3.2 The cumulative incidence of VTE within 28 days
Over the 28 days, 25 patients developed VTE: 1 patient with both PE and lower extremity proximal DVT, 11 patients with proximal DVT, and 13 patients with distal DVT. The cumulative incidence of VTE at 7, 14, and 21 days was 4.45% (95% CI, 2.55–7.71), 7.14% (4.61–10.97), and 7.53% (range, 4.92–11.43), respectively, while the cumulative incidence at 28 days was 9.55% (95% CI, 6.55–13.81). The hazard rates for the time intervals of 1 to 7 days, 8 to 14 days, 15 to 21 days, and 22 to 28 days were 0.0056 (12 VTEs), 0.0036 (7 VTEs), 0.0005 (1 VTEs), and 0.0054 (5 VTEs), respectively (Fig. 2).
3.3 Univariate analysis of risk factors for patients with VTE
The statistical analysis is shown in Table 2. There were significant differences between patients with or without VTE in ICU length of stay (13.6 ± 8.8 vs 6.7 ± 2.7 days, P < .01). Significant differences in the other factors, such as APACHE II score, Caprini score, sedation, mechanical ventilation, CVC, and abdominal hypertension, were also found between patients with and without VTE (P < .05). However, other factors of age, sex, body mass index, maximum strength muscle, CRRT, and platelet transfusion had no influence on the occurrence of VTE (P > .05).
3.4 Multivariate analysis of risk factors for VTE
In multivariable analysis, 3 factors were found to have an influence on the incidence of VTE. Table 3 shows that CVC (P = .002, OR = 4.50), Caprini score (P = .012, OR = 1.20), and ICU length of stay (P = .006, OR = 1.08) were independent risk factors related to the occurrence of VTE.
3.5 Odds for VTE substratified by caprini score
Table 4 suggests the proportions of patients with a Caprini score of 1 to 5, 6 to 10, and greater than 10 were 40.9%, 51.6%, and 7.5%, respectively. Patients with a Caprini score of 1 to 5 were significantly less likely to develop VTE events compared with those with a Caprini score of 6 to 10 (OR = 3.44; 95% CI, 1.12–10.60) and greater than 10 (OR = 8.67; 95% CI, 2.11–35.71). However, there was no significance between the group with Caprini scores of 6 to 10 and the group with a score greater than 10.
VTE is a life-threatening complication, and its incidence is a sign of quality care for patients in the ICU. We designed a prospective observational study to investigate the cumulative VTE incidence, risk factors, and outcomes for those patients. VTE prophylaxis was an effective way to decrease the occurrence of VTE. In our study, all patients received guideline-recommended VTE prophylaxis. The cumulative VTE incidence within 7 days after ICU admission was as high as 4.45%, and the incidence increased between 14 and 28 days. In a prospective review of 261 patients with critical medical-surgical illness, 9.6% patients developed VTE during their ICU stay. Similarly, in other studies, the rate of VTE ranged from 5% to 15% for patients admitted to the ICU.[18–20] However, in contrast to another study reported by Jia et al, our incidence was higher than the 3.1% of patients with symptomatic VTE in the ICU after surgery. We believe that the following reasons may have contributed to the high cumulative VTE incidence. First and foremost, in the prior study, only proximal DVT was included. In our study, both proximal DVT and symptomatic distal DVT were recorded when we counted the number of VTEs. Moreover, our study was a cumulative VTE incidence study, whereas the former study was a cross-sectional retrospective survey study. Another prospective study by Kaplan et al of 113 patients with severe sepsis and septic shock showed a VTE incidence of 37.5%. This high VTE rate might be attributed to special observation patients and the very small sample size. Indeed, in our study, the incidence of thrombosis was higher in patients with sepsis than those without sepsis.
In our prospective study, nearly half of the events occurred within 7 days after ICU admission. This may be because a higher proportion of patients received mechanical ventilation within first 7 days. In our study, 75 of 132 patients received mechanical ventilation in the first 7 days. In addition, we also found that the rate of CVC in the location of the femoral vein was higher in the 7 days after ICU admission as compared with other times. To our knowledge, mechanical ventilation and CVC were the risk factor of VTE.[7,22]
Factors in the dynamic Caprini score were found to associate with occurrence of VTE in ICU patients. The Caprini score is widely used in the risk assessment of VTE for medical, surgical, and trauma patients, by which patients are divided into different risks and corresponding measures implemented.[7,16,23] Use of the Caprini score is recommended in the guidelines of VTE prevention for Western surgical patients. To our knowledge, this is the first prospective study that dynamically recorded patents’ Caprini scores, and the maximum Caprini score was used in the analysis. It may increase the accuracy of the assessment compared with other retrospective studies. Our findings identified those patients with a Caprini score >5 had a higher risk of developing VTE than those with a Caprini score of 1 to 5. However, we also found that the Caprini scores of patients with VTE were higher than in those patients without VTE (8.0 vs 6.2). This means that many non-VTE patients were classified into the highest group (Caprini score ≥5). This limited the ability to distinguish VTE risk from ICU patients. Therefore, increasing the cut-off point for classifying patients might be a solution. Bahl et al reported that this changed the Caprini risk assessment model and added a classification of a “super high risk” group (>8) on the basis of the highest risk group. Similarly, a Caprini score >10 may be more effective in distinguishing VTE risk among cancer patients admitted to the ICU for postoperative care. The other solution was the combination of the Caprini score and thrombotic biomarkers for assessment of VTE risk in ICU patients. Fu et al reported that the combination of plasma markers (D-dimer and thrombomodulin) and Caprini score could increase the predictive value.
Our findings also identified that ICU length of stay and CVC in the location of the femoral vein were the independent risk factors of VTE. We found that patients had a longer ICU stay with VTE compared with those without VTE. Similarly, Kumar et al and Malato et al reported that a prolonged ICU stay was a risk factor for DVT. This may be because patients usually rest in bed and are subject to long-term immobilization, especially patients with mechanical ventilation. Long-term immobilization could lead to venous reflux obstruction. What is worse, if the patient had VTE, the ICU stay would be prolonged. However, other studies also showed that differences in ICU stay were not significant between the VTE and non-VTE groups.[29,30] CVC use was an important risk factor for VTE, especially if it was inserted in the femoral vein. The incidence of VTE ranged from 10% to 69% with a femoral catheter.[2,31] In our study, 12 of 44 patients with a femoral catheter had developed VTE. The majority cause of a high rate of femoral catheter use was that 25 of 44 patients had received CRRT. Similarly, many studies showed that CVC was an independent risk factor for VTE, and the incidence of CVC-related VTE ranged from 1.81% to 26%.[32–35] Our findings emphasize the importance of removing CVCs as soon as possible when patients are no longer receiving CRRT.
Among the other factors, APACHE II, sedation, mechanical ventilation, and abdominal hypertension, no significant differences were found between patients with or without VTE in the multivariate analysis. The duration of mechanical ventilation was associated with occurrence of VTE, as identified in other studies.[2,7] This may be because we recorded only whether the patient was on mechanical ventilation. This means that mechanical ventilation itself does not increase the incidence of VTE but rather the prolongation of mechanical ventilation. At the same time, other studies reported sedation and abdominal hypertension to be risk factors of VTE.[2,6] To our knowledge, the major influence of sedation is its result of immobilization for ICU patients. However, our study showed that 76.2% patients received early mobilization. Therefore, sedation may not be a risk factor for ICU patients who have received prophylaxis of early mobilization. In terms of abdominal hypertension, the lack of effect may be due to the small sample size. In our study, only 21 of 281 patients had abdominal hypertension. Similarly, APACHE II was also found to have no influence on the development of VTE.
Our findings have several clinical implications for ICU medical staff treating and caring for patients. First, since nearly half of the events occurred within 7 days after ICU admission, medical staff should maintain a high suspicion and strengthen the prevention and screening of VTE for this population. Moreover, VTE risk may be overestimated when the Caprini score alone is used to assess ICU patients’ risk of developing VTE. Therefore, the Caprini score should be combined with biochemical indicators, such as D-dimer. Finally, if there are no contraindications, early mobilization should be performed, especially for patients receiving sedation.
A limitation of our prospective study includes the small sample size. This may have decreased the sensitivity of our statistics in the univariate and multivariate analysis of risk factors for VTE. However, based on the sample size calculation, 140 patients were enough for our study. Moreover, in our study, we used only duplex scan to determine whether patients had DVT rather than venography, which may have reduced the sensitivity of screening asymptomatic distal DVT. However, asymptomatic distal DVT was not recorded when we analyzed the incidence of VTE. Furthermore, CTPA was not examined for all patients, but only for those with suspected PE who already had DVT or respiratory dysfunction. Therefore, the incidence of PE may be underestimated. Finally, we collected patient's information only within 28 days of the ICU stay, and do not follow patients for VTE who the length of ICU stay is less than 28 days and discharge from ICU without VTE. Because we are unable to collect risk factors of VTE after patient discharge from the ICU. In addition, it is difficult to determine whether the patient has VTE without ultrasound examination. Therefore, it is unclear whether following patients with an ICU stay <28 days up to the 28th day had any influence on the cumulative incidence of VTE.
In conclusion, our prospective observational study found that the 28-day cumulative incidence of VTE is relatively high for patients admitted to the ICU, despite the use of guideline-recommended thromboprophylaxis. Patients with femoral CVC, a prolonged ICU length of stay, or a high Caprini score may have an increased risk of developing VTE.
Conceptualization: Chuanlin Zhang, Jie Mi.
Data collection: Xueqin, Wang; Yujun, Zou; Xinyi, Luo; Xiaoya, Chen.
Data curation: Yujun Zou, Ruiying Gan.
Formal analysis: Ruiying Gan.
Funding acquisition: Chuanlin Zhang, Jie Mi.
Investigation: Zeju Zhang, Xueqin Wang, Xiaoya Chen, Zhi Nie, Xinyi Luo.
Literature search: Zeju Zhang.
Manuscript preparation: Chuanlin Zhang.
Methodology: Zhi Nie.
Statistical analysis: Zhi, Nie; Ruiying, Gan.
Study design: Chuanlin Zhang; Jie Mi.
Writing – original draft: Chuanlin Zhang, Jie Mi.
Writing – review and editing: Xueqin Wang.
. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism
: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6 Suppl):381s–453s.
. Minet C, Potton L, Bonadona A, et al. Venous thromboembolism
in the ICU: main characteristics, diagnosis and thromboprophylaxis. Crit Care 2015;19:287–95.
. Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism
in older acute medical patients: randomised placebo controlled trial. BMJ 2006;332:325–9.
. Leizorovicz A, Cohen AT, Turpie AG, et al. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism
in acutely ill medical patients. Circulation 2004;110:874–9.
. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism
: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004;126(3 Suppl):338s–400s.
. Boddi M, Peris A. Deep vein thrombosis in intensive care. Adv Exp Med Biol 2017;906:167–81.
. Kaplan D, Casper TC, Elliott CG, et al. VTE incidence
and risk factors in patients with severe sepsis and septic shock. Chest 2015;148:1224–30.
. Parikh KC, Oh D, Sittipunt C, et al. Venous thromboembolism prophylaxis
in medical ICU patients in Asia (VOICE Asia): a multicenter, observational, cross-sectional study. Thromb Res 2012;129:e152–8.
. Caprini JA. Risk assessment as a guide for the prevention of the many faces of venous thromboembolism
. Am J Surg 2010;199(1 Suppl):S3–10.
. Dauzat M, Laroche JP, Deklunder G, et al. Diagnosis of acute lower limb deep venous thrombosis with ultrasound: trends and controversies. J Ultrasound 1997;25:343–58.
. Zhang C, Fu Q, Zhao Y, et al. Short-term anticoagulant therapy and thrombus location are independent risk factors for delayed recanalization of deep vein thrombosis. Med Sci Monit 2016;22:219–25.
. Wang L, Zhang C, Mu S, et al. Safety of catheter-directed thrombolysis for the treatment of acute lower extremity deep vein thrombosis: a systematic review and meta-analysis. Medicine (Baltimore) 2017;96:e7922–33.
. Li W, Chuanlin Z, Shaoyu M, et al. Catheter-directed thrombolysis for patients with acute lower extremity deep vein thrombosis: a meta-analysis. Rev Lat Am Enfermagem 2018;26:e2990–3001.
. Kahn SR, Lim W, Dunn AS, 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(2 Suppl):e195S–226S.
. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e419S–96S.
. Serrano PE, Parpia S, Linkins LA, et al. Venous thromboembolic events following major pelvic and abdominal surgeries for cancer: a prospective cohort study. Ann Surg Oncol 2018;25:3214–21.
. Cook D, Crowther M, Meade M, et al. Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence
, and risk factors. Crit Care Med 2005;33:1565–71.
. Boddi M, Cecchi A, Bonizzoli M, et al. Follow-up after four-year quality improvement program to prevent inferior limb deep vein thrombosis in intensive care unit
. Thromb Res 2014;134:578–83.
. Boddi M, Barbani F, Abbate R, et al. Reduction in deep vein thrombosis incidence
in intensive care after a clinician education program. J Thromb Haemost 2010;8:121–8.
. Lawall H, Oberacker R, Zemmrich C, et al. Prevalence of deep vein thrombosis in acutely admitted ambulatory non-surgical intensive care unit
patients. BMC Res Notes 2014;7:431–7.
. Xu JX, Dong J, Ren H, et al. Incidence
and risk assessment of venous thromboembolism
in cancer patients admitted to intensive care unit
for postoperative care. J BUON 2018;23:500–6.
. Ibrahim EH, Iregui M, Prentice D, et al. Deep vein thrombosis during prolonged mechanical ventilation despite prophylaxis
. Crit Care Med 2002;30:771–4.
. Bateman DK, Dow RW, Brzezinski A, et al. Correlation of the caprini score
and venous thromboembolism incidence
following primary total joint arthroplasty-results of a single-institution protocol. J Arthroplasty 2017;32:3735–41.
. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients. Chest 2012;141:e227S–77S.
. Bahl V, Hu HM, Henke PK, et al. A validation study of a retrospective venous thromboembolism
risk scoring method. Ann Surg 2010;251:344–50.
. Fu Y, Liu Y, Chen S, et al. The combination of Caprini risk assessment scale and thrombotic biomarkers to evaluate the risk of venous thromboembolism
in critically ill patients. Medicine (Baltimore) 2018;97:e13232–9.
. Kumar A, Mehta Y, Ali T, et al. Deep vein thrombosis in medical and surgical intensive care unit
patients in a tertiary care centre in North India: incidence
and risk factors. J Anaesthesiol Clin Pharmacol 2017;33:181–6.
. Malato A, Dentali F, Siragusa S, et al. The impact of deep vein thrombosis in critically ill patients: a meta-analysis of major clinical outcomes. Blood Transfus 2015;13:559–68.
. Gibson CD, Colvin MO, Park MJ, et al. Prevalence and predictors of deep vein thrombosis in critically Ill medical patients who underwent diagnostic duplex ultrasonography. J Intensive Care Med 2018;19:1–5.
. Lyman GH, Culakova E, Poniewierski MS, et al. Morbidity, mortality and costs associated with venous thromboembolism
in hospitalized patients with cancer. Thromb Res 2018;164(Suppl 1):S112–8.
. Merrer J, De Jonghe B, Golliot F, et al. Complications of femoral and subclavian venous catheterization in critically ill patients: a randomized controlled trial. JAMA 2001;286:700–7.
. Malinoski D, Ewing T, Bhakta A, et al. Which central venous catheters have the highest rate of catheter-associated deep venous thrombosis: a prospective analysis of 2,128 catheter days in the surgical intensive care unit
. J Trauma Acute Care Surg 2013;74:454–60.
. Amankwah EK, Atchison CM, Arlikar S, et al. Risk factors for hospital-associated venous thromboembolism
in the neonatal intensive care unit
. Thromb Res 2014;134:305–9.
. Hrdy O, Strazevska E, Suk P, et al. Central venous catheter-related thrombosis in intensive care patients - incidence
and risk factors: a prospective observational study. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2017;161:369–73.
. White D, Woller SC, Stevens SM, et al. Comparative thrombosis risk of vascular access devices among critically ill medical patients. Thromb Res 2018;172:54–60.
. Miri M, Goharani R, Sistanizad M. Deep vein thrombosis among intensive care unit
patients; an epidemiologic study. Emerg (Tehran) 2017;5:e13–7.
Keywords:Copyright © 2019 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
caprini score; incidence; intensive care unit; prophylaxis; venous thromboembolism