Sudden cardiac death (SCD) represents a major public health problem in the United States and throughout the world, with a frequently cited estimate of more than 300,000 adult sudden deaths occurring annually in the United States, and an overall incidence of 0.1% to 0.2% per year, accounting for more than half of all cardiovascular deaths. Contemporary evidence demonstrates that the risk of SCD has declined over the past 50 years, based on data from the Framingham Heart Study, coincident with the decline in deaths from coronary disease. In Seattle, a decline in annual incidence of treated SCD occurred, and if this data were applied nationally, there would be 184,000 sudden deaths annually, in contrast to earlier estimates. This is similar to 2008 data from the American Heart Association (AHA) Statistics Committee, which reports that approximately 166,200 out-of-hospital cardiac arrests occur annually in the United States.
Myerburg and colleagues illustrated the relationship between the incidence and the total number of SCDs per year for the overall adult population in the United States and for higher risk subgroups ( Figure 23-1 ). With identification of more powerful risk factors, the incidence progressively increases, but this higher incidence is associated with a progressive decrease in the number of patients identified. Primary and secondary prevention implantable cardioverter-defibrillator (ICD) trials have focused on the higher risk subgroups that have either already demonstrated a sustained ventricular arrhythmia or have been identified to have underlying coronary disease with prior infarction or cardiomyopathy (see Chapter 22 ). However, most of the individuals in the general population who have had a cardiac arrest were not previously identified to be at risk based on traditional risk factors.
Epidemiologic studies show that most cardiac arrests occur outside the hospital, and initial recordings by emergency personnel reveal that ventricular tachyarrhythmias are the most common mechanisms leading to SCD. In an older study, ventricular fibrillation (VF) was the initial recorded rhythm in 75% of patients who had a cardiac arrest in Seattle, a city with an effective rapid response system. More updated evidence reveals that the annual incidence of cardiac arrest with VF as the first identified rhythm has decreased significantly from 1980 to 2000. Defining the initial rhythm at the time of the arrest may be difficult because of delay between the onset of the event and time of arrival of emergency personnel because ventricular tachycardia (VT) may rapidly degenerate to VF, and tachyarrhythmias may change to bradyarrhythmias, pulseless electrical activity, or asystole within a short period of time. Study of patients who were wearing ambulatory monitors at the time of death reveals that the most frequent cause of sudden death was related to ventricular tachyarrhythmias, observed in 84% of cases, most often VT degenerating into VF in 62% of cases. Rapid defibrillation is the most effective therapy for resuscitation of these patients. Use of automated external defibrillators (AEDs) by trained lay responders or by Good Samaritans with little or no training in community-based programs can increase survival after SCD, with impressive results seen in studies examining use in airports, airplanes, and casinos. Unfortunately, similar results were not seen with home AEDs, where overall survival was not improved when compared with reliance on conventional resuscitation methods. Most out-of-hospital cardiac arrests occur in the home, and this location presents a particular challenge for provision of timely care by emergency medical services.
Patients who have a cardiac arrest or sustained VT frequently have underlying structural heart disease, most frequently coronary artery disease (CAD); such structural disease accounts for approximately 62% to 80% of cases of SCD. Other etiologies include left ventricular (LV) hypertrophy, cardiomyopathy (dilated, hypertrophic, and right ventricular [RV] cardiomyopathy/dysplasia), valvular disease, myocarditis, and congenital heart disease. Ion channel defects, preexcitation syndromes, and proarrhythmic effects of antiarrhythmic drugs are less frequently seen etiologies. In addition, sudden cardi ac arrest may rarely occur in patients without any identified structural defect. This is called idiopathic VF . Because the substrate abnormality is continually present, there must also be a trigger that initiates sustained ventricular arrhythmias. For example, common triggers include heart failure, transient ischemia, and electrolyte disturbances, such as hypokalemia.
Myerburg and colleagues described a model of SCD showing the interactions among structure, function, and electrogenesis of VT/VF ( Figure 23-2 ). Structural abnormalities such as myocardial infarction (MI), hypertrophy, myopathic ventricle, and primary structural electrical abnormalities interact with one or more functional perturbations that can lead to transient destabilization. The major categories of functional influences include transient ischemia and reperfusion, metabolic and hemodynamic abnormalities, neurochemical or neurophysiologic fluctuations, and toxins. This interaction between structural abnormalities and functional perturbations may convert chronic, benign, ambient arrhythmias such as premature ventricular contractions (PVCs) into triggering events for sustained VT/VF.
Treatment of cardiac arrest and sustained VT has evolved over the years, and advancements in therapy have improved outcome. This chapter will focus on the pharmacologic treatment of acute episodes of monomorphic VT, drug use during cardiac arrest, and early management of cardiac arrest survivors.
Ventricular Tachycardia: Acute Management
Sustained Monomorphic Ventricular Tachycardia with a Pulse
Sustained monomorphic VT may occur with a variety of clinical features and symptoms. Most patients have underlying structural heart disease, including CAD and nonischemic cardiomyopathy in the setting of LV systolic dysfunction, and VT is most often related to scar-related reentry. Monomorphic VT may also occur in the setting of RV cardiomyopathy/dysplasia, again likely related to a reentrant mechanism. Automatic VT may also occur, although this is seen more often in a periinfarction setting. Bundle branch reentry VT, which is related to a macroreentrant circuit, should be treated the same as scar-related VT. Less frequently, special forms of VT or idiopathic VT may occur in the setting of a structurally normal heart. The latter may respond to adenosine, β-blocker, or calcium channel blocker therapy and are not discussed in this chapter. If these special forms of VT cannot be recognized with certainty, the arrhythmia should be treated similarly to VT related to scar and underlying structural heart disease.
A wide spectrum of clinical presentations and symptoms are associated with sustained monomorphic VT. Patients may present with pulseless VT or cardiac arrest or may come to medical attention with less severe symptoms—palpitations, lightheadedness, shortness of breath, or chest pain. Others may experience presyncope or brief loss of consciousness. Although loss of consciousness may occur during sustained monomorphic VT because of transient severe hypotension while upright, patients may awaken as blood pressure improves after assuming a supine position. Underlying cardiac disease and LV function, as well as the cycle length of the tachycardia, are important factors that influence clinical presentation.
The most rapid and effective way to terminate sustained VT is electrical cardioversion, but this requires use of anesthesia for appropriate sedation. Intravenous (IV) antiarrhythmic drugs can be used for the treatment of hemodynamically stable VT, and they may also help prevent recurrent ventricular arrhythmias. A retrospective study showed that 77% of patients who came to the emergency department with sustained VT were initially classified as hemodynamically stable, and 33 (60%) of 55 patients had their VT terminated with first-line IV antiarrhythmic therapy. If hemodynamic instability occurs during or after IV antiarrhythmic drug therapy without termination of VT, direct current cardioversion is the class I treatment recommendation per the American College of Cardiology (ACC)/AHA/European Society of Cardiology (ESC) Guidelines for the Treatment of Patients with Ventricular Arrhythmias.
According to the current AHA Advanced Cardiovascular Life Support (ACLS) recommendations, IV amiodarone is the first-line therapy for sustained monomorphic VT. Although other parenteral antiarrhythmic agents for life-threatening ventricular arrhythmias are discussed in this section for historic purposes, these drugs are selected for use either as single agents or in combination with amiodarone for treatment of recurrent, incessant VT. In particular, VT storm—recurrent, incessant, sustained monomorphic VT—may require the combination of multiple antiarrhythmic agents for continued suppression of recurrent arrhythmias until more definitive therapy, such as catheter ablation or surgical approaches for the treatment of arrhythmias, can be instituted.
Lidocaine is a class Ib antiarrhythmic agent that has been used for many years for the treatment of ventricular arrhythmias associated with ischemia and acute MI. However, the efficacy of lidocaine in terminating sustained monomorphic VT is low—only 8% to 27%. Because of poor efficacy, it is no longer recommended as first-line therapy for the treatment of monomorphic VT in the ACLS protocol. According to the 2000 version of the AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care, if electrical cardioversion is not possible, desirable, or successful, IV procainamide, IV sotalol (not available in the United States), or IV amiodarone is preferred over IV lidocaine. A randomized study that compared the efficacy of IV procainamide with lidocaine revealed that procainamide was superior to lidocaine in terminating spontaneously occurring monomorphic VT.
Although the ACLS protocol no longer recommends lidocaine as an initial treatment option, the ACC/AHA/ESC Guidelines for the Treatment of Patients with Ventricular Arrhythmias state that IV lidocaine might be reasonable for the initial treatment of patients with stable, sustained monomorphic VT specifically associated with acute myocardial ischemia or infarction, with a class IIb recommendation (level of evidence C). It is thought that lidocaine may be useful in suppressing automatic VT associated with acute MI. Although lidocaine was previously used routinely for prophylaxis against VF in the setting of acute MI, a meta-analysis suggested that this antiarrhythmic agent may actually increase overall mortality rate, and this practice has long since been abandoned.
The recommended IV loading dose of lidocaine is 100 mg (or 1.0 to 1.5 mg/kg), administered slowly, for attempted termination of VT ( Table 23-1 ); this is followed by a maintenance infusion at 1 to 4 mg/min. Dosage adjustments are required for patients with heart failure or hepatic disease. An advantage of this antiarrhythmic drug is that it can be infused rapidly with minimal hemodynamic effects at therapeutic levels. In addition, it is also less likely than other agents to cause bradycardia when maintained at therapeutic levels.
|DRUG||LOADING DOSE||MAINTENANCE DRIP|
|Lidocaine||1-1.5 mg/kg over 2-3 min; may repeat 0.5-0.75 mg/kg over 2-3 min in 5-10 min (max. total, 3 mg/kg)||1-4 mg/min|
|Procainamide||10-15 mg/kg, up to 1-1.5 g (typically 20 mg/min, not to exceed 50 mg/min)||2-4 mg/min|
|Sotalol||0.2-1.5 mg/kg over 30 min||0.008 mg/kg/min|
|Amiodarone||150 mg over 10 min (additional loading doses as needed, up to max. 2.2 g/24 h)||1 mg/min for 6 h, then 0.5 mg/min|
Although lidocaine is no longer recommended as initial therapy in the ACLS protocol, our group still finds this agent useful as adjunctive therapy in patients with recurrent, incessant, sustained VT, particularly following initiation of amiodarone, which may take several days to suppress ventricular arrhythmias. In addition, it can be useful in suppressing ambient frequent ventricular ectopy, which may promote spontaneous induction of sustained monomorphic VT in some situations, including periinfarction. In the setting of recurrent sustained VT, a second dose of 50 mg may be administered after the initial 100-mg bolus, which tends to be initially well tolerated in most patients; however, drug levels need to be closely monitored on a maintenance drip because central nervous system side effects often occur in patients with rising lidocaine levels, particularly in patients with abnormal hepatic function or low cardiac output.
Procainamide is a class Ia antiarrhythmic agent that has been available for over 50 years and has demonstrated clinical utility for treatment of VT. It has been studied in the electrophysiology (EP) laboratory for suppression of inducibility of VT by programmed ventricular stimulation, with an efficacy of 33% to 61%. With respect to acute termination of sustained monomorphic VT, the efficacy of IV procainamide is 80% to 93%. In contrast, one retrospective analysis reported a much lower efficacy, only 30%, for the termination of sustained, stable monomorphic VT, perhaps because of a lower infusion rate in this study, although it did appear to be more effective when used as the initial antiarrhythmic medication with termination in 57% of patients. In a randomized study that compared the efficacy of IV procainamide with lidocaine, procainamide was superior to lidocaine in terminating spontaneously occurring monomorphic VT. Although it is no longer listed as an early treatment option in the ACLS protocol, IV procainamide is reasonable for initial treatment of patients with stable sustained monomorphic VT, according to the ACC/AHA/ESC guidelines, as a class IIa recommendation (level of evidence B). This is consistent with the 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, which states that procainamide is recommended for patients with hemodynamically stable monomorphic VT and without concomitant severe congestive heart failure or acute MI.
Procainamide is also administered with the aim to prevent recurrent VT in an acute setting. Even when VT recurs in patients taking this antiarrhythmic agent, it may be better tolerated because of its effects on prolongation of the VT cycle length. This increase in VT cycle length may help in pace termination of the arrhythmia, although less often it may actually stabilize the reentrant circuit and make it more difficult to terminate with pacing maneuvers. The ability of the drug to terminate the arrhythmia does not necessarily correlate with the ability of the drug to prevent inducibility in the EP laboratory.
Procainamide may be administered orally, intravenously, or intramuscularly, although the latter is rare. For the acute termination of VT, it is typically used intravenously. The recommended IV loading dose of procainamide is 10 to 15 mg/kg (see Table 23-1 ). The drug may be administered at a rate of 20 mg/min, not to exceed 50 mg/min, for a maximum dose of 1 to 1.5 g. Administration of procainamide may lead to hypotension; therefore blood pressure should be monitored at least every 5 minutes, and electrocardiographic (ECG) monitoring should be continuous. Slowing the rate of infusion may help prevent hypotension because the initial fall in blood pressure may be related to the vasodilatory effect; volume repletion may also be useful. When a maintenance drip is required, dosing should be individualized because the half-life for elimination is no longer present in patients with reduced renal function and/or low cardiac output. Drip rates typically range from 2 to 4 mg/min. In addition, N-acetylprocainamide (NAPA) is an active metabolite with class III antiarrhythmic effects, and further dosage adjustment may be needed in the setting of renal insufficiency because this metabolite is also renally excreted. Serum levels of procainamide and NAPA are available for clinical monitoring, and therapeutic procainamide levels are reported to be 3 to 10 µg/mL. Frequent ECGs should also be performed to monitor the QT interval because procainamide prolongs repolarization and can lead to proarrhythmia in the form of polymorphic VT with a long QT interval or to torsades de pointes (TdP).
Although this antiarrhythmic agent is no longer included in the ACLS protocol, our group still finds this drug useful for some patients who have frequent episodes of sustained monomorphic VT in the critical care setting. Because it may take days for amiodarone to suppress VT, procainamide significantly slows the VT rate and may be used initially as adjunctive therapy to help reduce the need for external cardioversions or internal ICD shocks. This slowing of the tachycardia rate may make the arrhythmia hemodynamically better tolerated and more amenable to pace termination, thereby reducing painful shock therapy. It is also occasionally used in the EP laboratory during VT catheter ablation procedures to help slow the VT rate and improve hemodynamic tolerance to allow entrainment mapping, although newer substrate-mapping techniques and electroanatomic mapping have reduced this need. In a closely monitored setting such as the EP laboratory, procainamide may be administered at a rate of up to 50 mg/min, with careful attention to blood pressure and QT interval changes.
Although the IV formulation of sotalol is not currently marketed in the United States, efficacy in acute termination of hemodynamically tolerated VT has been shown. IV sotalol was superior to lidocaine for the acute termination of spontaneous sustained VT in a randomized double-blind study, with acute termination of VT occurring in 69% of patients versus 18%, respectively. In fact, the 2000 version of the AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care recommended IV sotalol over lidocaine for treatment of hemodynamically stable VT.
The recommended dose of sotalol is 1.5 mg/kg or 100 mg intravenously (see Table 23-1 ). It is renally excreted and should be used with caution in patients with renal insufficiency. With its negative inotropic effects, it may precipitate congestive heart failure in patients with depressed LV systolic function.
Although already available for many years in other countries, IV amiodarone was approved by the FDA for use in the United States in 1995 for the acute suppression of hemodynamically unstable VT or VF refractory to therapy with conventional antiarrhythmic drugs. Amiodarone is a class III antiarrhythmic agent with class I, II, and IV antiarrhythmic properties. The IV form of amiodarone has initial sympatholytic and calcium channel–blocking effects, with class I and III activity appearing later. Kowey and colleagues reviewed the use of IV amiodarone, including efficacy of this agent for treatment of frequently recurrent destabilizing VT and VF, with suppression rates of 63% to 91% in uncontrolled trials. IV amiodarone reduced the frequency of recurrent VT/VF and terminated arrhythmias in severely ill patients. However, these studies were either retrospective reviews or uncontrolled studies with relatively small numbers of patients who might also have concomitantly received other antiarrhythmic agents.
Three prospective trials confirmed these findings, and one study demonstrated a dose-response relationship, with an efficacy at least comparable to bretylium, an antiarrhythmic agent no longer available in the United States (and therefore not discussed in this chapter). In all three studies, enrollment criteria included at least two episodes of hemodynamically unstable VT or VF within 24 hours despite treatment with lidocaine, procainamide, and bretylium (except in the bretylium comparison study). Most of the patients enrolled in these trials had VT, and few initially presented with VF. Because placebo-controlled studies would not be ethical in this cohort, a dose ranging study design was used in two of the studies, and a placebo-controlled comparison with bretylium was used in the third study. In these studies, 40% to 43% of patients were event free at 24 hours after administration of 1000 mg. The time to first event showed significant differences among the three IV amiodarone dose groups ( P = .0247), and the most significant contribution to that difference was the paired comparison between the 1000- and 125-mg dose groups ( Figure 23-3 ). The higher dose of amiodarone (1000 mg) and bretylium had similar efficacy rates ( Figure 23-4 ). However, there was a high crossover rate from bretylium to amiodarone as a result of hypotensive effects that occurred more often with bretylium than with amiodarone. The specific presenting arrhythmia—hypotensive VT, VF, or incessant VT—or severity of LV dysfunction did not influence efficacy of amiodarone.