A Strategy for Rescuing a Child From Clonazepam Poisoning: A Case Study.

BACKGROUND: This report describes the successful rescue of a 12-year-old girl who ingested large quantities of clonazepam tablets. METHODS: The patient was promptly treated with flumazenil and hemoperfusion to alleviate the symptoms of central depression. Therapeutic drug monitoring was used to evaluate detoxification efficacy. The authors analyzed the rescue protocol for clonazepam poisoning based on the pathophysiology, clinical manifestations, and pharmacokinetics of clonazepam overdose. RESULTS: The patient responded well to the treatment and was discharged from the hospital without adverse events. CONCLUSIONS: This case study demonstrated the effectiveness and safety of combining flumazenil with hemoperfusion as a treatment for clonazepam poisoning. This study aimed to provide insights into more effective methods for treating clonazepam overdose and contribute to the ongoing issue of managing this condition.

Calcium Channel Blocker Toxicity Causing Acute Respiratory Distress Syndrome: A Commonly Used Drug Triggering a Life-Threatening Condition.

INTRODUCTION: Calcium channel blockers (CCBs) are commonly used but have the potential to cause substantial toxicity. One such underreported toxicity of CCB use is the development of acute respiratory distress syndrome (ARDS). CASE PRESENTATION: 44-year-old previously healthy woman presented to the emergency department (ED) having taken 60 tablets of 125 mg extended-release verapamil and 90 tablets of 0.25 mg clonazepam with the intent to commit suicide. On presentation to the ED, she was sedated and intubated for airway protection. She received aggressive medical resuscitation and was ventilated using low tidal volume mechanical ventilation. The hospital course was complicated by worsening hypoxia and a chest x-ray demonstrating bilateral patchy geographic areas of airspace opacities consistent with ARDS. On day 5 of hospitalization, the patient's clinical status improved significantly, and she was subsequently weaned off vasopressors and extubated. DISCUSSION: CCB toxicity can result in profound hypotension, shock, bradycardia, and conduction blocks, as well as hyperglycemia, acidosis and acute kidney injury, and ARDS. It is important for clinicians to understand the signs and symptoms of CCB toxicity, as well as how to treat it.

Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes.

The present study is an unsubstantiated qualitative assessment of the abused drugs-tramadol and clonazepam. The aim of this study is to evaluate whether the effects of tramadol, clonazepam, and their combination on mitochondrial electron transport chain (ETC) complexes were influential at therapeutic or at progressively increasing doses. The study comprised of a total of 70 healthy male rats, aged 3 months. According to the drug intake regimen, animals were divided into seven groups: control, tramadol therapeutic, clonazepam therapeutic, combination therapeutic, tramadol abuse, clonazepam abuse, and combination abuse group. At the end of the experiment, brain mitochondrial ETC complexes (I, II, III, and IV) were evaluated. Histopathological examinations were also performed on brain tissues. The results showed that groups that received tramadol (therapeutic and abuse) suffered from weight loss. Tramadol abuse group and combination abuse group showed significant decrease in the activities of I, III, and IV complexes but not in the activity of complex II. In conclusion, tramadol but not clonazepam has been found to partially inhibit the activities of respiratory chain complexes I, III, and IV but not the activity of complex II and such inhibition occurred only at doses that exceeded the maximum recommended adult human daily therapeutic doses. This result explains the clinical and histopathological effects of tramadol, such as seizures and red neurons (marker for apoptosis), respectively.

Toxic leukoencephalopathy in the intensive care unit.

In this article, we report two cases of acute toxic leukoencephalopathy to highlight this acute clinicoradiological syndrome as an important, although uncommon, consideration in the undifferentiated comatose patient who fails to wake following drug overdose or has unexplained neurology with a history of drug exposure. We then review the current literature and discuss potential differential diagnoses in this setting, along with proposed treatments for this condition. The cases presented demonstrate a more fulminant onset than previously well-defined acute toxic leukoencephalopathy subtypes and highlight the prognostic importance of magnetic resonance imaging in diagnosing a condition from which significant functional recovery seems possible.

Serial monitoring of sedation scores in benzodiazepine overdose.

Benzodiazepines are widely used for many diseases, and benzodiazepine overdose is globally increasing in proportion to its prescriptions. Although most benzodiazepine overdoses are known to be safe and nonfatal without coingestions, morbidity or mortality after benzodiazepine overdose is closely related with the duration of unconsciousness or depth of compromised airway. Proper use of flumazenil, a potent antidote of benzodiazepine, seems to accelerate the recovery from the toxicity after benzodiazepine overdose.However, as the case we present demonstrates, careful attention and repetitive evaluations before and after use of flumazenil may be needed in benzodiazepine overdose because resedation occurs in approximately 30% of total flumazenil-treated cases, which suggests that the risk of aspiration or incidental death after administrating flumazenil might be significant without careful monitoring.

Positive lidocaine toxicology screen after J-Tip for venipuncture.

Venipuncture is common in children, and topical anesthetics are often used to alleviate the pain of the procedure. The J-Tip (National Medical Products, Inc, Irvine, Calif) device has become popular as a rapid and effective means of delivering lidocaine noninvasively. We report a case of a positive lidocaine blood toxicology screen after the use of the J-Tip device in a child pre-venipuncture. A repeat toxicology screen obtained 1 hour later by venipuncture without J-Tip use was negative. This report serves to remind clinicians that topical anesthetics may interfere with toxicology assays, leading to unreliable toxicology results.

Benzodiazepine-associated atrioventricular block.

Dysrhythmias, although common in overdose situations, are not often seen after benzodiazepine exposures. We report two cases of transient atrioventricular block after benzodiazepine misuse. Case 1 is a 4-year-old boy who was found unresponsive after an ingestion of clonazepam. An electrocardiogram (EKG) performed on emergency department presentation demonstrated first-degree atrioventricular block (PR 206 ms). After flumazenil administration, he developed second-degree atrioventricular block (Mobitz Type 1). EKG abnormalities resolved by morning. Serum clonazepam was 478 ng/mL (laboratory clonazepam reference range, 10-75 ng/mL with a dose of up to 6 mg/day) 5 hours after being found unresponsive. Case 2 is a 23-year-old man who presented to the emergency department after ingesting risperidone, combination hydrocodone/acetaminophen, and alprazolam. On arrival, his EKG demonstrated sinus bradycardia with a PR interval of 182 msec. He subsequently developed second-degree atrioventricular block (Mobitz Type I). Sinus bradycardia with resolution of his atrioventricular block (PR 200 ms) was seen on a third EKG performed 5 hours after presentation. These two patients demonstrated transient first- and second-degree atrioventricular block after benzodiazepine exposure. Benzodiazepines have been shown to alter L-type Ca2+ channel function. This alteration in function may account for the dysrhythmias seen in our patients. Together, these cases serve to remind clinicians of this rare but potentially serious complication associated with benzodiazepine exposure.

Blood concentrations of clonazepam and 7-aminoclonazepam in forensic cases in Denmark for the period 2002-2007.

The benzodiazepine clonazepam is a prescription drug used to treat epilepsy and anxiety. In addition, it is frequently used to treat drug addicts and is itself a popular drug of abuse. In this study, we report the incidence and blood concentrations of clonazepam and its metabolite 7-aminoclonazepam in cases referred to the Section of Forensic Chemistry at the University of Copenhagen in 2002-2007. Using LC-MS/MS, clonazepam was detected in 297 traffic cases, 92 criminal cases (perpetrators or victims of a crime) and in 140 postmortem cases. The concentration ranges of clonazepam+7-aminoclonazepam were 0.002-0.840 mg/kg (median 0.067) for traffic cases, 0.005-0.913 (median 0.071) for criminal cases (offenders), 0.002-0.720 (median 0.030) for criminal cases (victims) and 0.002-1.676 (median 0.115) for postmortem cases. The concentrations were thus similar among the groups, although the median value was highest in the postmortem group. In most cases, other drugs were also present. For the postmortem group, the cases (n=27) with relatively high (>0.2 mg/kg) clonazepam+7-aminoclonazepam values were examined in greater detail. Other drugs were present in all cases, with clonazepam judged to be the primary cause of death in five cases. The range of clonazepam+7-aminoclonazepam concentrations in these five cases ranged from 0.26 to 0.54 mg/kg (median 0.29 mg/kg).

Hemoperfusion in the treatment of acute clozapine intoxication in China.

BACKGROUND AND AIMS: No systematic study has focused on the characteristics and outcome of acute clozapine intoxication, although clozapine is the most widely used antipsychotic agent in China. The study reported herein examined the features of clozapine intoxication and the therapeutic effect of hemoperfusion (HP). METHODS: In a retrospective chart review, the notes of 47 patients who attempted suicide by ingesting large amounts of clozapine and were treated at the only psychiatric emergency service in Beijing were analyzed. Of the 20 unconscious patients with plasma clozapine concentrations of more than 2000 ng/mL, 14 received a combination of HP and symptomatic treatment, whereas the other 6 and the remaining 27 patients received only symptomatic treatment. Patients' psychiatric conditions and both plasma clozapine and norclozapine concentrations were closely monitored and registered. RESULTS: One patient died of pulmonary edema and subsequent heart failure, but the rest of the patients recovered without any sequelae. Patients who received HP regained consciousness significantly faster than their counterparts with the same level of clozapine plasma concentration (>2000 ng/mL) who did not receive HP. CONCLUSIONS: A combination of HP and symptomatic treatment is the best therapeutic option when plasma clozapine concentration is high.

Brugada electrocardiographic pattern due to tricyclic antidepressant overdose.

The Brugada syndrome is an arrhythmogenic disease with characteristic coved ST-segment elevation 2 mm or greater in the right precordial leads (type 1 Brugada electrocardiogram [ECG] pattern or "Brugada sign"] and is estimated to be responsible for at least 20% of sudden deaths in patients with structurally normal hearts [Circulation 2005;111(5):659-70]. The Brugada sign has been described in asymptomatic patients after exposure to various drugs. As published reports of the drug-induced Brugada sign have become increasingly prevalent, there is growing interest in the mechanisms responsible for this acquired ECG pattern and its clinical significance. We report a case of a patient who developed the type 1 Brugada ECG pattern after intentional overdose of a tricyclic antidepressant agent, review the literature concerning tricyclic antidepressant agent-induced Brugada sign, discuss potential mechanisms, and evaluate the clinical significance of this ECG abnormality.

A fatal drug interaction between oxycodone and clonazepam.

A case is presented of a fatal drug interaction caused by ingestion of oxycodone (Oxycontin) and clonazepam (Klonapin). Oxycodone is an opium alkaloid used in long-term pain management therapy. Clonazepam is a benzodiazepine used for the treatment of seizures and panic disorders. The Drug Abuse Warning Network (DAWN) has reported an increase of 108% in the last two years of emergency department episodes related to Oxycontin. Six billion prescriptions were written for Oxycontin in the year 2000, an 18-fold increase from four years previous (1). Oxycontin has recently gained enormous notoriety at the local and national levels; however, there are very few previously documented cases of lethal drug interactions between oxycodone and clonazepam. Synergistic effects between these two drugs are postulated to arise from different agonistic mechanisms producing similar physiological changes. It is also theorized that clonazepam may inhibit the metabolism of oxycodone. A 38-year-old white female was found dead in Jefferson County, Tennessee in March of 2001. The deceased had physical evidence of previous drug abuse and positive serological findings of hepatitis B and C. Prescription pill bottles filled under the name of the deceased, as well as another name, were found with the body. Serum, urine and gastric contents from the deceased were screened for numerous drugs and metabolites using a combination of thin layer chromatography and immunoassay techniques (EMIT and FPIA). Analysis of biological specimens from the deceased revealed the presence of: benzodiazepines, opiates (oxycodone), and trazodone metabolites in the serum; cannabinoids, benzodiazepines, opiates (oxycodone), trazodone, trazodone metabolites, nicotine, and nicotine metabolite in the urine; and benzodiazepines, opiates (oxycodone), nicotine, and nicotine metabolite in the gastric contents. Quantitative analyses for clonazepam was performed by high performance liquid chromatography (HPLC) and revealed a plasma concentration of 1.41 microg/mL. Plasma oxycodone and urine 11-nor-carboxy-delta-9-tetrahydrocannabinol concentrations were determined by gas chromatography/mass spectrometry and revealed concentrations of 0.60 microg/mL and 27.9 ng/mL, respectively. The deceased had pathologies consistent with severe central nervous system (CNS) and respiratory depression produced by high concentrations of clonazepam and oxycodone including collapsed lungs, aspirated mucus, and heart failure. The pathologies were sufficient to cause death, which was officially attributed to a drug overdose; however, the manner of death was unknown.

Life threatening intoxication with sodium valproate.

Two female epileptics, 19 and 27 years old, were admitted after ingestion of an overdose of sodium valproate. The patients were comatose for 6 and 7 days and required mechanical ventilation for 7 and 10 days. Both patients were in deep coma for several days after serum concentrations had dropped into the therapeutic range. Serum concentrations of sodium valproate were 3348 mumol/L (482 mg/mL) in one patient and more than 10,000 mumol/L (1440 mg/mL) in the other. Drug elimination followed first order kinetics, and the plasma half-lives of sodium valproate were 19 and 20 hours, respectively. Their anemia, leucopenia and thrombocytopenia required transfusion. Liver enzymes were only moderately elevated, but one of the patients developed acute pancreatitis. There were no apparent sequelae two weeks after discharge from the hospital.

Clonazepam overdose resulting in cyclic coma.

Cyclic coma in a 4-year-old boy followed an ingestion of clonazepam, a new benzodiazepine, utilized in treatment of convulsive disorders. Alternation between coma and a hyperalert state occurred even after further gastrointestinal absorption had, presumably, been precluded. Laboratory identification by routine examination for benzodiazepines was unsuccessful.