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ICU Physiology in 1000 Words: Pulmonary Embolism & Syncope
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.
Loss of consciousness typically requires that the mean arterial pressure fall by 30 – 40 mmHg for at least 7 seconds . 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 , 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 . 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 . 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 . Above this, there is a disproportionate rise in RV end-systolic volume relative to RV end-diastolic volume in response to preload . 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 , 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 . Additionally, coronary venous congestion [say from high right atrial pressure] also stiffens the LV .
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 . 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 . It is possible that some anti-hypertensive medications blunt the rise in central aortic pressure in the face of a falling cardiac output ; 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 .
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 . 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 . Indeed, extreme bradydysrhythmias in response to large PE have been documented . 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 . 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.
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
Busch U, Renner U, Wirtzfeld A et al: Floating pulmonary embolus: unusual cause of recurrent syncope. European heart journal 1984, 5(7):602-605.
Prandoni P, Lensing AW, Prins MH et al: Prevalence of pulmonary embolism among patients hospitalized for syncope. New England Journal of Medicine 2016, 375(16):1524-1531.
Costantino G, Ruwald MH, Quinn J et al: Prevalence of pulmonary embolism in patients with syncope. JAMA internal medicine 2018, 178(3):356-362.
Demircan A, Aygencel G, Keles A et al: Pulmonary embolism presenting as syncope: a case report. Journal of medical case reports 2009, 3(1):7440.
Edelson G, Reis ND, Hettinger E: Syncope as a premonitory sign of fatal pulmonary embolism Two case reports. Acta Orthopaedica Scandinavica 1988, 59(1):71-73.
Thames MD, Alpert JS, Dalen JE: Syncope in patients with pulmonary embolism. Jama 1977, 238(23):2509-2511.
Simpson RJ, Podolak R, Mangano CA et al: Vagal syncope during recurrent pulmonary embolism. Jama 1983, 249(3):390-393.
Koutkia P, Wachtel TJ: Pulmonary embolism presenting as syncope: case report and review of the literature. Heart & lung 1999, 28(5):342-347.
Wood KE: Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest 2002, 121(3):877-905.
Sharma G, McIntyre K, Sharma S et al: Clinical and hemodynamic correlates in pulmonary embolism. Clinics in chest medicine 1984, 5(3):421-437.
Prewitt RM: Hemodynamic management in pulmonary embolism and acute hypoxemic respiratory failure. Critical care medicine 1990, 18(1 Pt 2):S61-69.
Ducas J, Prewitt R: Pathophysiology and therapy of right ventricular dysfunction due to pulmonary embolism. Cardiovascular clinics 1987, 17(2):191-202.
Calvin Jr JE: Acute right heart failure: pathophysiology, recognition, and pharmacological management. Journal of cardiothoracic and vascular anesthesia 1991, 5(5):507-513.
McIntyre KM, Sasahara AA: The hemodynamic response to pulmonary embolism in patients without prior cardiopulmonary disease. The American journal of cardiology 1971, 28(3):288-294.
Calvin J, Quinn B: Right ventricular pressure overload during acute lung injury: Cardiac mechanics and the pathophysiology of right ventricular systolic dysfunction. Journal of Critical Care 1989, 4(4):251-265.
Calvin JE: Right ventricular afterload mismatch during acute pulmonary hypertension and its treatment with dobutamine: A pressure segment length analysis in a canine model. Journal of Critical Care 1989, 4(4):239-250.
Kontos HA, Levasseur JE, Richardson D et al: Comparative circulatory responses to systemic hypoxia in man and in unanesthetized dog. Journal of applied physiology 1967, 23(3):381-386.
Eckstein J, Horsley A: Effects of hypoxia on peripheral venous tone in man. The Journal of laboratory and clinical medicine 1960, 56:847-853.
Naeije R, Badagliacca R: The overloaded right heart and ventricular interdependence. Cardiovascular research 2017, 113(12):1474-1485.
Hamzaoui O, Monnet X, Teboul J-L: Pulsus paradoxus. In.: Eur Respiratory Soc; 2013.
Bove AA, Santamore WP: Ventricular interdependence. Progress in cardiovascular diseases 1981, 23(5):365-388.
Takata M, Harasawa Y, Beloucif S et al: Coupled vs. uncoupled pericardial constraint: effects on cardiac chamber interactions. Journal of Applied Physiology 1997, 83(6):1799-1813.
Calvin Jr JE, Langlois S, Garneys G: Ventricular interaction in a canine model of acute pulmonary hypertension and its modulation by vasoactive drugs. Journal of critical care 1988, 3(1):43-55.
Kasner M, Westermann D, Steendijk P et al: Left ventricular dysfunction induced by nonsevere idiopathic pulmonary arterial hypertension: a pressure–volume relationship study. American journal of respiratory and critical care medicine 2012, 186(2):181-189.
Kingma I, Tyberg J, Smith ER: Effects of diastolic transseptal pressure gradient on ventricular septal position and motion. Circulation 1983, 68(6):1304-1314.
Watanabe J, Levine MJ, Bellotto F et al: Effects of coronary venous pressure on left ventricular diastolic distensibility. Circulation research 1990, 67(4):923-932.
Goswami N, Blaber AP, Hinghofer-Szalkay H et al: Orthostatic intolerance in older persons: etiology and countermeasures. Frontiers in physiology 2017, 8:803.
Castelli R, Tarsia P, Tantardini C et al: Syncope in patients with pulmonary embolism: comparison between patients with syncope as the presenting symptom of pulmonary embolism and patients with pulmonary embolism without syncope. Vascular Medicine 2003, 8(4):257-261.
Dalen JE, Mathur VS, Evans H et al: Pulmonary angiography in experimental pulmonary embolism. American heart journal 1966, 72(4):509-520.