Transcatheter arterial embolization of severe blunt liver injury in hemodynamically unstable patients: a retrospective 15-year study

Background Non-operative management with Transcatheter arterial embolization(TAE) was the rst line of treatment for severe blunt liver injury in hemodynamically stable patients, but in the case of hemodynamically unstable, Operative management(OM) was recommended. We evaluated the ecacy of TAE in our hospital where intervention radiology was available 24 hours a day if the patient responds to initial infusion therapy even unstable. Methods We conducted a retrospective study of severe blunt liver injury of AAST Organ Injury Scale(OIS) grade 3–5 transported to our hospital between 2005 and 2019. If the patient responded to initial infusion therapy, even though hemodynamically unstable(Shock Index ≧ 1), CT was taken and initial treatment was decided. We compared patients who underwent OM or TAE on initial treatment. Results 62 patients were included (8 OM, 54 TAE), with a mean ISS of 26.6, in hospital mortality of 6%(13% OM VS 6% TAE, p = 0.50), hemodynamically unstable of 35% (88% OM VS 28% TAE, p < 0.01) and Time from Door to start OM/TAE 81.8 min(120.0 OM VS 76.1 TAE, p = 0.02). Unstable patients who undergo TAE were associated with 7% in hospital mortality and 7% clnical failure. After logistic regression the choice of treatment was not a predictor of outcome, the predictor of in-hospital mortality death was GCS on arrival(OR0.48, P < 0.01), hemodynamically unstable was independent predictor of duration of ICU ≧ 7 days(OR 3.80, p = 0.05) and massive blood transfusion(OR 7.25, p = 0.01). the predictor of complication was OIS grade4-5(OR 6.61 p < 0.01). Conclusions The strategy of performing TAE even in the presence of hemodynamically unstable in a facility where TAE can be performed promptly was acceptable mortality and clinical failure. The choice of treatment did not affect the outcome, and hemodynamically unstable and OIS affected the prognosis. hepatic ischemia, pseudoaneurysm, gallbladder necrosis, arterioportal shunt, and rebleeding detected on CT scanning undertaken 1 week after admission. stable from In the present good and shortening of the duration from ER visit to could have contributed to the


Background
The nonoperative management (NOM) through transcatheter arterial embolization (TAE) of blunt liver injury is reportedly associated with a success rate of 80-97% when used with advanced techniques in interventional radiology (IR). 1 In addition, guidelines recommend TAE as the rst-line therapy in hemodynamically stable patients with blunt liver injury. 2 However, there are recommendations (Level of Evidence I) for laparotomy in patients who are hemodynamically unstable, and NOM should not be selected for the management of patients with hemodynamic instability. 3A small case series reported that TAE could be useful for hemodynamically unstable patients in facilities that could facilitate quick and accurate application of the procedure, 4 but there are no reports from comparative studies of TAE and operative management (OM) in hemodynamically unstable patients with liver injury.
Our institution has an IR-equipped emergency department, which facilitates a quick TAE; therefore, we attempted TAE even in hemodynamically unstable patients with liver injury.This retrospective study of a 15-year study period was undertaken to determine whether TAE for severe blunt liver injury is associated with poorer prognosis in hemodynamically unstable patients.Moreover, we comparatively evaluated the differences in prognosis between TAE and OM.

Study Design and Methodology
This retrospective observational study reviewed all patients with severe blunt liver injury (American Association for the Surgery of Trauma [AAST] grades III-V) who were treated at the Kitasato University Hospital Emergency and Critical Care Center from 2005 to 2019.We excluded patients with cardiac arrest on arrival.Regardless of age, all patients who received OM or TAE as initial treatment were included in this study.The OM group included patients who underwent laparotomy for hemostasis and the TAE group included patients who underwent embolization for the treatment of severe blunt liver injury.
Our facility was the only regional trauma center serving a population of more than one million people, and our IR physicians were fulltime staff at this center.Therefore, 24-hour IR facility was available at the study center.

Clinical Management and Procedures
All trauma patients received initial infusion therapy, and patients in shock without elevated blood pressure were treated by OM and underwent damage control surgery.If the clinical condition of the patient responded to initial infusion therapy, the patient underwent computed tomography (CT) scanning.If an intestinal injury was detected, the patient was transferred to the operating room (OR) for OM and, in patients with an extravascular leak of contrast on CT, a TAE was undertaken in the IR room.A Shock Index > 1 at the time of the admission to the emergency department or immediately before transfer to the OR/IR room was de ned as hemodynamic instability.
For embolization, the celiac artery was selected and accessed by using a 5-Fr shepherd hook-type catheter (Hanaco Disposable Torque Catheter, Hanaco Medical Co., Saitama, Japan) or a 5-Fr cobra-type catheter (Torcon NB Advantage Catheter, Cook Japan, Tokyo, Japan).
In pediatric patients, we used 4-Fr catheters.The site of hemostasis was selected by using a microcatheter and a TAE was carried out.In principle, we undertook selective embolization; however, embolization from the right and left hepatic arteries or a more proximal site was acceptable if the patient was hemodynamically unstable.The embolic agents included gelatin sponge (via pumping method) and coils or N-butyl cyanoacrylate, if there was an arterioportal shunt or coagulopathy, although choice of embolization material was determined at the IR physician's discretion.

Data Collection
From electronic and paper medical records, we collected data on age, sex, mechanism of injury, vital signs at the time of visit, base excess (BE), brinogen, Injury Severity Score (ISS), Trauma and Injury Severity Score (TRISS), time from arrival to CT, time from arrival to admission into OR/IR room, and Operation/TAE time.The AAST classi cation 5 was used to grade patients based on intraoperative ndings or on a retrospective examination of CT images.The following outcomes were compared between the two study groups: inhospital mortality, the number of units of blood transfusion within 24 h of admission, massive transfusions (≥ 10 units of RBC), length of intensive care unit (ICU) stay, complications, and clinical failure.Clinical failure was de ned as patient death due to hemorrhage within 24 h of OM (OM group) and switching from TAE to OM (TAE group) due to hemostatic challenges.Complications included biloma, hepatic ischemia, pseudoaneurysm, gallbladder necrosis, arterioportal shunt, and rebleeding detected on CT scanning undertaken 1 week after admission.

Statistical Analysis
Statistical analyses were undertaken in JMP ® (SAS Institute Inc., Cary, NC, USA) by using the Student's t-, chi-square, and Wilcoxon rank sum tests for comparisons between the OM and TAE groups as well as the stable TAE and unstable TAE groups.A p-value < 0.05 was considered indicative of statistical signi cance.Logistic regression analysis was conducted with regard to the outcome, and incorporated variables with p < 0.10 and treatment choice as the variables on univariate analysis.A multivariate analysis was carried out after organizing the cointegrated variables.The odds ratios (OR) for each explanatory variable were calculated.
On univariate analyses of outcomes, only the GCS score (OR 0.65, p < 0.01) showed statistical signi cance for in-hospital mortality.However, multivariate analysis with GCS, age, and TAE as objective variables found that the GCS score (OR 0.48, p < 0.01) and age (OR 1.08, p = 0.04) were statistically signi cant factors.

Discussion
The present study showed that, in the treatment of severe blunt liver injury, the mortality rate was 6% in patients with hemodynamic instability who underwent TAE but responded to initial infusion therapy; TAE for hemodynamically unstable patients did not increase the mortality rate versus the stable group.A recent observational study from a trauma center reported a mortality rate of 3-8% 6,7 for blunt liver injury and 15% for grades IV and V liver injury, with comparable results.The choice of treatment was not a predictor of outcome; the GCS score on arrival was a predictor of in-hospital mortality, and hemodynamic instability was an independent predictor of length of ICU stay ≥ 7 days and massive blood transfusion.The AAST grades and were a predictor of complication.
There are reports that, under certain conditions, TAE for hemodynamically unstable patients with liver injury does not increase mortality.
[13] A cohort study of 3627 patients with severe blunt liver injury of AAST Grade IV or higher reported that SBP < 90 mmHg was more likely to result in failed NOM (OR 2.07) and that higher rates of NOM failure and mortality in hypotensive patients were associated with higher rates of NOM. 13 There are a few case reports of successful NOM with TAE for hemodynamically unstable patients, [14][15][16] but a recent observational study reported that failure and mortality from NOM with TAE were independent of hemodynamic status, when hemodynamic instability was de ned as a case where the patient required rapid infusion or transfusion to maintain SBP > 90 mmHg. 4e success rate of TAE in patients with cardiovascular instability may depend on how quickly the procedure is initiated and completed.
A historical cohort study 17 at the same institution reported that the introduction of a protocol wherein CT scanning and TAE was performed within 30 minutes in case of a response to the initial infusion therapy, even if the patient was in shock at the time of admission, resulted in a decreased rate of OM without alterations in the failure or mortality rates.On the other hand, it was reported that only 6% of the NOM were TAE undertaken in facilities with IRs situated far from the trauma unit. 18In the present study, good access to IR and shortening of the duration from ER visit to TAE could have contributed to the results.
Patients who underwent TAE had fewer massive transfusions and shorter ICU stay than patients who received OM.These results are consistent with those in previous reports 6,7 and suggest that TAE is less invasive than OM and, thus, results in fewer transfusions and a faster recovery.However, in multivariate analysis, hemodynamic status was the only predictor of ICU stay and massive transfusion and may not depend on treatment.With regard to complications, only AAST showed a correlation.This nding is consistent with reports that major complications after NOM occurred only in patients with AAST grade 3 or higher injuries 12 and that risk factors for complications in 453 NOMs were AAST Grade 4 (OR 4.4) and AAST Grade 5 (OR 12) independent of other factors. 19The most common complications after TAE include hepatic necrosis, abscess, and biloma, according to a systematic review. 20Complications are reported to occur in 70% of cases, 21 suggesting that TAE may increase the rate of complications. 22There are reports that embolization should be undertaken more selectively than at the level of the proper hepatic artery to reduce complications. 23,24In the present study, we tried to use selective embolization if the circulation dynamics so permitted.
There were more severe cases in the OM group than in the TAE group because of the inability to undertake CT scanning if the patient was hemodynamically unstable and did not respond to initial infusion therapy.The mortality rate of severe blunt liver injury requiring OM is more than 50%, 25 and there are two ways to effectively utilize TAE in such cases.One is the resuscitative endovascular balloon occlusion of the aorta (REBOA), which has been reported to improve prognosis in severe trauma refractory to initial infusion therapy. 26Thus, the inclusion of REBOA in our strategy may have further improved the prognosis in the TAE group.The other option to effectively utilize TAE is the hybrid ER, where all examinations and treatments for trauma are carried out in a single station composed of a carbon-ber uoroscopic table with a self-propelled C-arm combined with a sliding gantry CT scanner.The hybrid ER is reported to increase the rate of IVR, shorten the time to treatment initiation, and improve the prognosis in the treatment of severe trauma, 27 and it is effective in shortening the time to treatment because TAE can be conducted as soon as CT scanning is completed.
Limitations of this study include the fact that it was a single-center retrospective study.Moreover, the ndings of this study may not be easily generalizable as the study center was a facility with immediate access to TAE.Future prospective studies will be needed to speci cally control the institutional and patient enrollment criteria for validation of the ndings from this research.In addition, the longterm prognosis was not considered in this study.

Conclusion
In centers with good access to TAE facility, TAE may be an effective NOM option in hemodynamically unstable patients with severe blunt liver injury.Prospective and large-scale studies are needed to verify the speci c criteria for treatment selection for the application of these research ndings in the clinical setting.

Declarations
Ethics approval and consent to participate: This observational design study involved human participants, and it was conducted in conformance with the principles of the Declaration of Helsinki and its amendments.The study protocol was approved by the Kitasato University Hospital Ethics Committee (approval no.B20-034).This committee waived the need for informed consent because of the retrospective design. Tables Management algorithm for patients with liver injury.NOM, nonoperative management; TAE, transcatheter arterial embolization.

Table 1 :
Comparison between the operative management and transcatheter arterial embolization groups