Short-term Control of Supraventricular Tachycardia with Verapamil Infusion and Calcium Pretreatment

Short-term Control of Supraventricular Tachycardia with Verapamil Infusion and Calcium Pretreatment* J

Craig Barnett, M.D.;t and Robert C. 1buchon, M.D. F.C.C.P.t

Nineteen consecutive patients with atrial6brillation!flutter or other types of supraventricular tachycardia were given intravenous (IV) calcium salts (I g) foUowed by verapamil infusion at a rate of I mglmin. Successful treatment was defined as control of ventricular response to s U)() beats per minute (bpm) or conversion to sinus mechanism in patients with atrial arrhythmias: II patients bad atrial &briUation; three bad atrial flutter; four bad reentrant supraventricular tachycardias (SVf); and one had paroxysmal SVT. Therapy was successful in all patients. The mean dose of verapamil required to achieve desired out-

Intravenous (IV) verapamil has been proven effective in blocking atrioventricular (AV) nodal conduction in supraventricular tachycardia (SVI') and terminating svr due to extranodal or intranodal reentrant mechanisms. 1-' Traditional therapy with verapamil uses small IV bolus injections for short-term control of ventricular response or conversion of the rhythm to a sinus mechanism.• Verapamil injections followed by continuous infusion have been used for extended therapy in postoperative patients in the intensive care unit (ICU} and to minimize fluctuations in hemodynamic responses. s-s In both situations, verapamil may be associated with significant hypotension, presumably due to its inhibition of calcium flux in vascular smooth muscle that results in vasodilation of peripheral vessels. 10 Prior treatment with calcium salts has been shown to prevent hypotension in patients given verapamil infusion to treat multifocal atrial tachycardia or bolus injections to treat SVf. 11 - 13 In a sequential series of patients with various atrial fibrillation/flutter or svr who received a two-step, continuous verapamil infusion preceded by IV calcium, we documented efficacy of treatment and noted no detrimental blood pressure response. Patients were treated prospectively at the Veterans Administration Medical Center, Saint Mary's Hospital, and Cabell-Huntington Hospital in Hun*From the West Virginia University Health Sciences Center (Dr. Barnett) and the Marsball University School of Medicine (Dr. Touchon), Huntington. tAssistant Professor of Medicine. tChief of Cardiology, Professor of Internal Medicine. November 30. Manuscript received June 8; revision ac<:e~!ed Reprint requests: Dr. lbuchon, MarshaU University School of Medicine, Huntington, WVA 25701

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come was !0 mg. Heart rate showed no significant change as a result of calcium pretreatment (I60 bpm v I51 bpm). However, heart rate was significantly decreased, to 95 bpm, after treatment with verapamil. Blood pressure showed no change from baseline with either calcium or verapamil therapy. Verapamil infusion foUowing IV calcium successfully treats atrial 6brillation!flutter or svrs withoot depressing systemic blood pressure. (Cheat 1990; 97:1106-09)

I

AV =atrioventricular; SVT =supraventricular tachycardia

tington, WV. This prospective protocol was initiated in January 1988 and continued through November 1988, enrolling a total of 19 sequential patients. PATIENTS AND METHODS

Consecutive patients with established svr unresponsive to conservative measures (eg, Valsalva maneuver, carotid massage, or Trendelenburg position with ocular pressure) who required acute therapy were examined- There were no exclusion criteria, except for immediate previous initiation of an antiarrhythmic or P-blocker. Specifically, hypotensive patients were not excluded, unless at initial examination emergent electrical cardioversion was deemed necessary due to fuU cardiovascular coUapse. Any medication administered for at least one week previous were allowed. Patient 3 had received a vasopressor (dopan~ine at various dosages) and other resuscitative measures within 30 minutes of initiating therapy. The clinical indication for treatment was the presence of dyspnea, hypotension, peripheral hypoperfusion, or rapid ventricular response. Initial heart rate and blood pressure on evaluation fur therapy were recorded and then monitored for 16 ± 4 minutes prior to therapy. Patients then had baseline heart rate and blood pressure measurements, along with single-lead rhythm strip and 12-lead ECG. After baseline measurements, 1 g of calcium gluconate or calcium chloride (10 ml of 10 percent solution) was administered IV over three to six minutes. Postcalcium blood pressure, heart rate, and rhythm strip were respectively measured and recorded. Verapamil infusion (25 mg in 50 ml of 5 percent dextrose in water) was started at 120 mllh (I mg/min), after calcium administration. Rhythm was monitored constantly by visual assessment of the bedside monitor until successful therapy was achieved. Final rhythm strips were recorded for five seconds and rhythm and rate were confirmed by caliper. Blood pressure was recorded every four to five minutes until successful therapy was achieved. Successful therapy was defined as control of ventricular response to s 100 bpm or conversion to sinus mechanism. Once this goal was obtained, the infusion was decreased to 60 mllh for the remaining volume. Patients were then treated clinically by the responsible physician. If indicated, they received additional antiarrhythmia therapy, which did not necessarily include verapamil, on a long-term basis. Shorl-tenn Control of Supraventricular Tachycardia (Barnett, Touchon)

Table 1-lbtient Characterilltics* Cardiopulmonary DiagnoSis·

Arrhythmia

EF%

COPD, Pneumonia COPD CAD CAD, MRIAI, COPD COPD COPD COPD COPD

A fib A fib A fib A flut

.. ·* .. ·* ..40·*

A fib

'l:l

MR,COPD CAD,COPD COPD CAD,COPD Idiopathic SVf COPD CAD,COPD CAD,COPD COPD, Sepsis Idiopathic A fib CADIMI, COPD pneumonia

A fib A flut A fib

..21·*

Patient No./Age, yr/Sex

V661M 2/72/M

3188/M 4/68/M 5/67/M

6170/M 7/67/M &'75/M 9rl'1/F 10/65/M

1V69/M 12/68/M 13164/M 14/68/M 15168/M 16/65/M 17n81M 18164/M 19n2/M

svr svr svr

Concomitant Antiarrhythmic Medicationt Digoxin Digoxin Digoxin Digoxin, quinidine None None Digoxin Digoxin, Procainamide Digoxin Digoxin, metoprolol Digoxin, diltiazem Digoxin Flecainide Digoxin Digoxin, atenolol Digoxin Digoxin None Digoxin

70

..46·* 60

svr svr

17 62

..17·*

A fib A flut A fib A fib A fib A fib

55

..63·* 56

*COPD=chronic obstructive pulmonary disease; CAD=coronary artery disease; MR=mitral valve regurgitation; AI=aortic valve insufficiency; A fib= atrial fibrillation; A flut =atrial flutter; SVf =supraventricular tachycardia; MI =myocardial infarction; and EF =ejection fraction. tPatients who previously received P-blocker therapy are included, see text. tUnknown.

190

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w 130 ~ a:

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110

I

90

7o_J~::::::::::::::~::~P~~~o~.~oo~1~::~::::::::::::::~ Initial Rate

Baseline

After Calcium Salts

After Verapamil Infusion

FIGURE 1. Response of heart rate in patients with supraventricular tachycardia to intravenous calcium salts pretreatment followed by verapamil infusion. Individual values are shown by closed circles. Squares with vertical bars represent means with SDs.

CHEST

I 97 I

5 I MAY, 1990

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Heart rate and blood pressure, defined as mean arterial pressure, were compared in a multivariant analysis of variance using Wilks' criteria as a statistical model. Significance between variables was defined at the 0.05 level. Results were expressed as mean± 1 SD. RESULTS

Therapy was successful in all 19 patients, whose mean ages were 70 ± 6 years. Clinical features of the patients studied appear in Table l. The mean dose of verapamil needed to achieve a ventricular rate :S100 bpm or to convert the atrial rate to sinus mechanism was 19.9±7.5 mg. Individual doses required for response ranged from 0 to 24 mg. In one patient, calcium pretreatment alone was sufficient for conversion to sinus mechanism. Time to successful response was also a mean of 19.9 minutes, since verapamil was administered at 1 mglmin. The total dose was 25 mg for each patient and total volume of infused medication was 60 mi. Initial mean heart rate of 158± 19 bpm and arterial pressure of 88 ± 20 mm Hg did not vary significantly (p>0.50 for both) from baseline. The mean baseline heart rate (Fig 1) of 160± 17 bpm decreased after calcium pretreatment to 151 ± 20 bpm, a nonsignificant (p = 0.45) change of 6 percent. The mean heart

rate decreased by 41 percent from baseline to 95 ± 11 bpm (p<0.001) with verapamil infusion. Mean arterial pressure (Fig 2) did not change significantly (p = 0.38) from baseline calcium pretreatment or with verapamil administration: 89 ± 18 mm Hg to 93 ± 18 mm Hg to 93 ± 15 mm Hg, respectively. Therapeutic success and hemodynamic stability was not influenced by previous long-term digoxin therapy. No symptomatic or hemodynamically significant side effects occurred. DISCUSSION

Verapamil reduced the heart rate in 18 of 19 patients with various SVTs in our study. Even though patients were not randomized to a control group vs a treatment group, each patient had a stable initial rhythm and rate for a mean of 16 minutes before therapy. Verapamil restored sinus rhythm in five patients had reduced atrial rate/controlled ventricular response in the remaining patients. Hypotension can be a common side effect in the treatment of SVT with IV verapamil by traditional bolus methods. In a specific group of patients, Salerno and associates 11 showed that continuous verapamil

140

120 Ci

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(/)

(/)

w

a: a.. ....J <

a: ....a:w

80

< z < w

:::::!E

60

Initial BP

Baseline

After Calcium Salts

After Verapamil Infusion

FIGURE 2. Response of mean arterial blood pressure in patients with supraventricular tachycardia to pretreatment with intravenous calcium salts followed by verapamil infusion. Individual values are shown by closed circles. Squares with vertical bars represent means with SDs.

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Short·tenn Control of Supra118111ricular Tachycardia (Barnett, Touchon)

infusion (without bolus load) did not result in hypotension when patients were pretreated with calcium. Previously, Haft and Habbab 12 as well as Weiss and colleagues 13 demonstrated that calcium pretreatment prevents the drug-induced hypotension associated with bolus injections of verapamil. At our institution, when bolus verapamil regimens have been used to treat SVfs, hypotension has occurred in various patients, especially a subset with significant ventricular dysfunction. When this clinical scenario came to our attention, we began using our protocol. Since we instituted this method of treatment, we have not observed hypotensive episodes associated with verapamil for short-term therapy of SVfs. Verapamil is a potent inhibitor of intracellular calcium influx in the AV node, slowing AV conduction. 10·14-1 6 This same mechanism in smooth muscle is responsible for the vasodilatory properties of verapamil.10·14·17·18 However, there appears to be a dose response and a corresponding plasma calcium threshold: lower doses of calcium are required to block the decrease in peripheral vascular resistance from verapamil therapy than are needed to interfere with its electrophysiologic effects. 19·20 To our knowledge, the amount of calcium needed to affect these verapamil mechanisms in the conduction system and contractile smooth muscle is unknown. The possibility of high-grade AV nodal block or bradycardia is greater when verapamil is administered concomitantly with other antiarrhythmic treatment, including p-blocking agents. We have not observed this using such an individual, response-titrated protocol. Also, as has been confirmed by Lewis and associates, 18 the observed hemodynamic effects were uniform regardless of concomitant previous digitalis therapy with our patients. Finally, several of our patients had significantly diminished left ventricular ejection fractions. We witnessed no clinical evidence of worsening heart failure. In summary, we confirm that (I) continuous verapamil infusion effectively lowers the ventricular rate and may convert aberrant rhythms to sinus mechanism in patients with various forms of svr, and (2} pretreatment with 1 g of calcium chloride or calcium gluconate effectively blunts the hypotensive response associated with IV verapamil without interfering with its antiarrhythmic properties. We recommend this regimen for short-term control of ventricular response. REFERENCES 1 Singh B, Ellrodt G, Peter cr. Veraparnil: a review of its pharmacologic properties and therapeutic use. Drugs 1978; 15:169-97 2 Rinkenberger RL, Prystowsky EN, Heger JJ, Troup PJ, Jackman WM, Zipes DP. Effects of intravenous and chronic oral veraparnil

administration in patients with supra-ventricular tachyarrhythmias. Circulation 1980; 62:996-1010 3 Waxman HL, Myerburg RJ, Appel R, Sung J. Verapamil for control of ventricular rate in paroxysmal supraventricular tachycardia and atrial fibrillation or flutter. Ann Intern Med 1981; 94:1-6 4 Tommasco C, McDonough T, Parker M, Talano JV, Atrial fibrillation and flutter: immediate control and conversion with intravenously administered verapamil. Arch Intern Med 1983; 143:877-81 5 Iberti 1J, Benjamin E, Paluch TA, Gentili DR, Gabrielson GV. Use of constant-infusion verapamil for the treatment of postoperative supraventricular tachycardia. Crit Care Med 1986; 14:283-84 6 Haug MT, DeRespino J, Zimmerman J, Johnson V, Traeger S. Extended verapamil infusion for recurrent atrial tachy-arrhythmias complicating acute myocardial infarction. Clio Pharm 1984; 3:540-44 7 Barbarash RA, Bauman JL, Lukazewski AA, Srebro JP, Rich S. Verapamil infusions in the treatment of atrial tachy-arrhythmias. Crit Care Med 1986; 14:88(Hl8 8 Reiter MJ, Shand DG, Asnonsen LM, Wagoner R, McCarthy E, Prichett ELC. Pharmacokinetics of verapamil: experience with a sustained intravenous infusion regimen. Am J Cardiol 1982; 50:716-21 9 Weber RJ, DastaJF, Traetow WD. Long-term verapamil infusion in paroxysmal supraventricular tachycardia. Crit Care Med 1984; 12:465-66 10 Singh BN, Hect HS, Koonlawee N, Chew CYC. Electrophysiological and hemodynamic effects of slow-channel blocking drugs. Prog Cardiovasc Dis 1982; 25:103-32 11 Salerno DM, Anderson B, Sharkey PJ, Iber C. Intravenous verapamil for treatment of multifocal atrial tachycardia with and without calcium pretreatment. Ann Intern Med 1987; 107:62328 12 Haft JI, Habbab MA. Treatment of atrial arrhythmias: effectiveness of verapamil when preceded by calcium infusion. Arch Intern Med 1986; 146:1085-89 13 Weiss AT, Lewis BS, Halon DA, Hasin DA, Hasin Y, Gotsman MS. The use of calcium with verapamil in the management of supraventricular tachyarrhythmias. Int J Cardiol1983; 4:275-80 14 Mangiardi LM, Hariman RJ, McAllister RG, Bhargava V, Surawicz B, Shabetai R. Electrophysiologic and hemodynamic effects of verapamil: correlation with plasma drug concentrations. Circulation 1978; 57:366-72 15 Husaini MH, Kvasnizka J, Ryden L, Holmberg S. Action of verapamil on sinus node, atrioventricular, and intra-ventricular conduction. Br Heart J 1973; 35:734-37 16 Roy PR, SpurreD RAJ, Sowton E. The effect ofverapamil on the cardiac conduction system in man. Postgrad Med J 1974; 50:27075 17 Singh BN, Roche AHG. Effects of intravenous verapamil on hemodynamics in patients with heart disease. Am Heart J 1977; 94:593-99 18 Lewis BS, Mitha AS, Gotsman MS. Immediate haemodynamic effects ofverapamil in man. Cardiology 1975; 60:366-76 19 Hariman RJ, Mangiardi LM, McAllister RG, Surawicz B, Shabetai R, Kishida H. Reversal of the cardiovascular effects of verapamil by calcium and sodium: differences between electrophysiologic and hemodynamic responses. Circulation 1979; 59:797-804 20 Lang J, Ttmour-Chah Q, Chebly ME, Faucon G. Effect of gradual rise in plasma calcium concentration on the impairment of atrioventricular nodal conduction due to verapamil. J Cardiavase Pharmacol1986; 8:6-13 CHEST I 97 I 5 I MAY, 1990

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