Faculty Bibliography

Objective. Dabigatran is a direct thrombin inhibitor approved for anticoagulation in non-valvular atrial fibrillation and, in some countries, for thromboembolism prophylaxis following select orthopedic surgeries. Despite decreased rates of thromboembolism, bleeding remains a risk due to the inability to conveniently monitor anticoagulant effect and the lack of a reversal agent. Case series. We present four cases of dabigatran-related bleeding. A 79-year-old man on aspirin, clopidogrel, and dabigatran presented with rectal bleeding and epistaxis. He died despite transfusion and administration of prothrombin complex concentrate. A 73-year-old woman on dabigatran and aspirin survived after transfusion and an emergent sternotomy for cardiac tamponade. An 86 year-old man with kidney disease and thrombocytopenia received packed red blood cells, platelets, and fresh frozen plasma for rectal bleeding while on dabigatran. An 80 year-old man on dabigatran had a subdural hematoma after falling and hitting his head. Serial imaging showed no progression. Conclusion. The absence of a reversal agent for dabigatran raises concern for uncontrollable bleeding and death. Dabigatran's listed contraindications include active bleeding and a history of dabigatran hypersensitivity reaction. Wider use may result in bleeding rates higher than anticipated from clinical trials. Risks factors that may have contributed to bleeding in these patients include concomitant bleeding diathesis, antiplatelet agent use, renal insufficiency, advanced age, and fall risks.

Although wolf spider venom has been implicated in necrotic arachnidism without acceptably documented verification, limited, prospectively collected data demonstrate a lack of cutaneous necrosis. The infrequent nature of exposure and inherent difficulty in confirming wolf spider bites in humans makes it challenging to study such envenomations. We present the case of a 20 year-old man with confirmed exposure to the wolf spider who developed cutaneous erythema with ulceration following the bite. There was no evidence of skin necrosis. He was treated with aggressive wound care and systemic antibiotics for wound infection, with subsequent resolution of symptoms. This case adds to the limited knowledge regarding wolf spider envenomations and describes the clinical effects and management of wolf spider envenomation.

A paradoxical drug reaction constitutes an outcome that is opposite from the outcome that would be expected from the drug's known actions. There are three types: 1. A paradoxical response in a condition for which the drug is being explicitly prescribed. 2. Paradoxical precipitation of a condition for which the drug is indicated, when the drug is being used for an alternative indication. 3. Effects that are paradoxical in relation to an aspect of the pharmacology of the drug but unrelated to the usual indication. In bidirectional drug reactions, a drug may produce opposite effects, either in the same or different individuals, the effects usually being different from the expected beneficial effect. Paradoxical and bidirectional drug effects can sometimes be harnessed for benefit; some may be adverse. Such reactions arise in a wide variety of drug classes. Some are common; others are reported in single case reports. Paradoxical effects are often adverse, since they are opposite the direction of the expected effect. They may complicate the assessment of adverse drug reactions, pharmacovigilance, and clinical management. Bidirectional effects may be clinically useful or adverse. From a clinical toxicological perspective, altered pharmacokinetics or pharmacodynamics in overdose may exacerbate paradoxical and bidirectional effects. Certain antidotes have paradoxical attributes, complicating management. Apparent clinical paradoxical or bidirectional effects and reactions ensue when conflicts arise at different levels in self-regulating biological systems, as complexity increases from subcellular components, such as receptors, to cells, tissues, organs, and the whole individual. These may be incompletely understood. Mechanisms of such effects include different actions at the same receptor, owing to changes with time and downstream effects; stereochemical effects; multiple receptor targets with or without associated temporal effects; antibody-mediated reactions; three-dimensional architectural constraints; pharmacokinetic competing compartment effects; disruption and non-linear effects in oscillating systems, systemic overcompensation, and other higher-level feedback mechanisms and feedback response loops at multiple levels. Here we review and provide a compendium of multiple class effects and individual reactions, relevant mechanisms, and specific clinical toxicological considerations of antibiotics, immune modulators, antineoplastic drugs, and cardiovascular, CNS, dermal, endocrine, musculoskeletal, gastrointestinal, haematological, respiratory, and psychotropic agents.

STUDY OBJECTIVE: The ECG is an essential tool in the care of poisoned patients. This study is designed to investigate the accuracy of ECG interpretation reported to a poison center. METHODS: In this prospective study, all cases in which both an electronically faxed copy of the ECG and the caller's interpretation of the ECG were available were eligible for inclusion. ECG interpretation of callers was compared with that of a blinded electrophysiologist. In cases of disagreement, a Delphi panel of toxicologists decided whether the differences were clinically significant or would have changed recommendations. RESULTS: Two hundred cases were included, with complete agreement in 78. In 23 cases, the sole difference was nonspecific ST-T-wave changes, which were believed insignificant and classified as agreement for a total of 101. The Delphi panel reviewed the remaining 99. In 42 cases, the differences in ECG interpretations were thought to be clinically significant; 37 of these would have resulted in a change in management recommendations. Forty-five cases were thought not likely to be clinically significant and would not have resulted in a recommendation change. Twelve cases were thought not clinically significant but would still have resulted in a change in recommendations. CONCLUSION: Initial interpretation of the ECG reported by callers to the poison center is frequently inaccurate. In this study, the misinterpretation was clinically significant or would have resulted in a change in management recommendations in approximately one quarter of all calls

The treatment of patients poisoned with drugs and pharmaceuticals can be quite challenging. Diverse exposure circumstances, varied clinical presentations, unique patient-specific factors, and inconsistent diagnostic and therapeutic infrastructure support, coupled with relatively few definitive antidotes, may complicate evaluation and management. The historical approach to poisoned patients (patient arousal, toxin elimination, and toxin identification) has given way to rigorous attention to the fundamental aspects of basic life support--airway management, oxygenation and ventilation, circulatory competence, thermoregulation, and substrate availability. Selected patients may benefit from methods to alter toxin pharmacokinetics to minimize systemic, target organ, or tissue compartment exposure (either by decreasing absorption or increasing elimination). These may include syrup of ipecac, orogastric lavage, activated single- or multi-dose charcoal, whole bowel irrigation, endoscopy and surgery, urinary alkalinization, saline diuresis, or extracorporeal methods (hemodialysis, charcoal hemoperfusion, continuous venovenous hemofiltration, and exchange transfusion). Pharmaceutical adjuncts and antidotes may be useful in toxicant-induced hyperthermias. In the context of analgesic, anti-inflammatory, anticholinergic, anticonvulsant, antihyperglycemic, antimicrobial, antineoplastic, cardiovascular, opioid, or sedative-hypnotic agents overdose, N-acetylcysteine, physostigmine, L-carnitine, dextrose, octreotide, pyridoxine, dexrazoxane, leucovorin, glucarpidase, atropine, calcium, digoxin-specific antibody fragments, glucagon, high-dose insulin euglycemia therapy, lipid emulsion, magnesium, sodium bicarbonate, naloxone, and flumazenil are specifically reviewed. In summary, patients generally benefit from aggressive support of vital functions, careful history and physical examination, specific laboratory analyses, a thoughtful consideration of the risks and benefits of decontamination and enhanced elimination, and the use of specific antidotes where warranted. Data supporting antidotes effectiveness vary considerably. Clinicians are encouraged to utilize consultation with regional poison centers or those with toxicology training to assist with diagnosis, management, and administration of antidotes, particularly in unfamiliar cases