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Ventricular tachyarrhythmias (out of hospital cardiac arrests)

Search date May 2006 Eddy S Lang and Marwan Al Raisi

Cardiovascular disorders

QUESTIONS What are the effects of antiarrhythmic drug treatments for use in out of hospital cardiac arrest associated with shock resistant ventricular tachycardia or ventricular fibrillation? . . . .3 INTERVENTIONS ANTIARRHYTHMIC DRUG TREATMENTS Unknown effectiveness Amiodarone . . . . . . . . . . . . . . . . . . . . . .3 Lidocaine . . . . . . . . . . . . . . . . . . . . . . . .4 Key Messages Pulseless ventricular tachycardia and ventricular fibrillation are the main causes of sudden cardiac death, but other ventricular tachyarrhythmias can occur without haemodynamic compromise. Ventricular arrhythmias occur mainly as a result of myocardial ischaemia or cardiomyopathies, so risk factors are those of cardiovascular disease. Cardiac arrest associated with ventricular tachyarrhythmias is managed with cardiopulmonary resuscitation and electrical defibrillation, where available. Adrenaline is given once intravenous access is obtained or endotracheal intubation has been performed. Amiodarone may increase the likelihood of arriving alive at hospital in people with ventricular tachyarrhythmia that has developed outside hospital, compared with placebo or with lidocaine, but has not been shown to increase longer term survival. Amiodarone is associated with hypotension and bradycardia. We dont know whether lidocaine or procainamide improve survival in people with ventricular tachyarrhythmias in out of hospital settings, as very few studies have been found. Procainamide is given by slow infusion, which may limit its usefulness to people with recurrent ventricular tachyarrhythmias. We dont know whether bretylium improves survival compared with placebo or lidocaine, and it may cause hypotension and bradycardia. It is no longer recommended for use in ventricular fibrillation or pulseless ventricular tachycardia. Procainamide . . . . . . . . . . . . . . . . . . . . .5 Unlikely to be beneficial Bretylium . . . . . . . . . . . . . . . . . . . . . . . .4

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Cardiovascular disorders

Ventricular tachyarrhythmias (out of hospital cardiac arrests)

DEFINITION Ventricular tachyarrhythmias are defined as abnormal patterns of electrical activity originating within ventricular tissue. The most commonly encountered ventricular tachyarrhythmias of greatest clinical importance to clinicians and which will be the focus of this chapter are ventricular tachycardia and ventricular fibrillation. Ventricular tachycardia is further classified as monomorphic when occurring at a consistent rate and amplitude and polymorphic when waveforms are more variable and chaotic. Torsades de pointes is a specific kind of polymorphic ventricular tachycardia associated with a prolonged QT interval and a characteristic twisting pattern to the wave signal. It is often associated with drug toxicity and electrolyte disturbances and is commonly treated with intravenous magnesium. Torsades de pointes will not be specifically covered in this chapter. Pulseless ventricular tachycardia results in similar clinical manifestations but is diagnosed by a QRS width complex of > 120 milliseconds and electrical rhythm of 150200 beats a minute. Waveforms in ventricular fibrillation are characterised by an irregular rate, usually exceeding 300 beats a minute as well as amplitudes generally exceeding 0.2 mV. Ventricular fibrillation usually fades to asystole (flat line) within 15 minutes. Ventricular fibrillation and ventricular tachycardia associated with cardiac arrest and sudden cardiac death (SCD) are abrupt pulseless arrhythmias. Non-pulseless (stable) ventricular tachycardia has the same electrical characteristics as ventricular tachycardia but without haemodynamic compromise. The treatment of stable ventricular tachycardia is not covered in this chapter. Ventricular fibrillation is characterised by irregular and chaotic electrical activity and ventricular contraction in which the heart immediately loses its ability to function as a pump. Pulseless ventricular tachycardia and ventricular fibrillation are the primary causes of SCD. Population: In this chapter we focus on drug treatments, given generally by paramedics, for ventricular tachycardia and ventricular fibrillation associated with cardiac arrest in an out of hospital setting.

INCIDENCE/ PREVALENCE

The annual incidence of SCD is believed to approach 2/1000 population but can vary depending on the prevalence of cardiovascular disease in the population.1 It is estimated that 300 000 SCDs are recorded annually in the US, representing 50% of all cardiovascular mortality in that country.2 Data from Holter monitor studies suggest that about 85% of SCDs are the result of ventricular tachycardia/ventricular fibrillation.3

AETIOLOGY/ RISK FACTORS

Ventricular arrhythmias occur as a result of structural heart disease arising primarily from myocardial ischaemia or cardiomyopathies. In developed nations, ventricular tachycardia or ventricular fibrillation associated cardiac arrest is believed to occur most typically in the context of myocardial ischaemia. As a result, major risk factors for SCD reflect those that lead to progressive coronary artery disease. Specific additional risk factors attributed to SCD include dilated cardiomyopathy (especially with ejection fractions of < 30%), age (peak incidence 4575 years), and male sex.

PROGNOSIS

Ventricular fibrillation and ventricular tachycardia associated with cardiac arrest results in lack of oxygen delivery and major ischaemic injury to vital organs. If untreated this condition is uniformly fatal within minutes.

AIMS OF In conjunction with defibrillation, to restore sinus rhythm or a sufficiently organised electrical rhythm INTERVENTION that will support the systemic circulation with minimal adverse effects.

OUTCOMES

Survival/mortality; functional neurological recovery; survival to hospital discharge; survival to hospital admission; adverse effects of treatment; quality of life.

METHODS

For this chapter the following sources were used for the identification of studies: Medline 1966 to May 2006, Embase 1980 to May 2006 and the Cochrane Library 2006 issue two. Additional searches were carried out on the NHS Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA), Turning Research into Practice (TRIP) & the National Institute of Health and Clinical Excellence guidance (NICE) websites. Abstracts of studies retrieved in the search were assessed independently by two information specialists. Pre-determined criteria were used to identify relevant studies. Study design criteria included the following: study types systematic reviews and RCTs only; RCT criteria at least clinician / outcome assessor blinded, minimum number of individuals in each trial is 20, minimum size of follow-up is 80%, no minimum length of follow-up.
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Ventricular tachyarrhythmias (out of hospital cardiac arrests)

QUESTION What are the effects of antiarrhythmic drug treatments for use in out of hospital cardiac arrest associated with shock resistant ventricular tachycardia or ventricular fibrillation?

Cardiovascular disorders

OPTION

AMIODARONE

One high quality RCT found that more people survived to hospital admission with amiodarone compared with placebo. However, it found no significant difference in survival to hospital discharge. Another RCT found that more people survived to hospital admission with amiodarone compared with lidocaine. However, it also found no significant difference in survival to hospital discharge. Amiodarone was associated with more hypotension and bradycardia than placebo. Benefits: We found no systematic review. Amiodarone versus placebo: One RCT (504 people with cardiac arrest and shock resistant ventricular fibrillation or pulseless ventricular fibrillation developing at some point during resuscitation) found that there were significantly more people who survived to admission to hospital in people who were given amiodarone compared with placebo (108/246 [44%] with amiodarone v 89/258 [34%] with placebo; P = 0.03) (see table 1, p 6).4 However, it found no significant difference in survival to hospital discharge between amiodarone compared with placebo (33/246 [13.4%] with amiodarone v 34/258 [13.2%] with placebo; reported as non-significant). The RCT also found similar results between Amiodarone and placebo in the number of the people who survived to discharge from hospital who returned to independent living or work (18/33 [55%] with amiodarone v 17/34 [50%] with placebo; significance not reported). Amiodarone versus lidocaine: One RCT (347 people with cardiac arrest and shock resistant ventricular tachycardia or ventricular fibrillation developing at some point during their resuscitation) found that a significantly larger proportion of people survived to hospital admission with amiodarone compared with lidocaine (41/180 [22.8%] with amiodarone v 20/167 [12.0%] with lidocaine; OR 2.17, 95% CI 1.21 to 3.83; P = 0.009) (see table 1, p 6). However, it found no significant difference in survival to discharge from hospital between amiodarone and lidocaine (9/180 [5%] with amiodarone v 5/167 [3%] with lidocaine; P = 0.34) (see table 1, p 6).5 (Both groups also received placebo.) Amiodarone versus bretylium: We found no RCTs. Amiodarone versus procainamide: We found no RCTs. See comment under procainamide, p 5. Amiodarone versus placebo: The RCT found that there was significantly more hypotension (91/153 [59%] with amiodarone v 69/145 [48%] with placebo; P = 0.04) and bradycardia (63/153 [41%] with amiodarone v 36/145 [25%] with placebo; P = 0.004) in people who took amiodarone compared with placebo and who had either a transient or a sustained return of spontaneous circulation.4 Amiodarone versus lidocaine: The RCT reported that pressor drugs were needed both for people who took amiodarone and people who took lidocaine (13/180 [7%] with amiodarone v 6/167 [4%] with lidocaine; reported as non-significant).5 The RCT also reported that treatment for bradycardia was required in both groups (43/180 [24%] with amiodarone v 38/167 [23%] with lidocaine; reported as non-significant). As neither study4,5 found an advantage with regards to hospital discharge or meaningful neurological recovery it is conceivable that amiodarone use might simply lead to increased consumption of hospital intensive care unit (ICU) resources without patient benefit. Although methodologically sound, the selection of admission to hospital ICU as the studys primary outcome is problematic. However, important developments in post-resuscitative care (i.e. therapeutic hypothermia) might actually allow the increased ICU admission rate associated with amiodarone to translate into a clinical benefit as it relates to neurological recovery from cardiac arrest. See comment under procainamide, p 5. 3

Harms:

Comment:

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Cardiovascular disorders

Ventricular tachyarrhythmias (out of hospital cardiac arrests)

OPTION BRETYLIUM

One small RCT comparing bretylium versus placebo in an emergency department setting found no significant difference in survival to discharge from emergency department. Two RCTs found no difference in clinical outcomes between bretylium and lidocaine. One RCT suggested an increase in the rate of hypotension and bradycardia associated with bretylium compared with placebo. We found no studies comparing bretylium with amiodarone or procainamide in this context. Benefits: We found no systematic review. Bretylium versus placebo: One small RCT (59 people presenting to an emergency department, as opposed to the pre-hospital setting with cardiopulmonary arrest, 29 of whom had ventricular fibrillation) found no significant difference in survival from emergency department between bretylium compared with placebo (7/18 [39%] with bretylium v 1/11 [9%] with placebo; P < 0.13) (see table 1, p 6).6 The RCT did not report on survival to discharge from hospital. Bretylium versus lidocaine: See benefits of lidocaine, p 4. Bretylium versus procainamide or amiodarone: We found no RCTs. Bretylium versus placebo: One RCT found that there were significantly more adverse events in survivors with bretylium compared with survivors with placebo (reported adverse events with bretylium: tachycardia 5/8 [63%], hypotension 4/8 [50%], bradycardia 1/8 [13%], hypertension 1/8 [13%] v reported adverse events with placebo: hypotension 1/3 [33%]; P < 0.05).6 Although the RCT found no significant difference in survival to discharge from emergency department between bretylium and placebo in people with ventricular fibrillation, there was a significant difference when a population with either ventricular fibrillation or asystole was taken into consideration (8/23 [35%] with bretylium v 1/16 [6%] with placebo; P < 0.05).6 Clinical guide: The absence of evidence showing benefit of bretylium use in clinical trials compounded with adverse effects such as refractory hypotension and the lack of availability of this compound from 19982000, led the American Heart Association to remove bretylium from the Advanced Cardiac Life Support (ACLS) algorithm for ventricular fibrillation/pulseless ventricular tachycardia in 2000. LIDOCAINE

Harms:

Comment:

OPTION

We found no RCTs comparing lidocaine versus placebo in an out of hospital setting. One high quality RCT suggested that lidocaine is inferior to amiodarone for the outcome of admission to the hospital intensive care unit. Two small RCTs found no difference in clinical outcomes between lidocaine and bretylium. Benefits: We found no systematic review. Lidocaine versus placebo: We found no RCTs. Lidocaine versus bretylium: We found two small RCTs.7,8 The first RCT (100 people with out of hospital ventricular fibrillation, with persistent ventricular fibrillation after initial shock) found no significant difference between lidocaine and bretylium given after the first shock in discharge from hospital (10/44 [23%] with lidocaine v 12/56 [21%] with bretylium; P > 0.1) (see table 1, p 6).7 The second RCT (91 people with refractory ventricular fibrillation) found no significant difference between lidocaine and bretylium in the proportion of people who survived to hospital discharge (5/48 [10%] with lidocaine v 2/43 [5%] with bretylium; reported as non-significant; P value not reported).8 However, in this RCT, people were given the alternative drug if they did not respond to the first drug (see table 1, p 6). Lidocaine versus procainamide: We found no RCTs. Lidocaine versus amiodarone: See benefits of amiodarone, p 3. Lidocaine versus bretylium: The first RCT reported that pressor drugs were need both for people who took lidocaine and people who took bretylium (14/43 [33%] with lidocaine v 16/43 [37%] with bretylium; P > 0.1).7 The second RCT did not report on adverse events.8 Lidocaine versus amiodarone: See harms of amiodarone, p 3. Although methodologically sound, the selection of admission to hospital intensive care unit (ICU) as the studys primary outcome is problematic. With the effect of amiodarone as compared with lidocaine uncertain in regards to functional neurological recovery it is
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Harms:

Comment:

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Ventricular tachyarrhythmias (out of hospital cardiac arrests)

conceivable that use of amiodarone can simply increase resource consumption through ICU and nursing home facilities without achieving any meaningful clinical benefit. However, important developments in post-resuscitative care (i.e. therapeutic hypothermia) might actually allow the increased ICU admission rate associated with amiodarone to translate into a clinical benefit as it relates to neurological recovery from cardiac arrest. OPTION PROCAINAMIDE

Cardiovascular disorders

We found no systematic review or RCTs comparing procainamide versus placebo or the other antiarrhythmic drugs included in this chapter (lidocaine, bretylium, amiodarone) for the clinical outcomes of interest. Benefits: We found no systematic review or RCTs comparing procainamide versus placebo or the other antiarrhythmic drugs included in this chapter (lidocaine, bretylium, amiodarone) for the clinical outcomes of interest. We found no RCTs. One RCT (CASCADE [Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation]) showed better results for amiodarone in comparison with procainamide for the secondary prevention of cardiac arrest.9 Clinical guide: The time required to infuse procainamide is usually long (slow infusion over several minutes) and this would make it a less favourable choice in acute or unstable condition as a preferred drug. It might be considered an option for recurrent ventricular tachycardia/ventricular fibrillation.

Harms: Comment:

REFERENCES
1. Engelstein ED, Zipes DP . Sudden cardiac death. In: Alexander RW, Schlant RC, Fuster V, eds. The heart, arteries and veins. New York: McGraw-Hill, 1998:10811112. 2. Myerburg RJ, Castellanos A. Cardiac arrest and sudden cardiac death. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. Philadelphia: WB Saunders, 1997:742779. 3. de Vreede-Swagemakers JJ, Gorgels AP , Dubois-Arbouw WI, et al. Out-of-hospital cardiac arrest in the 1990s: a population-based study in the Maastricht area on incidence, characteristics and survival. J Am Coll Cardiol 1997;30:15001505. 4. Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med 1999;341:871878. 5. Dorian P , Cass D, Schwartz B, et al. Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med 2002;346:884890. [Erratum in: N Engl J Med 2002;347:955] 6. Nowak RM, Bodnar TJ, Dronen S, et al. Bretylium tosylate as initial treatment for cardiopulmonary arrest: randomized comparison with placebo. Ann Emerg Med 1981;10:404407. 7. Haynes RE, Chinn TL, Copass MK, et al. Comparison of bretylium tosylate and lidocaine in management of out of hospital ventricular fibrillation: a randomized clinical trial. Am J Cardiol 1981;48:353356. 8. Olson DW, Thompson BM, Darin JC, et al. A randomized comparison study of bretylium tosylate and lidocaine in resuscitation of patients from out-of-hospital ventricular fibrillation in a paramedic system. Ann Emerg Med 1984;13:807810. 9. Greene HL. The CASCADE Study: randomized antiarrhythmic drug therapy in survivors of cardiac arrest in Seattle. CASCADE Investigators. Am J Cardiol 1993;72:70F74F.

Eddy S Lang Assistant Professor McGill University Quebec Canada Marwan Al Raisi Resident Emergency Medicine Residency Program McGill University Montreal Canada
Competing interests: None declared.

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Cardiovascular disorders
Further treatment* Amiodarone 300 mg or placebo while CPR continued. Single dose only Included: 504 adults with non-traumatic out of hospital cardiac arrest, with VF or VT (at any time in the resuscitation attempt) after 3 pre-cordial shocks, iv access, and paramedics present with drug/placebo Inclusion/exclusion criteria Survival to hospital discharge 33/246 [13.4%] with amiodarone v 34/258 [13.2%] with placebo (P = NS)

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Amiodarone 5 mg/kg or lidocaine 1.5 mg/kg plus further shocks and advance cardiac life support. If VF persisted, same drug given (amiodarone 2.5 mg/kg; lidocaine 1.5 mg/ kg) and attempts at resuscitation (American Heart Association guidelines for ACLS) In emergency department: Bretylium (510 mg/kg) or placebo plus American Heart Association guidelines for ACLS. If person in cardiopulmonary arrest after 20 minutes, a second dose of same drug given 10 mL bolus of bretylium 500 mg or lidocaine 100 mg. If persistent VF after second shock or fibrillation recurrence, second bolus of same drug plus routine resuscitation measures Included: 347 adults with out of hospital VF 9/180 [5%] with tested electrocardiographically. VF resistant amiodarone v 5/167 [3%] with lidocaine to initial treatment (see left). (P = 0.34) Included: 29 people presenting with cardiopulmonary arrest and assessed by study investigator Survival to discharge from emergency department: 7/18 [39%] with bretylium v 1/11 [9%] with placebo (P < 0.13) 10/44 [23%] with lidocaine v 12/56 [21%] with bretylium (P > 0.1) Included: 91 adults with refractory ventricular fibrillation failure to convert from VF with the initial American Heart Association protocol, or return to VF before antiarrhythmics were given. Excluded: drugs given out of sequence; not fulfilling definition of refractory VF 5/48 [10%] with lidocaine v 2/43 [5%] with bretylium (P = NS) Included: 100 adults aged 13 years whose rhythm became organised or remained in VF. Excluded: people converting to asystole or profound bradycardia with initial shock

TABLE 1

Resuscitation protocols as reported in the included RCTs*.48

Intervention

Initial treatment*

Amiodarone or Basic life support including shocks by automated external defibrillator; placebo4 then: advanced life support measures including adrenaline 1 mg after tracheal intubation

Amiodarone or 3 shocks, 1 dose of iv adrenaline, lidocaine5 fourth shock (further details not reported)

Bretylium or placebo6

Basic cardiac life support

Lidocaine or bretylium7

CPR, then basic life support, 320 J defibrillatory shock, ET tube, iv catheter

Lidocaine or bretylium8

Ventricular tachyarrhythmias (out of hospital cardiac arrests)

Bretylium (1030 mg/kg total) or lidocaine (23 mg/kg total). If failure to convert, other drug given. If further failure to convert procainamide given (100 mg over 5 minutes, up to 1000 mg). Countershock and resuscitation by ACLS protocols given after each intervention *Treatments in out of hospital settings unless otherwise specified.

Countershocks to people in VF twice at 200 Ws, iv line of D5W and ET tube; sodium bicarbonate 1 mEq/kg and adrenaline 0.51.0 mg if VF persists

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