The single ventricle pathway in paediatrics for anaesthetists

Key points.

• •Single ventricle defects are characterised by the absence of two well developed ventricles, with one dominant ventricle providing both systemic and pulmonary blood flow.
• •Surgical approaches include staged palliation, two-ventricle repairs, and transplantation.
• •Understanding differences in anatomy and the impact of anaesthesia on cardiovascular and respiratory physiology are essential for safe perioperative care.
• •Hybrid (i.e. combined surgical and catheterisation interventions) and right ventricle-to-pulmonary artery (Sano) shunts are being used increasingly for Stage 1 surgical palliation.

Learning Objectives.

• •Recall the variables that determine the direction and flow of blood within the pulmonary and systemic circulatory beds in a child with an uncorrected single ventricle defect.
• •Describe the key pathophysiological issues in the single ventricle circulation that require surgery to ensure adequate delivery of oxygen to the tissues.
• •Briefly describe the surgical technique and physiological rationale for each of the staged surgical interventions in patients with single ventricle defects.

Single ventricle defects affect approximately 31 per 100,000 live births.¹ They are characterised by the absence of two well developed ventricles, one of which is typically rudimentary or hypoplastic.² These defects and their subsequent surgical palliative procedures have profound differences in circulation and physiology. Understanding of these differences is crucial for safe perioperative management.

Single ventricle defects are classified as complex congenital heart defects (CHD) where there is complete mixing of pulmonary venous and systemic venous blood and one functioning ventricle ejects to both systemic and pulmonary vascular beds.

However, there is a large variation in morphology. Hypoplastic left heart syndrome (HLHS) is the most common single ventricle defect (accounting for 25% of all single ventricle lesions).¹ Other common defects include double inlet ventricle (dominant left or right ventricle), pulmonary atresia with intact ventricular septum (dominant left ventricle), tricuspid atresia (dominant left or right ventricle), and unbalanced atrioventricular canal defect (dominant left or right ventricle). Given the large variation in morphology of single ventricle defects, this article focuses on HLHS and does not specifically address other anatomical subtypes.

Epidemiology

Despite differences in estimates between populations, the birth incidence of single ventricle defects has been largely constant over the past two decades.³ The prenatal detection rate of complex CHD is typically 50–60%.4, 5 Delayed presentation can still occur, and up to 25% of newborn infants with CHD first present after discharge from hospital.⁶

Perioperative and long-term survival continues to improve and surgical interventions are being performed more frequently for single ventricle defects.⁷ Even with recent advances, the transplant-free survival at 6 yrs for patients with HLHS who undergo surgical palliation is approximately 60%.⁸ However, for those children who complete the staged surgical palliative pathway, approximately 70% will survive beyond 20 yrs of age.9, 10

As a result, children with single ventricle defects are now presenting more frequently for non-cardiac surgery, and 40% of children who undergo cardiac surgery in the first year of life subsequently undergo at least one non-cardiac surgery before 5 yrs of age.¹¹ This frequency is expected to increase.¹² An overview of the anaesthetic management of children with congenital heart disease for non-cardiac surgery has been published previously in this journal.¹³

Unpalliated single ventricle defects

Because of the variety of anatomical defects that give rise to single ventricle physiology, patients may have insufficient or excessive pulmonary blood flow, with or without systemic outflow tract obstruction. For unpalliated defects, two shunts are required for: (i) mixing of venous and arterial blood and (ii) perfusion of both pulmonary and systemic circulations.¹⁴ This underlying principle is the same for all single ventricle defects, although the exact location of the shunts is dependent on the type of cardiac lesion. First, an intracardiac shunt, usually at the atrial level, is required for complete mixing of deoxygenated and oxygenated blood from the systemic and pulmonary vascular beds, respectively. With complete intracardiac mixing of pulmonary and systemic venous blood, the partial pressure of oxygen (PaO₂) in the proximal pulmonary artery and the ascending aorta approximate each other. Not infrequently (approximately 6% of children with HLHS), the atrial septum is either intact or restrictive and prevents adequate intracardiac venous mixing.¹⁵ Without adequate mixing, pulmonary venous hypertension and inadequate systemic oxygenation can occur requiring an urgent balloon atrial septostomy to create an unobstructed common atrium.

Next, a systemic-to-pulmonary shunt (usually via the ductus arteriosus) is needed to bridge these circulations. This systemic-to-pulmonary shunt either provides blood flow to the lungs in the event of obstructed pulmonary blood flow (e.g. pulmonary atresia, tricuspid atresia) or to the systemic circulation in the event of systemic outflow tract obstruction (e.g. aortic atresia, HLHS).

In an anatomically normal heart, blood flows in series to the pulmonary (Q_p) and systemic (Q_s) vascular beds and is said to be ‘balanced’ (i.e. Q_p:Q_s=1). For unpalliated single ventricle defects when the pulmonary and systemic circulations are in parallel and there is no anatomical obstruction, Q_p:Q_s is dependent on the relative resistance of the vascular beds. Alterations in Q_p:Q_s can cause profound changes in oxygen delivery and systemic arterial saturation (Fig 1).

Fig. 1.

This graph demonstrates oxygen delivery at increasing Q_p:Q_s, at a cardiac output of 300 ml min⁻¹ kg⁻¹ (neonatal normal) or 450 ml min⁻¹ kg⁻¹ (neonatal supranormal). Oxygen delivery is maximal when Q_p:Q_s is just <1 Note that oxygen decreases markedly with increasing Q_p:Q_s, and that improving cardiac output significantly increases oxygen delivery.

When pulmonary vascular resistance (PVR) decreases or systemic vascular resistance (SVR) increases, there is increased pulmonary blood flow and decreased systemic blood flow (i.e. Q_p:Q_s>1). In this situation, although the systemic oxygen saturation can be high, there is inadequate systemic perfusion and oxygen delivery. In the shorter term, the degree of excess pulmonary blood flow determines the clinical sequelae, from alveolar oedema and impaired gas exchange to cardiovascular collapse. In the longer term, increased pulmonary flow and pressure will induce alterations in vascular tone and reactivity, ultimately causing pulmonary vasculature hypertrophy and irreversible pulmonary hypertension. In contrast, when PVR increases or SVR decreases, there is reduced pulmonary blood flow (i.e. Q_p:Q_s<1), and although there is preferential flow to the systemic circulation, arterial blood will be poorly oxygenated.

After birth, PVR decreases from thinning of the pulmonary arteriolar media in response to increased PaO₂ and alveolar ventilation. For single ventricle defects, this physiologically normal reduction in PVR has several consequences. Increased pulmonary artery flow is associated with increased arterial oxygen saturations but decreased systemic perfusion. Increased pulmonary venous return also results in volume loading of the functioning ventricle and increases myocardial work. Together, these processes can lead to heart failure and shock, and can be significantly advanced in children who present with delayed diagnosis of single ventricle defects.

The need to maintain a balanced circulation in the unpalliated (and Stage 1) single ventricle defect has important consequences for both the induction and maintenance of anaesthesia. For the infant who is breathing spontaneously, PVR is higher because of factors such as small tidal volumes, increased interstitial lung water, atelectasis, and hypoxic pulmonary vasoconstriction. However, tracheal intubation, increased oxygenation, and mechanical lung expansion can cause a precipitous decrease in PVR and pulmonary overcirculation can occur. The effects of oxygenation and positive pressure ventilation on SVR and PVR are summarised in Table 1.

Table 1.

Typical effects of physiological variables and pharmacological agents on myocardial contractility, PVR, and SVR.

	Myocardial contractility	PVR	SVR
Physiological
Acidosis	↓	↑↑	↓
FiO2	↔	↓↓↓	↔
PEEPa	↑	↑ or ↓	↔
Sympathetic stimulationb	↑↑	↑ - ↑↑↑	↑ - ↑↑↑
Pharmacological
Dexmedetomidine	↔	↑ or ↓	↑ or ↓
Fentanyl	↔	↓	↔
Ketaminec	↓	↔	↑↑
Propofol	↓	↔	↓↓
Adrenaline	↑↑↑	↑	↑
Noradrenaline	↑	↑	↑↑↑
Milrinone	↑↑↑	↓↓	↓↓
Calcium	↑↑↑	↔	↔
Sevoflurane	↓	↓	↓
Isoflurane	↓	↓	↓↓
Nitric oxide	↑	↓↓↓	↓

This applies only to ventilated alveoli. Nitric oxide rapidly inactivated by circulating haemoglobin.

^aVentilation at optimal PEEP can decrease PVR. However, inadequate PEEP (atelectasis, alveolar derecruitment, hypoxic pulmonary vasoconstriction) or excessive PEEP (mechanical compression of extra-alveolar vasculature) can increase PVR.

^bThe degree of increase in PVR depends on pulmonary arterial medial sensitivity. As a result, the relative increases in PVR and SVR can be unpredictable.

^cCardiac output may be either increased by the direct sympathomimetic effects of ketamine (increased SVR and HR), or decreased in patients with depressed ventricular function.

Ductus arteriosus

The ductus arteriosus usually closes functionally within the first 24–48 h of life from smooth muscle contraction in response to increased oxygen concentration and lower prostaglandin levels. Fibrosis and anatomical closure typically occurs within 2–3 weeks.

After diagnosis of a ductus arteriosus-dependent single ventricle defect, prostaglandin E₁ (alprostadil) is usually administered to delay or prevent duct closure by directly relaxing vascular smooth muscle. This still does not provide stability of blood flow because of dynamic changes in both PVR and dimensions of the ductus arteriosus. Common adverse effects of prostaglandins include respiratory depression and apnoea, CNS disturbances, bone cortical hyperostosis, electrolyte imbalances, pyrexia, and systemic hypoperfusion. In children with ductus arteriosus-dependent congenital heart disease, closure of the duct will either lead to cyanosis if the duct is needed for blood flow to the pulmonary circulation (e.g. tricuspid atresia) or impaired systemic perfusion and cardiorespiratory collapse if the duct is needed for blood flow to the systemic circulation (e.g. HLHS).

Myocardium

Heart failure is responsible for significant morbidity and mortality associated with single ventricle defects during the surgical palliation pathway.¹⁶ In neonates, there is typically limited preload reserve from an imbalance in the ratio of elastic to contractile tissue, which restricts volume augmentation by the Frank-Starling mechanism. Afterload increases are also poorly tolerated. A disproportionately mature parasympathetic system predisposes to sudden profound bradycardia, and hypocalcaemia is tolerated poorly as a result of immature sarcoplasmic reticulum intracellular calcium handling.

In addition to an increased myocardial workload, neonates with unrepaired HLHS are at risk of significant myocardial ischaemia for a number of reasons. Pressure and volume overload in the functioning ventricle, reduced ventricular compliance, and diastolic run-off to the pulmonary circulation reducing diastolic coronary flow creates a tenuous, unpredictable environment for coronary perfusion. The ventricular wall tension created by the rudimentary left ventricle in an attempt to overcome systemic outflow obstruction commonly leads to thickening of the endocardium (endocardial fibroelastosis), thus increasing the diastolic pressure within the ventricular cavity and further impairing myocardial perfusion in diastole.

In utero development of the aortic root is also flow dependent. Infants with HLHS are at risk of inadequate proximal aortic flow from maldevelopment of the left ventricle, mitral or aortic valve stenosis or atresia. As a consequence, coronary artery flow, especially in unrepaired HLHS, can be tenuously dependent on flow of blood via the patent ductus arteriosus through a hypoplastic aortic arch. Children with HLHS, particularly when associated with mitral stenosis and aortic atresia, are also at increased risk of developing coronary cameral fistulae between the left ventricular cavity and the coronary arteries. When these occur, ventricular perfusion can be compromised if the ventricular cavity is decompressed (e.g. after palliative surgery).

Cardiopulmonary effects of anaesthetic drugs

Anaesthetic drugs used in the management of children with single ventricle defects also have clinically significant effects on myocardial contractility, SVR, PVR, and chronotropy. Typical effects of drugs commonly used in the perioperative period are summarised in Table 1.

Staged surgical palliation

Without surgical intervention, mortality for HLHS approaches 100% in early infancy. Surgical palliation refers to a series of staged procedures that aim to maximise functional cardiac reserve, rather than restoring normal anatomical arrangement, in the context of age-related physiology (Fig 2). The principles guiding decision-making during the surgical palliative pathway are to: (i) provide anatomical stability for pulmonary and systemic blood flow, (ii) maintain optimal myocardial function, and (iii) ensure adequate systemic oxygen delivery.

Fig 2.

Staged palliation pathway for HLHS. DKS, Damus-Kaye-Stansel; PDA, patent ductus arteriosus; RPA, right pulmonary artery.

Other surgical options include transplantation, hybrid interventions, and, in select cases, biventricular repair. Decision-making depends on the underlying anatomical lesion, and surgical, institutional, and family preferences. Staged left ventricular recruitment to promote both ventricular growth and function before choosing a definitive surgical approach is also being used with increasing frequency. This allows consideration of a biventricular repair or defers definitive single ventricle palliation to a later stage when the child is more robust physiologically.¹⁷ The guiding physiological and management principles regarding all subtypes of single ventricle defects are similar; however, considering the anatomical variation between types of single ventricle defects, we use the most common variant, HLHS, as the underlying defect for each of the descriptions below.

Stage 1 palliation

The overall goals of Stage 1 palliation are to: (i) promote complete intracardiac mixing of oxygenated and deoxygenated blood, (ii) control pulmonary blood flow, and (iii) provide unobstructed systemic perfusion. Recent advances in perioperative management have resulted in some variation in surgical techniques preferred by institutions for Stage 1 palliation. The rationale and techniques for commonly used Stage 1 procedures are summarised below.

Norwood procedure

The Norwood procedure encompasses the following: (i) an unobstructed ventricular outflow is created using an aortopulmonary anastomosis called a Damus-Kaye-Stansel (DKS) anastomosis, when the main pulmonary artery is detached and joined to proximal ascending aortic tissue to form a neo-aorta, (ii) the hypoplastic aortic arch is augmented and reconstructed using homograft or autologous pericardial tissue, (iii) an atrial septectomy decompresses the left atrium to facilitate pulmonary venous drainage and allow unobstructed intracardiac mixing, (iv) the ductus arteriosus is ligated, and (v) a surgical systemic-to-pulmonary shunt is created to provide an anatomical route for flow to the lungs.

There is considerable variation in the method of creating a systemic-to-pulmonary shunt. A synthetic (usually 3–3.5 mm) Blalock-Taussig (BT) shunt can be placed to connect the subclavian or innominate artery to the right pulmonary artery. However, in recent years the use of a synthetic 5–6 mm right ventricle-to-pulmonary artery (RV-PA) (also known as a Sano) shunt has grown in popularity.

Within the first few weeks of life, systemic arterial pressure normally exceeds pulmonary arterial pressure. As a consequence, flow through a BT shunt occurs continuously throughout both systole and diastole, and there is a concomitant decrease in systemic arterial diastolic pressure. In contrast, with an RV-PA conduit, flow to the pulmonary vessels only occurs in systole, resulting in increased systemic diastolic pressure. This theoretically improves coronary perfusion, provides a more physiologically appropriate Q_p:Q_s, and is associated with a lower incidence of shunt thrombosis at the expense of focal ventricular scarring and increased arrhythmias. A randomised controlled trial found greater transplant-free survival at 12 months in patients with RV-PA shunts, but functional strain was reduced and the requirement for catheter-based interventions was increased.18, 19 However, at 3- and 6-yr follow-up, there was no significant difference in the risk of death between children receiving RV-PA or BT shunts.⁸

Thus, while there is a physiological rationale for using RV-PA shunts, it remains unclear which approach is optimal for Stage 1 palliation and both are still commonly used.²⁰ After Norwood Stage 1 palliation, the overall risk of death between Stages 1 and 2 is 12%.⁸

Hybrid Stage 1 procedure

The hybrid approach to Stage 1 palliation aims to provide reliable pulmonary and systemic blood flow while minimising surgical stress and neurological injury in early life. This approach combines: (i) percutaneous stenting of the patent ductus arteriosus to prevent closure and allow stopping of prostaglandins, (ii) off-cardiopulmonary bypass surgical control of pulmonary blood flow with bands encircling the right and left pulmonary arteries, mechanically limiting pulmonary blood flow but allowing unobstructed flow from the RV, through the patent ductus arteriosus, to the aorta, and (iii) if required, a percutaneous atrial septostomy is performed, either at the same time or as a separate procedure, to ensure complete intracardiac mixing.

As a result, early surgical injury (e.g. inflammatory and stress responses) is minimised, and cardiopulmonary bypass is avoided until the child is more robust in both physiological and neurological terms. While hybrid Stage 1 procedures are the default intervention in some institutions, others use this approach for only higher risk children (e.g. low weight [<2.5 kg] or prematurity).

Stage 2: bidirectional cavopulmonary shunt

As PVR continues to decrease over the first few months of life, there is an accompanying increase in pulmonary flow, risking pulmonary overcirculation and long term sequelae. By 3–6 months of age, PVR has decreased sufficiently to allow pulmonary vascular perfusion via non-pulsatile venous flow from the superior vena cava (SVC) alone.

In Stage 2 palliation, also called a Glenn shunt: (i) an end-to-side anastomosis of the SVC and the right pulmonary artery is used to create a superior cavopulmonary connection, (ii) the BT or RV-PA shunt is taken down, and (iii) in some circumstances, the azygous vein is tied off to prevent retrograde decompression of the SVC to the inferior vena cava (IVC).

The benefits are two-fold: first, adequate perfusion of the pulmonary vasculature to meet the oxygenation requirements of the growing child is maintained at lower pulmonary artery pressures and second, there is volume unloading of the systemic ventricle with subsequent remodelling of the functioning ventricle at a lower end-diastolic volume.

For newborn infants who undergo a hybrid Stage 1 procedure, a more comprehensive Stage 2 surgery is required. In addition to the creation of a superior cavopulmonary connection, the pulmonary artery band(s) and ductus arteriosus stent are removed, and, if indicated, procedures delayed by the hybrid Stage 1 must be completed (i.e. aortic arch reconstruction, aortopulmonary anastomosis, ductus arteriosus ligation).

The proportional distribution of cardiac output to the brain is highest among young children. In infants, blood flow via the SVC accounts for 50% of venous return to the heart, increasing to a maximum of 55% at age 2.5 yrs but gradual decreasing to adult values of 35% by 6 yrs of age.²¹ As a result, for children with a Stage 2 circulation, hypoventilation and slight hypercarbia is desirable in the acute postoperative phase to promote cerebral blood flow, which in turn improves pulmonary blood flow and systemic oxygen saturations. As the ratio of SVC:IVC blood flow decreases with age, there is proportionally less pulmonary blood participating in pulmonary gas exchange. Consequently, increasing cyanosis will occur in the older child with a Stage 2 circulation.

In addition, a number of vascular issues can affect systemic saturation and Q_p:Q_s before Stage 3 palliation, many of which require percutaneous intervention. These include coiling of blood vessels that decompress the SVC to the IVC (coiling increases systemic saturations), aortopulmonary collaterals (coiling reduces left to right shunt and volume strain on systemic ventricle and lowers pulmonary vascular pressure, but potentially at the expense of systemic oxygenation)²², or intrapulmonary collaterals (coiling increases systemic saturations by reducing intrapulmonary shunt).

Stage 3: Fontan or total cavopulmonary connection

In a total cavopulmonary connection, also called a Fontan circulation, all systemic venous blood returns to the pulmonary arteries without passing through a ventricle. This provides continuous non-pulsatile pulmonary blood flow from both the IVC and SVC, putting the pulmonary and systemic circulations in series for the first time. This has the advantages of further volume unloading the functioning ventricle, increasing systemic oxygen saturations, and reducing the risks of systemic thromboembolism. The Fontan circulation is normally completed between 2 and 5 yrs of age.

Two types of surgical anastomosis are commonly performed: the intracardiac lateral tunnel, where the IVC is tunnelled via the common atrium, or an extracardiac synthetic graft from the IVC to the pulmonary artery. Often a fenestration (typically 4 mm) is created between the cavopulmonary connection and the common atrium to support cardiac output. Without a fenestration, increases in PVR can decrease systemic ventricular preload and systemic perfusion. The fenestration supports cardiac output by allowing blood to shunt from right-to-left at the atrial level, but at the expense of some systemic oxygen desaturation. Fenestration is associated with a shortened postoperative ICU stay, decreased pleural drainage, and less future interventions.²³ Once PVR is consistently low, the fenestration may be closed percutaneously in the catheterisation lab to increase systemic oxygenation and decrease the risk of paradoxical thromboembolism.

Pulmonary circulation, and hence cardiac output, is entirely dependent on venous filling, and in consequence is exquisitely sensitive to hypovolaemia and alterations in vascular tone. Although the Fontan circulation is commonly described as a ‘passive circulation’ it is better considered as an active circulation with three resistance beds (systemic vascular, cavopulmonary connection, and pulmonary vascular) in series operating in a chronically high afterload state.²⁴ The principles and acute management of the Fontan patient requiring non-cardiac surgery are described in detail separately in this journal.²⁵

Conclusions

There is significant heterogeneity in the anatomy and physiology of children with single ventricle defects, depending on the underlying anatomy and stage of surgical palliation. The principles guiding decision-making during surgical palliation are to provide anatomical stability for pulmonary and systemic blood flow, maintain optimal myocardial function, and ensure adequate systemic oxygen delivery. There is increasing variation in the surgical management of single ventricle defects, and the pathway chosen will depend on both institutional preferences and factors specific to the lesion.

Declaration of Interest

The authors declare that they have no conflicts of interest.

MCQs

The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.

Acknowledgements

We thank Viviane Nasr and James DiNardo, Boston Children's Hospital, for permission to partly reproduce Figure 24.2 from The Pediatric Cardiac Anesthesia Handbook (2017) for this article.

Biographies

David Greaney MSc FRCA FCAI FJFICMI is a fellow in cardiac anaesthesia at the Hospital for Sick Children, Toronto. His clinical and research interests include medication safety, perioperative outcomes, and haemostasis in cardiac surgery.

Osami Honjo MD PhD is a consultant surgeon at the Hospital for Sick Children and assistant professor at the University of Toronto. His clinical and research practice focuses on surgical palliation for patients with a single ventricle and mechanical cardiopulmonary support in children.

James O'Leary MM MD is a cardiac anaesthesiologist at the Hospital for Sick Children and associate professor at the University of Toronto. His research focuses on improving clinical outcomes in paediatric anaesthesia and evaluating risk factors for adverse child development after paediatric surgery.

Matrix codes: 1A02, 2B07, 3D00