Exercise-Induced QRS Prolongation in Brugada Syndrome: Implications for Improving Disease Phenotyping and Diagnosis.

BACKGROUND: Abnormal ventricular activation at rest is reported in Brugada syndrome (BrS). OBJECTIVES: The aim of this study was to evaluate the usefulness of dynamic changes in ventricular activation during exercise to improve disease phenotyping and diagnosis of BrS. METHODS: Digital 12-lead electrocardiograms during stress testing were analyzed retrospectively at baseline, peak exercise, and recovery in 53 patients with BrS and 52 controls. Biventricular activation was assessed from QRS duration (QRSd), whereas right ventricular activation was assessed from S wave duration in the lateral leads (I and V6) and terminal R wave duration in aVR. Exercise-induced changes in QRS parameters to predict a positive procainamide response were assessed in separate test and validation cohorts with suspected BrS. RESULTS: Baseline electrocardiogram parameters were similar between BrS and controls. QRSd shortened with exercise in all controls but prolonged in all BrS (-6.1 ± 6.0 ms vs 7.1 ± 6.5 ms [P < 0.001] in V6). QRSd in recovery was longer in BrS compared with controls (90 ± 12 ms vs 82 ± 11 ms in V6; P = 0.002). Both groups demonstrated exercise-induced S duration prolongation in V6, with greater prolongation in BrS (8.2 ± 14.3 ms vs 1.2 ± 12.4 ms; P < 0.001). Any exercise-induced QRSd prolongation in V6 differentiated those with a positive vs negative procainamide response with 100% sensitivity and 95% specificity in the test cohort, and 87% sensitivity and 93% specificity in the validation cohort. CONCLUSIONS: Exercise-induced QRSd prolongation is ubiquitous in BrS primarily owing to delayed right ventricular activation. This electrocardiogram phenotype predicts a positive procainamide response and may provide a noninvasive screening tool to aid in the diagnosis of BrS before drug challenge.

Procainamide pharmacokinetics during extracorporeal membrane oxygenation.

Procainamide is a useful agent for management of ventricular arrhythmia, however its disposition and appropriate dosing during extracorporeal membrane oxygenation (ECMO) is unknown. We report experience with continuous procainamide infusion in a critically ill adult requiring venoarterial ECMO for incessant ventricular tachycardia. Pharmacokinetic analysis of procainamide and its metabolite, N-acetylprocainamide (NAPA), was performed using serum and urine specimens. Kidney function was preserved, and sequencing of the N-acetyltransferase 2 gene revealed the patient was a phenotypic slow acetylator. Procainamide volume of distribution and half-life were calculated and found to be similar to healthy individuals. However, despite elevated serum procainamide concentrations, NAPA concentrations remained far lower in the serum and urine. The magnitude of procainamide and NAPA discordance suggested alternative contributors to the deranged pharmacokinetic profile, and we hypothesized NAPA sequestration by the ECMO circuit. Ultimately, the patient received orthotopic cardiac transplantation and was discharged home in stable condition. Procainamide should be used cautiously during ECMO, with close therapeutic drug monitoring of serum procainamide and NAPA concentrations. The achievement of therapeutic NAPA concentrations while maintaining safe serum procainamide concentrations during ECMO support may be challenging.

Procainamide for shockable rhythm cardiac arrest in the Resuscitation Outcome Consortium.

BACKGROUND: With recent negative studies of amiodarone and lidocaine for cardiac arrest, research into other antiarrhythmics is warranted. Literature on procainamide in cardiac arrest is limited. We evaluated procainamide for out-of-hospital cardiac arrests (OHCA) from the Resuscitation Outcomes Consortium (ROC). METHODS: We included all ROC Epistry 3 OHCAs with an initial shockable rhythm that received an antiarrhythmic. We stratified cases by antiarrhythmic: procainamide, amiodarone, or lidocaine. The outcomes were prehospital return of spontaneous circulation (ROSC), ROSC in the ED, and survival to hospital discharge. We defined propensity scores based on possible confounders utilizing 1:1 propensity score matching to compare procainamide to amiodarone and lidocaine. We analyzed the matched data using logistic regression. We also used multivariable logistic regression to evaluate the association between antiarrhythmic and outcomes. RESULTS: 3087 subjects met inclusion criteria; 51 patients received only procainamide, 1776 received amiodarone, and 1418 received lidocaine. On propensity score analysis and compared to procainamide, amiodarone had similar prehospital ROSC (OR 0.7, 95% CI 0.3-1.8), ED ROSC (OR 0.6, 95% CI 0.3-1.3), and survival (OR 1.0, 95% CI 0.3-3.1). Lidocaine also had a similar prehospital ROSC (OR 0.9, 95% CI 0.4-2.2), ED ROSC (OR 1.2, 95% CI 0.5-2.7), and survival (OR 1.4, 95% CI 0.5-4.0). However, using multivariable regression, amiodarone had lower prehospital ROSC than procainamide (aOR 0.3, 95% CI 0.1-0.6). CONCLUSIONS: While associated with increased prehospital ROSC when compared with amiodarone using multivariable regression, procainamide otherwise had similar prehospital ROSC, ED ROSC, and survival. The role of procainamide in OHCA remains unclear.

Chemical screens in a zebrafish model of CHARGE syndrome identifies small molecules that ameliorate disease-like phenotypes in embryo.

CHARGE syndrome is an autosomal dominant congenital disorder caused primarily by mutations in the CHD7 gene. Using a small molecule screen in a zebrafish model of CHARGE syndrome, we identified 4 compounds that rescue embryos from disease-like phenotypes. Our screen yielded DAPT, a Notch signaling inhibitor that could ameliorate the craniofacial, cranial neuronal and myelination defects in chd7 morphant zebrafish embryos. We discovered that Procainamide, an inhibitor of DNA methyltransferase 1, was able to recover the pattern of expression of isl2a, a cranial neuronal marker while also reducing the effect on craniofacial cartilage and myelination. M344, an inhibitor of Histone deacetylases had a strong recovery effect on craniofacial cartilage defects and could also modestly revert the myelination defects in zebrafish embryos. CHIC-35, a SIRT1 inhibitor partially restored the expression of isl2a in cranial neurons while causing a partial reversion of myelination and craniofacial cartilage defects. Our results suggest that a modular approach to phenotypic rescue in multi-organ syndromes might be a more successful approach to treat these disorders. Our findings also open up the possibility of using these compounds for other disorders with shared phenotypes.

Flecainide Versus Procainamide in Electrophysiological Study in Patients With Syncope and Wide QRS Duration.

OBJECTIVES: This study sought to compare the differences between procainamide and flecainide to stress the His-Purkinje system during electrophysiological study (EPS) in patients with syncope and bundle branch block (BBB). BACKGROUND: Patients with syncope and BBB are at risk of developing atrioventricular block. EPS is recommended including class I drug challenge to unmask His-Purkinje disease in cases with baseline normal His-ventricular interval. There is little data on differences between different class I drugs. METHODS: This was a prospective study of all consecutive patients undergoing EPS for syncope and BBB at a single center (January 1, 2012 to June 30, 2017). Of those patients with negative baseline EPS, 2 cohorts were compared: group A (historical cohort: procainamide) and group B (flecainide). RESULTS: During the study, 271 patients (age 73.9 ± 12.1 years, 64.9% male, QRS duration: 139.4 ± 13.9 ms) underwent EPS. In 166, baseline EPS was negative and class I drug challenge was performed (90 procainamide, 76 flecainide). The final value and percentage increase in the His-ventricular interval (76 ± 16 ms vs. 64 ± 10 ms and 22.5 ± 6.2% vs. 11.8 ± 5.3%; p < 0.001) and diagnostic yield (14.5% vs. 7.8%, p = 0.04) were higher with flecainide. No differences were found in baseline characteristics. During follow-up (25.8 ± 6.3 months), 39 patients (24.8%) with negative EPS (19.2% with flecainide vs. 30.1% with procainamide: relative risk: 5.1; 95% confidence interval: 2.6 to 10.2; p < 0. 001) received a pacemaker. CONCLUSIONS: Flecainide has a higher diagnostic yield than does procainamide in patients with BBB, syncope, and negative baseline EPS due to a greater increase of the His-ventricular interval. Additionally, there is a lesser need for pacemaker implantation in patients in whom the class I drug test using flecainide was negative.

Best Clinical Practice: Emergency Medicine Management of Stable Monomorphic Ventricular Tachycardia.

BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation are the causes of approximately 300,000 deaths per year in the United States. VT is classified based on hemodynamic status and appearance. Stable, monomorphic VT treatment is controversial. OBJECTIVE: Our aim was to provide emergency physicians with an evidence-based review of the medical management of stable, monomorphic VT. DISCUSSION: Stable, monomorphic VT is part of a larger class of ventricular dysrhythmias defined by a rate of at least 120 beats/min with QRS > 120 ms without regularly occurring P:QRS association. Little controversy exists for the treatment of hemodynamically unstable VT. The medical management of hemodynamically stable monomorphic VT is surrounded by controversy. Direct current cardioversion is most efficacious. Guidelines for the treatment of stable VT from the American Heart Association provide a IIa recommendation for procainamide, compared with a IIb recommendation for both amiodarone and sotalol. Studies evaluating procainamide, lidocaine, amiodarone, and sotalol suffer from poor design, difference in inclusion and exclusion criteria, small sample size, and outcome determination. Procainamide demonstrates the greatest efficacy. If procainamide is selected, a maximum dose of 10 mg/kg at 50-100 mg/min intravenous (IV) over 10-20 min should be provided with monitoring of blood pressure and electrocardiogram. Monomorphic VT with acute myocardial ischemia requires further study. CONCLUSIONS: Optimal management of stable, monomorphic VT includes direct current cardioversion. If medical management is chosen, procainamide is most efficacious, though current literature suffers from poor design.

Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats.

Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1) used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS). Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg) accompanied by procainamide therapy (50 mg/kg). During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6) levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis.

Continuous intravenous antiarrhythmic agents in the intensive care unit: strategies for safe and effective use of amiodarone, lidocaine, and procainamide.

The development of cardiac arrhythmias in the intensive care unit is common and associated with poor prognoses and outcomes. Because of the complexity of patients admitted to the intensive care unit, the management of arrhythmias is often difficult and may require multiple therapeutic interventions. In order for clinicians to appropriately manage arrhythmias, a thorough understanding of all available therapies, including intravenous antiarrhythmic agents, is essential. Suitable antiarrhythmic agents for use in the critical care setting include amiodarone, lidocaine, and procainamide. While these agents can be effective in managing cardiac arrhythmias, they also possess significant disadvantages and require additional monitoring during use. Therapy with these agents is often complicated because of the presence of significant associated adverse effects, clinician unfamiliarity, variable dosing strategies, and the potential for drug-drug interactions. The purpose of this review is to discuss indications and strategies for safe and effective use of amiodarone, lidocaine, and procainamide.

Performance of an expedited rhythm control method for recent onset atrial fibrillation in a community hospital.

BACKGROUND: A standard approach to recent onset atrial fibrillation (AF) in the emergency department (ED) in the United States has not been established. PURPOSE: The purpose of this prospective clinical trial was to determine how an ED protocol emphasizing rhythm control for recent onset AF compared similar patients receiving standard therapy in the same facility. METHODS: We enrolled consecutive patients presenting to our community hospital with recent onset AF into a protocol, which called for rhythm control with procainamide and if unsuccessful electrical cardioversion and discharge home. We compared this prospective cohort with matched historical controls. Primary outcome was admission rate. We also compared ED conversion rates and lengths of stay (LOS). We reported 30-day data on the study group including ED recidivism, recurrent AF, outpatient follow-up, and any important adverse events. RESULTS: Fifty-four patients were enrolled in the study group with 4 being admitted compared with 30 of 50 in the historical control group. Ninety-four percent of the study group converted compared with 28% in the historical control. Both hospital and ED LOS were significantly shorter for the study group. Six patients had recurrent AF, and 4 of those returned to the ED. CONCLUSION: An ED protocol that uses rhythm control decreased hospital admission and LOS, and there were no adverse events at 30 days.

Verapamil-sensitive idiopathic left ventricular tachycardia in a 6-month-old: unique considerations in diagnosis and management in an infant.

Idiopathic left ventricular tachycardia of the Belhassen type is rare in infants. We present a 6-month-old infant girl with a wide-complex tachycardia with right bundle branch block QRS morphology, a superior axis, and atrioventricular dissociation, consistent with a left anterior fascicular tachycardia. Initial echocardiogram revealed depressed ventricular function. The tachycardia was unresponsive to therapeutic trials of adenosine, esmolol, procainamide, and lidocaine. There was brief conversion of the tachycardia to sinus rhythm with transesophageal atrial overdrive pacing, suggesting a reentrant mechanism of the arrhythmia. Ultimately, the judicious administration of intravenous verapamil resulted in termination of the arrhythmia, which has been sustained on oral therapy.

Use of procainamide for conversion of acute onset AF following pericardiocentesis in a dog.

A 9 yr old spayed female golden retriever was evaluated for anorexia and suspected gastric dilatation. Subsequent evaluation the following day determined the dog to have pericardial effusion. Muffled heart sounds and jugular pulses were noted on physical exam, and the dog was diagnosed with pleural and pericardial effusion. A sinus rhythm with a rate of 142 beats/min was documented on a surface electrocardiogram (EKG). Following pericardiocentesis, the heart rate increased to 260 beats/min, the rhythm became irregular, and the systemic blood pressure decreased. Atrial fibrillation (AF) was confirmed by EKG. Procainamide was administered IV over 15 min, resulting in successful conversion of AF to sinus rhythm and clinical improvement. Procainamide is one of several antiarrhythmic medications that are used for the conversion of acute AF in humans; however, its utility and efficacy in dogs in the setting of AF has not previously been reported. This case highlights a unique complication of performing a pericardiocentesis that requires immediate treatment and describes a potential treatment option for the conversion of acute AF in dogs.

[Clinico-economical aspects of cardioversion of paroxysmal atrial fibrillation at phehospital stage and during hospitalization].

We carried out clinico-economical analysis of 2 tactics of rhythm restoration in patients with paroxysmal atrial fibrillation (AF) lasting less than 48 hours: cardioversion at prehospital stage with intravenous procainamide and inhospital cardioversion with any method. This retrospective study was based on the data from department of urgent aid of an outpatient clinic. The results showed that within 48 hours inhospital was a was more effective, safe, and more economically profitable compared with administration of procainamide at prehospital stage. Intravenous procainamide resulted in effective cardioversion in 70.6% of patients. It was associated with arterial hypotension and proarrhythmogenic action in 14,7% of cases. Patients with effective cardioversion with procainamide had lesser mean values of left ventricular anterior-posterior dimension (echocardiography) and shorter duration of arrhythmia.

Use of rate control medication before cardioversion of recent-onset atrial fibrillation or flutter in the emergency department is associated with reduced success rates.

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.

Intraosseous infusion is unreliable for adenosine delivery in the treatment of supraventricular tachycardia.

Supraventricular tachycardia (SVT) is a common tachyarrhythmia in the pediatric population that can necessitate immediate treatment. Adenosine has been well studied as a mainstay treatment, but the methods of adenosine administration have not been very well delineated. The intraosseous technique has presented itself as a possible method of administration. We describe 2 cases in which adenosine was administered through bone marrow infusion to convert SVT without success. The cases we describe show that intraosseous is not a reliable method of administering adenosine to stop SVT. Both patients presented with SVT refractory to vagal maneuvers and difficult intravenous placement. Intraosseous access was achieved, but administration of adenosine at increasing doses was unable to successfully convert the arrhythmia.

Síncope y bloqueo de rama. Rendimiento del uso escalonado del estudio electrofisiológico y de la monitorización electrocardiográfica prolongada / Syncope and bundle branch block. Diagnostic yield of a stepped use of electrophysiology study and implantable loop recorders

Introducción y objetivos. El objetivo del estudio es evaluar la utilidad de un protocolo diagnóstico escalonado mediante estudio electrofisiológico (EEF) y registrador de eventos implantable (REI) en pacientes con síncope y bloqueo de rama (BR). Métodos. Se realizó un EEF con provocación farmacológica con procainamida en 85 pacientes consecutivos remitidos por síncope y BR tras una evaluación inicial no diagnóstica. En aquellos sin indicación de desfibrilador implantable, se implantó un REI. Se realizó seguimiento hasta el diagnóstico o el agotamiento de la batería del dispositivo. Resultados. El EEF fue diagnóstico en 36 pacientes (42%); el mecanismo más frecuente fue el bloqueo auriculoventricular (BAV) paroxístico (n=27), seguido por la taquicardia ventricular (TV) (n=6). Todos los pacientes con TV tuvieron cardiopatía estructural y mayor prevalencia de BR izquierda. Se implantó un REI a 38 pacientes, y se alcanzó un diagnóstico en 13 (34%); el BAV paroxístico fue el más frecuente (n=10). La mediana de seguimiento hasta el diagnóstico de BAV paroxístico mediante el REI fue 97 días (intervalo intercuartilo, 60-117 días). El BAV paroxístico fue más frecuente en los pacientes con BR derecha y PR prolongado y/o desviación del eje. No se observaron TV o muertes arrítmicas durante el seguimiento. Conclusiones. En pacientes con síncope y BR, la etiología principal está representada por el BAV paroxístico, seguido por la TV. El uso escalonado del EEF y del REI en los casos negativos permite alcanzar un rendimiento diagnóstico alto y con seguridad, dado que la TV suele identificarse durante el EEF(AU)

Introduction and objectives: The objective of this study was to determine the diagnostic yield of a stepped protocol involving an electrophysiologic study (EPS) and implantable loop recorders (ILR) in patients with syncope and bundle branch block (BBB). Methods: Eighty-five consecutive patients referred for syncope and BBB after initial non-diagnostic assessment underwent EPS including a pharmacological challenge with procainamide. Those patients without indication for defibrillator implantation received ILRs. Follow-up continued until diagnosis or end of battery life. Results: The EPS was diagnostic in 36 patients (42%). The most frequent diagnoses were paroxysmal atrioventricular block (AVB) (n = 27), followed by ventricular tachycardia (VT) (n = 6). All patients with VT had structural heart disease; left BBB was more prevalent in this group. Thirty-eight patients received ILRs and diagnosis was achieved in 13 (34%) of them; paroxysmal AVB (n = 10) was the most frequent diagnosis. Median follow-up to diagnosis of paroxysmal AVB was 97 days (interquartile range 60-117 days). Paroxysmal AVB was more frequent in patients with right BBB and prolonged PR interval and/or axis deviation. We found no occurrence of VT or arrhythmic death during follow-up. Conclusions: The most common etiology of syncope in patients with BBB was paroxysmal AVB, followed by VT. The stepped use of EPS and ILR in negative patients enables us to safely achieve a high diagnostic yield, given that VT is usually diagnosed during EPS(AU)

Variation in management of recent-onset atrial fibrillation and flutter among academic hospital emergency departments.

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.

Procainamide and survival in ventricular fibrillation out-of-hospital cardiac arrest.

OBJECTIVES: Procainamide is an antiarrhythmic drug of unproven efficacy in cardiac arrest. The association between procainamide and survival from out-of-hospital cardiac arrest was investigated to better determine the drug's potential role in resuscitation. METHODS: The authors conducted a 10-year study of all witnessed, out-of-hospital, ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) cardiac arrests treated by emergency medical services (EMS) in King County, Washington. Patients were considered eligible for procainamide if they received more than three defibrillation shocks and intravenous (IV) bolus lidocaine. Four logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) describing the relationship between procainamide and survival. RESULTS: Of the 665 eligible patients, 176 received procainamide, and 489 did not. On average, procainamide recipients received more shocks and pharmacologic interventions and had lengthier resuscitations. Adjusted for their clinical and resuscitation characteristics, procainamide recipients had a lower likelihood of survival to hospital discharge (OR = 0.52; 95% CI = 0.36 to 0.75). Further adjustment for receipt of other cardiac medications during resuscitation negated this apparent adverse association (OR = 1.02; 95% CI = 0.66 to 1.57). CONCLUSIONS: In this observational study of out-of-hospital VF and pulseless VT arrest, procainamide as second-line antiarrhythmic treatment was not associated with survival in models attempting to best account for confounding. The results suggest that procainamide, as administered in this investigation, does not have a large impact on outcome, but cannot eliminate the possibility of a smaller, clinically relevant effect on survival.