Utility of electroencephalography in toxin-induced seizures.

INTRODUCTION: Toxin-induced seizures differ from seizures occurring in epilepsy and have a high rate of complications. Electroencephalography (EEG) is routinely obtained when there is concern for nonconvulsive status epilepticus (NCSE). The purpose of this study was to characterize the typical findings after toxin-induced seizures, assess the rate of epileptiform discharges and NCSE, and identify any changes in management resulting from EEG. METHODS: Patients older than 16 years who had an EEG during hospitalization for drug-induced seizure or seizure-like activity were included. We reviewed 10 years of data (2013-2022) across our hospital system (four community hospitals and one academic center). Patients with a history of seizures and those with cardiac arrest prior to EEG were excluded. The primary outcome was incidence of epileptiform discharges on EEG. The secondary outcome was number of antiseizure medications (ASM) added after EEG. RESULTS: A total of 256 encounters were screened with 83 patient encounters included. A total of 53% (44/83) of EEGs showed some degree of generalized slowing. A total of 2.4% (2/83) of cases had epileptiform activity on EEG. No cases of nonconvulsive status were identified. No ASM was started in the two cases where epileptiform discharges were identified. CONCLUSIONS: During usual care of toxin-induced seizures, epileptiform discharges are uncommon.

Increasing number and shifting demographics of adolescent opioid use disorder presentations to the emergency department.

INTRODUCTION: Opioid use has been increasing in adolescents; however, lacking are data describing sex, ethnicity, and age groups most affected. We identified and characterized the trend in the adolescent population who presented to the emergency departments (ED) of a large hospital system. METHODS: We obtained data directly from the electronic medical record for patients aged 12-21 years from January 2014 to December 2022. We identified opioid-related visits by primary diagnosis. Trends were compared amongst age groups and by sex and reported ethnicity. RESULTS: Opioid-related presentations increased in all age groups and were significantly increased in adolescents aged 13-17 years compared to patients aged 18-21 years (1700% [range: 1000-3300%] v 400% [200-800%]; p = 0.02). Adolescents presenting to the ED with opioid-related primary diagnoses were more likely to be Hispanic and male in our region. DISCUSSION: Over the last two years (2021-22) there was a significant increase in opioid-related presentations to our hospital system amongst adolescents and an acceleration post-COVID. In 2022, emergency department presentations shifted to younger teenagers and from white young adults to Hispanic adolescents. The increased number of cases posed management problems in the ED given the lack of outpatient treatment options. CONCLUSION: Opioid-related ED presentations are increasing in adolescents with post-COVID increases in male, Hispanic, and younger patients in our region. Pathways for outpatient treatment need to be developed for adolescents with OUD.

Hyperammonemia in acetaminophen toxicity.

INTRODUCTION: Acetaminophen-induced hepatotoxicity can result in hyperammonemia, but it is not clear if elevated ammonia concentrations predict encephalopathy. METHODS: We retrospectively studied patients with acetaminophen toxicity at a liver transplant center over 8 years (January 1, 2010-December 31, 2017), who developed hepatotoxicity (AST and/or ALT >1000 IU/L) or hyperammonemia (ammonia > 40 µmol/L). We recorded baseline characteristics, laboratory data, documented grade of encephalopathy, and treatments administered. Sensitivity and specificity values were calculated for varying ammonia concentrations. RESULTS: A total of 102 patient encounters were included with 75 having ammonia concentrations. On presentation, 40% (30/75) of patients had concentrations greater than 100 µmol/L. However, an [ammonia] > 100 µmol/L was neither sensitive (46 % [95% CI: 26-67%]) nor specific (63% [48 - 76%]) for encephalopathy. Only an increasing ammonia concentration had a significant, but small (1.53 (95% CI: 1.06 - 2.20)) positive likelihood ratio for the development of hepatic encephalopathy. DISCUSSION: Animal models have suggested that in acetaminophen toxicity, encephalopathy may be secondary to an alternative mechanism other than hyperammonemia which may explain the lack of correlation between initial hyperammonemia and encephalopathy in this cohort. Additionally, a lack of empiric treatment for hyperammonemia did not appear to alter the course of any of the patients. None of these patients developed encephalopathy. CONCLUSION: In cases of acetaminophen-induced hepatotoxicity, ammonia concentrations do not correlate with encephalopathy and empiric treatment for hyperammonemia does not appear to be beneficial.

Single versus continued dosing of fomepizole during hemodialysis in ethylene glycol toxicity.

BACKGROUND: In cases of ethylene glycol (EG) toxicity requiring hemodialysis (HD), fomepizole is dosed every four hours. HD efficiently clears EG and its toxic metabolites, and it's unclear if multiple doses (MD) of fomepizole improve patient outcomes or whether a single dose (SD) prior to initiation of HD is sufficient. METHODS: We reviewed cases of EG toxicity at a toxicology referral center from 2008 to 2018. Patients treated with HD with EG levels greater than 20 mg/dL were included. Duration of dialysis, creatinine at discharge, hospital length of stay (LOS), and complications were analyzed. We compared patients who received a single dose of fomepizole prior to HD to those who received continued dosing during and after HD. RESULTS: Twenty-five patient encounters were identified (MD: 20; SD: 5). Initial bicarbonate (11 [SD] vs. 9 mg/dL [MD]) and pH (7.1 vs. 7.1) were similar between the groups; however, there was a trend toward a greater proportion of patients with renal dysfunction in the MD group: 11 (55%) vs. 1 (20%). HD was initiated a median interval of 5.2 h [SD] vs. 5.7 h [MD] after a dose of fomepizole. There was one death in the MD group and none in the SD group. Median creatinine on the day of discharge was 0.7 mg/dL (IQR: 0.57-3.8) in the SD group and 2.0 mg/dL (0.90-7.0) in the MD group. LOS was similar (5.8 days [95% CI 3.6-8.0] vs. 7.6 days [5.3-9.9]) (p = .61). CONCLUSION: Patients with moderately severe EG toxicity (acidosis and no initial renal dysfunction) treated with a single dose of fomepizole prior to HD had similar outcomes to those receiving continued dosing of fomepizole during or after HD. This raises the possibility that a single dose of fomepizole may be sufficient if HD is initiated quickly.

Serotonin toxicity from isolated bupropion overdoses.

Background: Bupropion is a synthetic cathinone, which acts therapeutically through norepinephrine and dopamine reuptake inhibition. Recent evidence suggests that serotonin receptor activation occurs with high doses of bupropion and severe serotonin toxicity can occur after isolated bupropion overdoses. Prior observational studies may therefore underestimate the incidence of serotonin toxicity.Methods: A retrospective study of patients with bupropion toxicity at a toxicology referral center from 2015-2017 was performed. Patients who overdosed on other serotonergic medications were excluded. Serotonin toxicity was diagnosed retrospectively using Hunter Criteria.Results: Overall, 96 patients were identified with bupropion toxicity. Of these, 18 patients ingested bupropion in the absence of other serotonergic drugs. The incidence of serotonin toxicity was 33% in this population. Serotonin toxicity was more likely after a suicide attempt than those with an accidental ingestion or after recreational drug use. The median dose of bupropion ingested was 2,250 mg in the cohort diagnosed with serotonin syndrome.Conclusion: The incidence of bupropion induced serotonin toxicity is higher than reported. Clinicians should monitor for serotonergic toxicity when evaluating patients after bupropion overdose.

Feasibility of Intermittent Hemodialysis in Metformin Toxicity With Shock.

BACKGROUND: Metformin toxicity can lead to profound shock and has a high mortality rate. Supportive care and enhanced elimination are the mainstays of therapy. Intermittent hemodialysis (HD) produces a higher clearance of metformin than continuous veno-venous hemofiltration or hemodiafiltration (CVVH/HDF). Nevertheless, CVVH/HDF has been proposed as an alternative in critically ill patients with the suggestion that hypotension may limit the use of HD. OBJECTIVE: This study sought to analyze the feasibility of performing hemodialysis in patients with persistent shock from metformin toxicity. METHODS: We performed a 6-year (2012-2017) retrospective chart review of patients with metformin toxicity managed at a large academic institution with a toxicology service. We included patients with persistent shock on vasopressor support who were treated with HD. Baseline characteristics, complications from treatment, timing of dialysis, and differences between mean arterial pressures before, during, and at the end of dialysis were recorded and analyzed. RESULTS: Despite critical mean peak lactate (23.9 mMol/L [range 17.6-27.9]), pH (6.91 [range 6.78-7.01]), and metformin levels (range 25-58 µg/mL], 6 of 7 patients recovered. All patients required prolonged HD (mean 19 h). Upon completion of HD, hemodynamics had improved (45 mm Hg [95% confidence interval 35-55 mm Hg] vs. 80 mm Hg [95% confidence interval 74-86 mm Hg]) and vasopressor support decreased. Mortality in this patient cohort was 14.3% (1/7). CONCLUSION: Intermittent HD is feasible in metformin toxicity despite persistent shock and high-dose vasopressor support. Mean arterial pressures improved during the course of HD and high blood flow rates were tolerated.

Intrathecal bupivacaine and morphine toxicity leading to transient hypotension and delayed status epilepticus.

BACKGROUND: Local anesthetic systemic toxicity characteristically occurs after inadvertent intravascular injection of local anesthetics; however, it is unclear if similar symptoms arise after intrathecal adminstration. Intrathecal use of local anesthetics for chronic pain is increasing and carries a potential risk of toxicity. Experience with the presenting symptoms and appropriate treatment for intrathecal local anesthetic toxicity is limited. CASE STUDY: A 74-year-old woman with an intrathecal bupivacaine/morphine pump developed lower extremity sensory neuropathy followed by obtundation, hypotension, and lower extremity flaccidity after an intrathecal pump refill. Her condition evolved to status epilepticus (SE) refractory to standard treatment. Intravenous fat emulsion (IFE) was administered, but was not immediately effective thus necessitating phenobarbital loading and propofol infusion. Despite significant bupivacaine neurotoxicity, no cardiotoxicity developed. DISCUSSION: The patient developed intrathecal local anesthetic and opioid toxicity after a malfunction of her intrathecal pump during a refill. We hypothesize that no cardiotoxicity developed secondary to sequestration of bupivacaine within the central nervous system. Likewise, poor CNS penetration of intravenous lipid emulsion may have negated or delayed any antidotal effect. CONCLUSION: We present a case of intrathecal toxicity leading to prolonged spinal anesthesia, progressive encephalopathy, and SE refractory to intravenous lipid emulsion. Management of SE with benzodiazepines and barbiturates may be more effective than lipids in cases of toxicity from intrathecal administration of bupivacaine.