QT prolongation, torsades des pointes, and cardiac arrest after 4 mg of IV ondansetron.

Ondansetron is a commonly used antiemetic in the emergency department despite a 2011 FDA warning regarding dose-related QTc prolongation and torsades des pointes (TdP). Cases of TdP from small ondansetron doses administered in the emergency department are lacking. A 41-year-old-woman with alcohol use disorder on no medications or supplements presented to an emergency department with one day of nausea, vomiting, and epigastric pain. Examination revealed a pulse of 77 beats/min and epigastric tenderness. The patient received 4 mg IV ondansetron, 30 mg IV ketorolac, and was placed on cardiac monitoring. ECG obtained one minute after ondansetron demonstrated premature ventricular contractions with QTc = 653 ms. Thirteen minutes after receiving ondansetron she suffered TdP and cardiac arrest. She received immediate CPR and IV epinephrine with successful defibrillation at one minute. She then received IV magnesium. Post-arrest ECGs demonstrated persistent QTc prolongation immediately and at three hours post-arrest. Laboratory studies, drawn prior to arrest, demonstrated hypokalemia (3.2 mEq/L), hypomagnesemia (1.3 mg/dL), and elevated lipase (4918 IU/L). She received no additional QT-prolonging agents. Transthoracic echocardiogram and troponins were normal; ECG intervals completely normalized within 12 h and she was discharged neurologically intact. The patient returned 18 months later with recurrent pancreatitis and similar electrolyte abnormalities; QT-prolonging drugs were avoided at that time and her course was uncomplicated. QT prolongation with subsequent torsades des pointes and cardiac arrest may occur in high-risk patients receiving small doses of ondansetron. Further studies are warranted to determine the safest antiemetic for use in the emergency department.

Vasodilation in patients with calcium channel blocker poisoning treated with high-dose insulin: a comparison of amlodipine versus non-dihydropyridines.

Background: High dose insulin (HDI), an inotrope and vasodilator, is a standard therapy for calcium channel blocker (CCB) poisoning. HDI causes vasodilation by stimulating endothelial nitric oxide synthase (eNOS). Most literature supporting HDI for CCB poisoning involves verapamil toxicity; however, amlodipine now causes more CCB poisonings. Unlike other CCBs, amlodipine stimulates eNOS and may cause synergistic vasodilation with HDI. The purpose of this study was to determine if amlodipine-poisoned patients treated with HDI had more evidence of vasodilation than similarly treated patients with non-dihydropyridine (non-DHP) poisoning.Methods: This was a retrospective study from a single poison center. Cases were identified via the generic code "Calcium Antagonists" in which the therapy "High Dose Insulin/Glucose" was "performed, whether or not recommended" from 2019-2021. Evidence of vasodilation was assessed via maximum number of vasopressor infusions per case, vasopressor doses, and use of rescue methylene blue to treat refractory vasoplegia.Results: Thirty-three patients were enrolled: 18 poisoned with amlodipine, 15 with non-DHPs (verapamil n = 10, diltiazem n = 5). The median number of maximum concomitant vasopressors in the amlodipine group was 3 (IQR: 2-5; range 0-6) and 2 in the non-DHP group (IQR: 1-3; range 0-5; p = 0.04); median difference in maximum concomitant vasopressors between groups was 1 (95% confidence interval: 0-2). Median maximum epinephrine dosing was higher in the amlodipine group (0.31 mcg/kg/min) compared to non-DHPs (0.09 mcg/kg/min; p = 0.03). Use of rescue methylene blue was more common in the amlodipine group (7/18 [39%]) than in the non-DHP group (0; p = 0.009).Conclusions: Amlodipine poisoned patients treated with HDI required more vasopressors, higher doses of epinephrine, and more often received rescue methylene blue than similarly treated patients with verapamil or diltiazem poisoning. These differences suggest amlodipine-poisoned patients had more evidence of vasodilation. Further study is warranted to determine if synergistic vasodilation occurs when HDI is used to treat amlodipine poisoning.

Cardiotoxic Medication Poisoning.

Beta-blockers and calcium channel blockers result in a disproportionate number of fatalities from cardiac medication overdoses, and share similar characteristics. High-dose insulin is a superior therapy for both overdoses, but is likely synergistic with vasopressors; therefore we recommend starting vasopressors and high-dose insulin simultaneously. Digoxin remains an important cardiac poison and can likely be safely treated with smaller doses of fab fragments than in the past, except for patients in extremis. Extracorporeal membrane oxygenation is an invasive but promising nonspecific therapy for refractory shock from cardiotoxic overdose and should be considered primarily in cases of refractory cardiogenic shock.

Fatal Yellow Oleander Poisoning Masquerading as Benign Candlenut Ingestion Taken for Weight Loss.

BACKGROUND: Candlenuts (Aleurites moluccana) and yellow oleander seeds (Thevetia peruviana) bear a physical resemblance to one another. Candlenuts are benign and marketed as weight loss supplements. Yellow oleander seeds, however, contain toxic cardioactive steroids; as few as 2 seeds may cause fatal poisoning. Because of their physical similarities, the potential for a lethal substitution exists. CASE REPORT: A 63-year-old woman presented to the emergency department with vomiting after ingesting 5 of what she believed to be candlenuts that were ordered online under the colloquial name "Nuez de la India" for the purpose of weight loss. She was bradycardic (nadir pulse of 30 beats/min) and hyperkalemic (serum potassium 7.3 mEq/L). Within hours of presentation she suffered a ventricular fibrillation arrest, followed by a terminal asystolic arrest. Postmortem analyses of liver tissue and the seeds were consistent with fatal T. peruviana poisoning. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: T. peruviana seeds contain toxic cardioactive steroids; their physical resemblance to candlenuts poses a risk of potentially fatal substitution. Therapy with high-dose digoxin specific immune fragments (20-30 vials) may be helpful.

Persistent Hyperinsulinemia Following High-Dose Insulin Therapy: A Case Report.

INTRODUCTION: Overdoses of beta-adrenergic antagonists and calcium channel antagonists represent an uncommonly encountered but highly morbid clinical presentation. Potential therapies include fluids, calcium salts, vasopressors, intravenous lipid emulsion, methylene blue, and high-dose insulin. Although high-dose insulin is commonly used, the kinetics of insulin under these conditions are unknown. CASE REPORT: We present a case of a 51-year-old male who sustained a life-threatening overdose after ingesting approximately 40 tablets of a mixture of amlodipine 5 mg and metoprolol tartrate 25 mg. Due to severe bradycardia and hypotension, he was started on high-dose insulin (HDI) therapy; this was augmented with epinephrine. Despite the degree of his initial shock state, he ultimately recovered, and HDI was discontinued. Insulin was infused for a total of approximately 37 hours, most of which was dosed at 10 U/kg/hour; following discontinuation, serial serum insulin levels were drawn and remained at supraphysiologic levels for at least 24 hours and well above reference range for multiple days thereafter. CONCLUSION: The kinetics of insulin following discontinuation of high-dose insulin therapy are largely unknown, but supraphysiologic insulin levels persist for some time following therapy; this may allow for simple discontinuation rather than titration of insulin at the end of therapy. Dextrose replacement is frequently needed; although the duration is often difficult to predict, prolonged infusions may not be necessary.

Use of hyperbaric oxygen therapy in quinine-associated visual disturbances.

INTRODUCTION: Hyperbaric oxygen (HBO2 ) therapy is infrequently reported as a treatment for poison-induced retinal damage. We describe a case in which HBO2 therapy was used to treat suspected retinal toxicity induced by quinine. CASE REPORT: We present a case in which HBO2 was used to treat visual disturbances thought to be caused by quinine-induced retinal damage. The patient intentionally ingested undisclosed amounts of citalopram and quinine. Following a complicated hospital course, including profound shock requiring treatment with four vasopressors and a peripheral left-ventricular assist device, the patient, once extubated, reported visual abnormalities consistent with those described from quinine-induced retinal toxicity. Visual disturbances seemed to show improvement following HBO2 treatment. Several months following hospitalization visual defects continued to be present on examination. However, with corrective lenses the patient's visual acuity was normal. No adverse events were attributed to the use of HBO2. DISCUSSION: HBO2 for treatment of quinine-induced retinal damage is infrequently reported or studied. In the reported case, use of HBO2 appeared to be associated with substantial improvement in visual disturbances occurring in the setting of an overdose of quinine. The patient's improvement is remarkable, given her retinas were also jeopardized by her profound shock. Additional data are needed to understand the risks and benefits of this procedure, but due to limited treatment options for poison-induced retinal toxicity and the low likelihood for implementation of a controlled randomized trial of HBO2 in this population, the procedure may be considered in quinine-induced retinal toxicity.

High dose insulin for beta-blocker and calcium channel-blocker poisoning.

BACKGROUND/OBJECTIVES: High dose insulin (HDI) is a standard therapy for beta-blocker (BB) and calcium channel-blocker (CCB) poisoning, however human case experience is rare. Our poison center routinely recommends HDI for shock from BBs or CCBs started at 1U/kg/h and titrated to 10U/kg/h. The study objective was to describe clinical characteristics and adverse events associated with HDI. METHODS: This was a structured chart review of patients receiving HDI for BB or CCB poisoning with HDI defined as insulin infusion of ≥0.5U/kg/h. RESULTS: In total 199 patients met final inclusion criteria. Median age was 48years (range 14-89); 50% were male. Eighty-eight patients (44%) were poisoned by BBs, 66 (33%) by CCBs, and 45 (23%) by both. Median nadir pulse was 54 beats/min (range 12-121); median nadir systolic blood pressure was 70mmHg (range, 30-167). Forty-one patients (21%) experienced cardiac arrest; 31 (16%) died. Median insulin bolus was 1U/kg (range, 0.5-10). Median starting insulin infusion was 1U/kg/h (range 0.22-10); median peak infusion was 8U/kg/h (range 0.5-18). Hypokalemia occurred in 29% of patients. Hypoglycemia occurred in 31% of patients; 50% (29/50) experienced hypoglycemia when dextrose infusion concentration ≤10%, and 30% (31/105) experienced hypoglycemia when dextrose infusion concentration ≥20%. CONCLUSIONS: HDI, initiated by emergency physicians in consultation with a poison center, was feasible and safe in this large series. Metabolic abnormalities were common, highlighting the need for close monitoring. Hypoglycemia was more common when less concentrated dextrose maintenance infusions were utilized.

Hyperbaric oxygen therapy for the prevention of arterial gas embolism in food grade hydrogen peroxide ingestion.

Food grade hydrogen peroxide ingestion is a relatively rare presentation to the emergency department. There are no defined guidelines at this time regarding the treatment of such exposures, and providers may not be familiar with the potential complications associated with high concentration hydrogen peroxide ingestions. In this case series, we describe four patients who consumed 35% hydrogen peroxide, presented to the emergency department, and were treated with hyperbaric oxygen therapy. Two of the four patients were critically ill requiring intubation. All four patients had evidence on CT or ultrasound of venous gas emboli and intubated patients were treated as if they had an arterial gas embolism since an exam could not be followed. After hyperbaric oxygen therapy each patient was discharged from the hospital neurologically intact with no other associated organ injuries related to vascular gas emboli. Hyperbaric oxygen therapy is an effective treatment for patients with vascular gas emboli after high concentration hydrogen peroxide ingestion. It is the treatment of choice for any impending, suspected, or diagnosed arterial gas embolism. Further research is needed to determine which patients with portal venous gas emboli should be treated with hyperbaric oxygen therapy.

Asystole immediately following intravenous fat emulsion for overdose.

Use of intravenous fat emulsion (IFE) for the treatment of poisoned patients in extremis is increasing. Little literature exists describing failures and complications of IFE. We describe two cardiac arrests temporally associated with IFE. A 50-year-old woman presented after ingesting 80 total tablets of metoprolol 25 mg and bupropion 150 mg. Bradycardia and hypotension were refractory to calcium salts, catecholamines, and high dose insulin (HDI). With a pulse of 40/min and mean arterial pressure (MAP) of 30 mmHg, 100 mL of 20 % IFE was given; within 30 s, brady-asystolic arrest occurred. Pulses returned after 3 min of CPR. The patient died on hospital day 4 of multisystem organ failure (MSOF). A 53-year-old man presented after ingesting of 3,600 mg of diltiazem and 1,200 mg of propranolol. Bradycardia and hypotension were refractory to calcium salts, catecholamines, HDI, bicarbonate, and atropine. With a pulse of 30/min and a MAP of 40 mmHg, 150 mL of 20 % IFE was given; within 1 min, a brady-asystolic arrest occurred. Pulses returned after 6 min of CPR. The patient died on hospital day 7 of MSOF. Reported cases of IFE failures or potential complications are sparse. This report adds only case experience, not clarity. We report two cardiac arrests that were temporally associated with IFE.

High-dose insulin: a consecutive case series in toxin-induced cardiogenic shock.

CONTEXT: Cardiovascular medication overdoses can be difficult to treat. Various treatment modalities are currently recommended. OBJECTIVE: To describe patient outcomes and adverse events of high-dose insulin therapy in consecutive overdose patients in cardiogenic shock after implementation of a high-dose insulin protocol (1-10 U/kg/h, while avoiding or tapering off vasopressors). METHODS: This is an observational consecutive case series of patients identified from a registry. Data were collected by retrospective chart review of patients treated by our toxicology service with this protocol from February 2007 until March 2010. RESULTS: Twelve patients were treated with high-dose insulin. The mean age was 36.5 years (SD 11.7). Seven patients had pre-existing vasopressor therapy, and all were tapered off vasopressors while on insulin. Two patients experienced pulseless electrical activity cardiac arrest prior to high-dose insulin therapy. Intravenous fat emulsion was given to two patients. The mean maximum insulin infusion rate was 8.35 U/kg/h (mean = 8.35, SD 6.34). The mean duration of insulin infusion was 23.5 h (SD 19.7). The mean duration of glucose infusion post-insulin was 25.2 h (SD 17.7). The primary toxins were ß-blocker in five, calcium channel blocker in two, combined ß-blocker/calcium channel blocker in two, tricyclic antidepressant in one, and polydrug in 2. CLINICAL OUTCOMES: Eleven of 12 patients survived. One patient expired 9 h into insulin therapy from cardiac arrest shortly after the insulin was stopped and a vasopressor re-initiated (protocol deviation). ADVERSE EVENTS: Six patients experienced a total of 19 hypoglycemic events. Hypokalemia (defined as < 3.0 mEq/L) developed in eight patients. ADVERSE SEQUELAE: Necrotic digits occurred in one patient with known clotting disorder after receiving high-dose norepinephrine and INR reversal with fresh frozen plasma prior to insulin therapy. One patient was discharged with mild anoxic injury thought due to pulseless electrical activity arrest prior to insulin therapy. Three of these 12 patients have been previously described in published case reports. CONCLUSION: High-dose insulin therapy based on a 1-10 U/kg/h dosing guideline and recommending avoidance of vasopressors appears to be effective in the treatment of toxin-induced cardiogenic shock. Hypoglycemia was the most frequent adverse event, followed by hypokalemia. Adverse events did not lead to adverse sequelae.

Addition of phenylephrine to high-dose insulin in dihydropyridine overdose does not improve outcome.

INTRODUCTION: Vasopressors are commonly used for calcium channel blocker (CCB)-induced cardiogenic shock after calcium and high-dose insulin (HDI). Vasopressor therapy is frequently used in combination with HDI to increase blood pressure and improve outcome. However, no studies have compared the efficacy of HDI to the combination of a vasopressor and HDI in dihydropyridine overdose. We conducted a study to compare the efficacy of HDI to phenylephrine (PE) plus HDI in a porcine model of dihydropyridine toxicity. METHODS: Cardiogenic shock was induced by administering a nifedipine (NP) infusion of 0.0125 mcg/kg/min until a point of toxicity, defined as a 25% decrease in the baseline product of mean arterial pressure (MAP) × cardiac output (CO). Each arm was resuscitated with 20 mL/kg of saline (NS). The nifedipine infusion continued throughout a 4-h resuscitation protocol. The HDI group was titrated up to 10 units/kg/h of insulin and the HDI/PE group was titrated up to a dose of HDI 10 units/kg/h plus PE 3.6 mcg/kg/min. RESULTS: No baseline differences were found among groups including time to toxicity. Survival was not different between the HDI and HDI/PE arms. When comparing the HDI to the HDI/PE arm no differences were found for cardiac index (CI) (p = 0.06), systemic vascular resistance (p = 0.34), heart rate (HR) (p = 0.95), mean arterial pressure (p = 0.99), pulmonary vascular resistance (PVR) (p = 0.07), or base excess (p = 0.36). CONCLUSION: In this model of nifedipine-induced cardiogenic shock, the addition of PE to HDI therapy did not improve mortality, cardiac output, blood pressure, systemic vascular resistance (SVR), or base excess.