William Fishley, Mihovil Plecko, Rasmus Tyrsted Mikkelsen, Ivan Bohacek, Per Kjaersgaard-Andersen, Oliver Marín-Peña, Mike Reed.
Response/Recommendation: The “enhanced recovery” concept including early mobilization is likely to reduce the risk of venous thromboembolism (VTE) in patients undergoing primary total hip arthroplasty (THA) or total knee arthroplasty (TKA). However, the literature lacks studies with a high level of evidence considering this topic.
Strength of Recommendation: Limited.
Rationale: Data from The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database demonstrates a risk of VTE in patients undergoing THA of 0.6% within 30 days of surgery, and 1.4% in patients who undergo TKA1. Santana et al., report similar rates, highlighting that due to the total number of THA and TKA performed worldwide, a large number of patients suffer from VTE, which can be associated with marked morbidity and mortality2. Therefore, it is of high importance to minimize complications in these patients.
The Enhanced Recovery After Surgery (ERAS) concept has been developed as a multidisciplinary and multimodal approach with the goal of improving clinical outcomes and maximizing the efficiency of healthcare resource use. The utilization of the ERAS concept has been effective in reducing lengths of stay and complications3. However, no previous review has defined the effect of the ERAS concept on the incidence of VTE. The ERAS society issued a consensus statement for peri-operative care in THA and TKA in 2019, making evidence-based recommendations across 17 topic areas4. With regards to antithrombotic prophylaxis treatment, the ERAS society recommended that patients should be mobilized as soon as possible after surgery and receive VTE prophylaxis in accordance with local policies.
A summary of studies analyzed in this current recommendation is shown in Table 15-16. Studies were selected for inclusion if they compared the incidence of VTE in patients undergoing surgery using an ERAS protocol to a control group. In addition, comparative studies of ‘early mobilization’ were included. There were only 12 published studies meeting the inclusion criteria and the majority were retrospective in design.
One randomized controlled trial was identified, which showed no statistically significant difference in the incidence of deep venous thrombosis (DVT) between the ERAS and control group in patients undergoing THA for osteonecrosis8. However, the quality of this evidence was determined to be low due to the lack of a defined randomization process, allocation concealment, and the procedure for identification and diagnosis of DVT, with no blinding of assessors. In addition, the primary outcome of the trial was post-operative function, and the study is unlikely to have sufficient power to detect a difference in the incidence of symptomatic DVT. Two non-randomized, prospective cohort studies reported a lower frequency of DVT with the use of an ERAS protocol in both THA and TKA patients, and of both DVT and pulmonary embolism (PE) in TKA patients6,9. These differences were not statistically significant in either study. Venditolli et al., also observed a non-statistically significant decrease in the incidence of DVT in a prospective cohort of THA and TKA patients using an ERAS protocol, compared to a historical control10.
In the majority of the remaining retrospective studies, VTE was less frequent in the group where the ERAS concept was utilized, but only two studies identified a statistically significant difference5,12. After full implementation of an ERAS pathway in a large cohort of both TKA and THA patients, Glassou et al., observed a reduction in the incidence of DVT from 0.8 to 0.5%12. Millar et al., observed a reduction in DVT from 1.5 to 0.7% and from 3.6 to 1.6% in both THA and TKA respectively, after the introduction of an ERAS pathway5. However, it is noted that the ERAS measures used were not clearly defined in the study and were introduced alongside a specific focus on VTE prophylaxis, in addition to the ERAS concept.
No comparative studies using ‘early mobilization’ as a specific intervention were identified in the systematic search. However, additional observational papers in the wider literature have been considered for the purpose of discussion. Immobility is a recognized risk factor for developing VTE17,18. However, Chindamo and Marques considered that there was currently insufficient evidence in the wider literature that early mobilization in isolation reduces the risk of VTE19. In the context of arthroplasty surgery, Lei et al., found an incidence of DVT of 0.71% in a cohort of patients mobilized within 24 hours after TKA, compared to 1.41% in patients beginning mobilization beyond this time point20. This study was purely observational and there was no difference in the mobilization protocol between the two groups. Therefore, although baseline demographics were comparable for both groups, it is possible that the early mobilization group represented patients who have higher pre-operative mobility and performance status, which may predispose them to a lower risk of VTE. Chandrasekaran et al., reported that mobilization in the first 24 hours after TKA is an effective way to reduce the incidence of DVT21. However, the follow-up was at longest, seven days post-surgery. Furthermore, Husted et al., analyzed the importance of early mobilization within the ERAS concept for TKA and THA, highlighting that the incidence of VTE was lower in patients mobilized two to four hours post-surgery in comparison to patients mobilized six to eight hours post-surgery22. Therefore, it should be further investigated whether early mobilization per se or inclusion into an ERAS protocol reduces the risk of VTE in THA and TKA patients.
Limitations of this review include heterogeneity of the included studies, with major variations in mobilization and ERAS protocols, thus complicating the estimation of any intervention effect. Furthermore, as most of the studies are retrospective, reporting on multiple outcomes of the ERAS concept, and not focused specifically on VTE, it is likely that many are under-powered to detect any significant difference in rates of DVT and PE.
In summary, the data on VTE in the context of ERAS in the literature is limited. Two retrospective studies with a large number of patients identified an association between the use of ERAS concept and a lower incidence of DVT in both TKA and THA. No studies demonstrated a statistically significant difference in the rate of PE in patients undergoing THA and TKA in an ERAS setting. Future interventional studies using well-defined ERAS protocols may provide greater insight into the effect of ERAS concept, including early mobilization, on the incidence of DVT and PE.
References:
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2. Santana DC, Emara AK, Orr MN, Klika AK, Higuera CA, Krebs VE, et al. An Update on Venous Thromboembolism Rates and Prophylaxis in Hip and Knee Arthroplasty in 2020. Medicina (Kaunas). 2020;56(9):416. https://doi.org/10.3390/medicina56090416
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4. Wainwright TW, Gill M, McDonald DA, Middleton RG, Reed M, Sahota O, et al. Consensus statement for perioperative care in total hip replacement and total knee replacement surgery: Enhanced Recovery After Surgery (ERAS(®)) Society recommendations. Acta Orthop. 2020;91(1):3-19. https://doi.org/10.1080/17453674.2019.1683790
5. Millar JS, Lawes CM, Farrington B, Andrew P, Misur P, Merriman E, et al. Incidence of venous thromboembolism after total hip, total knee and hip fracture surgery at Waitemata District Health Board following a peer-reviewed audit. N Z Med J. 2020;133(1511):52-60.
6. Ripollés-Melchor J, Abad-Motos A, Díez-Remesal Y, Aseguinolaza-Pagola M, Padin-Barreiro L, Sánchez-Martín R, et al. Association Between Use of Enhanced Recovery After Surgery Protocol and Postoperative Complications in Total Hip and Knee Arthroplasty in the Postoperative Outcomes Within Enhanced Recovery After Surgery Protocol in Elective Total Hip and Knee Arthroplasty Study (POWER2). JAMA Surg. 2020;155(4):e196024. https://doi.org/10.1001/jamasurg.2019.6024
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9. Jiang HH, Jian XF, Shangguan YF, Qing J and Chen LB. Effects of Enhanced Recovery After Surgery in Total Knee Arthroplasty for Patients Older Than 65 Years. Orthop Surg. 2019;11(2):229-35. https://doi.org/10.1111/os.12441
10. Vendittoli PA, Pellei K, Desmeules F, Massé V, Loubert C, Lavigne M, et al. Enhanced recovery short-stay hip and knee joint replacement program improves patients outcomes while reducing hospital costs. Orthop Traumatol Surg Res. 2019;105(7):1237-43. https://doi.org/10.1016/j.otsr.2019.08.013
11. Berg U, BüLow E, Sundberg M and Rolfson O. No increase in readmissions or adverse events after implementation of fast-track program in total hip and knee replacement at 8 Swedish hospitals: An observational before-and-after study of 14,148 total joint replacements 2011-2015. Acta Orthop. 2018;89(5):522-7. https://doi.org/10.1080/17453674.2018.1492507
12. Glassou EN, Pedersen AB and Hansen TB. Risk of re-admission, reoperation, and mortality within 90 days of total hip and knee arthroplasty in fast-track departments in Denmark from 2005 to 2011. Acta Orthop. 2014;85(5):493-500. https://doi.org/10.3109/17453674.2014.942586
13. Khan SK, Malviya A, Muller SD, Carluke I, Partington PF, Emmerson KP, et al. Reduced short-term complications and mortality following Enhanced Recovery primary hip and knee arthroplasty: results from 6,000 consecutive procedures. Acta Orthop. 2014;85(1):26-31. https://doi.org/10.3109/17453674.2013.874925
14. Duncan CM, Moeschler SM, Horlocker TT, Hanssen AD and Hebl JR. A self-paired comparison of perioperative outcomes before and after implementation of a clinical pathway in patients undergoing total knee arthroplasty. Reg Anesth Pain Med. 2013;38(6):533-8. https://doi.org/10.1097/aap.0000000000000014
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17. Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med. 2010;153(1):8-18. https://doi.org/10.7326/0003-4819-153-1-201007060-00004
18. Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med. 2000;160(22):3415-20. https://doi.org/10.1001/archinte.160.22.3415
19. Chindamo MC and Marques MA. Role of ambulation to prevent venous thromboembolism in medical patients: where do we stand? J Vasc Bras. 2019;18:e20180107. https://doi.org/10.1590/1677-5449.180107
20. Lei Y-T, Xie J-W, Huang Q, Huang W and Pei F-X. Benefits of early ambulation within 24 h after total knee arthroplasty: a multicenter retrospective cohort study in China. Military Med Res. 2021;8(1):1-7.
21. Chandrasekaran S, Ariaretnam SK, Tsung J and Dickison D. Early mobilization after total knee replacement reduces the incidence of deep venous thrombosis. ANZ J Surg. 2009;79(7-8):526-9. https://doi.org/10.1111/j.1445-2197.2009.04982.x
22. Husted H, Otte KS, Kristensen BB, Ørsnes T, Wong C and Kehlet H. Low risk of thromboembolic complications after fast-track hip and knee arthroplasty. Acta Orthop. 2010;81(5):599-605. https://doi.org/10.3109/17453674.2010.525196