Cynthia K. Aaron

Fomepizole for the Treatment of Methanol Poisoning

BACKGROUND Methanol poisoning may result in metabolic acidosis, blindness, and death. The inhibition of alcohol dehydrogenase is fundamental to the treatment of methanol poisoning. We performed a multicenter study to evaluate fomepizole, an inhibitor of alcohol dehydrogenase, in the treatment of patients with methanol poisoning. METHODS We administered intravenous fomepizole to 11 consecutive patients who presented with methanol poisoning at a participating center. Serial clinical and laboratory studies, including measurements of plasma formic acid and fomepizole, were performed. The outcomes measured were the preservation of visual acuity, the resolution of metabolic acidosis, the inhibition of formic acid production, the achievment of therapeutic plasma concentrations of fomepizole with the dosing regimen, residual illness or disability, and death. RESULTS Plasma formic acid concentrations were detectable in eight patients, and these concentrations were closely correlated with the initial arterial pH values (r=0.92, P<0.001). In response to fomepizole, plasma formic acid concentrations fell and metabolic abnormalities resolved in all patients. Nine patients survived. Seven patients initially had visual abnormalities, but at the end of the trial no surviving patient had any detectable visual deficits related to methanol poisoning. Fomepizole had few adverse effects. The two patients who died had anoxic brain injury that was present at the time of enrollment. During treatment, methanol had an elimination half-life of 54 hours. CONCLUSIONS Fomepizole appears to be safe and effective in the treatment of methanol poisoning.

Lethal Serotonin Syndrome After Methylone and Butylone Ingestion

IntroductionA new generation of designer phenethylamines have emerged and aggressively marketed as “legal highs.” The drugs are labeled “not for human consumption” to avoid widespread recognition and prosecution under the existing analog drug laws. The newest generation includes methylone and butylone. Methylone and butylone have minor structural changes and similar pharmacodynamics properties to scheduled drugs.Case ReportWe report a case of a healthy 24-year-old who ingested a capsule containing methylone and butylone sold as “Ecstasy” at a concert. The patient presented to the emergency department, comatose febrile, tachycardic, tachypnic, and hypertensive. On exam, she was diaphoretic, tremulous, hyperreflexic, and had sustained clonus. The patient was aggressively cooled, and despite maximal supportive care, the patient progressed to multi-system organ failure and ultimately expired. We obtained and analyzed both her urine and a capsule found on her person similar to the capsules ingested. In both samples, laboratory analysis identified only methylone and butylone.ConclusionThis is the first reported death for methylone or butylone and the first human or animal ingestion of butylone. Clinicians and public health officials should work together as new designer drugs emerge.

Treatment of Methanol Poisoning With Intravenous 4-Methylpyrazole

Treatment of human methanol poisoning with the alcohol dehydrogenase inhibitor, 4-methylpyrazole (fomepizole), has not been previously described. We report the clinical and toxicokinetic data of a patient with methanol poisoning who was treated with fomepizole. Formic acid levels remained undetectable during fomepizole treatment, the toxic effects of methanol were prevented, and the patient made a full recovery.

Organophosphates and Carbamates

ORGANOPHOSPHATES Organophosphate (OP) compounds were first synthesized in significant quantities during the 1940s, when tetraethylpyrophosphate was developed as an insecticide. Azamethiphos General Information. Azamethiphos is an OP pesticide that was probably procured locally during the PGW as a fly bait. While there is no EPA registration number for azamethiphos, it has been used in Canada, Scandinavia, the United Kingdom, and France to control sea lice infestations in fish farms. Azamethi-phos is also available in Mexico, primarily for fly control. Commercially available azamethiphos products outside the United States include Alfacron 10 and Snip. Alfacron 10 contains 10 percent azamethiphos as the active ingredient and is used as a wettable powder. A thick paste is obtained by mixing 200 mL of tepid water with 250 g of Alfacron 10, which will cover either 100 m 2 of floor space or 200 m 2 of walls. Alfacron can also be applied by spraying or painting with a liquid solution of 500 g Alfacron 10 in 4 L of tepid water. This mixture will cover 50 m 2 of floor space or 100 m 2 of wall surfaces. Snip is a 1 percent azamethi-phos fly bait that contains Z-9 tricosene (female housefly pheromone), which attracts flies to eat the granular bait. The recommended application is 200 g of Snip spread on a 100 m 2 space frequented by flies. The bait becomes more effective if the space has been previously wetted with water or milk. The chemical identity of azamethiphos is shown in Table 7.1, and Table 7.2 summarizes its physical and chemical properties.

Organophosphate and carbamate poisoning.

Organophosphates (OPs) and carbamates have a wide variety of applications, most commonly as pesticides used to eradicate agricultural pests or control populations of disease-carrying vectors. Some OP and carbamates have therapeutic indications such as physostigmine. Certain organophosphorus compounds, known as nerve agents, have been employed in chemical warfare and terrorism incidents. Both classes inhibit acetylcholinesterase (AChE) enzymes, leading to excess acetylcholine accumulation at nerve terminals. In the setting of toxicity from either agent class, clinical syndromes result from excessive nicotinic and muscarinic neurostimulation. The toxic effects from OPs and carbamates differ with respect to reversibility, subacute, and chronic effects. Decontamination, meticulous supportive care, aggressive antimuscarinic therapy, seizure control, and administration of oximes are cornerstones of management.

Acute clenbuterol overdose resulting in supraventricular tachycardia and atrial fibrillation

ObjectiveWe are presenting a case illustrating the complex metabolic and rhythm disturbances associated with acute clenbuterol intoxication.BackgroundClenbuterol is a long-acting β2-adrenergic agonist primarily used in veterinary medicine in the United States. It has become a common drug of abuse by body builders because of its reported anabolic and lipolytic properties. In this case report, a body builder using veterinary clenbuterol developed significant electrolyte and cardiac manifestations.Case ReportA 31-year-old man presented to the emergency department approximately 30 minutes after ingesting 1.5 ml (a tenfold dosing error) of Ventipulmin® syrup (72.5 mcg/ml clenbuterol HCl). The product was brought to the emergency department (ED) by the patient. He reported no current use of anabolic steroids. He presented in an anxious state with complaints of palpitations and shortness of breath. Vital signs upon examination were as follows: BP, 122/77 mmHg (16.3/10.3 kPa); HR 254 bpm; RR, 22 bpm; Temperature, 97.1°F (36°C); and oxygen saturation, 100% on ambient air. His electrocardiogram (ECG) demonstrated supraventricular tachycardia with a ventricular rate of 254 bpm. Esmolol was recommended for rate control after the unsuccessful use of adenosine and diltiazem. Laboratory studies showed potassium, 2.1 mmol/L; magnesium, 1.3 mg/dL (0.54 mmol/L); phosphorus, 1.0 mg/dL (0.32 mmol/L); serum glucose, 209 mg/dL (11.6 mmol/L); creatinine, 0.8 mg/dL (70.7 μmol/L); AST, 20 U/L; ALT, 55 U/L; hemoglobin, 12.6 g/dL (126 g/L); CPK total, 87 U/L; and troponin I, 0.23 μg/L. The patient’s urine was negative for any drugs of abuse. Clenbuterol levels were not obtained. A second ECG, 16 hours post ingestion, reflected atrial fibrillation with a ventricular rate of 125 to 147 bpm. On hospital day 3, he was electively cardioverted to sinus rhythm; heart rate and rhythm returned to normal, and he was discharged with oral metoprolol.DiscussionClenbuterol is approved for use in countries outside the U.S. as a bronchodilator for the treatment of acute asthma exacerbations in humans. Although clenbuterol is not a steroid hormone, it possesses anabolic properties that increase muscle mass. Its longer duration of action compared to other β2-agonists (such as albuterol) make it a desired agent for body-building because of its high and prolonged serum level. The mechanism for the short and long-term cardiovascular complications of clenbuterol is complex. The anabolic effects of clenbuterol are associated with its β2-adrenoreceptor agonist activity on striated skeletal muscles. In addition, clenbuterol promotes lipolysis through adipocyte β3-adrenoreceptors.ConclusionConsidering the significant number of body-building enthusiasts, physicians will continue to encounter clenbuterol abuse in their clinical practices.

Delayed Peak Serum Valproic Acid in Massive Divalproex Overdose—Treatment with Charcoal Hemoperfusion

BACKGROUND Increased clearance and apparent clinical improvement in valproic acid overdose has been reported following in-series hemodialysis/hemoperfusion therapy. We report a case of divalproex sodium and chlorpheniramine overdose treated with charcoal hemoperfusion and multiple-dose activated charcoal. CASE REPORT A 32-year-old female presented alert three hours postingestion of her own medication. Serum valproic acid was 105 micrograms/mL. No anticholinergic toxicity was seen. Despite three doses of activated charcoal over 14 hours, serum valproic acid continued to rise. Whole bowel irrigation and multiple-dose activated charcoal were commenced 17 h postingestion when serum valproic acid was 1380 micrograms/mL. Charcoal hemoperfusion was instituted three hours later when serum valproic acid had not fallen and the patient remained obtunded. RESULTS Initial extraction ratio of the hemoperfusion cartridge was 0.54 with plasma clearance of 54.5 mL/min. Valproic acid elimination half-life was 3 h during the 190 min hemoperfusion cycle. Posthemoperfusion elimination half-life was 4.8 h with continued multiple-dose activated charcoal dosing. The clinical condition improved during hemoperfusion. CONCLUSION Enteric coated valproic acid preparations may cause delayed toxicity in overdose, particularly with coingested anticholinergic medications. In our case, charcoal hemoperfusion appeared to increase valproic acid clearance.

Efficacy of charcoal cathartic versus ipecac in reducing serum acetaminophen in a simulated overdose

The traditional role of gastric emptying as the initial step in the management of the poisoned patient has recently been questioned; immediate activated charcoal administration has been recommended by some. In the setting of acetaminophen overdose, ipecac-induced emesis may interfere with subsequent oral antidotal therapy. Therefore, we conducted a study to compare the efficacy of initial therapy with ipecac with therapy with activated charcoal-cathartic in a simulated acetaminophen overdosage. Ten healthy volunteers participated in a randomized, crossover trial. Subjects ingested 3.0 g acetaminophen, followed by either no intervention, 30 mL syrup of ipecac, or 50 g activated charcoal-sorbitol solution at one hour. Serial acetaminophen levels were determined at intervals over eight hours. Both interventions significantly reduced the area under the curve compared with control (P less than .05). When comparing ipecac with activated charcoal-cathartic, no significant difference was noted among these groups.

Sorbitol catharsis does not enhance efficacy of charcoal in a simulated acetaminophen overdose

The use of a 70% sorbitol solution has recently been advocated as an adjunct to activated charcoal. This results in rapid and profuse catharsis that could possibly cause fluid and electrolyte imbalance. An investigation was undertaken to determine if sorbitol catharsis enhanced the antidotal efficacy of activated charcoal. Eight healthy volunteers participated in a randomized, crossover trial. Subjects ingested 3 g of acetaminophen followed by either no intervention, 50 g of plain activated charcoal at one hour, or 50 g activated charcoal-sorbitol solution at one hour. Serial acetaminophen levels were determined at intervals over eight hours and side effects noted. Both interventions significantly reduced the area under the curve versus control (P less than .05). The addition of sorbitol did not enhance the efficacy of activated charcoal but did increase the side effects noted. Sorbitol has not been proven effective in enhancing drug removal and has side effects that can be significant in a poisoned patient. Current data do not warrant its use, and further investigations should be carried out with other ingested drugs.

Regional intravenous infusion of calcium gluconate for hydrofluoric acid burns of the upper extremity

STUDY OBJECTIVE To describe regional intravenous infusion of calcium gluconate as a therapy for hydrofluoric acid (HF) burns of the forearm, hand, or digits. METHODS This study describes seven patients with HF burns. Calcium gluconate, 10 mL of 10% solution with 30 to 40 mL normal saline solution, was injected intravenously into the affected limb using a Bier block technique. Ischemia was maintained for 20 to 25 minutes. Therapy was considered successful if significant reduction of pain and tenderness was noted after tourniquet release. RESULTS Seven patients were treated. HF concentration varied from 5% to 49%. Exposure sites included the forearm (two cases), thenar eminence and digits (two cases), or digits only (three cases). Complete pain resolution occurred on tourniquet release in four patients (two with burns to the forearm, two with burns to digits only). One patient had partial relief (thenar but not digital exposure site), and two had no relief of symptoms. Intraarterial calcium gluconate perfusion was subsequently administered to the three patients with persistent subungual and pulp, or thenar pain. Recovery was complete in all cases. No adverse effects were noted. CONCLUSION Regional intravenous infusion of calcium gluconate should be considered a therapeutic option in HF burns of the forearm, hand, or digits when topical therapy fails.