Chapter 8 / Pulseless Electrical Activity



Pulseless Electrical Activity
John M. Field, MD

A small group of patients with acute myocardial infarction who die suddenly present
with a most unusual sequence of events: there is loss of consciousness, pulse and blood
pressure; heart sounds are inaudible; respiration is gasping; and yet the electrocardiogram is seemingly unaltered.
Eugene Braunwald in The Heart, 1980

In the early resuscitation guidelines, electrical mechanical dissociation (EMD) referred
to the prescence of organized electrical activity in the absence of synchronous myocardial
contraction (1–3). As such, electrical activity was detected on the surface electrocardiogram but no effective cardiac output was present owing to the absence of coupled mechanical activity. The clinical result was the absence of pulse, blood pressure, and heart tones.
EMD was observed in a variety of resuscitation situations and was felt to be secondary
to prolonged global cardiac ischemia. The organized rhythm varied from sinus tachycardia with a normal duration QRS complex to brady-dysrhythmias with wide aberrant or
idioventricular ventricular morphologies. A poor resuscitation outcome and dismal prognosis was a common shared observation. Collectively, this ominous rhythm was found
to have a resuscitation rate of only about 20% and a hospital discharge rate of 4 to 5%
Early animal studies and resuscitation attempts with inotropic and chronotropic drugs,
calcium chloride, and electrical pacing proved ineffective (5–11). Recent evaluations of
clinical predictors and prognosis have found that pulseless electrical activity (PEA)
continues to be poor predictor of survival. Only 15% of victims of prehospital cardiac
arrest (CA) are admitted alive to hospital and only 2.4% were discharged alive (12). PEA
From: Contemporary Cardiology: Cardiopulmonary Resuscitation
Edited by: J. P. Ornato and M. A. Peberdy © Humana Press Inc., Totowa, NJ


The heart stores energy as ATP. The term electromechanical dissociation poorly characterized the heterogeneous group of clinical rhythms confronting rescuers and presenting with some form of organized electrical activity and no detectable pulse. inorganic phosphate and a proton (H+) are released generating energy. PEA is observed in a broad spectrum of clinical disorders that have global severe cardiac ischemia or myocyte dysfunction as a final common pathway yet diverse inciting etiologies. Another compartment of the sarcoplasmic reticulum surrounds the contractile proteins and is called the sarcotubular network and contains adenosine triphosphate (ATP)asedependent proteins that actively pump calcium back into the cisternae. PATHOBIOLOGY An improved understanding of the mechanisms responsible for PEA has provided a refined pathophysiology of this disorder. and flood the cytosol initiating systolic contraction. The flux and interaction of calcium with myofibrillar elements initiates and terminates contraction by concentration characteristics at regulatory sites. ready for the next excitatory stimulus. When ATP is cleaved into adenosine diphosphate (ADP). and myofilaments. The Energy of Heart Muscle Contraction A heart muscle cell must convert chemical or stored energy into kinetic energy for effective cardiac contraction. This interaction is very complex and excitation–contraction coupling involves cell components called the plasma membrane. The specialized and working myocytes form a functional syncytium with cells linked electrically and mechanically. This system is called the sarcoplasmic reticulum. A dismal prognosis reflects the fact that PEA is a preterminal rhythm and not a specific entity. the resuscitation community began to refer to this clinical presentation of CA as PEA. sarcoplasmic reticulum. Physiologists have also identified an intracellular transfer system in addition to the plasma membrane separating the extracellular space from myocyte. After electrical excitation. As such. called cisternae. an effective cardiac contraction requires synchronized myocyte contraction. Transitional cells. intermediate between His-Purkinje and working . The coupling of an electrical signal to myocyte shortening is referred to as excitation–contraction coupling. Working myocytes have a centrally located nucleus and abundant contractile protein elements organized into myofibrils. Myosin ATPase is only active when interacting with another muscle protein called actin. If PEA was unwitnessed. Specialized cardiac myocytes initiate and propagate an electrical signal called an action potential (nodal cells and His-Purkinje cells). An envelope called the plasma membrane surrounds and penetrates the working myocardial cell. PEA was perceived as subcellular myocyte failure occurring in the presence of electrical excitation. In the early 1990s. The surrounding plasma membrane is called the sarcolemma. As described originally.148 Cardiopulmonary Resuscitation as the presenting CA for inhospital resuscitation attempts has the lowest survival rate. A terminal pyrophosphate bond (P-O-P) releases this energy as it is split by a muscle enzyme called myosin ATPase. ATP + H2O A ADP + Phosphate (Pi) + H+ + energy However. calcium ions are released from storage compartments of the sarcoplasmic reticulum. Plasma membrane that penetrates into the cells interior and internally transmits the action potential is called the transverse-tubular (t-tubular) system. no patient survived to hospital discharge (13).

In fact. Fifty are oriented to each end of the sarcomere. Global ischemia develops when the entire heart is deprived of coronary flow and oxygen supply. ATP is hydrolyzed and provides the energy necessary for shortening. Regional ischemia occurs in the presence of a flow limiting epicardial stenosis when downstream myocardium is placed under an increased workload. cytosolic calcium occupies receptor sites on troponin C (TnC). The situation may be compounded if accompanying hypoxemia or demand conditions that increase myocardial oxygen consumption are present. this is because PEA has diverse etiologies and the clinical presentation represents a pathological outcome and not a resuscitation rhythm disorder. ISCHEMIA. myocyte to myocyte coupling is effected by proteins called connexins located in low resistance gap junctions between cells. In addition to electrical coupling of the specialized Purkinje fibers with working myocytes. troponin T. In part. myosin and actin.Chapter 8 / Pulseless Electrical Activity 149 myocytes. ischemia develops and cell death occurs unless reperfusion is established. This interaction increases the amount of actin available for interaction with myosin heads through complex mechanisms. the myocardium is incapable of the burden of recovery owing to a phenomenon called myocardial stunning. tropomyosin and the troponins (troponin I. Typically. Global ischemia is potentially reversible. the absence of this event is evidence of myocardial ischemia or necrosis. however. . The first set. The second. At some point. When a thrombus occludes an artery. The most likely common final mechanism and injury is global MI caused by a severe reduction in coronary flow. this results in effort angina pectoris. During a very short period. In the crossbridges. MYOCARDIAL STUNNING. The Biomechanics of Heart Muscle Contraction The heart muscle thickens prior to contraction when observed by echocardiography or gated nuclear studies. Swelling occurs since myocyte (and sarcomere) volume is constant. are involved with the mechanics of contraction. global ischemia can be produced in 30 seconds with aortic cross-clamping impeding left ventricular ejection. are found in ventricular locations where the Purkinje network of fibers communicates with the working myocytes. The interaction of the bilobed myosin heads is however controlled by cytosolic calcium. Experimentally. calcium uptake occurs and troponin-I (TnI) inhibits calcium interaction with binding sites on the myosin heads. The swelling of myocardial sarcomeres causes this gross cardiac muscle observation during contraction. Each myosin filament ends in a bilobed structure that acts like an oar and pulls the thin actin filament longitudinally along its length. Critical to actin and myosin interaction are crossbridges extending from myosin toward the actin thin filament. Cardiac contraction occurs as interlacing myosin thick filaments slide over actin thin filaments causing myocardial sarcomere shortening and swelling. The contractile biomechanics of the heart involve two sets of proteins. During diastole. and troponin C) are regulatory in nature and allow interaction with calcium for coupling of electrical to mechanical events. The reasons for this are diverse. The degree and duration of ischemia determine the amount of residual myocardial function available to “recover” the patient from an insult resulting in decreased coronary perfusion. AND CELL DEATH Ineffective cardiac contraction in clinical situations of PEA is poorly understood. Each thick filament of myosin is composed of approx 100 myosin molecules.

The majority of clinical situations likely result in initial systolic failure as ischemia begins a continuum of electrical and contractile failure (see below). No resuscitation methodology. regardless the pathological etiology. Unfortunately. total ATP falls to very low levels. . First. but decreased muscle function is observed. Pioneer cardiac surgeons feared this postoperative infrequent but catastrophic cardiac condition and coined the term “stone heart” recognizing the irreversibility and demise of the patient (Fig. PEA most likely represents a continuum initially presenting with organized rhythm that deteriorates to true PEA. Finally. insufficient ATP is present to resupply the contractile proteins resulting in a state of rigor and ischemic contracture. This sequence of events accounts for the poor prognosis observed when a wide complex rhythm is associated with unwitnessed arrest or long arrest times. The Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recognize this fact. or only transiently so. current evidence also supports an effect of oxidative metabolites. activation of phospholipases. such as phosphates and protons that accumulate. TREATMENT Identification of Underlying Cause A patient’s small chance for survival lies in the rapid identification of a correctable cause. and ischemic contracture (14). The above mechanisms cause either contractile (systolic) failure of the myocardium or (diastolic) ischemic contracture and demise of the heart. 1). as cellular transport and efflux are impaired. including early cardiopulmonary resuscitation (CPR). true PEA/EMD occurs as the myocardium is mechanically incapable of responding to any action potential delivered. The low and rapidly decreasing availability of oxygen results in increasing levels of toxic metabolites and an acidic myocyte environment leading to systolic contractile failure. As such. In the intermediate stage. Proposed mechanisms include mitochondrial damage. Also. as the amount of stunned myocardium is excessive or the stone heart has arrived (15). has been shown to be effective.150 Cardiopulmonary Resuscitation Three mechanisms are currently thought to contribute to contractile dysfunction and left ventricular myocardial impairment. An attempt to resuscitate these functionally impaired hearts is unsuccessful. ischemic metabolites accumulate and ATP stores are depleted. Originally. no clinical pulse is detected but patients may have ineffective low amplitude waveforms (low cardiac output) detectable in the central aorta. During this brief window of time. In anoxic arrest and following severe and prolonged ischemia. Next. failure of adequate oxygen delivery to myocyte mitochondria reduces energy supplies for cytoplasmic processes. Finally. obvious within minutes of presentation. amenable to a specific rapid intervention. these changes are reversible depending on the ability to correct a precipitating cause and the amount of myocardium available to meet coronary flow and systemic recovery requirements. The effects of increased cytosolic calcium in ischemia are unclear. as the electrical cells fail and QRS widens. residual CO2 generation from mitochondria and generation from bicarbonate lower myocyte pH and further impairs contractility. This finding has been referred to as pseudo-PEA. This results in higher intracellular calcium levels as membrane pumps lack energy to reestablish ionic concentration gradients. discernible causes amenable to favorable clinical intervention are present in a small minority of patients. loss of high-energy phosphates was felt to be responsible for contractile failure. Protons can compete with calcium for activator sites on the contractile proteins. increased depolarization.

and hypothermia. Success or failure of the resuscitation is determined by the opportunity and ability to identify and correct the underlying cause of PEA. 15a. severe electrolyte abnormalities (hypo/hyperkalemia). pulmonary embolism (PE). . (Modified from ref. When adenosine triphosphate (ATP) stores remain high or the high calcium is opposed by inorganic phosphate and cellular acidosis. THE FIVE Hs and THE FIVE Ts of PEA • • • • • Hypovolemia Hypoxia (oxygen.) but have organized the most common causes for PEA and listed the five “Hs” and the five “Ts” for rapid recall and review (16). Other causes include cardiac tamponade. If there is prolonged ischemia or when glycolysis is impaired and ATP levels are low. Pulmonary Using the available history. Cardiac Tension Pneumothorax Thrombosis. toxicological emergencies. This situation is observed most often in clinical pulseless electrical activity (PEA) or pseudo-PEA. severe acidosis (hydrogen ion). Cardiac Thrombosis. clinical presentation. ventilation) Hyper/Hypokalemia Hypothermia • • • • • Tablets (drug OD) Tamponade.Chapter 8 / Pulseless Electrical Activity 151 Fig. a possible etiology may be identified. The clinical differential and initial treatment often occur concurrently due to the brief window of treatment opportunity. survival is often linked to the prognosis of the inciting pathological condition. In this regard also. and electrocardiogram if available. Contractile failure occurring in the setting of ischemia. systolic contractile failure occurs with a flaccid. ventilation) Hydrogen Ion (buffer. hypoxia. 1. poorly contracting heart. and acute coronary syndromes. tension pneumothorax. A decrease in oxygen supply results in a rise in intracellular calcium. These conditions include hypovolemia. diastolic tension increases and an ischemic contracture occurs that is irreversible.

152 Cardiopulmonary Resuscitation .

Suggesting survival is PEA with a narrow QRS complex. the increased calcium released by epinephrine would be available to bind with troponin C and increase effective cardiac force generation. Recently. short resuscitation times. Approximately 30% of patients with AICDs still suffer from sudden death. searching for an underlying abnormality amenable to targeted intervention. global ischemia with myocardial stunning. Unfortunately. Myocardial generation of force (dP/dt. The most common mechanism of death in these patients is postshock EMD after an appropriate shock for ventricular fibrillation and ventricular tachycardia.Chapter 8 / Pulseless Electrical Activity 153 Special mention should be made of PEA occurring after electrical defibrillation. only one-half of the contractile sites are occupied by calcium. The five “Hs” and five “Ts” should be recalled in the context of available clinical history and scenario. Calcium was recommended in earlier resuscitation strategies. both experimental trials and clinical data found these interventions to be ineffective. In normal states. in the later. Advanced Cardiac Life Support Treatment Algorithm: Epinephrine and Atropine The advanced cardiac life support treatment algorithm shares similarities with asystole. 2. A reasonable strategy assumed that supplemental calcium administered intravenously would increase intracellular calcium available to interact with contractile proteins or increase available calcium in the sarcoplasmic reticulum. this phenomenon has been studied in patients with automatic implantable cardiac defibrillators (AICDs). The reasons are likely multifactorial but may be related to the observation that calcium desensitization occurs in the presence of ischemia owing to the accumulation of inorganic phosphate and acidification of the cytosol. and a relatively rapid return to a supraventricular mechanism with detectable pulses. lower ejection fraction. another highly fatal rhythm and calls for CPR and epinephrine. as well as atropine for slower rates. Theoretically. the calcium interaction with troponin C is crucial to effective contraction. long resuscitation times. accumulation of free radicals and ATP depletion preclude effective institution of a recovery hemodynamic situation leading to sustained coronary perfusion and some degree of myocardial function. Cytosolicfree calcium is both released and lowered more quickly in the presence of catecholamines. or the developed pressure over a period of time) increases with catecholamine `-adrenergic stimulation. Fig. and higher energy defibrillation requirements. Another potential treatment involved the use of epinephrine as a cytosolic catecholamine stimulant. transient recovery of a supraventricular mechanism and subsequent deterioration suggest a poor prognosis. Likely. The authors have referred to this phenomenon as cardiac annihilation (17). A wide complex. The largest subgroup of patients was younger with poor New York Heart Association functional classification (III–IV). The algorithm was modified to emphasize the need to immediately consider and search for a correctable cause in this usually fatal clinical situation. . (opposite page) The International Guidelines Treatment Algorithm for Pulseless Electrical Activity. PEA can be seen after defibrillation and may be a recovery rhythm in a small percentage of patients. As discussed above.

Pineda EA.). Sometimes. Circulation 2000. JAMA 1986. NY: Raven Press. More often. Lindqvist J. Milnor JP. 167:343–348.and long-term prognosis among 1069 patients with out-of-hospital cardiac arrest and pulseless electrical activity. left ventricular rupture and tamponade following myocardial ischemia. Drowning and near drowning. 4. hypovolemia. Engdahl J. American Heart Association Emergency Cardiac Care Committee. Benditt DG. 15. Caregivers need to recognize the futility of a prolonged resuscitation and prepare the family for compassionate counseling. Part 6: advanced cardiovascular life support: 7B: understanding the algorithm approach to ACLS. J Am Coll Cardiol 2002. American Heart Association. De Backer D. and cardiac pacing have not been shown to improve survival in PEA. Pelikan PC. Kutsogiannis DJ. Mayers I. Factors affecting short. Ann Emerg Med 1985. Can the victim be saved? Postgrad Med 1983. 10. Martin GB. REFERENCES 1. Markland DM. Clinical and experimental studies on electromechanical dissociation. Herlitz J. 102(Suppl):I140–I141. Opie LH. Sudden death in patients with implantable cardioverter defibrillators: the importance of post-shock electromechanical dissociation. Ann Emerg Med 1981. Transthoracic pacing during CPR. Resuscitation 2001. Standards for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC). Benton C. Nowak RM. Carden DL. The Heart: Physiology and Metabolism (2nd ed. 15:324–327. 13. e. Circulation 1981. calcium. aortic dissection with hemopericardium. Circ Res 1990. Guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC). Predictors of survival following in-hospital adult cardiopulmonary resuscitation. the diagnosis is arrived at postmortem and an intervention would have produced little chance of success even had the diagnosis been identified at the bedside. 64:18–27. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. American Heart Association. J Amer Med Assoc 1974. Glucose flux rate regulates onset of ischemic contracture in globally underperfused rat hearts. 268:2171–2295.154 Cardiopulmonary Resuscitation SUMMARY Standard CPR. Huynh CH. 2. 11. 39:1323–1328. Calcium chloride in experimental electromechanical dissociation: a placebo-controlled trial in dogs.g. 10:113–116. 255:2841–3044. Opie JC. J Thorac Cardiovasc Surg 1981. Crit Care Med 1981. Taylor G. Bang A. 12. Predictive value of the ECG in determining cardiac resuscitation outcome in a canine model of postcountershock electromechanical dissociation after prolonged ventricular fibrillation. et al. Ionized calcium during CPR in the canine model. 17:183–193. buffer therapy. Crit Care Med 1987. 9. Transvenous cardiac pacing in cardiopulmonary resuscitation. Bartosch PM. JAMA 1992. 5. Resuscitation 1989. Ann Emerg Med 1988. Titus JL. . Foreback C. Stueven HA. Hazard PB. Blecic S. Michaels S. 6. saddle PE. Vincent JL. these therapies addressing electrocardiographic and clinical patterns are only temporizing measures while conducting a rapid search and identifying a specific treatment for a correctable precipitating disorder. et al. Tintinalli JE. Brindley PG. Jagels G. Thijs L. Niemann JT. Cmaj 2002. White BC. 17. Kalousek D. Redding JS. 74:85–97. Best R. Silverberg RA. As such. Mitchell LB. 15a. epinephrine. 81:459–463. Electrocardiographic characteristics in EMD.Opie LH. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. “Stone heart” in a neonate.. 51:17–25. atropine. Owen P. 66:344–354. Tomlanovich MC. 9:666–668. 7. and blunt trauma. New York. 3. 16. Ashmore PG. 14:633–635. Standards and guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiac care (ECC). Weil MH. 17:567–571. Aufderheide TP. Dennis S. Thakur RK. Garner D. 1991. the presenting clinical scenario will suggest a cause leading to a targeted intervention. 8. 14. 227:833–868.