Faculty Bibliography

INTRODUCTION/UNASSIGNED:Unfortunately, children are not spared from the devastating effects of the ongoing opioid epidemic. In rare cases, young children exposed to opioids present with unique neuroimaging findings affecting the white matter, reminiscent of what was once seen with diacetylmorphine (heroin)-associated leukoencephalopathy. This constellation of findings is termed the pediatric opioid use-associated neurotoxicity with cerebellar edema (POUNCE) syndrome. CASE SUMMARY/UNASSIGNED:A 31-month-old child was found floppy and unresponsive. Upon hospital arrival, there was right gaze deviation, shaking of the arms and legs, miosis, and bradypnea. Response to naloxone was incomplete, and methadone was confirmed in the child's urine. IMAGES/UNASSIGNED:Magnetic resonance imaging of the brain performed 24 h after admission showed abnormal T2/FLAIR hyperintensity with associated restricted diffusion symmetrically involving the cerebellar hemispheres. CONCLUSION/UNASSIGNED:The imaging findings, although far from pathognomonic, should be recognizable by radiologists and toxicologists when considering possible opioid exposure in a young child.

We report a case of Western Gaboon viper (Bitis rhinoceros) envenomation in which the patient's symptoms progressed despite treatment with North American crotalid antivenom but improved after receiving South African Institute for Medical Research (SAIMR) polyvalent antivenom. A 59-year-old man was hospitalized after reportedly being bitten by a Gaboon viper (Bitis gabonica). On arrival, he had normal vital signs, two puncture wounds on his left hand, and edema distal to the wrist. The hospital contacted the local poison center who conveyed that crotalid antivenom would be ineffective and recommended transfer to a snakebite center for species-appropriate antivenom. However, this recommendation was disregarded. Initial laboratory tests 2 hours after envenomation revealed a platelet count of 77 x 10⁹/L; other parameters were normal. He received six vials of crotalid antivenom (CroFab®) followed by three maintenance doses (total 12 vials). The next morning, swelling had progressed proximal to the elbow and platelets decreased to 37 x 10⁹/L. He was subsequently transferred and received SAIMR polyvalent antivenom. Six hours later, his platelets were 130 x 10⁹/L. The next morning, his swelling had significantly improved. He was discharged the following day. After discharge, it was discovered that the snake was a Bitis rhinoceros. Bitis gabonica and Bitis rhinoceros are popular captive snakes in the United States. Bitis rhinoceros was formerly a sub-species of B. gabonica, and they are often referred to interchangeably. Their venoms cause tissue edema, coagulopathy, and in severe cases, hemorrhage, dysrhythmias, and death. Antivenom is not widely available in the United States often necessitating patient transfer or antivenom delivery. This case addresses the question of whether crotalid antivenom, which is ubiquitous in the United States, can treat B. gabonica and B. rhinoceros envenomations and highlights the need for consultation with a poison center to facilitate administration of species-appropriate antivenom.

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.

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:Chronic nitrous oxide use can lead to neurological findings that are clinically and radiographically identical to those found in patients with pernicious anemia, specifically subacute combined degeneration of the spinal cord and peripheral neuropathy. CASE SUMMARY/UNASSIGNED:A 22-year-old man presented with lower extremity weakness and ataxia in the setting of inhaling 250 nitrous oxide cartridges two to three times weekly for two years. IMAGES/UNASSIGNED:Magnetic resonance imaging showed T2 hyperenhancement of the dorsal columns of the cervical spine from the first to the sixth vertebrae, which helped to establish a diagnosis of nitrous oxide-induced subacute combined degeneration of the spinal cord. CONCLUSIONS/UNASSIGNED:Chronic nitrous oxide use should be included in the differential diagnosis of any patient with otherwise unexplained neurological complaints that localize to the dorsal columns and has the changes on magnetic resonance imaging described here.

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.

INTRODUCTION/UNASSIGNED:Changes in the commercialization of nonprescription drugs have made large quantities of paracetamol available to individuals, resulting in larger overdoses than previously observed. Although most patients with paracetamol overdose can be managed with acetylcysteine, patients with a massive overdose may become critically ill earlier and fail standard antidotal therapy. Several strategies are proposed for the management of these patients, including using increased doses of acetylcysteine, extracorporeal removal, and fomepizole. However, the benefits of these strategies remain largely theoretical, with sparse evidence for efficacy in humans. METHODS/UNASSIGNED:This cross-sectional study surveys international practice patterns of medical toxicology providers regarding the management of a hypothetical patient with a massive paracetamol overdose. RESULTS/UNASSIGNED:A total of 342 responses from 31 different nations were obtained during the study period. Sixty-one percent of providers would have increased their acetylcysteine dosing when treating the hypothetical massive overdose. Thirty percent of respondents recommended an indefinite infusion of acetylcysteine at 12.5 mg/kg/hour after the bolus dose, whereas 20 percent recommended following the "Hendrickson" protocol, which advocates for a stepwise increase in acetylcysteine dosing to match high paracetamol concentrations at the 300 mg/L, 400 mg/L, and 600 mg/L lines on the Rumack-Matthew nomogram. Ten percent of respondents stated they would have given "double dose acetylcysteine" but did not specify what that entailed. Forty-seven percent of respondents indicated that they would have given fomepizole, and 28 percent of respondents recommended extracorporeal removal. DISCUSSION/UNASSIGNED:Our survey study assessed the approach to a hypothetical patient with a massive paracetamol overdose and demonstrated that, at minimum, most respondents would increase the dose of acetylcysteine. Additionally, almost half would also include fomepizole, and nearly one-third would include extracorporeal removal. CONCLUSIONS/UNASSIGNED:There is considerable international variation for the treatment of both non-massive and massive paracetamol overdoses. Future research is needed to identify and standardize the most effective treatment for both non-massive and massive paracetamol overdoses.