There are an estimated 80 to 100,000 people with sickle cell disease (SCD) in the United States.1 Because the homozygous genotype for hemoglobin-S is associated with an abbreviated life span of approximately 42 to 48 years, approximately one-third of this group is children.2 Surgical intervention is often indicated for complications of SCD; in addition, children with SCD can undergo surgery for the indications generally common in the pediatric population. Although children make up a significant proportion of patients with SCD who undergo surgery,3–9 there are limited current epidemiological data for this pediatric population. Such information is important in prioritizing research efforts in this field, in establishing the feasibility of clinical trials, and in guiding clinical practice. We, therefore, analyzed a nationwide inpatient database to estimate nationwide population characteristics, surgical procedures, and perioperative outcomes in pediatric patients with SCD.
We used the Nationwide Inpatient Sample (NIS) database that is maintained and distributed by the Agency for Healthcare Research and Quality as part of the Healthcare Cost and Utilization Project. The NIS database comprises an approximately 20% sample of the nationwide discharges from inpatient care that is designed to be maximally representative of all U.S. hospital admissions. Sampling weights are provided to allow nationwide estimates to be made using the dataset. This study was exempt from IRB review.
We queried the NIS database for discharge records of patients younger than 18 years of age with SCD, defined by appearance of ICD-9 codes corresponding to SCD (Table 1, patients), discharged between years 2000 and 2010. We excluded patients with sickle cell trait (ICD-9 code 282.5). Initial identification of most common procedures was performed using the Clinical Classifications Software procedure codes.10 We restricted our analysis to only those procedures for which there were >30 individual discharge records (approximately 150 weighted records). Because these coding categories may include a wide variety of related procedures, final record of frequency of surgical procedures was made using ICD-9 procedure codes (Table 1, procedures). Complications were identified using ICD-9 diagnostic codes as acute chest syndrome (ACS), splenic sequestration, stroke, or fever in the presence of a diagnostic code for SCD (Table 1, complications).
Patient characteristics (age group, gender, race, genetic type of SCD, income quartile, expected primary payer), procedural characteristics (elective versus emergency versus urgent admission, receipt of blood transfusion during in-hospital stay), and in-hospital outcomes (occurrence of complications, mortality) were noted. We chose to explore complications after surgery only among patients who had an elective admission, under the premise that these patients are not likely to have a complication of SCD at the time of admission for an elective procedure, and therefore, any recorded complications must have occurred intra- or postoperatively. In addition, we abstracted data on all children undergoing the 6 procedures of interest within the NIS database between 2000 and 2010, with a view to calculate the procedures among children with SCD as a proportion of all patients.
Data were analyzed using SAS 9.3 (SAS Corp., Cary, NC), using the survey procedures included in the software, to account for the complex survey design of the NIS (PROC SURVEYFREQ and PROC SURVEYMEANS). Standard measures of frequencies (percent [SE]) and central tendency were calculated to summarize characteristics of patients, procedures, and in-hospital outcomes. Length of stay was summarized as medians and compared between patients with complications and those without complications by using the general extension of the Wilcoxon test procedure to complex surveys.11 In addition, the mean and (SE) are also presented and compared using the extension of the t test to complex survey data as implemented in the SAS SURVEYREG procedure.12 A P value <0.05 was considered statistically significant.
During 2000 to 2010, there were 313,385 individual discharges of pediatric-age patients with SCD.
Table 2 presents the demographic characteristics of the cohort of 9948 children who underwent one of the 9 most common surgical procedures with 150 or more surgeries in the 10 years. There were an equal number of men and women (50.68%). Most of these patients were African American (88.43%), homozygous for Hb-S (85.30%), and were admitted electively (59.79%). Age distribution is presented in Table 2. Economically, 41.22% were in the lowest income quartile; most patients (64.78%) had Medicaid as their primary expected payer.
Overall Frequency of Surgical Procedures
The most frequent surgical procedures were cholecystectomy (n = 4610; 1.47% [0.08]), tonsillectomy/adenoidectomy (n = 2538; 0.81% [0.06]), splenectomy (n = 1956; 0.62% [0.06]), repair of umbilical hernia (n = 588; 0.19% [0.02]), appendectomy (n = 545; 0.17% [0.02]), myringotomy (n = 482; 0.15% [0.02]), cesarean delivery (n = 254; 0.08% [0.01]), repair of inguinal and/or femoral hernia (n = 185; 0.06% [0.02]), and replacement of hip joint (n = 148; 0.05% [0.01]) (Table 3).
Splenectomy (n = 1090; 55.73%), myringotomy (n = 252; 52.28%), and repair of inguinal or femoral hernia (n = 109; 58.99%) were most commonly performed on children 4 years or younger. Cesarean delivery (n = 249; 98.18%) and appendectomy (n = 176; 32.32%) were most common among children aged 15 to 17 years. Patients undergoing repair of inguinal/femoral hernia (1.48 days) or myringotomy (1.49 days) had the shortest length of stay, while those undergoing a cesarean delivery (4.17 days) or splenectomy (3.41 days) had the longest stay.
All procedures, besides appendectomy and cesarean delivery, were most commonly performed after an elective admission. Medicaid was the primary expected payer for most patients across all procedures. One or more instances of blood transfusion during hospital stay were recorded for 45.34% patients undergoing an appendectomy, the highest proportion across all procedures, followed by cholecystectomy (n = 1722; 37.36%). The lowest incidence of blood transfusion was noted for inguinal/femoral hernia repair (n = 52; 28.20%) followed by cesarean delivery (n = 74; 29.05%).
Complications After Surgery During an Elective Admission
Among the 5579 discharges for patients who underwent surgery after an elective admission, ACS was recorded in 172 (3.08% [0.60]), postoperative fever in 26 (0.47% [0.20]), and stroke in 11 (0.20% [0.11]). Splenic sequestration and in-hospital death were each recorded in <11 patients (<0.20%) respectively. There were no reports of blood transfusion reactions. Patients developing a complication had a longer median length of stay compared with those who did not (5.48 vs 1.99 days; P < 0.001; mean [SE]: 6.69 [0.65] vs 3.17 [0.10] days; P < 0.001). The incidence of ACS was 3.90% [(n = 180) for patients undergoing cholecystectomy, 1.98% (n = 50) for patients undergoing adenotonsillectomy, 2.76% (n = 54) for patients undergoing splenectomy, 4.24% (n = 25) for patients undergoing umbilical hernia repair, 8.73% (n = 48) for appendectomies, 2.28% (n = 11) for myringotomy, and 5.95% (n = 15) for cesarean delivery. Most patients (87.22%) underwent only 1 procedure during the admission. The most common combinations for multiple procedures recorded in a single discharge record were myringotomy and tonsillectomy/adenoidectomy (n = 360), umbilical hernia repair and cholecystectomy (n = 265), and cholecystectomy and splenectomy (n = 258).
This retrospective analysis of 11 years of U.S. national billing data showed that 3.6% of hospital discharges of children with SCD involved surgery. Nationwide, there were an estimated 1028 surgery-related discharges annually. Of these, the 6 most common inpatient surgical procedures were cholecystectomy, tonsillectomy/adenoidectomy, splenectomy, umbilical hernia repair, appendectomy, and myringotomy. ACS complicated 3.08% of elective surgical procedures. Stroke, sequestration, and death were rare complications.
The burden of surgical disease in SCD children differs from both the broader pediatric population and the adult SCD population. Cholecystectomy and splenectomy are unusual procedures in the general pediatric population but are relatively common in the SCD population as a consequence of the disease (Table 4). Although cholecystectomy is commonly performed in both adult and pediatric SCD populations,6 hip surgery is more typically required in adults with SCD.3,8,13
ACS is among the common complications in children with SCD undergoing elective surgery. By contrast, this complication is rare after minor pediatric surgical procedures, many of which are performed in outpatient settings.14,15 The incidence of death and stroke is low and consistent with other studies that reported an incidence of <1%.3–5,9,14–16 By comparison with adults, ACS presenting in children from outside the hospital is more often associated with pulmonary infection, of shorter duration and of less severity.17,18 Although fatal consequences were unusual in the current study, postoperative complications such as ACS did prolong hospital stay considerably (5.48 vs 1.99 days; P < 0.001).
This study demonstrates that surgical pathology is a small but significant proportion of hospital admissions in the SCD pediatric population (3.6%), with perioperative exacerbations of the disease producing a significant morbidity reflected in extended hospital stay. Despite this, there have been few adequately powered trials to determine optimal perioperative management. There is a range of opinion on best practice.19,20 Possible reasons for the paucity of controlled outcome data include the low absolute number of cases and large number of associated variables. This study estimates only about 1000 annual admissions nationwide for diverse surgical procedures of differing urgency distributed across a varied pediatric population with different genotypes. International collaborations may be a way to address the considerable logistic challenges of prospective studies,5 while registries could provide information about potential predictors of surgical outcomes.21
The main limitation of this study is the source of the data: billing records rather than actual clinical reports. Because the billing codes did not record the timing of or indication for transfusion, we were unable to examine associations between transfusions and complications. In addition, because acute and prior pain crises were not differentiated within the billing codes (282.62, 282.64, and 282.69), we could not determine the incidence of postoperative vaso-occlusive pain. However, the study was able to estimate the incidence of complications such as ACS, stroke, and death. Although billing reports reflect hospital discharge codes, not primary accounts of clinical features, cautious indirect estimates can be derived to provide a broad overview of disease burden.
In conclusion, this study demonstrates that surgical procedures such as cholecystectomy, tonsillectomy, splenectomy, hernia repair, and appendectomy account for a small but significant proportion of hospital admissions in children with SCD. ACS is among the most common complications of elective surgery, while stroke and death are rare. Future research should determine how to predict and decrease perioperative complications.
Name: Omar Hyder, MD, MS.
Contribution: This author helped to design the study, collect and analyze the data, and prepare the manuscript.
Attestation: Omar Hyder approved the final manuscript. Omar Hyder attests to the integrity of the original data and the analysis reported in this manuscript.
Name: Myron Yaster, MD.
Contribution: This author helped to design the study and prepare the manuscript.
Attestation: Myron Yaster approved the final manuscript.
Name: Brian T. Bateman, MD, MS.
Contribution: This author helped to design the study and prepare the manuscript.
Attestation: Brian T. Bateman approved the final manuscript.
Name: Paul G. Firth, MBChB, BA.
Contribution: This author helped to design the study, analyze the data, and prepare the manuscript.
Attestation: Paul G. Firth approved the final manuscript and attests to the integrity of the original data and the analysis reported in this manuscript.
This manuscript was handled by: Peter J. Davis, MD.
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