Author + information
- Received October 5, 2015
- Accepted November 3, 2015
- Published online February 23, 2016.
- David Faraoni, MD, PhD∗ (, )
- David Zurakowski, PhD,
- Daniel Vo, MD,
- Susan M. Goobie, MD,
- Koichi Yuki, MD,
- Morgan L. Brown, MD, PhD and
- James A. DiNardo, MD
- Department of Anesthesiology, Peri-operative and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. David Faraoni, Department of Anesthesiology, Peri-operative and Pain Medicine, Boston Children’s Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115.
Background Significant advances have been made in the diagnosis and treatment of children with congenital heart disease (CHD), allowing for longer life expectancies and an increasing number who will require noncardiac surgery.
Objectives This study sought to compare the incidence of mortality and major adverse post-operative outcomes following noncardiac surgery in children with and without CHD.
Methods Data from the 2012 pediatric database of the American College of Surgeons National Surgical Quality Improvement Program were analyzed. After propensity score matching, and stratification by severity of CHD, mortality and adverse post-operative outcomes were compared between controls and children with CHD.
Results Among the 51,008 children included in the database, 4,520 children with CHD underwent noncardiac surgery. After propensity score matching, we included 2,805 children with minor CHD, 1,272 with major CHD, and 417 with severe CHD. Children in each subgroup were matched and compared with controls without CHD who underwent noncardiac surgery of comparable complexity. The incidence of overall mortality was significantly higher in children with moderate (3.9%) and severe (8.2%) CHD compared with their controls (respectively, 1.7% [p < 0.001] and 1.2% [p = 0.001]). Both 30-day and overall mortality were significantly increased in children with severe CHD (odds ratio [OR]: 8.43, 95% confidence interval [CI]: 2.52 to 28.21; p < 0.001; OR: 7.32, 95% CI: 2.83 to 18.90; p < 0.001) compared with their matched controls. Overall mortality was also significantly increased in children with major CHD compared with their controls (OR: 2.28; 95% CI: 1.37 to 3.79; p = 0.002), whereas no difference was observed between children with minor CHD and their matched controls.
Conclusions Children with major and severe CHD, undergoing noncardiac surgery, have an increased risk of mortality compared with children without CHD. Further studies need to identify the optimal environment for surgical procedures, develop trained multidisciplinary teams to care for children with CHD, and define management strategies for improving outcomes in this high-risk population.
Over the past decades, significant advances have been made in the diagnosis and treatment of children with congenital heart disease (CHD) (1). Although the overall incidence of CHD has remained stable during the last 50 years, the natural history of lesions and the overall survival rate have significantly changed (2). Advances made in surgical procedures (e.g., cardiac catheterization, systemic-to-pulmonary arterial shunts) and techniques (3,4), in concert with improvements in diagnosis, anesthesia practices, intensive care, and medical treatments, have transformed many of these fatal lesions into manageable chronic conditions (5).
As life expectancy of children with CHD has improved, this population increasingly seeks medical attention for other illnesses, and a significant number of these patients will undergo noncardiac surgeries (6–8). To date, studies addressing mortality and adverse outcomes in children with and without CHD undergoing noncardiac surgery have largely been performed at single centers and have included small patient numbers (9–11).
In this study, we compared the incidence of mortality and major adverse post-operative outcomes following noncardiac surgery in a large group of children with and without CHD, after stratification for severity of the underlying CHD.
This study was performed using data from the 2012 pediatric database of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP Pediatric). The ACS NSQIP Pediatric collects de-identified data on children <18 years of age undergoing noncardiac surgery, and includes 129 variables, including pre-operative risk factors, demographic characteristics, 30-day post-operative outcomes, and mortality in both the inpatient and outpatient settings (12). A systematic sampling strategy is used to avoid bias in case selection and to ensure a diverse surgical case mix. A site’s trained and certified surgical clinical reviewer captures these data using a variety of methods, including medical chart review. To ensure the quality of the data collected, the ACS NSQIP Pediatric conducts inter-rater reliability audits of selected participating sites (13). The results of the audits completed to date reveal an overall disagreement rate of approximately 2% for all assessed program variables. For the 2012 database, exclusion criteria included: patients ≥18 years of age, trauma cases, solid organ transplantation, and patients undergoing multiple procedures performed by different surgical teams under the same anesthetic. In addition, cases coming from hospitals with an inter-rater reliability audit disagreement rate >5%, or a 30-day follow-up rate <80% were excluded.
Study population and outcome
We included all children undergoing noncardiac surgery recorded in the 2012 ACS NSQIP Pediatric database. The following demographic variables were included: sex, American Society of Anesthesiologists (ASA) physical status classification score, elective versus emergent surgery, surgical type (e.g., thoracic, neurological, orthopedic, general pediatric [including ear, nose, and throat], plastics, and urogynecology), age, body weight, and height. Children were stratified into 5 age groups: <6 months, 6 to 12 months, 1 to 6 years, 6 to 12 years, and >12 years old. Operative complexity was assessed using each procedure’s relative value unit (RVU) based on current procedure terminology codes (14). RVUs have replaced the original ACS NSQIP complexity score as a measure of surgical complexity, and have been shown in database analyses to independently predict post-operative morbidity following general surgery (15–17).
The outcomes included 30-day mortality, overall mortality (defined as any death occurring within the study interval, whether within the first 30 days or not), and the incidence of the following major post-operative outcomes occurring within 30 days after the primary surgical procedure: post-operative cardiac arrest, post-operative reintubation, infections (defined as superficial or deep surgical site, respiratory tract, and urinary tract infections), renal failure (defined as renal failure ± dialysis), neurological complication (defined as seizures, coma, cerebrovascular events, intraventricular hemorrhage), thromboembolic complication, reoperation, and any hospital readmission. Children with CHD were further classified into 3 groups, minor, major, or severe CHD, as defined in the ACS NSQIP database, based on residual lesion burden and cardiovascular functional status (Table 1).
Continuous variables are expressed as median and interquartile range, and categorical variables are expressed as number and percentage (%). Demographic and post-operative outcomes variables were compared between CHD and controls using the Wilcoxon rank sum test for continuous variables, and chi-square for categorical variables.
We defined a priori 5 confounding variables to be used in the propensity-matched analysis: sex, age group, ASA classification, elective versus emergent surgery, and RVU. We used a saturated logit model predicting CHD status using the 5 categorical covariates (sex, age group, ASA classification, elective versus emergent surgery, and RVU) to find the exact matches for each CHD patient (18,19).
Demographic variables were compared between post-matched groups using the Wilcoxon rank sum test for continuous variables, and the Pearson chi-square test for categorical variables and proportions. Outcomes variables, including mortality and adverse post-operative complications, were compared using univariate logistic regression analysis, and results are expressed as the odds ratio (OR) as a measure of risk, and the 95% confidence interval (CI), with p values obtained by the Wald test (20). Because this study included 10 binary outcomes, a conservative Bonferroni-adjusted 2-tailed p value of 0.005 or less (0.05/10) was considered the α-level criterion for statistical significance to account for multiple comparisons performed after propensity-matched analysis to protect against type I errors. Statistical analysis was performed using IBM SPSS Statistics (version 22.0, IBM, Armonk, New York), and STATA (version 14.0 for Mac OS, Stata Corp, College Station, Texas).
We performed power calculations to estimate the required number of total CHD patients and required sample sizes within each of the 3 ACS NSQIP severity classifications for achieving 80% statistical power for detecting differences compared with controls for each of 10 post-operative outcomes using the OR as the effect size measure (21). The sample sizes within each CHD severity category provided 80% power to detect an OR of 4.0 using logistic regression and a conservative α-level of 0.005 for each of the 10 outcomes of interest (e.g., mortality and adverse post-operative complications) (nQuery Advisor, version 7.0, Statistical Solutions, Cork, Ireland).
From the 51,008 children included in the 2012 ACS NSQIP Pediatric database, there were 4,520 with CHD (Figure 1). Demographic characteristics of children with CHD versus controls are summarized in Table 2. Children with CHD were younger (p < 0.001), had higher ASA scores (p < 0.001), and underwent more elective procedures (p < 0.001), and more complex procedures (p < 0.001). After propensity score matching, no difference was observed between sex, age groups, the number of children with an ASA classification >2, the number of elective versus emergent procedures (Table 1) (p = 1.00 for all comparisons). Children with CHD underwent fewer neurosurgical procedures (442 [10%] vs. 761 [17%]), and more general pediatric surgical procedures (2,561 [57%] vs. 2,234 [50%]), but no difference was observed for orthopedic surgery (11%), urologic and gynecological procedures (15%), and plastic surgery (7%). However, the operative complexity, defined as the RVU, was perfectly matched between CHD and controls (p = 1.00). We included children with CHD divided into 3 subgroups based on the severity of the CHD: 2,805 children with minor CHD, 1,272 with major CHD, and 417 with severe CHD (Figure 1).
Children with CHD had similar length of hospital stay compared with their matched controls (severe: 4 days [1 to 29] vs. 3 days [1 to 8]; p = 0.09); moderate; 3 days [1 to 20] vs. 3 days [1 to 11]; p = 0.24; minor: 2 days [1 to 10] vs. 2 days [1 to 8]; p = 0.79). The incidence of overall mortality was significantly higher in children with moderate (3.9%) and severe (8.2%) CHD compared with their matched controls (respectively, 1.2% [p < 0.001] and 1.7% [p = 0.001]). No difference was observed between children with minor CHD (1.5%) and their own controls (1.0%; p = 0.07). Both 30-day and overall mortality were significantly increased in children with severe CHD (OR: 8.43, 95% CI: 2.52 to 28.21; p < 0.001; OR: 7.32, 95% CI: 2.83 to 18.90; p < 0.001) compared with their controls (Table 3). Overall mortality (Table 4) was also significantly increased in children with major CHD (OR: 2.28; 95% CI: 1.37 to 3.79; p = 0.002) compared with their controls, whereas no difference was seen in children with minor CHD (Table 5). In addition, the incidence of post-operative reintubation was higher in children with major and severe CHD (OR: 3.11, 95% CI: 1.31 to 7.39; p = 0.005; OR: 2.46, 95% CI: 1.58 to 3.82; p < 0.001) compared with their controls (Figure 2).
Children with major and severe CHD undergoing noncardiac surgery have an increased risk of mortality, and a higher incidence of post-operative reintubation compared with matched controls undergoing comparable procedures (Central Illustration).
Using the University Hospital Consortium database, Baum et al. (22) reviewed data from 191,261 children undergoing noncardiac procedures between 1993 and 1996, and assessed 1-, 3-, and 30-day mortality. The authors reported that 6.5% of the children undergoing noncardiac surgical procedures had a diagnosis of CHD, and observed a 3.5 higher incidence of 30-day mortality (95% CI: 3.2 to 3.9) in this population compared with children without CHD. They also observed that children with severe CHD had higher mortality than those with minor cardiac lesions (mortality rate: 11.3% vs. 5.9%; p < 0.001). In our study, overall mortality in children with CHD was 2.8% compared with 1.2% in children without CHD, corresponding to a 2.3-fold higher mortality rate in children with CHD. Not surprisingly, the mortality rate increased to 3.9% in children with major CHD, and 8.2% in children with severe CHD.
In another study, Carmosino et al. (23) reviewed perioperative complications in children with pulmonary hypertension undergoing noncardiac surgery or cardiac catheterization. The authors reported that major complications, including cardiac arrest and pulmonary hypertensive crisis, occurred in 4.5% of patients undergoing noncardiac surgery. Although the overall incidence of post-operative cardiac arrest was lower in our study, the incidence was significantly increased in children with severe CHD (3.1%) as compared with controls (0.0%). We also observed that the incidence of post-operative reintubation was significantly increased in children with major (5.4%) and severe CHD (5.0%), compared with their controls without CHD (respectively, 2.3% and 1.7%).
Although the incidence of renal failure and reoperation did not meet the significance criterion, we observed that the incidences of both outcomes were increased in the major/severe CHD groups. This observation is important because it has been recently demonstrated that the development of post-operative complications, including renal failure, are significantly associated with outcome and hospital cost in children with CHD undergoing both cardiac and noncardiac surgeries (24,25).
Presence of major or severe CHD is associated with an increased risk of anesthesia and surgery in children. Although there are guidelines for the perioperative management in children with CHD undergoing noncardiac surgery, these recommendations are essentially based on expert opinion without strong objective evidence to support their use (26,27). The diversity of structural malformations, each with specific physiological perturbations, hemodynamic consequences, and severity, makes perioperative management challenging (28). Children with CHD, particularly those with a residual lesion burden and compromised cardiovascular status require an individualized approach to anesthetic and surgical cares delivered by trained multidisciplinary teams (29). Practitioners who care for children with CHD must address a number of challenges including identifying the best location for procedures (e.g., children hospital), identifying qualified team (e.g., cardiac anesthesiologists, surgeons), improving expertise of the noncardiac subspecialties (e.g., nephrology, hematology, pediatricians). In 2001, a task force of the American College of Cardiology highlighted the need for creating cohorts of specialists trained to take care of adults with CHD, and the development of a network of specialized centers (30). As suggested, the creation of such networks could improve management of CHD patients with better outcomes (31). In 2008, the ACC/AHA guidelines for the management of adults with CHD recommended that when possible, high-risk CHD patients should be managed at centers for the care of adults CHD patients under all circumstances, unless the surgery an absolute emergency (Level of Evidence: C) (32). Although no comparable guidelines have been published for children with CHD undergoing noncardiac surgery thus far, the results obtained from our and previous investigations support the creation of such networks (22,33).
Despite the strengths of our methodology and the consistency of our findings, this study presents some limitations. Analyses were performed using a large multi-institutional database that likely includes missing data, miscoded diagnoses, and miscoded procedures. However, ACS NSQIP is both a well-designed and well-administered database, which has rigorous quality controls built in. It is likely that the use of a clinical database such as ACS NSQIP provides more accurate information than an administrative database (34). It is also important to note that the ACS NSQIP does not allow the identification for the type and the characteristics of the hospital (e.g., teaching, children’s hospital, bed size), and the perioperative management strategies. In addition, all reported values and incidence are absolute values measured from the dataset, and could not be considered as representative of national prevalence. Although the use of a propensity score approach adjusts for baseline group differences, as opposed to including potential confounders, and is the best method available to perform a matched analysis, there could still be undetermined covariates that were not matched for and may consequently influence patients outcomes. Finally, one limitation inherent in observational studies is that variables other than those incorporated in the model, or matched for, may partially contribute to the outcomes. Although we controlled for operative complexity using RVU, it is possible that CHD patients underwent a somewhat different spectrum of surgical procedures than their controls.
Children with major or severe CHD who undergo noncardiac surgery have an increased risk of mortality with a higher incidence of life-threatening post-operative outcomes compared with children without CHD. Further studies need to identify the optimal environment for surgical procedures, build trained multidisciplinary teams to care for children with CHD, and define management strategies for improving outcomes in this high-risk population.
COMPETENCY IN MEDICAL KNOWLEDGE: Children with severe congenital heart disease undergoing noncardiac surgery face an increased risk of mortality compared with children without congenital heart disease.
TRANSLATIONAL OUTLOOK: Further studies are needed to identify the optimal care setting in which children with complex congenital heart disease should undergo noncardiac surgical procedures and to define management strategies that improve outcomes.
The authors thank the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) and the hospitals participating in the ACS NSQIP, source of the data used herein. ACS NSQIP has not verified and is not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.
This work was solely supported by the Department of Anesthesiology, Peri-operative and Pain Medicine, Boston Children’s Hospital, Boston. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- ACS NSQIP
- American College of Surgeons National Surgical Quality Improvement Program
- American Society of Anesthesiologists
- congenital heart disease
- confidence interval
- odds ratio
- relative value unit
- Received October 5, 2015.
- Accepted November 3, 2015.
- American College of Cardiology Foundation
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