BACKGROUND: Significant blood loss is still one of the most frequent complications in spinal surgery, which often necessitates blood transfusion. Massive perioperative blood loss and blood transfusion can create additional risks. Aprotinin, tranexamic acid (TXA), and epsilon-aminocaproic acid (EACA) are antifibrinolytics currently offered as prophylactic agents to reduce surgery-associated blood loss. The aim of this study was to evaluate the efficacy and safety of aprotinin, EACA, and low/high doses of TXA in spinal surgery, and assess the use of which agent is the most optimal intervention using the network meta-analysis (NMA) method. METHODS: Five electronic databases were searched, including PubMed, Cochrane Library, ScienceDirect, Embase, and Web of Science, from the inception to March 1, 2018. Trials that were randomized and compared results between TXA, EACA, and placebo were identified. The NMA was conducted with software R 3.3.2 and STATA 14.0. RESULTS: Thirty randomized controlled trial (RCT) studies were analyzed. Aprotinin (standardized mean difference [SMD]=-0.65, 95% credibility intervals [CrI;-1.25, -0.06]), low-dose TXA (SMD = -0.58, 95% CrI [-0.92, -0.25]), and high-dose TXA (SMD = -0.70, 95% CrI [-1.04, -0.36]) were more effective than the respective placebos in reducing intraoperative blood loss. Low-dose TXA (SMD = -1.90, 95% CrI [-3.32, -0.48]) and high-dose TXA (SMD = -2.31, 95% CrI [-3.75, -0.87]) had less postoperative blood loss. Low-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) and high-dose TXA (SMD = -1.07, 95% CrI [-1.82, -0.31]) significantly reduced total blood loss. However, only high-dose TXA (SMD = -2.07, 95% CrI [-3.26, -0.87]) was more effective in reducing the amount of transfusion, and was significantly superior to low-dose TXA in this regard (SMD = -1.67, 95% CrI [-3.20, -0.13]). Furthermore, aprotinin (odds ratio [OR] = 0.16, 95% CrI [0.05, 0.54]), EACA (OR = 0.46, 95% CrI [0.22, 0.97]) and high dose of TXA (OR = 0.34, 95% CrI [0.19, 0.58]) had a significant reduction in transfusion rates. Antifibrinolytics did not show a significantly increased risk of postoperative thrombosis. Results of ranking probabilities indicated that high-dose TXA had the greatest efficacy and a relatively high safety level. CONCLUSIONS The antifibrinolytic agents are able to reduce perioperative blood loss and transfusion requirement during spine surgery. And the high-dose TXA administration might be used as the optimal treatment to reduce blood loss and transfusion.
Aminocaproic Acid ; therapeutic use ; Antifibrinolytic Agents ; therapeutic use ; Aprotinin ; therapeutic use ; Humans ; Randomized Controlled Trials as Topic ; Spine ; surgery ; Tranexamic Acid ; therapeutic use

OBJECTIVE: To systematically evaluate the hemostatic efficacy of tranexamic acid and ε-aminocaproic acid in total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: Randomized controlled trials (RCT) and retrospective case-control studies about tranexamic acid and ε-aminocaproic acid for the comparison of THA or TKA were searched electronically in PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP from the time of building databases to July 2020. Two investigators carried out literature screening and data extraction according to the inclusion and exclusion criteria respectively. The methodological quality of the included randomized controlled studies was evaluated through the Cochrane Handbook, and the methodological quality of the included retrospective case-control studies was evaluated through the NOS scale. Blood loss, the incidence of thrombosis complications, per capita input of hemoglobin were Meta-analyzed by Review Manager 5.3 software. RESULTS: A total of 6 articles were included, including 4 RCTs and 2 retrospective case-control studies. A total of 3 174 patients, including 1 353 in the tranexamic acid group and 1 821 in the ε-aminocaproic acid group. Meta-analysis results showed that there were no difference statistical significance in blood loss [MD=-88.60, 95%CI(-260.30, 83.10), P=0.31], blood transfusion rate [OR=1.48, 95%CI(0.96, 2.27), P=0.08], thrombotic complications [OR=0.80, 95%CI(0.07, 8.83), P=0.85], per capita hemoglobin input [MD=0.04, 95%CI(-0.02, 0.10), P=0.18] between tranexamic acid group and ε-aminocaproic acid group during THA. While in TKA, the blood loss of the tranexamic acid group was less than that of the ε-aminocaproic acid group [MD=-147.13, 95%CI(-216.52, -77.74), P<0.0001], the difference was statistically significant. The blood transfusion rate [OR=1.30, 95%CI(0.74, 2.28), P=0.37], thrombotic complications [OR=0.95, 95%CI(0.38, 2.36), P=0.92], per capita hemoglobin input [MD=-0.00, 95%CI(-0.05, 0.06), P=0.48], tourniquet time [MD=1.54, 95%CI(-2.07, 5.14), P=0.40] were similar between two groups, the difference was not statistically significant. CONCLUSION In THA, tranexamic acid and ε-aminocaproic acid have similar hemostatic effects, while in TKA, tranexamic acid can effectively reduce the patient's blood loss and has a better hemostatic effect. Tranexamic acid is recommended as one of the first choice hemostatic drugs for TKA.
Aminocaproic Acid/therapeutic use* ; Antifibrinolytic Agents/therapeutic use* ; Arthroplasty, Replacement, Hip/methods* ; Arthroplasty, Replacement, Knee/methods* ; Blood Loss, Surgical/prevention & control* ; Hemoglobins ; Hemostatics ; Humans ; Tranexamic Acid/therapeutic use*

OBJECTIVETo investigate the effect of intravesical instillation of antifibrinolytic agents with bacillus Calmette-Guerin (BCG) on preventing recurrence of superficial bladder transitional cell carcinoma (BTCC) after surgical management.

METHODSA total of 326 cases of superficial BTCC undergoing transurethral resection of bladder tumor (TURBT) or partial cystectomy were divided into 5 groups. Then the different dosage BCG with or without antifibrinolytic agents was regular instilled into bladders (once a week, then once a month after 6 times). Group A including 66 cases received intravesical instillation of 100-120 mg BCG plus 100 mg para-aminomethyl benzoic acid (PAMBA). Group B including 64 cases: instillation of 50-60 mg BCG plus 100 mg PAMBA; Group C including 65 cases: 100-120 mg BCG plus 2.0 g epsilon-aminocaproic acid (EACA); Group D including 64 cases: 50-60 mg BCG plus 2.0 g EACA; Group E (control group) including 67 cases: 100-120 mg BCG. All the cases had been followed up for 4 to 69 months (mean, 28.5 months). Not only was cystoscopy performed every 3 months, but also biopsy was carried out to identify recurrence when necessary. Side effect was recorded after instillation.

RESULTSThe rate of tumor recurrence of Group A, Group B, Group C and Group D was 12%, 10%, 9%, 9% respectively, which was significantly lower than that of Group E (30%) (chi(2) = 5.699, 6.818, 7.380, 7.867, P = 0.017, 0.009, 0.007, 0.005). And there was no significant difference of tumor recurrence rate between Group A and Group B or between Group C and Group D (Group A and Group C: high dosage BCG plus antifibrinolytic agents, while Group B and Group D: low dosage BCG plus antifibrinolytic agents) (P > 0.05). But the side effects developing in Group B and Group D after BCG instillation were less than those in Group A and Group C.

CONCLUSIONSThe efficacy of BCG on prevention the recurrence of superficial BTCC can be enhanced when combined with antifibrinolytic agents. Even if the dosage of BCG was reduced by half, the efficacy didn't changed. A new approach of low dosage BCG plus antifibrinolytic agents is recommended in the prophylaxis of recurrence of bladder cancer.

4-Aminobenzoic Acid ; administration & dosage ; Adjuvants, Immunologic ; therapeutic use ; Administration, Intravesical ; Adult ; Aged ; Aged, 80 and over ; Aminocaproic Acid ; administration & dosage ; Antifibrinolytic Agents ; therapeutic use ; BCG Vaccine ; therapeutic use ; Carcinoma, Transitional Cell ; drug therapy ; surgery ; Combined Modality Therapy ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Urinary Bladder Neoplasms ; drug therapy ; surgery ; para-Aminobenzoates