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Calcium before Diltiazem may reduce hypotension in rapid atrial dysrhythmias

Posted May 22 2013 12:00am



The Case
A 56 y/o man presents to the ED via ambulance. He was sent from clinic for 'new onset afib.' His pulse ranges between 130 and 175 bpm, while his blood pressure is holding steady at 106/58 mm Hg. He has a past medical history significant for hypertension and hypercholesterolemia. His only medications are hydrochlorothiazide and atorvastatin. The decision is made to administer an IV medication to 'rate control' the patient with a goal heart rate < 100 bpm.

The Clinical Question 
Calcium channel blockers, such as diltiazem and verapamil, can both cause hypotension. In the case above, the patient has borderline hypotension. 

What is the evidence behind giving IV calcium as a pre-treatment to prevent hypotension from calcium channel blockers?

The Data

The following table only includes studies where patients received calcium before the calcium channel blocker:


Citation
Study Design
N
Drug
Calcium Form/Dose
Results
Weiss AT , et al. Int J Cardiol 1983; 4:275-84.
Prospective
13
Verapamil
Calcium gluconate 1 gm
SBP ↑ 5 mm Hg
Roguin  N, et al. Clin  Cardiol 1984; 7:613-6.
Case series
2
Verapamil
Calcium gluconate (pediatric pts)
No hypotentsion
Haft JI , et al. Arch Intern Med  1986; 146:1085-9.
Sequential study of 2 treatment protocols
50
Verapamil
CaCl 1 gm
SBP ↑ 2 mm Hg
Salerno DM , et al. Ann Intern Med  1987; 107:623-8.
Sequential study of 2 treatment protocols
5
Verapamil
Calcium gluconate 1gm
SBP ↓ 12 mm Hg
Stringer KA , et al. Drug Intell ClinPharm 1988; 22:575-6.
Case Report
1
Verapamil
CaCl 1gm
No hypotension
Barnett JC , et al. Chest 1990; 97:1106-9.
Prospective report of protocol
19
Verapamil
Calcium gluconate 1gm or CaCl 1gm
SBP ↑ 4 mm Hg
Kuhn M , et al. Am Heart J 1992; 124:231-2.
Retrospective chart review
18
Verapamil
Calcium gluconate 3gm or CaCl 1gm
No hypotension
Miyagawa K , et al. J Cardiovasc Pharmacol  1993; 22:273-9.
Sequential study of 2 treatment protocols
7
Verapamil
Calcium gluconate 3.75 mg/kg
SBP: no change






Kolkebeck T , et al. J Emerg Med 2004;  26(4):395-400.
Prospective, randomized, double-blind, placebo-controlled
34
Diltiazem
CaCl 0.333 gm
SBP ↓ 8 mm Hg (placebo had SBP ↓14 mm Hg)
  SBP: systolic blood pressure
  CaCl: calcium chloride

Clinical Impact
The data supports administering calcium before verapamil to prevent hypotension, without negatively impacting the desired rate control effect.

There has been only one study trying this approach with diltiazem ( Kolkebeck 2004 ). Although there was NOT a statistically significant difference, the group that received calcium did have less of a blood pressure decrease than the group receiving placebo (SBP difference -8 vs -14 mm Hg). 

Limitations The biggest weakness of this study, to me, is that the authors used the manufacturer-recommended dose for diltiazem of 0.25 mg/kg first (max 20 mg), then 0.35 mg/kg (max 25 mg). This dose is rather large and often causes hypotension. The authors note limitations including the small sample size, the convenience sample design, and that a low dose of calcium was used (333 mg of 10% calcium chloride, 90 mg elemental calcium)

Why not use smaller doses of diltiazem starting at 5 or 10 mg and repeat as needed? We have had good success using this approach with diltiazem combined with pre-treatment calcium gluconate 1-2 gm. Others have utilized diltiazem infusions without a bolus to avoid the hypotensive effects. This approach allows for slow titration and the option to stop (or slow) the infusion if hypotension occurs.

Still others might argue to just give metoprolol. Actually, calcium channel blockers have performed admirably versus beta-blockers in this scenario and are recommended as first line (more to come in a future post).



Conclusions
  • Although most of the data is with verapamil, administering calcium before diltiazem may prevent some of the hypotension. 
  • There currently isn't much published data for diltiazem. The one study, which was a negative one, had some limitations. 
  • The appropriate calcium dose is unknown, but 90 mg of elemental calcium (calcium gluconate 1 gm or calcium chloride 0.333 gm) is often used. We use 1 or 2 gm of calcium gluconate.
- Bryan Hayes, PharmD 
@PharmERToxGuy )

Reference
Moser LR, et al. The use of calcium salts in the prevention and management of verapamil-induced hypotension. Ann Pharmacother 2000;34:622-9. [ PMID 10852091 ]
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