Faculty Bibliography

Unadjusted doses of valacyclovir can cause neurotoxicity in patients with chronic kidney disease. There are no well documented reports of valacyclovir or acyclovir toxicity providing pre- and postdialysis concentrations of acyclovir in the blood, dialysate and urine of acutely neurotoxic patients. We report an elderly woman with stage 5 chronic kidney disease who developed neurotoxicity after being prescribed unadjusted doses of valacyclovir and provide measurements of the amount of the drug eliminated through haemodialysis vs. native renal clearance. The patient's estimated body-burden of drug before the first session of dialysis was estimated at 580.3 mg. During the first haemodialysis session acyclovir plasma concentrations decreased from 8.8 to 3.2 mg/L (63.6%). Her body-burden of drug before the second session of haemodialysis was estimated as 131.9 mg. During the 2.5 h of the second dialysis session a total of 66.6 mg was eliminated based on measured dialysate concentrations. Urinary elimination was 17.7 mg over 30 h. Despite minimal urinary elimination her blood concentration fell from 8.8 to 0.88 mg/L with a total of 4.5 h of haemodialysis. Haemodialysis appears to be an effective method of eliminating acyclovir, especially in patients with advanced kidney disease.

BACKGROUND:Ischemic heart disease is a leading cause of death globally with a disproportionate burden in low- and middle-income countries (LMICs). Natural language processing (NLP) allows for data enrichment in large datasets to facilitate key clinical research. We used NLP to assess gender differences in symptoms and management of patients hospitalized with acute myocardial infarction (AMI) at Aga Khan University Hospital-Pakistan. OBJECTIVE:The primary objective of this study was to use NLP to assess gender differences in the symptoms and management of patients hospitalized with AMI at a tertiary care hospital in Pakistan. METHODS:We developed an NLP-based methodology to extract AMI symptoms and medications from 5358 discharge summaries spanning the years 1988 to 2018. This dataset included patients admitted and discharged between January 1, 1988, and December 31, 2018, who were older than 18 years with a primary discharge diagnosis of AMI (using ICD-9 [International Classification of Diseases, Ninth Revision], diagnostic codes). The methodology used a fuzzy keyword-matching algorithm to extract AMI symptoms from the discharge summaries automatically. It first preprocesses the free text within the discharge summaries to extract passages indicating the presenting symptoms. Then, it applies fuzzy matching techniques to identify relevant keywords or phrases indicative of AMI symptoms, incorporating negation handling to minimize false positives. After manually reviewing the quality of extracted symptoms in a subset of discharge summaries through preliminary experiments, a similarity threshold of 80% was determined. RESULTS:Among 1769 women and 3589 men with AMI, women had higher odds of presenting with shortness of breath (odds ratio [OR] 1.46, 95% CI 1.26-1.70) and lower odds of presenting with chest pain (OR 0.65, 95% CI 0.55-0.75), even after adjustment for diabetes and age. Presentation with abdominal pain, nausea, or vomiting was much less frequent but consistently more common in women (P<.001). "Ghabrahat," a culturally distinct term for a feeling of impending doom was used by 5.09% of women and 3.69% of men as presenting symptom for AMI (P=.06). First-line medication prescription (statin and β-blockers) was lower in women: women had nearly 30% lower odds (OR 0.71, 95% CI 0.57-0.90) of being prescribed statins, and they had 40% lower odds (OR 0.67, 95% CI 0.57-0.78) of being prescribed β-blockers. CONCLUSIONS:Gender-based differences in clinical presentation and medication management were demonstrated in patients with AMI at a tertiary care hospital in Pakistan. The use of NLP for the identification of culturally nuanced clinical characteristics and management is feasible in LMICs and could be used as a tool to understand gender disparities and address key clinical priorities in LMICs.

Colchicine has an expanding role in cardiovascular disease treatment. Colchicine overdose is a toxicologic emergency. Direct cellular toxicity interferes with myocardial contractility, leading to cardiovascular collapse. We present a case of a patient with a colchicine overdose supported with venoarterial extracorporeal membrane oxygenation, highlighting the challenges and limitations.

INTRODUCTION/UNASSIGNED:The use of the osmol gap as a surrogate marker of toxic alcohol poisoning is common. Unfortunately, many patients with alcoholic ketoacidosis have elevated osmol gaps and are misdiagnosed with toxic alcohol poisoning. We aimed to characterize the range of osmol gaps in patients with alcoholic ketoacidosis. METHODS/UNASSIGNED:This was a retrospective poison center study. Data from 24 years were reviewed using the following case definition of alcoholic ketoacidosis: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or an elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential cases of alcoholic ketoacidosis that failed to fulfill all three criteria were adjudicated by three toxicologists. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other diagnoses that lead to a metabolic acidosis. Demographics, pH, anion gap, lactate concentration, and osmol gap were extracted. RESULTS/UNASSIGNED:Of 1,493 patients screened, 55 met criteria for alcoholic ketoacidosis. Sixty-four percent were male, and their median age was 52 years. The median osmol gap was 27 [IQR 18-36]. The largest anion gap was 57 mmol/L, and the lowest pH was 6.8. Forty-five (82%) of the patients with alcoholic ketoacidosis had osmol gaps >10; 38 (69%) had osmol gaps >20; 24 (44%) had osmol gaps >30; 11 (20%) had osmol gaps > 40. DISCUSSION/UNASSIGNED:The large range of osmol gaps in patients with alcoholic ketoacidosis often reaches values associated with toxic alcohol poisoning. The study is limited by the potential for transcribing errors and the inability to identify the cause of the osmol gap. CONCLUSIONS/UNASSIGNED:In this retrospective study, patients with alcoholic ketoacidosis had a median osmol gap of 26. Given that alcoholic ketoacidosis is easily and inexpensively treated, proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.

A 22-kg female in early childhood with a history of reactive airway disease presented to a paediatric emergency department with acute shortness of breath, tachypnoea and wheezing. Despite treatment with albuterol and corticosteroids, her bronchospasm persisted, prompting the administration of terbutaline. The patient received 220 mcg (10 mcg/kg) terbutaline intravenously, followed immediately by an inadvertent supratherapeutic intravenous dose of 10 000 mcg (454.5 mcg/kg). The patient's laboratory results obtained minutes after the medication error were notable for: potassium, 3.1 mmol/L, lactate, 2.6 mmol/L and troponin I, 0.30 ng/mL (normal <0.03 ng/mL). Over the next 48 hours, serial serum troponin values decreased. The patient was discharged home approximately 72 hours after the initial presentation and she remained well based on follow-up calls over the next several months. Given the timing and trend of troponin concentrations, we do not believe the terbutaline overdose to be responsible for the myocardial injury.

Bupropion is a substituted cathinone (β-keto amphetamine) norepinephrine/dopamine reuptake inhibitor andnoncompetitive nicotinic acetylcholine receptor antagonist that is frequently used to treat major depressive disorder. Bupropion overdose can cause neurotoxicity and cardiotoxicity, the latter of which is thought to be secondary to gap junction inhibition and ion channel blockade. We report a patient with a confirmed bupropion ingestion causing severe cardiotoxicity, for whom prophylactic veno-arterial extracorporeal membrane oxygenation (ECMO) was successfully implemented. The patient was placed on the ECMO circuit several hours before he experienced multiple episodes of hemodynamically unstable ventricular tachycardia, which were treated with multiple rounds of electrical defibrillation and terminated after administration of lidocaine. Despite a neurological examination notable for fixed and dilated pupils after ECMO cannulation, the patient completely recovered without neurological deficits. Multiple bupropion and hydroxybupropion concentrations were obtained and appear to correlate with electrocardiogram interval widening and toxicity.

INTRODUCTION/UNASSIGNED:Many hospitals are unable to determine toxic alcohol concentrations in a clinically meaningful time frame. Thus, clinicians use surrogate markers when evaluating potentially poisoned patients. INDEX CASE/UNASSIGNED:A patient presented after an intentional antifreeze (ethylene glycol) ingestion with an osmol gap of -10.6 that remained stable one hour later. Further investigation revealed that the serum osmolality was calculated and not measured. The true osmol gap was 16.4, which correlated to a measured ethylene glycol concentration of 808 mg/L (80.8 mg/dL, 13.0 mmol/L). SURVEY/UNASSIGNED:A telephone survey of hospital laboratories in our catchment area was performed to investigate the potential for similar events. RESULTS/UNASSIGNED:Thirty-eight (47 percent) hospitals responded. No laboratories were able to test for toxic alcohols. One hospital (2.6 percent) reported routinely calculating osmolality based on chemistries, while two hospitals (5.3 percent) reported scenarios in which this might occur. Thirty-five (92.1 percent) hospitals could directly measure osmolality. Two hospitals (5.3 percent) were reliant on outside laboratories for osmolality measurement. LIMITATIONS/UNASSIGNED:The 47 percent response rate and one geographic area are significant limitations. DISCUSSION/UNASSIGNED:Over 10 percent of hospitals that responded could have significant difficulty assessing patients with toxic alcohol ingestion. CONCLUSIONS/UNASSIGNED:Until the standard of rapidly obtaining toxic alcohol concentrations is broadly implemented, we recommend that policies and procedures be put in place to minimize errors associated with the determination of the osmol gap.