The primary function of the right ventricle (RV) is to facilitate blood flow through the lung. In order to achieve this, the RV is anatomically and physiologically designed as a volume pump, which keeps central venous pressure low. Until recently, its importance was frequently overlooked. Studies from the 1950s seemed to indicate that cauterisation of the RV free wall resulted in only modest changes in cardiac output and central venous pressure.1,2 In 1971, Brooks et al.3 demonstrated that isolated RV ischaemia had virtually no impact on RV developed pressure, left ventricular developed pressure or cardiac output, because a slightly elevated central venous pressure provided the driving force needed to create sufficient blood flow through the lungs. This phenomenon is applied in many congenital cardiac heart surgery strategies, such as the Fontan sequence. Brooks however also noted that, in the presence of even a small elevation in pulmonary artery pressure, cardiac output could not be maintained.3 Thus, if left ventricular filling pressure or pulmonary vascular resistance is too high, central venous pressure will not be able to provide adequate pulmonary arterial flow, and normal RV function becomes critically important.
Over recent decades, numerous studies have underlined the importance of RV function. It has been shown that RV dysfunction is an important predictor of overall survival and morbidity in various clinical situations.4–7 Right heart failure is the main cause of death in pulmonary hypertension.8 Perioperative mortality is even higher in right ventricular failure and then in left ventricular failure, and it is important to note that progressive right ventricular failure has a similar incidence as left ventricular failure.9–11 In a French national survey, the overall prevalence of pulmonary arterial hypertension was 15 per million.12 Consequently, RV research was named a cardiovascular research priority in 2006 by the USA National Institutes of Health.13
RV failure is also an underdiagnosed entity in the noncardiac surgery perioperative setting.9–11 Here, we present a review of multiple specific aspects of perioperative RV failure, especially aimed at the noncardiac anaesthesiologist who may be confronted with RV failure. We discuss the anatomical and physiological peculiarities, practical assessment and specific perioperative measures useful in perioperative RV failure. We searched Pubmed, Embase and Web of Science databases using (combinations of) the following search terms: ‘right ventricular function’, ‘right ventricular failure’, ‘perioperative’, ‘anatomy’, ‘physiology’, ‘epidemiology’, ‘ventricular interaction’, ‘volume overload’, ‘pressure overload’, ‘ischaemia’, ‘perioperative assessment’, ‘echocardiography’, ‘pulmonary artery catheter’, ‘pulse pressure variation’, ‘afterload reduction’, ‘mechanical ventilation’, ‘inotropic support’ and ‘vasopressin’.
Basic anatomy and physiology
Compared with the left ventricle (LV), the right-sided myocardium is thin. The lower RV mass to volume ratio is a hallmark of its physiological function. On cross-sectional view, one can appreciate the crescent shape of the RV, as opposed to the circular shape of the thick walled LV. As is apparent on three-dimensional imaging, the RV is partially wrapped around the LV, which is of importance in systolic ventricular interaction (Fig. 1).14 RV anatomy is typically divided into the trabeculated apical component and a separate inflow and outflow (infundibulum) region.15 This results in the typical peristaltic RV ejection pattern.16 Due to less prominent circumferential fibres, RV ejection relies more on longitudinal shortening than in the LV.17 Under normal conditions, the interventricular septum is concave towards the LV during the entire cardiac cycle.
Arterial perfusion of the right ventricular free wall is mainly provided by the right coronary artery. Blood flow to the apex and the interventricular septum is mainly (anterior two-thirds) provided by the left anterior descending artery, whereas the posterior third of the interventricular septum is perfused by the right coronary artery. The right ventricular veins drain into the anterior cardiac veins, which empty individually into the right atrium just above the tricuspid valve.18
Pressure-volume loops provide a suitable framework to discuss the determinants of RV function. If instantaneous pressures and volumes are plotted throughout the cardiac cycle, the characteristic triangular shape of the RV pressure-volume loop can be observed.19 This framework allows various haemodynamic variables to be identified (Fig. 2). The RV is characterised by a high diastolic compliance. Its unique thin walled architecture allows for a great variation in accommodation to venous return without large changes in end-diastolic pressures.20 The RV end-diastolic pressure-volume curve is thus less steep than its left-sided counterpart (Fig. 2). The drawback of the highly compliant RV free wall is that it results in high afterload dependence. Even small elevations in pulmonary artery pressure lead to a marked reduction in RV stroke work.20 Therefore, as the heart is tightly coupled to the lungs and mechanical ventilation has profound effects on intrathoracic pressures, heart–lung interactions are an important phenomenon. These are described in more detail below (see Perioperative Management). In contrast to the LV, right coronary flow is maintained throughout systole and diastole as a result of the lower intraventricular pressures. Thus, the effects of the decrease in diastolic perfusion time due to tachycardia are less important for the RV than for the LV.18
The importance of ventricular interaction is well established. Up to 40% of systolic RV function may be attributable to LV systolic function through this mechanism.21 Ventricular interdependence is defined as any interaction between the LV and the RV, with the exclusion of neuronal and humoral effects. It can be divided into direct and indirect components. Direct ventricular interdependence is mostly mediated through the interventricular septum and pericardium and can be further subdivided into a direct diastolic and a direct systolic interaction. The indirect component is the result of the normal closed loop circulation, in which RV output equals LV input.22 In the volume overloaded RV, septal flattening occurs only in diastole.23,24 In contrast, in the pressure overloaded RV, the septal flattening is maintained from diastole into systole. Thus, in this situation, RV systolic function cannot be aided as much by the septum and RV dilatation will initiate a negative spiral with a decrease in RV ejection, a compressed LV and deteriorating LV function.25–28 Originally, Slinker and Glantz29 found in an open-chest canine model that parallel diastolic and systolic interaction is reduced after pericardiotomy. More recent studies however, concluded that the precise effect of the pericardium on ventricular interaction is still controversial.30,31
Causes of right ventricular failure
It is useful to classify clinical RV failure on the basis of the underlying pathophysiological mechanisms. Due to its anatomical and physiological properties, the single most common cause of RV systolic failure is afterload augmentation. The updated 2008 WHO clinical classification of pulmonary hypertension defines the different causes.32 Modest pressure overload at first mostly leads to increased RV contractility. From animal models, it appears that this is first accomplished by the Anrep phenomenon (homeometric autoregulation) by which adequate ventriculo-arterial coupling can be maintained.33 As pulmonary afterload increases, additional catecholamine release allows for an increased inotropic state.34 Finally, an increase in end-diastolic volume is observed, and the Frank–Starling mechanism is addressed.33 However, after prolonged and sustained RV pressure overload – even in the absence of ischaemia – RV contractility becomes downregulated.35–37 Once the RV decompensates, systemic pressures and cardiac output suddenly decrease. RV dilation results in a leftward septal diastolic shift, with decreased LV compliance and eventually systemic hypotension. This starts a downward spiral, with a further reduction in biventricular function. As septal reversal is maintained from diastole into systole in RV pressure overload, the RV can make less use of systolic ventricular interaction, which under normal circumstances accounts for 20 to 40% of RV systolic function.21
A second cause of RV dysfunction and failure is RV volume overload. Typical examples are tricuspid or pulmonary valve regurgitation and atrial or ventricular septal defects.4 Due to its anatomical features to act as a volume pump, the RV can more easily accommodate to volume then to pressure overload. In contrast to the situation of pressure overload, the chronically volume-overloaded right heart primarily uses the Frank–Starling mechanism.11 Of note, in RV isolated volume overload, the RV can still make use of ventricular interaction. Although the septum is shifted towards the left in diastole, the septum returns to its normal position in systole, thereby adding substantially to RV systolic function.23,24 Inflow limitation, for example by tricuspid or vena cava stenosis, is also a potential cause of right heart failure.
RV ischaemia can lead to failure directly, as in RV myocardial infarction, or indirectly as a result of systemic hypotension. Under normal circumstances the RV is less prone to ischaemia than the LV, because of the thinner myocardium, the more continuous perfusion throughout diastole and systole and the lower resting oxygen extraction of the RV.18 Under resting conditions, the RV has an oxygen extraction ratio of only 50%.38 An exercise-induced increased oxygen demand in the RV is first provided by increasing oxygen extraction ratio and only secondarily by increased right coronary blood flow.38 However, the extent to which ischaemia is important in RV dysfunction and failure is controversial. Canine experiments, in which the RV and the LV were mechanically uncoupled and right coronary perfusion pressure or flow was manipulated, suggest that aortic cross-clamping improves RV function not through its effect on coronary perfusion pressure or flow, but through ventricular interaction.39–41 The relative importance of coronary perfusion pressure versus other mechanisms contributing to the development of RV failure remains to be fully elucidated. Numerous intrinsic causes, such as sepsis, dysplasia after longstanding RV arrhythmias and constrictive pericarditis, can also lead to RV dysfunction and/or failure. The many complex congenital causes are beyond the scope of this review.
Typical causes of perioperative RV failure include mechanical as well as metabolic factors associated with increased RV afterload, such as volaemia disorders, pulmonary emboli, hypoxia, sepsis, (inappropriate) mechanical ventilation and acute RV ischaemia. Acute on chronic deterioration of RV function can be common in the perioperative setting. An overview of the pathophysiological vicious cycle of RV dysfunction is shown in Fig. 3. Patients with LV assist devices are particularly prone to develop RV failure; initiation of univentricular mechanical assist to support the failing LV often unmasks a latent RV dysfunction that was hidden in the clinical picture of LV dysfunction. Furthermore, LV assist devices operate by offloading the LV during systole and diastole, hence eliminating ventriculovascular interaction while exposing the RV to full venous return and by challenging it to resume its function at the level of normal or supranormal cardiac output.
Perioperative anaesthetic considerations
The symptoms and signs of right ventricular failure have been discussed extensively elsewhere.33,42 Apart from typical clinical symptoms and signs such as dyspnoea, hypotension, right upper quadrant discomfort and jugular vein distension, several electrocardiographic and radiographic clues should trigger further investigations.42 Electrocardiographic specificities may include sinus tachycardia, T-wave inversion in III and aVF or in the precordial leads V1 to V4, right bundle branch block and a rightward axis. Right-sided precordial leads can help in diagnosing RV disease.42 Chest radiography in patients with RV failure can reveal dilation of the proximal pulmonary arteries and RV enlargement (with filling of the retrosternal space) or right atrial enlargement. Dilation of the inferior vena cava may be seen and pleural effusions are possible.42 Ideally, all technical investigations should be performed sufficiently in advance of surgery in order to allow sufficient time for potential therapeutic optimisation. Troponin concentrations are of importance in the diagnosis of pulmonary emboli and suspected RV myocardial ischaemia, although the low mass of the RV may cause only a slight elevation in troponin levels.43 B-type natriuretic peptide, which is secreted by the myocardium in the presence of increased shear stress and dilatation, can be used to differentiate cardiac and pulmonary acute dyspnoea. In pulmonary hypertension, increasing concentrations of B-type natriuretic peptide may correlate with the degree of RV dysfunction.44,45 To date, the usefulness of B-type natriuretic peptide in the setting of acute RV failure remains unclear.46
As echocardiography is noninvasive and available at the bedside, it has become the most important tool in the evaluation of RV dysfunction and its associated conditions. Care has to be taken to minimise its intrinsic and operator dependent limitations. Important findings include chamber dilatation, increased wall thickness (in chronic pulmonary hypertension) and wall motion abnormalities.42 RV dilatation can be defined as a ratio of RV end-diastolic area to LV end-diastolic area of more than 0.6.47 The McConnell sign, defined as RV free wall hypokinesis with apical sparing, is seen in acute pulmonary embolism.48 Normal RV ejection fraction is between 35 and 45%. This lower value compared with the LV is the result of larger end-diastolic volumes with comparable stroke volumes.49 As RV contraction is predominantly longitudinal in nature, tricuspid annular plane systolic excursion is a well defined measure of RV function. The total displacement from apex to tricuspid annulus during systole is measured.50 Doppler echocardiography allows assessment of the severity of pulmonary hypertension. Pulmonary artery pressures can be estimated by adding a surrogate of right atrial pressure (e.g. collapsibility of the inferior vena cava) to the calculated peak pressure gradient. For an extensive review of right heart echocardiography, we refer the reader to an excellent review by Rudski et al.51
Cardiac MRI may yield more reproducible data than echocardiography but its use is currently limited. Similar morphological findings as in echocardiography can be evaluated, and RV mass and volume measurements can be made. With the use of gadolinium, cardiac MRI can detect ischaemia and delayed images can differentiate this from infarction, even in patients with enzyme-negative unstable angina.52
Right heart catheterisation with end-expiratory measurements of pulmonary artery, right-sided and left-sided pressures remains the gold standard for the diagnosis of pulmonary hypertension. These provide prognostic markers of survival.53 The latest Dana Point 4th World Symposium on Pulmonary Hypertension (2008) defined pulmonary hypertension as a resting mean pulmonary arterial pressure of at least 25 mmHg. It needs to be kept in mind that, in the case of severe RV heart failure, decreased output can lead to decreasing pulmonary artery pressures.4,54 We believe that preoperative invasive pulmonary artery catheterisation is indicated especially in cases in which moderate to severe right ventricular dysfunction is combined with severe pulmonary hypertension.55 To further specify diagnosis and reversibility, vasoreactivity testing can be useful in subgroups of pulmonary hypertension patients. Here, the haemodynamic effects of a short-acting vasodilator (e.g. epoprostenol or inhaled nitric oxide) are examined.56
Preoperative consultation and premedication
Preoperative consultation should include a thorough anamnestic and clinical search for right ventricular dysfunction. Individualised anxiolysis to avoid tachycardia and increased pulmonary resistances may be provided with benzodiazepines, but great care should be taken to avoid respiratory depression. Preoperative oral sildenafil, calcium channel blockers, inhaled nitric oxide and nebulised iloprost can be used to reduce pulmonary artery pressures. It is important that these chronic therapies are not interrupted in the perioperative period. Maintenance of sinus rhythm (e.g. electrical cardioversion of new onset atrial fibrillation) and optimal ventricular rate should be targeted to prevent RV dilatation and optimise ejection. It is often accomplished at a minimum of 90 beats per minute.57 When using pharmaceuticals to maintain sinus rhythm, associated negative inotropic and systemic vasodilatory side effects should be kept in mind.
In the setting of RV failure due to left heart disease, optimisation of left heart function and corrective valve surgery can result in regression of the associated pulmonary hypertension.58 Percutaneous coronary interventions may be indicated in the case of acute myocardial infarction. In pulmonary hypertension due to thromboembolic events, thrombolysis, thrombectomy or pulmonary endarterectomy can be considered. Patients with RV failure due to severe tricuspid regurgitation may need tricuspid valve surgery.59 More aggressive surgical end-stage management may include atrial septostomy, in which the atrial shunt decompresses the right side, at the cost of decreased oxygenation. However, because of the increased cardiac index, oxygen delivery appears to improve.60 Total RV exclusion procedures have been used in the setting of RV volume overload, and assist devices or cardiac transplantation may be indicated in selected patients.61,62
Although an individualised approach is of paramount importance, some recommend a cascade of invasive perioperative monitoring based on the severity of RV dysfunction and pulmonary hypertension, intraoperative mode of ventilation and type of procedure.55 Central venous catheter insertion is useful in the case of positive pressure ventilation and invasive blood pressure monitoring in severe cases of RV failure. Some authors suggest that the use of a pulmonary artery catheter should be reserved for patients with severe RV failure with pulmonary hypertension, but it must be remembered that pressure measurements alone provide less information than pulmonary vascular resistance measurements. In our opinion, transoesophageal echocardiography is mandatory in any case of RV failure and should be omitted only if an absolute contraindication is present.
Anaesthetic management in RV failure patients can be challenging. At all times, haemodynamic management should focus on maintaining the ratio of systemic to pulmonary arterial pressures at the preinduction level, because a decrease in this ratio often predicts imminent collapse.63 Of note, a higher sympathetic tone is present in the setting of pulmonary artery hypertension.64 Theoretically, etomidate or ketamine may be superior induction agents to avoid postinduction hypotension while providing sufficiently deep anaesthesia to prevent large sympathetic responses.55 Although no studies are available, propofol and inhalational induction have also been used. All volatile anaesthetics can reduce preload and contractility. The use of desflurane and nitrous oxide is discouraged, because they increase pulmonary vascular resistance.65,66 No severe adverse effects of opioids on RV function have been described.55 Lumbar neuraxial anaesthesia can be used if preload decrease and subsequent hypotension are anticipated.55 However, thoracic epidural anaesthesia has been shown to inhibit the inotropic response to increased RV afterload in animals; the clinical impact is currently unclear (Table 1, https://links.lww.com/EJA/A33).67
The management of RV failure should focus on restoring RV function with the underlying cause kept in mind. At all times, disruption of metabolic homeostasis (hypoxaemia and hypercapnia) and haemodynamic stressors (in particular, in children with reactive pulmonary hypertension) should be avoided. Optimisation of RV preload, afterload and contractility, as well as ventricular interdependence, has to be achieved. It has been suggested that in primary RV failure, the first step is to lower RV afterload, whereas in RV failure secondary to LV dysfunction, treatment should focus on the LV.68 Chronic pulmonary hypertension leads to a RV with a much higher contractile reserve, but this may also result in reduced coronary flow reserve and impaired diastolic function.68 As we note in the following paragraphs, multiple approaches are feasible, but the impact of such supportive measures on long-term outcome has not yet been clearly established.
Judicious volume management should optimise RV preload. Although the RV is preload-dependent up to a certain point, overfilling can cause RV dilatation and tricuspid valve insufficiency, as will be the case in most RV failure patients.69 The resulting increased RV wall stress and decrease in LV compliance can result in diminished cardiac output and in further RV dilatation. Care must be taken to estimate the position of the patient on the Starling curve, which is dependent on volume status as well as on cardiac function and RV afterload. Fluid withdrawal can be accomplished with diuretics or ultrafiltration. Empirically, a frequently used cut off point is a transmural right atrial pressure of 15 mmHg. At all times, it needs to be kept in mind that any pressure-based indicator of a volume measurement is subject to inherent limitations. We, therefore, prefer volume-based (e.g. echocardiographic) variables to assess RV preload and fluid responsiveness. Although generally a useful indicator of fluid responsiveness,70,71 pulse pressure variation cannot be used reliably in the setting of RV failure, and the lack of a decrease in high pulse pressure variations after fluid administration has been suggested as a diagnostic tool for RV failure.72–74 Echocardiographically guided volume challenges may provide an adequate therapeutic approach, for example by measuring vena cava diameters.
Active attempts to decrease RV afterload must be undertaken. Preferential use of spontaneous breathing or low ventilating pressures, use of a high inspiratory oxygen fraction and mild hyperventilation can reduce RV afterload. Recruitment manoeuvres and appropriate positive end-expiratory pressures should minimise atelectasis formation.55 The use of negative pressure ventilation could be of interest. Intrathoracic pressure regulators, devices that allow application of a negative intrathoracic pressure between positive pressure tidal volumes, have been shown to increase pulmonary artery pressure and cardiac output in animal hypovolaemic and shock models and in normovolaemic anaesthetised patients.75–77 Their long-term effects on RV afterload (by potentially creating atelectasis) have yet to be established. Intravenous vasodilators should be used with extreme caution, because the resulting systemic hypotension may counter any advantage on pulmonary vasculature.68
Inhaled pulmonary vasodilators such as inhaled nitric oxide or nebulised iloprost are preferable. Because of its local action and its short half-life, inhaled nitric oxide causes no systemic hypotension. It causes vasodilatation only in ventilated areas, and thus improves ventilation/perfusion mismatch. In acute respiratory distress syndrome patients, it has been shown to decrease pulmonary vascular resistance and increase RV ejection fraction.78 However, despite its haemodynamic benefits, no reduced mortality has been found in acute RV failure patients.79 Rebound pulmonary hypertension following sudden withdrawal has been described.80
Prostacyclin (or prostaglandin I2) causes pulmonary vasodilatation and improves right ventriculo-arterial coupling in afterload-induced RV failure.81 It may worsen ventilation-perfusion mismatch, and can worsen pulmonary capillary wedge pressure in the setting of LV dysfunction. With inhaled use, no rebound pulmonary hypertension has been reported. It has no known toxic metabolites. Inhaled iloprost is an analogue with a significantly longer duration of action and has similar haemodynamic benefits.82 Inhaled milrinone has also been shown to be effective.83 Acute sildenafil treatment has been shown on magnetic resonance studies to promote RV relaxation.84 It decreases RV afterload without significantly affecting systemic haemodynamics and decreases RV hypertrophy.85,86 First-line oral endothelin antagonist treatment resulted in improved survival in a study in primary pulmonary hypertension.87
Due to their different modes of action (inhaled nitric oxide activates soluble guanylate cyclase, prostacyclin activates adenylate cyclase, phosphodiesterase inhibitors work directly on the enzyme type 3 or 5 subfamilies, endothelin antagonist inhibits vasoconstriction), combinations are suggested to be synergistic.55,68 We suggest that, after a timely preoperative consultation, prompt referral of patients with chronic pulmonary hypertension to an experienced cardiology department should allow for optimisation of chronic therapy.
Vasopressors increase systemic arterial pressure, and thus coronary perfusion pressures. The importance of the absolute value of right coronary perfusion pressure in the maintenance of RV function has been debated. Experimental studies uncoupling systemic pressure from the right coronary perfusion pressure suggest that the benefit from a raised systemic pressure may be due to increased ventricular systolic interdependence.39,41 At all times, the benefit of systemic vasoconstriction (with increased perfusion pressures) has to be balanced against the impact of pulmonary vasoconstriction.88 When acute RV pressure overload is caused by mechanical factors, it has been suggested that vasopressors may be beneficial because systemic blood pressure increases with little additional augmentation of RV afterload.68 With isolated phenylephrine use in patients with chronic pulmonary hypertension, the net effect was a decrease in cardiac output because of increased pulmonary arterial elastance.89 Low-dose vasopressin has been shown to be effective in reversing hypotension in chronic pulmonary hypertension.90
In contrast to the LV, a RV that has not been exposed to chronic pressure overload has limited contractile reserve. Systemic hypotension is a risk, and care has to be taken with inodilators in isolated, primary right ventricular failure. With all inotrope use, it is important to avoid arrhythmias. Norepinephrine may be indicated to increase systemic blood pressure in the setting of low cardiac output.91 Epinephrine and high-dose dopamine have also been used to increase RV contractility, but there is no evidence for superiority, and side-effects are greater. Intravenous milrinone reduces mean pulmonary artery pressure and improves right heart performance after cardiac surgery.92 Phosphodiesterase III inhibitors can be beneficial, especially in a setting in which left ventricular backward failure is the major cause. However, if systemic hypotension develops, a vasopressor must also be given. Increased LV contractility can also result in increased RV systolic function through ventricular interdependence. In a randomised trial in patients with advanced LV systolic dysfunction and associated RV failure, echocardiographic measures of RV function were shown to benefit from levosimedan compared with placebo.93 This drug also reduced pulmonary vascular resistance in animals and patients with decompensated heart failure and improved RV–pulmonary artery coupling more than dobutamine in an experimental acute RV failure setting.94–97 Clinically, these effects have been shown in multiple settings, such as RV ischaemia, acute respiratory distress syndrome and after mitral valve replacement.98,99
This review provides an overview of the pathophysiology and clinical management of right ventricular function and failure in the perioperative setting. We highlight the specific functionality of the RV. Accordingly, the need for distinct measures of assessment as opposed to the LV is emphasised. Several therapeutic options for the management of right ventricular failure are discussed. Additional basic physiological as well as clinical therapeutic research seems mandatory to obtain a better insight in the pathophysiology of perioperative RV failure in order to provide better care to our patients.
Assistance with the study: none declared.
Financial support and sponsorship: this work was supported by the Department of Anaesthesiology, Ghent University Hospital, Ghent, Belgium.
Conflicts of interest: none declared.
Comment from the editor: SDH is an associate editor of the European Journal of Anaesthesiology.
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