Authors

EAST Practice Parameter Workgroup for DVT Prophylaxis

Frederick B. Rogers, MD, FACS
University of Vermont Department of Surgery
Director of Trauma and Critical Care
Fletcher Allen Heath Care
Burlington, VT

Mark D. Cipolle, MD, Ph.D.
Surgical Practice Center
Allentown, PA

George Velmahos, MD, Ph.D.
Department of Surgery, Division of Trauma and Critical Care
University of Southern California
Los Angeles, CA

Grace Rozycki, MD
Emory USM, Department of Surgery
Atlanta, GA

I. Statement of the Problem

The role of intermittent sequential compression devices (SCDs) for prophylaxis against DVT has been studied and increasingly utilized in general surgery patients,^[1] orthopedic patients,^[2-4] and trauma patients.^[5-8]

Attacking the long-recognized risk factor of stasis, SCDs have been shown to increase mean and peak femoral venous blood velocities on the lower extremity.^{[9] [10]} Additionally, SCDs have been shown to have a direct effect on the fibrinolytic pathway acting to shorten the euglobulin lysis time, increase levels of coagulation cascade inhibitor molecules, as well as affecting the balance of plasminogen activation.^[12-14] In a number of prospective, randomized studies, SCDs have been shown to reduce the incidence of both DVT and PE.^{[3] [6] [15] [16]} Unanswered questions regarding the use of SCDs include the mechanism by which SCDs act, the efficacy of SCDs worn on the upper extremities or a single lower extremity compared to both lower extremities, the nature of risk involved in discontinuing SCDs periodically during use, and the duration of SCD use.Reports suggest that SCDs should be worn with thromboembolism-deterrent stockings (i.e. TEDS), however, this practice has not been widely studied and is not standard. Complications of SCDs have been noted in case reports and have been associated with improper positioning of the lower extremity during surgery which should be avoided.

II. Process

A Medline search from 1986 to the present produced a large number of articles on this topic. Those articles pertinent to trauma-related thromboembolism prevention were reviewed.Twenty-three of these articles were evaluated to formulate the following guidelines.

III. Recommendations

A. Level I

There are insufficient data to support a standard on this topic.

B. Level II

There is insufficient data at this time that SCD decreases the risk of VTE in multiply injured patients.

C. Level III

1. In the subset of spine-injured head-injured patients, SCD may have some benefit in isolated studies.
2. For patients in whom the lower extremity is inaccessible to place SCDs at the calf level, foot pumps may act as an effective alternative to lower the rate of DVT formation.

IV. Scientific Foundation

Since their description in 1858 by Rudolf Virchow, the factors that are felt to form the basis of the pathophysiology of venous thromboembolic disease are stasis (reduction of blood flow in the veins),injury (to the intimal surface of the vessel) and hypercoagulability. Scientific and clinical evaluations of SCDs strongly suggest that the nature of their effect on DVT prophylaxis derives from their ability to increase mean and peak femoral vein velocity as well as their effect on the systemic coagulation and fibrinolytic mechanisms.

The sequential pattern of compression has been well described: chambers of the extremity garment are sequentially inflated from ankle to knee (or mid thigh) to a maximum pressure of 45-50mm Hg at the ankle, 35 mm Hg at the calf, and 30mm at the thigh (hence the term “gradient” compression). The durat ion of compression is 11 seconds with a 60 second relaxation period between compressions.

Keith et al.^[9] measured peak venous velocity (PVV) at the common femoral vein in postoperative (non-trauma) patients and in healthy control subjects using Doppler ultrasound.In the control subjects, PVV was increased from a mean velocity of 23.8 cm/sec at rest to 45.5 cm/sec with knee-high SCDs and 53.2 cm/sec with thigh-high SCDs. In postoperative patients, the PVV was similarly raised from a resting velocity of 21.8 cm/sec to 55.1 cm/sec. In both of these evaluations, the differences were statistically significant when compared to controls and were not further augmented by the concomitant use of compression stockings (e.g. TEDS). Spectral recording of blood flow velocity during inflation and deflation of the SCDs reveal a temporal association with inflation and increased PVV which suggests a mechanical effect derived from inflation of the SCDs. Another study examined the role of SCDs on femoral vein flow velocity in patients undergoing laparoscopic abdominal procedures.^[10] It was noted that the effect of pneumoperitoneum to lower the velocity of flow through the femoral vein could be abrogated with the use of lower extremity SCDs.

Several studies in the selected bibliography^[12-14] have evaluated in vivo fibrinolytic effects of SCDs. Inada et al.^[12] reported a prospective study comparing euglobulin lysis times and a fibropeptide concentration in a cohort of cancer patients with and without SCDs. Both of these measurements are non-specific indicators of the relative activity of the fibrinolytic pathway in humans. They showed that the presence of SCDs vs. no-SCDs shortened the euglobulin lysis time and by the fifth postoperative day had increased the fibropeptide concentration suggesting increased plasminogen activity. In a well-designed study, Jacobs et al.^[14] showed that euglobulin lysis times were not reproducible as a marker for fibrinolytic activation, and their study focused on measured changes in tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI -1) and tPA-PAI­1 complex. They demonstrated a significant increase in tPA-PAI-1 (hence an obligatory decrease in PAI) in patients undergoing SCD and postulated a (complex and incompletely proven) role of SCDs in the systemic balance of plasminogen activation and inhibition. In Jacob’s study, they found that fibrinolytic activity begins to decay within minutes of discontinuing SCDs. This observation has important clinical implications in that SCDs must be worn continuously in order to avoid rapid decay in fibrinolytic activity.A recent study has documented patients in whom SCDs have been ordered, spent less than 50% of the time actually wearing the devices, possibly decreasing their effectiveness.^[17] Another important finding in Jacob’s study was that there appeared to be an incremental decrease in fibrinolytic activity when blood was sampled in sites remote form the area of placement of the SCDs. This difference in local and systemic effects has important implications on the ability of SCDs worn on the arms to prevent DVT in the legs.

Hoppensteadt et al.^[13] studied levels of tissue factor pathway inhibitor (TFPI) in surgical patients before and after one hour of intermittent pneumatic compression.The authors describe TFPI as the key feedback inhibitor of the extrinsic activation of coagulation, a protease molecule which acts by binding to Factor Xa to inactivate the TF-FVIIa complex. They demonstrated a significant increase in TFPI concentrations in patients following pneumatic compression. The authors describe TFPI as being stored intima-bound on the endothelial cells, and suggest its release is mediated from these cells by the action of SCDs. This would represent a speculative mechanism whereby SCDs have a direct inhibitory effect on thrombin generation as well as the primary effect on flow enhancement.

There is a paucity of studies specifically regarding the use of SCDs in the multiply-injured trauma patient.In a prospective study in which 113 trauma patients received either SCDs and TED stockings or low dose heparin (LDH), Knudson et al.^[5] showed a 12% rate of venous thromboembolism (VTE) in the SCD vs. 8% in the LDH group, which was not significantly different. This study did not demonstrate that either method of attempted prevention (LDH or SCD) was better than no prophylaxis. Dennis et al.,^[6] in a prospective, nonrandomized study of 395 trauma patients admitted with an ISS > 9 who received either SCD, LDH or no prophylaxis, demonstrated a VTE rate of 8.8% in the no prophylaxis group, 2.7% with SCD and 3.2% in the LDH group. There was no statistically significant difference in VTE rate in the prophylaxis groups, but there was a significant difference in those who received prophylaxis vs. no prophylaxis (p<0.02).Two very high risk groups seemed especially to benefit from prophylaxis were the head and spinal cord-injured patients.Overall risk reduction of VTE with prophylaxis was from 16.7% to 1.4% in head injured patients and from 27.3%to 10.3% in spinal cord-injured patients.The study suffers from the fact that there were randomization problems during the course of the study in which 67 patients (37%) originally assigned to receive no prophylaxis were switched to receive some sort of prophylaxis at the discretion of the attending surgeon.In a prospective trial, Knudson et al.^[18] compared SCD, LDH and no prophylaxis. Neither LDH or SCD appeared to offer any protection to multiply-injured trauma patients, except in the specific subgroup of patients with neurotrauma in which SCD was more effective than control in preventing DVT (p=0.057). In contrast to Knudson’s study, Gersin et al.^[7] in a non-randomized prospective study, looked at the incidence of VTE in a group of 32 severely head-injured patients(GCS < 8).Fourteen patients received SCD and 18 did not because of concomitant lower extremity fractures. Within the group receiving SCD, four (28%) developed PE; none developed DVT. In the group not receiving prophylaxis, two developed PE and two developed DVT.Although the study population was small, the findings in this study call into question the efficacy of SCD even in severe head-injured patients.In a group of 304 orthopaedic trauma patients with hip and pelvic fractures, SCDs were found to reduce thromboembolic events significantly over those who had no prophylaxis (11% vs. 4%; p=0.02). In subgroup analysis, SCD was only effective in the hip fracture group, not in those with pelvic fractures.

Compression devices appear to be well-tolerated with minimal side effects.Isolated case reports of pressure necrosis from a too tightly fitted SCD have been reported.^[19] Also peroneal palsy and compartment syndromes have been reported with SCDs.^[20] A potential complication of SCD is to elevate intracranial pressure in those patients with severe head-injury.This question was addressed by Davidson et al.^[21] in 24 severely brain-injured patients (mean GCS=6) who had intracranial pressure (ICP) and cerebral perfusion pressure (CPP) calculated after 0, 10, 20, and 30 minutes of intermittent pneumatic leg compression. The authors found no significant increase in ICP or CPP at any time points studied with the use of SCDs, and concluded that SCDs can be used safely in stable head-injured patients.

In an evidenced-based meta-analysis sponsored by the Agency of Healthcare Research and Quality on the incidence of DVT following trauma, Velmahos et al^[25] found that SCD offered no benefit over no prophylaxis in both pooled randomized control studies (OR, 0.769; 95% CI, 0.265, 2.236) and in pooled non-randomized controlled studies (OR, 0.527; 95% CI, 0.190, 1.460). Velmahos et al^[24] compared SCD, LDH and a combination of SCD and LDH in a prospective study of 200 critically injured patients followed by weekly Doppler ultrasound to detect proximal DVT. In all three groups, the proximal DVT rate was 13%, leading the authors to question whether any of the three prophylactic regimens are sufficient in the high-risk patient.

Two studies have compared SCD to A-V foot pumps.Anglen et al^[26] in a prospective, randomized, controlled study of 124 high risk orthopedic patients (pelvic, acetabular or femur fracture) were included in the study and followed with serial duplex ultrasound. The incidence of DVT was 0% in the SCD groups and 4% in A-V foot pump group. However, one patient in the A -V foot pump group suffered a nonfatal PE despite 3 negative duplex scans. Overall, the incidence of DVT seems low relative to other studies in similar high-risk population.Nevertheless, it is a Level I study because it is prospective, randomized, controlled trial. In a non- randomized study of 184 high-risk patients, Spain et al^[27] divided patients into SCD prophylaxis, or A-V foot pumps in patients with lower extremity fractures.The incidence of DVT was similar between groups (7% SCD; 3% A-V foot pump) as was the incidence of PE (2 A-V foot pump; 1 SCD).

V. Summary

The use of SCDs worn on the lower extremity in patients at high risk for DVT and to reduce the rate of DVT is widely accepted, however, clinical studies demonstrating their effectiveness in trauma patients are few. While the exact mechanism of action of SCDs is not known, their effect is felt to be based on a combination of factors addressing stasis and hypercoagulability.Until these mechanisms are better studied and understood, answers to specific questions regarding the appropriate use of SCDs are forthcoming.

VI. Future Investigation

More studies need to be done specifically related to the use of SCDs in trauma patients at risk for VTE. Questions regarding the efficacy of using the device on one lower extremity vs. two, and whether an arm vs. a leg provides equal protection, all need to be addressed. There are a number of commercial vendors of compression devices.Whether they all provide equal protection or one vendor is superior needs to be determined. Finally, the role of multimodality therapy (mechanical and pharmacologic) to provide any additional protection from VTE needs to be ascertained.

VII. References

1. Caprini JA, Arcelus JI, Hoffman K, et al: Prevention of venous thromboembolism in North America: Results of a survey among general surgeons. J Vasc Surg 20:751-8, 1994
2. Pidala MJ, Donovan DL, Kepley RF: A prospective study on intermittent pneumatic compression in the prevention of deep vein thrombosis in patients undergoing total hip or total knee replacement. Surg Gynecol Obstet 175:47-51, 1992
3. Bradley JG, Krugener GH, Jager HJ: The effectiveness of intermittent plantar venous compression in prevention of deep venous thrombosis after total hip arthroplasty. J Arthroplasty8:57 -61, 1993
4. Woolson ST, Watt JM: Intermittent pneumatic compression to prevent proximal deep venous thrombosis during and after total hip replacement. A prospective, randomized study of compression alone, compression and aspirin, and compression and low-dose warfarin. J Bone Joint Surg 73-A:507-12, 1991
5. Knudson MM, Collins JA, Goodman SB, et al: Thromboembolism following multiple trauma. J Trauma 32:2-11, 1992
6. Dennis JW, Menawat S, Von Thron J, et al: Efficacy of deep venous thrombosis prophylaxis in trauma patients and identification of high-risk groups. J Trauma 35:132-9, 1993
7. Gersin K, Grindlinger GA, Lee V, et al: The efficacy of sequential compression devices in multiple trauma patients with severe head injury. J Trauma 37:205-8, 1994
8. Gibbons GH, Dzau VJ: The emerging concept of vascular remodeling. N Engl J Med 330:1431-8, 1994
9. Keith SL, McLaughlin DJ, Anderson FA Jr, et al: Do graduated compression stockings and pneumatic boots have an additive effect on the peak velocity of venous blood flow? Arch Surg127:727-30, 1992
10. Christen Y, Reymond MA, Vogel JJ, et al: Hemodynamic effects of intermittent pneumatic compression of the lower limbs during laparoscopic cholecystectomy. Am J Surg 170:395-8, 1995
11. Killewich LA, Sandager GP, Nguyen AH, et al: Venous hemodynamics during impulse foot pumping. J Vasc Surg 22:598-605, 1995
12. Inada K, Koike S, Shirai N, et al: Effects of intermittent pneumatic leg compression for prevention of postoperative deep venous thrombosis with special reference to fibrinolytic activity. Am J Surg 155:602-5, 1988
13. Hoppensteadt DA, Jeske W, Fareed J, et al: The role of tissue factor pathway inhibitor in the mediation of the antithrombotic actions of heparin and low-molecular-weight heparin. Blood Coagul Fibrinolysis 6:S57­S64, 1995
14. Jacobs DG, Piotrowski JJ, Hoppensteadt DA, et al: Hemodynamic and fibrinolytic consequences of intermittent pneumatic compression: Preliminary results. J Trauma 40:710-7, 1996
15. Fisher CG, Blachut PA, Salvian AJ, et al: Effectiveness of pneumatic leg compression devices for the prevention of thromboembolic disease in orthopaedic trauma patients: A prospective, randomized study of compression alone versus no prophylaxis. J Orthop Trauma 9:1-7, 1995
16. Ramos R, Salem BI, De Pawlikowski MP, et al: The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery. Chest 109:82-5, 1996
17. Comerota AJ, Katz ML, White JV: Why does prophylaxis with external pneumatic compression for deep vein thrombosis fail? Am J Surg 164:265-8, 1992
18. Knudson MM, Lewis FR, Clinton A, et al: Prevention of venous thromboembolism in trauma patients. J Trauma 37:480-7, 1994
19. Parra RO, Farber R, Feigl A: Pressure necrosis from intermittent-pneumatic-compression stockings. [Letter] N Engl J Med 321:1615, 1989
20. Lachmann EA, Rook JL, Tunkel R, et al: Complications associated with intermittent pneumatic compression. Arch Phys Med Rehabil 73:482-5, 1992
21. Davidson JE, Willms DC, Hoffman MS: Effect of intermittent pneumatic leg compression on intracranial pressure in brain-injured patients. Crit Care Med 21:224-7, 1993
22. Hull RD, Pineo GF: Intermittent pneumatic compression for the prevention of venous thromboemb olism (ed.). Chest 109:6-9, 1996
23. Tarnay TJ, Rohr PR, Davidson AG, et al: Pneumatic calf compression, fibrinolysis, and the prevention of deep venous thrombosis. Surgery 88:489-96, 1980
24. Velmahos GC, Nigro J, Tatevossian R, et al: Inability of an aggressive policy of thromboprophylaxis to prevent deep venous thrombosis (DVT) in critically injured patients: are current methods of DVT prophylaxis insufficient? J Am Coll Surg 187:529-533, 1998
25. Velmahos GC, Kern J, Chan L et al: Prevention of venous thromboembolism after injury: an evidence-based report-Part I: analysis of risk factors and evaluation of the role of vena cava filters. J Trauma 49:132­139,2000
26. Anglen JO, Bagby C, George R: A randomized comparison of sequential-gradient calf compression with intermittent plantar compression for prevention of venous thrombosis in orthopedic trauma patients: preliminary results. Am J Ortho 33:53-57, 1998
27. Spain DA, Bergamini, Hoffman JF, et al. Comparison of sequential compression devices and foot pumps for prophylaxis of deep venous thrombosis in high-risk trauma patients. Am Surg64:522-526,1998

Table

Deep Venous Thrombosis (Dvt) in Trauma: A Literature Review