Calcium Channel Blockers - Med Spotlight

I am starting a series called “Med Spotlight.” I thought this would give providers a good place to go for reference on different medications. In these blogs I’ll point out some mechanism of action information, as well as logistics of how to give the medication. I’ve received some questions on cardizem from different clinicians lately, so we will focus mostly on that medication in this blog. First, let's take a look at all the different types of calcium channel blockers that are used. Calcium channel blockers are broken down into several sections, all having different actions on cardiac conduction, inotropic force, and vascular tone.

Calcium channel blockers generally block the L-type calcium channels. For our purposes today, these L-types are found in cardiac muscle, nodal tissue (SA and AV), as well as the arteries. When these channels are blocked, less calcium can influx, resulting in a depression of those cells main function. In the cardiac muscle, less inotropic squeeze. In the nodal tissue, a slow firing rate/slower heart rate (negative chronotropic). In the arterial smooth tissue, a wider diameter (lower peripheral vascular resistance).

Here is quickly how they break down of the different types:

Classes

Dihydropyridines (die-high-dro-para-deen)

These calcium channel blockers almost only alter the vascular tone, reducing the systemic vascular resistance. Many of these medications are taken by patients at home, while others, like Nicardipine, are used for IV administration. In retrieval medicine, we mostly see Nicardipine for BP control in head bleeds. These medications have little to no chronotropic or inotropic effects.

Non-dihydropyridines (non-die-high-dro-para-deen)

The Non-dihydropyridines are broken down into two different subcategories. The first is the Phenylalkylamines, then Benzothiazepines. See the next two:

Phenylalkylamines (fen-nel-al-ki-low-meen)

Phenylalkylamines are medications like Verapamil. These medications primarily decrease contractility (negative inotropic effects). They may reduce peripheral vascular resistance to a small degree, but usually not enough to cause much reflex tachycardia.

Benzothiazepine (ben-zow-thigh-as-o-peen)

Benzothiazepines are medications like Diltiazem. Benzothiazepines has actions that are a mix of the Dihydropyridines and the Phenylalkylamines. These medications depress the hearts inotropic and chronotropic action, while reducing peripheral vascular resistance at the same time.

Like I just mentioned, Cardizem is a Non-dihydropyridine class of calcium channel blocker. More specifically, Cardizem is a Benzothiazepine (not to be confused with a benzodiazepine). This means its actions may cause hypotension and bradycardia (so it's probably not a good idea to give Cardizem if either of those are present). When we think of Cardizem, we usually think of A-Fib or A-Flutter with rapid ventricular response (RVR). This is absolutely the most common reason we administer this medication. What dose is currently recommended? And how could we administer it in retrieval medicine?

Dosing Logistics

Current guidelines offer the following dose ranges:

Initial dose: 0.25mg/kg of ACTUAL BODY WEIGHT, given over at least 2 minutes.

I have often found that when given by "Slow IV Push"....... No one actually does it very slow. I constantly hear people say: 'the patient became really hypotensive and bradycardic after we gave Cardizem.' In my experience, this is usually just the result of people pushing the medication over about 15 seconds. This is why I recommend setting up the dosing in the following manor:

Draw up 50mg of Cardizem (usually 10ml of 5mg/ml solution) along with 40ml of NS into a 50ml syringe. This makes a 1:1 solution. Place this onto a half-set IV pump infusion set (one where you can place the syringe right onto the tubing because it has no IV bag spike). Then, run your dose over 5 minutes. How? here is how the math breaks down:

1. Figure out you dose.

Let's say your patient weighs 80 kg, so you multiply by 0.25mg to give you a starting dose of 20mg. This is equal to 20mL out of your syringe. I love 1:1 concentrations for the reason of this simple math.

2. Do the 'fluid over time' calculation

Now that you know you have to give 20mL over 5 minutes, you can do the 'fluid over time' calculation. The formula for this calculation is: Desired fluid to be infused X 60 / desired minutes to be infused over. For this problem, it would breakdown like this: 20 x 60 / 5 = 240 mL/h. Make sure to type in your total volume to be infused (VTBI) is only set to 20mL. You do not want to risk infusing your whole bag or syringe.

Secondary Dose: 0.35mg/kg of ACTUAL BODY WEIGHT, given over at least 2 minutes.

If you do not see adequate results after approximately 15 minutes, you can adminster 0.35mg/kg of actual body weight to the patient. Guidelines say over 2 minutes, but I would push this to 5 minutes. You can use the same method as I outlined above to administer your second dose.

Continuous infusion: 5-15 mg/hour

After either your first or second dose, you can set an infusion to try and maintain whatever heart rate you have reached. I usually will start at 5mg/hour and then titrate in 2.5mg/hour increments to try and attain my desired heart rate. If you start this maintenance infusion after your first dose, you will have enough left in the syringe to do a maintenance infusion. However, if you had to give a second infusion, you probably will not have enough left for maintenance infusion unless your patient is pretty lightweight. There are cautions about running cardizem infusions longer than 24 hours, and at doses at or above 15mg/hr. Be aware of this, and always check with your institutions policies / guidelines / procedures / protocols.

Uses

I mentioned above that we usually think of A-Fib and A-Flutter as reasons to give cardizem (always consider hypovolemia first). However, there is also some place for it in SVT/PSVT. Small rant... "PSVT" or "SVT" is not a diagnosis. It isn't even a rhythm. Saying that your patient is in "SVT" is just a description of the rhythm itself. What you are basically saying by calling a rhythm "SVT" is that there is a fast rhythm with no discernable P wave. This could be any number of rhythms:

Sinus tachycardia (hidden P wave)

AVNRT

A-Flutter with a consistent conduction ratio

A-Tach

MAT

Orthodromic AVRT - beware

Antidromic AVRT - beware

Pacer malfunction

Junctional tachycardia

A-Fib that you didn't notice was slightly irregular

Just remember that the diagnosis of "SVT" is just describing a rhythm, not a diagnosis.

The rant is now over. Back to the cardizem for SVT/PSVT topic. I read an excellent article from ALIEM about the efficacy of CCB for SVT vs. that of Adenosine. ***SVT WITHOUT WPW*** See the article here:

https://www.aliem.com/2016/03/calcium-channel-blockers-stable-svt-alternative-to-adenosine/

Here is some quick information for your reference about Cardizem (from UpToDate):

Contraindications:

Intravenous (IV): Hypersensitivity to diltiazem or any component of the formulation; sick sinus syndrome (except in patients with a functioning artificial pacemaker); second- or third-degree AV block (except in patients with a functioning artificial pacemaker); severe hypotension; cardiogenic shock; administration concomitantly or within a few hours of the administration of IV beta-blockers; atrial fibrillation or flutter associated with accessory bypass tract (eg, Wolff-Parkinson-White syndrome, short PR syndrome); ventricular tachycardia (with wide-complex tachycardia [QRS ≥0.12 seconds], must determine whether origin is supraventricular or ventricular)

Side Effects:

>10%:

Cardiovascular: Edema (2% to 15%)

Central nervous system: Headache (5% to 12%)

2% to 10%:

Cardiovascular: Atrioventricular block (2% to 8%; first degree), edema (2% to 8%; lower limb), bradycardia (2% to 6%), hypotension (<2% to 4%), vasodilatation (2% to 3%), extrasystoles (2%), flushing (1% to 2%), palpitations (1% to 2%)

Central nervous system: Dizziness (3% to 10%), pain (6%), nervousness (2%)

Dermatologic: Skin rash (1% to 4%)

Endocrine & metabolic: Gout (1% to 2%)

Gastrointestinal: Dyspepsia (1% to 6%), constipation (<2% to 4%), vomiting (2%), diarrhea (1% to 2%)

Local: Injection site reaction (4%; itching, burning)

Neuromuscular & skeletal: Weakness (1% to 4%), myalgia (2%)

Respiratory: Rhinitis (<2% to 10%), pharyngitis (2% to 6%), dyspnea (1% to 6%), bronchitis (1% to 4%), cough (≤3), sinus congestion (1% to 2%)

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Hypertrophic obstructive cardiomyopathy (HOCM): Use with caution in patients with HOCM; routine use is currently not recommended due to insufficient evidence (Maron 2003).

• Left ventricular dysfunction: Use with caution in left ventricular dysfunction; due to negative inotropic effects, may exacerbate condition. The ACCF/AHA heart failure guidelines recommend to avoid use in patients with heart failure due to lack of benefit and/or worse outcomes with calcium channel blockers in general (ACCF/AHA [Yancy 2013]).

• Renal impairment: Use with caution in patients with renal impairment.

Concurrent drug therapy:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.