|Year : 2019 | Volume
| Issue : 3 | Page : 95-98
Should pneumatic compression be used in conjunction with pharmacologic venous thromboprophylaxis: Lessons from the PREVENT trial
Yaseen M Arabi, Sami J Alsolamy, Abdulaziz Al-Dawood
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 Submission||09-Jul-2019|
|Date of Decision||10-Jul-2019|
|Date of Acceptance||04-Sep-2019|
|Date of Web Publication||30-Oct-2019|
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
Source of Support: None, Conflict of Interest: None
|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 2020 Jan 21];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. 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|| |
Pneumatic compression provides a mechanical method of delivering compression to the lower extremities. The devices consist of an automatic pump which inflates and deflates sleeves placed on the lower limbs. 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.
In addition, pneumatic compression may also increase endogenous fibrinolysis and stimulate vascular endothelial cells. 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.,,,,,,
Pneumatic compression may have cardiovascular effects. Pneumatic compression was reported to significantly increase cardiac output in healthy volunteers. 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. 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.,
| Using Pneumatic Compression Alone|| |
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. 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).
However, when pneumatic compression used alone is compared to pharmacologic prophylaxis used alone, pneumatic compression is less effective in reducing DVT than pharmacologic thromboprophylaxis.,,
| Adjunctive Use of Pneumatic Compression With Pharmacologic Thromboprophylaxis|| |
Limited data exist about the efficacy of adjunctive use of intermittent pneumatic compression (IPC)., 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.,,,,
The Pneumatic Compression for Preventing Venous Thromboembolism Trial
The PREVENT trial was conducted in 20 sites in Saudi Arabia, Canada, Australia, and India.,, 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. 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. 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.
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