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

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

A 10-year-old boy (37.5 kg; body surface area 1.26m2) with osteosarcoma of the right humerus received a planned 4-hour infusion of high-dose methotrexate (16 g, 12.7 g/m(2)). His previous medical history was notable for an implanted central venous catheter placement complicated by Horner's syndrome. Renal and hepatic functions were normal at baseline. A postinfusion methotrexate concentration was uninterpretable, but the significance of this result was not initially appreciated by the treating clinicians. Over the next 48 hours, the child developed blurry vision, painful mucositis, stomatitis, and facial blistering. Reported vital signs were: BP, 121/82 mm Hg; pulse, 111/minute; respirations, 16/minute. A physical examination was consistent with the reported symptoms. The 48-hour postinfusion serum methotrexate concentration at the time of poison control center (PCC) consultation was 171 micromol/L

PLAN C, an Agent-Based Model platform for urban disaster simulation and emergency planning, features a variety of reality-based agents interacting on a realistic city map and can simulate the complex dynamics of emergency responses in different urban catastrophe scenarios. Work reported here focuses on the incorporation of specific subpopulations of person agents, reflecting the existence of individuals with specific defining characteristics and needs, and their interactions with the available resources. Performance of these subpopulations are compared in both point-source attack and distributed disaster scenarios for disasters of different magnitudes. Specific ""recovery points"" can be derived both for total- and sub-populations, which estimate the duration of a response system's/city's vulnerability. The effect of varying topologies of available resources, i.e. different hospital maps, provides particular insight into the dynamics that can emerge in this complex system. PLAN C produces interesting emergent behavior which is often consistent with the literature on emergency medicine of previous events.

T cell receptor (TCR) V alpha and V beta chain usage of HTLV-I tax-specific, HLA class I restricted CD8+ cytotoxic T cells (CTL) was determined from lymphocytes obtained from peripheral blood of patients with HTLV-I associated neurological disease. To characterize TCR repertoire, CD8+ lymphocytes from peripheral blood were cloned in limiting dilution, and the resulting wells were screened for HTLV-I-specific precursor CTL activity. RNA was isolated from HLA-A2 restricted HTLV-I tax peptide-specific (tax 11-19; LLFGYPVYV) CD8+ CTL lines and cDNA was analyzed by PCR amplification using V alpha and V beta chain family-specific oligonucleotide primers. The results indicate that CD8+ cytotoxic T cell lines from HLA-A2 HAM/TSP patients express a limited repertoire of T cell receptor chains which may correlate with duration and severity of disease. The restricted use of TCR genes expressed by antigen-specific CTL may play a critical role in the pathogenesis of HAM/TSP and may be of value in developing immunotherapeutic strategies that focus on eliminating these cells or inhibiting their activity.