Critically ill patients are susceptible to thrombus formation and embolism due to factors such as advanced age, prolonged immobility related to disease severity or sedative use, and vascular damage from central venous catheters or other invasive procedures. The incidence of Deep Vein Thrombosis (DVT) in this population is approximately 15~30% [1, 2].

DVT primarily affects the lower extremities, with blood clots forming in the deep veins and obstructing blood flow [3]. DVT is the leading cause of Pulmonary Embolism (PE); in recent times, DVT and PE together are referred to as Venous Thromboembolism (VTE) [3]. When VTE occurs in the popliteal vein, it is classified as proximal VTE, whereas its occurrence in the calf vein is termed distal VTE. DVT often presents without symptoms or may manifest as edema, tenderness, and fever. However, these symptoms can be difficult to distinguish from those of other conditions. Additionally, post-thrombotic syndrome, which is challenging to treat, may develop following DVT. Therefore, preventing the formation of venous thrombi is highly important [3, 4].

The American College of Chest Physicians and the American Society of Hematology have issued guidelines recommending the use of anticoagulants for thrombus prevention in critically ill patients without contraindications [5, 6]. However, in cases where there is active bleeding or a high risk of bleeding, Intermittent Pneumatic Compression (IPC) is advised as an alternative until the bleeding risk diminishes [5, 6]. The efficacy of anticoagulants, such as Unfractionated Heparin (UFH) or Low-Molecular-Weight Heparin (LMWH), in thromboprophylaxis has been well-documented [1]. Nonetheless, their use may be limited due to concerns about bleeding or the potential for bleeding. In the realm of critical care nursing, IPC is frequently chosen for its low bleeding risk and its ability to address Virchow's triad, making it a viable option for preventing VTE either alone or in conjunction with anticoagulants [7].

However, there is a lack of studies on the thromboprophylactic effects of IPC, the available evidence is inconsistent, and the efficacy of IPC remains uncertain. Only one previous meta-analysis [1] has examined the thromboprophylactic efficacy of anticoagulants and included the effects of mechanical thrombosis prevention. Limpus et al. [8] conducted a systematic review of two Randomized Clinical Trials (RCTs) comparing IPC with LMWH in trauma patients, revealing no significant difference in the incidence of DVT between the two interventions. A prior network meta-analysis comparing IPC, a control group, and LMWH [9] suggested a trend toward reduced DVT risk, but the difference was not statistically significant.

However, other studies [10, 11] have reported that IPC was effective in reducing the incidence of VTE and DVT compared to the control group. However, there was no significant difference when compared to LMWH. Additionally, combining IPC with LMWH did not yield any extra benefits, and the bleeding rate was higher with LMWH. These findings suggest that IPC is relatively safe and is widely recognized and selected in critical care nursing [9, 12]. Nonetheless, there is a lack of robust evidence to guide clinical practitioners regarding the thrombosis prevention effects of IPC.

The evidence-based clinical practice guidelines of the American College of Chest Physicians [6] recommend strategies for VTE prevention. These recommendations are based on two RCTs that compared the combined effect of IPC and an anticoagulant with that of an anticoagulant alone in patients undergoing major orthopedic surgery [5]. Consequently, it is important to determine the effectiveness of IPC in critically ill patients. This includes assessing the thromboprophylactic effect of IPC alone on VTE prevention in general inpatients, as well as its potential additional benefits when used in conjunction with anticoagulants. Previous secondary analyses of the efficacy of IPC in preventing VTE [9, 11] were limited by the small number of RCTs and non-RCTs or observational follow-up studies available, as there were few primary RCTs on the subject. Therefore, further research is required to provide robust evidence for the use of IPC in clinical practice. This study aimed to evaluate the characteristics and efficacy of IPC interventions for VTE prevention in critically ill patients. To achieve this, we conducted a systematic review of RCTs that implemented IPC interventions to prevent thrombosis in this patient population.

This study aimed to investigate the characteristics of IPC interventions for thromboprophylaxis in critically ill patients and to analyze their effectiveness. In this section, we discuss the results of the six finally selected RCTs in the sequence of participants, interventions, and outcomes.

The risk factors for VTE are known to include age, BMI, surgery, trauma, cancer, chemotherapy, lower extremity surgery, pelvic fractures, severe infections, inflammatory bowel disease, severe cardiopulmonary disease, stroke, spinal cord injury, immobility due to paralysis, oral contraceptive use, pregnancy and childbirth, anticoagulant disorders, and obesity [6, 17]. The studies reviewed here exhibited inconsistencies due to varying inclusion and exclusion criteria related to bleeding risk factors or VTE risk factors associated with anticoagulant use. Furthermore, the studies differed in terms of disease type, severity, age, and BMI of the participants. These factors can influence the outcomes. Therefore, it is necessary to validate the effectiveness of thromboprophylaxis in a controlled setting, where participant selection or exclusion criteria are standardized, using tools that assess the risk based on severity evaluation criteria or VTE [18, 19, 20, 21].

Anticoagulants, such as warfarin, UFH, and LMWH, are recommended to reduce the risk of VTE in acute or critically ill patients. However, their use is limited by an increased risk of bleeding, which can counterbalance the benefits of thromboprophylaxis [6, 17]. Mechanical thromboprophylaxis, which addresses most elements of Virchow's triad without raising the risk of bleeding, is advised for use either alone or in conjunction with anticoagulants [6, 7]. Among the mechanical thromboprophylaxis options for preventing VTE in critically ill patients who are at risk of bleeding from anticoagulant use, IPC is regarded as the most appropriate and cost-effective choice [22]. The thrombosis prevention guidelines for non-surgical critically ill patients [5] also suggest the use of IPC when anticoagulation is contraindicated or when there are concerns about bleeding.

Our findings identified the following types of IPC interventions: IPC alone, IPC combined with GCS, IPC combined with LMWH, and IPC combined with both ECS and LMWH. IPC alone was compared with either a control group or LMWH, while the combined interventions were compared in a manner that allowed for the assessment of additional effects beyond those of the individual interventions. A previous study [23] reported on the effectiveness of IPC alone and anticoagulant therapy alone in inpatients, as well as the combined use of IPC and LMWH. A retrospective study of ICU patients [24] analyzed the use of IPC alone, LMWH alone, and the combination of IPC and LMWH. Additionally, we identified existing systematic reviews and meta-analyses [9, 10, 11] that compared IPC alone and LMWH alone with a control group, as well as studies comparing IPC alone directly with LMWH alone.

Meanwhile, our findings indicate that the sleeve-type IPC device was utilized in both thigh and calf configurations. A previous non-RCT [25] comparing the effectiveness of calf-thigh and foot types in patients undergoing hip replacement surgery demonstrated that the calf-thigh type was more effective at reducing postoperative thigh edema than the foot type. Future research should focus on comparing the effectiveness of IPC devices according to sleeve type in critically ill patients.

Next, we will discuss the effectiveness of IPC interventions based on the prevention of the risk of developing DVT, PE, and VTE, which are primary outcomes, and the risk of bleeding as a secondary outcome. The impacts on DVT incidence will be discussed in the following three categories.

First, the risk of DVT when using IPC alone was reduced compared to the control group [A1]; however, there was no significant difference when compared to the LMWH group [A2,A3]. The effectiveness of IPC alone in lowering the incidence of DVT in acutely ill patients has been confirmed in surgical patients [26], and its significant thromboprophylactic efficacy has also been established in stroke patients through large-scale, multi-organ RCTs [27]. A systematic review and meta-analysis examining the efficacy and safety of IPC and anticoagulants in neurosurgery patients found that both IPC and anticoagulants were significantly effective in preventing DVT, with comparable efficacy between the two [10]. Our findings align with a study [24] that analyzed the DVT prevention effects of IPC application by reviewing the medical records of 500 medical-surgical ICUs. Another meta-analysis [11] reported on the DVT prevention effect of IPC in ICU patients. Park et al. [9] suggested that IPC alone may reduce the tendency for DVT incidence, but the efficacy in reducing DVT incidence was not definitive; the effect of IPC in lowering the risk of DVT incidence in critically ill patients was not as pronounced as that of prophylactic anticoagulants.

Second, our findings showed that there was no significant difference in the incidence of either proximal or distal DVT when comparing the combined use of IPC and GCS with the use of GCS alone [A4]. A meta-analysis examining the effect of mechanical thromboprophylaxis on DVT in stroke patients [28] found that the included studies were unable to draw definitive conclusions regarding the benefits and risks due to limitations such as small sample sizes, diverse intervention methods, and varying DVT diagnostic techniques. In 2009, a multicenter RCT conducted across 64 centers in the UK, Italy, and Australia involved 2,518 patients who were immobilized and hospitalized within one week of an acute stroke [27]. The study reported that the incidence of DVT in patients who were administered thigh-level GCS did not significantly differ from that in the control group [27]. Additionally, the GCS group experienced a higher occurrence of skin damage, including ulcers, blisters, and skin necrosis, leading to the conclusion that thigh-length GCS provided no benefit to patients hospitalized for acute stroke [27]. Previous studies analyzing 326 medical records of critically ill patients found no difference in the incidence of DVT when comparing interventions with IPC, GCS, or elastic bandages [29]. However, when the venous blood flow rate was examined to compare the thromboprophylactic effects of CS and IPC in neurosurgical ICU patients, it was suggested that IPC might be more effective in preventing DVT than CS [30]. Furthermore, two meta-analyses [10, 31] confirmed that IPC is more effective than GCS in preventing DVT. Fernando et al. [32] reported that LMWH was effective in reducing the incidence of DVT in critically ill patients compared to the control group. In contrast, the effects of UFH, IPC, and mechanical pressure (both IPC and GCS) did not differ significantly. Additionally, the study could not confirm the thromboprophylactic effect of combining mechanical pressure with anticoagulant interventions.

Third, there was no observed difference in the incidence of DVT and P-DVT between the combined intervention of LMWH and IPC compared to LMWH alone [A5]. Similarly, no difference in P-DVT incidence was found when comparing the combined use of ECS and LMWH to LMWH alone, although differences in D-DVT incidence were noted. Furthermore, the additional benefit of combining IPC with anticoagulants could not be established. A previous meta-analysis [23] indicated that adding anticoagulants to IPC did not significantly affect the reduction of DVT incidence. However, another study suggested that incorporating IPC with anticoagulants decreased the incidence of DVT in surgical patients [33]. In summary, the efficacy of IPC alone in preventing DVT in critically ill patients was confirmed, and it was found to be as effective as LMWH. However, the study could not confirm either the added benefit of combining IPC with anticoagulants or its relative superiority to GCS. These conclusions are tentative due to the small number of studies included, the variability in participant characteristics and conditions, and the differences in the types of interventions across studies. Consequently, the generalizability of these results is limited until further research is available.

The efficacy of IPC alone in preventing PE was established in comparison with a control group [A1]. However, no significant difference was observed in the incidence of PE between the IPC and LMWH groups [A2,A3], indicating neither an additional benefit of LMWH nor an enhanced effect from the triple intervention involving IPC [A6]. Previous systematic reviews and meta-analyses [23, 33] have been unable to confirm the benefit of adding anticoagulants to reduce the risk of PE in inpatients, although the supplementary effect of IPC has been verified. In contrast, no difference in PE prevention was noted among critically ill patients [24]. Therefore, while the efficacy of IPC in preventing proximal DVT and PE has not been conclusively demonstrated, one study [3] did find that IPC significantly reduced the occurrence of proximal DVT and PE. Consequently, further research is necessary to determine the thromboprophylactic impact of IPC on proximal DVT and PE.

The efficacy of interventions to reduce the incidence of VTE was confirmed in one study that compared a triple intervention of IPC, LMWH, and ECS with a combined intervention of anticoagulants and GCS [A6]. However, no difference in VTE incidence was observed between the combined use of IPC and GCS [A4] and the combination of IPC and LMWH [A5]. A previous study [34] reported that IPC was as effective as anticoagulants in preventing VTE in surgical patients. Furthermore, combining anticoagulants with IPC could reduce the risk of VTE more than anticoagulants alone, and IPC was associated with a lower risk of major bleeding compared to anticoagulants [34]. Meta-analyses [10, 11] investigating the efficacy of IPC in preventing VTE in critically ill patients found no difference between IPC and LMWH, nor was there an additional effect when IPC was added to LMWH. However, this study included research that demonstrated effectiveness in preventing VTE, leading to results that differed from previous studies [10, 11]. Since the criteria for VTE occurrence varied across studies, further research with clearly defined indicators is necessary to validate these findings.

For the secondary outcome, which was the prevention of bleeding, there was no significant difference in efficacy between IPC and LMWH [A2,A3]. In a comparison of a triple intervention involving IPC, LMWH, and ECS with a combined intervention of IPC and ECS, there was a trend toward reduced bleeding with the addition of IPC, but the difference was not statistically significant [A4,A6]. A previous study [23] confirmed the effectiveness of combining IPC with anticoagulants for all patients requiring thromboprophylaxis; however, the addition of an anticoagulant increased the risk of bleeding compared to using IPC alone. No increase in bleeding risk was observed when IPC was combined with anticoagulants, as opposed to anticoagulant therapy alone. Other studies [9, 24] found no significant difference in bleeding risk between IPC and LMWH in critically ill patients, although IPC was associated with a lower risk of bleeding than LMWH in some reports [10]. Haykal et al. [11] noted that due to insufficient data, conclusions regarding the incidence of bleeding from IPC and LMWH interventions should be reserved until more empirical evidence is available.

Considering the bleeding risk associated with anticoagulants, our findings revealed that IPC alone is effective for thromboprophylaxis, showing no difference in efficacy compared to LMWH. Therefore, this study is significant as it confirms the value of both anticoagulants and IPC as thromboprophylaxis interventions in critical care nursing.

This study systematically reviewed six RCTs that assessed the impact of IPC alone or in combination with other interventions on DVT, PE, VTE, and bleeding as a thromboprophylactic strategy in ICU patients. The interventions included three studies of IPC alone, one study of IPC with GCS, one study of IPC with anticoagulants, and one study combining IPC, GCS, and anticoagulants. Additionally, the comparison groups in the three studies of IPC alone consisted of one with no prophylaxis and two with anticoagulants. Consequently, this study was limited by the inability to derive pooled estimates from the meta-analysis to confirm quantitative efficacy.

Based on our findings, we make the following recommendations: First, considering the application of IPC and the administration methods of LMWH, as well as the diagnostic methods for DVT, PE, and VTE, we propose a systematic review and meta-analysis that includes non-RCT studies in addition to the limited number of RCTs. Second, we suggest further research into the various application modes of combined interventions with anticoagulants and IPC as a thromboprophylactic strategy for patients who require thrombus prevention but are at high risk of bleeding or are contraindicated for anticoagulant use. Third, there is a need for a study to compare the application modes of IPC devices and the efficacy of thromboprophylaxis according to the type of sleeve used. Fourth, we recommend a study to compare and validate the effectiveness of thromboprophylaxis using IPC against that of a foot pump. Fifth, we advocate for research to verify the efficacy of IPC alone or in combination with other interventions, taking into account patient severity, the presence of risk factors, and the assessment of VTE risk.

This study systematically reviewed RCTs that evaluated IPC interventions for thrombus prevention in critically ill patients. The effectiveness of IPC alone in preventing thrombus formation was established, and additional benefits were observed when IPC was combined with anticoagulants and GCS. However, these effects were each demonstrated in only a single study, and no significant differences in effectiveness were noted when comparing anticoagulants or GCS with IPC alone. The findings suggest the potential for using IPC as a thromboprophylactic strategy in critically ill patients who are at an increased risk of bleeding or for whom anticoagulants are contraindicated. Consequently, there is a need for studies that consider the unique characteristics of critically ill patients and RCTs that assess the thromboprophylactic efficacy of IPC, either as a standalone intervention or in combination with other treatments.