Carson R. Harris

Fatal Bupropion Overdose

BACKGROUND Bupropion is a unique monocyclic antidepressant that has been known to cause seizures in high therapeutic doses and in acute overdoses. Death due to ingestion, however, is a rare occurrence. CASE REPORT We report a case of a 26-year-old man who ingested 23 g bupropion, developed seizures and hypoxia, and presented in cardiac arrest. The patient was resuscitated in the emergency department, but died 4 d after supportive intensive care. CONCLUSIONS Bupropion overdose may lead to recurrent seizures, hypoxia and death. Aggressive management of severe bupropion overdose is recommended.

Intentional overdose with cardiac arrest treated with intravenous fat emulsion and high-dose insulin.

Introduction. Nebivolol, a beta blocker with 3–10 times more β1 cardioselectivity than metoprolol, has caused hypotension and bradycardia in overdose. We report a nebivolol-induced cardiac arrest in the setting of a polydrug ingestion, successfully resuscitated with intravenous fat emulsion (IFE) and high-dose insulin (HDI). Case report. A 48-year-old man was brought to the emergency department after ingesting nebivolol and ethanol, along with possibly diazepam and cocaine. He had a heart rate of 71/min and a blood pressure of 98/61 mmHg. The initial ECG showed sinus rhythm with a QTc of 483 ms and a QRS of 112 ms. Over the subsequent 4 h, he became bradycardic and hypotensive and developed bradyasystolic cardiac arrest. Standard resuscitation including epinephrine had no effect. Spontaneous circulation returned 30 s after a 100 mL bolus of 20% IFE, and the patient then became briefly hypertensive and tachycardic with heart rate and blood pressure measured as high as 123/min and 251/162 mmHg, respectively. His care included IFE infusion along with HDI bolus and infusion with doses as high as 21.8 units/kg/h. With subsequent hypotension, vasopressors were withheld in favor of HDI and supportive care. He was discharged with baseline neurologic function. Discussion. We hypothesize that after the administration of IFE the epinephrine was able to exert its effect on receptors previously occupied with the nebivolol. This would be congruent with the lipid sink theory of IFE mechanism. Conclusion. We report an overdose involving nebivolol in a polydrug ingestion resulting in cardiac arrest, successfully treated with IFE and a very HDI infusion.

Insulin versus vasopressin and epinephrine to treat β-blocker toxicity

Objective. We compared insulin and glucose (IN/G) to vasopressin plus epinephrine (V/E) in a pig model of β-blocker toxicity. Primary outcome was survival over four hours. Methods. Ten pigs received a 0.5 mg/kg bolus of propranolol IV followed by a continuous infusion. At the point of toxicity 20 ml/kg normal saline was rapidly infused and the propranolol drip continued at 0.125 mg/kg/min over four hours of resuscitation. Each pig was randomized to either IN/G or V/E. The V/E group began with epinephrine at 10 mcg/kg/min titrated up by 10 mcg/kg/min every 10 min to 50 mcg/kg/min or until baseline was obtained. Simultaneously, these pigs received vasopressin at 0.0028 units/kg/min, titrated upwards every 10 min to 0.014 units/kg/min or until baseline was obtained. The IN/G group began with a 2 units/kg/hr drip and increased by 2 units every 10 minutes to 10 units/kg/hr, or until baseline hemodynamics were obtained. CO, SVR, systolic blood pressure, HR, MAP, glucose, and potassium were monitored. Glucose was given for values <60 mg/dl. Results. The study was terminated early due to marked survival differences after five pigs were entered in each group. All IN/G group pigs survived four hours. All V/E group pigs died within 90 min. CO in the IN/G group increased throughout the four hours, rising above pre-propranolol levels, while MAP, SBP, and SVR all trended slightly downward. CO in the V/E group dropped until death, while MAP, SBP, and SVR rose precipitously until 30–60 minutes when these dropped abruptly until death. Glucose was required in the IN/G group. Conclusion. In this swine model, IN/G is superior to V/E to treat β-blocker toxicity. IN/G has marked inotropic properties while the vasopressor effects of V/E depress CO and contribute to death. Increasing SVR in this condition is detrimental to survival.

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 β-blocker in five, calcium channel blocker in two, combined β-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.

Cardiotoxicity and late onset seizures with citalopram overdose

A 31-year-old man ingested 400 mg of citalopram (Celexa) after an argument with his parents and girlfriend 13 h before presentation. Paramedics witnessed the patient having a generalized clonic seizure. The electrocardiogram (EKG) revealed a wide QRS complex, prolongation of the QTc interval, and left bundle branch pattern. He was treated with sodium bicarbonate with resolution of these changes. The patient was continued on a sodium bicarbonate infusion and demonstrated no further EKG abnormalities. Sodium bicarbonate should be considered as a treatment modality in patients with EKG abnormalities of prolongation of QRS or QTc interval after citalopram overdose.

Methanol ingestion: prevention of toxic sequelae after massive ingestion.

Methanol ingestion, a rare but potentially fatal poisoning, is often difficult to diagnose in the emergency department (ED) and historically has been difficult to treat. In this article, we report a methanol ingestion with a blood concentration of 692 mg/dL, which was treated with 4-methylpyrazole (Fomepizole) and dialysis, without sequelae. To our knowledge, such a massive ingestion has never been treated with this modality without development of long-term disability. Another unusual feature of this case is the significantly elevated serum osmolal gap at presentation without elevation in anion gap, demonstrating the effects of co-ingestion of ethanol. Additionally, there was a marked disparity between the patients breath alcohol analyzer level and the blood ethanol concentration, illustrating the inability of the breath alcohol analyzer to differentiate between volatile alcohols. Treatment of the methanol-poisoned patient with Fomepizole is discussed.

A Comparison of Vasopressin and Glucagon in Beta-Blocker Induced Toxicity

Objective. We compared the efficacy of vasopressin and glucagon in a porcine model of β-blocker toxicity. Our primary outcome was survival over 4 hours. Methods. Sixteen pigs received a 1-mg/kg bolus of propranolol IV followed by continuous infusion at 0.25 mg/kg/minute. Toxicity was defined as a 25% decrease in the product of heart rate (HR) and mean arterial pressure (MAP), at which point 20 mL/kg normal saline was rapidly infused. Each pig was randomly assigned to receive either vasopressin or glucagon after the saline bolus. The vasopressin group received a continuous infusion at 0.0028 U/kg/minute, titrated up to a maximum of 0.014 U/kg/minute. The glucagon group received a 0.05-mg/kg bolus followed by continuous infusion at 0.15 mg/kg/hour. The HR, MAP, systolic BP (SBP), cardiac output (CO), glucose, and pH were monitored for 4 hours from toxicity or until death. Results. One pig survived at 4 hours (vasopressin group). Analysis of the 4-hour Kaplan-Meier survival curves found no differences between the groups (log-rank test 0.059, p = 0.81). No overall differences were identified in MAP, systolic BP, cardiac output, glucose, pH, or HR. However, over the first hour MAP and SBP were significantly higher in the vasopressin group (p = 0.004, p = 0.006, respectively). Conclusion. In this β-blocker toxicity model, there were no differences in the survival curves between vasopressin- and glucagon-treated pigs during a 4-hour analysis period. No overall differences were noted in MAP, systolic BP, CO, HR, pH, or glucose levels, although vasopressin treatment yielded higher MAP and systolic BP early in resuscitation.

Repeated ingestion of 2-butoxyethanol: case report and literature review

Background: Ethylene glycol monobutyl ether (2-butoxyethanol) is not commonly associated with significant human poisoning. Exposures are usually through occupational contact and typically involve inhalation injury. Animal studies report severe hemolysis occurring in rats and mice. Rare published human cases give varied descriptions of the clinical course associated with 2-butoxyethanol poisoning including reports of metabolic acidosis, ethylene glycol production, oxaluria, renal failure, and anemia. We report a case of two separate ingestions (80 to 100 grams) of a glass cleaner concentrate containing 22% 2-butoxyethanol, and its primary metabolite butoxyacetic acid. Case Report: An 18-year-old male ingested 360–480 mL of 22% 2-butoxyethanol on two separate occasions. Approximately 10 hours after the first ingestion, the patient developed severe CNS depression, metabolic acidosis, hematuria, and mild elevation of hepatic enzymes. He was treated initially with ethanol therapy but continued to deteriorate and was started on hemodialysis. Approximately 10 days after discharge, the patient ingested 480 mL of the same product and received ethanol and hemodialysis within four hours of ingestion. During his second admission the patient did not develop the delayed severe CNS depression or profound metabolic acidosis. Clinically significant hemolytic anemia, oxaluria, ethylene glycol production, and renal failure were not noted in either episode. The patient recovered on both occasions without sequelae. Conclusion: Hemodialysis may be an effective treatment intervention for managing severe acute 2-butoxyethanol intoxication; however, further investigation is warranted.

Reversal of quetiapine-induced altered mental status with physostigmine: a case series☆

Quetiapine overdose is a clinical entity commonly encountered in emergency departments. Quetiapine is a drug with many mechanisms, including antimuscarinic effects. Traditionally, treatment of quetiapine toxicity has been primarily supportive care. Case reports exist documenting improvement in mental status in these patients after administration of physostigmine, a carbamate capable of reversing antimuscarinic toxicity. In this descriptive case series, 3 patients with quetiapine toxicity treated with physostigmine are reported. In each case, the patient had significant altered mental status that was rapidly reversed with administration of physostigmine. In all 3 cases, patient disposition was changed to a lower level of care, requiring less invasive monitoring. In 1 case, intubation was prevented. Because quetiapine toxicity is commonly encountered and the use of physostigmine in this setting is a potentially practice-altering treatment, emergency physicians should be aware of this phenomenon.

Gastrointestinal decontamination. Which method is best

Why has ipecac syrup become less popular in emergency management of poisoning and overdose? When should gastric lavage, activated charcoal, cathartics, or a combination of methods be used? Which patients are candidates for whole-bowel irrigation with polyethylene glycol-electrolyte solution? Drs Harris and Kingston answer these questions and present their recommendations for each of the available management options.