Assessing the Role of Initial Serum Calcium Concentration in Patients with Ethylene Glycol Poisoning.

INTRODUCTION: Assays for ethylene glycol (EG) with a rapid turn-around time are not routinely available. Clinicians must rely on historical features and readily available clinical tests, combined with clinical acumen, to guide the initial management of suspected EG poisoning. Hypocalcemia has been suggested as a clue supporting the diagnosis of EG poisoning in patients presenting with an unexplained high anion gap metabolic acidosis (HAGMA). A previous small study challenged this assumption. METHODS: This was a retrospective case series of one state's poison control system of confirmed EG-poisoned patients between September 2017 and April 2021. The definition of EG poisoning was based on suspected EG ingestion and a serum EG concentration > 5 mg/dL. Patients who were suspected to have EG toxicity but did not have a confirmed EG concentration or the EG concentration was less than 5 mg/dL were excluded. Routine laboratory studies were recorded for all patients. Comparisons between serum calcium on presentation to presenting blood pH, bicarbonate, anion gap, and creatinine were assessed for correlation. RESULTS: There was no correlation between the presenting calcium and either pH or creatinine. There was a weak positive correlation between the initial serum calcium and anion gap, a weak negative correlation between the initial serum calcium and bicarbonate. CONCLUSION: On hospital presentation, hypocalcemia was not associated with EG poisoning, even in patients with a HAGMA. A normal serum calcium on presentation does not exclude the diagnosis of EG poisoning.

Massive Apixaban Overdose Confirmed with Blood Concentrations and Managed Without Bleeding: A Single Case Report.

BACKGROUND: Acute overdoses of apixaban, and other direct oral anticoagulants are relatively uncommon. The number of direct oral anticoagulants prescriptions in the United States is increasing, however reports on patient outcomes after documented overdose are sparse. CASE REPORT: A 76-year-old man with a past medical history of atrial fibrillation and taking apixaban 5 mg twice daily presented to the emergency department 10 hours after reportedly ingesting 60-70 of his pills. He was alert and had a normal physical examination. Blood tests demonstrated an INR of 12, platelets of 161 000 cells/mm3, hemoglobin 9.7 g/dL, and creatinine 1.81 mg/dL. He received 60 g of activated charcoal and 4 units of fresh frozen plasma prophylactically. Initial blood apixaban concentration was 4 000 ng/mL. Repeat blood apixaban concentrations were 3 000 ng/mL and 2 200 ng/mL at 7 and 14 hours, respectively (thrapeutic range 91-321 ng/mL for a 5 mg twice daily dose). The hybrid anti-factor Xa activity did not correlate with blood apixaban concentrations. Apixaban elimination followed first-order kinetics with an apparent elimination half-life of 14 hours in the presence of impaired renal function. He did not have any minor or major bleeding events.

Massive intentional enoxaparin overdose managed with minimal protamine: A single case report.

PURPOSE: The case of a patient with a massive acute enoxaparin overdose managed with observation and minimal doses of protamine sulfate is reported. SUMMARY: Acute enoxaparin overdoses are uncommonly reported and management is widely variable. A 25-year-old man presented to the emergency department (ED) shortly after reporting that he had attempted suicide by injecting himself with 31 syringes of 80 mg of enoxaparin (a total of 2,480 mg) in the abdomen and other areas of his body. The patient also had self-inflicted superficial lacerations of the forearm. Due to concern over suspected compartment syndrome in the forearm, 25 mg of protamine was administered. Approximately 11 hours after reported enoxaparin self-injection, the patient's activated partial thromboplastin time (aPTT) was 206 seconds, prompting administration of an additional 50 mg of protamine. Three hours later, the aPTT had decreased to 79 seconds, then rose over several hours to 127 seconds before gradually declining to normal values. Protamine administration had no appreciable impact on anti-factor Xa activity. The patient did not require any blood products during the hospital admission. There were no further complications, and the patient was discharged to the inpatient psychiatry service on hospital day 8. CONCLUSION: The case highlights the role of protamine as a reversal agent in the management of low-molecular-weight heparin overdoses. The optimal dosing and efficacy of protamine for this indication needs further investigation.

Intravenous Acetaminophen Overdose in an Infant With Toxicokinetic Data.

CASE REPORT: A 12-month-old (former 24 week gestational age), 8.7 kg male was hospitalized after an uneventful colostomy reversal. In the postoperative unit, the patient unintentionally received 1000 mg IV (114.9 mg/kg) acetaminophen instead of the intended 100 mg IV. Serial acetaminophen concentrations were drawn. The patient received IV Nacetylcysteine and ultimately had no adverse outcomes. DISCUSSION: This case report adds to the existing literature regarding toxicokinetics of IV APAP in infants. Our patient had a calculated ke of 0.263 h-1, correlating with a half-life of 2.63 hours. Based on current available data, the half-life of IV APAP in infants varies (2.6 to 4.9 hours). The reason for this variation is unknown and further research is needed in this area.

Clozapine Toxicity in Two Young Siblings Due to a Pharmacy Dispensing Error: a Pediatric Case Report.

INTRODUCTION: Clozapine is an atypical antipsychotic used to treat refractory schizophrenia; in both therapeutic use and overdose, it can cause significant toxicity. We report two young siblings who developed altered mental status after ingesting clozapine due to a pharmacy dispensing error. CASE REPORT: A 5-year-old girl and her 19-month-old sister presented to the emergency department (ED) with altered mental status after they took their first dose of what was believed to be cimetidine, prescribed to treat molluscum contagiosum. Both children were discharged after a brief period of observation in the ED. Two days later, when the older child continued to be symptomatic, their mother used a web-based pill identifier and discovered that the pills dispensed by the pharmacy were 200 mg clozapine tablets, not the cimetidine that had been prescribed. Ingestion was confirmed with an elevated serum clozapine concentration in the older child of 17 mcg/L at 85 hours post-ingestion (adult therapeutic range: 350-600 mcg/L). Both children had complete resolution of their symptoms 4 days following the ingestion with supportive care alone. DISCUSSION: We report two cases of pediatric clozapine toxicity due to a pharmacy dispensing error. The error was due, in part, to similarly named medications being stored adjacent to each other on a shelf. Dispensing errors are not rare occurrences and their root causes are multi-factorial. This case demonstrates the importance of reducing such errors, particularly for medications with potential for severe toxicity.

Two Cases of Acute Direct Oral Anticoagulant Overdose Without Adverse Effect.

We report 2 pediatric patients who had acute overdoses of the direct oral anticoagulants medications. Both patients were managed conservatively; neither required reversal agents or blood products nor had any major or minor bleeding events. With therapeutic usage of direct oral anticoagulants, routine coagulation studies typically are considered insufficient measures of anticoagulation and the preferred chromogenic anti-Factor Xa assay is recommended but not widely available. Using a routine hybrid heparin anti-Factor Xa assay, 1 patient demonstrated a strong linear correlation up to a serum rivaroxaban concentration of 940 ng/mL.

Thromboelastography in the setting of acetaminophen-induced hepatotoxicity.

BACKGROUND: 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: We performed a retrospective review of patients who were admitted for APAP toxicity and received TEG testing at a single transplant center. RESULTS: 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: 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.

A Case of Massive Diphenhydramine and Naproxen Overdose.

BACKGROUND: Diphenhydramine, a first generation H1 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: 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.

A Pharmacokinetic Analysis of Hemodialysis for Metformin-Associated Lactic Acidosis.

OBJECTIVE: Although hemodialysis is recommended for patients with severe metformin-associated lactic acidosis (MALA), the amount of metformin removed by hemodialysis is poorly documented. We analyzed endogenous clearance and hemodialysis clearance in a patient with MALA. METHODS: A 62-year-old man with a history of type II diabetes mellitus presented after several days of vomiting and diarrhea and was found to have acute kidney injury (AKI) and severe acidemia. Initial serum metformin concentration was 315.34 µmol/L (40.73 µg/mL) (typical therapeutic concentrations 1-2 µg/mL). He underwent 6 h of hemodialysis. We collected hourly whole blood, serum, urine, and dialysate metformin concentrations. Blood, urine, and dialysate samples were analyzed, and clearances were determined using standard pharmacokinetic calculations. RESULTS: The total amount of metformin removed by 6 h of hemodialysis was 888 mg, approximately equivalent to one therapeutic dose. Approximately 142 mg of metformin was cleared in the urine during this time. His acid-base status and creatinine improved over the following days. No further hemodialysis was required. CONCLUSION: We report a case of MALA likely secondary to AKI and severe volume depletion. The patient improved with supportive care, sodium bicarbonate, and hemodialysis. Analysis of whole blood, serum, urine, and dialysate concentrations showed limited efficacy of hemodialysis in the removal of metformin from blood, contrary to previously published data. Despite evidence of acute kidney injury, a relatively large amount of metformin was eliminated in the urine while the patient was undergoing hemodialysis. These data suggest that clinical improvement is likely due to factors besides removal of metformin.

Toxicokinetics of hydroxychloroquine following a massive overdose.

BACKGROUND: We report a patient with a massive hydroxychloroquine overdose manifested by profound hypokalemia and ventricular dysrhythmias and describe hydroxychloroquine toxicokinetics. CASE REPORT: A 20-year-old woman (60 kg) presented 1 h after ingesting 36 g of hydroxychloroquine. Vital signs were: BP, 66 mmHg/palpation; heart rate, 115/min; respirations 18/min; oxygen saturation, 100% on room air. She was immediately given intravenous fluids and intubated. Infusions of diazepam and epinephrine were started. Activated charcoal was administered. Her initial serum potassium of 5.3 mEq/L decreased to 2.1 mEq/L 1 h later. The presenting electrocardiogram (ECG) showed sinus tachycardia at 119 beats/min with a QRS duration of 146 ms, and a QT interval of 400 ms (Bazett's QTc 563 ms). She had four episodes of ventricular tachydysrhythmias requiring cardioversion, electrolyte repletion, and lidocaine infusion. Her blood hydroxychloroquine concentration peaked at 28,000 ng/mL (therapeutic range 500-2000 ng/mL). Serial concentrations demonstrated apparent first-order elimination with a half-life of 11.6 h. She was extubated on hospital day three and had a full recovery. CONCLUSION: We present a massive hydroxychloroquine overdose treated with early intubation, activated charcoal, epinephrine, high dose diazepam, aggressive electrolyte repletion, and lidocaine. The apparent 11.6 hour half-life of hydroxychloroquine was shorter than previously described.

Poison control centers and alternative forms of communicating with the public: what's all the chatter about?

Context: Short messaging service (SMS or text messaging) allows for the exchange of electronic text messages. Online chatting refers to Internet-based transmission of messages for real-time conversation. Poison Control Centers (PCCs) in the United States communicate with the public primarily via telephone. However, people increasingly prefer the convenience of SMS and chatting. Our objective is to describe the use of SMS and chatting by PCCs in the United States. Methods: An electronic survey questionnaire was distributed to all 55 US poison control center members of the American Association of Poison Control Centers. The survey assessed protocols for SMS and chatting, inquiry volume, and staff satisfaction. Centers reporting use of SMS or chatting services were administered follow-up questions, which further documented SMS and chatting interfaces and startup and maintenance costs. Descriptive statistics were used to describe the data. No statistical analysis was performed. Results: Of the 55 PCCs, 51 (93%) responded to the survey, 6 (12%) of which currently use or formerly used SMS and/or chatting. Inquiry volume ranged from 0 to 1 per day for SMS and 0 to 20 per day for chats. Startup costs ranged from $0 to $25,000. The most beneficial aspect, reported by 4 of the 6 PCCs (66.6%), was providing an alternative contact for inquiries. Most SMS and chatting interactions were completed within 10 and 30 min, respectively. All six centers completed telephone interactions within 10 min. The most disadvantageous aspects, reported by 2 of the 6 PCCs (33.3%), were staff apprehension and interaction length. Technology, such as syncing with existing call queuing software and databases, presented the greatest barrier to implementation. Conclusions: A minority of PCCs in the United States use SMS and chatting. Further research may investigate the economic feasibility of these systems, if SMS and chatting effectively expands public access, and patient comfort in contacting PCCs.