Rat Bait, Not Healthy Rice!

Bromadiolone, a potent, long-acting anticoagulant rodenticide is frequently tinted to a red or pink color and mixed with cereals as rat bait. Six peoples working in a small factory suffered from a severe bleeding tendency several weeks after consuming a rice meal that was tainted with bromadiolone mistaken to be healthy food. High serum levels of bromadiolone and excessive bleeding were found in these individuals, and they needed vitamin K1 therapy for weeks. These cases indicated that long-acting anticoagulant rodenticide might induce cumulative toxicity in repeated, low-dose exposure, and the blood levels of bromadiolone might be an indicator for antidote therapy if available.

A successful experience using labetalol and hemodialysis to treat near-fatal caffeine poisoning: A case report with toxicodynamics.

Caffeine poisoning is relatively rare, and a near-fatal caffeine overdose is highly uncommon. We present an 18-year-old male who attempted suicide with 295 mg/kg pure caffeine powder (lethal oral dose: 150-200 mg/kg) and was successfully rescued. He presented with seizures, refractory supraventricular tachycardia and hypertension for 6 h with no response to medications and cardioversion. Even with the high level of caffeine, labetalol, which is seldom administered as a treatment for caffeine poisoning-induced tachycardia, successfully relieved refractory tachycardia. Then, hemodialysis ultimately eliminated serum caffeine and completely alleviated caffeine-related central nervous system toxicity. We discuss the clinical symptoms, management and toxicodynamics based on the concentration of caffeine and its metabolites in serum and urine.

Presentations of tetramethylammonium hydroxide dermal exposure and the valuable potential of diphoterine solution in decontamination: a retrospective observational study.

BACKGROUND: Tetramethylammonium hydroxide (TMAH) is a quaternary ammonium compound that is both a base corrosive and a cholinergic agonist, and it is widely used in the photoelectric and semiconductor industries. It causes corrosive skin injuries and systemic cholinergic toxicity with death primarily resulting from respiratory failure without efficacious early decontamination. METHODS: A retrospective observational study was performed of all cases of TMAH exposure reported to the Taiwan Poison Control Center between July 2010 and October 2017. Retrieved medical records were independently reviewed by two trained clinical toxicologists. RESULTS: Despite immediate (< 5 min) skin decontamination with copious amounts of tap water, one patient exposed to 25% TMAH involving ≥5% of total body surface area (TBSA) developed significant systemic toxicity. Patients exposed to 25% TMAH involving ≤1% TBSA developed first-degree chemical skin injuries but no systemic toxicity. Among patients exposed to lower concentrations (≤2.38%) of TMAH, the majority only experienced first-degree chemical skin injuries without systemic signs. Patients exposed to 0.5% TMAH involving nearly their entire TBSA developed no chemical skin injuries or systemic toxicity. All patients who had only first-degree chemical skin injuries did not develop systemic toxicity after exposure to either 2.38% or 25% TMAH. CONCLUSIONS: TMAH acts as an alkaline corrosive and cholinergic agonist. Systemic signs attributable to TMA+ can rapidly lead to respiratory failure and death after dermal exposure. We have demonstrated that an amphoteric solution may be efficacious for skin decontamination on-site immediately to prevent or ameliorate such toxicity. This practice especially carries a valuable potential in managing victims (patients) who have been exposed to those chemicals with immediate life-threatening toxicity (e.g. TMAH), suggesting that its early utilization deserves further study.

Who is the real killer? Chlorfenapyr or detergent micelle-chlorfenapyr complex?

1. Chlorfenapyr [4-bromo-2-(4-chlorophenyl)-1-(ethoxymethl)-5-(trifluoromethyl)-1H-pyrrole-3-carbonitrile] is a commonly employed pesticide throughout the world. The mechanism of chlorfenapyr action is to uncouple oxidative phosphorylation in the mitochondria. The characteristic features of chlorfenapyr intoxication are high fever, rhabdomyolysis and neurologic symptoms that gradually get worse until death. 2. In recent years, suicide attempt cases using commercial chlorfenapyr pesticide were reported. Even small doses of commercial chlorfenapyr pesticide intoxication caused human fatality. However, world health organization (WHO) has classified chlorfenapyr as class 2-moderately hazardous chemical. Animal studies using technical grade (94.5%; AC 7504-59A) chlorfenapyr in 0.5% carboxy methyl cellulose as the vehicle, single dose through oral route in male rats were well tolerated. 3. We planned a therapeutic strategy for suicidal chlorfenapyr intoxication, therefore we evaluated the three different toxic doses of chlorfenapyr (10% chlorfenapyr and 90% detergent) through oral route in male rats for human extrapolation. The major difference between the technical grade chlorfenapyr and commercial grade chlorfenapyr was the vehicle. In the technical grade chlorfenapyr study, 0.5% carboxy methyl cellulose was used as a vehicle, whereas in the present study 90% detergent acted as a vehicle. The LD50 of commercial grade chlorfenapyr-40.63 mg/kg bw, which was approximately tenfold decrease than technical grade chlorfenapyr, LD50 - 441 mg/kg bw. 4. The combination of chlorfenapyr and detergent, a deadly cocktail to form micelle complex that can greatly influence bioavailability by attaching to biological membranes in vivo. To conclude, the enhanced bioavailability of chlorfenapyr by the detergent causes the fatality in suicidal attempts using chlorfenapyr.

Neurotoxicity associated with exposure to 1-bromopropane in golf-club cleansing workers.

BACKGROUND: 1-Bromopropane (1-BP) is an alternative to ozone-depleting solvent that is used in degreasing, dry cleaning, spray adhesives, and aerosol solvents. Occupational exposure to 1-BP is associated with adverse peripheral sensory, motor, and central nervous system (CNS) effects. We report our Health Hazard and Medical Evaluation of 6 patients with neurotoxicity associated with occupational exposure to 1-BP. Case series and environmental evaluation. Six workers, 1 male and 5 female, were exposed to high ambient 1-BP concentrations while employed in a golf club cleaning factory. 1-BP was identified in the bulk solvent sample used by the workers and confirmed the workers' daily occupational exposure to 1-BP for 3-10 months. The major presenting symptoms were tingling pain, soreness in lower extremities, and paresthesia. N-acetyl-S-(n-propyl)-L-cysteine (AcPrCys), a 1-BP metabolite, was identified by LC/MS/MS in the urine (0.171-1.74 mg/g-Cr) of these workers 5-26 days following 1-BP exposure. DISCUSSION AND CONCLUSION: An occupational outbreak of 1-BP poisoning occurred as a result of recurrent power outages, condenser, and exhaust fans malfunction, and inadequate personal protection. Occupational exposure to 1-BP may result in peripheral neuropathy as well as adverse CNS effects. Urine AcPrCys may be a specific biomarker for 1-BP exposure.

Longitudinal changes in the dopamine transporter and cognition in suicide attempters with charcoal burning.

Suicide with charcoal burning, which results in carbon monoxide (CO) poisoning, is common in Asia. This study was designed to elucidate associations between changes in the dopamine transporter (DAT) and cognitive function in patients following CO poisoning during a follow-up period of 6 months. Participants comprised 31 healthy controls (HCs) and 21 CO poisoning patients. Each subject underwent single photon emission computed tomography with [(99m)Tc] TRODAT-1 to measure DAT availability and completed a cognitive battery assessing attention, memory, and executive function. For CO poisoning patients, a second DAT measurement and repeated cognitive evaluations were performed 6 months later. At baseline, DAT availability over bilateral striatum in CO poisoning subjects was significantly lower than in HCs. After 6 months, there was no significant change of DAT availability in CO poisoning patients. CO poisoning patients also had worse cognitive performance in all domains compared with HCs at baseline. After 6 months, most cognitive functions were significantly improved, except for the Wisconsin Card Sorting Test (WCST), a measure of executive function. Interestingly, changes in the WCST were significantly correlated with changes in DAT availability during the 6-month follow-up period. The persistence of reduced DAT availability and its association with impaired performance on the WCST indicate a crucial role of DAT in the recovery of executive function following CO poisoning.

Hyperkalemia, hyperphosphatemia, acute kidney injury, and fatal dysrhythmias after consumption of palytoxin-contaminated goldspot herring.

Severe electrolyte disturbances caused by fish poisoning are rarely reported in the literature. We present an unusual outbreak of palytoxin poisoning associated with the consumption of Goldspot herring (Herklotsichthys quadrimaculatus). Four family members became ill after eating 2 species of marine fish. The presenting symptoms and signs included bitter taste, oral numbness, nausea, vomiting, abdominal pain, and hypertension, which were followed by myalgia, limb numbness, sensorimotor polyneuropathy, and abnormal cold and warm sensations. The index case manifested hyperkalemia, hyperphosphatemia, and acute kidney injury, and developed severe cardiac dysrhythmias. He died 21 hours postingestion. Palytoxin and related compounds were identified by liquid chromatography tandem mass spectrometry in one of the leftover fish. Palytoxin poisoning is rarely reported and is difficult to diagnose in the absence of laboratory confirmation. Palytoxin poisoning should be considered in patients who manifest hyperkalemia and hyperphosphatemia after the consumption of marine fish, and timely laboratory analysis should be sought.

Late diagnosis of an outbreak of leanness-enhancing agent-related food poisoning.

INTRODUCTION: Ractopamine is a leanness-enhancing agent approved in the United States and 26 other countries to reduce body fat content, increase muscle mass, and improve growth rate of certain food-producing animals. Other ß-agonists with stronger pharmacologic effects, especially clenbuterol, had been illegally used as leanness-enhancing agents in the United States, China, and the European Union, and foodborne poisonings related to clenbuterol residue in meat or liver were rarely reported in the European Union and China. We describe an unusual outbreak of leanness-enhancing agent-related food poisoning in Taiwan and its associated diagnostic challenge. REPORT OF THE OUTBREAK: Twelve patients presented to the emergency department of a regional hospital after having dinner together. Their clinical manifestations included nausea, vomiting, palpitation, facial flush, trunk or limb numbness, tremor, headache, weakness, chill, and dyspnea. Laboratory workup revealed the presence of hypokalemia, leukocytosis, and hyperglycemia. Poisoning attributable to ß-agonists was suspected; however, the diagnosis of leanness-enhancing agent poisoning was delayed because there was no leftover meat for analysis and because the veterinary medicine was illegal in Taiwan. Clenbuterol and salbutamol were eventually detected in 10 patients' urine sample by using liquid chromatography-tandem mass spectrometry, and the concentrations ranged from 54 to 806 µg/L and from 0 to 4052 µg/L, respectively. CONCLUSION: ß-Agonist leanness-enhancing agent-related food poisonings are rarely encountered, especially in those countries where relevant veterinary medicines are banned, and may thus pose diagnostic challenge to both emergency physicians and clinical toxicologists.

Lead, mercury, and arsenic poisoning due to topical use of traditional Chinese medicines.

BACKGROUND: Metal poisonings through a mucocutaneous route are reported rarely in the literature. METHODS: We report 2 cases of heavy metal intoxication from inappropriate use of Chinese mineral medicines confirmed by toxicologic investigations. RESULTS: A 51-year-old man developed perianal gangrene and a high fever after a 2-week anal use of hong-dan herbal mixtures for anal fistula. He presented gastrointestinal and constitutional symptoms, followed by skin rash, anemia, hair loss, peripheral neuropathy, and muscle atrophy. Elevated urine arsenic and mercury confirmed the heavy metal poisonings. The hong-dan mixture contained lead tetraoxide, arsenic, and mercury. He was treated with 2,3-dimercapto-1-propanesulfonic acid, with partial improvement, but peripheral neuropathy persists 4 years later. A 75-year-old man developed anorexia, weight loss, headache, dizziness, nausea, vomiting, constipation, weakness, and anemia after a 3-month use of an herbal patch for chronic leg ulcer. His blood lead concentration was 226 µg/dL, and the lead content of the herbal patch was 517 mg/g. Chelation with ethylene diamine tetraacetic acid and dimercaptosuccinic acid was followed by clinical recovery. CONCLUSION: These cases documented serious systemic poisoning after the short-term use of traditional Chinese medicines containing heavy metals in damaged or infected tissue.

Drug abuse-related accidents leading to emergency department visits at two medical centers.

BACKGROUND: Drug abuse is becoming more prevalent in Taiwan, as evidenced by increasing reports of drug trafficking and drug abuse-related criminal activity, and the wide use of more contemporary illicit drugs. Consequently, drug abuse-related accidents are also expected to occur with greater frequency. However, no study has yet specifically evaluated the prevalence, pattern, and outcomes of drug abuse-related accidents among patients visiting emergency departments (EDs) in Taiwan. METHODS: We conducted an ambidirectional study with patients who visited the EDs of Taipei Veterans General Hospital (TVGH) and China Medical University Hospital (CMUH) due to drug abuse-related accidents from January 2007 through September 2009. Information on the patients' baseline characteristics and clinical outcomes was collected and analyzed. RESULTS: During the study period, a total of 166 patients visited the EDs of one of the two study hospitals due to drug abuse-related accidents. This yielded a prevalence of drug abuse of 0.1% among all patients visiting the ED due to accident and/or trauma. Fifty-six out of the 166 patients visited the ED at TVGH, most patients being between 21 and 40 years old. Opioids (41.1%) were the drugs most commonly abused by the patients, followed by benzodiazepines (32.1%). More than two-thirds of the patients (n=38, 67.9%) required hospitalization, and three patients died (5.4%). In contrast, 110 patients with drug abuse-related accidents visited the ED at CMUH during the study period. Most of these subjects had abused benzodiazepines (69.1%), were between 21 and 40 years old, and were female. Fewer than one-fifth of the patients (n=19, 17.3%) required hospitalization, with no deaths reported. There were significant between-hospital differences in terms of patient gender, drugs of choice, injury mechanisms, method and time of the ED visit, triage levels, and need for hospitalization. CONCLUSION: Although the prevalence of drug abuse-related accidents was low, and only three patient deaths were reported in this study, many patients presented to the EDs with severe effects and later required hospitalization. Better and timely management of such patients will help to minimize the adverse health impacts associated with drug abuse. Governmental agencies and all healthcare professionals should also work together to fight against the surging trend of drug abuse in Taiwan.

Acute human glufosinate-containing herbicide poisoning.

BACKGROUND: Glufosinate-containing herbicides are commonly used worldwide. Data on acute human glufosinate poisoning however remain scarce. METHODS: We retrospectively reviewed the medical records of all glufosinate poisoned cases reported to the Taiwan National Poison Control Center and two medical centers in Taiwan from August 1993 through February 2010. Their demographic and clinical data were then analyzed to identify potential predictors of severe effects following acute glufosinate poisoning. RESULTS: One hundred and thirty-one patients, including 115 oral and 16 non-oral exposures, were eligible for final analysis. Among patients with oral exposure, 25 were asymptomatic, while the others developed gastrointestinal, neurological, cardiovascular, and/or respiratory manifestations. Seven patients (6.1%) died following deliberate glufosinate ingestion. The median dose of glufosinate ingestion was 30.4 grams (interquartile range 18.5-45.6 grams) in the severe/fatal group compared to 6.8 grams (interquartile range 3.7-16.2 grams) in the non-severe group (p <0.001). Older age (≥ 61 years; adjusted OR 4.9, 95% CI 1.3-17.9) and larger amount of glufosinate ingestion (≥ 13.9 grams; adjusted OR 25.2, 95% CI 4.8-132.5) were positively associated with the development of severe toxicity, whereas ethanol consumption (adjusted OR 0.1, 95% CI <0.1-0.5) was inversely associated with the risk of severe toxicity. CONCLUSION: Although glufosinate is generally thought to be of low toxicity to humans, severe effects can occur and may be associated with older age, larger amount of ingestion and absence of concomitant ethanol consumption.

Essential trace element status and clinical outcomes in long-term dialysis patients: a two-year prospective observational cohort study.

BACKGROUND & AIMS: Essential trace elements are involved in many biological processes for normal cell function including immunological defense against oxidation and infection. Deficiency of these elements generally leads to illness or even death in the general population. Therefore, we investigated the predictive values of trace element status on clinical outcomes in dialysis patients, who are more prone to trace element deficiency. METHODS: We enrolled 111 prevalent patients on maintenance dialysis from a Taipei tertiary-care referral hospital and measured serum levels of selenium, copper, and zinc. Patients were followed for 2 years or until death or withdrawal. RESULTS: Multivariate Cox regression analysis indicated that patients with diabetes mellitus (HR, 2.162 [95% CI, 1.105-4.232], p=0.024), prior stroke (HR, 3.876 [95% CI, 1.136-13.221], p=0.030), and zinc deficiency (HR, 0.979 [95% CI, 0.966-0.992], p=0.002) were more likely to be hospitalized for infectious diseases. Furthermore, beyond traditional risk factors, such as old age and hypoalbuminemia, multivariate Cox regression also indicated that lower serum level of zinc independently predicts overall mortality (HR, 0.973 [95% CI, 0.948-0.999], p=0.046). CONCLUSIONS: In long-term dialysis patients, the serum level of zinc was an independent predictor of future hospitalization due to infectious diseases and of overall mortality.

Determination of caprolactam and 6-aminocaproic acid in human urine using hydrophilic interaction liquid chromatography-tandem mass spectrometry.

A simple and rapid assay based on hydrophilic interaction liquid chromatography with tandem mass spectrometry has been first developed and validated for simultaneous determination of caprolactam (CA) and 6-aminocaproic acid (6-ANCA) in human urine using 8-aminocaprylic acid as internal standard. A 20µL aliquot of urine was injected directly into the liquid chromatography tandem mass spectrometry (LC-MS-MS) system. The analytes were separated on a Phenomenex Luna HILIC column with gradient elution. Detection was performed on Triple Quadrupole LC-MS in positive ions multiple reaction monitoring mode using electrospray ionization. The calibration curves were linear (r(2)≥0.995) over the concentration range from 62.5 to 1250ng/mL for CA and 31.25 to 1000ng/mL for 6-ANCA. The detection limits of CA and 6-ANCA were 62.5 and 15.6ng/mL, respectively. The intra-day and inter-day precisions were within 8.7% and 9.9%, respectively. The intra-day and inter-day accuracy were between 5.3% and 3.5%, and between 6.1% and 6.6%, respectively. The method proved to be simple and time efficient, and was successfully applied to evaluate the kinetics of caprolactam in one unusual case of caprolactam poisoning.

Fatal serotonin toxicity caused by moclobemide and fluoxetine overdose.

Both moclobemide and fluoxetine are used in the treatment of depression, and have been shown to produce fewer side effects than conventional tricyclic antidepressants. A combination of moclobemide and fluoxetine has been used in refractory depression, however there is potential for severe serotonin toxicity. We describe a lethal case of serotonin toxicity in a 36 year-old woman after she ingested multiple drugs, including moclobemide 4500 mg, fluoxetine 200 mg, propranolol 300 mg and several benzodiazepines. The clinical features included coma, mydriasis, hyperthermia, tremor, hyperreflexia, rhabdomyolysis, renal failure and respiratory insufficiency. Eventually, the patient died of disseminated intravascular coagulation and circulatory collapse at 22.5 h postingestion. Toxicological analysis of the patient's blood confirmed high levels of moclobemide 150 µg/mL (therapeutic 1-3 µg/mL), fluoxetine 3750 ng/mL (therapeutic 47-469 ng/mL) and several benzodiazepines. In conclusion, a combination of moclobemide and fluoxetine should be avoided in depressed patients with high suicidal tendencies. Moreover, early recognition and aggressive intervention are the mainstays in the management of potentially life-threatening serotonin toxicity.

Striatal dopamine transporter binding for predicting the development of delayed neuropsychological sequelae in suicide attempters by carbon monoxide poisoning: A SPECT study.

Carbon monoxide poisoning (COP) after charcoal burning results in delayed neuropsychological sequelae (DNS), which show clinical resemblance to Parkinson's disease, without adequate predictors at present. This study examined the role of dopamine transporter (DAT) binding for the prediction of DNS. Twenty-seven suicide attempters with COP were recruited. Seven of them developed DNS, while the remainder did not. The striatal DAT binding was measured by single photon emission computed tomography with (99m)Tc-TRODAT. The specific uptake ratio was derived based on a ratio equilibrium model. Using a logistic regression model, multiple clinical variables were examined as potential predictors for DNS. COP patients with DNS had a lower binding on left striatal DAT binding than patients without DNS. Logistic regression analysis showed that a combination of initial loss of consciousness and lower left striatal DAT binding predicted the development of DNS. Our data indicate that the left striatal DAT binding could help to predict the development of DNS. This finding not only demonstrates the feasibility of brain imaging techniques for predicting the development of DNS but will also help clinicians to improve the quality of care for COP patients.