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Benzodiazepine Overdose

Benzodiazepine overdose is a serious condition resulting from administration of high doses of drug belonging to the group benzodiazepines. Consequences of such disorder may be lethal and associated with respiratory or cardiac failure. The frequency of benzodiazepine overdose is increasing, designating the prompt diagnosis to be a crucial factor.


Presentation

Benzodiazepine overdose is a common cause of hospitalization in the United States, associated with about 30% of overdose cases. Such incidences fixedly increase in quantity and are important to consider when dealing with patients who have a history of drug abuse or predisposing factors for a possible overdose. These comprise e.g. psychological disorders, post-traumatic stress syndrome in patients with a military background, depressive or suicidal states.

Benzodiazepines are a class of medication with anxiolytic, analgesic, sedative and hypnotic features marking them a target of drug abuse and subsequent overdose [1]. Illegitimate practices and 'doctor shopping', involving patients visiting multiple doctors, lead to the unreasonable prescription of benzodiazepines and consecutive abuse [2]. Psychiatric patients, on the other hand, are known to use benzodiazepines in an attempt of suicide or intentional self-harm [3].

Often, polydrug users execute the administration of benzodiazepines in combination with alcohol, antidepressants or opioids giving rise to the failure of cardiovascular and respiratory systems [4]. Other complications include neurological, renal impairment, muscular complications like hypotonia, and possible hearing loss.

Acute manifestations in overdosed patients usually involve collapse with seizures, cyanosis due to respiratory failure, loss of consciousness, coma and possible cardiac arrest [5]. On examination of the eyes, the patient might have fixed miosis or pinpoint pupil.

Hypothermia
  • Hypothermia may occur. Serious complications are more likely when newer short-acting agents are involved or when other depressant drugs have been ingested. Diagnosis usually is based on the history of ingestion ...[mhmedical.com]
  • 3.7 Overdose Overdose with a benzodiazepine can cause drowsiness, dysarthria and nystagmus ; very large overdose may cause hypothermia and rhabdomyolysis.[mhra.gov.uk]
  • Apnoea indicated airway obstruction Large ingestions can rarely cause hypothermia, bradycardia and hypotension.[lifeinthefastlane.com]
  • Gastrointestinal symptoms such as nausea and vomiting have also been occasionally reported. [10] Cases of severe overdose have been reported and symptoms displayed might include prolonged deep coma or deep cyclic coma, apnea, respiratory depression, hypoxemia, hypothermia[en.wikipedia.org]
Gastric Lavage
  • 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.[ncbi.nlm.nih.gov]
  • Initiate gastric lavage for clinically significant recent ingestions (ie, within 30 minutes). Ensure/monitor airway patency/protective reflexes during the above treatments.[anesth.unboundmedicine.com]
  • Occasionally, gastric lavage and administration of activated charcoal is indicated, but only if the patient is awake and potentially sensitive to benzodiazepines and if a large dose has been ingested within the last 1 to 2 hours.[link.springer.com]
  • Lyons, Juan Ochoa and Christopher King, Hypothermia: An Unusual Indication for Gastric Lavage, The Journal of Emergency Medicine, 40, 2, (176), (2011). T.[doi.org]
  • It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. [44] Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended. [44] Enhancing elimination of the[en.wikipedia.org]
Dyspnea
  • Note: preexisting conditions that compromise respiratory function such as chronic obstructive pulmonary disease, sleep apnea, asthma, or pneumonia clinical indicators of changes in respiratory function, such as respiratory rate, dyspnea, hypoxemia, and[mdedge.com]
Sputum
  • All of his blood and sputum cultures did not grow any organisms. Human immunodeficiency virus (HIV) antibodies were negative by Enzyme-linked immunosorbent assay (ELISA) and the screening for hepatitis B and C was also negative.[bmcneurol.biomedcentral.com]
Hypotension
  • Aggressive/expectant airway management for frank/anticipated inadequacy of protective airway reflexes Supine/Trendelenburg positioning and aggressive IV fluid therapy for hypotension GI decontamination Activated charcoal 1 g/kg PO or per NG tube is effective[anesth.unboundmedicine.com]
  • […] anxiety, and mood changes Dizziness Slurred speech or acting drunk Amnesia Physical weakness or lack of coordination Hypotonia (lack of muscle tone) Blurry vision Difficulty breathing or depressed breathing Stupor or unresponsiveness Hallucinations Hypotension[americanaddictioncenters.org]
  • In addition to excessive sedation, potential symptoms of a typical benzodiazepine overdose include hypotension (low blood pressure), diminished respiratory function (shallow breathing) and a condition called nystagmus, which involves rapid, involuntary[drugaddictiontreatment.com]
Musculoskeletal Pain
  • Trends in opioid prescribing and co-prescribing of sedative hypnotics for acute and chronic musculoskeletal pain: 2001-2010. Pharmacoepidemiol Drug Saf. 2015 ;24: 885 – 892. Crossref, Medline, Google Scholar 9.[doi.org]
Confusion
  • Extreme drowsiness or trouble staying awake Slurred speech or confusion Agitation Lack of muscle coordination Coma How is a benzodiazepine overdose diagnosed? Your healthcare provider will ask about the medicines you take.[drugs.com]
  • The signs and symptoms of benzodiazepine overdose are: Somnolence Confusion Diminished reflexes Respiratory depression Apnea Respiratory arrest Cardiac arrest The treatment for benzodiazepine overdose is: Discontinue dental treatment Call for assistance[dentalcare.com]
  • Some people exhibit mental confusion and slurred speech, but vital signs are often normal.[drugrehab.com]
  • Signs of an Overdose on Xanax, Valium, or Klonopin Symptoms of overdose on Xanax, Valium, or Klonopin include: Drowsiness or extreme fatigue Confusion, agitation, anxiety, and mood changes Dizziness Slurred speech or acting drunk Amnesia Physical weakness[americanaddictioncenters.org]
  • Some of the signs of acute toxicity or overdose are: Drowsiness Confusion Dizziness Blurred vision Weakness Poor judgment and decision making Slurred speech Lack of coordination Difficulty breathing Coma Death from respiratory arrest (ceased breathing[arizonadetoxhelpline.com]
Slurred Speech
  • The most common symptoms of overdose include the central nervous system (CNS); depression and intoxication with impaired balance, and slurred speech. Severe symptoms include coma and respiratory depression.[healthguidance.org]
  • Signs of an Overdose on Xanax, Valium, or Klonopin Symptoms of overdose on Xanax, Valium, or Klonopin include: Drowsiness or extreme fatigue Confusion, agitation, anxiety, and mood changes Dizziness Slurred speech or acting drunk Amnesia Physical weakness[americanaddictioncenters.org]
  • Some of the signs of acute toxicity or overdose are: Drowsiness Confusion Dizziness Blurred vision Weakness Poor judgment and decision making Slurred speech Lack of coordination Difficulty breathing Coma Death from respiratory arrest (ceased breathing[arizonadetoxhelpline.com]
  • Lethargy, slurred speech, ataxia, coma, and respiratory arrest may occur. Generally, patients with benzodiazepine-induced coma have hyporeflexia and midposition or small pupils. Hypothermia may occur.[mhmedical.com]
  • Extreme drowsiness or trouble staying awake Slurred speech or confusion Agitation Lack of muscle coordination Coma How is a benzodiazepine overdose diagnosed? Your healthcare provider will ask about the medicines you take.[drugs.com]
Amnesia
  • BACKGROUND: A prospective study was conducted to investigate the presence of anterograde amnesia in those who attempted suicide by benzodiazepine overdose and to study the correlation with sedation.[ncbi.nlm.nih.gov]
  • One hundred and thirty patients responded positively to flumazenil, characterized by improved response to painful stimuli, and decreased amnesia.[mjiri.iums.ac.ir]
  • It provides anxiolysis, sedation, hypnosis, skeletal muscle relaxation, anterograde amnesia, respiratory depression and an anticonvulsant effect but has no analgesic properties.[dentalcare.com]
  • Signs of an Overdose on Xanax, Valium, or Klonopin Symptoms of overdose on Xanax, Valium, or Klonopin include: Drowsiness or extreme fatigue Confusion, agitation, anxiety, and mood changes Dizziness Slurred speech or acting drunk Amnesia Physical weakness[americanaddictioncenters.org]
Ataxia
  • Ataxia was the most common clinical finding following benzodiazepine ingestion in this series. Flumazenil appeared beneficial for the treatment of severe benzodiazepine toxicity in only two patients.[doi.org]
  • Lethargy, slurred speech, ataxia, coma, and respiratory arrest may occur. Generally, patients with benzodiazepine-induced coma have hyporeflexia and midposition or small pupils. Hypothermia may occur.[mhmedical.com]
  • Initial signs and symptoms include intoxication, somnolence, diplopia, impaired balance, impaired motor function, anterograde amnesia, ataxia, and slurred speech.[en.wikipedia.org]
Stupor
  • Drowsiness or extreme fatigue Confusion, agitation, anxiety, and mood changes Dizziness Slurred speech or acting drunk Amnesia Physical weakness or lack of coordination Hypotonia (lack of muscle tone) Blurry vision Difficulty breathing or depressed breathing Stupor[americanaddictioncenters.org]
  • These were identical with those described by McCarron et al for assessing the severity of barbiturate intoxication. 7 A 7 point scale of conscious state (alert, drowsy, stuporous, coma 1–4) was used.[bmj.com]
  • She says her mother accidentally drank methadone while in a stupor brought on by benzodiazepines. That mix of drugs killed her. The CBC's David Burke has more.[cbc.ca]

Workup

Benzodiazepine overdose is managed according to possible complications.

A magnetic resonance imaging (MRI) of the brain is a necessity if the patient appears unconscious, comatose and with a possible risk of acidosis. The MRI will expose herniations, edema and diffuse white matter injury (leukoencephalopathy) relatively excluding the lesions of the gray matter. The white matter injury may also be of connection with the use of chemotherapy agents and exposure to toxins e.g. carbon monoxide. Signs of edema and herniation may evolve and be the cause of death if not handled or monitored appropriately [6] [7].

A computed tomography (CT) examination findings include hypodensity in the affected area of the white brain matter, correlating to the clinical picture found in MRI. Reports suggest that early in the disease, the imaging of the patient's brain can appear normal which leads to discharge from the hospital. After about two weeks, a rapid deterioration of the white matter precedes and involves serious changes in consciousness, behavior, gait, parasympathetic system, etc., advancing to dramatic complications like coma or quadriparesis. Thus the importance of monitoring the affected patient is suggested [8].

Urine sample analysis may expose high levels of benzodiazepines [6].

Lumbar puncture with a collection of the cerebrospinal fluid is useful to exclude other diagnoses e.g. herpes simplex virus infection, Epstein-Barr virus disease or other infections associated with brain tissues that cause similar radiologic findings. The analysis includes cell count, protein, and glucose level determination [9].

Electroencephalography (EEG) is optional and used to discover electrical potential abnormalities if the patient experienced neurologic signs e.g. seizures. The EEG might reveal slowing of background in low frequencies [6].

Atelectasis
  • The chest x-ray showed focal segmental atelectasis on the left lung field. Before flumazenil administration, we examined the patient’s airway and assessed the presence of contraindications for flumazenil administration.[jstage.jst.go.jp]

Treatment

  • Samples for toxicological analysis were taken before and after treatment. The patients were divided into three groups.[ncbi.nlm.nih.gov]
  • […] to speak to a treatment support advisor, who can help you find the right treatment program for your needs.[recovery.org]
  • Flumazenil is the first specific benzodiazepine antagonist, used as a specific antidote in known or suspected benzodiazepine overdose treatment.[anesthesiageneral.com]
  • This is a treatment approach that may be used in both inpatient and outpatient treatment programs.[drugabuse.com]

Prognosis

  • Please find relevant information on First Aid for Benzodiazepine Overdose regarding cause, signs & symptoms, administration of first aid treatment, prognosis, preventive measures, and additional resources HERE .[dovemed.com]
  • Three Part Question [In adults with acute opiate overdose] is [concomitant use of benzodiazepines] associated with a [poorer prognosis in terms of death aspiration, admission to ITU] Clinical Scenario A 27 year old man comes into the emergency department[bestbets.org]
  • With good supportive care prognosis is excellent. Toxic Mechanism: Simple mechanism, they enhance the inhibitory neurotransmitter GABA by increasing the opening frequency of chlorine.[lifeinthefastlane.com]
  • Prognosis in nontraumatic coma. Ann Int Med 1981; 94: 293–301 PubMed Google Scholar 72. Plum F, Posner JB, editors. Approach to the unconscious patient. In: The diagnosis of stupor and coma. Philadelphia: FA Davis Co, 1980: 345–64 Google Scholar 73.[link.springer.com]
  • 9.1.1 Ingestion 9.1.2 Inhalation 9.1.3 Skin exposure 9.1.4 Eye contact 9.1.5 Parenteral exposure 9.1.6 Other 9.2 Chronic poisoning 9.2.1 Ingestion 9.2.2 Inhalation 9.2.3 Skin exposure 9.2.4 Eye contact 9.2.5 Parenteral exposure 9.2.6 Other 9.3 Course, prognosis[inchem.org]

Etiology

  • Acute poisoning with benzodiazepines and other hypnotics: etiologic cause, sex/age distribution and clinical outcome. J of IMAB. 2016 Oct-Dec;22(4):1371-1374. DOI: 10.5272/jimab.2016224.1371.[journal-imab-bg.org]
  • Etiology 4. Clinical Course IV. Benzodiazepine Withdrawal 1. Signs and Symptoms 2. Treatment V. Benzodiazepine Overdose 1. Clinical Presentation 2. Treatment VI. Case Study: Benzodiazepine Drug-Drug Interaction VII.[ce4less.com]
  • Use of flumazenil in the diagnosis and treatment of patients with coma of unknown etiology. Crit Care Med 1993; 21: 538–42 PubMed CrossRef Google Scholar 63. Skeie B, Emhjellen S, Wickstrom E, et al.[link.springer.com]
  • Gökel, Etiological and demographical characteristics of acute adult poisoning in Adana, Turkey, Human & Experimental Toxicology, 26, 5, (401), (2007). M. Schmidt, Benzodiazepine, Suchtmittel in der AINS, 10.1007/978-3-540-33734-8_5, (79-89), (2007).[doi.org]
  • Use of flumazenil in the diagnosis and treatment of patients with coma of unknown etiology. Crit Care Med 1993; 21(4): 538–42 PubMed CrossRef Google Scholar 53. Hojer J, Magnusson A, Gustafsson LL.[doi.org]

Epidemiology

  • International Journal of Epidemiology, 22, 838 – 847. Shader, I. R. & Greenblat, D. J. ( 1993 ) Use of benzodiazepines in anxiety disorders. New England Journal of Medicine, 328, 1398 – 1405.[doi.org]
  • […] specialist a, D L O'Connell, senior lecturer in biostatics b a Departments of Clinical Toxicology and Pharmacology, University of Newcastle and Newcastle Mater Misericordiae Hospital, Newcastle, New South Wales 2298, Australia b Centre for Clinical Epidemiology[bmj.com]
  • Jaden Brandt and Christine Leong, Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research, Drugs in R&D, 10.1007/s40268-017-0207-7, (2017).[doi.org]
  • Anne Lamminpää, Vesa Riihimäki and Jussi vilska, Hospitalizations due to poisonings in Finland, Journal of Clinical Epidemiology, 46, 1, (47), (1993).[doi.org]
Sex distribution
Age distribution

Pathophysiology

  • Unfortunately, this syndrome remains of an unclear pathophysiology and with no successful treatment.[ncbi.nlm.nih.gov]
  • Pharmacotherapy: A Pathophysiologic Approach, 9th edition. Chapter 53: Anxiety Disorders I; Generalized Anxiety, Panic, and Social Anxiety Disorders. Access Pharmacy [online]. DiPiro et al. Pharmacotherapy: A Pathophysiologic Approach, 9th edition.[rxlist.com]
  • Pharmacotherapy: A Pathophysiologic Approach. 8th ed. . Accessed June 9, 2012.[accesspharmacy.mhmedical.com]
  • […] over 10 years (1992–2001), compared with 30 fatal deliberate self-poisonings involving diazepam. [36] In a New Zealand study (2003) of 200 deaths, Zopiclone, a benzodiazepine receptor agonist, had similar overdose potential as benzodiazepines. [37] Pathophysiology[en.wikipedia.org]

Prevention

  • Centers for Disease Control and Prevention. National Vital Statistics System. Multiple Cause of Death 1999-2013. Hyattsville, MD: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2014. Available at: .[doi.org]
  • "Though broad efforts are underway to prevent overdose from opioid painkillers, there is another class of prescription drugs that require attention—benzodiazepines," she said.[forbes.com]
  • Vancouver’s Overdose Prevention Society says there were 16 overdoses in the city over two days last week.[globalnews.ca]
  • We examined data from the Medical Expenditure Panel Survey and multiple-cause-of-death data from the Centers for Disease Control and Prevention.[ncbi.nlm.nih.gov]
  • Incremental intravenous bolus injections of flumazenil 0.1 to 0.3 mg 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[ncbi.nlm.nih.gov]

References

Article

  1. Bachhuber MA, Hennessy S, Cunningham CO, Starrels JL. Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996–2013. Am J Public Health. 2016;106(4):686-688.
  2. Peirce GL, Smith MJ, Abate MA, Halverson J. Doctor and pharmacy shopping for controlled substances. Med Care. 2012;50:494–500.
  3. Shin HI, Lin MC, Lin CC, et al. Benzodiazepine therapy in psychiatric outpatients is associated with deliberate self-poisoning events at emergency departments—a population-based nested case-control study. Psychopharmacology (Berl). 2013;229:665–71.
  4. Slavova S, Bunn TL, Talbert J. Drug Overdose Surveillance Using Hospital Discharge Data. Public Health Rep. 2014;129(5):437-445.
  5. Martins SS, Sampson L, Cerdá M, Galea S. Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature. Am J Public Health. 2015;105(11):e29-e49.
  6. Aljarallah S, Al-Hussain F. Acute fatal posthypoxic leukoencephalopathy following benzodiazepine overdose: a case report and review of the literature. BMC Neurol. 2015;15:69.
  7. Kim JH, Chang KH, Song IC, et al. Delayed encephalopathy of acute carbon monoxide intoxication: diffusivity of cerebral white matter lesions. AJNR Am J Neuroradiol. 2003;24(8):1592–7.
  8. Chang WL, Chang YK, Hsu SY, Lin GJ, Chen SC. Reversible delayed leukoencephalopathy after heroin intoxication with hypoxia: a case report. Acta Neurologica Taiwanica. 2009;18(3):198–202.
  9. Wallace IR, Dynan C, Esmonde T. One confused patient, many confused physicians: a case of delayed post-hypoxic leucoencephalopathy. QJM Monthly J Assoc Physicians. 2010;103(3):193–4.

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Last updated: 2019-07-11 20:41