Balancing a single-ventricle circulation: ‘physiology to therapy’

Abstract

The parallel supply of the pulmonary and systemic circuits complicates the management of single-ventricle lesions. Achieving a balance between the two limbs of the circulation forms the basis of optimizing the systemic oxygen delivery, with the oxygen availability being highly sensitive to alterations in pulmonary/systemic blood flow ratio (Q_p/Q_s). The identification of a ‘balanced’ circulation is challenging wherein various parameters should be evaluated in close conjunction with each other. The prompt identification of circulatory maldistribution should be backed up with a sound management strategy aimed at attaining an equitable systemic and pulmonary perfusion. Any degree of ventricular dysfunction compromises the total output (Q_p + Q_s) supplying the two circuits explaining the role of inodilators in improving the myocardial performance in addition to lowering the systemic vascular resistance and optimizing Q_p/Q_s in setting of a single-ventricle physiology. Moreover, the pulmonary circulation is modulated by a multitude of factors intricately linked to the single-ventricle lesion, including anatomical characteristics unique to the underlying lesion (branch pulmonary arterial and venous stenosis), preoperative interventions, associated aortopulmonary and venovenous collaterals, plastic bronchitis, pulmonary arteriovenous fistulae, underlying ventricular dysfunction,, and many others. The article highlights the physiology, diagnosis, therapeutic optimization of a single-ventricle circulation, and the peculiarities pertaining to the pulmonary circulation of the uni-ventricular lesions.

Single-ventricle physiology: the concept of a ‘balanced’ circulation

A functional single-ventricle physiology is characterized by the parallel supply of the pulmonary and systemic circuits. The goal of an ideal perioperative management is aimed at achieving an equitable pulmonary and systemic perfusion, thereby accounting for a ‘balanced’ circulation. A ‘balanced’ circulation results in maximal oxygen delivery at the tissue level [1]. Maldistribution of the cardiac output (CO) between the pulmonary and systemic limbs of a single-ventricle circulation has been proposed as a potential cause of hemodynamic deterioration after first-stage palliation for hypoplastic left heart syndrome (HLHS) in various studies [2]. The subsequent discussion outlines the various pitfalls in achieving a ‘balanced’ circulation and the measures aimed at the therapeutic optimization of the single-ventricle physiology.

Q_p/Q_s and the ‘balanced’ circulation: the nuances

The management strategy in a single-ventricle physiology aims at accomplishing a Q_p/Q_s (pulmonary/systemic blood flow ratio) of around 1, as it is presumed to ensure a ‘balanced circulation’. The Q_p/Q_s ratio can be estimated by the modified Fick equation, where

$$\mathrm{Qp}/\mathrm{Qs}=\frac{\text{Aortic saturation}\left(\mathrm{Sa}{\mathrm{O}}_2\right)–\text{Mixed venous saturation}\left(\mathrm{Smv}{\mathrm{O}}_2\right)}{\text{Pulmonary vein saturation}\left(\mathrm{Spv}{\mathrm{O}}_2\right)–\text{Pulmonary artery saturation}\left(\mathrm{Spa}{\mathrm{O}}_2\right)}$$

Given the fact that the saturation of the pulmonary artery (PA) is identical to the aortic saturation in a single-ventricle physiology, the calculation of Q_p/Q_s gets simplified as:

$$\mathrm{Qp}/\mathrm{Qs}=\frac{\text{Aortic saturation}\left(\mathrm{Sa}{\mathrm{O}}_2\right)–\text{Mixed venous saturation}\left(\mathrm{Smv}{\mathrm{O}}_2\right)}{\text{Pulmonary vein saturation}\left(\mathrm{Spv}{\mathrm{O}}_2\right)–\text{Aortic saturation}\left(\mathrm{Sa}{\mathrm{O}}_2\right)}$$

Therefore, the arterial oxygen saturation (SaO₂ or aortic saturation) is often employed as a surrogate estimate of Q_p/Q_s, with the assumption that the SmvO₂ and the SpvO₂ are within the normal physiological range. Consequently, a SaO₂ of 75–80% is believed to reflect a ‘balanced’ circulation with a Q_p/Q_s of 1 considering a normal SmvO₂ and SpvO₂. This SaO₂ target serves as a surrogate of adequate perfusion to the two parallel limbs of the circulation [1]. On either end of this target, one of the parallel limbs of the circulatory system suffers malperfusion [3].

However, the estimation of Q_p/Q_s with the interpretation of a SaO₂ of 75–80% can be misleading in certain situations [4, 5]. A SaO₂ of 75–80% may provide a false sense of security in suggesting a ‘balanced’ circulation, in the setting of a low SmvO₂ owing to compromised CO. A resultant fall in SmvO₂ is offset by an increase in the amount of well-saturated blood returning from the lungs with an elevated Q_p/Q_s in background of an unaltered SaO₂. At the same time, the inability to account for pulmonary venous desaturation (a low SpvO₂) leads to a false impression of a ‘balanced’ circulation, with a much higher actual Q_p/Q_s [6]. In both the scenarios, the prediction of Q_p/Q_s on the basis of SaO₂ results in an erroneous inference that the circulation is well ‘balanced’ with the actual Q_s being critically low.

Several investigators have advocated SmvO₂ monitoring as a useful adjunct for the identification of a ‘balanced’ circulation [4, 5]. The investigators proposed the superior vena cava blood as a representative of mixed venous blood (as there is no site of true systemic mixed venous blood in single-ventricle physiology). Their findings were suggestive of the fact that the SaO₂values alone without the knowledge of SmvO₂ can be illusive and are not useful indicators of the circulatory status in an underlying single-ventricle physiology. In fact, all the models aimed at optimizing the single-ventricle circulation describe the role of combined evaluation of various clinical parameters in achieving a ‘balanced’ circulation. For instance, in face of a decreased SmvO₂ and increased SaO₂, the pulmonary blood flow (PBF) should be decreased, whereas the flow to the pulmonary circulation should be increased in situations characterized by a declining SmvO₂ and SaO₂.

Manipulations aimed at preventing circulatory maldistribution: aiming an adequacy of tissue perfusion and oxygenation

Barnea et al. demonstrated that the systemic oxygen delivery (the product of systemic blood flow and oxygen content) for a given single-ventricle output is maximum with a Q_P/Q_S ratio of 1 or just below 1 [1]. The tissue oxygen availability is very sensitive to subtle alterations in the Q_P/Q_S ratio with either the systemic perfusion or oxygenation suffering on the two extreme sides of the ratio. The practical manoeuvres aimed at balancing the Q_p/Q_s at the bedside is through the differential manipulation of the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with the use of oxygen, CO₂, and acid–base status modulation (Fig. 1) [6].

Fig. 1.

Manoeuvres aimed at manipulating the Q_p/Q_s [6]. fiO₂, fractional inspired concentration of oxygen; p_aCO₂, partial pressure of arterial carbon dioxide; PEEP, positive end-expiratory pressure; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; Q_p/Q_s, pulmonary/systemic blood flow ratio

Sudden drifts in the relative resistances in either of the two vascular beds are sufficient to result in circulatory maldistribution. The abovementioned manoeuvres can effectively optimize the flow in the two parallel circulations. Subatmospheric oxygen (FiO₂ 0.17–0.19) or induction of respiratory acidosis can effectively raise PVR, decrease SVR, and thus decrease the tendency towards pulmonary over-circulation in infants with an unrestricted Q_p. PVR can also be elevated almost independently of SVR with the well-directed use of positive end-expiratory pressure (PEEP) [7]. However, not all the neonates with single-ventricle physiology demonstrate pulmonary over-circulation. Elevated PVR can persist in the newborn with single-ventricle physiology. The occurrence of respiratory acidosis in the setting of decrease Q_P is of grave concern, as this will further elevate the PVR. The management of high PVR is essentially multimodal. The alveolar recruitment strategies help in alleviating underlying atelectasis, limiting the incremental rise in the airway pressures. High-frequency ventilation may prove effective in inducing hyperventilation simultaneously avoiding the high mean airway pressures. Oxygen therapy, hyperventilation, and alkalosis (administration of sodium bicarbonate) are advocated. Inhaled nitric oxide (NO) and prostaglandin E infusion are instituted as a continuation of strategies aimed at selectively lowering the PVR.

Moreover, ventricular dysfunction leading to low CO (Q_p + Q_S) contributes significantly to increased morbidity and mortality in addition to the circulatory maldistribution. Metabolic acidosis, volume overload, inadequate myocardial protection, prolonged circulatory arrest times, and coronary vascular injury all contribute to poor post-operative ventricular performance. Considering the fact that the ventricular function plays an important role in augmenting Q_p + Q_S, inodilator agents that improve the myocardial energetics in addition to lowering the SVR, such as phosphodiesterase inhibitors (e.g. milrinone), are the optimal drugs to use in these infants. The use of α-antagonists (phenoxybenzamine) has also been advocated to optimize the Q_p/Q_s by attenuating the elevations in SVR, but the clinical use is compounded by a concomitant decrease in systolic blood pressure [8].

Pulmonary circulation in single-ventricle lesions: altered anatomy, much altered physiology

Patients with a functionally uni-ventricular heart demonstrate an abnormal growth, development, and physiology of the pulmonary vasculature [9–12]. The various additional factors compounding the abovementioned fact are enlisted in Table 1.

Table 1.

Factors affecting the pulmonary circulation in a uni-ventricular physiology [9–12]

• Abnormal pre-existing anatomy

• Altered baseline PBF

• Pre-existing endothelial dysfunction

• Un-physiological or a non-pulsatile PBF at staged palliation (promotes endothelial dysfunction)

• Architectural distortion as a result of repeated interventions (e.g. post-systemic-pulmonary shunts)

• Patent ductus arteriosus, pulmonary arteriovenous, venovenous and aortopulmonary collaterals

• Other factors: ventricular function, atrioventricular valve regurgitation, obstruction to pulmonary venous return, etc.

PBF, pulmonary blood flow

All these factors taken into consideration, the premise of optimizing the PVR is pivotal, particularly in background of a non-pulsatile PBF and pre-existing endothelial dysfunction owing to the absence of shear stress–mediated release of endothelium-derived relaxation factors [11]. Pharmacological modulation of the NO, prostacyclin, and endothelin pathways can assist the palliative course of these patients by augmenting pulmonary vasodilation and constitutes an area of recent clinical interest [13].

Conclusion

The parallel supply of the pulmonary and systemic circuits complicates the management in a single-ventricle circulation. A subtle alteration in the cardiovascular milieu, volume status, acid–base status, or ventilation can have a profound influence on the relative resistances in the two circuits, thereby disturbing the tenuously ‘balanced’ circulation and compromising systemic oxygen delivery. The monitoring of the patient cohort should be directed towards an early identification of an over-circulation in one of the circuits, with a resultant ‘steal’ from the other, and the subsequent management should include various pharmacological and ventilatory manipulations to achieve a ‘balanced’ circulation. At the same time, focussed endeavours should be aimed at an adequate protection of the altered pulmonary circulation while managing the cohort of single-ventricle patients at various stages of surgical palliation.

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The authors declare that they have no conflict of interest.