8 Pulseless Electrical Activity

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From: Contemporary Cardiology: Cardiopulmonary Resuscitation Edited by: J. P. Ornato and M. A. Peberdy © Humana Press Inc., Totowa, NJ

8 Pulseless Electrical Activity

John M. Field, ^MD

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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 electrocardio- gram is seemingly unaltered.

Eugene Braunwald in The Heart, 1980

INTRODUCTION

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 electrocardio- gram but no effective cardiac output was present owing to the absence of coupled mechani- cal 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 tachycar- dia with a normal duration QRS complex to brady-dysrhythmias with wide aberrant or idioventricular ventricular morphologies. A poor resuscitation outcome and dismal prog- nosis 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%

(4,5).

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

as the presenting CA for inhospital resuscitation attempts has the lowest survival rate. If PEA was unwitnessed, no patient survived to hospital discharge (13).

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. In the early 1990s, the resuscitation commu- nity began to refer to this clinical presentation of CA as PEA. A dismal prognosis reflects the fact that PEA is a preterminal rhythm and not a specific entity. As such, 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.

PATHOBIOLOGY

An improved understanding of the mechanisms responsible for PEA has provided a refined pathophysiology of this disorder. As described originally, PEA was perceived as subcellular myocyte failure occurring in the presence of electrical excitation. Working myocytes have a centrally located nucleus and abundant contractile protein elements organized into myofibrils. The flux and interaction of calcium with myofibrillar elements initiates and terminates contraction by concentration characteristics at regulatory sites.

This interaction is very complex and excitation–contraction coupling involves cell com- ponents called the plasma membrane, sarcoplasmic reticulum, and myofilaments.

An envelope called the plasma membrane surrounds and penetrates the working myocardial cell. The surrounding plasma membrane is called the sarcolemma. Plasma membrane that penetrates into the cells interior and internally transmits the action poten- tial is called the transverse-tubular (t-tubular) system. Physiologists have also identified an intracellular transfer system in addition to the plasma membrane separating the extra- cellular space from myocyte. This system is called the sarcoplasmic reticulum. After electrical excitation, calcium ions are released from storage compartments of the sarco- plasmic reticulum, called cisternae, and flood the cytosol initiating systolic contraction.

Another compartment of the sarcoplasmic reticulum surrounds the contractile proteins and is called the sarcotubular network and contains adenosine triphosphate (ATP)ase- dependent proteins that actively pump calcium back into the cisternae, ready for the next excitatory stimulus.

The Energy of Heart Muscle Contraction

A heart muscle cell must convert chemical or stored energy into kinetic energy for effective cardiac contraction. The heart stores energy as ATP. When ATP is cleaved into adenosine diphosphate (ADP), inorganic phosphate and a proton (H

) are released gen- erating energy. A terminal pyrophosphate bond (P-O-P) releases this energy as it is split by a muscle enzyme called myosin ATPase. Myosin ATPase is only active when inter- acting with another muscle protein called actin.

ATP + H₂OA ADP + Phosphate (Pi) + H⁺ + energy

However, an effective cardiac contraction requires synchronized myocyte contrac-

tion. The coupling of an electrical signal to myocyte shortening is referred to as excita-

tion–contraction coupling. Specialized cardiac myocytes initiate and propagate an

electrical signal called an action potential (nodal cells and His-Purkinje cells). The spe-

cialized and working myocytes form a functional syncytium with cells linked electrically

and mechanically. Transitional cells, intermediate between His-Purkinje and working

myocytes, are found in ventricular locations where the Purkinje network of fibers com- municates with the working myocytes. In addition to electrical coupling of the special- ized Purkinje fibers with working myocytes, myocyte to myocyte coupling is effected by proteins called connexins located in low resistance gap junctions between cells.

The Biomechanics of Heart Muscle Contraction

The heart muscle thickens prior to contraction when observed by echocardiography or gated nuclear studies. In fact, the absence of this event is evidence of myocardial ischemia or necrosis. The swelling of myocardial sarcomeres causes this gross cardiac muscle observation during contraction. Swelling occurs since myocyte (and sarcomere) volume is constant.

Cardiac contraction occurs as interlacing myosin thick filaments slide over actin thin filaments causing myocardial sarcomere shortening and swelling. The contractile biome- chanics of the heart involve two sets of proteins. The first set, myosin and actin, are involved with the mechanics of contraction. The second, tropomyosin and the troponins (troponin I, troponin T, and troponin C) are regulatory in nature and allow interaction with calcium for coupling of electrical to mechanical events.

Critical to actin and myosin interaction are crossbridges extending from myosin toward the actin thin filament. Each myosin filament ends in a bilobed structure that acts like an oar and pulls the thin actin filament longitudinally along its length. Each thick filament of myosin is composed of approx 100 myosin molecules. Fifty are oriented to each end of the sarcomere. In the crossbridges, ATP is hydrolyzed and provides the energy necessary for shortening. The interaction of the bilobed myosin heads is however controlled by cytosolic calcium. During a very short period, cytosolic calcium occupies receptor sites on troponin C (TnC). This interaction increases the amount of actin avail- able for interaction with myosin heads through complex mechanisms. During diastole, calcium uptake occurs and troponin-I (TnI) inhibits calcium interaction with binding sites on the myosin heads.

MYOCARDIAL STUNNING, ISCHEMIA, AND CELL DEATH Ineffective cardiac contraction in clinical situations of PEA is poorly understood. In part, this is because PEA has diverse etiologies and the clinical presentation represents a pathological outcome and not a resuscitation rhythm disorder. The most likely common final mechanism and injury is global MI caused by a severe reduction in coronary flow.

The situation may be compounded if accompanying hypoxemia or demand conditions that increase myocardial oxygen consumption are present. 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. Global ischemia is potentially reversible. At some point, however, the myocardium is incapable of the burden of recovery owing to a phenomenon called myocardial stunning.

Regional ischemia occurs in the presence of a flow limiting epicardial stenosis when downstream myocardium is placed under an increased workload. Typically, this results in effort angina pectoris. When a thrombus occludes an artery, ischemia develops and cell death occurs unless reperfusion is established. Global ischemia develops when the entire heart is deprived of coronary flow and oxygen supply. The reasons for this are diverse.

Experimentally, global ischemia can be produced in 30 seconds with aortic cross-clamp-

ing impeding left ventricular ejection.

Three mechanisms are currently thought to contribute to contractile dysfunction and left ventricular myocardial impairment. First, regardless the pathological etiology, fail- ure of adequate oxygen delivery to myocyte mitochondria reduces energy supplies for cytoplasmic processes. As such, ischemic metabolites accumulate and ATP stores are depleted. Originally, loss of high-energy phosphates was felt to be responsible for con- tractile failure. Next, current evidence also supports an effect of oxidative metabolites, such as phosphates and protons that accumulate, as cellular transport and efflux are impaired. Protons can compete with calcium for activator sites on the contractile proteins.

Finally, residual CO

generation from mitochondria and generation from bicarbonate lower myocyte pH and further impairs contractility. The effects of increased cytosolic calcium in ischemia are unclear, but decreased muscle function is observed. Proposed mechanisms include mitochondrial damage, activation of phospholipases, increased depolarization, and ischemic contracture (14).

The above mechanisms cause either contractile (systolic) failure of the myocardium or (diastolic) ischemic contracture and demise of the heart. The majority of clinical situations likely result in initial systolic failure as ischemia begins a continuum of elec- trical and contractile failure (see below). The low and rapidly decreasing availability of oxygen results in increasing levels of toxic metabolites and an acidic myocyte environ- ment leading to systolic contractile failure. During this brief window of time, 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 require- ments. In anoxic arrest and following severe and prolonged ischemia, total ATP falls to very low levels. This results in higher intracellular calcium levels as membrane pumps lack energy to reestablish ionic concentration gradients. Also, insufficient ATP is present to resupply the contractile proteins resulting in a state of rigor and ischemic contracture.

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. 1).

PEA most likely represents a continuum initially presenting with organized rhythm that deteriorates to true PEA. In the intermediate stage, no clinical pulse is detected but patients may have ineffective low amplitude waveforms (low cardiac output) detectable in the central aorta. This finding has been referred to as pseudo-PEA. Finally, as the electrical cells fail and QRS widens, true PEA/EMD occurs as the myocardium is mechani- cally incapable of responding to any action potential delivered. This sequence of events accounts for the poor prognosis observed when a wide complex rhythm is associated with unwitnessed arrest or long arrest times. An attempt to resuscitate these functionally impaired hearts is unsuccessful, or only transiently so, as the amount of stunned myocar- dium is excessive or the stone heart has arrived (15).

TREATMENT

Identification of Underlying Cause

A patient’s small chance for survival lies in the rapid identification of a correctable cause, obvious within minutes of presentation, amenable to a specific rapid intervention.

No resuscitation methodology, including early cardiopulmonary resuscitation (CPR),

has been shown to be effective. Unfortunately, discernible causes amenable to favorable

clinical intervention are present in a small minority of patients. The Guidelines 2000 for

Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recognize this fact,

Fig. 1. Contractile failure occurring in the setting of ischemia. A decrease in oxygen supply results in a rise in intracellular calcium. When adenosine triphosphate (ATP) stores remain high or the high calcium is opposed by inorganic phosphate and cellular acidosis, systolic contractile failure occurs with a flaccid, poorly contracting heart. This situation is observed most often in clinical pulseless electrical activity (PEA) or pseudo-PEA. If there is prolonged ischemia or when glyco- lysis is impaired and ATP levels are low, diastolic tension increases and an ischemic contracture occurs that is irreversible. (Modified from ref. 15a.)

but have organized the most common causes for PEA and listed the five “Hs” and the five

“Ts” for rapid recall and review (16). These conditions include hypovolemia, hypoxia, severe acidosis (hydrogen ion), severe electrolyte abnormalities (hypo/hyperkalemia), and hypothermia. Other causes include cardiac tamponade, tension pneumothorax, toxi- cological emergencies, pulmonary embolism (PE), and acute coronary syndromes.

THE FIVE Hs and THE FIVE Ts of PEA

• Hypovolemia • Tablets (drug OD)

• Hypoxia (oxygen, ventilation) • Tamponade, Cardiac

• Hydrogen Ion (buffer, ventilation) • Tension Pneumothorax

• Hyper/Hypokalemia • Thrombosis, Cardiac

• Hypothermia • Thrombosis, Pulmonary

Using the available history, clinical presentation, and electrocardiogram if available,

a possible etiology may be identified. The clinical differential and initial treatment often

occur concurrently due to the brief window of treatment opportunity. Success or failure

of the resuscitation is determined by the opportunity and ability to identify and correct

the underlying cause of PEA. In this regard also, survival is often linked to the prognosis

of the inciting pathological condition.

Special mention should be made of PEA occurring after electrical defibrillation.

PEA can be seen after defibrillation and may be a recovery rhythm in a small percentage of patients. Suggesting survival is PEA with a narrow QRS complex, short resuscitation times, and a relatively rapid return to a supraventricular mechanism with detectable pulses. A wide complex, long resuscitation times, transient recovery of a supraventricu- lar mechanism and subsequent deterioration suggest a poor prognosis. Likely, in the later, global ischemia with myocardial stunning, 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. Recently, this phenomenon has been studied in patients with automatic implantable cardiac defibrillators (AICDs). Approximately 30% of patients with AICDs still suffer from sudden death. The most common mechanism of death in these patients is postshock EMD after an appropriate shock for ventricular fibrillation and ventricular tachycardia.

The largest subgroup of patients was younger with poor New York Heart Association functional classification (III–IV), lower ejection fraction, and higher energy defibril- lation requirements. The authors have referred to this phenomenon as cardiac annihi- lation (17).

Advanced Cardiac Life Support Treatment Algorithm:

Epinephrine and Atropine

The advanced cardiac life support treatment algorithm shares similarities with asys- tole, another highly fatal rhythm and calls for CPR and epinephrine, as well as atropine for slower rates. Calcium was recommended in earlier resuscitation strategies. As discussed above, the calcium interaction with troponin C is crucial to effective contrac- tion. In normal states, only one-half of the contractile sites are occupied by calcium. 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.

Another potential treatment involved the use of epinephrine as a cytosolic catechola- mine stimulant. Myocardial generation of force (dP/dt, or the developed pressure over a period of time) increases with catecholamine `-adrenergic stimulation. Cytosolic- free calcium is both released and lowered more quickly in the presence of catechola- mines. Theoretically, the increased calcium released by epinephrine would be available to bind with troponin C and increase effective cardiac force generation.

Unfortunately, both experimental trials and clinical data found these interventions to be ineffective. The reasons are likely multifactorial but may be related to the obser- vation that calcium desensitization occurs in the presence of ischemia owing to the accumulation of inorganic phosphate and acidification of the cytosol.

Fig. 2. (opposite page) The International Guidelines Treatment Algorithm for Pulseless Electrical Activity. The algorithm was modified to emphasize the need to immediately consider and search for a correctable cause in this usually fatal clinical situation. The five “Hs” and five “Ts” should be recalled in the context of available clinical history and scenario, searching for an underlying abnormality amenable to targeted intervention.

SUMMARY

Standard CPR, epinephrine, calcium, buffer therapy, atropine, and cardiac pacing have not been shown to improve survival in PEA. As such, these therapies addressing electrocardiographic and clinical patterns are only temporizing measures while conduct- ing a rapid search and identifying a specific treatment for a correctable precipitating disorder. Sometimes, the presenting clinical scenario will suggest a cause leading to a targeted intervention. More often, the diagnosis is arrived at postmortem and an interven- tion would have produced little chance of success even had the diagnosis been identified at the bedside, e.g., saddle PE, left ventricular rupture and tamponade following myocar- dial ischemia, aortic dissection with hemopericardium, hypovolemia, and blunt trauma.

Caregivers need to recognize the futility of a prolonged resuscitation and prepare the family for compassionate counseling.

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