This manuscript is one component of a larger series of articles produced by the Neonatal Cardiac Care Collaborative that are published in this supplement of Pediatrics. In this review article, we summarize the contemporary physiologic principles, evaluation, and management of acute care issues for neonates with complex congenital heart disease. A multidisciplinary team of authors was created by the Collaborative’s Executive Committee. The authors developed a detailed outline of the manuscript, and small teams of authors were assigned to draft specific sections. The authors reviewed the literature, with a focus on original manuscripts published in the last decade, and drafted preliminary content and recommendations. All authors subsequently reviewed and edited the entire manuscript until a consensus was achieved. Topics addressed include cardiopulmonary interactions, the pathophysiology of and strategies to minimize the development of ventilator-induced low cardiac output syndrome, common postoperative physiologies, perioperative bleeding and coagulation, and common postoperative complications.
The field of pediatric cardiac intensive care continues to advance in tandem with improvements in congenital heart surgery and catheter-based interventions. Outcomes for neonates with congenital heart disease (CHD) undergoing surgery have improved significantly. Nonetheless, reducing morbidity and preventing mortality remain the central objectives of neonatal cardiac ICU care. In this manuscript, we summarize contemporary thinking regarding the management of low cardiac output syndrome (LCOS), common postoperative physiologies, perioperative bleeding and coagulation, and common complications seen in neonates after cardiac repair.
When writing this manuscript, the authors searched the published literature using a variety of medical subject terms to identify peer-reviewed articles on acute care issues relevant to the management of neonates and young infants with congenital heart disease published in English since 2010. Additional studies were included on the basis of personal knowledge of the writing group members (including publications before 2010) as well as additional studies in which pediatric evidence was insufficient and adult data was needed. Nonfull text publications in languages other than English were excluded.
This manuscript is part of a larger series of articles simultaneously published as a Supplement in Pediatrics by the Neonatal Cardiac Care Collaborative. Please refer to the Executive Committee introductory paper for a discussion on Class of Recommendations and Level of Evidence (LOE), writing committee organization, and document review and approval.
Low Cardiac Output Syndrome
Pathophysiology of LCOS
Several factors implicated in the pathophysiology of LCOS ultimately result in an imbalance of oxygen supply and demand: (1) underlying myocardial function before surgery, (2) changes to loading conditions after surgical intervention, (3) exposure to the inflammatory effects of cardiopulmonary bypass (CPB), (4) atrioventricular synchrony, and (5) oxygen-carrying capacity (ie, hemoglobin level). Impairment in ventricular performance is directly proportional to the degree of inherent myocyte dysfunction. Preoperative factors that predict myocardial dysfunction and increase the risk of prolonged postoperative LCOS include the need for inotropic support, prematurity, infection, arrhythmia, respiratory failure, and genetic abnormalities.7 Changes to loading conditions after surgery can also drastically impact ventricular function (eg, new volume loads from shunted physiology resulting in increased pulmonary venous return, increased ventricular afterload after pulmonary artery banding or ductal ligation, and changes to inherent systemic and pulmonary vascular resistance). These alterations can greatly affect the contractile reserve leading to difficulty preserving cardiac output.3,8 Lastly, exposure to CPB elicits a systemic inflammatory response causing myocardial inflammation and decreased ventricular performance.9–12 Myocardial ischemia-reperfusion injury is proportional to the duration of aortic cross clamp time and length of cardioplegic arrest and is more pronounced in neonates.13,14 Loss of atrioventricular synchrony from atrial tachycardias or atrioventricular nodal conduction delay leads to abnormal filling pressures and decreased output. Treatment of arrhythmias is dictated by the underlying rhythm disturbance and the patient’s clinical condition. Because neonates have limited ability to increase stroke volume, relative bradycardia may be poorly tolerated, and the provision of chronotropic support with temporary pacing or exogenous catecholamines may be helpful.
An increased systemic oxygen demand (VO2) may contribute to a low cardiac output state. For every degree Celsius increase in temperature, VO2 increases by ∼10%. Excessive agitation also increases VO2. Treatment of either condition should be promptly provided for neonates with appropriate thermoregulation and adequate sedation and analgesia.
Structural Differences in Neonatal Myocardium
Characteristic differences between neonatal and more mature myocardial structures greatly impact the pathophysiology of LCOS found in Table 1.15–17 Immature myocytes are primarily composed of connective tissue and noncontractile organelles that are disorganized with minimal contribution to force generation.18 Myofilaments, the fundamental unit of cross-bridge formation, are generally sparse, disorganized, and typically found along the periphery, unlike mature adult myocytes which are tightly organized in parallel rows.19–21 Mitochondria are fewer in number compared with adult myocytes, leading to a deficiency in oxidative capacity.19 Intracellular calcium handling is also impaired because of the immature cytoarchitecture of the sarcoplasmic reticulum. T-tubules, calcium regulatory proteins, and key activation of ryanodine receptors are all underdeveloped in neonates leading to inefficient excitation-contraction coupling. Neonatal cardiomyocytes are, therefore, primarily dependent on cytosolic concentrations of calcium.22–27 Sympathetic innervation of the heart is also incomplete at birth. Although there is no quantitative difference in β-adrenergic receptors found on myocardial cell surfaces in neonates and adults, there is a functional deficiency of the β-receptor-G protein-adenylate cyclase complex in newborns that limits the effectiveness of catecholamine-modulated contractility.21,28–31
Differences in Neonatal Versus Adult Myocardium
. | Neonate . | Adult . |
---|---|---|
Myocytes | Disorganized, large nuclei | Organized, small nuclei |
Myofilaments | Sparse, found along periphery, disorganized | Arranged tightly in parallel rows, organized |
Mitochondria | Decreased | Abundant |
Noncontractile elements | High, predominance of connective tissue | Low |
Calcium handling | Immature sarcoplasmic reticulum, shallow T-tubules | Mature sarcoplasmic reticulum, deep T-tubules with functional regulatory proteins |
β-adrenergic receptors | Decreased number of functional receptors | Mature functional G protein-coupled complexes |
. | Neonate . | Adult . |
---|---|---|
Myocytes | Disorganized, large nuclei | Organized, small nuclei |
Myofilaments | Sparse, found along periphery, disorganized | Arranged tightly in parallel rows, organized |
Mitochondria | Decreased | Abundant |
Noncontractile elements | High, predominance of connective tissue | Low |
Calcium handling | Immature sarcoplasmic reticulum, shallow T-tubules | Mature sarcoplasmic reticulum, deep T-tubules with functional regulatory proteins |
β-adrenergic receptors | Decreased number of functional receptors | Mature functional G protein-coupled complexes |
Limitations of Neonatal Myocardial Performance
The contractile reserve and the ability to augment ventricular performance are relatively diminished in neonates compared with older children.32,33 Neonates have limited capability to increase muscle fiber stretch because of decreased recruitable preload volume, constraints from the size of the ventricle itself, and overall reduced diastolic compliance compared with adult hearts. Therefore, neonates rely on increasing heart rate as a compensatory mechanism to augment cardiac output. Figure 1 describes the Frank-Starling relationship of stroke volume with increases in both left ventricular end-diastolic volume and afterload. Compared with the mature adult heart, neonatal stroke volume increases only modestly in response to increases in preload and declines more rapidly with increases in afterload.33–36
Relationship of stroke volume with an increase in (A) left ventricular end-diastolic volume and (B) afterload in neonatal hearts.
Relationship of stroke volume with an increase in (A) left ventricular end-diastolic volume and (B) afterload in neonatal hearts.
Neonatal Considerations for Postoperative Care
Strategies for preserving cardiac output in the acute postoperative period rely on optimization of ventricular preload, inotropic support, systemic afterload, and appropriate heart rate and rhythm. There are various monitoring strategies that can be employed to assess hemodynamic status and response to applied therapies37 that are beyond the scope of this manuscript to be delineated in detail.
Neonates have limited preload reserve compared with older children and adults (Fig 1A). Moreover, transcapillary fluid shifts and spontaneous fluid mobilization to extracellular spaces predispose neonates to quickly develop pulmonary edema, ascites, and capillary leak syndrome. Therefore, when fluid resuscitation is provided, it warrants a careful assessment of response. In the absence of bleeding, there is no consensus regarding the choice of replacement fluid.38–41 However, recent adult studies suggest that balanced crystalloid solutions (ie, lactated Ringer’s, Plasma-Lyte) rather than normal saline are associated with less hyperchloremic metabolic acidosis and reduction in acute kidney injury.42–44
Augmentation of systolic function and afterload reduction with inotropic and vasoactive agents is the mainstay treatment of LCOS (Fig 1B). The use of milrinone for this purpose has been well-studied in pediatric postoperative patients.45–48 In the PRIMACORP study, the use of high-dose milrinone (0.75 µg/kg/min) was associated with a reduction in the risk of LCOS.47 Neonates, in general, possess higher adrenergic states and, therefore, may have less inotropic response compared with older children.49 Variable maturation of α- and β-adrenergic receptors result in inconsistent exogenous catecholamine response to renal, cardiac, and systemic vascular tone. Renal clearance is also reduced in premature neonates, making the cardiovascular effects of dopamine exaggerated or prolonged.50–52 Epinephrine and norepinephrine provide more reliable inotropy compared with dopamine but are more prone to increase myocardial oxygen demand and are arrhythmogenic in elevated doses.53 Metabolic effects of epinephrine can also result in hyperlactatemia and hyperglycemia.54 The use of intravenous calcium may be used to increase contractility and smooth muscle tone in peripheral vasculature due to immature intracellular calcium handling previously described above. Vasopressin in neonates has also been found to decrease the need for fluid and catecholamine requirements after cardiac surgery.55–57 Lastly, the use of glucocorticoids in the postoperative period has been shown to improve hemodynamics, particularly in neonates who may be more susceptible to catecholamine-resistant hypotension.58–60 However, the use of intraoperative, empirical steroids in neonates remains controversial61,62 and the subject of an ongoing investigation with a prospective, double-blind, multicenter, placebo-controlled safety and efficacy study.63 Those neonates who have been on glucocorticoids in the preoperative period (ie, for bronchopulmonary dysplasia) may require perioperative steroids to avoid an adrenal crisis.
Recommendations:
In patients at risk for low cardiac output after cardiac surgery, milrinone should be used empirically to minimize its occurrence and severity (Class I, LOE B-R)
In neonates and infants with low cardiac output or myocardial dysfunction, intravenous calcium can be effective to augment cardiac output without associated tachycardia (Class IIa, LOE B-NR)
In patients with postoperative catecholamine refractory shock, hydrocortisone is reasonable to be administered (Class IIa, LOEe A-R)
Common Postoperative Physiologies
Single Ventricle Physiology After Stage 1 Palliation
Primary goals of first-stage surgical palliation (ie, Norwood operation or hybrid palliation) include providing unobstructed systemic blood flow, controlled pulmonary blood flow, and unrestricted egress of pulmonary venous blood flow to allow for complete mixing (Table 2). Achieving and maintaining a balanced pulmonary and systemic blood flow ratio, in addition to maintaining adequate systemic perfusion and oxygen delivery, is one of the unique challenges of caring for these patients. Computer models reveal that maximal oxygen delivery occurs at a systemic blood flow ratio of slightly <1.0,64 a ratio that is roughly approximated by a systemic arterial oxygen saturation (SaO2) of 75%–85%. When SaO2 is not in this target range, additional evaluation may be warranted (Table 3). Note that this rule of thumb is imperfect because the SaO2 may be in the target range, yet in the setting of systemic or pulmonary venous desaturation, the circulation may be grossly imbalanced.
Surgical Approaches to Stage I Single Ventricle Palliation
Objective . | Surgical or Transcatheter Intervention . |
---|---|
Provide unobstructed systemic blood flow | Aortic arch reconstruction |
Damus Kaye Stansel | |
Ductal stent | |
Ensure stable pulmonary blood flow while limiting pulmonary overcirculation | Classic Blalock-Taussig Shunt |
Modified Blalock-Taussig Shunt | |
Right ventricle to pulmonary artery shunt (Sano) | |
Central aortopulmonary shunt | |
Bilateral pulmonary artery bands | |
Central pulmonary artery band | |
Address associated lesions | Atrial septectomy or septostomy |
Repair of anomalous pulmonary venous return | |
Atrioventricular valve repair |
Objective . | Surgical or Transcatheter Intervention . |
---|---|
Provide unobstructed systemic blood flow | Aortic arch reconstruction |
Damus Kaye Stansel | |
Ductal stent | |
Ensure stable pulmonary blood flow while limiting pulmonary overcirculation | Classic Blalock-Taussig Shunt |
Modified Blalock-Taussig Shunt | |
Right ventricle to pulmonary artery shunt (Sano) | |
Central aortopulmonary shunt | |
Bilateral pulmonary artery bands | |
Central pulmonary artery band | |
Address associated lesions | Atrial septectomy or septostomy |
Repair of anomalous pulmonary venous return | |
Atrioventricular valve repair |
Common Stage I Single Ventricle Physiologic Perturbations and Potential Etiologies
SaO2 . | Physiology . | Examples . |
---|---|---|
>85% | High Qp | Oversized shunt |
High SVR | ||
Aortic arch obstruction | ||
Good CO | High SvO2 | |
Low VO2 | Deep sedation or anesthesia | |
<75% | Low Qp | Small shunt size or shunt stenosis |
Shunt thrombosis | ||
Pulmonary artery stenosis or distortion | ||
Elevated pulmonary vascular resistance | ||
Low Qp and pulmonary venous desaturation | Pulmonary venous obstruction | |
Left atrial hypertension | ||
Restrictive atrial septum | ||
Ventricular diastolic dysfunction | ||
Atrioventricular valve regurgitation | ||
Pulmonary venous desaturation | Pulmonary edema | |
Atelectasis | ||
Pneumonia | ||
Systemic venous desaturation | Anemia (may be “relative”) | |
Low cardiac output | ||
High VO2 |
SaO2 . | Physiology . | Examples . |
---|---|---|
>85% | High Qp | Oversized shunt |
High SVR | ||
Aortic arch obstruction | ||
Good CO | High SvO2 | |
Low VO2 | Deep sedation or anesthesia | |
<75% | Low Qp | Small shunt size or shunt stenosis |
Shunt thrombosis | ||
Pulmonary artery stenosis or distortion | ||
Elevated pulmonary vascular resistance | ||
Low Qp and pulmonary venous desaturation | Pulmonary venous obstruction | |
Left atrial hypertension | ||
Restrictive atrial septum | ||
Ventricular diastolic dysfunction | ||
Atrioventricular valve regurgitation | ||
Pulmonary venous desaturation | Pulmonary edema | |
Atelectasis | ||
Pneumonia | ||
Systemic venous desaturation | Anemia (may be “relative”) | |
Low cardiac output | ||
High VO2 |
CO, cardiac output; Qp, pulmonary blood flow; SvO2, systemic venous oxygen saturation; SVR, systemic vascular resistance; VO2, oxygen consumption
Postoperative single-ventricle physiology varies depending on the type of systemic to pulmonary artery shunt. The modified Blalock-Taussig-Thomas shunt (mBTTS) and other forms of aortopulmonary shunts provide continuous pulmonary blood flow both in systole and diastole and, as such, can result in diastolic steal, risking insufficiency to coronary and splanchnic beds. In recent years many centers have preferred the right ventricular to pulmonary artery (RV-PA) conduit (ie, Sano shunt) as the primary source of pulmonary blood flow.65 Patients with an RV-PA conduit provide pulsatile antegrade pulmonary blood flow, which allows improved coronary perfusion pressures and are less prone to pulmonary overcirculation.66 In a multicenter, randomized clinical trial, Norwood patients assigned to the RV-PA conduit group had reduced interstage mortality67 and higher 1-year transplant-free survival when compared with the mBTTS group.68 However, subsequent follow-up of patients in this trial revealed no significant differences in longer-term transplant-free survival.69,70 Risks related to the RV-PA conduit revolve around performing a ventriculotomy, increasing the risk of myocardial dysfunction, developing ventricular arrhythmias, and pseudoaneurysms. Irrespective of the shunt type, thromboprophylaxis with aspirin is recommended to prevent shunt thrombosis71 and has been associated with reduced mortality.72
Recommendations:
In neonates undergoing Norwood operation, the RV-PA conduit (unless contraindicated by anatomic concerns) is reasonable as the source of pulmonary blood flow when compared with a modified Blalock-Taussig shunt (Class IIa LOE B-R)
In the postoperative neonate, after Norwood operation, augmentation of total cardiac output and lowering of systemic vascular resistance can be beneficial to optimize systemic perfusion (Class Iia, LOE B-NR)
In patients with a systemic to pulmonary shunt, thromboprophylaxis with aspirin is recommended (Class I, LOE B-NR)
Cyanosis
In contemporary clinical practice, the term “cyanosis” is used interchangeably with systemic desaturation. From a physiologic perspective, systemic desaturation reflects a reduced oxygen-carrying capacity of hemoglobin and, therefore, impaired oxygen delivery. Excessive cyanosis after neonatal cardiac surgical repair or palliation may be caused by 1 or more anatomic or physiologic problems. In patients with palliated single ventricle physiology or right-to-left shunt lesions, excessive desaturation (∼SaO2 <75%) may be attributable to inadequate pulmonary blood flow, pulmonary venous desaturation, and/or systemic venous desaturation (Table 3). In patients having undergone a biventricular repair, desaturation (ie, SaO2 <93%) is most commonly due to pulmonary venous desaturation, although residual right-to-left shunting at the atrial level may be contributory. Treatment of cyanosis is dictated by the underlying cause(s).
Postoperative Pulmonary Hypertension
Pulmonary hypertension (PH) after CPB may be caused by a combination of preoperative, intraoperative, and postoperative factors. Common preoperative risk factors include obstructed pulmonary venous return, left atrial hypertension, pulmonary overcirculation, or persistent fetal circulation (persistent pulmonary hypertension). CPB increases pulmonary vascular resistance by contributing to pulmonary endothelial cell dysfunction with a secondary imbalance between primary pulmonary vasoconstrictors (ie, endothelin 1) and vasodilators (ie, nitric oxide).2,73,74 Postoperatively, large residual left-to-right shunts, obstruction to pulmonary venous return, or left atrial hypertension may all increase pulmonary vascular resistance. Finally, noxious stimuli, particularly suctioning of the endotracheal tube, may trigger a pulmonary hypertensive crisis.
PH may manifest as low cardiac output after a biventricular repair, particularly when both septa are completely intact, or as excessive cyanosis in patients with intracardiac shunts, including palliated single ventricle physiology. PH can also cause or exacerbate postoperative right ventricular dysfunction. The severity of PH may be estimated noninvasively by Doppler interrogation of a tricuspid regurgitation jet on an echocardiogram. However, the gold standard for diagnosis is a direct assessment of pulmonary arterial pressures by cardiac catheterization or using an indwelling pulmonary artery catheter. The use of these modalities must be weighed against the procedural risk in the immediate postoperative setting.75
A combination of relatively simple postoperative strategies diminishes the likelihood of pulmonary hypertensive crises in at-risk patients and can also be employed as therapeutic interventions when needed.13 In the acute care setting, inhaled nitric oxide (iNO) is the primary therapeutic modality, typically starting at 20 ppm.74,76,77 Nitric oxide diffuses to adjacent smooth muscle cells, in which relaxation occurs by activation of guanylate cyclase, which increases intracellular guanosine 3′, 5′-monophosphate (cyclic). Side effects associated with iNO include a rebound effect after withdrawal of the drug, and methemoglobinemia.78 Phosphodiesterase type 5 (PDE-5) inhibitors, including sildenafil and tadalafil, may be used to minimize rebound PH and thus facilitate the weaning of iNO.79,80 In severe PH refractory to either iNO or PDE-5 inhibitors, inhaled or systemic prostacyclins may be used although experience is limited.
Recommendations:
In patients with postoperative PH, iNO can be effective in lowering pulmonary artery pressures and improving cardiac output (Class IIa, LOE B-R)
A PDE-5 inhibitor may be considered to facilitate weaning and minimize rebound PH in patients receiving iNO (Class IIa, LOE B-R)
Postoperative Diastolic Dysfunction/Restrictive Right Ventricle Physiology
Restrictive right ventricular physiology, or impaired elastance of the right ventricle, occurs as a consequence of right ventricular hypertrophy, hypoplasia, fibrosis/endomyocardial fibroelastosis, myocardial injury (ie, ventriculotomy), or some combination of all of these factors. Restrictive physiology is common after complex right heart reconstructions or interventions, including repair of Tetralogy of Fallot, pulmonary atresia/critical pulmonary stenosis, and truncus arteriosus.
Patients with restrictive right ventricular physiology demonstrate diastolic dysfunction with elevated ventricular end-diastolic filling pressures resulting in increased right atrial filling pressures and systemic venous congestion. They may manifest a low cardiac output state with tachycardia, hypotension, poor perfusion, and narrow pulse pressure, along with oliguria and metabolic acidosis. If an atrial or ventricular communication is present, then right-to-left blood flow through these defects would result in systemic desaturation. Hepatic congestion, ascites, increased chest tube output, and pleural effusions are more insidious manifestations. Because of ventricular-interdependence, changes in right ventricular shape and septal position may affect left ventricular compliance and outflow.
Anticipatory treatment of restrictive right ventricular physiology begins in the operating room (Table 4). In neonates at risk, it may be helpful for the surgeon to leave an atrial communication to function as a “pop off” allowing for left ventricular preload to be maintained and, therefore, preserve cardiac output, albeit with desaturated blood. Postoperative management strategies should focus on maintaining adequate systemic oxygen delivery while minimizing myocardial oxygen consumption. The right heart is preload-sensitive because of elevated right-sided filling pressures, and right ventricular preload should be maintained carefully. Strategies include volume replacement and avoidance of excessive tachycardia to allow for adequate diastolic filling. Myocardial function may be augmented using inotropic agents such as low-dose epinephrine (0.03–0.05 mcg/kg/min) or milrinone (0.25–0.75 mcg/kg/min) which may provide additional lusitropy. Concomitantly, right ventricular afterload should be minimized through a combination of ventilator management strategies and by avoiding factors that might contribute to elevated pulmonary vascular resistance. Sedation and paralysis may be helpful for the first 24 to 48 hours to minimize the stress response and associated myocardial workload. Right ventricular compliance generally improves over time.
Treatment Options for Restrictive Right Ventricular Physiology
Physiologic Goals . | Specific Treatment Strategies . |
---|---|
Optimize ventricular preload | Target right atrial pressure of 10–15 mmHg |
Drain ascites | |
Leave patent foramen ovale to preserve left ventricular preload | |
Maintain atrioventricular synchrony; treat arrhythmias | |
Inotropic support | Judicious use of dopamine, milrinone and/or epinephrine |
Lusitropy | Milrinone |
Optimize myocardial oxygen supply and demand | Maintain coronary perfusion pressure |
Heart rate control | |
Judicious use of inotropes | |
Maintain low right ventricular afterload | Use lowest mean airway pressure to maintain FRC of lungs |
Avoid acidosis | |
Drain pleural effusions, pneumothoraces, or hemothoraces | |
Minimize systemic oxygen consumption | Maintain normothermia |
Provide adequate sedation and analgesia | |
Consider muscle relaxant |
Physiologic Goals . | Specific Treatment Strategies . |
---|---|
Optimize ventricular preload | Target right atrial pressure of 10–15 mmHg |
Drain ascites | |
Leave patent foramen ovale to preserve left ventricular preload | |
Maintain atrioventricular synchrony; treat arrhythmias | |
Inotropic support | Judicious use of dopamine, milrinone and/or epinephrine |
Lusitropy | Milrinone |
Optimize myocardial oxygen supply and demand | Maintain coronary perfusion pressure |
Heart rate control | |
Judicious use of inotropes | |
Maintain low right ventricular afterload | Use lowest mean airway pressure to maintain FRC of lungs |
Avoid acidosis | |
Drain pleural effusions, pneumothoraces, or hemothoraces | |
Minimize systemic oxygen consumption | Maintain normothermia |
Provide adequate sedation and analgesia | |
Consider muscle relaxant |
FRC, functional residual capacity
Recommendations:
For neonates with expected restrictive right ventricle physiology, utilization of atrial-level communication can be effective to preserve cardiac output (Class IIb, LOE C-EO)
For neonates with restrictive right ventricle physiology, utilization of fluid and heart rate control to optimize cardiac output can be beneficial (Class IIb, LOE C-EO)
The Neonatal Coagulation System and Cardiac Surgery
Although all the key components of the hemostatic system are present at birth, important quantitative and qualitative differences exist between neonates and adults. Procoagulant factors (ie, prothrombin, Factors II, VII, IX, and X) and anticoagulant factors (ie, proteins C and S, and antithrombin) are low at birth and do not reach adult ranges until 6 months of age. As a result, the amount of thrombin that a neonate can generate is about 50% of adult levels.81 Although fibrinogen concentrations are comparable between neonates and adults, the fetal form of fibrinogen is qualitatively dysfunctional until ∼1 year of age.82 In fact, clinically, a normal newborn prothrombin time can be up to 20 seconds, 60 seconds for a partial thromboplastin time, and fibrinogen >150 mg/dL. Despite this immature hemostatic system, neonatal coagulation is regarded as adequate and in balance, but prone to disturbance because of limited factor reserves.
Neonates and infants undergoing cardiac surgery with CPB are at high risk for bleeding because of multiple factors (Table 5). To restore the hemostatic balance, excessive postoperative bleeding is treated with blood products, including packed red blood cells, fresh-frozen plasma, platelets, and cryopre cipitate. The absence of a standardized definition of excessive postoperative bleeding among major congenital cardiac surgical programs is a barrier to improving bleeding-related outcomes.83 Excessive postoperative bleeding in neonates after CPB is independently associated with increased adverse events, specifically the need for postoperative dialysis and extracorporeal membrane oxygenation support.84 Similarly, increased blood transfusion requirements after pediatric CPB are independently associated with increased major postoperative adverse events and an increased duration of mechanical ventilation and length of hospital stay.85,86 Overall, the administration of allogenic blood products, derived from adult donors, is associated with significant infectious and noninfectious risks that increase morbidity and mortality. Therefore, many centers have developed transfusion algorithms with point-of-care testing, used to guide patient- and condition-specific blood product administration. The use of viscoelastic tests, such as thromboelastography and rotational thromboelastometry, is now recommended in both American and European guidelines for perioperative bleeding management in children and adults.87,88 The use of age-specific reference ranges and functional fibrinogen assays will further help guide appropriate therapies. Routine use of these assays, however, has not yet been adopted in the management of perioperative bleeding in children.
Factors Associated With Increased Bleeding Risk in Neonatal Patients With Congenital Heart Disease Undergoing Cardiac Surgery With Cardiopulmonary Bypass
Patient . | Surgery . | Cardiopulmonary Bypass . |
---|---|---|
Age | Complexity of repair | Hemodilution |
Comorbidities | Elective versus urgent | Hypothermia |
Anticoagulation and antiplatelet therapies | Surgical skill | Hypocalcemia |
Cyanotic induced changes in the hemostatic system | Heparin/protamine | |
Low factor levels | Inflammatory response | |
Fetal fibrinogen |
Patient . | Surgery . | Cardiopulmonary Bypass . |
---|---|---|
Age | Complexity of repair | Hemodilution |
Comorbidities | Elective versus urgent | Hypothermia |
Anticoagulation and antiplatelet therapies | Surgical skill | Hypocalcemia |
Cyanotic induced changes in the hemostatic system | Heparin/protamine | |
Low factor levels | Inflammatory response | |
Fetal fibrinogen |
The search for other effective options to treat coagulopathy after CPB in neonates remains an important challenge. The off-label use of factor concentrates, including recombinant activated factor VII, fibrinogen, and prothrombin complex concentrates, helps to limit exposure to allogenic blood product transfusion. Some advantages of their use include that they do not require crossmatch, involve a small volume of administration, are readily available, are easy to reconstitute, and pose no infectious risks.89 However, these factor concentrates have not been adequately studied in neonates with respect to the best timing of administration, dose, risk of thrombosis, and cost-effectiveness. The thrombotic risk is particularly concerning in neonates undergoing complex congenital heart surgeries resulting in surgically created shunts, such as the mBTTS, because large-volume blood product transfusion is also associated with an increased incidence of thrombosis.90 In summary, the delicate balance of the neonatal hemostatic system requires additional research to develop better methods of monitoring neonatal coagulation and improved therapeutic approaches to excessive perioperative bleeding.
Complications
Neurologic Complications
Neonates with CHD have a multitude of risk factors for brain injury. Please refer to the section on neurodevelopmental outcomes for longer-term sequelae outside of the acute postoperative period. Neonates with CHD have relatively immature brain development relative to their gestational age, and this alone predisposes them to injury.91 Risk factors for neurologic injury in neonates with CHD can be organized by perioperative time period (Table 6).
Risk Factors for Neurologic Injury in Neonates With Congenital Heart Disease
Prenatal . | Preoperative . | Intraoperative . | Postoperative . |
---|---|---|---|
Delayed brain maturation | Waiting time to operating room (d-TGA; HLHS) | Lower hematocrit | Seizures |
Alterations in brain oxygen delivery | Hypotension | Hypoglycemia | Length of stay |
Prematurity | Impaired oxygen delivery | DHCA | Hypotension |
IUGR | Postnatal diagnosis | Hypotension | |
Cardiac arrest | |||
Thromboembolism |
Prenatal . | Preoperative . | Intraoperative . | Postoperative . |
---|---|---|---|
Delayed brain maturation | Waiting time to operating room (d-TGA; HLHS) | Lower hematocrit | Seizures |
Alterations in brain oxygen delivery | Hypotension | Hypoglycemia | Length of stay |
Prematurity | Impaired oxygen delivery | DHCA | Hypotension |
IUGR | Postnatal diagnosis | Hypotension | |
Cardiac arrest | |||
Thromboembolism |
DHCA, deep hypothermic circulatory arrest; d-TGA, dextro-transposition of the great arteries; HLHS, hypoplastic left heart syndrome; IUGR, intrauterine growth retardation.
Postoperative neurologic injury for this population acutely presents primarily with seizures, cerebrovascular accidents (ischemic or embolic), and/or intracranial hemorrhage. The incidence of seizures in the postoperative period is variable.92–96 More concerning, in 1 study of patients having seizures, 85% were subclinical and found by continuous electroencephalogram (cEEG) only.96 The incidence of perioperative stroke documented on MRI has been reported as high as 10%97 whereas white matter injury has been described in a range of 35% to 75%.91,98,99 Brain injury depicted on MRI has been associated with worse neurodevelopmental outcomes, which may support early imaging.91
Monitoring plays an important role in both mitigating risks for injury as well as aiding in diagnosis. Multiple monitoring tools are available, but the most used are near-infrared spectroscopy (NIRS) and cEEG. NIRS is a noninvasive technology that measures regional tissue oxygen saturation and is used clinically as a marker of regional oxygen delivery. NIRS is used to assess regional cerebral perfusion and may be an effective monitor for neurologic injury in postoperative neonates.100 Given the incidence of perioperative seizures, particularly those that are subclinical, cEEG can be considered in high-risk neonates.
Recommendations:
In patients with clinical or elec trical neurologic abnormalities in the postoperative period, head imaging should be strongly considered (Class I, LOE B-NR)
In neonates with prolonged CPB and/or deep hypothermic circulatory arrest times, especially when usual neurologic assessment is not possible, continuous EEG may be considered (Class IIb, LOE C-NR)
Surgical Site Infection
Hospital-acquired infections are a potential major source of morbidity and mortality after CHD surgery. The incidence of surgical site infection in this patient population ranges from <1% to as high as 11%.101 Patients with delayed sternal closure have up to a 3-fold-increased risk of postoperative surgical site infection with the risk increased in children who also had extracorporeal support and multiple episodes of delayed sternal closure.102
Acute Kidney Injury
Acute kidney injury (AKI) occurs commonly after neonatal cardiac surgery involving CPB and is associated with increased mortality.103–105 Neonatal AKI has increasingly been described via modified Kidney Disease Improving Global Outcomes serum creatinine criteria (Table 7).106–108 However, creatinine is a delayed, nonspecific marker of renal injury that may be confounded by fluid overload and muscle mass.109 Biomarkers of renal tubular injury, such as neutrophil gelatinase-associated lipocalin, are more sensitive, specific, and earlier indicators of AKI, but access to testing is limited.110,111
Kidney Disease Improving Global Outcomes Serum Creatinine Criteria
Stage . | Serum Creatinine . |
---|---|
1 | 1.5–1.9 times baseline OR ≥0.3 mg/dL increase |
2 | 2.0–2.9 times baseline |
3 | 3.0 times baseline OR increase in serum creatinine to ≥0.4 mg/dL OR initiation of renal replacement therapy OR, in patients <18 y, decrease in eGFR to <35 mL/min/1.73 m2 |
Stage . | Serum Creatinine . |
---|---|
1 | 1.5–1.9 times baseline OR ≥0.3 mg/dL increase |
2 | 2.0–2.9 times baseline |
3 | 3.0 times baseline OR increase in serum creatinine to ≥0.4 mg/dL OR initiation of renal replacement therapy OR, in patients <18 y, decrease in eGFR to <35 mL/min/1.73 m2 |
eGFR, estimated glomerular filtration rate.
Preoperative cardiac output, central venous pressure, preexisting AKI, and chronic renal insufficiency, as well as intraoperative perfusion and the inflammatory cascade triggered by CPB, influence postoperative AKI.112,113 Postoperative risk factors include low cardiac output, elevated venous pressure, and nephrotoxic medications.
Perioperative prevention of postoperative AKI includes minimizing CPB exposure, limiting preexisting AKI, and optimizing renal perfusion. The efficacy of individual preoperative and intraoperative interventions, such as agents that potentially augment renal perfusion, is uncertain.114–117 Strategies to decrease AKI postoperatively are limited. Attention to renal perfusion pressure and avoidance or careful dosing and monitoring of nephrotoxic medications are reasonable.118,119 The optimal renal perfusion pressure remains unclear and likely variable by age. A general guideline based on expert opinion would be to maintain a renal perfusion pressure target of 35 to 50 mmHg with the following age-based suggestions (excluding prematurity):
Age 0 to 1 month: Renal perfusion pressure ≥ 35 mmHg
Age 1 month to 5 years: Renal perfusion pressure ≥ 40 mmHg
Age 6 to 11: Renal perfusion pressure ≥ 45 mmHg
Age 12 to adult: Renal perfusion pressure ≥ 50 mmHg
Recommendations:
In patients at risk for or with any stage of AKI, attention to renal perfusion pressure and limitation of nephrotoxic drugs may be beneficial (Class IIa, LOE C-NR)
Cardiac Tamponade
Cardiac tamponade after neonatal cardiac surgery is uncommon but confers a risk of morbidity and mortality.120 Although echocardiographic signs of tamponade exist, tamponade is a clinical diagnosis defined by impaired cardiac output.121 Fluid accumulates within the pericardial sac and, when pericardial pressure exceeds that of the cardiac chambers, venous return, preload, and cardiac output are impaired.122,123 Echocardiographic signs of tamponade include right atrial collapse during systole, right ventricular collapse during diastole, respiratory flow variation across the tricuspid and/or mitral valve, and inferior vena cava distension with little/no respiratory variability. The rate of fluid accumulation rather than absolute volume is correlated with clinical manifestations of tamponade (acute versus chronic).124
Early signs of tamponade may include tachycardia, respiratory distress, Beck’s triad (elevated central venous pressure, muffled/distant heart sounds, and hypotension), and pulsus paradoxus.125,126 Late signs of tamponade include hemodynamic compromise and inadequate end-organ perfusion. Tamponade is classically a clinical emergency temporized by volume resuscitation and necessitating catheter-based or surgical intervention. Pericardiocentesis under echocardiographic or fluoroscopic guidance with pericardial drain placement is reasonable.127–129 Recurrent pericardial effusion and tamponade are more likely with pericardiocentesis without placement of a pericardial drain. Surgical options include evacuation of clot or fluid from the pericardium, creation of a pericardial window, and, rarely, pericardiectomy.130,131
Recommendations:
In patients with clinical and/or echocardiographic evidence of tamponade physiology, mediastinal exploration or pericardial drain placement should be performed (Class I, LOE C-LD)
Respiratory Complications
Respiratory complications in the postoperative setting are common and include pulmonary edema, pleural effusions, prolonged respiratory insufficiency, phrenic nerve injury/diaphragm paresis, and chylothorax. The mainstay of therapy for pulmonary edema and/or pleural effusion is diuretics, which are effective in most instances, and, if not, effusions can be drained with chest tube placement. Phrenic nerve injury can result from intraoperative topical hypothermia or mechanical trauma at any point along the nerve’s course, resulting in paresis or paralysis of the ipsilateral diaphragm. The most severe form of injury will result in paradoxical movement of the diaphragm and significantly impair respiratory mechanics, especially in infants. Spontaneous recovery from postsurgical paralysis is rare; however, older children may tolerate diaphragmatic paralysis without the need for intervention. If respiratory support cannot be weaned, then plication of the diaphragm to help manage respiratory insufficiency is indicated.132
The use of noninvasive ventilation (NIV) therapies, including high-flow nasal cannula and positive airway pressure support, for respiratory insufficiency in infants with critical cardiac disease continues to increase. NIV therapy may provide an opportunity to decrease ICU length of stay, decrease complications associated with invasive respiratory support, and improve other clinical outcomes for patients in the cardiac ICU. To date, NIV use is common in cardiac ICU practice and varies considerably by institution.133 The effectiveness of high-flow nasal cannula over standard oxygen therapy or positive airway pressure support to improve morbidity is still debated.134,135
Chylothorax can develop in the wake of cardiac surgery because of high venous pressures, obstruction or variation of the lymphatic system, or damage to the lymphatic drainage system (ie, thoracic duct). Initial therapies include pleural fluid drainage, restricting fat content in a low- or fat-free diet, enteric rest, and/or parenteral nutrition.136 Although octreotide has been employed as a treatment for refractory chylothorax, there are limited data on its efficacy in the postoperative setting. Somatostatin may be considered before surgical intervention in refractory chylothorax after initial therapies have been deemed unsuccessful.137,138
Recommendations:
Diaphragm plication should be performed in patients with postsurgical diaphragm paralysis and an inability to wean from respiratory support (Class I, LOE C-LD)
For neonates with respiratory insufficiency, the use of high-flow nasal cannula may be reasonable to provide support and avoid reintubation (Class IIb, LOE B-NR)
In patients with postoperative chylothorax, a stepwise strategy to limit fat intake, octreotide therapy, and surgical duct ligation can be effective (Class IIa, LOE B-NR)
Residual Lesions
Residual lesions after cardiac surgery are considered one of the most important factors in determining short- and long-term outcomes. Significant residual lesions after surgery have been associated with higher morbidity and mortality, longer ICU length of stay, greater hospital cost, and worse neurodevelopmental outcomes. Several factors may contribute to the impact of residual lesions on outcomes including age, univentricular versus biventricular repair, presence of noncardiac anomalies, and impact on cardiopulmonary interactions.139–141 The severity of the residual lesion and its patient impact will determine the need for unplanned reintervention or reoperation. In multiple studies, unplanned reinterventions are associated with increased length of stay and mortality.142–144
Recommendations:
In patients who are deviating from the expected postoperative course, it may be beneficial to promptly evaluate for potential significant residual cardiac defects, and if an important lesion is identified, undertake a timely intervention (Class IIa, LOE B-NR)
Cardiac Arrest
Cardiac arrest occurs more frequently in hospitalized children with acquired and congenital cardiac disease compared with children without cardiac disease.145,146 Children with cardiac disease suffer cardiac arrest at rates of 2.6% to 6%, with corresponding survival ranging from 32% to 50.6%.146,147 A study from the Pediatric Cardiac Critical Care Consortium4 revealed that neonates have twice the prevalence of cardiac arrest compared with infants and 70% of postoperative cardiac arrest events occur between admission from the operating room and postoperative day 7.148 Of note, prematurity, at any Society of Thoracic Surgery preoperative risk factor and STAT complexity category 4 or 5 level procedures had the strongest association with cardiac arrest. The Pediatric Cardiac Critical Care Consortium4 is currently engaging in a quality improvement initiative to prevent cardiac arrest in these high-risk patient cohorts.149
Recommendations:
In patients at high risk for cardiac arrest, specific measures aimed at preventing cardiac arrest can be effective (Class IIa, LOE C-LD)
Conclusions
Reducing morbidity and preventing mortality remain the central objectives of neonatal cardiac ICU care. Identifying abnormal physiologic states and potential or real complications in a timely manner is key to impacting outcomes in neonates with cardiac disease.
Dr Cooper helped conceptualize the manuscript, drafted the initial manuscript outline, assigned other authors to draft initial content for specific sections, drafted certain sections, compiled the contributions of other authors, and reviewed and revised the manuscript; Dr McBride helped conceptualize the manuscript, drafted sections of the manuscript, and critically reviewed the manuscript for important intellectual content; Dr Sen drafted sections of the manuscript and critically reviewed the manuscript for important intellectual content; Drs Hill, Krishnamurthy, Costello, Lehenbauer, Twite, James, Mah, and Ms Taylor drafted sections of the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
FUNDING: The Neonatal Heart Society contributed an educational grant to the project, Neonatal Cardiac Care Collaborative (NeoC3). The Neonatal Heart Society regularly applies and receives several unrestrictive educational grants for several internal projects from the following organizations and companies: Abbott Formula, Mead Johnson, Cheisi, Mallinckrodt, Prolacta, and Medtronic.
The grants received from industry partners were used solely to offset the cost of publishing this supplement in Pediatrics. The industry supporters did not suggest manuscript content, nor did they participate in any way in the writing or editing of the manuscript.
CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest relevant to this article to disclose.
The guidelines/recommendations in this article are not American Academy of Pediatrics policy, and publication herein does not imply endorsement.
- AKI
acute kidney injury
- cEEG
continuous electroencephalogram
- CHD
congenital heart disease
- CPB
cardiopulmonary bypass
- iNO
inhaled nitric oxide
- LCOS
low cardiac output syndrome
- LOE
Level of Evidence
- mBTTS
modified Blalock-Taussig-Thomas shunt
- NIRS
near infrared spectroscopy
- NIV
noninvasive ventilation
- PDE-5
phosphodiesterase type 5
- PH
pulmonary hypertension
- RV-PA
right ventricle to pulmonary artery
- SaO2
oxygen saturation
- VO2
oxygen consumption
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