Background
Pulseless electrical activity (PEA) is a clinical condition characterized by unresponsiveness and the lack of a palpable pulse in the presence of organized cardiac electrical activity. Pulseless electrical activity has previously been referred to as electromechanical dissociation (EMD). (See Etiology.)
Although a lack of ventricular electrical activity always implies a lack of ventricular mechanical activity (asystole), [1] the reverse is not always true. That is, electrical activity is a necessary, but not sufficient, condition for mechanical activity. In a situation of cardiac arrest, the presence of organized ventricular electrical activity is not necessarily accompanied by meaningful ventricular mechanical activity. The qualifier “meaningful” is used to describe a degree of ventricular mechanical activity that is sufficient to generate a palpable pulse.
PEA does not mean mechanical quiescence. Patients may have weak ventricular contractions and recordable aortic pressure ("pseudo-PEA"). True PEA is a condition in which cardiac contractions are absent in the presence of coordinated electrical activity. PEA encompasses a number of organized cardiac rhythms, including supraventricular rhythms (sinus versus nonsinus) and ventricular rhythms (accelerated idioventricular or escape). The absence of peripheral pulses should not be equated with PEA, as it may be due to severe peripheral vascular disease. (See Etiology, Presentation, and Workup.)
Etiology
Pulseless electrical activity (PEA) occurs when a major cardiovascular, respiratory, or metabolic derangement results in the inability of cardiac muscle to generate sufficient force in response to electrical depolarization. PEA is always caused by a profound cardiovascular insult (eg, severe prolonged hypoxia or acidosis or extreme hypovolemia or flow-restricting pulmonary embolus).
The initial insult weakens cardiac contraction, and this situation is exacerbated by worsening acidosis, hypoxia, and increasing vagal tone. Further compromise of the inotropic state of the cardiac muscle leads to inadequate mechanical activity, despite the presence of electrical activity. This event creates a vicious cycle, causing degeneration of the rhythm and subsequent death of the patient.
Transient coronary occlusion usually does not cause PEA, unless hypotension or other arrhythmias are involved.
Hypoxia secondary to respiratory failure is probably the most common cause of PEA, with respiratory insufficiency accompanying 40-50% of PEA cases. Situations that cause sudden changes in preload, afterload, or contractility often result in PEA.
The use of antipsychotic agents has been found to be a significant and independent predictor of PEA. [2]
Decreased preload
Cardiac sarcomeres require an optimal length (ie, preload) for an efficient contraction. If this length is unattainable because of volume loss or pulmonary embolus (causing decreased venous return to the left atrium), the left ventricle is unable to generate sufficient pressure to overcome its afterload. Volume loss resulting in PEA is most likely to occur in cases of major trauma. In these situations, rapid blood loss and subsequent hypovolemia can exhaust cardiovascular compensatory mechanisms, culminating in PEA. Cardiac tamponade may also cause decreased ventricular filling.
Increased afterload
Afterload is inversely related to cardiac output. Severe increases in afterload pressure cause a decrease in cardiac output. However, this mechanism is rarely solely responsible for PEA.
Decreased contractility
Optimal myocardial contractility is dependent on an optimal filling pressure, afterload, and the presence and availability of inotropic substances (eg, epinephrine, norepinephrine, or calcium). Calcium influx and binding to troponin C is essential for cardiac contraction. If calcium is not available (eg, calcium channel blocker overdose) or if calcium's affinity to troponin C is decreased (as in hypoxia), contractility suffers.
Depletion of intracellular adenosine triphosphate (ATP) reserves causes an increase in adenosine diphosphate (ADP) levels, which can bind calcium, further reducing energy reserves. Excess intracellular calcium can result in reperfusion injury by causing severe damage to the intracellular structures, predominantly the mitochondria.
Additional etiologic factors
Additional factors contribute to the etiolgy of PEA, including the following mnemonic of “Hs and Ts” favored by the American Heart Association (AHA) and European Resuscitation Council (ERC) [3, 4] :
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Hypovolemia
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Hypoxia
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Hydrogen ion (acidosis)
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Toxins
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Thrombosis (coronary or pulmonary)
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Trauma
The "3 and 3 rule" of Desbiens [5] is of more practical use, because it allows easy recall of the most common correctable causes of PEA. This rule organizes PEA causes into three major ones:
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Severe hypovolemia
-
Pump failure
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Obstruction to circulation
The three main causes of obstruction to circulation are as follows:
Pump failure is the result of massive myocardial infarction, with or without cardiac rupture, and severe heart failure. Major trauma can be responsible for hypovolemia, tension pneumothorax, or cardiac tamponade.
Metabolic derangements (acidosis, hyperkalemia, hypokalemia), although rarely the initiators of PEA, are common contributing factors. Drug overdose (tricyclic antidepressants, digitalis, calcium channel blockers, beta blockers) or toxins are also rare causes of PEA. [9] Hypothermia should be considered in the appropriate clinical context of out-of-hospital PEA.
Postdefibrillation PEA is characterized by the presence of organized electrical activity, occurring immediately after electrical cardioversion in the absence of a palpable pulse. Postdefibrillation PEA may be associated with a better prognosis than continued ventricular fibrillation. A spontaneous return of pulse is likely, and cardiopulmonary resuscitation should be continued for as long as 1 minute to allow for spontaneous recovery.
Epidemiology
United States data
The frequency of pulseless electrical activity (PEA) varies among different US patient populations. This condition accounts for approximately 20% of cardiac arrests that occur outside of the hospital setting.
Raizes et al found that PEA was responsible for 68% of monitored in-hospital deaths and 10% of all in-hospital deaths. [10] Because of the increased disease acuity observed in patients who are admitted, PEA may be more likely to occur in patients who are hospitalized. Also, these patients are more likely to have pulmonary emboli and such conditions as ventilator-induced auto–PEEP (positive–end-expiratory pressure). PEA is the first documented rhythm in 32-37% of adults with in-hospital cardiac arrest. [11, 12]
The use of beta blockers and calcium channel blockers may increase the frequency of PEA, presumably by interfering with cardiac contractility.
Sex- and age-related demographics
Females are more likely to develop PEA than males. The reasons for this predilection are unclear but may relate to different etiologies of cardiac arrest.
Patients older than 70 years are more likely to have PEA as an etiology of cardiac arrest. Whether the patient outcome differs based on age is not known; however, advanced age is likely associated with a worse outcome.
Prognosis
The overall prognosis for patients with pulseless electrical activity (PEA) is poor unless a rapidly reversible cause is identified and corrected. Evidence suggests that electrocardiographic (ECG) characteristics are related to the patient's prognosis. The more abnormal the ECG characteristics, the less likely the patient is to recover from PEA; patients with a wider QRS (>0.2 sec) fare worse.
Interestingly, patients with out-of-hospital cardiac arrest (OHCA) in PEA are more likely to recover than are patients who develop this condition in the hospital. In a study, 98 of 503 (19.5%) patients survived OHCA PEA. [13] This difference is likely because of different etiologies and severity of illness. Patients who are not in the hospital are more likely to have reversible etiologies (eg, hypothermia).
In addition, the rate of electrical activity and QRS width do not appear to correlate with survival or neurologic outcome in patients who present with PEA-associated OHCA. [14]
Overall, PEA remains a poorly understood entity with a dismal prognosis. Reversing this otherwise lethal condition may be possible by aggressively seeking and promptly correcting reversible causes.
The Oregon Sudden Unexpected Death Study, which included more than 1,000 cases of patients who presented with PEA (vs ventricular fibrillation), indicated a significantly higher prevalence of syncope that was distinct from cases of ventricular fibrillation. Potential links between future manifestations of PEA and syncope require further investigatation. [15]
Mortality
A systematic review and meta-analysis of 12 studies comprising 1,108,281 OHCA patients with initial nonshockable cardiac rhythms revealed that conversion to shockable rhythms, particularly when occurring early, was associated with higher likelihoods of prehospital return of spontaneous circulation (ROSC), 1-month survival, and 1-month favorable neurologic outcome, but not with survival to hospital discharge (SHD). [16] Shockable rhythm conversion from asystole, but not PEA, was associated with prehospital ROSC and SHD.
The overall mortality rate is high in patients in whom PEA is the initial rhythm during cardiac arrest. In a study by Nadkarni et al, only 11.2% of patients who had PEA as their first documented rhythm survived to hospital discharge. [11] In a study by Meaney et al, patients with PEA as the first documented rhythm had a lower rate of survival to discharge than did patients who had ventricular fibrillation or ventricular tachycardia as their first documented rhythm. [12]
In a study of 314 cases of OHCA that assessed the futility of resuscitative efforts, no resuscitation was attempted in 34 cases for futility, and 74 cases were partial resuscitation attempts that were quickly discontinued owing to dismal prognostic factors. [17] Among the factors associated with partial attempts were asystole or PEA as the initial rhythm, multiple trauma, unwitnessed OHCA, and a first-response unit being the first unit on scene. The calculated SHD rate was 14% when partial resuscitation attempts were included (there was a 5% increase when partial resuscitation attempts were excluded). Positive factors associated with survival were shockable initial rhythm, public location, and bystander cardiopulmonary resuscitation (CPR). [17]
Data from the American Heart Association's Get With The Guidelines Resuscitation registry (2001-2011) of 1-year survival trends overall and by rhythm in 45,567 Medicare beneficiaries (age ≥65 years) with in-hospital cardiac arrest (IHCA) revealed an unadjusted 1-year survival of 9.4%; it was 6.2% among 36,344 patients with PEA or asystole and 21.8% in 9,223 patients with ventricular fibrillation or pulseless ventricular tachycardia. [18] However, overall adjusted 1-year survival rates for IHCA improved from 8.9% in 2000-2001 to 15.2% in 2011; for the same time points, they improved from 4.7% to 10.2% for PEA/asystole, and 19.4% to 25.6% for ventricular fibrillation or pulseless ventricular tachycardia. [18]
Given these grim outlooks, the rapid initiation of advanced cardiac life support (ACLS) and swift identification of a reversible cause are critical. Initiation of ACLS may improve patient outcome if a reversible cause is identified and rapidly corrected.
