Bre tylium To syla teVe rsusLid o c a ine in Exp e rim e nta l C a rdia c A rre st JEAN-LUC VACHIERY, MD, CHARLES REUSE, MD, SERGE BLECIC, MD, BERNARD CONTEMPRC, MD, JEAN-LOUIS VINCENT, MD, PHD Bralylium tosylate zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA has been shown effecttve in the treatment of ventric- ular fibrillation and in the prevention of Its recurrence. However, Bdocaine is generally preferred because bretylium could have adverse hemodynamiceffects related to its antladmnerglc action. To explore fur- ther the differences between these two antiarrhythmic agents, the authors compared the effects of bmtyllum, lidocaine, and saline on a standard- ized dog model of ventricular Bbrlllation followed by electromechanicat dissociation (EM). The protocol included three successive apisodes of cardiac arrest in each animal. Three minutes before each episode of ventricular ftbrlllation, 5 mg/kg of bmtyllum tosylate (n = ll), 1 mglkg of lidocafne (n = 9) or saline (n = 12) were admlnlstered blindly. There was no difference In the duration of cardiac arrest (bmtyllum, 6 mln 18 set; lidocaine, 7 min 54 set; sallne, 8 min 20 set) or the total doses of epinephrine requimd to resuscitate the animals. Both bretylium and lidocalne appeared to pmserve cardiac function 5 minutes after recovery, as stroke volume increased from 17.8 -c 6.7 to 18.7 f 6.7 ml (NS) after bretyllum and from 17.7 f 7.7 to 19.0 f 7.0 ml (NS) after Ildoceine, but decreased from 19.0 2 5.3 lo 14.6 + 6.0 ml (f < .06) after saline. During the first 10 minutes of EMD, ventrfcular fibrillation or ventricular tachycardia recurred in 4 dogs treated with Bdocafne, 3 dogs tmated with saline, but no dog treated with bretylium (f < .05 between bmtylium and saline). On this dog model of cardiac arrest, bretylium had no adverse effect on hemodynamfemcovery and was mom effective than Bdocaine in preventlng the early mcurmnce of malignant ventrfcular arrhythmias. Nevertheless, thare was no clear superiority of one agent over the other, and the protective effects of alther agent were very limited. (Am J Emerg Mad 1990;8:492-495. 0 1990 by W.B. Saunders Company.) Bretylium tosylate and lidocaine are the two major antiar- rhythmic agents used in cardiopulmonary resuscitation (CPR) but their relative place is a subject of continuing con- troversy. The American Heart Association presently recom- mends lidocaine as the drug of choice in the management of ventricular tachycardia or ventricular fibrillation that is re- sistant to defibrillation and also for the prevention of recur- rence of these arrhythmias. Bretylium is recommended as a second-line drug for cases resistant to lidocaine.’ The rela- tive potency of the two agents in lifethreatening arrhythmias has been disputed. Some studies have shown that lidocaine facilitated defibrillation’ but others have shown the opposite.3*4 On the other hand, it is relatively well estab- lished that bretylium can facilitate defibrillation.5’6 From the Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium. Manuscript received May 26,1989; revision accepted March 3, 1990. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Key Words: Bretylium tosylate, lidocaine, ventricular fibrilla- tion, electromechanical dissociation. Address reprint requests to Dr Vincent, Department of Inten- sive Care, Erasme University Hospital, Route de Lennik 808, B- 1070, Brussels, Belgium. 0 1990 by W.B. Saunders Company. 07356757/90/0806-0004$5.00/O 492 Lidocaine effectively decreases the incidence of ectopic ven- tricular arrhythmias but does no necessarily prevent the sub- sequent development of ventricular fibrillation.‘-9 On the other hand, bretylium has been shown to prevent the devel- opment of malignant ventricular arrhythmias’@13; however, some of these observations have been challenged because their models used a train of stimuli that could be influenced by the adrenergic blocking effects of bretylium.14 In the ab- sence of evidence that one agent is superior to the other, the ultimate reason evoked for the preference of lidocaine over bretylium is that bretylium might have adverse hemody- namic effects during CPR.’ However, these differences have not been well studied. Therefore, the present study compared the effects of bretylium tosylate, lidocaine, and saline on the hemody- namic status and on the recurrence of ventricular arrhyth- mias during CPR. We used a dog model of ventricular fibril- lation followed by electromechanical dissociation (EMD) on which standard CPR maneuvers are applied.15.r6 As there is no attempt to restore blood flow during the ventricular fi- brillation on this model, each drug is administered shortly before the induction of cardiac arrest. MATERIAL AND METHODS Eighteen mongrel dogs (24 * 5 kg) were anesthetized with sodium pentobarbital (25 mg!kg), intubated and mechani- cally ventilated (Elema 9OOB, Siemens, Solna, Sweden) on control mode with air. Respiratory rate was set at 12 breaths/min and tidal volume adjusted to obtain an initial Pace, between 30 mm Hg and 35 mm Hg. Heart rate was monitored by electrocardiographic electrodes transcutane- ously attached to the four limbs. A thermistor-tipped pulmo- nary artery catheter (model 93A-131-F, Edwards Laborato- ries, Santa-Ana, CA) was inserted in the pulmonary artery through the right femoral vein for pulmonary arterial and right atria1 pressure measurements, mixed venous blood sampling, and cardiac output determinations by the ther- modilution technique. An arterial catheter (Becton, Dickin- son and Co, Rutherford, NJ) was advanced in the aorta via the right femoral artery for systemic arterial pressure mea- surements and arterial blood gases sampling. A pacing catheter (Swan-Ganz [Baxter Healthcare Corp, Irvine, CA] J-tip femoral pacing catheter 97-130-5F, Ed- wards Laboratories) was positioned via the right external jugular vein in the right ventricle to induce ventricular fibril- lation and administer drugs. The balloon of the pacing cath- eter had been bursted to allow pressure guidance during in- sertion of the catheter and also drug administration through the lumen. Heart rate and intravascular pressures were con- tinuously recorded on a four channel paper tracing (HP 7404, Hewlett Packard, Palo Alto, CA). Measurements were made