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The number of spinal fusion surgeries in the US is rapidly rising but little is known about optimal venous thromboembolism prophylaxis after spinal surgery.
To examine the use and outcomes associated with venous thromboembolism prophylaxis after spinal fusion surgery in a cohort of 244 US hospitals.
We identified all patients with a principal procedure code for spinal fusion surgery in hospitals participating in the Premier Perspective database from years 2003 – 2005 and searched for receipt of pharmacologic prophylaxis (subcutaneous unfractionated heparin, low molecular weight heparin, or fondaparinux) and/or mechanical prophylaxis (compression devices and elastic stockings) within the first 7 days after surgery. We also searched for discharge diagnosis codes for venous thromboembolism and post-operative hemorrhage during the index hospitalization and within 30 days after surgery.
Among 80,183 spinal fusion surgeries performed during the time period, cervical fusions were the most common (49.0%) followed by lumbar fusions (47.8%). Thromboembolism prophylaxis was administered to 60.6% of patients within the first week post-operatively, with the most frequent form being mechanical prophylaxis alone (47.6%). Of the 244 hospitals, 26.2% provided prophylaxis to ≥ 90% of their patients undergoing spinal fusion; however, 33.2% provided prophylaxis to fewer than 50% of their patients. The rate of diagnosed venous thromboembolism within 30 days after surgery was 0.45% and the rate of postoperative hemorrhage was 1.1%.
Substantial variation exists in the use of thromboembolism prophylaxis after spinal fusion surgery in the US. Nevertheless, overall rates of diagnosed thromboembolism after spinal fusion appear low.
The number of spinal fusion surgeries performed in the United States has rapidly increased, approaching the rate of joint arthroplasties[1–3]. Although pharmacologic prophylaxis for venous thromboembolism (VTE) is strongly recommended after hip and knee arthroplasty and supported by randomized clinical trial data, the optimal mode of prophylaxis for patients undergoing spinal fusion surgery is unknown. As such, guidelines have been vague about the optimal choice of antithrombotic therapy after spinal fusion. Although a number of risk factors appear to increase the risk of thromboembolism after neurosurgical procedures, including the type of surgery, older age, and underlying malignancy, it is not clear how individual risk factors should incorporated into decision-making regarding VTE prophylaxis.
Various guidelines have suggested subcutaneous unfractionated heparin, low molecular weight heparins, and mechanical means of prophylaxis as reasonable options for patients undergoing spinal fusion surgery. The American College of Chest Physicians 8th Guidelines on Antithrombotic and Thrombolytic Therapy recommends administering VTE prophylaxis after spinal fusion surgery, but does not specify whether mechanical or pharmacologic modalities are preferred. The National Institute of Health and Clinical Excellence (NICE) guidelines recommend that mechanical plus low molecular weight heparin be provided to patients with at least 1 risk factor for thromboembolism. Finally, the North American Spine Society recommends using mechanical prophylaxis after spine surgery, but recommends withholding low molecular weight heparin for routine procedures unless there are additional risk factors for VTE. Perhaps related to the lack of evidence, surveys of real-world surgical practice suggest variability among individual surgeons.
Because of the lack of evidence to support specific recommendations for VTE prophylaxis after spine surgery, we conducted an analysis of a large, retrospective cohort of patients undergoing spine fusion to describe the prevalence and type of VTE prophylaxis use after surgery as well as the rates of post-operative VTE.
We conducted a retrospective analysis using data from 244 hospitals that participated in Premier Incorporated’s Perspective database. The Perspective database is a voluntary, fee-supported database developed to measure the quality and utilization of health care and is composed of mostly small to midsize non-teaching hospitals in urban locations. The database contains a date-stamped log of all items and services billed during a hospitalization, including medications, laboratory tests, and therapeutic services, as well as information about patient and hospital characteristics, primary and secondary discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) diagnostic codes, and disposition status.
We included in our analysis patients aged 18 years or older admitted to participating hospitals between October 1, 2003 and September 30, 2005 with a principal procedure code for spinal fusion surgery, subdivided into cervical fusion (codes 81.01–03, 81.31–33), lumbar fusion (81.06–08, 81.36–38), and other/unspecified spinal fusion (81.05, 81.34–35, 81.00, 81.30, 81.39). Surgical approach was categorized into anterior, posterior, circumferential, and other/unknown, based on ICD-9 codes. We also searched for secondary codes that indicated the number of vertebrae fused: fusion of 2–3 vertebrae (81.62) and fusion of 4 or more vertebrae (81.62, 81.64).
Demographic and hospital data including patient age, sex, race/ethnicity, insurance status, admission type (emergency, outpatient, or transfer from another acute hospital), and hospital region were obtained from the database, in addition to a general measure of illness severity calculated using APR-DRG software (version 15.0, 3M™) that is used to predict mortality. We searched for diagnosis codes for major medical comorbidities using software developed by the Agency of Healthcare Research and Quality, as major medical illnesses increase overall VTE risk. Finally, we searched for individual comorbid conditions that were part of a validated VTE risk score described by Caprini et al.. The VTE risk score included the following risk factors: myocardial infarction/congestive heart failure, age, varicose veins, immobility, obesity, hyperviscosity/hypercoagulable syndromes, estrogen therapy, history of venous thromboembolism, and malignancy. This VTE risk score has been validated in other surgical settings.
We searched the database for all charges corresponding to provision of either mechanical or pharmacologic VTE prophylaxis administered at any point within the first 7 days after the index spinal surgery date. This time period was chosen because the majority of patients undergoing surgery were discharged within 7 days. Mechanical means of prophylaxis was considered present when billing charges for intermittent compression devices or antiembolism stockings of the lower extremities were identified. Pharmacologic prophylaxis was considered present if any of the following medications were dispensed: injectable heparin sodium at doses between 5,000 and 7,500 units, low molecular weight heparins (specifically enoxaparin and dalteparin, as there were no other types of low molecular weight heparins administered), and fondaparinux. We excluded 6,067 patients who received either intravenous heparin or warfarin sodium within the first 7 days because these agents are not used for routine venous thromboembolism prophylaxis and because it was not possible to determine whether their use was for preexisting conditions requiring full-dose anticoagulation.
We searched for secondary discharge diagnosis codes consistent with deep venous thromboses (DVT) or pulmonary embolism (PE) during the index hospitalization (ICD-9 codes: 415.1x, 451.1x, 451.2, 451.81, 451.9, 453.1, 453.2, 453.40, 453.41, 453.42, 453.8, 453.9, and 997.2 with a secondary diagnosis of DVT or PE). In addition, we determined whether patients were readmitted within 30 days with a primary discharge diagnosis code for VTE. Adverse surgical outcomes were identified by searching for specific ICD-9 diagnosis and procedure codes. Post-operative hemorrhages were identified using codes for hemorrhage/hematoma complicating a procedure (998.1, 998.11, 998.12) and extradural hemorrhage (852.4, 432.0). We also searched for codes associated with other surgical complications, specifically wound disruption (998.3, 998.31, 998.32), post-operative infection (998.5, 998.51, 998.59), other complications (998.13, 998.7, 998.8), and for procedure codes associated with control of hemorrhage and re-operation (39.98, 39.99, 83.14, 83.19, 83.39, 83.44, 83.49, 86.04, 86.22, 86.28, 96.58, 96.59, 97.15, 97.16). Finally, we searched for charges indicating transfusion of ≥ 2 units of packed red blood cells within the first 4 days after the index surgery.
Rates of pharmacologic prophylaxis, mechanical prophylaxis, both forms, and no prophylaxis after surgery were determined for different categories of spinal fusion. Bivariable analysis using chi-squared tests for categorical variables, and t-tests and non-parametric tests for continuous variables, were performed to test the association between subject/hospital characteristics and receipt of prophylaxis. We then developed multivariable logistic regression models to test the independent association between clinical characteristics and receipt of VTE prophylaxis. Candidate variables significant at a p < 0.2 were considered for model inclusion. Generalized estimating equations using PROC GENMOD (SAS Institute Inc., Cary, NC) were used to account for potential clustering effects at the hospital and individual provider level. We next developed multivariable logistic regression models using generalized estimating equations modeling the association of clinical characteristics and receipt of prophylaxis with the likelihood of developing diagnosed VTE within 30 days, with the significance level set at 0.05.
We recognized that patients did not receive VTE prophylaxis at random, which introduced the threat of treatment and allocation biases unaccounted for in our base multivariable models. To address these biases, we developed a propensity score representing the likelihood that each patient received VTE prophylaxis. The propensity score was derived using a separate multivariable logistic regression model including all available patient and hospital predictor covariates, where covariates for the propensity score were retained at a significance level set at p < 0.2. The final propensity score was then included as a separate covariate in the multivariable models modeling VTE outcomes. All analyses were performed using SAS version 9.2 (SAS Institute Inc, Cary, NC).
We identified a total of 80,183 spinal fusion surgeries performed between October 1, 2003 and September 30, 2005 in 244 hospitals. The median number of spinal fusions performed by each hospital was 223 (interquartile range 57 – 466). The most common procedures were cervical fusions (39,292, 49.0%), followed by lumbar fusions (38,309, 47.8%), and then miscellaneous fusions (2,582, 3.2%) which were primarily thoracic spinal fusions and fusions not otherwise specified (Table 1). The mean age of subjects was 53.3 years and 45.9% were male. The median length of hospital stay was 3 days and most patients were discharged home after the hospitalization (Table 1).
Venous thromboembolism prophylaxis, either mechanical or pharmacologic, was administered in the hospital setting to 60.6% of subjects within the first 7 days after surgery. Mechanical prophylaxis alone was the most common practice (47.6%) while 13.0% of subjects received pharmacologic prophylaxis (either alone or in combination with mechanical means). A total of 39.4% of subjects received neither mechanical nor pharmacologic prophylaxis. The most common drug used in patients receiving pharmacologic prophylaxis was heparin (66%), followed by low molecular weight heparins (37%). Fondaparinux was rarely used, found in only 0.1% of all patients receiving pharmacologic prophylaxis. Patients undergoing lumbar fusion were more likely than those undergoing cervical fusion to receive pharmacologic prophylaxis: 20.2% compared to 4.8%, p<0.01.
There was wide variation in the proportion of subjects receiving prophylaxis after spinal surgery across the 244 hospitals. On average, hospitals provided VTE prophylaxis to 61.7% (standard deviation 32.4%) of their patients undergoing spinal fusion, and 26.2% of hospitals administering prophylaxis to ≥ 90% of their patients. However, 33.2% of hospitals administered prophylaxis to fewer than 50% of their patients post-operatively (Figure 1).
Table 1 presents the bivariate associations between clinical variables and receipt of prophylaxis. Due to the large size of the dataset, many associations were statistically significant. All factors that reached a significance level of < 0.2 on bivariate analyses were entered into a multivariable model, adjusted for clustering at the hospital and surgeon level. There were no missing data in any of the final included variables. The factors that were significantly associated with VTE prophylaxis in the multivariable model were undergoing lumbar or other fusions compared to cervical fusions, insurance type, depression, higher DRG severity of illness score, higher Caprini VTE risk score, and an intensive care unit stay (Table 2).
There were 5,414 patients who received both pharmacologic and mechanical prophylaxis during their hospitalization. On multivariable analysis, patients more likely to receive combined prophylaxis strategies had risk factors for thromboembolism, including undergoing lumbar fusion (adjusted odds ratio and 95% confidence interval [OR] 4.7 [3.8, 5.7] compared to cervical fusion), surgery involving ≥ 4 vertebral levels (OR 1.2 [1.1, 1.3] compared to 2–3 levels), an intensive care unit stay (OR 1.6 [1.4, 1.7]), higher severity of illness (OR 3.2 [1.4, 1.7] for DRG score of 4 compared to 1), and higher VTE risk score (OR 1.1 [1.1, 1.2]).
There were 222 deep venous thromboses and 149 pulmonary emboli diagnosed in 359 patients in our study, for an overall cohort rate of 0.45%. Of patients with VTE, 56% were diagnosed during the index hospitalization and an additional 44% were diagnosed after discharge but within 30-days of the index surgery. The rate of post-operative hemorrhage was 1.1% and only 1.2% of patients had ≥ 2 units of transfused blood in the first 4 days after surgery (Table 3).
Factors associated with higher thromboembolism rates on unadjusted analysis included surgery on multiple vertebral levels (0.88% for surgeries involving ≥ 4 levels vs. 0.38% with < 4 levels, p<0.001), and with lumbar and other spinal fusions (0.5% and 1.9%, respectively as compared to 0.3% after cervical fusions, p<0.001). Higher unadjusted thromboembolism rates were also observed in subjects who received pharmacologic or pharmacologic plus mechanical prophylaxis, compared to subjects who did not receive prophylaxis (Table 3). Despite adjusting for the propensity to receive VTE prophylaxis, we continued to observe in multivariable models a higher risk of post-operative VTE among patients who received prophylaxis (Table 4).
We identified 896 (1.1%) surgical site hemorrhages in the cohort. On bivariate analysis, receipt of pharmacologic prophylaxis was associated with a greater unadjusted odds of surgical site bleeding compared to receiving no prophylaxis: OR 1.7 [1.4, 2.2] with pharmacologic therapy alone and 2.0 [1.6, 2.5] for pharmacologic plus mechanical prophylaxis. However, when we adjusted for other clinical factors (including age, sex, type of surgery, number of fusion levels, and DRG severity score), the association was not statistically significant: adjusted OR 1.1 [0.8, 1.5] for pharmacologic therapy alone, and OR 1.2 [0.9, 1.5] for pharmacologic plus mechanical therapy.
The primary analyses excluded 6,067 patients who received intravenous heparin or warfarin after their surgery because we were unable to determine whether these patients had pre-existing VTE. However, because excluding these patients may have also excluded patients treated for incident thromboembolism during the hospitalization, we conducted an additional analysis including individuals who received intravenous heparin or warfarin during their hospitalization. When these patients were included, the total number of patients with diagnosis codes of VTE increased to 674, for an overall cohort VTE rate of 0.78%. The number of surgical site hemorrhages increased to 1057, or 1.2% of the cohort, and the number of patients with ≥ 2 units of transfused blood to 1142 (1.3% of the cohort).
In this large sample of patients undergoing spinal fusion surgery, 39.4% of patients received neither pharmacologic nor mechanical forms of VTE prophylaxis in the post-operative period. Significant practice variation was observed across hospitals in terms of the proportion of spinal surgery patients receiving prophylaxis. Overall rates of diagnosed VTE after spinal fusion surgeries were low, even among patients who did not receive VTE prophylaxis, as were rates of surgical site bleeding.
Prophylaxis was more commonly administered to patients with a higher baseline risk for VTE. Patients undergoing lumbar or thoracic fusions were more likely to receive prophylaxis than patients undergoing cervical spine fusion. In addition, physicians were more likely to administer prophylaxis to patients with a higher estimated VTE risk score and to patients who had greater cumulative severity of illness. These findings probably reflect selective administration of prophylaxis to patients who were considered more likely to develop VTE post-operatively. However, these patterns were not consistent across all participating sites, as there was wide variability in the proportion of patients receiving postoperative prophylaxis across individual medical centers.
There is no consensus as to the optimal choice of VTE prophylaxis after spinal fusion surgery. Prior small studies have reported generally low rates of clinically significant thromboembolism after spinal surgery in patients receiving mechanical prophylaxis, ranging from 0.0% to 4% [14–20]. Asymptomatic DVT rates may be higher however, with one study using venography to screen patients undergoing spine surgery reporting a DVT rate of 26.5% after lumbar surgery. A meta-analysis of 4,383 patients undergoing elective spine surgery found a DVT rate of 1.09% and a PE rate of 0.06%; this analysis also found pharmacologic prophylaxis to be more effective in preventing VTE than mechanical means or no prophylaxis, at the expense of a higher rate of epidural hematomas. The 0.45% rate of diagnosed post-operative VTE in our study compares favorably to the 0.81% rate of symptomatic DVT in medical patients not receiving anticoagulant prophylaxis, and the 2%-5% symptomatic VTE rate after elective hip arthroplasty[23,24].
The rate of any post-operative hemorrhage in our cohort was 1.1% and 1.2% of patients received ≥ 2 units of transfused blood in the first 4 days after surgery. In comparison, 0.4% of 1954 spine surgery patients who received nadroparin for VTE prophylaxis developed major hemorrhage post-operatively. We lacked detailed information about the location or management of hemorrhages in our cohort, and so were unable to determine the severity or consequences of such bleeds. However, concerns about hemorrhagic complications, particularly epidural hemorrhages, may contribute to cautious use of pharmacologic prophylaxis after spinal procedures.
Our analyses found paradoxically higher rates of VTE in subjects who received pharmacologic prophylaxis when compared to patients who received neither pharmacologic nor mechanical means of prophylaxis. Randomized trials have clearly shown that pharmacologic prophylaxis reduces VTE rates in medical and surgical patients and our findings should not be used to suggest a lack of efficacy with VTE prophylaxis. The higher VTE rates observed in patients who received pharmacologic prophylaxis in our study are likely due to confounding by indication, where patients at higher baseline risk for thrombosis were more likely to receive more effective forms of VTE prophylaxis. This supposition is supported by the observations that patients with higher severity of illness and higher estimated VTE risk scores were more likely to receive combined mechanical and pharmacologic prophylaxis. Although we attempted to control for baseline risk for VTE and minimize confounding by indication through use of a propensity score analysis, residual confounding remains a major limitation of observational studies such as ours. Thus, the direction and effect size of the odds ratios from our multivariable analysis of the efficacy of VTE prophylaxis should be interpreted with caution and our study should not be used to draw firm conclusions about the relative efficacy and safety of different approaches to VTE prophylaxis.
There are a number of limitations to this analysis. We used a window of 7 days to assess for VTE prophylaxis, although the median length of stay was shorter than this. Patients with uncomplicated procedures may have been discharged prior to consideration of VTE prophylaxis. The diagnosis of postoperative VTE and hemorrhage were dependent on ICD-9 codes. Although prior studies have shown that ICD-9 codes are sensitive for the presence of clinical VTE, the positive predictive value may be lower when the codes are in the secondary position. In addition, reliance on administrative codes may underestimate the true prevalence of VTE, as asymptomatic clots were unlikely to be detected. We were not able to assess for severity of hemorrhage in our study, although rates of transfusion and reoperation were low. Patients who presented with VTE after discharge to an institution other than the index hospital or who were managed only in the outpatient or emergency department setting would not have been captured by our study, potentially underestimating the true rate of VTE. Our primary analysis excluded patients who received intravenous heparin or warfarin after their surgery, which may have also led us to underestimate the rate of events. Finally, as discussed above, our study was an observational study of actual clinical practice and where VTE prophylaxis was not randomly assigned to patients. Residual confounding due to non-randomized allocation of prophylaxis prevent our study from being able to support one thromboprophylaxis strategy over another.
A large proportion of patients undergoing spinal fusion surgery received neither pharmacologic nor mechanical means of thromboembolism prophylaxis in the US. However, rates of diagnosed thromboembolism after spinal fusion surgery appear low, even amongst patients who received no VTE prophylaxis. These low rates of adverse outcomes support the lack of definitive recommendations regarding the optimal form of VTE prophylaxis after spinal fusion.
This study was supported by National Institutes of Health grants K23 AG028978 (MF) and K24 HL098372 (AA). The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
The corresponding author had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Financial disclosure: Dr. Lurie has served as a consultant for the Foundation for Informed Medical Decision Making, Blue Cross-Blue Shield, Sanofi-Aventis, and Regeneron