[Successful lipid rescue therapy in a case of severe amitriptyline/quetiapine intoxication]. / Erfolgreiche "Lipidrescuetherapie" bei Amitriptylin-Quetiapin-Mischintoxikation in mehrfach letaler Dosis.

A 25-year-old patient was admitted urgently due to mixed amitriptyline/quetiapine intoxication at a potentially lethal dose. Alongside severe anticholinergic toxidrome, she presented with antiadrenergic and quinidin-like cardiotoxic findings, including ventricular tachycardia. In the present case, arrhythmia and circulatory shock responded neither to alkalization and elevated sodium levels after infusion of sodium bicarbonate, nor to any other established therapies. Following the lipid rescue paradigm, bolus infusion of a 20% lipid emulsion led to rapid stabilization and continued reversal of all intoxication features.

Neurologic and Cardiovascular Complications in Pediatric Life Threatening Imipramine Poisoning.

We present an 18-month boy with imipramine poisoning to illustrate the neuro-cardiac toxic effects of this potentially deadly poison in children. The toddler ingested an unknown amount of imipramine from a non-childproof bottle which clearly labelled that the drug must be kept out of reach from children. He developed neurologic and cardiac symptoms. Electrocardiography (ECG) showed tachycardia and widened QRS. He was immediately treated with bicarbonate infusion and made an uneventful recovery. This is the youngest and only reported case of symptomatic imipramine ingestion in our locality. Imipramine has been surpassed by newer antidepressants for the treatment of depression in the past decade. Literature is searched to review the mortality rate in young children. Intensive care neuro-cardiac support contributes to the favorable outcome. Despite clear labelling of the bottle, carelessness on the part of the adult and the use of non-childproof bottle are definite preventable factor to such potentially fatal ingestion.

Successful use of therapeutic hypothermia after cardiac arrest due to amitriptyline and venlafaxine intoxication.

The prognosis of out-of-hospital cardiac arrest (OHCA) due to intoxication is dismal. Tricyclic antidepressants (TCAs) are widely used in the treatment of depression, but possess significant cardiotoxicity, and are one of the most common medications used in suicide attempts worldwide. TCA poisoning can cause hypotension, seizures, and cardiac conduction disturbances, which can lead to life-threatening arrhythmia. Current guidelines recommend mild therapeutic hypothermia (TH) for unconscious survivors of OHCA, but hypothermia treatment itself can cause disturbances in cardiac conduction, which could aggravate the effect of TCAs on cardiac conduction. We report the successful use of TH in a 19-year-old woman who was resuscitated from ventricular tachycardia after intentional ingestion of amitriptyline and venlafaxine, a serotonin-norepinephrine reuptake inhibitor. The cardiac arrest was witnessed, but no bystander cardiopulmonary resuscitation (CPR) was performed. The initial rhythm was ventricular tachycardia with no detectable pulse. Three defibrillations, magnesium sulfate, and sodium bicarbonate were given and her trachea was intubated, after which return of spontaneous circulation (ROSC) was achieved in 26 minutes. After ROSC, she had seizures and was sedated with propofol. Out-of-hospital TH was initiated with 1500 mL of cold Ringer's acetate. An infusion of norepinephrine was initiated for low blood pressure. On arrival at the university hospital, she was unconscious and had dilated pupils. She was tachycardic with a body temperature of 33.5°C. She was transferred to the intensive care unit and TH was maintained with invasive cooling. During the TH treatment, she did not experience any serious cardiac arrhythmia, transthoracic echocardiogram was normal, and the electrocardiogram (ECG) returned to normal. The patient was extubated 45 hours after the cardiac arrest. After the extubation, she was alert and cooperative, but slightly delusional. She was transferred to a ward on the third day and discharged from hospital on the sixth day of admission. Ambulatory psychiatric follow-up was organized. Neuropsychological examinations were later performed and she was estimated to be able to work at her previous job. This case report suggests that mild TH is safe even in case of intoxication with a drug known to cause serious cardiac conduction disturbances and arrhythmia.

A case series of patients with lamotrigine toxicity at one center from 2003 to 2012.

INTRODUCTION: Lamotrigine is a phenyltriazine compound that inhibits voltage-gated sodium channels, decreasing release of glutamate and aspartate, and inhibits serotonin, norepinephrine and dopamine reuptake. Reports of toxicity in the literature are limited to case reports and primarily involve coingestants. This case series is intended to report the clinical manifestations of lamotrigine toxicity. METHODS: This retrospective case series from 2003 to 2012 studies the effects of lamotrigine toxicity when not confounded by coingestants. Admission records at an inpatient toxicology center were reviewed for lamotrigine-only exposure based on history with supporting laboratory data when available. After identification, these charts were reviewed again to characterize vital signs, neurological examination findings, specific laboratory and electrocardiography parameters, and complications. RESULTS: Fifty-seven patients were identified with possible lamotrigine toxicity. Nine patients, including three toddlers, had lamotrigine-only ingestions. Three of these patients had seizures, four were hypertensive, five were tachycardic, and four experienced tachypnea. Mental status was altered in all nine (depressed (n = 4), agitated (n = 5) or both (n = 3)). Five patients were hyperreflexic and experienced intermittent myoclonus, and two had inducible clonus. On electrocardiogram, two patients experienced QRS prolongation (114-116 ms), and four had QTc prolongation (463-586 ms). No patient had life-threatening symptoms or signs. Serum levels of lamotrigine were available in seven patients, and averaged 35.4 mg/L (17-90 mg/L). The therapeutic range for sLTG is 3-14 mg/L. CONCLUSIONS: Lamotrigine toxicity manifested with minor-moderate neurologic and/or electrocardiographic effects. Toxicity reflects the known pharmacologic actions of lamotrigine: serotonin, norepinephrine and dopamine reuptake inhibition, and sodium channel blockade.

A retrospective review of isolated duloxetine-exposure cases.

BACKGROUND: Duloxetine is a serotonin norepinephrine reuptake inhibitor (SNRI) approved in the US for the treatment of major depression, generalized anxiety, fibromyalgia, diabetic peripheral neuropathy, and chronic musculoskeletal pain. Given the limited published information regarding human overdoses to this medication, our goal was to characterize such exposures. METHODS: We retrospectively reviewed a state poison system's database for all single agent exposures to duloxetine from 2004-2011. Data collected included age, gender, circumstances surrounding exposure, symptoms, and outcome. Patients with co-ingestants, confirmed non-exposure, unknown outcomes, or other coding errors were excluded. RESULTS: 159 cases were identified. 106 were included for review. Of 61 pediatric and adolescent cases (0-19 years old) identified, 53 involved unintentional overdose. Three patients experienced symptoms and none were admitted. All intentional ingestions(8) were seen in the emergency department, two patients experienced symptoms. No intentional ingestion was admitted for medical care. Fifty-one adult cases were included for review. Four adult patients were admitted following intentional duloxetine overdose with resolution of symptoms within 24 hours. Three adults were evaluated in a HCF following non-self-harm exposures to duloxetine. None of these patients were admitted. The remaining 15 adult patients with non-self-harm exposures were safely managed at home. CONCLUSION: The majority of non-self-harm duloxetine-exposed adult and pediatric/adolescent patients were safely managed at home and when evaluated in a healthcare facility, did not require further hospitalization. Intentional pediatric/adolescent and adult duloxetine exposures were managed in a healthcare facility but rarely resulted in further hospitalization, serious morbidity, or mortality.

Management of attention-deficit disorder and attention-deficit/hyperactivity disorder drug intoxication in dogs and cats.

Two types of drugs are generally used for treating attention-deficit/hyperactivity disorder or attention-deficit disorder in humans: amphetamines or similar stimulants and the nonamphetamine atomoxetine. We describe the toxicity and treatment of both amphetamines and similar medications and atomoxetine in dogs and cats. Amphetamine intoxication can cause life-threatening stimulatory signs. Treatment is aimed at preventing absorption, controlling the stimulatory signs, and protecting the kidneys; prognosis is generally good. Atomoxetine also has a fast onset of action; stimulatory signs such as hyperactivity and tachycardia are often seen. There are little published data about treatment of atomoxetine toxicity in cats and dogs.

Repeated treatment with a low dose of reserpine as a progressive model of Parkinson's disease.

Animal models are widely used to study alterations caused by Parkinson's disease (PD). However, in general, pharmacological models do not express the progressive nature of the disease, being characterized by immediate severe motor impairment after a single dose of the drug. Reserpine administration in rodents has been suggested as a pharmacological model of PD based on the effects of this monoamine-depleting agent on motor activity. Here, we describe that repeated administration with a low dose (0.1 mg/kg) of reserpine in rats induces a gradual appearance of motor signs, evaluated by catalepsy behavior. Furthermore, these motor signs are accompanied by increased levels of striatal lipid peroxidation. However, treatment with reserpine failed to induce memory impairments (evaluated by novel object recognition and discriminative avoidance tasks) and alterations in hippocampal lipid peroxidation. Thus, repeated treatment with low doses of reserpine progressively induces alterations in motor function and an increase in striatal oxidative stress, indicating a possible application of this model in the study of the neuroprogressive nature of the motor signs in PD.

Coma after overdose with duloxetine.

OBJECTIVE: To describe a case of a patient who became comatose after taking an overdose of duloxetine, a serotonin-norepinephrine reuptake inhibitor. CASE SUMMARY: A 49-year-old male ingested an overdose of duloxetine approximately 2 hours before presentation to the emergency department. On arrival he was drowsy, but easily awakened and oriented, with Glasgow Coma Score 14 (eyes 3, motor 6, verbal 5). Immediately after admission, charcoal and magnesium sulfate were given to prevent further systemic absorption of medication through the gastrointestinal tract. No gastric lavage was performed. Six hours after drug intake the patient became unconscious (Glasgow Coma Score 7, eyes 2, motor 4, verbal 1). Full toxicologic screening showed a toxic duloxetine plasma concentration of 0.86 mg/L. The patient was admitted to the intensive care unit (ICU) and, on arrival, urinary retention was noted. During ICU admission the patient remained hemodynamically stable; approximately 12 hours after ingestion of duloxetine, he regained consciousness. Over the next 3 days the urinary output decreased to 60 mL/day. After 4 days patient was discharged without any remaining symptoms. Based on repeated plasma duloxetine serum concentration determinations, a plasma half-life of duloxetine was calculated to be 18 hours (reference range 9-19). DISCUSSION: The Naranjo probability scale suggested that duloxetine was the probable cause for the symptoms described. CONCLUSION: Overdose with duloxetine can induce coma several hours after intake, with a fast reversal in our case.

The outcome of unintentional pediatric bupropion ingestions: a NPDS database review.

Unintentional bupropion pediatric exposures uncommonly report severe clinical effects such as seizures. We sought to determine the clinical effects and case outcomes for unintentional bupropion ingestions in children age

Suicidal antidepressant overdoses: a comparative analysis by antidepressant type.

INTRODUCTION: The safety of antidepressants following overdose is critical because of the high risk of suicide attempts in depressed patients. This study was conducted to decrease the fatality rate of antidepressant overdoses by providing data to shift prescribing toward safer antidepressants. METHODS: US poison control data for 2000-2004 were analyzed by 25 antidepressant types. Medical outcome differences were quantified using a hazard index (number of major or fatal outcomes per 1000 reported antidepressant ingestions). RESULTS: Of 82,802 suicidal single-agent ingestions of identifiable antidepressants approved for use in the US, cases occurred predominantly in females and peaked in teens. Fatal cases peaked at 40 to 49 years of age. Suicidal ingestions of the SSRIs, SNRIs, and other antidepressants peaked in teens, lithium in the twenties, tricyclics and tetracyclics in the thirties, and MAO inhibitors in the forties. There were 40 major or fatal outcomes per 1000 cases. Weighted by antidepressant type, the mean hazard index for the 25 antidepressants was 79 (range: 0 to 292). Amoxapine (292), maprotiline (211), and desipramine (187) had the highest hazard indices. The tricyclic antidepressants, MAO inhibitors, maprotiline, and bupropion were in the more severe half of antidepressants, ranked by hazard index. All SSRIs had low hazard indices. Hazard index and exposure frequency were inversely correlated (R = -0.423, p = 0.035), while hazard index and use of critical care were positively correlated for the 25 antidepressant types (R = 0.797, p < 0.001). Clinical effect profiles for each antidepressant type are presented. CONCLUSION: Suicidal overdose severity varied considerably by antidepressant type. Prescribing decisions should be informed by regularly updated comparative overdose severity data.

Pediatric atomoxetine ingestions reported to Texas poison control centers, 2003-2005.

Limited information exists on potentially adverse consequences following pediatric atomoxetine ingestions reported to poison control centers. Using pediatric atomoxetine ingestions reported to Texas poison control centers during 2003-2005, the proportion of cases involving serious outcomes (medical outcomes classified as moderate effects, major effects, death, or judged as potentially toxic exposures) was determined for selected variables and evaluated for statistical significance by calculating the rate ratio (RR) and 95% confidence interval (CI). Of 501 cases identified, 31 (6%) involved serious outcomes. Higher serious outcome rates were found with a maximum dose of >2.8 mg/kg or >200 mg or >4 tablets. Serious outcome rates were also higher if the exposure involved intentional self-harm or the patient was already at or en route to a health care facility when the poison control center was contacted or referred to a health care facility by the poison control center. The severity of the outcome associated with pediatric atomoxetine ingestions was dependent upon the dose and the circumstances of the ingestion (whether intentional self-harm was involved). The management of patients with serious outcomes was more likely to involve health care facilities. This information is useful for creating triage guidelines for the management of pediatric atomoxetine ingestions.

Isolated atomoxetine overdose resulting in seizure.

BACKGROUND: Atomoxetine (Strattera), has recently been approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adolescents and adults. Atomoxetine acts by inhibiting the reuptake of norepinephrine. There are limited reports of the effects of atomoxetine in overdose. We report a case of isolated atomoxetine overdose resulting in seizure and mild cardiac toxicity. CASE REPORT: A 17-year-old female ingested 2840 mg of atomoxetine in an attempt to kill herself. She presented to an Emergency Department 2-3 hours after ingestion and soon after arrival had a tonic clonic seizure that lasted one minute. An initial electrocardiogram (ECG) revealed a sinus tachycardia with a rate of 110 beats per minute (bpm) and a QRS interval of 93 ms. She was transferred to a pediatric toxicology referral center and had progressive improvement in her symptoms. Gas chromatography and mass spectometry of the urine detected the following drugs: atomoxetine, naproxen, and nicotine. A quantitative serum atomoxetine level of 1995 ng/ml and a quantitative serum naproxen level of 12 mcg/L (30-90 mcg/L anti-inflammatory or analgesic range) were obtained. The patient had no further complications and was without symptoms within 24 hours of hospitalization. Repeat ECG 14 hours following ingestion revealed QRS interval of 79 ms. CONCLUSION: We report a case of atomoxetine overdose resulting in seizure and mild widening of the QRS interval on ECG. It is important to be aware of the potential for atomoxetine to cause central nervous system and cardiac toxicity.

Isolated atomoxetine (Strattera) ingestions commonly result in toxicity.

Atomoxetine is a recently approved medication for attention deficit disorder. It is a selective norepinephrine reuptake inhibitor with an onset of action within 2 h, and a duration of effect up to 40 h in therapeutic doses. Experience in the overdose setting is limited. After brief training in systematic chart review, reviewers blinded to the purpose of the study completed a standardized data collection sheet. Two years after atomoxetine was released, poison center patient encounters were reviewed. Age, outcomes, and signs and symptoms were recorded. All patients were followed until the cessation of symptoms or 24 h. Seventeen cases of isolated atomoxetine were reviewed. The age range of these 6 patients was 9 months to 28 years old with a mean of 15.6 years. The range of amount ingested was 10-1200 mg. The onset of symptoms was delayed as long as 3 h in 3 patients. All neurological symptoms were preceded by tachycardia. Ten of 17 patients had tachycardia, 6/17 had emesis, and 3/17 had agitation that required benzodiazepines to control. All symptoms resolved within 30 h. Supratherapeutic ingestions of atomoxetine can result in transient tachycardia, vomiting, and cognitive disturbances.

[Consideration on serotoninergic syndrome based on a clinical situation ]. / Consideratii asupra sindromului serotoninergic pornind de la un caz clinic.

The diagnosis criteria for serotoninergic syndrome was first time proposed in 1991 by Sternbach, mixing clinical, biological and historical features. Drugs inducing serotonin accumulation by decreasing the synaptic recapture or increasing the serotoninergic transmission are responsible for the onset of this syndrome even in small amounts. We are describing a case of a young patient developing a comatose stage of serotoninergic syndrome as a result of Amitriptylinum and Sertralinum poisoning.

[Fatal ecstasy intoxication]. / Letalt forløbende ecstasyforgiftning.

A case of full-blown, lethal MDMA intoxication, owing to abuse of ecstasy is described. The increasing popularity of ecstasy among young, otherwise healthy, people prompts health care providers to recognise better the symptoms of systemic intoxication in order to initiate early treatment, such as rehydration, cooling in cases of hyperthermia, seizure treatment, correction of cardiac arrhythmia, and metabolic and electrolyte abnormalities.

ECG abnormalities in tricyclic antidepressant ingestion.

The tricyclic antidepressant (TCA) agents are recognized for their potentially lethal cardiovascular and neurological effects in poisoned patients. The 12-lead electrocardiogram (ECG) has emerged as a popular bedside tool in the evaluation of TCA toxicity. Although the history and physical examination play a key role in the assessment of the patient with potential TCA poisoning, the presence or absence of features of the TCA toxidrome are not sufficient to detect or exclude toxicity from this class of drugs. A variety of ECG findings occur with TCA toxicity. Aside from the sinus tachycardia due principally to anticholinergic effects, TCA-toxic changes seen on the ECG are attributable primarily to the sodium channel blockade caused by these agents. The majority of patients at significant risk for developing cardiac or neurological toxicity will have a QRS complex greater than 0.10 seconds or a rightward shift of the terminal 40 ms of the frontal plane QRS complex vector. The majority of these patients will also display these changes early in their emergency department stay. However, the appearance of these findings, either alone or in combination, does not mean the patient will develop significant cardiac or neurological toxicity. The ECG can neither unequivocally rule in nor rule out impending toxicity; recognizing these limitations, the emergency physician can use this bedside tool in combination with other clinical data during the assessment of the poisoned patient.