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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[Chronic myelogenous leukemia complicated by drug-induced agranulocytosis].

We describe a patient with chronic myelogenous leukemia (CML) who developed drug-induced agranulocytosis. A 75-year-old female was diagnosed with CML in December 2001. She had been receiving imatinib therapy for more than five years. In August 2007, she was hospitalized due to a severe neutropenia 10 days after colonoscopy. She was diagnosed as having agranulocytosis induced by colonoscopy premedication including scopolamine butylbromide and flumazenil. Severe neutropenia was resolved by G-CSF treatment without CML progression. Agranulocytosis in patients with CML is rare, but potentially lethal. Here, we report the clinical course in this patient.

Segurança da ecocardiografia transesofágica em adultos: Estudo em um hospital multidisciplinar / Safety of transesophageal echocardiography in adults: study in a multidisciplinary hospital / Seguridad de la ecocardiografía transesofágica en adultos: Estudio en un hospital multidisciplinario

FUNDAMENTO: A ecocardiografia transesofágica (ETE) é um exame semi-invasivo amplamente utilizado e seu uso associado a sedativos poderá influenciar a segurança do procedimento. OBJETIVO: analisar aspectos da segurança da ETE associada ao uso de midazolam (MZ) e flumazenil (FL) e a influência de variáveis clínicas na taxa de eventos. MÉTODO: estudo prospectivo com 137 pacientes que realizaram ETE com MZ associado à sedação moderada. Analisamos as seguintes ocorrências: complicações com anestesia tópica, ao uso do MZ e complicações relacionadas ao procedimento. Análises uni e multivariada foram usadas para testar a influência das variáveis clínicas: idade, sexo, acidente vascular cerebral (AVC), miocardiopatia (MP), duração do exame, insuficiência mitral (IM) e dose de MZ. RESULTADOS: todos pacientes (65±16 anos; 58 por cento masculino) completaram o exame. As doses médias de MZ e FL foram de 4,3±1,9 mg e 0,28±0,2 mg, respectivamente. A duração do exame e a fração de ejeção (FE) média foram de 16.4±6.1 minutos e 60±9 por cento, respectivamente. O evento mais comum foi a hipóxia leve (SO2<90 por cento), em 11 pacientes; 3 pacientes (2 por cento) apresentaram hipóxia transitória por obstrução da via aérea superior na passagem da sonda, enquanto 8 (5,8 por cento) apresentaram hipóxia devido ao uso do MZ. Hipotensão transitória (PAS<90 mmHg) ocorreu em 1 paciente (0,7 por cento). A análise multivariada mostrou que insuficiência mitral (IM) importante, MP (FE<45 por cento) e altas doses do MZ (>5mg) tiveram associação com tais eventos (p<0,001). A FE no grupo com MP foi de 40 por cento, ao passo que, no grupo com insuficiência mitral (IM), esse percentual foi de 44 por cento, podendo ser este um fator associado a eventos clínicos neste último grupo. CONCLUSÃO: ETE com sedação tem baixas taxas de eventos. Não se observou eventos graves e não houve a necessidade de interrupção dos exames.

BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65±16 yrs; 58 percent males) finished the examination. The mean doses of MZ and FL were 4.3±1.9 mg and 0.28±0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4±6.1 minutes and 60±9 percent, respectively. Mild hypoxia (SO2<90 percent) was the most common event (11 patients); 3 patients (2 percent) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8 percent) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7 percent). The multivariate analysis showed that severe MR, MP (EF<45 percent) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40 percent, in the group with MP and 44 percent in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.

FUNDAMENTO: La ecocardiografía transesofágica (ETE) es un examen semiinvasivo ampliamente utilizado y su uso asociado a sedantes puede influir sobre la seguridad del procedimiento. OBJETIVO: Analizar aspectos de la seguridad de la ETE asociada al uso de midazolam (MZ) y flumazenil (FL) y la influencia de variables clínicas en la tasa de complicaciones. MÉTODO: Estudio prospectivo con 137 pacientes, a quienes se realizó ETE con MZ asociado a la sedación moderada. Analizamos los siguientes eventos: complicaciones con anestesia local, relacionadas al uso de MZ y complicaciones relacionadas con el procedimiento. Se utilizaron análisis uni y multivariados para evaluar la influencia de las variables clínicas: edad, sexo, accidente cerebrovascular (ACV), miocardiopatía (MP), duración del estudio, insuficiencia mitral (IM) y dosis de MZ. RESULTADOS: Todos los pacientes (65±16 años; 58 por ciento masculino) completaron el estudio. Las dosis promedio de MZ y FL fueron de 4,3±1,9 mg y 0,28±0,2 mg, respectivamente. La duración del estudio y la fracción de eyección (FE) promedio fueron de 16.4±6.1 minutos y 60±9 por ciento, respectivamente. El evento más común fue la hipoxia leve (SO2<90 por ciento), en 11 pacientes; 3 pacientes (2 por ciento) presentaron hipoxia transitoria por obstrucción de la vía aérea superior con el pasaje de la sonda, mientras que 8 (5,8 por ciento) presentaron hipoxia debido a la utilización del MZ. Un paciente (0.7 por ciento) padeció hipotensión transitoria (PAS<90 mmHg). El análisis multivariado mostró que IM significativa, MP (FE<45 por ciento) y altas dosis de MZ (>5mg) se asociaron a tales complicaciones (p<0,001). La FE en el grupo con MP fue de 40 por ciento, mientras que, en el grupo con insuficiencia mitral, ese porcentaje fue de 44 por ciento, pudiendo ser éste un factor asociado a complicaciones clínicas en este último grupo. CONCLUSIÓN: ETE con sedación presenta bajas tasas de ...

Actividad del Flumazenil sobre el efecto depresor del Baclofén / Flumazenil acctivity on the depressing effect induced by Baclofen

Es un estudio experimental tipo ensayo terapéutico realizado en 200 ratones machos cepa NMRI, de 8 a 12 semanas de edad y peso de 31,7 gr pertenecientes al bioterio de la Uni versidad de Los Andes, con la finalidad de determinar si el Flumazenil es un antagonista competitivo o no competitivo, y su actividad sobre el efecto depresor inducido por el Baclofén mediante la evaluación de la actividad locomotora y la prueba de la barra horizontal. Previamente se estableció la dosis letal del Baclofén en 110 ratones, obteniendo una DL50 de 40,88 mg/kg para este estudio. Los resultados indican que el Flumazenil elevó la dosis letal a 47,92 mg/kg. En la prueba de la barra horizontal, prolongó el tiempo de caída de los ratones. Sobre la actividad locomotora, la administración de Baclofén produjo una reducción durante la 1ª hora (22,71%), y elevación durante la 2ª y 3ª ho ras (45,27% y 30,62% respectivamente). En el grupo trata do con Flumazenil más Baclofén se observó una reducción de la actividad locomotora en la tres horas de observación (67,47%, 60,12% y 45,85%) Se comprobó que no existe desvío de paralelismo entre las dos rectas de la curva gráfica de dosis-respuesta. Conclusión: No se conoce un antídoto efectivo para contrarrestar la depresión del SNC inducida por el Baclofén. El Flumazenil es un antagonista competitivo que actúa a nivel de los receptores gammaaminobutíricos. Se demostró en este estudio que el Flumazenil retrasó la mortalidad inducida por el Baclofén.

It is a comparative study and experimental field conducted in 100 male mice NMRI class, 8 to 12 weeks and weighing 31.7 grams of bioterio de la Universidad de Los Andes, with the aim of establishing the locomotor activity and test bar horizontal Flumazenil on the depressing effect induced by Baclofen. Before establishing the dose lethality of baclofen in 40.88 mg / kg for this study. The results indicate that Flumazenil rose 47.92 a lethal dose mg / kg. In proof of the horizontal bar, prolonged the time to drop in mice. In the group treated with Flumazenil more Baclofen was observed a reduction in activity locomotive to three hours, while Baclofen produced declined during the first hour, 1, and elevators during the 2 nd and 3 rd hour. It was found that there is no parallelism between the two lines of the dose-response curve. Conclusion: There is no known antidote to counteract the effects of the central nervous system depression induced by Baclofen. The Flumazenil is an antagonist benzodiazepines, which operates a level of receptors ganmaaminobutíricos, was demonstrated in this study decrease in mortality induced by Baclofen.

Midazolam-flumazenil topical anaesthesia for microlaryngoscopy with jet ventilation.

A comparison between midazolam and midazolam-flumazenil for total intravenous anaesthesia in combination with topical anaesthesia and muscle relaxants was performed in a double-blind, parallel study in 40 patients scheduled for microlaryngoscopy with or without bronchoscopic procedures using jet ventilation with oxygen. A single intravenous injection of midazolam 0.3 mg/kg, lignocaine spray and muscle relaxants provided adequate anaesthesia and good operative conditions throughout the procedures, which took 20 to 30 minutes. Patients who had placebo at the end of the procedures had a longer recovery and a high incidence of airway obstruction (20%). Administration of flumazenil provided prompt awakening in 19 of 20 patients (95%) within five minutes, resulting in rapid and favourable recovery without resedation or other side-effects, while only three of 20 (15%) patients in the placebo-treated group had improved consciousness within five minutes. The simplicity and reliability of the midazolam-flumazenil technique is attractive. We consider it worthy of further investigation for wider application in clinical practice.

Clinical applications of commonly used contemporary antidotes. A US perspective.

Poisonings are a common problem. In 1995, over 2 million exposures were reported to American poison information centres alone. The majority of poisoning exposures can be treated without major therapeutic intervention. If therapy is indicated, it is usually in the form of gastrointestinal decontamination with activated charcoal, to prevent absorption of the toxin and the subsequent toxicity that may occur. In a limited number of cases, more aggressive life-support measures may be necessary to treat the adverse effects of poisons. Occasionally, that intervention may include the use of pharmacological antagonists, more commonly referred to as antidotes. According to the American Association of Poison Control Centers, the most commonly used antidotes are acetylcysteine, naloxone, atropine, deferoxamine (desferrioxamine) and antivenins. Overall, 17 antidotes account for 99% of all antidote use and those agents are reviewed in this article. With the exception of naloxone, most antidotes have pharmacological effects that are independent of their inherent antidotal properties. Therefore, antidotes should be used judiciously because their pharmacological properties may exacerbate pre-existing toxicity and only in rare circumstances are they used prophylactically. Some antidotes, such as digoxin-specific antigen binding fragments (digoxin immune Fab), are very expensive, and both the risk: benefit ratio and the associated cost should be considered before the antidote is administered. The principle aims are to "treat the patient, not the poison' and to do no harm to the patient. Antidotes should be used only when they are indicated and may help a patient.

A placebo controlled study of flumazenil in bronchoscopic procedures.

METHODS: A double-blind, randomized, placebo controlled trial of the efficacy of flumazenil was conducted in 22 consecutive patients admitted for bronchoscopy. Sedation was induced by individually titrated amounts of intravenous diazepam (mean +/- s.d., 15.75 +/- 4.4 mg). Post bronchoscopy, patients received up to 1 mg of the benzodiazepine antagonist flumazenil (Anexate) or placebo intravenously. Clinical scores for the degree of sedation, orientation in time and space, co-operation and anterograde amnesia were used. These, together with three psychometric tests were performed twice prior to bronchoscopy and on eight occasions in the following 24 h. The psychometric tests were: Tapping Test (TT), Simple Reaction Time (SRT) and Critical Flicker Fusion (CFF) and these were carried out using the automated Multipsy test system. RESULTS: The level of co-operation, orientation in time and space and anterograde amnesia were similar in both groups pre-and-post procedure. However compared with the pre-bronchoscopy assessment, the maximum degree of apparent sedation was significantly less in the flumazenil group in the first 4 h. In support of this, the patients in the flumazenil group also showed a significantly greater proficiency with the TT and CFF test post bronchoscopy (P < 0.05). There was no difference in the incidence of side effects and flumazenil was well tolerated. CONCLUSIONS: In this highly controlled setting, the use of flumazenil (Anexate) was shown to be safe and effective in aiding recovery from benzodiazepine facilitated bronchoscopy and as such provides an additional level of safety for this procedure.

Antidotes: benefits and risks.

The ability of naloxone and flumazenil to reverse serious toxicity due to their respective agonists is well known. Their adverse effects are minor and few but flumazenil administration may unmask seizures in poisoning with combinations of benzodiazepines and tricyclic antidepressants. The desferrioxamine challenge test is frequently falsely negative and should be abandoned. In addition to being cytoprotective, N-acetylcysteine has potent vasodilator and positive inotropic actions which may be partly responsible for its beneficial effect in late-presentation paracetamol overdosage with hepatic damage and failure.

Distúrbio de pânico e comorbidade clínica / Panic disorder and clinical comorbidity

Os autores abordam o distúrbio do pânico considerando nao só as manifestaçoes psiquiátricas mas também as possibilidades biológicas bem como as várias patologias que podem cursar com sintomatologia semelhante às crises de pânico.

Sedation with midazolam during regional anaesthesia: is there a role for flumazenil?

The aim of this study was to reassess the efficacy of flumazenil for reversal of sedation with midazolam. Twenty-four ASA I or II patients undergoing elective surgery under epidural anaesthesia participated. Following epidural block, midazolam was administered to keep the patient sleepy but still responsive to verbal commands. At the end of surgery the patients were randomly allocated to receive, in a double-blind manner, either flumazenil (0.1 mg.ml-1) or placebo. The study drug (maximum dose: 10 ml) was titrated until the patient became fully awake. Sedation was assessed with the Modified Steward Coma Scale (MSCS), the Trieger test (TT) and Critical Flicker Frequency (CFF). The assessments were done before anaesthesia (baseline), at the end of surgery immediately before administration of study drug, and serially afterwards, at 10, 30, 60, 90, 120, 150 and 180 min. Analyses of variance for repeated measures and pooled t tests were used. The duration of surgery was (mean +/- SD) 0.72 +/- 0.25 hr in the flumazenil group and 0.74 +/- 0.28 hr in the placebo group. The total dose of midazolam was 7.2 +/- 2.2 mg for the flumazenil group and 8.9 +/- 2.7 mg for the placebo group. The volume of study drug administered was 5.5 ml +/- 1.9, equivalent to 0.55 mg, for the flumazenil group and 6.7 +/- 2.2 ml for the placebo group. Critical Flicker Frequency is the only measure which revealed a difference (P < 0.005) between the flumazenil and placebo groups and this occurred only at the ten-minute assessment.(ABSTRACT TRUNCATED AT 250 WORDS)

Flumazenil: a benzodiazepine antagonist.

The mechanism of action, pharmacokinetics, and use of flumazenil in benzodiazepine overdose, as well as in the management of other disease states, are reviewed. Flumazenil interacts at the central benzodiazepine receptor to antagonize or reverse the behavioral, neurologic, and electrophysiologic effects of benzodiazepine agonists and inverse agonists. Flumazenil has been studied for a variety of indications, including as an antidote to benzodiazepine overdose and for awakening of comatose patients, reversal of sedation after surgery and in critically ill patients, and management of hepatic encephalopathy. It improves the level of consciousness in patients with benzodiazepine overdose; however, resedation may occur within one to two hours after administration, so repeated doses or a continuous infusion may be required to maintain therapeutic efficacy. It appears to be effective in reversing sedation induced by midazolam or diazepam, and case reports suggest that it is useful in awakening comatose patients, although its clinical utility is questionable. Flumazenil has proved useful in reversing conscious sedation in critically ill patients, although response may be dose dependent. Animal models indicate that flumazenil is of some benefit in hepatic encephalopathy, but until well-designed clinical trials are conducted, hepatic encephalopathy must be considered an investigational indication for flumazenil. Adverse reactions include CNS manifestations, resedation, cardiovascular effects, seizures, and alterations in intracranial pressure and cerebral perfusion pressure. Hepatic dysfunction results in a substantial change in the pharmacokinetic profile of flumazenil; therefore, dosage adjustment may be necessary in patients with hepatic dysfunction or in those receiving medications that alter flumazenil metabolism. Flumazenil has been shown to reverse sedation caused by intoxication with benzodiazepines alone or benzodiazepines in combination with other agents, but it should not be used when cyclic antidepressant intoxication is suspected. It may be beneficial after surgery when benzodiazepines have been used as part of anesthesia and after a diagnostic or surgical procedure when assessment of CNS function is necessary.

[Tetraplegia after colonoscopy: benzodiazepine withdrawal syndrome induced by flumazenil?]. / Tétraplégie au décours d'une colonoscopie: syndrome de sevrage aux benzodiazépines induit par le flumazénil?

A case is reported of a 68-year-old female patient who developed a flaccid tetraplegia on recovering from a colonoscopy, carried out under general anaesthesia (3 mg of midazolam, 20 mg of etomidate). During the preanaesthetic visit, she omitted to report a 15-year-addiction to lorazepam 2.5 mg every night. At the end of the procedure, 0.2 mg of flumazenil were injected. Recovery was immediate but followed by neurological signs associating general weakness, paraesthesia and tetraplegia. These symptoms discontinued spontaneously two hours later. She was discharged the same day but complained of myalgia and paraesthesia for a week. The physiopathology of this accident is unknown. The differential diagnosis and the influence of flumazenil on benzodiazepine withdrawal are discussed.

A randomised controlled trial to evaluate the effects of flumazenil after midazolam premedication in outpatients undergoing colonoscopy.

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.

Reversal of benzodiazepine sedation with the antagonist flumazenil.

The effectiveness of the benzodiazepine antagonist, flumazenil, was evaluated in a randomized double-blind clinical study in which diazepam 0.2 mg kg-1 or midazolam 0.1 mg kg-1 was used for i.v. sedation. We studied 120 day-case patients undergoing gastroscopy and treated with either flumazenil 0.1-2 mg or placebo after the procedure. Psychometric assessment of four aspects of recovery over a 3-h period showed that flumazenil attenuated the sedative effects of the benzodiazepines, but did not antagonize the sedation completely. For patients sedated with diazepam, there was a significant effect of flumazenil on speed of motor co-ordination after 90 min (P less than 0.01), and for those given midazolam a similar effect was found at 20 min (P less than 0.01). However, after 3 h all four groups of patients had not returned to baseline performance in accuracy of motor co-ordination (P less than 0.01) and cortical arousal (P less than 0.05), and the two groups sedated with diazepam still displayed memory deficits (P less than 0.05). Flumazenil did not attenuate the subjective experience of sedation as measured by visual analogue scales. These results indicate that sedation is multidimensional, differentially affecting the hierarchy of cognitive functions. In day-cases, antagonism of benzodiazepine sedation with flumazenil would not hasten the safe discharge of patients.

[Antagonizing the effect of midazolam by flumazenil in gastroscopy: results of a randomized double blind study]. / Zur Aufhebung der Wirkung von Midazolam durch Flumazenil bei der Gastroskopie: Ergebnisse einer randomisierten Doppelblindstudie.

The action and side effects of the benzodiazepine antagonist Flumazenil were evaluated and compared with placebo in a double blind parallel group randomized trial involving 40 patients having upper gastrointestinal endoscopy under Midazolam premedication. Flumazenil reversed the hypnotic effect of midazolam within a few minutes. The patients were alert, cooperative, oriented and had recall of events after endoscopy. The effects were better than placebo concerning alertness for up to 30 minutes after administration whereas drowsiness remained almost stable after placebo. Time to reach full alertness was shorter after Flumazenil compared with placebo (42 vs 62 minutes). There were no significant side effects. Flumazenil allows effective reversal of midazolam premedication after upper gastrointestinal endoscopy.

Additional subcutaneous administration of flumazenil does not shorten recovery time after midazolam.

We assessed the efficacy of subcutaneous administration of flumazenil (Anexate, Roche), a specific benzodiazepine antagonist, in preventing resedation after initial reversal of midazolam sedation in 30 patients (ASA I-II) undergoing gynaecological surgery. In the post-operative period, the patients received flumazenil i.v. and placebo s.c. (group A), flumazenil i.v. and flumazenil s.c. (group B), or placebo i.v. and placebo s.c. (control group) in a randomized, double-blind procedure. Flumazenil (group A: 0.47 (SD 0.12) mg i.v., group B: 0.48 (0.06) mg i.v.) was significantly more effective than placebo in antagonizing the sedative effects of midazolam, but was accompanied by rebound sedation after 90 min. Additional s.c. administration of flumazenil 0.1 mg (group B) did not eliminate resedation. Undesirable side effects include nausea and vomiting. Local tolerance of the subcutaneous administration of flumazenil was good.

The use of midazolam and flumazenil in diagnostic and short surgical procedures.

Benzodiazepines, used correctly, provide a relatively safe means of providing sedation in a variety of clinical situations and midazolam, which is shorter acting than other benzodiazepines (BZ), is the drug of choice in ambulatory patients. Flumazenil is a highly effective specific competitive BZ antagonist which provides a safe means of rapidly attenuating or terminating BZ sedation. Its mean half-life is 54 min, and in this contact the optimal dosage is 0.2 to 0.5 mg. Although it reverses sedation and amnesia, there is still a question about whether its efficacy in reversing the respiratory depressant effects of benzodiazepines is adequate. This remains an area of critical debate, as does resedation and also its administration to chronic benzodiazepine users. The use of flumazenil to reverse midazolam-induced sedation introduces, for the first time, the possibility of terminating sedation at a predetermined time. Were it to be adopted routinely, it has major implications for the improvement of patient management affecting all aspects of post-operative care.