Chapter 8 / Pulseless Electrical Activity

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Pulseless Electrical Activity

John M. Field, MD
CONTENTS
INTRODUCTION
PATHOBIOLOGY
MYOCARDIAL STUNNING, ISCHEMIA, AND CELL DEATH
TREATMENT
SUMMARY
REFERENCES

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

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 (13). 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%
(4,5).
Early animal studies and resuscitation attempts with inotropic and chronotropic drugs,
calcium chloride, and electrical pacing proved ineffective (511). 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

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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 community 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 excitationcontraction coupling involves cell components 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 potential is called the transverse-tubular (t-tubular) system. Physiologists have also identified
an intracellular transfer system in addition to the plasma membrane separating the extracellular space from myocyte. This system is called the sarcoplasmic reticulum. After
electrical excitation, calcium ions are released from storage compartments of the sarcoplasmic 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)asedependent 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 generating 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 interacting with another muscle protein called actin.
ATP + H2O A ADP + Phosphate (Pi) + H+ + energy
However, an effective cardiac contraction requires synchronized myocyte contraction. The coupling of an electrical signal to myocyte shortening is referred to as excitationcontraction coupling. Specialized cardiac myocytes initiate and propagate an
electrical signal called an action potential (nodal cells and His-Purkinje cells). The specialized and working myocytes form a functional syncytium with cells linked electrically
and mechanically. Transitional cells, intermediate between His-Purkinje and working

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myocytes, are found in ventricular locations where the Purkinje network of fibers communicates with the working myocytes. In addition to electrical coupling of the specialized 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 biomechanics 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 available 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-clamping impeding left ventricular ejection.

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Three mechanisms are currently thought to contribute to contractile dysfunction and

left ventricular myocardial impairment. First, regardless the pathological etiology, failure 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 contractile 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 CO2 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 electrical and contractile failure (see below). 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. 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 requirements. 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 mechanically 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 myocardium is excessive or the stone heart has arrived (15).

TREATMENT
Identification of Underlying Cause
A patients 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,

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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 glycolysis 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, toxicological emergencies, pulmonary embolism (PE), and acute coronary syndromes.

THE FIVE Hs and THE FIVE Ts of PEA

Hypovolemia
Hypoxia (oxygen, ventilation)
Hydrogen Ion (buffer, ventilation)
Hyper/Hypokalemia
Hypothermia

Tablets (drug OD)

Tamponade, Cardiac
Tension Pneumothorax
Thrombosis, Cardiac
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.

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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 supraventricular 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 (IIIIV), lower ejection fraction, and higher energy defibrillation requirements. The authors have referred to this phenomenon as cardiac annihilation (17).

Advanced Cardiac Life Support Treatment Algorithm:

Epinephrine and Atropine
The advanced cardiac life support treatment algorithm shares similarities with asystole, 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 contraction. 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 catecholamine stimulant. Myocardial generation of force (dP/dt, or the developed pressure over
a period of time) increases with catecholamine `-adrenergic stimulation. Cytosolicfree calcium is both released and lowered more quickly in the presence of catecholamines. 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 observation 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.

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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 conducting 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 intervention 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 myocardial 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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