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Background: Plasma cholinesterase (PChE) metabolizes cocaine to ecgonine methyl ester (EME). Limited data demonstrate that EME is a mild vasodilator. Exogenous PChE protects against cocaine-induced seizures and lethality. It is unclear whether this protective effect results from enhanced degradation of cocaine, the loss of active metabolites (benzoylecgonine, norcocaine), or the production of a beneficial metabolite (EME). This study was designed to further investigate the pharmacologic effects of EME., Methods: All experiments used female ICR Swiss albino mice weighing 20-30 grams. Mice were acclimated to 12 h alternating light-dark cycles and given food and water ad libitum. Using a randomized, blinded protocol, 80 mice were then pretreated with either IP EME (50 mg/kg) in a 0.9% sodium chloride solution or an equal volume of 0.9% sodium chloride solution as control. Five minutes later, all animals received 126 mg/kg of cocaine IP and were observed for seizures and death. Fatality was compared using a Fisher's exact test, and the time to seizures and death were compared using a Mann-Whitney U statistic., Results: Pretreatment with EME increased survival following cocaine (9/40 vs. 2/40, for EME vs. control, respectively, p<0.05). The median times to seizure and death for both groups were 2.0 vs. 1.5 min (p>0.05), and 4.5 vs. 4.6 min (p>0.05) (EME vs. control for seizures and death, respectively)., Conclusion: In this animal model, EME is protective against cocaine lethality. This effect is consistent with the previously described vasodilatory effects of EME. Further studies are indicated to determine whether the increase in EME produced by exogenous PChE administration contributes to the benefits that occur when PChE is given to cocaine-poisoned animals.

Background: "Chasing the dragon" involves placing heroin on aluminum foil, heating it from below with a flame, and inhaling the pyrolysate through a straw. It has rarely been associated with the development of a progressive spongiform leukoencephalopathy., Case Report: A 43-year-old woman presented with 2 weeks of bizarre behavior, forgetfulness, and slowed speech and movements. Serum, cerebrospinal fluid, and head computed tomography (CT) scan were normal. The patient progressed to coma and expired during week 4 of hospital admission. The family confirmed that she "chased the dragon." Cause of death at post mortem examination was spongiform leukoencephalopathy., Conclusion: The diagnosis of heroin pyrolysate-induced spongiform leukoencephalopathy should be considered in a patient with a history of "chasing the dragon" and neurobehavioral changes, including confusion, apathy, cerebellar signs, and motor restlessness.

The temporal association of symptoms consistent with ephedrine toxicity after ingestion of ephedrine-containing dietary supplements is heavily relied upon to confirm exposure. Few reports in the literature attempt to associate toxicity with serum levels of these drugs. We report a case of ephedrine-induced cardiac ischemia confirmed by a plasma level. A 22-year-old woman ingesting an ephedrine- and caffeine-containing product for 2 days presented with multiple symptoms, including palpitations, nausea, tremulousness, abdominal pain, and vomiting. The initial electrocardiogram (ECG) revealed a normal sinus rhythm with 1 mm of ST segment depression in leads V3 and V4, along with inverted T waves in leads V1-V4. Her symptoms and ST segment depression resolved over several hours with medical management. The amplitude of her T wave inversions notably diminished with therapy; however, they did not completely resolve. Troponins at presentation and the following morning were negative, and an echocardiogram showed only trace tricuspid regurgitation. A serum ephedrine level, drawn approximately 6 to 7 hr after ingestion, was 150 ng/mL. She was discharged from the hospital after being instructed to avoid ephedrine-containing products.

Topiramate (Topamax) is an anti-epileptic medication for which acute toxicity is infrequently reported. A 5-yr-old girl, not previously taking topiramate, developed neurological symptoms after acute ingestion of this medication. She was intermittently agitated, complained of "not being able to feel anything," demonstrated arching movements of the back, and perseverated upon questioning. Computerized tomography of the head and electroencephalography were both normal, and urine toxicology testing for drugs of abuse was negative. A serum topiramate level was 10.5 mcg/mL, confirming the ingestion. The patient was observed for 24 h, over which time her symptoms completely resolved.

Introduction: The following case report demonstrates the severe consequences of refractory convulsive status epilepticus from an unfamiliar imported toxin, tetramethylenedisulfotetramine (TETS), and the difficulties of identifying the offending agent., Case Report: A previously healthy 15-month-old girl was found by her parents playing with a white rodenticide powder brought from China. Fifteen minutes later, the child developed generalized seizures and was brought to an Emergency Department (ED). Her initial fingerstick blood glucose was 108 mg/dL. In the ED, the child was intubated for status epilepticus. Despite aggressive therapy with lorazepam, phenobarbital, and pyridoxine, she had 4 h of intermittent generalized seizure activity. She was extubated on the third hospital day, but appeared to have absence seizures and cortical blindness. Continuous electroencephalogram monitoring, performed weeks later, revealed severe diffuse cerebral dysfunction with multiple epileptogenic foci. The child remains developmentally delayed and is on valproic acid therapy for seizure control. Translation of the Chinese package labeling did not clarify its contents. Tetramethylenedisulfotetramine was finally confirmed by gas chromatography-mass spectrometry (GC-MS) in this rodenticide product and then quantified against a TETS standard that was synthesized in our laboratory., Conclusion: Tetramethylenedisulfotetramine is grouped with other "cage convulsants," such as picrotoxin, since they have a similar intercalating cyclical molecular structure and cause seizures through non-competitive gamma-aminobutyric acid (GABA) antagonism. The oral lethal dose 50% (LD50) in humans is estimated to be as low as 100 microg/kg. Our patient has severe diffuse cerebral dysfunction likely secondary to prolonged seizure activity after exposure to TETS.

Introduction: Gamma-hydroxybutyrate is a potent sedative-hypnotic agent and a popular drug of abuse. In the United States, gamma-hydroxybutyrate is a Schedule I controlled substance (sodium oxybate) with orphan drug status for the treatment of narcolepsy within approved clinical studies. Physostigmine is a carbamate inhibitor of acetylcholinesterase that is reported to attenuate the sedative effects of a number of drugs, including gamma-hydroxybutyrate. We reviewed the literature that pertains to the use of physostigmine to treat gamma-hydroxybutyrate-induced sedation., Methods: A structured literature search was performed to identify articles in which physostigmine and gamma-hydroxybutyrate were mentioned. Keywords were used to identify relevant articles in the Medline database, and the reference sections of articles identified by this method were hand-checked to identify additional articles. Those articles that presented original evidence pertaining to the use of physostigmine to treat gamma-hydroxybutyrate-induced sedation were included in this review; those that did not were rejected., Results: The literature search identified 22 articles, six of which did not pertain to the subject matter. Of the 16 articles which remained, 12 were rejected because they offered opinions without presenting original evidence. Of the four articles that presented original evidence, there were no in vitro studies and no animal studies. There were two small case series in which physostigmine was given to treat acute gamma-hydroxybutyrate toxicity in an emergency department setting, and two larger series in which physostigmine was given to attenuate the sedation induced by gamma-hydroxybutyrate in a more structured anesthesia setting. Although these references report that physostigmine attenuates gamma-hydroxybutyrate-induced sedation, there are methodological flaws and confounding factors that limit the scope of the conclusions that can be drawn from them., Conclusions: There is currently insufficient scientific evidence to support the routine use of physostigmine in the treatment of gamma-hydroxybutyrate toxicity. Further studies are needed to determine the role, if any, for physostigmine in this setting.

A 34-year-old male with lumbar disc disease and surgery was placed on gabapentin daily for chronic back pain. He remained on a steady dose of 8000 mg/day for 9 months, almost doubled what is considered therapeutic. He ran out of medication, was unable to refill his prescription for 2 days and presented to the emergency department in status epilepticus. There was no previous history of seizure disorder and he was on no other medications. A medical evaluation for an alternative etiology of his seizures was negative. Although gabapentin withdrawal has been previously reported and usually consists of anxiety, diaphoresis, and palpitations, this is the first reported patient with generalized seizures and status epilepticus secondary to gabapentin withdrawal.

Objective: Ferric chloride (FeCl3) is used to qualitatively test the urine of patients with presumed salicylate exposure. FeCl3 testing of an unidentified poison might provide evidence of salicylate exposure in situations where FeCl3 urine testing cannot be used. Such situations include the absence of a urine sample, immediately after ingestion before urine contains a detectable quantity of salicylate, or for patients chronically using salicylatesfor which FeCl3 testing is unhelpful. This study seeks to determine if FeCl3 can be used to identify salicylate-containing products., Methods: We assessed the reactivity of FeCl3 with commercially available salicylate-containing products. We applied 0.1 mL of 10% FeCl3 solution to each of 15 various salicylate-containing products including: regular and buffered acetylsalicylic acid, bismuth subsalicylate, methylsalicylate, physostigmine salicylate, salicylic acid, trolamine salicylate, and herbal tablets with salicin-containing white willow bark (Salix sp.). These products tested were: regular and enteric-coatedpills (n = 4), powder (n = 1), topical creams (n = 5), topical liquids (n = 4), and intravenous solution (n = 1). FeCl3 was applied to crushed tablets and added directly to liquids and creams. Fifteen salicylate-free controls including liquids, pills, and creams similar in appearance to experimental samples were also tested. Three blinded physiciansfamiliar with FeCl3 testing independently observed the addition of FeCl3 to each sample and rated a positive or negative result., Results: All salicylate-containing products were interpreted to be clearly FeCl3 positive and all control samples were interpreted to be clearly FeCl3 negative., Conclusion: Salicylate-containing products may be identified using FeCl33. When using FeCl3

Background: Levetiracetam (Keppra) is a new anticonvulsant used to treat partial complex seizures that is also being investigated for its mood-stabilizing properties. Although its precise mechanism of action is unknown, levetiracetam does not appear to directly interact with the GABA system. We report the first intentional overdose with levetiracetam including clinical effects and serial serum concentrations., Case Report: A 38-year-old woman reportedly ingested 60 (500 mg) tablets of levetiracetam that she used as a mood-stabilizing medication for bipolar disorder. She had no other prescription medications available and no other medical history. She vomited 4 hours after ingestion and presented to the ED 2 hours later. In the ED, the patient was obtunded and was intubated secondary to respiratory depression. Her only other significant clinical finding was diminished deep tendon reflexes. Serum ethanol, lithium, carbamazepine, phenytoin, and valproic acid levels were all negative as was a subsequent urine screen for drugs of abuse. Her levetiracetam serum concentration was 400 microg/mL at 6 hours, 72 microg/mL at 18 hours, and 60 microg/mL at 20.5 hours (therapeutic serum concentration is 10-37 microg/mL). The elimination half-life was calculated to be 5.14 hours. She was extubated the next hospital day and recovered without sequelae., Conclusion: In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care. This is the first reported case of levetiracetam overdose; serial serum concentrations suggest first-order elimination even at concentrations 10-40 fold higher than therapeutic.

Objective: Although intentional and unintentional rodenticide poisoning is common, most readily available agents are of relatively low acute toxicity. A four-year long epidemic of severe toxicity from rodenticide exposure continues among patients predominantly of Dominican descent living in New York City. This study characterizes the ongoing epidemic of acute cholinesterase inhibitor poisoning due to an illicit rodenticide and identifies its etiology., Methods: A prospectively collected case series of poisoned patients referred to the New York City Poison Control Center. The main outcome measures include the clinical characteristics upon presentation, antidotal and other therapeutic requirements, and patient outcome. Product analysis was performed with paper chromatography, gas chromatography/mass spectrometry, and high-performance liquid chromatography. A murine model assessing both clinical effect and cholinesterase activity was also performed., Results: Thirty-five patients were referred following exposure to Tres Pasitos. Patients developed signs of cholinergic hyperactivity and many required high doses of atropine (>10 mg) to control these symptoms. The source was identified as a rodenticidal compound sold illicitly in local groceries primarily within the Dominican community. Murine cholinesterase activity fell significantly following exposure to the rodenticide. High-performance liquid chromatography identified aldicarb, an extremely potent carbamate-type cholinesterase inhibitor, not licensed for rodenticidal use in this country., Conclusion: Illicit sale of undocumented compounds poses a substantial public health threat. Despite several public health interventions, the epidemic continues.

Background: Clenbuterol is a long acting beta2-adrenergic agonist used in the treatment of pulmonary disorders. Acute clenbuterol toxicity resembles that of other beta2-adrenergic agonists. Most previously reported cases of clenbuterol toxicity describe patients who ate livestock illicitly treated with clenbuterol., Case Report: We report a case of human clenbuterol toxicity confirmed and correlated with qualitative and quantitative serum clenbuterol assays. This poisoned patient, a 28-year-old woman, developed sustained sinus tachycardia at 140/min, hypokalemia (2.4 mEq/L, 2.4 mmol/L), hypophosphatemia (0.9 mg/dL, 0.29 mmol/L), and hypomagnesemia (1.52 mg/dL, 0.76 mmol/L) after ingesting a reportedly small quantity of clenbuterol. The patient received repeated doses of metoprolol to treat her cardiovascular stimulation and potassium chloride to treat her hypokalemia. She remained symptomatic for more than 20 hours after the ingestion. Analysis by enzyme-linked immunosorbent assay and liquid chromatography/mass spectrometry revealed a serum clenbuterol concentration of 2.93 mcg/L 3 hours after the ingestion and an undetectable serum concentration 20 hours after ingestion. It is noteworthy that at a serum concentration below the limit of detection by liquid chromatography/mass spectrometry, the patient remained symptomatic. Acute clenbuterol toxicity is rarely reported following illicit use in humans, and this is the first such case to provide confirmatory toxicological analysis.

Background: Although ingestion of sustained-release potassium supplements can cause life-threatening hyperkalemia in patients with abnormal renal function, only a few previous reports suggest that this may occur in patients with normal renal function. We report 2 cases of hyperkalemia in patients with normal renal function who developed hyperkalemia after ingesting sustained-release potassium preparations and describe the use of radiography and whole-bowel irrigation in their care., Case Reports: The first patient is a 50-year-old woman who ingested 100 K-Dur tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 1 hour prior to presenting to the emergency department. She developed a peak serum potassium level of 9.7 mEq/L and had transient, potentially life-threatening electrocardiographic changes. The second patient was a 17-year-old man who ingested 20 to 30 Klor-Con tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 10 hours prior to presentation. Although he developed a peak serum potassium level of 6.1 mEq/L, he had a persistently normal electrocardiogram. In both patients, the tablets were visualized on abdominal radiographs and the gastrointestinal tracts of both were successfully decontaminated using whole-bowel irrigation., Discussion: Although the sensitivity and specificity are unknown, the abdominal radiograph appears to be useful in detecting sustained-release potassium tablets. Whole-bowel irrigation as a primary method of gastrointestinal decontamination also appears to be effective although its use is not previously reported for sustained-release potassium overdoses.

Background: Thallium salts were once used to treat a variety of disorders such as tuberculosis, sexually transmitted diseases, and ringworm of the scalp. Although the clinical manifestations and treatment of patients with thallium poisoning are well characterized, little information is available on the outcome of pregnancy in thallium-poisoned women. A case of thallium poisoning that began during the first trimester of pregnancy and resulted in fetal demise is reported., Methods: An extensive literature search identified reported cases of thallium poisoning during pregnancy from 1903 until the present time. All articles were obtained, translated, and abstracted using a standardized data collection form. References were hand-searched and abstracted to identify additional cases., Results: From a total of 25 cases identified, only 18 met satisfactory criteria for inclusion. Five exposures occurred during the first trimester, 5 during the second trimester, and 8 during the third trimester. Mothers developed classic signs and symptoms of thallium poisoning. Summary of these cases demonstrates a range of fetal effects from severe toxicity with residual sequelae to outwardly normal development. Interestingly, some newborns appeared normal despite severe maternal toxicity. The only consistent effect identified was a trend toward prematurity and low birth weight in children exposed during early gestation., Conclusions: These cases document the transfer of thallium both across the placenta and in breast milk. Insufficient data are available to evaluate prognostic markers of fetal outcome, or the risks and benefits of various treatment regimens in pregnant patients with thallium poisoning.

Background: Although Prussian blue is considered the antidote of choice for thallium poisoning, the lack of a Food and Drug Administration-approved pharmaceutical formulation has led to the search for other adsorbents. Activated charcoal has been demonstrated to adsorb thallium in vitro, and the similarity between thallium and potassium has led some authors to consider the use of sodium polystyrene sulfonate as a potential adsorbent. This experiment was designed to compare the relative thallium binding efficacy of these agents in a standard isotherm model., Methods: A standard aqueous solution of thallium acetate buffered to pH 7.0 was agitated at 25 degrees C with activated charcoal, Prussian blue, or sodium polystyrene sulfonate at adsorbent:thallium ratios ranging from 1.5:1 to 100:1. In order to further simulate physiologic conditions, all trials were repeated in a solution containing 4 mmol/L potassium phosphate. After thorough agitation, the mixtures were allowed to settle and were centrifuged and filtered through a 0.22-micron filter. Supernatant thallium concentrations were measured by atomic absorption spectrophotometry. Langmuir isotherms were used to calculate the maximal adsorptive capacity of each adsorbent, using linear regression with Pearson's correlation coefficients (r). Maximal adsorptive capacities were compared statistically with a p < 0.05 considered significant., Results: The maximal adsorptive capacities defined as milligrams of thallium per gram of adsorbent (shown with linear regression p and r values) were as follows: activated charcoal, 59.7 mg/g (p = 0.005, r = 0.995); Prussian blue, 72.7 mg/g (p = 0.004, r = 0.996); and sodium polystyrene sulfonate, 713 mg/g (p = 0.049, r = 0.951). All three values were statistically different from each other. At a physiologic potassium concentration, the maximal adsorptive capacities for activated charcoal and Prussian blue were essentially unchanged (58.3 mg/g and 69.8 mg/g, respectively, p > 0.05 for each vs trials without potassium), while the maximal adsorptive capacity for sodium polystyrene sulfonate fell to 39.1 mg/g (p = 0.003, r = 0.997, p = 0.005 vs sodium polystyrene sulfonate without potassium)., Conclusions: This in vitro study confirms the utility of Prussian blue and activated charcoal as thallium adsorbents. Although sodium polystyrene sulfonate demonstrates exceptional in vitro adsorption of thallium, its greater affinity for potassium probably renders it clinically ineffective.

Background: Inadvertent intrathecal administration of vincristine has been reported and is uniformly fatal except in two of three cases treated with spinal fluid exchange. We report a case of inadvertent direct intraventricular vincristine administration., Case Report: A 59-year-old woman developed acute lymphocytic leukemia with meningeal involvement and was being treated with intraventricular cytarabine (beta-cytosine arabinoside, Ara-C) injected via an Ommaya reservoir, intravenous (i.v.) vincristine, prednisone, and i.v. daunorubicin. The vincristine (2 mg in 10 mL diluent) was inadvertently injected into her Ommaya reservoir. Within 10 minutes, the error was realized. Despite optimal care, nausea and vomiting developed the first night, followed sequentially by coarse tremor, disorientation, horizontal nystagmus, and stupor. Her mental status waxed and waned until day 9, at which time she became responsive only to noxious stimuli. By day 11, she was deeply comatose and on day 40 she died without regaining any neurological function., Conclusion: Despite aggressive and immediate therapy, intraventricular vincristine infusion produced neurologic toxicity, with progressive loss of mental function, followed by coma and death. Systems need to be developed to prevent inadvertent central nervous system administrations.

Background: Cocaine is metabolized by a number of enzymes, the activity of one of which, plasma cholinesterase has been associated with dinical manifestations of toxicity. Patients with life-threatening complications of cocaine intoxication have lower plasma cholinesterase activity than less toxic controls. In addition, relatively healthy cocaine users have lower plasma cholinesterase activity than noncocaine using controls. Thus, low plasma cholinesterase activity could be a contributing factor to cocaine toxicity, a consequence of cocaine use, or a confounding variable. The following study was designed to further assess the relationship between cocaine use and plasma cholinesterase activity., Methods: We studied fluctuations in plasma cholinesterase activity in nine subjects enrolled in an inpatient study of the behavioral pharmacology of smoked cocaine. Subjects used at least 2 g of cocaine weekly for at least 1 year prior to enrollment. The subjects were admitted to the research unit where they remained drug-free for 2 days. They then received smoked cocaine for 4 days (up to 405 mg over 5 hours daily) and were then drug-free again for 2 days. Plasma cholinesterase activity was measured at 9 AM and 4 PM each day., Results: Baseline plasma cholinesterase ranged from 265 to 930 U/L (normal > 450 U/L). The mean plasma cholinesterase increased 112+/-100 U/L from day 1 to day 8 (p = 0.025). There was no daily change in plasma cholinesterase levels from 9 AM to 4 PM (15+/-165 U/L, p > 0.6), and there was no difference in the daily change between high- and low-dose cocaine days (-3+/-137 U/L vs 28+/-165 U/L, p = 0.52)., Conclusion: These preliminary data suggest that plasma cholinesterase levels do not change over a 7-hour period as a result of cocaine administration, but may increase during a period of inpatient study. Such an increase could potentially influence the pharmacokinetics or effects of cocaine studied in an inpatient setting and may give insight into the etiology of the observed low-plasma cholinesterase activity in cocaine users.

Background: Low plasma cholinesterase activity is associated with severe cocaine toxicity in human subjects and animal experiments. Exogenously enhanced plasma cholinesterase activity is protective against cocaine toxicity in animals. Cocaine users tend to have lower plasma cholinesterase activity than controls. Yet, when cocaine users are allowed to use cocaine in controlled settings without dietary restriction, their plasma cholinesterase activity increases. This study evaluates the influence of diet on plasma cholinesterase activity and cocaine toxicity., Methods: Forty-five Swiss albino mice were maintained on a high (30%) protein diet for 3 weeks. They were then randomized into equal groups and given either the high protein diet, an isocaloric low protein diet, or a protein and calorie deficient diet which consisted of reduced intake of the high protein diet. Body weights and plasma cholinesterase activities were measured after a 21-day study period. All animals then received a fixed dose of intraperitoneal cocaine and were observed for seizures and death., Results: Body weights and plasma cholinesterase activities of the high protein animals remained stable. Weights for the low protein and reduced intake animals fell by 5% and 15%, respectively (p < 0.05 for both vs baseline). Similarly, plasma cholinesterase activities for the low protein and reduced intake animals fell by 4% and 10%, respectively (p = 0.06 for low protein and < 0.05 for reduced intake vs baseline). Cocaine caused seizures in 67% of the high protein animals as compared to 93% and 100% of the low protein and reduced intake animals, respectively (p < 0.05 for high protein vs reduced intake). None of the high protein animals died as compared to 20% and 100% of the low protein and reduced intake animals, respectively (p < 0.05 for high protein vs reduced intake)., Conclusion: Protein and calorie malnutrition is associated with a reduction in plasma cholinesterase activity and enhanced cocaine toxicity in mice. Further study is needed to determine if dietary factors are partially responsible for variations in plasma cholinesterase activity and cocaine susceptibility in humans.

Background: Thallium poisoning is now rare but still occurs as a result of homicide attempts. Prussian blue's efficacy in the treatment of experimental thallium poisoning has been demonstrated in animal models, and its use in humans is supported by anecdotal data. Since thallium binds sulfhydryl groups, the use of N-acetylcysteine is also considered as a potential antidote., Study Objective: To compare the efficacy of Prussian blue and N-acetylcysteine in a murine model of thallium poisoning., Methods: Female Swiss albino mice with free access to food and water were used. Two study doses of thallium, given as a subcutaneous injection of thallium acetate dissolved in sterile water, were chosen: 70 mg/kg (LD90) and 85 mg/kg (> LD100). A randomized, placebo controlled study was conducted with survival at 120 h chosen as the outcome measure. Four treatment groups were studied: control, Prussian blue, N-acetylcysteine, and the combination of Prussian blue and N-acetylcysteine. Prussian blue was dissolved in water and given by oral gavage at a dose of 50 mg/kg. N-acetylcysteine was diluted in normal saline and given as intraperitoneal injections of 200 mg/kg. Sterile water by gavage and normal saline by peritoneal injection were given as control treatments whenever an active agent was not given. Survival was recorded over a 120 h study period and compared at 120 h by a Fisher's exact test., Results: At 120 h following subcutaneous injection of thallium 70 mg/kg, only 10% of the control animals survived. Treatment with N-acetylcysteine or Prussian blue increased survival to 35% (p = 0.13) and 50% (p = 0.014), respectively. The addition of N-acetylcysteine to Prussian blue offered no benefit over Prussian blue therapy alone., Conclusions: Prussian blue was found to decrease mortality from thallium poisoning at a dose equal to the LD90 in this model, but not a dose greater than the LD100. No role for N-acetylcysteine in the treatment of thallium poisoning was demonstrated by this study.

Background: Although topical salicylates are widely used, toxicity from this route is rare., Case Report: We present an unusual case of salicylism from a topical salicylate preparation in an 80-year-old woman. The patient was admitted to the dermatology service with a diagnosis of erythroderma and was treated with salicylate containing ointments. After six days of treatment the patient became confused and paranoid. A serum salicylate was 3.36 mmol/L (46 mg/dL). The patient was admitted to the intensive care unit were she was rehydrated and treated with bicarbonate and activated charcoal., Results: Her serum salicylate fell to 1.90 mmol/L (26 mg/dL) over a two day period and she regained a normal mental status.

Background: Cocaine is metabolized in part by plasma cholinesterase to form ecgonine methyl ester. Decreased plasma cholinesterase activity is associated with enhanced cocaine toxicity in both humans and animals. This study was designed to determine whether the administration of exogenous plasma cholinesterase is protective against cocaine toxicity., Methods: Using a blinded protocol, female Swiss albino mice were randomized to receive an intraperitoneal injection of either 13.7 mg/kg of purified human plasma cholinesterase dissolved in phosphate buffered saline, or an equal volume of phosphate buffered saline as a control. One hour later, all animals received an intraperitoneal injection of either 100 or 125 mg/kg of cocaine, and the incidence of seizures and death was recorded. In a similar fashion, another group of animals was randomized to receive a human plasma cholinesterase dose of either 13.7 or 27.4 mg/kg, followed by 150 mg/kg of cocaine., Results: Administration of 13.7 mg/kg of human plasma cholinesterase increased plasma cholinesterase activity by a mean of 63 +/- 13 fold, with a Tmax of 90 minutes and a Vd of 85 +/- 13 mL/kg. Cocaine's effects on seizures and death were attenuated by human plasma cholinesterase. A cocaine dose of 150 mg/kg represents an ED100 for seizures and an LD100. At this dose, lethality was reduced to 30% (p < 0.001) and seizures were reduced to 40% (p < 0.001) by administration of 27.4 mg/kg of human plasma cholinesterase., Conclusions: Pretreatment with purified human plasma cholinesterase protects mice against the convulsive and lethal effects of cocaine.

Background: Many authors currently recommend infusing the adult dose (1 g) of pralidoxime over a 15-30 minute period. When administered in this manner, computer simulations predict that plasma pralidoxime concentrations will fall below 4 mg/L as early as one and one half hours after administration. The objective of this study was to assess whether a loading dose followed by a continuous infusion would maintain therapeutic levels longer than the traditional short infusion regimen of pralidoxime if the same total dose was administered., Methods: Utilizing a randomized, crossover design, healthy volunteers were administered either 16 mg/kg of pralidoxime intravenous over 30 minutes or 4 mg/kg of pralidoxime intravenous over 15 minutes followed by 3.2 mg/kg/h for 3.75 h (for a total dose of 16 mg/kg). Pralidoxime levels were obtained at 0, 10, 20, 30, 60, 120, 180, 240, 300, and 390 minutes and patients were observed for vital sign changes and adverse effects., Results: Seven subjects completed both arms of the study. One subject's data were excluded from pharmacokinetic analysis due to aberrant plasma pralidoxime analysis. The loading dose followed by the continuous infusion maintained therapeutic levels for 257.3 +/- 50.5 minutes whereas the short infusion maintained therapeutic levels for 118.1 +/- 52.1 (p < 0.001). Adverse effects were encountered during the short infusion regimen which did not occur during the continuous infusion. Dizziness or blurred vision occurred in all subjects during the short infusion regimen. Additionally, statistically significant increases in diastolic blood pressure occurred during the short infusion regimen., Conclusions: The results of this study indicate that a loading dose followed by a continuous infusion of pralidoxime maintains therapeutic concentrations for a longer period of time than the currently recommended short infusion regimen in healthy volunteers.

Background: The purpose of this trial was to compare the pharmacokinetics of the two available acetaminophen dosage forms in simulated human overdose., Methods: Ten healthy volunteers received acetaminophen, 75 mg/kg orally, either as the regular release or extended relief formulation in a random, crossover fashion. Blood samples were analyzed using a TDx assay and a best fit correlation of data points was determined by PCNONLIN., Results: The area under the curves for extended relief acetaminophen and regular release acetaminophen were 426 mg h/L and 432 mg h/L, respectively (p = 0.768). The mean half times for extended relief acetaminophen and regular release acetaminophen were 4.02 h and 2.56 h, respectively (p < 0.001). The mean maximum serum acetaminophen concentrations were 62.6 mg/L (414.4 mmol/L:) and 94.3 mg/L (624.3 mmol/L) for extended relief acetaminophen and regular release acetaminophen, respectively (p < 0.001) and the mean time to maximum serum acetaminophen concentrations were 0.87 h and 0.75 h for extended relief acetaminophen and regular release acetaminophen, respectively (p = 0.508)., Conclusions: Although the formulations appear to have equal bioavailability, their half-lives and peak concentrations were significantly different. Further study is required to determine whether these differences affect the assessment and management of poisoned patients.

Propoxyphene overdose is known to cause widening of the QRS complex on ECG. We report a case of a 54-year-old female who ingested approximately 100 propoxyphene hydrochloride tablets in a suicide attempt. She developed a wide complex dysrhythmia which responded to sodium bicarbonate therapy. Propoxyphene-induced wide complex dysrhythmia responsive to sodium bicarbonate therapy has not been previously reported in the literature.

The optimal medical regimen for the treatment of cocaine associated myocardial ischemia has not been defined. While animal and human data demonstrate the risks of beta-adrenergic blockade, studies in the cardiac catheterization laboratory suggest a beneficial role of nitroglycerin. We performed a prospective multicenter observational study to evaluate the clinical safety and efficacy of nitroglycerin in the treatment of cocaine associated chest pain at six municipal hospital centers. Of 246 patients presenting with cocaine associated chest pain, 83 patients were treated with nitroglycerin at the discretion of the treating physician. Relief of chest pain and/or adverse hemodynamic outcome were the primary endpoints. Baseline comparisons of patients treated with nitroglycerin to those not treated with nitroglycerin found that the treated patients were at higher risk of ischemic heart disease. They were older (36 years vs 32 years, p = 0.0008), more likely to have an ischemic electrocardiogram (27% vs 4%, p < 0.0001), to be admitted (94% vs 40%, p < 0.0001), and to have a discharge diagnosis of ischemic heart disease (41% vs 9%, p < 0.0001). Nitroglycerin was beneficial in 41 patients (49%; 95% CI, 38-60%): 37 patients (45%) had relief or reduction in the severity of chest pain and 4 patients (5%) had other beneficial effects. Only one patient had an adverse outcome (transient hypotension in the setting of a right ventricular infarct). Nitroglycerin is safe and possibly effective in the treatment of cocaine associated chest pain.

We report three cases of 4-aminopyridine overdose resulting in seizure activity. All patients were on therapeutic regimens for the treatment of multiple sclerosis. All patients were responsive to intensive supportive care, although the length of toxicity was prolonged more than 24 hours in one patient. Seizure activity was responsive to benzodiazepine and phenytoin therapy.

A fatality associated with the inhalational exposure to a pyrethrin insecticide is described. Death was attributed to sudden irreversible bronchospasm. While less severe allergic reactions have been reported, this is the first death associated with pyrethrin inhalation.

Guanabenz (Wytensin Wyeth-Ayerst Laboratories, Philadelphia, PA) is a centrally acting alpha 2 adrenergic agonist. Guanabenz shares structural and pharmacologic properties with the more commonly known sympatholytic agent clonidine. Little is known about guanabenz in overdose. Eleven cases of guanabenz poisoning have been reported in the literature and to the manufacturer to date and followed a clinical course comparable to clonidine poisoning. We report this case of guanabenz poisoning in an elderly woman who sustained protracted hypothermia following overdose. Hypothermia has been commonly associated with clonidine toxicity but has not been previously reported with guanabenz. Postulated mechanisms of clonidine induced hypothermia are discussed.

Two workers from the same factory presented to the same emergency department within six weeks of one another with moderate (Case 1) and severe (Case 2) methemoglobinemia. Subsequent investigation revealed that the factory produces phenylpropanolamine and that both patients, shortly before becoming ill, were inadvertently exposed to methyl nitrite, a critical reagent in this production. Although other nitrites induce methemoglobinemia, exposure to methyl nitrite during phenylpropanolamine production appears to be a new cause of occupational methemoglobinemia.

Few cases of mexiletine overdose have been reported in the literature. The available case reports have invariably noted significant hemodynamic or electrocardiographic abnormalities. A 41-year-old woman, on mexiletine for arrhythmia control, ingested up to 90 of her 200 mg mexiletine tablets in a suicide attempt. She presented to the emergency department awake with a normal blood pressure and pulse. Shortly afterwards, the patient had a generalized motor seizure, which responded after 40 minutes to intravenous diazepam 100 mg, phenobarbital 1 g and pyridoxine 5 g. Recurrent status epilepticus at one hour required an additional 40 mg of diazepam and a loading dose of pentobarbital. During the entire episode, her electrocardiogram remained normal. The patient's mexiletine level was 20 micrograms/mL (therapeutic 1-2 micrograms/mL) and the patient's urine screen was negative for cocaine. Mexiletine is a group Ib antidysrhythmic agent with electrophysiologic effects similar to lidocaine. Mexiletine has a little first pass hepatic metabolism and a large volume of distribution along with a high lipid solubility, and prolonged central nervous system toxicity may be expected. As with lidocaine, the toxic deaths from mexiletine have resulted from hypotension and bradycardia. The patient reported had a significant mexiletine overdose which resulted in convulsive status epilepticus, but was devoid of hemodynamic or electrocardiographic abnormalities.

Four young adults presented two days after one of them had received marzipan balls packaged in a box from an expensive candy manufacturer. Two ate one candy ball, while two others shared a third. The next day, variable gastrointestinal symptoms developed. On the third day, two patients developed painful paresthesiae of the hands and feet, an early but nonspecific clinical marker of thallium poisoning. A tentative diagnosis of thallium poisoning was made based on symptoms, and treatment was initiated. The remaining candies were radiographed. Metallic densities in the candies supported the diagnosis, and atomic absorption spectroscopy was used to quantitate thallium content. Each candy contained a potentially fatal dose. Five to seven days later, hypertension and tachycardia developed in the two patients who had ingested an entire candy. All patients developed alopecia but recovered without overt neurologic or other sequelae. While the diagnosis of thallium poisoning is often delayed until alopecia develops, an early diagnosis favors an effective treatment strategy.

A study was designed to define the osmol gap in patients whose serum ethanol concentrations are known, to reevaluate several accepted equations for calculating osmolarity, and to apply the results to the theoretical clinical scenario of a toxic alcohol ingestion. The design for the study used consecutive, prospective enrollment of all patients presenting to a large inner city hospital who clinically required determination of their serum ethanol and electrolytes. Three hundred and twenty one consecutive adult patients were enrolled in the study, sixteen were excluded from the final analysis. A stepwise multiple linear regression analysis was performed to determine the best coefficients for sodium, blood urea nitrogen, and ethanol from the data set. Osmolarity was then calculated using these coefficients and traditional models. The osmol gap (measured osmolality minus calculated osmolarity [2*Na + BUN/2.8 + Glu/18 + Etoh/4.6]) was -2 +/- 6 mOsm. Although different equations produced different osmol gaps (ranging from -5 to + 15 mOsm) the standard deviations and correlation coefficients were similar. Large variations exist in the range of osmol gaps. Absolute values are very dependent on the equations used to calculate osmolarity. Because of the larger range of values, small osmol gaps should not be used to eliminate the possibility of toxic alcohol ingestion.

Cocaine body-packers and body-stuffers have become a common medical problem. Significant morbidity and mortality result when cocaine is absorbed from the gastrointestinal tract due to cocaine package compromise. The clinical prevention of gastrointestinal absorption of cocaine includes oral activated charcoal and/or whole bowel irrigation with polyethylene glycol--electrolyte lavage solution. This in vitro study investigates the maximal adsorptive capacity of activated charcoal for cocaine at varying activated charcoal:cocaine ratios, at pH 1.2 and pH 7.0, and the effect of polyethylene glycol--electrolyte lavage solution upon this binding. The percent adsorption of cocaine to activated charcoal was significantly better at pH 7.0 for all ratios of activated charcoal:cocaine tested and the maximal adsorptive capacity was 29% greater at pH 7.0 (273 micrograms/mg) than at pH 1.2 (212 micrograms/mg) (p < 0.05). Addition of polyethylene glycol--electrolyte lavage solution to the cocaine-activated charcoal slurry caused significant desorption of cocaine from activated charcoal at all pHs and ratios tested (except the 1:1 ratio at pH 7.0) and was most pronounced at pH 1.2. The addition of polyethylene glycol--electrolyte lavage solution to activated charcoal prior to adding cocaine solution further decreased the adsorption of cocaine to activated charcoal. This difference was significant at both pHs and all ratios tested except the 1:1 ratio at pH 1.2. The maximal adsorptive capacity of activated charcoal for cocaine at pH 1.2 was reduced 75% by pretreatment with polyethylene glycol--electrolyte lavage solution from 212 to 54.2 micrograms/mg, while at pH 7.0 the maximal adsorptive capacity was reduced by 11%, from 273 to 243 micrograms/mg. Polyethylene glycol--electrolyte lavage solution significantly reduces the adsorption of cocaine to activated charcoal particularly if the two are combined at a low pH prior to the addition of cocaine. The in vitro effects suggest that activated charcoal mixed in water should be administered first, followed by the polyethylene glycol--electrolyte lavage solution.

Whole bowel irrigation with polyethylene glycol electrolyte lavage solution has been recommended as an adjunct to traditional overdose management. Although combined activated charcoal and whole bowel irrigation could enhance the efficacy of both modalities, this improvement remains largely speculative. An in vitro experiment was designed to determine whether polyethylene glycol electrolyte lavage solution alters the adsorption of theophylline to activated charcoal. Theophylline was agitated with activated charcoal in either water or polyethylene glycol electrolyte lavage solution, at each of three activated charcoal:theophylline ratios; 1:1, 3:1, and 10:1. The concentration in the supernatant was determined by high pressure liquid chromatography, and the maximal adsorptive capacity of activated charcoal for theophylline was calculated from the Langmuir equation. The percent of theophylline adsorbed by activated charcoal in water was 16 +/- 4%, 67 +/- 5%, and 97 +/- 3% for the 1:1, 3:1, and 10:1 ratios, respectively. This was decreased to 17 +/- 5%, 37 +/- 3%, and 62 +/- 2% when polyethylene glycol electrolyte lavage solution was added. A statistical difference (p less than 0.05) occurred at the 3:1 and 10:1 activated charcoal:theophylline ratios. Similarly the maximal adsorptive capacity was decreased 23% from 264 mg/g to 203 mg/g when polyethylene glycol electrolyte lavage solution was added to activated charcoal prior to theophylline. Polyethylene glycol electrolyte lavage solution significantly decreases adsorption of theophylline to activated charcoal in vitro. In vivo studies are required to confirm these findings. If activated charcoal is to be used clinically for theophylline toxicity, the authors suggest the possibility of larger quantities of activated charcoal, and administering activated charcoal in a slurry of water before the initiation of whole bowel irrigation.

Exposure to caustic agents is a common problem, affecting thousands of individuals annually. Despite this incidence, the factors responsible for the production of injury remain poorly defined. Although extremes of pH seem to correlate well with the production of esophageal lesions, pH alone fails to explain the damage resulting from exposure to agents with near neutral pH, such as soldering flux containing zinc chloride. We determined titratable acid/alkaline reserve (TAR) in 38 potentially caustic household agents. A subset of these products was evaluated in an in-vitro canine esophageal model to determine whether TAR correlated with esophageal injury. The results indicate that for the products evaluated TAR correlated better than pH with the production of caustic esophageal injury.

Newer Rodenticides of the long-acting anticoagulant or "superwarfarin" class are gaining popularity. Since few cases of severe, prolonged anticoagulation after ingestion have been reported, the course of toxicity is not precisely understood. In this case of an intentional ingestion of brodifacoum, a longitudinal analysis of specific coagulation factor derangements was carried out in an attempt to guide a future treatment strategy for this type of toxicity. Results of this analysis demonstrated a profound decrease in levels of factors II, VII, IX, and X, lasting at least 43 days post ingestion. Treatment with subcutaneous vitamin K1 in doses up to 100 milligrams per day was without complication and was effective in reversing the coagulopathy produced by brodifacoum.