ISSN : 1301-5680
e-ISSN : 2149-8156
Turkish Journal of Thoracic and Cardiovascular Surgery     
Ultrasound-guided thrombin injection versus ultrasound-guided compression repair in the treatment of post-catheterization femoral artery pseudoaneurysm: King Saud University Medical Center Experience
Talal Altuwaijri1, Mussaad Alsalman1, Abdulamjeed Altoijry1, Kaisor Iqbal1, Hesham AlGhofili1
1Department of Surgery, Division of Vascular Surgery, King Saud University, College of Medicine, King Saud University Medical City, Riyadh, Saudi Arabia
DOI : 10.5606/tgkdc.dergisi.2020.18814

Abstract

Background: This study aims to evaluate the effectiveness of ultrasound-guided thrombin injection versus ultrasound-guided compression repair in the management of iatrogenic femoral artery pseudoaneurysms.

Methods: Between June 2006 and December 2015, a total of 29 consecutive patients (15 males, 14 females; mean age 54 years; range 26 to 81 years) with a femoral pseudoaneurysm treated by ultrasound-guided thrombin injection were retrospectively analyzed. These patients were compared with a historical group of 36 patients (21 males, 15 females; mean age 44 years; range 32 to 65 years) who underwent ultrasound-guided compression repair between February 1999 and May 2006. Medical records and vascular laboratory findings of all patients were reviewed. Successful treatment was defined as complete cessation of flow into the false lumen with preservation of flow in the femoral artery.

Results: The ultrasound-guided thrombin injection showed a success rate of 100%, whereas ultrasound-guided compression repair had a success rate of 80.5%, which was possibly affected by anticoagulant therapy, hypertension, and an aneurysm size of >6 cm. However, none of these factors did not affect the success of thrombin injections.

Conclusion: Ultrasound-guided thrombin injection is a highly successful, easy to perform, accepted, and well-tolerated method by patients. It is more effective compared to compression therapy in patients with hypertension, large aneurysms, and who are on anticoagulant therapy.

Historically, the common femoral artery catheterization has been, by far, the most widely used procedure for percutaneous arterial access. It is commonly used for diagnostic investigations and therapeutic interventions.[1,2] Iatrogenic femoral artery pseudoaneurysms develop following endovascular procedures, if the arteriotomy is not adequately sealed or if the occluding clot in the arteriotomy is dislodged in the post-procedural period. There is a communication with the arterial lumen (neck) and blood extravasating into the surrounding soft tissue. The wall of the pseudoaneurysm consists solely of compressed thrombus and surrounding soft tissue.

Femoral pseudoaneurysms may be a complication in 0.5 to 1% of diagnostic procedures and in 3.2 to 7.7% of therapeutic procedures.[3] Multiple factors can increase the incidence, such as poor selection of puncture site and technique, therapeutic interventional procedures, use of large-bore needle and sheaths, use of anticoagulant and multiple antithrombotic drugs, poor control of puncture site bleeding after the procedure, and diseased calcified vessels.[4] To avoid rupture risk, the traditional management of iatrogenic femoral pseudoaneurysms consisted of surgical repair. However, surgery was invasive and increased the hospital stay and cost.[5-7] In 1991, Fellmeth et al.[8] introduced ultrasound-guided compression repair (UGCR) which rapidly replaced by surgery as the firstchoice treatment modality in most patients. Although the success rate varied between 27 and 100% and the compression time for pseudoaneurysms ranged from 30 to 120 min,[4,9,10] it has multiple drawbacks including local discomfort and pain and requires sedation and analgesia with a high rate of recurrence, particularly in patients on anticoagulant, antiplatelet medications, or both.[11] Also, compression therapy requires at least one additional day in the hospital.

As an alternative to surgery and UGCR, in 1986, Cope and Zeit[12] reported percutaneous thrombin injection with occlusion of the feeding vessels for the treatment of femoral pseudoaneurysms. In 1997, Liau et al.[13] published a series of five patients treated by ultrasound-guided thrombin injection (UGTI). In 1998, Kang et al.[14] reported that UGTI was safe, effective, and free of compression repair limitations. This report was rapidly followed by similar several publications.[15-19] The success rate of this technique has been shown to range between 69 and 100% with a very low complication rate.[13,20]

In the light of literature data, we aimed to evaluate the effectiveness of UGTI versus UGCR in the treatment of post-catheterization femoral pseudoaneurysms.

Methods

This single-center, retrospective, non-randomized clinical study of prospectively maintained data was conducted at King Saud University Medical Center between June 2006 and December 2015. A total of 29 consecutive patients (15 males, 14 females; mean age 54 years; range 26 to 81 years) with a femoral pseudoaneurysm treated by UGTI were retrospectively analyzed. These patients were compared with a historical group of 36 patients (21 males, 15 females; mean age 44 years; range 32 to 65 years) who underwent UGCR between February 1999 and May 2006. Medical records and vascular laboratory findings of all patients were reviewed. A written informed consent was obtained from each patient. The study protocol was approved by the King Saud University Institutional Review Board. The study was conducted in accordance with the principles of the Declaration of Helsinki.

In our institution"s vascular laboratory, a protocol for femoral pseudoaneurysm is followed for all patients with clinical signs of post-catheterization femoral pseudoaneurysms such as pain, murmur, or swelling. All patients are evaluated by an experienced technician using a color Doppler scanner (Philips-ATL HDI-5000, Bothell, USA) utilizing a linear 4-7 MHz probe. The ankle-brachial indices (ABIs) are measured bilaterally. Ultrasound images, precise location, aneurysmal sizes, and status of the peripheral pulses for all patients before and during the procedure are recorded immediately after the treatment and at 24 h and on Days 7 and 30 after the post treatment. Conservative follow-up by ultrasonography is performed in all patients, until spontaneous resolution was achieved in patients with an aneurysm size of <1.5 cm. Patients with larger aneurysms are considered eligible for non-invasive management.

In our institution, until 1998, all femoral pseudoaneurysms were treated surgically. From 1999 until 2006, they were treated by UGCR. As of 2006, UGTI has been increasingly adopted, as this was the period when the bovine thrombin was available in our country, and UGTI showed promising results. Exclusion criteria for thrombin injection include all indications for surgical repair or known hypersensitivity to thrombin.

Surgical technique
In the UGCR group, the operation was performed in accordance with the Fellmeth et al."s technique.[8] In brief, after local anesthesia by 1% lidocaine solution, a manual straight downward force was applied with the ultrasound transducer under continuous ultrasound guidance. Compression was applied for 10 to 15 min on the aneurysmal neck and increased, until the flow within the pseudoaneurysm sac was stopped; however, the flow in the femoral artery was still maintained. After 10 to 15 min, the pressure was released gradually and repeated after 5 to 10 min, if there was still flow in the pseudoaneurysm, up to three times per treatment session. If compression therapy was not effective, the same procedure was repeated the following day, up to a maximum of three sessions. If the treatment still failed or the patient was unsuitable for UGCR, the patient was indicated for surgery. If compression therapy was successful, compression bandage was applied for a minimum of 12 h.

The UGTI was performed according to Kang et al.'s[14] technique. In brief, under sterile conditions, a 20-gauge needle was inserted into the lumen of the pseudoaneurysm using real-time ultrasound guidance. Quick aspiration and reinjection of blood led to characteristic color Doppler images, confirming the correct position of the needle tip. The needle tip was directed away from the neck of the pseudoaneurysm. Bovine thrombin solution (Thrombin-JMI®, King Pharmaceuticals, Inc., Bristol, TN, USA) was diluted to a concentration of 1,000 µ/mL in 0.9% sterile saline. The diluted thrombin was, then, slowly injected until the flow within the pseudoaneurysm ceased. If the treatment failed, the procedure was repeated up to a maximum of three sessions. If the treatment was successful, we repeated the ultrasound examination for nearby femoral vessels to ensure patency. In addition, we evaluated the ipsilateral peripheral pulses before and immediately after thrombin injection. All patients were kept in bed for four h following the procedure and were reevaluated before discharge based on clinical signs, ultrasonography, and ABI values to confirm complete resolution.

Successful treatment was defined as complete cessation of flow into the false lumen with preservation of flow in the femoral artery.

Statistical analysis
Statistical analysis was performed using the IBM SPSS version 22.0 software (IBM Corp., Armonk, NY, USA). Descriptive data were expressed in mean ± standard deviation (SD), median (min-max), or number and frequency. The Student's t-test was used to compare categorical variables between the UGCR and UGTI groups, while the Fisher's exact test was used to compare continuous variables. A p value of <0.05 was considered statistically significant.

Results

Of a total of 65 patients included in the study, 29 underwent UGTI and 36 underwent UGCR. There was no significant difference in the age, gender, femoral catheterization procedures, aneurysm size, and artery of origin between the two groups. Anticoagulant medications were not modified in any groups: three patients in the UGTI group and four patients in the UGCR group were on anticoagulant treatment. There were 19 and eight hypertensive patients in the UGTI group and UGCR group, respectively. The femoral catheterization procedures did not significantly differ between the groups (UGTI vs. UGCR), cardiac catheterization (n=20 vs. 22), peripheral angiography (n=6 vs. 10), and femoral pseudoaneurysms resulting from iatrogenic injury during dialysis catheter insertion (n=3 vs. 4). The mean aneurysm sizes for UGTI and UGCR groups were 4.3 and 4 cm, respectively. Most of the pseudoaneurysms arose from the common femoral artery (Table 1).

Table 1: Demographic and clinical characteristics of patients (n=65)

As shown in Table 2, thrombin injections were successful (n=29, 100%) in all designated patients from the initial session (10-40 s). The mean dose of thrombin injections was 1,000 U (range, 500 to 1,500 U). None of them needed surgery, developed complications, or required analgesia or sedation. On the contrary, the success rate with the UGCR was 80.6% (n=29), and 58.6% (n=17) of them required more than one session. In addition, UGCR required more time (30 to 60 min) to completely obliterate the pseudoaneurysms. Some patients (n=7, 19.4%) also required surgery due to the UGCR failure.

Table 2: Procedural outcomes of UGTI and UGCR (n=65)

No complications or recurrence were observed in any patients receiving UGCR. Further, compression therapy failed in all patients on anticoagulant therapy (n=4, p=0.001), and aneurysm size >6 cm also resulted in failure of the compression therapy (n=3, p<0.005). Of eight hypertensive patients in the UGCR group, treatment failed in five of them (p<0.003). These factors did not affect the success of thrombin injections (Table 3).

Table 3: Factors affecting compression therapy outcomes in the UGCR group (n=36)

Discussion

In the present study, we examined the effectiveness of UGTI versus UGCR in the treatment of postcatheterization femoral pseudoaneurysms. The results of the study indicated that UGTI was more effective compared to UGCR for the treatment of iatrogenic femoral pseudoaneurysms. We achieved successful results in all patients who received thrombin injections, regardless of anticoagulant treatment used, hypertension status, and aneurysm size. Furthermore, our high success rate can be attributed to a meticulous selection of the patients and careful monitoring of multiple factors during and after the procedure.

Iatrogenic femoral pseudoaneurysms occur twice as frequently after therapeutic interventions as it does after diagnostic interventions.[6] Although spontaneous resolution of the femoral pseudoaneurysms has been reported in the literature,[21] a spontaneous rupture rate of 24% within 72 h has been reported, as well.[22] Unfortunately, it is difficult top redict which aneurysm should be observed or which required an intervention.[23]

Thrombin is a major clotting factor that catalyzes the conversion of fibrinogen to fibrin and activates procoagulant factors 5, 8, 11, and 13. However, thrombin may result in thromboembolic complications.[24] Allergic reactions are other concerns of UGTI, and can be seen only with bovine thrombin.[25] In our study, we examined any history of allergy to thrombin prior to the procedure, and we were prepared to take actions, if any event took place. In addition, we were accurately able to visualize the tip of the needle during the insertion inside the cavity of the pseudoaneurysm. Also, injections were done very slowly at a rate of 0.1 to 0.3 mL/s to avoid downstream embolization.

Ultrasound-guided compression repair is still considered a successful treatment modality. However, patients who failed the compression therapy still need a surgical intervention. Compression distorts the anatomy of the pseudoaneurysm, preventing the adequate placement of the thrombin needle, which can put the patient at risk of thrombin escaping into the lumen of the femoral artery and occluding a healthy vessel, resulting in an ischemic limb.[26] There are a few reports on the occlusion of a healthy artery after UGTI and were successfully treated by thrombolysis, thrombectomy, or bypass without enduring damage.[14,24,27]

Pain is one of the major disadvantages of UGCR and, despite adequate analgesia, pain may persist. Langella et al.[11] reported that they abandoned UGCR procedure in three patients due to pain. On the contrary, thrombin injections were painless except for a slight discomfort due to skin puncture. In the light of this fact, no analgesia was required. The mean compression time in our study was 45 min, which is relatively short than earlier publications.[10] Time efficiency is a very significant advantage of thrombin injections. Compression therapy failed in all patients on anticoagulant treatment, consistent with previous publications.[10,28-30]

The size of ≥6 cm of femoral pseudoaneurysm was found to be a factor determining the success of UGCR in our study. This finding is consistent with that of Dean et al.[31] However, this is an area of controversy, since some authors have advocated that the pseudoaneurysm volume does not affect the compression outcome. However, most of the pseudoaneurysms in previous studies were <4 cm in size, which may have affected their conclusions.[10,32] In our study, we observed no complication or recurrence after both treatments. Conceivably, time efficiency, technical ease, patient comfort, and excellent results of thrombin injections considerably made it superior to compression therapy.

Nonetheless, this study has some limitations. First limitation is our small sample size. Another limitation is the retrospective study design. However, our results are consistent with earlier studies.[13,20] Of note, this was a single-center experience and, thus, uniformity in the technique and staff was a strong point of our study.

In conclusion, this study shows the superiority of UGTI over UGCR in the treatment of iatrogenic femoral pseudoaneurysms. As thrombin injection treatment is simple, safe, convenient for the patient, and applicable in most cases, it has a high rate of success. Furthermore, UGTI is more effective than UGCR in patients on anticoagulant treatment, hypertensive patients, or those with large aneurysms (>6 cm). Ultrasound-guided thrombin injection has become the procedure of choice in our practice with a word of caution. However, as the number of published cases treated by UGTI has been on the rise, largerscale sample, prospective, randomized, or design with reproduction of published studies are warranted to better evaluate the effectiveness and risk of thrombin injections.

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The authors received no financial support for the research and/or authorship of this article.

References

1) Asrar Ul Haq M, Tsay IM, Dinh DT, Brennan A, Clark D, Cox N, et al. Prevalence and outcomes of trans-radial access for percutaneous coronary intervention in contemporary practise. Int J Cardiol 2016;221:264-8.

2) Feldman DN, Swaminathan RV, Kaltenbach LA, Baklanov DV, Kim LK, Wong SC, et al. Adoption of radial access and comparison of outcomes to femoral access in percutaneous coronary intervention: an updated report from the national cardiovascular data registry (2007-2012). Circulation 2013;127:2295-306.

3) Hughes MJ, McCall JM, Nott DM, Padley SP. Treatment of iatrogenic femoral artery pseudoaneurysms using ultrasoundguided injection of thrombin. Clin Radiol 2000;55:749-51.

4) Weinmann EE, Chayen D, Kobzantzev ZV, Zaretsky M, Bass A. Treatment of postcatheterisation false aneurysms: ultrasoundguided compression vs ultrasound-guided thrombin injection. Eur J Vasc Endovasc Surg 2002;23:68-72.

5) Babu SC, Piccorelli GO, Shah PM, Stein JH, Clauss RH. Incidence and results of arterial complications among 16,350 patients undergoing cardiac catheterization. J Vasc Surg 1989;10:113-6.

6) Lumsden AB, Miller JM, Kosinski AS, Allen RC, Dodson TF, Salam AA, et al. A prospective evaluation of surgically treated groin complications following percutaneous cardiac procedures. Am Surg 1994;60:132-7.

7) Omoigui NA, Califf RM, Pieper K, Keeler G, O"Hanesian MA, Berdan LG, et al. Peripheral vascular complications in the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I). J Am Coll Cardiol 1995;26:922-30.

8) Fellmeth BD, Roberts AC, Bookstein JJ, Freischlag JA, Forsythe JR, Buckner NK, et al. Postangiographic femoral artery injuries: nonsurgical repair with US-guided compression. Radiology 1991;178:671-5.

9) Agarwal R, Agrawal SK, Roubin GS, Berland L, Cox DA, Iyer SS, et al. Clinically guided closure of femoral arterial pseudoaneurysms complicating cardiac catheterization and coronary angioplasty. Cathet Cardiovasc Diagn 1993;30:96-100.

10) Hajarizadeh H, LaRosa CR, Cardullo P, Rohrer MJ, Cutler BS. Ultrasound-guided compression of iatrogenic femoral pseudoaneurysm failure, recurrence, and long-term results. J Vasc Surg 1995;22:425-30.

11) Langella RL, Schneider JR, Golan JF. Color duplex-guided compression therapy for postcatheterization pseudoaneurysms in a community hospital. Ann Vasc Surg 1996;10:27-35.

12) Cope C, Zeit R. Coagulation of aneurysms by direct percutaneous thrombin injection. AJR Am J Roentgenol 1986;147:383-7.

13) Liau CS, Ho FM, Chen MF, Lee YT. Treatment of iatrogenic femoral artery pseudoaneurysm with percutaneous thrombin injection. J Vasc Surg 1997;26:18-23.

14) Kang SS, Labropoulos N, Mansour MA, Baker WH. Percutaneous ultrasound guided thrombin injection: a new method for treating postcatheterization femoral pseudoaneurysms. J Vasc Surg 1998;27:1032-8.

15) Wixon CL, Philpott JM, Bogey WM Jr, Powell CS. Duplexdirected thrombin injection as a method to treat femoral artery pseudoaneurysms. J Am Coll Surg 1998;187:464-6.

16) Taylor BS, Rhee RY, Muluk S, Trachtenberg J, Walters D, Steed DL, et al. Thrombin injection versus compression of femoral artery pseudoaneurysms. J Vasc Surg 1999;30:1052-9.

17) Kang SS, Labropoulos N, Mansour MA, Michelini M, Filliung D, Baubly MP, et al. Expanded indications for ultrasound-guided thrombin injection of pseudoaneurysms. J Vasc Surg 2000;31:289-98.

18) Vermeulen EG, Umans U, Rijbroek A, Rauwerda JA. Percutaneous duplex-guided thrombin injection for treatment of iatrogenic femoral artery pseudoaneurysms. Eur J Vasc Endovasc Surg 2000;20:302-4.

19) Lennox AF, Delis KT, Szendro G, Griffin MB, Nicolaides AN, Cheshire NJ. Duplex-guided thrombin injection for iatrogenic femoral artery pseudoaneurysm is effective even in anticoagulated patients. Br J Surg 2000;87:796-801.

20) McCoy D, Scharfstein B, Walker W, Evans J. Ultrasoundguided percutaneous thrombin injection for femoral artery pseudoaneurysms. Am Surg 2000;66:975-7.

21) Kent KC, McArdle CR, Kennedy B, Baim DS, Anninos E, Skillman JJ. A prospective study of the clinical outcome of femoral pseudoaneurysms and arteriovenous fistulas induced by arterial puncture. J Vasc Surg 1993;17:125-31.

22) Graham AN, Wilson CM, Hood JM, Barros D"Sa AA. Risk of rupture of postangiographic femoral false aneurysm. Br J Surg 1992;79:1022-5.

23) Paulson EK, Hertzberg BS, Paine SS, Carroll BA. Femoral artery pseudoaneurysms: value of color Doppler sonography in predicting which ones will thrombose without treatment. AJR Am J Roentgenol 1992;159:1077-81.

24) Lennox A, Griffin M, Nicolaides A, Mansfield A. Regarding "Percutaneous ultrasound guided thrombin injection: a new method for treating postcatheterization femoral pseudoaneurysms". J Vasc Surg 1998;28:1120-1.

25) Pope M, Johnston KW. Anaphylaxis after thrombin injection of a femoral pseudoaneurysm: recommendations for prevention. J Vasc Surg 2000;32:190-1.

26) Sanmartín Fernández M, Goicolea Ruigómez J, Mantilla González R, Ruiz-Salmerón R, Calvo Iglesias F, Bravo Amaro M. Percutaneous thrombin injection for closure of femoral pseudoaneurysms: preliminary experience. Rev Esp Cardiol 2002;55:771-4. [Abstract]

27) Sadiq S, Ibrahim W. Thromboembolism complicating thrombin injection of femoral artery pseudoaneurysm: management with intraarterial thrombolysis. J Vasc Interv Radiol 2001;12:633-6.

28) Paulson EK, Kliewer MA, Hertzberg BS, Tcheng JE, McCann RL, Bowie JD, et al. Ultrasonographically guided manual compression of femoral artery injuries. J Ultrasound Med 1995;14:653-9.

29) Kazmers A, Meeker C, Nofz K, Kline R, Groehn H, Oust G, et al. Nonoperative therapy for postcatheterization femoral artery pseudoaneurysms. Am Surg 1997;63:199-204.

30) Feld R, Patton GM, Carabasi RA, Alexander A, Merton D, Needleman L. Treatment of iatrogenic femoral artery injuries with ultrasound-guided compression. J Vasc Surg 1992;16:832-40.

31) Dean SM, Olin JW, Piedmonte M, Grubb M, Young JR. Ultrasound-guided compression closure of postcatheterization pseudoaneurysms during concurrent anticoagulation: a review of seventy-seven patients. J Vasc Surg 1996;23:28-34.

32) Chua TP, Howling SJ, Wright C, Fox KM. Ultrasoundguided compression of femoral pseudoaneurysm: an audit of practice. Int J Cardiol 1998;63:245-50.

Keywords : Femoral pseudoaneurysm, ultrasound-guided compression, ultrasound-guided thrombin injection
Viewed : 3159
Downloaded : 627