Arrhythmias in Chronic Pulmonary Disease Phillip S. Wolf,
M.D.
DENVER, COLORADO ’
’
A bstract
Arrhythmias often complicate the course of patients with severe respiratory disease; the frequency of arrhythmias in patients with this condition approaches that seen with acute myocardial infarction. No one rhythm disturbance predominates, but rapid atrial and ventricular rhythms are characteristic. In the setting of acute respiratory failure, several conditions may predispose to arrhythmias. Hypoxemia, a serum pH that is too high or too low, and a low serum potassium may produce arrhythmias by disturbing the myocardial cellular milieu. Drugs such as digitalis, epinephrine, and theophylline may also act as myocardial irritants. The first step in therapy is to assess the patient’s clinical status. In addition to careful examination, it is helpful to note the specific effect of the arrhythmia on the patient. Some rhythm disturbances are well tolerated, while others are . associated with serious problems in ventilation and perfusion. In many cases the control of respiration, correction of pH and electrolyte imbalance, and provision of bronchial hygiene will restore a normal sinus rhythm. Such measures are essential even when antiarrhythmic drugs or cardioversion are needed. Introduction
Arrhythmias occur commonly in patients with respiratory disease. The basic lung disorder causing arrhythmias includes a variety of conditions such as chronic obstructive pulmonary disease (COPD), acute or chronic pulmonary hypertension (often as a result of pulmonary embolism), and acute respiratory failure. Both atrial and ventricular rhythm disorders occur. In fact, in acute respiratory failure, the frequency of major arrhythmias (47%) approaches that of myocardial infarction. In ambulatory patients with COPD, 84% of those monitored with a 10-hour electrocardiographic recording displayed some rhythm disturbance.’ These reports confirm earlier observations that acute and chronic pulmonary diseases are associated with a wide variety of arrhythmias which often adversely affect prognosis. The most common arrhythmia in severely ill patients with respiratory disease is sinus tachycardia. Others frequently seen include paroxysmal atrial ’
From the
University of Colorado Medical Center,
and the Division of
Center, Denver, Colorado.
676
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
Cardiology,
Rose Medical
677
chaotic atrial rhythm (also termed multifocal atrial tachycardia), atrial flutter, and atrial fibrination.3-s Virtually any disturbance of rhythm, however, may be recorded, and several different rhythms may be observed in a
tachycardia,
given patient. number of reasons the patient with COPD is unusually susceptible to arrhythmias. Metabolic abnormalities contribute to most cases. The most consistent metabolic defects include hypoxemia, alterations of serum pH (especially alkalosis), and hypokalemia.1 Hypoxemia occurs very frequently in the critically ill patient. Diffuse atelectasis is probably the most common cause of hypoxemia which is seen in virtually any patient immobilized in bed even for short intervals. Hypoxemia may lead to respiratory alkalosis by stimulating respiratory drive. When observed in conjunction with hypoxemia, respiratory alkalosis increases the likelihood of developing arrhythmias. Respiratory alkalosis may also occur as a result of severe pain, apprehension, salicylate intoxication, or For
a
improper settings on a respirator. It is noteworthy that tracheal suctioning may cause hypoxemia, often leading to arrhythmias.1 Patients requiring suctioning should receive 100% oxygen for 5 minutes preceding suctioning, and the suctioning maneuver should be limited to 10 seconds on each attempt. Hypokalemia, itself capable of producing a metabolic alkalosis, develops when patients are given potent diuretics or corticosteroid therapy. Acting singly or together, hypoxemia, alkalosis, and hypokalemia appear to increase the firing rate of automatic cells within the heart. Rapid atrial or ventricular rhythms may result. Many drugs used in the treatment of chronic pulmonary disease are also arrhythmogenic. Aminophylline, for example, is a powerful myocardial stimulant which is capable of causing cardiac arrhythmias if given in high concentrations. Other bronchodilators such as epinephrine and isoproterenol have a wellknown tendency to induce tachycardias. Digitalis is sometimes used in patients with COPD with right ventricular failure. Its usefulness in this setting has yet to be resolved, but the risk of digitalis toxicity has clearly been shown to be increased when hypoxemia and hypokalemia are present.88
Therapy The treatment of
metabolically induced arrhythmias requires correction of the underlying problem. It is inappropriate (and usually ineffective) to manage such patients exclusively with drugs. On the other hand, correcting the metabolic disorder often is all that is needed to revert the arrhythmia to a sinus mechanism.
Hypoxemia requires oxygen in appropriate concentrations. In some patients with COPD, however, hypoxemia serves as the stimulus for ventilation, and O2
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
678
depress the ventilatory drive resulting in hypoventilation Oxygen should never be withheld from such patients. Appropriate ventilatory assistance and regulation of oxygen flow will control
administration may and CO2 retention.
both the O2 and CO2 levels. Arterial blood gas determinations are an invaluable means of guiding therapy for these seriously ill patients. Atelectasis, the basis for many cases of hypoxemia, will often respond to a simple regimen of deep breathing and coughing. The physician can encourage the patient in these maneuvers while on bedside rounds. Early mobilization, when feasible in the seriously ill patient, helps prevent atelectasis. When the patient must remain confined to bed, atelectasis also can be minimized by frequently turning the patient to either side. More complex measures are required with advanced atelectasis, including inhalation therapy, use of heated mist, back clapping, or postural drainage. Bronchoscopy has proved helpful when a large area of atelectasis is due to a localized mucus plug. Bronchospasm can be treated by oral, intravenous, or inhaled agents. When aminophylline is used intravenously, it must be given with caution if the heart rate is elevated. A constant infusion at a slow rate (0.9 mg/ kg/hour) is preferable. Finding the exact dose may be difficult, because the clinican is forced to choose between clinical benefit (relief of bronchospasm) and toxicity (aggravation of tachycardia). If the heart rhythm is very rapid, it may be preferable to avoid aminophylline and to use corticosteroids in high doses for brief periods. The correction of severe abnormalities in pH, p.C02, and p02 often requires intensive respiratory therapy, which is beyond the scope of this discussion. Hypokalemia, especially when potassium losses are sudden and severe, may trigger arrhythmias.’ Frequent measurements of serum potassium in patients on potent diuretics will detect the problem early. The preferred form of potassium replacement is oral potassium chloride in liquid form. In patients with good renal function, 20 mEq of potassium chloride is given following meals two to four times a day. Paradoxically, dangerously high serum levels of potassium are occasionally seen after treatment for hypokalemia is begun. It is wise to avoid standing orders for potassium replacement in seriously ill patients and to monitor serum potassium levels frequently.
Antiarrhythmic Drugs The ideal antiarrhythmic agent does not exist. Each of the commonly used drugs has significant and occasionally lethal side effects. Moreover, any given antiarrhythmic agent will at times be ineffective in a specific clinical situation. The clinician is often forced to make an intelligent guess in choosing the type of drug and dosage level. Therapy is helped by an understanding of the pharmacokinetics of commonly used agents,10 a brief discussion of which follows. Digoxin. This agent is often the first selected for patients with supra-
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
679
ventricular arrhythmias such as atrial fibrillation or flutter. Digoxin has little effect on multifocal atrial tachycardia. Digitalization may result in either reversion to a normal sinus rhythm or slowing of the ventricular rate to a more acceptable level. Digoxin should not be used to treat sinus tachycardia except when the tachycardia occurs secondary to congestive heart failure. The slowing in patients with heart failure results from improved cardiac output. Approximately 80% of an oral dose of digoxin is absorbed, and about onethird of the drug is excreted daily by the renal route. When given intravenously (which is preferable for many seriously ill patients), the usual starting dose of 0.5 mg is followed by 0.25 mg every 4 hours. Total dosage requirements vary widely. Some patients will not respond to customary doses of digoxin. To avoid the risks of digoxin toxicity, the following options should be considered. o Stop treatment if the heart rate has reached a satisfactory, although not ideal, level and if further doses produce no further slowing (for example, atrial fibrillation with a ventricular rate of 100-120). ~ Choose a second drug, such as propranolol, to control the heart rate. ~ Attempt electrical cardioversion. Cardioversion may be performed on a fully digitalized patient if the following precautions are observed: 1. The patient must not be obviously digitalis-intoxicated. 2. Intravenous lidocaine or diphenylhydantoin may be given immediately before cardioversion. 3. Low energy levels ( to 10 watt seconds) must be used initially. Should the initial level of countershock not produce signs of digitalis toxicity, the energy level can be increased in stepwise fashion with relative safety. o Propranolol or quinidine may effect cardioversion. The dosage of digoxin should be reduced in patients with renal failure, hypokalemia, hypothyroidism, severe hypoxemia, or acute myocarditis due to a greater than usual risk of digitalis intoxication in these cases. Lidocaine. This drug has great value in the management of ventricular premature contractions (VPCs) or ventricular tachycardia. Lidocaine, which must be given IV, has the advantages of rapid effectiveness and minimal effect on cardiac contractility in usual doses. An initial intravenous dose of 50 to 100 mg will ordinarily suppress VPCs for about 20 minutes. If the VPCs return, the bolus is repeated and a constant IV infusion is begun at a rate of 1-4/minute. The drug is metabolized very effectively by the liver, and excretion is reduced in patients with impaired liver function (congestive heart failure or intrinsic liver disease). In excessive doses lidocaine produces agitation or seizures and rarely heart block. Allergic reactions do not occur with this drug. The therapeutic blood level for lidocaine is 2 to 5 JIg/m1. Procainamide. This drug is effective whether used IV, IM, or orally. The IV route is generally reserved for patients with serious ventricular arrhythmias not responding to lidocaine. When given orally, procainamide has moderate effec-
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
680
tiveness
against ventricular arrhythmias. It is somewhat less effective than quinidine in the management of supraventricular arrhythmias. Procainamide is given intravenously in initial doses of 100 mg by slow infusion and repeated every 5 minutes until either a therapeutic effect is reached or toxicity (hypotension or widening of the QRS complex) develops. The total dose should probably not exceed 1 g. The loading dose is followed by a sustained infusion of 2 to 4 mg/minute. When used orally, the dosage ranges from 250 to 500 mg every 3 to 6 hours. The therapeutic blood level for procainamide is 4 to 8 ~g/m1. The dosage should be reduced in patients with heart failure or liver or renal disease. In low doses procainamide enhances cardiac conduction. Higher doses depress atrioventricular conduction, and when heart block is present the drug should be used with great caution. Toxic levels of the drug widen the QRS complex and the drug must be stopped if this occurs. Procainamide is known to depress cardiac contractility and produce hypotension, especially when given in large doses to patients with preexisting heart disease. The side effects of procainamide include nausea, vomiting, abdominal cramps, and diarrhea. Another reaction mimics some features of systemic lupus erythematosus (fever, pleuropericarditis, rash and joint pains). The lupus reaction tends to occur more often in patients maintained on procainamide for prolonged periods and disappears when the drug is withdrawn. Propranolol. Of the drugs that induce beta blockade, propranolol is widely used in this country. Propranolol is useful in a variety of arrhythmias, including atrial fibrillation or flutter, atrial tachycardia, ventricular tachycardia, and recurrent ventricular fibrillation following defibrillation. Propranolol may slow the ventricular response to atrial fibrillation or flutter or may revert these rhythms on occasion to a normal sinus rhythm. Propranolol may be used alone
adjunct to digoxin or quinidine. Propranolol depresses cardiac output and therefore is contraindicated in patients with significant congestive heart failure. Judicious use of digoxin or diuretics will permit the use of propranolol in patients with mild congestive heart failure. A special indication for propranolol is the patient with heart failure due to a supraventricular tachyarrhythmia. Reducing the ventricular rate in this situation may improve cardiac output and offset any depressant action of propranolol on the heart. The drug should be used with great caution in patients with asthma. Propranolol may aggravate airway obstruction in patients with increased airway resistance and may also interfere with beta-2 stimulating bronchodilators. Hypoxemia and occasionally irreversible bronchospasm sometime result. The dosage of propranolol varies considerably and should be adjusted on an individual basis. When given orally the dose ranges from 5 to 160 mg every 6 hours. The IV route is used infrequently and with great caution. A suggested or as an
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
681 test dose
of 0.3 to 1.0 mg given every 2 minutes to a total dose of 4 mg is advisable because of the tendency of propranolol to precipitate heart failure in susceptible patients. The therapeutic blood level for propranolol has not been established. Quinidine. Newer techniques have established blood levels of quinidine with greater accuracy. The range is from 2.3 to 5 J.Lg/ml, a range considerably lower than that obtained with older methods. Quinidine is a highly effective but toxic drug. It is useful for both supraventricular and ventricular ectopic rhythms. In each case the advantages of rhythm control must be weighed against the risks of the drug. Side effects consist of gastrointestinal complaints (nausea, vomiting, diarrhea), cinchonism (tinnitus, blurred vision, delirium and vertigo) and arrhythmias-in particular, ventricular tachycardia and heart block. A 2 to 3% incidence of sudden death has been ascribed to quinidine therapy. Quinidine sulfate is rapidly absorbed and reaches a peak blood level at about 1.5 hours. In contrast, quinidine gluconate absorbs more slowly with a peak level of about 4 hours.&dquo; It would be expected that the gluconate could be given less frequently (every 8 to 12 hours) than the sulfate (every 6 to 8 hours) because of the more prolonged absorption of the gluconate salt, which also results in lower
levels. The effective dosage in any given patient will vary quite widely as a result of patient variation, the disease state, the presence of other drugs, and differences in the composition of the commercial products. An initial total dose of 600 to 900 mg daily is usually given. The dose should be gradually increased with attention directed to electrocardiographic signs of toxicity (prolonged QRS and Q-T intervals). Blood levels are very helpful, although an occasional patient may show signs of toxicity with &dquo;therapeutic&dquo; blood levels, which others may be markedly benefited at &dquo;subtherapeutic&dquo; levels. Quinidine should be used with great caution in patients with a slow heart rate, because the propensity for toxicity is greater in these individuals. Renal disease, hepatic failure, and congestive heart failure appear to have a relatively small effect on dosage levels. The intravenous route should be avoided because of the tendency of the drug to induce circulatory collapse in single large doses. The IM route does not provide effective blood levels. Finally, patients who receive quinidine for conversion of atrial fibrillation or flutter should first be digitalized since quinidine increases conduction through the AV junction in low doses and may thereby raise the ventricular rate to dangerously high levels. This effect is blocked by digoxin.
peak
S. Wolf, M.D. 4545 East 9th A venue Suite 600 Denver, Colorado 80220
Phillip
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
682 The author wishes to thank David Shander, M.D., Robert S. Baum, M.D., and Lane D. Craddock, M.D., for their comments, and Mrs. Diane Yacovetta for preparation of the manuscript.
References 1. Hudson, L. D., Kurt, T. L., Petty, T. L., et al.: Arrhythmias associated with acute respiratory failure in patients with chronic airway obstruction. Chest, 63: 661-665, 1963. 2. Kleiger, R. E., Senior, R. M.: Long-term electrocardiographic monitoring of ambulatory patients with chronic airway obstruction. Chest, 65: 483-488,1974. 3. Thomas, A. J., Valabhji, P.: Arrhythmia and tachycardia in pulmonary heart disease. Br. Heart J., 3l: 491-496, 1969. 4. Shine, K. I., Kastor, J. A., Yurchak, P. M.: Multifocal atrial tachycardia. N. Engl. J. Med., 279: 344-349, 1968. 5. Kones, R. J., Phillips, J. H.: Chaotic atrial mechanism: Characteristics and treatment. Critical Care Med., 2: 243-250, 1974. 6. Ayres, S. M., Grace, W. J.: Inappropriate ventilation and hypoxemia as causes of car-
7.
8.
9.
10.
11.
diac arrhythmias. Am. J. Med., 46: 495-506, 1969. Shim, C., Fine, N. Fernandez, R., et al.: Cardiac arrhythmias resulting from tracheal suctioning. Ann. Intern. Med., 71: 1149-1154, 1969. Harrison, D. C., Robinson, M. D., Kleiger, R. E.: Role of hypoxia in digitalis toxicity. Am. J. Med. Sci., 256: 352-360, 1968. Schwartz, A. B.: Potassium-related cardiac arrhythmias and their treatment. Angiology, 29: 194-206, 1978. Singh, B. N.: Rational basis of antiarrhythmic therapy: Clinical pharmacology of commonly used antiarrhythmic agents. 29: 206-243, 1978. tAngiology, Woosley, R. L., Shand, D. G.: Pharmacokinetics of antiarrhythmic drugs. Am. J. Cardiol., 41: 986-996, 1978.
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
M.D.
DENVER, COLORADO ’
’
A bstract
Arrhythmias often complicate the course of patients with severe respiratory disease; the frequency of arrhythmias in patients with this condition approaches that seen with acute myocardial infarction. No one rhythm disturbance predominates, but rapid atrial and ventricular rhythms are characteristic. In the setting of acute respiratory failure, several conditions may predispose to arrhythmias. Hypoxemia, a serum pH that is too high or too low, and a low serum potassium may produce arrhythmias by disturbing the myocardial cellular milieu. Drugs such as digitalis, epinephrine, and theophylline may also act as myocardial irritants. The first step in therapy is to assess the patient’s clinical status. In addition to careful examination, it is helpful to note the specific effect of the arrhythmia on the patient. Some rhythm disturbances are well tolerated, while others are . associated with serious problems in ventilation and perfusion. In many cases the control of respiration, correction of pH and electrolyte imbalance, and provision of bronchial hygiene will restore a normal sinus rhythm. Such measures are essential even when antiarrhythmic drugs or cardioversion are needed. Introduction
Arrhythmias occur commonly in patients with respiratory disease. The basic lung disorder causing arrhythmias includes a variety of conditions such as chronic obstructive pulmonary disease (COPD), acute or chronic pulmonary hypertension (often as a result of pulmonary embolism), and acute respiratory failure. Both atrial and ventricular rhythm disorders occur. In fact, in acute respiratory failure, the frequency of major arrhythmias (47%) approaches that of myocardial infarction. In ambulatory patients with COPD, 84% of those monitored with a 10-hour electrocardiographic recording displayed some rhythm disturbance.’ These reports confirm earlier observations that acute and chronic pulmonary diseases are associated with a wide variety of arrhythmias which often adversely affect prognosis. The most common arrhythmia in severely ill patients with respiratory disease is sinus tachycardia. Others frequently seen include paroxysmal atrial ’
From the
University of Colorado Medical Center,
and the Division of
Center, Denver, Colorado.
676
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
Cardiology,
Rose Medical
677
chaotic atrial rhythm (also termed multifocal atrial tachycardia), atrial flutter, and atrial fibrination.3-s Virtually any disturbance of rhythm, however, may be recorded, and several different rhythms may be observed in a
tachycardia,
given patient. number of reasons the patient with COPD is unusually susceptible to arrhythmias. Metabolic abnormalities contribute to most cases. The most consistent metabolic defects include hypoxemia, alterations of serum pH (especially alkalosis), and hypokalemia.1 Hypoxemia occurs very frequently in the critically ill patient. Diffuse atelectasis is probably the most common cause of hypoxemia which is seen in virtually any patient immobilized in bed even for short intervals. Hypoxemia may lead to respiratory alkalosis by stimulating respiratory drive. When observed in conjunction with hypoxemia, respiratory alkalosis increases the likelihood of developing arrhythmias. Respiratory alkalosis may also occur as a result of severe pain, apprehension, salicylate intoxication, or For
a
improper settings on a respirator. It is noteworthy that tracheal suctioning may cause hypoxemia, often leading to arrhythmias.1 Patients requiring suctioning should receive 100% oxygen for 5 minutes preceding suctioning, and the suctioning maneuver should be limited to 10 seconds on each attempt. Hypokalemia, itself capable of producing a metabolic alkalosis, develops when patients are given potent diuretics or corticosteroid therapy. Acting singly or together, hypoxemia, alkalosis, and hypokalemia appear to increase the firing rate of automatic cells within the heart. Rapid atrial or ventricular rhythms may result. Many drugs used in the treatment of chronic pulmonary disease are also arrhythmogenic. Aminophylline, for example, is a powerful myocardial stimulant which is capable of causing cardiac arrhythmias if given in high concentrations. Other bronchodilators such as epinephrine and isoproterenol have a wellknown tendency to induce tachycardias. Digitalis is sometimes used in patients with COPD with right ventricular failure. Its usefulness in this setting has yet to be resolved, but the risk of digitalis toxicity has clearly been shown to be increased when hypoxemia and hypokalemia are present.88
Therapy The treatment of
metabolically induced arrhythmias requires correction of the underlying problem. It is inappropriate (and usually ineffective) to manage such patients exclusively with drugs. On the other hand, correcting the metabolic disorder often is all that is needed to revert the arrhythmia to a sinus mechanism.
Hypoxemia requires oxygen in appropriate concentrations. In some patients with COPD, however, hypoxemia serves as the stimulus for ventilation, and O2
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
678
depress the ventilatory drive resulting in hypoventilation Oxygen should never be withheld from such patients. Appropriate ventilatory assistance and regulation of oxygen flow will control
administration may and CO2 retention.
both the O2 and CO2 levels. Arterial blood gas determinations are an invaluable means of guiding therapy for these seriously ill patients. Atelectasis, the basis for many cases of hypoxemia, will often respond to a simple regimen of deep breathing and coughing. The physician can encourage the patient in these maneuvers while on bedside rounds. Early mobilization, when feasible in the seriously ill patient, helps prevent atelectasis. When the patient must remain confined to bed, atelectasis also can be minimized by frequently turning the patient to either side. More complex measures are required with advanced atelectasis, including inhalation therapy, use of heated mist, back clapping, or postural drainage. Bronchoscopy has proved helpful when a large area of atelectasis is due to a localized mucus plug. Bronchospasm can be treated by oral, intravenous, or inhaled agents. When aminophylline is used intravenously, it must be given with caution if the heart rate is elevated. A constant infusion at a slow rate (0.9 mg/ kg/hour) is preferable. Finding the exact dose may be difficult, because the clinican is forced to choose between clinical benefit (relief of bronchospasm) and toxicity (aggravation of tachycardia). If the heart rhythm is very rapid, it may be preferable to avoid aminophylline and to use corticosteroids in high doses for brief periods. The correction of severe abnormalities in pH, p.C02, and p02 often requires intensive respiratory therapy, which is beyond the scope of this discussion. Hypokalemia, especially when potassium losses are sudden and severe, may trigger arrhythmias.’ Frequent measurements of serum potassium in patients on potent diuretics will detect the problem early. The preferred form of potassium replacement is oral potassium chloride in liquid form. In patients with good renal function, 20 mEq of potassium chloride is given following meals two to four times a day. Paradoxically, dangerously high serum levels of potassium are occasionally seen after treatment for hypokalemia is begun. It is wise to avoid standing orders for potassium replacement in seriously ill patients and to monitor serum potassium levels frequently.
Antiarrhythmic Drugs The ideal antiarrhythmic agent does not exist. Each of the commonly used drugs has significant and occasionally lethal side effects. Moreover, any given antiarrhythmic agent will at times be ineffective in a specific clinical situation. The clinician is often forced to make an intelligent guess in choosing the type of drug and dosage level. Therapy is helped by an understanding of the pharmacokinetics of commonly used agents,10 a brief discussion of which follows. Digoxin. This agent is often the first selected for patients with supra-
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
679
ventricular arrhythmias such as atrial fibrillation or flutter. Digoxin has little effect on multifocal atrial tachycardia. Digitalization may result in either reversion to a normal sinus rhythm or slowing of the ventricular rate to a more acceptable level. Digoxin should not be used to treat sinus tachycardia except when the tachycardia occurs secondary to congestive heart failure. The slowing in patients with heart failure results from improved cardiac output. Approximately 80% of an oral dose of digoxin is absorbed, and about onethird of the drug is excreted daily by the renal route. When given intravenously (which is preferable for many seriously ill patients), the usual starting dose of 0.5 mg is followed by 0.25 mg every 4 hours. Total dosage requirements vary widely. Some patients will not respond to customary doses of digoxin. To avoid the risks of digoxin toxicity, the following options should be considered. o Stop treatment if the heart rate has reached a satisfactory, although not ideal, level and if further doses produce no further slowing (for example, atrial fibrillation with a ventricular rate of 100-120). ~ Choose a second drug, such as propranolol, to control the heart rate. ~ Attempt electrical cardioversion. Cardioversion may be performed on a fully digitalized patient if the following precautions are observed: 1. The patient must not be obviously digitalis-intoxicated. 2. Intravenous lidocaine or diphenylhydantoin may be given immediately before cardioversion. 3. Low energy levels ( to 10 watt seconds) must be used initially. Should the initial level of countershock not produce signs of digitalis toxicity, the energy level can be increased in stepwise fashion with relative safety. o Propranolol or quinidine may effect cardioversion. The dosage of digoxin should be reduced in patients with renal failure, hypokalemia, hypothyroidism, severe hypoxemia, or acute myocarditis due to a greater than usual risk of digitalis intoxication in these cases. Lidocaine. This drug has great value in the management of ventricular premature contractions (VPCs) or ventricular tachycardia. Lidocaine, which must be given IV, has the advantages of rapid effectiveness and minimal effect on cardiac contractility in usual doses. An initial intravenous dose of 50 to 100 mg will ordinarily suppress VPCs for about 20 minutes. If the VPCs return, the bolus is repeated and a constant IV infusion is begun at a rate of 1-4/minute. The drug is metabolized very effectively by the liver, and excretion is reduced in patients with impaired liver function (congestive heart failure or intrinsic liver disease). In excessive doses lidocaine produces agitation or seizures and rarely heart block. Allergic reactions do not occur with this drug. The therapeutic blood level for lidocaine is 2 to 5 JIg/m1. Procainamide. This drug is effective whether used IV, IM, or orally. The IV route is generally reserved for patients with serious ventricular arrhythmias not responding to lidocaine. When given orally, procainamide has moderate effec-
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
680
tiveness
against ventricular arrhythmias. It is somewhat less effective than quinidine in the management of supraventricular arrhythmias. Procainamide is given intravenously in initial doses of 100 mg by slow infusion and repeated every 5 minutes until either a therapeutic effect is reached or toxicity (hypotension or widening of the QRS complex) develops. The total dose should probably not exceed 1 g. The loading dose is followed by a sustained infusion of 2 to 4 mg/minute. When used orally, the dosage ranges from 250 to 500 mg every 3 to 6 hours. The therapeutic blood level for procainamide is 4 to 8 ~g/m1. The dosage should be reduced in patients with heart failure or liver or renal disease. In low doses procainamide enhances cardiac conduction. Higher doses depress atrioventricular conduction, and when heart block is present the drug should be used with great caution. Toxic levels of the drug widen the QRS complex and the drug must be stopped if this occurs. Procainamide is known to depress cardiac contractility and produce hypotension, especially when given in large doses to patients with preexisting heart disease. The side effects of procainamide include nausea, vomiting, abdominal cramps, and diarrhea. Another reaction mimics some features of systemic lupus erythematosus (fever, pleuropericarditis, rash and joint pains). The lupus reaction tends to occur more often in patients maintained on procainamide for prolonged periods and disappears when the drug is withdrawn. Propranolol. Of the drugs that induce beta blockade, propranolol is widely used in this country. Propranolol is useful in a variety of arrhythmias, including atrial fibrillation or flutter, atrial tachycardia, ventricular tachycardia, and recurrent ventricular fibrillation following defibrillation. Propranolol may slow the ventricular response to atrial fibrillation or flutter or may revert these rhythms on occasion to a normal sinus rhythm. Propranolol may be used alone
adjunct to digoxin or quinidine. Propranolol depresses cardiac output and therefore is contraindicated in patients with significant congestive heart failure. Judicious use of digoxin or diuretics will permit the use of propranolol in patients with mild congestive heart failure. A special indication for propranolol is the patient with heart failure due to a supraventricular tachyarrhythmia. Reducing the ventricular rate in this situation may improve cardiac output and offset any depressant action of propranolol on the heart. The drug should be used with great caution in patients with asthma. Propranolol may aggravate airway obstruction in patients with increased airway resistance and may also interfere with beta-2 stimulating bronchodilators. Hypoxemia and occasionally irreversible bronchospasm sometime result. The dosage of propranolol varies considerably and should be adjusted on an individual basis. When given orally the dose ranges from 5 to 160 mg every 6 hours. The IV route is used infrequently and with great caution. A suggested or as an
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
681 test dose
of 0.3 to 1.0 mg given every 2 minutes to a total dose of 4 mg is advisable because of the tendency of propranolol to precipitate heart failure in susceptible patients. The therapeutic blood level for propranolol has not been established. Quinidine. Newer techniques have established blood levels of quinidine with greater accuracy. The range is from 2.3 to 5 J.Lg/ml, a range considerably lower than that obtained with older methods. Quinidine is a highly effective but toxic drug. It is useful for both supraventricular and ventricular ectopic rhythms. In each case the advantages of rhythm control must be weighed against the risks of the drug. Side effects consist of gastrointestinal complaints (nausea, vomiting, diarrhea), cinchonism (tinnitus, blurred vision, delirium and vertigo) and arrhythmias-in particular, ventricular tachycardia and heart block. A 2 to 3% incidence of sudden death has been ascribed to quinidine therapy. Quinidine sulfate is rapidly absorbed and reaches a peak blood level at about 1.5 hours. In contrast, quinidine gluconate absorbs more slowly with a peak level of about 4 hours.&dquo; It would be expected that the gluconate could be given less frequently (every 8 to 12 hours) than the sulfate (every 6 to 8 hours) because of the more prolonged absorption of the gluconate salt, which also results in lower
levels. The effective dosage in any given patient will vary quite widely as a result of patient variation, the disease state, the presence of other drugs, and differences in the composition of the commercial products. An initial total dose of 600 to 900 mg daily is usually given. The dose should be gradually increased with attention directed to electrocardiographic signs of toxicity (prolonged QRS and Q-T intervals). Blood levels are very helpful, although an occasional patient may show signs of toxicity with &dquo;therapeutic&dquo; blood levels, which others may be markedly benefited at &dquo;subtherapeutic&dquo; levels. Quinidine should be used with great caution in patients with a slow heart rate, because the propensity for toxicity is greater in these individuals. Renal disease, hepatic failure, and congestive heart failure appear to have a relatively small effect on dosage levels. The intravenous route should be avoided because of the tendency of the drug to induce circulatory collapse in single large doses. The IM route does not provide effective blood levels. Finally, patients who receive quinidine for conversion of atrial fibrillation or flutter should first be digitalized since quinidine increases conduction through the AV junction in low doses and may thereby raise the ventricular rate to dangerously high levels. This effect is blocked by digoxin.
peak
S. Wolf, M.D. 4545 East 9th A venue Suite 600 Denver, Colorado 80220
Phillip
Downloaded from ang.sagepub.com at UNIV OF MONTANA on April 8, 2015
682 The author wishes to thank David Shander, M.D., Robert S. Baum, M.D., and Lane D. Craddock, M.D., for their comments, and Mrs. Diane Yacovetta for preparation of the manuscript.
References 1. Hudson, L. D., Kurt, T. L., Petty, T. L., et al.: Arrhythmias associated with acute respiratory failure in patients with chronic airway obstruction. Chest, 63: 661-665, 1963. 2. Kleiger, R. E., Senior, R. M.: Long-term electrocardiographic monitoring of ambulatory patients with chronic airway obstruction. Chest, 65: 483-488,1974. 3. Thomas, A. J., Valabhji, P.: Arrhythmia and tachycardia in pulmonary heart disease. Br. Heart J., 3l: 491-496, 1969. 4. Shine, K. I., Kastor, J. A., Yurchak, P. M.: Multifocal atrial tachycardia. N. Engl. J. Med., 279: 344-349, 1968. 5. Kones, R. J., Phillips, J. H.: Chaotic atrial mechanism: Characteristics and treatment. Critical Care Med., 2: 243-250, 1974. 6. Ayres, S. M., Grace, W. J.: Inappropriate ventilation and hypoxemia as causes of car-
7.
8.
9.
10.
11.
diac arrhythmias. Am. J. Med., 46: 495-506, 1969. Shim, C., Fine, N. Fernandez, R., et al.: Cardiac arrhythmias resulting from tracheal suctioning. Ann. Intern. Med., 71: 1149-1154, 1969. Harrison, D. C., Robinson, M. D., Kleiger, R. E.: Role of hypoxia in digitalis toxicity. Am. J. Med. Sci., 256: 352-360, 1968. Schwartz, A. B.: Potassium-related cardiac arrhythmias and their treatment. Angiology, 29: 194-206, 1978. Singh, B. N.: Rational basis of antiarrhythmic therapy: Clinical pharmacology of commonly used antiarrhythmic agents. 29: 206-243, 1978. tAngiology, Woosley, R. L., Shand, D. G.: Pharmacokinetics of antiarrhythmic drugs. Am. J. Cardiol., 41: 986-996, 1978.
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