Specific Problems Encountered in Discontinuing Cardiopulmonary Bypass

Left Ventricular Dysfunction

The contractile state of the LV may be reduced after pediatric cardiac surgery. This is due to surgically induced ischemia during the repair, the preoperative condition of the myocardium, the effects of deep hypothermia and circulatory arrest on myocardial compliance, and new, altered loading conditions on the LV caused by the repair.^{[170] [171] [172]} Left ventricular dysfunction can be treated by optimizing preload, increasing heart rate, increasing coronary perfusion pressure, correcting ionized calcium levels, and adding inotropic support. The neonate's heart rate-dependent cardiac output, reduced myocardial compliance, and diminished response to calcium and catecholamines are factors influencing the need for inotropic support. Inotropic support is usually begun with dopamine (3–10 µg/kg/min). Several studies suggest that the effect of dopamine in children is age dependent. Following cardiac surgery in young children, dopamine increases cardiac output, which correlates more with elevations in heart rate than augmentation of stroke volume, ^[173] whereas in young adults, dopamine clearly increases stroke volume.^[13] Nonetheless, infants and neonates respond favorably to dopamine infusions with increased systemic blood pressure and cardiac output and improved systemic perfusion.

Calcium supplementation is important in augmenting cardiac contractility. Although calcium supplementation has fallen into some disfavor because of concerns over reperfusion injury, it remains an important therapy after pediatric cardiac surgery. Fluctuations in ionized calcium levels occur commonly in the immediate post-CPB period in children. This is most often due to the relatively large transfusions of citrate and albumin-rich blood products such as whole blood, fresh frozen plasma, platelets, and cryoprecipitate necessary for hemostasis, all of which bind calcium. ^[174] Routine calcium supplementation during the early post-CPB period is especially helpful in patients with diminished left ventricular function. In patients with a slow sinus or junctional rate, calcium must be administered cautiously because marked slowing of AV conduction may occur.

Epinephrine (0.02–0.2 µg/kg/min) is useful in patients with significant left ventricular dysfunction who remain hypotensive with high left atrial filling pressures or echo-Doppler evidence of reduced contractility or regional ischemia.^[175]

Milrinone, a potent phosphodiesterase-3 inhibitor, is also an effective inotrope-vasodilator in infants and children. Studies in neonates after open heart surgery reveal significant reductions in SVR and PVR and increases in cardiac index, primarily due to larger stroke volume.^[180] Infants and children demonstrate a larger volume of distribution and clearance of milrinone compared to adults; thus, the loading dose necessary to achieve therapeutic levels may be as high as 100 µg/kg.^[181] In neonates, the loading dose of milrinone on CPB is 100 µg/kg, followed by a continuous infusion to be started within 90 minutes of the load dose at a rate of 0.2 µg/kg/minute to maintain a therapeutic level. In older infants and children, the rate of continuous infusion is higher, usually 0.5 to 1.0 µg/kg/minute.

Dobutamine is an effective, albeit weaker, inotropic agent in children. Although it is reported to have fewer chronotropic effects than dopamine in neonates, significant tachyarrhythmias may occur. This may be related to structural similarities between dobutamine and isoproterenol.^[175] In children after cardiac surgery, dobutamine increases cardiac output primarily through increased heart rate. The efficacy of dobutamine seems to be reduced in immature animals.^[182] This is consistent with reduction in β-receptors and a higher level of circulating catecholamines in newborns.

Right Ventricular Dysfunction

Primary right ventricular dysfunction is a common finding after CPB in neonates, infants, and children. For example, after repair of tetralogy of Fallot, pre-existing right ventricular hypertrophy, a right ventriculotomy, and the placement of a transannular patch across the right ventricular outflow tract, resulting in acute pulmonary regurgitation and right ventricular volume overload, are common causes of postoperative right ventricular dysfunction.^[23] The treatment of right ventricular dysfunction consists of measures directed at lowering PVR and preserving coronary perfusion without distending the RV. Metabolic acidosis should be addressed and inotropic agents selected for their vasodilating properties (e.g., dopamine, amrinone, or milrinone). In cases of extreme ventricular dysfunction, low-dose epinephrine (0.01 to 0.03 µg/kg/min) may provide inotropy without vasoconstriction.^{[171] [183] [184]} Mechanical ventilation should be adjusted to assist right ventricular function and minimize PVR.

In contrast to the LV, the low intracavitary pressure of the normal RV receives two thirds of its coronary filling during ventricular systole.^[185] In patients with right ventricular dysfunction, maintaining a normal or slightly elevated systolic arterial pressure maximizes coronary perfusion to the RV and augments contractility. If the need for inotropic support persists after the early post-CPB period, a critical evaluation for other structural and functional abnormalities should be aggressively pursued. Preload should be maintained at a normal to slightly elevated level. Since right ventricular contractility is reduced, it is important to maximize preload to the highest portion of the Starling curve.^[183] Overdistention of the RV, however, is not well tolerated, owing to diminished ventricular compliance and diastolic dysfunction. Excessive volume loading may result in significant diastolic dysfunction, tricuspid regurgitation, and worsening forward flow. Generally, CVP much above 12 to 14 mm Hg is poorly tolerated in neonates and infants with right ventricular dysfunction.^[186] If right ventricular dysfunction is severe, the sternum should be left open.^[187] This eliminates the impedance imposed by the chest wall and mechanical ventilation, allowing the RV to maximize its

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If right ventricular dysfunction persists to the extent that systemic cardiac output is compromised, consideration should be given to extracorporeal life support (extracorporeal membrane oxygenation [ECMO]). When ECMO is used for circulatory support, venoarterial cannulation is preferred. Venous and arterial access may be achieved through a large central artery and vein, usually the carotid artery and internal jugular vein, or by direct chest cannulation. Recovery from severe ventricular dysfunction is predicated on the concept that the myocardium has sustained a transient injury (i.e., "stunned myocardium") and is capable of recovery with time.^{[188] [189]} ECMO is used to decrease ventricular wall tension, increase coronary perfusion pressure, and maintain systemic perfusion with oxygenated blood. ECMO may also be used for left ventricular failure, although success with this condition is less common than that seen with right ventricular dysfunction or pulmonary artery hypertension. Patients placed on ECMO because they fail to separate from CPB demonstrate significantly higher mortality than those for whom ECMO was instituted later in the postoperative course.^[190] The children who consistently have the lowest survival rate are those who require ECMO after a Fontan operation.^[191] The role of ECMO in patients with myocardial injury or pulmonary hypertension is to provide adequate systemic oxygen transport and systemic perfusion while allowing the ventricles to rest and recover. ECMO may even provide an effective means of resuscitation for postoperative cardiac patients, particularly if instituted promptly.^[192] In larger infants and children with predominantly right ventricular dysfunction and satisfactory pulmonary function, a selective RV assist device may be preferable to ECMO.^[193]

Pulmonary Artery Hypertension

Therapy for elevated pulmonary artery pressures is directed at lowering PVR and unloading the RV. Reduction of PVR is accomplished by altering ventilation pattern, inspired oxygen concentration, and blood pH. Specifically, manipulating the pulmonary vascular bed in newborns and infants is a matter of regulating PaCO₂ , pH, PaO₂ , PAO₂ , and ventilatory mechanics.^{[194] [195]} PaCO₂ is a potent mediator of PVR, especially in the newborn and young infant. Reducing PaCO₂ to 20 mm Hg and increasing pH to 7.6 produces a consistent and reproducible reduction in PVR in infants with pulmonary artery hypertension.^[194] Manipulating serum bicarbonate levels to achieve a pH of 7.5 to 7.6 while maintaining a PaCO₂ of 40 mm Hg has equal salutary effects on PVR.^[196] Both the PaO₂ and the PAO₂ decrease PVR as well.^[197] In the circumstance of intracardiac shunts, changes in FIO₂ have little effect on PaO₂ . Thus, by inference, a reduction in PVR induced by increasing the inspired oxygen concentration is probably a direct pulmonary vasodilatory effect of PAO₂ rather than PaO₂ .

Ventilatory mechanics also play a major role in reducing PVR. ^{[198] [199]} Newborns and infants have a closing volume above functional residual capacity. Thus, at the end of a normal breath, some airway closure occurs.^[200] This process results in areas of lung that are perfused and yet underventilated. As these lung segments become increasingly hypoxemic, secondary hypoxic vasoconstriction occurs. The net effect is an increase in PVR. Therefore, careful inflation of the lungs to maintain functional residual capacity will selectively reduce PVR. In practice, this is accomplished with relatively large tidal volumes and low respiratory rates, which produce an exaggerated chest excursion. Generally, tidal volumes of 15 to 25 mL/kg are required. Respiratory rates of 15 to 25 breaths per minute are used for newborns and infants. A reduced ventilatory rate with large tidal volumes reduces mean airway pressure and provides a longer expiratory phase of ventilation.

Because pulmonary blood flow occurs predominantly during the expiratory phase of the respiratory cycle, the ventilatory pattern should be adjusted to allow an adequate distribution of gas throughout the lung during inspiration and a more prolonged expiratory phase to promote blood flow through the lungs. End-expiratory pressure must be applied cautiously during the post-CPB period. Low positive end-expiratory pressure (3 to 5 mm Hg) prevents narrowing of the capillary and precapillary blood vessels, thereby reducing PVR.^[201] Higher positive end-expiratory pressure or excessive mean airway pressure results in alveolar overdistention and compression of the capillary network in the alveolar wall and interstitium. This condition elevates PVR and reduces pulmonary blood flow.^[147]

The final and perhaps the least well-recognized use of the mechanical ventilator is to assist in unloading the RV. During inspiration, intrathoracic pressure increases and creates an increased pressure gradient from the lung to the left atrium, promoting cardiac output. This ventilatory assist is commonly seen in patients with pulmonary artery hypertension or right ventricular dysfunction. An augmentation of the arterial pressure trace during inspiration is seen. The use of the ventilator to augment systemic blood flow is very similar to the thoracic pump concept used to explain blood flow during CPR.^[202] The inspiratory assist must be balanced by the potential negative effects of increased mean airway pressure on PVR and right ventricular afterload. To maximize these cardiopulmonary interactions, high tidal volume with low respiratory rates should be employed.

Attempts to manipulate PVR through pharmacologic interventions have been generally unsatisfactory.

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Because of the lack of specificity of vasodilator drugs on the pulmonary bed, newer pharmacologic methods of controlling pulmonary artery hypertension and elevated PVR are being sought. Two new concepts include ultrashort-acting intravenous vasodilators and inhaled vasodilating agents such as nitric oxide. Ultrashort-acting intravenous vasodilators are nonspecific potent vasodilators, with a half-life measured in seconds. Infusion of these drugs into the right side of the circulation produces a potent short-lived relaxation of the pulmonary artery smooth muscle. Once the drug reaches the systemic circulation, it is no longer functional. Adenosine and ATP-like compounds have these properties and may have clinical applicability in pulmonary artery hypertension in the future.^[208]

Nitric oxide, an endothelium-derived vasodilator that is administered as an inhaled gas, represents the most promising development in the therapy of elevated PVR in patients with congenital heart disease. Although nonselective, it is rapidly inactivated by hemoglobin and, when inhaled, produces no systemic vasodilation.^[209] Nitric oxide reduces pulmonary artery pressure in adult patients with mitral valve stenosis and in selected pediatric cardiac patients with pulmonary artery hypertension. ^{[210] [211] [212]} The congenital cardiac patient population in whom nitric oxide appears to be effective is those patients with acute PVR elevation following open heart surgery, as well as preoperative pulmonary hypertension accompanying specific anatomic conditions (e.g., total anomalous pulmonary venous return, congenital mitral stenosis).^{[211] [212]} Because it acts directly on vascular smooth muscle, nitric oxide remains effective despite the post-CPB endothelial injury frequently encountered in children.^[213] Some centers routinely employ nitric oxide in low dose (1 to 5 ppm) following a Fontan operation when the CVP-LAP gradient exceeds 10 mm Hg.^[214] Finally, nitric oxide can provide diagnostic information that helps distinguish reactive pulmonary vasoconstriction from fixed anatomic obstructive disease either in the postoperative surgical patient or in the patient undergoing pretransplant evaluation.^{[215] [216]} In the latter, the distinction between pulmonary vasoconstriction and advanced pulmonary vascular occlusive disease will influence the prediction as to whether a child with pulmonary hypertension in association with either congenital heart disease or cardiomyopathy will survive a heart transplant or requires replacement of both heart and lungs.