Christine M. Stork

Propoxyphene-Induced Wide QRS Complex Dysrhythmia Responsive to Sodium Bicarbonate – A Case Report

Propoxyphene overdose is known to cause widening of the QRS complex on ECG. We report a case of a 54-year-old female who ingested approximately 100 propoxyphene hydrochloride tablets in a suicide attempt. She developed a wide complex dysrhythmia which responded to sodium bicarbonate therapy. Propoxyphene-induced wide complex dysrhythmia responsive to sodium bicarbonate therapy has not been previously reported in the literature.

Aldicarb Poisoning by an Illicit Rodenticide Imported into the United States: Tres Pasitos

Objective: Although intentional and unintentional rodenticide poisoning is common, most readily available agents are of relatively low acute toxicity. A four-year long epidemic of severe toxicity from rodenticide exposure continues among patients predominantly of Dominican descent living in New York City. This study characterizes the ongoing epidemic of acute cholinesterase inhibitor poisoning due to an illicit rodenticide and identifies its etiology. Methods: A prospectively collected case series of poisoned patients referred to the New York City Poison Control Center. The main outcome measures include the clinical characteristics upon presentation, antidotal and other therapeutic requirements, and patient outcome. Product analysis was performed with paper chromatography, gas chromatography/mass spectrometry, and high-performance liquid chromatography. A murine model assessing both clinical effect and cholinesterase activity was also performed. Results: Thirty-five patients were referred following exposure to Tres Pasitos. Patients developed signs of cholinergic hyperactivity and many required high doses of atropine (>10 mg) to control these symptoms. The source was identified as a rodenticidal compound sold illicitly in local groceries primarily within the Dominican community. Murine cholinesterase activity fell significantly following exposure to the rodenticide. High-performance liquid chromatography identified aldicarb, an extremely potent carbamate-type cholinesterase inhibitor, not licensed for rodenticidal use in this country. Conclusion: Illicit sale of undocumented compounds poses a substantial public health threat. Despite several public health interventions, the epidemic continues.

The use of vasopressin in the setting of recalcitrant hypotension due to calcium channel blocker overdose

Treatment of hypotension caused by calcium channel blocker overdose (CCB) remains a challenge. We describe the successful use of vasopressin in two patients with massive CCB overdoses in whom hypotension was unresponsive to calcium, glucagon, insulin, and conventional vasopressor therapies. While various modes of treatments have been used to treat the hypotension of CCB overdose, this is the first report to our knowledge of the successful use of vasopressin in this clinical setting.

Sustained-Release Potassium Chloride Overdose

Background: Although ingestion of sustained-release potassium supplements can cause life-threatening hyperkalemia in patients with abnormal renal function, only a few previous reports suggest that this may occur in patients with normal renal function. We report 2 cases of hyperkalemia in patients with normal renal function who developed hyperkalemia after ingesting sustained-release potassium preparations and describe the use of radiography and whole-bowel irrigation in their care. Case Reports: The first patient is a 50-year-old woman who ingested 100 K-Dur® tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 1 hour prior to presenting to the emergency department. She developed a peak serum potassium level of 9.7 mEq/L and had transient, potentially life-threatening electrocardiographic changes. The second patient was a 17-year-old man who ingested 20 to 30 Klor-Con® tablets (each tablet containing 750 mg KCl or 10 mEq potassium) in a suicide attempt 10 hours prior to presentation. Although he developed a peak serum potassium level of 6.1 mEq/L, he had a persistently normal electrocardiogram. In both patients, the tablets were visualized on abdominal radiographs and the gastrointestinal tracts of both were successfully decontaminated using whole-bowel irrigation. Discussion: Although the sensitivity and specificity are unknown, the abdominal radiograph appears to be useful in detecting sustained-release potassium tablets. Whole-bowel irrigation as a primary method of gastrointestinal decontamination also appears to be effective although its use is not previously reported for sustained-release potassium overdoses.

Evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning*

Abstract Background: Although intravenous lipid emulsion (ILE) was first used to treat life-threatening local anesthetic (LA) toxicity, its use has expanded to include both non-local anesthetic (non-LA) poisoning and less severe manifestations of toxicity. A collaborative workgroup appraised the literature and provides evidence-based recommendations for the use of ILE in poisoning. Methods: Following a systematic review of the literature, data were summarized in four publications: LA and non-LA poisoning efficacy, adverse effects, and analytical interferences. Twenty-two toxins or toxin categories and three clinical situations were selected for voting. Voting statements were proposed using a predetermined format. A two-round modified Delphi method was used to reach consensus on the voting statements. Disagreement was quantified using RAND/UCLA Appropriateness Method. Results: For the management of cardiac arrest, we recommend using ILE with bupivacaine toxicity, while our recommendations are neutral regarding its use for all other toxins. For the management of life-threatening toxicity, (1) as first line therapy, we suggest not to use ILE with toxicity from amitriptyline, non-lipid soluble beta receptor antagonists, bupropion, calcium channel blockers, cocaine, diphenhydramine, lamotrigine, malathion but are neutral for other toxins, (2) as part of treatment modalities, we suggest using ILE in bupivacaine toxicity if other therapies fail, but are neutral for other toxins, (3) if other therapies fail, we recommend ILE for bupivacaine toxicity and we suggest using ILE for toxicity due to other LAs, amitriptyline, and bupropion, but our recommendations are neutral for all other toxins. In the treatment of non-life-threatening toxicity, recommendations are variable according to the balance of expected risks and benefits for each toxin. For LA-toxicity we suggest the use of Intralipid® 20% as it is the formulation the most often reported. There is no evidence to support a recommendation for the best formulation of ILE for non-LAs. The voting panel is neutral regarding ILE dosing and infusion duration due to insufficient data for non-LAs. All recommendations were based on very low quality of evidence. Conclusion: Clinical recommendations regarding the use of ILE in poisoning were only possible in a small number of scenarios and were based mainly on very low quality of evidence, balance of expected risks and benefits, adverse effects, laboratory interferences as well as related costs and resources. The workgroup emphasizes that dose-finding and controlled studies reflecting human poisoning scenarios are required to advance knowledge of limitations, indications, adverse effects, effectiveness, and best regimen for ILE treatment.

Pharmacokinetics of Extended Relief vs Regular Release Tylenol in Simulated Human Overdose

BACKGROUND The purpose of this trial was to compare the pharmacokinetics of the two available acetaminophen dosage forms in simulated human overdose. METHODS Ten healthy volunteers received acetaminophen, 75 mg/kg orally, either as the regular release or extended relief formulation in a random, crossover fashion. Blood samples were analyzed using a TDx assay and a best fit correlation of data points was determined by PCNONLIN. RESULTS The area under the curves for extended relief acetaminophen and regular release acetaminophen were 426 mg h/L and 432 mg h/L, respectively (p = 0.768). The mean half times for extended relief acetaminophen and regular release acetaminophen were 4.02 h and 2.56 h, respectively (p < 0.001). The mean maximum serum acetaminophen concentrations were 62.6 mg/L (414.4 mmol/L:) and 94.3 mg/L (624.3 mmol/L) for extended relief acetaminophen and regular release acetaminophen, respectively (p < 0.001) and the mean time to maximum serum acetaminophen concentrations were 0.87 h and 0.75 h for extended relief acetaminophen and regular release acetaminophen, respectively (p = 0.508). CONCLUSIONS Although the formulations appear to have equal bioavailability, their half-lives and peak concentrations were significantly different. Further study is required to determine whether these differences affect the assessment and management of poisoned patients.

Oral administration of fomepizole produces similar blood levels as identical intravenous dose.

Introduction. Fomepizole is available intravenously (IV) for the treatment of methanol and ethylene glycol poisoning. Few studies demonstrate that fomepizole achieves effective serum concentrations after IV or oral (PO) use. The objective was to describe the comparative pharmacokinetics of fomepizole after a single PO and IV dose. Methods. This was a prospective, randomized, crossover trial in 10 healthy volunteers. Each received 15 mg/kg fomepizole, PO and by 30 minute IV infusion. Serum was collected at 0, 0.25, 0.5, 1, 2, 4, 7, 12, 24, 36, and 48 hours (h) and stored at −70°C. Candidate models were fit to the IV and PO data, simultaneously, using iterative 2-stage analysis weighted by the estimated inverse observation variance. Time above the MEC (T>MEC) was determined by numeric integration of the fitted functions using 10 μmoles/L as the minimum effective concentration (MEC). Results. Seven females and 3 males were enrolled. Sole complaints included headache and dizziness in 3 subjects and 10/10 reported an unpleasant taste. The final PK model was 2-compartment with 0-order IV and 1st-order PO input (following a fitted TLag) and Michaelis-Menten elimination. PO fomepizole was rapidly absorbed with a bioavailability of ∼100%. The Km was 0.935 ± 0.98 μmoles/L and the Vmax was 18.57 ± 9.58 μmoles/L/h. T>MEC was 32 h with agreement between PO and IV dosing. Conclusions. This is the first study that effectively determines a human Vmax and Km for PO and IV fomepizole. PO and IV administration of fomepizole result in similar pharmacokinetic parameters.

A Rare Ingestion of the Black Locust Tree

Background: The Black Locust (Robinia Pseudoacacia) tree contain toxalbumins, robin and phasin, that exert their toxic effects by inhibition of protein synthesis. Despite the potential dangers of Black Locust intoxication, reports of human toxicity after ingestion are rare. We report the first human intoxication of Black Locust bark in North America in over one hundred years. Case Report: An eight‐year‐old male was brought to the emergency department 6 hours after chewing and expelling the Black Locust bark. He presented with emesis, which began approximately 2.5 hours after exposure. His vital signs were as follows: oral temperature, 97.5° F; blood pressure, 128/75 mmHg; heart rate, 114 beats per minute; respiratory rate, 15 breaths per minute. Initial treatment included 4 mg IV ondansetron, which resolved the vomiting, one dose of activated charcoal, and intravenous fluids. He was then admitted to the intensive care unit (ICU) for observation of signs of toxicity. Laboratory findings were unremarkable except for a white blood cell of 18.4 K/uL and an elevated alkaline phosphatase of 183 U/L. The patient remained asymptomatic throughout his stay in the ICU and was discharged on the fifth day of admission with a normal white blood cell of 4.1 K/uL and an alkaline phosphatase of 251 U/L. Conclusion: Patients with clinical toxicity following the ingestion of Black Locust are expected to do well with supportive care and observation.

Hospital Pharmacology: An Alternative Model for Practice and Training in Clinical Pharmacology

External pressures continue to be exerted on hospitals to prioritize programs that minimize costs and improve the safety of medication use. Clinical pharmacologists are in an ideal position to provide leadership for such programs. At academic health centers, an added dimension is the exposure of physicians‐in‐training to the practical application of clinical pharmacology principles. At SUNY Upstate Medical University, the approach is led by a physician with clinical pharmacists and pharmacy practice residents. To align the clinical pharmacists with the overall goals of the program, a faculty promotions track system designed specifically for them has been enacted within the college of medicine. This report summarizes the “hospital pharmacology” program that provides funding for an academic physician‐clinical pharmacologist. With this report, the authors hope to outline an alternative practice and training paradigm to potentially address the decline in physicians being trained in and practicing clinical pharmacology since the late 1970s.

Penile angioedema associated with the use of angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers

PURPOSE Two cases of penile angioedema associated with the use of angiotensin-converting-enzyme inhibitors and angio-tensin II receptor blockers are reported. SUMMARY The first case of penile angioe-dema involved a 68-year-old man who arrived at the emergency department (ED) with a 2-12-hour history of penile swelling occurring three days after initiation of irbesartan in addition to longstanding lisinopril therapy. All parts of the physical examination were normal, except for the genital examination. The patients penis was edematous at midshaft only and was nontender with normal skin coloring. The edema was nonpitting and limited to the skin. The patient was instructed to stop taking both lisinopril and irbesartan, and symptoms resolved within 48 hours with supportive care alone. In the second case, a 48-year-old man arrived at the ED complaining of penile swelling over the previous two days. Enalapril had been initiated one month before his arrival at the ED. The patients penis was nontender and edematous at midshaft. The edema was nonpitting and limited to the skin. The patient was instructed to stop taking enalapril, given oral prednisone 60 mg, and asked to continue his prednisone for five days after discharge. The swelling resolved within two days of stopping enalapril, and he had no further episodes of penile swelling. Neither patient was rechallenged with the offending medications. CONCLUSION Penile angioedema was reported in two patients. The first case involved a patient receiving both lisinopril and irbesartan. The second patient was receiving enalapril only.