Nov 112019
 

Jon-Emile S. Kenny MD [@heart_lung]

The transient and reversible loss of consciousness that may accompany pulmonary embolism [PE] is well-documented [1-7].  This brief post will not address the controversy regarding the prevalence of PE in ‘unexplained’ syncope; rather, it will focus on pathomechanisms and serve as the foundation for a few forthcoming entries on pulmonary thromboembolism physiology.

Basics

Loss of consciousness typically requires that the mean arterial pressure fall by 30 – 40 mmHg for at least 7 seconds [8].  The dreadful experiments [i.e. the ‘Red Wing Studies’] that confirmed this were described previously.  An acute fall in MAP demands either an abrupt drop in cardiac output [i.e. flow] and/or in vascular resistance.  When the central aortic pressure, or MAP, falls below the auto-regulatory threshold of the cerebrovascular system, cerebral perfusion plunges into darkness, so to speak.

Yet how, exactly, does PE lead to a transient fall in MAP?  As expected, it’s complicated and it depends upon the underlying reserve of the patient’s cardiopulmonary system [9-12].

Stroke Volume in PE: free from cardiopulmonary disease

As above, the response of the right ventricle to a PE depends upon co-morbidities.  To consider the effects of a PE in a patient free of cardiopulmonary disease helps clarify the pathophysiology.

Right ventricular [RV] stroke volume [SV] is directly proportional to its end-diastolic volume, and indirectly proportional to pulmonary vascular load [9, 13].  In other words, RV SV tends to rise as the RV fills in end-diastole, but falls if there is a high outflow impedance [i.e. pulmonary vascular obstruction].  In a healthy RV, a relatively large obstruction is required to impair RV SV.  In a classic set of observational studies [10], it was documented that a ~ 25-35% obstruction by angiography is required to increase mean pulmonary arterial pressure [mPAP] and cause RV dilatation and even anatomically profound obstruction [i.e. > 50%] is well adapted to by the healthy heart [14].  In animal models of PE, similar degrees of obstruction of the pulmonary vascular bed and elevations of mPAP resulted in little, if any fall in SV [13, 15, 16]; why?

RV SV is maintained by an increase in RV end-diastolic volume, as a consequence of adrenergic effects on the peripheral venous beds, which preserve the gradient for venous return and, therefore, preload [9].  Additionally, an increase in RV contractility lowers RV end-systolic volume which also saves SV [14, 16].  Importantly, acute hypoxemia is a profound stimulus for adrenergic tone which maintains the aforementioned adaptive mechanisms [17, 18].

Yet, there must be some obstruction threshold in the pulmonary circulatory system beyond which RV compensatory mechanisms fail.  In one animal investigation, this was noted to be ~ 1000 dynes • sec / cm5 [11].  Above this, there is a disproportionate rise in RV end-systolic volume relative to RV end-diastolic volume in response to preload [15].  In other words, SV falls coincident to rising RV end-diastolic volume and pressure; this event is also known as RV failure.

How does this fall in RV SV translate to the left heart?  There are, essentially, two broad mechanisms – so called, ‘series’ and ‘parallel’ effects [9, 13].  The series effect simply means that as RV SV falls, so too must LV preload as 2-3 cardiac cycles after RV output changes, the LV preload responds accordingly; the LV can only eject what it receives from its ventricular partner.  ‘Parallel’ effects occur when the RV directly impinges upon the function of the LV and these are well-known and validated mechanisms of impaired LV output [19-21].  Via coupled pericardial restraint [22], an increase in RV diameter stiffens [i.e. decreases the compliance] of the LV; this has been convincingly demonstrated in animal models and in human models of pulmonary hypertension [23, 24].  The effect may also be mediated via a fall, or even reversal, in the trans-septal pressure gradient [25].  Additionally, coronary venous congestion [say from high right atrial pressure] also stiffens the LV [26].

A decrease in SV by the mechanisms above – and if not buffered by tachycardia – leads to diminished central arterial blood volume.  Accordingly, without an acute, compensatory rise in peripheral vascular resistance, MAP and cerebral perfusion fall.

Stroke Volume in PE: with cardiopulmonary disease

The mechanisms above also apply to the unhealthy cardiopulmonary system, yet their effects are magnified.  In patients with PE and underlying cardiopulmonary disease, the average percent obstruction of the pulmonary vasculature observed is much lower with greater elevations in mPAP and diminished cardiac outputs [10].  That large obstructions are rare in those with inadequate cardiopulmonary reserve suggests that obstruction beyond 50% is a terminal event in these patients.  Additionally, in the unhealthy, a fall in stroke volume is less likely to be compensated for by reflex mechanisms that increase vascular resistance and MAP [27].  It is possible that some anti-hypertensive medications blunt the rise in central aortic pressure in the face of a falling cardiac output [27]; the implications for right coronary perfusion pressure will be discussed in a subsequent entry.  Finally, paroxysms of tachydysrhythmias may also impair SV following a PE [8].

Transient Nature of Syncope

While the aforementioned describes diminished flow into the central arterial space and the ensuing fall in MAP, it doesn’t quite address how cerebral perfusion and, therefore, consciousness returns.

One potential mechanism is that a large PE induces neurocardiogenic syncope [8].  As above, an abrupt rise in RV volume and pressure can ‘squeeze out’ the LV; high contractility from adrenergic tone, coupled with diminished LV preload favours a vasodepressor response from the brain – the Bezold-Jarisch reflex [28].  Indeed, extreme bradydysrhythmias in response to large PE have been documented [7].  Vasodilation drops MAP and consciousness is lost, only to return when the patient is supine and venous return rises.

A second, non-mutually exclusive, mechanism is a rapid fall in pulmonary vascular resistance following an initial embolic event.  Animal models have shown that while the anatomic location of a PE may change minimally after it initially wedges itself into the pulmonary circulation, hemodynamics and angiographic blood flow distribution may spontaneously improve [29].  This suggests recruitment and dilation of adjacent pulmonary vascular beds – allowing blood flow to find its way to the left heart.  Notably, the supine position might promote parallel recruitment up to the lung apices.  Clearly, this would be blunted in a patient with diminished cross-sectional pulmonary vascular area [e.g. severe emphysema]; thus, cardiopulmonary reserve and peripheral vasoconstrictive reflexes to maintain MAP may define the slim difference between transient and permanent loss of consciousness following pulmonary embolism.

Please see other posts in this series,

JE

Dr. Kenny is the cofounder and Chief Medical Officer of Flosonics Medical; he also the creator and author of a free hemodynamic curriculum at heart-lung.org

References

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ICU Physiology in 1000 Words: Pulmonary Embolism & Syncope