Daniel M. Lugassy

Not your regular high: cardiac dysrhythmias caused by loperamide

Abstract Objective: Loperamide, a non-prescription anti-diarrheal agent, is a peripheral mu-opioid receptor agonist that is excluded from the blood-brain barrier by p-glycoprotein at therapeutic doses. Overdoses of loperamide penetrate the central nervous system (CNS), leading to abuse. We report cardiac conduction abnormalities and dysrhythmias after ingestion of a recreational supra-therapeutic dose of loperamide confirmed with an elevated blood loperamide concentration. Case details: A 48-year-old woman with a history of alcohol and benzodiazepine abuse presented to the emergency department (ED) with somnolence, weakness and slurred speech. She was taking 20 to 40 tablets of 2 mg loperamide 1–2 times/day for weeks along with clonazepam and whiskey. Vital signs were: blood pressure (BP), 124/90 mmHg; heart rate (HR), 88/min; respiratory rate(RR), 20/min; T, 36.9 °C; O2 saturation 100% on room air (RA). Glucose was 6.4 mmol/L. Electrocardiogram (ECG) had a ventricular rate of 58/min, QRS 164 ms, QT 582 ms with no discernable p-waves. Lactate was 3.5 mmol/L and potassium was 6.2 mEq/L. Labs were notable for an anion gap of 20 mEq/L, ethanol of 3.9 mmol/L, creatinine of 2.3 mg/dL and loperamide concentration of 210 ng/mL (average therapeutic plasma concentration 1.2 ng/mL). She became hypotensive, but responded to fluids. Following treatment for hyperkalemia with calcium, insulin, dextrose, and hypertonic sodium bicarbonate a repeat ECG had a ventricular rate of 66/min, QRS 156 ms, and QT 576 ms. Magnesium was given and pacer pads were placed. During the infusion of magnesium, her BP fell to 92/58 mmHg with a HR of 54/min, RR 14/min, O2 saturation of 97% on RA so the infusion was stopped. The ECG after the magnesium infusion had a ventricular rate of 51/min, QRS of 134 ms, and QT 614 ms. In the ICU she had multiple runs of non-sustained ventricular tachycardia that did not require therapy. Over the next 48 h she improved and was transferred to a floor bed. On day four of hospitalization the patient left against medical advice. At that time, her ECG showed sinus tachycardia with a heart rate 114/min, QRS 82 ms, QT 334 ms. Discussion: Loperamide produces both QRS and QT prolongation at supra-therapeutic dosing. A blood loperamide concentration of 210 ng/mL is among the highest concentrations reported. Supra-therapeutic dosing of loperamide is promoted on multiple drug-use websites and online forums as a treatment for opioid withdrawal, as well as for euphoric effects. With the current epidemic of prescription opioid abuse, toxicity related to loperamide, an opioid agonist that is readily available without a prescription is occurring more frequently. It is important for clinicians to be aware of the potentially life-threatening toxicity related to loperamide abuse in order to provide proper diagnosis, management and patient education.

Metabolic and Hepatobiliary Side Effects of Antiretroviral Therapy (ART)

Although antiretroviral therapy (ART) for human immunodeficiency virus (HIV) has been in use since 1987, the initiation of highly active ART has produced an increase in adverse drug reactions. This is a new challenge as many of the adverse drug reactions attributable to ART may be indistinguishable from non-drug-related illnesses. The emergency physician must be aware of the potential complications of ART as affected patients may present with nonspecific symptoms. The focus of this article is the metabolic and hepatobiliary adverse effects of ART.

Case files of the medical toxicology fellowship at the New York City Poison Control: Bromism: Forgotten, but not gone

ConclusionAfter an extensive literature review, this appears to be the first case documenting bromide toxicity in a patient exposed to the product called Cordial de Monell, which contains potassium bromide. We have identified this product on store shelves in areas of New York City. We believe this child suffered from excess therapeutic sedative exposure due to her size, age, and repeated exposure. Bromism is not nearly as common as it once was, but several forms of bromide are still readily available. This diagnosis should be included in the differential diagnosis of patients who present with sedative-hypnotic-type intoxication. Elevations in the reported serum chloride levels and a negative anion gap are helpful findings if present, but our case and others before confirm that the lack of these features do not rule out this poisoning. This case further illustrates the need for clinicians to be diligent in obtaining thorough medication, dietary, herbal supplement, social, occupational, and cultural histories from their patients. Aggressive hydration with chloride-containing solutions is the cornerstone of treatment, and in severe cases dialysis may be considered. Bromides are not gone, and bromism should not be forgotten.

Effects of hydroxocobalamin on carboxyhemoglobin measured under physiologic and pathologic conditions

Abstract Context. Pre-hospital administration of hydroxocobalamin (B12a) is used for empiric treatment of cyanide poisoning because cyanide poisoning is difficult to identify and requires immediate treatment. B12a interferes with the accuracy of several blood laboratory tests. This study aimed to explore how B12a affects carboxyhemoglobin (COHb) measurements in human blood at both physiologic and pathologic COHb levels. Methods. Several clinically relevant concentrations of B12a were added to human blood samples containing physiologic (∼ 3%) and pathologic (30% and 50%) COHb levels. We then measured the COHb levels of the samples using two different co-oximeters, the Radiometer ABL 700 and the Rapidpoint 500, and compared to their actual baseline COHb levels. Results. B12a had minimal effects on the COHb measured at both physiologic and pathologic levels when measured on the Radiometer. In contrast, the Rapidpoint B12a caused a dose-dependent decrease in the COHb measured, especially of pathologic COHb levels (∼ 30 and 50%). Conclusion. The magnitude of B12a interference on measured COHb is dependent upon the specific co-oximeter used, the actual COHb level and the serum B12a concentration. These errors may potentially influence clinical decision making and thus affect patient outcomes. Our findings emphasize the importance of measuring COHb levels on blood samples collected prior to B12a administration.

In Response to Leppikangas H, et al, Levosimendan as a Rescue Drug in Experimental Propranolol-Induced Myocardial Depression: A Randomized Study

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Comment: Evaluation of Adjunctive Ketamine to Benzodiazepines for Management of Alcohol Withdrawal Syndrome

We read with interest the recent article evaluating ketamine as adjunctive treatment in the management of alcohol withdrawal syndrome (AWS). Although the authors used a rigorous and validated assessment tool for AWS that sought to standardize benzodiazepine administration, we are concerned that significant variations in the administration of drugs, including haloperidol, dexmedetomidine, and propofol, prior to ketamine initiation may have altered their findings. An accurate assessment of the effectiveness of ketamine in AWS requires a standardized approach to benzodiazepines or other sedative-hypnotic dosing. Also, following ketamine initiation, several patients received additional adjunctive agents, making it difficult to assess the beneficial effects of ketamine alone. Finally, the authors were unable to detect a statistically significant decrease in benzodiazepine requirements at 12 and 24 hours post–ketamine initiation. Although a trend toward decreased benzodiazepine requirements was seen, it remains uncertain whether this is an effect of ketamine or simply reflects the natural course of AWS. We submit that the lack of a significant finding may have been a consequence of a limited study design. Whereas a prospective trial may be unwise without more preliminary data, we suggest that future retrospective trials match cases in which ketamine is the sole adjunctive agent used against control patients with similar AWS severity scores who did not receive ketamine. This method would also provide 567919 AOPXXX10.1177/1060028014567919Annals of Pharmacotherapy research-article2015

Acetylcysteine for Acetaminophen Overdose in Patients Who Weigh >100 kg.

that was presented by the FDA reviewer. This made a balanced assessment of the FDA’s position. Therefore, the title of this article is erroneous because this is Dr. Serebruany’s assessment of the FDA’s review. The FDA’s review is different and is published. We have also published an article reviewing the FDA analysis, which comes to a different conclusion from Dr. Serebruany’s, namely, it suggests that there is no clear signal for excess risk of cancer within the context of an acute coronary syndromes (ACS) trial. We further point out that the adverse event reporting as was used in the TRITON trial is unreliable for detecting noncardiovascular events by the sheer nature of the complexity of information that needs to be obtained. Dr. Serebruany makes a statement about the TaRgeted platelet Inhibition to cLarify the Optimal strateGy (TRILOGY) ACS trial, which is also factually wrong. The TRILOGY ACS trial has now enrolled .6000 patients and is on target to be completed in 2011. Thus, it is not “woefully slow.” Furthermore, it should be recognized that because the TRILOGY ACS trial is an eventdriven trial, it is not the number of patients that is important but the number of events that the trial accrues. The protocol is now also published. Therefore, the comments made are inaccurate. E. Magnus Ohman, MD Matthew T. Roe, MD Department of Medicine, Division of Cardiovascular Medicine Duke University Medical Center Durham, NC

Letter in response to “Acquired methemoglobinemia after hydroxocobalamin administration in a patient with burns and inhalation injury”

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The Use of 3- and 4-Factor Prothrombin Complex Concentrate in Patients With Elevated INR:

Background: PCC (Kcentra®) is an Food and Drug Administration (FDA)–approved 4-factor PCC used for the treatment of warfarin-related coagulopathy (WRC), but it has also been used off-label to treat non-WRC. Three-factor PCC in the form of coagulation factor IX human (Bebulin®) has also been used for WRC and off-label to treat non-WRC. It is unclear whether the use of 3- or 4-factor PCCs is effective for the treatment of non-WRC,. Objective: Our aim is to characterize the use of 3- and 4-factor PCCs for patients identified with a non-WRC. Methods: A retrospective analysis of patients who received PCCs for both WRC and non-WRC between January 2012 and July 2015 was conducted. Results: A total of 187 patients with elevated international normalized ratio (INR) who received PCCs were analyzed; 53.9% of patients in the WRC group and 27.7% in the non-WRC group corrected to an INR of 1.3 or less after 3- or 4-factor PCC administration. In those patients with non-WRC and who had underlying liver disease, 3- and 4-factor PCCs reduced mean INR by 0.98 and 1.43, respectively. Conclusion: Three and 4-factor PCCs can reduce INR in patients with WRC and in those with non-WRC secondary to liver disease.

Cocaine-related Aortic Dissection: Questions yet to Be Resolved

We commend Dean et al on their use of the International Registry of Acute Aortic Dissection to investigate cocainerelated aortic dissection. Cocaine is a widely used drug of abuse and a recognized risk factor for aortic dissection. Among the 3584 patients enrolled in the International Registry of Acute Aortic Dissection, the authors identified only 63 patients with documented cocaine use in the setting of aortic dissection. Unfortunately, cocaine use was defined as “a patient who uses cocaine to the detriment of his/her health and social functioning,” a method of self-report that may be subject to significant reporting bias. Although hypertension was present in most of the cocaine-using patients on presentation (92.6%), the results cannot elucidate whether acute cocaine use was temporally associated with aortic dissection in these patients. The use of urine toxicology screening could have identified patients who had used cocaine within the past 2 to 4 days and helped to determine which cocaine-using patients had detectable cocaine metabolites. In addition, it remains uncertain whether the atherogenic effects of cocaine use that predispose chronic users to myocardial infarction also may affect a predisposition for aortic dissection. Finally, because previous studies report an increased prevalence of cocaine-related aortic dissection among