Laura K. Bechtel

Critical Care Toxicology

Emergency physicians are regularly called on to care for critically poisoned patients. This article reviews the general approach and management of the critically poisoned patient. Specific clinical characteristics are identified that may clue the clinician into a specific toxin class as a diagnosis. Appropriate testing in the poisoned patient is reviewed. Complications of poisoning that may bring a rapid demise of the critically ill poisoned patient are highlighted and the management of those complications is discussed.

Management of the critically poisoned patient

BackgroundClinicians are often challenged to manage critically ill poison patients. The clinical effects encountered in poisoned patients are dependent on numerous variables, such as the dose, the length of exposure time, and the pre-existing health of the patient. The goal of this article is to introduce the basic concepts for evaluation of poisoned patients and review the appropriate management of such patients based on the currently available literature.MethodsAn unsystematic review of the medical literature was performed and articles pertaining to human poisoning were obtained. The literature selected was based on the preference and clinical expertise of authors.DiscussionIf a poisoning is recognized early and appropriate testing and supportive care is initiated rapidly, the majority of patient outcomes will be good. Judicious use of antidotes should be practiced and clinicians should clearly understand the indications and contraindications of antidotes prior to administration.

Verapamil Toxicity Dysregulates the Phosphatidylinositol 3‐Kinase Pathway

OBJECTIVES Recent animal research and clinical case reports suggest benefit from high-dose insulin therapy (HDIT) for the treatment of calcium channel blocker (CCB) toxicity. One molecular signaling pathway, the phosphatidylinositol 3-kinase (PI3K) pathway, that contributes to CCB toxicity and the efficacy of HDIT, was examined for a role in this phenomenon. METHODS A differentiated 3T3-L1 adipocyte model system was utilized to characterize metabolic and molecular signaling events dysregulated in response to acute CCB toxicity. Glucose uptake assays were performed in the presence of representatives of three classes of CCB drugs, and the ability of HDIT to reverse observed inhibition was assessed. Western blot analyses were utilized to probe which insulin-dependent signaling pathway was inhibited by CCB toxicity. RESULTS Representative compounds from the dihydropyridine and phenylalkylamine classes of CCBs were more effective at inhibiting glucose uptake in differentiated 3T3-L1 adipocytes than a representative from the benzothiazepine class. Phosphorylation at serine 473 of the Akt protein (P-Akt), a protein representing a common pathway for insulin receptors (IR), insulinlike growth factor receptors (IGFR), and hybrid receptors formed by IR and IGFR subunits, was abolished in the presence of toxic doses of the phenylalkylamine CCB verapamil. Phosphorylation at serine 473 of Akt was rescued in the presence high concentrations of insulin. CONCLUSIONS These data suggest that dysregulation of the insulin-dependent PI3K pathway is partially responsible for insulin resistance and the hyperglycemic state observed in response to acute CCB toxicity.

Ingestion of false hellebore plants can cross-react with a digoxin clinical chemistry assay.

Introduction. We report a case of digoxin-like toxicity because of ingestion of foraged plants. This patient presented with nausea, vomiting, bradycardia, and hypotension after ingesting Veratrum viride (false hellebore). The patients serum specimen demonstrated a positive digoxin level (0.38 ng/mL) measured by a clinical tubidimetric immunoassay. We hypothesize that steroidal alkaloid compounds contained in V. viride cross-react with the Multigent™ Digoxin immunoassay reagent antibodies. Results. Plant extracts from V. viride demonstrated cross-reactivity to Multigent™ reagent antibodies but did not bind therapeutic DigiFab™ antibodies. Gas chromatography/mass spectrometry analyses identified several steroidal alkaloid compounds present in the V. viride extracts: jervine, ribigirvine, solanidine, and veratraman. Conclusions. This study indicates that compounds extracted from V. viride can cross-react with a clinical Digoxin immunoassay. Yet these extracts did not bind DigiFab™ antibody fragments used for therapeutic intervention. Providers should not unnecessarily administer DigiFab™ fragments as an antidote in symptomatic V. viride toxic patients.