clinically relevant sedation in ball pythons and should be useful for minor procedures such as venipuncture and diagnostic imaging. However, caution should be used when sedating snakes with compromised cardiopulmonary function. (J Am Vet Med Assoc 2020;256:573-579.

Airway emergency during general anesthesia in a child with plastic bronchitis following Fontan surgery: a case report

BackgroundPlastic bronchitis (PB) is a complication of Fontan surgery, results in the formation of mucus plug in the tracheobronchial tree, causing potentially fatal airway obstruction. We report critical airway emergency during general anesthesia in a child with plastic bronchitis.Case presentationA 5-year-old boy was scheduled for intrapulmonary lymphatic embolization through percutaneous catheterization under general anesthesia. He underwent Fontan surgery at the age of 2 and frequently developed respiratory failure due to plastic bronchitis. After induction of general anesthesia and tracheal intubation, mechanical ventilation became difficult even with an inspiratory pressure ≥ 50 mmHg due to airway obstruction. He expectorated a large mucus plug through the tracheal tube after administration of sugammadex, naloxone, and flumazenil, and respiratory condition was stabilized thereafter.ConclusionGeneral anesthesia for a patient with plastic bronchitis should be planned with extracorporeal membrane oxygenation or cardiopulmonary bypass stand by.

Tolerance and dependence following chronic alprazolam treatment: quantitative observation studies in female rhesus monkeys.

In order to understand mechanisms underlying tolerance and dependence following chronic benzodiazepine treatments, quantitative and reproducible behavioral models of these phenomena are required. This research evaluated the ability of chronic treatment with a commonly prescribed benzodiazepine, alprazolam, to induce tolerance to sedative effects and physical dependence using a novel set of behavioral measurements in rhesus monkeys. Four female rhesus monkeys (Macaca mulatta) were implanted with chronic intravenous catheters and administered i.v. alprazolam (1.0mg/kg every 4h, 38days total). Quantitative observation measures were obtained during the 38days of treatment. Acute administration of the benzodiazepine receptor antagonist flumazenil (0.1, 0.3mg/kg, i.v.) was given to assess precipitated withdrawal. On day 39, saline was substituted for alprazolam and withdrawal signs were assessed for 7days. Maximal sedation ("deep sedation") was evident on day 1 but was not significantly different from baseline levels by day 4 and was absent for the remainder of the 38days of treatment. A milder form of sedation, "rest/sleep posture," emerged by day 3 and did not decline over 38days. Cessation of alprazolam treatment resulted in significant withdrawal signs (nose rub, vomit, procumbent posture, tremor/jerk, rigid posture) that dissipated by day 3. These signs also were observed with flumazenil (0.3mg/kg). Chronic alprazolam treatment resulted in rapid tolerance to some behaviors (e.g., deep sedation) but no tolerance to others (e.g., rest/sleep posture). Physical dependence was observed via both spontaneous and precipitated withdrawal. Based on previous research, these phenomena may reflect differential plasticity at GABAA receptor subtypes.

Antagonizing the errors of history: bedside experience with flumazenil

Toxicity from sedatives (e.g. benzodiazepines) affects cognition, behavior, and functional status. Although a direct antidote is available, it is rarely used due to fears of withdrawal and seizures. At one toxicology center, flumazenil is routinely employed in the emergency department and acute hospital setting. A dose of 0.5 mg is given IV over 30 s, with repeat doses q1-2h as needed to sedated patients with relaxed autonomic indices and peripheral neurologic status. The following reports a six-year retrospective review of the practice and a one-year close observational study of bedside use of the antidote. Flumazenil was given to 731 patients. The overall positive response rate was over 80%. There were no instances of arrhythmias or seizures. In the prospective year, there were 12 instances of side effects out of 212 patients treated. Three patients experienced drooling, 7 experienced transient anxiety, and there were 2 separate episodes of odd behavior upon awakening from coma in a patient with personality disorder. Comorbid anxiety disorders were associated with anxiety upon arousal, but no patient required medical intervention. No clinically significant adverse events occurred with flumazenil administration in patients who chronically used benzodiazepines or had a history of seizures. We conclude that flumazenil is a safe diagnostic and therapeutic antidote for cases of suspected sedative-hypnotic toxicity.

Anxiolytic activity of Berberis aristata root extract in mice

BACKGROUND: Anxiety is a common emotional response in humans and it is one of most common psychiatric illnesses. Interest in herbal drugs is growing nowadays for the optimum treatment of anxiety. The aim of the present study was to explore the anxiolytic effect of berberine chloride (BER). MATERIALS AND METHODS: Elevated plus maze model was used to know its anxiolytic effect and possible mechanism on acute administration in mice. Six groups of mice with six in each group were used. Group I served as control group; Group II received diazepam (0.5 mg/kg); and Groups III, IV, and V received BER in doses of 2.5, 5, and 10 mg/kg, respectively. Group VI received BER 5 mg/kg after flumazenil 5 mg/kg. RESULTS: As compared to control, berberine chloride solution at all three doses 2.5 mg/kg (P CONCLUSION: Anxiolytics effect of berberine is comparable to diazepam, likely to be mediated by gamma-aminobutyric acid A – Cl− channel complex as effects of berberine were blocked by prior administration of flumazenil. Further studies are needed to identify the phytoconstituents of the berberine which mediated the observed anxiolytic effects.

Flumazenil but not bicuculline counteract the impairing effects of anesthetic ketamine on recognition memory in rats. Evidence for a functional interaction between the GABAA-benzodiazepine receptor and ketamine?

Experimental evidence indicates that anesthetic doses of the non-competitive NMDA receptor antagonist ketamine impair memory abilities in rodents. The mechanism by which anesthetic ketamine produces its adverse behavioural effects is not yet clarified. In this context, it has been proposed that the effects of anesthetic ketamine on memory might be attributed to its agonistic properties on the GABA type A receptor. The present study was designed to address this issue. Thus, we investigated the ability of the benzodiazepine receptor antagonist flumazenil (1, 3, 6 mg/kg, i.p.) and the GABAA receptor antagonist bicuculline (0.5, 1.5, 3 mg/kg, i.p.) to counteract recognition memory deficits produced by anesthetic ketamine (100 mg/kg, i.p.) in rats. For this purpose, the novel object recognition task, a behavioural paradigm assessing recognition memory abilities in rodents was used. Compounds were coadministered 24 h before testing or retention. Pre (24 h before testing) or post-training (24 h before retention) administration of flumazenil (6 mg/kg, i.p.) counteracted anesthetic ketamine-induced performance deficits in the novel object recognition memory task. Conversely, bicuculline failed to attenuate the recognition memory deficits caused by anesthetic ketamine. Our findings propose a functional interaction between anesthetic ketamine and the GABAA receptor allosteric modulator flumazenil on recognition memory.

The Efficacy of Aminophylline on Raising Consciousness in Benzodiazepines-Intoxicated Patients

Background: Loss of consciousness and respiratory failure are the most important medical problems in acute benzodiazepines (BZDs) toxicity. The possibility of respiratory apnea increases in intentional cases and also in the presence of underlying cardiopulmonary diseases. The inhibitory effect of aminophylline on adenosine receptor may be the cause of recovery of consciousness in patients intoxicated by BZDs. The effect of aminophylline as an agonist of cAMP (cyclic adenosine monophosphate), on reversal of inhibitory effects of BZDs (benzodiazepines) on the brain and increasing the level of consciousness is the main question. Method: we reviewed literature sources on topic of aminophylline and consciousness. 29 articles were compiled from prestigious scientific databases such as PubMed, Scopus and Elsevier, from 1983 to 2017. Results: This review showed that intravenous aminophylline can lead to clinical improvement of both consciousness and respiration via antagonizing sedation that induced by BZDs. Although administration of flumazenil is still the first choice for apnea related to BZDs overdose and it is also more potent than aminophylline on reversing sedation, aminophylline can be substituted when flumazenil is not available or when it has contraindication such as in epileptic patients and in overdoses with drugs capable of causing convulsion. Also, aminophylline is useful in those BZD-intoxicated patients with coincident underlying COPD and asthma. Conclusion: intravenous aminophylline could decrease the sedative effects of BZDs and also speed up the recovery of consciousness in patients under sedative effects of BZDs.

The Efficacy of Aminophylline on Raising Consciousness in Benzodiazepines-Intoxicated Patients

Background: Loss of consciousness and respiratory failure are the most important medical problems in acute benzodiazepines (BZDs) toxicity. The possibility of respiratory apnea increases in intentional cases and also in the presence of underlying cardiopulmonary diseases. The inhibitory effect of aminophylline on adenosine receptor may be the cause of recovery of consciousness in patients intoxicated by BZDs. The effect of aminophylline as an agonist of cAMP (cyclic adenosine monophosphate), on reversal of inhibitory effects of BZDs (benzodiazepines) on the brain and increasing the level of consciousness is the main question. Method: we reviewed literature sources on topic of aminophylline and consciousness. 29 articles were compiled from prestigious scientific databases such as PubMed, Scopus and Elsevier, from 1983 to 2017. Results: This review showed that intravenous aminophylline can lead to clinical improvement of both consciousness and respiration via antagonizing sedation that induced by BZDs. Although administration of flumazenil is still the first choice for apnea related to BZDs overdose and it is also more potent than aminophylline on reversing sedation, aminophylline can be substituted when flumazenil is not available or when it has contraindication such as in epileptic patients and in overdoses with drugs capable of causing convulsion. Also, aminophylline is useful in those BZD-intoxicated patients with coincident underlying COPD and asthma. Conclusion: intravenous aminophylline could decrease the sedative effects of BZDs and also speed up the recovery of consciousness in patients under sedative effects of BZDs.

The use of flumazenil for benzodiazepine associated respiratory depression in postanesthesia recovery: risks and outcomes

The primary aim was to determine risk factors for flumazenil administration during postanesthesia recovery. A secondary aim was to describe outcomes among patients who received flumazenil. Patients admitted to the postanesthesia recovery room at a large, academic, tertiary care facility after surgery under general anesthesia from January 1, 2010, to April 30, 2015, were identified and matched to 2 controls each, by age, sex, and surgical procedure. Flumazenil was administered in the recovery phase immediately after general anesthesia, according to the clinical judgment of the anesthesiologist. Demographic, procedural, and outcome data were extracted from the electronic health record. Conditional logistic regression, accounting for the 1:2 matched-set case-control study designs, was used to assess characteristics associated with flumazenil use. The incidence of flumazenil administration in the postanesthesia care unit was 9.9 per 10,000 (95% CI, 8.4-11.6) general anesthetics. History of obstructive sleep apnea (Odds Ratio [OR]=2.27; 95% CI 1.02-5.09), longer anesthesia (OR=1.13; 95% CI 1.03-1.24 per 30minutes), use of total intravenous anesthesia (OR=6.09; 95% CI 2.60-14.25), and use of benzodiazepines (OR=8.17; 95% CI 3.71-17.99) were associated with risk for flumazenil administration. Among patients who received midazolam, cases treated with flumazenil received a higher median (interquartile range) dose than controls: 3.5mg (2.0-4.0mg) vs. 2.0mg (2.0-2.0mg), respectively (p<0.001). Flumazenil use was correlated with a higher rate of unanticipated noninvasive positive pressure ventilation, longer postanesthesia care unit stay, and increased rate of intensive care unit admissions. Patients who required flumazenil postoperatively had received a higher dosage of benzodiazepines and utilized more postoperative health care resources. More conservative perioperative use of benzodiazepines may improve postoperative recovery and use of health care resources.

The use of flumazenil for benzodiazepine associated respiratory depression in postanesthesia recovery: risks and outcomes

Background and objectivesThe primary aim was to determine risk factors for flumazenil administration during postanesthesia recovery. A secondary aim was to describe outcomes among patients who received flumazenil. MethodsPatients admitted to the postanesthesia recovery room at a large, academic, tertiary care facility after surgery under general anesthesia from January 1, 2010, to April 30, 2015, were identified and matched to 2 controls each, by age, sex, and surgical procedure. Flumazenil was administered in the recovery phase immediately after general anesthesia, according to the clinical judgment of the anesthesiologist. Demographic, procedural, and outcome data were extracted from the electronic health record. Conditional logistic regression, accounting for the 1:2 matched-set case-control study designs, was used to assess characteristics associated with flumazenil use. ResultsThe incidence of flumazenil administration in the postanesthesia care unit was 9.9 per 10,000 (95% CI, 8.4–11.6) general anesthetics. History of obstructive sleep apnea (Odds Ratio [OR]=2.27; 95% CI 1.02–5.09), longer anesthesia (OR=1.13; 95% CI 1.03–1.24 per 30minutes), use of total intravenous anesthesia (OR=6.09; 95% CI 2.60–14.25), and use of benzodiazepines (OR=8.17; 95% CI 3.71–17.99) were associated with risk for flumazenil administration. Among patients who received midazolam, cases treated with flumazenil received a higher median (interquartile range) dose than controls: 3.5mg (2.0–4.0mg) vs. 2.0mg (2.0–2.0mg), respectively (p<0.001). Flumazenil use was correlated with a higher rate of unanticipated noninvasive positive pressure ventilation, longer postanesthesia care unit stay, and increased rate of intensive care unit admissions. ConclusionsPatients who required flumazenil postoperatively had received a higher dosage of benzodiazepines and utilized more postoperative health care resources. More conservative perioperative use of benzodiazepines may improve postoperative recovery and use of health care resources.

Efficacy and safety of flumazenil injection for the reversal of midazolam sedation after elective outpatient endoscopy.

Midazolam sedation during elective endoscopy is widely performed and flumazenil is frequently administered after endoscopy to reverse sedation in clinical practice. This study aimed to investigate the safety and efficacy of flumazenil injections after elective endoscopy under midazolam sedation. Participants who underwent an upper endoscopy under midazolam sedation were randomly divided into two groups. In group I, flumazenil was administered i.v. 10 min after the patient's transfer to the recovery room, and no antidote was injected in group II. The time of stay in the recovery room and adverse events were reviewed through the nursing records. We asked the patients about their pain and degree of satisfaction according to a visual analogue scale (VAS), their memory of the procedure, mental status and the presence of uncomfortable symptoms on the day of the procedure and the day afterwards. The length of stay in recovery was significantly shorter in group I than in group II. No significant differences were found in the number of patients with pain (VAS ≥1), adverse events and discomfort between the two groups. Additionally, there were no differences in the patients' memory of the procedure, satisfaction with sedation, willingness to repeat the endoscopy and mental status. The time in the recovery room after flumazenil administration was significantly shortened, and the use of the drug did not increase the risk of adverse events or discomfort. The use of flumazenil for reversing midazolam sedation seems to be safe and effective.

Midazolam use for dental conscious sedation: how safe are we?

Aim: To explore the safety awareness of midazolam use amongst dentist in the UK. Materials and methods: A cross-sectional study on 203 dentists was undertaken, 146 of whom currently practice conscious sedation using intravenous midazolam. Use of high strength midazolam; awareness of the Rapid Response Report (RRR) and the National Reporting and Learning System (NRLS); and midazolam related incidents were explored. Results: Formal training in conscious sedation was variable with 35.6% holding a postgraduate sedation qualification. Flumazenil administration was common practice (63%) although used very selectively. Use to reverse respiratory depression was minimal (4%). Awareness of the RRR and the NRLS was generally low but higher among those working in general dental practice (p<0.05). Comparative analysis showed that high dose midazolam was administered more frequently in gastroenterology than in dentistry (p<0.001) with higher incidences of overdose (12.4% Vs 4.8%) and death (8.3% Vs 0%) within a 3 year period. Conclusions: High strength midazolam administration remains prevalent in dentistry, despite recommendations by the DoH. Use of flumazenil for reasons other than respiratory depression in dentistry should warrant little concern. The low incidence of reported harm is positive but may be due to a lack of uptake of national reporting systems.