Faculty Bibliography

INTRODUCTION/BACKGROUND:Aripiprazole is an atypical antipsychotic with unique receptor-binding properties that has a favorable safety profile in therapeutic doses compared to other antipsychotics. Massive aripiprazole overdose in children, however, presents with profound lethargy and may have neurologic, hemodynamic, and cardiac effects, often requiring admission to a high level of care. CASE REPORT/METHODS:We describe a case of a 21-month-old male with a reported 52-milligram aripiprazole ingestion. Initial vital signs were remarkable for tachycardia and hypertension, which rapidly resolved. The patient did not develop hypotension throughout hospitalization. He experienced 60 hours of lethargy. Irritability associated with upper extremity spasms and tremors occurred from 36-72 hours post ingestion, which resolved without intervention. The initial electrocardiogram demonstrated ST-segment depressions in the anteroseptal leads; further cardiac workup was normal. Concurrent medical workup was unrevealing. Aripiprazole and dehydro-aripiprazole serum concentrations sent 46 hours after reported exposure were 266.5 nanograms per milliliter (ng/mL) and 138.6 ng/mL, respectively. He returned to neurologic baseline and was discharged 72 hours after ingestion. CONCLUSION/CONCLUSIONS:Antipsychotics, including aripiprazole, should be considered as a potential toxicological cause of persistent central nervous system depression; ingestion of a single dose has the potential to cause significant toxicity.

BACKGROUND/UNASSIGNED:Severe acetaminophen (APAP) poisoning can result in fulminant hepatic failure and abnormal tests of coagulation. Although the international normalized ratio (INR) may be elevated, the actual hemostatic status of patients with APAP-induced hepatotoxicity is unknown. Few studies exist investigating the clinical use of thromboelastography (TEG) to evaluate the hemostatic status in the setting of APAP-induced hepatotoxicity. METHODS/UNASSIGNED:We performed a retrospective review of patients who were admitted for APAP toxicity and received TEG testing at a single transplant center. RESULTS/UNASSIGNED:Nine patients had detectable APAP concentrations and exhibited elevated aspartate and alanine aminotransferase activities. Seven had thrombocytopenia. TEG revealed a decreased median alpha angle and maximum amplitude but other values were within the normal reference range. DISCUSSION/UNASSIGNED:Based on our study of APAP-induced hepatotoxicity, TEG showed a decreased rate of fibrin formation and cross-linking, as well as reduced clot strength. These findings suggest that patients with APAP-induced hepatotoxicity and thrombocytopenia have a theoretically increased bleeding risk as demonstrated by both elevated INR and abnormal TEG values. However, these TEG findings are more likely related to thrombocytopenia rather than directly to APAP-induced hepatotoxicity. Further studies should be performed to elucidate the potential role of TEG in various stages of APAP-induced hepatotoxicity.

INTRODUCTION/BACKGROUND:The term "lactic acidosis" reinforces the misconception that lactate contributes to acidemia. Although it is common to discover an anion gap acidosis with a concomitant elevated lactate concentration, the two are not mutually dependent. CASE REPORT/METHODS:Here we describe two patients exhibiting high lactate concentrations in the setting of metabolic alkalemia. CONCLUSION/CONCLUSIONS:Lactate is not necessarily the direct cause of acid-base disturbances, and there is no fixed relationship between lactate and the anion gap or between lactate and pH. The term "metabolic acidosis with hyperlactatemia" is more specific than "lactic acidosis" and thus more appropriate.

BACKGROUND:histamine receptor antagonist, is a commonly used nonprescription medication that is used for the treatment of allergy, as a sleep aid, or combined with cough and cold remedies. Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), is used commonly for analgesia. Although most cases of diphenhydramine or naproxen overdose require excellent supportive care only, meticulous attention should be given to cardiovascular and neurologic status. CASE REPORT/METHODS:A 22-year-old woman presented with altered mental status secondary to intentional ingestion of 240 combination caplets of naproxen sodium 220 mg and diphenhydramine hydrochloride 25 mg. While in the emergency department, she manifested a wide-complex tachycardia in the setting of hypotension that required repeated administration of sodium bicarbonate to overcome the sodium channel blockade caused by diphenhydramine. Aggressive potassium repletion was performed simultaneously. Her clinical course was complicated by status-epilepticus that required intubation. Orogastric lavage was performed, which returned blue pill slurry consistent with the ingested caplets. The patient was extubated on hospital day 2 and transferred to psychiatry thereafter. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In light of recent social media trends, such as the "Benadryl challenge" and its widespread availability, emergency providers should be familiar with diphenhydramine toxicity, especially the life-threatening neurologic consequences and risk of cardiovascular collapse. NSAIDs, such as naproxen, and other nonprescription analgesics are becoming more and more important in light of the current opioid crisis. There should be an emphasis on understanding these medications and their potential implications when taken in overdose.

INTRODUCTION/BACKGROUND:Acetaminophen is a commonly used analgesic and antipyretic, with the potential to cause significant injury when ingested in toxic amounts. Although the antidote n-acetylcysteine (NAC) is available, evidence supporting dose recommendations for patients weighing over 100 kg are lacking. We performed a retrospective, multi-center analysis to determine if a capped NAC dosing scheme is similar to a non-capped dosing scheme in patients weighing over 100 kg. METHODS:Between January 2009 and January 2016, we identified patients presenting to 12 different centers who were evaluated for acetaminophen poisoning treatment. Patients must have weighed greater than 100 kg and were evaluated and identified as needing treatment for acetaminophen-related poisoning with NAC. The primary outcome was occurrence of hepatic injury, defined as an AST or ALT ≥ 100 IU/L. Secondary endpoints included number of drug-related adverse events, occurrence of hepatotoxicity, cumulative NAC dose, regimen cost, length of hospital and intensive care unit stays, and in-hospital mortality. RESULTS:There were 83 patients identified as meeting the pre-specified inclusion and exclusion criteria. A capped NAC dosing scheme resulted in no difference in hepatic injury when compared to a non-capped regimen (49.4% vs 50%, p = 1.000). The capped dosage regimen was associated with a lower cumulative dose (285.2 mg/kg vs 304.6 mg/kg, p < 0.001) and cost. No other statistically significant differences were identified among the secondary endpoints. CONCLUSION/CONCLUSIONS:A capped NAC dosing scheme was not associated with higher rates of hepatic injury or hepatotoxicity in obese patients in the setting of acetaminophen poisoning when compared to a non-capped regimen. Further research is needed to verify these results.