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Background: Certain species of tarantulas have 'urticating hairs' on their abdomen that produce dermal and ocular irritation. When served as a delicacy, a hot fire or blow torch is recommended to destroy these hairs prior to consumption. We report several cases of pharyngeal irritation which probably resulted from the ingestion of poorly prepared tarantulas. Case Series: Several members of a club, whose purpose it is to undertake novel experiences, shared an exotic dinner which included batter-dipped, deep-fried Chilean Rose-haired tarantula (Grammostola spatulata). Although a blow torch was used prior to batter-dipping, the ventral surfaces of the spiders were not properly treated. Symptoms consisting of tingling in the mouth and throat occurred in several people who ate the tarantula dish. There was no suggestion of systemic allergic reaction in any patient, and no patient was ill enough to seek medical care. Epidemiological investigation revealed that symptoms did not develop in dinner guests who did not ingest tarantula. Evaluation of a remaining cooked specimen by an entomologist confirmed the presence of urticating hairs on the spider's abdomen. Conclusion: Tarantula hairs, which have previously been reported to cause both dermal and ocular irritation, appeared to cause pharyngeal irritation in a group of persons eating them as part of a prepared dinner. Although other causes of symptoms could not be rigorously excluded, we conclude that cooked tarantula is a potentially irritating food, and those who consume it should be aware of this potential toxicity., Traub SJ, Hoffman RS, Nelson LS. New York City Poison Control Center, New York, [...]

Background: Thiamine deficiency (TD), a recognized complication of alcoholism, can result in substantial morbidity and mortality if untreated. Until recently, insensitive laboratory techniques hampered both an understanding of the incidence of TD and the role of T supplementation. The following study was designed to prospectively evaluate TD in the ED. Methods: Adult ED alcoholics by DSM criteria were enrolled if they were able to give informed consent, and had no other conditions associated with or clinical signs of TD. Trained observers recorded standardized demographic data that included vitamin use and previous T supplementation. Blinded T levels were determined by a highly sensitive HPLC technique. A healthy control group was included to confirm normal laboratory values. TD was defined as a T level [is less than] 0.7pg/mg of total protein (P) to correlate with predicted pyruvate dehydrogenase dysfunction. Mean T levels were compared using the student's t-test. Numbers of TD subjects in each group were compared by Fisher's exact test. A p [is less than] 0.05 was considered statistically significant. Results: 105 alcoholics were enrolled; 20 used vitamins or had recently received T. There were 18 controls. The study groups were therefore defined as follows: C = 18, A = 85, A + V = 20. The A + V group was not demographically different from the A group. Mean T levels (in pg/ mg P) were: C = 1.67; A = 0.856; A + V = 1.95. (p values: C vs A, [is less than] 0.001; A vs A + V, [is less than] 0.00l; C vs A + V, NS). Numerical TD was identified in 1/18 C patients, compared with 35/85 A and 0/20 A + V patients (p = 0.003, RR 1.3, 95% CI = 1.12-1.51 for C vs A). Conclusions: Although severely ill and clinically TD patients were excluded from study by design, numerical TD remains prevalent in alcoholic ED patients with obvious metabolic, neurologic and cardiovascular implications. Supplementation appears to protect against numerical TD in alcoholic patients and should be continued., Hexdall A, Pardo S, Hoffman RS, Goldfrank LR. Bellevue Hospital Center, New York, [...]

Background: Although it is commonly stated that metal salts are not adsorbed to activated charcoal (AC), when studied, mercury, arsenic and thallium are adsorbed in small, but clinically significant, quantities. We began to systematically study adsorptive properties of other metals. Methods: Stock aqueous solutions of copper sulfate and lead acetate were prepared in distilled, deionized water. Norit A[R] AC was desiccated for 24 hours at 100 [degrees] C. Known quantities of AC were added to the stock solutions in AC:metal ratios ranging from approximately 10:1 to 250:1. The mixtures were agitated at 25 [degrees] C for 15 minutes, then gravity filtered. Supernatant metal concentrations were analyzed in triplicate using atomic absorption spectrophotometry. Each experiment was run 3 times. Langmuir isotherms were plotted and best straight lines were fitted by the least squares method. Maximum adsorptive capacity (MAC) for each metal was calculated from the Langmuir equations. Results: Lines representing the Langmuir isotherms had p values [is less than] 0.05 and [R.sup.2] (Pearson's correlation coefficient) values [is greater than] 0.98 for both metals. Copper had a MAC of 9.1 mg/g AC, and lead had a MAC of 10.3 mg/g AC. Conclusions: Many drugs and toxins adsorb to AC with MACs on the order of 100-300 mg/ g AC. By comparison, these metals demonstrate relatively poor adsorption. However, the significance of MAC must be considered in the context of dose-lethality. Lethal doses of copper sulfate are reported on the order of 1-2 grams. With a MAC of 9.1 mg Cu/gm AC, 100 grams of AC would be expected to bind up to 3.6 grams of copper sulfate pentahydrate, which could be consequential. Similarly, a 20 g dose of AC could theoretically adsorb all 200 mg of lead present in a typical paint chip. Further studies in-vitro (to determine the effects of varied pH on MAC) and in vivo are necessary to help define the clinical implications of these results., Traub SJ, Nelson LS, Hoffman RS. New York City Poison Control Center, New York, [...]

Objective: Reported cases of positive point-of-care urine PCPIa results associated with ketamine administration motivated us to systematically evaluate the effect of ketamine on these tests. Methods: A blinded, anonymous study of patients receiving parenteral ketamine was conducted. Patients (n = 50) submitted urine prior to, and 1-2 hours after receiving parenteral ketamine. Gas chromatography/mass spectrometry was performed on all urine samples to detect PCP, ketamine and ketamine metabolites. Urine was also tested with 5 point-of-care urine PCPIa to determine if ketamine administration caused a change in test result from negative pre-treatment to positive post-treatment. These PCPIa were devices by Forefront Diagnostics (Laguna Hills, CA), Princeton BioMeditech (Princeton, NJ), Roche Diagnostic Systems (Sommerville, NJ), American BioMedica (Kinderhook, NY), and Technical Chemicals and Products (Pompano Beach, FL). Results: No urine contained PCP, no pre-treatment sample contained ketamine or metabolites and all post-treatment samples contained ketamine and metabolites. No urine was PCPIa positive. Several assays appeared to have a weak partial reaction with post-treatment urine, and determination of a negative result was possible only after careful inspection of these test cassettes. Conclusions: Ketamine and metabolites are present in urine 1-2 hours after parenteral ketamine administration. In a previous report we note that these urine PCPIa performed after ketamine administration are negative. However, several assays were difficult to interpret: Reaction of ketamine or ketamine metabolites with these point-of-care urine PCPIa may cause ambiguous results leading to a false-positive interpretation., Hoffman RJ, Saddock V, Nelson L, Hoffman RS. New York City Poison Control Center, New York, [...]

Background: Tacrolimus is a potent immunosuppressive agent that prevents organ rejection after transplantation. Chronic therapy is associated with nephrotoxicity, neurotoxicity, and increased risk of infections, malignancies and diabetes. Data on acute overdose in humans are rare and suggest no significant adverse effects. Although a single recent report associated myocardial ischemia with overdose, causality was lacking. We report a case of acute tacrolimus overdose confirmed by serum levels without the development of significant toxicity. Case Report: A 20-year-old female with a history of dysplastic kidneys and subsequent renal transplanation presented to the emergency department 14 hours after an acute intentional ingestion of approximately 41 mg (41 (1 mg) tablets) of tacrolimus. She also admitted to ingesting two tablets of prednisone and several tablets of mycophenolate mofetil. The patient complained of nausea, vomiting and headache but had normal vital signs. She was treated only with intravenous fluids and was admitted to the ICU for observation. A tacrolimus level of 42.6 ng/mL (therapeutic trough levels range from 9.8 to 19.4 ng/mL) was recorded. The next day she had a mild increase in serum creatinine from 0.8 mg/dL to 1.1 mg/dL but remained asymptomatic. No other signs or symptoms of toxicity occurred and she was discharged home after 48 hours. Conclusion: Although chronic tacrolimus use is associated with multiple adverse effects, we report one of the highest serum tacrolimus levels obtained following an acute ingestion with no associated significant toxicity. This single case report cannot be used to exclude potential toxicity following acute tacrolimus overdose and a prospective study is therefore necessary to properly evaluate this problem., Su M, Hoffman RS, Nelson LS. New York City Poison Control Center, New York, [...]

Background: Despite being widely reported, life-threatening metformin-associated lactic acidosis (MALA) may not be initially considered in patients with distracting chief complaints. The therapeutic range for metformin is 1-2 [micro]g/mL, but MALA is reported with metformin levels ranging from 0.03-84.9 [micro]g/mL. We describe severe MALA initially mistaken for mesenteric ischemia, and its successful treatment with hemodialysis (HD). Case Report: A 46-year-old man presented with 18 hours of severe, generalized abdominal pain without nausea, vomiting, or diarrhea. His PMH was significant for NIDDM, alcohol abuse, and an appendectomy. Medications included metformin, glyburide and quinapril. Initial vital signs were: BP, 80/50 mmHg; HR, 93/min; RR, 30/min; temperature, 92 [degrees] F. Physical examination revealed an awake but uncomfortable man with dry mucosa, epigastric tenderness without rebound, and guaiac positive stools. Laboratory abnormalities included: WBC, 14.8 x [10.sup.3]/[micro]L; [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII], 3 mEq/L; BUN, 40 mg/dL; Cr, 4.2 mg/dL; pH, 6.65; lactate, 21 mmol/L; and ethanol, 162 mg/dL. An abdominal x-ray showed mild ileus. He received IV crystalloids and sodium bicarbonate but continued to deteriorate. An exploratory laparatomy was negative for presumed mesenteric ischemia. In the ICU, he received 4 hours of HD for a presumed MALA during which time serial metformin levels were sent. The peak lactate was 40 mmol/L; pre-dialysis metformin was 8 [micro]g/mL; and post-dialysis metformin was 3.7 [micro]g/mL. The mean plasma clearance of metformin was 67.8 mL/minute. His hospital course was complicated by acute renal failure, which eventually recovered. Conclusion: Patients with MALA can present with nonspecific symptoms masquerading as mesenteric ischemia. After excluding ischemia, MALA is responsive to treatment with fluids, bicarbonate and HD., Chu J, Hoffman RS, Nelson LS. New York City Poison Control Center, New York, [...]

Background: Patients with intentional HF ingestions have a high mortality. Death results both from local injury and systemic complications of hypocalcemia and hyperkalemia. Calcium is a frequently used topical and systemic antidote, but inherent toxicity limits large intravenous doses. Comparatively, large doses of magnesium are better tolerated, however treatment with magnesium is not well described. We present a patient who survived a large HF ingestion after receiving only oral and intravenous magnesium therapy. Case Report: A 38-year-old man intentionally ingested about 50 mL of an HF containing rust remover (12% HF acid and 16% ammonium bifluoride). Initial vital signs were: BP, 139/83 mmHg; HR, 94/min; RR, 20/min; temperature, 96.8 [degrees] F. Physical examination revealed a normal oropharynx and epigastric tenderness without guarding. On arrival, he received 60 mL of 50% magnesium sulfate via a nasogastric tube and 4 g magnesium sulfate intravenously. Calcium therapy was recommended but not given because there were no cardiac dysrhythmias. Pertinent initial laboratories were: [Ca.sup.++], 9.2 mg/L; [Mg.sup.++], 1.7 mEq/L; and [K.sup.+], 3.8 mEq/L. A 12-lead ECG showed sinus tachycardia at 100 beats/minute with a QTc interval of 450 msec. Repeat laboratories 10 hours later revealed: [Ca.sup.++], 8.3 mg/L; [Mg.sup.++], 3.4 mEq/L and [K.sup.+], 5.1 mEq/L. Esophageal endoscopy revealed severe erosive esophagitis and gastritis, a CT scan of the chest and abdomen was negative. The patient had an uneventful recovery. Conclusions: In HF ingestions, oral magnesium may provide a source of cations to complex with the toxic fluoride ions. This patient survived a potentially fatal ingestion of HF with magnesium sulfate therapy. Limited animal data suggests magnesium treatment as an alternative or addition to calcium therapy in HF burns., Chu J, Ying R, Hoffman RS, Nelson LS. New York City Poison Control Center, New York, NY; Saratoga Hospital Saratoga Springs, [...]

Background: Methotrexate, a dihydrofolate reductase and thymidine synthetase inhibitor, is used in cancer chemotherapy, and in the treatment of rheumatoid arthritis and trophoblastic disease. Because of its ability to inhibit purine synthesis, methotrexate is also used to abort ectopic and intrauterine pregnancies. Although leucovorin is routinely used to limit the toxic effects of methotrexate during chemotherapy, it has never been used to inhibit fetal demise. Case Report: A 31-year-old female who was 2 months pregnant presented to the ED immediately after maliciously receiving multiple intramuscular methotrexate injections into her thigh in an attempt 'to induce an abortion.' Although the exact dose was unknown, it was reported to be 'a couple of milliliters' of the standard methotrexate solution (25 mg/mL). Thus her estimated dose was likely to be between 25-150 mg/[m.sup.2], which is consistent with the 50 mg/[m.sup.2] dose routinely used for abortion. Her initial vital signs, physical examination, and laboratory results were normal. An ultrasound showed a viable intrauterine pregnancy dated 7 weeks and 3 days. Leucovorin, 25 mg/[m.sup.2] (42.5 mg), was administered intravenously every 6 hours for 6 doses. A 3 hour post injection methotrexate level was 0.1 [micro]mol/L, and repeat 24 hr methotrexate level was 0.0 [micro]mol/L. The patient never developed signs or symptoms of methotrexate poisoning. Repeat ultrasound 10 days after the incident still revealed a normal viable pregnancy. A healthy baby boy was ultimately delivered. Conclusion: Although methotrexate is used as an abortifacient, there is no documentation of leucovorin use in preventing fetal demise. This case report suggests that leucovorin may be used to protect a fetus following an errant exposure of methotrexate., Hahn I, Hoffman RS, Nelson LS. St. Luke's-Roosevelt Hospital Center, New York City Poison Control Center, New York, [...]

Background: Methotrexate (MTX), usual dose 50 mg/[m.sup.2] intramuscularly, is a common therapy for elective termination of pregnancies (ETOP) and non-ruptured ectopic pregnancies. Adverse effects from this regimen are rarely reported, and monitoring of patients for toxicity is believed unnecessary. However, complications may result from inappropriate dosing, idiosyncratic reactions, hypersensitivity or impaired renal function. We report the case of a woman developing significant toxicity from MTX therapy for an ETOP. Case Report: A healthy 30-year-old female, 6 weeks pregnant, received an intramuscular injection of 125 mg (80 mg/[m.sup.2]) of MTX for an ETOP. Four days later, she presented to the ED with nausea, diarrhea, a rash on her hands, swelling to the face and a serum creatinine of 3.3 mg/dL. Her serum MTX level on admission was elevated at 1.1 x [10.sup.-7] M which when plotted on the MTX nomogram, necessitated leucovorin rescue therapy. During her hospital stay, she developed mucositis and severe bone marrow suppression with an absolute neutrophil count nadir of 358 on hospital day 9. The patient was treated with leucovorin (100 mg/[m.sup.2]) every six hours continuously beginning on her second hospital day and was given a single dose of granulocyte colony stimulating factor for neutropenia on hospital day 9. She was discharged home on hospital day 11 with normal renal function and normal white blood cell and absolute neutrophil counts. Conclusion: MTX as therapy for ETOPs may cause significant toxicity particularly if the administered dose is higher than recommended based on body surface area. The narrow therapeutic index and potentially serious adverse effects of MTX, may thus require closer patient monitoring., Su M, Rahman S, Howland MA, Nelson LS, Hoffman RS. New York City Poison Control Center; St John's University College of Pharmacy; Jacobi Medical Center, New York, [...]

Objective: Loratidine is considered less cardiotoxic than terfenidine and astemizole, and clinically relevant loratidine-associated cardiotoxicity is rare. Though conflicting data exist, most suggest that loratidine does not affect cardiac conduction or prolong QTc. We report a case of loratidine-associated QTc prolongation and syncope. Case Report: A 46-year-old woman without cardiac disease presented to medical care after syncope. On the 5 previous days she had taken a loratidine 5 mg/pseudoephedrine 120 mg tablet. In response to focused questioning regarding other agents that cause QTc prolongation or syncope, she denied use of any other product. Her vital signs and physical examination were normal and an otherwise normal 12-lead ECG revealed a prolonged QTc segment of 478 msec. Extensive laboratory investigations were all normal, including: potassium 4.4 mEq/L, magnesium 1.7 mg/dL, and calcium 8.7 mg/dL. The patient was monitored, received no medication and abstained from loratidine. The following day, her 12-lead ECG was normal with a QTc of 398 msec. Serum analysis by liquid and gas chromatography revealed therapeutic, non-toxic serum levels of: pseudoephedrine, 680 ng/mL; loratidine, undetectable in ng/mL; and descarboethoxyloratidine (loratidine metabolite), 3.6 ng/mL. Conclusions: Dysrhythmia from QTc prolongation was concluded to cause this patient's syncope. The clear history of loratidine use with non-toxic drug levels, syncope, QTc prolongation without other causality, and prompt normalization of QTc interval upon loratidine abstinence is apparently cogent evidence that this patient experienced QTc prolongation from loratidine use., Hoffman RJ, deSouza I, Stetz JE, Chu J, Nelson LS, Hoffman RS. New York City Poison Control Center, New York, [...]

Background: 4-Aminopyridine (4-AP) is a potassium channel blocker which increases the release of neurotransmitters, particularly acetylcholine and norepinephrine. It is currently under investigation for the treatment of multiple sclerosis; typical doses are 25-40 mg twice daily. Elimination is predominantly renal, and the half-life in therapeutic dosing is reported as 170-220 minutes. Case reports of 4-AP toxicity are rare, and kinetic data in human overdose is lacking. Case Report: A 14-year-old male intentionally ingested between 100 and 150 mg of 4-AP and soon thereafter complained of feeling 'twitchy'. Initial vital signs were: pulse, 114/minute; blood pressure, 146/89 mm Hg; respiratory rate, 20/ minute; temperature, 96 [degrees] F. The patient was diaphoretic. He had marked neuromuscular excitability, including fasciculations and increased muscle tone. Bowel sounds were hyperactive. The electrocardiogram showed sinus tachycardia with normal QRS and QTc intervals. The patient was intubated, underwent orogastric lavage, and received activated charcoal. He suffered one generalized seizure, which terminated after treatment with intravenous benzodiazepines and propofol. Sedation was weaned over the next few days, and the patient was extubated without sequelae. Analysis of serial 4-AP levels suggested first-order elimination with a half-life of 170 minutes. Conclusion: We report the first case of human 4-aminopyridine overdose with pharmacokinetic data. In this patient, who developed severe toxicity and whose peak serum level of 256 ng/mL is the highest yet reported, elimination appeared to be first-order with a half-life of 170 minutes. This value is similar to the half-life previously established for therapeutic dosing., Traub SJ, Howland MA, Hoffman RS, Nelson LS. New York City Poison Control Center, New York, NY; St. John's University College of Pharmacy, Queens, [...]

Background: Until recently, hemodialysis (HD) was not considered an effective means of extracorporeal removal of valproic acid (VPA). The protein saturation kinetics of VPA enable extracorporeal removal using current HD filters. Although two previous case reports describe successful treatment of VPA toxicity with high-flux HD, this is the first reported case of VPA toxicity effectively treated with high-efficiency HD. Valporate kinetics are also discussed. Case Report: A 19-year-old male taking VPA for an affective disorder presented to the hospital after ingesting approximately 84 Depakote tablets (total of ~21 grams). He was lethargic with an initial serum VPA concentration of 82.2 mg/L. The remainder of his initial evaluation was WNL. The patient received MDAC and WBI, but despite these measures his VPA concentration continued to rise and peaked at approximately 850 mg/L. Because of worsening mental status high-efficiency HD was performed at the bedside for 7 hours. Serial arterial, venous and dialysate VPA concentrations were obtained. Within six hours of HD therapy the patient awoke and his VPA concentration dropped from 849 to 240 mg/L. The extraction ratio ranged from 21.2 to 56.3%, HD clearance was 43.6 mL/min and 9.3 grams of VPA were removed over six hours of HD. VPA [T.sub.1/2] was 3.3h during HD and 7.44h after HD. Conclusion: High-efficiency HD of VPA achieved 69% of the extraction ratio and approximately 36% of the plasma clearance rate of high-flux HD and removed approximately 50% of VPA ingested. High-efficiency HD, which can be performed at the bedside and requires lower blood flow rates, is effective in removing VPA and should be considered when high-flux HD is unobtainable., Sharma AN, Ilamathi E, Nelson LS, Hoffman RS, Howland MA. New York City Poison Center, St. Catherine of Siena Medical Center and St. John's School of Pharmacy, New York, [...]

Background: In the past, carbon dioxide therapy (CDT) was advocated as a treatment for various psychiatric disorders. The beneficial effects of carbon dioxide ([CO.sub.2]) were presumed to be mediated through CNS alterations although a more precise mechanism of action was never elucidated. Although four deaths from CDT were reported prior to 1966, significant toxicity has not been reported since. We report a case of a woman having respiratory and cardiac arrest following CDT. Case Report: A 38-year-old female with a history of depression was being treated with CDT by an alternative medicine physician. She had 12 uneventful prior sessions. Therapy typically began with pretreatment of 100 mg of atenolol and two tablets of Fiorecet[R]. Approximately two hours later, the patient received via facemask varying mixtures of [CO.sub.2], nitrous oxide ([N.sub.2]O), and oxygen ([O.sub.2]). During the therapy, the physician adjusted the concentrations of the gases initially to attain a 1:1 ratio of [CO.sub.2] and [O.sub.2] and ultimately a 3:2 ratio of [CO.sub.2] and [O.sub.2]. The [CO.sub.2]/[O.sub.2] was then discontinued and the patient was given 100% [O.sub.2]. Shortly thereafter, the patient was noted to be in respiratory and subsequently cardiac arrest. EMS was called and they found the patient receiving CPR by her physician. The patient was orotracheally intubated and initial cardiac rhythm determined to be asystole. She was resuscitated with a total of 8 mg of epinephrine and 3 mg of atropine, defibrillated 6 times, and given amiodarone 300 mg and 88 mEq of sodium bicarbonate with return of spontaneous circulation. She was subsequently admitted to the MICU with severe anoxic encephalopathy. Conclusion: Although the extent of CDT as an alternative form of psychotherapy is unknown and likely uncommon, this case highlights severe morbidity from its modern day use., Su M, Donnabella V, Hoffman RS, Nelson LS. Bellevue Hospital Center, New York, [...]

Background: EH is an FDA approved treatment for acute hepatic encephalopathy and drug OD, but its use in postpartum patients with APAP (FHF) is unreported. We present a pregnant woman with poor prognostic criteria for APAP-induced FHF who was successfully treated by NAC and EH with a Liver Dialysis Unit[R]. Case Report: A 23-year-old woman, 27 weeks pregnant, presented with nausea and vomiting after heavy acetaminophen use for the 2 preceding days. She denied abdominal pain, fever, alcohol use or hepatitis. Vital signs were: BP, 144/98 mmHg; HR, 100/min; RR, 18/ min; temperature, 97.8 [degrees] F. She was alert, and her physical examination was unremarkable except for a gravid abdomen. Laboratory data were: APAP, 90 [micro]g/mL, 6 hours after her last dose; AST, 1208 U/L; [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII], 6 mEq/L; Ct, 1.4 mg/ dL; and INR, 1.7. She was started on standard oral NAC but required an emergent C-section for fetal distress. Despite maximal support, the baby expired soon after delivery. Cord blood revealed: APAP, 19.1 [micro]g/mL and AST, [is less than] 6 U/L. An autopsy on the baby was not performed. Following surgery, her clinical condition and laboratory values worsened to: AST, 9190 U/L; Ct, 3.1 mg/dL; INR, 3.8; and pH of 7.12. She was changed to intravenous NAC at 70mg/kg every 4 hours and underwent 2 courses of EH resulting in both numerical and clinical improvement. Recovery was complicated by pancreatitis and wound dehiscence. Conclusion: This patient met King's College criteria for poor outcome in APAP-induced FHF. Despite NAC therapy, she had worsening liver toxicity. Extracorporeal hemodiabsorption is designed as a bridge to liver transplant and may benefit those patients who fail NAC therapy., Chu J, Regan LA, Nelson LS, Hoffman RS. New York City Poison Control Center, New York, [...]

Objective: Ginseng (Panax spp.) has been used for centuries as a natural remedy for numerous varied ailments. We report a life-threatening vaginal hemorrhage that resulted from the use of therapeutic Chinese ginseng douche. Case Report: A 38-year-old nulliparous, virginal, Asian woman presented to the emergency department after vaginal bleeding for 30 minutes. Her past medical history was significant only for a vaginal yeast infection 6 months earlier for which her gynecologist prescribed a douche of Chinese ginseng extract. She used this douche every three days for the previous six months, despite the fact that her yeast infection had resolved. She denied any sexual activity ever, and denied vaginal instrumentation other than use of the douche, which was inserted with a standard soft, flexible tapered plastic tip on a bottle. She reported her last menstrual period 5 weeks earlier. Her vital signs were: heart rate 100/minute, blood pressure 150/100 mmHg, respirations 16/minute, and she was afebrile. Her physical examination was normal excepting for skin pallor and an actively hemorrhaging erosion of the vaginal mucosa. The cervical os was closed and was not bleeding. Initial laboratory investigations were: white blood count 7.8 x [10.sup.9]/L, hemoglobin (Hb) 13.3 g/dL, hematocrit (Hct) 39.6%, platelet count 288 x [10.sup.9]/L, prothrombin time (PT) 12 seconds, partial thromboplastin time (PTT) 30.1 seconds, INR 1.07, and a negative serum pregnancy test. Her blood pressure decreased to 80/40 mmHg and a repeat Hb was 7.5 g/dL. The patient received 2 liters of crystalloid and 500 mL of packed red blood cells. After the blood transfusion, her Hb increased to Hb 11 g/dL. The vaginal hemorrhage ceased after conservative treatment with intravaginal packing, and the patient was discharged the following day with instructions to avoid further use of ginseng douche. The patient suffered no further gynecologic problem after discontinuation of the douche. Conclusions: For centuries, Eastern and Asian cultures have used herbal remedies such as ginseng for numerous ailments. Traditional Western medicine is increasingly accepting and engaging in the use of ginseng and other natural therapies. Ginseng douche has been advocated as a treatment for vaginal yeast infections and cervical dysplasia. Unfortunately, the safety, efficacy, and side-effects of ginseng and many other potentially effective herbal therapies has not been well-studied. This patient suffered a life-threatening vaginal hemorrhage as a consequence of using therapeutic Chinese ginseng extract douche to treat and prevent vaginal yeast infection., Hoffman RJ, Burke JM, Hahn IH, Hoffman RS. New York City Poison Control Center, New York, New York, [...]

Background: Although lithium salts are commonly used and gastrointestinal and CNS toxicity well recognized, cardiac toxicity is rarely reported. Case Report: A 72-year-old female with bipolar disorder presented with increasing lethargy, ataxia, fever, anorexia, and cough. She had no history of cardiac problems. The patient was only taking lithium which was administered by family. There was no change in her lithium dose for the past 2 years. Her vital signs included a rectal temperature 101 [degrees] F, RR 25/min, HR 42 bpm, BP 117/40 mmHg, and [O.sub.2]Sat 80%. Her physical examination revealed coarse breath sounds bilaterally, bradycardia without murmurs or rubs. Her neurologic examination was significant for lethargy, hyperactive deep tendon reflexes, hypertonic muscle tone, and clonus. Her electrocardiogram showed a junctional bradycardia at a rate of 39 bpm, QRS duration of 100ms, and no acute ST-T changes. The patient received mechanical ventilation and a transvenous pacemaker was placed. She did not respond to atropine or transcutaneous pacing. The laboratory data was unremarkable except for a lithium level of 4.1 mEq/L. Serum digoxin and drugs of abuse urine screen were also negative. Shortly after dialysis, she developed tachycardia. Blood and cerebral spinal cultures ultimately were negative. During a second dialysis for rebound to 2.28 mEq/L, the patient became hypotensive, developed ventricular fibrillation, and could not be resuscitated. Conclusion: Lithium toxicity typically occurs in the setting of dehydration and chronic use. This patient's heart rate was blunted with the elevated lithium concentration and responded appropriately after dialysis. Although neurologic signs predominate, cardiotoxicity may occur and should be routinely assessed in all patients taking lithium., Hahn I, Blancaflor G, Hoffman RS, Nelson LS. New York City Poison Control Center and Bellevue Hospital Center, New York, New York, [...]

Background: Alum is any group of chemical compounds made up of water molecules and two kinds of salts, one of which is typically aluminum sulfate ([Al.sub.2][([SO.sub.4]).sub.3]). Therapeutically, alum is typically used for its astringent properties. We describe a pediatric patient who performed an ethnic healing practice improperly and subsequently sustained severe vaginal injury. Case Report: A 17-year-old nulliparous Haitian female presented to the emergency department complaining of severe vaginal pain. Two days prior, the patient had inserted alum 'crystals' to increase her vaginal tone. Her motivation for using intravaginal alum stemmed from a cultural practice of Haitian women, who use alum postpartum as a means to increase vaginal tone for enhanced sexual pleasure. The patient did not understand that this practice typically involves use of a dilute douche and instead inserted solid crystals. On presentation, the patient had normal vital signs. Intravenous conscious sedation was necessary in order to conduct an adequate pelvic examination, which was significant for vulvar edema and gray-yellow charring of the vaginal mucosa with areas of ulceration. There were no signs of vaginal perforation and there was no active bleeding. The remainder of the physical examination was normal. Laboratory investigations revealed a normal PT/PTT, normal CBC and a negative pregnancy test. Initial treatment consisted of vaginal irrigation with normal saline and administration of analgesics. The patient was observed for 24 hours and discharged. The crystals were identified using atomic absorption spectroscopy for aluminum sodium and barium sulfate precipitation and turbidometric analysis for the sulfate ion. Percentage composition determined after analysis was consistent with the theoretical composition of AlK[([SO.sub.4]).sub.2] [multiplied by] 12 [H.sub.2]O or aluminum potassium sulfate, otherwise known as alum. Conclusion: Intravesicular alum instillation is a common treatment for hemorrhagic cystitis. Aluminum sulfate is also used as an antiperspirant for its astringent properties. Rare complications associated with various different uses for alum include fistulas, encephalopathy and death. In certain ethnic groups, the alum douche is used in conjunction with sitz baths after postpartum to enhance healing in the perineal area. This case describes an ethnic practice that can cause severe injury. This practice should be recognized by physicians living in the multi-cultural urban environment because it may aid in diagnosis and management for an unusual cause of vaginal pain., Hahn I, O'Connor J, Melville L, Blancaflor G, Heller MB, Hoffman RJ, Hoffman RS. St. Luke's-Roosevelt Hospital Center, Kings County Hospital, New York City Department of Health, Bellevue Hospital Center, [...]

Objective: For centuries, herbal remedies have been used as abortifacients. The use of specific agents tends to follow cultural lines. An abortifacient tea made from the leaves of common rue (Ruta graveolens) is a well-established remedy in Mexican culture. We report a case of toxicity in a healthy woman after consumption of such a tea. Case Report: A 26-year-old female of Mexican descent presented to the hospital complaining of abdominal pain and a sensation of ants crawling over her body. The previous day the patient had been informed that she was pregnant and received counseling regarding an elective termination of pregnancy. A relative cautioned her that the surgical procedure involved would be very painful and advised her to make a tea from chocolate, cinnamon and the leaves of a plant growing in her garden. After consuming the beverage, the patient developed abdominal cramps and yellow vaginal discharge. She drank a second dose 5 hours later, vomited several times and developed formication. At this point she sought medical attention. Her physical examination was unremarkable and all standard laboratory tests were within normal limits, except for large ketonuria and a positive urine pregnancy test. A family member was sent home to retrieve the plant used, which was identified as common rue (Ruta graveolens). The treating physicians were also concerned about quinine and sent serum for a quinine assay, which was negative. After two days, her symptoms resolved without any complications. The patient was discharged and sent for pregnancy counseling. Conclusion: The most common adverse affect of rue is a furanocoumarin-induced photodermatitis. Psoralens present in the plant can act as a vesicant and may induce vomiting. However, animal studies have suggested that certain chemicals present in the plant (chalepensin and quinoline) can prevent implantation or increase muscle activity (i.e. abdominal cramps). Either of these mechanisms can induce an abortion. The list of herbal abortifacients and emmenagogues is too extensive for clinicians to remember. Awareness of specific ethnic remedies can assist in the management of patients poisoned by such remedies., Sharma AN, Nelson LS, Hoffman RS. New York City Poison Control Center, New York, New York, [...]

Background: The evidence- and consensus-based development of these published guidelines for poisoned patients will be reviewed.[1] The scarcity of RCT on these topics made an exclusively evidence-based evaluation impossible. This work highlights the need for properly designed clinical studies in developing medical toxicology treatment guidelines. The following topics, evidence overview and recommendations will be discussed. Use of alpha- and beta-adrenergic receptor antagonists in the management of cocaine-associated, acute coronary syndrome (Coc-ACS): The reviewed evidence consisted of 2 randomized clinical trials (RCT) of very good quality, 1 prospective study and 4 cath lab studies of very good to excellent quality, three case series of poor to fair quality and 4 animal studies of good to excellent quality. Recommendations: First line therapies of Coc-ACS include nitrates and benzodiazepines. The use of an alpha-adrenergic receptor antagonist (i.e. phentolamine) should be considered in Coc-ACS patients refractory to vigorous nitrate and benzodiazepine therapy. The use of non-selective beta-adrenergic receptor blockers (i.e. propranolol) is contraindicated in Coc-ACS. Non-selective beta-adrenergic receptor blockers may worsen cocaine induced hypertension and/or coronary vasoconstriction. The use of selective beta-adrenergic receptor blockers (i.e. esmolol and metoprolol) and mixed alpha/beta-adrenergic receptor blockers (i.e. labetalol) are not recommended in Coc-ACS. Use of bicarbonate, lidocaine, propranolol and epinephrine in cocaine-associated, ventricular tachycardia or fibrillation (Coc-VT/VF): For bicarbonate in Coc-VT, two very small case series of good quality and 7 animal studies of fair to good quality were reviewed with most addressing the electrophysiological effects and only one specifically addressing Coc-VT. For lidocaine in Coc-VT, one retrospective clinical study of good quality and 5 animal studies of fair to good quality were reviewed with most addressing the electrophysiological effects and only one specifically addressing Coc-VT. On the safety of lidocaine when given in cocaine toxicity, three animal studies were reviewed. For propranolol in Coc-VT/ VF, 2 animal studies of good quality were reviewed with both addressing ventricular arrhythmias. There were no studies of the efficacy of epinephrine in Coc-VF. Recommendations: First-line drug therapies for hemodynamically stable Coc-VT or refractory Coc-VF are sodium bicarbonate and lidocaine. The use of non-selective beta-adrenergic receptor blockers (i.e. propranolol) is contraindicated in Coc-VT. Use of calcium in calcium channel blocker (CCB) and beta-blocker (BB) poisoning: Evidence evaluated included 2 case series of fair to very good quality, 10 animal studies of good to excellent quality and numerous case reports concerning the use of calcium in CCB poisoning. There are more than 130 published case reports on the use of calcium in calcium channel blocker poisoning. Because multiple treatments were usually attempted and severity of poisoning quite varied, it was impossible to reach definitive conclusions from them. Recommendations: First-line drug therapy for calcium channel blocker CCB drug-induced shock (DI shock) remains catecholamine type vasopressors. Calcium chloride infusions (1-3 gm slow IV push) are recommended in CCB-induced shock refractory to conventional catecholamine vasopressor therapy. Additional calcium infusions via bolus or constant infusion would be warranted in patients demonstrating a beneficial hemodynamic response to the initial calcium infusions. Calcium infusions may be beneficial in other types of drug induced (DI) shock but cannot be recommended because of limited supportive data. Use of insulin euglycemia in CCB and BB poisoning: Evidence reviewed included 1 small case series of fair quality and 8 animal studies that were of very good to excellent quality. Recommendation: Insulin-euglycemia '-pump or -clamp' therapy may be beneficial in CCB-DI shock and BB-DI shock but cannot be recommended because of limited supportive data. Timing of assisted ventilation and dose of naloxone in opiate-induced respiratory failure: There were no articles, which compared the safety and efficacy of naloxone reversal of opioid overdose before or after the initiation of artificial ventilation. The impact of naloxone therapy on blood catecholamine levels was evaluated in two prospective human trials of good quality and four animal studies of good to very good quality. Four cases series of good to very good quality were reviewed for data on efficacy and safety of opioid reversal in ECC. Recommendation: Assisted ventilation and reversal with an opioid antagonist, such as naloxone, should be attempted as soon as possible and prior to intubation in patients with a palpable pulse. Naloxone therapy need not be withheld until assisted ventilations have begun. In opioid dependent patients, a lower initial dose of naloxone (i.e. 0.1-0.2 mg IV, repeated until 0.4 mg) is preferable to a larger initial dose (i.e. 2.0 mg IV). When an opioid overdose is suspected, one should not conclude that the patient was unresponsive until a total naloxone dose of 4-6 mg has been given. Systemic alkalosis in tricyclic antidepressant (TCA) poisoning: The evidence supporting the proposal consisted of four case series (n = 3, 4, 5 and 91) that were of good quality and 24 animal or in vitro studies that were of good to excellent quality. There was one small case report (n = 2) of fair quality with questionable opposing evidence. The numerous published individual cases reporting beneficial effects of systemic alkalosis in TCA poisoning were not included in this review. Recommendation: Sodium bicarbonate is the drug of choice for ventricular dysrhythmias and/or shock due to tricyclic antidepressant (TCA) poisoning. The beneficial effects of sodium bicarbonate result from systemic alkalosis and hypertonic sodium effects. More rapid systemic alkalosis may be achieved via hyperventilation but further benefit often results from the hypertonic sodium. In cases of serious TCA-induced CV toxicity, the goal is a systemic pH of 7.50-7.55. Intermittent bolus sodium bicarbonate administration is preferable to a constant infusion until the desired pH is attained. Procainamide for TCA-induced ventricular dysrhythmias: The panel members could find very little evidence on the use of procainamide in TCA-induced VT/VF. Reports of use in one dog and two rabbits and two case reports were reviewed. Recommendation: When TCA-VT/VF is resistant to sodium bicarbonate, lidocaine is the antiarrhythmic of choice. The use of procainamide for TCA-VT/VF is contraindicated. Because both procainamide and TCA have class Ia antiarrhythmic properties, procainamide would be expected to worsen TCA CV toxicity. Use of high dose vasopressors in DI shock in cases refractory to conventional therapy: Evidence supporting high dose vasopressors consisted 9 case reports of very good quality. Two animal that were either neutral or opposing were of good quality. Recommendation: In DI-shock refractory to conventional therapy, high dose vasopressors may be life saving. While most patients with refractory DI shock have a very low systemic vascular resistance (SVR), some patients have a very high SVR. Therefore, central hemodynamic monitoring should be implemented in patients with DI shock refractory to high dose vasopressors. In most cases vasopressors may be rapidly titrated until shock is adequately treated or recurrent ventricular dysrhythmias, signs of severe peripheral vasoconstriction or an excessively high SVR is observed. Use of circulatory assist devices (IABP or emergency bypass) in DI-shock refractory to maximal medical therapy: Evidence supporting the use of cardiopulmonary bypass consisted of 6 animal studies of very good quality and more than 30 case reports. Evidence supporting the use of the intra-aortic balloon pump consisted of 1 animal study of fair quality and more than 10 case reports. Recommendation: Circulatory assist devices may be live saving in DI-shock refractory to maximal medical therapy. If these heroic measures are to be effective, they must be implemented before the stage of irreversible shock has been reached. Early implementation usually requires advanced planning and approval from multiple disciplines including cardiology, cardiothoracic surgery and cardiopulmonary perfusion. Reference: [1] Circ 2000;102(suppl I):223-228., Martin TG, Latorre F de, Ross MP, Albertson TE, Dawson A, Hoffman RS, Hollander JE, Jaeger A, Kerns W. UW Medical Toxicology Program, University of Washington Medical Center, Seattle, Washington, [...]

Background: Medical therapy of glaucoma involves multiple topical medications to decrease aqueous humor production and increase aqueous outflow. Brimonidine is a relatively selective [[Alpha].sub.2] adrenergic agonist with effects similar to the antihypertensive medication clonidine. Cosopt[R] is a combination of a carbonic anhydrase inhibitor (dorzolamide) and a [Beta] adrenergic antagonist (timolol). We report a case of apnea associated with ophthalmic brimonidine and Cosopt[R] use in an infant. Case Report: A 6-month-old infant born prematurely at 27 weeks gestation with no prior history of respiratory difficulties was treated for glaucoma with 2 ophthalmic eye drops, brimonidine 0.2% and dorzolamide hydrochloride/timolol maleate/20mg/5mg/mL. One drop of each medication was instilled in each eye, and about 30 minutes later, the patient developed several episodes of apnea, each lasting 10-15 seconds with no associated cyanosis, witnessed by her parents. In the hospital, her vital signs were: pulse, 120/min; BP, 101/49 mmHg; respirations, 42/ min; [O.sub.2] sat, 100%; temperature, afebrile. She was easily arousable with normal pupils and an unremarkable physical examination. Interventions were not needed. She was observed in the PICU overnight and did not have further apneic episodes. Her vital signs the next day were: pulse, 135; BP, 87/41; respirations, 35; temperature, 96.9 [degrees] F. The brimonidine and Cosopt[R] were discontinued, and her apnea did not recur. Conclusions: Apnea has been previously reported for both the [alpha.sub.2] adrenergic agonists especially clonidine and beta adrenergic antagonists. Both medications have only one formulation for both adults and children. This case illustrates the potentially severe side effects of using adult strength ophthalmic solutions in infants., Chu J, Nelson LS, Howland MA, Hoffman RS. New York City Poison Control Center, New York, New York, St. John's University, New York, New York, [...]

Objective: Ethanol competitively inhibits alcohol dehydrogenase and is used therapeutically to treat ethylene glycol (EG) ingestions to prevent EG metabolism to toxic organic acids. We report an apparently previously unpublished phenomenon: Classic EG toxicity including high anion-gap metabolic acidosis, hypocalcemia, and renal insufficiency in a patient with a 'therapeutic' ethanol level. This patient ingested ethanol subsequent to ingesting and metabolizing EG, thus developed EG toxicity despite presenting to medical care with a therapeutic ethanol level and a non-toxic EG level. Case Report: A 60-year-old man found unresponsive was brought to the emergency department. Hypoglycemia with glucose 1.33 mmol/L (24 mg/dL) was treated with IV infusion of 50 mL of 50% dextrose. Laboratory investigations revealed: initial serum ethanol 46.2 mmol/L (213 mg/dL), ethylene glycol 2.2 mmol/L (14 mg/dL), bicarbonate 3 mmol/L, blood urea nitrogen (BUN) 12.1 mmol/L (34 mg/dL), creatinine 274 [micro]mol/L (3.1 mg/dL), calcium 2.2 mmol/ L (9.1 mg/dL), anion gap 39 mmol/L; and 45 minutes later calcium 2 mmol/L (8.3 mg/dL), anion gap 35 mmol/L. The patient received one liter of intravenous normal saline and sodium bicarbonate (132 mEq, IV). Serial laboratory investigations were: at three hours; ethanol 27.7 mmol/L (128 mg/dL), pH 6.92; [PCO.sub.2] 14 mmHg, serum electrolytes unchanged; at seven hours, calcium 1.7 mmol/L (7.1 mg/dL), anion gap 28 mmol/L, osmolal gap 67 mOsm/L, pH 7.01, and [PCO.sub.2] 39 mmHg; at 10 hours ethanol 2.1 mmol/L (10 mg/dL), bicarbonate 7 mmol/L, BUN 13.5 mmol/L (38 mg/dL), creatinine 291.7 [micro]mol/L (3.3 mg/dL), anion gap 24 mmol/L, osmolal gap 44 mOsm/kg; at 20 hours, bicarbonate 7 mmol/L, BUN 14.2 mmol/L (40 mg/dL), creatinine 282.8 [micro]mol/L (3.2 mg/dL), calcium 1.9 mmol/L (7.7 mg/dL), anion gap 29, pH 7.29, [PCO.sub.2] 32 mmHg; and at 28 hours, BUN 14.9 mmol/L (42 mg/dL), creatinine 194.4 [micro]mol/L (2.2 mg/dL), calcium 1.3 mmol/L (5.5 mg/dL). After four-hour hemodialysis, the bicarbonate was 28 mmol/L, BUN 3.9 mmol/L (11 mg/dL), creatinine 79.5 [micro]mol/L (0.9 mg/dL), and calcium 1.9 mmol/L (7.7 mg/dL). Subsequent serum chemistry remained normal or rapidly normalized. Conclusion: A serum ethanol of 21.7 mmol/L (100 mg/dL) prevents EG metabolism up to 128 mmol/L (800 mg/dL) and is considered adequate empiric treatment of EG ingestions. This patient's presenting levels of ethanol 46.2 mmol/L (213 mg/dL) and ethylene glycol 2.2 mmol/L (14 mg/dL) might mislead clinicians to inappropriately exclude the diagnosis of EG toxicity. This patient developed classic EG toxicity including high anion-gap metabolic acidosis, hypocalcemia, and renal insufficiency that corrected after hemodialysis. The patient later admitted to ingesting EG and subsequently ingesting ethanol. As a result, he metabolized EG in the absence of a protective serum ethanol level, resulting in severe EG toxicity despite his initial misleading ethanol and EG levels. This unusual case demonstrates that EG toxicity cannot be excluded based on a therapeutic ethanol level or a non-toxic EG level., Hoffman RJ, Hoffman RS, Nelson LS. New York City Poison Control Center, New York, New York, [...]

Background: Although CNS, renal, and GI effects are commonly encountered in lithium toxicity, cardiovascular effects are less well understood and infrequently described. Case Report: An 11-year-old, nonverbal, autistic female with no history of cardiac abnormalities presented with 1 week of fever, anorexia, and vomiting and subsequently developed ataxia, lethargy, and respiratory distress. In the PICU, she had several general tonic-clonic seizures that were managed with benzodiazepines and phenobarbital. She had no independent access to her medications which were continuously dispensed by her parents even throughout her GI illness despite her anorexia. They included sustained release lithium, methylphenidate, haloperidol, benztropine, and guanfacine. The initial vital signs were: BP, 80/40 mmHg; P, 30-40 bpm; RR, 24-44 min; T, 102 [degrees] F rectal; [O.sub.2]Sat, 80% on room air. The physical examination was significant for bradycardia without murmurs, clonus, and hyperreflexia. Her ECG showed a junctional bradycardia with a QRS 64 ms and [QT.sub.c] 507 ms. Transesophageal esophogram showed an ejection fraction of 21% and global hypokinesis of the left ventricle. The laboratory results were normal except for her BUN/Cr (24/0.9) and a lithium level of 6.54 mEq/L for which she received emergent hemodialysis. During dialysis, the patient's cardiac rhythm spontaneously reverted to normal sinus rhythm. A repeat echocardiogram following her second dialysis showed an ejection fraction of 31% and a normal LV shortening fraction. Conclusion: Although lithium poisoning is infrequently associated with reversible cardiac conduction abnormalities, this has not been previously reported in children. This case also demonstrates lithium-induced myocardial depression and its reversal by hemodialysis., Hahn I, Kwok M, Hoffman RS, Nelson LS. New York City Poison Control Center and Long Island Jewish Medical Center, New York, New York, [...]

Background: Tizanidine, an imidazoline with central [[Alpha].sub.2] adrenergic agonist properties, is used to treat spasticity from spinal cord injuries. Although hypotension and bradycardia are adverse effects occasionally described in therapeutic doses, overdose data are limited. We report a case of severe hypotension following an unintentional overdosage of tizanidine. Case Report: A 47-year-old woman with spastic paraplegia secondary to sarcoidosis mistakenly took four (4 mg) tablets of tizanidine rather than her usual dose of one (4 mg) tablet and presented to the hospital within 15 minutes of her ingestion. On arrival, she was drowsy with the following vital signs: blood pressure, 107/69 mmHg; pulse, 86/min; respirations, 16/min; temperature, 97.4 [degrees] F; [O.sub.2] saturation 100%. Her physical examination was remarkable only for pinpoint pupils. An electrocardiogram showed a normal sinus rhythm and was otherwise unremarkable. Activated charcoal with sorbitol was administered and a crystalloid infusion was started at 150 mL/hour. About 3 hours post ingestion; she became hypotensive to a blood pressure of 74/48 mmHg. There were no mental status changes or other clinical symptoms associated with the hypotension. The crystalloid infusion was increased, and her blood pressure normalized after 4 L of normal saline. She was observed in an intensive care unit overnight with no further episodes of hypotension. Her vital signs the next day were: pulse, 70/min; blood pressure, 130/80 mmHg; respirations 12/ min; temperature, 98.8 [degrees] F. She was restarted on her normal doses of antispasticity medications including tizanidine and discharged home. Conclusions: Centrally acting [[Alpha].sub.2] adrenergic agonists are known to cause lethargy, hypotension and bradycardia. Interestingly, this patient was also mildly hypothermic, which is described with centrally acting [Alpha] adrenergic agonists. Clinical trials of tizanidine reported that the most common side effects were fatigue, dizziness, muscular weakness, and dry mouth. Hypotension occurred only occasionally and was altogether absent in some trials. There has only been one previously reported overdose case, and the patient developed hypotension with sino-atrial and atrio-ventricular node dysfunction. Although tizanidine may be well tolerated in therapeutic dosages, this case illustrates the potentially severe side effects from a small overdosage of tizanidine., Chu J, Nelson LS, Hoffman RS. New York City Poison Control Center, New York City, New York, [...]

Objective: Ketamine hydrochloride is a dissociative anesthetic commercially produced as a liquid preparation with benzethonium chloride preservative intended for parenteral administration. Ketamine has become a major drug of abuse in dance parties and dance clubs in urban areas of Europe, North America, and Asia. Illicit use of ketamine is typically by intranasal insufflation of ketamine powder. Evaporating the liquid diluent in which ketamine hydrochloride is dissolved produces ketamine powder. Evaporation is typically performed by one of three methods: 1) allowing the solution to evaporate under ambient conditions, 2) heating the solution with a double-boiling apparatus, or 3) heating the solution in a microwave oven. The medical and forensic management of patients using such powder is based on the assumption that the substance patients are using is ketamine hydrochloride. Illicit preparation involving heating may cause the ketamine hydrochloride to form ketamine free base, react with itself, or with the preservative benzethonium chloride to produce products other than ketamine hydrochloride. Methods: Equal aliquots of ketamine hydrochloride (100mg/mL) in benzethonium chloride preservative were processed by: 1) evaporation at ambient conditions with room temperature of 23.8 [degrees] C, 766 mmHg, 2) use of a double-boiler with water temperature at 99.4 [degrees] C; 3) and use of a microwave oven producing 2450 MHz for 60 seconds. The products of each of these processes were analyzed by GC/MS and compared to each other as well as a standard of ketamine hydrochloride. Results: Evaporation required approximately 30 hours at ambient conditions, 23 minutes when double-boiled, and less than 60 seconds when microwave was used. GC/MS analysis of products demonstrated three peaks at 16.59 minutes 18.25 minutes, and 19.59 minutes, corresponding to two unidentified ketamine-like products, and ketamine free base, respectively. Trace amounts of dibenzofuran were also identified in an earlier peak of the same GC/MS analysis. Conclusions: These methods are precisely those used to convert ketamine hydrochloride solutions to solid form for illicit intranasal use. The products of such preparation aren't pure ketamine hydrochloride: All contained free base of ketamine, and as well, all illicitly prepared forms contained two unidentified ketamine-like products and trace amounts of dibenzofuran. The ketamine hydrochloride standard was converted to free base as a result of heating in the GC/MS analyzer. It is unknown whether the products of illicit ketamine preparation contain benzethonium chloride because this substance may not elute from the chromatography column. Illicit preparation of commercially available ketamine hydrochloride solution by evaporation at ambient conditions, double boiling, and microwaving produces ketamine free base as well as other currently unidentified products., Hoffman RJ, Ravikumar PR, Nelson L, Hoffman RS. New York City Poison Control Center, New York, New York, [...]

Objective: Although most existing data suggest that thallium distributes into the central nervous system (CNS) within 24 hours, CNS toxicity usually progresses over days. To date, no previous reports document human CSF thallium concentrations. We report a patient with thallium poisoning whose CSF thallium concentrations rose despite a falling serum concentration. This observation may offer insight into the progression of thallium-induced CNS toxicity. Case Report: A 48-year-old male presented to the hospital complaining of painful tingling of his arms, legs, tongue and lips, and stated that it felt as if he were suffering from frostbite. He refused to walk because of severe burning in his feet. The patient denied headache, fever, gastrointestinal symptoms or weakness, but recalled partially eating an unpalatable sandwich the previous night. Physical examination was significant only for the absence of ankle jerk reflexes and vibratory sensation in both legs. All standard laboratory tests were within normal limits, except for slight proteinuria. Viral encephalitis was considered, and a lumbar puncture (LP) was only significant for a protein of 62 g/L. A head CT scan was also normal. Over the subsequent 48 hours his symptoms progressed to include altered mental status, ptosis, slurred speech, weakness (4/5 in UE and 3/5 in LE) and loss of positional sense. Deep tendon reflexes were 2+ in the UE and absent in the LE. A second LP was performed. Because of a suspicion of malicious poisoning, a toxicology consult was obtained, and a diagnosis of thallium poisoning was considered. A urine assay revealed a thallium concentration of 50,000 mcg/L (normal [is less than] 5 mcg/L). Unfortunately, as the assay was being performed the patient suffered a cardiac arrest and could not be resuscitated. Stored specimens of serum and CSF were analyzed for thallium by atomic absorption spectroscopy, as shown below. Serum Thallium CSF Thallium Concentration Concentration Hospital Day mcg/L (Normal < 2) mcg/L Day 1 8700 1200 Day 3 7200 2100 Conclusion: Thallium toxicity often presents with a mild gastrointestinal syndrome followed by a classically painful ascending neuropathy and alopecia. In severe cases CNS toxicity progresses to include cranial neuropathies and altered consciousness. Although animal models suggest that thallium penetrates rapidly and completely into the CNS, the correlation between this patient's rising CSF concentrations and worsening CNS symptoms might suggest a slower rate of distribution in humans. This further suggests that the progressive deterioration that occurs in thallium-poisoned patients may be related to ongoing CSF distribution rather than progression of an initial insult. This finding also argues for aggressive early therapy to help lower serum thallium concentrations. Sharma AN, Nelson LS, Hoffman RS. New York City Poison Control Center, New York, New York, USA, Sharma AN, Nelson LS, Hoffman RS. New York City Poison Control Center, New York, New York, [...]

Background: Thallium salts were once commonly used to treat venereal diseases, tuberculosis and ringworm. This practice was curtailed because significant morbidity and mortality resulted from a narrow therapeutic index. Similarly, whereas thallium salts were highly successful rodenticides, their use in the United States was abandoned because substantial human and animal toxicity frequently followed unintentional exposures. Although still used worldwide in industry, and as a rodenticide in some countries, most reported thallium poisonings result from its use as a homicidal agent. Thallium salts can be absorbed through intact skin, alveolar membranes and the gastrointestinal tract, with the latter route being the most consequential. Distribution is rapid into the central compartment, but may take days to complete into the central nervous system. An ionic radius that is similar to potassium allows rapid uptake into cells via potassium channels and Na-K-ATPase. Once inside cells, thallium replaces potassium and disrupts many critical enzyme systems such as succinic dehydrogenase, pyruvate kinase and Na-K-ATPase. Additional toxicity results from binding to riboflavin and various sulfhydryl-containing enzyme systems. Elimination occurs through feces and urine, with a relatively short half-life of about 2 days when renal function is preserved. Clinical effects: Clinically, toxicity from thallium salts bears some resemblance to toxicity from other metal salts. Initially, gastrointestinal symptoms predominate, with nausea and vomiting most commonly reported. Rarely, constipation also occurs and highlights the comparatively benign course of thallium's gastrointestinal toxicity. These symptoms are followed over subsequent hours to days by a characteristically painful ascending peripheral neuropathy. Additional findings include pleuritic chest pain, renal insufficiency, and an autonomic neuropathy, which presents as tachycardia and hypertension. Severe cases develop cranial nerve abnormalities as well as changes in consciousness and respiratory insufficiency. The second characteristic finding, alopecia, occurs about one week following exposure and can progress to complete hair loss. Later, Mee's lines may develop. Diagnosis: The diagnosis of thallium poisoning is usually established based on history and physical examination revealing the characteristic neuropathy and alopecia. Additionally, like most metals, thallium salts are radiopaque. X-rays of patients and contaminated food products may be revealing. Analysis of hair roots by simple light microscopy may demonstrate characteristic pigment changes at the root. The diagnosis can be confirmed by atomic absorption spectroscopy of either the blood or urine. Management: Treatment begins with gastrointestinal decontamination. Unlike most metals, activated charcoal has a high affinity for thallium salts, and multiple dose activated charcoal was beneficial in an animal model. When thallium is demonstrable on an abdominal radiograph, whole bowel irrigation has been suggested, based on theoretical grounds. Although forced potassium diuresis enhances renal elimination, it exacerbates both neurological toxicity in humans and lethality in animals. Furthermore, traditional metal chelators all exacerbate toxicity in animal models and are therefore not used in humans. Prussian blue (at a dose of 250 mg/kg/day) has proven benefit in animals and humans. In severe cases combined hemodialysis and hemoperfusion may provide additional benefit, although this is unclear. Many patients with thallium poisoning will significantly recover with aggressive therapy, the extent of which seems best defined by their clinical condition at the time of diagnosis., Hoffman RS. New York City Poison Center, New York, New York, [...]

Background: Fluvoxamine, an antidepressant that predominantly inhibits serotonin reuptake, is rarely associated with seizures in the absence of an underlying seizure disorder. Hypotension is unreported and fatalities are rare. Case Report: A 40-year-old male with depression presented to the ED one hour after reportedly ingesting 10 g of fluvoxamine. Prior to arrival, the patient had a self-limited generalized seizure witnessed by EMS. His initial vital signs in the ED were BP, 72/palp mmHg; P 124/min; R 28/min; T 101.4 [degrees] F; and [O.sub.2] saturation 98% on room air. On physical examination the patient was lethargic and had mydriasis, peripheral cyanosis, and dry mucous membranes. An ECG revealed sinus tachycardia with a normal QRS duration and a normal T40 axis. His laboratory evaluation was unremarkable. He remained hypotensive despite 3 liters of intravenous saline but responded to intravenous pressors. Following endotracheal intubation he received orogastric lavage, which retrieved many pill fragments, and activated charcoal was administered. He suffered multiple self-limited seizures during the first hospital day for which he received several doses of lorazepam, phenytoin and empiric pyridoxine. A chest radiograph, which was initially normal, revealed bibasilar infiltrates on day 2. He developed progressive hypoxia and ultimately succumbed to necrotizing pneumonia believed to be secondary to aspiration. His presenting serum fluvoxamine concentration was 3500 ng/mL (therapeutic range 88-543 ng/mL). Screening for tricyclic antidepressants and drugs of abuse were negative. Conclusion: Fluvoxamine poisoning typically causes only CNS depression and death in isolated overdose remains unreported. This is the first reported case of status epilepticus and refractory hypotension following isolated overdose., Hahn I, Blancaflor G, Hoffman RS, Howland MA, Nelson LS. New York City Poison Control Center, Bellevue Hospital Center, St. John's University, New York, [...]

Background: Given its wide availability, diphenhydramine (DPH) is commonly taken in intentional overdose. Its ability to block sodium channels may result in QRS widening that should respond to Na[HCO.sub.3], similar to that occurring with TCAs. To date, only one case of DPH-induced wide-complex tachycardia has been reported to respond to Na[HCO.sub.3]. We report three additional DPH overdoses with bicarbonate responsive wide-complex tachycardia. Case Reports: On three separate occasions patients presented to the emergency department following massive DPH overdoses. All patients had tachycardia, an altered mental status and other symptoms of anticholinergic toxicity. In addition, each patient had an initial QRS complex duration greater than 100 msec. IV Na[HCO.sub.3] at 1 mEq/kg was administered to each patient with QRS complex width narrowing. Serum assays for antihistamines and TCAs revealed only elevated DPH levels and no detectable co-ingestants. Initial QRS QRS Width Diphenhydramine Patient Width Post Na[HCO.sub.3] Level 1 128 msec 89 msec 1600 ng/mL 2 161 msec 155 msec Qualitative positive, no quant. 3 102 msec 86 msec 380 ng/mL Conclusion: In our case series, diphenhydramine overdose with resultant wide-complex tachycardia was amenable to sodium bicarbonate therapy. Although the clinical benefit of this therapy is unknown, we recommend Na[HCO.sub.3] for patients presenting with diphenhydramine-induced cardiotoxicity. Sharma AN, Hexdall AH, Nelson L, Hoffman RS. New York City Poison Control Center, New York, NY, Sharma AN, Hexdall AH, Nelson L, Hoffman RS. New York City Poison Control Center, New York, [...]

Background: Fetal acetaminophen (APAP) toxicity is presumed to increase with gestational age and fetal production of NAPQI. Oral feeding of premature infants is associated with necrotizing enterocolitis (NEC), a life-threatening illness. We report a case that deals with presumed APAP toxicity in a premature infant and the complex dilemma associated with NAC therapy. Case: A 27-year-old female, 30 weeks pregnant, reportedly ingested 100 x 325 mg tablets of APAP over a two-day period for a toothache, four days prior to admission. She reported no APAP use for the two days immediately prior to admission, but did report cocaine use. Initial laboratory abnormalities included: INR 8; AST 11,316 U/L; ALT 3440 U/L; APAP 10 [micro]g/mL and Cr 2.1 mg/dL. At presentation she was in active labor and was taken for an immediate Cesarean section. The neonate, born at 30 weeks gestation, 1.5 kg, was admitted to the NICU. His initial cord blood analysis revealed: APAP 7 [micro]g/mL; AST 229 U/L and Cr 2.4 mg/dL. The decision was made to treat with NAC, but the ideal route of administration was debated. The neonate was maintained NPO due to the risk of NEC and his 24-hour IV fluid intake was limited to 80 mL. Both the British and US IV protocols were considered, but fluid restrictions made IV NAC difficult to administer. Ultimately, it was decided to treat the child with oral NAC using the standard US protocol. The neonate tolerated all 18 doses without any evidence of NEC. Mother and child recovered without further complication. Conclusion: Oral NAC was administered without complication in this premature infant with presumed acetaminophen toxicity., Sharma AN, Howland MA, Hoffman RS. New York City Poison Control Center, St. John's University, New York, [...]

Background: Anecdotal evidence leads us to hypothesize that physicians completing fellowship training in medical toxicology are unlikely to practice toxicology primarily. Methods: Using a telephone survey, we contacted all physician fellows in toxicology fellowships in North America to determine if they will practice toxicology after graduation. Fellows in their final year of training were asked what their medical practice would be after completion of their fellowship, and were asked if they would primarily practice toxicology. Results: Seventeen graduating toxicology fellows from eighteen programs were surveyed. No graduating toxicology fellow remaining in North America after graduation (n = 12) intends to practice toxicology primarily. Most indicated that they would practice their primary specialty, usually emergency medicine (n = 9), and would practice toxicology to a limited extent or part-time (n = 9). Several had no plan to practice toxicology to any extent (N = 3). These latter such fellows reported preferring to practice toxicology, but stated that they had no employment opportunity to do so. All foreign nationals returning to their home country (n = 5) indicated that they would practice toxicology, 4 working primarily as toxicologists and 1 practicing pediatrics primarily and toxicology part-time. Conclusion: No graduating toxicology fellows remaining in North America intend to practice toxicology primarily. Several may not practice toxicology at all. Foreign nationals returning to their home country will all practice medical toxicology, most as a primary practice. Efforts may be needed to develop employment opportunities for medical toxicologists in North America., Hoffman RJ, Kwok MY, Nelson LS, Hoffman RS. New York City Poison Control Center, New York, [...]

Background: Poison prevention often includes using cabinet safety locks to deter young children from accessing household toxins. Few poison prevention programs report parents' use of cabinet safety locks. Methods: Poison prevention kits containing telephone stickers, brochures, and a slide cabinet safety lock were distributed to parents enrolled in a Women, Infants, and Children (WIC) program. Poison education was also provided to participants. Telephone follow up calls were made approximately four weeks later to determine if the cabinet safety lock was used, in which room, reasons for not using the lock, and if the poison control center's telephone number was posted. Results: Preliminary data of an ongoing study (n = 21) showed that 62% (13) of participants reported that the safety lock was installed in the home. The locks were usually used in the kitchen (85%, n = 11). The respondents (n = 8) who did not use the lock cited reasons that the lock did not fit the cabinets in the home (n = 4), have gates blocking entry to the kitchen (n = 1), didn't know how to install (n = 1), products are kept out of reach (n = 1), and one didn't remember receiving the lock. Twenty respondents reported at least one child in the home under the age of five years old. The majority of respondents (76%) stated that they knew the poison center telephone number and 71% (n = 15) of respondents had the poison center telephone number posted on or near the telephone. Conclusion: Parents will usually use cabinet safety locks when distributed if the lock fits the cabinets in the home. Distributing a variety of types of locks may accommodate a wider range of cabinets and improve compliance. Poison prevention programs should continue to focus on the importance of using cabinet safety locks and posting the poison center's telephone number in the home., Schwartz L, Howland MA, Mercurio-Zappala M, Hoffman RS. New York City Poison Control Center, New York City Department of Health, St. John's University, New York, [...]

Background: Pressure-treated wood contains copper, chromium, and arsenate (CCA) to prevent decay. Arsenic poisoning from burning pressure-treated wood usually presents with immediate symptomatology. Case: An 11-year-old-male presented with a 6-8 week history of leg cramping, paresthesias, and disabling pain in his feet prior to evaluation. His past medical history was significant for lactose intolerance and chronic sinusitis secondary to a mild IgG subclass deficiency. His medications were Augmentin[R] and guaifesin/pseudoephedrine. There was no patient or family history of pica, vitamin deficiency, metabolic disorders, neuropathy, or illicit drug use. While building an indoor fire alone, the patient unknowingly used pressure-treated wood and was singularly exposed for 10-15 minutes several months prior to his initial medical evaluation. Apparently the damp wood was smoldering and caused smoke to enter the room because the flue was initially closed before the parents realized the problem. Irritability, a gastrointestinal illness, and lower extremity symptoms began 2 weeks after the experience. On his day of presentation, the patient only complained of bilateral pain and tingling of his feet as well as difficulty sleeping and walking secondary to the pain. The patient had normal vital signs. His neurologic examination, which was reportedly normal 2 months earlier when he was evaluated for a minor head contusion after snowboarding, was now significant for bilateral symmetric hyporeflexia, decreased sensation to vibration and position sense of feet, and hypesthesia. Soft tissue swelling was also noted in the dorsum of both feet. No skin changes or nail abnormalities were noted. The patient had normal EMGs of the lower extremities. Laboratory evaluation was normal except for a 24 hour urine total arsenic test of 128 [micro]g/950 mL urine, inorganic fraction was 32 [micro]g/g creatinine ([is less than] 25 [micro]g/g creatinine toxic). Four days after the initiation of succimer therapy, his vibration and position sense normalized but his hypesthesias remained. The patient is still being followed. Conclusions: This case suggests a single exposure to inhalational arsenic can cause significant and persistent toxicity that may be reversible with chelation., Hahn I, Kline SA, Howland MA, Hoffman RS, Nelson LS. New York City Poison Control Center, St. John's University, New York, NY; Eden Prairie Clinic, Eden Prairie, [...]

Background: Sedative-hypnotic withdrawal is generally treated with benzodiazepines or barbiturates. Propofol, a sedative-hypnotic with unique pharmacokinetics, may theoretically be useful for the management of patients not responding to conventional therapy. We report the first case of refractory sedative-hypnotic withdrawal successfully treated with propofol. Case Report: A 35-year-old female with a history of migraine headaches, who had been taking 750-1500 mg of butalbital per day, started outpatient chlordiazepoxide-based detoxification the week prior to admission. The morning prior to presentation the patient took over 200 mg of chlordiazepoxide and presented asking for further detoxification. Initial evaluation revealed a normal physical examination and normal vital signs. A routine psychiatric evaluation revealed a subtle cognitive disorder that required admission to the medical service for evaluation. The following day the patient developed severe psychomotor agitation, auditory hallucinations and autonomic instability (HR of 166 bpm and BP of 158/106 mmHg). Initial therapy including 3 mg of IV lorazapam and 600 mg of IV phenobarbital failed to improve the patient's clinical status. Subsequently, the patient received thiopental, succinylcholine, was intubated and started on a propofol infusion at 50 mcg/kg/min. Within an hour, the patient's heart rate was 95 bpm and her blood pressure was 124/84 mmHg. Twenty-four hours later the propofol drip was discontinued and the patient remained calm, had a normal mental status and was extubated. No further therapy was required. Conclusion: Propofol should be considered as an alternate therapy for refractory sedative-hypnotic withdrawal., Sharma AN, Nelson L, Hoffman RS. New York City Poison Control Center, New York, [...]

Background: Treatment of methemoglobinemia in G6PD deficient patients may induce hemolysis and be ineffective. We report a case of successful treatment in such a patient with profound hemolytic anemia and methemoglobinemia without any further complications. Case Report: A 40-year-old male with end stage AIDS was admitted for respiratory depression. The patient was empirically treated for pneumonia with primaquine and clindamycin. An initial CBC was positive for bands but had no evidence of hemolysis. The patient's condition deteriorated despite therapy and he was intubated. A subsequent CBC revealed a decrease in hemoglobin from 8.0 to 5.6 gm/dL and the presence of schistocytes and reticulocytes on a peripheral blood smear. Further evaluation revealed a methemoglobin level of 14.7% that rose to 23.1% over 2 days. As the patient's religious convictions prevented transfusion the risk of further hemolysis from methylene blue therapy was of great concern. Intravenous methylene blue was administered at 0.5 mg/kg with a subsequent drop in the methemoglobin level to 15.5% within a few hours of therapy. The patient's tachycardia resolved, mental status improved and his hemoglobin stabilized at 3.6 mg/dL with minimal evidence of hemolysis on subsequent peripheral blood smears. His methemoglobin level returned to normal within 48 hours without further therapy. Conclusion: This case demonstrates that methylene blue can be used effectively, in appropriate doses, for the treatment of methemoglobinemia in G6PD deficient patients., Sharma AN, Chawla S, Nelson L, Hoffman RS. New York City Poison Control Center, New York, [...]

Background: Propofol (2,6-diisopropylphenol) is a rapidly acting intravenous sedative-hypnotic agent unrelated to other available agents. Propofol is formulated in an emulsion of 10% soybean oil, 2.25% glycerol, and 1.2% purified egg phosphatide. It is widely used for sedation of mechanically ventilated adult patients. In children, however, prolonged high-dose propofol infusion ([is greater than] 6 mg/kg/h) is associated with hyperthermia, metabolic acidosis, rhabdomyolysis, hepatic steatosis, and lipemia. Nine of twelve cases previously reported resulted in death. Critics declare that the evidence is circumstantial and without clear etiology. We report the death of a child who developed these characteristics after a 42-hour propofol infusion. Case Report: A 28-month-old boy with history of Apert Syndrome underwent elective surgical correction of craniosynostoses. Sedation was maintained with a propofol infusion up to 18 mg/kg/h (total 372 mg/ kg). On postop day 2, he developed hyperthermia ([T.sub.max] = 103 [degrees] C), hypertension (BP = 150/85 mmHg), and tachycardia (Pulse = 140 BPM). Laboratory findings revealed metabolic acidosis (pH 7.32, p[CO.sub.2] 35 mm Hg, [HCO.sub.3] 17 mm Hg), rhabdomyolysis (peaked CPK 246,380 U/L on postop day 3), hypocalcemia (6.0 mg/dL), and hyperphosphatemia (8.5 mg/dL). Additionally, his blood was noted to be lipemic. Despite discontinuation of the propofol infusion, he was unresponsive. Electrolyte abnormalities were corrected. On postop day 3 he developed ventricular tachycardia unresponsive to standard therapy and he died. Autopsy revealed CNS changes consistent with Apert Syndrome (status postcraniotomy), hepatic microvesicular steatosis and degenerative changes in skeletal muscle fibers. All cultures were negative. A postmortem propofol level was 2.2 [micro]g/mL (therapeutic 1.0 [micro]g/mL). Autopsy findings in other propofol-associated deaths were similar. Conclusion: Prolonged propofol infusion may have caused this patient's rapidly deteriorating clinical syndrome. The finding of microvesicular steatosis points to a toxic-metabolic etiology of this syndrome. Propofol's safety in critically ill children remains undetermined., Olmedo RE, Hoffman RS, Howland M, Nelson L. New York City Poison Control Center, St. John's University, New York, [...]

Background: Severe alcohol withdrawal resistant to high doses of benzodiazepines (over 1 gram of diazepam) is reported. Such patients usually require the administration of barbiturates, which frequently causes hypotension, the need for ventilatory support, and unpredictable awakening. Propofol, a [GABA.sub.A] agonist, is used in sedation of critically ill patients because of its predictably rapid pharmacodynamics. Although a single previous report suggested that propofol was efficacious in delirium tremens, that patient's diagnosis was debated. We describe the use of propofol for a clear case of delirium tremens. Case Report: A 34-year-old alcohol-dependent man presented to the hospital with one-day history of alcohol abstinence. Within a few hours in the Emergency, Department, he developed tremulousness, diaphoresis, and had a self-limited seizure with a short postictal period. He was confused, delirious, agitated, and was hallucinating. His vital signs were: HR 110-120 BPM, BP 170/120 mmHg, and T 99.2 [degrees] C. Administration of diazepam (1130 mg) and phenobarbital (650 mg) over 36 hours failed to control his agitated delirium. 40 mg of Propofol was administered and the patient was endotracheally intubated. A propofol infusion of 50 [micro]g/kg/min was continued for 80 hours during which time the patient remained sedated with normal vital signs. The propofol infusion was stopped and he was extubated on hospital day 5. Although mild alcohol withdrawal symptoms continued following discontinuation of propofol, they were easily controlled with conventional therapy and he was transferred to psychiatry asymptomatic. Conclusion: Propofol may be safely used for delirium tremens after conventional therapy fails. Propofol's rapid and short-lived pharmaco-dynamics makes it ideal for following signs of alcohol withdrawal syndrome., Olmedo RE, Nelson L, Howland M, Hoffman RS. New York City Poison Control Center, St. John's University, New York, [...]

Background: Since its inception in 1988, proponents of UROD claim high degrees of safety and efficacy. The procedure reportedly minimizes early intolerable opioid withdrawal symptoms. Treatment consists of administration of opioid antagonists under general anesthesia, followed by maintenance therapy with a long lasting subcutaneous naltrexone implant. This method of naltrexone administration is nonFDA approved. Subsequent withdrawal symptoms are managed as an outpatient. Case Report: A 30-year-old opioid-dependant man (300 mg methadone daily for 2 years) underwent treatment with UROD under general anesthesia with propofol, midazolam, and ketamine. Withdrawal symptoms were treated with clonidine and octreotide. The patient was discharged and was advised to administer octreotide, trazodone, baclofen, acetaminophen, and diphenhydramine for withdrawal symptoms. Three days following the procedure, the patient's family brought him to the hospital comatose and with hematemesis. Vital signs were BP 170/100 mmHg, P 140 BPM, and T 104 [degrees] C. After immediate sedation and intubation, he was cooled, fluid resuscitated, cultured and given antibiotics. Four naltrexone pellets were removed from his abdominal subcutaneous tissue. Laboratories were significant for marked prerenal azotemia. (BUN 72 mg/mL, creatinine 2.6 mg/mL) Endoscopy revealed nonbleeding esophageal varices. His ICU course was complicated by seizures and cardiovascular instability characterized by persistent tachycardia, hypertension and episodic ventricular dysrhythmias requiring cardiopulmonary resuscitation. Despite treatment, he died within 18 hours of arrival. Autopsy revealed an esophageal tear with mediastinitis, and alcoholic liver disease. Pre-mortem blood analysis revealed a naltrexone level of 39 ng/mL (therapeutic 10-60 ng/mL). Drugs of abuse testing was negative. Conclusion: UROD has many potential complications including intractable vomiting with resultant dehydration, esophageal tears, hemorrhage, mediastinitis, and ultimately death. This case may represent unrecognized sedative-hypnotic or alcohol withdrawal. Public awareness of the potential dangers of UROD is necessary., Olmedo RE, Hoffman RS, Howland M, Nelson L. New York City Poison Control Center, St. John's University, New York, [...]

Background: Although gamma hydroxybutyrate (GHB) withdrawal has been previously reported, only one prior abstract reports gamma butyrolactone (GBL) withdrawal. We report two nearly identical cases of severe GBL withdrawal. Case: Two 29-year-old males presented separately to the ED agitated. Both patients suffered GBL overdoses complicated by unresponsiveness (2) and intubation (1) at different times during the preceding 48 hours. They were discharged home within 12 hours and had subsequently discontinued their GBL use abruptly. On readmission, both reported being unable to sleep since discontinuation of GBL, were confused, agitated, hallucinating and had autonomic instability. Initial vital signs were as follows: patient #1: HR 130 bpm; BP 140/106 mmHg; patient #2: HR 133 bpm; BP 142/100 mmHg. Both had normal physical examinations except for tremor and slight diaphoresis. They received diazepam ([is greater than] 50 mg) over 4 hours with reduction in HR to [is less than] 100 bpm and BP to [is less than] 130/90 mmHg. However, they still alternated between periods of lucidity and confusion. Subsequently large doses of diazepam ([is greater than] 100 mg) were required over the next 12 hours and the patients became less confused, but somnolent. Patient #2 had all elevated CPK level (5770 IU/L) that resolved quickly. Both required high dose benzodiazepine therapy followed by a taper for the remainder of their admissions. Conclusion: GBL withdrawal is clinically similar to GHB withdrawal, but can be cause severe life threatening agitation consistent with alcohol withdrawal induced delirium tremens and may require high dose benzodiazepine treatment., Sharma AN, Nelson L, Hoffman RS. New York City Poison Control Center, New York, [...]

Background: Although electromagnetic interference (EMI) with medical equipment is described in the engineering community, little documentation exists in the medical literature to address this largely theoretical concern. The FDA collects data on EMI, but often faces resistance from health care facilities during their investigations. Case Report: An 18-year-old male with metastatic chondrosarcoma, who was receiving an epinephrine infusion for septic shock, developed acute onset of agitation, hematemesis, and chest pain nine hours after the infusion began. Physicians diagnosed acute epinephrine poisoning and noted that the infusion bag contained less than the expected volume. Calculations determined that the patient received 10.5 mg of unintended epinephrine. The infusion pump was turned off and, despite myocardial ischemia and pulmonary edema, the patient ultimately recovered with supportive care. Examination of the implicated infusion pump found it was in normal working condition. Further scene investigation noted that a cellular phone in 'standby mode' as present in the immediate area during the event. When exposed to a similar 'standby' cellular phone in a laboratory setting, the infusion pump reproduced its bolus delivery. During the event the pump displayed '999' mL/h and corrected to the previous setting upon cessation of the signal. Interrogation of the pump's memory revealed that it did not record this event. The investigators thereby concluded the EMI was responsible for the infusion pump failure. Conclusions: This is the first documented case in which EMI with sensitive medical equipment caused substantial human morbidity. The implications of this interference are potentially grave and the health care industry should be cognizant of such possibilities. Reporting of all potential EMI events to the FDA and assistance in their inquiry is suggested., Hahn I, Schnadower D, Dakin RJ, Hoffman RS, Nelson LS. New York City Poison Control Center, New York University, New York, [...]

Background: Ma Huang (Ephedra sinica) is a natural form of ephedrine commonly sold as a nutritional supplement. Ephedrine is rarely reported to cause chest pain syndrome. However, we were unable to find any other cases of Ma Huang-induced myocardial infarction with angiographic evaluation. Case Report: A 30-year-old male body builder took four pills of a weight loss product containing Ma Huang (334 mg each) as instructed by the product label. The patient also reported taking testosterone, but his last cycle was one month prior. He presented to the emergency department complaining of right-sided chest pain. Initial vital signs were: HR 112 bpm; BP, 132/82; RR 16 rpm; 97.8 [degrees] F and physical examination only revealed mild right chest wall tenderness. Initial therapy with ketorolac was ineffective. Subsequently, and ECG revealed T wave inversions in leads III and AVF with poor R waver progression. Aspirin, sublingual nitroglycerin and morphine were given to control pain and a repeat ECG now showed normal R wave progression. Urine toxicology screen was negative for cocaine and amphetamines. The patient's first cardiac enzymes were as follows: CPK 447 IU/L; Troponin I 14.4 ng/mL; MB 6.2%. An emergent cardiac catheterization demonstrated normal coronary arteries, mild global LV hypokinesis and mild LVH. He was admitted to the CCU with subsequent normalization of cardiac enzymes and was discharged on day 3 with warnings regarding stimulant use. Conclusion: Ma Huang (ephedrine) is a vasoactive stimulant capable of causing cardiac injury in 'recommended doses' even in the absence of underlying heart disease. As such, stricter regulation of these agents should be considered., Sharma AN, Cinci PM, Hoffman RS. New York City Poison Control Center, New York, [...]

Objective: Clenbuterol is a long acting [beta.sub.2] adrenoreceptor agonist used clinically in the treatment of pulmonary disorders. Due to its unique ability to shunt metabolic energy from lipid production to protein and muscle production, clenbuterol is used illicitly as an anabolic agent in livestock and human bodybuilders. We report a case of clenbuterol toxicity confirmed and correlated with qualitative and quantitative serum clenbuterol assays. Case Report: A 28-year-old healthy female tasted a small amount of clenbuterol powder that belonged to a friend. Two to three hours later she presented to the ED with tremor, palpitations, and vomiting. Vital signs included: pulse 140/min and BP 120/80 mm Hg. A fine hand tremor was noted. An ECG revealed sinus tachycardia, and serum chemistries were remarkable only for hypokalemia (2.4 mmol/L), and hypophosphatemia (0.9 mg/dL). Metoprolol (50 mg PO) was given, and her pulse slowed to 115/min, but returned to 130/min within 30 minutes. Twice subsequently, metoprolol (5mg IV) was administered, with only a transient response each time. Hypokalemia was supplemented with KCl (40 mEq PO and 10 mEq IV). After 10 hours of persistent tremor and tachycardia, she refused further treatment and left against medical advice. She returned seven hours later, still symptomatic. Her pulse was 123/min and a fine hand tremor was again noted. The ECG was unchanged, and hypokalemia (3.3 mmol/L) and hypophosphatemia (2.0 mg/dL) persisted. Metoprolol (50 mg PO) was given, and again she refused further treatment. Qualitative and quantitative serum clenbuterol assays were performed on blood samples taken at each presentation, 3 hours and 20 hours after the clenbuterol ingestion, respectively. The qualitative technique, ELISA, was positive for the first and indeterminate for the second serum sample. Liquid chromatography/mass spectrometry (LC/MS) quantitation revealed a serum clenbuterol concentration of 2.93 mcg/L in the first sample and was undetectable ([is less than] 1 mcg/L) in the second sample. Conclusion: Clenbuterol toxicity resembles other [beta.sub.2] adrenoreceptor agonist toxicities. Most reported cases describe patients who ate livestock illicitly treated with clenbuterol. In this case, the clenbuterol belonged to a bodybuilder who used clenbuterol for the purpose of increasing muscle mass and decreasing body fat. Although acute clenbuterol toxicity has been rarely reported following illicit use in humans, this is the first such case to provide confirmatory toxicological analysis. This patient developed sustained tachycardia, hypokalemia and hypophosphatemia after ingesting an apparently small quantity of clenbuterol. It is noteworthy that even at a serum concentration below the limit of detection by LC/MS, the patient remained symptomatic for several hours. Hoffman RJ, Hoffman RS, Freyberg C, Poppinga R, Nelson L. New York City Poison Control Center, New York City, New York, USA

Objective: GBL is converted in vivo to gamma-hydroxybutyrate (GHB), a drug known for multiple adverse health effects. A withdrawal syndrome of insomnia, tremor, and anxiety has been observed in chronic GHB users. We describe a patient with history of benzodiazepine and GBL use who presented with a withdrawal syndrome. The pattern of benzodiazepine and GBL discontinuance and response to therapy suggests a potential for GBL or GHB to treat benzodiazepine withdrawal, or vice-versa. Case Report: A 30-year-old male presented to the ED with 2 days of insomnia, tremor, anxiety, diaphoresis and abdominal cramping. His past medical history was notable for insomnia. He denied use of illicit drugs or alcohol, but reported a three-year history of benzodiazepine use for his insomnia. Additionally, he had a three-month history of using GBL to augment the soporific effects of diazepam, which had lost efficacy. During this time period he concomitantly used diazepam (10 mg PO) and an undetermined but consistent quantity of GBL daily to induce sleep. Seven days prior to presentation, he discontinued diazepam use due to a concern that he was becoming tolerant to the drug. He remained asymptomatic while continuing to use his usual daily dose of GBL. His symptoms began shortly after he discontinued use of GBL at the urging of the supplier, who warned the patient of potential adverse health effects. In the ED, he had normal vital signs, 5 mm reactive pupils, gross tremor and was diaphoretic. Although he complained of anxiety, the remainder of his physical examination was unremarkable. The patient was treated with diazepam (5 mg IV). Within minutes, his tremor, diaphoresis and anxiety ceased. The patient refused admission, but agreed to an outpatient taper of oral diazepam. Over the following four days, he continued to take diazepam (10-20 mg PO daily) in divided doses, including one dose to induce sleep. One the fifth day he discontinued use of all medications. He remained asymptomatic and free from benzodiazepines and GBL, but noted difficulty falling asleep. Conclusion: Since GBL is converted to GHB in-vivo, the similarity between this patient's symptoms and previously reported GHB withdrawal is expected. His abdominal discomfort may be a unique feature of GBL withdrawal. The similarity of GHB, GBL and benzodiazepine withdrawal syndromes suggests a common mechanism, potentially related to GABA. It appears that either this patient's withdrawal from GBL was successfully treated with diazepam or that his GBL use masked symptoms of diazepam withdrawal. Either scenario suggests the potential interchangeability, of GBL, GHB, and benzodiazepines for treatment of withdrawal from any of these substances. Hoffman RJ, Hoffman RS, Nelson L. New York City Poison Control Center, New York City, New York, USA

Objective: Levo-[Alpha]-acetylmethadol (LAAM) is an opioid agonist with an extremely long half-life and minimal euphoriant effects. Like methadone, it is used as substitution therapy for opioid addiction. In part due to its limited use, there are no published cases describing the clinical effects or pharmacological properties of LAAM overdose. This report describes an unintentional, iatrogenic overdose in a participant in a LAAM maintenance program. Case Report: A 39-year-old man with a history of heroin abuse who had discontinued LAAM therapy 6 months earlier was restarted on therapy five days prior to presentation because of renewed craving for heroin. He received an initial dose of 20 mg orally, followed 3 days prior to admission by the same dose. On the day prior to admission, the treating physician doubled the dose to 40 mg orally. That evening, the patient's spouse noted that the patient was acting `high' and vomited several times. After having remained immobile for approximately 16 hours while `sleeping', he was found unresponsive and `foaming at the mouth'. In the ED, the patient was unresponsive, had constricted pupils, and shallow respirations with an oxygen saturation of 80% by pulse oximetry. Vital signs were: pulse 86/min; BP 140/80 mm Hg; and respiratory rate 18/min. Administration of naloxone (2 mg IV) produced agitation and vomiting. Standard laboratory analyses were normal except for a CPK level of 6778 IU/L (normal [is less than] 40 IU), and urine analysis demonstrating hematuria and proteinuria. Urine toxicology screening for morphine, methadone, methaqualone, propoxyphene, barbiturates, and benzodiazepines was negative. Several hours after arrival, the patient required endotracheal intubation for respiratory distress, and a chest radiograph demonstrated bilateral pulmonary edema without cardiomegaly. He received supportive care, including mechanical ventilation, for 2 days at which time his respiratory status normalized and rhabdomyolysis resolved. The patient denied taking any drug or substance other than LAAM. Serum collected at the time of presentation was analyzed by gas chromatography/mass spectrometry for LAAM and its metabolites, norLAAM and dinorLAAM. LAAM was below the limit of detection ([is less than or equal to] 10 ng/dL), norLAAM concentration was 15.8 ng/dL, and dinorLAAM concentration was 11.4 ng/dL. Conclusion: LAAM overdose may produce respiratory failure, non-cardiogenic pulmonary edema, and rhabdomyolysis, which is consistent with other opioids. Due to the prolonged clinical action and half-life of LAAM, overdose may require a longer period of observation or treatment than that needed for overdose of other opioids. Additionally, it is noteworthy that this patient responded to standard dosing of naloxone, suggesting that this dose may be appropriate, for treating LAAM intoxication. Hoffman RJ, Nelson L, Hoffman RS. New York City Poison Control Center, New York City, New York, USA

Although recent data suggest that the use of cocaine is declining, it is still the leading cause of illicit drug-related visits to the Emergency Department. The complications of acute cocaine intoxication result from its ability to modulate neurochemical transmission by blocking the reuptake of biogenic amines. Animal models demonstrate that inhibition of dopamine reuptake is responsible for the psychomotor agitation, which commonly accompanies cocaine use. Blockade of norepinephrine reuptake produces cocaine's hypertensive effects, while blockade of epinephrine reuptake produces tachycardia. While the serotonergic effects of cocaine are not as well characterized, inhibition of serotonin reuptake is most likely responsible for the anorexia and hallucinations associated with cocaine use. Furthermore, cocaine enhances central nervous system arousal by potentiating the effects of excitatory amino acids. Studies with excitatory acid antagonists demonstrate that these neurotransmitters are the most likely etiology of cocaine-induced seizures. Additionally, cocaine has a direct proarrhythmic effect on the myocardium which results from sodium and potassium channel blockade, and most resembles the type I antiarrhythmic agents. Finally, cocaine effects of unclear etiology include enhanced platelet aggregation, impaired thrombolysis, and accelerated atherogenesis. The metabolites of cocaine may contribute to clinical toxicity as well. A minority of cocaine undergoes demethylation in the liver to form norcocaine, which has effects that are essentially indistinguishable from the parent drug. Approximately half of a given dose of cocaine undergoes non-enzymatic degradation to benzoylecgonine. This metabolite is a direct vasoconstrictor with a much longer half-life than the parent drug. Whereas other metabolites may have clinical toxicity, these effects are not well described. In the presence of ethanol, however, cocaine (benzmethylecgonine) is transesterified to benzethylecgonine, a metabolite also known as ethylcocaine or cocacethylene, which has potent and long-lasting effects similar to cocaine. The above mechanisms produce multiple organ toxicity that largely results from hyperthermia, vasospasm, and increased vessel shear force from the combined effects hypertension and tachycardia. Bland or hemorrhagic infarctions of all vascular beds have been described, but seem to predominate in the central nervous and cardiovascular systems. Rhabdomyolysis with multiple electrolyte abnormalities and resultant renal insufficiency commonly occurs. However, hyperthermia, with subsequent DIC, multiple organ failure and cerebral edema is the gravest complication of cocaine use. Currently there is no specific antidote for cocaine poisoning. As such, treatment is largely supportive, with specific attention given toward control of behavior. Sedation (with a benzodiazepine) is the safest method of control, with strong support from animal models and clinical practice. Active external cooling is also required when temperatures exceed 41 [degrees] C. Although some authors have used haloperidol with reported success, animal experience advises against this practice because of its potential to exacerbate hyperthermia, lower seizure threshold and produce malignant dysrhythmias. Hypertension and tachycardia usually respond to sedation and cooling. In the event that specific antihypertensive therapy is required, beta-adrenergic antagonists and mixed alpha- and beta-adrenergic antagonists are absolutely contraindicated. Phentolamine or another direct-acting vasodilator can be used. Coronary syndromes typically respond to above measures. In addition nitroglycerin has documented efficacy, and aspirin and heparin seem reasonable. Rarely, in the setting of coronary infarction, thrombolytic therapy has had favorable use. Pending the development of specific antidotal therapy, evidence supports an approach that emphasizes sedation and rapid cooling for patients with acute cocaine intoxication. Rarely, adjunctive vasodilatory agents can be used. Hoffman RS. New York City Poison Center, New York, New York, USA