Electromechanical dissociation: Diagnosis, pathophysiology, and management

CURRICULUM

IN CARDIOLOGY

Electromechanical pathophysiology, Shlomo William

dissociation: Diagnosis, and management

Charlap, MD, Sam Kahlam, MD, Edgar Lichstein, Frishman, MD. Brooklyn, N. Y.

Electromechanical dissociation (EMD), a usually fatal cause of cardiac arrest, describes a diverse group of pathophysiologic processes resulting in the loss of effective cardiac output despite adequate ECG complexes.ly 2 Failure of the heart muscle to produce an effective contraction in response to normal electrical excitation has been described as a primary form of EMD. Abrupt changes in the loading conditions of the heart, resulting in marked reductions in cardiac output despite preserved cardiac function, are causes of the secondary form of EMD.lv 2 This article reviews the clinical features, mechanisms, and therapeutic options in the management of EMD, both the primary and secondary forms. PRIMARY EMD

Patients with primary EMD frequently present with an abrupt loss of consciousness, not immediately preceded by cardiac or respiratory symptoms. Heart sounds are inaudible and there are no palpable pulses. Intraarterial monitoring may record arterial pressures, but to be consistent with the diagnosis, these are low with systolic arterial pressure generally less than 40 mm Hg.3 The initial rhythm is usually sinus or junctional but may quickly deteriorate to an idioventricular rhythm, asystole, or ventricular fibrillation. Patients may occasionally have EMD while in a pacemaker rhythm.39 4 Primary EMD may occur as an end-stage event in advanced heart disease or as a manifestation of an acute ischemic insult.4 It also frequently occurs at the end stage of a prolonged cardiac arrest.b 5 The role of EMD as the cause of sudden out-

From the Division of Cardiology, Department Medical Center, and The Long Island College New York Health Science Center at Brooklyn, lege of Medicine. Received Reprint 11219.

for publication requests:

Shlomo

Jan.

30, 1989;

Charlap,

MD,

of Medicine, Hospital, State and the Albert

accepted 4802

March 10th

Maimonides University of Einstein Col-

15, 1989. Ave.,

Brooklyn,

NY

MD, and

of-hospital cardiac death is difficult to determine but appears limited, ranging from 3 % to 22 % .617 On the other hand, EMD has been documented as a frequent cause of in-hospital sudden cardiac death. Raizes et al4 found that although only a small subgroup (15 of 663; 2.3%) of hospitalized patients with acute myocardial infarction had EMD, the syndrome accounted for 68% of the monitored sudden deaths (10% of all in-hospital deaths). Vincent et a1.3 reported EMD as the initial symptom in 36 of 54 episodes of monitored cardiac arrest, with none of the patients with EMD being successfully resuscitated. Although the episodes described by Vincent et a1.3 all appear to be the result of primary EMD, autopsies were not performed and secondary causes cannot be excluded. Raizes et a1.4 did perform autopsies in seven of their patients and found no evidence in any to suggest a secondary cause of EMD. In a review of results of 50 autopsies of patients dying in EMD at the John Hopkins Hospital, Pirolo et a1.8 found that 22 of 50 cases (44 % ) were due to primary EMD with 10 of these patients initially seen with ventricular tachycardia or fibrillation, which was then converted to EMD after resuscitation maneuvers. The remaining patients in the study had either secondary causes of EMD or the cause could not be determined (22 and 6 patients, respectively). PATHOPHYSIOLOGY

The precise cause and pathogenesis of primary EMD remains poorly understood, but the bulk of the evidence points toward ischemia as the underlying cause of the myocardial excitation and contraction uncoupling.2F g Under experimental conditions, occlusion of a coronary vessel rapidly leads to disappearance of myocardial contraction in the area at risk, although sinus rhythm may persist49 lo It has been postulated that the clinical syndrome of EMD is seen when a large enough area of the myocardium is rendered ischemic. However, the development of EMD is not thought to be dependent on occlusion of 355

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a second artery that supplies an area of the myocardium distinct from the site of the initial infarction.4 In patients with an initial large infarction, subsequent local ischemia may result in systolic or diastolic left ventricular dysfunction severe enough to produce hypotension and thereby global ischemia. The presence of global ischemia appears to make the myocardium vulnerable to global depolarization and the uncoupling of excitation and contraction.8 Calcium has been proposed as the final link in the pathophysiologic processess underlying the development of EMD in myocardial ischemia.2 This is not surprising considering the critical role played by calcium in excitation and contraction of myocardial cells. EMD has been created experimentally in cardiac preparations with the use of a calcium-free perfusate.l> 2yl3 Caufield et all4 observed six patients who had a sudden abrupt decrease in blood pressure shortly after intracoronary injection of a contrast agent containing EDTA and sodium citrate; the ECG continued to show sinus rhythm, but all of the patients died despite resuscitative attempts. When EMD has been created with calcium-free perfusate, subsequent reinstitution of calcium ions has not restored contractility.13 There are several mechanisms by which calcium may be involved in the development of EMD, including loss of the triggering calcium current, failure of calcium release from the sarcoplasmic reticulum, or reduction in the sensitivity of the contraction process to calcium.2 It is not clear which if any of these mechanisms is actually involved. It has been reported that action potentials continue early after the onset of ischemia15 and that it is only after several minutes that the cells may become inexcitable because of the accumulation of extracellular potassium.16 Allen and Orchard17 found that in cardiac cells the release of calcium from the sarcoplasmic reticulum was unchanged at the onset of ischemia, although the muscle did lose its contraction. A plausible explanation for the contraction failure is that the acidosis of ischemia led to a shift in the affinity of calcium for the contractile proteins. EMD has been created experimentally with perfusion of acetoacetate into the aortas of dogs.18 Some investigators have proposed that ischemiainduced decreases in intracellular creatine phosphate and adenosine triphosphate (ATP) have a role in the development of EMD.32 lg Others27 g have suggested that levels of ATP are maintained with ischemia, but that increases in inorganic phosphates and adenosine diphosphate limit the free energy available from ATP.2 It has also been proposed that the modulatory function of ATP is disrupted by ischemia, thereby

American

August 1999 Heart Journal

effecting calcium entry into cells, calcium efflux from the sarcoplasmic reticulum, or both.g The increased inorganic phosphates may also contribute to the development of EMD by forming insoluble calcium phosphate precipitates, thus trapping calcium in the sarcoplasmic reticulum and mitochondria.9 The greater incidence of inferior infarctions in patients with EMD suggests a role of the autonomic nervous system in this disorder.4 Acute increases in parasympathetic activity or withdrawal of sympathetic activity may be possible trigger mechanisms for the syndrome. Precipitous decreases in heart rate and blood pressure attributed to the Bezold-Jarisch reflex are frequently seen with inferior infarctions and may play a role in the development of EMD.20 Still, although bradycardia and atrioventricular block have been seen before or at the initiation of EMD, many patients are in normal sinus rhythm. This argues against increased parasympathetic or decreased sympathetic activity playing a major role in its development, Moreover, by means of a dog model, Kostreva et a1.21 found that the onset of EMD was significantly delayed by either surgical or pharmacologic sympathectomy, whereas sympathetic stimulation decreased the time to its onset. CONTROVERSIES Catecholamines.

IN TREATMENT

Stimulation of spontaneous contraction and increased inotropy and chronotropy as caused by beta-adrenergic agonists should theoretically be of benefit in the treatment of EMD. However, results of experimental work in cardiac arrest by Redding and Pearson22 and others23 have shown that potent beta agonists with little or no alpha-adrenergic activity are ineffective in resuscitative efforts. Conversely, all drugs with potent alpha-agonist activity, for example, epinephrine, metaraminol, and phenylephrine, are equally successful irrespective of beta-adrenergic potency. Results of further studies have supported the fact that only alpha-adrenergic stimulation is necessary for successful resuscitation.24 Beta activity on the myocardium is potentially deleterious in that it increases oxygen consumption, predisposes to arrhythmias, and shunts blood from the endocardium to the epicardium.25 On the other hand, beta agonists also increase coronary and cerebral blood flow. Alpha agonists may be helpful in maintaining a high coronary perfusion pressure and coronary blood flow, but the increased afterload or reduced flow to other vital organs could prove harmful.25 Presently there is no evidence to suggest that cat-

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echolamines that are primarily alpha agonists are superior to the mixed agonists (e.g., ephinephrine). There is also concern about the suitability of using potent alpha agonists in the immediate postresuscitation period. As such epinephrine has remained the catecholamine of choice for EMD and other emergency cardiac care26 (Table I). Bicarbonate. The lack of a documented effect on outcome and the high incidence of side effects reported with its use has led to the deemphasizing of bicarbonate in the treatment of EMD or other presentations of cardiac arrest.27* 28In globally ischemic myocardium, intramyocardial Pco:! is substantially elevated and can result in depressed myocardial function.27 Increased CO2 generated by the use of bicarbonate can potentially exacerbate this effect. Also bicarbonate itself can depress myocardial function.2g Hyperventillation and chest compression alone can maintain acid-base homeostasis in most patients. The role of acid-base imbalance in the development of EMD in itself remains in dispute. Whereas some authors believe that intracellular acidosis plays an important role in contractile failure,2 others have reported a protective effect of acidosis during myocardial hypoxia. 30,31 Vincent et a1.3 found that neither acidemia nor alkalemia altered the time of onset of EMD. Calcium. A beneficial role of calcium in EMD had been assumed because calcium increases myocardial contractility. This favorable effect was “confirmed” by Kay and Blalock32 in 1951. In four pediatric patients with cyanotic congenital heart disease, the administration of calcium restored or seemed to augment resuscitation of these patients from cardiac arrest. The fact that all four patients had massive hemorrhage requiring blood transfusions before the cardiac arrest and that they were probably hypocalcemic was not considered very significant. This and other anecdotal reports32 led the American Heart Association in 1974 to recommend that calcium be given in EMD,33 despite the absence of controlled studies showing its efficacy or safety. In 1981 Dembo34 questioned the value of calcium in advanced life support. He reported potentially dangerous levels of serum calcium 5 minutes after the standard 0.5 gm dose of intravenous calcium chloride. Subsequently other investigators35 also questioned the use of calcium in cardiopulmonary resuscitation because of both its lack of proven efficacy and questions about its safety. Results of retrospective studies surveying the use of calcium for EMD showed it to be of no value and possibly harmful.es-3s A prospective double-blind study of the use of calcium in EMD was carried out in the Milwaukee

Electromechanical

Table

dissociation

357

I. Therapy for primary EMD Accepted Cathecholamines Investigated Bicarbonate Calcium Calcium channel blockers Atropine Prostacyclin Glucose-insulin-potassium Methylprednisolone Glucagon Naloxone

County Paramedic system.3g There was a successful resuscitation in 8 of 48 patients (16.7 % ) receiving calcium compared to 2 of 42 patients (4.8%) receiving saline solution (p < 0.07). Calcium was of greatest benefit in a subset of patients with a widened QRS, peaked T waves, or elevated ST segments (8 of 39 receiving calcium were resuscitated compared to 1 of 31 not receiving it (p < 0.03). However, only 1 of the 90 patients in the study was discharged from the hospital. The potentially detrimental effects of calcium on the cardiovascular system are well established.4@43 The accumulation of calcium into the cytosolic and mitochondrial mileu with ischemic injury can contribute to postanoxic tissue damage. Other mechanisms by which calcium could further injure cells during cardiac arrest and reperfusion include: (1) production of vasoconstriction further limiting blood flow to the heart and brains; (2) increasing contractility, which may hasten myocardial cell death; (3) activation of a protease leading to increased production of xanthine oxidase and ultimately free radicals; and (4) activation of phospholipases that degrade the cell membrane and produce high levels of arachidonic acid. Arachidonic acid may be converted to thromboxane, which activates platlets thereby inducing further vascular spasm. At present the use of calcium in EMD and cardiac arrest is not recommended unless there is a strong clinical suspicion of hypocalcemia, hyperkalemia, or calcium channel blocker toxicity.26 A recent studti4 suggested that patients with out-of-hospital cardiac arrests of at least 10 minutes’ duration frequently have severe ionized hypocalcemia despite a normal total calcium level. Further study will determine whether this subset of patients may benefit from the administration of calcium in EMD. Calcium channel blockers. As disdussed, calcium mediates several cytotoxic events during cardiac arrest and the reperfusion period that can lead to irre-

358

Chariap

Table

II. Diagnosis

August

et al.

American

of secondary

EMD

History

Recent myocardial infarction, chest surgery, or trauma: cardiac tamponade Thrombophlebitis: pulmonary embolism Pneumonia, urinary infection: septicemia History or signs of bleeding: hypovolemia Abdominal pain: ruptured abdominal aneurysm Allergies: anaphylatic shock Physical

examination

Tachycardia: common finding Bradycardia: cardiac tamponade, myocardial ischemia Temperature: hypothermia, hyperthermia Neck vein distention: common finding Absent neck vein distention: septicemia, hemorrhage, hypovolemia Absent breath sounds: pneumothorax Heart murmur: valvular obstruction, atria1 myxoma, ischemia Abdominal distention: ruptured abdominal aneurysm Head trauma: neurogenic shock ECG

Low voltage: cardiac tamponade Right-heart strain: pulmonary embolism, pneumothorax Heart block arrhythmias: myocardial ischemia, metabolic abnormalities ST deviations, Q waves: myocardial ischemia or infarction Emergency

studies

Chemistries: hypoglycemia, hypocalcemia, hyperkalemia Chest x-ray: pneumothorax Cardiac echocardiogram: cardiac tamponade, valvular obstruction, atria1 myxoma Abdominal x-ray, ultrasound: ruptured abdominal aneurysm Pulmonary angiogram: pulmonary embolism

1989 Journal

calcium channel blockers during or after cardiac arrest is currently not recommended. Atropine. Atropine has been used in cardiopulmonary arrest for its parasympatholytic effect, primarily in patients with sinus and atrioventricular nodal blocks.52 The early use of a full vagolytic dose has also been recommended for ventricular asystole in the hope that parasympathetic suppression of the sinoatrial and atrioventricular nodes would be reversed, allowing capture of the atria and ventricles.26 General autonomic dysfunction with increased parasympathetic activity has been suggested to have a role in the development of EMD.4 However, results of experimental studies have not shown atropine to be effective in improving recovery from EMD.5 Other treatment modalities. Several other therapies have been tried for EMD with mixed results. Neither prostacyclin (PGIB), glucose-insulin-potassium (GIK3), nor methylprednisolone delayed the onset or helped to terminate EMD in various dog models.“, 5;1 In one uncontrolled study54 14 of 19 postcountershock episodes of either asystole or EMD (12 and 7 patients, respectively), which were unresponsive to cardiopulmonary resuscitation, had effective spontaneous circulation restored with administration of glucagon (the authors did not state how many of the patients in EMD responded). In a study of dogs, Rothstein et al.55 found naloxane to have salutory effects in reversing EMD but only after administration of epinephrine and successful defibrillation. SECONDARY

versible cell injury. Reduction of cellular influx of calcium after ischemia and reperfusion should in theory attenuate cerebral and myocardial injury.43 Results of experimental studies have shown that administration of calcium channel blockers before (and less consistently during and after) ischemic insults results in increased cerebral blood flow and improved neurologic recovery45-47 and in reduced myocardial injury and improved myocardial performance.48-50 In dog models of ventricular fibrillation, administration of calcium channel blockers has delayed the onset of EMD.51 The calcium blockers may decrease the use of energy during the cardiac arrest, allowing for maintenance of intracellular ionic homeostasis and preservation of the ATP stores necessary for cardiac function. It has been suggested that use of the calcium channel blockers may increase the possibility of successful resuscitation of patients in ventricular fibrillation and possibly those in EMD. The safety and clinical efficacy of such treatments in humans has yet to be shown.43 As such routine empiric therapy with

Heart

EMD

Secondary EMD results from profound changes in the loading conditions of the heart rather than intrinsic myocardial contractile failure.’ Disorders that profoundly decrease preload or afterload or cause severe inflow or outflow obstructions may lead to the clinical signs of EMD. Hypoxemia, severe acidosis, or both may contribute to the development of EMD in these conditions. Although no heart sounds may be heard or pulses felt, results of intraarterial monitoring usually show the presence of a systolic blood pressure that on occasion may not be significantly reduced.56 Results of echocardiographic evaluation show continued myocardial wall and valve motion.57 Recognition of the secondary form of EMD is important in that unlike primary EMD prompt treatment can result in a favorable outcome. Awareness of previous history and immediate preceding events, as well as clinical and ECG features of individual patients at the time they are first seen, increases the likelihood of a successful resuscitation (Table II). Massive pulmonary embolism. Patients have marked neck vein distention with evidence of peripheral

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Electromechanical

venous congestion. The ECG may show tachycardia and findings of right-sided overload. Arterial blood gas may show hypoxia. Acute cardiac tamponade. A history of acute myocardial infarction, recent cardiac surgery, or chest injury, associated with the sudden occurrence of EMD with bradycardia, should suggest acute cardiac tamponade.’ Venous pressure is high. One may see a relatively normal ECG, but changes that are frequently seen with tamponade include low QRS voltage with preserved P wave voltage, leftward axis shift, ST and T wave changes, and electrical alternans. Tension pneumothorax. By causing increased intrathoracic pressure, there is decreased return to the heart. Neck veins are distended, and there is tracheal deviation away from the affected lung. Results of careful auscultation of the chest may show hyperresonance with diminished breath sounds on the affected side. An ECG may show sinus tachycardia and rightward axis shift. Systemic shock. Venous pressure is decreased. Whereas external hemorrhage is often obvious, internal hemorrhage may be difficult to diagnose. Freidmanl suggested that the triad of EMD, tachycardia, and abdominal distention should suggest a ruptured abdominal aortic aneurysm. Patients with septic, anaphylactic, or neurogenic shock may develop EMD from the dramatic loss of vascular tone seen in these conditions. Sudden

obstruction

to inflow and outflow

of the heart.

Atria1 myxoma and intracardiac thrombus can produce a “ball valve phenomenon,” that is, the patient may be symptomatic only in certain positions. Malfunctioning prosthetic valves may also cause sudden obstruction to inflow or outflow of the heart. Transient EMD in hypertrophic cardiomyopathy leading to recurrent syncopal episodes has been described.58 Severe aortic or pulmonic stenosis may initially appear as EMD. Myocardial ischemia. Severe myocardial ischemia may at times be associated with profound decreases in heart rate and blood pressure but without global uncoupling of excitation and contraction. Aggressive treatment of the myocardial ischemia may lead to improvement in myocardial function. Miscellaneous. There are a number of other toxicmetabolic conditions that can cause or contribute to EMD, including hypoglycemia, hyperkalemia, hypocalcemia, and hypo- and hyperthermia. Patients who take overdoses of various agents, including calcium blockers, /3 blockers, ganglionic blockers, and cyclic antidepressants, may develop EMD. Vagotonia can also induce EMD. Of 22 cases of secondary EMD reviewed in the autopsy study of Pirolo et al.*,

Table

dissociation

359

Ill. Managing EMD

1. 2. 3. 4.

Establish diagnosis Begin cardiopulmonary resuscitation Establish intravenous access Epinephrine, l:lO,OOO, 0.5 to 1.0 mg intravenous push Repeat every 5 minutes If intubated and no intravenous line, epinephrine, mg diluted, via endotracheal tube 5. Intubation Earlier if done during other techniques Epinephrine first if adequate ventillation 6. Consider bicarbonate 7. Search for correctable causes (secondary EMD)

nine were due to myocardial to pulmonary embolization, to left-sided pneumothorax.

1.0

or arterial rupture, eight three to sepsis, and two

MANAGEMENT

Unless it is clearly determined that one is dealing with the secondary form of EMD, it is suggested that patients with EMD be initially treated with epinephrine as per protocol (Table III). Failure to respond to therapy should lead to a search for causes of secondary EMD. Various treatment modalities in secondary EMD include pericardiocentesis for cardiac tamponade, fluid and pressors for hemorrhage and sepsis, needle decompression for pneumothorax, and fluids and thrombolytic therapy for pulmonary embolism. Emergency surgery may be considered for atria1 myxoma or thrombus (possibly also thrombolytic therapy), valvular obstruction, prosthetic dysfunction, myocardial or arterial rupture, and some cases of pulmonary vascular compromise. We thank

Laura

Scalera

for help in preparing

this manuscript.

REFERENCES

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