Characteristics of ivermectin toxicity in patients taking veterinary and human formulations for the prevention and treatment of COVID-19.

BACKGROUND: US poison control centers reported increased cases of ivermectin toxicity during the COVID-19 pandemic. Previous descriptions of ivermectin toxicity have evaluated heterogeneous groups with a variety of ivermectin sources and dosage patterns. We sought to compare the clinical effects of ivermectin toxicity in patients taking human- vs. veterinary-formulations and acute- vs. chronic-ingestion patterns. METHODS: We performed a retrospective analysis of cases from the Oregon Poison Center of ivermectin exposures for the prevention or treatment of COVID-19 that resulted in a healthcare visit over a 24-week period (14 August 2021 - 31 January 2022). RESULTS: We identified 37 cases of ivermectin toxicity. The median age of patients was 64 years, and most patients were male. The majority of patients were hospitalized (21) or treated in an emergency department (13). A minority were treated in an outpatient setting (3) and one patient died. Seventeen ingested veterinary formulations and fifteen ingested prescription tablets. Patients reported taking ivermectin for treatment (23) and prevention (14) of COVID-19. Clinical effects included neurotoxicity (30), gastrointestinal symptoms (14), and musculoskeletal complaints (7). Patients taking veterinary products took higher doses of ivermectin and had higher rates of altered mental status than those taking prescription tablets. Patients taking ivermectin chronically took smaller doses (daily dose of 13.5 mg) over a prolonged period (median 3.8 weeks) and developed toxicity that was milder than those with acute ingestions. CONCLUSION: Ivermectin toxicity developed in predominantly male patients >60 years old who ingested higher than recommended doses and developed neurologic symptoms. Patients who took a veterinary formulation of ivermectin ingested large single doses or large daily doses for several days and developed rapid onset of neurotoxicity. Patients with chronic toxicity developed milder symptoms and tended to take typical therapeutic doses, but continued therapy for weeks rather than days.

Continuous extracorporeal clearance in metformin-associated lactic acidosis and metformin-induced lactic acidosis: a systematic review.

INTRODUCTION: Metformin poisoning with lactic acidosis is an uncommon yet clinically serious condition related to the inhibition of normal aerobic metabolism. Toxicity may occur after an acute overdose although it is much more common after a systemic insult, such as acute kidney injury, in the setting of chronic use. Hemodialysis is currently the preferred extracorporeal treatment modality (Grade 1D evidence) although some patients may be too hemodynamically unstable to tolerate it. Continuous renal replacement therapy is considered an alternative if hemodialysis is unavailable but an evaluation of survival amongst this specific treatment class is lacking. OBJECTIVES: To assess overall survival and provide an updated review of the toxicokinetic elimination parameters of patients receiving continuous renal replacement therapy for metformin poisoning. METHODS: A comprehensive search was performed using the EMBASE and MEDLINE libraries from inception until November 30, 2021. Data was extracted and findings were summarized. Toxicokinetic parameters were analyzed and confirmed for accuracy when data permitted. RESULTS: Eighty-three reports met inclusion criteria. These consisted of only low-quality evidence including 75 case reports, four case series, and four descriptive retrospective reviews. Overall survival among patients suffering from metformin toxicity who received continuous extracorporeal treatment was 85.8%. When stratified between metformin-induced lactic acidosis and metformin-associated lactic acidosis, survival was 75.0% and 87.4%, respectively. Available continuous renal replacement therapy toxicokinetic parameters were quite heterogeneous. Errors in previously published toxicokinetic calculations were noted in only two instances. The overall average and median peak metformin concentrations were 70.5 mg/L and 41.9 mg/L, respectively. The average and median extracorporeal clearance rates were 39.0 mL/min and 42.1 mL/min (range 9.0-58.7 mL/min). The average and median elimination half-life parameters were 27.5 h and median 23.0 h. Elimination half-life ranged from seven to 74 h. There was no meaningful relationship between peak metformin concentration and continuous extracorporeal treatment half-life at lower concentrations, though at very high concentrations (over 200 mg/L), there was a trend towards a half-life below 20 h. There is insufficient data to robustly evaluate overall survival in relation to the extracorporeal clearance rate. Finally, there was no relevant relationship between maximal lactate concentration and survival, nor nadir pH and survival, for patients with either type of metformin toxicity. CONCLUSIONS: This retrospective systematic analysis of published cases treating metformin related lactic acidosis with continuous renal replacement therapy notes an overall slightly greater survival percentage compared to previous publications of individuals requiring any modality of renal replacement therapy. Because of publication bias, these results should be interpreted with caution and serve as hypothesis generating for future research. Prospective study focusing on the most clinically meaningful endpoint - survival - will help elucidate if continuous modalities are non-inferior to intermittent hemodialysis in metformin toxicity.

Methicillin-Resistant Staphylococcus aureus Septic Internal Jugular Thrombophlebitis: Updates in the Etiology and Treatment of Lemierre's Syndrome.

BACKGROUND: Lemierre's syndrome is classically precipitated by oropharyngeal infections that progress to suppurative internal jugular vein thrombophlebitis via direct extension. Metastatic pneumonia from septic emboli is nearly universal and bacterial seeding frequently results in disseminated septic foci. Fusobacterium necrophorum is the most commonly reported etiologic agent, though methicillin-resistant Staphylococcus aureus (MRSA) is an emerging pathogen and a myriad of oropharyngeal flora must be covered until blood cultures return. Prompt identification is paramount to minimizing morbidity. Empiric treatment with antibiotics exhibiting predominantly anaerobic activity has been standard, but now may be insufficient, given an evolving microbial landscape. Anticoagulation continues to be debated. CASE REPORT: We describe an uncommon presentation of Lemierre's syndrome in a diabetic patient secondary to MRSA, where the only identifiable source of entry was atraumatic post-auricular cellulitis. Why Should an Emergency Physician Be Aware of This? Given the evolving landscape of organisms implicated in septic internal jugular thrombophlebitis, empiric treatment should entail consideration of MRSA. Patients at an elevated risk include those who are undomiciled or incarcerated, injection drug users, human immunodeficiency virus-positive, and have recently been hospitalized or completed a course of antibiotics. The existing evidence evaluating empiric anticoagulation is low-powered and retrospective and would benefit from randomized controlled trials. Although it does not appear valuable for most, those with thrombus extension, persistent bacteremia, or central venous thrombosis may benefit.

A 10-year review of single medication double-dose ingestions in the nation's largest poison control system.

BACKGROUND: Most Americans take at least one medication on a daily basis. Inadvertently ingesting a double-dose of a medication with a narrow therapeutic index may lead to adverse effects. When a patient or medical professional contacts the local poison center after an overdose, a poison specialist fields the incoming information and, depending on the caller, provides specific recommendations. We sought to determine which medication classes were most likely to lead to significant adverse outcomes when an extra dose was ingested. METHODS: This was a retrospective review of all double-dose medication ingestions reported to the California Poison Control System (CPCS) between January 2006 and December 2015. Inclusion criteria were single-instance, single-medication ingestions where the dose was known. All ages and both sexes were included. We evaluated generalized outcomes per AAPCC criteria stratified as no effect, minor, moderate, major or death. We also documented specific symptoms and interventions noted by the poison control specialists. RESULTS: Out of 1286 cases, 876 ingestions met the inclusion criteria. Medications with antihypertensive and behavior modulating effects each accounted for over a third of all moderate and major effects. The medications/medication classes implicated in the 12 major outcomes included propafenone, beta blockers (ßBs), calcium channel blockers (CCBs), bupropion, and tramadol. Of these, vasoactive medications were associated with the most severe effects requiring cardiac pacing and vasopressor drips. Analgesics, antimicrobials, and anti-allergy medications were well tolerated. There were no deaths. CONCLUSIONS: Major adverse outcomes after a double dose ingestion were rare. Most double dose medication ingestions can be safely monitored at home, albeit with a few exceptions. Vigilance is warranted in cases of ßB and CCB ingestion due to the risk of hemodynamic collapse or seizures with tramadol and bupropion.

Recurrent Diffuse Large B-Cell Lymphoma Presenting with Pancoast Syndrome: A Rare Cause of Radicular Neck Pain in the Emergency Department.

BACKGROUND: Pancoast syndrome is an uncommon complication of apical lung tumors. Symptoms include pain, brachial plexopathy, and Horner's syndrome, and are the result of extrinsic compression of tissues within the thoracic inlet. Lymphoma is a very rare etiology. CASE REPORT: We describe the presentation of a 59-year-old male with recurrent diffuse large B-cell lymphoma presenting with Pancoast syndrome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Cancer is an uncommon cause of radicular neck pain but should be considered in the differential, particularly when constitutional complaints are also present. Symptoms and physical examination findings associated with Pancoast syndrome are the consequence of compression of the C7-T2 vertebral roots and sympathetic chain. Computed tomography is usually required to definitively visualize the mass.