Is dosage and efficacy data on use of procainamide in patients experiencing persistent ventricular tachycardia cardiac arrest in whom amiodarone and lidocaine were not effective?

Is dosage and efficacy data on use of procainamide in patients experiencing persistent ventricular tachycardia cardiac arrest in whom amiodarone and lidocaine were not effective?

Comment by InpharmD Researcher

There is limited, conflicting data regarding the use of procainamide for cardiac arrest. A study observed procainamide in refractory ventricular fibrillation (VF) out-of-hospital cardiac arrest despite IV lidocaine and triple shock with no benefit in survival. In general, antiarrhythmics and vasopressors have not demonstrated improved outcomes for out-of-hospital refractory cardiac arrest.

Background

A 2018 article reviews the available literature on refractory ventricular fibrillation and out-of-hospital cardiac arrest. The authors did not find that antiarrhythmic or vasopressor medications observed consistent benefit in improving survival or neurological benefits. Procainamine, in particular, was noted to have fallen out of favor since the publication of the Markel et al. study (Table 1) which found no improvements in survival to hospital admission or discharge when used for refractory out-of-hospital cardiac arrest. [1]

A 1995 observational, cohort study observing the different Advanced Cardiac Life Support (ACLS) drugs used in adults undergoing cardiac arrest examine the use of procainamide in 20 patients. The specific dosing of procainamide was not described aside from being utilized as a simple administration during cardiopulmonary resuscitation and was likely the primary ACLS drug of choice. The odds ratio of 21.0 (95% confidence interval [CI] 5.2 to 84.0) were reported in favor of procainamide for survival for one-hour. [2]

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Is dosage and efficacy data on use of procainamide in patients experiencing persistent ventricular tachycardia cardiac arrest in whom amiodarone and lidocaine were not effective?

Level of evidence

C - Multiple studies with limitations or conflicting results Read more→

Please see Tables 1-2 for your response.

Procainamide and Survival in Ventricular Fibrillation Out-of-hospital Cardiac Arrest
Design	Retrospective cohort study N= 665
Objective	To examine the association between procainamide and survival from out-of-hospital cardiac arrest due to shock- and lidocaine-refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT)
Study Groups	Procainamide (n= 176) No procainamide (n= 489)
Inclusion Criteria	Age > 18 years; suffered a witnessed, nontraumatic, out-of-hospital cardiac arrest caused by heart disease with VF or pulseless VT as the first documented rhythm on emergency medical service (EMS) arrival; received more than three defibrillation shocks and at least one IV bolus dose of lidocaine
Exclusion Criteria	Arrested upon arrival of EMS, resuscitation judged to be futile by EMS upon arrival
Methods	Data were collected from a European surveillance system for cardiac arrest. Other modes of treatment for out-of-hospital cardiac arrest were allowed and could include epinephrine, norepinephrine, atropine, lidocaine, procainamide, magnesium, sodium bicarbonate, and calcium. Procainamine was considered a second-tier antiarrhythmic therapy reserved for refractory VF or pulseless VT patients use after failure of chock and lidocaine. Procainamide was typically dosed at 500 mg rapid IV infusion, repeated if necessary, up to a total dose of 17 mg/kg.
Duration	January 1, 1998 to December 31, 2007
Outcome Measures	Primary: live admission to hospital and survival to hospital discharge Secondary: odds ratio (OR) between procainamide and the outcome after adjusting for patient demographic and resuscitation characteristics, then further adjusting for other cardiac medication used during resuscitation (epinephrine, magnesium, and bretylium)
Baseline Characteristics		Procainamide (n= 176)	No procainamide (n= 489)
	Age, years	63.0 ± 12.5	63.7 ± 13.9
	Male	152 (86.4%)	388 (79.3%)
	Arrest in public Bystander CPR performed	62 (35.2%) 112 (63.6%)	174 (35.6%) 338 (69.1%)
	Dispatch to arrival of first EMS unit, min	4.9 ± 2.2	4.8 ± 2.0
	Total number of shocks	12.4 ± 6.6	7.0 ± 3.2
	Estimated length of resuscitation, min	47.3 ± 15.9	38.5 ± 13.3
	EMS interventions Epinephrine Magnesium Bretylium	174 (98.9%) 58 (33.0%) 30 (17.0%)	415 (84.9%) 49 (10.0%) 26 (5.3%)
	Procainamide dose administered, mg Lidocaine dose administered, mg	742.9 ± 341.6 266.5 ± 67.5	-- 189.0 ± 79.0
Results	Endpoint	Procainamide (n= 176)	No procainamide (n= 489)	p-Value
	Admitted alive to the hospital Survived to hospital discharge	80 (45.5%) 33 (18.8%)	305 (62.4%) 156 (31.9%)	<0.001 <0.001
	Surviving in hospital, adjusted OR for clinical and resuscitation characteristics (95% confidence interval [CI])	0.52 (0.36 to 0.75)
	Surviving in hospital, adjusted OR for other cardiac medications (95% CI)	1.02 (0.66 to 1.57)
Adverse Events	N/A
Study Author 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.
InpharmD Researcher Critique	This study took place in a well-established EMS service system which was associated with high survival rates. Whether the findings can be applied to the general communities cannot be determined. There was not enough power to sufficiently establish statistical importance of the findings. Certain patient-related parameters, such as neurological status, upon discharge was not reported in this retrospective study.

References:

Markel DT, Gold LS, Allen J, et al. Procainamide and survival in ventricular fibrillation out-of-hospital cardiac arrest. Acad Emerg Med. 2010;17(6):617-623. doi:10.1111/j.1553-2712.2010.00763.x

Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study
Design	A randomized, multicentre, open-label, comparison study N= 62
Objective	To determine the safety and efficacy of intravenous procainamide and amiodarone for the acute treatment of tolerated wide QRS complex (probably ventricular) tachycardia
Study Groups	Procainamide (n= 33) Amiodarone (n= 29)
Inclusion Criteria	Age > 18 years, regular wide QRS complex tachycardia requiring medical attention, regular heart rhythm with rate ≥ 120 bpm, tachycardia QRS duration ≥120 ms, good hemodynamic tolerance defined as; systolic blood pressure ≥ 90 mmHg, absence of dyspnoea at rest, absence of peripheral hypoperfusion signs, and no severe anginal symptoms
Exclusion Criteria	Treatment with either intravenous amiodarone or intravenous procainamide during the previous 24 hours, poor hemodynamic tolerance that required urgent termination, irregular tachycardia, supraventricular tachycardia
Methods	Patients were randomly assigned in an open-labeled fashion to receive either intravenous procainamide, single-dose 10 mg/kg over 20 min, or intravenous amiodarone, single-dose 5 mg/kg over 20 min with a 1:1 ratio. There was an observation period of 24 hours after the end of the study period.
Duration	Duration: 40 min from infusion initiation, 20 min for drug administration, and 20 min following administration
Outcome Measures	Primary outcome: major cardiac adverse event Secondary outcome: acute termination of tachycardia, safety
Baseline Characteristics		Procainamide (n= 33)	Amiodarone (n= 29)
	Age, years	62 ± 16	69 ± 11
	Emergency Room	26 (79%)	24 (83%)
	Heart Disease Structural heart disease Coronary artery disease Dilated cardiomyopathy Arrhythmogenic right ventricular cardiomyopathy Other	26 (79%) 15 (45%) 6 (18%) 1 (3%) 4 (12%)	23 (79%) 15 (52%) 4 (14%) 1 (3%) 3 (10%)
	LVEF	40% ± 13% (n= 29)	37% ± 15% (n= 24)
	Potassium (mmol/L)	4.4 ± 0.6 (n= 28)	4.6 ± 0.7 (n= 26)
	Adenosine at the emergency room	4 (12%)	0
	Previous pharmacological treatments Amiodarone Beta-Blocker ACE/ARB Calcium channel blocker Other class I or III antiarrhythmic drugs	0 11 (33%) 16 (48%) 2 (6%) 0	5(17%) 10 (34%) 14 (48%) 2 (7%) 0
Results	Endpoint	Procainamide (n= 33)	Amiodarone (n= 29)	p-Value
	Major cardiac adverse events during study period	3 (9%)	12 (41%)	0.006
	Total adverse events during the study period	8 (24%)	14 (48%)	0.052
	Tachycardia termination during the study period	22 (67%)	11 (38%)	0.026
	Time to tachycardia termination, min	14 ± 10	16 ± 5	0.3
Adverse Events	Common Adverse Events: hypotension (procainamide 3/33, amiodarone 5/29)
	Serious Adverse Events: severe hypotension requiring immediate DCCV (procainaminde 2/33, amiodarone 6/29)
	Percentage that Discontinued due to Adverse Events: not disclosed
Study Author Conclusions	Procainamide therapy was associated with fewer major cardiac adverse events and a higher proportion of tachycardia termination within 40 min.
InpharmD Researcher Critique	The study did not meet the required number of patients to achieve sufficient power (due to the low number of eligible patients for recruitment). Along with the small sample size, results are exploratory at best.

References:

Ortiz M, Martín A, Arribas F, et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. Eur Heart J. 2017;38(17):1329-1335. doi:10.1093/eurheartj/ehw230