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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.
ACADEMIC EMERGENCY MEDICINE 2010; 17:617–623 © 2010 by the Society for Academic Emergency Medicine
Antiarrhythmic medications are frequently during resuscitation from cardiac arrest, although research supporting their efficacy in this setting is scarce.1–4 Supporting evidence is stronger for their use in the treatment of hemodynamically stable arrhythmias,5 which, along with encouraging results from some animal studies,6 has spurred the extension of their use to the resuscitation of hemodynamically unstable cardiac arrest in humans. Antiarrhythmic agents currently recommended by the American Heart Association (AHA) for the treatment of cardiac arrest include amiodarone, lidocaine, and magnesium.4
Procainamide is a Vaughn Williams Class IA antiarrhythmic with conduction-slowing and vasodilatory properties. Currently, the AHA recommends procainamide for hemodynamically stable ventricular arrhythmias and atrial arrhythmias in patients with preserved ventricular function, but makes no recommendations about the use of the drug for the treatment of cardiac arrest.4 Indeed, the sum of the world’s published experience with intravenous (IV) procainamide in cardiac arrest is limited to the reporting of outcomes in a subgroup of only 20 patients from a larger observational study7 and no randomized clinical trials.
For patients with cardiac arrest in whom defibrillation or first-line cardiac medications are unsuccessful, alternative treatments are limited. A better understanding of alternative treatments such as procainamide may have important ramifications for determining the treatment of cardiac arrest. In the King County, Washington, emergency medical services (EMS) system, procainamide is a second-line treatment option, and its use is systematically tracked in a comprehensive out-of-hospital cardiac arrest surveillance system. Using this 10-year data set, we examined 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).
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During the 10-year study period, 8,092 patients were treated by EMS personnel in King County for out-of-hospital cardiac arrest, of whom 1,448 were at least 18 years of age and suffered a witnessed, nontraumatic VF or pulseless VT arrest caused by heart disease. Of this group, we excluded 196 patients whose arrests occurred after the arrival of EMS personnel and 587 patients who did not meet the minimum resuscitation criteria used in this study (more than 3 shocks and at least one IV bolus of lidocaine). The final study population consisted of 665 patients, 176 of whom received procainamide and 489 of whom did not (Figure 1).
Figure 1. Overall composition of the study population. EMS = emergency medical services; VF = ventricular fibrillation; VT = ventricular tachycardia.
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Baseline demographics, event characteristics, and intervention characteristics of the final study population are presented in Table 1. On average, procainamide recipients were comparable to nonrecipients in age, but were more likely than nonrecipients to be male, to have received a greater numbers of shocks, and to have had a longer duration of resuscitation. They were also more likely to have received epinephrine, magnesium, and bretylium (all but one patient received at least one of these medications) and to have received higher total doses of epinephrine and lidocaine. Procainamide recipients did not significantly differ from nonrecipients in terms of the location of their arrests, the frequency of bystander CPR, or EMS response intervals.
Table 1. Baseline Characteristics of the 665 Study Patients
|Characteristic||All Procainamide Recipients (n = 176)||Patients Not Treated With Procainamide (n = 489)|
|Age (yr), mean (±SD), median (n)||63.0 (±12.5), 63.0||63.7 (±13.9), 64.0|
|Males||62.7 (±12.7), 63.0 (152)||63.5 (±13.8), 64.0 (388)|
|Females||64.9 (±11.5), 64.0 (24)||64.7 (±14.7), 65.0 (101)|
|Male sex, n (% of group)||152 (86.4)|| 388 (79.3)|
|Arrest in public, n (% of group)|| 62 (35.2)|| 174 (35.6)|
|Bystander CPR, n (% of group)||112 (63.6)|| 338 (69.1)|
|Continuous variables, mean (±SD), median|
| Dispatch to arrival of first EMS unit (BLS or ALS) (minutes)||4.9 (±2.2), 5.0 (valid n = 161)||4.8 (±2.0), 4.8 (valid n = 453)|
| Dispatch to ALS arrival (minutes)||8.3 (±3.6), 8.0 (valid n = 176)||8.5 (±3.7), 8.0 (valid n = 461)|
| Total number of shocks (BLS and ALS)||12.4 (±6.6), 10.0||7.0 (±3.2), 6.0|
| Estimated length of resuscitation (minutes)*||47.3 (±15.9), 46.9 (valid n = 149)||38.5 (±13.3), 37.5 (valid n = 423)|
|EMS interventions, n (% of group)|
| Epinephrine||174 (98.9)|| 415 (84.9)|
| Magnesium|| 58 (33.0)|| 49 (10.0)|
| Bretylium|| 30 (17.0)|| 26 (5.3)|
|Medication dosages (mg), mean (±SD), median (n)|
| Epinephrine (mg)||6.8 (±4.2), 6.0 (174)||4.4 (±3.2), 4.0 (414)|
| Lidocaine (mg)||266.5 (±67.5), 300.0 (175)||189.0 (±79.0), 200.0 (488)|
| Magnesium (g)||2.6 (±1.4), 2.0 (58)||2.7 (±1.9), 2.0 (49)|
| Bretylium (mg)†||870.0 (±481.5), 950.0 (30)||692.3 (±376.2), 500.0 (26)|
| Procainamide (mg)||742.9 (±341.6), 500.0||—|
|Outcomes, number (% of group)|
| Admitted alive to hospital|| 80 (45.5)|| 305 (62.4)|
| Survived to hospital discharge|| 33 (18.8)||1 56 (31.9)|
Univariate (unadjusted) analysis showed that procainamide recipients, compared with nonrecipients, were less likely to be admitted alive to the hospital (45.5% vs. 62.4%, respectively, p < 0.001) or survive to hospital discharge (18.4% vs. 31.9%; p < 0.001; Table 1). This adverse association between procainamide and outcome persisted after adjusting for patient demographics and resuscitation characteristics (Table 2, Models 1 and 2). After adjusting for other cardiac medications used during the resuscitation (epinephrine, magnesium, and bretylium), we no longer observed a significant association between the receipt of procainamide and outcome (Table 3, Models 3 and 4). We also observed no significant interactions between procainamide and epinephrine, magnesium, or bretylium on outcome in any of the four models (data not shown).
Table 2. Operating Rooms and 95% CIs for Associations Between Procainamide and Patient Outcome
| ||Model 1*||Model 2*||p-value†|
| Procainamide (dichotomous)||0.52 (0.36–0.75)||—||0.76|
| Procainamide (categorical)|
| Total dose < 1000 mg||—||0.66 (0.42–1.04)|| |
| Total dose ≥ 1000 mg||—||0.39 (0.23–0.64)|| |
|Survival to hospital discharge|
| Procainamide (dichotomous)||0.51 (0.32–0.79)||—||0.90|
| Procainamide (categorical)|
| None|| ||Reference‡||0.27|
| Total dose < 1000 mg|| ||0.60 (0.35–1.03)|| |
| Total dose ≥ 1000 mg|| ||0.38 (0.19–0.76)|| |
Table 3. Operating Rooms and 95% CIs for Associations Between Procainamide and Patient Outcomes, Adjusted for Other Cardiac Medications
| ||Model 3*||Model 4*||p-value†|
| Procainamide (dichotomous)||1.02 (0.66–1.57)||—||0.27|
| Procainamide (categorical)|| || || |
| None|| ||Reference‡||0.13|
| Total dose < 1000 mg|| ||1.29 (0.77–2.17)|| |
| Total dose ≥ 1000 mg|| ||0.72 (0.40–1.32)|| |
| Epinephrine (categorical)|| || || |
| None|| ||Reference‡|| |
| Total dose < 5.0 mg||0.17 (0.06–0.49)||0.17 (0.06–0.50)|| |
| Total dose ≥ 5.0 mg||0.02 (0.01–0.06)||0.02 (0.01–0.06)|| |
| Magnesium||1.15 (0.65–2.01)||1.21 (0.68–2.12)|| |
| Bretylium§||1.14 (0.60–2.16)||1.16 (0.61–2.21)|| |
|Survival to hospital discharge||Model 1*||Model 2*||p-value†|
|Procainamide (dichotomous)||1.22 (0.72–2.05)||—||0.40|
|Procainamide (categorical)|| || || |
| —||—||1.47 (0.80–2.70)|| |
| —||—||0.90 (0.42–1.93)|| |
|Epinephrine (categorical)|| || || |
| None||Reference‡||Reference‡|| |
| Total dose < 5.0 mg||0.16 (0.09–0.30)||0.17 (0.09–0.30)|| |
| Total dose ≥ 5.0 mg||0.02 (0.01–0.05)||0.02 (0.01–0.05)|| |
|Magnesium||1.23 (0.66–2.29)||1.29 (0.69–2.41)|| |
|Bretylium§||0.73 (0.30–1.80)||0.73 (0.29–1.80)|| |
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This was a retrospective cohort study with a fixed sample size and was susceptible to bias, confounding, and incomplete power to detect more modest, yet still clinically important, survival associations. The study took place in a mature EMS system with relatively high survival rates. Whether the findings would be similar in other EMS systems and communities is not certain. Procainamide was used as a second-line antiarrhythmic given as a rapid infusion following unsuccessful administration of lidocaine. The results could vary were a different sequence, dose, or manner of antiarrhythmic administration used. Finally, since data regarding neurologic status at hospital discharge were not routinely collected throughout the period of this study, we were unable to assess how receipt of procainamide may have affected the long-term neurologic status of survivors of cardiac arrest.