The Year in Review: Anesthesia for Congenital Heart Disease 2021

Abstract

This review focuses on the literature published during the calendar year 2021 that is of interest to anesthesiologists taking care of children and adults with congenital heart disease. Four major themes are discussed, including cardiovascular disease in children with COVID-19, aortic valve repair and replacement, bleeding and coagulation, and enhanced recovery after surgery (ERAS).

Keywords

anesthesia cardiac surgery aortic valve pediatric cardiology congenital heart disease bleeding coagulation research corona virus 2019 enhanced recovery after surgery

Introduction

The 2021 literature was searched via the US National Library of Medicine PubMed database using the terms congenital heart disease (CHD), anesthesia, cardiac surgery, cardiopulmonary bypass (CPB), pediatric cardiology, adult congenital heart disease, coagulation, and COVID-19. From the resulting articles, we chose 4 prominent themes to highlight: cardiovascular disease in children with COVID-19, aortic valve repair and replacement, bleeding and coagulation, and enhanced recovery after surgery (ERAS). This review will highlight relevant research in these areas.

COVID-19 and Cardiovascular Disease in Children

The effects of COVID-19 and COVID-19 vaccines on the cardiovascular system

The SARS-CoV-2 virus is unusual among coronaviruses in its frequent association with cardiovascular and thromboembolic complications. (Table 1) The virus may damage myocardial and vascular cells either directly or as a secondary effect of a maladaptive hyperinflammatory immune response. Cardiovascular damage from COVID-19 is relatively common in adults of all ages and elevated cardiac enzymes have been demonstrated in up to 20% of hospitalized adults with COVID-19.¹ In children, infection with SARS-CoV-2 can also result in a post-infectious Multisystem Inflammatory Syndrome in Children (MIS-C) which typically presents 2–6 weeks after initial infection. MIS-C shares many features with severe acute COVID-19 and can present with ventricular dysfunction, coronary aneurysms, and cardiovascular shock along with other non-cardiovascular manifestations. Feldstein et al evaluated the characteristics and outcomes in children and adolescents with MIS-C and severe acute COVID-19. Compared to children with severe acute COVID-19, children with MIS-C were younger, more likely to be non-Hispanic black, and more likely to have cardiorespiratory (56 vs 8.8%) or cardiovascular without respiratory involvement (10.6 vs 2.9%). Children with severe acute COVID-19 were more likely to have respiratory without cardiac involvement. Forty-five percent of patients with MIS-C vs 9% of patients with severe acute COVID-19 required vasopressor support. Mortality rate was similar; 1.9% of the children with MIS-C and 1.4% of the children with severe acute COVID-19 died during the hospitalization. Of the children with MIS-C with reduced ventricular function (34%) and coronary aneurysms (13.4%), 91 and 79.1%, respectively, normalized within 30 days.²

Table 1.

Key 2021 Articles on COVID-19 and Heart Disease.

Author	Title	Key Points
Feldstein et al	Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19.	Cardiovascular involvement much more common in MIS-C than severe acute COVID-19. Similar mortality rate for MIS-C and severe acute COVID-19. In a majority of children with MIS-C, ventricular function and coronary aneurysms normalized within 30 days.
Shimabukuro	June 23, 2021 ACIP Meeting Slides	Increased risk of myocarditis after mRNA vaccination, especially in young males.
Broberg et al	COVID-19 in Adults With Congenital Heart Disease.	Overall COVID-19 mortality rate in adults with CHD similar to general population. Highest risk in eisenmenger, cyanosis, PHTN.
Strah et al	Worse Hospital Outcomes for Children and Adults with COVID-19 and Congenital Heart Disease.	Children with CHD hospitalized with COVID-19 had longer LOS, higher complications rate, and higher mortality.
Bottio et al	COVID-19 in Heart Transplant Recipients: A Multicenter Analysis of the Northern Italian Outbreak	Heart transplant patients have higher prevalence of COVID-19 infection and higher case fatality rate.
Itzhaki et al	Immunogenicity of the BNT162b2 mRNA vaccine in heart transplant recipients—a prospective cohort study.	Heart transplant patients have reduced antibody response to immunization.
Joshi et al	Coronavirus disease 2019 convalescent children: Outcomes after congenital heart surgery	Patients infected with COVID-19 in the post-op period had 46% mortality rate. Recovered COVID-19 infection did not increase risk. COVID-19 reduced surgical volume and shifted case mix toward higher acuity.

CHD, congenital heart disease; PHTN, pulmonary hypertension.

Although vaccination has dramatically reduced the risk of morbidity and mortality from COVID-19, mRNA vaccines have been shown to be associated with cardiovascular complications in certain groups of patients. Utilizing safety data generated by the Vaccine Adverse Event Reporting System (VAERS) for vaccine doses administered prior to June 11, 2021, the Advisory Committee on Immunization Practices (ACIP) found 1,226 reports of myocarditis, most occurring 2–3 days after the second vaccine dose. Overall, the rate of reported myocarditis was 18.1 per million doses in 12–17 year olds and 15.9 for 18–24 year olds with a dramatically higher reporting rate in young males vs young females.³ (Table 2) Other sources have confirmed these preliminary findings. The United States military reported an incidence of 8.2 cases of myocarditis per 100,000 male service members and an Israeli study utilizing a large national data set demonstrated an average of 2.7 cases of myocarditis per 100,000 vaccinated patients overall.^4,5

Table 2.

Myocarditis/Pericarditis risk following mRNA COVID-19 Vaccination.

Age Group	Reporting Rate, all (per Million doses)	Reporting Rate, Females (per Million Doses)	Reporting Rate, Males (per Million doses)
12–17 yrs	18.1	4.2	32.4
18–24 yrs	15.9	3.6	30.7
25–29 yrs	6.7	2.0	12.2
30–39 yrs	4.2	1.8	6.9
40–49 yrs	2.7	2.0	3.5
50–64 yrs	1.7	1.6	1.9
65+ yrs	1.1	1.1	1.2

Based on data from VAERS through June 11, 2021, reported by the CDC.

Unlike the cardiovascular manifestations of COVID-19, vaccine-related myocarditis is generally benign and self-limited. Thus, comparison of the rates of complications and associated morbidity of vaccination vs COVID-19 infection clearly favors universal vaccination in teenagers and young adults.¹

COVID-19 in Congenital Heart Disease

As baseline hypertension and cardiovascular disease are thought to play a role in COVID-19 related cardiac complications, pediatric and adult patients with congenital heart disease (CHD) may be at increased risk of morbidity and mortality. In a large study from 58 international adult CHD centers including patients with various type of CHD, Broberg et al found a COVID-19 case fatality rate of 2.3%, similar to the cumulative case fatality rate across all global populations. Male sex, diabetes, cyanosis, pulmonary hypertension, renal disease, heart failure, and higher physiologic disease stage were associated with increased risk of mortality in this population, whereas anatomic complexity, type of defect, systemic ventricular dysfunction, and systemic hypertension were not. The highest risk of mortality was observed in patients with Eisenmenger physiology (13%), cyanosis (12%), and pulmonary hypertension (10%).⁶

In a database study from the United States, Strah et al demonstrated that children with CHD are at higher risk of COVID-19 complications than healthy children. In their cohort of nearly 10,000 children hospitalized with COVID-19, children with CHD had a longer length of stay (22 vs 6 days), higher complication rate (6.9% vs 1.1%), and higher mortality (3.8% vs .8%).⁷

COVID-19 in Heart Transplant Patients

Patients who have undergone heart transplantation represent a particularly high-risk group for complications from COVID-19 infection due to their comorbidities and immunosuppression. In one study conducted by Bottio et al⁸ during the height of the pandemic in Northern Italy before the introduction of vaccines, heart transplant patients had both a higher prevalence of infection (18 vs 7 cases per 1,000) and higher case fatality rate (29.7 vs 15.4%) compared to the general population.

Ideally, the availability of effective vaccines should substantially decrease the risk of mortality, but unfortunately there is significant evidence that transplant patients mount a suboptimal response to vaccination. Itzhaki et al studied the antibody response to vaccination in 42 heart transplant patients who received the Pfizer vaccine. They demonstrated that only 15% of patients had positive antibody titers after the first dose and only 49% had positive titers in response to the 2-dose vaccination series. Anti-metabolite immunosuppression (mycophenolate mofetil) was associated with decreased immunogenic response to vaccination.⁹ However, there is emerging evidence that a third vaccine dose enhances the immunogenic response in solid organ transplant recipients and may help improve outcomes in this vulnerable group.¹⁰

COVID-19 in Heart Surgery

The COVID-19 Pandemic has had a profound effect on hospital resource utilization and surgical case volumes around the world. Joshi et al conducted a survey of congenital heart surgery programs in Brazil and found that nearly all centers experienced decreased surgical volume with over 70% of programs reporting significantly decreased volume, resulting in a shift in case mix toward more complex surgery with an associated increase in mortality rates. The authors also evaluated the impact of preoperative and postoperative COVID-19 infection on surgical outcomes. They found that children who have previously recovered from COVID-19 had no higher rate of adverse surgical outcomes than children without recent COVID-19 infection; however, in patients who were infected with COVID-19 in the postoperative period, the mortality rate was 46%.¹¹ (Table 2)

Aortic Valve Procedures

The surgical treatment of aortic valvulopathies in children and adults has recently been transformed by new and improved versions of old procedures such aortic valve repairs, the Ozaki procedure, and the Ross procedure (Table 3).

Table 3.

Key 2021 Articles on Aortic Valve Procedures.

Author	Title	Key Points
Wallace et al	Aortic valve repair in children without use of a patch.	More durable aortic valve repairs in pediatric patients without the use of patch material. Repairs can delay more definitive aortic valve procedures especially in infants and older children.
Si et al	Unicuspid Aortic Valve Repair Using Geometric Ring Annuloplasty.	Excellent results for repairing unicuspid aortic valve disease in 20 young patients using a reproducible technique.
Baird et al	Congenital aortic and truncal valve reconstruction using the Ozaki technique: Short-term clinical results	For the Ozaki Procedure, younger age at surgery was associated with increased risk of AS. Low dose warfarin may be needed to prevent leaflet dysfunction.
Aboud et al	Long-Term Outcomes of Patients Undergoing the Ross Procedure	Excellent survival over a 25-year follow-up. Rates of re-intervention and endocarditis were low.
Stelzer et al	Operative risks of the Ross procedure.	Excellent operative results for the ross even when re-operation or concomitant procedures are required.
Romeo et al	Long-term Clinical and Echocardiographic Outcomes in Young and Middle-aged Adults Undergoing the Ross Procedure.	Excellent short- and long-term outcome for Ross procedures performed in young and middle-aged adults at experienced centers.

AS, aortic stenosis.

Mechanical and bioprosthetic aortic valves and aortic homografts have been used reliably for years with apparently good results. Mechanical valves have been touted as the valve of choice in pediatric patients whenever possible because of their durability, but long-term data demonstrates that these valves are associated with decreased long-term survival and increased morbidity.^12,13 Mechanical aortic valve replacement in young patients has a major impact on the duration and quality of life. Patients fall off their expected survival curves within 10–17 years of surgery compared to their peers due to complications of additional cardiac operations, endocarditis, valve thrombosis, and anticoagulation.^12,14,15 (Table 4)

Table 4.

Comparison Between Aortic Valve Replacement Options.

Valve Type	Effective Orifice Area	Thrombo-Embolic Risk	Endocarditis Risk	Durability	Misc
Valve repair	Variable	Minimal	Minimal	Finite in young patients, good in older patients	• Growth potential
Valve repair	Variable	Minimal	Minimal	Finite in young patients, good in older patients	• Steep learning curve
Ozaki	Good	Mild-moderate	Data accruing	Finite and likely shorter in pediatric patients	• No growth potential
Ozaki	Good	Mild-moderate	Data accruing	Finite and likely shorter in pediatric patients	• Steep learning curve
Ross	Excellent	Minimal	Minimal	Good in older patients and likely younger patients	• Growth potential
					• Requires a pv autograph w/o disease (not possible in TA, TOF rarely ASO)
					• may require konno
					• Conduit and pulmonary valve replacement
					• Excellent quality of life
					• Steep learning curve
Mechanical	Decreased and worsens with somatic growth	High	Moderate	Limited	• No growth potential
					• may require konno
					• Requires full anticoagulation
					• Predicable results and easier insertio
Bioprosthetic	Significantly decreased (especially small valve sizes), worsens with somatic growth	Minimal	Moderate	Very limited	• No growth potential
					• may require konno
					• Predicable results and easier insertion
Homograft	=native	None	Minimal	Very limited	• Graft calcifies increasing risk on re-entry
					• Growth potential
					• Intermediate complexity (between mechanical and ross)

pv, pulmonary valve; TA, truncus arteriosus; TOF, Tetralogy of Fallot; ASO, arterial switch operation.

Aortic Valve Repair

Aortic valve repair theoretically offers an ideal solution for pediatric patients. However, despite acceptable early results, long-term results have historically been less promising with some series reporting a reoperation rate as high as 46% at 7.5 years.¹⁶ A group in Melbourne recently demonstrated improved long-term results for aortic valve repair in 102 patients including 25 neonates and 17 infants. Only 47% of those operated on as neonates and 40% of those operated on as infants or older children required a second aortic valve procedure (usually a Ross) at 15 years. Neonatal survival was 98% at 10 years and survival for the entire cohort was 95% at 15 years.¹⁷ The authors recommend initial surgical repair over transcatheter procedures in very young patients because the valve is less likely to be repairable after balloon dilation, and surgical repair has been shown to delay the need for subsequent intervention compared to balloon valvuloplasty.¹⁸ Importantly, re-operative surgery was delayed for 7 years even in patients with only suboptimal repair. This surgical approach is reminiscent of the treatment strategies employed for mitral valve disease in pediatric patients.

In adolescents and young adults, aortic valve repair techniques with or without root replacement are now being performed routinely in patients with aortic insufficiency (AI) secondary to unicuspid and bicuspid valve disease with excellent early and late results.^19,20

Ozaki Procedure

The Ozaki procedure uses a template to create a neoaortic valve from bovine pericardium or glutaraldehyde treated autologous pericardium which is then sewn to the native aortic root, maximizing the effective orifice area. Baird et al report on short-term results with this procedure in 57 patients aged .7-25 years, with a mean age of 12 years. They reported an 88% freedom from moderate or greater AI or aortic stenosis (AS) at 2 years and 91% freedom from reoperation at 1.5 years. Notably, the 4 patients with post op moderate AS all had their procedures at a younger age compared to those without AS.²¹ Ozaki recently reported on 850 adult patients. There was 96% freedom from reoperation and 93% freedom from moderate or greater AI at a mean follow up of 53 months.²² However, there are concerns about performing this procedure in pediatric patients as there is no growth potential of the leaflets, and valve degeneration and calcification are likely similar to bioprosthetic valves. It is also important to note that this procedure may not eliminate the need for warfarin anticoagulation. There has not yet been sufficient follow up in children to endorse this procedure over a Ross or mechanical valve replacement.²³

Ross Procedure

There has been a resurgence of enthusiasm for the Ross procedure based on multiple reports of excellent short- and long-term results.^13,24,25 Major concerns include the high surgical complexity and risk of degeneration of the aortic autograft and the pulmonic homograft. However, surgical improvements that limit dilation of the autograft, the use of acellular homografts, and the availability of percutaneous pulmonic valve replacement address some of these limitations. Romeo et al evaluated the long-term mortality and re-intervention data on 1431 patients between 18 and 65 years undergoing the Ross procedure in 5 experienced centers. Early post op mortality was .7%, and 10 and 15 year survival was 95.1 and 88.5%, respectively. Freedom from autograft and homograft intervention was 92 and 97%, respectively, during that time.²⁶

Conclusion

In summary, recent research suggests that whenever possible a valve repair is preferred over valve replacement. AI is more treatable with valve repair in older patients whereas AS in this group often requires valve replacement. In young children, an adequate result is acceptable as it delays the need for re-operative surgery. When valve repair fails or is not feasible, a Ross procedure is likely the next best option with good quality of life and similar life expectancy to that of sex- and age-matched controls for at least 15 years after surgery. The role of the Ozaki procedure is unclear at this time, but it may play a role in children with truncal valve disease where the Ross procedure is not an option.

Bleeding and Coagulopathy

Perioperative bleeding and coagulopathy remain a significant source of morbidity and mortality in congenital cardiac surgery. Data from the National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III from 2013 to 2016 show that children undergoing CBP are frequently transfused. Of 185 single ventricle patients, 81% received red blood cells (RBCs), 79% received platelets, 86% received plasma, and 56% received cryoprecipitate. Patients in this cohort were transfused at a median intraoperative hemoglobin of 13.5 g/dL.²⁷

Antifibrinolytic Dosing

Antifibrinolytic medications such as tranexamic acid (TXA) and aminocaproic acid have become mainstays in cardiac surgery. Despite their widespread use, there remains considerable dosing heterogeneity in pediatrics. Siemens et al evaluated the efficacy of high-dose (>50 mg/kg cumulative) and low-dose (<50 mg/kg cumulative) TXA regimens in a systematic review and meta-analysis of 12 randomized controlled trials. While there was a larger decrease in postoperative blood loss in the higher dose group (10 vs 5.4 mL/kg), the reduction was not statistically significant. Both dosing strategies led to a reduction in RBC and FFP transfusion compared with placebo. There was also no difference is transfusion between patients who received continuous vs bolus dosing.²⁸ A review by Hovgesen et al²⁹ of 50 studies evaluating the efficacy of different TXA doses across all pediatric surgical disciplines also demonstrated efficacy of lower dose TXA. This research supports the use of the lowest efficacious dose of TXA and highlights the need for development of a standardized dosing regimen in pediatrics.

Viscoelastic Testing

Pediatric patients, particularly neonates and young infants, frequently receive empiric transfusion of blood products after separation from bypass. Point of care viscoelastic testing using thromboelastography (TEG) or rotational thromboelastography (ROTEM) has shown promise in decreasing unnecessary transfusion of blood products by providing qualitative information regarding clot formation and stability.³⁰ While these tests can help distinguish between coagulopathy and inadequate surgical hemostasis, the tests take up to 30–45 minutes to complete, and the results may lag behind the need to make immediate clinical decisions. Visual assessment of the surgical field is often used to guide initial transfusion decisions, but visual inspection may not reliably distinguish between surgical and coagulopathic bleeding and may lead to excessive and inappropriate transfusion. In a prospective blinded study, Restin et al examined the ability of surgeons to distinguish between coagulopathic and surgical bleeding using a clinical intraoperative bleeding score. In their cohort of 49 patients, bleeding was scored numerically by the surgeon every hour and compared with simultaneous ROTEM measurements. Severe bleeding (score 5–8) was seen at 24 time points and correlated to abnormal ROTEM values only 58.3% of the time. Transfusion based on the visual bleeding score in this study would have resulted in a 1.7-fold increase in blood product administration.³¹ In a single center retrospective study of 537 surgical patients, Emani and colleagues evaluated whether early TEG testing could predict post-bypass bleeding. They found good correlation (r = .76) between rewarming and post-protamine values of maximum amplitude (MA), a marker of platelet function and fibrinogen concentration. They also demonstrated that a rewarming MA of less than 45 mm compared to an MA of 45 mm or more was associated with a 38 vs 22% incidence of attaining the composite bleeding outcome (blood product transfusion, recombinant factor VIIa use, and surgical re-exploration).³²

In addition to TEG and ROTEM, preoperative multiple impedance platelet aggregometry (Multiplate) has shown promise in predicting platelet transfusion requirements in adults undergoing cardiac surgery. Multiple studies this year investigated the role of Multiplate in pediatric cardiac surgery. Harris et al examined whether Multiplate testing preoperatively could predict bleeding in a retrospective single center cohort of 225 patients. While there was a statistically significant improvement in their predictive model using preoperative testing in combination with clinical characteristics, this translated to an increase in identification of only .9% of children at risk for bleeding intraoperatively and only .4% postoperatively.³³ Di Gregorio investigated the use of Multiplate in a retrospective case-controlled study of 31 children and found that the platelet function tests were not significantly different between bleeders and non-bleeders.³⁴ Dieu et al³⁵ investigated the use of Multiplate as a POC test post-CPB as compared to ROTEM and found no significant difference between the tests in predicting which patients required a platelet transfusion but did find an association between platelet transfusion and maximum clot firmness (MCF) (regression coefficient = −.348 [95% confidence interval −1.006 to −.028]; P = .039).

Current guidelines from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative (TAXI), Pediatric Critical Care Blood Research Network (BloodNet), and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) make a weak recommendation to use viscoelastic testing in the intraoperative and postoperative periods to guide platelet and plasma transfusion (grade 2B). The group also recommended standardization of bleeding endpoints in future studies to allow for more robust meta-analysis and comparison between studies.³⁶ (Table 5)

Table 5.

Key 2021 Articles on Bleeding and Coagulopathy.

Author	Title	Key Points
Siemens et al	Antifibrinolytic Drugs for the Prevention of Bleeding in Pediatric Cardiac Surgery on Cardiopulmonary Bypass: A Systematic Review and Meta-analysis	Similar efficacy of low-dose and high-dose TXA in pediatric cardiac surgery.
Hovgesen	Efficacy and Safety of Antifibrinolytic Drugs in Pediatric Surgery: A Systematic Review	Similar efficacy of low-dose and high-dose TXA in pediatric surgery.
Restin et al	Comparison between intraoperative bleeding score and ROTEM(R) measurements to assess coagulopathy during major pediatric surgery	Higher bleeding score based on clinical observation was correlated with abnormal ROTEM only 58.3% of the time. Transfusion based on clinical score results in 1.7x increase in blood product administration.
Emani et al	Thromboelastography During Rewarming for Management of Pediatric Cardiac Surgery Patients	Correlation between rewarming and post-protamine values of MA on TEG. Rewarming MA <45 mm vs ≥ 45 mm was associated with increased risk of transfusion, recombinant factor VIIa use, or surgical re-exploration.
Harris et al	Prediction of bBleeding in Pediatric cardiac surgery Using Clinical Characteristics and Prospective Coagulation Test Results.	Statistically but not clinically significant improvement in predictive bleeding model using multiplate testing.
Dieu et al	Combined Use of Rotational Thromboelastometry (Rotem) and Platelet Impedance Aggregometry (Multiplate Analyzer) in Cyanotic and Acyanotic Infants and Children Undergoing Cardiac Surgery with Cardiopulmonary Bypass: Subgroup Analysis of a Randomized Clinical Trial	Platelet function tests similar between bleeders and non-bleeders. No difference between ROTEM and multiplate in predicting platelet transfusion.
Cholette et al	Plasma and Platelet Transfusions Strategies in Neonates and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass or Neonates and Children Supported by Extracorporeal Membrane Oxygenation: From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding	Week recommendation to use viscoelastic testing to guide intraoperative and postoperative platelet and plasma transfusion.

TXA, tranexamic acid; ROTEM, rotational thromboelastometry; MA, maximum amplitude; TEG, thromboelastography

Enhanced Recovery After Pediatric Cardiac Surgery

Enhanced recovery after surgery (ERAS) programs are multidisciplinary, multimodal perioperative pathways which aim to expedite the patient’s return to baseline after surgery.³⁷ Improved outcomes have been demonstrated for numerous adult and pediatric surgeries, including pediatric cardiac surgery. (Table 6)

Table 6.

Key 2021 Articles on ERAS in Cardiac Surgery.

Author	Title	Summary
Fuller et al	The American Association for Thoracic Surgery Congenital Cardiac Surgery Working Group 2021 consensus document on a comprehensive perioperative approach to enhanced recovery after pediatric cardiac surgery	An evidence-based consensus document on a comprehensive perioperative approach to facilitate enhanced recovery in children after pediatric cardiac surgery
Shin et al	Target-Based Care: An Intervention to Reduce Variation in Postoperative Length of Stay	Displaying target goals for postoperative milestones at the point of care significantly reduced days of intubation and postoperative ICU and total LOS.
Li et al	Early extubation is associated with improved outcomes after complete surgical repair of pulmonary atresia with ventricular septal defect and hypoplastic pulmonary arteries in pediatric patients	Early extubation in this cohort was feasible and led to reduced LOS, reduced costs, and decreased pulmonary complications. The rate of mortality and other complications was unchanged.
Samuel et al	Intraoperative Extubation Post Arterial Switch Operation for Transposition of the Great Arteries With Intact Ventricular Septum: A One-Year, Single Center Experience	In this small cohort of 10 neonates, intraoperative extubation was associated with decreased ICU LOS. None required re-intubation, and morality and other complications were unchanged.
Murin et al	Fast-track extubation after cardiac surgery in infants: Tug-of-war between performance and reimbursement?	Fast-track extubation led to shorter ICU and hospital LOS, fewer postoperative transfusions and trend toward lower early mortality. Re-intubation rates were unchanged.
Tamariz-cruz et al	Early Extubation in a Pediatric Cardiac Surgery Program Located at High Altitude	Early extubation (81% of children) was feasible with low re-intubations at a high-altitude center (2691 m above sea level).
Miura et al	Recurrent Extubation Failure Following Neonatal Cardiac Surgery Is Associated with Increased Mortality	Neonates with a single or recurrent extubation failure have a 5-fold and 24-fold risk of mortality, respectively, compared to neonates without extubation failure.
Roy et al	Bilateral Erector Spinae Blocks Decrease Perioperative Opioid Use After Pediatric Cardiac Surgery	Bilateral erector spinae blocks were associated with a clinically small reduction in opioid use in the first 48 hours after pediatric cardiac surgery compared with a matched cohort.
Sahajanandan et al	Efficacy of paravertebral block in “Fast-tracking” pediatric cardiac surgery - Experiences from a tertiary care center	Compared to historical controls, 100 children with paravertebral blocks had lower postoperative pain scores, opioid usage, and ICU LOS.
Cakmak et al	Transversus Thoracic Muscle Plane Block for Analgesia After Pediatric Cardiac Surgery	33 children receiving transversus thoracic muscle plane block demonstrated lower intraoperative and postoperative fentanyl doses, lower pain scores, and faster extubation times.
Staveski et al	Prevalence of ICU Delirium in Postoperative Pediatric Cardiac Surgery Patients	A multi-institution study analyzed children within 30 days of cardiac surgery at a single point in time. The prevalence of delirium was 40%.
Chomat et al	Changes in Sedation Practices in Association with Delirium screening in Infants After Cardiopulmonary Bypass	A single-institution study demonstrating a 92% prevalence of delirium in infants after cardiac surgery.

ICU, intensive care unit; LOS, length of stay.

In 2021, the American Association for Thoracic Surgery (AATS) Congenital Cardiac Surgery Working Group published a consensus document on a comprehensive perioperative approach to enhanced recovery after pediatric cardiac surgery. Based on published data and expert opinion, the working group proffered 29 recommendations to facilitate enhanced recovery after pediatric cardiac surgery. The authors emphasize that ERAS programs require careful and strategic multidisciplinary planning and must be tailored to the individual institution. Once integrated, it is critical to have a quality assurance infrastructure to regularly evaluate and fine-tune each subcomponent of the ERAS program based on outcomes. Another point of emphasis, considering the high acuity and mortality inherent to congenital heart disease, is that the ERAS pathway will require modifications for individual children with mitigating risk factors (e.g.,, open chest, residual lesions, and pulmonary hypertension) or when inadequate staffing or available clinical expertise would jeopardize safety. The guidelines highly recommend immediate or early extubation as a component of ERAS in select patients and highly recommend application of protocol-based multimodal analgesia with limited intraoperative use of respiratory depressants. The authors recommend postoperative delirium screening and sedative/analgesic strategies that limit delirium. Lastly, the guidelines state that peripheral regional anesthesia or neuraxial anesthesia may be an effective opioid-sparing analgesic modality.³⁸

Target-Based Care

Shin et al instituted a target-based care intervention for ten different congenital heart surgeries. Targets of expected time to extubation, intensive care unit (ICU) length of stay (LOS), acute care LOS, and hospital LOS for each child were visibly displayed at bedside. This simple intervention, essentially a visible reminder of the timeline for milestone goals, markedly reduced interpatient variation between the pre- and post-intervention cohorts. Notably, children post-intervention had .7 fewer days intubated, .97 fewer ICU days, and 1.18 fewer total LOS days.³⁹

Early Extubation

Over the past decade, data have supported early extubation (EE) as an important component of ERAS.^38,40,41 Reported benefits across studies include decreased LOS, decreased costs, and hemodynamic benefits realized with return of spontaneous ventilation and reduced sedation. In 2021, Li et al retrospectively analyzed 113 children undergoing pulmonary atresia with ventricular septal defect (VSD) and hypoplastic pulmonary arteries at a mean age of 2.5 years old who were extubated early. The children were propensity matched with peers experiencing prolonged ventilation. EE was associated with a significant decrease of ICU LOS, hospital LOS, medical costs, and pulmonary complications.⁴² Samuel et al reported successful intraoperative extubation of 10 consecutive neonates undergoing arterial switch operation for D-transposition of the great arteries with intact ventricular septum. These patients were compared to a control group undergoing the same procedure prior to the change in extubation practice. Neonates who were intraoperatively extubated had a shorter hospital LOS with no difference in morbidity. Importantly, none of the intraoperatively extubated neonates required re-intubation.⁴³

Murin et al reported the results of 182 infants <7 kg who were fast-track extubated within 8 hours of surgery. After propensity matching to pairs who were not fast-tracked, fast-track infants had shorter ICU LOS (1.8 vs 4.2 days), hospital LOS (7 vs 10 days), lower postoperative transfusion rates: 61 vs 77%, and a trend toward lower early mortality. Reintubation rates did not differ.⁴⁴ Tamariz-Cruz et al published the outcomes of EE after pediatric cardiac surgery in the relatively high altitude of Mexico City, located at 2691 m (8828 ft.) above sea level. Of their 478 children, 66% were extubated in the operating room, and an additional 15% were extubated within 24 hours after surgery. Those who were extubated early had significantly lower mortality, reintubation, infection, and both ICU and hospital LOS. Importantly, the exclusion criteria for EE in this study included weight <10 kg, age <30 days, and CPB times >90 minutes. These exclusion criteria place those at greatest risk of prolonged hospital course and postoperative complications in the non-EE group.⁴⁵ Miura et al reported that extubation failure is associated with increased mortality following neonatal cardiac surgery. Over 1000 neonates at a single institution were studied. Predicted mortality with recurrent extubation failure it was 29%, with single extubation failure it was 6.5%, and with no extubation failure it was 1.2%. Reintubation due to cardiovascular reasons was the greatest predictor of heightened mortality.⁴⁶

Although these studies suggest a benefit to EE, the retrospective, single-institution nature of these studies presents a significant risk of selection bias. For example, a hemodynamically unstable child may be kept intubated for a longer period, and any accrued morbidity or prolonged LOS may be more accurately attributed to the cardiovascular issue rather than prolonged intubation. Without proper randomized controlled trials, we are thus left with association rather than causality between EE and improved outcomes.

Regional Anesthesia

Regional anesthesia is another important subcomponent of ERAS at many institutions. Several publications in 2021 have broadened our understanding of the role of regional anesthesia in a multimodal analgesic plan. Roy et al reported a prospective cohort study of 10 children receiving a bilateral erector spinae plane block (ESPB) with catheters at the end of surgery. Children in the ESPB cohort received less opioids in the first 48 hours, but the clinical difference was small. Pain scores were also slightly higher in the ESPB cohort at half of the time intervals during the first 48 hours.⁴⁷ While 2 prior studies have demonstrated efficacy of ESPB in cohorts of 40 and 50 children, larger studies are needed to confirm the efficacy of ESPBs in pediatric cardiac surgery.^48,49 Sahajanandan et al reported an analysis of 100 children under the age of 8 years receiving a paravertebral block (PVB) vs 100 historical matched controls undergoing a range of cardiac surgeries. In the PVB group, time to extubation and ICU LOS were shorter, intraoperative and postoperative opioid use was lower, and postoperative pain scores were lower.⁵⁰ Cakmak et al reported the efficacy of transversus thoracic muscle plane block (TTPB), a fascial plane block which provides analgesia of the anterior branches of the T2 to T6 intercostal nerves. Thirty-three children received a single-shot TTPB (.25 mL/kg of .25% bupivacaine bilaterally between fourth and fifth ribs) prior to sternotomy and were compared to 37 children without the block. Pain scores were significantly lower in the TTPB group despite receiving significantly lower intraoperative doses of fentanyl. The time to extubation was also significantly lower in the TTPB group than in the non-TTPB group.⁵¹

Post-Operative Delirium

Two publications in 2021 studied the burden of delirium after pediatric cardiac surgery. Staveski et al prospectively enrolled 181 children at 27 North American cardiac ICUs, and a 1 day, point-prevalence study of delirium was conducted on all children who had undergone cardiac surgery in the past 30 days. The spot prevalence of delirium was 40%. Modifiable risk factors associated with a positive delirium screen were higher pain score at time of screen, total opioid exposure, pain medication or sedative administered in the previous 4 hours, no progressive physical therapy or ambulation schedule, and parents absent from the bedside.⁵² Chomat et al⁵³ reported a delirium prevalence of 92% in infants after cardiac surgery, supporting prior research stating infants are at the highest risk for delirium after CPB.

Additional data are needed to guide intraoperative and postoperative multimodality analgesic and sedation regimens that limit delirium, improve LOS, and lead to increased patient and family satisfaction.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Faith J Ross

Denise C Joffe

Gregory J Latham

References

Bozkurt

Kamat

Hotez

. Myocarditis with COVID-19 mRNA vaccines. Circulation. 2021;144(6):471-484.

Feldstein

Tenforde

Friedman

, et al Characteristics and outcomes of us children and adolescents with multisystem inflammatory syndrome in children (MIS-C) compared with severe acute COVID-19. JAMA. 2021;325(11):1074-1087.

Shimabukuro

. cdc.gov. CDC; 2021. Available from: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-06/03-COVID-Shimabukuro-508.pdf.

Montgomery

Ryan

Engler

, et al Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military. JAMA Cardiology. 2021;6(10):1202-1206.

Barda

Dagan

Ben-Shlomo

, et al Safety of the BNT162b2 mRNA Covid-19 vaccine in a nationwide setting. N Engl J Med. 2021;385(12):1078-1090.

Broberg

Kovacs

Sadeghi

, et al COVID-19 in adults with congenital heart disease. J Am Coll Cardiol. 2021;77(13):1644-1655.

Strah

Kowalek

Weinberger

, et al Worse hospital outcomes for children and adults with COVID-19 and congenital heart disease. Pediatr Cardiol. 2021;43(3):541–546.

Bottio

Bagozzi

Fiocco

, et al COVID-19 in heart transplant recipients. JACC (J Am Coll Cardiol): Heart Fail. 2021;9(1):52-61.

Itzhaki Ben Zadok

Shaul

Ben-Avraham

, et al Immunogenicity of the BNT162b2 mRNA vaccine in heart transplant recipients - A prospective cohort study. Eur J Heart Fail. 2021;23(9):1555-1559.

10.

Kamar

Abravanel

Marion

Couat

Izopet

Del Bello

. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med. 2021;385(7):661-662.

11.

Joshi

Keshava

Murthy

, et al Coronavirus disease 2019 convalescent children: Outcomes after congenital heart surgery. Cardiol Young. 2021; 1–6.

12.

Alsoufi

Knight

St. Louis

Raghuveer

Kochilas

. Are mechanical prostheses valid alternatives to the ross procedure in young children under 6 years old? Ann Thorac Surg. 2022;113(1):166-173.

13.

Sharabiani

MTA

Dorobantu

Mahani

, et al Aortic valve replacement and the ross operation in children and young adults. J Am Coll Cardiol. 2016;67(24):2858-2870.

14.

Buratto

Shi

Wynne

, et al Improved survival after the ross procedure compared with mechanical aortic valve replacement. J Am Coll Cardiol. 2018;71(12):1337-1344.

15.

Bouhout

Stevens

L-M

Mazine

, et al Long-term outcomes after elective isolated mechanical aortic valve replacement in young adults. J Thorac Cardiovasc Surg. 2014;148(4):1341-1346. e1341.

16.

Bacha

McElhinney

Guleserian

, et al Surgical aortic valvuloplasty in children and adolescents with aortic regurgitation: Acute and intermediate effects on aortic valve function and left ventricular dimensions. J Thorac Cardiovasc Surg. 2008;135(3):552559-559553.

17.

Wallace

FRO

Buratto

Naimo

, et al Aortic valve repair in children without use of a patch. J Thorac Cardiovasc Surg. 2021;162(4):1179-1189.

18.

Atik

Eroğlu

Çinar

Bakar

Saltik

İL

. Comparison of Balloon Dilatation and Surgical Valvuloplasty in Non-critical Congenital Aortic Valvular Stenosis at Long-Term Follow-Up. Pediatr Cardiol. 2018;39(8):1554-1560.

19.

M-S

Conte

Romano

, et al Unicuspid aortic valve repair using geometric ring annuloplasty. Ann Thorac Surg. 2021;111(4):1359-1366.

20.

Lansac

Di Centa

Sleilaty

, et al Remodeling root repair with an external aortic ring annuloplasty. J Thorac Cardiovasc Surg. 2017;153(5):1033-1042.

21.

Baird

Cooney

Chávez

Sleeper

Marx

Del Nido

. Congenital aortic and truncal valve reconstruction using the Ozaki technique: Short-term clinical results. J Thorac Cardiovasc Surg. 2021;161(5):1567-1577.

22.

Ozaki

Kawase

Yamashita

Uchida

Takatoh

Kiyohara

. Midterm outcomes after aortic valve neocuspidization with glutaraldehyde-treated autologous pericardium. J Thorac Cardiovasc Surg. 2018; 155(6):2379-2387.

23.

Konstantinov

Naimo

Buratto

. Commentary: Ozaki valve reconstruction in children: Is it still a valve replacement?. J Thorac Cardiovasc Surg. 2021; 161(5):1579-1581.

24.

Aboud

Charitos

Fujita

, et al Long-term outcomes of patients undergoing the ross procedure. J Am Coll Cardiol. 2021;77(11):1412-1422.

25.

Stelzer

Mejia

Varghese

. Operative risks of the Ross procedure. J Thorac Cardiovasc Surg. 2021;161(3):905-915.

26.

Romeo

JLR

Papageorgiou

da Costa

FFD

, et al Long-term clinical and echocardiographic outcomes in young and middle-aged adults undergoing the ross procedure. JAMA Cardiology. 2021;6(5):539-548.

27.

Hanson

Karam

Birch

, et al Transfusion practices in pediatric cardiac surgery requiring cardiopulmonary bypass: A secondary analysis of a clinical database. Pediatr Crit Care Med. 2021;22(11):978-987.

28.

Siemens

Sangaran

Hunt

Murdoch

Tibby

. Antifibrinolytic drugs for the prevention of bleeding in pediatric cardiac surgery on cardiopulmonary bypass: A systematic review and meta-analysis. Anesth Analg. 2021;134(5):987–1001.

29.

Hovgesen

Larsen

Fenger-Eriksen

Hansen

Hvas

. Efficacy and safety of antifibrinolytic drugs in pediatric surgery: A systematic review. Semin Thromb Hemost. 2021;47(5):538-568.

30.

Cohen

Faraoni

Vener

. Understanding and managing the complex balance between bleeding and thrombosis following cardiopulmonary bypass in paediatric cardiac surgical patients. Cardiol Young. 2021;31(8):1251-1257.

31.

Restin

Schmugge

Cushing

Haas

. Comparison between intraoperative bleeding score and ROTEM measurements to assess coagulopathy during major pediatric surgery. Transfus Apher Sci. 2021;60(5):103191.

32.

Emani

Diallo

, et al Thromboelastography during rewarming for management of pediatric cardiac surgery patients. Ann Thorac Surg. 2021;113(4):1248–1255.

33.

Harris

Sheehan

Rogers

Murphy

Caputo

Mumford

. Prediction of bleeding in pediatric cardiac surgery using clinical characteristics and prospective coagulation test results. Semin Thorac Cardiovasc Surg. 2021;;34(1):277–288.

34.

Di Gregorio

Sella

Spiezia

, et al Cardiopulmonary bypass-induced coagulopathy in pediatric patients: The role of platelets in postoperative bleeding. A preliminary study. Artif Organs. 2021;45(8):852-860.

35.

Dieu

Van Regemorter

Detaille

, et al Combined use of rotational thromboelastometry (rotem) and platelet impedance aggregometry (multiplate analyzer) in cyanotic and acyanotic infants and children undergoing cardiac surgery with cardiopulmonary bypass: subgroup analysis of a randomized clinical trial. J Cardiothorac Vasc Anesth. 2021;35(7):2115-2123.

36.

Cholette

Muszynski

Ibla

, et al Plasma and platelet transfusions strategies in neonates and children undergoing cardiac surgery with cardiopulmonary bypass or neonates and children supported by extracorporeal membrane oxygenation: from the transfusion and anemia expertise initiative-control/avoidance of bleeding. Pediatr Crit Care Med: A Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2022;23(13 suppl 1 1S):e25-e36.

37.

Engelman

Ben Ali

Williams

, et al Guidelines for perioperative care in cardiac surgery. JAMA Surgery. 2019;154(8):755-766.

38.

Fuller

Kumar

Roy

, et al The american association for thoracic surgery congenital cardiac surgery working group 2021 consensus document on a comprehensive perioperative approach to enhanced recovery after pediatric cardiac surgery. J Thorac Cardiovasc Surg. 2021;162(3):931-954.

39.

Shin

Rao

Bassett

, et al Target-based care: An intervention to reduce variation in postoperative length of stay. J Pediatr. 2021;228:208-212.

40.

Akhtar

Momeni

Szekely

Hamid

El Tahan

Rex

. Multicenter international survey on the clinical practice of ultra-fast-track anesthesia with on-table extubation in pediatric congenital cardiac surgery. J Cardiothorac Vasc Anesth. 2019;33(2):406-415.

41.

Alghamdi

Singh

Hamilton

BCS

, et al Early extubation after pediatric cardiac surgery: systematic review, meta-analysis, and evidence-based recommendations. J Card Surg. 2010;25(5):586-595.

42.

Jia

Wang

, et al Early extubation is associated with improved outcomes after complete surgical repair of pulmonary atresia with ventricular septal defect and hypoplastic pulmonary arteries in pediatric patients. J Cardiothorac Surg. 2021;16(1):31.

43.

Samuel

Froese

Betts

Gandhi

. Intraoperative extubation post arterial switch operation for transposition of the great arteries with intact ventricular septum: A one-year, single center experience. Semin Thorac Cardiovasc Surg. 2021;33(1):134-140.

44.

Murin

Weixler

VHM

Romanchenko

, et al Fast-track extubation after cardiac surgery in infants: Tug-of-war between performance and reimbursement?. J Thorac Cardiovasc Surg. 2021;162(2):435-443.

45.

Tamariz-Cruz

García-Benítez

Díliz-Nava

, et al Early extubation in a pediatric cardiac surgery program located at high altitude. World Journal for Pediatric and Congenital Heart Surgery. 2021;12(4):473-479.

46.

Miura

Butt

Thompson

Namachivayam

. Recurrent extubation failure following neonatal cardiac surgery is associated with increased mortality. Pediatr Cardiol. 2021;42(5):1149-1156.

47.

Roy

Brown

Parra

, et al Bilateral erector spinae blocks decrease perioperative opioid use after pediatric cardiac surgery. J Cardiothorac Vasc Anesth. 2021;35(7):2082-2087.

48.

Macaire

Nguyen

, et al Bilateral ultrasound-guided thoracic erector spinae plane blocks using a programmed intermittent bolus improve opioid-sparing postoperative analgesia in pediatric patients after open cardiac surgery: a randomized, double-blind, placebo-controlled trial. Reg Anesth Pain Med. 2020;45(10):805-812.

49.

Kaushal

Chauhan

Magoon

, et al Efficacy of bilateral erector spinae plane block in management of acute postoperative surgical pain after pediatric cardiac surgeries through a midline sternotomy. J Cardiothorac Vasc Anesth. 2020;34(4):981-986.

50.

Sahajanandan

Varsha

Kumar

, et al Efficacy of paravertebral block in “Fast-tracking” pediatric cardiac surgery - Experiences from a tertiary care center. Ann Card Anaesth. 2021;24(1):24-29.

51.

Cakmak

Isik

. Transversus thoracic muscle plane block for analgesia after pediatric cardiac surgery. J Cardiothorac Vasc Anesth. 2021;35(1):130-136.

52.

Staveski

Pickler

Khoury

, et al Prevalence of ICU delirium in postoperative pediatric cardiac surgery patients. Pediatr Crit Care Med. 2021;22(1):68-78.

53.

Chomat

Said

Mann

Wallendorf

Bickhaus

Figueroa

. Changes in sedation practices in association with delirium screening in infants after cardiopulmonary bypass. Pediatr Cardiol. 2021;42(6):1334-1340.