Risk Factors for Post-Colorectal Endoscopic Submucosal Dissection Bleeding and Efficacy of Carbazochrome Sodium Sulfonate: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Carbazochrome sodium sulfonate (CSS) is a hemostatic agent that reduces capillary permeability and enhances capillary resistance. However, its specific effects on colorectal endoscopic submucosal dissection (ESD) outcomes remain uncertain. This study aimed to assess the risk factors for post-ESD bleeding and the effect of CSS on colorectal ESD outcomes. METHODS: First, we retrospectively analyzed the risk factors for post-ESD bleeding using data from 1,315 lesions in 1,223 patients who underwent ESD for superficial colorectal neoplasms at eight institutions. Second, patients were divided into CSS and non-CSS groups using propensity score matching, and their outcomes from colorectal ESD were analyzed. RESULTS: The risk factors for post-colorectal ESD bleeding were identified as age of ≥70 years, tumor located in the rectum, tumor size of ≥40 mm, and post-ESD defect unclosure in both univariate and multivariate analyses. The CSS and non-CSS groups each consisted of 423 lesions after propensity score matching. The post-colorectal ESD bleeding rate was 3.5% (15/423) and 3.3% (14/423) in the CSS and non-CSS groups, respectively, indicating no significant differences. Among patients with the high-risk factors for post-ESD bleeding, the administration of CSS also did not demonstrate a significant reduction in the post-ESD bleeding rate compared to the non-CSS group. CONCLUSION: CSS administration is ineffective in preventing post-colorectal ESD bleeding in both the general population and individuals at a high risk for such bleeding. Our results indicate the necessity to reconsider the application of CSS for preventing post-colorectal ESD bleeding.

Carbazochrome sodium sulfonate and tranexamic acid combination therapy to reduce blood transfusions after 24 h of injury: A retrospective study.

Aim: Reducing the blood transfusion volume is important in severe trauma. We hypothesized that carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) would reduce blood transfusions in severe trauma. Methods: From April 2017 to March 2023, data were collected from patients (aged ≥16 years) admitted to our hospital for trauma and administered packed red blood cells (pRBC) and plasma transfusions within 12 h postinjury. Patients infused with CSS and TXA (CSS + TXA group) were compared with those infused with TXA alone (TXA group). The outcomes were blood product transfusion volumes within and after 24 h, the number of patients receiving >6 units of pRBC transfusion after 24 h, duration of intensive care unit and in-hospital stays, and 28-day in-hospital mortality. Results: In total, 138 patients were included in the study. In the univariate analyses, the CSS + TXA group (n = 62) showed a significant reduction in the total pRBC transfusion volume, in-hospital days, and number of patients receiving >6 units of pRBCs in the delayed phase. Based on the multivariate logistics regression analysis, only the CSS + TXA group had a significantly lower adjusted odds ratio for receiving >6 units of pRBC transfusion after 24 h. During the in-hospital days, the CSS + TXA group did not experience an increased incidence of major complications when compared with the TXA group. Conclusion: In patients with trauma, treatment with CSS with TXA may reduce the requirement for blood transfusion after 24 h. Moreover, this treatment can improve admission outcomes without increasing complications.

Micelle-mediated chemiluminescence of 6-aza-2-thiothymine-protected gold nanoclusters for carbazochrome sodium sulfonate detection.

Chemiluminescence (CL) intensity of luminol-H2O2 system was dramatically enhanced by cetyltrimethylammonium bromide (CTAB) micelle-mediated 6-aza-2-thiothymine-protected gold nanoclusters (ATT-AuNCs). It is proved that spherical micelles of CTAB in aqueous solution improved the dispersity of ATT-AuNCs, thus enhancing their catalytic activity, which brought in the increased CL intensity of luminol-H2O2 system. Carbazochrome sodium sulfonate (CSS) with a hemostatic containing tetrahydroindole structure broke the spherical micelles and notably quenched the CL intensity of luminol-H2O2-CTAB-ATT AuNCs system. Based on these results, a simple, fast, and sensitive CL method has been developed for the detection of CSS with a linear range of 0.25-25 µM and a detection limit of 0.11 µM. The method has also been successfully applied to the determination of CSS in serum with satisfied recoveries in the range of 89.6 % to 103.7 %. This study not only provides an effective approach for CSS detection but also paves the way for AuNCs-based CL applications.

Comparative study of carbazochrome sodium sulfonate and tranexamic acid in reducing blood loss and inflammatory response following direct anterior total hip arthroplasty: a prospective randomized controlled trial.

PURPOSE: Carbazochrome sodium sulfonate (CSS) is a haemostatic agent. However, its hemostatic and anti-inflammatory effects in patients undergoing total hip arthroplasty (THA) via a direct anterior approach (DAA) are unknown. We investigated the efficacy and safety of CSS combined with tranexamic acid (TXA) in THA using DAA. METHODS: This study enrolled 100 patients who underwent primary, unilateral THA through a direct anterior approach. Patients were randomly divided into two groups: Group A used a combination of TXA and CSS, while Group B used TXA only. The primary outcome was total perioperative blood loss. The secondary outcomes were hidden blood loss, postoperative blood transfusion rate, inflammatory reactant levels, hip function, pain score, venous thromboembolism (VTE), and incidence of associated adverse reactions. RESULTS: The total blood loss (TBL) in group A was significantly lower than in group B. The levels of inflammatory reactants and the rate of blood transfusion were also significantly lower. However, the two groups had no significant differences in intraoperative blood loss, postoperative pain score, or joint function. There were no significant differences in VTE or postoperative complications between the groups. CONCLUSION: As a haemostatic agent, CSS combined with TXA can reduce postoperative blood loss in patients undergoing THA via DAA and seems to have an anti-inflammatory effect. Moreover, it did not increase the incidence of VTE or its related complications.

Effect of Carbazochrome Sodium Sulfonate in Addition to Tranexamic Acid in Bleeding Trauma Patients.

BACKGROUND: It is important to evaluate the effects of drugs considered to control hemorrhage. Tranexamic acid (TXA) has been shown to reduce the risk of death in bleeding trauma patients. Carbazochrome sodium sulfonate (CSS) is often used in combination with TXA; however, it is unknown whether CSS additionally improves the control of bleeding in trauma patients. METHODS: The aim of this study was to examine whether CSS reduces blood transfusion and death in addition to TXA by improving the control of bleeding. We retrospectively analyzed medical records of trauma patients from 2011 to 2019. We included patients aged ≥16 years, with significant hemorrhage, and who received TXA within eight hours from injury as per CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) study. The primary outcome was the total amount of red blood cells (RBC), fresh frozen plasma (FFP), and platelet concentrate (PC) received within the first 24 hours from injury. Secondary outcomes were death in hospital within four weeks after injury, vascular occlusive events, and treatment. RESULTS: During this retrospective evaluation period, 5764 admissions with trauma were registered. A total of 326 cases met the selection criteria: 259 cases who received CSS in addition to TXA (CSS group; n=259) and 67 cases who received only TXA (no-CSS group; n=67). The mortality rate was 6% in the no-CSS group and 15.1% in the CSS group. There was no significant difference in mortality and vascular occlusive events between the two groups. We performed multiple regression analyses, with the amount of blood transfusion for each type as explanatory variables. The administration of CSS was an independent factor for the reduction of RBC transfusion (standard partial regression coefficient -0.1, 95% CI [-3.1 to -0.1], p=0.04), but not for transfusion of FFP or PC. We also performed multiple logistic regression analysis, with death as an explanatory variable. CSS was not an independent factor for any cause of death. CONCLUSION: CSS decreased RBC transfusion in trauma patients, without increasing the risk of vascular occlusion. However, CSS did not decrease mortality. This study can contribute to managing bleeding with trauma, but further research aimed at clarifying the effect of CSS is needed.

Effects of carbazochrome sodium sulfonate combined with tranexamic acid on hemostasis and inflammation during perioperative period of total hip arthroplasty: A randomized controlled trial.

BACKGROUND: The hemostatic effect of tranexamic acid (TXA) combined with carbazochrome sodium sulfonate (CSS) in total hip arthroplasty (THA) has not been determined. Therefore we performed a randomized study aiming to evaluate the effects of CSS combined with TXA on perioperative blood loss and inflammatory response of THA. HYPOTHESIS: CSS combined with TXA can effectively reduce perioperative blood loss and immune response compared to TXA. MATERIAL AND METHODS: This randomized placebo-controlled trial assigned 150 patients undergoing unilateral primary total hip arthroplasty who underwent direct anterior approach surgery to 3 groups: group A received TXA plus topical CSS; group B received TXA only; and group C received placebo. The main outcome was total blood loss. Secondary outcomes included reduction in hemoglobin concentration, coagulation parameters, inflammatory marker levels, perioperative visual analog scale (VAS) pain score, transfusion rates, postoperative hospital stay, and incidence of thromboembolic events. RESULTS: Total blood loss in group A (668.84±230.95ml) was lower than in group B (940.96±359.22ml) and C (1166.52±342.85ml, p<0.05). We also found that compared with group B, postoperative hip pain, biomarker level of inflammation, visual analogue score (VAS) pain score in group A were significantly improved. The transfusion rate and unit of group A were significantly lower than group C (8 patients; 17.5 units), but there was no statistical difference between group A (no transfusion) and group B (2 patients; 4 units). No differences were observed in thromboembolic and other outcomes among the groups. DISCUSSION: The combined application of topic CSS and TXA is more effective than TXA alone following THA in regard of reducing total blood loss. In addition, CSS combined with TXA is better than TXA alone in terms of improving postoperative hip pain and reducing the level of inflammatory factors. LEVEL OF EVIDENCE: I; randomized controlled study.

Effect of carbazochrome sodium sulfonate combined with tranexamic acid on blood loss and inflammatory response in patients undergoing total hip arthroplasty.

AIMS: The purpose of this study was to examine the efficacy and safety of carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) on blood loss and inflammatory responses after primary total hip arthroplasty (THA), and to investigate the influence of different administration methods of CSS on perioperative blood loss during THA. METHODS: This study is a randomized controlled trial involving 200 patients undergoing primary unilateral THA. A total of 200 patients treated with intravenous TXA were randomly assigned to group A (combined intravenous and topical CSS), group B (topical CSS), group C (intravenous CSS), or group D (placebo). RESULTS: Mean total blood loss (TBL) in groups A (605.0 ml (SD 235.9)), B (790.9 ml (SD 280.7)), and C (844.8 ml (SD 248.1)) were lower than in group D (1,064.9 ml (SD 318.3), p < 0.001). We also found that compared with group D, biomarker level of inflammation, transfusion rate, pain score, and hip range of motion at discharge in groups A, B, and C were significantly improved. There were no differences among the four groups in terms of intraoperative blood loss (IBL), intramuscular venous thrombosis (IMVT), and length of hospital stay (LOS). CONCLUSION: The combined application of CSS and TXA is more effective than TXA alone in reducing perioperative blood loss and transfusion rates, inflammatory response, and postoperative hip pain, results in better early hip flexion following THA, and did not increase the associated venous thromboembolism (VTE) events. Intravenous combined with topical injection of CSS was superior to intravenous or topical injection of CSS alone in reducing perioperative blood loss. Cite this article: Bone Joint Res 2021;10(6):354-362.

Hemostatic and Anti-Inflammatory Effects of Carbazochrome Sodium Sulfonate in Patients Undergoing Total Knee Arthroplasty: A Randomized Controlled Trial.

BACKGROUND: Postoperative recovery after total knee arthroplasty (TKA) is associated with postoperative anemia, allogeneic transfusion, and stress immune responses to surgery. Carbazochrome sodium sulfonate (CSS) reduces bleeding through several mechanisms. We assessed the effect of CSS combined with tranexamic acid (TXA) on postoperative anemia, blood transfusion, and inflammatory responses. METHODS: This study was designed as a randomized, placebo-controlled trial of 200 patients undergoing unilateral primary TKA. Patients were divided into 4 groups: group A received TXA plus topical and intravenous CSS; group B received TXA plus topical CSS only; group C received TXA plus intravenous CSS only; group D received TXA only. RESULTS: Total blood loss in groups A (609.92 ± 221.24 mL), B (753.16 ± 247.67 mL), and C (829.23 ± 297.45 mL) was lower than in group D (1158.26 ± 334.13 mL, P < .05). There was no difference in total blood loss between groups B and C. We also found that compared with group D, the postoperative swelling rate, biomarker level of inflammation, visual analog scale pain score, and range of motion at discharge in groups A, B, and C were significantly improved (P < .05). No thromboembolic complications occurred. There were no differences in transfusion rate, intraoperative blood loss, platelet count, or average length of stay among the 4 groups (P > .05). CONCLUSION: CSS combined with TXA was more effective than TXA alone in reducing perioperative blood loss and inflammatory response and did not increase the incidence of thromboembolism complications.

Effect of tranexamic acid combined with carbazochrome sodium sulfonate on blood loss and safety after total knee arthroplasty / 中国组织工程研究

BACKGROUND: The application of tranexamic acid in knee and hip arthroplasty can reduce blood loss safely and effectively. As a kind of hemostatic agent for strengthening blood vessels, the hemostasis process of carbazochrome sodium sulfonate does not depend on the coagulation system of human body, so it has better security. OBJECTIVE: To explore the safety and blood loss of tranexamic acid combined with carbazochrome sodium sulfonate in total knee arthroplasty. METHODS: From July 2018 to December 2019, 67 patients with knee osteoarthritis were selected from the Affiliated Hospital of Xuzhou Medical University, including 18 males and 49 females. They were randomly divided into two groups. The observation group (n=32) received intravenous injection of tranexamic acid before total knee arthroplasty, followed by intravenous injection of carbazochrome sodium sulfonate after total knee arthroplasty. The control group (n=35) received intravenous injection of tranexamic acid before total knee arthroplasty, followed by intravenous injection of saline after total knee arthroplasty. The total blood loss, hidden blood loss, maximum hemoglobin drop, blood transfusion rate, incidence of thrombotic events (lower limb intermuscular vein thrombosis, deep vein thrombosis and pulmonary embolism), perioperative fibrinolytic parameters (fibrin and fibrinogen degradation products, D-dimer), inflammation markers (C-reactive protein, interleukin-6) were compared between the two groups. The study was approved by Medical Ethics Committee of Affiliated Hospital of Xuzhou Medical University. RESULTS AND CONCLUSION: (1) The decrease of total blood loss, hidden blood loss and maximum hemoglobin drop in the observation group was less than those in the control group (P 0.05). (3) The C-reactive protein level of the observation group was lower than that of the control group on day 1 and day 3 after surgery (P 0.05). (4) There was no blood transfusion, deep venous thrombosis of lower limbs or pulmonary embolism in the two groups during their hospitalization. (5) The results showed that tranexamic acid combined with carbazochrome sodium sulfonate can further reduce the total blood loss, hidden blood loss and hemoglobin drop of patients after total knee arthroplasty, reduce the inflammatory reaction, and do not increase the risk of thrombosis, so it was safe.

Stability Analysis of Levofloxacin Hydrochloride and Carbazochrome Sodium Sulfonate in 0.9% Sodium Chloride Injection / 中国药房

OBJECTIVE:To explore the stability of levofloxacin hydrochloride and carbazochrome sodium sulfonate in 0.9%So-dium chloride injection,and provide reference for their compatible use in clinic. METHODS:HPLC was performed on the column of Phenomenex Gemini C18 with mobile phase A of acetonitrile and B of 0.01 mol/L Ammonium biphosphate solution(adjusted to pH 3.0 with phosphoric acid)(gradient elution)at a flow rate of 1.0 ml/min,the detection wavelength was 295 nm for levofloxa-cin hydrochloride and 364 nm for carbazochrome sodium sulfonate,temperature was 30 ℃,and the injection volume was 20 μl. The changes of contents,appearance and pH value of the solution in the mixture were investigated. RESULTS:The linear range was 7.03-80.06 μg/mL for levofloxacin hydrochloride(r=0.9995)and 1.70-34.04 μg/mL for carbazochrome sodium sulfonate(r=0.9998);RSDs of precision and reproducibility tests were no more than 2.0%;recoveries were 98.75%-100.63%and 98.00%-100.83%, and RSDs were 0.65% and 0.99%(n=9),respectively. In normal temperature,the contents of levofloxacin hydrochloride and car-bazochrome sodium sulfonate after mixing with 0.9% Sodium chloride injection within 6 h showed no significant decrease,and the appearance and pH value showed no obvious changes. CONCLUSIONS:The mixing of levofloxacin hydrochloride and carbazo-chrome sodium sulfonate with 0.9% Sodium chloride injection in room temperature is stable within 6 h,they can compatibly use synergistically in clinic.

Quality Analysis of Carbazochrome Sodium Sulfonate Injection in National Assessment Programs / 中国药师

Objective:To evaluate the quality of carbazochrome sodium sulfonate Injection from different manufacturers, analyze the existing problems and provide the reference for the improvement of clinical medication safety. Methods:Statutory testing methods and the exploratory research methods were used to examine the samples, and the quality status of carbazochrome sodium sulfonate Injec-tion was evaluated according to the results. Results:Totally 89 batches of the samples were tested by the current standard. The quali-fied rate was 97. 8%, and the two batches of unqualified samples were carbazochrome sodium sulfonate and sodium chloride Injection with unqualified insoluble particles. Overall, the quality risk of carbazochrome sodium sulfonate for injection was low, and the safety of carbazochrome sodium sulfonate and sodium chloride Injection needed further research. Conclusion:The quality of carbazochrome so-dium sulfonate Injection basically meets the current standard, and the exploratory research suggests that the current standard is imper-fect. It is urgent to improve the related substance detection in the standard and determine the reasonable limits for the degradation im-purities and the other impurities. The clinical medication safety of carbazochrome sodium sulfonate and sodium chloride Injection needs further research.

Optimization of solid phase extraction clean up and validation of quantitative determination of carbazochrome sodium sulfonate in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry.

A mixed-mode anion exchange solid phase extraction (SPE) method for extraction and clean up of carbazochrome sodium sulfonate (CSS) and (1S)-(+)-10-camphorsulfonic acid (IS) was optimized for quantification by high-performance liquid chromatography/negative electrospray ionization mass spectrometry. The analytes were extracted from 1mL of human plasma via SPE on Oasis(®) WAX cartridge. Chromatographic separation was achieved on a Zorbax SB-Aq (4.6×250mm, 5µm) column under an isocratic condition. Detection was performed using electrospray ionization in negative ion multiple reaction monitoring (MRM) mode. The deprotonated precursor to product ion transitions monitored for CSS and IS was at m/z 299.0→256.0 and m/z 230.9→79.8, respectively. The method was fully validated for its selectivity, sensitivity, precision, accuracy, recovery, matrix effect and stability. Linear range was 0.189-37.8ng/mL with a high square regression coefficient (r=0.9995). The intra-and inter-day precision (RSD, %) ranged from 0.95% to 4.17%, and the intra-and inter-day accuracy was between 95.03% and 105.9%. This method was successfully applied to a bioequivalence study of 90mg CSS formulation in 18 healthy Chinese male subjects under fasting condition.

Determination of related substances in carbazochrome sodium sulfonate injection by HPLC / 中国药学杂志

OBJECTIVE: To develop a method for separating and determining the related substances in carbazochrome sodium sulfonate injection. METHODS: HPLC Gradient elution was performed on an HP-ODS Hypersil colum. The mixture of 0.01 mol·L-1 phosphate buffer (pH 3.0) and acetonitrile (94:6) was used as mobile phase A, and acetonitrile as mobile phase B. The flow rate was 1.0 mL·min-1, the detection wavelength was set at 220 nm. RESULTS: After being treated with acid, base, heat and oxidation, carbazochrome sodium sulfonate underwent more or less degradation, the degradation products could be detected by the proposed method. Among the practical carbazochrome sodium sulfonate injection and carbazochrome sodium sulfonate and sodium choloride injection samples, the thermo degradation impurities but no impurities resulted from other treatments were detected in carbazochrome sodium sulfonate injections and carbazochrome sodium sulfonate sodium chloride injections. CONCLUSION: The proposed method can be used to separate and determine the related substances in carbazochrome sodium sulfonate injection, and is suitable for the quality control of this drug.

Pharmacokinetics of carbazochrome sodium sulfonate in rabbits given by needle-free injection / 中国药学杂志

OBJECTIVE: To research the pharmacokinetic characteristics of carbazochrome sodium sulfonate given by needle-free injection in rabbits, to compare it with that of carbazochrome sodium sulfonate given by traditional syringe injection. METHODS: Japanese big ear white rabbits were administered carbazochrome sodium sulfonate solution by needle-free injection and intramuscular injection with needle syringe. Plasma samples were extracted and assayed by high performance liquid chromatography technology. The mobile phase was composed of 0.12% NH4H2PO4 and acetonitrile (91:9), and the detection wave length was 363 nm. RESULTS: The measured blood drug concentration-time data was fitted by DAS 2.1.1 pharmacokinetic software. The pharmacokinetic processes of carbazochrome sodium sulfonate given by both needle-free injection and intramuscular injection were in line with one-compartment model, and the major pharmacokinetic parameters AUC0-t, tmax, ρmax and t1/2 were (162.43±17.09)μg · min · mL-1, (5.00±1.41) min, (5.93±0.02)μg · mL-1, (23.54±3.89) min and (180.82±15.29)μg · min · mL-1, (23.00±2.01) min, (5.09±0.29)μg · mL-1 and (18.28±2.47) min, respectively. CONCLUSION: Compared with the traditional needle syringe injection, the peak time was significantly shortened and the peak concentration was increased with needle-free injection, while the other pharmacokinetic parameters showed no statistically significant difference, which indicated that carbazochrome sodium sulfonate given by needle-free injection may have similar effect with that of traditional injection.

Determination of Carbazochrome Sodium Sulfonate in Carbazochrome Sodium Sulfonate for Injection by HPLC / 中国药房

OBJECTIVE:To establish a method for determination of carbazochrome sodium sulfonate for injection.METH_ ODS:C 18 was used as chromatographic column;the mobile phase consisted of0.12%ammonium dihydrogen phosphate buffer solution-absolute alcohol(925∶75)with detection wavelength at363nm and flow rate at0.8ml/min.The sample size was10?l and the column temperature was25℃.RESULTS:Linear relation was achieved when the concentration of carbzochrome sodium sulfonate was within the range of0.08865mg/ml～0.4432mg/ml(r=0.9999,n=5).The mean recovery rate was99.89%(RSD=1.53%,n=9).CONCLUSION:This method is simple,rapid,accurate,precise,and which can be used as the quality control of carbzochrome sodium sulfonate for injection.