Energy Drink-Associated Electrophysiological and Ischemic Abnormalities: A Narrative Review

An increasing number of cardiovascular adverse effects, emergency room visits, and deaths have been linked to energy drinks. In this review, we summarized available published literature assessing electrophysiological and ischemic adverse effects associated with energy drink consumption. Overall, 32 case reports and 19 clinical trials are included in this review. Ventricular arrhythmia, supraventricular arrhythmia, and myocardial ischemia were amongst the most commonly reported in case reports with 3 having a fatal outcome. Although serious ischemic changes, arrhythmias, or death were not observed in clinical trials, significant electrophysiological changes, such as PR/PQ interval shortening/prolongation, QT/QTc shortening/prolongation, and ST-T changes, were noted. QT/QTc interval prolongation appears to be the most significant finding in clinical trials, and there appears to be a dose-response relationship between energy drink consumption and QTc prolongation. The exact mechanisms and the particular combination of ingredients behind energy drink-induced cardiac abnormalities require further evaluation. Until more information is available, energy drink use should be considered as part of the differential diagnosis in appropriate patients presenting with electrocardiographic changes. Further, certain patient populations should exercise caution and limit their energy drink consumption.

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Abstract 12689: Cardiovascular Responses to Energy Drinks in a Healthy Population: The C-energy Study

Circulation ◽

10.1161/circ.132.suppl_3.12689 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Teri M Kozik ◽

Mouchumi Bhattacharyya ◽

Teresa T Nguyen ◽

Therese F Connolly ◽

Walther Chien ◽

...

Keyword(s):

Blood Pressure ◽

Systolic Blood Pressure ◽

Vital Signs ◽

Cardiovascular Responses ◽

Energy Drinks ◽

Energy Drink ◽

Emergency Department Visits ◽

Qtc Interval ◽

Cardiac Responses ◽

Energy Drink Consumption

Introduction: Energy drinks are presumed to enhance energy, physical endurance, mood, and boost metabolism. Serious health risks have been reported with energy drink consumption such as myocardial infarction, cardiac arrest, stroke, seizures, and arrhythmias. More than 20,000 emergency department visits related to energy drink consumption were reported in 2011. Little is known about the possible pathophysiological mechanisms and adverse events associated with energy drinks. Unlike the tobacco and alcohol industry, there are limited restrictions regulating the purchasing and marketing of these drinks. Purpose: To determine if consumption of energy drinks alter; vital signs (blood pressure, temperature), electrolytes (magnesium, potassium, calcium), activated bleeding time (ACT), or cardiac responses measured with a 12-lead electrocardiographic (ECG) Holter. Method: Subjects consumed two-16 ounce cans of an energy drink within one hour and remained in the lab where data was collected at base line (BL) and then during four hours post consumption (PC). Vital signs were taken every 30 minutes; blood samples were collected at BL, one, two and four hours PC and ECG data was collected throughout the entire study period. Paired students t-test and a corresponding non-parametric test (Wilcoxon signed rank) were used for analysis of the data. Results: Fourteen healthy young subjects were recruited (mean age 28.6 years). Systolic blood pressure (BL=132, ±7.83; PC= 151, ±11.21; p=.001); QTc interval (BL=423, ±22.74; PC=503, ±24.56; p<.001); magnesium level (BL 2.04, ± 0.09; PC=2.13, ±0.15; p=.05); and calcium level (BL=9.31, ±.28; PC=9.52, ±.22; p=.018) significantly increased from BL. While potassium and ACT fluctuated (increase and decrease) no significant changes were observed. Eight of the fourteen subjects (57%) developed a QTc >500 milliseconds PC. Conclusions: In our sample, consumption of energy drinks increased systolic blood pressure, serum magnesium and calcium, and resulted in repolarization abnormalities. Because these physiological responses can lead to arrhythmias and other abnormal cardiac responses, further study in a larger sample is needed to determine the effects and possible consequences of energy drink consumption.

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Anticoagulation with Warfarin in Infants and Children

Annals of Pharmacotherapy ◽

10.1177/106002809603001117 ◽

1996 ◽

Vol 30 (11) ◽

pp. 1316-1322 ◽

Cited By ~ 15

Author(s):

Marcia L Buck

Keyword(s):

Clinical Trials ◽

Adverse Effects ◽

Case Reports ◽

Initial Dosage ◽

Case Series ◽

Infants And Children ◽

Target Range ◽

Search Term ◽

Cardiac Valves ◽

In Infants And Children

OBJECTIVE: TO provide a comprehensive review of warfarin use in infants and children, including recommendations for appropriate dosage and monitoring parameters. DATA SOURCES: A MEDLINE search (1966-1995) was used to identify pertinent English-language articles in the medical literature. The key search term was warfarin. Additional material was obtained from references cited in articles retrieved through MEDLINE. STUDY SELECTION: All articles involving children younger than 18 years were evaluated. In addition, articles on the pharmacokinetics and pharmacodynamics in adults, adverse effects, and drug interactions were included. DATA EXTRACTION: Material selected for review included clinical trials, case reports, and surveys of practice. DATA SYNTHESIS: Warfarin has been used as prophylactic therapy in children with prosthetic cardiac valves as well as for prevention of thromboembolic complications associated with autoimmune disorders and protein C or protein S deficiency. Warfarin also has been used to prevent embolization in children with deep-vein thrombosis or clots in central venous catheters. According to the literature, an initial dosage of 0.1 mg/kg/d should provide anticoagulation without significant adverse effects. As in adults, dosing should be adjusted to achieve a target international normalized ratio (INR). Although the target range in children is not well established, INR values of 1.5–3 are recommended for most patients. Higher values have been used in children with prosthetic cardiac valves and hereditary clotting disorders. CONCLUSIONS: Due to its infrequent use, there is limited information on the effects of warfarin in children. Basic guidelines for initiating and monitoring warfarin were developed by using data gathered from clinical trials, retrospective reviews, case series, and surveys of practice.

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Abstract 12640: Energy Drinks Prolong Early Repolarization (J-T Peak ) Phase in a Healthy Population

Circulation ◽

10.1161/circ.142.suppl_3.12640 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Samuel R Kaplan ◽

Ghufran Syed ◽

Teri Kozik

Keyword(s):

Torsade De Pointes ◽

Energy Drinks ◽

Energy Drink ◽

Healthy Population ◽

Specific Marker ◽

Qtc Interval ◽

Qtc Prolongation ◽

Early Repolarization ◽

Increased Risk ◽

Energy Drink Consumption

Introduction: Energy drinks continue to be the fastest growing beverage market with sales expected to reach $60 billion in the next few years, yet have demonstrated adverse cardiovascular effects such as prolongation of the QTc interval on EKG. While QTc prolongation observed with certain drugs has long been used as an indicator of increased risk of torsade de pointes, recent data has identified the early repolarization interval J-T peak (JTp) as a more specific marker for proarrhythmic potential. Drugs that selectively block the human ether-a-go-go related (hERG) potassium ion channel prolong QTc by prolonging both early repolarization (JTp) and late repolarization (T peak -T end [Tpe] interval), and are associated with an increased risk of torsade. In contrast, drugs that additionally block inward late sodium and L-type calcium prolong QTc by prolonging Tpe but not JTp, and have demonstrated reduced risk of torsade. In 2018, the C-Energy-X study demonstrated QTc prolongation in 22 healthy subjects (mean age 28 ± 7yrs) who consumed energy drink while at rest and following short periods of exercise. Our study provides a secondary analysis of this data in terms of its effect on JTp, a potentially more specific marker for torsade risk. Methods: Using H-Scribe software, two evaluators independently measured JTp and RR intervals from C-Energy-X subjects pre- and post-energy drink consumption in the rest and exercise phases. Values were corrected for heart rate using the linear correction formula JTpc=JTp + 0.150(1-RR), where RR is R-to-R interval. Mean JTpc values from each phase were analyzed using a paired sample two-tailed t -test. Results: In the resting phase following energy drink consumption (PCr), there was a statistically significant increase in JTpc intervals for 77% of subjects by a mean of 10.5ms (baseline=234 ± 21.3ms; PCr=245 ± 22.0ms; p =0.015). In the exercise phase following energy drink consumption (PCe), 64% of subjects increased JTpc intervals by a mean of 0.8ms which was not significant (baseline=225 ± 15.7ms; PCe=226 ± 17.9ms; p =0.845). Conclusion: In the resting phase, energy drink consumption was associated with statistically significant prolongation of JTpc, suggesting a theoretical increased risk of torsade de pointes.

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Aplidin Cardiac Safety Analysis.

Blood ◽

10.1182/blood.v114.22.4820.4820 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4820-4820

Author(s):

Arturo Soto-Matos ◽

Sergio Szyldergemajn ◽

Javier Gomez ◽

Sonia Extremera ◽

Bernardo Miguel-Lillo ◽

...

Keyword(s):

Risk Factors ◽

Clinical Trials ◽

Multivariate Analysis ◽

Drug Exposure ◽

Single Agent ◽

Fatal Outcome ◽

Healthy Population ◽

Qtc Interval ◽

Cardiac Safety ◽

Frequent Type

Abstract Abstract 4820 Background Aplidin (plitidepsin) is a cyclic depsipeptide of marine origin, with activity in relapsed/refractory multiple myeloma and T-cell NHL[1],[2]. Some depsipeptides have been linked to increased cardiac toxicity in the literature[3]. PharmaMar Pharmacovigilance and Clinical Trials Data Management databases were reviewed for cardiac adverse events (CAEs) occurring during clinical trials evaluating plitidepsin as single-agent as of November 2008. Data were analyzed for potential risk factors associations with the occurrence of CAE by univariate and multivariate logistic regression analyses. Results Forty-six of the 578 patients (8.0%) treated had at least one CAE. Eleven patients of 578 (1.9%) had CAE related to plitidepsin, none of them with fatal outcome. CAEs were retrospectively classified into 3 main groups after clinical review of all available data. The most frequent type of CAE were rhythm abnormalities (RA) (n=31; 5.4%), whereas atrial fibrillation (AF)/flutter accounted for most cases (n=15; 2.6%). Most events occurred randomly during plitidepsin treatment. Of note, no cases of life-threatening ventricular arrhythmias have been reported to date. The myocardial injury events (MI) (n=17; 3.0%) included possible ischemic related events as well as non-ischemic events. Finally, miscellaneous events (M) (n=6; 1.0%) included all other cardiac events that did not fit into the aforementioned categories. None of the M events was related to plitidepsin Demographic, clinical and pharmacological variables were explored by univariate and multivariate analysis. Significant association was found with prostate or pancreas cancer diagnosis (p=0.002), known baseline cardiac risk factors (p=0.002), myalgia at baseline (p=0.004), lower hemoglobin levels (p= 0.006) and ≥ grade 2 hypokalemia (p=0.006). Multivariate analysis confirmed all these associations. Importantly, treatment related variables, such as plitidepsin dose, number of cycles or schedule of administration did not result in any statistically significant association. Serial ECGs performed before and after plitidepsin administration (n=136) did not show any relevant effect on QTc interval. None of the PK parameters analyzed (Cmax and AUC from day 0 to day 28) had any significant impact on the probability of developing a CAE. Conclusions CAEs observed to date in plitidepsin trials fit into three clinical categories. The most frequent type observed was AF/atrial flutter, although its incidence was not different to what is reported in age-matched healthy population[4]. All other events were relatively infrequent. No dose-cumulative pattern was observed; moreover, neither plitidepsin dose nor schedule was associated with occurrence of CAEs. Relevant predisposing factors identified in univariate and multivariate analyses were related to patient's baseline and/or disease-related characteristics rather than to drug exposure or treatment-related variables. Data available on 578 adult patients with advanced cancer treated with singe-agent plitidepsin support a favorable cardiac safety profile. Disclosures: Soto-Matos: PharmaMar SAU: Employment. Szyldergemajn:PharmaMar SAU: Employment. Gomez:PharmaMar SAU: Employment. Extremera:PharmaMar SAU: Employment. Miguel-Lillo:PharmaMar SAU: Employment. Alfaro:PharmaMar SAU: Employment. Coronado:PharmaMar SAU: Employment. Lardelli:PharmaMar SAU: Employment. Roy:PharmaMar SAU: Employment. Corrado:PharmaMar SAU: Employment. Yovine:PharmaMar SAU: Employment. Kahatt:PharmaMar SAU: Employment.

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I. Cloroquina / hidroxicloroquina y azitromicina. Revisión narrativa de seguridad

Latin american journal of clinical sciences and medical technology ◽

10.34141/ljcs2866115 ◽

2020 ◽

Vol 2 (2) ◽

pp. 71-82

Author(s):

Raquel Herrera Comoglio

Keyword(s):

Clinical Trials ◽

Adverse Effects ◽

Scientific Evidence ◽

Safety Information ◽

Torsades De Pointes ◽

Pharmacovigilance System ◽

Qtc Interval ◽

Number Of Patients ◽

Hospital Patients ◽

Repurposed Drugs

The SARS-Co-2 pandemic is affecting millions of people, producing hundreds of thousands of deaths, and collapsing healthcare systems worldwide. Due to the lack of specific treatments, repurposed drugs are routinely used in in-hospital patients, though there is no sound-based scientific evidence. The quinine derivatives chloroquine (CQ) and hydroxychloroquine (HCQ) —used as antimalarials, and in autoimmune diseases—, and the antibiotic macrolide azithromycin have been proposed as possible therapies against the SARS-CoV-2 infection and COVID-19. Shortly after this outbreak began, many clinical trials have been registered to evaluate the efficacy of CQ/HCQ, alone or combined with azithromycin, in the treatment of COVID-19 or the prevention of SARS-CoV-2 infection. In the meantime, media information about the possible use of these drugs, politic leaders’ statements and further decisions concerning their efficacy soared public expectations. Both CQ/HCQ and azithromycin are relatively inexpensive and can be administered orally; adverse effects are known at doses used in approved indications. However, their use in a much more significant number of patients increases the risk of occurrence of adverse events. Notably, the potential of both drugs to prolong QTc interval raises concerns about the potentiality to lead to fatal arrhythmias, including torsades de pointes (TdP). The potential blood-glucose-lowering effect of CQ/HCQ could also produce serious adverse effects. The Spanish Pharmacovigilance system has received six cases of serious neuropsychiatric adverse reactions.This narrative review presents a summary of safety information of CQ/HCQ in approved indications, and the emerging experience of their use in the SARS-CoV-2 infection and COVID-19. With randomised clinical trials’ results not available yet, to May 20th 2020, the evidence of efficacy and effectiveness of CQ/HCQ do not suggest a benefit of this use as a treatment of COVID-19. For these purposes, CQ/HCQ alone or in combination with azithromycin should be used only in clinical trials.

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Effect of “Energy Drink” Consumption on Hemodynamic and Electrocardiographic Parameters in Healthy Young Adults

Annals of Pharmacotherapy ◽

10.1345/aph.1l614 ◽

2009 ◽

Vol 43 (4) ◽

pp. 596-602 ◽

Cited By ~ 66

Author(s):

Leah Steinke ◽

David E Lanfear ◽

Vishnuprabha Dhanapal ◽

James S Kalus

Keyword(s):

Cardiovascular Effects ◽

Energy Drink ◽

Chronic Medical Conditions ◽

Qtc Interval ◽

Ecg Changes ◽

Baseline Blood Pressure ◽

Chronic Medication ◽

Fasted State ◽

Energy Drink Consumption ◽

Electrocardiographic Parameters

Background: Energy drinks are frequently purported to improve cognitive function and concentration. However, the cardiovascular effects of these drinks have not been adequately studied. Objective: To determine the cardiac effects of a commercially available, multicomponent energy drink in healthy volunteers. Methods: Fifteen healthy adults were Included in this prospective study. Individuals who had chronic medical conditions, ware on chronic medication, or were pregnant or breast-feeding were excluded. Subjects abstained from caffeine for 48 hours prior to and during the study. In the morning on Day 1 of the study, while subjects were in a fasted state, baseline blood pressure (BP), heart rate (HR), and electrocardiographic (ECG) parameters were measured. Participants then consumed 500 mL (2 cans) of an energy drink and measurements were repeated 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours later. Participants then drank 500 mL of energy drink daily for the next 5 days. Day 1 protocol was repeated on Day 7. Results: On Days 1 and 7, maximum mean systolic BP (SBP), HR, and QTc interval occurred at 4 hours. Maximum diastolic BP (DBP) occurred at 2 hours on Days 1 and 7. Within 4 hours of energy drink consumption, on Days 1 and 7, respectively, SBP increased by 7.9% (p = 0.006) and 9.6% (p < 0.001), HR increased by 7.8% (p = 0.009) and 11.0% (p < 0,001). and QTc interval increased by 2.4% (p = 0.368) and 5.0% (p = 0.052), DBP increased by 7.0% < p = 0.046) and 7.8% (p = 0.063) within 2 hours of energy drink consumption on Days 1 and 7, respectively. Conclusions: Although no significant ECG changes were observed, HR increased 5–7 beats/min and SBP increased 10 mm Hg after energy drink consumption.

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Uncommon Adverse Effects of Deoxycholic Acid Injection for Submental Fullness: Beyond the Clinical Trials

Journal of Cutaneous Medicine and Surgery ◽

10.1177/1203475420943270 ◽

2020 ◽

Vol 24 (6) ◽

pp. 619-624

Author(s):

Kristy C. Metzger ◽

Erika L. Crowley ◽

Dorota Kadlubowska ◽

Melinda J. Gooderham

Keyword(s):

Clinical Trials ◽

Adverse Effects ◽

Deoxycholic Acid ◽

Case Reports ◽

Case Series ◽

Phase Iii ◽

Patient Counselling ◽

Medical Environment ◽

Phase Iii Clinical Trials ◽

Health Canada

Deoxycholic acid (BELKYRATM, Allergan, Markham, ON, Canada) is a minimally invasive injectable treatment approved by Health Canada for the nonsurgical reduction of submental fullness. Multiple phase III clinical trials have proven the efficacy and safety of deoxycholic acid. In the clinical trials, the most common adverse events (AEs) reported, such as injection site pain, numbness, swelling, bruising and induration, were transient and mild-to-moderate in severity. Additional postmarketing AEs have been reported in the literature. In this study, we reviewed the uncommon reported events and aimed to increase clinician awareness of the potential adverse effects for patient counselling of risks and benefits, identify AEs of procedures that may be performed outside of the medical environment, and identify factors that increase the risk of an adverse event. Beyond the clinical trials, real-world case reports and case series have been reported for the AEs of alopecia, transient neuropraxia, vascular occlusive events/vascular injury, and skin necrosis. Dermatologists need to be aware of these risks, for the treatment and management of their own patients and for those patients who may be treated outside the medical clinic environment that present for medical management of these AEs.

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A Case of Psychosis and Renal Failure Associated with Excessive Energy Drink Consumption

Case Reports in Psychiatry ◽

10.1155/2019/3954161 ◽

2019 ◽

Vol 2019 ◽

pp. 1-5

Author(s):

D. Kelsey ◽

A. J. Berry ◽

R. A. Swain ◽

S. Lorenz

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Case Report ◽

General Population ◽

Case Reports ◽

Energy Drinks ◽

Energy Drink ◽

First Case ◽

Energy Drink Consumption ◽

Nonalcoholic Beverages

Energy drinks are nonalcoholic beverages that are widely consumed in the general population, and worldwide usage is increasing. The main stimulant component of energy drinks is typically caffeine. Few case reports exist that link energy drink consumption to psychosis, and similarly few reports exist that associate energy drink consumption with acute renal failure. We present a patient who simultaneously developed psychosis and acute renal failure associated with excessive energy drink consumption. The patient required haemodialysis, and his psychosis resolved on cessation of energy drinks and a brief course of antipsychotic medication. We perform a review of similar cases where excessive caffeinated energy drink consumption has been linked to psychosis or acute renal failure. To our knowledge, this is the first case report describing both renal failure and psychosis occurring simultaneously in a patient. Recognising the spectrum of disorders associated with excessive energy drink consumption is vital for both physicians and psychiatrists, as this has important implications for both prognosis and treatment.

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Energy Drinks and Their Adverse Health Effects: A Systematic Review and Meta-analysis

Sports Health A Multidisciplinary Approach ◽

10.1177/1941738120949181 ◽

2020 ◽

pp. 194173812094918

Author(s):

Ibrahim M. Nadeem ◽

Ajaykumar Shanmugaraj ◽

Seaher Sakha ◽

Nolan S. Horner ◽

Olufemi R. Ayeni ◽

...

Keyword(s):

Systematic Review ◽

Adverse Effects ◽

Adverse Events ◽

Pediatric Population ◽

Adult Population ◽

Energy Drinks ◽

Energy Drink ◽

Control Group ◽

Pertinent Data ◽

Energy Drink Consumption

Context: Energy drinks are the fastest growing product in the beverage industry. However, there is concern regarding potential for adverse effects with use. Objective: To evaluate the reported adverse effects of energy drink consumption. Data Sources: The electronic databases MEDLINE, EMBASE, and PubMed were searched for relevant studies from inception to November 2019, and pertinent data were abstracted. Study Selection: Only clinical studies reporting adverse events after energy drink consumption were included. Study Design: Systematic review. Level of Evidence: Level 4. Data Extraction: Data regarding sample size characteristics, energy drink characteristics, comparators, and all adverse events were extracted in duplicate and recorded. Results: A total of 32 studies and 96,549 individuals were included. Frequently reported adverse events in the pediatric population were insomnia (35.4%), stress (35.4%), and depressive mood (23.1%). Frequently reported adverse events in the adult population were insomnia (24.7%), jitteriness/restlessness/shaking hands (29.8%), and gastrointestinal upset (21.6%). Alcohol mixed with energy drinks significantly reduced the likelihood of sedation effects but increased the likelihood of stimulatory effects. Energy drink consumption significantly increased the odds of insomnia (OR, 5.02; 95% CI, 1.72-14.63) and jitteriness/activeness (OR, 3.52; 95% CI, 1.28-9.67) compared with the control group. Conclusion: The authors recommend that individuals avoid frequent energy drink consumption (5-7 energy drinks/week) and avoid co-consumption with alcohol; increased regulatory standards should be placed in the sale of energy drinks, particularly with regard to the pediatric population.

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Transition of Products From Prescription to Over the Counter: The H2 Antagonists

Journal of Pharmacy Practice ◽

10.1177/089719009200500106 ◽

1992 ◽

Vol 5 (1) ◽

pp. 22-30 ◽

Cited By ~ 2

Author(s):

Edward J. Drea

Keyword(s):

Clinical Trials ◽

Drug Use ◽

Adverse Effects ◽

Drug Interactions ◽

Case Reports ◽

Rational Selection ◽

Over The Counter ◽

H2 Antagonists ◽

Reporting Systems

In general, the histamine type-2 receptor antagonists (H2RA) enjoy an enviable record of safety. These agents, notably cimetidine, have been studied extensively in clinical trials, case reports, and worldwide drug use reporting systems. Of the available agents (cimetidine, famotidine, nizatidine, and ranitidine) several similarities exist from compound to compound and use data to support that each of the agents is equally safe and efficacious in equipotent dosing. A review of H2RA pharmacology, pharmacokinetics, adverse effects, and drug interactions is included to provide the clinician with a basis for rational selection and use of an H2RA.

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