Continuing Education Activity

Procainamide is a medication used to manage and treat ventricular arrhythmias, supraventricular arrhythmias, atrial flutter/fibrillation, and Wolf-Parkinson-White syndrome. It is in the antiarrhythmic Agent Class 1A class of medications. This activity reviews the indications, action, and contraindications for procainamide as a valuable agent in treating these arrhythmias.

Objectives:

• Identify the mechanism of action of procainamide.
• Describe the potential adverse effects of procainamide.
• Review the appropriate monitoring of procainamide.
• Summarize interprofessional team strategies for improving care coordination and communication to advance the use of procainamide and improve outcomes.

Indications

Procainamide is a medication used to manage and treat ventricular arrhythmias, supraventricular arrhythmias, atrial flutter, atrial fibrillation, AV nodal re-entrant tachycardia, and Wolf-Parkinson-White syndrome. It is a Class 1A antiarrhythmic agent.  This activity reviews the literature, indications, action, and contraindications for procainamide as a valuable agent in the treatment of arrhythmias.

Procainamide was initially approved by the US FDA in 1950 and fell out of favor due to its side effect profile and the development of newer antiarrhythmics. Procainamide usage has increased in recent years, and it is now seen as a viable option for several arrhythmias.

Procainamide has been used for chemical cardioversion in atrial flutter and atrial fibrillation. These are common arrhythmias seen in emergency department patients, but there is no consensus for optimal management. Stiell et al. looked at the usage of IV procainamide in 341 patients over five years. Adverse events were infrequent and included hypotension, bradycardia, atrioventricular block, and ventricular tachycardia. There were no cases of torsades de pointes, cerebrovascular accidents, or death. Most patients (94.4%) received a discharge to home. IV procainamide had a 52% conversion rate of atrial fibrillation to normal sinus and a 28% conversion rate from atrial flutter to normal sinus.[1]

One recent major study looked at the difference between amiodarone and procainamide in stable ventricular tachycardia. The PROCAMIO study has concluded that in patients with stable ventricular tachycardia, procainamide should be considered over the traditionally used amiodarone due to faster resolution of the arrhythmia, fewer major cardiac events, and is more efficacious in a subgroup of patients with structural heart disease.[2]

Researchers have also studied the utility of procainamide compared to lidocaine in terminating sustained ventricular tachycardia in patients with structural heart defects. In this retrospective study from Circulation Journal, procainamide was found to be more effective than lidocaine in the termination of the arrhythmia.[3]

Procainamide is indicated in patients with Wolf-Parkinson-White syndrome as it is important for acute termination of antidromic AV re-entrant tachycardia in stable patients. In particular, because the use of an AV nodal blocking agent in this patient population may enhance conduction down the accessory pathway and therefore induce ventricular tachycardia or ventricular fibrillation.[4]

Procainamide has also historically been used in diagnostic testing for Brugada syndrome; this was known as the “procainamide challenge,” which produces the standard Brugada-like pattern on ECG, which may have been otherwise unnoticed and thus identifying patients at risk for sudden cardiac death. However, this usage has fallen out of favor, as it has low sensitivity for detecting Brugada-like patterns and may also put the patient at risk of going into ventricular arrhythmia.[5]

Mechanism of Action

Procainamide is a class 1A anti-arrhythmic that binds to fast sodium channels inhibiting recovery after repolarization. It also prolongs the action potential and reduces the speed of impulse conduction. This action results in decreased myocardial excitability, slowed conduction velocity, and reduced myocardial contractility. It is possible that it acts as a negative inotrope and may cause peripheral vasodilation and hypotension, which may require cardioversion.

Administration

Procainamide is given IV or PO with the onset of action in 10 to 30 minutes. The loading dose is of IV procainamide is 10 to 17 mg/kg and administered at a rate of 20 to 50 mg/min. Alternatively, this may be dosed at 100 mg every 5 minutes in adult patients. The administration of this maintenance dose is from 1 to 4 mg/minute; however, the manufacturer labeling recommends 2 to 6 mg/minute.

Administration of oral procainamide dosing for supraventricular arrhythmia is at 50 mg/kg/24 hours divided into doses every 6 hours.

In the pediatric population, dosing divides into those less than 12 months in which a bolus dose of 7 to 10 mg/kg given over 15 to 30 minutes and those older than 12 months in which a bolus dose of 10 to 15 mg/kg is the regimen. An infusion rate of 20 to 50 mcg/kg/min follows the initial bolus.[6]

Procainamide is metabolized hepatically via acetylation to form N-acetyl procainamide (NAPA) via a substrate of CYP2D6. This compound is then excreted as NAPA. The half-life of procainamide is 2.5 to 5 hrs, and the maximum dose in current recommendations is 17 mg/kg. As such, clinicians may consider decreasing the dosing or frequency of procainamide in cases of hepatic impairment.[7]

Adverse Effects

The adverse effects of procainamide include cardiac toxicity, bradycardia, hypotension, drug-induced lupus erythematosus-like syndrome, and blood dyscrasias. QRS, QTc, and PR prolongation are the most potentially harmful cardiac side effects of procainamide and may become worse when levels of procainamide rise. Serial electrocardiograms are useful for monitoring these toxic effects during treatment with procainamide. Procainamide infusion may also increase the number of premature ventricular contractions in patients.

Another side effect of procainamide is hypotension, more commonly seen at doses of 20 mg/min. Drug-induced lupus erythematosus-like syndrome is rare and occurs due to the creation of positive ANA titers when taking the medication chronically. The symptoms of chronic use may include arthritis, arthralgias, and pleuritis and commonly resolve when usage stops.

Lastly, procainamide is known to cause certain blood dyscrasias. Procainamide has been known to cause bone marrow toxicity, leading to pancytopenia or agranulocytosis; this is usually due to hypersensitivity or varied immunologic mechanisms.[8][9]

Contraindications

Use with caution in patients with heart failure, electrolyte imbalances (particularly hypokalemia and hypomagnesemia), myasthenia gravis patients, and in hepatic or renal impairment. Procainamide also crosses the placenta and may be present in the milk of breastfeeding mothers, and as such, chronic use requires caution in this population.[10]

Monitoring

Procainamide monitoring during therapy of an acute arrhythmia should involve monitoring QRS duration via cardiac monitoring, and the clinician should stop therapy QRS increases by 50% of its original width. Also, blood pressure requires frequent monitoring during treatment.

Toxicity

Toxicity from procainamide overdose is rare as it is usually given IV in a monitored setting. However, it is plausible to administer a toxic dose accidentally or when a patient with renal impairment receives an inaccurate dose. Consultation of a medical toxicologist and regional poison control center is necessary in cases of oral procainamide overdose. Treatment would theoretically be similar to an overdose of other Class 1A antiarrhythmics, including quinidine and disopyramide, in which the patient receives hypertonic sodium bicarbonate to block sodium channels.[11]

Enhancing Healthcare Team Outcomes

There have been several high-quality studies as well as recommendations from the American Heart Association in utilizing procainamide as a viable option to terminate several different arrhythmias. However, procainamide should be used carefully in inpatient settings as it has several side effects that require monitoring. An interprofessional team that includes the treating physician, nurse, and pharmacist can help achieve the best possible outcomes. Care requires coordination between all interprofessional healthcare team members to ensure that everyone involved in the patient's care takes appropriate measures during therapy with procainamide. Cardiovascular monitoring, serial electrocardiograms, and frequent reassessments of the patient’s clinical status will ensure safety during usage. Instruction should be given for possible cardioversion if hypotension, bradycardia, or clinical deterioration occurs.[12] [Level 1]

The coordinated efforts of an interprofessional team will optimize therapeutic results with procainamide while minimizing adverse events. [Level 5]

Review Questions

• Access free multiple choice questions on this topic.
• Comment on this article.

References

1.

Stiell IG, Sivilotti MLA, Taljaard M, Birnie D, Vadeboncoeur A, Hohl CM, McRae AD, Rowe BH, Brison RJ, Thiruganasambandamoorthy V, Macle L, Borgundvaag B, Morris J, Mercier E, Clement CM, Brinkhurst J, Sheehan C, Brown E, Nemnom MJ, Wells GA, Perry JJ. Electrical versus pharmacological cardioversion for emergency department patients with acute atrial fibrillation (RAFF2): a partial factorial randomised trial. Lancet. 2020 Feb 01;395(10221):339-349. [PubMed: 32007169]

2.

Ortiz M, Martín A, Arribas F, Coll-Vinent B, Del Arco C, Peinado R, Almendral J., PROCAMIO Study Investigators. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. Eur Heart J. 2017 May 01;38(17):1329-1335. [PMC free article: PMC5410924] [PubMed: 27354046]

3.

Komura S, Chinushi M, Furushima H, Hosaka Y, Izumi D, Iijima K, Watanabe H, Yagihara N, Aizawa Y. Efficacy of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Circ J. 2010 May;74(5):864-9. [PubMed: 20339190]

4.

Correction to: 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Circulation. 2016 Sep 13;134(11):e232-3. [PubMed: 27619721]

5.

Obeyesekere MN, Klein GJ. Preventing Sudden Death in Asymptomatic Wolf-Parkinson-White Patients. JACC Clin Electrophysiol. 2018 Apr;4(4):445-447. [PubMed: 30067482]

6.

Guerrier K, Shamszad P, Czosek RJ, Spar DS, Knilans TK, Anderson JB. Variation in Antiarrhythmic Management of Infants Hospitalized with Supraventricular Tachycardia: A Multi-Institutional Analysis. Pediatr Cardiol. 2016 Jun;37(5):946-52. [PubMed: 27033244]

7.

Klotz U. Antiarrhythmics: elimination and dosage considerations in hepatic impairment. Clin Pharmacokinet. 2007;46(12):985-96. [PubMed: 18027986]

8.

Lawson DH, Jick H. Adverse reactions to procainamide. Br J Clin Pharmacol. 1977 Oct;4(5):507-11. [PMC free article: PMC1429167] [PubMed: 911600]

9.

Danielly J, DeJong R, Radke-Mitchell LC, Uprichard AC. Procainamide-associated blood dyscrasias. Am J Cardiol. 1994 Dec 01;74(11):1179-80. [PubMed: 7977085]

10.

Pittard WB, Glazier H. Procainamide excretion in human milk. J Pediatr. 1983 Apr;102(4):631-3. [PubMed: 6187910]

11.

Kim SY, Benowitz NL. Poisoning due to class IA antiarrhythmic drugs. Quinidine, procainamide and disopyramide. Drug Saf. 1990 Nov-Dec;5(6):393-420. [PubMed: 2285495]

12.

Writing Group Members. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm. 2019 Aug;16(8):e66-e93. [PubMed: 30703530]

Disclosure: Brian Pritchard declares no relevant financial relationships with ineligible companies.

Disclosure: Holly Thompson declares no relevant financial relationships with ineligible companies.