Noel Chan, Dina Brooks, David Beverland.
Response/Recommendation: Following orthopaedic surgery, when a diagnosis of pulmonary embolism (PE) has been made and the patient is therapeutically anticoagulated, post-operative rehabilitation should proceed without delay. In patients who have high/intermediate risk PE, the rehabilitation, not only should address regaining function of the operated area, but also should include respiratory training and closely monitored aerobic exercise to gradually increase the pulmonary functional capacity and the patient’s quality of life. This recommendation is made in the absence of evidence that an early mobilization or rehabilitation program is associated with a higher risk of adverse events (namely recurrent PE or bleeding), and that there are clear established benefits to rehabilitation. We recognize that some patients who have PE may have poor cardio-pulmonary tolerance or other medical complications, and for these patients, the exercise regimen may need to be modified based on symptoms.
Strength of Recommendation: Limited.
Rationale: Rehabilitation post-orthopaedic procedures (e.g., total hip or knee arthroplasty) aims to maximize the function and independence of patients and is an essential step on the road to recovery. This consists of exercises to improve joint range of motion and strength, transfer training, gait training, and instructions on how to optimize activities of daily living. Studies performed in patients undergoing major orthopaedic surgery have consistently shown beneficial effects of exercise on functional outcomes, quality of life metrics, pain outcomes, shortening lengths of stay, and preventing post-operative complications1. In current practice, it is recommended that rehabilitation begins as soon as possible after all orthopaedic surgery2,3. However, some patients may experience post-operative complications, including PE, which may incorrectly prompt healthcare teams to consider delaying rehabilitation and extending bed rest because of concerns about recurrent PE, particularly fatal PE, and bleeding while receiving anticoagulation.
Patients diagnosed with PE following orthopaedic surgery frequently have a prolonged hospital stay and a longer rehabilitation period. However, there is a lack of randomized trials or high-quality observational studies to inform on the optimal timing and intensity of rehabilitation in patients who have PE after orthopaedic surgery, and whether these patients would benefit from cardio-pulmonary rehabilitation in the long term. One study retrospectively reviewed 325 patients who had a hip fracture and measured the length of stay, Geriatric depression scale, Modified Barthel index, and Berg balance scale score as well as 10-meter gait speed of their patients post-operatively. Fifteen patients were diagnosed with symptomatic venous thromboembolism (VTE) (six cases of both symptomatic deep venous thrombosis (DVT) and PE, four cases of symptomatic PE, and five cases of symptomatic DVT). Patients who had symptomatic VTE had a significantly more prolonged length of stay (p = 0.012). Interestingly, at discharge, there were no statistically significant differences between the VTE cases and non-VTE cases regarding other outcome measures. The duration of physical therapy between the two groups was similar. But due to the retrospective nature of the study, no information was available about the exact protocol of rehabilitation for the two mentioned groups4.
In the absence of high-quality evidence in the orthopaedic setting, we examined the potential risk of early mobilization and cardio-pulmonary rehabilitation in any patient who had a PE (regardless of its association with orthopaedic surgery). Considerations in patients who have a diagnosis of PE include the risk of progression to a fatal event, the risk of bleeding while on anticoagulant therapy, and on occasion, poor cardio-pulmonary tolerance that may affect adherence to an exercise program. Therapeutic anticoagulation is thought to reduce the risk of PE recurrence but increases the risk of bleeding.
For low-risk PE cases, early discharge is recommended5. A randomized clinical trial evaluated the effect of outpatient rehabilitative exercise on the low-risk acute PE patient. During their six months mean follow up, they did not observe any added benefit of outpatient rehabilitation in these patients6.
Regarding intermediate/high-risk PE cases, a prospective study managed 23 PE patients with 3-phase rehabilitation (phase 1 in hospital initiated within 28 days after the diagnosis of PE, phase 2 and 3 could be performed in the inpatient/ outpatient setting). Around 8.7% of their patients had a low-risk PE, 69.9% of them had a submassive PE (an acute PE without systemic hypotension) and 21.7% of their cases had a massive PE. They found that rehabilitation was associated with improvement in quality of life and functional capacity. During their 6-month follow up, only one case of DVT recurrence and one case of bleeding was observed7. In a retrospective study, acute (within two weeks after the PE) inpatient rehabilitation, including respiratory training and heart rate monitored aerobic exercise, was applied on 422 patients. During their 3-week rehabilitation program, three cases of bleeding occurred and only one of them was clinically relevant8. In a prospective study of 70 patients who had PE, similar inpatient rehabilitation was associated with 2.8% bleeding, 1.4% newly diagnosed PE, and 5.7% death in their 12-month follow up period9. In a short sample controlled clinical trial (including six PE cases in the intervention group, and five PE cases in the control group), Lakoski et. al., used an outpatient rehabilitation program for patients who had subacute PE (≥ six weeks and < three months since the index injury). They demonstrated that the program was associated with increased physical fitness and insignificant weight loss of the participants. They did not observe any associated adverse events10. Another study prospectively followed PE patients managed with outpatient pulmonary rehabilitation (median period of follow up 39 months). The rehabilitation was started at a median period of 19 weeks after the acute PE event. They observed that while rehabilitation led to no adverse events, it was associated with significant improvement in the 6-minute walk test11.
Also, a systematic review of mostly observational studies has consistently reported that early mobilization in patients who have acute PE or DVT was associated with a decrease in recurrent PE, new/progressive DVT, and did not increase the risk of recurrent PE or bleeding12,13. Consequently, the current evidence in patients who have PE do not support the concern that an early mobility and/or exercise program within one to two weeks after PE increases the risk of adverse events.
Regarding chronic PE, there are two clinical trials that studied chronic PE patients who have stable pulmonary hypertension14,15. They have demonstrated that closely monitored inpatient rehabilitation programs can improve the World Health Organization (WHO) functional class and exercise capacity. However, one study reported syncope/pre-syncope in 4.4% of patients15.
We recognize that there is heterogeneity in the severity of PE, and that some patients who have severe right ventricular strain and cardio-pulmonary intolerance with severe symptoms may require a modified rehabilitation program based on symptoms. Finally, to minimize the risk and consequences of falls in patients on anticoagulation therapy, we also suggest assessment of fall risk, evaluating the maximal exercise capacity before starting rehabilitation, monitoring of vital signs including heart rate, and O2 saturation during rehabilitation, and implementation of measures (in either inpatient or outpatient) rehabilitation programs for harm minimization.
In summary, there is a lack of evidence guiding the optimal timing and intensity of rehabilitation in patients diagnosed with PE after orthopaedic surgery. In the absence of evidence suggesting harm, we suggest that mobilization and post-operative rehabilitation proceed as rapidly as the patient’s cardio-pulmonary status permits.
References:
1. Ibrahim MS, Khan MA, Nizam I, and Haddad FS. Peri-operative interventions producing better functional outcomes and enhanced recovery following total hip and knee arthroplasty: an evidence-based review. BMC Med. 2013;11:37.
2. McGrory BJ, Weber KL, Jevsevar DS, and Sevarino K. Surgical Management of Osteoarthritis of the Knee: Evidence-based Guideline. J Am Acad Orthop Surg. 2016;24(8):e87-93.
3. Rees HW. Management of Osteoarthritis of the Hip. J Am Acad Orthop Surg. 2020;28(7):e288-e91.
4. Lee YK, Choi YH, Ha YC, Lim JY, and Koo KH. Does venous thromboembolism affect rehabilitation after hip fracture surgery? Yonsei Med J. 2013;54(4):1015-9.
5. Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, et al., 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35(43):3033-69, 69a-69k.
6. Rolving N, Brocki BC, Bloch-Nielsen JR, Larsen TB, Jensen FL, Mikkelsen HR, et al., Effect of a Physiotherapist-Guided Home-Based Exercise Intervention on Physical Capacity and Patient-Reported Outcomes Among Patients With Acute Pulmonary Embolism: A Randomized Clinical Trial. JAMA network open. 2020;3(2):e200064.
7. Cires-Drouet RS, Mayorga-Carlin M, Toursavadkohi S, White R, Redding E, Durham F, et al., Safety of exercise therapy after acute pulmonary embolism. Phlebology. 2020;35(10):824-32.
8. Noack F, Schmidt B, Amoury M, Stoevesandt D, Gielen S, Pflaumbaum B, et al., Feasibility and safety of rehabilitation after venous thromboembolism. Vascular health and risk management. 2015;11:397-401.
9. Amoury M, Noack F, Kleeberg K, Stoevesandt D, Lehnigk B, Bethge S, et al., Prognosis of patients with pulmonary embolism after rehabilitation. Vascular health and risk management. 2018;14:183-7.
10. Lakoski SG, Savage PD, Berkman AM, Penalosa L, Crocker A, Ades PA, et al., The safety and efficacy of early-initiation exercise training after acute venous thromboembolism: a randomized clinical trial. J Thromb Haemost. 2015;13(7):1238-44.
11. Nopp S, Klok FA, Moik F, Petrovic M, Derka I, Ay C, et al., Outpatient Pulmonary Rehabilitation in Patients with Persisting Symptoms after Pulmonary Embolism. Journal of clinical medicine. 2020;9(6).
12. Aissaoui N, Martins E, Mouly S, Weber S, and Meune C. A meta-analysis of bed rest versus early ambulation in the management of pulmonary embolism, deep vein thrombosis, or both. Int J Cardiol. 2009;137(1):37-41.
13. Liu Z, Tao X, Chen Y, Fan Z, and Li Y. Bed rest versus early ambulation with standard anticoagulation in the management of deep vein thrombosis: a meta-analysis. PLoS One. 2015;10(4):e0121388.
14. Mereles D, Ehlken N, Kreuscher S, Ghofrani S, Hoeper MM, Halank M, et al., Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation. 2006;114(14):1482-9.
15. Grünig E, Lichtblau M, Ehlken N, Ghofrani HA, Reichenberger F, Staehler G, et al., Safety and efficacy of exercise training in various forms of pulmonary hypertension. Eur Respir J. 2012;40(1):84-92.