Early mobilization in acute stage of deep venous thrombosis of the lower limbs

Abstracts

O tratamento convencional da trombose venosa profunda na fase aguda consiste em restrição ao leito. Porém, estudos recentes contestam essa abordagem terapêutica, enfatizando que a mobilização precoce propicia resultados clínicos favoráveis. O objetivo deste estudo foi pesquisar em literatura científica, principalmente ensaios clínicos controlados, sobre a mobilização precoce de pacientes portadores de trombose venosa profunda de membros inferiores na fase aguda. Utilizou-se como estratégia de pesquisa o site PubMed para a busca de estudos relacionados à mobilização precoce, deambulação e trombose venosa profunda na fase aguda. Os artigos consultados abrangeram o período de 1992 a 2007. Em todos os estudos, a mobilização precoce esteve associada à heparina de baixo peso molecular e a terapia de compressão. Estudos avaliados nesta revisão têm demonstrado os benefícios na redução da dor e edema, com melhora da qualidade de vida, pela estratégia terapêutica de mobilização precoce em combinação com anticoagulação e compressão da perna na trombose venosa profunda, sem que ocorra maior risco de desfechos relevantes, como embolia pulmonar e morte.

Trombose venosa; deambulação; compressão; extremidade inferior

REVIEW ARTICLE

Early mobilization in acute stage of deep venous thrombosis of the lower limbs

Geane de Souza Penha^I; Ana Paula Damiano^II; Tales de Carvalho^III; Vinícius Lain^IV; João Daniel Serafim^IV

^I

^IIMSc. student, UDESC, Florianópolis, SC, Brazil

^IIIPhD. Specialist physician, Cardiology and Sports Medicine. Head, professor, Center of Cardiology and Sports Medicine, Centro de Ciências da Saúde e do Esporte (CEFID), UDESC, Florianópolis, SC, Brazil

^IVSpecialist, Vascular Surgery, Hospital Regional de São José Dr. Homero de Miranda Gomes, São José, SC, Brazil

^{Correspondence}

ABSTRACT

Conventional treatment of deep venous thrombosis in the acute phase includes bed rest. However, recent studies have challenged such therapeutic approach, emphasizing that early mobilization provides favorable clinical outcomes. This study aimed at finding qualified scientific studies, especially controlled clinical trials, on early mobilization of patients with acute deep venous thrombosis of the lower limbs. PubMed was used to search for articles related to early mobilization, ambulation and acute deep venous thrombosis. Articles covered the period from 1992 to 2007. In all studies, early mobilization was associated with low molecular weight heparin and compression therapy. Studies evaluated in this review showed benefits in reducing pain and edema, with improvement in quality of life, using the therapeutic strategy of early mobilization in combination with anticoagulation and compression of the leg in patients with deep venous thrombosis, without increased risk of relevant outcomes, such as pulmonary embolism and death.

Keywords: Venous thrombosis, ambulation, compression, lower extremity.

Introduction

Deep venous thrombosis (DVT) is a disease characterized by acute formation of thrombi that affect deep veins of the limbs, causing partial or total occlusion.^1-3

According to Labas et al.,⁴ DVT is a common vascular disease and potentially life threatening. In Brazil Maffei⁵ reported an incidence of 0.6 cases per 1,000 inhabitants/year based on cases of DVT confirmed by phlebography or duplex scan. In a systematic review study (meta-analysis) conducted in 2003, Fowkes et al.⁶ estimated a worldwide DVT incidence of 0.5 cases per 1,000 inhabitants/year. DVT, which is quite common in hospitals, affects 84 individuals per 100,000 inhabitants/year,⁷ and is the most common cause of morbidity and mortality in surgical patients. It accounts for 300,000-600,000 hospitalizations each year.⁸ DVT is present in 20-35% of in-hospital deaths and is associated with pulmonary embolism (PE) in 10-20% of cases in studies based on necropsies.^9-11

The complications resulting from DVT have negative consequences in socioeconomic terms and in quality of life; it is a cause of early death in affected individuals. PE is one of the most feared manifestations and is the third cause of death due to cardiovascular diseases.^1,2 Another non-lethal complication of such disease, which has major consequences to daily activities, is chronic venous insufficiency, called post-thrombotic syndrome. It results from progressive and permanent damage of the venous valve system during the slow process of blood clot lysis. Such syndrome causes severe sequelae, such as varicose veins and venous ulcer, which underlines the importance of an early and adequate therapeutic intervention that reduces the possibility of severe complications and death.¹ Early mobilization has been considered a contraindicated procedure during the acute stage of DVT, as it is believed that muscle contraction might cause the thrombus detachment from the vascular wall, resulting in PE.^1-3

On the other hand, recent studies have suggested that early mobilization would not increase risk of PE, but provide benefits in the acute stage of DVT.^12-18 Due to such controversy, this study aimed at investigating qualified scientific studies, especially controlled clinical trials, on early mobilization of patients with DVT of the lower limbs in the acute stage.

Risk factors

DVT is considered as a multifactorial disease.¹ Immobility in bed and varicose veins are major risk factors of venous stasis.¹⁹ Thrombogenic factors might be present in neoplasms, since tumors may increase the action of procoagulating factors.³ Old age is also considered a risk factor for DVT because during the aging process there is reduction in fibrinolytic activity, increase in vascular resistance and venous dilatation, with subsequent reduction in blood flow velocity.^1,2 There is higher incidence in the female gender, which is frequently associated with use of contraceptives, taking into account that estrogens increase blood levels of coagulation factors.²⁰ Obesity is an independent risk factor for the development of DVT, as it inhibits fibrinolytic activity and impairs walking.^1,5

In total hip surgery, the anterolateral approach generates higher incidence of DVT²¹ due to the torsion of the deep femoral vein during maneuvers of forced abduction and external rotation.²²

Etiopathogeny

The etiopathogeny of DVT is explained by the classical Virchow's triad: venous stasis, endothelial lesion and hypercoagulability.^1-3.5 Venous stasis is seen as the main predisposing factor of DVT. Reduction in blood flow leads to increase in amount of blood in veins, dilating them passively, with consequent reduction in blood flow velocity. Thus, such changes are a result of: 1) fall in cardiac debt, muscular relaxation during rest, anesthesia and paralysis; 2) deficit of the peripheral venous pump. Therefore, reduction in blood flow velocity in veins causes disturbance of laminar flow, causing local accumulation of red cells, platelets and leukocytes. Such cell deposit is stabilized by the creation of a fibrin network that captures such elements, culminating in thrombus formation.^2,5

Normal endothelium is a non-thrombogenic surface on which platelets do not adhere, and there is no activation of coagulating proteins. However, an endothelial lesion causes exposure of the subendothelium, favoring aggregation of platelet and white cells, which triggers activation of coagulation mechanisms, with thrombus formation.²³

Hypercoagulability is present when there is increase in coagulation factors and reduction in coagulation inhibiting factors, which may occur in given physiological, pathological and therapeutic factors, such as pregnancy, cancer, thrombophilia and use of steroids and chemotherapeutic drugs.²⁴

Clinical diagnosis

Most DVT have insidious onset, with few clinical manifestations or may be asymptomatic. The classical signs and symptoms of DVT are pain at muscle palpation, spontaneous pain, calf tenderness, subcutaneous and muscular edema, superficial venous distension and increased temperature of the affected limb. Changes in skin color are more common in severe proximal DVT, with cyanotic color due to segment obstruction (phlegmasia cerulea) or paleness due to presence of vasospasm (phlegmasia alba).^1-3

Diagnostic methods

Ultrasonography has been the method of choice for the diagnosis of proximal DVT, as it it not invasive and has good sensitivity and specificity.^5,24 Doppler ultrasound enables detection of lower influence of pulmonary ventilatory movements in modulation of blood flow velocity, which contributes to diagnosis of DVT. Assessment by ultrasonography provides higher sensitivity and specificity when the femoropopliteal iliofemoral segment is involved.⁵

However, phlebography, an invasive procedure, is considered the gold standard for the diagnosis of DVT. It provides a global visualization of the venous system through application of iodinated contrast in foot veins. The lack of venous filling in a given segment indicates presence of thrombus.^3,5 Radioisotopic phlebography is a method with historic value used in some scientific studies. It consists of injection of microspheres of technetium 99m-labeled albumin, whose paths through veins are seen by scintigraphy. Thrombus diagnosis is performed by absence of vessel visualization and, further, by presence of concentration of radioactive substance at a thrombus site. It is possible to use it in patients with suspicion of PE, as it can be performed simultaneously to pulmonary scintigraphy.²⁴

Drug treatment

Hospital treatment of DVT can be performed by unfractioned heparin intravenously or subcutaneously. However, preference is currently being given to low-molecular-weight heparin in the treatment of DVT, using the subcutaneous approach, so that it can be used in outpatient treatment of non-complicated venous thrombosis because it has lower hemorrhagic potential compared with unfractioned heparin. Low-molecular-weight heparin differs from unfractioned heparin because it has higher anti-Xa activity, higher bioavailability with lower doses, higher half-life and higher predictability in anticoagulating response when administered in fixed doses, not requiring strict laboratory control, as the others.²⁵ After the acute stage, the patient should be maintained anticoagulated through oral therapy.^4,25

Venous compression

Compression therapy is the symptomatic treatment of DVT, with application of pressure to the tissues with the aim of increasing intravenous pressure, guiding venous return flow and enhancing the potential of calf ejection fraction, so that there is edema resolution.^17,26 Bandages are strips of elastic or inelastic material. The lower the degree of elasticity, the deeper it will act. Unna's boot is an inelastic compression comprised of gauze bandages impregnated with gelatin, glycerin, zinc oxide and water, normally used in the treatment of venous ulcer. Elastic compression stockings are added to the treatment of DVT to prevent post-thrombotic syndrome.²⁶ Maximum compression is applied to the ankle and diminishes toward the thigh.²⁷

Methods

A search in indexes such as PubMed, LILACS and SciELO was performed to find articles related to early mobilization, walking and DVT in its acute stage. Fifteen references were selected (all in English). The articles were published between 1992 and 2007.

Results

In the past, prolonged rest in bed was considered essential for the treatment of DVT with the aim of controlling thrombotic propagation and reducing risk of PE.¹⁴ On the other hand, rest in bed for 7-10 days is still part of the treatment for DVT in many hospitals.¹² However, results of some controlled experiments suggested that early walking is a safe and efficacious therapeutic modality to treat clinical aspects of DVT.^12-15,17,18 Partsch & Blättler¹⁶ reported a controlled experimental study with the aim of evaluating the benefits of compression and walking exercises in comparison with rest in bed in acute proximal DVT, diagnosed by Doppler ultrasound or phlebography. The sample was comprised of 45 heparinized patients, divided into three groups of 15 patients, according to different therapeutic modalities for a 10-day period. Individuals in group A received inelastic compression bandage (Unna's boots) on their legs and adhesive bandage on their thighs, while individuals in group B used class II compressive elastic stockings (ankle compression between 23 and 32 mmHg)²⁶ until the thigh extension. Patients in the first two groups were submitted to a walking program. On the other hand, individuals in group C were maintained at rest and not submitted to compression treatment. A pedometer showed that the walking distance in groups A and B ranged between 600 and 1,200 m, while in group C the mean daily walking distance was only 66 m. Pain level was estimated on a daily basis using a visual analogue scale (VAS - Visual Analogue Scale), which is the subjective measurement of pain intensity by numeric variation from 0 to 10,¹⁷ and also Lowenberg's test, through which pressure is applied in the musculature using a cuff and the pressure level that the patient reports pain is recorded.¹⁷ In groups A and B, the degree of pain had a statistically significant decrease (p < 0.05) on the second day and, in the rest group, only after 10 days. On the last day of the study, reduced edema (evaluated by tape measure) and improvement in clinical scoring (evaluated by clinical score containing seven items: pain during walking; pain at the foot in the upright position; painful palpation in the calf; subfascial and prefascial edema; hyperemia; cyanosis; and increased temperature) was significantly more marked (p < 0.01) in compression groups in relation to the rest group. There was no significant difference as to occurrence of new PE events and progression of thrombus evaluated on the first and second day of the study using scintigraphy and Doppler ultrasound, respectively. In addition, no complications resulting from the therapies used were detected. It is interesting to stress that comparison between compression groups revealed that the strategy applied to group A patients had superior effects in reduction of acute clinical signs and symptoms. The study by Partsch & Blättler¹⁶ suggested that patients with proximal DVT should be encouraged to walk with bandages or compression stockings, aiming at a major reduction in acute clinical signs and symptoms without increasing risk of PE.

Blättler & Partsch²⁷ conducted a prospective randomized study with the aim of investigating whether use of heparin associated with compression and walking could provide better clinical evolution than rest in bed. The sample was comprised of 53 patients with proximal symptomatic DVT, all heparinized, divided into three groups submitted to different therapies. Group A patients (n = 18) received inelastic compression bandage, and group B patients (n = 18) received elastic compression stockings. Patients in both groups were immediately referred for walking. Patients in group C (n = 17) remained at absolute rest without being submitted to compressive therapy. Pulmonary screening and Doppler ultrasound of the leg were performed at days 0 and 9. In groups that received compressive therapy, daily walking distance, as measured by a pedometer, increase through time, reaching 4 km/day in average. Improvement in general well being (evaluated by VAS) and quality of life (quality of life questionnaire specific for venous disease containing 10 items) were significantly better in compression groups (p < 0.05 for stockings and p < 0.001 for bandage) compared with the rest group. Rest meant little influence on leg edema, while compression therapy associated with early walking led to a fast and drastic reduction in leg circumference (p < 0.001). In clinical scoring, compression groups had significantly better results than the rest group (p < 0.001). Pain assessed daily by VAS indicated that there was a gradual reduction in pain in all groups (p < 0.001), but there was faster improvement during the first 4 days in compression groups (p < 0.01). The best effect was achieved in the bandage group, in which there was nearly absence of pain at the end of the observation period (p < 0.01). Pain induced by Lowenberg's test revealed that in the rest group pain considerably reduced in 3 days, but there was recurrence and pain was constant and intense during the 6 subsequent days. However, in groups of early walking there was progressive reduction in pain since the therapy started, with no recurrence. Thrombus progression, verified in the first and second days of study using Doppler ultrasound, was less frequent and less marked in groups A and B in relation to group C (p < 0.01). There was no difference in new events of PE in the second examination of pulmonary screening between groups. The study by Blättler & Partsch²⁷ suggested that leg compression combined with walking is the best therapeutic strategy for the treatment of symptomatic patients with proximal DVT, and is better than the strategy of absolute rest in bed.

Isma et al.¹⁴ performed a randomized study at Hospital Universitário de Malmo, Sweden with the aim of evaluating whether early, supervised exercises improve recanalization and reduce the clinical symptoms of DVT diagnosed by phlebography. All 72 patients included in the study were followed for 6 months, after being divided into experimental group (n = 36), with anticoagulation, class II compression stockings and supervised exercise; and control group (n = 36), which was given the same therapy, except for the exercise. Patients were encouraged to walk during hospitalization. Between 5 and 7 days after diagnosis of DVT, all individuals in the experimental group were encouraged to exercise daily at home for 15 minutes over a 6-month period. During the first month, they had a weekly 45-minute session supervised by a physical therapist. In subsequent months they only had 1 weekly, supervised session. The exercise program was primarily consisted of walking and resisted exercises, focusing on lower limbs. We assessed: Quality of life (evaluated by VAS), quadriceps muscular strength, balance and thigh and calf circumference were evaluated. Such parameters were measured at three different intervals: at admission, during the study and after 6 months. Results revealed that there was no difference between groups. To evaluate DVT extension and severity in the leg, Bjorgell's classification system was used, ranging from 0 to 3 (0 = no DVT, 1 = less than 1/3, 2 = 1/3 or more, 3 = 2/3 or more of the leg, relative to the affected venous segment), applied during diagnostic evaluation and after 6 months, when the study protocol was concluded. Results indicated that degree of recanalization of affected venous segments was high and did not differ between groups. There was no DVT resulting from PE or other complications of the treatment in any individual during the 6-month follow-up, therefore it can be concluded that the therapy proposed in this study did not acutely exacerbate the risk of complications in patients with DVT. No benefit of mobilization was seen in relation to degree of recanalization of thrombosis or fast resolution of pain or edema and improvement in quadriceps muscular strength and balance. However, this study showed that early walking was safe in association with anticoagulation and compression stockings when applied in patients with DVT.

In a randomized study by Aschwanden et al.¹³ the aim was to show that early walking does not increase frequency of PE in 129 patients with proximal DVT diagnosed by Doppler ultrasound. All patients were given heparin and were submitted to strict mobilization (group A: n = 60) for 4 days or walking (group B: n = 69) for 4 h/day under supervision. Individuals of both groups wore class II compression stockings. Patients were examined by perfusion/ventilation lung scintigraphy as to presence of PE at the beginning of the study and on the fourth day. Changes in leg circumferences, rest pain and pain during the exercise were evaluated by tape measure and VAS, respectively. Results showed no statistically significant difference between groups relative to reduction in circumference and rest pain in legs. However, in the experimental group there was significant decrease in pain during practice of exercises. All patients were contacted after 3 months and interviewed about recurrent DVT, clinical signs of PE, new concomitant diseases and occurrence of major complications. Incidence of PE at the beginning of the study was 53 and 44.9%, respectively in motion and motionless individuals. During the 4 days of observation there were new episodes of PE, with incidences of 10 and 14.4%, respectively, in group A and B patients. Of 16 cases of DVT on the fourth day, 12 occurred in individuals with previous PE, corresponding to 3.65 relative risk, taking into account the incidence of thromboembolic events in patients that had already had it compared with those that had it for the first time. There was no death during the 4 days of observation. Throughout the 3 months, the mortality rate was 3.9% (two deaths in group A and three deaths in group B). The deaths were caused by malignant diseases and there were three cases of recurrent DVT (one in group A and two in group B). Results of this study suggested early mobilization as an effective and safe therapeutic resource to be routinely used in patients with DVT, taking into account a comparison with immobilization.

Partsch et al.¹⁵ developed a prospective study with the aim of determining incidence of PE in 139 hospitalized patients that had proximal DVT diagnosed by radioisotopic phlebography, submitted to anticoagulation therapy, walking program and venous compression. At the beginning of the study, 80 patients were diagnosed with PE, but only 11 were symptomatic. On the last hospitalization day (mean of 11 days), pulmonary scintigraphy detected new cases of PE in four of 59 patients with no history and in seven patients with PE in the first examination. However, 33 patients (23.7%) had regression of perfusion defects in scintigraphy. An 80-year-old patient with prostate carcinoma had fatal PE. The study corroborated the information that there is a direct relationship between DVT and PE, regardless of early mobilization.

Partsch et al.,¹⁶ in 1,289 patients with symptomatic DVT, treated by low-molecular-weight heparin, compression and walking exercises, determined the short-time incidence of PE, hemorrhage, heparin-induced thrombocytopenia and death. Individuals were assessed using five parameters during hospital stay: presence of PE at admission (V/Q scan) and incidence of PE after 10 days (second V/Q scan), fatal events (necropsy), presence of malignant disease, hemorrhagic complications and heparin-induced thrombocytopenia. Incidence of PE at hospital admission was 53.4% in the iliofemoral segment; 52.6% in the femoral vein; and 35.1% in leg veins. In 2/3 of such PE patients were asymptomatic. In this study, the low incidence of recurrence and fatal PE is in favor of early walking with compression in the lower limbs of patients with DVT symptoms.

In addition to the studies mentioned in this article, there are many others confirming the efficacy and safety of early mobilization in the therapeutic context of DVT.^{4,12,18,28-32}

Discussion

For a long time absolute rest in bed was recommended as treatment for acute DVT. The protocol commonly used in hospital practice consists of rest, elevation of lower limbs and anticoagulation until obtaining thrombus stability.^1,15 However, many studies recommend early walking for most patients with DVT, but more attention should be given to individuals with history of PE.^{13,15,17,18,29,30,32} Studies have shown that prescription of rest in bed for patients with DVT did not reduce incidence of PE to the extent of significantly influencing clinical evolution.^{13,15,17,18,30,32} From the physiopathological perspective, immobilization produces consequences resulting from venous stasis, and is one of the most important factors identified by Virchow as being responsible for thrombogenesis. Inactivity of the venous system pump mechanism provided by lower limb muscles ("muscle pump") and depressed fibrinolytic activity are other factors that contribute to formation and propagation of thrombus, with severe post-thrombotic sequelae.^4,33

When the progress of patients left to rest in bed is compared with that of patients that had early walking, there is no significant difference in PE occurrence,^13-17,28 although it is claimed that early mobilization contributes to reduction in thrombus progression.^16,28 Partsch et al.¹⁶ argued that early walking could have a protective aspect, since it reduces venous stasis, one of the risk factors for recurrent or progressive DVT. The data reported by Partsch & Blättler¹⁶ suggested that walking in association with anticoagulation and leg compression in patients with acute DVT might lead to a faster regression of clinical signs and symptoms, such as pain, edema, hyperemia and temperature increase. Isma et al.¹⁴ corroborated that, indicating that early walking is a proper treatment for patients' clinical symptoms, and observing improvement in the quality of life of such individuals.

Killewich et al.³⁴ reported that regression of acute DVT is due to increase in endogenous fibrinolytic activity and in tissue plasminogen activator. Physical exercise enhances endogenous fibrinolytic activity manifested as a reduction in tissue plasminogen activator.³⁴

Fischer³⁵ in 1910 recommended zinc bandages to treat patients with thrombosis, speculating that a firm external compression might attach clots to vein walls. The physical effect of external compression verified in the study by Partsch et al.,³⁶ shown by phlebography, revealed activity against formation of an edema resulting from narrowing of superficial and deep veins. The same authors concluded that inelastic materials, such as zinc bandages, are more efficacious than elastic material to reduce local venous stasis. Therefore, results found in the studies by Partsch & Blättler¹⁶ and Blättler & Partsch²⁷ showed that the inelastic compression group had superior effects in reduction of clinical signs and symptoms. In all the studies mentioned above, there was use of compression stockings, which prevented evaluation of the effect of early walking alone.

Thrombus propagation was observed in about 20% of patients, despite adequate treatment with heparin and late mobilization. However, such value falls to 1% if mobilization is applied early.³⁷ Thrombus propagation was related to anticoagulation level, and was probably influenced by stasis degree.³⁷ For that reason, mobilization associated with low-molecular-weight heparin has been proposed for DVT patients immediately after diagnosis.^{28,29,31,32,34}

In a study conducted by Isma et al.,¹⁴ there was no substantial effect of exercise on venous recanalization, since follow-up was late (6 months after the end of the study protocol), preventing analysis of mobilization effect in the acute stage. A relatively low severity score in both groups made assessment of occasional effects of exercise difficult.

DVT symptoms partially result from increased intracapillary pressure and further transudation of capillary fluid into the interstitial space,³⁸ caused by obstacle to venous blood flow and valve insufficiency.³⁹ Such phenomena impair leg muscle perfusion, resulting in muscle fatigue.³⁸

The potentially beneficial effects of early mobilization are related to the calf muscle pump theory and to muscle training.¹⁷ During muscle contraction, there is increase in ejection ability, facilitating venous reflow, which in turn reduces the gradient of hydrostatic pressure, responsible for edema formation,^40-42 as well as improvement in muscle perfusion, enhancing the potential of its action.³⁸ The study by Partsch et al.¹⁶ corroborated this by reporting that external compression of the leg, associated with a walking program, might provide reduction in blood hydrostatic pressure and, consequently reduction in venous signs and symptoms.

The quality of the studies, clinical trials and epidemiological studies used in this study provided a good level of scientific evidence for the results, discussion and, consequently conclusions. The main studies are international, from developed countries. There is a lack of research in Brazil and Latin America about this issue. Therefore, experimental studies should be performed in Brazil, which could provide subsidies in favor of early mobilization in hospitals.

Conclusion

Opposed to the strategy of maintaining patients in bed, recent studies, evaluated in this review, showed the benefits of reduction in pain and edema, with improvement in quality of life using the therapeutic strategy of early walking in association with anticoagulation and leg compression in patients with DVT without a higher incidence of relevant outcomes, such as PE and death.

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Manuscript received August 2, 2008, accepted November 7, 2008.

No conflicts of interest declared concerning the publication of this article.

Publication Dates

• Publication in this collection
  26 May 2009
• Date of issue
  Mar 2009

History

• Received
  02 Aug 2008
• Accepted
  07 Nov 2008