Abstract
Purpose
To evaluate the clinical outcomes of transcatheter arterial embolization (TAE) with n-butyl-2-cyanoacrylate (NBCA) for treatment of bleeding in cirrhotic patients.
Materials and methods
A total of 35 cirrhotic patients (26 men, 9 women; mean age, 48.4 ± 11.1) who underwent TAE with NBCA for bleeding from January 2011 to December 2020 were retrospectively analysed. Only cirrhotic patients with active arterial bleeding confirmed on computed tomography (CT) were included. Fifteen patients were hemodynamically unstable before embolization procedure, and coagulopathy was observed in 32 patients. The mean MELD score and Child Pugh score were 24 ± 9.9 and 9.9 ± 2.2, respectively. The mean haemoglobin level and mean number of RBC units transfused before embolization were 7.4 ± 1.4 g/dL and 10.2 ± 4, respectively. The technical, clinical success rate and 30-day mortality rate were evaluated.
Results
Technical success and clinical success rates were achieved in 100% and 82.8% of patients, respectively. Overall 30-day mortality rate was 48%. No major complications related to the embolization procedure was seen. Only the greater number of RBC units transfused before the embolization procedure (OR = 1.81, 95% CI = 1.17–2.80, P = 0.007) was significantly associated with clinical failure. Greater number of RBC units transfused (OR = 1.53, 95% CI: 1.00–2.34, P = 0.004) and higher Child Pugh score (OR 2.44, 95% CI 1.26–4.71, P = 0.008) were significantly associated with higher 30-day mortality rate.
Conclusion
Transcatheter arterial embolization using NBCA can be used as the effective treatment option for bleeding in cirrhotic patients which has a high technical and clinical success despite the grave prognosis associated with cirrhosis.
Keywords: transcatheter arterial embolization, NBCA, cirrhotic patients, coagulopathy, acute arterial bleeding
Abbreviations: CT, computed tomography; INR, international normalized ratio; IQR, Interquartile range; MELD, model for end-stage liver disease; NASH, non-alcoholic steatohepatitis; NBCA, N-butyl-2-cyanoacrylate; OR, Odds ratio; PVA, polyvinyl alcohol; RBC, red blood cell; TAE, transarterial embolization
Transarterial embolization is widely used as the first-line treatment of choice for arterial bleeding in cirrhotic patients. Various embolic agents including polyvinyl alcohol (PVA) particles, gelatin sponge, coils, or their combination was used for occlusion of the bleeding vessels. Although these embolic agents were effective in the majority of cases, they failed to achieve haemostasis in certain conditions such as patients with coagulopathies, small and tortuous arteries, collateral circulation or recanalized embolized arteries.1, 2, 3, 4 N-butyl-2-cyanoacrylate (NBCA) is a permanent liquid embolic agent and a tissue adhesive that immediately polymerizes and forms a permanent cast when it comes in contact with any ionic fluid such as blood. Initially, it was approved for use in cerebral arteriovenous malformations by the U.S. Food and Drug Administration.5 Recently, it has been widely used in the management of active intramuscular haemorrhage, renal artery bleeding, ruptured pseudoaneurysm, uterine arterial bleeding, upper and lower gastrointestinal bleeding.6, 7, 8, 9, 10 It offers various advantages when compared to other embolic agents. It can be used in patients with coagulopathies as it does not depend on the normal physiology of coagulation.11 However, coil or PVA particles are dependent on patients’ normal coagulation function for thrombus formation. Moreover, glue is highly penetrable because of its liquid nature and when compared to a microcoil, it can embolize the small, tortuous arteries and arteries which are difficult to access. N-butyl-2-cyanoacrylate can also simultaneously embolize the collateral channels connected to a bleeding focus as it is highly penetrable. Besides, it is a potential embolic agent used for the treatment of active intramuscular haemorrhage in cases where the bleeding foci are from distal small branches that are difficult to access with a microcatheter.10 Furthermore, glue can be administrated quickly in comparison to microcoils which is important especially in achieving immediate hemostasis in a setting of hemodynamic instability.11 Despite its advantages, NBCA is underutilized in interventional radiology because it is difficult to handle precisely and having high ischemic complication rates as compared to other embolic agents. The purpose of this study is to assess the clinical outcomes of transcatheter arterial embolization with NBCA for the treatment of active bleeding in cirrhotic patients and to determine the factors predicting the clinical outcomes and 30-day mortality rate.
Material and methods
Statement of Ethics
The study was approved by the ethics committee of Institute of Liver and Biliary Sciences. The study protocol conforms to the ethics guidelines of the 1975 Declaration of Helsinki.
Study Design
Retrospective review of cirrhotic patients who underwent transcatheter arterial embolization with NBCA for active bleeding from January 2011 to December 2020 was conducted. The requirement to obtain informed consent was waived considering the retrospective nature of the study. Only cirrhotic patients with active arterial bleeding diagnosed on computed tomography (CT) who underwent embolization with NBCA were included. Non-cirrhotic patients, patients embolized with other embolic agents, no active contrast extravasation on CT, patients with active variceal bleed or bleeding from a venous origin were excluded from the study.
Embolization Technique
All angiographic procedures were done usually via a transfemoral approach using a 6 F introducer sheath. Angiography of the suspected bleeding artery was performed by standard 4-F or 5-F catheter after aortography followed by superselective arteriography with 2.7-F coaxial microcatheter (Progreat; Terumo, Leuven, Belgium). Considering the risk of ischemic injury after embolization, the microcatheter was advanced proximal to the bleeding site in all the cases (Figure 3c). All affected/injured arteries were embolized using N-butyl cyanoacrylate mixed with lipiodol. The solution of NBCA to lipiodol was used in ratios between 1:2 to 1:5 depending on the distance from the tip of the microcatheter to the bleeding point, the size of the vessel, the speed of blood flow and the location of the injured artery. Approximately, 0.2–1.5 mL of NBCA mixture was needed to achieve target embolization in all patients. Before the injection of NBCA mixture, the microcatheter was flushed with 5% dextrose solution to prevent the unwanted polymerization in the microcatheter due to exposure from saline or blood. The NBCA mixture was injected into the bleeding focus, and the extravasation or filling of a pseudoaneurysm was visualized under fluoroscopic monitoring. To prevent inadvertent complications such as catheter adhesion, the microcatheter was removed quickly after the injection of the mixture. The microcatheter was removed, and follow-up angiography was performed from the parent catheter to confirm the cessation of bleeding after the procedure (Figure 2, Figure 3d). If the cessation of bleeding was not achieved, additional transcatheter arterial embolization using an NBCA mixture was performed.
Figure 3.
CT angiography (CTA) of lower abdominal images: (a) CTA coronal and (b) axial image showing large left rectus sheath hematoma with small pseudoaneurysmal sac (white arrow) arising from the branches of left deep circumflex iliac artery (black arrow) (c) Superselective left deep circumflex iliac artery angiogram showing small pseudoaneurysmal sac (black arrow) supplied by branch of left deep circumflex iliac artery. (d) Post-embolization angiographic run showing complete obliteration of pseudoaneurysmal sac and left deep circumflex iliac artery by glue cast (black arrow). (e) Fluoroscopy spot image showing adequate filling of pseudoaneurysmal sac and left deep circumflex iliac artery with glue cast (black arrow). (f) Post-procedure CTA coronal image showing dense linear hyperdense glue cast with no extravasation of contrast (black arrow).
Figure 2.
CT angiography (CTA) of pelvis images: (a) CTA axial and (b) sagittal image showing hyperdense extravasation of contrast in corpous spongiosum adjacent to penile bulbar urethra (white arrow) through the spongiosal branches of internal pudendal artery. (c) Right internal iliac artery angiogram showing small pseudoaneurysmal sac with active extravasation of contrast (white arrow) which is supplied by branch of right internal pudendal artery (black arrow). (d) Post-embolization angiographic run showing complete obliteration of spongiosal branches with glue cast (black arrow). (e) Fluoroscopy spot image showing adequate filling of aneurysm sac with glue cast (black arrow). (f) Post procedure CTA sagittal image showing linear hyperdense glue cast with no extravasation of contrast in corpous spongiosum adjacent to penile-bulbar urethra region (black arrow).
Definitions and Study Endpoints
Hospital data, discharge summary and telephonic survey were used to collect data regarding technical, clinical success or failure and the 30-day mortality rate. Technical success was defined as cessation of active haemorrhage/contrast extravasation of the injured vessel or opacification of pseudoaneurysm or complete occlusion of the target vessels on postprocedural angiography. Clinical success was defined as the combination of technical success with the absence of recurrent or persistent bleeding within 30 days. Persistent bleeding was defined as failure of cessation of bleeding less than 48 h after the initial transarterial embolization or prolonged hypotension/hemodynamic instability or drop in haemoglobin (>2 g) inspite of continuous blood transfusions. Recurrent bleeding was defined as any new episode of bleeding at the same site, confirmed by CT angiography as more than 48 h and less than 30 days after initial successful embolization. Clinical failure was defined as the presence of one or more of the following two conditions seen within 30 days after the initial transarterial embolization. Hemodynamic instability/compromised was defined as hypotension with systolic pressure <100 mmHg and heart rate >100 beats/min or clinical shock secondary to blood loss that had not responded to conservative medical treatment including blood transfusion. Coagulopathy was defined as either the patient having international normalized ratio (INR) of more than 1.5 and/or the platelet count less than 50,000/mm³. Treatment time in our study was defined by the time interval between identification of the active haemorrhage by CECT till the cessation of active haemorrhage/embolization of the culprit artery. Embolization time was defined by the time interval between the identification of bleeding foci on angiography till embolization or cessation of the culprit artery. Procedure-related complications were defined according to the Society of Interventional Radiology clinical practice guidelines.12 Clinical outcomes were stratified as death or discharge from the hospital with or without surgery/transplant after the NBCA embolization procedure for the affected/injured arteries that received embolization.
Statistical Analysis
Qualitative variables were described as numbers (percentages). Continuous data were expressed as means (standard deviation) or medians (range). The means were compared in two groups using student t test and proportions were compared by Chi square or Fisher's exact test. Univariate and multivariable forward logistic regression analyses were performed to evaluate the predictors of clinical failure and 30-day mortality rate. All P values less than 0.05 were considered as statistically significant. All statistical analyses were performed using IBM Statistical Package for Social Sciences (SPSS) version 22.0.
Results
Patient Demographics and Clinical Profile
Baseline patient demographics are summarized in Table 1. A total of 35 cirrhotic patients with active arterial bleeding on CT who underwent embolization with NBCA were included in the study, as shown in the workflow of the study (Figure 1). There were 26 men (74%) and 9 women (26%) with a mean age of 48.4 ± 11.1. All patients had chronic liver disease. Thirty-two patients (91%) had coagulopathy before the procedure. The mean MELD score and Child-Pugh score were 24 ± 9.9 and 9.9 ± 2.2, respectively. Etiology of the cirrhosis are summarized in Table 1. The most common etiology of cirrhosis was related to alcohol-induced cirrhosis. Hemodynamic instability was noted in 15 of the 35 patients (42.9%) before the embolization procedure. These patients needed active resuscitation with blood transfusion because of active bleeding and inotropic support to stabilize blood pressure. The mean number of RBC units transfused before embolization were 10.2 ± 4, and the mean haemoglobin level before embolization was 7.4 ± 1.4.
Table 1.
Baseline Characteristic of Patients.
| Characteristic | Value |
|---|---|
| Age (years) | |
| Mean ± SD | 48.4 ± 11.1 |
| Sex, n (%) | |
| Male | 26 (74) |
| Female | 9 (26) |
| Coagulopathy, n (%) | 32 (91) |
| Etiology of Cirrhosis, n (%) | |
| Alcohol | 20 (57) |
| NASH | 8 (22) |
| Hepatitis B related | 2 (6) |
| Hepatitis C related | 1 (3) |
| Autoimmune | 2 (6) |
| Cryptogenic | 1 (3) |
| Budd chiari syndrome | 1 (3) |
| Hemodynamic Instability, n (%) | 15 (42.9) |
| Hemoglobin (g/dl) | |
| Mean ± SD | 7.4 ± 1.4 |
| INR | |
| Mean ± SD | 2.4 ± 0.9 |
| Platelets level (x 10³/mm³) | |
| Mean ± SD | 82 ± 35.4 |
| RBC Units Transfused | |
| Mean ± SD | 10.2 ± 4 |
| Disease Score | |
| MELD, Mean ± SD | 24 ± 9.9 |
| Child Pugh Score, Mean ± SD | 9.9 ± 2.2 |
| Serum Creatinine (g/dl) | |
| Mean ± SD | 1.0 ± 0.7 |
| Angiographic findings | |
| Extravasation, n (%) | 24 (69) |
| Pseudoaneurysm, n (%) | 6 (17) |
| None, n (%) | 5 (14) |
| Treatment time (hours) | |
| Median (IQR) | 6 (2–20) |
| Embolization time (min) | |
| Mean ± SD | 11.1 ± 3.6 |
NASH = Non-alcoholic steatohepatitis; INR = International Normalized Ratio; RBC = Red blood cells; MELD = Model for end stage liver disease; IQR = Interquartile range.
Figure 1.
Study flow chart.
All patients underwent contrast-enhanced CT scan, and sites of bleeding were identified prior to embolization as per the inclusion criteria (Figure 2, Figure 3a). Arteriography showed active contrast extravasation in 24 of 35 patients (69%) and pseudoaneursym in 6 of 35 patients (17%) (Figure 2c). The median embolization time taken to embolize the injured vessels/pseudoaneurysm was 10 (8–14) minutes. The procedure, artery injured and site of bleeding are summarized in Table 2 with the most common artery injured being inferior epigastric artery.
Table 2.
Procedure, Artery Injured and Site of Bleeding.
| Procedure, n (%) | Artery Injured, (n) | Site of Bleeding |
|---|---|---|
| Paracentesis, 24 (68) | Inferior epigastric artery (IEA), (16) | Rectus sheath |
| Deep Circumflex iliac artery (DCIA), (4) | Iliopsoas muscle | |
| Both IEA & DCIA, (4) | Rectus sheath & Iliopsoas muscle | |
| Thoracocentesis, 2 (6) | Intercostal artery, (2) | Pleural cavity |
| Transjugular Liver Biopsy, 2 (6) | Hepatic artery, (2) | Peritoneal cavity |
| Percutaneous Liver Biopsy, 1 (3) | Hepatic artery, (1) | Liver |
| Bone Marrow Biopsy, 1 (3) | Inferior gluteal artery, (1) | Gluteal muscle |
| Uretheroscopy, 1 (3) | Internal pudendal artery, (1) | Penile bulbar urethra |
| Spontaneous, 4 (11) | Inferior epigastric artery, (4) | Peritoneal cavity |
Technical Success and Clinical Outcomes
Positive angiographic findings which include extravasation and pseudoaneurysm were observed in 30 of 35 patients (85.7%). The remaining 5 patients (14.3%) had undergone empirical embolization. The technical success rate was 100%. Approximately, 0.2–1.5 mL of NBCA mixture was needed to achieve target embolization in all patients. Nearly all patients achieved complete haemostasis after a single session of NBCA embolization with no evidence of active bleeding on postprocedural angiography. The overall clinical success rate was 82.8% (n = 29). Clinical failure (n = 6; 17.2%) was due to persistent bleeding (n = 3) and recurrent bleeding (n = 3). Among these 6 cases, repeat embolization with NBCA was done for two cases. However, all these six patients died because of massive transfusion-related disseminated intravascular coagulopathy. In 15 of 35 cases (43%), patients were discharged from the hospital after embolization without the need for further intervention or surgery/liver transplant. Three patients underwent liver transplantation after embolization and discharged from the hospital.
30-Days Mortality Rate
The overall 30-day mortality rate was 48% (n = 17), and direct bleeding-related mortality rate was 17% (n = 6). Among these six patients, three had persistent bleeding and died within 48 h. The other three recurrent bleeding patients died after 48 h because of transfusion-related disseminated intravascular coagulopathy (DIC) and multiorgan failure. Five patients having acute on chronic liver failure with MELD (Model for end-stage liver disease) and Child-Pugh score of more than 34 and 12, respectively, died because of liver failure complicated by sepsis after 48 h. Four patients died after 48 h because of septic shock secondary to pulmonary infections, and two patients died because of cardiac arrest.
Procedure-related Complications
Nearly all patients tolerated well with no major complications. The overall complications rate was 8.5% (n = 3). Minor complications such as puncture site hematoma and post-embolization syndrome were noted in 5.7% (n = 2) and 2.8% (n = 1) patients, respectively. None of the patients had femoral artery pseudoaneurysm or muscle infarct or liver abscess after embolization.
Predictors of Outcomes
Multivariate analysis showed that a higher number of the RBC units transfused (OR = 1.53, 95% CI: 1.00–2.34, P = 0.004) before the procedure and high Child Pugh score (OR = 2.44, 95% CI: 1.26–4.71, P = 0.008) were statistically associated with a higher 30-day mortality rate. On univariate analysis, the higher number of RBC units transfused (OR 1.81, 95% CI 1.17–2.80, P = 0.007) before the procedure was the only factor statistically associated with the high clinical failure rate. Other variables such as coagulopathies, mean haemoglobin, serum creatinine level, hemodynamic instability and embolization time were not statistically associated with a 30-day mortality rate or clinical failure. Predictors of clinical failure and 30-day mortality rate are summarized in Table 3, Table 4.
Table 3.
Predictors of Clinical Failure After Transcatheter Arterial Embolization With N-Butyl-2-Cyanoacrylate (NBCA).
| Clinical characteristics | Clinical Success (n = 29) | Clinical Failure (n = 6) | Univariate Analysis |
|
|---|---|---|---|---|
| OR (95% CI) | P value | |||
| Age (Yrs), Mean ± SD | 48 ± 10.9 | 50.5 ± 12.7 | 1.02 (0.94–1.10) | 0.622 |
| Hemoglobin (g/dL), Mean ± SD | 7.4 ± 1.5 | 7.5 ± 1 | 1.05 (0.57–1.95) | 0.860 |
| Platelet (x 10³/mm³), Mean ± SD | 79.8 ± 37.5 | 92.3 ± 22.7 | 1.01 (0.98–1.03) | 0.431 |
| INR, Mean ± SD | 2.4 ± 0.9 | 2.5 ± 0.5 | 1.06 (0.41–2.73) | 0.893 |
| Creatinine (mg/dL), Mean ± SD | 1.0 ± 0.2 | 1.0 ± 0.2 | 1.77 (0.67–4.62) | 0.243 |
| Coagulopathy, n (%) | 26 (81.2%) | 6 (18.8%) | 1.23 (1.04–1.45) | 0.410 |
| Child Pugh Score, Mean ± SD | 9.6 ± 2.2 | 11.3 ± 1.7 | 1.55 (0.90–2.66) | 0.112 |
| MELD, Mean ± SD | 22.9 ± 10 | 29.8 ± 6.9 | 1.08 (0.97–1.19) | 0.131 |
| Hemodynamic Instability, n (%) | 11 (73.3%) | 4 (26.7%) | 3.27 (0.51–20.9) | 0.195 |
| Embolization Time (min), Mean ± SD | 10.7 ± 3.2 | 13 ± 4.8 | 1.20 (0.92–1.56) | 0.169 |
| No. of RBC Transfused, Mean ± SD | 9.1 ± 3.3 | 15.8 ± 1.7 | 1.81 (1.17–2.80) | 0.007 |
INR = Internalized normalized ratio; MELD = Model for end stage liver disease; RBC = Red blood cells; SD = Standard Deviation; OR = Odds ratio.
Table 4.
Predictors of 30-Day Mortality After Transcatheter Arterial Embolization With N-Butyl-2-Cyanoacrylate (NBCA).
| Clinical characteristics | Alive (n = 18) | Dead (n = 17) | Univariate Analysis |
Multivariate Analysis |
||
|---|---|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | |||
| Age (Yrs), Mean ± SD | 48 ± 2 | 50.5 ± 5.2 | 1.03 (0.96–1.09) | 0.347 | – | – |
| Hemoglobin (g/dL), Mean ± SD | 7.4 ± 0.2 | 7.5 ± 0.4 | 0.60 (0.34–1.60) | 0.080 | – | – |
| Platelet (x 10³/mm³), Mean ± SD | 90.8 ± 40.3 | 75.2 ± 30 | 0.99 (0.97–1.01) | 0.482 | – | – |
| INR, Mean ± SD | 2.4 ± 0.1 | 2.5 ± 0.2 | 5.91 (1.37–25.4) | 0.017 | – | – |
| Creatinine (mg/dL), Mean ± SD | 0.98 ± 0.2 | 1.0 ± 0.2 | 4.18 (0.16–10.71) | 0.387 | – | – |
| Coagulopathy, n (%) | 16 (50%) | 16 (50%) | 2.0 (0.16–24.32) | 0.581 | – | – |
| Child Pugh Score, Mean ± SD | 9.6 ± 0.4 | 11.3 ± 0.7 | 2.61 (1.49–4.54) | 0.001a | 2.44 (1.26–4.71) | 0.008a |
| MELD, Mean ± SD | 22.9 ± 1.8 | 29.8 ± 2.8 | 1.24 (1.09–1.41) | 0.001 | – | – |
| Hemodynamic Instability, n (%) | 7 (46.7%) | 8 (53.3%) | 1.39 (0.36–5.35) | 0.625 | – | – |
| No. of RBC Transfused, Mean ± SD | 7.9 ± 2.5 | 12.7 ± 3.9 | 1.54 (1.15–2.07) | 0.004a | 1.53 (1.00–2.34) | 0.004a |
INR = Internalized normalized ratio; RBC = Red blood cells; MELD = Model for end stage liver disease; SD = Standard Deviation; OR = Odds ratio.
represents statistically significant in both univariate and multivariate analysis.
Discussion
This study exhibited that transarterial embolization with NBCA is a safe, technically feasible and effective method of treatment for acute arterial bleeding in cirrhotic patients. In this study, the overall technical and clinical success rate was 100% and 82.8% (29/35), respectively. The overall 30-day mortality rate was 48%. Both univariate and multivariable logistic regression analysis showed that the higher number of RBC units transfused and high Child Pugh score before the procedure were significantly associated with a high 30-day mortality rate. Despite poor prognosis and a high mortality rate, TAE with NBCA had a high technical and clinical success rate in the treatment of acute arterial bleeding in cirrhotic patients.
Various studies have reported the effectiveness of TAE with NBCA.10,13, 14, 15, 16, 17 Yoo et al10 reported a technical success and clinical success rate of 100% and 83%, respectively, among 18 patients with active intramuscular haemorrhage. Albuquerque et al13 also reported a technical success and clinical success rate of 100% and 64%, respectively, among 11 patients with active abdominal wall haemorrhage. Similarly, Ozyer et al14 and Yata et al15 also reported a high technical and clinical success rate in the range of 97.6–100% and 92–95%, respectively. These high success rates are in concordance with the present study. However, this study has shown a higher 30-day mortality rate than those reported in the literature despite the successful embolization with glue. This discrepancy occurred because most of the patients had a high MELD score (>30) and Child Pugh score (>10), and death was due to liver failure rather than bleeding.
Several previous studies have analysed the factors predicting the clinical outcomes and 30-day mortality rate after NBCA embolization. Two retrospective studies were done by Jawhari et al16 and Abdulmalak et al17 in patients on anticoagulation using Glubran 2 (n-butyl cyanoacrylate methacryloxy sulfolane). They both reported that the higher number of RBC transfusion before the embolization was significantly associated with poor clinical outcome and a higher 30-day mortality rate. These results correlate well with the present study and indicate that the initial profound haemorrhage and the higher number of RBC transfusion before the embolization procedure increases the risk of clinical failure and mortality rates. Most probable explanation of clinical failure in all our six cases would be all our six patients had a massive blood transfusion before the embolization procedure and would have developed transfusion-related disseminated intravascular coagulopathy before the procedure. Therefore, the addition of disseminated intravascular coagulopathy with cirrhosis would be the reason for failure of glue in these patients. Furthermore, the present study also reports that high Child Pugh score was significantly associated with increased 30-day mortality rates.
There are few benefits of using NBCA as an embolic agent. Firstly, it shortened the procedural time with a median embolization time of 10 min (8–14 min) which was in concordance to the previous study done by Yonemitsu et al11 and Abdulmalak et al.17 This suggests that NBCA is particularly important in case of massive life-threatening haemorrhage which requires fast and urgent hemostasis.11,17,18 Secondly, NBCA has a high rate of clinical success and a low recurrent bleeding rate despite coagulopathy being present in 91% (32/35) patients. Several studies have described the relationship of coagulopathy with clinical failure after TAE.1, 2, 3 Encarnacion et al2 and Schenker et al1 reported that embolization was 2.9 times and 2.8 times more likely to fail in patients with coagulopathy respectively. Further, Yonemitsu et al11 reported that NBCA had a low recurrent bleeding rate as compared to the coils and gelatin sponge particles in patients with coagulopathy. Similar to present study, Jae et al9 reported that TAE with NBCA has a high clinical success rate (83%) in patients with coagulopathy. Hence, this fact suggests that the polymerisation of NBCA does not depend on the normal coagulation process unlike other embolic agents like PVA/coil and can be effectively used as a primary embolizing agent over PVA/coil particularly in cirrhotic patients with coagulopathy.
N-butyl-2-cyanoacrylate has a few limitations related to the injection technique and polymerization rate. Lipiodol is added to the NBCA to make the NBCA mixture radio-opaque and to modulate the polymerization rate.19, 20, 21 A high NBCA/lipiodol ratio caused by adding a small amount of lipiodol leads to rapid polymerization of the NBCA mixture resulting in proximal artery embolization without sufficient embolization of the bleeding foci. In contrast, a low NBCA/lipiodol ratio causes a slower rate of polymerisation of the NBCA mixture and can result in more distal embolization of the vessel leading to tissue ischemia or necrosis.20 Pollack et al22 proposed that the estimated in vivo polymerization time for the NBCA to iodized oil mixtures of 1:1–1:4 ratio was 1–4 s, with a linear relationship between time and mixture ratio. Based on this evidence, we used 1:2 to 1:5 mixture ratio according to the vessel size, shape, speed of blood flow and distance from the catheter tip to the bleeding point. Another important point to remember is the injection rate of the NBCA mixture. Careless rapid injection of the mixture will lead to reflux and can cause non-target embolization leading to infarction.21
No technical complications like catheter adherence, no inadvertent distal embolization or non-target embolization were experienced in the present study. These results are in concordance with the previous study done by Yoo et al10 and Yata et al.15 Tissue ischemia, subcritical limb ischemia and abscess were the other common complications reported with the use of NBCA.10,16,21,23, 24, 25 However, in present study none of the patients had experienced ischemic complications or abscess after NBCA embolization. These results correlate well with the previous study done by Kish et al4 and Yoo et al.10 The lower rate of complications is probably due to the experience and familiarity of the interventional radiologist with the properties of NBCA and meticulous in-handling to avoid glue penetration into the distal capillaries or arteriolar beds.
There are some limitations to the present study. It is a retrospective study conducted in a single centre. The sample size was small. The cirrhotic patient's cohort which was included in the study group was heterogeneous with respect to disease score, mechanism of injury and bleeding site. Moreover, present study did not compare the clinical efficacy and safety of NBCA with other embolic agents such as coils or PVA particles. Finally, no long-term follow-up of the patients was done as the study aimed to assess the clinical efficacy and safety of N-butyl-2-cyanoacrylate (NBCA). Thus, further studies should be conducted in future with a longer duration of follow-up in a systemically classified larger population to monitor clinical outcomes and establish the role of embolization with NBCA in cirrhotic patients.
In conclusion, transarterial embolization using NBCA in well-trained hands could be an effective treatment option for control of acute bleeding in cirrhotic patients with a high rate of technical and clinical success despite the high mortality rate and grave prognosis associated with cirrhosis. NBCA is especially useful in patients with coagulopathy, hemodynamic instability and tortuous arteries that are not amenable to microcoils. In addition, the interventional radiologist should be aware of the properties of the NBCA and should meticulously handle it during the procedure to avoid inadvertent complications.
Credit authorship contribution statement
PY, SJ, MA, SMK, SKS - Conceptualized the study design, PY, SVS, PRK, CK.- Collect the data, analysed the data, prepare the manuscript.
Conflicts of interest
The authors have none to declare.
Funding
None.
References
- 1.Schenker M.P., Duszak R., Jr., Soulen M.C., et al. Upper gastrointestinal hemorrhage and transcatheter embolotherapy: clinical and technical factors impacting success and survival. J Vasc Intervent Radiol. 2001;12:1263–1271. doi: 10.1016/s1051-0443(07)61549-8. [DOI] [PubMed] [Google Scholar]
- 2.Encarnacion C.E., Kadir S., Beam C.A., Payne C.S. Gastrointestinal bleeding: treatment with gastrointestinal arterial embolization. Radiology. 1992;183:505–508. doi: 10.1148/radiology.183.2.1561358. [DOI] [PubMed] [Google Scholar]
- 3.Aina R., Oliva V.L., Therasse E., et al. Arterial embolotherapy for upper gastrointestinal hemorrhage: outcome assessment. J Vasc Intervent Radiol. 2001;12:195–200. doi: 10.1016/s1051-0443(07)61825-9. [DOI] [PubMed] [Google Scholar]
- 4.Kish J.W., Katz M.D., Marx M.V., Harrell D.S., Hanks S.E. N-butyl cyanoacrylate embolization for control of acute arterial hemorrhage. J Vasc Intervent Radiol. 2004;15:689–695. doi: 10.1097/01.rvi.0000133505.84588.8c. [DOI] [PubMed] [Google Scholar]
- 5.n-BCA Trial Investigators N-butyl cyanoacrylate embolization of cerebral arteriovenous malformations: results of a prospective, randomized, multi-center trial. Am J Neuroradiol. 2002;23:748–755. [PMC free article] [PubMed] [Google Scholar]
- 6.Kanematsu M., Watanabe H., Kondo H., et al. Postpartum hemorrhage in coagulopathic patients: preliminary experience with uterine arterial embolization with N-butyl cyanoacrylate. J Vasc Intervent Radiol. 2011;22:1773–1776. doi: 10.1016/j.jvir.2011.08.016. [DOI] [PubMed] [Google Scholar]
- 7.Kim J., Shin J.H., Yoon H.K., et al. Transcatheter renal artery embolization with N-butyl cyanoacrylate. Acta Radiol. 2012;53:415–421. doi: 10.1258/ar.2012.110595. [DOI] [PubMed] [Google Scholar]
- 8.Huang C.C., Lee C.W., Hsiao J.K., et al. N-butyl cyanoacrylate embolization as the primary treatment of acute hemodynamically unstable lower gastrointestinal hemorrhage. J Vasc Intervent Radiol. 2011;22:1594–1599. doi: 10.1016/j.jvir.2011.07.018. [DOI] [PubMed] [Google Scholar]
- 9.Jae H.J., Chung J.W., Jung A.Y., et al. Transcatheter arterial embolization of nonvariceal upper gastrointestinal bleeding with N-butyl cyanoacrylate. Korean J Radiol. 2007;8:48–56. doi: 10.3348/kjr.2007.8.1.48. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Yoo D.H., Jae H.J., Kim H.C., Chung J.W., Park J.H. Transcatheter arterial embolization of intramuscular active hemorrhage with N-butyl cyanoacrylate. Cardiovasc Intervent Radiol. 2012 Apr;35:292–298. doi: 10.1007/s00270-011-0162-6. Epub 2011 May 4. PMID: 21541812. [DOI] [PubMed] [Google Scholar]
- 11.Yonemitsu T., Kawai N., Sato M., et al. Evaluation of transcatheter arterial embolization with gelatin sponge particles, microcoils, and n-butyl cyanoacrylate for acute arterial bleeding in a coagulopathic condition. J Vasc Intervent Radiol. 2009 Sep;20:1176–1187. doi: 10.1016/j.jvir.2009.06.005. Epub 2009 Jul 30. PMID: 19643634. [DOI] [PubMed] [Google Scholar]
- 12.Sacks D., McClenny T.E., Cardella J.F., Lewis C.A. Society of Interventional Radiology clinical practice guidelines. J Vasc Intervent Radiol. 2003 Sep;14(9 Pt 2):S199–S202. doi: 10.1097/01.rvi.0000094584.83406.3e. PMID: 14514818. [DOI] [PubMed] [Google Scholar]
- 13.Albuquerque T.V.C., Monsignore L.M., de Castro-Afonso L.H., Elias-Junior J., Muglia V.F., Abud D.G. Transarterial embolization with n-butyl cyanoacrylate for the treatment of abdominal wall hemorrhage. Diagn Interv Radiol. 2020 May;26:216–222. doi: 10.5152/dir.2019.19348. PMID: 32209512; PMCID: PMC7239359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Ozyer U. Transcatheter arterial embolization with N-Butyl-2-Cyanoacrylate in the management of spontaneous hematomas. Cardiovasc Intervent Radiol. 2017 Jan;40:41–49. doi: 10.1007/s00270-016-1463-6. Epub 2016 Sep 19. PMID: 27646523. [DOI] [PubMed] [Google Scholar]
- 15.Yata S., Ihaya T., Kaminou T., et al. Transcatheter arterial embolization of acute arterial bleeding in the upper and lower gastrointestinal tract with N-butyl-2-cyanoacrylate. J Vasc Intervent Radiol. 2013 Mar;24:422–431. doi: 10.1016/j.jvir.2012.11.024. Epub 2013 Feb 4. PMID: 23380738. [DOI] [PubMed] [Google Scholar]
- 16.Jawhari R., Chevallier O., Falvo N., et al. Outcomes of transcatheter arterial embolization with a modified n-butyl cyanoacrylate glue for spontaneous iliopsoas and rectus sheath hematomas in anticoagulated patients. J Vasc Intervent Radiol. 2018;29:210–217. doi: 10.1016/j.jvir.2017.08.006. [DOI] [PubMed] [Google Scholar]
- 17.Abdulmalak G., Chevallier O., Falvo N., et al. Safety and efficacy of transcatheter embolization with Glubran®2 cyanoacrylate glue for acute arterial bleeding: a single-center experience with 104 patients. Abdom Radiol. 2018;43:723–733. doi: 10.1007/s00261-017-1267-4. [DOI] [PubMed] [Google Scholar]
- 18.Toyoda H., Nakano S., Kumada T., et al. Estimation of usefulness of N-butyl-2-cyanoacrylate-lipiodol mixture in transcatheter arterial embolization for urgent control of life-threatening massive bleeding from gastric or duodenal ulcer. J Gastroenterol Hepatol. 1996;11:252–258. doi: 10.1111/j.1440-1746.1996.tb00071.x. [DOI] [PubMed] [Google Scholar]
- 19.Cromwell L.D., Kerber C.W. Modification of cyanoacrylate for therapeutic embolization: preliminary experience. AJR Am J Roentgenol. 1979 May;132:799–801. doi: 10.2214/ajr.132.5.799. PMID: 107749. [DOI] [PubMed] [Google Scholar]
- 20.Takasawa C., Seiji K., Matsunaga K., et al. Properties of N-butyl cyanoacrylate-iodized oil mixtures for arterial embolization: in vitro and in vivo experiments. J Vasc Intervent Radiol. 2012;23:1215–1221. doi: 10.1016/j.jvir.2012.06.022. [DOI] [PubMed] [Google Scholar]
- 21.Takeuchi Y., Morishita H., Sato Y., et al. Committee of practice guidelines of the Japanese society of interventional radiology. Guidelines for the use of NBCA in vascular embolization devised by the committee of practice guidelines of the Japanese society of interventional radiology (CGJSIR), 2012 edition. Jpn J Radiol. 2014 Aug;32:500–517. doi: 10.1007/s11604-014-0328-7. Epub 2014 Jun 3. PMID: 24889662. [DOI] [PubMed] [Google Scholar]
- 22.Pollak J.S., White R.I., Jr. The use of cyanoacrylate adhesives in peripheral embolization. J Vasc Intervent Radiol. 2001;12:907–913. doi: 10.1016/s1051-0443(07)61568-1. [DOI] [PubMed] [Google Scholar]
- 23.Maleux G., Van Sonhoven F., Hofkens P.J., et al. Soft tissue bleeding associated with antithrombotic treatment: technical and clinical outcomes after transcatheter embolization. J Vasc Intervent Radiol. 2012 Jul;23 doi: 10.1016/j.jvir.2012.04.005. 910-916.e1. Epub 2012 May 19. PMID: 22609289. [DOI] [PubMed] [Google Scholar]
- 24.Koo H.J., Shin J.H., Kim H.J., et al. Clinical outcome of transcatheter arterial embolization with N-butyl-2-cyanoacrylate for control of acute gastrointestinal tract bleeding. AJR Am J Roentgenol. 2015 Mar;204:662–668. doi: 10.2214/AJR.14.12683. PMID: 25714300. [DOI] [PubMed] [Google Scholar]
- 25.Hill H., Chick J.F.B., Hage A., Srinivasa R.N. N-butyl cyanoacrylate embolotherapy: techniques, complications, and management. Diagn Interv Radiol. 2018 Mar-Apr;24:98–103. doi: 10.5152/dir.2018.17432. PMID: 29467116; PMCID: PMC5873510. [DOI] [PMC free article] [PubMed] [Google Scholar]