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 Table of Contents  
EDITORIAL
Year : 2019  |  Volume : 3  |  Issue : 3  |  Page : 95-98

Should pneumatic compression be used in conjunction with pharmacologic venous thromboprophylaxis: Lessons from the PREVENT trial


Department of Intensive Care, Ministry of National Guard Health Affairs; King Abdullah International Medical Research Center; College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia

Date of Submission09-Jul-2019
Date of Decision10-Jul-2019
Date of Acceptance04-Sep-2019
Date of Web Publication30-Oct-2019

Correspondence Address:
Yaseen M Arabi
Department of Intensive Care, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, ICU 1425, P.O. Box 22490, 11426, Riyadh
Kingdom of Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sccj.sccj_15_19

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How to cite this article:
Arabi YM, Alsolamy SJ, Al-Dawood A. Should pneumatic compression be used in conjunction with pharmacologic venous thromboprophylaxis: Lessons from the PREVENT trial. Saudi Crit Care J 2019;3:95-8

How to cite this URL:
Arabi YM, Alsolamy SJ, Al-Dawood A. Should pneumatic compression be used in conjunction with pharmacologic venous thromboprophylaxis: Lessons from the PREVENT trial. Saudi Crit Care J [serial online] 2019 [cited 2019 Nov 12];3:95-8. Available from: http://www.sccj-sa.org/text.asp?2019/3/3/95/270094



Pneumatic compression is a widely used method for venous thromboprophylaxis in conjunction with pharmacologic thromboprophylaxis (unfractionated heparin [UFH] and low molecular-weight heparin [LMWH]) among patients admitted to the intensive care units (ICUs). Recently, the Pneumatic Compression for Preventing Venous Thromboembolism (PREVENT) trial (clinicaltrials.gov identifier: NCT02040103, Current controlled trials ISRCTN44653506) was published.[1] The PREVENT trial, a multicenter randomized controlled study, assessed whether adjunctive pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis would result in lower incidence of proximal lower limb deep vein thrombosis (DVT) than pharmacologic thromboprophylaxis alone.


  Physiologic Effects Of Pneumatic Compression Top


Pneumatic compression provides a mechanical method of delivering compression to the lower extremities.[2] The devices consist of an automatic pump which inflates and deflates sleeves placed on the lower limbs.[3] The configuration of the sleeves and pump, the inflation rate and pressure, and the compression sequence vary between manufacturers. Some provide sequential compression through multiple chambers of the sleeve, and others provide rapid inflation, thus inducing high blood flow in the legs, stripping out any forming venous thrombi before they become significant, and producing flow disturbance in venous valve pockets, where the initial growth of thrombi occurs.[3]

In addition, pneumatic compression may also increase endogenous fibrinolysis and stimulate vascular endothelial cells.[2] Earlier work using global fibrinolysis tests, such as the euglobulin lysis time, suggested that pneumatic compression might increase fibrinolysis, although more recent studies of specific assays of fibrinolytic proteins have questioned this finding.[4],[5],[6],[7],[8],[9],[10]

Pneumatic compression may have cardiovascular effects. Pneumatic compression was reported to significantly increase cardiac output in healthy volunteers.[11] Among fifty healthy patients undergoing elective cesarean section under spinal anesthesia, pneumatic compression was associated with less reduction in mean arterial pressure, although there were no significant differences in systolic arterial pressure, diastolic arterial pressure, heart rate, and pulse pressure between the groups.[12] The clinical effects among critically ill patients are uncertain. In a study of patients admitted to surgical ICU, the mean cardiac output did not change significantly during activation of pneumatic compression of the legs, as measured by the thermodilution technique.[13],[14]


  Using Pneumatic Compression Alone Top


In patients who cannot receive pharmacologic thromboprophylaxis, pneumatic compression has been shown to reduce DVT. The Clots in Legs Or sTockings after Stroke (CLOTS 3) trial randomized 2876 stroke patients in 94 centers in the UK to receive pneumatic compression versus no pneumatic compression.[15] The primary outcome was DVT in the proximal veins detected on a screening ultrasound or any symptomatic DVT in the proximal veins, confirmed on imaging, within 30 days of randomization. The primary outcome occurred in 8.5% of patients allocated to pneumatic compression and 12.1% of patients allocated to no pneumatic compression; with an absolute risk reduction of 3.6% (95% confidence interval [CI] 1.4–5.8).[15]

However, when pneumatic compression used alone is compared to pharmacologic prophylaxis used alone, pneumatic compression is less effective in reducing DVT than pharmacologic thromboprophylaxis.[16],[17],[18]


  Adjunctive Use of Pneumatic Compression With Pharmacologic Thromboprophylaxis Top


Limited data exist about the efficacy of adjunctive use of intermittent pneumatic compression (IPC).[16],[19] The lack of clear evidence has been reflected in the wide variability in the use of these devices as documented in surveys from Canada, France, Australia, and Germany.[20],[21],[22],[23],[24]

The Pneumatic Compression for Preventing Venous Thromboembolism Trial

The PREVENT trial was conducted in 20 sites in Saudi Arabia, Canada, Australia, and India.[1],[25],[26] In this trial, adult patients who were eligible for pharmacologic thromboprophylaxis with either UFH or LMWH were randomized to receive either pneumatic compression in addition to pharmacologic thromboprophylaxis (the intervention group) or to pharmacologic thromboprophylaxis alone (the control group). The primary outcome was the occurrence of incident proximal lower limb DVT detected by twice-weekly lower limb ultrasonography. A total of 2003 patients were enrolled and included in the modified intention-to-treat analysis. The two groups were balanced in baseline characteristics including the use of UFH versus LMWH thromboprophylaxis, with approximately 58% receiving UFH at enrollment. Pneumatic compression was used for a median of 22 h daily (interquartile range 21–23) in the intervention group while IPC use in the control group was minimal. Knee-length sleeves were most commonly used (79.4%) followed by thigh-length sleeves (18.7%) and foot pumps (12.2%) used less often.

The trial found no difference in the primary outcome; incident proximal DVT occurred in 3.9% of patients in the IPC group and 4.2% of patients in the control group (relative risk 0.93; 95% CI 0.60–1.44; P = 0.74). All lower limb DVTs (proximal, distal, prevalent, or incident) were not significantly different between the two groups (9.6% vs. 8.4%). Pulmonary embolism (PE) occurred in 0.8% of patients in the IPC group and 1.0% in the control group. Mortality was not different. There was no significant between-group difference in lower limb skin injury or ischemia.

For purposes of the trial, the primary outcome was defined as incident (i.e., new) proximal lower limb DVT, as detected by twice-weekly lower limb ultrasonography after the 3rd calendar day (i.e., after the first ultrasound). DVTs that were detected within the first 3 days on the first ultrasound were defined as prevalent (i.e., preexisting). The idea was to include in the primary outcome of the trial only DVTs that were new. This definition probably contributed to the apparent low “incidence” of DVT. Obviously, new DVT could occur within 3 days of admission to the ICU. In fact, total DVT (proximal, distal, incident, or prevalent lower limb DVT) occurrence was 9.6% in the pneumatic compression group and 8.4% in the control group, which is similar to what has been observed in other studies. For that reason, multiple sensitivity analyses were carried out using different cutoff points to define “incident DVT.” All sensitivity analyses that considered all proximal lower limb DVT as incident if detected on day 1 and later, day 2 or later, or day 3 later were consistent with the primary analysis.

Multiple predefined subgroup analyses were performed, and all showed no heterogeneity in the effect of pneumatic compression. In some groups, like the subgroup of femoral central venous catheter, in which the incidence of DVT was high, pneumatic compression was not associated with decreased DVT (incident DVT of 14.2% in the pneumatic compression group and 11.5% in the control group [relative risk 1.23, 95% CI 0.67–2.24]).

Because patients were enrolled if they were started on pharmacologic thromboprophylaxis within a 48-h window from admission to ICU, trauma patients constituted only 7%–8% of enrolled patients. This is a particularly high-risk group; more data may be required in this group on the effectiveness of adjunctive pneumatic compression. The PREVENT trial enrolled critically ill patients in the ICU; therefore, patients with postorthopedic surgery, such as total knee or hip replacement who are typically not admitted to the ICU, may not be represented in the PREVENT study population.

One of the main differences between PREVENT and CLOTS 3 is that only a small proportion of CLOTS 3 patients were on anticoagulation.[15] Approximately 24% of the patients at recruitment were on heparin or warfarin or had received thrombolysis. Postrandomization, 17% of CLOTS 3 patients received prophylactic dose of heparin and 14% received therapeutic dose of heparin. This is probably the main reason for the different results between the two trials; pneumatic compression was effective in CLOTS 3, in which patients were largely not on pharmacologic thromboprophylaxis, but not effective in PREVENT, in which patients were already receiving pharmacologic thromboprophylaxis. Another difference is that thigh-length sleeves were used in CLOTS 3. In comparison, in the PREVENT trial, knee-length sleeves were used in 79% of patients and thigh-length in 19% of patients in the IPC group. Obviously, the PREVENT trial was not designed to compare the effect of thigh-length compared to knee-length sleeves. To be answered adequately, this question would require a randomized controlled trial comparing thigh-length to knee-length sleeves.

An accompanying editorial highlighted the importance of rigorous testing for the effectiveness of devices, such as pneumatic compression, as done in PREVENT trial.[27] Devices should be put on trial to examine their effectiveness on patient-centered outcomes (not only mechanisms but also properties). The editorial highlighted the value of global collaboration in critical care and that PREVENT trial marks a milestone for the Saudi Critical Care Trials Group, with an investigative team that is diverse in terms of perspectives, professions, gender, and geographic region.

In summary, the PREVENT trial demonstrated that adjunctive use of IPC had no effect on the rate of incident proximal DVT in critically ill patients when used in conjunction with pharmacologic thromboprophylaxis.



 
  References Top

1.
Arabi YM, Al-Hameed F, Burns KE, Mehta S, Alsolamy SJ, Alshahrani MS, et al. Adjunctive intermittent pneumatic compression for venous thromboprophylaxis. N Engl J Med 2019;380:1305-15.  Back to cited text no. 1
    
2.
Kurtoǧlu M, Güloǧlu R, Ertekin C, Taviloǧlu K, Alimoǧlu O. Intermittent pneumatic compression in the prevention of venous thromboembolism in high-risk trauma and surgical ICU patients. Ulus Travma Acil Cerrahi Derg 2005;11:38-42.  Back to cited text no. 2
    
3.
Morris RJ, Giddings JC, Ralis HM, Jennings GM, Davies DA, Woodcock JP, et al. The influence of inflation rate on the hematologic and hemodynamic effects of intermittent pneumatic calf compression for deep vein thrombosis prophylaxis. J Vasc Surg 2006;44:1039-45.  Back to cited text no. 3
    
4.
Kessler CM, Hirsch DR, Jacobs H, MacDougall R, Goldhaber SZ. Intermittent pneumatic compression in chronic venous insufficiency favorably affects fibrinolytic potential and platelet activation. Blood Coagul Fibrinolysis 1996;7:437-46.  Back to cited text no. 4
    
5.
Christen Y, Wütschert R, Weimer D, de Moerloose P, Kruithof EK, Bounameaux H. Effects of intermittent pneumatic compression on venous haemodynamics and fibrinolytic activity. Blood Coagul Fibrinolysis 1997;8:185-90.  Back to cited text no. 5
    
6.
Comerota AJ, Chouhan V, Harada RN, Sun L, Hosking J, Veermansunemi R, et al. The fibrinolytic effects of intermittent pneumatic compression: Mechanism of enhanced fibrinolysis. Ann Surg 1997;226:306-13.  Back to cited text no. 6
    
7.
Labropoulos N, Leon LR Jr., Bhatti A, Melton S, Kang SS, Mansour AM, et al. Hemodynamic effects of intermittent pneumatic compression in patients with critical limb ischemia. J Vasc Surg 2005;42:710-6.  Back to cited text no. 7
    
8.
Killewich LA, Cahan MA, Hanna DJ, Murakami M, Uchida T, Wiley LA, et al. The effect of external pneumatic compression on regional fibrinolysis in a prospective randomized trial. J Vasc Surg 2002;36:953-8.  Back to cited text no. 8
    
9.
Macaulay W, Westrich G, Sharrock N, Sculco TP, Jhon PH, Peterson MG, et al. Effect of pneumatic compression on fibrinolysis after total hip arthroplasty. Clin Orthop Relat Res 2002;399:168-76.  Back to cited text no. 9
    
10.
Murakami M, Wiley LA, Cindrick-Pounds L, Hunter GC, Uchida T, Killewich LA. External pneumatic compression does not increase urokinase plasminogen activator after abdominal surgery. J Vasc Surg 2002;36:917-21.  Back to cited text no. 10
    
11.
Bickel A, Shturman A, Grevtzev I, Roguin N, Eitan A. The physiological impact of intermittent sequential pneumatic compression (ISPC) leg sleeves on cardiac activity. Am J Surg 2011;202:16-22.  Back to cited text no. 11
    
12.
Adsumelli RS, Steinberg ES, Schabel JE, Saunders TA, Poppers PJ. Sequential compression device with thigh-high sleeves supports mean arterial pressure during caesarean section under spinal anaesthesia. Br J Anaesth 2003;91:695-8.  Back to cited text no. 12
    
13.
Horiuchi K, Johnson R, Weissman C. Influence of lower limb pneumatic compression on pulmonary artery temperature: Effect on cardiac output measurements. Crit Care Med 1999;27:1096-9.  Back to cited text no. 13
    
14.
Hickey R, Erian R. Pneumatic compression stockings increase the variability of thermodilution cardiac output measurements: Do they truly affect cardiac output? Crit Care Med 1999;27:1039-41.  Back to cited text no. 14
    
15.
Dennis M, Sandercock P, Graham C, Forbes J, Smith J. CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. The clots in legs or sTockings after stroke (CLOTS) 3 trial: A randomised controlled trial to determine whether or not intermittent pneumatic compression reduces the risk of post-stroke deep vein thrombosis and to estimate its cost-effectiveness. Health Technol Assess 2015;19:1-90.  Back to cited text no. 15
    
16.
Qaseem A, Chou R, Humphrey LL, Starkey M, Shekelle P, Clinical Guidelines Committee of the American College of Physicians. Venous thromboembolism prophylaxis in hospitalized patients: A clinical practice guideline from the american college of physicians. Ann Intern Med 2011;155:625-32.  Back to cited text no. 16
    
17.
Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, et al. Prevention of VTE in nonsurgical patients: Antithrombotic therapy and prevention of thrombosis, 9th ed.: American college of chest physicians evidence-based clinical practice guidelines. Chest 2012;141:e195S-e226S.  Back to cited text no. 17
    
18.
Kakkos SK, Caprini JA, Geroulakos G, Nicolaides AN, Stansby GP, Reddy DJ. Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thromboembolism in high-risk patients. Cochrane Database Syst Rev 2008;(4):CD005258.  Back to cited text no. 18
    
19.
Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest 2012;141:7S-47S.  Back to cited text no. 19
    
20.
Limpus A, Chaboyer W, McDonald E, Thalib L. Mechanical thromboprophylaxis in critically ill patients: A systematic review and meta-analysis. Am J Crit Care 2006;15:402-10.  Back to cited text no. 20
    
21.
Cook D, Laporta D, Skrobik Y, Peters S, Sharpe M, Murphy P, et al. Prevention of venous thromboembolism in critically ill surgery patients: A cross-sectional study. J Crit Care 2001;16:161-6.  Back to cited text no. 21
    
22.
Müllges W, Steinke E, Moldenhauer G, Berens N. Customary use of compression stockings for prevention of thrombosis in medical intensive care units in Germany. Dtsch Med Wochenschr 2001;126:867-71.  Back to cited text no. 22
    
23.
Lacherade JC, Cook D, Heyland D, Chrusch C, Brochard L, Brun-Buisson C. Prevention of venous thromboembolism in critically ill medical patients: A Franco-canadian cross-sectional study. J Crit Care 2003;18:228-37.  Back to cited text no. 23
    
24.
Limpus A, Chaboyer W. The use of graduated compression stockings in Australian intensive care units: A national audit. Aust Crit Care2003;16:53-8.  Back to cited text no. 24
    
25.
Arabi YM, Alsolamy S, Al-Dawood A, Al-Omari A, Al-Hameed F, Burns KE, et al. Thromboprophylaxis using combined intermittent pneumatic compression and pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically ill patients: Study protocol for a randomized controlled trial. Trials 2016;17:390.  Back to cited text no. 25
    
26.
Arabi Y, Al-Hameed F, Burns KE, Mehta S, Alsolamy S, Almaani M, et al. Statistical analysis plan for the pneumatic compREssion for preVENting venous thromboembolism (PREVENT) trial: A study protocol for a randomized controlled trial. Trials 2018;19:182.  Back to cited text no. 26
    
27.
Lauzier F, Douketis JD, Cook DJ. A device on trial-intermittent pneumatic compression in critical care. N Engl J Med 2019;380:1367-8.  Back to cited text no. 27
    




 

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