Successful management of minoxidil toxicosis in a dog.

CASE DESCRIPTION A 2-year-old sexually intact female mixed-breed dog was evaluated at an emergency hospital approximately 5 hours after ingestion of an unknown amount of over-the-counter topical hair growth promoter containing 5% minoxidil foam. Vomiting and signs of lethargy were reported by the owner, and physical examination revealed tachycardia and hypotension. No treatments were performed, and the dog was transferred to a veterinary referral hospital for management of suspected minoxidil toxicosis. CLINICAL FINDINGS On arrival at the referral hospital, the dog was tachycardic (heart rate, 200 to 220 beats/min) and hypotensive (systolic arterial blood pressure, 70 mm Hg). Electrocardiography revealed a regular, narrow-complex tachycardia with no evidence of ventricular ectopy. TREATMENT AND OUTCOME Hypotension was effectively managed with a constant rate infusion of dopamine hydrochloride (12.5 µg/kg/min [5.7 µg/lb/min], IV). Once normotensive, the dog remained tachycardic and a constant rate infusion of esmolol hydrochloride (40 µg/kg/min [18.2 µg/lb/min], IV) was initiated for heart rate control. A lipid emulsion was administered IV as a potential antidote for the toxic effects of the lipophilic minoxidil, with an initial bolus of 1.5 mL/kg (0.7 mL/lb) given over 15 minutes followed by a continuous rate infusion at 0.25 mL/kg/min (0.11 mL/lb/min) for 60 minutes. While hospitalized, the dog also received maropitant citrate and ondansetron. Resolution of clinical signs was achieved with treatment, and the dog was discharged from the hospital 36 hours after admission. Four days later, the owner reported that the dog had made a full recovery and had returned to its typical behavior and activity level at home. CLINICAL RELEVANCE To the authors' knowledge, this is the first report of successful clinical management of accidental minoxidil toxicosis in a dog.

A Case of Severe, Refractory Hypotension After Amlodipine Overdose.

Calcium channel blockers (CCBs) are responsible for a substantial portion of the mortality associated with cardiovascular medication overdose cases. Amlodipine, a dihydropyridine CCB, can cause prolonged hypotension in overdose. This report describes a severe amlodipine overdose case that was refractory to multiple therapeutic approaches. A 53-year-old male presented after ingesting eighty 10 mg amlodipine tablets in a suicide attempt. The patient was initially managed with calcium boluses, glucagon, multiple vasoactive agents, lipid emulsion infusions and hyperinsulinemic euglycemic therapy. Methylene blue boluses were initiated when hypotension persisted despite conventional treatments. Refractory hypotension prompted the use of plasmapheresis in an attempt to lower serum amlodipine levels. Finally, the patient was placed on extracorporeal membrane oxygenation (ECMO) to maintain perfusion while the effects of the amlodipine ingestion dissipated. Following an episode of asystole and pulseless electrical activity prior to the start of ECMO, the patient suffered an anoxic brain injury and suspected herniation prompting the family to withdraw medical care. There is limited evidence in the literature describing the refractory treatment modalities utilized in this patient. This report is unique as it describes the clinical course of a patient when a multitude of unique treatments were combined.

Massive diltiazem and metoprolol overdose rescued with extracorporeal life support.

The management of overdoses of cardioactive medications in the emergency department can be challenging. The reversal of severe toxicity from one or more types of cardioactive medication may fail maximal medical therapies and require extreme invasive measures such as transvenous cardiac pacing and extracorporeal life support. We present a case of massive diltiazem and metoprolol overdose refractory to maximal medical therapy, including intravenous calcium, glucagon, vasopressors, high dose insulin, and lipid emulsion. The patient experienced refractory bradydysrhythmia that responded only to transvenous pacing. Extracorporeal life support was initiated and resulted in successful organ perfusion and complete recovery of the patient. This case highlights the potential utility of extracorporeal life support in cases of severe toxicity due to multiple cardioactive medications.

Availability and cost of extracorporeal treatments for poisonings and other emergency indications: a worldwide survey.

BACKGROUND: Extracorporeal treatments (ECTRs) are used for different conditions, including replacement of organ function and poisoning. Current recommendations for ECTRs in various poisonings suggest that intermittent haemodialysis (IHD) is the most efficient technique. However, the practicality of these recommendations is poorly defined in view of limited information on availability and cost worldwide. METHODS: A survey invitation to an Internet-based questionnaire was emailed between January 2014 and March 2015 to members of international societies to determine the availability, time to initiation and cost of ECTRs (including filters, dialysate, catheter, anticoagulant and nursing/physician salary). The median cost ratio of every ECTR compared with IHD performed in the same institution were presented. RESULTS: The view rate was estimated at 28.1% (2532/9000), the participation rate was 40.1% (1015/2532) and the completion rate was 16.0% (162/1015). Respondents originated from 89 countries, and nearly three-fourths practiced in a tertiary care centre. A total of 162 respondents provided sufficient data for in-depth analysis. IHD was the most available acute ECTR (96.9%), followed by therapeutic plasma exchange (TPE; 68.3%), continuous renal replacement therapy (CRRT; 62.9%), peritoneal dialysis (PD; 44.8%), haemoperfusion (HP; 30.9%) and liver support devices (LSDs; 14.7%). IHD, CRRT and HP were the shortest to initiate (median = 60 min). The median cost ratios of each ECTR compared with IHD were 1.7 for CRRT and HP, 2.8 for TPE, 6.5 for LSDs and 1.4 for PD (P < 0.001 for all). The median cost ratio of a 4-h IHD treatment compared with 1 day in the intensive care unit was 0.6 (P = 0.2). CONCLUSIONS: IHD appears to be the most widely available ECTR worldwide and is at least 30% less expensive than other ECTRs. The superior efficacy of IHD for enhanced elimination, added to its lower cost and wider availability, strengthens its preference as the ECTR of choice in most cases of acute poisoning. KEYWORDS: costing, CRRT, EXTRIP, hemodialysis, hemoperfusion.

Multi-drug intoxication fatality involving atorvastatin: A case report.

Mixed antihypertensive drug intoxication poses a significant risk for patient mortality. In tandem to antihypertensives, hypolipidemic medicines (especially statins) are often prescribed. Among their well-known adverse effects belongs rhabdomyolysis. We report a case of fatal multi-drug overdose in a 65-year-old female alcoholic. The patient was unconscious at admission. Empty blister packs indicated the abuse of 250 tablets of urapidil, 42 tablets of verapamil/trandolapril, 50 tablets of moxonidin, 80 tablets of atorvastatin and 80 tablets of diacerein. Standard measures (gastric lavage, activated charcoal, mechanical ventilation, massive doses of vasopressors, volume expansion, diuretics and alkalinization) failed to provide sufficient drug elimination and hemodynamic support and the sufferer deceased on the fourth day. Dramatic elevations of serum myoglobin (34,020 µg/L) and creatine kinase (219 µkat/L) were accompanied by rise in cardiac troponin I and creatinine. Gas chromatography revealed ethanol 1.17 g/kg (blood) and 2.81 g/kg (urine). Thin layer chromatography and gas chromatography of gastric content and urine verified verapamil, moxonidin and urapidil fragment (diacerein method was unavailable). Atorvastatin and trandolapril concentrations (LC-MS(n)) equaled 277.7 µg/L and 57.5 µg/L, resp. (serum) and 8.15 µg/L and 602.3 µg/L, resp. (urine). Histology confirmed precipitates of myoglobin with acute necrosis of proximal renal tubules in association with striated muscle rhabdomyolysis and myocardial dystrophy. Cardiogenic-distributive shock in conjunction with acute renal failure due to the combined self-poisoning with vasoactive agents and atorvastatin were determined to be this decedent's immediate cause of death. The manner of death was assigned to be suicidal.

Topical minoxidil: accidental poisoning in children.

Hypotension and persistent tachycardia in a young girl after ingesting minoxidil cutaneous solution intended for her father.

Multiple poisonings with sodium azide at a local restaurant.

BACKGROUND: Sodium azide is a chemical with a mechanism similar to cyanide. There is concern that it could be used as a chemical warfare agent. OBJECTIVES: We report a cluster of poisonings that occurred at a public restaurant and the subsequent investigation that identified iced tea contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. CASE REPORT: Five patients became ill within minutes of drinking iced tea at a restaurant. They all presented to the same Emergency Department with similar symptoms, and improved with fluids, antiemetics, and supportive care. A joint investigation by the Dallas County Department of Health and Human Services, the Texas State Health Department, the Dallas County Southwestern Institute of Forensic Sciences, and the medical toxicologists at the University of Texas Southwestern School of Medicine identified iced tea, contaminated with sodium azide (NaN3) and hydrazoic acid, as the foodborne vehicle and agents, respectively. CONCLUSION: The recurrence, and seriousness, of these events suggests a need for continued education of emergency providers. Emergency physicians should consider exposures to toxic chemicals in their differential when a cluster of patients presents with similar symptoms over a short period of time.

Papaverine intoxication in a newborn: an unusual case report.

Herbal agents are increasingly used for medicinal purposes, but there is a lack of knowledge about the content of these agents. Indiscriminate use of herbal agents may cause severe side effects and also death. We report a newborn who developed convulsions and respiratory arrest after oral intake of an opium poppy preparation containing papaverine for its antitussive effect. The infant experienced a good outcome with supportive treatment. To the best of our knowledge, this is the first time a newborn with papaverine intoxication has been described. Parents should avoid self-medication of their children, and the possibility of exposure to foreign products should be kept in mind in any seizure of a newborn with unexplained origin.

Acute toxicity of some synthetic cyanogens in rats: time-dependent cyanide generation and cytochrome oxidase inhibition in soft tissues after sub-lethal oral intoxication.

Cyanogens include complex nitrile-containing compounds that can generate free cyanide of toxicological significance. Acute toxicity, time-dependent cyanide generation and cytochrome oxidase (CYTOX) inhibition in soft tissues, and urinary thiocyanate levels were measured after acute cyanogen intoxication in rats. Order of cyanogens in terms of LD50 was: malononitrile (MCN)>propionitrile (PCN)≈sodium nitroprusside (SNP)>acrylonitrile (ACN)>succinonitrile (SCN)>acetonitrile (ATCN) for oral, and SNP>MCN>ACN>PCN>SCN>ATCN for intraperitoneal and subcutaneous routes. MCN was most toxic by oral (LD50=66.4 mg/kg) and SNP by intraperitoneal (LD50=16.7 mg/kg) and subcutaneous (LD50=11.9 mg/kg) routes. Minimum survival time (25 min) was recorded after 4.0 LD50 ATCN. Order of cyanogens (0.75 LD50; oral) on the basis of maximum blood cyanide and time of peak cyanide generation were: ATCN>SNP>SCN>PCN>MCN>ACN, and MCN (30 min)

Pseudo-blood leak? A hemodialysis mystery.

Hydroxocobalamin is a treatment for cyanide toxicity with few side effects. We report a case of a hemodialysis patient whose treatment was compromised by hydroxocobalamin interference with the blood leak detector.

Safety profile assessment of buflomedil: an overview of adverse reactions between 1975 and 2011.

PURPOSE: Review all the individualized cases of adverse drug reaction (ADR) potentially related to buflomedil, a vasodilator with the indication for peripheral arterial disease (PAD), marketed in Europe since the 1970s but recently suspended by the European Medicines Agency. METHODS: A review of all available individualised case safety data relating to oral buflomedil from the buflomedil global safety database (provided by the manufacturer of buflomedil), the worldwide published medical literature, toxicology/poison centres and regulatory authorities. RESULTS: The main ADRs reported were in the cardiovascular (CVS) and nervous systems (NS), grouped under four (MedDRA) System Organ Classes (SOCs): (i) Cardiac disorders; (ii) Vascular disorders; (iii) Investigations; (iv) NS disorders. From an initial cumulative number of 1054 case reports, there were 401 cases of intentional overdose (IOD) of which 63 were fatal, and 137 cases of accidental overdose, with two fatalities, and 516 case reports of ADRs under normal conditions of use of the product at normal therapeutic dosage with 11 fatalities. Overdosage (intentional or accidental) represented 50.9% of cases, with 47.6% of patients <40 years of age. The indications for which these young patients were prescribed buflomedil were not reported in most cases. CONCLUSIONS: The main indication of buflomedil is PAD; however, because most cases of IOD occurred in people <40 years of age, where PAD is unlikely, it is possible that buflomedil was prescribed for other indications and/or that it was not directly prescribed to the end user, who rather gained access to the medication prescribed to family members or friends.

Sodium azide poisoning at a restaurant - Dallas County, Texas, 2010.

In April 2010, Dallas County Health and Human Services (DCHHS) staff members investigated reports of acute-onset dizziness among patrons in a local restaurant. Symptoms, which included fainting resulting from low blood pressure, occurred within minutes of consuming food from the restaurant and were consistent with chemical poisoning. Toxicologic and epidemiologic investigations were begun to determine the cause of the poisonings and identify potentially exposed persons. This report summarizes the results of those investigations, including a case-control study that identified iced tea as the likely contaminated food or drink (odds ratio [OR] = 65; 95% confidence interval [CI] = 2.4-3,292). Approximately 5 months after the incident, extensive laboratory testing identified sodium azide (NaN3) and hydrazoic acid (formed when sodium azide contacts water) as the toxic agents in the iced tea. All five ill restaurant patrons recovered from their symptoms. For rapid-onset foodborne illnesses, chemical poisons should be considered as a potential cause, regardless of negative initial toxicologic screening tests. Although unusual chemicals can be challenging to detect, a multidisciplinary approach involving public health officials and forensic and medical toxicologists can lead to appropriate testing. In the absence of an identified agent, epidemiologic tools are valuable for active case-finding and confirming suspected contaminated food vehicles.

Refractory hypotension due to Rogaine® (minoxidil) ingestion managed with midodrine.

BACKGROUND: Minoxidil (Rogaine®) is a direct vasodilator that can cause significant toxicity when ingested. We report a case of ingestion of topical minoxidil [Rogaine® (Johnson & Johnson Healthcare Products, Division of McNeil-PPC, Inc)] resulting in refractory hypotension that was successfully managed with the oral α (1) agonist midodrine. CASE REPORT: A 48-year-old male who ingested an eight ounce bottle of Rogaine® presented to the emergency department. The patient presented with a blood pressure of 57/45 mmHg and a pulse of 84 beats per minute. The patient received IV fluids and multiple vasopressors to maintain an adequate mean arterial pressure. Midodrine, an oral α (1) vasopressor, was added 10 hours post ingestion and was able to maintain an adequate mean arterial pressure. Over the next two days, midodrine was titrated down as his blood pressure returned to baseline. CONCLUSION: Midodrine may serve as an additional option to treat toxicant induced hypotension.

[Minoxidil intoxication, the pharmacological agent of a hair lotion]. / Intoxication par le minoxidil, principe actif d'une lotion capillaire. À propos d'un cas.

Accidental intoxications in children are frequent but most of them are without serious consequences. We describe herein the case of a young girl who drank 100 mg of a topical hair lotion with minoxidil. On arrival, she had no symptoms except flush on the face and ears. Four and half hours after ingestion, tachycardia appeared with a pulse above 170 beats per min with hypotension at 76/24 mmHg. The heart rate remained between 170 and 190 beats per min for 12 h and then lowered to between 140 and 160 beats per min. Thirty-six hours after ingestion, the heart beat was at 140 beats per min. Minoxidil is a strong vasodilator used first in the 1970s for severe hypertension. It produces hypotension by direct arteriolar vasodilatation. Only a few cases of minoxidil intoxication have been described in the literature, including only one pediatric case. This young boy had only tachycardia of 160 beats per min for 40 h. Most serious cases have been described in adults. They suffered long-lasting tachycardia, hypotension, and ECG changes. Most patients need a bolus of normal saline fluid and some with hemodynamic problems need vasoactive drugs such as dopamine and/or phenylephrine. All patients need to be under medical supervision for a long time because of the product's very long action.

Methylene blue in the treatment of refractory shock from an amlodipine overdose.

Amlodipine is a potent vasodilator with a long half-life and delayed onset of action that is particularly concerning after an overdose. Vasodilation occurs through stimulation of nitric oxide release with increased cyclic guanosine monophosphate (cGMP) production. Methylene blue inhibits guanylate cyclase. This enzyme is responsible for the production of cGMP. Methylene blue also has the ability to scavenge nitric oxide, as well as inhibit nitric oxide synthase. We report the use of methylene blue for refractory shock in a patient with amlodipine toxicity.

Fatal intoxication with naftidrofuryl.

A 52-year-old man was found dead in his bed. He had financial and psychosocial problems like separation from his wife and children or unemployment due to alcoholism. Under treatment of disulfiram he was presently abstinent from alcohol. As he had suffered from epileptic seizures and dizziness, he received valproic acid and the vasodilator naftidrofuryl, respectively. Autopsy showed no morphologic cause of death. Chemical analysis of blood revealed concentrations for valproic acid and disulfiram in the therapeutic and above the therapeutic range but far below the lethal level, respectively. No ethanol was found. However, the very high concentration of 7500 microg/L naftidrofuryl in whole blood was considered as cause of death, and the most probable manner of death seemed to be suicide. To our knowledge, this is the first reported case of a fatal poisoning with naftidrofuryl.

A series of hospital homicides.

Patient deaths in hospitals due to medical staff are very rare. In the autumn of 2006, preliminary proceedings were initiated against a nurse on account of an overdose of medication leading to death, administered during her care of the patient. In the course of these proceedings, exhibits relating to the deaths of a total of 13 patients who had died due to chemical-toxicological causes were reviewed. Nine of them were exhumed. On average, death had occurred 22 months prior to exhumation (range of 1-34 months). The average age of the deceased was 76 years (range of 65-92 years). In five of the cases, analysis results and an evaluation of the medical records confirmed that a final, undocumented dose of sodium nitroprusside or midazolam was administered. After administration of sodium nitroprusside, the active agent rapidly releases nitrogen monoxide, itself undetectable. Another indicator that can be detected, however, is the cyanide that is also released. In one of the exhumed patients, cyanide could still be detected 18 months after death. The nurse stated that her motive was sympathy towards seriously ill patients. She was sentenced res judicata to life imprisonment on five counts of causing the death of a patient.