Neurosurgical patients are at risk for developing

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1 J Neurosurg 121: , 2014 AANS, 2014 What clinical factors predict the incidence of deep venous thrombosis and pulmonary embolism in neurosurgical patients? Clinical article John D. Rolston, M.D., Ph.D., 1 Seunggu J. Han, M.D., 1 Orin Bloch, M.D., 2 and Andrew T. Parsa, M.D., Ph.D. 2 1 Department of Neurological Surgery, University of California, San Francisco, California; and 2 Department of Neurological Surgery, Northwestern University, Chicago, Illinois Object. Venous thromboembolisms (VTEs) occur frequently in surgical patients and can manifest as pulmonary emboli (PEs) or deep venous thromboses (DVTs). While many medical therapies have been shown to prevent VTEs, neurosurgeons are concerned about the use of anticoagulants in the postoperative setting. To better understand the prevalence of and the patient-level risk factors for VTE, the authors analyzed data from the National Surgical Quality Improvement Program (NSQIP). Methods. Retrospective data on 1,777,035 patients for the years from 2006 to 2011 were acquired from the American College of Surgeons NSQIP database. Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as neurological surgery. Univariate statistics were calculated using the chi-square test, with 95% confidence intervals used for the resultant risk ratios. Multivariate models were constructed using binary logistic regression with a maximum number of 20 iterations. Results. Venous thromboembolisms were found in 1.7% of neurosurgical patients, with DVTs roughly twice as common as PEs (1.3% vs 0.6%, respectively). Significant independent predictors included ventilator dependence, immobility (that is, quadriparesis, hemiparesis, or paraparesis), chronic steroid use, and sepsis. The risk of VTE was significantly higher in patients who had undergone cranial procedures (3.4%) than in those who had undergone spinal procedures (1.1%). Conclusions. Venous thromboembolism is a common complication in neurosurgical patients, and the frequency has not changed appreciably over the past several years. Many factors were identified as independently predictive of VTEs in this population: ventilator dependence, immobility, and malignancy. Less anticipated predictors included chronic steroid use and sepsis. Venous thromboembolisms appear significantly more likely to occur in patients undergoing cranial procedures than in those undergoing spinal procedures. A better appreciation of the prevalence of and the risk factors for VTEs in neurosurgical patients will allow targeting of interventions and a better understanding of which patients are most at risk. ( Key Words pulmonary embolus deep venous thrombosis venous thromboembolism complication quality improvement vascular disorders Abbreviations used in this paper: ACS = American College of Surgeons; COPD = chronic obstructive pulmonary disease; DVT = deep venous thrombosis; NSQIP = National Surgical Quality Improvement Program; PE = pulmonary embolus; SIRS = systemic inflammatory response syndrome; VTE = venous thromboembolism. Neurosurgical patients are at risk for developing potentially catastrophic deep venous thromboses (DVTs) and pulmonary emboli (PEs). 7,13 Unfractionated heparin, low-molecular-weight heparin, compression stockings, and sequential compression devices all reduce the risk of DVTs and PEs. 2,4,7,13 Some of these prophylactic treatments bear specific risks, including intracerebral hemorrhage and bleeding, and concerns about these risks can limit the use of these treatments. 2,6 8,13 Here we used data from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 9,10 to identify predictors of developing venous thromboembolism (VTE) and analyzed VTE occurrence over time. Efficient management paradigms will probably depend on identifying those patients most at risk for developing VTE. The long-term goal of the present study is to facilitate a better understanding of which patients will most likely 908 J Neurosurg / Volume 121 / October 2014

2 Pulmonary embolism and deep venous thrombosis in neurosurgery benefit from prophylactic treatments that mean added costs to health care while potentially incurring risk. Methods Data on 1,777,035 patients for the years 2006 to 2011 were acquired from the ACS NSQIP database. 9,10 This database contains a nationwide data set representing cases from a wide range of academic and private hospitals across 47 US states. 14 Cases are analyzed for a predetermined collection of complications, including VTEs. Reviewers are frequently audited, and stringent criteria for each complication are used. In particular, DVTs must be diagnosed within 30 days of an operation by using duplex ultrasound, venography, or CT scanning, and patients must be treated for these clots with an inferior vena cava filter, inferior vena cava ligation, or anticoagulation therapy. Pulmonary embolisms must occur within 30 days of an operation and must be confirmed with a highprobability ventilation-perfusion (VQ) scan, CT scan, or pulmonary arteriogram. Database files were acquired in delimited text format and parsed using both SPSS version 20 (IBM Corp.) and MATLAB R2012a (MathWorks Inc.). Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as neurological surgery and further classified as spine or cranial depending on the current procedural terminology (CPT) code (Table 1). Descriptive statistics are represented as the means ± standard deviation. Univariate statistics were calculated using the chi-square test, and 95% confidence intervals are presented for the resultant risk ratios. Predictors included in the models are listed in Table 2. Multivariate models were constructed using binary logistic regression with a maximum of 20 iterations. Variables that were significant (p < 0.05) on univariate analysis were included in the multivariate model. During model building, insignificant predictors (p > 0.05) were removed in a stepwise fashion using the Wald statistic. Significant predictors from this model were identified, and their odds ratios were presented along with the 95% confidence intervals. Results Demographics and Prevalence Using the NSQIP database, we identified 38,058 neurosurgical cases for the years 2006 to Patient demographics are shown in Table 3. Six hundred forty cases of VTE were identified, corresponding to 1.7% of the neurosurgical cases. Of these cases, 244 (0.6%) involved PEs and 484 (1.3%) involved DVTs requiring treatment. Asymptomatic and untreated DVTs were not included in this analysis. The prevalence of VTEs was consistent from year to year, ranging from a low of 1.3% in 2007 to a high of 1.8% in There was no significant trend in the percentage of VTEs over time (F = 0.759; p = 0.45). This consistency in prevalence was also true for DVTs (min 1.0% in 2007 and max 1.5% in 2008; F = 0.305; p = 0.62) and PEs (min 0.4% in 2007 and max 0.7% in 2009; F = 0.304; p = 0.62). J Neurosurg / Volume 121 / October 2014 TABLE 1: Current procedural terminology (CPT) codes included in study Spine Codes Cranial Codes 0090T T T T T T T T T

3 J. D. Rolston et al. TABLE 2: Predictors included in models* sex race Patient Characteristic type of surgery age year of operation height weight diabetes tobacco use ethanol use dyspnea ventilator dependence in 48 hrs prior to surgery severe COPD preop pneumonia ascites esophageal varices congestive heart failure recent MI prior PCI prior cardiac surgery angina hypertension requiring medication peripheral vascular disease rest pain renal failure dialysis altered mental status coma hemiparesis TIA stroke w/ persistent deficit stroke w/o persistent deficit CNS tumor paraparesis quadriparesis disseminated cancer wound infection chronic steroid use recent weight loss bleeding disorder transfusion chemotherapy radiotherapy sepsis Value M, F white, African American, Asian or Pacific Islander, American Indian or Alaskan Native cranial, spinal yrs none, insulin independent, insulin dependent none, SIRS, sepsis, septic shock * MI = myocardial infarction; PCI = percutaneous coronary intervention; TIA = transient ischemic attack. TABLE 3: Basic demographics for 38,058 neurosurgical patients in the NSQIP database* Characteristic No. (%) mean age in yrs ± SD 56.0 ± 15.0 mean weight in lbs ± SD ± 46.9 mean height in inches ± SD 66.9 ± 4.2 sex M 19,349 (50.8) F 18,634 (49.0) unknown 75 (0.2) race white 30,104 (79.1) African American 2922 (7.7) Asian or Pacific Islander 722 (1.9) American Indian or Alaskan Native 221 (0.6) unknown 4089 (10.7) surgery type cranial 10,041 (26.4) spinal 28,017 (73.6) inpatient vs outpatient inpatient 32,628 (85.7) outpatient 5430 (14.3) diabetes no 32,630 (85.7) yes 5428 (14.3) insulin dependent 1906 (5.0) not insulin dependent 3522 (9.3) tobacco use no 28,434 (74.7) yes 9623 (25.3) unknown 1 (0.0) ethanol use no 26,530 (69.7) yes 1064 (2.8) unknown 10,464 (27.5) ventilator dependence in 48 hrs before op no 37,401 (98.3) yes 657 (1.7) severe COPD no 36,507 (95.9) yes 1551 (4.1) preop pneumonia no 27,505 (72.3) yes 69 (0.2) (continued) 910 J Neurosurg / Volume 121 / October 2014

4 Pulmonary embolism and deep venous thrombosis in neurosurgery TABLE 3: Basic demographics for 38,058 neurosurgical patients in the NSQIP database* (continued) Characteristic No. (%) ascites no 38,037 (99.9) yes 21 (0.1) esophageal varices no 27,566 (72.4) yes 8 (0.0) CHF no 37,931 (99.7) yes 127 (0.3) prior MI no 27,497 (72.3) yes 77 (0.2) prior PCI no 26,173 (68.8) yes 1401 (3.7) prior cardiac surgery no 26,450 (69.5) yes 1123 (3.0) unknown 10,485 (27.6) angina no 27,430 (72.1) yes 143 (0.4) unknown 10,485 (27.6) hypertension requiring medication no 20,205 (53.1) yes 17,853 (46.9) peripheral vascular disease no 27,311 (71.8) yes 263 (0.7) rest pain no 27,521 (72.3) yes 52 (0.1) unknown 10,485 (27.6) renal failure no 38,003 (99.9) yes 54 (0.1) unknown 1 (0.0) dialysis no 37,899 (99.6) yes 158 (0.4) unknown 1 (0.0) J Neurosurg / Volume 121 / October 2014 (continued) TABLE 3: Basic demographics for 38,058 neurosurgical patients in the NSQIP database* (continued) Characteristic No. (%) altered mental status no 26,524 (69.7) yes 1050 (2.8) coma no 27,350 (71.9) yes 224 (0.6) hemiparesis before surgery no 26,396 (69.4) yes 1178 (3.1) prior TIA no 26,918 (70.7) yes 656 (1.7) history of stroke w/ persistent deficit no 26,441 (69.5) yes 1133 (3.0) history of stroke w/o persistent deficit no 27,048 (71.1) yes 526 (1.4) CNS tumor no 24,669 (64.8) yes 2905 (7.6) paraparesis no 26,463 (69.5) yes 1111 (2.9) quadriparesis no 27,339 (71.8) yes 235 (0.6) disseminated cancer no 36,527 (96.0) yes 1531 (4.0) wound infection no 37,427 (98.3) yes 631 (1.7) steroid use no 35,740 (93.9) yes 2318 (6.1) (continued) 911

5 J. D. Rolston et al. TABLE 3: Basic demographics for 38,058 neurosurgical patients in the NSQIP database* (continued) Predictors of VTE Characteristic No. (%) recent weight loss no 37,633 (98.9) yes 425 (1.1) bleeding disorder no 36,966 (97.1) yes 1091 (2.9) unknown 1 (0.0) transfusion no 37,913 (99.6) yes 145 (0.4) chemotherapy no 27,300 (71.7) yes 274 (0.7) radiotherapy no 27,218 (71.5) yes 173 (0.5) unknown 10,667 (28.0 sepsis none 36,581 (96.1) SIRS 896 (2.4) sepsis 281 (0.7) septic shock 59 (0.2) unknown 241 (0.6) emergency case no 35,806 (94.1) yes 2252 (5.9) * CHF = congestive heart failure. Multivariate statistical analysis was used to identify patient characteristics predictive of VTE, PE, and DVT formation. For VTEs (that is, DVTs requiring treatment and PEs), the rate of cranial cases was far higher than the rate of spinal cases (3.4% vs 1.1%; Table 4). This difference was significant, with an OR of 0.44 (95% CI ), showing the lower likelihood of a VTE developing in spinal patients as compared with cranial patients. This difference persisted when analyzing solely DVTs or PEs. For DVTs alone, there were events in 259 cranial cases (2.6%) versus 225 spinal cases (0.8%; OR 0.52, 95% CI ; Table 5). For PEs alone, there were events in 137 cranial cases (1.4%) as compared with 107 spinal cases (0.4%; OR 0.34, 95% CI ; Table 6). Other significant predictors of VTE included the presence of a CNS tumor (OR 2.24, 95% CI ), any significant motor weakness (whether hemiparesis [OR 1.80, 95% CI ], quadriparesis [OR 3.78, 95% CI ] or paraparesis [OR 2.56, 95% CI ]), chronic steroid use (OR 1.63, 95% CI ), and ventilator dependence prior to surgery (OR 2.41, 95% CI ; Table 4). Other notable predictors were the presence of systemic inflammatory response syndrome (SIRS) criteria (OR 2.32, 95% CI ), sepsis (OR 3.97, 95% CI ), or septic shock (OR 3.58, 95% CI ). These individual predictors were also identified when constructing a multivariate model exclusively with DVTs (Table 5). However, three additional significant protective predictors were found: severe chronic obstructive pulmonary disease (COPD; OR 1.62, 95% CI ), chemotherapy use (OR 2.16, 95% CI ), and tobacco use (OR 0.70, 95% CI ). Because there were fewer PEs than DVTs (244 vs 484) and consequently less power in the statistical analysis, fewer significant predictors were identified in the analysis of PEs when examined in isolation (Table 6). Nevertheless, the type of procedure (cranial vs spinal) remained significant, as did the presence of paraparesis (OR 2.78, 95% CI ) or SIRS (OR 2.69, 95% CI ). One additional predictor, not found in the analysis of either VTEs or DVTs, was an altered mental status (OR 1.93, 95% CI ). Again, these predictors were identified even when confounding variables, such as the presence of disseminated cancer or CNS tumors, were controlled for. Discussion Using the NSQIP database, which contains data from more than 1 million surgical patients, we analyzed patient-level predictors of VTE and, individually, of DVT and PE. Patients who underwent spine surgery were significantly less likely to develop DVTs or PEs than those who underwent cranial surgery, with an OR of 0.44 (95% CI ). This was true even when accounting for multiple confounders using multivariate logistic regression (see Table 2 for a list of variables). The cause of this difference is unknown. Perhaps the NSQIP data set is lacking important predictors of VTE that would otherwise account for the discrepancy, although a great deal of variables are included, such as the presence of a CNS tumor, paralysis, stroke, coma, ventilator dependence, and so forth (Table 3). Alternatively, physician practice could explain some of the difference. Perhaps cranial surgeons are less likely than spinal surgeons to prescribe VTE prophylaxis. If so, this tendency could be attributable to a heightened concern among cranial surgeons for postoperative bleeding and the devastating consequences thereof, despite the fact that multiple studies refute this idea. 1,3,5,7,12 It should be noted that the NSQIP database contains no information about whether thromboprophylaxis was used. A last possibility relates to follow-up time. Perhaps cranial patients are hospitalized longer and thus have more time for VTEs to present themselves in the hospital setting and to show up as complications within the medical record. Other predictors of VTE identified in this study have been previously mentioned and thus offer validity to the methodology used herein. These predictors include the presence of cancer and venostasis, such as that found in 912 J Neurosurg / Volume 121 / October 2014

6 Pulmonary embolism and deep venous thrombosis in neurosurgery TABLE 4: Significant predictors of VTE in neurosurgical patients, both univariate and multivariate Factor No. of VTEs (%) Univariate OR (95% CI) Multivariate OR (95% CI) age 1.03 ( )* weight 1.01 ( )* surgery type cranial 345 (3.4) 1 [reference] 1 [reference] spinal 295 (1.1) 0.30 ( )* 0.44 ( )* hemiparesis before surgery no 387 (1.5) 1 [reference] 1 [reference] yes 70 (5.9) 4.25 ( )* 1.80 ( )* history of stroke w/o persistent deficit no 437 (1.6) 1 [reference] 1 [reference] yes 20 (3.8) 2.41 ( )* 1.85 ( )* chemotherapy no 437 (1.6) 1 [reference] 1 [reference] yes 20 (7.3) 4.84 ( )* 1.94 ( )* ventilator dependence in 48 hrs before op no 581 (1.6) 1 [reference] 1 [reference] yes 59 (9.0) 6.25 ( )* 2.41 ( )* CNS tumor no 322 (1.3) 1 [reference] 1 [reference] yes 135 (4.6) 3.69 ( )* 2.24 ( )* paraparesis no 412 (1.6) 1 [reference] 1 [reference] yes 45 (4.1) 2.67 ( )* 2.56 ( )* quadriparesis no 445 (1.6) 1 [reference] 1 [reference] yes 12 (5.1) 3.25 ( )* 3.78 ( )* steroid use no 550 (1.5) 1 [reference] 1 [reference] yes 90 (3.9) 2.58 ( )* 1.63 ( )* sepsis none 538 (1.5) 1 [reference] 1 [reference] SIRS 64 (7.1) 5.15 ( )* 2.32 ( )* sepsis 24 (8.5) 6.26 ( )* 3.97 ( )* septic shock 6 (10.2) 7.58 ( )* 3.58 ( )* severe COPD no 592 (1.6) 1 [reference] yes 48 (3.1) 1.94 ( )* tobacco use no 532 (1.9) 1 [reference] yes 108 (1.1) 0.60 ( )* patient sex M 353 (1.8) 1 [reference] F 286 (1.5) 0.84 ( )* race white 487 (1.6) 1 [reference] African American 81 (2.8) 1.74 ( )* Asian or Pacific Islander 8 (1.1) 0.68 ( ) American Indian or Alaskan Native 3 (1.4) 0.84 ( ) (continued) J Neurosurg / Volume 121 / October

7 TABLE 4: Significant predictors of VTE in neurosurgical patients, both univariate and multivariate (continued) J. D. Rolston et al. Factor No. of VTEs (%) Univariate OR (95% CI) Multivariate OR (95% CI) ethanol use no 443 (1.7) 1 [reference] yes 14 (1.3) 0.79 ( ) hypertension requiring medication no 279 (1.4) 1 [reference] yes 361 (2.0) 1.47 ( )* preop pneumonia no 453 (1.7) 1 [reference] yes 4 (5.8) 3.67 ( )* dialysis no 638 (1.7) 1 [reference] yes 2 (1.3) 0.75 ( ) renal failure no 637 (1.7) 1 [reference] yes 3 (5.6) 3.45 ( )* altered mental status no 383 (1.4) 1 [reference] yes 74 ( ( )* coma no 438 (1.6) 1 [reference] yes 19 (8.5) 5.69 ( )* history of TIA no 438 (1.6) 1 [reference] yes 19 (2.9) 1.80 ( )* history of stroke w/ persistent deficit no 394 (1.5) 1 [reference] yes 63 (5.6) 3.89 ( )* disseminated cancer no 575 (1.6) 1 [reference] yes 65 (4.2) 2.77 ( )* wound infection no 616 (1.6) 1 [reference] yes 24 (3.8) 2.36 ( )* recent weight loss no 629 (1.7) 1 [reference] yes 11 (2.6) 1.56 ( ) bleeding disorder no 592 (1.6) 1 [reference] yes 48 (4.4) 2.83 ( )* transfusion no 632 (1.7) 1 [reference] yes 8 (5.5) 3.44 ( )* radiotherapy no 441 (1.6) 1 [reference] yes 12 (6.9) 4.53 ( )* CHF no 635 (1.7) 1 [reference] yes 5 (3.9) 2.41 ( ) (continued) 914 J Neurosurg / Volume 121 / October 2014

8 Pulmonary embolism and deep venous thrombosis in neurosurgery TABLE 4: Significant predictors of VTE in neurosurgical patients, both univariate and multivariate (continued) Factor No. of VTEs (%) Univariate OR (95% CI) Multivariate OR (95% CI) prior MI no 455 (1.7) 1 [reference] yes 2 (2.6) 1.58 ( ) prior PCI no 436 (1.7) 1 [reference] yes 21 (1.5) 0.90 ( ) prior cardiac surgery no 425 (1.6) 1 [reference] yes 31 (2.8) 1.74 ( )* angina no 452 (1.6) 1 [reference] yes 4 (2.8) 1.72 ( ) peripheral vascular disease no 451 (1.7) 1 [reference] yes 6 (2.3) 1.39 ( ) rest pain no 455 (1.7) 1 [reference] yes 1 (1.9) 1.17 ( ) esophageal varices no 456 (1.7) 1 [reference] yes 1 (12.5) 8.49 ( )* ascites no 639 (1.7) 1 [reference] yes 1 (4.8) 2.93 ( ) * Indicates a statistically significant odds ratio. Constant for multivariable model was the many forms of immobility documented in the NSQIP (quadriparesis, paralysis, hemiparesis, and ventilator dependence). 17 Perhaps less anticipated was steroid use as a risk factor. There is some evidence that steroid use is a risk factor for VTE in patients with Crohn s disease: In one study, 61.5% of patients on steroids developed portal venous thrombosis versus 28.9% of patients not on steroids. 11 This association with steroids is also supported by studies showing that patients with Cushing s disease have an elevated risk of VTE, presumably through a variety of increased procoagulant factors. 16 Another underappreciated risk factor identified in this study was sepsis, which has been illustrated outside the neurosurgical context. 15 There are a variety of proposed mechanisms for the observed increased thrombogenesis, including overproduction of plasminogen activator inhibitor-1, dysfunctional endothelial cells, and aberrant expression of tissue factor. 15 Further study of these pathways in neurosurgical patients may be warranted. A number of limitations to our analysis are worth noting. The NSQIP database documents only VTEs that were symptomatic and required treatment, which probably results in an underrepresentation of the true incidence of VTE since asymptomatic events are not documented. In the same regard, patients with symptomatic VTE who J Neurosurg / Volume 121 / October 2014 had contraindications to treatment were also probably not included in the analysis. As the NSQIP database collects and tracks data across multiple surgical specialties, the comorbidities and risk adjustment variables that are tracked tend to be general and broad. The presence of cardiac, pulmonary, or endocrinological comorbidities are well documented, as are a number of procedural risk factors, such as whether a case was done in an emergent setting; however, these procedural risk factors are general and not specific to neurosurgery. For example, within spinal surgeries, a single-level laminotomy is included in the same analysis group as a multilevel deformity correction, and it is difficult to differentiate cases by complexity based on variables specific to neurosurgery (for example, levels performed for the same procedure). Another limitation is the lack of information regarding DVT prophylaxis, which is now used more frequently than in the past. The proportion of patients with sequential compression devices, subcutaneous heparin, or low-molecular-weight heparin is unknown, as is the degree to which these interventions lower the rates of VTEs in this patient population. It is our hope that future databases, such as the National Neurosurgery Quality and Outcomes Database (N 2 QOD), include this and other more granular data to better learn about VTE mitigation strategies and their potential risks in neurosurgical patients. 915

9 TABLE 5: Significant predictors of DVTs requiring treatment in neurosurgical patients, multivariate model Factor No. of Patients w/ DVTs Requiring Therapy (%) J. D. Rolston et al. OR (95% CI) for Multivariate Model* surgery type cranial 259 (2.6) 1 [reference] spinal 225 (0.8) 0.52 ( ) age 1.02 ( ) weight 1.01 ( ) tobacco use no 402 (1.4) 1 [reference] yes 82 (0.9) 0.70 ( ) ventilator dependence in the 48 hrs before op no 431 (1.2) 1 [reference] yes 53 (8.1) 3.39 ( ) severe COPD no 448 (1.2) 1 [reference] yes 36 (2.3) 1.62 ( ) hemiparesis before surgery no 303 (1.1) 1 [reference] yes 53 (4.5) 1.81 ( ) CNS Tumor no 245 (1.0) 1 [reference] yes 111 (3.8) 2.67 ( ) paraparesis no 319 (1.2) 1 [reference] yes 37 (3.3) 2.48 ( ) quadriparesis no 345 (1.3) 1 [reference] yes 11 (4.7) 4.44 ( ) steroid use no 417 (1.2) 1 [reference] yes 67 (2.9) 1.52 ( ) chemotherapy no 340 (1.2) 1 [reference] yes 16 (5.8) 2.16 ( ) sepsis none 399 (1.1) 1 [reference] SIRS 51 (5.7) 2.09 ( ) sepsis 21 (7.5) 4.26 ( ) septic shock 6 (10.2) 3.91 ( ) * Constant for multivariable model was Conclusions Venous thromboembolism is a common complication in neurosurgical patients, having affected 1.7% of patients in the NSQIP database. Deep venous thromboses are roughly twice as common as PEs (1.3% vs 0.6%, respectively), and the rate of VTEs has not changed appreciably over the past several years. Many factors predictive of VTEs were identified in this population: ventilator dependence, immobility (as from quadriparesis, hemiparesis, or paraparesis), and malignancy. Less anticipated predictors included chronic steroid use and sepsis. Lastly, VTEs appear significantly more likely to occur in patients undergoing cranial procedures (3.4%) than in those undergoing spinal procedures (1.1%). The sources of this discrepancy are unknown but deserve more careful study. It is our hope that a better appreciation of the prevalence and risk factors of VTEs in neurosurgical patients will allow us to better target interventions and have a better understanding of which patients are most at risk. 916 J Neurosurg / Volume 121 / October 2014

10 Pulmonary embolism and deep venous thrombosis in neurosurgery TABLE 6: Significant predictors of PE in neurosurgical patients, multivariate results only Factor No. of PEs (%) OR (95% CI)* surgery type cranial 137 (1.4) 1 [reference] spinal 107 (0.4) 0.34 ( ) age 1.03 ( ) weight 1.01 ( ) altered mental status no 133 (0.5) 1 [reference] yes 23 (2.2) 1.93 ( ) stroke w/o persistent deficit no 154 (0.6) 1 [reference] yes 10 (1.9) 2.41 ( ) CNS tumor no 115 (0.5) 1 [reference] yes 49 (1.7) 1.86 ( ) paraparesis no 147 (0.6) 1 [reference] yes 17 (1.5) 2.78 ( ) radiotherapy no 157 (0.6) 1 [reference] yes 6 (3.5) 3.07 ( ) sepsis none 210 (0.6) 1 [reference] SIRS 25 (2.8) 2.69 ( ) sepsis 6 (2.1) 2.18 ( ) septic shock 2 (3.4) 3.82 ( ) * Constant for multivariable model was Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Dr. Rolston was supported in part by a Socioeconomic Fellowship from the Congress of Neurological Surgeons. The ACS NSQIP and the hospitals participating in the ACS NSQIP are the sources of the data used herein; however, they have not verified and are not responsible for the statistical validity of the data analysis or derived conclusions in this study. Author contributions to the study and manuscript preparation include the following. Conception and design: Parsa, Rolston. Acquisition of data: Rolston, Han. Analysis and interpretation of data: all authors. Drafting the article: all authors. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Parsa. Statistical analysis: Rolston. References 1. Agnelli G, Piovella F, Buoncristiani P, Severi P, Pini M, D Angelo A, et al: Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 339:80 85, Bikdeli B, Sharif-Kashani B: Prophylaxis for venous thromboembolism: a great global divide between expert guidelines and clinical practice? Semin Thromb Hemost 38: , Cerrato D, Ariano C, Fiacchino F: Deep vein thrombosis and J Neurosurg / Volume 121 / October 2014 low-dose heparin prophylaxis in neurosurgical patients. J Neurosurg 49: , Cheng JS, Arnold PM, Anderson PA, Fischer D, Dettori JR: Anticoagulation risk in spine surgery. Spine (Phila Pa 1976) 35 (9 Suppl):S117 S124, Constantini S, Kanner A, Friedman A, Shoshan Y, Israel Z, Ashkenazi E, et al: Safety of perioperative minidose heparin in patients undergoing brain tumor surgery: a prospective, randomized, double-blind study. J Neurosurg 94: , Hacker RI, Ritter G, Nelson C, Knobel D, Gupta R, Hopkins K, et al: Subcutaneous heparin does not increase postoperative complications in neurosurgical patients: an institutional experience. J Crit Care 27: , Hamilton MG, Yee WH, Hull RD, Ghali WA: Venous thromboembolism prophylaxis in patients undergoing cranial neurosurgery: a systematic review and meta-analysis. Neurosurgery 68: , Hawryluk GW, Furlan JC, Austin JW, Fehlings MG: Survey of neurosurgical management of central nervous system hemorrhage in patients receiving anticoagulation therapy: current practice is highly variable and may be suboptimal. World Neurosurg 76: , Ingraham AM, Richards KE, Hall BL, Ko CY: Quality improvement in surgery: the American College of Surgeons National Surgical Quality Improvement Program approach. Adv Surg 44: , Khuri SF, Henderson WG, Daley J, Jonasson O, Jones RS, Campbell DA Jr, et al: Successful implementation of the Department of Veterans Affairs National Surgical Quality Im- 917

11 J. D. Rolston et al. provement Program in the private sector: the Patient Safety in Surgery study. Ann Surg 248: , Leung GG, Sivasankaran MV, Choi JJ, Divino CM: Risk factors of portal vein thrombosis in Crohn s disease patients. J Gastrointest Surg 16: , Nurmohamed MT, van Riel AM, Henkens CM, Koopman MM, Que GT, d Azemar P, et al: Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery. Thromb Haemost 75: , Raslan AM, Fields JD, Bhardwaj A: Prophylaxis for venous thrombo-embolism in neurocritical care: a critical appraisal. Neurocrit Care 12: , Rolston JD, Han SJ, Lau CY, Berger MS, Parsa AT: Frequency and predictors of complications in neurological surgery: national trends from 2006 to Clinical article. J Neurosurg 120: , Semeraro N, Ammollo CT, Semeraro F, Colucci M: Sepsis, thrombosis and organ dysfunction. Thromb Res 129: , van der Pas R, de Bruin C, Leebeek FW, de Maat MP, Rijken DC, Pereira AM, et al: The hypercoagulable state in Cushing s disease is associated with increased levels of procoagulant factors and impaired fibrinolysis, but is not reversible after short-term biochemical remission induced by medical therapy. J Clin Endocrinol Metab 97: , Wun T, White RH: Venous thromboembolism (VTE) in patients with cancer: epidemiology and risk factors. Cancer Invest 27 (Suppl 1):63 74, 2009 Manuscript submitted July 28, Accepted June 24, Please include this information when citing this paper: published online August 1, 2014; DOI: / JNS Address correspondence to: Andrew T. Parsa, M.D., Ph.D., Department of Neurological Surgery, 400 Parnassus Ave., Box 0350, San Francisco, CA aparsa@nmff.org. 918 J Neurosurg / Volume 121 / October 2014