Scrutinizing the Mechanisms of West Non–Zone 3 Conditions during Tidal Ventilation

A long time ago, it was demonstrated that blood flow through arterioles, capillaries, or veins is well mediated by the Poiseuille law (the gradient between the upward and backward pressures of the vessel), provided the proper backward pressure is used, taking into account the surrounding pressure of the vessel and its closing pressure, leading to the principle of the vascular waterfall and the Starling resistor with different vessel zone conditions in which zone 3 regards the absence of any flow limitation (1). West zones are no more than the application of this principle to the pulmonary capillaries (2). Figure 1 illustrates its application to the vena cava as well as the pulmonary capillaries.

Figure 1.

Impact of mechanical ventilation on systemic venous return and pulmonary blood flow, with their potential interaction. A model of a vascular waterfall and the Starling resistor. Left part: Potential impact of mechanical ventilation on systemic venous return and right ventricular (RV) preload. The venous return is normally driven by the difference between the upward mean systemic pressure (Pms) and the backward right atrial pressure (Pra), with no influence of the surrounding pressure of the vena cava, which is the pleural pressure (Ppl), a situation corresponding to a zone 3 condition (Pms > Pra > Ppl). Pms is the equilibrium pressure into the circulatory system when the heart stops beating. The cyclic rise in airway pressure (Paw) induces a predominant rise in Ppl in case of normal lung compliance (Cl) (15), impeding partially or completely the systemic venous return by inducing a zone 2 (Pms > Ppl > Pra) or zone 1 (Ppl > Pms > Pra) condition, respectively. Middle part: Potential impact of mechanical ventilation on pulmonary blood flow and RV afterload. The pulmonary blood flow is normally driven by the difference between the upward systolic right ventricle pressure (Prv) and the backward left atrial pressure (Pla), with no influence of the surrounding pressure of lung capillaries, which is the transpulmonary pressure (Pl), a situation corresponding to a West zone 3 condition (Prv > Pla > Pl). The cyclic rise in Paw induces a predominant rise in Pl in case of altered Cl (15), impeding partially or completely the pulmonary blood flow by inducing a zone 2 (Prv > Pl > Pla) or zone 1 (Pl > Prv > Pla) condition, respectively. The preload effect, by impeding venous return and RV preload, may reduce Prv and Pla, inducing a transition from West zone 3 to zone 2 or from zone 2 to zone 1 (gray dashed arrows). Right part: Curvilinear relationship between transpulmonary pressure and RV afterload as a consequence of West zone condition alterations.

In this issue of the Journal, Slobod and colleagues (pp. 1311–1319) report interesting results regarding the prevalence of lung non–zone 3 conditions during inspiration across a 2- to 12-ml/kg range of Vt in 51 postoperative passively ventilated cardiac surgery patients (3). Using detailed invasive hemodynamic phenotyping, coupled with echocardiography in a few patients, the authors found that even low Vt was associated with a cyclic inspiratory increase in markers of right ventricular (RV) afterload and a decrease in RV stroke volume. Non–zone 3 conditions were present in >50% of subjects at a Vt ⩾ 6 ml/kg, with a corresponding mean driving pressure of 11–12 cm H₂O.

In non–zone 3 conditions, the backward pressure for the pulmonary flow is no longer the pulmonary venous pressure but now the distending pressure of the alveoli (i.e., transpulmonary pressure) (2). This usually suggests a partial (zone 2) or complete (zone 1) collapse of pulmonary capillaries with a limited or interrupted flow. Slobod and colleagues found a linear relationship between transpulmonary pressure at end inspiration and the rise in RV afterload. It is interesting to note that this relationship was already reported, but as being curvilinear (4), demonstrating that above a given value of transpulmonary pressure, West zone 2 or zone 1 conditions occur, abruptly increasing RV afterload. Jardin and colleagues (5) previously reported in patients with acute respiratory distress syndrome (ARDS) that transpulmonary pressure increased when Vt or positive end-expiratory pressure was increased; this generated an increase in RV isovolumetric contraction pressure (a good surrogate of RV afterload) and a decrease in pulmonary artery pulse pressure (a good surrogate of RV stroke volume), as reemphasized by Slobod and colleagues.

The new information in the Slobod and colleagues study is that the effect of tidal ventilation on RV afterload was also observed in patients without ARDS with a low Vt, whereas it was usually considered that such a deleterious effect of mechanical ventilation is especially pronounced in patients with ARDS, in whom transpulmonary pressure is more likely to be severely elevated. In patients without ARDS, mechanical ventilation is expected to cause a decrease in systemic venous return (preload effect) mediated by a significant change in intrathoracic pressure (pleural pressure), which may reduce the superior vena cava transmural pressure toward its critical closing pressure, inducing venous return flow limitation, according to a vascular waterfall effect and the Starling resistor principle (6, 7) (Figure 1). This is especially true in cases of central hypovolemia and fluid responsiveness status. Notably, compliance of the respiratory system, as well as that of the lung and chest wall, were far to be normal in the post–cardiac surgery patients evaluated by Slobod and colleagues. This could explain in part their results suggesting an afterload effect even in patients without ARDS with low Vt.

Other specific points in this study deserve discussion. First, the hemodynamic consequence of increased RV afterload is usually prominent when RV function was previously impaired. Slobod and colleagues report a decrease in RV stroke volume during insufflation, but, unfortunately, they do not report RV function at baseline. Second, the authors state that many critically ill patients have “RV limitation” (i.e., their right ventricle cannot increase its end-diastolic volume in response to increased afterload to maintain stroke volume). This assertion is questionable for several reasons. RV failure was defined in critically ill patients as a state in which the right ventricle is unable to meet the demands for blood flow without excessive use of the Frank-Starling mechanism (8). In many acute clinical situations, such as massive pulmonary embolism or ARDS, increased RV afterload is associated with RV dilatation and venous congestion (9). Interestingly, Slobod and colleagues not only reported an “RV limitation” during insufflation but also a decrease in transmural right atrial pressure (i.e., the distending pressure of the right atrium). This could suggest that alteration of the RV afterload parameters they observed was related to an upstream decrease in systemic venous return and RV preload mediated by mechanical ventilation, a crucial point to be well understood (Figure 1).

Indeed, lung West zones are supported by a potential competition between alveolar distending pressure and pulmonary capillary flow. This competition was reported by Zapol and colleagues many years ago to occur only in patients with acute lung injury and not in patients with normal lung compliance (10). A decrease in pulmonary blood flow, as a consequence of a preload effect of mechanical ventilation, may potentiate West non–zone 3 conditions, especially when lung compliance is depressed. This competition is corrected by fluid loading, especially when the patient is hypovolemic (11).

When the increase in RV afterload is really the primum movens, non–zone 3 conditions are usually related to lung overinflation (an abnormal and absolute increase in alveolar distending pressure) (Figure 1), and the decrease in RV stroke volume is associated with RV dilatation, as previously reported using echocardiography in patients with ARDS during tidal ventilation (12). The decrease in systemic venous return is then the consequence (transmural right atrial pressure is increased) and not the cause (transmural right atrial pressure is decreased) of the afterload effect (12). In this case, RV function may be worsened by fluid loading (13, 14) and requires adjustment of ventilator settings and strategies to relieve pulmonary vascular dysfunction.

In conclusion, the study of Slobod and colleagues is definitely interesting to analyze. Its main value is to allow intensivists to better understand heart–lung interactions and their respective mechanisms. Although some data on RV size and RV function are missing, we may assume that changes in RV afterload observed in their patients without ARDS were at least in part primarily related to a decrease in systemic venous return and RV preload. A “pure” RV afterload effect, as observed in patients with ARDS, is associated with RV dilatation and venous congestion. In clinical practice, echocardiography is therefore essential in depicting these respective effects because fluid management in these 2 conditions is opposite.