Effect of converting from propofol to remimazolam with flumazenil reversal on recovery from anesthesia in outpatients with mental disabilities: a randomized controlled trial.

BACKGROUND: General anesthesia is often necessary for dental treatment of outpatients with mental disabilities. Rapid recovery and effective management of postoperative nausea and vomiting (PONV) are critical for outpatients. This study aimed to investigate the effect of transitioning from propofol to remimazolam with flumazenil reversal administered toward the end of surgery during propofol-based total intravenous anesthesia (TIVA) on recovery. METHODS: Adults with mental disabilities scheduled to undergo dental treatment were randomly assigned to receive either propofol-based TIVA (Group P) or propofol-remimazolam-based TIVA with flumazenil reversal (Group PR). Propofol was replaced with remimazolam 1 h before the end of surgery in Group PR; moreover, 0.5 mg of flumazenil was administered after the neuromuscular blockade reversal agent. The primary outcome was the duration of stay in the post-anesthesia care unit (PACU). The secondary outcomes included time to eye-opening, time to extubation, occurrence of PONV, and quality of recovery. RESULTS: Fifty-four patients were included in this study. The duration of stay in the PACU in Group PR was significantly shorter than that in Group P (mean difference, 8.7 min; confidence interval [95% CI], 3.3-14.2; P = 0.002). Group PR exhibited a shorter time to eye opening (mean difference, 5.4 min; 95% CI, 3.3-8.1; P < 0.001) and time to extubation (mean difference, 5.5 min; 95% CI, 3.6-7.9; P < 0.001) than Group P. Neither group required the administration of rescue analgesics, and the incidence of PONV was not reported. CONCLUSIONS: Transitioning from propofol to remimazolam 1 h before the end of surgery followed by flumazenil reversal reduced the duration of stay in the PACU and the time to eye opening and extubation without affecting the incidence of PONV and quality of recovery. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (KCT0007794), Clinical trial first registration date: 12/10/2022.

Remimazolam Compared to Propofol for Total Intravenous Anesthesia with Remifentanil on the Recovery of Psychomotor Function: A Randomized Controlled Trial.

INTRODUCTION: This study aimed to compare remimazolam to propofol in psychomotor recovery after total intravenous anesthesia (TIVA) using the Trieger dot test. METHODS: Sixty-six patients who were scheduled to undergo endoscopic sinus surgery with American Society of Anesthesiologists (ASA) physical status I or II were randomly allocated to the remimazolam (group R) or propofol group (group P). In group R, all patients received flumazenil postoperatively. After discontinuation of anesthetic agents, the time to eye opening, response to verbal commands, extubation, and discharge from the operation room were measured. Psychomotor recovery was assessed using the Trieger dot test before induction and at 0, 30, 60, 90, 120, 150, and 180 min after anesthesia. RESULTS: The time to eye opening, response to verbal commands, extubation, and discharge from the operation room were significantly longer in group P compared to group R (group P: 9.8 ± 3.2 min, 11.5 ± 3.4 min, 12.7 ± 3.4 min, 18.1 ± 4.2 min; group R: 6.5 ± 2 min, 7.3 ± 2.6 min, 8.4 ± 2.9 min, 13.2 ± 3.2 min; respectively, p < 0.05). In the Trieger dot test, the number of dots missed was significantly increased in group R compared to group P at 30, 60, 90, and 120 min after discharge from the operation room (group R: 20.5 ± 9.3, 16 ± 8.8, 14.9 ± 11.1, 14.3 ± 10.8; group P: 14.6 ± 7.8, 10 ± 7.1, 8.7 ± 7.3, 7.3 ± 5.7; respectively, p < 0.05). The maximum distance of dots missed was significantly increased in group R compared to group P at 30 min after discharge from the operation room (group R: 3.9 ± 2.8; group P: 2.7 ± 1.6; p < 0.05). CONCLUSION: Our results suggest that remimazolam with flumazenil leads to rapid recovery following anesthesia; however, it may cause delayed psychomotor decline. CLINICAL TRIAL REGISTRATION: This trial is registered with the University Hospital Medical Information Network (registration number UMIN000044900).

Coma, Severe Hypotension, and Pinpoint Pupils After Olanzapine Intoxication in the Intensive Care Unit with Symptom Reversal After Administration of Flumazenil.

BACKGROUND Olanzapine is an antipsychotic drug and is used in critical care to treat delirium. There is no known antidote to olanzapine intoxication. Overdosing olanzapine can cause, tremor, bradykinesia, hypotension somnolence, coma, and miosis. CASE REPORT We present the case of a previously healthy 69-year-old man who after routine mitral valve surgery developed pneumonia and severe sepsis requiring several weeks on a ventilator in the Intensive Care Unit. He developed delirium and paranoia and was prescribed olanzapine. After 4 doses, he became hypotensive and nonresponsive and developed pinpoint pupils. The symptoms were reversed minutes after administration of flumazenil. The clinical picture in this case corresponds well with an olanzapine intoxication. No other drugs, such as benzodiazepines or opioids, had been administered that could explain the reaction. Olanzapine intoxication is known to present with hypotension, coma, and miosis. The doses given were normal starting doses for olanzapine in the outpatient setting but much higher than recommended doses in the intensive care setting. CONCLUSIONS This case illustrates a risk for severe adverse effects, even within normal prescription range, when olanzapine is used in the intensive care setting. Finally, it is intriguing that the symptoms were reversed after administration of flumazenil, a selective competitive antagonist of the GABA receptor. Olanzapine mainly effects dopamine, serotonin, a1-adrenergic, histamine, and muscarinic receptors, but a low affinity to GABA and benzodiazepine sites can perhaps explain the observed effect.

Midazolam-Induced Hiccups Reversed by Flumazenil: A Case Report.

Hiccups are a common phenomenon experienced by many people and are usually short-lived with spontaneous resolution of symptoms. Certain anesthetic medications have been associated with the development of hiccups, though the underlying pathophysiology and reflex arcs remain poorly understood. We describe a patient who developed hiccups lasting 9 days following an orthopedic surgery and again developed hiccups during a subsequent surgery after only having received midazolam; flumazenil administration led to sustained cessation of his hiccup symptoms immediately.

Bumetanide prevents diazepam-modified anxiety-like behavior in lipopolysaccharide-treated mice.

Benzodiazepine receptor agonists are widely prescribed therapeutic agents that alter gamma-aminobutyric acid (GABA)A receptor activity and have anxiolytic effects. Post-operative use of benzodiazepines is a risk factor of delirium. Inflammatory conditions alter the anxiolytic effects of benzodiazepine. We investigated the effect of diazepam, a typical benzodiazepine anxiolytic, on changes in the emotional behavior of mice in a hole-board test after lipopolysaccharide (LPS) treatment. Diazepam dose-dependently increased the number of head-dips at doses that did not alter locomotor activity; however, diazepam dose-dependently significantly decreased the number of head-dips at doses that did not alter locomotor activity in LPS-treated mice. Flumazenil, a benzodiazepine receptor antagonist, normalized the decrease in head-dipping behavior caused by diazepam treatment in normal and LPS-treated mice. The decrease of the head-dipping effect caused by diazepam was attenuated by minocycline in LPS-treated mice. We further found that the decrease in head-dipping behavior caused by diazepam was blocked by bumetanide, a Na+-K+-2Cl- cotransporter isoform 1 (NKCC1) antagonist, in LPS-treated mice. These findings suggest that diazepam induces the anxiety-like behavior under inflammation conditions, and may cause the GABAA receptor dysfunction associated with the chloride plasticity mediated by NKCC1, which contributes to benzodiazepine-induced delirium after surgery.

Cymbopogon citratus (DC.) Stapf, citral and geraniol exhibit anticonvulsant and neuroprotective effects in pentylenetetrazole-induced seizures in zebrafish.

ETHNOPHARMACOLOGICAL RELEVANCE: Cymbopogon citratus (DC.) Stapf (C. citratus) is consumed as an infusion in folk medicine due to its pharmacological properties and action in the central nervous system. Epilepsy is a neurological disorder that affects millions of people. Since the currently available antiepileptic drugs often cause undesirable side effects, new alternative therapeutic strategies based on medicinal plants have been proposed. AIM OF THE STUDY: This study aimed to investigate the anticonvulsant and neuroprotective effects of C. citratus essential oil (EO) and hydroalcoholic extract (E1) from its leaves, as well as of its related compounds citral (CIT) and geraniol (GER) against the effects of pentylenetetrazole (PTZ) induced seizures in zebrafish (Danio rerio). MATERIALS AND METHODS: To evaluate the anticonvulsant properties of the samples, adult animals were pre-treated (by immersion) and subsequently exposed to PTZ solution. The involvement of GABAA receptors in the antiepileptic effects was investigated by the coadministration of flumazenil (FMZ), a known GABAA receptor antagonist. Oxidative stress markers malondialdehyde (MDA), glutathione (GSH), catalase (CAT) and nitric oxide (NO) were assessed in zebrafish brain homogenates after PTZ exposure. RESULTS: All samples increased the latency time for the first seizure, which was reduced when animals were pretreated with FMZ, suggesting the involvement of GABAA receptors in the observed properties. The association between CIT and GER at the lowest concentration studied showed a synergistic effect on the anticonvulsant activity. Decreases in MDA and NO levels and increases in GSH and CAT levels in the brain of treated animals suggested the neuroprotective effect of the compounds investigated. CONCLUSIONS: Our results proved that C. citratus EO, E1, CIT and GER have anticonvulsant effects in zebrafish and could be used as a promising adjuvant therapeutic strategy for epilepsy treatment. Furthermore, zebrafish demonstrated to be an alternative animal model of epilepsy to evaluate the anticonvulsant and neuroprotective effects of C. citratus.

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

OBJECTIVES: This study aimed to investigate the epidemiology of intravenous midazolam-induced postoperative expressive aphasia (EA). METHODS: The 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. RESULTS: Patients 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%). CONCLUSION: Intravenous 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.

Pharmacological interventions for benzodiazepine discontinuation in chronic benzodiazepine users.

BACKGROUND: Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering. OBJECTIVES: To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use. SEARCH METHODS: We searched the following electronic databases up to October 2017: Cochrane Drugs and Alcohol Group's Specialised Register of Trials, CENTRAL, PubMed, Embase, CINAHL, and ISI Web of Science. We also searched ClinicalTrials.gov, the WHO ICTRP, and ISRCTN registry, and checked the reference lists of included studies for further references to relevant randomised controlled trials. SELECTION CRITERIA: We included randomised controlled trials comparing pharmacological treatment versus placebo or no intervention or versus another pharmacological intervention in adults who had been treated with benzodiazepines for at least two months and/or fulfilled criteria for benzodiazepine dependence (any criteria). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 38 trials (involving 2543 participants), but we could only extract data from 35 trials with 2295 participants. Many different interventions were studied, and no single intervention was assessed in more than four trials. We extracted data on 18 different comparisons. The risk of bias was high in all trials but one. Trial Sequential Analysis showed imprecision for all comparisons.For benzodiazepine discontinuation, we found a potential benefit of valproate at end of intervention (1 study, 27 participants; risk ratio (RR) 2.55, 95% confidence interval (CI) 1.08 to 6.03; very low-quality evidence) and of tricyclic antidepressants at longest follow-up (1 study, 47 participants; RR 2.20, 95% CI 1.27 to 3.82; low-quality evidence).We found potentially positive effects on benzodiazepine withdrawal symptoms of pregabalin (1 study, 106 participants; mean difference (MD) -3.10 points, 95% CI -3.51 to -2.69; very low-quality evidence), captodiame (1 study, 81 participants; MD -1.00 points, 95% CI -1.13 to -0.87; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -3.57 points, 95% CI -5.34 to -1.80; very low-quality evidence), tricyclic antidepressants (1 study, 38 participants; MD -19.78 points, 95% CI -20.25 to -19.31; very low-quality evidence), and flumazenil (3 studies, 58 participants; standardised mean difference -0.95, 95% CI -1.71 to -0.19; very low-quality evidence) at end of intervention. However, the positive effect of paroxetine on benzodiazepine withdrawal symptoms did not persist until longest follow-up (1 study, 54 participants; MD -0.13 points, 95% CI -4.03 to 3.77; very low-quality evidence).The following pharmacological interventions reduced symptoms of anxiety at end of intervention: carbamazepine (1 study, 36 participants; MD -6.00 points, 95% CI -9.58 to -2.42; very low-quality evidence), pregabalin (1 study, 106 participants; MD -4.80 points, 95% CI -5.28 to -4.32; very low-quality evidence), captodiame (1 study, 81 participants; MD -5.70 points, 95% CI -6.05 to -5.35; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -6.75 points, 95% CI -9.64 to -3.86; very low-quality evidence), and flumazenil (1 study, 18 participants; MD -1.30 points, 95% CI -2.28 to -0.32; very low-quality evidence).Two pharmacological treatments seemed to reduce the proportion of participants that relapsed to benzodiazepine use: valproate (1 study, 27 participants; RR 0.31, 95% CI 0.11 to 0.90; very low-quality evidence) and cyamemazine (1 study, 124 participants; RR 0.33, 95% CI 0.14 to 0.78; very low-quality evidence). Alpidem decreased the proportion of participants with benzodiazepine discontinuation (1 study, 25 participants; RR 0.41, 95% CI 0.17 to 0.99; number needed to treat for an additional harmful outcome (NNTH) 2.3 participants; low-quality evidence) and increased the occurrence of withdrawal syndrome (1 study, 145 participants; RR 4.86, 95% CI 1.12 to 21.14; NNTH 5.9 participants; low-quality evidence). Likewise, magnesium aspartate decreased the proportion of participants discontinuing benzodiazepines (1 study, 144 participants; RR 0.80, 95% CI 0.66 to 0.96; NNTH 5.8; very low-quality evidence).Generally, adverse events were insufficiently reported. Specifically, one of the flumazenil trials was discontinued due to severe panic reactions. AUTHORS' CONCLUSIONS: Given the low or very low quality of the evidence for the reported outcomes, and the small number of trials identified with a limited number of participants for each comparison, it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users. Due to poor reporting, adverse events could not be reliably assessed across trials. More randomised controlled trials are required with less risk of systematic errors ('bias') and of random errors ('play of chance') and better and full reporting of patient-centred and long-term clinical outcomes. Such trials ought to be conducted independently of industry involvement.

Neurobiological mechanisms of antiallodynic effect of transcranial direct current stimulation (tDCS) in a mice model of neuropathic pain.

BACKGROUND: Neuropathic pain is relatively common and occurs in approximately 6-8% of the population. It is associated with allodynia and hyperalgesia. Thus, non-pharmacological treatments, such as transcranial direct current stimulation (tDCS) may be useful for relieving pain. OBJECTIVES: This study aimed to investigate the antiallodynic effect of tDCS in a mice model of neuropathic pain, and the underlying neurotransmission systems that could drive these effects. METHODS: Male, Swiss mice, weighing 25-35 g, were subjected to partial sciatic nerve ligation (PSNL). Allodynia was assessed using a Von Frey filament (0.6 g). First, the behavioral time-course of these mice was assessed after 5, 10, 15 and 20 min of tDCS (0.5 mA). Second, the mice that underwent PSNL were assigned to either the tDCS (0.5 mA, 15 min) or tDCS sham group, and further assigned to receive either saline or a drug (i.e., naloxone, yohimbine, a-methyl-p-tyrosine, q-chlorophenylalanine methyl ester, caffeine, 1,3-dipropyl-8-cyclopentylxanthine, AM281, AM630, flumazenil, MK-801, or lidocaine). RESULTS: The antiallodynic effect of tDCS lasted 2 h and 4 h, after 10 min and 15 or 20 min of treatment, respectively (P < .001, P < .01, and P < .05, respectively). The antiallodynic effect of tDCS was associated with all the systems that were analyzed, i.e., the opioidergic (P < .01), adenosinergic (P < .001), serotonergic (P < .01), noradrenergic (P < .001), cannabinoid (P < .001), GABAergic, and glutamatergic (P < .001) systems. Lidocaine did not reverse the antiallodynic effect of tDCS (P > .05). CONCLUSION: The antiallodynic effect of tDCS was associated with different neurotransmitters systems; the duration of these after-effects depended on the time exposure to tDCS.

Sedation in the Ambulatory Endoscopy Center: Optimizing Safety, Expectations and Throughput.

In the United States, sedation and analgesia are the standard of practice when endoscopic procedures are performed in the ambulatory endoscopy center. Over the last 30 years, there has been a dramatic shift of endoscopic procedures from the hospital outpatient department to ambulatory endoscopy centers. This article will discuss sedation and analgesia in the ambulatory endoscopy center as it relates to optimizing safety, patient expectations, and efficiency.

Paradoxical reaction to midazolam in patients undergoing endoscopy under sedation: Incidence, risk factors and the effect of flumazenil.

BACKGROUND: The incidence, risk factors and management strategy of paradoxical reaction to midazolam during endoscopy are yet to be clarified. METHODS: This single center prospective study included 4140 adult patients (2263 males, mean age of 57.7 ± 12.6) undergoing endoscopy under sedation with midazolam and pethidine between September 2011 and December 2011. The characteristics of patients with and without paradoxical reaction were compared. For patients who experienced paradoxical reaction and received flumazenil, their endoscopic images were reviewed to assess whether European Society of Gastrointestinal Endoscopy guidelines were met as quality indicator of endoscopy. RESULTS: The incidence of paradoxical reaction was 1.4%. In multivariate analyses, male gender, unsuccessful sedation in previous endoscopy, upper endoscopy, higher dose of midazolam, and lower dose of pethidine were identified as independent risk factors for paradoxical reaction. Despite paradoxical reaction, endoscopic procedures were successfully completed in 93.3% of cases when flumazenil was administered. The rates of meeting quality indicator of endoscopy were 92.3% in patients receiving flumazenil for paradoxical reaction and 97.6% in patients without paradoxical reaction. CONCLUSIONS: For patients with risk factors for paradoxical reaction, active use of pethidine with a dose reduction of midazolam might be helpful to prevent the occurrence of paradoxical reaction. Administration of flumazenil might be positively considered in cases of paradoxical reaction.

Etomidate with or without flumazenil anesthesia for stem cell transplantation in autistic children.

BACKGROUND: The aim of this study was to investigate etomidate administration with or without flumazenil in autistic children who underwent intrathecal transplantation of stem cells by lumbar puncture. METHODS: Forty autistic children aged 2-12, who were scheduled for stem cell transplantation via lumbar puncture under anesthesia, were randomized for a double-blind study. The children were randomly assigned to two groups: the flumazenil group (group F, n=20) and the etomidate group (group E, n=20). All children received 0.2 mg/kg of etomidate. In the case of inadequate anesthesia, patients received repeated doses of 0.1 mg/kg of etomidate until reaching deep sedation. After operation, children in group F were given flumazenil (0.01 mg/kg) and children in group E received placebo. Heart rate (HR), mean arterial pressure, oxygen saturation, respiratory rate, the Ramsay sedation score (RSS), and recovery time of all children were continuously monitored and recorded during the entire procedure. RESULTS: After anesthesia, blood pressure and HR measurements were not significantly changed in both groups compared with the baseline. There were no respiratory depression, bradycardia, hypotension, nausea, and vomiting. Five patients complained of pain on the site of injection. Myoclonus occurred in seven patients. Recovery time in group F was significantly shorter than in group E (p<0.001), and after the injection of flumazenil, RSS in group F significantly decreased than in group E. There were no significant differences in operation time. Physician satisfaction in both groups was similar. CONCLUSIONS: Etomidate resulted in stable hemodynamic responses and relatively less adverse effects, and flumazenil antagonized the anesthetic effect of etomidate; thus, etomidate with flumazenil is suitable for performing stem cell transplantation in autistic children.

Stability of intraocular pressure after retinal reattachment surgery during electroconvulsive therapy for intractable self-injury in a 12-year-old autistic boy.

We present a 12-year-old autistic boy who underwent electroconvulsive therapy (ECT) for intractable self-injury toward his head and eyes in the context of acute bilateral retinal detachment and reparative surgery. The patient received 3 ECTs before retinal reattachment surgery, and resumed ECT 2 weeks postoperatively. Bilateral intraocular pressures were monitored before and after the first 7 ECTs and intermittently after ECT for 10 months of maintenance ECT. There was no evidence of sustained intraocular pressure elevation or instability. This report supports the safety of ECT for repetitive self-injury in youth before and after emergent ophthalmologic surgery for trauma-related injury.

Sedation-associated complications in endoscopy are not reduced significantly by implementation of the German S-3-guideline and occur in a severe manner only in patients with ASA class III and higher.

INTRODUCTION: The German guideline for sedation in gastrointestinal endoscopy was published in 2008. Several recommendations in this guideline, especially concerning staffing and structural requirements for sedation, have low evidence and therefore are subject to discussion in the field. AIM: Comparison of endoscopic complications in a department specialized for gastrointestinal and pulmological diseases before and after implementation of the German guideline grouped in sedation-associated and non-sedation-associated complications. METHODS: Prospective documentation of complications with retrospective analysis of two patient groups (before guideline: 1.5.2008-30.4.2010; after guideline: 1.5.2010-30.4.2012) at which the sedation technique remained the same (balanced propofol sedation, BPS). RESULTS: Both investigation periods covered almost 7000 procedures. Interventional and general complications were nonsignificantly elevated in the latter group (1.27% before vs. 1.55% after guideline, p = 0.08). Saturation decline (in both groups 0.26%) was unchanged, and circulation-associated complications (0.27% vs. 0.13%, p = 0.07) were reduced nonsignificantly. Necessity for the administration of flumazenil and for intensive care monitoring was reduced in a nonsignificant manner after the implementation of the guideline. Severe complications (reanimation, apnea, and death) were unchanged, and no patient with ASA I-II suffered from a severe complication. Propofol consumption was higher after guideline implementation. CONCLUSIONS: The recommendations of the new German sedation guideline do not significantly reduce complications in endoscopic procedures. Especially, procedures involving patients with ASA classes I and II do not require an additional staff member solely for sedation. Prospective randomized studies might be necessary to optimize the utilization of resources.

Successful treatment of co-occurring catatonia and obsessive-compulsive disorder with concurrent electroconvulsive therapy and benzodiazepine administration.

Catatonia, associated with a variety of medical and psychiatric conditions such as mood disorders and schizophrenia, is frequently treated with either benzodiazepines or with electroconvulsive therapy (ECT) in treatment-resistant cases. Simultaneous treatment with both is usually avoided. Here, we report a case of the use of the benzodiazepine antagonist flumazenil before ECT to facilitate the simultaneous use of lorazepam and ECT for the treatment of co-occurring catatonia and obsessive-compulsive disorder. Both catatonia and obsessive-compulsive disorder symptoms improved in the patient. Physicians should be aware of flumazenil as a clinical tool for use in treatment-resistant cases.

[Case report: a 65-year-old man loses consciousness after colonoscopy]. / Kasuistik interaktiv: Bewusstlos nach Koloskopie. Ein neurologischer Notfall?

Following an uncomplicated outpatient colonoscopy, a patient was found unconscious with bradycardia in the waiting room of a practice of an internist. After a half an ampoule of atropine, the pulse quickened but the patient remained unconscious. Even flumazenil did not improve the situation. The now responding emergency physician was confronted with numerous, unspecific neurological symptoms and considered various differential diagnoses. The situation was aggravated by the rural infrastructure. In the course of the clinical investigation, the patient's condition deteriorated rapidly and intubation was necessary. The correct underlying diagnosis was finally made following a telephone call and disclosed an (almost) fatal chain of misunderstandings.

Ability to reverse deeper levels of unintended sedation.

During gastrointestinal endoscopy, patients may reach a level of sedation that is deeper (i.e. deep sedation) than intended to be (i.e. moderate sedation). In such cases the ability to restore respiratory and cardiovascular function is critical. Supportive measures should be combined with administration of specific pharmacologic antagonists in cases of imminent ventilatory failure. Naloxone rapidly reverses sedation and respiratory depression due to previously administered narcotics, whereas flumazenil overturns the effects of midazolam on the central nervous system. Both agents are administered intravenously in repeated doses according to the patient's response. Caution, however, is required, as the half-lives of these reversal agents are shorter than those of the respective agonists and re-sedation may occur. Acute withdrawal syndromes may take place in chronic users of opiates or benzodiazepine. Product monographs along with administration protocols may be demonstrated as a wall chart, to ascertain their safe and effective use in endoscopy units.

Prospective comparative assessment of buprenorphine overdose with heroin and methadone: clinical characteristics and response to antidotal treatment.

Buprenorphine is a partial opioid agonist with a "ceiling effect" for respiratory depression. Despite this, it has been associated with severe overdoses. Conflicting data exist regarding its response in overdose to naloxone. We compared clinical overdose characteristics of buprenorphine with heroin and methadone and assessed responses to naloxone and flumazenil. Patients admitted to two intensive care units with severe opioid overdoses were enrolled into this 4-year prospective study. Urine and blood toxicological screening were performed to identify overdoses involving predominantly buprenorphine, heroin, or methadone. Eighty-four patients with heroin (n = 26), buprenorphine (n = 39), or methadone (n = 19) overdoses were analyzed. In the buprenorphine group, sedative drug coingestions were frequent (95%), whereas in the methadone group, suicide attempts were significantly more often reported (p = .0007). Buprenorphine overdose induced an opioid syndrome not differing significantly from heroin and methadone in mental status (as measured by Glasgow Coma Score) or arterial blood gases. Mental status depression was not reversed in buprenorphine overdoses with naloxone (0.4-0.8 mg) but did improve with flumazenil (0.2-1 mg) if benzodiazepines were coingested. In conclusion, buprenorphine overdose causes an opioid syndrome clinically indistinguishable from heroin and methadone. Although mental status and respiratory depression are often unresponsive to low-dose naloxone, flumazenil may be effective in buprenorphine overdoses involving benzodiazepines.