Noteworthy Literature in 2015

Introduction

This article is a review of the literature published during the 12 months of 2015, which is of interest to the congenital cardiac anesthesiologist. The review does not aim to be exhaustive but to select key articles and themes that are relevant to the clinical practice of anesthesiologists who spend the majority of their time caring for patients with congenital heart disease (CHD). Similar to our last 2 “Years in Review” for 2013 and 2014, the same terms were used to search the US National Library of Medicine PubMed database: congenital heart disease, anesthesia, cardiac surgery, and cardiopulmonary bypass.^1,2 Seven themes emerged from the selected articles: neurological outcomes and cerebral oximetry; cardiopulmonary bypass and anticoagulation; cardiac catheterization laboratory and pulmonary hypertension; procedural sedation; adverse events; adult congenital heart disease and pregnancy; and Fontan physiology and right ventricular failure.

Neurological Outcomes and Cerebral Oximetry

Neurodevelopmental disability is the most common complication for survivors of surgery for CHD. Gaynor et al for the International Cardiac Collaborative on Neurodevelopment showed in a large multi-institutional multiyear study that early neurodevelopmental outcomes for survivors of cardiac surgery in infancy have improved modestly over time, but only after adjustment for patient risk factors. ³ Hoffman et al studied this abnormal neurodevelopment in more detail examining whether the acute physiologic effect of a surgical procedure, anesthesia, and hospitalization may offset any potential advantage gained from anatomic correction and circulatory palliation. ⁴ This study collected data on children at high risk for impaired neurodevelopment, including Bayley development scores, hospital stay data, and cerebral and somatic oxygenation saturations using near-infrared spectroscopy (NIRS). They showed that narrower arterial-cerebral and arterial-somatic saturation differences were associated with better or improving motor performance. However, total times for deep hypothermic circulatory arrest, extracorporeal membrane oxygenation, total surgical procedures, and birth weight were not risk factors. The authors concluded that patient physiological status assessed by cerebral and somatic NIRS is associated with neurodevelopmental performance and that treatment strategies that target improved physiological status may also improve neurodevelopmental outcomes. One of the final common paths for impaired neurodevelopment is cerebral hypoxia, which makes early detection and treatment of these events a priority. NIRS is a continuous, noninvasive monitor that is widely used in operating rooms and intensive care units (ICUs) where patients with CHD are cared for. There are many variables that influence cerebral oxygen saturation, including cardiac output, blood pressure, cerebral autoregulation, arterial oxygen and carbon dioxide partial pressures, hemoglobin level, and cerebral metabolism. NIRS is an indicator of the oxygen-supply consumption balance at a regional cerebral level. Studying individual factors of this cerebral oxygenation balance may improve patient’s “physiological status” and further improve neurodevelopmental outcomes.

In keeping with monitoring and improving a patient’s “physiological status,” a retrospective study of 399 children who underwent congenital cardiac surgery in Australia showed the NIRS-derived variables of low cerebral tissue oxygenation and an increase in deoxygenated hemoglobin from baseline were associated with worse outcomes. ⁵ The study authors conclude that simultaneous monitoring of cerebral oxygen saturation and hemoglobin concentration with NIRS would not only allow early detection of injurious cerebral deoxygenation but also help estimate the underlying physiology and thereby allow better management. Three additional parameters affecting NIRS have also been reported in the 2015 literature. Since hemoglobin level is one of the factors affecting cerebral oxygen saturation, a group in France explored if the introduction of NIRS monitoring into their practice influenced their intraoperative red blood cell transfusion threshold and volumes, as well as the duration of ICU stay. ⁶ They found that NIRS monitoring changed their transfusion strategy with an earlier transfusion but a reduced red blood cell volume and this was associated with a decreased length of ICU stay. The second reported parameter is blood pressure from a different group in France. ⁷ Pediatric hypotension has been defined as a decrease in mean arterial blood pressure of 20% to 30% from baseline, but there is little evidence to support this definition. In this study, the researchers sought to determine arterial blood pressure threshold values associated with cerebral desaturation in infants. NIRS monitoring was placed on 60 patients and 960 data points were recorded. The results indicate that falls in noninvasive systolic blood pressure of <20% from baseline are associated with a <10% chance of cerebral desaturation in neonates and infants <3 months of age undergoing noncardiac surgery. They conclude that maintaining blood pressure above this threshold value appears a valid clinical target. However, in an accompanying editorial, Skowno et al argue that a “dose-response” relationship must exist, with more significant desaturation, for a longer period, being associated with more neuronal damage. ⁸ Researchers in this area will need to cater to both desaturation and duration, as has been recently defined and reported in a clinical trial in neonatal ICU patients. ⁹ The third studied parameter is anatomy. In patients with single ventricle hearts, superior vena cava pressure after the bidirectional Glenn operation is usually higher than that associated with the preceding Blalock-Taussig or Sano shunt-dependent circulation. Bertolizio and colleagues studied whether this acute change in central venous pressure was associated with changes in cerebral oxygenation. ¹⁰ They found that transition from a shunt-dependent circulation to a bidirectional Glenn in infants is associated with an increase in cerebral oxygen saturation and a decrease in cerebral blood flow velocity, which is likely a response of intact cerebral autoregulation.

Although a proportion of neurological morbidity is attributable to injury occurring in the perioperative period, there is increasing evidence that CHD is associated with fetal brain dysmaturation. Sun and colleagues report a new magnetic resonance imaging (MRI) technology that offers the potential to investigate the relationship between fetal hemodynamics and brain dysmaturation. ¹¹ They measured fetal brain size, oxygen saturation, and blood flow in 30 late gestational fetuses with CHD and 30 normal controls using phase-contrast MRI and T2 mapping. They found, in fetuses with CHD, reductions in umbilical vein oxygen content and failure of the normal streaming of oxygenated blood from the placenta to the ascending aorta were associated with a mean reduction in ascending aortic saturation of 10%, whereas cerebral blood flow and cerebral oxygen extraction were no different from those in controls. This accounted for the mean 15% reduction in cerebral oxygen delivery and 32% reduction in cerebral oxygen consumption in CHD fetuses, which were associated with a 13% reduction in fetal brain volume. The study authors raise the possibility that in utero brain development could be improved with maternal oxygen therapy.

In the adult literature, a wide interindividual variability in the mean arterial pressure (MAP) at the lower limit of cerebral blood flow autoregulation during cardiopulmonary bypass (CPB) has been found, ranging from 40 to 90 mm Hg. Furthermore, the duration and magnitude that MAP is below or above the limits of cerebral autoregulation are associated with the risk of major morbidity and mortality as well as delirium. This suggests that MAP management based on physiological end points derived from cerebral blood flow autoregulation monitoring would more likely ensure cerebral and other organ perfusion during CPB than the current standard of care. Hori and colleagues used an innovative ultrasound-tagged near-infrared spectroscopy (UT-NIRS) method to measure cerebral microcirculatory flow and monitoring of cerebral autoregulation. ¹² When compared to the current standard of transcranial Doppler (TCD) monitored cerebral blood flow autoregulation there was good correlation. TCD is difficult to apply continuously whereas UT-NIRS is noninvasive with adhesive sensors, and continuous. This may offer significant advantages as a next-generation monitor of cerebral perfusion. In an accompanying editorial, Brady et al argue that like many new technologies in anesthesiology, it will be difficult to show that such a monitor improves patient outcomes, but not to adopt such technologies may deny some patients scientifically guided patient-specific anesthesia care. ¹³

Cardiopulmonary Bypass and Anticoagulation

This year, 3 reviews on pediatric CPB challenge us to think about novel cardiac and end-organ protective strategies during cardiac surgery.^14-16 The authors in all 3 reviews make the point that most patients have an uneventful CPB course during cardiac surgery. However, as we strive to improve outcomes in the higher risk patients, our efforts should include specific goal-directed, organ-targeted strategies. We need to better understand who the high-risk patients are and intervene more proactively. Possible strategies include the greater use of smaller volume heparin-coated CPB circuits, the administration of statins for their anti-inflammatory properties, and exploring the antioxidant and myocardial protective effects of inhalational and intravenous anesthetic agents. Utilization of pharmacological and ischemic preconditioning techniques and the administration of anesthetic agents in cardioplegia solutions may all further protect the myocardium compared to current strategies. Current cardioplegia techniques have been the subject of further investigation. Davidson and colleagues report on the technique of antegrade cardioplegia during congenital heart surgery. ¹⁷ Using transesophageal echocardiogram with Doppler, they showed an increase in left anterior descending coronary artery blood flow velocity following the use of antegrade cardioplegia in the immediate post-CPB period. The authors propose that this phenomenon may be related to the number of doses of cardioplegia and subsequent changes in coronary endothelial autoregulation.

There is a growing trend toward normothermic CPB for the repair of congenital cardiac defects in infants and children, with several studies investigating and advocating the safety of this practice.^18-21 Xiong and colleagues conducted a systematic review and meta-analysis of the benefits and risks of pediatric normothermic CPB compared to hypothermic CPB, and they identified 419 patients in 7 studies. ¹⁹ They acknowledge the limitations of very few published studies, small sample sizes, variable study quality, and an inconsistent definition of hypothermia. However, despite these significant limitations, they conclude that normothermic CPB is as safe as hypothermic CPB in pediatric patients undergoing surgical correction of simple congenital heart defects. This study was accompanied by a thought-provoking editorial suggesting that the end-organ protection benefits of mild to moderate hypothermia (32-35°C) are indeed beneficial during CPB-associated ischemic events, such as accidental aortic cannulation dislodgement, particularly in complex cardiac surgical repairs. ²² Therefore, before adopting normothermic CPB, large randomized controlled trials in patients with CHD need to be conducted. One such trial has been designed and is currently underway. ²⁰ Normothermic CPB is receiving greater attention as an alternate CPB strategy due to emerging reports of the deleterious effects of too rapid warming on the hypothermic brain. One study in adults showed a 3.9% incidence of stroke in 152 patients when the rate of rewarming was 0.3°C/min versus 0.2°C/min. ²³ In this study, cerebral ischemia was also assessed by measuring the release of a brain injury biomarker called astrocyte glial fibrillary acid protein (GFAP). Previously, GFAP has been shown to be elevated in children undergoing extracorporeal membrane oxygenation in association with acute brain injury and death. ²⁴ This year a study found GFAP was elevated in association with first-stage palliation of hypoplastic left heat syndrome. ²⁵

Managing the coagulation system in pediatric cardiac surgical patients in conjunction with perfusion is one of the roles of the cardiac anesthesiologist. Techniques utilized often depend on local institutional research and practice preferences, blood product availability, and what point of care testing is available. Fortunately, literature is emerging to help guide us more clearly in hemostasis management. Patients with long-standing cyanotic CHD, hypoxia, secondary erythrocytosis, and changes in their coagulation systems can be challenging to manage in the cardiac operating. A recent review explores these topics highlighting the need for a comprehensive perioperative plan to ensure there is no untoward bleeding or thrombosis following cardiac surgery. ²⁶ Another review examines the ability of tests of hemostasis to predict bleeding disorders in children, concluding that there are no currently available tests or devices to adequately predict which children will bleed abnormally during general surgery. ²⁷ Anticoagulation and hemostasis management during CPB is also challenging because infants with CHD, particularly those with cyanotic single ventricle physiology, have been shown to have significantly lower antithrombin levels than older children and adults. This persists during at least the first year of life as the coagulation system matures.^28,29 Administration of large volumes of fresh frozen plasma, which only contains 1 U/mL of antithrombin, is therefore not a practical solution to treat heparin resistance in infants and small children on CPB. ²⁹ In a recent heparin-based CPB anticoagulation study, 52% of infants required additional heparin to achieve adequate anticoagulation, which confirms that heparin anticoagulation efficacy in children on CPB is directly related to antithrombin levels.^29,30 One possible practice change in CPB anticoagulation management for select patients will be individualized patient heparin resistance assessment, followed by goal-directed antithrombin replacement therapy.^29-32

The process to improve the quality of anticoagulation, which is essential for CPB surgery, is being accompanied by greater availability of point of care testing providing better assessments of hemostasis. Investigators are increasingly finding novel ways to understand the hemostasis parameters during cardiac surgery in children more thoroughly. One group found the use of the HMS Plus Hemostasis Management System (HMS, Medtronic, Inc, Minneapolis, MN) in children less than 10 kg undergoing cardiac surgery decreases the incidence of the activated clotting time (ACT) <480 seconds by 61% and eliminates 100% of ACT values less than 400 seconds at any time during CPB. ³³ Another group of investigators studied the speed and quality of clot formation and fibrinolysis. They used velocity curves to plot total thrombus formation and maximal rate of thrombus formation utilizing rotational thromboelastometry (ROTEM, TEM; International GmbH, Munich, Germany). These authors also looked at the role of tranexamic acid to abolish fibrinolysis in the presence of tissue-type plasminogen activator. ³⁴ These studies are paving the way for further clinical studies that will predict subtle coagulation changes and minor degrees of fibrinolysis in patients during cardiac surgery.^35,36

Ongoing research in antifibrinolysis is important since aprotonin was removed from the US market in 2007. Since that time clinical studies on the use of tranexamic acid and ε-aminocaproic (EACA) have increased. This year, one study showed the rate of clearance of EACA is reduced in neonates compared to older children and adults. ³⁷ In this study, modeling demonstrated that a loading dose regimen of 40 mg/kg and an infusion of 30 mg/kg/h with a CPB pump prime of 100 mg/mL would maintain a plasma concentration of EACA greater than 50 mg/L in 90% of neonates during CPB. While adults require 130 mg/mL of EACA in plasma to inhibit fibrinolysis, the dose in neonates is 50 mg/mL. ³⁸ Despite the small number of patients in this study, it has prompted practice changes in a number of centers performing neonatal cardiac surgery. Interestingly, a retrospective study has demonstrated the safety of aprotonin in comparison to tranexamic acid in 552 consecutive neonates during surgery from 2003 to 2008 at a single institution. There was no increased risk of kidney injury with aprotonin, and there was a decreased requirement for blood product transfusion compared to tranexamic acid. ³⁹

Minimizing the transfusion of blood products during CPB remains an important goal. One recent retrospective study of 209 patients found that 81/136 (60%) of children weighing more than 6 kg undergoing biventricular cardiac repair on CPB received no blood products at all during their hospitalization. ⁴⁰ In their clinical practice, these authors utilize a hematocrit of 21% as a lower level transfusion threshold. An accompanying editorial cautioned on adopting too low a hematocrit transfusion threshold on CPB until further studies assess the neurodevelopmental outcomes using this lower hematocrit strategy. ⁴¹ Although fresh whole blood is not easily available at most congenital cardiac centers in the United States, a group of investigators at a single institution with the ability to administer fresh whole blood during cardiac surgery studied the administration of fresh whole blood in a cohort of 4111 children undergoing cardiac surgery over a 15-year period. ⁴² This study found a significant reduction in donor blood product unit exposure in patients less than 2 years of age receiving fresh whole blood during cardiac surgery.

Cardiac Catheterization Laboratory and Pulmonary Hypertension

Advances in technology over the past couple of decades have caused a shift in congenital cardiac catheterization from a primary focus on diagnostics to therapeutic interventions. These improvements offer all patients a wider range of nonsurgical options for the treatment of CHD. However, these therapeutic modalities may entail a higher risk of adverse events in an already complex patient population. Lam and colleagues provide a review of the latest catheterization modalities offered to patients with CHD and describe the challenges of working in the cardiac catheterization suite. ⁴³ There are currently no guidelines specific to the unique environment of the cardiac catheterization laboratory, and many cardiologists are concerned that different modes of sedation and airway management may directly affect their measurements of cardiopulmonary physiology. The heterogeneity of patients and procedures results in different approaches to sedation and airway management between and within institutions. Lin and colleagues analyzed data collected prospectively from the multicenter Congenital Cardiac Catheterization Project on Outcomes (C3PO) to address some of these issues. ⁴⁴ Data from 13 611 patients were analyzed and the researchers found 94 (0.69%) serious sedation-/airway-related adverse events. These events were more likely to occur in smaller patients under 4 kg, patients with noncardiac comorbidities, and patients with low mixed venous oxygenation. They also report that 9379 (69%) patients were initially managed with general endotracheal anesthesia, laryngeal mask airway, or tracheostomy, whereas 4232 (31%) were managed with procedural sedation without an artificial airway, of which 75 (1.77%) patients were converted to assisted ventilation/general anesthesia. Age less than 12 months, higher risk procedure, and continuous inotrope requirement were independently associated with conversion. A major limitation of this study is that the C3PO collaborative was designed by interventional cardiologists with the intent to study patient and procedural risk factors during cardiac catheterization. This data set is unable to address key questions such as the role of the specific expertise of the practitioner administering anesthesia and the anesthetic techniques used. After all, the goal of any experienced congenital cardiac anesthesiologist in the cardiac catheterization laboratory is to provide a balanced anesthetic to achieve hemodynamic stability, which is similar to the patient’s awake, baseline state. This may be achieved in many different ways with equal success. There are many studies that look at the effects of different anesthetic agents on myocardial contractility, pulmonary vascular resistance (PVR), and systemic vascular resistance (SVR). One such study this year finds that PVR and SVR were not significantly different when using propofol or isoflurane. However, the calculated resistance fraction (ratio of PVR to SVR) was lower when using propofol rather than isoflurane. ⁴⁵

This year the American Heart Association and American Thoracic Society assembled a panel of experts to publish guidelines for the management of pediatric pulmonary hypertension. ⁴⁶ The motivation for these guidelines came from the recognition that current approaches to caring for children with pulmonary hypertension have been limited by the lack of consensus guidelines. The resulting publication is a comprehensive guide to the diagnosis, classification, evaluation, and treatment of pediatric pulmonary hypertension. All centers with a large population of children with pulmonary hypertension recognize the increased risks associated with cardiac catheterization. One center has published their experience and outcomes of managing pediatric patients with pulmonary hypertension in the cardiac catheterization lab. ⁴⁷ Over the course of 5 years, 75 children with pulmonary hypertension underwent cardiac catheterization. During this time there were no deaths. Three patients who suffered adverse events had suprasystemic pulmonary arterial pressures, decreased right ventricular function, and were treatment naïve. These findings are consistent with an earlier study. ⁴⁸ One important aspect in the management of patients with pulmonary hypertension is their postprocedure disposition. There are very little data, and no guidelines, to help with the decision of whether patients can go home or should remain in the hospital overnight. Chau and colleague address this with a review of the literature and suggest that the total risk for postanesthetic adverse events includes the patient’s baseline risk factors and the incremental risks imposed by the procedure and anesthetic. ⁴⁹ The study authors provide common sense recommendations to help practitioners assess relevant risk factors to guide them in the best postoperative care of these high-risk patients. What is clear from all of these articles is the need for ongoing team work in the cardiac catheterization lab in caring for complex patients and future collaborations to develop management guidelines.

Procedural Sedation

Many young children are unable to cooperate during noninvasive imaging by laying still. This is most often seen during echocardiographic studies and cardiac magnetic resonance imaging (cMRI). Pediatric cardiac anesthesiologists are often involved in providing some form of sedation or anesthesia for these children. Two important questions that procedural sedation raises are does it improve the imaging results and what are the best drugs to use? The impact of procedural sedation on diagnostic errors in pediatric echocardiography was studied by Stern and colleagues. ⁵⁰ They found that most echocardiographic diagnostic errors among infants and young children are potentially preventable and sedation is associated with a lower likelihood of these diagnostic errors, fewer imaging quality concerns, and fewer incomplete reports. The choice of sedative drugs is limited for echocardiography studies. Two commonly used drugs are chloral hydrate and dexmedetomidine. Li and colleagues demonstrated in a prospective study of 115 children that sedation by intranasal dexmedetomidine, 3 µg/kg, is associated with a very high success rate in children undergoing echocardiography with no adverse events seen. ⁵¹ In a head to head comparison of oral chloral hydrate, 70 mg/kg, to 2 different doses of intranasal dexmedetomidine, 2 µg/kg and 3 µg/kg, Miller and colleagues found that all were effective for sedation for transthoracic echocardiographic exams with similar sedation onset, recovery times, and heart rate changes. ⁵² One of the downsides to using chloral hydrate and dexmedetomidine is the variable and prolonged recovery times. In addition, there has been concern expressed over the potential bradycardia seen with dexmedetomidine, especially during a loading dose. Subramanyam and colleagues examined whether the administration of a prophylactic anticholinergic before dexmedetomidine in pediatric imaging would blunt the hemodynamic changes seen. ⁵³ Their retrospective study concluded that there was no benefit to such a prophylactic anticholinergic drug administration. The correct dose of the anticholinergic drug, atropine, is surrounded by folklore in pediatric anesthesia. It is commonly believed that the minimum dose of atropine in children is 0.1 mg due to the risk of “paradoxical” bradycardia. In an elegant prospective clinical study in 60 infants, Eisa et al demonstrate that 5 µg/kg of intravenous atropine caused neither bradycardia nor asystole. ⁵⁴ They conclude that the risk of adhering to the erroneous 0.1 mg minimum dose of atropine is a relative overdose of atropine in very low birth weight and premature infants. Some clinicians argue that it is safest to use no medications in young infants for noninvasive imaging studies. In a 2-center study, infants under 6 months of age with complex CHD who required cMRI underwent a “feed-and-sleep” technique. ⁵⁵ This technique involves fasting the infant for 4 hours prior to the scan, placing the infant in a vacuum immobilizer, and feeding the infant just prior to the cMRI. A total of 60 infants were studied and all tolerated the procedure well with no complications. Importantly, cMRI images obtained were of sufficient quality to answer the clinical question and help with accurate cardiac diagnosis and surgical planning. The study authors argue that “feed-and-sleep” cMRI is not only safer but also more time and staff efficient compared to cMRI under anesthesia. The only limitation to this technique is that breath-holding is not possible.

Adverse Events

Patients with CHD are at increased risk of adverse events during noncardiac surgery. Certain subgroups, such as patients with single ventricle physiology or Williams syndrome, may be at particular high risk, but until new research this year, that risk was not well quantified. With respect to single ventricle physiology patients, Brown and colleagues reviewed charts on 417 patients after their first palliation and prior to bidirectional Glenn palliation. ⁵⁶ They found that the risk of a major adverse event in the perioperative period was 11.8% and there was no early mortality associated with noncardiac surgery. Future research may be able to define further subgroups within this single ventricle population who are at especially high risk for adverse events and develop methods to mitigate this risk.

Patients with Williams syndrome are at particular high risk of mortality during both cardiac and noncardiac surgery. However, there are no guidelines on how to quantify and stratify this risk. In an article by Matisoff et al, the clinical manifestations of Williams syndrome are reviewed and they propose a consensus, expert-informed method to estimate anesthetic risk based on the current literature and provide recommendations for perioperative management of this patient population. ⁵⁷ In another article, adverse events in children with Williams syndrome undergoing cardiac surgery were determined by an analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. ⁵⁸ In this multicenter analysis, major adverse cardiac events occurred in 9% of patients with Williams syndrome undergoing cardiac surgery. This applies a sobering statistic to what has been an assumed truth among congenital cardiac anesthesiologists, namely, that from initial anesthetic induction to ultimate hospital discharge, children with Williams syndrome are at high risk for an adverse cardiac event.

With an increasing number of children with CHD surviving to adulthood, there have been few studies that look at the risk of perioperative morbidity and mortality in this adult population. A retrospective structured analysis of cases from the Anesthesia Closed Claims Project examined perioperative factors that contributed to an adverse event in adults with CHD undergoing cardiac and noncardiac procedures. ⁵⁹ The study found that out of 21 confirmed cases, 11 (52%) involved cardiac procedures and 10 (48%) noncardiac procedures. The most common factors contributing to the adverse event in cardiac cases were surgical technique (73%) and intraoperative anesthetic care (55%), whereas in noncardiac cases, postoperative monitoring and care (50%), CHD (50%) and preoperative assessment and optimization (40%) were most common. These results should help affirm the role of congenital cardiac anesthesiologists in the perioperative care of adults with CHD.

Pregnancy and Adult Congenital Heart Disease

The significant decline in mortality among children and adolescents with CHD is associated with an increasing prevalence of CHD in adults, particularly those with moderate or severe disease. Nasr and Kussman provide an overview of CHD-associated factors that need to be considered in this patient population. ⁶⁰ In addition to the specific cardiac defect, the proposed procedure, and the patient’s current pathophysiological state, several other factors should be considered in the perioperative management of the adult with CHD. These include the type of setting (adult vs pediatric institution); coexisting diseases such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; and acquired diseases of aging and pregnancy. Many teenagers and young adults are lost to follow-up during their transition to adulthood. Nationally there is a shortage of adult CHD programs and there is still debate on the format these programs should take. Said et al point out that a careful transition from pediatric to adult care providers is important to avoid issues related to loss of continuity of care and any undue financial or psychological burdens to the patients and their families. ⁶¹

Adult patients with CHD who present with pregnancy also represent an opportunity to reestablish longitudinal adult congenital cardiac care. This year there were many excellent reviews of managing the adult with CHD and pregnancy.^62-65 These reviews agree on many principles of managing this population, especially the importance of multidisciplinary preconception evaluation and planning. Often this evaluation and planning occurs after the patient is pregnant, and it is essential that cardiologists, obstetricians, and anesthesiologists work together and understand the pathophysiological implications of the CHD. For women with complex CHD, pregnancy poses an increased risk for both the mother, with complications of arrhythmias and heart failure being most common, and the baby, with a higher chance of miscarriage, intrauterine growth retardation, and the need for early delivery. All 4 reviews discuss specific congenital heart lesions and provide recommendations for their management in the pregnant patient.

Two original research articles provide data on medical and obstetric outcomes among pregnant women who have CHD. Thompson and colleagues used the 2000 to 2010 Nationwide Inpatient Sample to examine associations between CHD and complications. ⁶⁶ They found there was a significant linear increase in the prevalence of CHD from 6.4 to 9.0 per 10 000 delivery hospitalizations. The data were not able to determine whether correction of the cardiac lesion affected outcomes but it did show these hospitalizations have a high burden of medical and obstetric complications. Sometimes “big data” does not produce the granularity that is most useful to clinicians. In a retrospective study, Warrick and colleagues undertook a retrospective cohort study of women with CHD who delivered at a single institution. They identified 117 pregnancies in 110 women with CHD. They found that most women tolerated pregnancy with few complications. Parturients with CHD were more likely to have operative vaginal deliveries, neonatal ICU admissions, and had prolonged hospital stays. Occurrence of CHD in neonates was 6%, which is in keeping with national estimates of 4% to 9%. They report an incidence of cardiac complications of 11% including arrhythmias, pulmonary edema, and congestive heart failure. Most deliveries were performed with neuraxial analgesia (86%) in their study cohort, which is comparable with similar studies. Early initiation of neuraxial analgesia is recommended in women with CHD to prevent the cardiovascular stress arising from unmedicated pain. ⁶⁷ This is further reinforced by studies that report the successful use of neuraxial anesthesia in patients with Fontan physiology.^65,68

Fontan Physiology and Right Ventricular Failure

After 40 years of surgery creating the Fontan circulation, a lot is now known about the unique physiological challenges of the single ventricle. A recent review highlights many of the problems faced by anesthesiologists caring for patients with the Fontan circulation. ⁶⁹ Any attempts to recruit ventricular stroke work or preload with increased intravascular fluid administration ends up costing the ventricle the same in terms of an increased afterload. It is not possible to increase preload to the single ventricle without making that ventricle work harder to maintain cardiac output across the pulmonary vascular bed. This is because one ventricle has to maintain cardiac output through 3 resistances in series: the systemic vascular resistance, the cavopulmonary connection resistance, and the pulmonary vascular resistance. Patients with a single ventricle function at a higher systemic and venous vascular resistance and their cardiac output is very susceptible to lowering of these resistances compared to patients with 2-ventricle physiology.

Heart failure in children with CHD is of growing concern. In patients with 2-ventricle cardiac surgical repairs, the chronic failing right ventricle does not respond to tried and tested adult therapeutic interventions for the failing left ventricle such as angiotensin-converting enzyme inhibitors, aldosterone antagonists, or β-blockers. ⁷⁰ Acute right ventricular failure due to pulmonary hypertension usually responds better with measures aimed at supporting the right ventricle with inotropes and lowering the pulmonary vascular resistance with agents like inhaled nitric oxide. Whether the administration of intravenous milrinone in acute right ventricular failure significantly improves right ventricular myocardial function has been debated. To help answer this question, a study of pulmonary artery banded pigs assessed after 10 weeks of banding has shown that the administration of milrinone does increase cardiac index significantly due to a 20% increase in heart rate with improved left ventricular diastolic function and maintenance of mean arterial pressure. Interestingly in this study, dopamine seemed to improve the right ventricular function to a greater extent than epinephrine. ⁷¹ Detecting acute or chronic right ventricular failure in children with CHD can be difficult until it is very severe. One group of researchers used a noninvasive measure of liver stiffness, transient elastography, and showed it to correlate with central venous pressure. ⁷² This could become a useful noninvasive screening tool to detect changes in right ventricular myocardial function before overt clinical signs of right ventricular failure develop.

Conclusion

It is encouraging to see so many publications this year that continue to advance the perioperative care of patients with CHD. In addition to the publications cited in this review article, there has also been 2 excellent “mini-series” on the multidisciplinary care of specific congenital heart lesions that should be mentioned: transposition of the great arteries^73-75 and Ebstein’s anomaly.^76,77 The congenital cardiac forum section of this journal was started to include the “medical village” of health care providers that it now takes to care for patients with CHD from “before the cradle” to the “grave.” ⁷⁸ The growing body of literature, some of it reviewed here for the year 2015, is evidence that we are taking steps in the right direction to shape the future care for all patients with CHD.