Intercirculatory mixing, complete mixing, and streaming

Confusing terminologies are often used interchangeably to describe common preoperative and postoperative physiologies. It is important for the care provider to understand the essential elements of the circulation in order to react appropriately to perturbations.

Intercirculatory mixing lesions

Patients with D‐transposition of the great arteries (D‐TGA) have parallel circulations: the deoxygenated systemic venous blood returns to the right ventricle (RV) and is ejected through the aorta while oxygenated pulmonary venous blood is returned to the left ventricle (LV) and is ejected into the pulmonary artery (PA) (Figure 36.2). Although the figure depicts simple transposition anatomy, transposition physiology can occur with other anatomic defects such as “Taussig‐Bing” type double‐outlet right ventricle, where a subpulmonary position of the ventricular septal defect (VSD) and malposition of the great arteries create an unfavorable streaming pattern resulting in parallel intracardiac circulation similar to D‐TGA. Transposition physiology is the term used for this parallel circulatory pattern where PA oxygen saturation is greater than the aortic oxygen saturation. Such a circulation is not compatible with survival over time unless there is adequate intercirculatory mixing allowing for the deoxygenated systemic venous blood into the pulmonary circulation (PA), as well as the oxygenated pulmonary venous blood into the systemic circulation (aorta) [3]. Although 25–50% of patients with D‐TGA have a VSD, the presence of a VSD does not guarantee adequate intercirculatory mixing, as mixing occurs most effectively at the atrial level. Newborns with D‐TGA, irrespective of whether they are diagnosed antenatally or postnatally, can present with profound cyanosis in the absence of respiratory distress due to inadequate mixing. Such patients should be transported to the CICU after commencing intravenous (IV) prostaglandin E₁ (PGE₁) to maintain a patent ductus arteriosus (PDA) as an additional location for mixing. After confirmation of the diagnosis of D‐TGA with a restrictive or intact atrial septum, a balloon atrial septostomy (BAS) can be performed at the bedside or in the cardiac catheterization laboratory to improve intercirculatory mixing and systemic oxygen delivery. If the atrial communication is restrictive, administration of usual therapies to improve pulmonary blood flow (e.g., supplemental oxygen, inhaled nitric oxide) are often detrimental if used as ongoing preoperative management strategies. These therapies can generate left atrial hypertension, leading to increasing pulmonary congestion and worsening pulmonary compliance with further impairment of atrial‐level mixing. Once an adequate atrial septal defect (ASD) is created, systemic oxygen delivery improves as mixing increases from left to right (saturated pulmonary to desaturated systemic) across the ASD. Subsequently, patients can have the PGE₁ infusion discontinued and wean and extubate to await an elective repair with the arterial switch operation within the first week of life [4]. Some patients with D‐TGA may remain hypoxemic despite creation of an unrestrictive atrial communication; such patients are often dependent on PGE₁ infusion in the preoperative period to maintain systemic saturations >65% [5]. The failure of adequate mixing at the atrial level may reflect not only differences in ventricular function, ventricular filling, and/or ventricular end‐diastolic pressures (ventricular compliance), but may also be secondary to unfavorable streaming effects. There may also be an element of rebound pulmonary hypertension from PGE₁ discontinuation that reduces the volume of pulmonary blood flow without affecting the amount of intercirculatory mixing. Some investigators have suggested a protracted weaning protocol for PGE₁ to mitigate this effect [6]. See Chapter 29 for further discussion of D‐TGA.

Shunts

Shunting between the pulmonary and systemic circulations can be intracardiac (across an ASD or a VSD) or extracardiac (across a PDA, aortopulmonary window, decompressing venovenous collaterals, aortopulmonary collateral, or arteriovenous malformation). Depending on the size of the communication and the differential pressures and resistances between the pulmonary and systemic circulations, patients may have decreased or increased pulmonary blood flow and may be either cyanotic or acyanotic, respectively.

Decreased pulmonary blood flow

Reductions to pulmonary blood flow from structural heart disease are ultimately related to intracardiac right‐to‐left shunting. The basis for this may be pulmonary outflow obstruction (supravalvar, valvar, subvalvar, or a combination of these), subpulmonary ventricle inflow obstruction (tricuspid stenosis or atresia), or the inability to generate adequate antegrade pulmonary blood flow (Ebstein anomaly, tricuspid valve dysplasia). In patients with noncardiac diseases, such as persistent pulmonary hypertension of the newborn (PPHN), sustained elevations in PVR result in intracardiac (or ductal) right‐to‐left shunting.

Pulmonary mechanics and lung volumes are generally normal in patients with reduced pulmonary blood flow. Dead space ventilation is increased, although minute ventilation is only slightly increased to maintain normocapnia, and the A‐aO₂ gradient may be increased as well. The lung fields appear oligemic on chest radiograph. Some patients may have impairments in pulmonary mechanics due to anatomic interactions between cardiovascular structures and the tracheobronchial tree. One such group are patients with TOF and absent pulmonary valve (APV) syndrome who can have massively dilated branch PAs; in the setting of a freely regurgitant pulmonary valve orifice, the RV and branch PAs become volume loaded and dilate, leading to compression of the large and small airways. These patients have significant gas‐trapping and expiratory flow limitations, which is a frequent cause of their respiratory failure. Surgical repair during the newborn period is often required to treat respiratory failure in this scenario. Often in neonates with TOF with APV, early prone positioning with positive pressure ventilation (PPV) is required to alleviate bronchial compression and achieve adequate gas exchange; however, emergent sternotomy in unrepaired patients may still be required in some cases to alleviate airway compression despite mechanical ventilation and proning [15, 16].

Outflow obstruction

Severe LV or RV outflow obstruction in the newborn may be associated with ventricular hypertrophy and vessel hypoplasia distal to the level of obstruction. If there is complete or near‐complete outflow obstruction, mixing or shunting at the ASD and/or VSD level is required to maintain systemic cardiac output (CO) with adequate arterial oxygen content.

A typical pressure–volume loop from a chronic pressure load on the ventricle is shown in Figure 36.3. The end‐diastolic pressure is elevated and the end‐systolic pressure volume line is shifted to the left, reflecting increased contractility in the compensated state (purple line), with an upwards shift along the new slope reflecting a higher afterload state (from 1^P to 2^P). Maintenance of preload, stability in afterload, adequate contractility, and normal sinus rhythm are important to prevent a fall in CO or coronary hypoperfusion in states of increased ventricular afterload. Since the time course to develop significant ventricular dysfunction is longer in patients with chronic pressure overload compared to chronic volume overload, symptoms of CHF are uncommon, unless obstruction is severe or prolonged.

In the immediate postoperative period, it is important to evaluate both systolic and diastolic ventricular function in a previously obstructed but still hypertrophied ventricle.

1. A hyperdynamic state may be present following LV outflow reconstruction. This will be manifest by systemic hypertension and should be treated promptly to reduce myocardial work and protect surgical suture lines, especially those in the aorta.
   
2. Systolic dysfunction of a hypertrophied ventricle may be apparent early after cardiac surgery secondary to myocardial ischemia and ventricular dysrhythmias. Ischemia may occur particularly if there has been a long aortic cross‐clamp time, inadequate myocardial protection with cardioplegia solution, or hypothermia. In the case of the RV, dysfunction may be related to a right ventriculotomy, direct injury to a coronary artery (e.g., a conal branch running across the RV outflow tract), air embolism, or due to inadequate myocardial protection with cardioplegia, hypothermia, or local cooling strategies. This should be evaluated and treated in the postoperative period with inotropic and/or inodilator support (i.e., dopamine or epinephrine, milrinone, and nitric oxide in the case of the RV). The evaluation of ventricular function includes echocardiography and potentially cardiac catheterization to assess hemodynamics and investigate potential coronary complications that may require reintervention.
   
3. Diastolic dysfunction is usually manifest as a poorly compliant or stiff ventricle that is hypertrophied. It may contract well, but it is unable to relax and fill effectively during diastole. On the left side of the heart, this is usually manifest as left atrial hypertension with either pulmonary edema, atrial dysrhythmias, or pulmonary hypertension. On the right side of the heart, an increase in RV end‐diastolic pressure is demonstrated by right atrial hypertension and elevated central venous pressures along with clinical signs such as atrial arrhythmias, lower SaO₂ from a right‐to‐left shunt (e.g., across a patent foramen ovale [PFO] or ASD), hepatomegaly, diffuse edema (especially in neonates), pleural effusions, and ascites. In the postoperative period, patients with diastolic dysfunction may benefit from lusitropic agents (e.g., milrinone) to improve myocardial relaxation, are typically dependent on adequate preload to maintain sufficient CO, do not tolerate aggressive diuresis because of preload dependency, and may not tolerate rapid volume resuscitation due to the inability of the noncompliant ventricle to accept a large increase in intravascular volume. Patients with RV diastolic dysfunction (e.g., TOF) may benefit from early tracheal extubation, as PPV can increase RV afterload and hinder RV preload. Significant and untreated postoperative tachycardia in this population can also lead to a limitation in CO and increase in myocardial oxygen consumption.

Airway management

Intubation of the trachea in a neonate or young infant with CHD may elicit undesirable hemodynamic and metabolic responses. Appropriate anesthetic techniques are thus desirable to secure the airway.

Traditionally, uncuffed endotracheal tubes (ETTs) were recommended for children younger than 8 years given the narrowest part of the airway is at the level of the cricoid cartilage. However, more recent studies suggest there is no difference between airway complications with cuffed and uncuffed tubes, particularly in the era of microcuff tubes (high‐volume, low‐pressure cuff) [17, 18]. If a significant air leak exists around the ETT, lung volume, and in particular functional residual capacity (FRC), will not be maintained and fluctuations in gas exchange can occur. During the ventilator weaning process, a significant leak will also increase the work of breathing for some neonates and infants. In these situations, it is, therefore, preferable to exchange the ETT for a larger‐sized tube or to change to a cuffed tube. In contrast, an ETT that is smaller than usual may be necessary in certain situations. This is particularly the case in patients with other congenital defects such as Down syndrome (trisomy 21). Tracheal stenosis may also occur in association with some congenital cardiac defects such as a PA sling. Extrinsic compression of the bronchi may occur by the PA or a dilated left atrium. This may be suspected by persistent hyperinflation or lobar atelectasis on a chest radiograph.

Mechanical ventilation

Altered lung mechanics and ventilation/perfusion abnormalities are common problems in the immediate postoperative period [14]. Patients who have Q_p/Q_s > 2 : 1 may have cardiomegaly and congested lung fields on chest radiograph. Patients who have an elevated left atrial pressure may demonstrate signs of pulmonary venous hypertension and pulmonary edema. Additional considerations include the surgical incision and lung retraction, increased lung water following cardiopulmonary bypass (CPB), possible pulmonary reperfusion injury, CPB‐induced surfactant depletion in neonates, and restrictive defects from atelectasis and pleural effusions.

In general, patients with limited physiologic reserve should not be weaned from mechanical ventilation until hemodynamically stable and any problems contributing to an increase in intrapulmonary shunt and altered respiratory mechanics have improved.

Cardiorespiratory interactions

Cardiorespiratory interactions vary significantly between patients and throughout the postoperative course. Consequently, the mode of ventilation must be matched to the hemodynamic status of each patient to achieve an adequate CO and gas exchange. The influence of PPV on preload and afterload is shown in Table 36.3. Frequent modifications to the mode and pattern of ventilation may be necessary during recovery after surgery, with attention to changes in lung volume, compliance, and airway pressure.

Influence of lung volume

Changes in lung volume have a major effect on PVR, which is lowest at FRC. Both atelectasis and hyperinflation may result in a significant increase in PVR, as shown in Figure 36.4 [19–21]. At low‐tidal volumes, alveolar collapse occurs because of reduced interstitial traction on alveolar septae. In addition, radial traction on extra‐alveolar vessels such as the branch PAs is reduced, therefore reducing the cross‐sectional diameter. Conversely, hyperinflation of the lung may cause stretching of the alveolar septae and compression of alveolar vessels.

An increase in PVR increases the afterload or wall stress on the RV, compromising RV function and contributing to decreased LV compliance secondary to interventricular septal shift (from right to left). In addition to low CO, signs of RV dysfunction, including tachycardia, tricuspid regurgitation, hepatomegaly, ascites, and pleural effusions, may be observed.

Influence of intrathoracic pressure

An increase in mean intrathoracic pressure during PPV decreases preload to both pulmonary and systemic ventricles, but has opposite effects on afterload of each ventricle [22–24].

Right ventricle

The increase in pressure in the right atrium and reduction in RV preload that occurs with PPV may reduce CO. Normally, RV diastolic compliance is high and the pulmonary circulation is able to accommodate changes in flow without a large change in pressure. An increase in mean intrathoracic pressure increases the afterload on the RV from direct compression of extra‐alveolar and alveolar pulmonary vessels. This has a number of clinical consequences (Table 36.3). An increase in afterload causes an increase in RV end‐diastolic pressure and myocardial work, which may lead to myocardial ischemia in a patient with limited coronary perfusion. An example of the increase in RV pressure during a positive pressure breath is demonstrated in Figure 36.5.

Patients with normal RV compliance and no residual volume or pressure load on the ventricle following surgery usually show little change in RV function from the alteration in preload and afterload that occurs with PPV. However, these effects can be magnified in patients with RV hypertrophy and those with restrictive RV physiology. At particular risk are neonates requiring a right ventriculotomy for repair of TOF with pulmonary atresia or truncus arteriosus; concentric RV hypertrophy poses additional risk. While systolic RV function may be preserved in these situations, the ventricle often demonstrates diastolic dysfunction with increased RV end‐diastolic pressure and impaired RV filling.

It is important to emphasize the potentially deleterious effects of mechanical ventilation on RV function. The aims should be to ventilate with a mode that enables the lowest possible mean airway pressure while maintaining adequate lung volume and limiting potential secondary injury to the lung. In patients with lung disease, such as pneumonia, adult respiratory distress syndrome, or lung disease of prematurity, a low tidal volume strategy (4–6 mL/kg) using a low peak inspiratory pressure, short inspiratory time, increased intermittent mandatory ventilation (IMV) rate, and higher levels of positive end‐expiratory pressure (PEEP) is recommended. However, this strategy is also associated with a higher mean intrathoracic pressure and afterload on the RV, which reduces antegrade pulmonary blood flow. In contrast, a strategy utilizing larger tidal volumes (10–12 mL/kg), lower IMV rates (15–20 breaths/min), and larger peak inspiratory pressure–PEEP difference with a shorter inspiratory time (0.4–0.5 seconds) may be preferential in patients with restrictive RV.

Positive end‐expiratory pressure

The use of PEEP in patients with CHD has two important effects: recruiting FRC and O₂ reserve capacity and redistributing lung water from alveolar septal regions to the more compliant perihilar regions. Gas exchange is improved, and the work of breathing reduced. This is particularly important in patients with a volume load, ventricular dysfunction, and elevated end‐diastolic volume. PEEP should, therefore, be used in all mechanically ventilated patients following congenital heart surgery. However, excessive levels of PEEP can be detrimental by increasing afterload on the RV. Usually 3–5 cmH₂O of PEEP will help maintain FRC and redistribute lung water without causing hemodynamic compromise.

The use of PPV and PEEP in patients who have undergone either a Glenn or Fontan procedure (cavopulmonary anastomosis) has also been debated. In this group of patients, pulmonary blood flow is nonpulsatile and depends on the pressure gradient between the superior vena cava and the pulmonary venous atrium. During PPV, pulmonary blood flow can be diminished, and during a Valsalva maneuver and at high levels of PEEP, retrograde pulmonary blood flow may be demonstrated by Doppler echocardiography. Nevertheless, the beneficial effects of using low‐pressure PPV and PEEP to achieve desired lung volume, minute ventilation and gas exchange following the Fontan procedure are apparent at the bedside. This strategy rarely contributes to a clinically significant decrease in effective pulmonary blood flow and, in fact, may be more than offset when compared to the elevations in PVR related to a strategy of low‐volume spontaneous ventilation [25, 26].

Alternative modes of ventilation and respiratory support

The use of high‐frequency oscillatory ventilation (HFOV) has been beneficial in the management of hypoxemic and hypercapneic respiratory failure where the goal is to optimize systemic oxygen delivery while minimizing lung injury. The mean airway pressure may be higher than when using conventional ventilation, but can be well tolerated hemodynamically, provided preload is maintained. There is no defined and agreed‐upon indication for HFOV in the literature, but it should be considered in the setting of ventilatory failure with a rising PaCO₂ and mean airway pressures >14 cmH₂O in neonates and >16 cmH₂O in older children using conventional ventilator modes. Recent data using propensity matching suggest that HFOV might reduce the length of ventilation after CHD surgery in neonates and infants [27].

Noninvasive ventilation (NIV) using either mask CPAP, bilevel positive airway pressure (PAP), or high‐flow nasal cannula (HFNC) can be a helpful adjunct in patients who are tachypneic with an increased work of breathing and those requiring improved oxygenation through maintenance of FRC. In addition, it can potentially improve CO and ventricular function by reducing wall stress and afterload. NIV also avoids the attendant risk of endotracheal intubation, including escalating sedation requirements and ventilator‐associated pneumonia and tracheitis [28].

HFNC with humidified oxygen at flow rates of between 3 and 10 L/min can be used to help minimize work of breathing and caloric expenditure in patients recently weaned from mechanical ventilation and/or those awaiting surgery. Although the PEEP delivered through this mode is variable, this mode is a helpful adjunct, especially in small patients with resting lung volumes approaching closing capacity [29].

Early extubation

Early extubation, generally defined as extubation within 6 hours of surgery, has been described for various cardiac lesions. Possible advantages of this strategy include fewer pulmonary complications, reduced sedative and analgesic use, shorter ICU and hospital LOS, and reduced resource utilization. Early extubation can be especially beneficial in patients with restrictive RV physiology or absent subpulmonary ventricle (cavopulmonary connection with the Fontan procedure). Some centers have employed collaborative learning models to develop clinical guidelines for early extubation practices. Although this improved rates of early extubation, ICU LOS did not change [30]. One notable exception is in the Fontan patient; not only will spontaneous ventilation improve pulmonary blood flow and CO, fast‐track extubation in the operating room (OR) is an important predictor of postoperative LOS [31, 32]. Furthermore, rates of successful early extubation vary across institutions, but increased specialized nursing in the CICU may improve outcomes [33]. NIV, including HFNC or PAP, has also been utilized, particularly in high‐risk, postcardiac surgical patients, to mitigate the risk of extubation failure. However, there is limited evidence regarding NIV utilization in pediatric CICUs to inform best practice [34].

Weaning from mechanical ventilation

Weaning from mechanical ventilation is a dynamic process that requires continued reevaluation. While most patients following uncomplicated congenital cardiac surgery will wean without difficulty, some patients with borderline cardiac function and/or residual defects may require prolonged mechanical ventilation and a slow weaning process. As spontaneous ventilation increases during the weaning process, swings in mean intrathoracic pressure may substantially alter afterload on the systemic ventricle. The transition to spontaneous ventilation may cause a sudden increase in wall stress, which then contributes to an increase in end‐diastolic pressure and volume, leading to pulmonary edema and low CO. Inotropic agents, vasodilators, and diuretics should be continued throughout the ventilator weaning process and early after extubation to maintain stable ventricular function as mechanical respiratory support is reduced.

The method of weaning is variable. Most patients can be weaned using either a volume‐limited or pressure‐limited mode by simply decreasing the IMV rate. Guided by physical examination, hemodynamic criteria, respiratory pattern, and arterial blood gas measurements, the mechanical ventilator rate is gradually reduced. Patients with limited hemodynamic and respiratory reserve may demonstrate tachypnea, diaphoresis, and reduced tidal volumes as they struggle to breathe spontaneously against the resistance of the ETT. The addition of pressure‐ or flow‐triggered pressure or volume support breaths above PEEP at a level related to the size of the ETT decreases this resistance and is often beneficial in reducing the work of breathing.

A flow‐triggered mode of pressure or volume support, with a backup ventilator rate if the patient becomes apneic (assist‐control mode), is particularly useful for neonates and infants who received prolonged ventilation following surgery or have a residual volume or pressure load compromising ventricular function. Patients are often more comfortable weaning in this mode and have reduced work of breathing; the level of pressure support is adjusted according to their gas exchange, respiratory rate, and tidal volume.

Numerous factors can contribute to the inability to wean from mechanical ventilation following congenital heart surgery (Table 36.4). As a general rule, however, suspected residual defects causing either a volume or pressure load must be excluded first by echocardiography or cardiac catheterization.

Assessment of cardiac output

The accurate assessment of the postoperative patient’s CO should be a focus of management in the CICU. Recognition and effective management of LCOS is critical, as this clinical entity is associated with increased morbidity, including longer duration of mechanical ventilatory support and CICU/hospital LOS, and mortality [41, 42]. Data from physical examination, routine laboratory testing, bedside hemodynamic and electrophysiologic monitoring, echocardiography, and occasionally bedside CO determination are typically sufficient to manage patients optimally. If patients are not progressing as expected and low CO persists, a systematic evaluation for residual lesions should occur. The imaging assessment for residual lesions typically occurs noninvasively first by echocardiography, with the addition of computed tomographic (CT) angiography, if needed. When a more complete assessment with direct hemodynamic measurements is required, then cardiac catheterization should be undertaken.

The systemic CO is defined as the product of ventricular stroke volume (in L/beat) multiplied by heart rate (in beats/min). The ventricular stroke volume is determined chiefly by three factors: afterload (the resistance to ventricular emptying), preload, and myocardial contractility. CO is usually indexed to body surface area (BSA, in m²) because it is a function of body mass. Thus, CO/BSA is designated as cardiac index (CI, in L/min/m²). The CI varies inversely with age: normal values in children at rest are 4.0–5.0 L/min/m², whereas the normal resting CI at age 70 years is 2.5 L/min/m² [43, 44].

Postoperative patients with low CO can present with a variety of abnormalities on physical examination, bedside monitoring, and laboratory assessment. These manifestations of low CO are listed in Table 36.5. Clinical signs on examination include cool extremities and diminished peripheral perfusion, tachycardia, hypotension, oliguria, and hepatomegaly. An increase in the arterial to mixed venous oxygen saturation (A‐VO₂) difference of >30% and a lactic acidosis provide biochemical evidence for low CO. The atrial pressure is a useful measure to follow, and either an increase or decrease could be observed in LCOS. Factors that should be considered when evaluating the atrial pressure following surgery are shown in Table 36.6.

The mechanism(s) underlying low CO in a specific patient can be related to either one or a combination of factors following surgery. Strategies for treating the patient with a low CO should focus on optimizing the balance between oxygen consumption (VO₂) and delivery (DO₂). In LCOS, oxygen and metabolic demand should be minimized by maintaining an adequate depth of analgesia and sedation, including chemical paralysis, in order to avoid movement, reduce muscle tone, and limit oxygen consumption. Strict avoidance of hyperthermia from any cause is essential, and in some circumstances, mild hypothermia may be preferable, although the effect of peripheral vasoconstriction and increase in SVR from hypothermia could have an adverse impact on myocardial wall stress and oxygen requirements.

Surgical factors

Cardiopulmonary bypass and the systemic inflammatory response

The effects of prolonged CPB relate in part to the interactions of blood components with the extracorporeal circuit. This is magnified in children due to the large bypass circuit surface area and priming volume relative to patient blood volume. Humoral responses include activation of complement, kallikrein, eicosinoid, and fibrinolytic cascades; cellular responses include platelet activation and an inflammatory response, with an adhesion molecule cascade stimulating neutrophil activation and release of proteolytic and vasoactive substances [46–49].

The clinical consequences can include increased interstitial fluid, generalized capillary leak, and potential multiorgan dysfunction. Total lung water is increased with an associated decrease in lung compliance and increase in A‐aO₂ gradient; some of these effects can be attenuated by hemofiltration or modified hemofiltration in the operating room (OR) [50, 51]. Myocardial edema results in impaired ventricular systolic and diastolic function. A secondary fall in CO by 20–30% is common in neonates in the first 6–12 hours following the arterial switch operation, contributing to decreased renal function and oliguria [52]. Sternal closure may need to be delayed due to mediastinal edema and associated cardiorespiratory compromise when closure is attempted. Ascites, hepatic congestion, and bowel edema may affect mechanical ventilation as well as intestinal function (e.g., a prolonged ileus causing a delay in enteral feeding). A coagulopathy post‐CPB may contribute to delayed hemostasis. The clinical manifestation of some of these issues may be attenuated with the lower priming volumes and higher hematocrits used on modern bypass circuits (see Chapter 12 for a detailed discussion of the inflammatory response to CPB).

Dysrhythmias

The ECG is an essential component of the initial postoperative evaluation because the CICU team must identify whether the patient is in sinus rhythm early in the recovery period. If the rhythm cannot be determined with certainty from a surface 12‐ or 15‐lead ECG, temporary epicardial atrial pacing wires, if present, can be used with the limb leads to generate an atrial ECG [53]. Also, right and left atrial waveforms are useful in diagnosing atrioventicular synchrony (see Chapter 13). Temporary epicardial atrial and/or ventricular pacing wires are routinely placed in many patients to allow mechanical pacing if sinus node dysfunction or heart block should occur in the early postoperative period. Because atrial wires are applied directly to the atrial epicardium, the electrical signal generated by atrial depolarization is significantly larger and thus easy to distinguish compared with the P‐wave on a surface ECG. Sinus tachycardia, which is common and often secondary to medications (e.g., sympathomimetics), pain and anxiety, or diminished ventricular function, must be distinguished from a supraventricular, ventricular, or junctional tachycardia. Any of these tachyarrhythmias can lower CO by either compromising diastolic filling of the ventricles or depressing their systolic function [54, 55]. High‐grade second‐ and third‐degree (or complete) heart block can diminish CO by producing either bradycardia or loss of atrioventricular synchrony or both. Third‐degree block is transient in approximately one‐third of cases. If it persists beyond postoperative days 9–10, it is unlikely to resolve, and a permanent pacemaker is indicated (see Chapter 22) [56].

Low preload

The diagnosis of insufficient preload is usually made by monitoring the mean atrial pressure or central venous pressure. The most common cause in the CICU is hypovolemia secondary to blood loss from postoperative bleeding. Initially after surgery and CPB, the filling pressures may be in the normal range or slightly elevated, but this often reflects a more centralized blood volume secondary to peripheral vasoconstriction and venoconstriction following hypothermic CPB. As the patient continues to rewarm and vasodilate in the CICU, additional intravascular volume may be necessary to maintain an adequate circulating blood volume and preload. There may also be significant third‐space fluid loss in neonates and small infants who manifest the greatest systemic inflammatory response following CPB. The “leaking” of fluid from vessels into serous cavities (e.g., ascites) and the extracellular space (peripheral edema that can progress to anasarca) requires that these patients receive close monitoring and volume replacement to maintain an adequate circulating blood volume. Patients with a hypertrophied or poorly compliant ventricle, and those with lesions dependent on complete mixing at the atrial level, also often require additional preload in the early postoperative period.

High afterload

Elevated afterload in both the pulmonary and systemic circulations frequently follows surgery with CPB [52, 57]. Excessive afterload in the systemic circulation (elevated SVR) results in diminished CO and is typically manifest by decreased peripheral perfusion and cool extremities. Treatment of elevated SVR includes recognizing and improving conditions that exacerbate vasoconstriction (e.g., pain and hypothermia) and administering a vasodilating agent. A vasodilator, which can be a phosphodiesterase inhibitor (e.g., milrinone), a nitric oxide donor (e.g., nitroprusside), a calcium channel blocker (e.g., nicardipine), or a peripheral α‐receptor antagonist (e.g., phenoxybenzamine or phentolamine), can be added to an inotropic agent such as epinephrine to augment CO. Neonates, who tolerate increased afterload less well than older infants and children, appear to derive particular benefit from afterload reduction therapy [58–60].

Decreased myocardial contractility

Because decreased myocardial contractility occurs frequently after reparative or palliative surgery with CPB, pharmacologic enhancement of contractility is used routinely in the CICU. Before initiating treatment with an inotrope, however, the patient’s intravascular volume status, serum‐ionized Ca²⁺ level, and cardiac rhythm should be considered. Inotropic agents enhance CO more effectively if preload is adequate, so IV colloid or crystalloid administration should be given if preload is low. If hypocalcemia (normal serum‐ionized Ca²⁺ levels are 1.14–1.20 mmol/L) is detected, supplementation with IV calcium gluconate or calcium chloride is appropriate, because Ca²⁺ is a potent positive inotrope itself, particularly in neonates and young infants. Supranormal supplementation of calcium should be avoided, however, as increased levels of diastolic myocardial calcium are potentially cytotoxic [61].

Dopamine is often the first‐line agent used to treat either mild hypotension (10–20% decrease in normal mean arterial blood pressure for age) or moderate hypotension (20–30% decrease in normal mean arterial blood pressure for age). This sympathomimetic agent promotes myocardial contractility by elevating intracellular Ca²⁺, both via direct binding to myocyte β₁ adrenoceptors and by increasing norepinephrine levels. Dopamine is administered by a constant infusion because of its short half‐life, and a usual starting dose for inotropy is 5 μg/kg/min. At a dose >5 μg/kg/min, dopamine should ideally be infused through a central venous catheter to avoid superficial tissue damage if extravasation were to occur. The dose is titrated to achieve the desired systemic blood pressure, although some patients, especially older children and adults, may develop an undesirable dose‐dependent tachycardia. The challenge with dopamine is its simultaneous effects on β, α, and dopaminergic receptors, often resulting in undesired rhythm disturbances despite maintaining an adequate blood pressure [62]. For this reason, low‐dose epinephrine, up to 0.05 μg/kg/min, is also a useful first‐line inotropic agent, and it may have fewer arrhythmogenic side effects than dopamine in pediatric patients. If a patient does not respond adequately to dopamine up to 10 μg/kg/min or has severe hypotension (more than 30% decrease in mean arterial blood pressure for age), treatment with epinephrine should be considered.

Epinephrine may also be used as a first‐line agent to treat mild‐to‐moderate hypotension. It should be given exclusively via a central venous catheter. A typical starting dose is 0.01–0.05 μg/kg/min with subsequent titration of the infusion to achieve the target systemic blood pressure. At high doses (i.e., ≥0.2 μg/kg/min), epinephrine can produce significant renal and peripheral vasoconstriction, tachycardia, and excessive myocardial oxygen demand (chronotropic and vasopressor effects) [58]. Patients with severe ventricular dysfunction who require persistent or escalating doses of epinephrine >0.15–0.2 μg/kg/min may benefit from opening of the sternum and/or should be evaluated for the possibility of mechanical circulatory support with a ventricular assist device (VAD) or extracorporeal membrane oxygenation (ECMO).

Norepinephrine is a direct‐acting α agonist that primarily causes arteriolar vasoconstriction, but it also has positive inotropic actions. At doses of 0.01–0.2 μg/kg/min, it can be considered in patients with severe hypotension and low SVR (e.g., “warm” or “distributive” shock), inadequate coronary artery perfusion, or inadequate pulmonary blood flow with a systemic‐to‐PA shunt. It is also useful in patients with preserved systemic ventricular function but failing or inadequate RV contractility (PVOD or postoperative TOF with restrictive RV physiology). In patients with normal hearts, variation in afterload is accommodated by varying stroke volumes and contractility; the normal heart works at peak efficiency and contractility exceeds afterload. This increased contractility is also transferred to the RV through the shared intraventricular septum. The increased afterload also improves the filling characteristics of the LV (by shifting of the interventricular septum) and augments RV coronary perfusion (especially in systemic RV pressure where the RV is now dependent exclusively on diastolic aortic root pressure for coronary perfusion). In the failing heart and in patients with limited ventricular reserve, an increase in afterload may not be matched by an increase in contractility, with a resultant fall in CO.

There can be a decrease in responsiveness to increasing doses of catecholamines over time; vasopressin at a dose of 0.1–0.5 mu/kg/min is a potent vasopressor that may help improve the hemodynamics in advanced shock without compromising cardiac function or other adverse sequelae [63].

A combination of epinephrine at lower doses (e.g., <0.1 μg/kg/min) or dopamine with an IV afterload reducing agent, such as milrinone, can help support patients with significant ventricular dysfunction accompanied by elevated afterload. Milrinone inhibits cyclic nucleotide phosphodiesterase III, thereby increasing cAMP, which results in an increased intracellular calcium concentration. In addition to acting as a positive inotrope, increased cAMP relaxes the systemic vasculature, leading to a decrease in afterload as well as a decrease in PVR [59]. The use of milrinone after neonatal and pediatric cardiac surgery has increased significantly over the past 15 years, in part due to the results of a double‐blind, placebo‐controlled multicenter trial that demonstrated a significant decrease in the incidence of LCOS (milrinone dose 0.75 mcg/kg/min) compared to placebo after infant and pediatric corrective heart surgery [42]. A more recent meta‐analysis evaluating the use of prophylactic milrinone in children undergoing surgery for congenital heart disease found that while there is some evidence it may lower the risk for LCOS, there is currently insufficient evidence to conclude that milrinone helps prevent LCOS or mortality [64].

Patients who have the clinical features of relative adrenal insufficiency may benefit from stress steroid therapy [65, 66]. This is primarily a clinical finding of poor vascular tone with persistent hypotension and volume requirement that is refractory to increasing inotrope and/or vasopressor support. The serum cortisol level may be low or show a limited response to adrenocorticotropic hormone stimulation testing [67]; however, the ranges of normal have not been established for pediatric patients after cardiac surgery, in particular for newborns and infants. There is no consistent correlation between serum cortisol level and the incidence of LCOS; nevertheless, stress doses of hydrocortisone (50 mg/m²/day) have been associated with increased systemic blood pressure and lower inotrope scores, although they have not been definitively demonstrated to improve eventual survival. A recent randomized controlled clinical trial also demonstrated that prophylactic, postoperative hydrocortisone infusion reduces the prevalence of LCOS after neonatal CPB [68]. The increased risk for infection and poor wound healing associated with stress dosing of steroids has led to a recommendation for shorter periods of administration (e.g., over 3–5 days) rather than continuing with a long taper [69].

Hypothyroidism is another cause for a persistent LCOS after cardiac surgery. Triiodothyronine (T₃) levels have been demonstrated to be low after CPB and may remain low for up to 5 days after surgery, particularly if a sick euthyroid state develops and there is decreased conversion of thyroxine (T₄) to the biologically active T₃ in peripheral tissues [70, 71]. A pediatric randomized controlled trial evaluating protocolized treatment with T₃ (two doses of 0.4 μg/kg during surgery and three doses of 0.2 μg/kg at 3, 6, and 9 hours after cross‐clamp release) demonstrated improvements in ejection fraction and time to extubation, specifically in patients younger than 5 months [72].

Delayed sternal closure

Sternal closure following cardiac surgery can restrict cardiac function and also interfere with efficient mechanical ventilation. This is particularly important for neonates and infants, in whom considerable capillary leak and edema can develop following CPB, and in whom cardiopulmonary interactions have a significant impact on immediate postoperative recovery. In the OR, mediastinal edema, unstable hemodynamic conditions from both systolic and diastolic dysfunction, and ongoing bleeding are indications for delayed sternal closure, although it may also be considered semi‐electively for patients in whom hemodynamic or respiratory instability is anticipated in the immediate postoperative period (e.g., following a modified Norwood procedure for HLHS). Urgent reopening of the sternum in the CICU following surgery is associated with higher mortality compared with leaving the sternum open in the OR [73], and successful sternal closure can be achieved for most patients by postoperative day 4 with a low risk of surgical site infection [74]. Patients in whom this cannot be achieved and who have additional risk factors (e.g., neonate, need for ECMO, modified Norwood procedure) have an 11% superficial sternal infection (SSI) rate and significantly greater mortality [75]. Additional discussion of hemodynamic management is presented in Chapter 21.