New trends in the pharmacologic management of cardiac arrest

New trends in the pharmacologic management of cardiac arrest

Ken Grauer

The pharmacologic approach to the management of cardiac arrest continues to evolve. Adding to the evolution are the recently revised and updated Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care, a concerted effort of a multidisciplinary panel of experts on the Emergency Cardiac Care Committee and Subcommittees of the American Heart Association.[1]

This article focuses on pharmacologic aspects of advanced cardiac life support that are reviewed in the new guidelines and attempts to integrate consensus recommendations from this document into a clinical perspective, based on recent developments in the field.

Recommendations contained in the new guidelines have not been put forth as the sole acceptable approach to cardiopulmonary resuscitation. Instead, the ECC Committee and Subcommittees of the American Heart Association acknowledge that “deviations from [the new] recommendations and guidelines may be warranted when a trained physician (or medical care provider) proficient in CPR and ECC recognizes that such is in the best interest of the patient.”[1] Thus word “guidelines,” rather than the term “standards,” is now part of the title of the consensus statement, a word choice that underscores the lack of “legalistic or prohibitory function” in the content of the guidelines.[1-5]

Clearly, much remains to be learned about the management of cardiac arrest. However, one of the few certainties that has been established is full appreciation of the fact that more than on approach may be appropriate for the management of cardiac arrest. Clinical judgment and flexibility remain essential components of the decision-making process.

Ventricular Fibrillation:

Initial Considerations

By far the most important aspect of the management of cardiac arrest caused by ventricular fibrillation is early application of unsyncronized countershock.[6,7] Even if emergency medical service personnel are able to do nothing more than defibrillate the patient, lives will be saved by prompt application of this key intervention.[8,9]

A similar urgency for the need for early defibrillation should carry over to the hospital setting. In both settings, a quick response is essential, and the sooner countershock can be applied, the better the chance for converting the patient from ventricular fibrillation into a spontaneously perfusing rhythm.[10-12]

Current recommendations favor early application of three successive countershocks, with 200 joules for the initial attempt, 200 to 300 J for the second attempt, and 360 J for the third attempt (if needed).[1] If ventricular fibrillation persists, basic life support measures should be continued while the patient is intubated and intravenous access is secured. A trial of medication is then in order.

The Role of Epinephrine

MECHANISM OF ACTION

Epinephrine is the pharmacologic agent of choice for treatment of ventricular fibrillation that has not responded to initial defibrillation attempts.10,11 Although the mechanism of action of the drug in this situation is complex, the beneficial effect of epinephrine in the nonperfusing heart appears to be primarily attributable to its alpha-adrenergic (or vasoconstrictor) activity.[10]

As a result of this vasoconstriction, aortic diastolic pressure is increased, and the flow gradient to the coronary arteries (i.e., coronary perfusion pressure, or CPP) is favored. Studies suggest that achieving an aortic diastolic pressure adequate for promoting coronary flow during cardiac arrest may be the single most important determinant of survival.[10,13,14] In human subjects with cardiac arrest, return of spontaneous circulation is rarely seen unless mean coronary perfusion pressure attains a value of at least 20 mm Hg, an objective that is rarely achieved through basic life support measures alone.

In addition to the beneficial effect of epinephrine on coronary flow in the arrested heart, the alpha-adrenergic-induced vasoconstrictdion it produces promotes a favorable redistribution of flow to the cerebral circulation. This redistribution is achieved by means of a preferential shunting effect that results in diversion of flow away from the external branch of the carotid artery (which supplies primarily the face, neck and tongue), and toward the internal branch (which supplies the brain).[15-17] Thus, the most important therapeutic actions of epinephrine in the nonperfusing heart derive from its ability to optimize blood flow to key organs (i.e., heart and brain) while resuscitation is taking place.[17]

Although clearly less important in the arrested heart than its alpha-adrenergic effect, epinephrine’s other actions also contribute to its clinical efficacy. Thus, the potent beta-adrenergic stimulating effect of the drug is responsible for epinephrine’s chronotropic and inotropic properties, which serve to increase the rate and force of myocardial contraction.

Epinephrine also produces an alteration in the conduction properties of individual myocardial cells, an effect that probably accounts for the mechanism by which the drug facilitates conversion of ventricular fibrillation to sinus rhythm at the time of electrical countershock. Because conduction velocity is increased and the period of repolarization in myocardial tissue is shortened, the degree of dispersion between refractory periods of individual myocardial cells is reduced. As a result, the tendency to sustain fibrillating activity following unified depolarization of myocardial cells (as is produced by electrical countershock) is reduced.[10]

Activation of beta-adrenergic receptors in and of itself may prove to be a counterproductive effect for the patient in cardiac arrest, because the vasodilatation produced by beta-adrenergic stimulation generally results in a lowering of aortic diastolic pressure. Thus, despite a potentially important chronotropic and inotropic action, the reduction in aortic diastolic pressure produced by beta-adrenergic stimulation is likely to lead to a corresponding reduction in the gradient for coronary flow and an overall adverse effect on myocardial perfusion. For this reason, pure beta-adrenergic-stimulating agents such as isoproterenol (Isuprel) are now not used for treatment of cardiac arrest from ventricular fibrillation or asystole.[10]

The beneficial effect of epinephrine on coronary perfusion in the arrested heart is not unique to this agent. Other pressor agents with predominantly alpha-adrenergic-stimulating activity will also produce a vadsoconstrictor effect that increases aortic diastolic pressure and enhances the gradient for coronary flow. This is particularly true for the potent, nonselective and predominantly alpha-adrenergic-stimulating agent norepinephrine (Levophed). It is probably Ww true for dopamine (Intropin) at high-dose infusion rates, since alpha-adrenergic activity usually predominates when infusion rates of this drug exceed 15 to 20 [mu]g per kg per minute.[1,10]

In contrast, selective [alpha.sub.1]-adrenergic-stimulating agents such as methoxamine (Vasoxyl) and phenylephrine are not nearly as likely as predominantly nonselective agents to produce a beneficial effect on coronary perfusion, because of the down-regulation in responsiveness to [alpha.sub.1]-receptor activity that is typically seen in patients with cardiac arrest.[13,18]

Whether the significant component of beta-adrenergic stimulation, which epinephrine also exerts, is in some way essential for the optimization of the distribution of flow to vital organ tissue beds or whether similar effects can be obtained from agents that exert a relatively greater degree of alpha-adrenergic activity (such as norepinephrine or high-dose dopamine) is not yet entirely clear. However, for practical purposes, epinephrine remains the pressor agent of choice for pharmacologic treatment of cardiac arrest.[17,19,20]

DOSAGE CONSIDERATIONS

The most controversial aspect of the use of epinephrine in the treatment of cardiac arrest concerns dosage recommendations. hi the past, the recommended adult dose of epinephrine for treatment of cardiac arrest was 0.5 to 1.0 Mg.4 This dose was administered either intravenously or endotracheally, and repeated at five-minute intervals if ventricular fibrillation or asystole persisted.[4]

Recently, interest has focused on the use of much larger doses of epinephrine.[13,21-23] Unfortunately, studies to date have not yet demonstrated that improved survival results from the use of high-dose epinephrine.[10,23-25] Other problematic issues are the specific amount of epinephrine to give and how to determine which patients (if any) with cardiac arrest would be most likely to benefit from a higher dose.[10,26]

Despite these uncertainties, several points have become dear about epinephrine use in the nonperfusing heart. First, the minimum dose of epinephrine recommended for treatment of adults in cardiac arrest has been increased to 1.0 mg.[1] This amount of drug has been designated “standard-dose epinephrine” (SDE), to differentiate it from the higher dose of the drug, which now carries the designation “high-dose epinephrine” (HDE).[10]

In a patient in cardiac arrest, intravenously administered epinephrine achieves a peak blood level in two to three minutes, which is significantly less time than was previously thought.[17,19] Thus, it is reasonable to repeat the dose of epinephrine as often as every three minutes (if there is no response), instead of at five-minute intervals as had been suggested by previous guidelines.[1]

Epinephrine given endotracheally is effective, but substantially higher doses (on the order of 2 to 3 mg or more at a time) are probably required to achieve physiologic effects comparable to those achieved by intravenous administration of 1 mg.[1,10,17,27]

Admittedly, controversy continues over the optimal protocol for use of epinephrine in cardiac arrest. The American Heart Association currently favors initial administration of standard-dose epinephrine, with repetition of this dose at three- to five-minute intervals as needed.”[1]

Given the failure of studies to date to demonstrate improved survival with the use of high-dose epinephrine, the new guidelines allow that after the 1-mg dose has been tried, administration of higher doses is certainly “acceptable – but can be neither recommended nor discouraged.[1]

Practically speaking, it may never be possible to truly determine if survival could be improved by the appropriate use of high-dose epinephrine, at least for certain select groups of patients with cardiac arrest. The difficulty derives from the small size of the pool of candidates with ventricular fibrillation who might potentially benefit from higher doses of epinephrine; this pool may not be large enough to allow adequate study in a prospective, randomized, placebo-controlled trial, using long-term outcome as the end point. That is, the number of patients with out-of-hospital ventricular fibrillation who might respond to appropriately administered high-dose epinephrine and be resuscitated with intact neurologic function is likely to be exceedingly small if initial attempts at defibrillation (with 200, 300 and 360 J), administration of standard-dose epinephrine, and a fourth countershock have all failed to result in supraventricular rhythm.[10,26]

Even if high-dose epinephrine were to successfully restore a pulse in such patients, a disproportionate number of patients might still be left with significant neurologic sequelae because of the relatively longer time from patient collapse until discovery and initiation of treatment.[17,26]

Clinically, high-dose epinephrine is much less likely to be required during the early minutes of a cardiac arrest, because vascular tone is at least partially preserved for a brief period of time.[26] As a result, the American Heart Association has recommended beginning treatment with standard-dose epinephrine, especially for patients with cardiac arrest that occurs in the hospital (where the time until discovery of the condition and initiation of treatment is likely to be short).[10-12] however, if one (or at most two) doses of standard-dose epinephrine are ineffective-and there is a reasonable chance that brain damage has not occurred – the clinician may want to consider increasing the dose of epinephrine to the high-dose level in the hope that this might improve the patient’s chance for neurologic recovery.[10,12]

The protocols that have been proposed for administration of high-dose epinephrine are varied. They include gradual upward titration of bolus increments (i.e., sequential administration of 1, 3, 5 and 10 mg of epinephrine); bolus dosing on a milligram-per-kilogram basis (usually calculated at 0.1 to 0.2 mg per kg); immediate high-dose bolus administration (i.e., beginning with a dose between 10 and 30 mg); or administration of high-dose epinephrine by intravenous infusion (usually beginning at 100 to 200 [mu]g per minute and titrating the dose upward as needed).[1,10,11,13,20-22]

A more rapid escalation to the higher-dose range of epinephrine may be most appropriate for cases of cardiac arrest in which the time from collapse until discovery and initiation of treatment is likely to be long (i.e., for out-of-hospital cardiac arrest and/or in cases where the mechanism of arrest is asystole or very fine ventricular fibrillation).[10-12,26]

Fortunately, despite bolus administration of even large doses of epinephrine to patients with cardiac arrest, long-lasting sequelae from the use of high-dose epinephrine are surprisingly uncommon among survivors during the immediate post-resuscitation period, as long as the drug is rapidly tapered as soon as spontaneous circulation has been restored.28 Dosing recommendations for the principal drugs used in the management of cardiac arrest are summarized in Table 1.

TABLE 1

Suggested Dosing for the Principal Drugs Used in the Management

of Cardiac Arrest

Epinephrine – until the optimal dose becomes known:

Administer standard-dose epinephrine (SDE), 1 mg by

intravenous bolus or endotracheally. Dose may be repeated

at 3- to 5-minute intervals.

If no response to one administration (or at most two

administrations) of SDE and there is a reasonable chance that

irreversible brain damage has not yet occurred, consider using

high-dose epinephrine (HDE), 0.1 to 0.2 mg per kg, with

intravenous boluses of 3,5 and/or 10 to 15 mg at a time

(or HDE in an intravenous infusion).

* SDE infusion: mix 1 mg of a 1:10,000 solution of

epinephrine in 250 mL of dextrose (5%) in water (D5W), 15 to

30 drops per minute (1 to 2 [mu]g per minute).

* HDE infusion: mix 50 mg of a 1:1,000 solution of

epinephrine in 250 mL of D5W, 30 to 60 drops per minute

(100 to 200 [mu]g per minute); increase drip as needed.

Administer epinephrine edotracheally if intravenous access is

unavailable. Higher doses epinephrine (2 to 3 mg or more) are

likely to be needed for endotracheal administration.

Lidocaine (Xylocaine) – 75 to 125 mg (1.5 mg per kg) for

initial intravenous bolus in refractory ventricular

fibrillation; dose may be repeated in 3 to 5 minutes if not

response (up to a total dose of 3 mg per kg). Consider

intravenous infusion of lidocaine at a rate of 2 mg per minute

at the time of bolus administration or delay initiation of

continuous intravenous infusion until patient is out of

ventricular fibrillation.

* Intravenous infusion: mix 1 g lidocaine in 250 mL of D5W, 30

drops per minute (2 mg per minute); maximum infusion rate:

4 mg per minute.

Sodium bicarbonate – 1 to 2 ampules (50 to 100 mEq) as

empiric dose, but use should probably be delayed until 5 to

10 minutes into the code period, if used at all.

Bretylium (Bretylol) – 5 mg per kg initially (1 ampule = 500

mg); circulate with cardiopulmonary resuscitation, then

defibrillate. If patient is still in ventricular fibrillation,

may give 10 mg per kg (1 to 2 ampules), and may repeat every 5

minutes, up to a total dose of 30 to 35 mg per kg.

* Intravenous infusion for treatment of ventricular

fibrillation: mix 1 g of bretylium in 250 mL of D5W, 15

drops per minute (1 mg per minute).

* Intravenous infusion for treatment of sustained ventricular

tachycardia: dilute 500 mg of bretylium in 50 mL of D5W and

infuse intravenously over 10 minutes.

Amiodarone – 150 to 500 mg intravenously over 5 to 10 minutes; may

repeat in 15 to 30 minutes.

Propranolol (Inderal) – 0.5 to 1.0 mg by slow intravenous

administration over 5 minutes, up to a total dose of 5.0 mg.

Magnesium sulfate – 1 to 2 g intravenously over 1 to 2 minutes;

may repeat in 5 to 15 minutes. More gradual intravenous

infusion of magnesium (i.e., 1 to 2 g over 10 to 20 minutes or

longer) may be preferred for cardiac arrhythmias with less

immediate hemodynamic consequences.

Adapted from Grauer K, Cavallaro D. ACLS: pocket reference. An

approach to the key algorithms for cardiopulmonary

resuscitation. St. Louis:

Mosby Lifeline, 1994, and from Emergency Cardiac Care Committee

and Subcommittees, American Heart Association. Guidelines for

cardiopulmonary resuscitation and emergency cardiac care. JAMA

1992;268:2171-2295. Used with permission.

Refractory Ventricular Fibrillation

LIDOCAINE

Ventricular fibrillation that fails to respond to initial attempts at defibrillation and treatment with one or more doses of epinephrine is referred to as refractory. Development of this situation is an indication for a trial of antifibrillatory therapy.[1] Traditionally, lidocaine (Xylocaine) has been the initial antifibrillatory agent selected for treatment of this condition. However, despite its frequency of use in this respect, lidocaine has shown disappointing efficacy in facilitating conversion of ventricular fibrillation with subsequent countershock. Nevertheless, administration of at least one dose of lidocaine to patients with refractory ventricular fibrillation is still recommended in the new guidelines.[1]

The dose of lidocaine recommended for intravenous bolus administration in patients with cardiac arrest has been increased to 1.5 mg per kg.[1] Although the new guidelines allow for repetition of this dose in three to five minutes (to a total dose of 3 mg per kg), the chance that lidocaine will work is probably small if one or two bolus doses are ineffective.

Pharmacokinetically, immediate initiation of an intravenous infusion of lidocaine is unnecessary when the drug is used to treat ventricular fibrillation,[1] because the marked reduction in clearance of the drug in the nonperfusing heart facilitates maintenance of adequate blood levels during the period of cardiac arrest.[10,29] Despite acknowledgement of this fact, the clinician may want to consider routine initiation of a continuous intravenous infusion of lidocaine (usually at a rate of 2 mg per minute) at the time of bolus administration.[9-11] The advantage of this practice is that it obviates the necessity for remembering to start the infusion as soon as the patient is converted out of ventricular fibrillation, without unduly increasing the risk of lidocaine toxicity.[9-11]

ADDITIONAL CONSIDERATIONS

Persistence of ventricular fibrillation beyond this point in the code should prompt reevaluation and consideration of additional antifibrillatory measures.

Although in most cases of cardiac arrest it is unlikely that a predisposing, potentially correctable cause of ventricular fibrillation will be discovered, it is important to keep this possibility in mind. For example, treatment of refractory cardiac arrest that results from unsuspected hypothermia, electrolyte disturbance (e.g., hyperkalemia, hypokalemia, hypomagnesemia), severe acidosis, hypoxemia or drug overdose (especially of cocaine, tricyclic antidepressants or narcotic agents) is unlikely to be successful unless the predisposing cause of the arrest is identified and corrected.[9-11,30]

Similarly, development of an unsuspected complication of basic life support (such as tension pneumothorax or pericardial tamponade) is likely to invalidate even the most intensive of resuscitative efforts unless the problem is promptly recognized and reversed.[9-11]

In the past, large amounts of sodium bicarbonate were routinely given to patients in cardiac arrest. Although contemplation of the relative merits of the drug in this setting is still appropriate, recent years have seen a marked reduction in its use. A major reason for this change is that sodium bicarbonate has never been shown to improve the prognosis of patients with cardiac arrest.[31-33] Use of sodium bicarbonate in this setting may result in a number of adverse effects, including iatrogenic alkalosis, hyperosmolality, hypokalemia, sodium overload, a leftward shift in the oxyhemoglobin dissociation curve (with consequent impairment of oxygen release to the tissues), precipitation of convulsions, aggravation of myocardial ischemia and/or cardiac arrhythmias, and production of a paradoxic intracellular acidosis.[9-12,31,32,34,35]

It is the paradoxic intracellular acidosis that is the most difficult effect to reconcile, since the clinician may be lulled into a false sense of security by improvement of the arterial blood gas pH value, despite a worsening of the degree of intracellular acidosis (i.e., within individual myocardial and cerebral cells).

Because the acidosis that develops during the early minutes of cardiopulmonary arrest is mainly respiratory in nature, optimal therapy should be directed primarily at improving ventilation.[1,31] Administration of sodium bicarbonate at this time is more likely to be counterproductive (because of its paradoxic effect on intracellular homeostasis) and should therefore be avoided.[35,36]

Practically speaking, sodium bicarbonate should probably not be given at all for at least the first five to 10 minutes of the resuscitation effort regardless of the arterial blood gas pH value, except in the presence of extenuating circumstances, such as a severe preexisting metabolic acidosis or certain types of drug overdose.[9-11]

BRETYLIUM

At this point in the resuscitation process, additional antifibrillatory measures should be considered. Pharmacologic agents that have been included in this category are bretylium (Bretylol), amiodarone, intravenous beta blockers and magnesium sulfate. Unfortunately, definitive studies are lacking on the use of these agents in the setting of cardiac arrest. As a result, the decision to initiate treatment with one or more of these drugs must be individualized to the clinical situation. Other unanswered questions concern dosing and ways of integrating these drugs with the standard treatment measures that have already been discussed.

Bretylium is a potent antiarrhythmic agent that has been recommended for acute treatment of malignant ventricular arrhythmias. The drug has a complex mechanism of action, including adrenergic stimulation (which results in an initial release of norepinephrine) that is followed several minutes later by adrenergic blockade.[10] As a result of these effects, ventricular ectopy may actually worsen when intravenous bretylium is first administered (from adrenergic stimulation and catecholamine release). Hypotension may then develop (as a result of catecholamine depletion), especially when the patient is maintained on an intravenous infusion of the drug.[10,37,38] Other antiarrhythmic agents, such as lidocaine and procainamide (Pronestyl), are therefore preferred for initial treatment of ventricular ectopy and ventricular tachycardia.[1]

Bretylium is most effective as an antifibrillatory agent. However, despite this action, bretylium has not been shown in clinical studies to improve the survival of patients in refractory ventricular fibrillation. Because lidocaine is more familiar than bretylium to most emergency care providers, is equally effective and potentially safer to use in this setting, it continues to be recommended as the initial antifibrillatory measure of choice.[1] Failure to respond to one or two bolus doses of lidocaine is an indication to consider using bretylium.[1,10,11] Whether bretylium will then act independently or synergistically to enhance the antifibrillatory action of lidocaine is uncertain.[10,39]

Dosing of bretylium in the setting of cardiac arrest is necessarily empiric. Recommendations are to initially administer an intravenous bolus of bretylium, 5 mg per kg, followed by electric defibrillation.[1] If ventricular fibrillation persists, the dose may be increased (to 10 mg per kg), and repeated every five minutes up to a total dose of 30 to 35 mg per kg.[1] Although bretylium usually begins to exert its antifibrillatory effect within two minutes of administration, its onset of action is sometimes delayed for as long as 10 to 15 minutes.[10,40,41] Consequently, once the decision is made to try bretylium, resuscitation efforts should probably continue for at least long enough to ensure that the drug has had an adequate opportunity to work.[10,11]

AMIODARONE

Because of the disappointing clinical response of refractory ventricular fibrillation to treatment with lidocaine and bretylium, increasing interest has developed in the intravenous formulation of amiodarone. Until recently, use of this potent class III antifibrillatory agent was primarily restricted to the ambulatory setting for treatment of malignant ventricular arrhythmias resistant to other drugs.[42] However, a small retrospective study by Williams and colleagues[43] suggests that intravenous administration of amiodarone, 150 to 600 mg over a five- to 15-minute period (and repeated if necessary) may convert at least some patients in refractory ventricular fibrillation who fail to respond to conventional therapy.

Although larger prospective trials are clearly required to determine the role (if any) of intravenous amiodarone in the setting of cardiac arrest, the emergency care provider may do well to keep this option in mind when confronted with a patient in persistent ventricular fibrillation that is refractory to other treatment.[9-12] Amiodarone may prove to be especially useful in the treatment of patients with recurrent ventricular tachycardia who are unable to maintain sinus rhythm with conventional antiarrhythmic therapy.[10]

BETA BLOCKERS

Intravenous beta-blocking agents are not always thought of as part of the pharmacologic armamentarium for the treatment of cardiac arrest. However, occasionally situations will arise in which all other treatment measures fail, and only intravenous beta blockers may save the patient.[44] Examples of such situations are those that implicate excessive sympathetic tone as an important factor in the etiology of the arrest. These situations include acute anterior infarction (especially when the event was preceded by tachycardia or hypertension), cocaine overdose or severe stress in the prearrest period.[10,11]

Even without predisposing factors, empiric use of an intravenous beta blocker may sometimes be effective when an other treatment measures have failed. Although any intravenous beta-blocking agent could be tried, intravenous propranolol (Inderal) is often preferred for its ease of administration and the greater familiarity with its use. The recommended dose of this drug in an emergency setting is 0.5 to 1.0 mg, which should be given by slow intravenous administration (i.e., over a five-minute period), up to a total dose of 5.0 mg.[1]

MAGNESIUM

Among the pharmacologic agents available for treatment of cardiac arrest and for use in emergency cardiac care, magnesium sulfate may be the drug that is most under-utilized. Increasing evidence suggests clinical efficacy of magnesium in the management of a variety of cardiac arrhythmias, including paroxysmal supraventricular tachycardia, multifocal atrial tachycardia and arrhythmias resulting from digitalis toxicity, and for treatment of cardiac arrest resulting from ventricular tachycardia or ventricular fibrillation.[9,10,45-50] It has become the medical treatment of choice for torsade de pointes.[9,45,48,51-53]

In addition, prophylactic infusion of magnesium in patients with acute myocardial infarction has been shown to significantly reduce the risk of mortality, the chance of heart failure and the incidence of malignant ventricular arrhythmias during the initial hours of the infarct.[9,54,55]

The mechanism responsible for the beneficial effect of magnesium in the management of cardiac arrhythmias and acute myocardial infarction is not completely understood. In all likelihood, a combination of factors is operative. Thus, the beneficial effect of magnesium may result from a restoration of myocardial cell membrane stability, correction of electrolyte abnormalities (adequate magnesium stores are essential for correction of hypokalemia as well as hypomagnesemia), prolongation of the effective refractory period of the atrioventricular (AV) node and of individual myocardial cells, and/or a “cardioprotective effect” (which results from the drug’s ability to limit infarct size, decrease platelet aggregation, reduce peripheral vascular resistance and produce coronary vasodilatation).[9,10,48-50-54-56-57]

Guidelines for the use and dosing of magnesium in the acute care setting are not well defined. Although the need for magnesium is clear in patients who develop problematic cardiac arrhythmias in association with low serum magnesium levels, the serum magnesium level by itself does not reliably identify which patients will benefit from administration of the drug.[9,10,58] Serum magnesium levels are merely a reflection of extracellular magnesium, whereas the overwhelming majority of the body’s store of this cation is contained within the intracellular compartment.

In practice, serum magnesium levels are rarely available to the emergency care provider at the moment of a cardiac arrest. Even when this information is available, its clinical utility may be of uncertain benefit because of two factors: (1) serum magnesium levels can be normal despite profound intracellular depletion of this cation and (2) a comparable beneficial antiarrhythmic effect may be achieved with magnesium in many patients who have cardiac arrhythmias that had been resistant to other measures, regardless of normal or low serum magnesium

Fortunately, for treatment of life-threatening ventricular arrhythmias, intravenous administration of a 10 percent solution of magnesium, 1 to 2 g over one to two minutes (and repeated in five to 15 minutes, if needed), is usually not associated with significant adverse effects. Thus, for practical purposes, there may be little to lose (and everything to gain) from empiric administration of magnesium in an emergency situation when other therapeutic measures have failed. As a result, the clinician may want to consider a trial of this drug for treatment of patients with refractory ventricular fibrillation, sustained ventricular tachycardia and other clinically significant cardiac arrhythmias that have not responded to standard measures.[9-11]

Empiric administration of intravenous magnesium is especially indicated for treatment of patients who are particularly likely to be intracellularly depleted in this cation. In addition to patients in whom serum magnesium levels are known to be low, this also includes persons with one or more of the conditions that predispose to hypomagnesemia or are commonly associated with reduced body stores of this cation, [45,58-60] (Table 2).

TABLE 2

Clinical Conditions and Settings Commonly Associated

with Intracellular Depletion of Magnesium

Hypomagnesemia (i.e., the presence of a low magnesium level

in the

extracellular comparments)

Electrolyte abnormalities (one or more):

Hypokalemia

Hyponatremia

Hypocalcemia

Hypophosphatemia

Congestive heart failure, acute myocardial infarction and/or

significant

cardiac arrythmias or cardiac arrest

Digitalis or diuretic therapy

History of alcohol abuse

Diabetes mellitus (especially if the patient is in diabetic

ketoacidosis at the

time of presentation)

Renal insufficiency

Malnourishment

Advance age

More gradual infusion of magnesium (i.e., giving 1 to 2 g over 10 to 20 minutes or longer) may be preferable when treating cardiac arrhythmias with less immediate hemodynamic consequences.

REFERENCES

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Ken Grauer, M.D. is professor and assistant director of the family practice residency program at the University of Florida College of Medicine, Gainesville. Dr. Grauer received his medical degree from the State University of New York Health Science Center at Syracuse and completed a residency in family practice at St. Margaret Memorial Hospital, Pittsburgh. He is the principal author of six books and many teaching aids on electrocardiography and advanced cardiac life support (ACLS).

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