the association between venous thromboembolism ( vte ) prophylaxis and anesthesia during orthopedic surgery has been well known for a long time . the association between the type of anesthesia and the risk of postoperative vte is well documented . vasodilation occurring during general anesthesia contributes to the onset of vte by causing venous stasis , increase in venous capacitance , and decrease in venous return . use of neuraxial blockade in orthopedic procedures has been shown to be safer in this respect with a low risk of vte , intraoperative bleeding , length of hospital stay , and risk of surgical site infection . however , the advantage of neuraxial blockade with respect to vte may no longer be relevant because of advances made in general anesthesia and pharmacological and mechanical thromboprophylaxis . furthermore , extended neuraxial blockade , such as that required for epidural analgesia , may delay the initiation of postsurgical pharmacological prophylaxis owing to the associated risk of spinal and/or epidural hematoma , possibly leading to a permanent neurological deficit , such as paraplegia . there are no specific clinical guidelines for the choice of anesthesia , largely because of insufficient recent evidence from studies comparing general anesthesia and neuraxial blocks for their association with vte . combined epidural / general anesthesia reduces blood loss and dosage requirement for anesthetic medication , is more effective in pain control , and causes fewer postoperative complications . the japanese study of prevention and actual situation of venous thromboembolism after total arthroplasty ( j - psvt ) is a multicenter , collaborative , prospective , observational study that investigates the efficacy and safety of vte prophylaxis after joint replacement surgery , across 34 japanese national hospital organization ( nho ) hospitals . in the present study , we compared the effects of different types of anesthetic modalities on the incidence of vte in patients undergoing total hip arthroplasty ( tha ) and total knee arthroplasty ( tka ) . this was a secondary analysis of j - psvt , a hospital - based , non - interventional , cohort study to assess the efficacy and safety of current practices for thromboprophylaxis . the design and main results of j - psvt have been previously reported . patients aged > 20 years who were scheduled for tha or tka for primary joint disease were eligible for inclusion . data were collected from all patients undergoing primary tha and tka between 2007 and 2010 in 34 nho hospitals . the trial was registered in the japan umin clinical trial registry ( umin000001366 ) , and the study protocol was approved by the ethics committee of the nho central institutional review board ( no 0623004 ) . written informed consent was obtained from all patients prior to the use of their clinical records . the study endpoint , which was a composite of asymptomatic / symptomatic deep vein thrombosis ( dvt ) up to postoperative day ( pod ) 10 and fatal / non - fatal pulmonary embolism ( pe ) up to pod 10 , was compared with different types of anesthetic modalities . all patients were assessed for dvt in the proximal and distal veins on pod 10 using standard compression ultrasonography ( cus ) . all sonographers were adequately trained . just prior to the start of study , the sonographers received detailed instructions for standardized procedures in a specially organized conference herein they acquired the necessary certification . symptomatic dvt and pe was diagnosed using cus , contrast computed tomography , and lung perfusion scan . data on patient demographics , primary diagnosis , pre - existing comorbid conditions , length of operation , anesthesia type , and vte prophylaxis were gathered using standard case report forms . discrete variables were compared using the chi - squared test ; continuous variables were compared using kruskal variables with a p value of < .2 on univariate logistic regression analysis were included in a multivariate logistic regression model with stepwise forward selection , with forced entry of sex , surgery type , and each pharmacological prophylactic drug . odds ratios ( ors ) and 95% confidence intervals ( cis ) were calculated as an approximation of the relative risk of vte with different types of anesthetic modalities , taking general anesthesia as reference . propensity - score matching was performed to minimize the effects of confounding caused by non - randomized assignment to the type of anesthetic modalities . this was done to reduce the impact of selection bias and allow relevant variables to be evenly balanced in the combined epidural / general and spinal anesthesia groups . tourniquet use was strongly associated with tka because it was used in almost all patients undergoing tka . therefore , all variables except tourniquet use were included in the multiple logistic regression model to estimate the propensity score , which represents the probability of the use of either combined epidural / general or spinal anesthesia . a markov chain monte carlo procedure was used for multiple imputation of missing values for numerical variables , such as body mass index and estimated glomerular filtration rate . a mode imputation procedure was used to impute missing values for categorical variables such as comorbidities . the multiple and mode imputation were performed using the xlstatbase 2015 ( addinsoft , paris , france ) . patients undergoing combined epidural / general or spinal anesthesia were matched on a 1:1 basis using nearest - number matching using a caliper of 0.01 . after matching , the incidence of postsurgical vte was compared using the chi - squared test . data processing and analyses were performed using the statistical analysis system and ibm spss statistics version 23.0 for windows ( spss , chicago , il ) . discrete variables were compared using the chi - squared test ; continuous variables were compared using kruskal variables with a p value of < .2 on univariate logistic regression analysis were included in a multivariate logistic regression model with stepwise forward selection , with forced entry of sex , surgery type , and each pharmacological prophylactic drug . odds ratios ( ors ) and 95% confidence intervals ( cis ) were calculated as an approximation of the relative risk of vte with different types of anesthetic modalities , taking general anesthesia as reference . propensity - score matching was performed to minimize the effects of confounding caused by non - randomized assignment to the type of anesthetic modalities . this was done to reduce the impact of selection bias and allow relevant variables to be evenly balanced in the combined epidural / general and spinal anesthesia groups . tourniquet use was strongly associated with tka because it was used in almost all patients undergoing tka . therefore , all variables except tourniquet use were included in the multiple logistic regression model to estimate the propensity score , which represents the probability of the use of either combined epidural / general or spinal anesthesia . a markov chain monte carlo procedure was used for multiple imputation of missing values for numerical variables , such as body mass index and estimated glomerular filtration rate . a mode imputation procedure was used to impute missing values for categorical variables such as comorbidities . the multiple and mode imputation were performed using the xlstatbase 2015 ( addinsoft , paris , france ) . patients undergoing combined epidural / general or spinal anesthesia were matched on a 1:1 basis using nearest - number matching using a caliper of 0.01 . after matching , data processing and analyses were performed using the statistical analysis system and ibm spss statistics version 23.0 for windows ( spss , chicago , il ) . in total , 2186 patients met the inclusion criteria and were enrolled in the j - psvt study . primary effectiveness outcome was not assessed in 24 patients owing to the lack of ultrasonography or a preoperative history of antiplatelet therapy . thus , the study population of this subgroup study consisted of 2162 patients . based on the type of anesthesia , they were classified into the following groups : general anesthesia ( n  =  646 ) , combined epidural / general anesthesia ( n  =  1004 ) , epidural anesthesia ( n  =  87 ) , and spinal anesthesia ( n  =  425 ) groups . the demographics and clinical characteristics of these patients are shown in table 1 . the incidence of vte in the four groups was as follows : general anesthesia , 16.3% ; combined epidural / general anesthesia , 17.3% ; epidural anesthesia , 10.3% ; and spinal anesthesia , 30.8% ( fig . 1 ) . there was a significant difference in the incidence of vte between these 4 groups ( p  <  .001 ) . composite effectiveness outcomes were the results of asymptomatic / symptomatic deep vein thrombosis up to postoperative day 10 and fatal / non - fatal pulmonary embolism up to postoperative day 10 . there was a significant difference in the incidence of venous thromboembolism between these 4 groups ( p  <  .001 ) . ceg  =  combined epidural / general anesthesia , ea  =  epidural anesthesia , ga  =  general anesthesia , sa  =  spinal anesthesia . on multivariate analysis , only spinal anesthesia was significantly associated with an increased risk of vte when compared with general anesthesia . female sex , older age , and tka were associated with increased vte rates , which is consistent with an earlier report . hypoalbuminemia and fondaparinux therapy was associated with a reduced incidence of vte ( table 2 ) . results of multivariate logistic regression analysis for composite effective outcomes . finally , we directly compared combined epidural / general anesthesia and spinal anesthesia using propensity - score matching to minimize the confounding effects caused by non - randomized assignment to the type of anesthetic modalities . concomitant liver and renal dysfunction and the use of antithrombotics may influence the choice in favor of neuraxial blockade . for this reason , comparison of combined epidural / general anesthesia versus spinal anesthesia is likely to have eliminated this bias in our cohort . moreover , the use of combined epidural / general anesthesia was the most frequent , whereas epidural anesthesia was the least frequent , in our cohort . propensity score matching allowed relevant variables to be balanced between the combined epidural / general anesthesia and spinal anesthesia groups , reducing the impact of selection bias . after propensity score matching baseline characteristics of propensity score - matched patients with combined epidural / general anesthesia and spinal anesthesia groups . in this study , spinal anesthesia increased vte incidence by 48% ( relative risk : 1.48 , 95% ci , 1.181.85 ) when compared with that by combined epidural / general anesthesia ( fig . 2 ) . incidence of venous thromboembolism among propensity - matched patients with combined epidural / general anesthesia and spinal anesthesia . white columns indicate the incidence of venous thromboembolism . there was a significant difference in the incidence of venous thromboembolism between 305 pairs of patients with combined epidural / general anesthesia and spinal anesthesia ( p <  .001 ) . ceg  =  combined epidural / general anesthesia ; sa  =  spinal anesthesia ; vte  =  venous thromboembolism . in this study , spinal anesthesia was significantly associated with an increased risk of vte in patients undergoing arthroplasty . on the other hand , vte incidence did not differ between general anesthesia and combined epidural / general anesthesia . although epidural anesthesia demonstrated a tendency for decreased vte risk , this was not statistically significant owing to the relatively small sample size . neuraxial blockade is associated with a lower risk of vte as compared with that associated with general anesthesia . rheological changes in the hyperkinetic blood flow in the lower limbs may explain this effect . in addition , epidural anesthesia exerts a profibrinolytic action . despite the good sensorimotor blockade , majority of previous studies have compared epidural with general anesthesia ; comparison between spinal and general anesthesia from the perspective of thromboprophylaxis in orthopedic surgery is not well - characterized . indeed , pharmacological vte prophylaxis is a standard component of the protocol of care for orthopedic patients . conversely , epidural anesthesia added to general anesthesia has some advantages over general anesthesia , such as reduction in blood loss and the requirement for anesthetic medication . moreover , combined epidural / general anesthesia markedly enhances venous flow in the leg because of its sympatholytic action ; thus , minimizing perioperative venous stasis . however , neuraxial blockade , including spinal anesthesia , has not been compared with combined epidural / general anesthesia . therefore , the mechanisms responsible for the effects of spinal anesthesia on postoperative thromboembolic events , relative to combined epidural / general anesthesia are unclear . one reason for a high vte incidence in patients with spinal anesthesia compared with those with epidural analgesia is the superior pain relief afforded by epidural analgesia , which facilitates the early postoperative mobilization of patients . other reasons may be that spinal anesthesia produces stronger freezing in the leg as compared with that by combined epidural / general anesthesia , whereas the outcome may vary according to the anesthetic agent used in epidural anesthesia . however , from a hematological perspective , there were no differences in perioperative hemostatic markers between general and spinal anesthesia . first , we consider dvt for lower leg to be an unsuitable endpoint for multicenter studies owing to the limitation of large inter - observer differences . second , detailed information on some anesthesia - related parameters such as , level of postoperative analgesia and the timing of epidural catheter removal was not included in the analysis . third , we did not include data on in  out balance ( blood / solution infusion vs. discharge volume ) , blood pressure , and cardiac output during anesthesia . despite these limitations , our data may provide useful information on the choice of anesthesia . surgeons who perform tha and tka for patients at high vte risk may consider avoiding spinal anesthesia , although careful risk and benefit assessment of spinal anesthesia should be conducted . further studies , such as randomized controlled trials , are warranted to confirm our results . in conclusion , our study suggests that spinal anesthesia may be associated with an increased risk of postoperative vte , as compared with that associated with combined epidural / general anesthesia , in patients undergoing tha and tka .
abstractclinical guidance on the choice of anesthetic modality vis -  - vis the risk of perioperative venous thromboembolism ( vte ) is largely lacking because of a paucity of recent evidence . 
 a comparative effect of general anesthesia and neuraxial blockade on the perioperative incidence of vte has not been well-investigated.we compared the effects of different types of anesthetic modalities on the risk of vte after total hip arthroplasty ( tha ) and total knee arthroplasty ( tka).this is a secondary analysis of the japanese study of prevention and actual situation of venous thromboembolism after total arthroplasty ( j - psvt ) . 
 data pertaining to a total of 2162 patients who underwent tha and tka at 34 hospitals were included in this analysis . 
 we compared the different anesthetic modalities with respect to the incidence of vte . 
 the composite end - point was asymptomatic / symptomatic deep vein thrombosis detected using scheduled bilateral ultrasonography up to postoperative day ( pod ) 10 and fatal / non - fatal pulmonary embolism up to pod 10.the study groups were as follows : general anesthesia ( n  =  646 ) , combined epidural / general anesthesia ( n  =  1004 ) , epidural anesthesia ( n  =  87 ) , and spinal anesthesia ( n  =  425 ) . 
 on multivariate analysis , only spinal anesthesia was associated with a significant increase in the risk of vte as compared with that associated with general anesthesia . 
 propensity score - matched analysis for  combined epidural / general anesthesia group  versus  spinal anesthesia group  demonstrated a 48% higher incidence of vte ( relative risk  =  1.48 , 95% confidence interval [ ci ] 1.181.85 ) in the latter.spinal anesthesia was associated with a higher risk of postoperative vte , as compared with that associated with combined epidural / general anesthesia , in patients undergoing total arthroplasty .