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1.
J Emerg Med ; 65(3): e229-e233, 2023 09.
Article in English | MEDLINE | ID: mdl-37495422

ABSTRACT

BACKGROUND: Brugada syndrome (BrS) is an inherited disease that can lead to sudden cardiac death. Medications, such as antidysrhythmics, and fevers can unmask or induce the Brugada pattern on an electrocardiogram (ECG). This case report highlights a patient who developed drug-induced Brugada type I pattern after a procainamide infusion for the treatment of new-onset atrial fibrillation (AF) or flutter and discusses the implications for this incidental but potentially lethal finding. CASE REPORT: We report a case of a young man who presented to the emergency department (ED) with new-onset AF with rapid ventricular response that began within 12 h of presentation. ED treatments included a crystalloid IV fluid bolus, diltiazem pushes, synchronized electrical cardioversion, and a procainamide infusion. After the procainamide infusion, the patient developed ECG findings consistent with Brugada pattern. Both the AF and Brugada pattern resolved spontaneously within 24 h. The patient was discharged without implantable cardioverter defibrillator placement due to presumed isolated procainamide-induced Brugada pattern and lack of concerning features, such as inducible dysrhythmia during electrophysiology study, family history of sudden death, and history of syncope. The patient was counseled to follow-up with genetics and avoid BrS-inducing medications. WHY SHOULD AN EMERGENCY PHYSICIANS BE AWARE OF THIS?: Procainamide, an option for the treatment of AF in the ED, can provoke Brugada pattern. If encountered, it is important to recall that some patients may not be diagnosed with BrS if determined to be low risk according to the Shanghai criteria. All patients should be referred to cardiology for further evaluation.


Subject(s)
Atrial Fibrillation , Brugada Syndrome , Male , Humans , Procainamide/adverse effects , Atrial Fibrillation/complications , China , Brugada Syndrome/diagnosis , Brugada Syndrome/complications , Death, Sudden, Cardiac/etiology , Electrocardiography
2.
Exp Physiol ; 107(8): 864-878, 2022 08.
Article in English | MEDLINE | ID: mdl-35561081

ABSTRACT

NEW FINDINGS: What is the central question of this study? Can the triangular appearance of ventricular action potential, indicating proarrhythmic profile of antiarrhythmic agent, be approximated by specific changes on an electrocardiogram (ECG)? What are the main finding and its importance? The triangulation of the ventricular action potential seen when antiarrhythmic drugs induce a greater lengthening of the late repolarization compared to the initial repolarization in epicardium is closely approximated by a greater prolongation of the T wave upslope relative to the interval between the J point and the start of the T wave (the JTstart interval) on the ECG. These findings may improve the power of ECG assessments in predicting the drug-induced arrhythmia resulting from slowed phase 3 repolarization. ABSTRACT: Antiarrhythmic drugs prescribed to treat atrial fibrillation can occasionally precipitate ventricular tachyarrhythmia through a prominent slowing of the phase 3 repolarization. The latter results in the triangular shape of ventricular action potential, indicating high arrhythmic risk. However, clinically, the utility of triangulation assessments for predicting arrhythmia is limited owing to the invasive nature of the ventricular action potential recordings. This study examined whether the triangulation effect can be detected indirectly from electrocardiogram (ECG) analysis. Epicardial monophasic action potentials and the ECG were simultaneously recorded in perfused guinea-pig hearts. With antiarrhythmics (dofetilide, quinidine, procainamide and flecainide), a prolongation of the initial repolarization seen in the action potential recordings was closely approximated by lengthening of the interval between the J point and the start of the T wave (the JTstart interval) on the ECG, whereas a prolongation of the late repolarization was paralleled by widening of the T wave upslope. Dofetilide, quinidine and procainamide induced a prominent slowing of the phase 3 repolarization in epicardium, leading to triangulation of the action potential. These effects were accompanied by a greater prolongation of the T wave upslope compared to the JTstart interval. Flecainide elicited a proportional prolongation of the initial and the late ventricular repolarization, and therefore failed to induce triangulation, based on analysis of both epicardial action potential and ECG profiles. Collectively, these findings suggest that the ratio between the durations of the T wave upslope and the JTstart interval may represent the ECG metric of the ventricular action potential triangulation induced by antiarrhythmic drugs.


Subject(s)
Anti-Arrhythmia Agents , Arrhythmias, Cardiac , Action Potentials , Animals , Anti-Arrhythmia Agents/adverse effects , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/drug therapy , Electrocardiography , Flecainide/adverse effects , Guinea Pigs , Pericardium/drug effects , Pericardium/physiology , Procainamide/adverse effects , Quinidine/adverse effects
3.
Ann Rheum Dis ; 78(4): 504-508, 2019 04.
Article in English | MEDLINE | ID: mdl-30793701

ABSTRACT

OBJECTIVE: Drug-induced lupus (DIL) is an idiosyncratic side effect of treatments in which symptoms overlap with those of systemic lupus erythematosus (SLE). The spectrum of DIL constantly evolves with that of the pharmacopoeia. Here, we used VigiBase, the WHO global individual case safety reports (ICSRs) database, to identify the main drugs associated with DIL. METHODS: We analysed all ICSRs classified as 'systemic lupus erythematosus' according to the Medical Dictionary for Drug Regulatory Activities term (preferred term level) in VigiBase. The drugs considered in the analysis were those not used to treat SLE, with a positive lower end of the 95% credibility interval for the information component (IC025) ≥0, an indicator value for disproportionate Bayesian reporting. RESULTS: A total of 12 166 DIL ICSRs were identified using VigiBase. From those, 8163 ICSRs reporting on 118 suspected drugs with IC025 ≥0 were extracted. The median age at DIL onset was 49 years and the female to male sex ratio was 4.3. The median delay between start of suspected treatment and DIL occurrence was 172 days. DIL was reported as serious adverse event in 55.4%. Among the 118 suspected drugs, 42 had not been previously reported in association with DIL. The drugs associated with the highest number of DIL cases were infliximab, adalimumab, etanercept, procainamide and hydralazine. CONCLUSION: This study enables the identification of 118 drugs associated with DIL. The list of suspected drugs may prove useful to physicians when confronted with potential DIL cases. TRIAL REGISTRATION NUMBER: NCT03480529.


Subject(s)
Lupus Erythematosus, Systemic/chemically induced , Adalimumab/adverse effects , Adult , Antirheumatic Agents/adverse effects , Databases, Factual , Etanercept/adverse effects , Female , Humans , Hydralazine/adverse effects , Infliximab/adverse effects , Male , Middle Aged , Pharmacovigilance , Procainamide/adverse effects , Retrospective Studies , World Health Organization
4.
Curr Opin Rheumatol ; 30(5): 490-497, 2018 09.
Article in English | MEDLINE | ID: mdl-29870500

ABSTRACT

PURPOSE OF REVIEW: Rapid introduction of newly developed drugs in the absence of clear understanding of the pathophysiologic mechanisms behind drug-induced lupus erythematosus (DILE) can sometimes make DILE difficult to recognize in clinical practice. The purpose of this review is to summarize drugs most recently reported to be involved in DILE and discuss the current landscape of diverse mechanisms involved. RECENT FINDINGS: A large number of proton pump inhibitor (PPI)-induced subacute cutaneous lupus erythematosus cases have been reported, suggesting a shift over time in the spectrum of drugs implicated in DILE. Twenty-two articles comprising 29 DILE case reports published within the last 2 years are summarized in this review, including 12 (41.4%) systemic DILE. Antitumor necrosis factor (anti-TNF) drugs were the most frequently (41.7%) reported to introduce systemic DILE in these cases. Chemotherapeutic drugs were the most common drug class (54.5%) involved in subacute cutaneous lupus erythematosus, with an observed higher incidence in female patients. Enhanced neutrophil extracellular trap (NET) formation induced by procainamide and hydralazine could be a new mechanism contributing to the pathogenesis of DILE. SUMMARY: The list of drugs implicated in triggering DILE is expanding as new drugs with novel mechanisms of action are being developed. It is important to recognize culprit drugs that may induce lupus erythematosus, as discontinuation usually results in improvement of drug-induced manifestations. Characterizing the mechanisms involved might help better understand the cause of idiopathic autoimmunity.


Subject(s)
Lupus Erythematosus, Systemic/chemically induced , Autoimmunity , Genetic Predisposition to Disease , Humans , Hydralazine/adverse effects , Immunologic Factors/adverse effects , Lupus Erythematosus, Cutaneous/chemically induced , Lupus Erythematosus, Cutaneous/genetics , Lupus Erythematosus, Cutaneous/immunology , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Procainamide/adverse effects , Tumor Necrosis Factor-alpha/antagonists & inhibitors
5.
PLoS One ; 13(1): e0191514, 2018.
Article in English | MEDLINE | ID: mdl-29352276

ABSTRACT

Non-uniform shortening of the action potential duration (APD90) in different myocardial regions upon heart rate acceleration can set abnormal repolarization gradients and promote arrhythmia. This study examined whether spatial heterogeneities in APD90 restitution can be amplified by drugs with clinically proved proarrhythmic potential (dofetilide, quinidine, procainamide, and flecainide) and, if so, whether these effects can translate to the appropriate changes of the ECG metrics of ventricular repolarization, such as JT intervals. In isolated, perfused guinea-pig heart preparations, monophasic action potentials and volume-conducted ECG were recorded at progressively increased pacing rates. The APD90 measured at distinct ventricular sites, as well as the JTpeak and JTend values were plotted as a function of preceding diastolic interval, and the maximum slopes of the restitution curves were determined at baseline and upon drug administration. Dofetilide, quinidine, and procainamide reverse rate-dependently prolonged APD90 and steepened the restitution curve, with effects being greater at the endocardium than epicardium, and in the right ventricular (RV) vs. the left ventricular (LV) chamber. The restitution slope was increased to a greater extent for the JTend vs. the JTpeak interval. In contrast, flecainide reduced the APD90 restitution slope at LV epicardium without producing effect at LV endocardium and RV epicardium, and reduced the JTpeak restitution slope without changing the JTend restitution. Nevertheless, with all agents, these effects translated to the amplified epicardial-to-endocardial and the LV-to-RV non-uniformities in APD90 restitution, paralleled by the increased JTend vs. JTpeak difference in the restitution slope. In summary, these findings suggest that arrhythmic drug profiles are partly attributable to the accentuated regional heterogeneities in APD90 restitution, which can be indirectly determined through ECG assessments of the JTend vs. JTpeak dynamics at variable pacing rates.


Subject(s)
Anti-Arrhythmia Agents/adverse effects , Arrhythmias, Cardiac/chemically induced , Arrhythmias, Cardiac/physiopathology , Action Potentials/drug effects , Action Potentials/physiology , Animals , Electrophysiological Phenomena , Female , Flecainide/adverse effects , Guinea Pigs , In Vitro Techniques , Perfusion , Phenethylamines/adverse effects , Procainamide/adverse effects , Quinidine/adverse effects , Sulfonamides/adverse effects
6.
Arthritis Rheumatol ; 70(3): 468-474, 2018 03.
Article in English | MEDLINE | ID: mdl-29121457

ABSTRACT

OBJECTIVE: Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce autoreactivity in individuals at risk of autoimmune diseases. The objective of this study was to assess whether medications implicated in cases of drug-induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug-induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation. METHODS: Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy. The ability of these drugs to interfere with NET degradation by serum nuclei was assessed. Pathways of drug-induced NET formation were studied with pharmacologic inhibitors of reactive oxygen species (ROS), peptidylarginine deiminases (PADs), and muscarinic receptors, and by assessment of intracellular calcium levels by flow cytometry. To determine if NET protein cargo varies by drug stimulus and/or neutrophil source, proteomic analysis of NET lysates induced by specific medications was compared using neutrophils from healthy donors and from patients with autoimmune diseases. RESULTS: Hydralazine and procainamide significantly induced NET formation while minocycline and clozapine did not. None of the medications significantly impaired NET degradation. NETosis induced by these drugs required NADPH oxidase and PAD4 activation. Procainamide triggered NETs via muscarinic receptor engagement on neutrophils, while hydralazine modulated calcium release from intracellular stores. Differences in protein cargo, particularly histone content, were observed in NETs induced by hydralazine and procainamide. CONCLUSION: Medications commonly implicated in drug-induced autoimmunity trigger NET formation displaying distinct protein cargo, via common and specific pathways. NETosis may play a role in the pathogenesis of drug-induced autoimmunity.


Subject(s)
Autoimmunity/drug effects , Extracellular Traps/drug effects , Neutrophils/drug effects , Anti-Arrhythmia Agents/adverse effects , Anti-Arrhythmia Agents/immunology , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/immunology , Antihypertensive Agents/adverse effects , Antihypertensive Agents/immunology , Antipsychotic Agents/adverse effects , Antipsychotic Agents/immunology , Autoimmunity/immunology , Clozapine/adverse effects , Clozapine/immunology , Extracellular Traps/immunology , Flow Cytometry , Humans , Hydralazine/adverse effects , Hydralazine/immunology , Microscopy, Fluorescence , Minocycline/adverse effects , Minocycline/immunology , Neutrophils/immunology , Procainamide/adverse effects , Procainamide/immunology , Proteomics , Signal Transduction/drug effects
7.
Eur Heart J ; 38(17): 1329-1335, 2017 May 01.
Article in English | MEDLINE | ID: mdl-27354046

ABSTRACT

AIMS: Intravenous procainamide and amiodarone are drugs of choice for well-tolerated ventricular tachycardia. However, the choice between them, even according to Guidelines, is unclear. We performed a multicentre randomized open-labelled study to determine the safety and efficacy of intravenous procainamide and amiodarone for the acute treatment of tolerated wide QRS complex (probably ventricular) tachycardia. METHODS AND RESULTS: Patients were randomly assigned to receive intravenous procainamide (10 mg/kg/20 min) or amiodarone (5 mg/kg/20 min). The primary endpoint was the incidence of major predefined cardiac adverse events within 40 min after infusion initiation. Of 74 patients included, 62 could be analysed. The primary endpoint occurred in 3 of 33 (9%) procainamide and 12 of 29 (41%) amiodarone patients (odd ratio, OR = 0.1; 95% confidence interval, CI 0.03-0.6; P = 0.006). Tachycardia terminated within 40 min in 22 (67%) procainamide and 11 (38%) amiodarone patients (OR = 3.3; 95% CI 1.2-9.3; P = 0.026). In the following 24 h, adverse events occurred in 18% procainamide and 31% amiodarone patients (OR: 0.49; 95% CI: 0.15-1.61; P: 0.24). Among 49 patients with structural heart disease, the primary endpoint was less common in procainamide patients (3 [11%] vs. 10 [43%]; OR: 0.17; 95% CI: 0.04-0.73, P = 0.017). CONCLUSIONS: This study compares for the first time in a randomized design intravenous procainamide and amiodarone for the treatment of the acute episode of sustained monomorphic well-tolerated (probably) ventricular tachycardia. Procainamide therapy was associated with less major cardiac adverse events and a higher proportion of tachycardia termination within 40 min.


Subject(s)
Amiodarone/administration & dosage , Anti-Arrhythmia Agents/administration & dosage , Procainamide/administration & dosage , Tachycardia, Ventricular/drug therapy , Aged , Amiodarone/adverse effects , Anti-Arrhythmia Agents/adverse effects , Cardiomyopathies/complications , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Patient Selection , Procainamide/adverse effects , Treatment Outcome
8.
Cardiovasc Pathol ; 24(4): 250-3, 2015.
Article in English | MEDLINE | ID: mdl-25770749

ABSTRACT

A 33-year-old African-American woman was bridged to heart transplantation with a left ventricular assist device. She had a 14-month history of heart failure secondary to viral cardiomyopathy. The patient's refractory ventricular tachycardia was treated with intravenous procainamide owing to the patient's history of amiodarone-induced thyroiditis. After orthotopic cardiac transplant, she experienced prolonged respiratory failure. Serial computed tomography evaluation of the lung revealed diffuse bilateral ground-glass opacities and septal thickening. Bronchoscopies with tissue biopsies were performed with no conclusive results. Specimen samples displayed septal fibrosis with loose fibromyxoid tissue and some hobnail nodularities with no indication of granulomas, neutrophilic infiltration, malignancy, or fungal, viral, or bacterial growth. Histopathological evaluation of the lung wedge biopsy supported a diagnosis of pulmonary fibrosis and noted interstitial fibrosis with areas of focal alveolar hemorrhage and increased macrophage infiltration. Antinuclear body was found to be negative. After in-depth evaluation of the patient's medication history, procainamide was identified as the cause of the toxicity. As procainamide-induced lung fibrosis is relatively uncommon, we present this case to highlight procainamide's potential harm and the need for careful monitoring in postsurgical patients.


Subject(s)
Anti-Arrhythmia Agents/adverse effects , Heart Failure/surgery , Heart Transplantation , Lung/drug effects , Procainamide/adverse effects , Pulmonary Fibrosis/chemically induced , Tachycardia, Ventricular/drug therapy , Adult , Biomarkers/metabolism , Biopsy , Bronchoscopy , Female , Heart Failure/diagnosis , Heart Failure/etiology , Humans , Immunohistochemistry , Lung/metabolism , Lung/pathology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Pulmonary Fibrosis/pathology , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/etiology , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
9.
J Autoimmun ; 48-49: 66-72, 2014.
Article in English | MEDLINE | ID: mdl-24456934

ABSTRACT

Since sulfadiazine associated lupus-like symptoms were first described in 1945, certain drugs have been reported to interfere with the immune system and induce a series of autoimmune diseases (named drug-induced autoimmunity, DIA), exemplified by systemic lupus erythematosus (SLE). Among the drugs, procainamide and hydralazine are considered to be associated with the highest risk for developing lupus, while quinidine has a moderate risk, and all other drugs have low or very low risk. More recently, drug-induced lupus has been associated with the use of newer biological modulators, such as tumor necrosis factor (TNF)-alpha inhibitors and cytokines. In addition to lupus, other major autoimmune diseases, including vasculitis and arthritis, have also been associated with drugs. Because resolution of symptoms generally occurs after cessation of the offending drugs, early diagnosis is crucial for treatment strategy and improvement of prognosis. Unfortunately, it is difficult to establish standardized criteria for DIA diagnosis. Diagnosis of DIA requires identification of a temporal relationship between drug administration and the onset of symptoms, but the relative risk with respect to dose and duration for each drug has rarely been determined. DIA is affected by multiple genetic and environmental factors, leading to difficulties in establishing a list of global clinical features that are characteristic of most or all DIA patients. Moreover, the distinction between authentic DIA and unmasking of a latent autoimmune disease also poses challenges. In this review, we summarize the highly variable clinical features and laboratory findings of DIA, with an emphasis on the diagnostic criteria.


Subject(s)
Autoimmune Diseases/classification , Autoimmune Diseases/diagnosis , Arthritis/chemically induced , Arthritis/classification , Arthritis/diagnosis , Autoimmune Diseases/epidemiology , Cytokines/adverse effects , Humans , Hydralazine/adverse effects , Lupus Erythematosus, Systemic/classification , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/epidemiology , Procainamide/adverse effects , Sex Factors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Vasculitis/chemically induced , Vasculitis/classification , Vasculitis/diagnosis
10.
CJEM ; 14(3): 169-77, 2012 May.
Article in English | MEDLINE | ID: mdl-22575297

ABSTRACT

OBJECTIVE: It is believed that when patients present to the emergency department (ED) with recent-onset atrial fibrillation or flutter (RAFF), controlling the ventricular rate before cardioversion improves the success rate. We evaluated the influence of rate control medication and other variables on the success of cardioversion. METHODS: This secondary analysis of a medical records review comprised 1,068 patients with RAFF who presented to eight Canadian EDs over 12 months. Univariate analysis was performed to find associations between predictors of conversion to sinus rhythm including use of rate control, rhythm control, and other variables. Predictive variables were incorporated into the multivariate model to calculate adjusted odds ratios (ORs) associated with successful cardioversion. RESULTS: A total of 634 patients underwent attempted cardioversion: 428 electrical, 354 chemical, and 148 both. Adjusted ORs for factors associated with successful electrical cardioversion were use of rate control medication, 0.39 (95% confidence interval [CI] 0.21-0.74); rhythm control medication, 0.28 (95% CI 0.15-0.53); and CHADS2 score > 0, 0.43 (95% CI 0.15-0.83). ORs for factors associated with successful chemical cardioversion were use of rate control medication, 1.29 (95% CI 0.82-2.03); female sex, 2.37 (95% CI 1.50-3.72); and use of procainamide, 2.32 (95% CI 1.43-3.74). CONCLUSION: We demonstrated reduced successful electrical cardioversion of RAFF when patients were pretreated with either rate or rhythm control medication. Although rate control medication was not associated with increased success of chemical cardioversion, use of procainamide was. Slowing the ventricular rate prior to cardioversion should be avoided.


Subject(s)
Anti-Arrhythmia Agents/adverse effects , Atrial Fibrillation/drug therapy , Atrial Flutter/drug therapy , Electric Countershock/methods , Premedication/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Amiodarone/adverse effects , Amiodarone/therapeutic use , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/therapy , Atrial Flutter/therapy , Canada , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Procainamide/adverse effects , Procainamide/therapeutic use , Propafenone/adverse effects , Propafenone/therapeutic use , Retrospective Studies , Treatment Outcome
11.
J Emerg Med ; 42(3): e47-50, 2012 Mar.
Article in English | MEDLINE | ID: mdl-19237259

ABSTRACT

BACKGROUND: Atrial fibrillation is a common dysrhythmia seen in the emergency department (ED). Chemical or electrical cardioversion may be performed on patients who have had atrial fibrillation for < 48 h duration and who are at low risk for thromboembolic events. Multiple studies suggest that intravenous procainamide is an appropriate agent in the treatment of acute atrial fibrillation due to its relatively low risk profile and high conversion rate. OBJECTIVES: A case is presented that demonstrates an adverse reaction to the use of intravenous procainamide for chemical cardioversion of atrial fibrillation in an otherwise hemodynamically stable patient. CASE REPORT: We report a case of lone paroxysmal atrial fibrillation in a patient with a structurally normal heart who suffered paradoxical accelerated atrioventricular nodal conduction and secondary hypotension in response to procainamide administration. CONCLUSION: When administering procainamide for chemical cardioversion of atrial fibrillation, a low threshold should be maintained for administration of a complementary rate-controlling agent, and facilities for immediate electrical cardioversion always must be available.


Subject(s)
Anti-Arrhythmia Agents/adverse effects , Atrial Fibrillation/drug therapy , Procainamide/adverse effects , Tachycardia/chemically induced , Atrioventricular Node/drug effects , Atrioventricular Node/physiopathology , Humans , Hypotension/chemically induced , Male , Middle Aged
13.
Ann Emerg Med ; 57(1): 13-21, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20864213

ABSTRACT

STUDY OBJECTIVE: Although recent-onset atrial fibrillation and flutter are common arrhythmias managed in the emergency department (ED), there is insufficient evidence to help physicians choose between 2 competing treatment strategies, rate control and rhythm control. We seek to evaluate variation in ED management practices for recent-onset atrial fibrillation and flutter patients at multiple Canadian sites and to determine whether hospital site was an independent predictor of attempted cardioversion. METHODS: We conducted a cross-sectional survey by health records review on an observational cohort of all eligible adult recent-onset atrial fibrillation and flutter cases, with onset of symptoms less than 48 hours, treated at 8 academic hospital EDs during a 12-month period, and evaluated the variation in practice among sites for important management strategies. RESULTS: Among the 1,068 study patients, 88.3% had atrial fibrillation and 11.7% had atrial flutter. The proportion of cases managed with rhythm control was 59.4% (interhospital range 42% to 85%) and, among these, electrocardioversion was attempted first for 44.2% (range 7% to 69%). There was variation in most management strategies, including use of rate control drugs 54.9% (range 37% to 65%), choice of procainamide as rhythm control drug 62.1% (range 15% to 89%), referral to cardiology in the ED 30.7% (range 16% to 64%), use of heparin 13.7% (range 1% to 29%), and outpatient cardiology referral 43.0% (range 30% to 65%). Adverse events were relatively uncommon and transient for patients undergoing attempts at pharmacologic (13.0%) or electrocardioversion (12.1%). Overall, 83.3% of patients were discharged home from the ED (range 73% to 90%). After controlling for 12 covariates, multivariate logistic regression found that factors independently associated with attempted cardioversion were age (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.95 to 0.98), history of electrocardioversion (OR 2.73; 95% CI 1.56 to 4.80), associated heart failure (OR 0.29; 95% CI 0.09 to 0.95), and hospital site (ORs ranged from 0.38 to 3.05). CONCLUSION: We demonstrated a high degree of variation in management approaches for recent-onset atrial fibrillation and flutter patients treated in academic hospital EDs. Individual hospital site, age, previous cardioversion, and associated heart failure were independent predictors for the use of rhythm control.


Subject(s)
Atrial Fibrillation/therapy , Atrial Flutter/therapy , Emergency Service, Hospital/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Academic Medical Centers/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Arrhythmia Agents/adverse effects , Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Atrial Flutter/drug therapy , Canada , Confidence Intervals , Cross-Sectional Studies , Electric Countershock/adverse effects , Electric Countershock/statistics & numerical data , Female , Fibrinolytic Agents/adverse effects , Fibrinolytic Agents/therapeutic use , Heparin/adverse effects , Heparin/therapeutic use , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Procainamide/adverse effects , Procainamide/therapeutic use , Young Adult
14.
CJEM ; 12(3): 181-91, 2010 May.
Article in English | MEDLINE | ID: mdl-20522282

ABSTRACT

OBJECTIVE: There is no consensus on the optimal management of recent-onset episodes of atrial fibrillation or flutter. The approach to these conditions is particularly relevant in the current era of emergency department (ED) overcrowding. We sought to examine the effectiveness and safety of the Ottawa Aggressive Protocol to perform rapid cardioversion and discharge patients with these arrhythmias. METHODS: This cohort study enrolled consecutive patient visits to an adult university hospital ED for recent-onset atrial fibrillation or flutter managed with the Ottawa Aggressive Protocol. The protocol includes intravenous chemical cardioversion, electrical cardioversion if necessary and discharge home from the ED. RESULTS: A total of 660 patient visits were included, 95.2% involving atrial fibrillation and 4.9% involving atrial flutter. The mean age of patients enrolled was 64.5 years. In total, 96.8% were discharged home and, of those, 93.3% were in sinus rhythm. All patients were initially administered intravenous procainamide, with a 58.3% conversion rate. A total of 243 patients underwent subsequent electrical cardioversion with a 91.7% success rate. Adverse events occurred in 7.6% of cases: hypotension 6.7%, bradycardia 0.3% and 7-day relapse 8.6%. There were no cases of torsades de pointes, stroke or death. The median lengths of stay in the ED were as follows: 4.9 hours overall, 3.9 hours for those undergoing conversion with procainamide and 6.5 hours for those requiring electrical conversion. CONCLUSION: This is the largest study to date to evaluate the Ottawa Aggressive Protocol, a unique approach to cardioversion for ED patients with recent-onset episodes of atrial fibrillation and flutter. Our data demonstrate that the Ottawa Aggressive Protocol is effective, safe and rapid, and has the potential to significantly reduce hospital admissions and expedite ED care.


Subject(s)
Atrial Fibrillation/therapy , Atrial Flutter/therapy , Clinical Protocols , Adult , Aged , Aged, 80 and over , Anti-Arrhythmia Agents/adverse effects , Anti-Arrhythmia Agents/therapeutic use , Electric Countershock/adverse effects , Emergencies , Female , Humans , Length of Stay , Male , Middle Aged , Ontario , Procainamide/adverse effects , Procainamide/therapeutic use , Retrospective Studies , Safety , Treatment Outcome
15.
Acad Emerg Med ; 17(3): 297-306, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20370763

ABSTRACT

OBJECTIVES: The objective was to compare the effectiveness of intravenous (IV) procainamide and amiodarone for the termination of spontaneous stable sustained ventricular tachycardia (VT). METHODS: A historical cohort study of consecutive adult patients with stable sustained VT treated with IV amiodarone or procainamide was performed at four urban hospitals. Patients were identified for enrollment by admissions for VT and treatment with the study agents in the emergency department (ED) from 1993 to 2008. The primary measured outcome was VT termination within 20 minutes of onset of study medicine infusion. A secondary effectiveness outcome was the ultimate need for electrical therapy to terminate the VT episode. Major adverse effects were tabulated, and blood pressure responses to medication infusions were compared. RESULTS: There were 97 infusions of amiodarone or procainamide in 90 patients with VT, but the primary outcome was unknown after 14 infusions due to administration of another antidysrhythmic during the 20-minute observation period. The rates of VT termination were 25% (13/53) and 30% (9/30) for amiodarone and procainamide, respectively. The adjusted odds of termination with procainamide compared to amiodarone was 1.2 (95% confidence interval [CI]=0.4 to 3.9). Ultimately, 35/66 amiodarone patients (53%, 95% CI=40 to 65%) and 13/31 procainamide patients (42%, 95% CI=25 to 61%) required electrical therapy for VT termination. Hypotension led to cessation of medicine infusion or immediate direct current cardioversion (DCCV) in 4/66 (6%, 95% CI=2 to 15%) and 6/31 (19%, 95% CI=7 to 37%) patients who received amiodarone and procainamide, respectively. CONCLUSIONS: Procainamide was not more effective than amiodarone for the termination of sustained VT, but the ability to detect a significant difference was limited by the study design and potential confounding. As used in practice, both agents were relatively ineffective and associated with clinically important proportions of patients with decreased blood pressure.


Subject(s)
Amiodarone/therapeutic use , Anti-Arrhythmia Agents/therapeutic use , Emergency Treatment/methods , Procainamide/therapeutic use , Tachycardia, Ventricular/drug therapy , Aged , Amiodarone/adverse effects , Anti-Arrhythmia Agents/adverse effects , Cohort Studies , Drug Administration Schedule , Electrocardiography , Female , Hospitals, Urban , Humans , Hypotension/chemically induced , Hypotension/epidemiology , Infusions, Intravenous , Linear Models , Logistic Models , Male , Massachusetts/epidemiology , Middle Aged , Multivariate Analysis , New York/epidemiology , Practice Guidelines as Topic , Procainamide/adverse effects , Retrospective Studies , Single-Blind Method , Tachycardia, Ventricular/diagnosis , Treatment Outcome
16.
Circ Arrhythm Electrophysiol ; 3(2): 134-40, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20194798

ABSTRACT

BACKGROUND: Intravenous amiodarone and procainamide are both used as therapies for refractory supraventricular tachycardia (SVT). However, no studies have compared the efficacy and safety of these agents in pediatric patients. METHODS AND RESULTS: All patients treated with intravenous amiodarone or procainamide during 25 consecutive months for the following mechanisms of SVT were included: orthodromic reciprocating tachycardia, intra-atrial reentrant tachycardia, and ectopic atrial tachycardia; junctional ectopic tachycardia was excluded. Treatment response was categorized as full success, partial success, or failure. Partial success was defined as clinical improvement and/or arrhythmia control but not meeting full success criteria. Adverse events were classified as major (requiring resuscitation) or minor (management changes). There were 40 episodes of SVT in 37 patients (median age, 34 days; 24 with congenital heart disease). Amiodarone was the initial therapy in 26 cases and procainamide in 14 cases. If partial and full success are combined, procainamide was successful in 71% of cases compared with 34% for amiodarone (P=0.046). If partial success is considered a treatment failure, procainamide was successful in 50% compared with 15% for amiodarone (P=0.029). Ten patients received the second medication after the first failed. Success was achieved in 5 of 8 amiodarone-to-procainamide crossovers compared with 1 of 2 procainamide-to-amiodarone crossovers. One major and 10 minor adverse events occurred in amiodarone patients versus 6 minor adverse events in procainamide patients (P=NS). CONCLUSIONS: In this cohort, procainamide achieved greater success compared with amiodarone in the management of recurrent SVT without statistically significant differences in adverse event frequency.


Subject(s)
Amiodarone/administration & dosage , Anti-Arrhythmia Agents/administration & dosage , Procainamide/administration & dosage , Tachycardia, Supraventricular/drug therapy , Acute Disease , Adolescent , Amiodarone/adverse effects , Anti-Arrhythmia Agents/adverse effects , Child , Child, Preschool , Female , Heart Defects, Congenital/complications , Humans , Infant , Infant, Newborn , Injections, Intravenous , Male , Practice Guidelines as Topic , Procainamide/adverse effects , Retrospective Studies , Secondary Prevention , Tachycardia, Supraventricular/complications , Treatment Outcome , Young Adult
17.
Lupus ; 18(11): 935-40, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19762393

ABSTRACT

Drug-induced lupus erythematosus (DILE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to continuous drug exposure and resolves after discontinuation of the offending drug. Similar to idiopathic lupus, DILE can be divided into systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Based on the literature review and retrospective analysis of our case series, we focused on the dermatological aspects of DILE. The cutaneous features of drug-induced SLE are protean, including particularly purpura, erythema nodosum and photosensitivity as well as the skin lesions characterizing both urticarial and necrotizing vasculitis. The typical laboratory profile of systemic DILE consists of positive antinuclear antibodies (ANA) and antihistone antibodies, the latter being regarded as the serum marker of this subset. The drugs most frequently implicated in the development of systemic DILE are hydralazine, procainamide, isoniazid and minocycline. Drug-induced SCLE usually presents with annular polycyclic or papulosquamous cutaneous manifestations as in the idiopathic form, but blisters or targetoid lesions mimicking erythema multiforme cannot rarely be associated. The clinical presentation is often generalized, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are usually present, whereas antihistone antibodies are uncommonly found. Drugs associated with SCLE include particularly calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide diuretics, terbinafine and the recently reported tumour necrosis factor (TNF)-alpha antagonists. Drug-induced CCLE is very rarely described in the literature and usually refers to fluorouracile agents or TNF-alpha antagonists. The picture is characterized by the occurrence of classic discoid lesions, but aspects of lupus tumidus can occasionally develop. ANA are demonstrated in around two-thirds of the cases. Management of DILE is based on the withdrawal of the offending drug. Topical and/or systemic corticosteroids and other immunosuppressive agents should be reserved for resistant cases.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Lupus Erythematosus, Cutaneous , Lupus Erythematosus, Discoid , Lupus Erythematosus, Systemic , Anti-Arrhythmia Agents/adverse effects , Anti-Bacterial Agents/adverse effects , Antihypertensive Agents/adverse effects , Antitubercular Agents/adverse effects , Autoantibodies/immunology , Humans , Hydralazine/adverse effects , Isoniazid/adverse effects , Lupus Erythematosus, Cutaneous/chemically induced , Lupus Erythematosus, Cutaneous/immunology , Lupus Erythematosus, Cutaneous/pathology , Lupus Erythematosus, Discoid/chemically induced , Lupus Erythematosus, Discoid/immunology , Lupus Erythematosus, Discoid/pathology , Lupus Erythematosus, Systemic/chemically induced , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/pathology , Minocycline/adverse effects , Procainamide/adverse effects , Skin Diseases/chemically induced , Skin Diseases/immunology , Skin Diseases/pathology
18.
Arch Dermatol Res ; 301(1): 99-105, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18797892

ABSTRACT

Drug-induced lupus erythematosus (DILE) is defined as a lupus-like syndrome temporally related to continuous drug exposure which resolves after discontinuation of the offending drug. There are currently no standard diagnostic criteria for DILE and the pathomechanisms are still unclear. Similarly to idiopathic lupus, DILE can be diveded into systemic (SLE), subacute cutaneous (SCLE) and chronic cutaneous lupus (CCLE). Systemic DILE is characterized by typical lupus-like symptoms including skin signs, usually mild systemic involvement and a typical laboratory profile with positive antinuclear and anti-histone antibodies, while anti-double strand (ds) DNA and anti-extractable nuclear antigens antibodies are rare. High risk drugs include hydralazine, procainamide and isoniazid. Drug-induced SCLE is very similar to idiopathic SCLE in terms of clinical and serologic characteristic, and it is more common than the systemic form of DILE. Drugs associated with SCLE include calcium channel blockers, angiotensin-converting enzyme inhibitors, interferons, thiazide diuretics and terbinafine. Drug-induced CCLE is very rarely reported in the literature and usually refers to fluorouracile agents or non steroidal anti-inflammatory drugs. Recently, cases of DILE have been reported with anti-TNFalpha agents. These cases present with disparate clinical features including arthritis/arthralgia, skin rash, serositis, cytopenia and variable laboratory abnormalities. DILE to anti-TNFalpha agents differs in several ways to classic DILE. The incidence of rashes is higher compared to classical systemic DILE. In most cases of classic DILE visceral involvement is rare, whereas several cases of anti-TNFalpha DILE with evidence of renal disease have been reported. Low serum complement levels as well as anti-extractable nuclear antigen antibodies and anti-dsDNA antibodies are rarely present in classic DILE, whereas they are reported in half the cases of anti-TNFalpha DILE; in contrast, anti-histone antibodies are described in classic DILE more often than in anti-TNFalpha DILE. Recognition of DILE in patients receiving anti-TNFalpha therapy can be difficult due to the symptoms of their underlying disease. A temporal association (months to years) of the offending drug with characteristic or suggestive symptoms, and resolution of symptoms on drug withdrawal is the best evidence for this diagnosis of DILE.


Subject(s)
Lupus Erythematosus, Cutaneous/chemically induced , Lupus Erythematosus, Systemic/chemically induced , Tumor Necrosis Factor-alpha/immunology , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Animals , Anti-Arrhythmia Agents/administration & dosage , Anti-Arrhythmia Agents/adverse effects , Antibodies/immunology , Antibodies/metabolism , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Antitubercular Agents/administration & dosage , Antitubercular Agents/adverse effects , Arthritis , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/adverse effects , Exanthema , Humans , Hydralazine/administration & dosage , Hydralazine/adverse effects , Interferons/administration & dosage , Interferons/adverse effects , Isoniazid/administration & dosage , Isoniazid/adverse effects , Lupus Erythematosus, Cutaneous/diagnosis , Lupus Erythematosus, Cutaneous/immunology , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/immunology , Naphthalenes/administration & dosage , Naphthalenes/adverse effects , Procainamide/administration & dosage , Procainamide/adverse effects , Serositis , Sodium Chloride Symporter Inhibitors/administration & dosage , Sodium Chloride Symporter Inhibitors/adverse effects , Terbinafine
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