Clinical Pearl 73: Should We Pretreat with IV Calcium When giving CCBs for Stable Afib with RVR

Calcium channel blockers have long been an accepted treatment of hemodynamically stable Afib with RVR.  For those patients with borderline blood pressures or for those patients who are especially responsive to the antihypertensive effects of calcium channel blockers, there are few options available to prevent a hypotensive response. 

L Type calcium channels are present in the vascular smooth muscle, mycardium, conducting system of the heart, and in the pacemaker cells of the SA and AV nodes.  Of the calcium channel blockers available for clinical use, dihydropyridines require a much higher serum concentration to achieve electrophysiological activity than the concentration needed to achieve potent vasodilation, so their application in cases requiring negative chronotropy are limited especially with their propensity for inducing a concomitant sympathetic response via the baroreceptor reflex pathway. The non-dihydropyridines, (e.g. verapamil and diltiazem) exert their effects on the L-type channels in the pacemaker cells and conducting system of the SA and AV nodes at much lower concentrations, and are therefore useful for any supraventricular arrhythmia requiring reduced frequency of conduction through the AV node.  This is the basis of choosing these drugs for the treatment of hemodynamically stable Afib with RVR.

Of the two non-dihydropyridines, both can result in hypotension via their action on the vascular smooth muscle, but diltiazem to a much lesser degree than verapamil.  When treating a patient with RVR, there is still a recognized risk to causing hypotension, and aside from the strategies of slowing the infusion rates of calcium channel blockers, or by administering fluid boluses, one thought is to pretreat the patients with intravenous calcium.  The thought arises from the treatment of calcium channel blocker toxicity which involves among other things, giving calcium chloride or calcium gluconate to overwhelm the receptor blocking effect of the drugs.   The question we explore here is whether pretreating with intravenous calcium when giving non-dihydropyridine calcium channel blockers actually works to prevent or mitigate hypotension.

The literature available on this topic is mainly from the 1980s and 1990s and focused completely on verapamil, except for one study in 2004 which looked at pretreatment with IV calcium for diltiazem.    All studies had a small N of 50 or less participants, and ranged from case series, to retrospective, prospective, and finally a prospective, randomized, double-blind, placebo-controlled study for diltiazem.  Each study and their findings are summarized in the references below. 

The summation of data support pretreatment with calcium when using verapamil to prevent hypotension without mitigating the desired rate control effect.  In contrast, the one study on diltiazem did not show a significant difference between either treatment arm.  The paper does not support routine use of intravenous calicum as pretreatment to prevent hypotension.  Until further research is performed with diltiazem, perhaps the prudent course would be to continue using IV fluid boluses for borderline blood pressure while keeping IV calcium ready for treatment in the case of diltiazem induced hypotension.  However this guideline is not supported by good evidence.  See below for a review of the literature

References and Results

1. Weiss AT, et al. Int J Cardiol 1983; 4:275-84.

Prospective study design,     N = 13, Verapamil, Ca gluconate 1 gm;                     Result: SBP ↑ 5 mmHg

2. Roguin N, et al. Clin Cardiol 1984; 7:613-6.

Case series                             N = 2,  Verapamil, Ca gluconate(peds);                   Result: No hypotension

3. Haft JI, et al. Arch Intern Med 1986; 146:1085-9.

Sequential study of                N = 50, Verapamil, CaCl 1 gm,                                   Result: SBP ↑ 2 mm Hg

2 treatment protocols

4. Salerno DM, et al. Ann Intern Med 1987; 107:623-8.

Sequential study of                N = 5,  Verapamil, Ca gluconate 1 gm                      Result: SBP ↓ 12 mmHg

2 treatment protocols

5. Stringer KA, et al. Drug Intell ClinPharm 1988; 22:575-6.

Case report                            N = 1,  Verapamil,  CaCl 1 gm,                                  Result: No hypotension

6.  Barnett JC, et al. Chest 1990; 97:1106-9.

Prospective report of protocol        N = 19, Verapamil, Ca gluconate 1 gm or CaCl 1 gm,           Result: SBP ↑ 4 mm Hg

7. Kuhn M, et al. Am Heart J 1992; 124:231-2.

Retrospective chart review  N = 18, Verapamil, Ca gluconate 3 gm or CaCl 1 gm,           Result: No hypotension

8. Miyagawa K, et al. J Cardiovasc Pharmacol 1993; 22:273-9.

Sequential study of                N = 7,  Verapamil, Ca gluconate 3.75 mg/kg,          Result: SBP no change

2 treatment protocols

9. Kolkebeck T, et al. J Emerg Med 2004; 26(4):395-400.

Prospective, randomized,     N = 34, Diltiazem, CaCl 0.333 gm                  Result: SBP ↓ 8  vs ↓ 14mmHg

double-blind, placebo-controlled