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Benzodiazepine Overdose

The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform

Valery Rudick – 1st expert on this subject based on the ideXlab platform

  • a risk benefit assessment of flumazenil in the management of Benzodiazepine Overdose
    Drug Safety, 1997
    Co-Authors: Avi A Weinbroum, Valery Rudick, Ron Flaishon, Patrick Sorkine, Oded Szold

    Abstract:

    The worldwide expansion in the use of Benzodiazepines has led to their frequent, and often inappropriate, use and to an increase in their involvement in self-induced poisoning and iatrogenic overdosing. Flumazenil is a specific and competitive antagonist at the central Benzodiazepine receptor, reversing all effects of Benzodiazepine agonists without tranquillising or anticonvulsant actions. Incremental intravenous bolus injections of flumazenil 0.1 to 0.3mg are the most effective and well tolerated in the diagnosis and treatment of pure Benzodiazepine Overdose; additional boluses or an infusion (0.3 to 0.5 mg/h) can be given to prevent patients from relapsing into coma. Intravenous flumazenil 10 to 20 µg/kg is effective in neonates and small children. Intramuscular, oral (20 to 25mg 3 times daily or as required) and rectal administration may be used as alternatives in long term regimens. Patients with mixed-drug Overdose require higher doses (up to 2mg bolus, ≈1 mg/h infusion) to regain consciousness. Children and the elderly, chronically ill patients, and pregnant women and their fetuses all respond satisfactorily to flumazenil, but the usefulness of the drug in patients with hepatic encephalopathy and alcohol Overdose is debatable.

  • A Risk-Benefit Assessment of Flumazenil in the Management of Benzodiazepine Overdose
    Drug Safety, 1997
    Co-Authors: Avi A Weinbroum, Ron Flaishon, Patrick Sorkine, Oded Szold, Valery Rudick

    Abstract:

    The worldwide expansion in the use of Benzodiazepines has led to their frequent, and often inappropriate, use and to an increase in their involvement in self-induced poisoning and iatrogenic overdosing. Flumazenil is a specific and competitive antagonist at the central Benzodiazepine receptor, reversing all effects of Benzodiazepine agonists without tranquillising or anticonvulsant actions. Incremental intravenous bolus injections of flumazenil 0.1 to 0.3mg are the most effective and well tolerated in the diagnosis and treatment of pure Benzodiazepine Overdose; additional boluses or an infusion (0.3 to 0.5 mg/h) can be given to prevent patients from relapsing into coma. Intravenous flumazenil 10 to 20 µg/kg is effective in neonates and small children. Intramuscular, oral (20 to 25mg 3 times daily or as required) and rectal administration may be used as alternatives in long term regimens. Patients with mixed-drug Overdose require higher doses (up to 2mg bolus, ≈1 mg/h infusion) to regain consciousness. Children and the elderly, chronically ill patients, and pregnant women and their fetuses all respond satisfactorily to flumazenil, but the usefulness of the drug in patients with hepatic encephalopathy and alcohol Overdose is debatable. The use of flumazenil results in complete awakening with restoration of upper airway protective reflexes, thus enabling gastric lavage to be performed and transfer of the patient from the emergency room to another hospital department. Resumption of effective spontaneous respiration allows for expeditious extubation, weaning off mechanical ventilation or the avoidance of endotracheal intubation. While flumazenil is not associated with haemodynamic adverse effects, caution should be exercised when using this agent in patients who have co-ingested chloral hydrate or carbamazepine or whose ECG shows abnormalities typical of those seen after Overdose with tricyclic antidepressants (TCAs); the use of flumazenil in the presence of these drugs can sometimes induce treatable cardiac dysrrhythmia. Flumazenil per se does not induce adverse effects. Coma reversal by flumazenil may cause mild, short-lived reactions caused by sudden awakening. Withdrawal symptoms in long term Benzodiazepine users and seizures in patients who have taken an Overdose of TCA or carbamazepine and a Benzodiazepine can occur with flumazenil; these symptoms are avoidable by utilising slow flumazenil dose titration.

Avi A Weinbroum – 2nd expert on this subject based on the ideXlab platform

  • a risk benefit assessment of flumazenil in the management of Benzodiazepine Overdose
    Drug Safety, 1997
    Co-Authors: Avi A Weinbroum, Valery Rudick, Ron Flaishon, Patrick Sorkine, Oded Szold

    Abstract:

    The worldwide expansion in the use of Benzodiazepines has led to their frequent, and often inappropriate, use and to an increase in their involvement in self-induced poisoning and iatrogenic overdosing. Flumazenil is a specific and competitive antagonist at the central Benzodiazepine receptor, reversing all effects of Benzodiazepine agonists without tranquillising or anticonvulsant actions. Incremental intravenous bolus injections of flumazenil 0.1 to 0.3mg are the most effective and well tolerated in the diagnosis and treatment of pure Benzodiazepine Overdose; additional boluses or an infusion (0.3 to 0.5 mg/h) can be given to prevent patients from relapsing into coma. Intravenous flumazenil 10 to 20 µg/kg is effective in neonates and small children. Intramuscular, oral (20 to 25mg 3 times daily or as required) and rectal administration may be used as alternatives in long term regimens. Patients with mixed-drug Overdose require higher doses (up to 2mg bolus, ≈1 mg/h infusion) to regain consciousness. Children and the elderly, chronically ill patients, and pregnant women and their fetuses all respond satisfactorily to flumazenil, but the usefulness of the drug in patients with hepatic encephalopathy and alcohol Overdose is debatable.

  • A Risk-Benefit Assessment of Flumazenil in the Management of Benzodiazepine Overdose
    Drug Safety, 1997
    Co-Authors: Avi A Weinbroum, Ron Flaishon, Patrick Sorkine, Oded Szold, Valery Rudick

    Abstract:

    The worldwide expansion in the use of Benzodiazepines has led to their frequent, and often inappropriate, use and to an increase in their involvement in self-induced poisoning and iatrogenic overdosing. Flumazenil is a specific and competitive antagonist at the central Benzodiazepine receptor, reversing all effects of Benzodiazepine agonists without tranquillising or anticonvulsant actions. Incremental intravenous bolus injections of flumazenil 0.1 to 0.3mg are the most effective and well tolerated in the diagnosis and treatment of pure Benzodiazepine Overdose; additional boluses or an infusion (0.3 to 0.5 mg/h) can be given to prevent patients from relapsing into coma. Intravenous flumazenil 10 to 20 µg/kg is effective in neonates and small children. Intramuscular, oral (20 to 25mg 3 times daily or as required) and rectal administration may be used as alternatives in long term regimens. Patients with mixed-drug Overdose require higher doses (up to 2mg bolus, ≈1 mg/h infusion) to regain consciousness. Children and the elderly, chronically ill patients, and pregnant women and their fetuses all respond satisfactorily to flumazenil, but the usefulness of the drug in patients with hepatic encephalopathy and alcohol Overdose is debatable. The use of flumazenil results in complete awakening with restoration of upper airway protective reflexes, thus enabling gastric lavage to be performed and transfer of the patient from the emergency room to another hospital department. Resumption of effective spontaneous respiration allows for expeditious extubation, weaning off mechanical ventilation or the avoidance of endotracheal intubation. While flumazenil is not associated with haemodynamic adverse effects, caution should be exercised when using this agent in patients who have co-ingested chloral hydrate or carbamazepine or whose ECG shows abnormalities typical of those seen after Overdose with tricyclic antidepressants (TCAs); the use of flumazenil in the presence of these drugs can sometimes induce treatable cardiac dysrrhythmia. Flumazenil per se does not induce adverse effects. Coma reversal by flumazenil may cause mild, short-lived reactions caused by sudden awakening. Withdrawal symptoms in long term Benzodiazepine users and seizures in patients who have taken an Overdose of TCA or carbamazepine and a Benzodiazepine can occur with flumazenil; these symptoms are avoidable by utilising slow flumazenil dose titration.

  • Use of flumazenil in the treatment of drug Overdose: a double-blind and open clinical study in 110 patients.
    Critical Care Medicine, 1996
    Co-Authors: Avi A Weinbroum, Patrick Sorkine, Valeri Rudick, Ygal Nevo, Pinchas Halpern, Eran Geller

    Abstract:

    Objectives To assess the efficacy, usefulness, safety, and dosages of flumazenil required when flumazenil is used in the diagnosis of Benzodiazepine-induced coma (vs. other drug-induced coma), and to reverse or prevent the recurrence of unconsciousness. Design A two-phase study: a controlled, randomized, doubleblind study followed by a prospective, open study. Setting An 800-bed, teaching, university-affiliated hospital. Patients Unconscious patients (n equals 110) suspected of Benzodiazepine Overdose, graded 2 to 4 on the Matthew and Lawson coma scale, were treated with flumazenil, the specific Benzodiazepine receptor antagonist. The first 31 patients were studied in a double-blind fashion, while the rest of the patients were given flumazenil according to an open protocol. Interventions All patients received supplemental oxygen; endotracheal intubation was performed, and synchronized intermittent mandatory ventilation was initiated whenever it was deemed necessary. A peripheral intravenous cannula was inserted, as were indwelling arterial and urinary bladder catheters. Blood pressure, electrocardiogram, respiratory rate, end-tidal CO2, and core temperature were continuously monitored. The first 31 double-blind patients received either intravenous flumazenil (to a maximum of 1 mg) or saline, while the rest of the patients were given flumazenil until either regaining consciousness or a maximum of 2.5 mg was injected. Patients remaining unconscious among double-blind patients or those patients relapsing into coma after the first dose were later treated in the open phase of the study. Treatment continued by boluses or infusion as long as efficacious. Measurements and Main Results Fourteen of 17 double-blind, flumazenil-treated patients woke after a mean of 0.8 plus minus 0.3 (SD) mg vs. one of 14 placebo patients (p less than .001). Seventy-five percent of the aggregated controlled and uncontrolled patients awoke from coma scores of 3.1 plus minus 0.6 to 0.4 plus minus 0.5 (p less than .01) after the injection of 0.7 plus minus 0.3 mg of flumazenil. These patients had high Benzodiazepine serum blood concentrations. Twenty-five percent of the patients did not regain consciousness. These patients had very high serum concentrations of nonBenzodiazepine drugs. Sixty percent of the responders who had primarily ingested Benzodiazepines remained awake for 72 plus minus 37 mins after flumazenil administration; 40% relapsed into coma after 18 plus minus 7 mins and various central nervous system depressant drugs were detected in their blood in addition to Benzodiazepines. Seventy-one percent of the patients had ingested tricyclic antidepressants. Seventy-eight percent of the responders were continually and efficaciously treated for less than equals 8 days. Fourteen (25%) of the intubated patients were extubated safely while 12 patients, who had shown increased respiratory insufficiency, resumed satisfactory respiration after flumazenil injection. Five cases of transient increase in blood pressure and heart rate were encountered. There were 27 mildly unpleasant “waking” episodes, such as anxiety, restlessness, and aggression, but no patient had Benzodiazepine withdrawal signs, convulsions, or dysrhythmia, most noticeably absent in tricyclic antidepressant-intoxicated patients. Conclusions Flumazenil is a valid diagnostic tool for distinguishing pure Benzodiazepine from mixed-drug intoxication or nondrug-induced coma. Flumazenil is effective in preventing recurrence of Benzodiazepine-induced coma. Respiratory insufficiency is reversed after its administration. Flumazenil is safe when administered cautiously, even in patients with coma caused by a mixed Overdose of Benzodiazepine plus tricyclic antidepressants.

Salman Aljarallah – 3rd expert on this subject based on the ideXlab platform

  • acute fatal posthypoxic leukoencephalopathy following Benzodiazepine Overdose a case report and review of the literature
    BMC Neurology, 2015
    Co-Authors: Salman Aljarallah, Fawaz Alhussain

    Abstract:

    Background
    Among the rare neurological complications of substances of abuse is the selective cerebral white matter injury (leukoencephalopathy). Of which, the syndrome of delayed post hypoxic encephalopathy (DPHL) that follows an acute drug Overdose, in addition to “chasing the dragon” toxicity which results from chronic heroin vapor inhalation remain the most commonly described syndromes of toxic leukoencephalopathy. These syndromes are reported in association with opioid use. There are very few cases in the literature that described leukoencephalopathy following Benzodiazepines, especially with an acute and progressive course. In this paper, we present a patient who developed an acute severe fatal leukoencephalopathy following hypoxic coma and systemic shock induced by Benzodiazepine Overdose.

  • Acute fatal posthypoxic leukoencephalopathy following Benzodiazepine Overdose: a case report and review of the literature
    BMC Neurology, 2015
    Co-Authors: Salman Aljarallah, Fawaz Al-hussain

    Abstract:

    Background Among the rare neurological complications of substances of abuse is the selective cerebral white matter injury (leukoencephalopathy). Of which, the syndrome of delayed post hypoxic encephalopathy (DPHL) that follows an acute drug Overdose, in addition to “chasing the dragon” toxicity which results from chronic heroin vapor inhalation remain the most commonly described syndromes of toxic leukoencephalopathy. These syndromes are reported in association with opioid use. There are very few cases in the literature that described leukoencephalopathy following Benzodiazepines, especially with an acute and progressive course. In this paper, we present a patient who developed an acute severe fatal leukoencephalopathy following hypoxic coma and systemic shock induced by Benzodiazepine Overdose. Case presentation A 19-year-old male was found comatose at home and brought to hospital in a deep coma, shock, hypoxia, and acidosis. Brain magnetic resonant imaging (MRI) revealed a strikingly selective white matter injury early in the course of the disease. The patient remained in a comatose state with no signs of neurologic recovery until he died few weeks later following an increase in the brain edema and herniation. Conclusion Toxic leukoencephalopathy can occur acutely following an Overdose of Benzodiazepine and respiratory failure. This is unlike the usual cases of toxic leukoencephalopathy where there is a period of lucidity between the Overdose and the development of white matter disease. Unfortunately, this syndrome remains of an unclear pathophysiology and with no successful treatment.