Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis

Y.M.Arabi. New England Journal of Medicine; February 18 2019; doi: 10.1056/NEJMoa1816150

Clinical Question

  • In adult critically ill patients receiving pharmacological thromboprophylaxis, does the use of adjunctive intermittent pneumatic compression devices result in a lower incidence of proximal deep vein thrombosis (DVT)?


  • Proximal deep vein thrombosis (DVT) is a relatively common complication of prolonged ICU stay, occurring in between 5 and 10% of patients Marik 1997
  • The occurrence of a DVT can lead to pulmonary embolism (PE), which is a potentially fatal complication
  • Prophylaxis using anticoagulation with low molecular weight or unfractionated heparin is considered standard of care in patients without contraindications Alhazzani 2013 Metanalysis
  • The use of sequential compression devices of the lower limbs aims to provide an additional protective effect to the use of chemical prophylaxis
  • These devices can potentially lead to pressure injuries and can be a significant use of resources
  • Mechanical DVT prevention has been shown to reduce the incidence of DVT in stroke patients CLOTS 3 trial
  • It is unclear whether sequential mechanical compression devices provide a benefit in reducing the rate of DVT in ICU patients who are already receiving chemical prophylaxis


  • An international, multi-centre randomised controlled trial
  • Computer-generated block randomisation with variable block size
  • Trial powered at 80% (20% risk of a type 2 error) to detect an absolute difference of 3% in the incidence of proximal lower limb DVT
  • Assumed baseline incidence of proximal DVT on ICU estimated at 7% with pharmacological prophylaxis alone
  • A sample size of 2000 patients was required, after accounting for a 5% loss to follow-up
  • Both a modified intention to treat and per protocol analysis performed
  • The primary outcome was the incidence of proximal deep vein thrombosis
  • Data were censored for patients at the time a pulmonary embolism developed, at the time of death, or at trial date 28, whichever occurred first
  • Results were reported as the relative risk of DVT using a generalised linear mixed model to account for clustering by site
  • Adjustment was made for binary variables (type of heparin used, location before ICU admission, type of admission, use of femoral lines and presence of heart failure) using a Cox proportional-hazards model, incorporating the trial site as a random effect
  • Secondary outcome measures included the percentage of patients who had prevalent proximal DVTs, the occurrence of any lower limb DVT, the occurrence of pulmonary embolism, a composite outcome of venous thromboembolism that included PE, or all prevalent and incidence lower-limb DVTs, a composite outcome of DVT or death from any cause at 28 days and safety outcomes
  • Certified ultrasonographers performed standardised proximal venous ultrasonography of both lower limbs within 48 hours after randomisation and then twice weekly and on clinical suspicion of DVT
  • Radiologists interpreting scans were blinded to trial-group assignments


  • 20 sites in Saudi Arabia, Canada, Australia and India
  • July 2014 to August 2018


  • Inclusion: Medical, surgical or trauma adult ICU patients, weighing at least 45kg who were expected to stay in ICU for at least 72 hours with no contraindications to pharmacologic thromboprophylaxis with either unfractionated or low molecular weight heparin
  • Exclusion: Patient treated with intermittent pneumatic compression for >24 hours in this current ICU admission; patient in ICU for > 48 hours; pharmacological prophylaxis other than unfractionated or low molecular weight heparin; contraindication to applying pneumatic compression devices; inability to perform ultrasound of lower limbs; allergy to sleeve material; palliative care patient
  • 16,053 patients screened.
    • 2,003 underwent randomisation and were included in the modified intention to treat analysis
      • 991 patients assigned to the pneumatic compression group
      • 1012 patients assigned to the control group
  • Baseline characteristics were similar between the two groups
    • APACHE II score 20.1 in treatment group and 20.2 in control group
    • Average age 57.6 in treatment group and 58.7 in control group
    • Most patients (around 80%) were medical ICU patients


  • Intermittent pneumatic compression device
  • When available, sequential compression devices (multichamber cuffs) and thigh-length sleeves were preferred
  • Non-sequential devices (single-chamber cuffs) and knee-length sleeves were permitted
  • Foot pumps could be used in addition to thigh-length or knee-length sleeves
  • Intermittent pneumatic compression was applied to both lower limbs for at least 18 hours a day, with the sleeves removed for skin inspection and care every 8 hours


  • Intermittent pneumatic compression permitted only during interruption of pharmacologic thromboprophylaxis

Management common to both groups

  • Graduated compression stockings not permitted in either trial group
  • Systemic anticoagulation for reasons other than venous thromboembolism and antiplatelet therapy were permitted


  • Primary outcome: Incident proximal deep-vein thrombosis occurred in 37 of 957 patients (3.9%) in the pneumatic compression group and in 41 of 985 patients (4.2%) in the control group (relative risk, 0.93; 95%confidence interval [CI], 0.60 to 1.44; P = 0.74).
  • Secondary outcome: No difference in prevalent proximal deep-vein thromboses between the pneumatic compression group and the control group (3.4% [34 of 991 patients] vs. 2.7% [27 of 1012 patients]; relative risk, 1.29; 95% CI, 0.78 to 2.12).
  • Lower limb DVT rates did not differ significantly between the pneumatic compression group and the control group (9.6% [95 of 991 patients] vs. 8.4% [85 of 1012 patients]; relative risk, 1.14; 95% CI, 0.86 to 1.51)
  • Pulmonary embolism occurred in 8 of 991 patients (0.8%) in the pneumatic compression group and in 10 of 1012 patients (1.0%) in the control group (relative risk, 0.82; 95% CI, 0.32 to 2.06)
  • A composite outcome of venous thromboembolism that included pulmonary embolism or all prevalent and incident lower-limb deep-vein thromboses occurred in 103 of 991 patients (10.4%) in the pneumatic compression group and in 95 of 1012 patients (9.4%) in the control group (relative risk, 1.11; 95% CI, 0.85 to 1.44)
  • The rates of death from any cause did not differ significantly between the two trial groups
  • The composite outcome of lower-limb DVT, PE, or death from any cause at 28 days occurred in 231 of 990 patients (23.3%) in the pneumatic compression group and in 243 of 1011 patients (24.0%) in the control group (relative risk, 0.97; 95% CI, 0.83 to 1.14)
  • There was no difference in adverse events related to the pneumatic compression devices

Authors’ Conclusions

  • Among critically ill patients who were receiving pharmacologic thromboprophylaxis, we found no benefit of adjunctive intermittent pneumatic compression in the prevention of incident proximal lower-limb deep-vein thrombosis


  • Radiologists interpreting ultrasound scans were blinded to the assigned group, reducing information bias
  • Both an intention to treat and a per-protocol analysis were performed
  • There was good compliance with the study protocol
  • Exclusion criteria were reasonable and the study sample recruited a heterogenous group of ICU patients
  • The majority of patients were mechanically ventilated and mean APACHE II scores were above 20 in both groups, so this was representative of a reasonably sick cohort of patients
  • The randomisation process was appropriate and the use of a computer-generated block sequence minimised selection bias
  • The authors adjusted the data to account for several potential confounding variables


  • Although this was an international study, over 75% of patients were recruited in Saudi Arabia, limiting the external validity of the study
  • The study was underpowered to detect a difference in DVT rates as these were lower than anticipated
  • 10% of patients in the control group received the intervention
  • The was heterogeneity in the type of compression device used between centres and nine different types of compression device were used
  • High-risk groups, such as trauma ICU patients, were under-represented (less than 10% of study population)
  • DVTs in the pelvic veins may not be detected by bedside ultrasonography

The Bottom Line

  • This study will change my practice as I will no longer use sequential mechanical compression devices in ICU patients who are receiving prophylactic anticoagulation
  • This does not apply to ICU patients who have contraindications to chemical thromboprophylaxis

External Links


Summary author: Fraser Magee
Summary date: 1 March 19
Peer-review editor: Duncan Chambler

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