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.

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.

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.

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.

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.

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.

Acute hemolysis caused by incidental trichlorfon exposure.

Trichlorfon (o-o-dimethyl-2,2,2-trichloro-hydroxyethylphosphate), an organophosphate, has a moderately potent anticholinesterase activity. Organophosphate poisoning is well known for its characteristic symptoms and signs, but acute hemolysis caused by trichlorfon is rarely reported. We present a patient who developed acute hemolysis and renal function impairment after percutaneous trichlorfon exposure. A 54-year-old man applied trichlorfon powder to his dog to kill its parasites. Half an hour later, the dog was suspected to die of cholinergic crisis and the patient felt abdominal cramping pain. Later, he developed severe nausea, vomiting, chills, high fever, and cold sweat. Laboratory work-up disclosed a picture of acute hemolysis, jaundice, renal function impairment and leukocytosis. However, there were no clinical features of acute cholinergic syndrome except gastrointestinal symptoms, and blood cholinesterase activities were also normal. He eventually had a full recovery. Trichlorfon should be added to the toxins known to cause acute hemolysis.

Acute severe chromium poisoning after dermal exposure to hexavalent chromium.

Severe acute chromium poisoning related to dermal involvement has rarely been reported in the literature. We report a case of acute severe chromium poisoning through skin exposure as a result of a chemical burn of 15% of the body surface area and multiple organ failure after short-term exposure. Medical interventions, including mechanical ventilation, continuous venovenous hemofiltration, and plasmapheresis were performed. In addition, a chelating agent, dimercaptopropane sulfonic acid, was infused intravenously, combined with intravenous N-acetylcysteine and ascorbic acid as adjuvant therapy. The patient was discharged on day 33 without long-term sequelae. The consequence of transdermal exposure of hexavalent chromium should not be overlooked.

Acute alachlor and butachlor herbicide poisoning.

BACKGROUND: Alachlor and butachlor are commonly used herbicides. However, data on acute human poisonings are scarce. We retrospectively analyzed the data of human alachlor/butachlor poisoning in Taiwan. METHODS: The study period ran from October 1986 through February 2007. Sixty-three alachlor and 70 butachlor poisoning cases were reported to the Taiwan National Poison Center during the study period. Clinical data were reviewed and analyzed. RESULTS: Most patients intentionally ingested the herbicides. The toxicities of alachlor and butachlor were largely similar. Twenty-eight out of 102 patients with oral exposure were asymptomatic, while the others developed vomiting, central nervous system depression, and other outcomes. Among patients using other exposure pathways, gastrointestinal effects were the main manifestation. Three patients died after manifesting profound hypotension and/or coma following alachlor ingestion. CONCLUSION: Alachlor and butachlor poisonings are usually of low toxicity. However, severe neurological and cardiovascular outcomes may develop rarely, especially following oral ingestion. Medical management of such poisonings is primarily supportive.

Intermediate syndrome following organophosphate insecticide poisoning.

Acute organophosphate insecticide poisoning can manifest 3 different phases of toxic effects, namely, acute cholinergic crisis, intermediate syndrome (IMS), and delayed neuropathy. Among them, IMS has been considered as a major contributing factor of organophosphate-related morbidity and mortality because of its frequent occurrence and probable consequence of respiratory failure. Despite a high incidence, the pathophysiology that underlies IMS remains unclear. Previously proposed mechanisms of IMS include different susceptibility of various cholinergic receptors, muscle necrosis, prolonged acetylcholinesterase inhibition, inadequate oxime therapy, downregulation or desensitization of postsynaptic acetylcholine receptors, failure of postsynaptic acetylcholine release, and oxidative stress-related myopathy. The clinical manifestations of IMS typically occur within 24 to 96 hours, affecting conscious patients without cholinergic signs, and involve the muscles of respiration, proximal limb muscles, neck flexors, and muscles innervated by motor cranial nerves. With appropriate therapy that commonly includes artificial respiration, complete recovery develops 5-18 days later. Patients with atypical manifestations of IMS, especially a relapse or a continuum of acute cholinergic crisis, however, were frequently reported in clinical studies of IMS. The treatment of IMS is mainly supportive. Nevertheless, because IMS generally concurs with severe organophosphate toxicity and persistent inhibition of acetylcholinesterase, early aggressive decontamination, appropriate antidotal therapy, and prompt institution of ventilatory support should be helpful in ameliorating the magnitude and/or the incidence of IMS. Although IMS is well recognized as a disorder of neuromuscular junctions, its exact etiology, incidence, and risk factors are not clearly defined because existing studies are largely small-scale case series and do not employ a consistent and rigorous definition of IMS. Without a clear understanding of the pathophysiology of IMS, specific therapy is not available. The prognosis of IMS, however, is likely to be favorable if respiratory failure can be promptly recognized and treated accordingly.

Acute hepatic injury and renal failure after ingestion of snake gallbladder.

Ingestion of snake gallbladder has been practiced in ancient Chinese civilizations to improve vision and relieve arthritic pain. Although little is known about the composition of snake gallbladder, ingestion is still practiced in some Chinese cultures. Adverse effects of ingesting snake gallbladder have not yet been reported. Here, we present a case of acute hepatic injury and delayed-onset renal failure after ingestion of snake gallbladders. The patient subsequently recovered after supportive care, combined with plasma exchange and hemodialysis. He was the only survivor of the four victims suffering from intoxication of snake gallbladder in the last three years in our hospital.

Acute Erycibe henryi Prain ("Ting Kung Teng") poisoning.

Erycibe henryi Prain ("Ting Kung Teng"), a species of Convolvulaceae, has been used in Chinese medicine to relieve pain involving the musculoskeletal system, such as arthritis, sciatica, and traumatic tissue swelling. E. henryi can be mistaken for another herbal plant, Tripterygium wilfordii Hook F, used to treat gouty arthritis. We report here three cases of E. henryi poisoning. All three cases presented with vomiting, diarrhea, salivation, diaphoresis, lacrimation, and rhinorrhea; two patients also had miosis, hypothermia, bradycardia, hypotension, and ventricular tachyarrhythmias. Laboratory abnormalities included leucocytosis, hyperglycemia, hyperamylasemia, hypocalcemia, and transiently elevated liver enzymes, creatinine and creatinine phosphokinase. The active constituents of E. henryi include several tropane alkaloids, which exhibit cholinergic activities. Gastrointestinal disturbances and ventricular tachyarrhythmias may occur with ingestion of either E. henryi or T. wilfordii, but the cholinergic symptoms can help to differentiate them.

Epinephrine protects against severe acute gastric bleeding in rats: role of nitric oxide and glutathione.

The aim of this study was to examine the effect of the systemic administration of epinephrine against severe acute gastric bleeding in rats. Epinephrine decreased gastric hemorrhage not only before but also after lipopolysaccharide-induced severe acute gastric bleeding. Epinephrine ameliorated severe gastric hemorrhage and decreased gastric mucosal lipid peroxidation through alpha- and beta-adrenoceptors. Epinephrine modulated alpha-adrenoceptors to increase the levels of gastric mucosal nitric oxide and glutathione. Nitric oxide synthase inhibitors potently reversed the effects of epinephrine on gastric mucosal glutathione. Thus, epinephrine might act through alpha-adrenoceptors to increase the levels of gastric mucosal nitric oxide and glutathione and thus protect against severe acute gastric bleeding in rats.

Identification of tetrodotoxin in a marine gastropod (Nassarius glans) responsible for human morbidity and mortality in Taiwan.

The toxicity of the gastropod Nassarius glans was investigated. This gastropod was implicated in an incident of food paralytic poisoning on Tungsa Island, Taiwan, in April 2004. Six victims consumed both digestive glands and muscle. These tissues contained high concentrations of toxin; their highest toxicity scores were 2,048 and 2,992 MU/g, respectively, based on the tetrodotoxin (TTX) bioassay. The toxin was purified from these gastropods and analyzed by high-performance liquid chromatography, which revealed TTX and related compounds 4-epi TTX and anhydro-TTX; paralytic shellfish poisons were not found. The urine and blood samples from patients were cleansed using a C18 Sep-Pak cartridge column and 3,000 molecular weight cutoff Ultrafree microcentrifuge filters, and the eluate was filtered and analyzed by liquid chromatography and mass spectrometry. The detection limit for TTX was 1 ng/ml. The standard curves were linear in the range 30 to 600 ng/ml for urine and 1 to 30 ng/ml for blood. TTX was detected in all urine samples but in only three of four blood samples tested. Thus, the causative agent of gastropod food poisoning was identified as TTX.

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.

Russell's viper snakebite in Taiwan: differences from other Asian countries.

Formosan Russell's viper (Daboia russelli siamensis) is the sixth most frequent cause of snakebite in Taiwan. Its venom has been thought to have both neurotoxic and hematoxic properties. This viper's snakebite is rare and thus scarcely subjected to systemic studies. In this paper, we retrospectively analyzed and described 18 cases of viper snakebite from 1987 to 1999. Like that of the Russell's viper snakebite in other South East Asian areas, varied degrees of acute renal failure, incoagulable blood with bleeding diathesis and hemolysis were the major symptoms found in the systemic envenoming patients. Systemic thrombosis seems to be the distinguishing feature in Formosan Russell's viper snakebite. Neither symptoms nor signs of neuromuscular junction blocking effects were observed, which is another difference from symptoms observed after bites of some other Russell's viper subspecies, suggesting a significant geographic variation. These findings confirmed the clinical importance of Russell's viper snakebite in Taiwan.