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Remember that SyncoPE Ends in PE

Roberts, James R. MD

Author Information
doi: 10.1097/01.EEM.0000521595.12875.d8
    syncope, pulmonary embolism
    syncope, pulmonary embolism:
    The causes of fainting are gargantuan, but one does not want to miss the diagnosis of pulmonary embolism in the ED. The ED evaluation of a patient with syncope should always conjure up the possibility of pulmonary embolism (PE). Remember that syncoPE ends in PE. If the Wells' score is 4 or greater or if the D-dimer is elevated, most clinicians will order a CT pulmonary angiogram or VQ scan upon presentation in the ED. The incidence of PE is elevated if the patient has signs of DVT or has cancer, recent immobilization, tachycardia, tachypnea, hypoxia, or hypotension, but even a large PE can be clinically subtle. Importantly, almost 25 percent of pulmonary artery angiograms are misread as false-positive for PE.

    Clinically differentiating between syncope and seizures is a common quandary for emergency physicians. It turns out that seizure activity is often the sequela of a hypotensive event of cardiovascular origin rather than a primary neurological event emanating from the central nervous system. Unless the cardiovascular origin is recognized, the patient may be diagnosed with epilepsy, carry that diagnosis for years, and be treated with a number of anticonvulsants.

    To make things even more complicated, another cause of syncope that might not readily come to mind in a patient presenting to the ED could be potentially fatal. From a mechanism standpoint, syncope is a transient loss of consciousness of rapid onset, and it usually has a short duration and spontaneous resolution, and is generally caused by a temporary halt in cerebral perfusion. The circulation to the central nervous system can be compromised by a number of causes, including arrhythmias, structural heart defects, and occasionally pulmonary embolism. Many of the specifics of pulmonary embolism (PE) among patients hospitalized for syncope are largely unknown, but some patients hospitalized for a first episode of syncope actually had a PE.

    Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope

    Prandoni P, Lensing AW, et al.

    New Engl J Med


    This recent article from a number of academic medical centers in Italy highlighted patients hospitalized for syncope who may have experienced their loss of consciousness because of a pulmonary embolism. The report garnered a lot of interest when it first came out, but it may have overstated the incidence of PE associated with syncope.

    The authors evaluated adults with a first episode of syncope who had a seizure, stroke, or head trauma. Those who had previous episodes of syncope, were on anticoagulation therapy, or were pregnant were excluded. The subjects included 560 adult patients who were admitted with first-time syncope. A complete medical history was obtained that asked about symptoms of autonomic activation such as sweating, nausea, the presence of noncardiac disease, bleeding, dehydration, and exposure to drugs that could cause bradycardia or tachycardia. The authors also queried whether patients had signs or symptoms that might suggest DVT or prolonged immobilization. It was also determined whether the patients had cancer or prior venous thromboembolism.

    Simplified Wells' Score for Assessment of the Pretest Clinical Probability of Pulmonary Embolism∗

    All patients underwent PE risk stratification using the Wells' criteria, and all had a chest x-ray, ECG, arterial blood gas testing, and D-dimer assay. Additional tests included carotid sinus massage, tilt testing, echocardiography, and prolonged ECG monitoring. As is commonly the case, patients who had a low Wells' score for the assessment of pretest clinical probability of PE and a negative D-dimer did not have further testing looking for PE. A CT angiogram or lung scanning was performed if the Wells' score suggested a likelihood of a PE, the patient had a positive D-dimer, or both. In essence, the authors performed a standard evaluation for PE in patients who were admitted with syncope.

    About 2500 patients presented with first-time syncope, but only 560 were admitted to the study. The average age was 76. The majority was sent home because PE was not suggested, nor was another serious cause of syncope entertained. Those discharged had vasovagal syncope, drug-induced hypotension, volume depletion, or declined hospitalization. Another 157 patients were excluded because they were already anticoagulated. The 560 patients who were included in the study were actually quite symptomatic, and the physicians observed signs of DVT in 40 percent, tachypnea in 45 percent, tachycardia in 33 percent; hypotension in 36 percent; and active cancer in 20 percent.

    A total of 330 (60%) of the 560 admitted patients had a PE ruled out because of a combination of a low pretest probability for PE and a negative D-dimer assay. Of the remaining 250 patients, a PE was diagnosed in 97 (42%). About 60 percent had a positive D-dimer only, and 1.3 percent had a high pretest clinical probability of PE. Only 40 percent of patients had a positive pretest probability and positive D-dimer.

    The incidence of PE was quite high among the patients studied. PE was found in 49 percent of those who underwent CT angiogram and in 40 percent of those who underwent VQ scanning. This is a much higher percentage of patients with positive tests than seen in other studies and in U.S. hospitals. A number of patients had minor or segmental pulmonary embolism, the significance of which was not certain. Overall, a PE was detected in 25 percent of patients who initially had syncope of undetermined origin. Interestingly, 12 percent of those who were first thought to have an alternative explanation for syncope other than a PE actually had a PE, and 25 percent of patients had a PE with no clinical manifestation of it, such as tachycardia, tachypnea, hypotension, or DVT.

    These authors wrote that this study demonstrated a high incidence of PE among patients with syncope. About 17 percent, or one in six patients, with syncope had a PE. This was a very select group, but this is an extremely high number no matter how you cut it. Of interest is the high number of patients with potentially alternative explanations for their syncope who had a PE. A high proportion of patients also did not have any other features commonly ascribed to PE, such as dyspnea, tachypnea, hypertension, or DVT.

    Chest X-Ray Findings in Patients with Pulmonary Embolism∗
    Fig. 1.
    Fig. 1.:
    Integrated phrenic (PH), thyroarytenoid (TA), posterior cricoarytenoid (PCA) and raw electrocorticogram (ECoG) in an anesthestized, vagotomized cat with seizures induced with subcortical penicillin. Irregular reduced phasic activity is demonstrated during a prolonged ictal discharge. Within about 10 seconds of the onset of reduction in ECoG spike frequency (i.e., 10 seconds after onset of an interictal period; arrow), these effects rapidly resolve, with a reduction in neural respiratory frequency and recovery of phasic nerve activities.
    Fig. 2.
    Fig. 2.:
    Integrated PH, TA, and PCA nerves and raw ECoG activities under control (left) and ictal seizure (right panel, conditions) in one pig. Arterial blood pressure (BP) and arterial partial pressure of expired carbon dioxide concentration (PaCO2) are displayed throughout. During control conditions, nerve patterns are regular, but activities become irregular during seizures. There is a sudden degradation in integrated activities, especially in PH and PCA neurograms, associated with a high-intensity cortical discharge (middle of right panel). Peak integrated activities of the PH, TA, and PCA return to approximately the same pre-high intensity cortical discharge levels when cortical discharge intensity lessens.

    The authors emphasize that diagnostic imaging for PE was performed only in patients who had an elevated D-dimer or high pretest clinical probability for PE. This was investigated because previous studies have shown that PE is highly unlikely in patients with a low pretest probability and a negative D-dimer.

    The authors stated that syncope is generally expected to occur in a PE that causes obstruction of a proximal pulmonary artery that leads to transient hypotension from decreased cardiac output. This was the case in 67 percent of their patients. The extent of thrombosis was not large enough to obstruct blood flow, however, in at least half of the patients with PE in this study. The authors concluded that patients with a small PE may have syncope that was associated with other conditions that were missed.

    Comment: At first glance, the conclusions of this paper are certainly rather dramatic, especially considering a previously unreported high incidence of PE in patients with syncope. But it may be an overinterpretation to conclude that one in six patients hospitalized for their first episode of syncope have a pulmonary embolism. Clearly this cannot be the case based on our current knowledge and experience. But these were high-risk patients. PE can be a clandestine event, and it certainly can cause syncope, but one must be careful in interpreting this paper. Many patients were sent home, and the incidence of false-positive CT scans and VQ scans is well known. These were certainly high-risk patients, most of them with obvious DVT, tachypnea, tachycardia, or hypotension. It is also not clear how many of the PEs were actually clinically relevant, and the overdiagnosis of PE by pulmonary angiogram is well known. (AJR Am J Roentgenol 2015;205[2]:271.) The incidence of false-positive PE on angiogram can be as high as 25 percent.

    This paper has a number of mythological flaws and the interpretation of the data was questionable, but one thing is clear: A pulmonary embolism can cause syncope, and clinicians should at least consider the possibility of a blood clot in the pulmonary artery in patients who faint. It's good to remember that the term syncope ends in PE. A patient should be worked up for PE in the ED if he has tachycardia, tachypnea, DVT, or a Wells' score of 4 or greater or an elevated D-dimer. Look for other causes if the Wells' score is low and the D-dimer is negative. Physicians in the United States clearly use excessive testing for PE on very low-risk patients.

    A clinician could be grossly led astray if the PE causes syncope accompanied by a brief seizure by concentrating on a primary CNS lesion or event. The careful and conscientious emergency clinician would unlikely withhold workup for a PE in most cases with classic signs and symptoms. Using the Wells' criteria and D-dimer testing will further hone one's accuracy. There will be, of course, patients with minimal symptoms whose fainting was caused by a PE that might escape detection in the ED. First-time syncope in a patient without an obvious etiology certainly raises a red flag for a more complete evaluation. The patients in this study were mostly in their 70s, but one should not use age as a discriminating factor.

    A Simplified Approach to Syncope and PE

    This study did not focus on an undifferentiated group of patients with syncope; these patients were sick and symptomatic, not run-of-the-mill people who passed out in church. The fact that 72 percent of patients with syncope were discharged is somewhat different from the American experience, where more patients would be admitted for monitoring or a workup for syncope than in this situation. Risk-stratifying and D-dimer testing are easily accomplished in the ED, and both should be performed in any patient with unexplained syncope.

    One should not take away the conclusion that one of six patients who presents to the ED with syncope has a pulmonary embolism, but this paper will have been worth publishing if the diagnosis is considered in those who faint.

    Reader Feedback: Readers are invited to ask specific questions and offer personal experiences, comments, or observations on InFocus topics. Literature references are appreciated. Pertinent responses will be published in a future issue. Please send comments to [email protected].

    Dr. Roberts: I read your article, “Sudden Deaths in Epilepsy May be Cardiac Disease,” about how cardiac disease may underlie causation of seizures for some patients. (EMN 2017;39[5]:14; The relationship between generalized seizures and their associated physiological changes are important. While heart rate changes and variability may be involved, respiratory alterations may offer another primary mechanism contributing to sudden unexpected deaths from epilepsy.

    We found that seizures induced in animals (cats, piglets) produced the expected stimulation of heart rate and arterial blood pressure during tonic-clonic seizures, but also evidence of entrainment of respiratory motor nerve activity (J Appl Physiol 1996;80[3]:924; Fig. 1).

    During prolonged ictal seizure discharges, increased phasic and sometimes tonic respiratory activity were demonstrated. A lack of coordination between activation of the phrenic nerve (driving the diaphragm) and of motor nerves controlling the opening and closing of the larynx was evident. (J Appl Physiol 1999;86[6]:2052; Fig. 2).

    In spontaneously breathing animals who had received a tracheotomy, tidal volume increased during seizures, but minute ventilation was reduced due to glottic obstruction in animals breathing through intact upper airways. (Epilepsy Res 1995;20[1]:21; Pediatr Res 1995;38[1]:61; Acad Emerg Med 1999;6[7]:682.)

    These findings indicate that respiratory impairment should be considered a mechanism potentially contributing to sudden unexpected death from epilepsy, and emphasize the therapeutic importance of maintaining upper airway patency during seizures. — Thomas Terndrup, MD, Columbus, OH

    Dr. Roberts responds: Interesting information, Dr. Terndrup, and one possible cause of death during seizures. Sudden death during a seizure is likely always a terminal event in individuals having seizures outside the hospital. Perhaps respiratory support would change the outcome if the event occurred in the hospital. I personally have not seen sudden death during a seizure in the ED, and fortunately, it is very uncommon.

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