超声造影引导下经皮注射止血剂治疗与传统手术治疗肝、脾、肾创伤对比，一个回顾性研究。

Ο rigin al P ap er 2021NEW FRONTIERS IN CLINICAL AND EXPERIMENTAL RESEARCH Hepato-Gastroenterology 2012; 59:2021-2026 doi 10.5754/hge12255© H.G.E. Update Medical Publishing S.A., Athens Key Words:Hemostatic agents; Transcutaneous contrast-enhanced ultrasound; Hepat-ic trauma; Kidney trauma; Splenic trauma. Background/Aims: There is lack of studies on the ef-fectiveness of transcutaneous contrast-enhanced ultra-sound-guided injections of hemostatic agents for liver, spleen and kidney trauma. We compared treatment by hemostatic agents to surgical treatment in a retrospec-tive interventional human study. Methodology: The study enrolled a total of 135 subjects from emergen-cy unit of the Chinese People’s Liberation Army Gen-eral Hospital in Beijing. Within the cohort, 62 patients received contrast enhanced ultrasound-guided injec-tion of hemostatic agents and the rest received surgical treatments. Results: The injury severity score was low-er in the hemostatic agent treatment group than surgi- cal treatment group (p<0.05), but Glasgow coma scale scores did not reach statistical significance. The pa- tients in the surgical treatment group had significantly higher hospital fees than those in the hemostatic treat-ment group (p<0.05), although the length of hospital- ization did not significantly differ between two groups. Safety outcome variables pre- and post-treatment re-mained within normal limits in both groups. Conclu- sions: Hemostatic agents were more cost-effective than surgery to treat patients with liver, spleen and kidney trauma. However, given the limited sample size, subse-quent studies drawing upon larger populations from multiple medical centers are necessary for follow-up. INTRODUCTIONActive bleeding often results from blunt or penetrat-ing trauma and can also occur after medical procedures such as surgery or needle biopsy. There are few effective methods available for non-invasive control of bleeding and often, if bleeding continues, surgical treatment is re-quired (1). In standard initial abdominal trauma manage-ment, ultrasonography is initially performed in the emer-gency department, followed by computed tomography (CT), the gold standard in the diagnosis of abdominal in-juries. However, more investigations, as documented by Clevert et al. show that contrast-enhanced ultrasonogra-phy (CEUS) provides a good alternative to CT, especially in hemodynamically compromised patients (2). CEUS al-lows increased contrast between the lesion and the pa-renchyma; consequently, it boosts sonographic sensitivi-ty for detecting traumatic and non-traumatic abnormali-ties. It can be used to guide percutaneous procedures and evaluate real time therapeutic effects (3). Several ultrasound-guided procedures including per-cutaneous microwave coagulation therapy (4), high-in-tensity focused ultrasound (5), percutaneous radiofre-quency ablation (6) and injection of hemostatic agents (3), have been developed for bleeding control. Howev-er, the former three require more complex equipment in comparison with the last one and still remain in animal experimental studies.Transcutaneous local injection of hemostatic agents has been found to effectively reduce severe liver trau-ma-related blood loss. Given its simplicity, convenience and effectiveness, the CEUS technique may be an alterna-tive hepatic hemorrhage management due to trauma (7-11). Although splenic artery embolization (SAE) and lap-aroscopic splenectomy are effective and safe procedures for delayed vascular complications, SAE may lead to var-ious hemorrhagic complications (11). Hence, CEUS-guid-ed percutaneous injection therapy can manage splenic trauma.Despite non-operative management becoming the fa-vored method of care for abdominal injuries (10,12), it still lacks clinical study to investigate the effectiveness and safety of CEUS-guided procedure for abdominal sol-id organs trauma. Our study evaluated the effectiveness of transcutaneous CEUS-guided hemostatic agent injec-tions into patients with liver, spleen, or kidney trauma and compared with surgery alone. The results provided insight into evaluating the effectiveness of injected hemo-static agents in treating liver, kidney or spleen trauma pa-tients. ABSTRACT Comparison of Transcutaneous Contrast-Enhanced Ultrasound-Guided Injected Hemostatic Agents with Traditional Surgery Treatment for Liver, Spleen and Kidney Trauma: A Retrospective Study Dong Wang1,2, Faqin Lv1, Yukun Luo1, Lichun An1, Junlai Li1, Xia Xie1, Jiangke Tian1, Weiyan Zhao1 and Jie Tang11Department of Ultrasound, Chinese People’s Liberation Army General Hospital, Beijing, China2Nankai University, Tianjin, China Corresponding author: Jie Tang, MD, Department of Ultrasound, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China; Tel.: +86-10-55499056, Fax: +86-10-55499056; E-mail: txiner@vip.sina.com 2022 Hepato-Gastroenterology 59 (2012) D Wang, F Lv, Y Luo, et al. METHODOLOGY Study design and patient populationThis was a retrospective medical chart review study of patients presenting with liver, kidney or spleen inju-ries to the emergency room of the Chinese People’s Liber-ation Army General Hospital in Beijing, China. The study received the approval of the institutional review board of the Chinese people’s liberation army general hospital. As this study was based on a retrospective review of medi-cal charts, informed consent could be waived. Data from all patients receiving CEUS-guided hemostatic agent in-jections during January 2007 to June 2011 was collect-ed, with 62 subjects receiving hemostatic agent injections. Indications for selecting patients into surgery or CEUS-guided hemostatic treatment were decided by clinicians according to the clinical information and preference of the patients and their family. The surgery group was also collected from the same period and matched by age, gen-der and organ injury scale (OIS) and therefore, only pa-tients with OIS grade III and IV were included in the sur-gery group.The results of the pre and post-treatment tests were collected from the patient charts. The initial evaluations included demographic data, past history, vital signs, ar-terial blood gas, imaging exam (CT or ultrasound), com-plete blood count (CBC), biochemistry tests and several trauma scales, including OIS by the American association for the surgery of trauma, (13) injury severity score (ISS), (14) and Glasgow coma scale (GCS). If the patient had two injured organs or more, we only calculated the highest OIS. The post-treatment tests (received 24-48 hours af-ter treatment) included vital signs, arterial blood gas, CBC and biochemistry tests. CEUS and hemostatic agentsA real-time, contrast enhanced, ultrasound-guided procedure was performed. The ultrasound examination was performed before each treatment using a high-end sonographic scanner (AcusonTM Sequoia 512; Siemens) with 3.0-5.0MHz Acuson 4V1 transducer and by the use of low mechanical index CEUS technology. The ultrasound contrast agent used in this study was SonoVue (Sono Vue®, Bracco Diagnostics, Inc., Italy). This is a suspension of stabilized sulfur hexafluoride microbubbles in saline and has been used in the evaluation of abdominal trau-ma in clinical patients. A bolus injection of contrast agents was administered into an antecubital vein. The location, morphology and size of the lesions and the cross-sections of the injured vessels was then determined. Under con-trast pulse sequencing mode, we injected 1.21±0.39kU hemocoagulase atrox (Reptilase®, Solco Basle Ltd., Swit-zerland) into the lesions and under microvessel display mode, we injected 1.09±0.4mL α-cyanoacrylate (Baiyun Medical Adhesive®, Guangzhou Baiyun Adhesive General Co., Ltd., China) into the cross-sections of the injured ves-sels but not into the renal parenchyma. OutcomesPatient assessments included both primary and sec-ondary outcomes. Primary outcome assessments includ-ed length of hospitalization, survival status, cost of hos-pitalization and rate of organ removal. Subsequently, pa-tients had assessments for secondary outcome assess-ments which included safety (adverse events), vital signs, arterial blood gas, CBC and biochemistry tests. Statistical analysisThe patient demographics, clinical characteristics and safety data were summarized as medians (interquartile range [IQR]: Q1, Q3) for continuous data and n (%) for categorical data of a given treatment group. The differ-ence between two groups of continuous data was calculat-ed using the Mann-Whitney U test. Categorical data were Variables Hemostatic agent treatment (n=62) Surgical treatment (n=73) p value Age, years 32.5 (21.0, 42.0) 32.0 (22.0, 43.5) 0.933 Gender 0.920Males 54 (87.1) 64 (87.7)Females 8 (12.9) 9 (12.3) BMI, kg/m2 22.8 (20.7, 24.9) 22.0 (20.2, 24.2) 0.254 Reasons of trauma 0.001*Car accident 20 (32.3%) 44 (60.3%)Falling 9 (14.5%) 9 (12.3%)Fight 6 (9.7%) 10 (13.7%)Others or unknowna 27 (43.5) 10 (13.7%) Organ injury scale 0.109Level III 36 (58.1) 52 (71.2)Level IV 26 (41.9) 21 (28.8) Injury severity score 17 (11, 22) 19 (14, 27) 0.006* Glasgow coma scale 5 (4, 6.3) 5 (4, 9) 0.876NA: Not Assessed. Data were summarized as medians (IQR: Q1, Q3) for continuous data and n (%) for categorical data by treatment group. The difference between two groups was calculated using Mann-Whitney U test in continuous data; χ2 test or Fisher’s exact test was used if any cell number less than 1 were performed in the categorical data. *p<0.05, significant difference between treatment groups. aOne patient receiving hemostatic agent treatment and two patients receiving surgical treatment were unknown. TABLE 1. Subject demographic and clinical characteristics (n=135). Variables Hemostatic agent treatment (n=62) Surgical treatment (n=73) p valueHospital days, days 10 (7.8, 13.3) 10 (7, 17) 0.996Hospital fees, ×104 RMB 2.1 (1.4, 4.6) 5.1 (2.6, 11.0) <0.001*Survival status NASurvival 62 (100) 62 (84.9)Expired 0 (0) 11 (15.1)Surgical typesSplenectomy 1 (1.6) 43 (58.9) <0.001*Nephrectomy 0 (0) 5 (6.8) NABlood bleeding, mL - a 2000 (1200, 3600) NABlood transfusion, mL - b 1805 (900, 3990) NAFailure to stop bleeding 3 (4.8) 0(0) NAPost-operative complications 0(0)c 0(0) NARMB: Renminbi (Chinese currency). Data were summarized as median (IQR: Q1, Q3) for continuous data and n (%) for categorical ones by treatment group. Difference among treatment groups were performed using Kruskall-Wallis test and between two groups using Mann-Whitney U test in continuous data; Fisher’s exact test was performed in the categorical one, survival status. NA: Not Assessed. aOne subject in hemostatic agent treatment group had splenectomy later and bled 1000mL. bOne subject in hemostatic agent treatment group had liver repair surgery and had a 2460mL blood transfusion. cPost-operative complications included infection, shock, stress ulcers, as well as respiratory, liver and renal failure. *p<0.05, significant difference between treatment groups. TABLE 2. Comparison of the post-operative outcomes, survival status, hospital times, hospital fees and complications between hemostatic agent and surgical treatment groups (n=135). 2023Hepato-Gastroenterology 59 (2012)Transcutaneous CEUS-Guided Trauma Treatmentcalculated using either the χ2 test or Fisher’s exact test. Safety data between treatment groups were compared using Mann-Whitney U test and the difference within groups (pre-operation vs. post-operation) was compared using the Wilcoxon signed-rank test, respectively. All sta-tistical assessments were two-sided and a level of p<0.05 was considered significant. Statistical analyses were per-formed using SPSS 15.0 statistical software (SPSS Inc, Chi-cago, IL, USA). RESULTS The 135 subjects included two groups of patients, 62 receiving hemostatic agent injection treatments and 73 receiving surgical treatments. They were enrolled into this study in the period from January 2007 to June 2011 and followed-up until July 2011. Table 1 shows the sub-jects’ demographics and clinical characteristics cate-gorized by treatment group. The age, gender distribu- tion and body mass index was not significantly differ-ent (p=0.933, p=0.920 and p=0.254, respectively) be-tween the treatment groups. Car accidents accounted for the most reasons of trauma, which were however, sig- nificantly different among these two groups (p=0.001). There were 19 patients (30.6%) with fractures in the he-mostatic treatment group and 35 patients (47.9%) with fractures in the surgical group, which was significantly different (p=0.041). No individuals in either group used anticoagulants. In the hemostatic agent treatment group, all patients were observed to be at OIS level III and level IV (58.1% at level III, 41.9% at level IV). The matched surgical treat-ment group had 71.2% patients at level III and 28.8% at level IV. In addition, the median ISS score was slight-ly lower in the hemostatic agent treatment group than the surgical treatment group (17 [11, 22] vs. 19 [14, 27], p=0.006), which was a significant difference between treatment groups. The median observed GCS score was 5 [4, 6.3] for the hemostatic agent treatment group and 5 [4, 10] for the surgical treatment group. The difference in the GCS between treatment groups did not reach statisti- cal significance (Table 1). Table 2 compared post-operative outcomes, survival status, hospital days, hospital fees and complications be-tween treatment groups. The number of median hospital days was observed to be 10 days [7.8, 13.3] and 10 days [7, 17] in both the hemostatic agent treatment and sur-gical treatment groups, respectively; the difference was not statistically significant. However the patients in the hemostatic agent treatment group had significantly low-er median hospital fees than those in the surgical treat-ment group (median hospital fees: 2.1×104 RMB [1.4×104, 4.6×104] vs. 5.1×104 RMB [2.6×104, 11.0×104], p<0.001). There were 11 patients (15.1%) in the surgical treat-ment group who died after therapy; in comparison, no one died in the hemostatic agent treatment group (Ta- ble 2). Post-operative complications included infection, shock, stress ulcers, as well as respiratory, liver and re-nal failure. The median hospital fees of surviving post-op-erative hemostatic treatment patients and surgical treat- ment patients were comparable to pre-operative fig-ures (2.1×104 RMB [1.4×104, 4.6×104] vs. 5.9×104 RMB [2.9×104, 1.17×104], p<0.001), showing a statistically significant difference (p< 0.05) in cost between groups. The median numbers of hospital stays were 10 days [7.8, 13.3] and 11 days [7, 22.5] for the hemostatic agent and surgical treatment groups, respectively. However, this did not reach statistical significance. The 11 subjects who died after surgical treatment had a median 1 day [1, 9] hospital stay and median hospital fees of 1.9×104 RMB [1.14×104, 6×104]. Table 3 summarized the pre- and post-treatment safe-ty outcomes for subjects in the hemostatic agent treat-ment group. In the hemostatic agent treatment group, di-astolic blood pressure (DBP), respiratory rate, pCO2, pH, WBC, RBC, hematocrit, platelet, neutrophils, HbA1c, AST, BUN, creatinine, prothrombin time (PT) and glucose lev-els decreased. However, total bilirubin, direct bilirubin and potassium levels increased post-treatment. The doc-umented decrease and increase in variable levels were all statistically significant (p<0.05) (Table 3). In the surgery treatment group, creatinine and chloride decreased post- treatment but body temperature, platelet, γ-GT, total bil-irubin, direct bilirubin, amylase, APTT and potassium in- Hemostatic agent treatment (n=62) Variables Pre-treatment Post-treatment p valueSBP, mmHg 75 (65, 85) 76.5 (70.8, 82.3) 0.507DBP, mmHg 123 (114.8, 138.3) 119 (108.5, 127) <0.001*Heart rate, beats/min 85 (77.8, 108.5) 86.5 (78, 95) 0.198Resp. rate, breaths/min 20 (18, 24) 20 (18, 22) 0.031*Body temperature, °C 37 (36.5, 37.4) 37.2 (36.9, 37.5) 0.145pO2, mmHg 83 (74.5, 100.5) 89.5 (84.5, 98.5) 0.124pCO2, mmHg 40 (36, 45) 37 (35, 39.3) <0.001*pH 7.5 (7.4, 7.5) 7.4 (7.4, 7.4) 0.002*WBC, ×109/L 12.7 (8.9, 19) 10.1 (6.8, 14.7) <0.001*RBC, ×1012/L 4.1 (3.6, 4.5) 3.7 (3.2, 4.4) 0.021*Hematocrit, % 0.4 (0.3, 0.4) 0.3 (0.3, 0.4) 0.019*Platelet, ×109/L 189 (145.8, 232) 152.5 (112.8, 207) 0.001*Neutrophils, % 0.9 (0.8, 0.9) 0.8 (0.7, 0.9) 0.001*hs-CRP, mol/L 2.6 (0.9, 6.4) 2.9 (1.3, 6.8) 0.268HbA1c, % 125.5 (111.8, 141.3) 120 (95.8, 133.3) 0.014*ALT, IU/L 49.8 (24.4, 285.7) 50.7 (28.2, 268.5) 0.225AST, IU/L 93.2 (26.2, 313.5) 39.9 (24, 182.5) <0.001*ALK-P, IU/L 65 (50.6, 83.5) 67.1 (54.1, 87) 0.49 γ-GT, IU/L 28.3 (18.2, 51.8) 30.3 (20.7, 52.6) 0.909 Total bilirubin, μmol/L 12.9 (10.1, 18.5) 17.1 (10.6, 25.5) 0.002* Direct bilirubin, μmol/L 4.3 (3.3, 6.8) 5.9 (3.7, 9.9) 0.001*Lipase, IU/L 92.9 (47.2, 209.3) 122.5 (55.6, 188.7) 0.793Amylase, IU/L 57.8 (44.9, 103.1) 72.5 (44.5, 108.2) 0.114Creatinine, IU/L 362.1 (125.3, 792.7) 238.3 (101.8, 991.6) 0.33 BUN, μmol/L 5.3 (4, 6.6) 4.7 (3.2, 6.4) 0.013* Creatinine, μmol/L 73.8 (57.1, 87.8) 60.4 (52.5, 79.3) 0.005*PT, seconds 15 (14.1, 16.1) 14.3 (13.6, 14.9) 0.001*APTT, seconds 35.2 (32.5, 39.3) 35 (33, 40.5) 0.279Glucose, mmol/L 6.9 (6.2, 8.5) 6.4 (5.7, 7.8) 0.015*Ca, mmol/L 2.2 (2, 2.3) 2.2 (2, 2.3) 0.264Na, mmol/L 138 (135.6, 140.4) 137 (134, 140.1) 0.391K, mmol/L 3.6 (3.3, 3.9) 3.9 (3.7, 4.3) <0.001*Chloride, mmol/L 104.8 (102.7, 107.8) 102.3 (100.4, 107.5) 0.071Mg, mmol/L 0.9 (0.8, 1) 0.9 (0.8, 1) 0.943SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; Resp rate: Respiratory Rate; hs-CRP: C-Reactive Protein; ALT: Alanine Transaminase; AST: Aspartate Transaminase; ALK-P: Alkaline Phosphatase; γ-GT: Gamma-Glutamyl Transferase; PT: Prothrombin Time; APTT: Activated Partial Thromboplastin Time; Ca: Calcium; Na: Sodium; K: Potassium; Mg: Magnesium. Data were summarized as median (IQR: Q1, Q3) for a given treatment group; Difference between within groups (pre-operation vs. post-operation) were compared using Wilcoxon signed-rank test; *p<0.05, significance within groups (preoperative vs. postoperative). TABLE 3. Safety outcomes before and after hemostatic agent treatment (n=62). 2024 Hepato-Gastroenterology 59 (2012) D Wang, F Lv, Y Luo, et al.creased post-treatment. Likewise, these documented de-creases and increases in variables were statistically sig- nificant (p<0.05, data not shown). In addition, there were significant differences (p<0.05) between variables in the hemostatic agent and surgi-cal treatment groups. At post-treatment, the hemostatic treatment and surgical groups had significant differenc-es in DBP, respiratory rate, WBC, amylase, BUN, PT, APTT and calcium levels (Table 4). DISCUSSION This study showed the benefit of hemostatic agents guided by CEUS for abdominal trauma. Most previous studies of hemostatic agent treatments for liver, kidney and spleen trauma were animal studies (3,7-9,11,15-17); most commonly rabbits, dogs, and pigs. For instance, in the study by Tang from 2010 (7), 30 rabbit livers were punctured and CEUS was used to inject hemocoagulase for treating liver hemorrhage. In the study from Li et al. (3), 12 dogs had blunt splenic injuries and received CEUS and contrast-enhanced computed tomography (CECT) examinations, and afterwards received hemocoagulase atrox and alpha-cyanoacrylate injections. More recently, hemocoagulase (18,19) and cyanoacrylate (9,20,21) have been used in patients for many purposes, including splen-ic trauma (12,22). Table 3 compared pre- and post- treatment chang-es of hemostatic agent treatment group. The hemostat-ic agent treatment group had some variables that were significantly different pre- and post-treatment. Howev-er we believed the hemostatic agents vital signs, arteri-al blood gases, hematological and electrolyte levels re-