Results of a randomized phase III/IV trial comparing intermittent bolus versus continuous infusion of antihaemophilic factor (recombinant) in adults with severe or moderately severe haemophilia A undergoing major orthopaedic surgery
Haemophilia : the official journal of the World Federation of Hemophilia. 2021
INTRODUCTION In patients with haemophilia A undergoing surgery, factor VIII (FVIII) replacement therapy by continuous infusion (CI) may offer an alternative to bolus infusion (BI). AIM: To compare the perioperative haemostatic efficacy and safety of antihaemophilic factor (recombinant) (ADVATE(®) ; Baxalta US Inc., a Takeda company, Lexington, MA, USA) CI or BI administration. METHODS In this multicentre, phase III/IV, controlled study (NCT00357656), 60 previously treated adult patients with severe or moderately severe disease undergoing elective unilateral major orthopaedic surgery (knee replacement, n = 48; hip surgery, n = 4; other, n = 8) requiring drain placement were randomized to receive antihaemophilic factor (recombinant) CI (n = 29) or BI (n = 31) through postoperative day 7. Primary outcome measure was cumulative packed red blood cell (PRBC)/blood volume in the drainage fluid within 24 h after surgery, used to establish non-inferiority of CI to BI. RESULTS CI:BI ratio of cumulative PRBC volume in the 24-h drainage fluid was 0.92 (p-value <.001 for non-inferiority; 95% confidence interval, 0.82-1.05). Total antihaemophilic factor (recombinant) dose per kg body weight received in the combined trans- and postoperative periods was similar with CI and BI to maintain targeted FVIII levels during/after surgery. Treatment-related adverse events (AEs) were reported in five patients treated by CI (eight events) and five treated by BI (six events), including two serious AEs in each arm. CONCLUSION CI administration of antihaemophilic factor (recombinant) is a viable alternative to BI in patients with haemophilia A undergoing major orthopaedic surgery, providing comparable efficacy and safety.
Autologous Fibrin Glue Versus Microsuture in the Surgical Reconstruction of Peripheral Nerves: A Randomized Clinical Trial
The Journal of hand surgery. 2021
PURPOSE This study compared the motor and sensory recovery and the operative time of autologous fibrin glue application with conventional microsuturing technique in repairing peripheral nerves at the forearm and wrist levels METHODS Eighty-five patients with injuries of the median, ulnar, or both nerves at the wrist and forearm levels underwent nerve repair between September 2014 and June 2018. Patients were randomly assigned at the time of diagnosis to a microsuture group (42 patients), in which standard epineurial microsurgical suturing was performed, or a fibrin glue group (43 patients), in which nerve repair was performed using autologous fibrin glue. The primary outcome measure was motor and sensory recovery. Operative time was the secondary outcome measure. Other outcome measures that were added post hoc, after trial initiation, included time to motor and sensory recovery; grip strength; pinch strength; Michigan hand outcome score; amplitude, latency, and duration of the compound motor unit action potential; and complications. All patients were followed up a minimum of 1 year. RESULTS At the final follow-up, both groups had regained similar motor and sensory function. The mean operative time was shorter in the fibrin glue group. Both groups had similar amplitude, latency, and duration of the compound motor unit action potential. Michigan Hand Outcome scores and mean percent recovery of grip strength and pinch strength were also similar. Six of 43 patients in the fibrin glue group compared with 8 of 42 patients in the microsuture group developed postoperative complications. CONCLUSIONS The use of fibrin glue to repair peripheral nerves is as effective as microsuturing in regaining motor and sensory functions and is associated with shorter operative time. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic II.
Is Intra-Articular Administration of Fibrinogen Effective in Postoperative Total Knee Arthroplasty Blood Loss? A Randomized Clinical Trial
Anesthesiology and pain medicine. 2021;11(1):e107431
OBJECTIVES The purpose of this study was to evaluate the effect of intra-articular injection of fibrinogen on postoperative bleeding following total knee arthroplasty. METHODS A double-blind randomized clinical trial was conducted on 40 patients aged 40 - 70 years under spinal anesthesia candidate for total knee arthroplasty in Golestan hospital, Ahwaz, Iran, in 2017-2018. Patients were divided into fibrinogen intra-articular injection (n = 20) and control (n = 20) groups. The amounts of blood loss and blood transfusion requirement were recorded. Hemoglobin (Hb), hematocrit (HCT), international normalized ratio (INR), platelet (PLT), prothrombin time (PT), and partial thromboplastin time (PTT) were recorded before and after the surgery. RESULTS There was no significant difference in the average amount of intraoperative blood loss between the groups (P > 0.05). The average amount of blood loss 24 hours after the surgery was significantly lower in the fibrinogen group than in the control group (fibrinogen group 350.61 ± 120.32 cc; control group 540.00 ± 170.21 cc; P = 0.0002). There were significant differences in transfusion between the groups (fibrinogen group 250 ± 20 cc; control group 350 ± 50 cc; P < 0.0001). There was a significant difference between the two groups in 24 h postoperative Hb and HCT (P < 0.001). CONCLUSIONS Intra-articular fibrinogen administration may reduce acute bleeding and can be used as an effective intervention to prevent further bleeding and the need for transfusion in patients undergoing total knee arthroplasty.
Current Concepts on Tissue Adhesive Use for Meniscal Repair-We Are Not There Yet: A Systematic Review of the Literature
The American journal of sports medicine. 2021;:3635465211003613
BACKGROUND Tissue adhesives (TAs) represent a promising alternative or augmentation method to conventional tissue repair techniques. In sports medicine, TA use has been suggested and implemented in the treatment of meniscal tears. The aim of this review was to present and discuss the current evidence and base of knowledge regarding the clinical usage of TAs for meniscal repair. STUDY DESIGN Systematic review; Level of evidence, 4. METHODS A systematic literature search was performed using the PubMed, Embase, and Cochrane Library databases for studies reporting on clinical outcomes of TA usage for meniscal repair in humans in the English language published before January 2020. RESULTS Ten studies were eligible for review and included 352 meniscal repairs: 94 (27%) were TA-based repairs and 258 (73%) were combined suture and TA repairs. Concomitant anterior cruciate ligament reconstruction was performed in 224 repairs (64%). All included studies utilized fibrin-based TA. Of the 10 studies, 9 were evidence level 4 (case series), and 8 reported on a cohort of ≤40 meniscal repairs. Rates of meniscal healing were evaluated in 9 of 10 studies, with repair failure seen in 39 repairs (11%). CONCLUSION The use of TAs, specifically fibrin-based TAs, for meniscal repair shows good results as either an augmentation or primary repair of various configurations of meniscal tears. However, this review reveals an absence of comparative high-quality evidence supporting the routine use of TAs for meniscal repair and emphasizes the lack of an ideal TA designed for that purpose. Further high-quality research, basic science and clinical, will facilitate the development of new materials and enable testing their suitability for use in meniscal repair.
A Prospective Randomized Controlled Trial of Aspiration and Fibrin Sealant Use Versus Aspiration Alone in the Treatment of Dorsal Wrist Ganglia
Plastic surgery (Oakville, Ont.). 2019;27(1):22-28
Purpose: Multiple treatments for dorsal wrist ganglia (DWG) exist but have high recurrence rates. We investigated whether aspiration followed by injection of Tisseel is more effective at reducing the DWG recurrence rate than aspiration alone. Methods: Adults with untreated DWG were randomly assigned to aspiration alone (A) or aspiration followed by Tisseel injection (AT). Patients were measured at baseline, 1, 6, and 12 months. Primary outcome was the rate of recurrence. Secondary outcomes included recurrent ganglion size and maximum pain experienced from the ganglion. Continuous data were compared with Student t tests and Mann-Whitney U tests. Categorical data were compared with chi(2) tests and Fisher exact tests. Treatment effect was reported as relative risk or mean differences (MD) with 95% confidence intervals. Results: Seventy-nine patients were randomized to the A (n = 39) or AT (n = 40) group. Twenty-five patients were lost to follow-up. There were no differences in recurrence risk between groups at 1, 6, or 12 months (P > .05). Ganglia were significantly smaller for both groups at 1 month versus baseline (P < .001). The A group demonstrated a significantly larger decrease in size at 1 month versus the AT group (MD = 0.75 cm(2), 95% confidence interval: 0.07-1.43, P = .03). Both groups experienced significantly less pain at 1, 6, and 12 months (P < .03), but this was not significantly different between groups. Conclusion: Aspiration and Tisseel injection does not decrease DWG recurrence versus aspiration alone. Both interventions produced a significant decrease in pain. Although aspiration alone carries a high recurrence risk, it may provide sufficient symptomatic relief for patients with DWG.
Prospective Study on the Impact of the Use of Human Fibrin Sealant free of Clot-Stabilizing Agents in Total Knee Arthroplasty
Revista brasileira de ortopedia. 2019;54(3):322-328
Objective The present study aimed to evaluate the results of the intraoperative topical use of a human fibrin sealant free of clot-stabilizing agents in total knee arthroplasties (TKAs), looking for differences between groups regarding blood loss, transfusion requirement, length of hospital stay, pain perception, range of motion (ROM), and incidence of complications. Methods We have analyzed prospectively an intervention group with 32 patients (Sealant) and a control group with 31 patients (Control) with symptomatic knee osteoarthritis who underwent TKA. Results The results were similar between the groups regarding visible blood loss in the drain in 24 hours (Control, 276.5 mL +/- 46.24 versus Sealant, 365.9 mL +/- 45.73), total blood loss in 24 hours (Control, 930 mL +/- 78 versus Sealant, 890 mL +/- 67) and in 60 hours after surgery (Control, 1,250 mL +/- 120 versus Sealant, 1,190 mL +/- 96), blood transfusion requirement (which occurred only in 1 control patient), length of hospital days stay (Control, 5.61 +/- 0.50 versus Sealant, 4.81 +/- 0.36), postoperative pain, and ROM. Sealant use was not related to wound healing complications, to infection, or to deep venous thrombosis. Conclusion We have concluded that the hemostatic agent composed of human fibrin was not effective in reducing bleeding volume and blood transfusion requirement, nor it interfered with hospital length of stay, pain perception, and ROM. Its use was not related to any complications.
A systematic review and meta-analysis of the topical administration of fibrin sealant in total hip arthroplasty
Scientific Reports. 2018;8((1)):78.
Patients who undergo total hip arthroplasty (THA) may experience a large amount of blood loss. The objective of our study is to include randomized controlled trials (RCTs) and compare the clinical outcomes of fibrin sealant (FS) versus placebo after a THA. In October 2015, we searched the following databases: Medline, Embase, PubMed, the Cochrane Controlled Trials Register, Web of Science, the China National Knowledge Infrastructure, the China Wanfang database and Google Scholar. Finally, seven studies that included 679 patients met the inclusion criteria. The meta-analysis indicated that the topical administration of FS was associated with a reduction of the need for transfusion compared to the control group (P = 0.05). And topical FS will reduce total blood loss after THA (P = 0.0003) and blood loss in drainage (P = 0.002). However, there was no significant difference in terms of the intraoperative blood loss (P = 0.62) and the rate of deep venous thrombosis (DVT), fever, pain, anemia, hematoma and oozing. In conclusion, the use of FS in patients who are undergoing THA may reduce perioperative blood loss and attenuate the decrease in Hb. Furthermore, FS do not decrease the intraoperative blood loss without an increase in the risk of postoperative DVT, fever, pain, anemia, hematoma and oozing.
The effect of a fibrin sealant on knee function after total knee replacement surgery. Results from the FIRST trial. A multicenter randomized controlled trial
Plos One. 2018;13((7)):e0200804.
BACKGROUND Total knee replacement (TKR) is increasingly performed in short term hospital stay, making same day mobilization an important issue is after surgery. This implies little joint effusion by reducing intra-articular blood loss, which will enhance knee range of motion. The application of a topical fibrin sealant on the intraoperative bare bone and synovial tissue may contribute to better early full mobilization and thus improved functional outcomes. Since ambulation with a fully extended knee is less strenuous, we hypothesized that patients who received fibrin sealant would demonstrate improved early knee extension after six weeks compared to patients who received standard care. METHODS A multicenter randomized controlled trial in a consecutive series of osteoarthritis patients scheduled for TKR surgery. Participants were randomized to receive fibrin sealant or not before closing the knee joint capsule. Primary outcome was change in knee extension angle( degrees ) at short term (2 weeks) follow-up (cExt). Secondary outcomes were 6-week extension angle, knee flexion angle, hemoglobin loss, blood transfusion rates, complication rates, the Knee Society Score, and the KOOS and EQ5D questionnaires. RESULTS When data on primary outcome became available from 250 patients, an interim analysis was performed by an independent Data Safety Monitoring Board for safety and effectivity assessment. This analysis showed that sufficient patients were included to detect a cExt of 10 degrees between both groups. Inclusion was stopped however, all in the meantime included patients were treated according to their randomization. A total of 466 were available for analysis. Both groups were comparable in terms of baseline characteristics. The estimated mean cExt difference was 0.2 degrees (95%CI -0.5 to 0.9). No differences in secondary outcomes were found. CONCLUSIONS No beneficial effects or side effects were found of a topically applied fibrin sealant during TKR surgery. These results discourage the clinical use of a fibrin sealant in TKR. TRIAL REGISTRATION Dutch Trial Register, NTR2500.
A systematic review and meta-analysis of the topical administration of fibrin sealant in total hip and knee arthroplasty
International Journal of Surgery (London, England). 2016;36((Pt A):):127-137
OBJECTIVE To evaluate the efficacy and safety of fibrin sealant for the reduction of postoperative blood loss and transfusion requirements in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS Electronic databases including PubMed, Embase, CENTRAL (Cochrane Controlled Trials Register), Web of Science and Google Scholar were searched from database inception to February 2016. All randomized controlled trials evaluating the efficacy and safety of topical administration of fibrin glue during primary THA or TKA were included in our meta-analysis. Transfusion requirements, total blood loss, length of hospital stay and the occurrence of infection were calculated using Stata 12.0 software. RESULTS A total of nineteen clinical trials with 1489 patients (405 hips and 1084 knees) were finally included for meta-analysis. The results indicated that the topical administration of fibrin sealant can decrease the need for transfusion (RR = 0.33, 95%CI 0.28-0.40, P < 0.001), total blood loss (MD = -138.25, 95% CI -203.49 to -75.00), blood loss in drainage (MD -321.44, 95% CI -351.96 to -290.92, P < 0.001) and hospital stay length (MD -0.98, 95% CI -1.35 to -0.62, P < 0.001) without increasing the occurrence of infection (RR = 0.87, 95% CI 0.33 to 2.27, P = 0.775). CONCLUSION The topical use of fibrin sealant can effectively reduce the need for transfusion, total blood loss and the volume of drainage without increasing the rate of infection.
The efficiency and safety of fibrin sealant for reducing blood loss in primary total hip arthroplasty: a systematic review and meta-analysis
International Journal of Surgery (London, England). 2016;37:50-57.
OBJECTIVE Total hip arthroplasty (THA) is associated with substantial blood loss. The objective of present systematic review and meta-analysis is to provide evidence from randomized controlled trials (RCTs) on the efficiency and safety of administration of fibrin sealant (FS) for reducing blood loss in patients undergoing primary THA. METHODS Potential relevant studies were identified from electronic databases including Medline, PubMed, Embase, ScienceDirect, web of science and Cochrane Library. Gray academic studies were also identified from the reference list of included studies. There was no language restriction. Pooling of data was carried out by using RevMan 5.1. RESULTS Six randomized controlled trials (RCTs) met the inclusion criteria. Current meta-analysis indicated that there were significant differences in terms of total blood loss (MD = -153.77, 95% CI: -287.21 to -20.34, P = 0.02), postoperative hemoglobin level (MD = -0.25, 95% CI: -0.46 to -0.05, P = 0.02) and transfusion rate (RD = -0.12, 95% CI: -0.22 to -0.03, P = 0.01) between groups. No significant differences were found regarding the incidence of deep venous thrombosis (DVT) (RD = 0.00, 95% CI: -0.01to 0.01, P = 0.51) or other side effects. CONCLUSION Administration of fibrin sealant in total hip arthroplasty may reduce total blood loss, postoperative hemoglobin decline and transfusion requirements. Moreover, no adverse effect was related to FS. Due to the limited quality of the evidence currently available, higher quality RCTs are required.