Venous thromboembolism in the setting of pediatric traumatic brain injury

Clinical article

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Object

The risk of venous thromboembolism (VTE) in children with traumatic brain injury (TBI) has not been well characterized given its rarity in the pediatric population. Investigation of risk factors for VTE in this group requires the use of a large sample size. Using nationally representative hospital discharge data for 2009, the authors of this study characterize the incidence and risk factors for VTE in children hospitalized for TBI.

Methods

The authors conducted a cross-sectional study using data from the Healthcare Cost and Utilization Project Kids' Inpatient Database to examine VTE in TBI-associated hospitalizations for patients 20 years of age or younger during the year 2009.

Results

There were 58,529 children with TBI-related admissions, including 267 with VTE diagnoses. Venous thromboembolisms occurred in 4.6 per 1000 TBI-associated hospitalizations compared with 1.2 per 1000 pediatric hospitalizations overall. By adjusted logistic regression, patients significantly more likely to be diagnosed with VTE had the following: older age of 15–20 years (adjusted odds ratio [aOR] 3.7, 95% CI 1.8–8.0), venous catheterization (aOR 3.0, 95% CI 2.0–4.6), mechanical ventilation (aOR 1.9, 95% CI 1.2–2.9), tracheostomy (aOR 2.3, 95% CI 1.3–4.0), nonaccidental trauma (aOR 2.8, 95% CI 1.1–6.9), increased length of stay (aOR 1.02, 95% CI 1.01–1.03), orthopedic surgery (aOR 2.4, 95% CI 1.8–3.4), and cranial surgery (aOR 1.8, 95% CI 1.1–2.8).

Conclusions

Using the Kids' Inpatient Database, the authors found that risk factors for VTE in the setting of TBI in the pediatric population include older age, venous catheterization, nonaccidental trauma, increased length of hospital stay, orthopedic surgery, and cranial surgery.

Abbreviations used in this paper:aOR = adjusted odds ratio; HCUP = Healthcare Cost and Utilization Project; ICD-9-CM = International Classification of Diseases; Ninth Revision; Clinical Modification; ICU = intensive care unit; KID = Kids' Inpatient Database; OR = odds ratio; TBI = traumatic brain injury; VTE = venous thromboembolism.

Abstract

Object

The risk of venous thromboembolism (VTE) in children with traumatic brain injury (TBI) has not been well characterized given its rarity in the pediatric population. Investigation of risk factors for VTE in this group requires the use of a large sample size. Using nationally representative hospital discharge data for 2009, the authors of this study characterize the incidence and risk factors for VTE in children hospitalized for TBI.

Methods

The authors conducted a cross-sectional study using data from the Healthcare Cost and Utilization Project Kids' Inpatient Database to examine VTE in TBI-associated hospitalizations for patients 20 years of age or younger during the year 2009.

Results

There were 58,529 children with TBI-related admissions, including 267 with VTE diagnoses. Venous thromboembolisms occurred in 4.6 per 1000 TBI-associated hospitalizations compared with 1.2 per 1000 pediatric hospitalizations overall. By adjusted logistic regression, patients significantly more likely to be diagnosed with VTE had the following: older age of 15–20 years (adjusted odds ratio [aOR] 3.7, 95% CI 1.8–8.0), venous catheterization (aOR 3.0, 95% CI 2.0–4.6), mechanical ventilation (aOR 1.9, 95% CI 1.2–2.9), tracheostomy (aOR 2.3, 95% CI 1.3–4.0), nonaccidental trauma (aOR 2.8, 95% CI 1.1–6.9), increased length of stay (aOR 1.02, 95% CI 1.01–1.03), orthopedic surgery (aOR 2.4, 95% CI 1.8–3.4), and cranial surgery (aOR 1.8, 95% CI 1.1–2.8).

Conclusions

Using the Kids' Inpatient Database, the authors found that risk factors for VTE in the setting of TBI in the pediatric population include older age, venous catheterization, nonaccidental trauma, increased length of hospital stay, orthopedic surgery, and cranial surgery.

Traumatic brain injury (TBI) is a major health problem among children and a leading cause of morbidity and mortality in the United States.23 With nearly 7400 deaths, 60,000 hospitalizations, and 600,000 emergency department visits annually, TBIs in children impose a significant burden on our health care system.25 In the adult population, a number of studies have found major trauma to be an independent risk factor for the development of venous thromboembolism (VTE) and pulmonary embolism.5,20,27 Several factors may contribute to this, including extended immobilization, inadequate VTE prophylaxis, or trauma-induced coagulopathy. Moreover, patients with TBIs are at high risk for coagulopathy and VTE formation.9,17 It is postulated that changes in the coagulation cascade are due to widespread release of tissue factor after a cerebral insult.9,17

Venous thromboembolism is a rare complication in children, with an incidence roughly one-tenth of that in adults.20,27 Its study thus requires the use of a large sample size. Risk factors for VTE in the pediatric population have been studied predominantly in single-institution settings. More recently, Vu et al.27 were able to use the Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) for the years 1997, 2000, and 2003 to estimate the incidence and risk factors for VTE in the overall pediatric population. Their analysis found older age (15–17 years); comorbid conditions of obesity, inflammatory bowel disease, and malignancy; and surgery (thoracoabdominal or orthopedic) to be significant risk factors for VTE. Interestingly, trauma was not found to be a significant risk factor despite trauma's association with VTE in the literature.3,7,15,20

Using nationally representative data from the KID for 2009 for a cross-sectional study, we characterize the incidence and risk factors for VTE for children hospitalized for TBI. To our knowledge, this is the first study to assess the risk of VTE specifically in children with TBI.

Methods

Data Source

Data were obtained from the 2009 Kids' Inpatient Database (KID), one of a family of administrative databases developed by the Healthcare Cost and Utilization Project (HCUP) sponsored by the Agency for Healthcare Research and Quality.11 The 2009 KID contains discharge-level data from over 3.4 million pediatric hospitalizations from 4121 nonfederal community hospitals in 44 states.11 The KID allows for more precise national and regional estimates for pediatric conditions, clinical outcomes, and hospital services, which are otherwise difficult to analyze given that children make up a relatively small proportion of hospital stays.

The KID contains randomly selected pediatric discharges stratified by non–birth related discharges and complicated or uncomplicated births.11 To obtain national estimates, patient records were provided with weights using the American Hospital Association universe of nonfederal community hospitals as the standard. Hospital data were stratified by the following 6 characteristics: ownership/control, bed size, teaching status, rural/urban location, US region, and status as a freestanding children's hospital.11

Patient Selection

We selected records associated with TBI for patients up to 20 years of age or younger. These records were identified using discharge diagnosis codes defined by the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The following ICD-9-CM codes representing TBI were used: fracture of the vault or base of the skull (800.0–801.9); other unqualified and multiple fractures of the skull (803.0–804.9); intracranial injury, including concussion, contusion, laceration, and hemorrhage (850.0–854.1); injury to the optic chiasm, optic pathways, or visual cortex (950.1–950.3); unspecified head injury (959.01); and shaken infant syndrome (995.55).23,24

Discharge records associated with venous thromboembolism (VTE) were identified using the ICD-9-CM codes: deep venous thrombosis (453.2, 453.40, 453.41, 453.42, 453.82–89, and 453.9), thrombophlebitis (451.11, 451.19, 451.2, 451.81, 451.83, 451.84, 451.89, and 451.9) of the upper and lower extremities, and pulmonary embolism (415.11, 415.13, and 415.19).22,26,28

Patient Characteristics

Patient characteristics obtained from the database include age (in years), sex, race (white, black, Hispanic, Asian or Pacific Islander, Native American, and other), hospital death, length of hospitalization (days), and primary payer (Medicaid, private, self-pay, or other).

Nonaccidental traumatic injuries were identified with the following ICD-9-CM codes: child abuse (995.50, 995.54, 995.55, 995.59) and E-codes (external causes) for inflicted injury (E-960–969). We created variables for surgical procedures (cranial, thoracic or abdominal, orthopedic, and other) using the following ICD-9-CM procedure codes: cranial surgery (01xx–02xx), orthopedic surgery (77xx–84xx), and thoracoabdominal surgery including surgeries related to the gastrointestinal tract (42xx–54xx), cardiovascular excluding procedures on vessels (35xx–37xx), and pulmonary (32xx–34xx). All remaining procedure codes for surgeries were included in the “other” category. Procedure codes not associated with surgeries were included in the “none” category.

We used ICD-9-CM procedure codes to create variables for the following inpatient procedures: venous catheterization (38.93 and 38.97), intubation and mechanical ventilation (96.04, 96.05, and 96.7×), tracheostomy (31.1, 31.21, and 31.29), and gastrostomy tube insertion (43.2, 43.11, 43.19, 43.2, and 44.32).2,28

Statistical Analysis

Descriptive statistics with weighted national estimates were conducted to evaluate the distribution of patient and hospital characteristics for those with or without VTE complications during their TBI-associated hospitalization. As KID is a sampled database, our results are reported as estimated values such as means and frequencies with 95% confidence intervals. These estimates represent national estimates for the associated year. Because of the sampling methodology, national medians cannot be obtained. Hence continuous data are expressed as estimated means. Standard errors were adjusted for stratification and clustering of the KID sampling design as described in the 2009 KID documentation published by the Agency for Healthcare Research and Quality.11 It is important to note that because the data in KID is a composite of de-identified state-level information, our unit of analysis is a patient discharge and not a patient. In order to evaluate the effect of patient and hospital characteristics on the incidence of VTE in this group, univariate and multivariate logistic regression were used to calculate unadjusted and adjusted odds ratios and 95% confidence intervals. Two-sided tests were used, with p values < 0.05 considered to be statistically significant. All statistical analyses were performed with Stata 12 (StataCorp).

Results

Of the 3,407,146 encounters from January 1, 2009, through December 31, 2009, 40,143 cases involved TBI. Among children up to 20 years of age, there were an estimated 58,529 hospitalizations in the US that were associated with TBI, or 7.9 per 1000 hospital discharges (95% CI 7.4–8.5). Among this subpopulation, an estimated 267 hospitalizations were associated with VTE, or 4.5 per 1000 TBI-associated hospitalizations (95% CI 3.8–5.3). The overall incidence of VTE in the pediatric population is very low, with an estimated prevalence of 1.2 cases per 1000 pediatric hospitalizations in 2009 (95% CI 1.1–1.3). Patient demographic data are summarized in Table 1.

TABLE 1:

Year 2009 national estimates of TBI-associated hospitalizations and VTE*

VariableActual SampleNat'l EstProportion % (95% CI)VTE GroupNon-VTE Group
Nat'l Est% (95% CI)Nat'l Est% (95% CI)
total40,14358,5290.79 (0.74–0.85)2670.45 (0.38–0.53)58,26299.5 (99.5–99.6)
age
 <1 yr5,0487,47712.8 (11.9–13.6)197.3 (3.5–11.0)7,45712.8 (11.9–13.7)
 1–9 yrs9,80514,51524.1 (23.5–26.1)186.7 (3.1–10.4)14,49724.9 (23.6–26.2)
 10–14 yrs5,9028,66614.8 (14.1–15.5)207.3 (3.2–11.4)8,64614.8 (14.1–15.5)
 15–20 yrs18,87527,11846.3 (44.0–48.7)20677.0 (70.3–84.7)26,91246.2 (43.8–48.6)
sex
 male26,60538,72266.2 (65.6–66.7)18970.6 (64.0–77.2)38,53366.1 (65.6–66.7)
 female12,88818,88532.2 (31.7–32.8)7929.4 (22.8–36.0)18,80632.3 (31.7–32.9)
race
 white19,73428,63148.9 (46.1–51.7)12647.2 (38.8–55.5)28,50548.9 (46.2–51.7)
 black4,7877,04112.0 (10.6–13.4)2810.5 (5.8–15.3)7,01312.0 (10.6–13.5)
 Hispanic6,3689,24215.8 (13.9–17.6)4416.4 (10.8–22.1)9,19815.8 (13.9–17.6)
 other2,7613,9826.8 (5.9–7.7)228.2 (3.9–12.3)3,9606.8 (5.9–7.7)
 not specified6,4939,63416.5 (13.4–19.5)4717.8 (10.0–25.6)9,58616.5 (13.4–19.5)
primary expected payer
 Medicaid13,32419,64033.6 (32.0–35.1)9535.4 (28.0–42.8)19,54633.5 (32.0–35.1)
 private20,76630,07651.3 (49.8–53.0)13851.7 (44.0–60.0)29,93851.4 (49.7–53.0)
 self-pay3,1814,5987.9 (7.2–8.5)176.5 (2.7–10.2)4,5807.9 (7.2–8.5)
 other2,7634,0526.9 (6.0–7.8)176.4 (2.7–10.0)4,0356.9 (6.0–7.8)
 not specified1091630.2 (0.1–0.4)1630.3 (0.1–0.4)
died in hospital1,3301,9603.4 (3.1–3.6)134.8 (1.8–7.8)1,9483.4 (3.1–3.6)
hospital bed size
 small2,3403,6926.3 (4.0–8.6)114.0 (0.7–7.2)3,6816.3 (4.0–8.6)
 medium7,32510,98418.8 (14.9–22.7)3713.8 (7.3–20.3)10,94818.8 (14.9–22.7)
 large26,94738,44265.7 (61.3–70.1)19773.6 (65.2–82.0)38,24565.7 (61.3–70.0)
 not specified3,5315,4129.2 (6.0–12.5)238.6 (2.7–14.6)5,3899.2 (6.0–12.5)
hospital type
 non-children's18,26525,81144.1 (39.5–48.7)11743.8 (34.3–53.2)25,69444.1 (39.5–48.7)
 children's general/specialty4,7787,71313.2 (9.6–16.7)217.8 (3.5–12.2)7,69213.2 (9.7–16.8)
 children's unit in general hospital12,83118,48031.6 (26.4–36.8)10238.0 (28.4–47.6)18,37831.5 (26.3–36.8)
 not specified4,2696,52511.1 (7.8–14.5)2810.4 (4.2–16.6)6,49711.2 (7.8–14.5)
surgery
 none25,00636,47762.3 (61.2–63.4)3211.9 (6.5–17.2)36,44562.6 (61.5–63.6)
 cranial4,3006,30810.8 (10.2–11.3)11342.3 (34.7–50.0)6,19510.6 (10.1–11.1)
 thoracoabdominal2,6023,7896.5 (6.0–6.9)10037.6 (30.6–44.6)3,6895.9 (5.6–6.3)
 orthopedic4,1666,04810.3 (9.8–10.9)9234.6 (28.0–41.1)5,95610.2 (9.7–10.8)
 other6,0608,79415.0 (14.5–15.6)3212.1 (7.3–16.9)8,85615.2 (14.6–15.8)
procedures
 venous catheterization2,6903,9606.8 (6.2–7.3)11844.0 (36.4–51.7)3,8426.6 (6.1–7.1)
 mechanical ventilation6,93210,14717.3 (16.5–18.1)16260.6 (52.8–68.4)9,98517.1 (16.3–17.9)
 tracheostomy1,0341,5032.6 (2.3–2.8)8431.3 (24.8–37.8)1,4192.4 (2.2–2.7)
 gastrostomy8521,2422.1 (1.9–2.3)5119.2 (13.6–24.8)1,1902.0 (1.8–2.2)
nonaccidental trauma1,1811,7833.0 (2.7–3.4)166.1 (2.7–9.6)1,7673.0 (2.7–3.4)

Values represent numbers of discharges unless otherwise indicated. Nat'l Est = national estimate.

Among the 267 TBI-associated hospitalizations that were complicated by VTE, there were an estimated 12.8 deaths (mortality rate 4.8%, 95% CI 1.8%–7.8%), compared with a mortality rate in TBI-associated hospitalizations not complicated by VTE of 3.4% (95% CI 3.1%–3.6%). This difference was not statistically significant.

In comparing characteristics of patients with and without VTE, there were no statistically significant differences in the sex, race (white, black, Hispanic, or other), or insurance status (Medicaid, private, self-pay, or other). There were also no statistically significant differences in hospital bed size and hospital type (non-children's, children's general or specialty, or children's unit in general hospital).

The use of hospital resources by the VTE and non-VTE groups are summarized in Table 2. Patients in the VTE group had a longer length of stay (28.6 days compared with 4.5 days), more procedures (8.2 compared with 1.8), and a higher percentage of hospitalizations involving major surgical procedures (76.4% compared with 21.4%). Additionally, the estimated average total charge for VTE-associated stays was $289,716 (95% CI $256,517–$322,915) compared with $48,201 in the non-VTE cases (95% CI $45,437–$50,966).

TABLE 2:

Year 2009 national estimates of hospital resources*

VariableOverallVTE GroupNon-VTE Group
length of stay in days4.6 (4.4–4.8)28.6 (24.5–32.8)4.5 (4.3–4.7)
no. of procedures1.9 (1.8–2.0)8.2 (7.3–9.0)1.8 (1.7–1.9)
no. of diagnoses5.3 (5.1–5.4)14.4 (13.4–15.4)5.2 (5.1–5.4)
no. of chronic conditions0.9 (0.8–0.9)2.4 (2.1–2.8)0.9 (0.8–0.9)
total charges$49,301 ($46,490–52,113)$289,716 ($256,517–322,915)$48,201 ($45,437–50,966)

Values represent means (95% CI).

Univariate and multivariate logistic regressions to assess risk factors for VTE among TBI-associated hospital stays are summarized in Table 3. In the multivariate analysis older children aged 15–20 years were nearly 4 times more likely to develop VTE (adjusted odds ratio [aOR], 3.7, 95% CI 1.8–8.0). Length of hospital stay was associated with a small but statistically significant increase in the adjusted odds of VTE (aOR 1.02, 95% CI 1.01–1.03). Accordingly, for every additional day of TBI admission, there was a 2% increase in the odds of VTE. Children hospitalized for nonaccidental trauma were 2.8 times more likely to develop VTE even after we controlled for other risk factors (aOR 2.8, 95% CI 1.1–6.9). Patients with venous catheterization (aOR 3.0, 95% CI 2.0–4.6), mechanical ventilation (aOR 1.9, 95% CI 1.2–2.9), and tracheostomy (aOR 2.3, 95% CI 1.3–4.0) were more likely to develop VTE. In addition, patients more likely to have VTE were those who had cranial surgery (aOR 1.8, 95% CI 1.2–2.8) or orthopedic surgery (aOR 2.4, 95% CI 1.8–3.4).

TABLE 3:

Univariate and multivariate logistic regression for risk of VTE*

VariableUnivariate OR (95% CI)p ValueMultivariate OR (95% CI)p Value
age
 <1 yrREFREF
 1–9 yrs0.48 (0.22–1.01)0.0530.78 (0.36–1.66)0.517
 10–14 yrs0.87 (0.41–1.83)0.7151.47 (0.61–3.52)0.390
 15–20 yrs2.94 (1.69–5.13)<0.0013.73 (1.75–7.96)0.001
 not specified2.32 (0.72–7.46)0.1585.22 (1.46–18.58)0.011
sex
 maleREFREF
 female0.85 (0.62–1.17)0.3290.97 (0.70–1.35)0.858
race
 whiteREFREF
 black0.91 (0.53–1.54)0.7120.92 (0.52–1.60)0.751
 Hispanic1.08 (0.72–1.62)0.7071.20 (0.78–1.84)0.402
 other1.24 (0.68–2.25)0.4771.19 (0.62–2.25)0.604
 not specified1.12 (0.68–1.83)0.6531.27 (0.75–2.14)0.371
length of stay1.04 (1.03–1.05)<0.0011.02 (1.01–1.03)<0.001
primary expected payer
 MedicaidREFREF
 private0.95 (0.68–1.33)0.7770.97 (0.65–1.46)0.890
 self-pay0.78 (0.41–1.48)0.4440.70 (0.34–1.43)0.327
 other0.87 (0.46–1.63)0.6630.61 (0.31–1.21)0.158
hospital bed size
 smallREFREF
 medium1.16 (0.45–2.98)0.7580.79 (0.26–2.37)0.676
 large1.77 (0.76–4.10)0.1820.97 (0.33–2.85)0.953
 not specified1.48 (0.52–4.18)0.4631.93 (0.38–9.86)0.431
hospital type
 non-children'sREFREF
 children's general/specialty0.60 (0.34–1.07)0.0830.98 (0.38–2.52)0.963
 children's unit in general hospital1.21 (0.84–1.75)0.2961.41 (0.95–2.09)0.090
 not specified0.94 (0.51–1.74)0.8400.57 (0.18–1.75)0.323
surgery
 noneREFREF
 cranial4.10 (2.77–6.06)<0.0011.78 (1.15–2.75)0.010
 thoracoabdominal4.58 (3.14–6.66)<0.0011.04 (0.63–1.73)0.897
 orthopedic3.59 (2.61–4.95)<0.0012.44 (1.75–3.41)<0.001
 other2.12 (1.32–3.42)0.0021.16 (0.70–1.92)0.575
procedure
 venous catheterization11.15 (8.28–15.01)<0.0013.04 (2.01–4.62)<0.001
 mechanical ventilation7.43 (5.36–10.32)<0.0011.86 (1.19–2.90)0.006
 tracheostomy18.25 (13.53–24.81)<0.0012.30 (1.31–4.04)0.004
 gastrostomy11.39 (7.83–16.57)<0.0010.59 (0.33–1.05)0.073
nonaccidental trauma2.09 (1.15–3.80)0.0162.78 (1.12–6.86)0.027

REF = reference.

Discussion

Using the national Kids' Inpatient Database (KID), we characterize venous thromboembolism (VTE) in pediatric TBI hospitalizations in the year 2009 in a cross-sectional analysis. To our knowledge, this is the first study to examine pediatric TBI and VTE. Significant risk factors for VTE in the setting of TBI include older age, longer length of hospital stay, nonaccidental trauma, venous catheterization, intubation with mechanical ventilation or tracheostomy, and cranial or orthopedic surgery.

There were an estimated 58,529 pediatric hospitalizations in the United States in 2009 that were associated with TBI, an incidence of 7.9 per 1000 hospital discharges. These results are consistent with what has been reported in the literature.23,25 Using the 2000 KID, Schneier et al.23 reported an estimated 50,658 TBI-associated hospitalizations among children under 17 years of age. Following the same ICD-9-CM definitions for TBI as Schneier et al., we extend the age range of this cohort to 20 years of age or younger, which is the age range included in KID.

Among children hospitalized for TBI, an estimated 4.5 per 1,000 TBI-associated hospitalizations were complicated by VTE. This is nearly 4 times the incidence in the general pediatric population. In a cross-sectional retrospective analysis, we determined the patient and hospitalization characteristics associated with increased likelihood of VTE in the setting of TBI. We found that older age of 15–20 years, cranial or orthopedic surgery, longer hospitalization, venous catheterization, mechanical ventilation, tracheostomy, and nonaccidental trauma were significant risk factors for VTE in this patient population. These findings are in keeping with other reports in the literature that have identified VTE risk factors.5,6,9,17,20,22,26,27

In particular, Vu et al.27 performed a cross-sectional study using the 1997, 2000, and 2003 KID to determine the risk factors for VTE in the hospitalized pediatric population. They found older age, thoracoabdominal and orthopedic surgery, obesity, malignancy, inflammatory bowel disease, and longer hospitalization to be independent risk factors for VTE. The authors did not find trauma to be a statistically significant risk factor. The authors note that minor trauma may have contributed to an underestimated risk of VTE. TBI was not examined. Grandas et al. report 3 cases of VTE in 2746 pediatric patients in a single-center retrospective review covering an 8-year period. TBI was not identified as an independent risk factor for VTE.8 Vavilala et al. examined 58,716 pediatric trauma discharges in a US proprietary database. The incidence of VTE was found to be 0.08%, with 45 events. Interventions associated with increased risk of VTE included craniotomy, central venous line placement, laparotomy, and open reduction and internal fixation of lower-extremity fractures. The TBI population was not examined as a subgroup.26

Our study found older age to be a significant risk factor for VTE. Patients aged 15 to 20 years were 3.7 times more likely develop VTE compared to children aged less than 12 months. In the literature, it is documented that younger children are at decreased risk for thrombotic events, largely due to differences in serum levels of coagulation factors compared with adults.1,13,18,22,27 In addition, older children are more likely to have comorbid conditions such as obesity and use oral contraceptives, which may also increase the risk of VTE in that age group.27 In keeping with our age-related findings, Vavilala et al. found that children older than 10 years of age had a 5-fold risk of VTE compared with children younger than 5 years.26

We investigated the associations of inpatient and surgical procedures with the risk of VTE among patients with TBI. Venous catheterization was found to be a significant risk factor for VTE, which is consistent with the growing evidence of an association between central venous catheterization and VTE in the pediatric population.12,22,26 Vu et al. did not directly examine central line placement in their analysis of risk factors for VTE. They attempted to address this by excluding thrombosis of the upper extremities. In our study, we identified patients who had undergone central venous catheterization with ICD-9-CM codes described and validated by Walkey et al.,28 who validated the codes using their own institutional data. In our study, an estimated 44% of VTEs in the population of patients with TBI were associated with venous catheterization. This is consistent with the incidence reported by Sandoval et al.22 in a single-institution study where 45% of VTEs in children were associated with central venous catheterization.

Regarding other inpatient procedures, mechanical ventilation and tracheostomy were also associated with an increased risk of VTE, but the association with gastrostomy did not achieve statistical significance on multivariate analysis (p = 0.073). Central venous catheterization, mechanical ventilation, and tracheostomy are procedures that tend to occur with prolonged intensive care unit (ICU) stay, the latter of which has been previously identified as a risk factor for VTE.22 Higgerson et al.,12 in a prospective institutional study of children admitted to the pediatric ICU, found that 85% of ICU patients with VTE had undergone mechanical ventilation compared with 30% in the non-VTE group. However, the authors reported that the relationship between mechanical ventilation and VTE was statistically insignificant after adjusting for age, length of stay, severity of illness, and central venous catheterization. The interpretation of our results may be limited due the inability to directly identify ICU admissions, severity of injury, or details of medical interventions using the KID database. Mechanical ventilation and tracheostomy may be independent risk factors for VTE in the setting of TBI, or they may be proxies for prolonged ICU care and/or higher severity of injury. Hanson et al.10 report on a single-institution retrospective chart review on 144 pediatric ICU trauma patients, identifying a relatively high 6.2% rate of symptomatic VTE in this critically ill population. Central venous catheterization, total parenteral nutrition, deep sedation, neuromuscular blockade, inotropic support, and administration of recombinant factor VIIa were associated with risk of thrombosis. Examination of most of these factors is not feasible with KID.

Additionally, we found cranial and orthopedic surgery to be associated with an increased likelihood of VTE. Other surgeries, including thoracoabdominal procedures, were not found to be statistically significant risk factors for VTE in the multivariate analysis. Orthopedic and neurological surgery are known to be risk factors for VTE in the pediatric26 and adult literature.6,16,19 Our study found TBI-associated hospitalizations involving orthopedic surgery and cranial surgery, respectively, to be 2.4 and 1.8 times more likely to be complicated by VTE. Surgery and length of hospital stay may also be useful proxy indicators for severity of injury. TBI patients who have undergone orthopedic surgery or neurosurgery likely sustained greater mechanical trauma and more severe injuries compared with children who did not have surgery. Long-bone fractures, direct endothelial disruption, release of tissue factors associated with neurotrauma, hypercoagulability from inflammation, and venous stasis from prolonged bed rest may be contributing factors in the increased risk of VTE in this TBI population.7,9,10,16,17

Finally, nonaccidental trauma was found to be an independent risk factor for VTE in our study population. Patients with nonaccidental trauma in our sample were younger, with a median of 0 years of age (interquartile range [IQR] 0–1 years). The TBI cohort overall had a median age of 14 years (IQR 4–18 years). While younger age is a protective factor, nonaccidental trauma was also found to be an independent risk factor for VTE. A number of studies have found nonaccidental trauma to be associated with higher morbidity and mortality independent of other risk factors.4,14,21 Roaten et al.,21 in a retrospective chart review of over 6000 patients with traumatic injuries, found nonaccidental trauma to be associated with more severe injuries, increased likelihood of surgery, longer hospital stays, and higher mortality rates (9.7% vs 2.2% in cases of accidental trauma, p < 0.05). Our study found that, among TBI-associated hospitalizations, children with nonaccidental trauma were about 2.8 times more likely to have VTE in the multivariate analysis. This finding corroborates the evidence that children with nonaccidental trauma tend to have increased morbidity. To our knowledge, the association of nonaccidental trauma and VTE has not been previously quantified.

There are a number of limitations to this study. First, an administrative data set is limited in the level of detailed clinical information that can be obtained for each patient. In using the KID, we have no information on the use of chemoprophylaxis, mechanical prophylaxis, or treatment for VTE, which are clinically important variables to consider in evaluating VTE outcomes. Further, severity of injury, critical care treatment details, length of ICU stay, level of disability, and functional outcome would also be important to understand in a clinical study but are not directly available in KID. Second, we used ICD-9-CM diagnosis and procedure codes to identify our study cohort and many of the key variables in our analysis. The possibility of coding errors exists and has been described in database studies.24 We have minimized variability in reporting by using published methodologies for identifying patients with VTE and with TBI.23,24,26–28 This study likely represents symptomatic VTE, as active VTE screening in pediatric populations is less common than in adult clinical practice.10 Another limitation is that with discharge-level data, we cannot identify children longitudinally if they were hospitalized multiple times. In addition, we are unable to determine whether VTEs were preexisting conditions or if they occurred during hospitalization. Since our study population is limited to children with hospitalizations linked with TBI and since chronic VTE codes were not included, an underlying assumption is that VTEs occurred after the patient's acute trauma. Despite these limitations, it is reassuring that our estimates from the national database have remained consistent with what has been reported in the literature both from clinical series and administrative data.

The major advantage of administrative data is the large sample size, which allows for more accurate characterization of low-incidence pediatric conditions. While the limitations of administrative data preclude definitive answers for the clinical questions posed here, the results of our study can suggest directions for future research. Our findings of risk factors for VTE in the setting of TBI highlight the need and the opportunity for examining pathophysiology of coagulation in neurotrauma as well as clinical best practices for thromboembolism prophylaxis and screening in higher risk pediatric groups. Further multicenter retrospective and prospective studies are warranted.

Conclusions

The risk of VTE in children hospitalized for TBI has not been well characterized given its rarity in the pediatric population. Using the KID database, we characterize VTE events in pediatric TBI hospitalizations. Significant risk factors for VTE include older age, longer length of hospital stay, nonaccidental trauma, venous catheterization, mechanical ventilation, tracheostomy, and cranial or orthopedic surgery.

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author contributions to the study and manuscript preparation include the following. Conception and design: Lam. Acquisition of data: both authors. Analysis and interpretation of data: both authors. Drafting the article: both authors. Critically revising the article: both authors. Reviewed submitted version of manuscript: both authors. Approved the final version of the manuscript on behalf of both authors: Lam. Statistical analysis: Harris. Administrative/technical/material support: Lam. Study supervision: Lam.

References

  • 1

    Andrew MDavid MAdams MAli KAnderson RBarnard D: Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 83:125112571994

  • 2

    Barnato AEFarrell MHChang CCLave JRRoberts MSAngus DC: Development and validation of hospital “end-of-life” treatment intensity measures. Med Care 47:109811052009

  • 3

    Denson KMorgan DCunningham RNigliazzo ABrackett DLane M: Incidence of venous thromboembolism in patients with traumatic brain injury. Am J Surg 193:3803842007

  • 4

    DiScala CSege RLi GReece RM: Child abuse and unintentional injuries: a 10-year retrospective. Arch Pediatr Adolesc Med 154:16222000

  • 5

    Ekeh APDominguez KMMarkert RJMcCarthy MC: Incidence and risk factors for deep venous thrombosis after moderate and severe brain injury. J Trauma 68:9129152010

  • 6

    Geerts WHBergqvist DPineo GFHeit JASamama CMLassen MR: Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133:381S453S2008

  • 7

    Geerts WHCode KIJay RMChen ESzalai JP: A prospective study of venous thromboembolism after major trauma. N Engl J Med 331:160116061994

  • 8

    Grandas OHKlar MGoldman MHFilston HC: Deep venous thrombosis in the pediatric trauma population: an unusual event: report of three cases. Am Surg 66:2732762000

  • 9

    Halpern CHReilly PMTurtz ARStein SC: Traumatic coagulopathy: the effect of brain injury. J Neurotrauma 25:99710012008

  • 10

    Hanson SJPunzalan RCGreenup RALiu HSato TTHavens PL: Incidence and risk factors for venous thromboembolism in critically ill children after trauma. J Trauma 68:52562010

  • 11

    Healthcare Cost and Utilization Project: Introduction to the HCUP KIDS' Inpatient Database (KID) 2009 Rockville, MDAgency for Healthcare Research and Quality2013. (http://www.hcup-us.ahrq.gov/db/nation/kid/kid_2009_introduction.jsp) [Accessed January 21 2014]

  • 12

    Higgerson RALawson KAChristie LMBrown AMMcArthur JATotapally BR: Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients. Pediatr Crit Care Med 12:6286342011

  • 13

    Ignjatovic VMertyn EMonagle P: The coagulation system in children: developmental and pathophysiological considerations. Semin Thromb Hemost 37:7237292011

  • 14

    Keenan HTRunyan DKNocera M: Child outcomes and family characteristics 1 year after severe inflicted or noninflicted traumatic brain injury. Pediatrics 117:3173242006

  • 15

    Knudson MMIkossi DGKhaw LMorabito DSpeetzen LS: Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank. Ann Surg 240:4904982004

  • 16

    Lapidus LJPonzer SPettersson Hde Bri E: Symptomatic venous thromboembolism and mortality in orthopaedic surgery—an observational study of 45 968 consecutive procedures. BMC Musculoskelet Disord 14:1772013

  • 17

    Laroche MKutcher MEHuang MCCohen MJManley GT: Coagulopathy after traumatic brain injury. Neurosurgery 70:133413452012

  • 18

    Miller BEBailey JMMancuso TJWeinstein MSHolbrook GWSilvey EM: Functional maturity of the coagulation system in children an evaluation using thrombelastography. Aesth Analg 84:7457481997

  • 19

    Patel APKoltz MTSansur CAGulati MHamilton DK: An analysis of deep vein thrombosis in 1277 consecutive neurosurgical patients undergoing routine weekly ultrasonography. Clinical article. J Neurosurg 118:5055092013

  • 20

    Reiff DAHaricharan RNBullington NMGriffin RLMcGwin G JrRue LW III: Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis. J Trauma 66:143614402009

  • 21

    Roaten JBPartrick DANydam TLBensard DDHendrickson RJSirotnak AP: Nonaccidental trauma is a major cause of morbidity and mortality among patients at a regional level 1 pediatric trauma center. J Pediatr Surg 41:201320152006

  • 22

    Sandoval JASheehan MPStonerock CEShafique SRescorla FJDalsing MC: Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vasc Surg 47:8378432008

  • 23

    Schneier AJShields BJHostetler SGXiang HSmith GA: Incidence of pediatric traumatic brain injury and associated hospital resource utilization in the United States. Pediatrics 118:4834922006

  • 24

    Shore ADMcCarthy MLSerpi TGertner M: Validity of administrative data for characterizing traumatic brain injury-related hospitalizations. Brain Inj 19:6136212005

  • 25

    Stanley RMBonsu BKZhao WEhrlich PFRogers AJXiang H: US estimates of hospitalized children with severe traumatic brain injury: implications for clinical trials. Pediatrics 129:e24e302012

  • 26

    Vavilala MSNathens ABJurkovich GJMackenzie ERivara FP: Risk factors for venous thromboembolism in pediatric trauma. J Trauma 52:9229272002

  • 27

    Vu LTNobuhara KKLee HFarmer DL: Determination of risk factors for deep venous thrombosis in hospitalized children. J Pediatr Surg 43:109510992008

  • 28

    Walkey AJWiener RSLindenauer PK: Utilization patterns and outcomes associated with central venous catheter in septic shock: a population-based study. Crit Care Med 41:145014572013

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Article Information

Address correspondence to: Sandi Lam, M.D., M.B.A., Department of Neurosurgery, Baylor College of Medicine, Texas Children's Hospital, 6701 Fannin St., Ste. 1230-01, Houston, TX 77030. email: sandilam@gmail.com.

Please include this information when citing this paper: published online February 21, 2014; DOI: 10.3171/2014.1.PEDS13479.

© AANS, except where prohibited by US copyright law.

Headings

References

1

Andrew MDavid MAdams MAli KAnderson RBarnard D: Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 83:125112571994

2

Barnato AEFarrell MHChang CCLave JRRoberts MSAngus DC: Development and validation of hospital “end-of-life” treatment intensity measures. Med Care 47:109811052009

3

Denson KMorgan DCunningham RNigliazzo ABrackett DLane M: Incidence of venous thromboembolism in patients with traumatic brain injury. Am J Surg 193:3803842007

4

DiScala CSege RLi GReece RM: Child abuse and unintentional injuries: a 10-year retrospective. Arch Pediatr Adolesc Med 154:16222000

5

Ekeh APDominguez KMMarkert RJMcCarthy MC: Incidence and risk factors for deep venous thrombosis after moderate and severe brain injury. J Trauma 68:9129152010

6

Geerts WHBergqvist DPineo GFHeit JASamama CMLassen MR: Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133:381S453S2008

7

Geerts WHCode KIJay RMChen ESzalai JP: A prospective study of venous thromboembolism after major trauma. N Engl J Med 331:160116061994

8

Grandas OHKlar MGoldman MHFilston HC: Deep venous thrombosis in the pediatric trauma population: an unusual event: report of three cases. Am Surg 66:2732762000

9

Halpern CHReilly PMTurtz ARStein SC: Traumatic coagulopathy: the effect of brain injury. J Neurotrauma 25:99710012008

10

Hanson SJPunzalan RCGreenup RALiu HSato TTHavens PL: Incidence and risk factors for venous thromboembolism in critically ill children after trauma. J Trauma 68:52562010

11

Healthcare Cost and Utilization Project: Introduction to the HCUP KIDS' Inpatient Database (KID) 2009 Rockville, MDAgency for Healthcare Research and Quality2013. (http://www.hcup-us.ahrq.gov/db/nation/kid/kid_2009_introduction.jsp) [Accessed January 21 2014]

12

Higgerson RALawson KAChristie LMBrown AMMcArthur JATotapally BR: Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients. Pediatr Crit Care Med 12:6286342011

13

Ignjatovic VMertyn EMonagle P: The coagulation system in children: developmental and pathophysiological considerations. Semin Thromb Hemost 37:7237292011

14

Keenan HTRunyan DKNocera M: Child outcomes and family characteristics 1 year after severe inflicted or noninflicted traumatic brain injury. Pediatrics 117:3173242006

15

Knudson MMIkossi DGKhaw LMorabito DSpeetzen LS: Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank. Ann Surg 240:4904982004

16

Lapidus LJPonzer SPettersson Hde Bri E: Symptomatic venous thromboembolism and mortality in orthopaedic surgery—an observational study of 45 968 consecutive procedures. BMC Musculoskelet Disord 14:1772013

17

Laroche MKutcher MEHuang MCCohen MJManley GT: Coagulopathy after traumatic brain injury. Neurosurgery 70:133413452012

18

Miller BEBailey JMMancuso TJWeinstein MSHolbrook GWSilvey EM: Functional maturity of the coagulation system in children an evaluation using thrombelastography. Aesth Analg 84:7457481997

19

Patel APKoltz MTSansur CAGulati MHamilton DK: An analysis of deep vein thrombosis in 1277 consecutive neurosurgical patients undergoing routine weekly ultrasonography. Clinical article. J Neurosurg 118:5055092013

20

Reiff DAHaricharan RNBullington NMGriffin RLMcGwin G JrRue LW III: Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis. J Trauma 66:143614402009

21

Roaten JBPartrick DANydam TLBensard DDHendrickson RJSirotnak AP: Nonaccidental trauma is a major cause of morbidity and mortality among patients at a regional level 1 pediatric trauma center. J Pediatr Surg 41:201320152006

22

Sandoval JASheehan MPStonerock CEShafique SRescorla FJDalsing MC: Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vasc Surg 47:8378432008

23

Schneier AJShields BJHostetler SGXiang HSmith GA: Incidence of pediatric traumatic brain injury and associated hospital resource utilization in the United States. Pediatrics 118:4834922006

24

Shore ADMcCarthy MLSerpi TGertner M: Validity of administrative data for characterizing traumatic brain injury-related hospitalizations. Brain Inj 19:6136212005

25

Stanley RMBonsu BKZhao WEhrlich PFRogers AJXiang H: US estimates of hospitalized children with severe traumatic brain injury: implications for clinical trials. Pediatrics 129:e24e302012

26

Vavilala MSNathens ABJurkovich GJMackenzie ERivara FP: Risk factors for venous thromboembolism in pediatric trauma. J Trauma 52:9229272002

27

Vu LTNobuhara KKLee HFarmer DL: Determination of risk factors for deep venous thrombosis in hospitalized children. J Pediatr Surg 43:109510992008

28

Walkey AJWiener RSLindenauer PK: Utilization patterns and outcomes associated with central venous catheter in septic shock: a population-based study. Crit Care Med 41:145014572013

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