Year : 2019 | Volume
: 14 | Issue : 4 | Page : 223--225
The journey to zero deep-vein thrombosis in critically ill patients
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
Dr. Yaseen M Arabi
Department of Intensive Care, King Abdulaziz Medical City, ICU 1425, P. O. Box: 22490, Riyadh 11426
Kingdom of Saudi Arabia
|How to cite this article:|
Arabi YM, Alsolamy SJ, Al-Dawood A. The journey to zero deep-vein thrombosis in critically ill patients.Ann Thorac Med 2019;14:223-225
|How to cite this URL:|
Arabi YM, Alsolamy SJ, Al-Dawood A. The journey to zero deep-vein thrombosis in critically ill patients. Ann Thorac Med [serial online] 2019 [cited 2020 Jul 15 ];14:223-225
Available from: http://www.thoracicmedicine.org/text.asp?2019/14/4/223/267950
Prevention of deep-vein thrombosis (DVT) among critically ill patients has been considered a high priority for patient safety initiatives. Recently, the Saudi Critical Care Trials Group published the results of the Pneumatic Compression for Preventing Venous Thromboembolism (PREVENT) trial in the New England Journal of Medicine. The trial examined whether the addition of pneumatic compression to pharmacological thromboprophylaxis reduced the incidence of DVT in critically ill patients.,, In this commentary, we review the lessons learned and implications of the PREVENT trial on clinical practice.
Venous thromboembolism (VTE), including DVT and pulmonary embolism (PE), is a common complication of critical illness. In prospective studies that performed screening, DVT was documented in 13%–31% of patients who were not receiving thromboprophylaxis during their intensive care unit (ICU) stay.,, However, DVT has also been documented in 5%–20% of patients who are receiving pharmacologic thromboprophylaxis., DVT is associated with increased duration of mechanical ventilation, duration of ICU stay, duration of hospital stay, and hospital mortality. Untreated PE is associated with a mortality of at least 25%. Furthermore, VTE remains clinically unsuspected in a large number of patients and is often diagnosed postmortem., In a large study of 6833 autopsies, fatal PE was recorded as the cause of death in 5.2% of adult autopsies, 80% among patients who were older than 60 years, and 80% among medical patients.
With the premise of improved DVT prevention, pneumatic compression is widely used in combination with pharmacologic thromboprophylaxis in critically ill patients. However, there has been limited data regarding this practice. The PREVENT trial examined whether the addition of pneumatic compression to pharmacological thromboprophylaxis reduced the incidence of DVT in critically ill patients.,, The study was conducted in twenty ICUs from Saudi Arabia, Canada, Australia, and India, and was sponsored by King Abdulaziz City for Science and Technology and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
In this trial, adult critically ill patients were randomly assigned within 48 h of ICU admission to receive either intermittent pneumatic compression for at least 18 h a day in addition to pharmacologic thromboprophylaxis (pneumatic compression group) or to pharmacologic thromboprophylaxis only (control group). The primary outcome was incident proximal lower-limb DVT as detected after the 3rd calendar day of randomization on twice-weekly screening ultrasound studies through ICU discharge, death, attainment of full mobility, or day 28 (whichever occurred first). DVT detected on days 1–3 was considered prevalent.
A total of 2003 patients were randomized. Most participants were medical patients; one half were admitted from emergency departments. Two-thirds of the patients were mechanically ventilated, and one-third were on vasopressors. Approximately 58% of the patients were receiving unfractionated heparin at randomization, and the rest were receiving low-molecular-weight heparin. Pneumatic compression was applied for a median of 22 h (interquartile range [IQR], 21–23) per day for a median of 7 days (IQR, 4–13) in the pneumatic compression group. Ultrasounds were performed as scheduled, averaging one ultrasound per 3.5 days in the pneumatic compression group and per 3.8 days in the control group. The primary outcome of incident proximal DVT was not different between the two groups: 3.9% in the pneumatic compression group and 4.2% in the control group (relative risk [RR], 0.93; 95% confidence interval [CI], 0.60–1.44). All lower-limb DVT events (proximal, distal, prevalent, and incident) were not different between the two groups (9.6% in the pneumatic compression group compared to 8.4% in the control group; RR, 1.14; 95% CI, 0.86, 1.51). Similarly, all VTE events were not different (10.4% in the pneumatic compression group and 9.4% in the control group [RR, 1.11; 95% CI, 0.85, 1.44]). Mortality was not different between the two groups. The PREVENT trial demonstrated that pneumatic compression was not associated with reduction in proximal lower-limb DVT rates compared with pharmacologic thromboprophylaxis alone.
Several lessons are learned from the PREVENT trial. The PREVENT study showed that the widely used practice of adjunctive pneumatic compression with pharmacologic thromboprophylaxis is not supported by objective evidence. As such, the PREVENT study is likely to influence this practice.
Second, the PREVENT trial highlights the importance of examining questions related to the effectiveness of therapeutic interventions in randomized controlled trials. This is particularly true for devices that are often introduced to the market with limited data regarding effectiveness on patient-centered outcomes. An accompanying editorial highlighted the need for adequately testing devices before wide implementation.
Third, because the PREVENT trial enrolled patients who could receive pharmacologic thromboprophylaxis early within 48 h of ICU admission, the study cohort consisted largely of medical patients. Trauma patients constituted a small proportion of the whole cohort, and further studies in this group may be warranted.
Finally, the journey for DVT prophylaxis dates back to more than five decades ago; a randomized controlled trial published in 1972 demonstrated that subcutaneous heparin in postoperative patients reduced DVT compared to controls. As this journey to zero DVT continued, other approaches for DVT prevention were tested. The Prophylaxis for Thromboembolism in Critical Care Trial demonstrated that the low-molecular-weight heparin (dalteparin) was of similar effect to unfractionated heparin in critically ill patients, although it was associated with reduction in the occurrence of PE. A systematic review of heparin (unfractionated and low-molecular-weight heparin) versus placebo showed that heparin reduces DVT by around 50% and PE by 50%. These data not only document the benefit of heparin in DVT prevention, but also demonstrate a substantial residual risk even when heparin is administered. To address this residual risk, mechanical thromboprophylaxis methods are often used. Unfortunately, graduated compression stockings were found to be of unclear benefit in DVT prophylaxis. The PREVENT trial demonstrates that adding pneumatic compression to pharmacologic thromboprophylaxis does not confer benefit. In fact, DVT occurred in almost 10% of patients in the PREVENT trial, confirming again that DVT is a common occurrence even in patients receiving pharmacologic thromboprophylaxis. The PREVENT trial highlights the need to explore innovative approaches for DVT prevention, perhaps beyond the existing traditional methods.
While the PREVENT trial showed that the adjunctive use of pneumatic compression with pharmacologic thromboprophylaxis is not effective in reducing incident DVT, pneumatic compression should probably be used in critically ill patients who cannot receive pharmacologic thromboprophylaxis, such as patients with active bleeding or those at high risk for bleeding. Finally, the effectiveness of pneumatic compression in reducing DVT risk in patients with coagulopathy (e.g., patients with a platelet count of <50 × 109/L) remains unclear and requires further study.
Financial support and sponsorship
The PREVENT trial was funded by King Abdulaziz City for Science and Technology (Grant AT 34-65) and King Abdullah International Medical Research Center (Grant RC12/045/R), both in Riyadh, Saudi Arabia.
Conflicts of interest
There are no conflicts of interest.
|1||Shekelle PG, Pronovost PJ, Wachter RM, McDonald KM, Schoelles K, Dy SM, et al. The top patient safety strategies that can be encouraged for adoption now. Ann Intern Med 2013;158:365-8.|
|2||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.|
|3||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.|
|4||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.|
|5||Cook DJ, Crowther MA. Thromboprophylaxis in the intensive care unit: Focus on medical-surgical patients. Crit Care Med 2010;38:S76-82.|
|6||Moser KM, LeMoine JR, Nachtwey FJ, Spragg RG. Deep venous thrombosis and pulmonary embolism. Frequency in a respiratory intensive care unit. JAMA 1981;246:1422-4.|
|7||Cade JF. High risk of the critically ill for venous thromboembolism. Crit Care Med 1982;10:448-50.|
|8||Fraisse F, Holzapfel L, Couland JM, Simonneau G, Bedock B, Feissel M, et al. Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD. The association of non-university affiliated intensive care specialist physicians of France. Am J Respir Crit Care Med 2000;161:1109-14.|
|9||Arabi YM, Khedr M, Dara SI, Dhar GS, Bhat SA, Tamim HM, et al. Use of intermittent pneumatic compression and not graduated compression stockings is associated with lower incident VTE in critically ill patients: A multiple propensity scores adjusted analysis. Chest 2013;144:152-9.|
|10||Cook D, Crowther M, Meade M, Rabbat C, Griffith L, Schiff D, et al. Deep venous thrombosis in medical-surgical critically ill patients: Prevalence, incidence, and risk factors. Crit Care Med 2005;33:1565-71.|
|11||Major KM, Wilson M, Nishi GK, Farber A, Chopra R, Chung A, et al. The incidence of thromboembolism in the surgical intensive care unit. Am Surg. 2003;69:857-61.|
|12||Alikhan R, Peters F, Wilmott R, Cohen AT. Fatal pulmonary embolism in hospitalised patients: A necropsy review. J Clin Pathol 2004;57:1254-7.|
|13||Lauzier F, Douketis JD, Cook DJ. A device on trial – Intermittent pneumatic compression in critical care. N Engl J Med 2019;380:1367-8.|
|14||Kakkar VV, Corrigan T, Spindler J, Fossard DP, Flute PT, Crellin RQ, et al. Efficacy of low doses of heparin in prevention of deep-vein thrombosis after major surgery. A double-blind, randomised trial. Lancet 1972;2:101-6.|
|15||PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group, Cook D, Meade M, Guyatt G, Walter S, Heels-Ansdell D, et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 2011;364:1305-14.|
|16||Alhazzani W, Lim W, Jaeschke RZ, Murad MH, Cade J, Cook DJ. Heparin thromboprophylaxis in medical-surgical critically ill patients: A systematic review and meta-analysis of randomized trials. Crit Care Med 2013;41:2088-98.|