Faculty Bibliography

OBJECTIVE: To report a case of erratic absorption, double peak serum concentrations, and hepatotoxicity following premature cessation of intravenous Nacetylcysteine (NAC) treatment in the setting of a massive acetaminophen overdose. CASE SUMMARY: A 78-year-old man reportedly ingested approximately 96 immediate-release acetaminophen 500-mg tablets (48 g) over a one-hour period in an apparent suicide attempt. The acetaminophen concentration at 2.25 hours was 264 microg/mL. Intravenous NAC was initiated 5 hours postingestion. At 6.25 hours postingestion, the acetaminophen concentration was 281 microg/mL. Following administration of intravenous NAC for 21 hours, therapy was discontinued despite a residual acetaminophen concentration of 116 microg/mL. The patient experienced hepatotoxicity, coagulopathy, and renal injury. Pharmacokinetic analysis revealed significantly prolonged acetaminophen absorption and a second peak acetaminophen concentration of 228 microg/mL approximately 48 hours postingestion. Direct in-hospital monitoring of the patient made a second ingestion unlikely. DISCUSSION: Acetaminophen overdose is usually effectively managed with NAC. Patients with massive ingestions may have altered absorption kinetics due to acetaminophen's solubility being exceeded, physiologically or chemically altered gastrointestinal emptying or motility, or other factors. These patients may benefit from gastrointestinal decontamination and prolonged NAC therapy. CONCLUSIONS: In patients with massive acetaminophen ingestion, erratic absorption may occur, and toxic serum concentrations may persist beyond a standard 21-hour course of intravenous NAC therapy. Acetaminophen concentrations and aminotransferase levels should be evaluated at the completion of therapy intravenous NAC infusion to ensure complete elimination of acetaminophen and absence of hepatotoxicity and to exclude the need for prolonged treatment

Objectives: While critically important, the rapid identification of the etiology of metabolic acidosis (MA) may be labor-intensive and time-consuming. Alcoholic, starvation, and severe diabetic ketoacidosis (AKA, SKA, and DKA, respectively) may produce beta-hydroxybutyrate (BOHB) in marked excess of acetone (ACET) and acetoacetate (AcAc). Unfortunately, current urine dipstick technology poorly detects ACET and cannot measure BOHB. The inability to detect BOHB might delay therapy for ketoacidoses or provoke unnecessary evaluation or empiric treatment of other causes of MA, such as toxic alcohol poisoning. The authors tested the previous assertion that commonly available hydrogen peroxide (H(2)O(2)) would improve BOHB detection. The effectiveness of alkalinization and use of a silver nitrate (AgNO(3)) catalyst was also assessed. Methods: Control and urine test specimens containing from 0.5 to 800 mmol/L ACET, AcAc, and BOHB were prepared. Urine specimens were oxidized with H(2)O(2) (3%) 1:9 (H(2)O(2):urine), alkalinized with potassium hydroxide (KOH; 10%), exposed to AgNO(3) sticks, or altered with a combination of these methods in a random fashion. Three emergency physicians (EPs) blinded to the preparation technique evaluated urine dipsticks (Multistix, Bayer Corp.) placed in the specimens for 'ketones.' Results: Multistix detected AcAc appropriately; ACET was detected only at high concentrations of >/=600 mmol/L. Multistix failed to measure BOHB at all concentrations tested. H(2)O(2) improved urinary BOHB detection, although not to clinically relevant levels (40 mmol/L). Alkalinization and AgNO(3) sticks did not improve BOHB detection beyond this threshold. Conclusions: Addition of H(2)O(2) (3%), alkalinization, or AgNO(3) sticks did not improve clinically meaningful urine BOHB detection. Clinicians should use direct methods to detect BOHB when suspected

OBJECTIVES: Many hospitals must send out ethylene glycol (EG) samples to a reference laboratory, and delays in diagnosis and treatment may occur. A qualitative colorimetric test (ethylene glycol test [EGT] kit), already in use by veterinarians, gives results in 30 minutes with little expertise or cost. The EGT reliably detects the presence of EG in spiked human serum samples. The objective of this study was to prospectively assess the sensitivity and specificity of the EGT kit in actual clinical samples submitted for EG testing by the criterion standard gas chromatography (GC). METHODS: Blood samples from patients with suspected toxic alcohol poisoning submitted to a reference laboratory were tested by GC. An investigator blinded to the GC results tested the same sample with the EGT kit following the manufacturer's instructions and using the internal control. Three physicians also blinded to the GC results categorized the sample as positive for EG, negative, or inconclusive. Interrater reliability was assessed with a kappa statistic (kappa). Results of the EGT kit testing were then compared to those from GC testing. RESULTS: Data are reported on 24 samples submitted. By GC, 15 samples were confirmed for EG (range 27-281 mg/dL), 5 were confirmed for methanol (ME; range 64-101 mg/dL), and 4 were negative for both alcohols. The EGT was unanimously positive in all confirmed EG samples and negative in all ME samples. In one of the negative samples, an ambiguous result occurred and was counted as a false-positive. Interobserver agreement with the EGT was high (kappa = 0.909; 95% confidence interval [CI] = 0.735 to 1.0). Sensitivity and specificity were 100% (95% CI = 70% to 100%) and 88.8% (95% CI = 52% to 100%), respectively. CONCLUSIONS: The EGT appears to be a reliable qualitative test in cases of suspected human EG poisoning

Carvedilol is a non-selective beta-adrenoreceptor antagonist that is also an antagonist at the alpha(1)-adrenoreceptor. This unique pharmacological effect may produce a different toxicodynamic profile compared to other beta-adrenoreceptor antagonists. Only one previous case of carvedilol overdose has been reported. Here, we report massive carvedilol ingestion confirmed by quantitative analysis. The case report deals with an 84-year-old man who chewed a total of 60 (6.25 mg) tablets and rapidly developed symptoms. Vital signs on presentation were systolic blood pressure 70 mmHg; heart rate 45 beats/min.; respirations 18 breaths/min.; temperature 37 degrees . The electrocardiogram showed a junctional rhythm at 49 beats/min. The patient was treated with normal saline boluses, repeated glucagon boluses (2-3 mg each) and a dopamine infusion. At 14 hr after ingestion, he was weaned off vasopressors and was in a normal sinus rhythm. Quantitative confirmation showed a carvedilol serum concentration of 472 ng/ml (steady-state concentration 8.5 ng/ml during 6.25 mg twice daily dosing). Despite its unique pharmacological properties, the clinical manifestations of carvedilol overdose appear similar to other beta-adrenoreceptor antagonists

INTRODUCTION: Compared to other calcium channel blockers (CCBs), overdose with dihydropyridine CCBs are considered relatively benign due to their vascular selectivity. Although not a sustained-release preparation, amlodipine's prolonged duration of effect is concerning following overdose. In addition, angiotensin II receptor blocker blunting of vasoconstrictive and sympathetic compensatory responses could exacerbate calcium channel blocker toxicity. We describe severe toxicity associated with an overdose of amlodipine and valsartan. CASE REPORT: A 75-year-old woman presented to the ED 45 minutes after a witnessed suicidal ingestion of a 'handful' of amlodipine and valsartan tablets. Hypotension, which appeared two hours after ingestion, was refractory to crystalloids and colloids, calcium gluconate, epinephrine, norepinephrine, phenylephrine, and vasopressin infusions. High-dose insulin euglycemia (HIE) therapy, and treatment with glucagon and naloxone were successful in improving her hemodynamic status. In this combined overdose, right heart catheterization demonstrated both negative inotropic effects and decreased systemic vascular resistance. CONCLUSION: Co-ingestion of amlodipine with valsartan produced profound toxicity. Early institution of HIE therapy may be beneficial to reverse these effects