Volume I:
First Thirty Minutes
- Section 1
  Acute Care Algorithm/ Treatment Plans/ Acronyms
- Section 2
  Universal Approach
  - CALS Universal Approach To Emergency Advanced Life Support
- Section 3
  Steps 1-6
- Section 4
  Preliminary Impression/Focused Clinical Pathways
Volume II:
Resuscitation Procedures
Volume III:
Definitive Care

Cardiovascular 3: Pharmacology of
Cardiovascular Agents Portal

Agents Reviewed in this Portal:

Amiodarone
Atropine
Epinephrine
Lidocaine
Magnesium
Procainamide
Sodium Bicarbonate
Vasopressin

Classes (I – III) refer to American Heart Association classification of recommendations.¹
See also CV 1, Classification of Pharmacological (Therapeutic) interventions.

Amiodarone (Cordarone)

Amiodarone has many physiologic effects, including both alpha and beta-adrenergic blocking properties along with effects on calcium, sodium, and potassium channels.¹ It is useful for the treatment of many atrial and ventricular arrhythmias. In patients with severely impaired cardiac function, the use of IV amiodarone is preferable to many other antiarrhythmic agents for the treatment of serious atrial and ventricular arrhythmias. Amiodarone has a lower incidence of proarrhythmic effects and greater efficacy then other antiarrhythmic drugs under similar circumstances.¹

Uses of Amiodarone

Amiodarone is now considered the drug of choice to use before lidocaine in shock-resistant VF/pulseless VT after the use of epinephrine/vasopressin.^1-3 The administration of amiodarone does require preparation before the drug may be given IV. The provider team must assure that the time needed to prepare and administer the amiodarone does NOT delay defibrillation or subsequent epinephrine doses.²
For control of hemodynamically stable VT (Class IIb), polymorphic VT (Class IIb), and wide-complex tachycardia of uncertain origin (Class IIb)¹
As adjunct to electrical cardioversion of refractory PSVT (Class IIa), atrial tachycardia (Class IIb), and pharmacological cardioversion of AF (Class IIa)¹
For ventricular rate control of rapid atrial arrhythmias in patients with severely impaired left ventricle when digitalis has been ineffective (Class IIb)¹
For control of rapid ventricular rate due to accessory pathway conduction in preexcited atrial arrhythmias (Class IIb)¹

Adverse Effects of Amiodarone
Major adverse effects of amiodarone that are rather commonly observed with IV infusion include bradycardia and hypotension. These adverse reactions may be best prevented by giving the amiodarone at a slower rate and can be best treated with fluids, pressors, chronotropic agents, or temporary pacing.¹ Nausea is also frequently observed when amiodarone is given too rapidly. Patients receiving IV infusions of amiodarone must be monitored for the potential of developing a prolongation of the QT interval and for the proarrhythmic effects that can result in arrhythmias like VT. If the concentration of the amiodarone infusion is greater than 3 mg/mL, peripheral vein phlebitis is commonly observed.

Contraindications to Amiodarone Use
Amiodarone is contraindicated for patients in cardiogenic shock, for patients with second- or third-degree AV block (if the patient does not have a pacemaker in place), and for patients with marked sinus bradycardia.

Dosage of Amiodarone

Arrest situations
In VF/pulseless VT, administer 300 mg of amiodarone as a bolus diluted with D5W to a total volume of 20 to 30 mL. Supplementary bolus doses of 150 mg may be administered for refractory or recurrent VF/VT. In successful resuscitations with amiodarone, follow these bolus doses with an infusion of 1 mg/min for 6 hours and then 0.5 mg/min up to a maximum cumulative dose of 2 g over 24 hours.¹

Non-arrest situations
In non-arrest situations, deliver amiodarone IV as 150 mg over 10 minutes, followed by 1 mg/min infusion for 6 hours and then slow the infusion to 0.5 mg/min. Supplemental 150 mg infusions given over 10 minutes may be repeated as necessary for resistant or recurrent arrhythmias to a maximum cumulative dose of 2 g over 24 hours.^1,4
PEDS: 5 mg/kg IV/IO push in cardiac arrest. Give same dose in non arrest situations over 10 minutes. Repeat as needed to 15 mg/kg.

Atropine

Atropine reverses cholinergic-mediated reductions in heart rate, blood pressure, and vascular resistance.¹

Uses of Atropine^1,4

For treatment of symptomatic sinus bradycardia (Class I)

For treatment of heart block at the AV nodal level - type I AV block (Class IIa)

For treatment of ventricular asystole

Caution in the Use of Atropine¹

The use of atropine increases the myocardial oxygen demand and may cause tachycardia; therefore, total vagolytic doses of atropine (0.04 mg/kg) should only be used for asystolic cardiac arrest.

Sub therapeutic doses of atropine (ie, < 0.5 mg in adults or PEDS: < 0.1 mg in neonates or children) may be parasympathomimetic and cause further slowing of the heart rate.

Use atropine with caution in patients with a bradycardia from AV block at the His-Purkinje level (type II AV block or third-degree block with new wide QRS complexes). In these situations, the atropine may cause an acceleration of the sinus rate with a paradoxical reduction in the number of impulses that are conducted through to the ventricle.¹ Be prepared to pace these rhythms.¹

Dosage of Atropine¹

In adults with asystole and slow PEA, give 1.0 mg IV and repeat every 3 to 5 minutes if asystole persists, up to the maximum of 0.04 mg/kg.

In adults with symptomatic bradycardia, give 0.5 mg IV and repeat every 3 to 5 minutes if needed.

In adults, a total dose of 3 mg (0.04 mg/kg) results in full vagal blockade.

PEDS: For pediatric patients, give 0.02 mg/kg (minimum dose of 0.1 mg) IV or IO to a maximum single dose of 0.5 mg in a child or 1.0 mg in adolescent. May repeat once.

See Vol III—CV4, Endotracheal Drug Delivery Portal for ET doses.

Epinephrine

For many years, epinephrine has been the first choice for treatment of patients in cardiac arrest, including VF/VT. Epinephrine does not act as an anti-fibrillatory drug but rather promotes its positive effects by stimulating the adrenergic receptors to increase cerebral and coronary blood flow, thus helping to prevent cerebral ischemia and rendering the heart more receptive to defibrillation by a converting shock.

Dosage of Epinephrine
The standard dose of epinephrine to use in adult cardiac arrest is 1 mg IV push (10 mL of 1:10 000 solution) followed by a 20 mL flush of IV saline and elevation of the arm to help facilitate distributing the epinephrine to the central circulation. This may be repeated every 3 to 5 minutes if clinically indicated.^1,4

PEDS: Pediatric use of epinephrine for symptomatic bradycardia¹:
IV/IO: 0.01 mg/kg (1:10 000 solution = 0.1 mL/kg)
ET: 0.1 mg/kg (1:1000 solution = 0.1 mL/kg)

PEDS: Pediatric use of epinephrine for pulseless arrest¹:
First dose: IV/IO: 0.01 mg/kg (1:10 000 solution = 0.1 mL/kg)
ET: 0.1 mg/kg (1:1000 solution = 0.1 mL/kg

Subsequent doses in cardiac arrest: administer epinephrine every 3 to 5 minutes as needed.

See Vol III—CV4, Endotracheal Drug Delivery Portal for ET doses.

Lidocaine

Evidence supporting lidocaine as an effective agent for shock-resistant VF/VT is lacking,² and a study has shown that there is greater likelihood of successful resuscitation from VF with amiodarone than with lidocaine.¹ Evidence indicates that in shock-refractory VF/VT, IV amiodarone (Class IIb) should be used next after epinephrine/vasopressin rather than lidocaine (Class Indeterminate).³

On the basis of established historical use and lack of evidence of significant harm, lidocaine is acceptable to use for¹:

VF/pulseless VT that persists after defibrillation and administration of epinephrine (Class Indeterminate)

Control of hemodynamically compromising PVCs (Class Indeterminate)

Hemodynamically stable VT (Class IIb)

Lidocaine remains a second choice behind other alternative agents (amiodarone, procainamide, or Sotalol) in many of these situations.¹

Dosage and Treatment Guidelines

In VF/pulseless VT, give an initial IV bolus of 1.0 to 1.5 mg/kg to obtain rapid therapeutic lidocaine levels. If the VF/VT persists, give additional boluses of 0.5 to 0.75 mg/kg every 3 to 5 minutes to a maximum dose not to exceed 3 mg/kg (or > 200 to 300 mg during a 1 hour period).¹

Giving a continuous infusion of prophylactic lidocaine after it has been used to assist in the conversion of a serious arrhythmia is controversial (Class Indeterminate). The continuous infusion, if used, should be initiated at 1 to 4 mg/min. The reappearance of serious arrhythmias during constant infusion of lidocaine should be treated with a small bolus (0.5 mg/kg) and the infusion rate increased in 0.5 to 1.0 mg/min incremental doses to a maximum of 4 mg/min.¹

The half-life of lidocaine increases after 24 to 48 hours so the rate of infusion needs to be reduced after 24 hours, if it hasn’t already been stopped.¹

Patients > 70 years old, with CHF, with hypotension or shock, or with hepatic dysfunction have reduced metabolism of lidocaine and thus need to have their infusion rates reduced by 50%.¹ (They do require the normal first bolus dose.)

Lidocaine is not recommended for the route prophylaxis of ventricular arrhythmias in the setting of acute myocardial infarction (Class III).²

PEDS: 1 to 1.5 mg/kg; repeat as needed to 3 mg/kg loading dose. Maintenance infusion of 20 to 50 μg/kg/min.

Magnesium

Magnesium has demonstrated effectiveness in two clinical situations: the treatment of torsades de pointes, for which it still has a Class IIb recommendation and VT/VF and other arrhythmias associated with known hypomagnesemia (Class IIb).² Hypomagnesemia should be especially suspected in patients who are chronic alcoholics or severely malnourished.

Dosage of Magnesium Sulfate
In life-threatening situations, give 1 to 2 g of magnesium sulfate diluted in 100 mL of D₅W and infuse over 1 to 2 minutes. Since rapid administration of magnesium sulfate can cause severe hypotension or asystole, avoid the very rapid infusion of magnesium sulfate as described here except in the most urgent situations.²

For non-emergency situations, give a loading dose of 1 to 2 g (8 to 16 mEq) of magnesium mixed in 50 to 100 mL of D5W and infuse over 5 to 60 minutes. Follow the loading dose with a continuous infusion of 0.5 to 1.0 g (4 to 8 mEq) per hour.²

Patients receiving magnesium sulfate IV need to be closely monitored with special attention paid to their deep tendon reflexes, respiratory rate, and urinary output. A loss of deep tendon reflexes, a significant slowing of the respiratory rate, or poor urinary output may be signs that the patient is developing symptomatic hypermagnesemia.
PEDS: 20 to 50 mg/kg

Procainamide

Uses of Procainamide
Procainamide suppresses both atrial and ventricular arrhythmias. Procainamide is acceptable treatment for the following uses:

For pharmacological conversion of supraventricular arrhythmias (especially atrial fibrillation and atrial flutter) to sinus rhythm (Class IIa)¹;

For control of rapid ventricular rate due to accessory pathway conduction in preexcited atrial arrhythmias (Class IIb)¹;

For treatment of wide-complex tachycardias where it is not possible to determine whether the origin is supraventricular or ventricular (Class IIb)¹; and

For treatment of intermittent or recurrent pulseless VT/VF (Class IIb).^1,5

Side Effects of Procainamide
The side effects of procainamide include hypotension and prolongation of the QT interval. Its use should be avoided in patients with preexisting QT prolongation and torsades de pointes.¹

Dosage of Procainamide

Procainamide is normally not infused at a rate faster than 20 mg/min, but in the life-threatening situation of pulseless VT/VF, the infusion of procainamide may be increased to 50 mg/min up to a total dose of 17 mg/kg.¹

In non-life-threatening situations, procainamide is given by IV infusion at a rate up to 20 mg/min until¹:

The arrhythmia is suppressed (or)

Hypotension occurs (or)

The QRS complex is prolonged by 50% from its original duration (or)

A total dose of 17 mg/kg (1.2 g for a 70 kg patient) of procainamide has been given

The IV maintenance dosage of procainamide is 1 to 4 mg/min. Reduce the maintenance dosage in patients with decreased renal function. Monitor procainamide drug levels in patients with decreased renal function and in patients receiving a continual IV infusion of greater than 3 mg/min for longer than 24 hours.

Sodium Bicarbonate

During times of low cardiac output or cardiac arrest, carbon dioxide accumulates in the tissues with the resulting acidemia. Adequate alveolar ventilation and circulation are the best ways of managing the acid-base balance during and after cardiac arrest. Hyperventilation removes CO₂ and thus corrects respiratory acidosis.

Sodium bicarbonate is used as follows¹:

* Class I (acceptable, supported by definitive evidence)
- If patient has known, preexisting hyperkalemia
* Class IIa (acceptable, good evidence supports)
- If known, preexisting bicarbonate-responsive acidosis
- In tricyclic antidepressant overdose
- To alkalinize the urine in aspirin or other drug overdoses
* Class IIb (acceptable, only fair evidence provides support)
- In intubated and ventilated patient with long arrest interval
* Class III (may be harmful)
78- In hypercarbic acidosis

Improper use of sodium bicarbonate¹:

Does not improve the ability to defibrillate or improve the survival rate

Can compromise coronary perfusion pressure

May cause extracellular alkalosis that decreases the ability of RBCs to release oxygen to the tissues

May induce hyperosmolarity and hypernatremia

Produces CO₂, which may paradoxically contribute to intracellular acidosis in heart and brain cells

Exacerbate central venous acidosis

May inactivate simultaneously administered catecholamines

Dosage of Bicarbonate
When bicarbonate is used, start with 1 mEq/kg IV by slow infusion. Guide further doses by calculated base deficit obtained from arterial blood gas (ABG) analysis when available. Remember that ABG analysis may not reflect venous or tissue pH during severe shock or cardiac arrest. Do not try to completely correct the base deficient.¹

PEDS: In pediatric patients, the initial sodium bicarbonate dose is 1 mEq/kg (1 mL/kg of 8.4% solution) given IV or IO. In neonates, a dilute solution (0.5 mEq/mL or a 4.2% solution) should be used to limit the osmotic load.¹

Vasopressin

The initial vasopressor agent for defibrillation refractory VF/pulseless VT can be either epinephrine (Class Indeterminate) or vasopressin (Class IIb). As a vasoconstrictor, vasopressin appears as effective as epinephrine, with fewer negative effects on the heart.² Vasopressin is a naturally occurring antidiuretic hormone. In very high doses it acts as a non-adrenergic peripheral vasoconstrictor. Vasopressin given during CPR to an animal in VF caused an increased coronary perfusion pressure,⁶ ventricular fibrillation median frequency,⁷ and cerebral blood flow.⁸ Vasopressin’s positive effects duplicate the positive effects of epinephrine during VF without most of the negative effects of epinephrine.¹Despite these theoretical advantages, clinical trials⁹and meta-analysis¹⁰ appear to demonstrate similar outcomes in cardiac arrest patients treated with vasopressin to those treated with epinephrine. Thus, vasopressin—differing in pharmacology but equivalent in efficacy—should be considered as an alternative to epinephrine in cardiac arrest.

Dosage: Vasopressin dosage is recommended as a single dose of 40 units given IV push. Vasopressin has a 10- to 20-minute half-life as opposed to the 3- to 5-minute half-life of epinephrine. If the patient remains in VF/VT after the vasopressin, the recommendation is to give epinephrine 1 mg IV every 3 to 5 minutes starting 10 to 20 minutes after the dose of vasopressin.1 It is possible that a second dose of vasopressin 10 to 20 minutes after the first dose may be helpful but there is inadequate evidence to recommend this at this time.

References

ECC Committee, Subcommittees and Task Forces of the American Heart Association. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2005;112(24 suppl):IV1-203.
ECC Committee, ECC Subcommittees, and ECC Task Forces; and Authors of Final Evidence Evaluation Worksheets. 2005 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care With Treatment Recommendations Conference. Circulation. 2005;112(24 suppl):b2-b5.
Kudenchuk PJ, Cobb LA, Copass MK, et al. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med. 1999;341:871-878.
Hazinski MF, Field JM, Gilmore D, editors. Handbook of Emergency Cardiovascular Care. Dallas, Tx: American Heart Association, 2008.
Stiell IG, Wells GA, Hebert PC, Laupacis A, Weitzman BN. Association of drug therapy survival in cardiac arrest: limited role of advanced cardiac life support drugs. Acad Emerg Med. 1995;2:264-273.
Babar SI, Berg RA, Hilwig RW, Kern KB, Ewy GA. Vasopressin versus epinephrine during cardiopulmonary resuscitation: a randomized swine outcome study. Resuscitation. 1999;41:185-192.
Strohmenger HU, Lindner KH, Prengel AW, Pfenninger EG, Bothner U, Lurie KG. Effects of epinephrine and vasopressin on median fibrillation frequency and defibrillation success in a porcine model of cardiopulmonary resuscitation. Resuscitation. 1996;31:65-73.
Prengel AW. et al. Cardiovascular function during the postresuscitation phase after cardiac arrest in pigs: a comparison of epinephrine versus vasopressin. Crit Care Med. 1996;24:2014-2019.
Wenzel V, Krismer AC, Arntz HR, Sitter H, Stadlbauer KH, Lindner KH; European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Eng. J Med 2004;350:105–113.
Aung K, Htay T. Vasopressin for cardiac arrest: a systematic review and meta-analysis. Arch Int Med. 2005:165;17-24.

Edition 13-October 2011

Cardiovascular 3: Pharmacology of Cardiovascular Agents Portal

References

Edition 13-October 2011

Cardiovascular 3: Pharmacology of
Cardiovascular Agents Portal