Combined Intravenous Research Articles

Low incidence of acute kidney injury with combined intravenous and topical antibiotic infusions in periprosthetic joint infection after total knee arthroplasty.

This study aimed to assess the risk of acute kidney injury (AKI) associated with combined intravenous (IV) and topical antibiotic therapy in patients undergoing treatment for periprosthetic joint infections (PJIs) following total knee arthroplasty (TKA), utilizing the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for classification. We conducted a retrospective analysis of 162 knees (162 patients) that received treatment for PJI post-TKA with combined IV and topical antibiotic infusions at a single academic hospital from 1 January 2010 to 31 December 2022. The incidence of AKI was evaluated using the KDIGO criteria, focussing on the identification of significant predictors and the temporal pattern of AKI development. AKI was identified in 9.26% (15/162) of the cohort, predominantly presenting as stage 1 AKI, which was transient in nature and resolved prior to discharge. The analysis highlighted moderate anaemia and lower baseline serum creatinine levels as significant predictors for the development of AKI. Notably, the study found no instances of severe complications such as wound dehiscence, skin erosion, or the need for haemodialysis following treatment. The findings suggest that the combined use of IV and topical antibiotic therapy in the management of PJIs post-TKA is associated with a low incidence of primarily transient stage 1 AKI. This indicates a potentially favourable renal safety profile, advocating for further research to confirm these outcomes and potentially influence treatment protocols in PJI management.

Comparative effectiveness of combined peri-articular and intra-articular injection versus intravenous and intra-articular injection of tranexamic acid in total knee arthroplasty: a randomized controlled trial study.

Tranexamic acid (TXA) administration is supported by numerous evidence in reducing blood loss after total knee arthroplasty (TKA). The combination of intravenous (IV) and intra-articular (IA) TXA administration revealed good result in blood loss reduction with less evidence of venous thromboembolism event (VTE). Several literature reviews portray that peri-articular (PA) administration yields similar hemostasis in comparison to IV route. However, there is no report on the clinical effect of combining PA + IA TXA in blood loss reduction and its complications, compared to combining IV + IA TXA after TKA. We conducted a double-blind, randomized controlled trial comparing the use of PA + IA TXA administration and IV + IA TXA administration in 70 patients who were scheduled for unilateral primary TKA. Thirty-five patients were assigned for PA + IA injection (Group 1) and anoter 35 patients were assigned for IV + IA injection (Group 2). Primary outcomes included total blood loss at 48h, and the need for blood transfusion. Secondary outcomes included thigh and leg circumference, degree of knee flexion, and postoperative complications. The calculated blood loss at 48h showed no difference between Groups 1 and 2 (617ml vs. 632ml, p = 0.425). The total hemoglobin and hematocrit changes were not different (1.89g/dL vs. 1.97g/dL, p = 0.371 and 5.66% vs. 5.87%, p = 0.391). There was no need for blood transfusion in either group. However, lower thigh swelling was significant in Group 1 (2.15cm vs. 2.79cm, p = 0.04). Leg circumferences at 48h was also lower in Group 1(42.12cm vs. 42.77cm, p = 0.04). There was no significant difference in knee flexion decrease between the two groups (38° vs. 37°, p = 0.425). There were no VTE complications or infections found in either group. Combined PA + IA TXA administration had similar efficacy in blood loss reduction and blood transfusion when compared to combined IV + IA TXA. The first group displayed less soft tissue swelling. The combination of PA + IA TXA administration can be used as an alternative regimen to avoid IV TXA administration.

Three-Year Outcomes of Oral Antibiotics vs Intravenous and Oral Antibiotics for Uncomplicated Acute Appendicitis

Current short-term evidence has shown that uncomplicated acute appendicitis can be treated successfully with oral antibiotics alone, but longer-term results are lacking. To assess the treatment effectiveness of oral antibiotic monotherapy compared with combined intravenous (IV) and oral antibiotics in computed tomography-confirmed uncomplicated acute appendicitis at a longer-term follow-up. This secondary analysis of a predefined year 3 follow-up of the Appendicitis Acuta II (APPAC II) noninferiority, multicenter randomized clinical trial compared oral moxifloxacin with combined IV ertapenem plus oral levofloxacin and metronidazole for the treatment of uncomplicated acute appendicitis. The trial was conducted at 9 university and central hospitals in Finland from April 2017 to November 2018, with the last follow-up in November 2022. Participants included patients aged 18 to 60 years, who were randomized to receive either oral antibiotics monotherapy (n = 301) or combined IV and oral antibiotics (n = 298). Antibiotics monotherapy consisted of oral moxifloxacin, 400 mg/d, for 7 days. Combined IV and oral antibiotics consisted of IV ertapenem sodium, 1 g/d, for 2 days plus oral levofloxacin, 500 mg/d, and metronidazole, 500 mg 3 times/d, for 5 days. The primary end point was treatment success, defined as the resolution of acute appendicitis and discharge from hospital without the need for surgical intervention and no appendicitis recurrence at the year 3 follow-up evaluated using a noninferiority design. The secondary end points included late (after 1 year) appendicitis recurrence as well as treatment-related adverse events, quality of life, length of hospital stay, and length of sick leave, which were evaluated using a superiority design. After exclusions, 599 patients (mean [SD] age, 36 [12] years; 336 males [56.1%]) were randomized; after withdrawal and loss to follow-up, 582 patients (99.8%) were available for the year 3 follow-up. The treatment success at year 3 was 63.4% (1-sided 95% CI, 58.8% to ∞) in the oral antibiotic monotherapy group and 65.2% (1-sided 95% CI, 60.5% to ∞) in the combined IV and oral antibiotics group. The difference in treatment success rate between the groups at year 3 was -1.8 percentage points (1-sided 95% CI, -8.3 percentage points to ∞; P = .14 for noninferiority), with the CI limit exceeding the noninferiority margin. There were no significant differences between groups in treatment-related adverse events, quality of life, length of hospital stay, or length of sick leave. This secondary analysis of the APPAC II trial found a slightly higher appendectomy rate in patients who received oral antibiotic monotherapy; however, noninferiority of oral antibiotic monotherapy compared with combined IV and oral antibiotics could not be demonstrated. The results encourage future studies to assess oral antibiotic monotherapy as a viable treatment alternative for uncomplicated acute appendicitis. ClinicalTrials.gov Identifier: NCT03236961.

Comparison of Intraarticular Versus Combined Intravenous and Intraarticular Tranexamic Acid Administration in Patients Undergoing Primary Unilateral Total Knee Arthroplasty: A Randomized Controlled Trial in the Middle Eastern Patient Population.

This study aimed to determine whether combined intravenous (IV) and intraarticular (IA) tranexamic acid (TXA) reduces blood loss and the requirement of blood transfusion compared to IA use alone in the middle eastern patients undergoing primary cemented unilateral total knee arthroplasty (TKA). The present study is a double-blind randomized controlled trial (RTC) comparing the efficacy of IA alone to combined IA and IV routes of TXA administration in patients undergoing primary cemented TKA using a tourniquet performed by two senior surgeons. There were 21 patients in the IA alone and 29 in the combined group. The primary outcome measure was blood transfusion requirement, hemoglobin drop, and the total estimated blood loss on day three of postoperative period. The secondary outcomes were complications including thromboembolic events, wound complications, periprosthetic infection, patient-reported outcomes (PROs) of pain visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and EuroQol 5-dimension (EQ-5D) as well as the range of motion (ROM) at one-year follow-up. None of the patients in either of the comparison group required blood transfusion in the perioperative period. The drop in hemoglobin levels (2.1±1.0 vs. 2.2±1.1, P=0.84) and the total estimated blood loss (884±489 vs. 877±324, P=0.96) on the third postoperative day in the IA alone group showed no statistically significant difference compared to that in the combined group. Moreover, there were no complications noted in patients of either group. At one-year follow-up, there was no significant difference between the two comparison groups regarding the mean PROs of pain VAS, WOMAC, and EQ-5D, as well as ROM. According to the obtained results, this RCT in the middle eastern patient population found no additional benefit of TXA administration through combined IV and IA route over the IA alone in reducing the requirement of blood transfusion and the total blood loss. Further similar studies with larger sample sizes are needed to ascertain the ideal route of TXA administration in patients undergoing primary TKA.

The Safety of Topical and Intravenous Tranexamic Acid in Endoscopic Sinus Surgery

Tranexamic acid (TXA) is an inexpensive and widely used medication indicated for the reduction of bleeding. There are data showing the efficacy of intravenous (IV) and topical TXA in endoscopic sinus surgery (ESS) but the safety of this practice is not well studied. The objective of this study was to assess the safety of using both IV and topical TXA in ESS. A scoping review was performed to investigate the effect of TXA on respiratory epithelia. A retrospective single-surgeon study was used to assess 177 comprehensive ESS cases from January 2017–December 2019 for the safety of combined IV and topical TXA. The scoping review demonstrated that respiratory epithelia could withstand a wide range of TXA concentrations without detrimental morphological effects. Topical TXA may have positive effects on wound healing and inflammation. The retrospective study showed no thromboembolic complications attributable to TXA in the 28 days after ESS. Only two patients (1.3%) who received TXA re-presented with post-operative bleeding. The use of IV and topical TXA is safe with regards to its effect on respiratory epithelium and thromboembolic disease. Topical TXA may have more positive effects than merely the reduction of bleeding following ESS.

The addition of oral Tranexamic acid to knee arthroplasty patients does not further improve blood loss: a double blinded randomized control trial.

Perioperative intravenous (IV) TA has become routine in knee and hip arthroplasty. Less evidence exists on the administration of oral TA in the post- operative period. Our study aims to identify the efficacy and safety of combined perioperative IV and post-operative oral TA on blood loss and Hemoglobin (Hb) drop compared to perioperative IV TA alone. Patients undergoing primary elective knee arthro- plasty at our institution were invited to participate in the study (n=50). A computer-generated randomisation sequence was created online (www.randomization. org), with an allocation ratio of 1:1 and a block size of 50. Group A received perioperative IV TA alone and post-operative oral TA (n= 26) and Group B received perioperative IV TA plus 48 hours additional oral placebo (n= 24). Day 3 total blood loss and Hb drop was calculated. Continuous, normally distributed data (total blood loss) was compared utilising using one-way analysis of variance with post hoc Tukey test. Continuous skewed data (Hb drop) was compared using the Kruskal-Wallis test. P <0.05 was considered statistically significant. Group A demonstrated a trend in decreased total blood loss that was close to statistical significance ( p = 0.072). No difference in Hb drop was identified between the 2 groups. Increased nausea was also observed in Group A. The administration of oral TA to post-operative knee arthroplasty patients does not improve further blood loss compared to patients receiving perioperative IV TA pre-operatively and at wound closure.

Efficacy and safety of tirofiban injection with intracranial stenting in early reocclusion due to intracranial atherosclerosis

ObjectiveWe aimed to develop an optimal protocol for failed mechanical thrombectomy (MT) in cases of emergent large vessel occlusion (ELVO) with intracranial atherosclerosis (ICAS). MethodsA total of 117 patients without underlying heart disease who were not taking antiplatelet drugs had early reocclusion during MT for ELVO due to ICAS. They were divided into the following 3 groups according to rescue treatment methods: 1) Combined intravenous (IV) + intra-arterial (IA) tirofiban group (n = 48), emergent percutaneous transluminal angioplasty (PTA) and intracranial stenting (ICS) followed by IA injection of tirofiban and a continuous IV tirofiban infusion for 8 h; 2) IA tirofiban group (n = 33), only IA 0.5–1.0 mg tirofiban infusion for 5 min regardless of PTA or ICS; and 3) no tirofiban group (n = 36), no tirofiban injection regardless of PTA or ICS. ResultsICS was more frequently performed in the combined IV + IA tirofiban group than in the IA tirofiban group (100% vs 46%, p < 0.05). The proportion of m-TICI grades 2b and 3 (93.8% vs. 63.6%, p < 0.05), especially the proportion of m-TICI grade 3 (81.3% vs. 36.4%, p < 0.05), was higher in the combined IV + IA tirofiban group than in the IA tirofiban group. The rate of postoperative intracranial hemorrhage was not significantly different among the three groups. The rate of modified Rankin scale scores of 0–2 at 3 months after MT was highest in the combined IV + IA tirofiban group (63%), followed by the IA tirofiban (46%) and no tirofiban groups (8%, p < 0.05). ConclusionICS with IA and continuous IV tirofiban injections for 8 h is an effective and safe protocol for failed MT in patients with ELVO with ICAS.

Is There a Synergistic Effect of Topical Plus Intravenous Tranexamic Acid Versus Intravenous Administration Alone on Blood Loss and Transfusions in Primary Total Hip and Knee Arthroplasties?

BackgroundThe optimal route and dosing regimen of tranexamic acid (TXA) in primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) remain unclear. As such, we sought to analyze if there was a synergistic effect of intravenous (IV) and topical TXA on blood loss and transfusions.MethodsWe retrospectively analyzed 6720 primary TKAs and 6559 THAs performed from February 1, 2016 to December 31, 2019 at a single institution in patients who received a double IV dose (6159 TKAs and 6276 THAs) compared with a combined single IV and topical dose (561 TKAs and 283 THAs) of TXA. Multivariate logistic regression models, adjusting for age, body mass index, American Society of Anesthesiologists class, preoperative hemoglobin, and TXA administration, were performed for significant variables from a univariate analysis.ResultsIn the TKA cohort, the mean total blood loss was statistically similar for double IV (305 mL, 95% confidence interval [CI] = 301-310 mL) TXA compared with combined TXA (310 mL, 95% CI = 299-321 mL) (P = .43). Furthermore, there was no difference in the rate of transfusion (odds ratio = 1.23, 95% CI = 0.57-2.67, P = .598). In the THA cohort, there was statistically higher blood loss with double IV (328 mL, 95% CI = 323-333 mL) TXA than in the combined group (295 mL, 95% CI = 280-310 mL) (P < .001). The rate of transfusion was statistically similar at ~2% (P = .970).ConclusionsA double IV TXA dose and a combined single IV and topical TXA dose were equally effective in minimizing blood transfusions (~2%) at primary TKA and THA. We did not find a synergistic effect when combining a systemic IV TXA with a topical TXA.Level of EvidenceLevel III.

IV/IT hUC-MSCs Infusion in RRMS and NMO: A 10-Year Follow-Up Study.

Background: Stem cell transplantation is emerging as a potential therapeutic strategy in several autoimmune diseases. However, the safety and feasibility of long-term combined intravenous (IV) and intrathecal (IT) administration of hUC-MSCs in relapse remitting multiple sclerosis (RRMS) and neuromyelitis optica (NMO) is largely unknown.Objectives: In this study, we followed up the long-term safety and feasibility of combined IV and IT human umbilical cord mesenchymal stem cells (hUC-MSCs) transplantation in patients with RRMS and NMO.Methods: Five NMO patients and 5 RRMS patients were treated intravenously (4 times) and intrathecally (3 times) over a 21-day period with low-dose allogeneic umbilical cord blood–derived MSCs. All of the patients were monitored regularly by an investigator in a blinded manner to access the Expanded Disability Status Scale, MRI characteristics, and adverse events every 3 months within 12 months and once every year thereafter for 10 years after transplantation.Results: During the long-term follow-up, our data suggested that combined IV and IT administration of hUC-MSCs transplantation is safe and feasible. None of the intolerant adverse events, such as tumor formation and peripheral organ/tissue disorders, were observed throughout the 10-year follow-up.Conclusions: These data suggest that combined intravenous and intrathecal low-dose hUC-MSCs transplantation is safe and feasible in RRMS and NMO patients in the long term. The conclusion requires confirmation by future clinical trials in a larger cohort.

Efficacy of the Combined Administration of Systemic and Intra-Articular Tranexamic Acid in Total Hip Arthroplasty Secondary to Femoral Neck Fracture: A Retrospective Study.

Background Total hip arthroplasty (THA) is associated with substantial blood loss in the postoperative course. Tranexamic acid (TXA) is a potent antifibrinolytic agent, routinely administered by intravenous (IV) and topical (intra-articular, IA) route, which can possibly interrupt the cascade of events due to hemostatic irregularities close to the source of bleeding. However, scientific evidence of combined administration of TXA in THA secondary to a femoral neck fracture is still meagre. The present study aims to compare the patients who were administered combined IV and topical TXA with a control group in terms of blood loss, transfusion rate, and incidence of deep vein thrombosis (DVT) and thromboembolism (TE). Patients and Methods. 195 patients with femoral neck fracture underwent THA and were placed into two groups: (1) IV and IA TXA group which had 58 patients and (2) no TXA control group which had 137 patients. In the TXA group, 1 g IV TXA was administered 30 minutes before incision, and 1 g IA TXA was administered intraoperatively after fascia closure. No drains were placed, and soft spica was applied to the hip. Results Combined usage of IV and IA TXA showed better results when compared to the control group in terms of blood transfusion rate (31%) and hemoglobin drop (28%). No cases of DVT or TE were noted among the two study groups. Conclusion Combined use of IV and IA TXA provided significantly better results compared to no TXA use with respect to all variables related to postoperative blood loss in THA. Moreover, TXA use is safe in terms of incidence of symptomatic DVT and TE.

Decreased blood loss with systemic and intraarticular tranexamic acid administration after total knee arthroplasty

Objective: Perioperative bleeding during total knee arthroplasty (TKA) is a lasting problem for surgeons. Intravenous or intra-articular administration of tranexamic acid (TXA) can effectively stop bleeding, but there is still no uniform standard for the best administration and dosing. Method: Between October 2017 and September 2019, ninety patients with unilateral primary knee osteoarthritis requiring knee replacement were retrospectively evaluated and investigated in three groups according to the route of TXA administration: Group 1 (n=30) intravenous (IV) injection, Group 2 (n=30) intra-articular injection (IAI), and Group 3 (n = 30) combined IV and IAI. Demographic characteristics, hematological indices, and the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) were studied. Results: Of the patients included in the study, 86% were female (n=78), and 14% were male (n=12). The gender distribution of the groups was homogeneous (p=0.749). The mean hemoglobin values of Group 2 were significantly lower than those of Group 1 and Group 3 (p=0.002 and p=0.045, respectively). Less postoperative blood loss was observed in the group receiving combined IV and IA TXA. The mean blood loss from the drain in Group 3 was significantly lower than that in Group 1 and Group 2 (p=0.001). Postoperative infection, DVT, and PE were not seen in any group. Conclusion: This study demonstrated that the use of intraarticular and intravenous tranexamic acid in primary unilateral TKA significantly reduced postoperative blood loss and consequently decreased the need for blood transfusion without an increase in adverse events, particularly thromboembolic complications.

Combined Intravenous and Intraarticular Tranexamic Acid Does Not Offer Additional Benefit Compared with Intraarticular Use Alone in Bilateral TKA: A Randomized Controlled Trial.

Tranexamic acid (TXA) is efficacious for reducing blood loss and transfusion use in patients who undergo bilateral TKA, and it is administered intravenously alone, intraarticularly alone, or as a combination of these. However, it is unclear whether combined intravenous (IV) and intraarticular TXA offers any additional benefit over intraarticular use alone in patients undergoing bilateral TKA. The purposes of our study was to determine (1) whether combined IV and intraarticular TXA reduces blood loss and blood transfusion use compared with intraarticular use alone and (2) whether the frequency of adverse events is different between these routes of administration in patients who undergo simultaneous or staged bilateral TKA. Between April 2015 and May 2017, one surgeon performed 316 same-day bilateral TKAs and 314 staged bilateral TKAs. Of those, 98% of patients in each same-day TKA (310) and staged bilateral TKA (309) groups were eligible for this randomized trial and all of those patients agreed to participate and were randomized. The study included four groups: simultaneous TKA with intraarticular TXA only (n = 157), simultaneous TKA with IV and intraarticular TXA (n = 153), staged TKA with intraarticular TXA only (n = 156), and staged TKA with IV and intraarticular TXA (n = 155). There were no differences in demographic data among the intraarticular alone and IV plus intraarticular TXA groups of patients who underwent simultaneous or staged bilateral TKA in terms of age, proportion of female patients, BMI, or preoperative hematologic values. The primary outcome variables were total blood loss calculated based on patient blood volume and a drop in the hemoglobin level and administration of blood transfusion. The secondary outcomes of this study were a decrease in the postoperative hemoglobin level; the proportion of patients with a hemoglobin level lower than 7.0, 8.0, or 9.0 g/dL; and the frequencies of symptomatic deep vein thrombosis, symptomatic pulmonary embolism, wound complications, and periprosthetic joint infection. Total blood loss with intraarticular TXA alone in patients undergoing simultaneous bilateral TKA and those undergoing staged procedures was not different from the total blood loss with the combined IV plus intraarticular TXA regimen (1063 mL ± 303 mL versus 1004 mL ± 287 mL, mean difference 59 mL [95% CI -7 to 125]; p = 0.08 and 909 ml ± 283 ml versus 845 ml ± 278 ml; mean difference 64 mL [95% CI 1 to 127]; p = 0.046, respectively). The use of blood transfusions between intraarticular alone and combined IV and intraarticular TXA was also not different among patients undergoing simultaneous (0% [0 of 152] versus 1%; p = 0.149) and staged TKA (1% [1 of 155] versus 0% [0 of 153]; p = 0.98). Furthermore, the frequency of symptomatic thromboembolic events, wound complications, and periprosthetic joint infections was low, without any differences among the groups with the numbers available. Because there was no difference between intraarticular alone and combined intraarticular plus IV regimen of TXA administration, we recommend that IV and intraarticular TXA should not be used in combination. Moreover, other studies have found no differences between intraarticular and IV TXA used alone, and hence to avoid potential complications associated with systemic administration, we recommend that intraarticular alone is sufficient for routine TKA. Level I, therapeutic study.

Reduction of Blood Loss by Tranexamic Acid Following Total Hip and Knee Arthroplasty: A Meta-Analysis.

This study involved a meta-analysis of 36 published studies to examine the efficacy of intravenous (IV) and intra-articular (IA) tranexamic acid (TXA) in reducing blood loss, drain output, thromboembolic complications, and hospital stay following total hip and total knee arthroplasty. This study also evaluated whether treatment with a combination of both IA and IV TXA has an effect on these outcomes. Lastly, this study attempted to analyze the method and technique of TXA administration in order to establish a best practice for its use in reducing overall blood loss in arthroplasty procedures. MEDLINE, Embase, and the Cochrane Library database were screened. Studies comparing IV TXA with IA TXA or with combined IV and IA TXA were included. Data including total blood loss, drain output, thromboembolic complications, and hospital stay, where available, were analyzed using meta-analysis with fixed effects. Results are presented as the standardized mean difference (SMD), and meta-regression was employed to explore plausible demographic contributions to heterogeneity. Twenty-eight randomized controlled trials, 3 prospective cohort studies, and 5 retrospective cohort studies with 5,499 patients were included in this review. IA administration during total knee arthroplasty showed a significant advantage in terms of total blood loss (SMD = -0.14, 95% confidence interval [CI] = -0.027 to -0.02, I = 78.2%) and drain output (SMD = -0.30, 95% CI = -0.43 to -0.18). There was no significant difference between IV and IA administration in total hip arthroplasty. Combined IA plus IV TXA was associated with a significant reduction in blood loss versus IV TXA alone in both total knee arthroplasty and total hip arthroplasty. IV TXA dosing varied, as 14 (39%) of the studies used a weight-based approach while 22 (61%) used a standard dose. Twenty-seven (96%) of 28 studies of IA administration used standard dosing while 1 study followed a weight-based protocol. There was no difference in symptomatic thromboembolic complications, with overall rates in total knee arthroplasty and total hip arthroplasty of 1.0% and 1.0% for IV administration and 1.1% and 0.3% for IA administration, respectively. There was no difference in length of hospital stay for IV versus IA TXA administration. IA TXA, either alone or in conjunction with IV TXA, reduces total blood loss and/or drain output in total knee arthroplasty and total hip arthroplasty. Optimal methodology remains to be clarified; however, there are substantial economic benefits of utilizing either IV or IA TXA, with greater cost benefits when using IA TXA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A prospective, randomized, comparative study of intravenous alone and combined intravenous and intraarticular administration of tranexamic acid in primary total knee replacement.

BackgroundStudies on the use of tranexamic acid (TXA) to improve clinical outcomes after joint arthroplasty have reported contrasting results between intravenous (IV) TXA alone and combined IV and intraarticular (IA) administration. We compared the effectiveness of the 2 methods in providing higher postoperative hemoglobin (Hb) levels in patients undergoing primary total knee arthroplasty (TKA).MethodsA total of 100 TKA patients were randomly assigned to receive either IV TXA alone (group 1) or combined IV and topical IA TXA (group 2). Hb and hematocrit levels were measured before and after surgery. The amount of drained blood and transfused blood for the 2 groups was compared.ResultsThe Hb level was significantly higher at postoperative day 4, together with a positive, albeit not significant, trend toward less postoperative blood loss in the group that received combined IV and IA TXA. No postoperative infections or deep venous thrombosis events occurred.ConclusionsThis study reinforces evidence that, as compared to IV TXA alone, combined IV and IA administration of TXA has a synergic effect, leading to higher postoperative Hb levels without influencing drug safety in TKA patients.

The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: Combined tranexamic acid for TKA.

ObjectivesTranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA.Materials and MethodsA systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software.ResultsA total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group.ConclusionsCompared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA.Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353–361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2.

Controversy in Tranexamic Acid Administration Route Continues: Commentary on an article by Zeng Yi, MD, et al.: "Tranexamic Acid Administration in Primary Total Hip Arthroplasty: A Randomized Controlled Trial of Intravenous Combined with Topical Versus Single-Dose Intravenous Administration".

Tranexamic acid (TXA) use is undeniably one of the most important recent advances in primary total hip arthroplasty. Pharmacologically, TXA, a synthetic drug, inhibits fibrinolysis and therefore fibrin clot degradation and also activates plasminogen, thus reducing hemorrhage in several surgical fields. TXA use has not been cleared by the U.S. Food and Drug Administration (FDA) for total hip arthroplasty and its use remains off-label. Many clinical studies, including randomized controlled trials (RCTs) and meta-analyses, demonstrated that TXA is safe and effective in reducing perioperative blood loss and significantly reduces blood transfusion1. Different methods of delivery, single or double intravenous (IV), topical, or combined IV and topical with various dosages, have all …

Combined Intra-Articular and Intravenous Tranexamic Acid Reduces Blood Loss in Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Trial.

In total knee arthroplasty, both intravenous (IV) and intra-articular (IA) administration of tranexamic acid (TXA) have been shown to reduce blood loss in several randomized controlled trials, although routine use of systemic TXA is considerably more common. However, to our knowledge, the additional benefit of IA administration of TXA when combined with IV administration, without the use of a tourniquet, has not been previously investigated. Thus, the aim of this study was to evaluate whether combined IV and IA administration of TXA reduced total blood loss compared with IV-only administration of TXA. In this randomized, double-blind, placebo-controlled trial, 60 patients scheduled for total knee arthroplasty were randomized to one of two interventions. The TXA IV and IA group received combined administration of TXA consisting of 1 g administered intravenously preoperatively and 3 g diluted in 100 mL of saline solution administered intra-articularly after closure of the capsule. The TXA IV and placebo group received 1 g of TXA administered intravenously only and 100 mL of saline solution administered intra-articularly. IA TXA was administrated through a needle. The primary outcome was the 24-hour calculated blood loss. Secondary outcomes were blood loss on postoperative day 2, thromboembolic complications, and transfusion rate. Blood loss was calculated by hemoglobin differences using the Gross formula. Data on the primary outcome were available for all 60 included patients. Baseline characteristics were comparable between the allocation groups. The mean 24-hour blood loss (and standard deviation) was 466 ± 313 mL in the TXA IV and IA group compared with 743 ± 358 mL in the TXA IV and placebo group; treatment effect (difference), 277 mL (95% confidence interval [CI], 103 to 451 mL) (p = 0.002). Second-day blood loss was 644 ± 382 mL in the TXA IV and IA group compared with 1017 ± 519 mL in the TXA IV and placebo group; treatment effect, 373 mL (95% CI, 132 to 614 mL) (p = 0.003). No thromboembolic complications were observed within 90 days postoperatively. The combined administration of IV and IA TXA resulted in a clinically relevant reduction in blood loss of 37% compared with IV TXA alone both at 24 hours postoperatively and on postoperative day 2. No thromboembolic complications were observed. Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Combined Administration of Systemic and Topical Tranexamic Acid for Total Knee Arthroplasty: Can It Be a Better Regimen and Yet Safe? A Randomized Controlled Trial

BackgroundTotal knee arthroplasty (TKA) is associated with substantial blood loss in postoperative period. Tranexamic acid (TXA) is potent antifibrinolytic agent, routinely administered by intravenous (IV) and topical route, which can possibly interrupt cascade of events due to hemostatic irregularities close to source of bleeding. However, scientific evidence of combined administration of TXA in TKA is still meagre. The present study aimed to compare efficacy of combined IV and topical TXA with IV use alone in terms of blood loss, transfusion rate, and incidence of deep vein thrombosis and thromboembolism. Patients and Methods119 patients undergoing unilateral TKA were randomized into IV alone and combined group. Patients assigned to IV group were given IV TXA as a preoperative and postoperative dose given 3 and 6 hours after surgery, whereas in combined group, topical TXA solution was applied intraarticularly about 5 minutes before closure of arthrotomy in addition to IV doses. ResultsCombined use of IV and topical TXA provided better results than IV use alone with mean calculated total blood loss (590.69±191.1 vs 385.68±182.5, P<.001), blood transfusion rate (6.6% vs 1.6%, P = .364), hemoglobin drop (1.82±0.6 vs 1.14±0.5, P<.001). No case of DVT or TE was noted among the 2 study groups. ConclusionCombined use of IV and intraarticular TXA provided significantly better results compared with IV use alone with respect to all variables related to postoperative blood loss in TKA. Moreover, TXA use is safe in terms of incidence of symptomatic DVT and TE.

Comparison of Outcomes after Reperfusion Therapy between In-Hospital and Out-of-Hospital Stroke Patients

Background: Patients may experience stroke while being admitted to the hospital (in-hospital stroke (IHS)) and they may be important candidates for reperfusion therapy. IHS patients may have various comorbidities and show worse outcomes compared with patients with an out-of-hospital stroke (OHS). On the other hand, the time from onset to treatment may be shorter in IHS patients than OHS patients. Most outcome studies of reperfusion therapy have been based on findings in OHS patients, and little information is currently available regarding outcomes of IHS, whether the outcomes differ between patients with IHS and those with OHS who receive reperfusion therapy. Methods: This is a retrospective observational study using prospectively registered data. Consecutive patients who underwent the reperfusion therapy (intravenous (IV), intra-arterial (IA), or combined IV and IA) between July 2002 and June 2014 in a university hospital were included for this study. We compared the demographics, time interval from symptom onset to treatment, and outcomes between IHS and OHS patients and analyzed the factors associated with in-hospital mortality. Results: A total of 686 patients received the reperfusion therapy during the study period. Of them, 256 (37.3%) patients received the IV tissue plasminogen activator (t-PA) therapy only, 243 (35.4%) patients received the IA therapy only, and 187 (27.3%) patients received the combined IV and IA therapy. Among these, 104 (15.2%) were IHS patients. The time intervals from symptom onset to IV t-PA administration (87.5 ± 48.4 vs. 113.4 ± 38.3 min, p < 0.001) and IA puncture (221.8 ± 195.0 vs. 343.6 ± 155.4 min, p < 0.001) were shorter for IHS than OHS. The rates of successful recanalization and symptomatic intracerebral hemorrhage, and the favorable functional outcome at 3 months were similar between the groups. In-hospital all-cause mortality was higher in IHS than OHS (16.3 vs. 8.4%, p = 0.019), but after adjustment, IHS was not an independent factor. The stroke mortality did not differ between the groups (9.6 vs. 6.9%, p = 0.432). Conclusions: Although IHS patients more frequently had comorbid diseases and higher overall in-hospital mortality, the standard outcomes of the reperfusion therapy were similar between IHS and OHS patients, which might be, in part, ascribed to the shorter interval from symptom onset to treatment in IHS. Considering a substantial portion of IHS patients, we should pay more attention to these patients.

Abstract T P8: Outcomes of Endovascular Treatment Using Solitaire Devices in Acute Ischemic Stroke With Favorable Penumbral Imaging Pattern

Introduction: Through emerging of novel devices and elaborated patient selection, endovascular treatment against acute ischemic stroke is gaining popularity. We investigated factors influencing outcomes after endovascular treatment in highly applicable patients. Methods: We enrolled consecutive 72 patients with favorable penumbral pattern, who underwent endovascular treatment with Solitaire from 2010 through 2013 in three hospitals of Korea. Inclusion criteria were these: the NIHSS and age were between 6 and 29, and 18 and 85, respectively, and endovascular procedures could begin within 8 h from onset. A favorable penumbral pattern was defined as a mismatch ratio ≥ 1.43 between hypoperfusion by Tmax &gt; 6 s and infarction core by DWI which should be &lt; 90 mL. The good outcome was defined as mRS ≤ 2 at 3 Mo. The recanalization was evaluated by TICI grading and successful recanalization was defined as grade 2b or 3. Results: Among 72 patients, 44 (61%) underwent combined treatment with intravenous (IV) and endovascular treatments, and 28 (39%) were treated by endovascular thrombectomy only. The overall recanalization rate was 82%, and the proportion of good outcome was 55.6%. Younger age and recanalization were associated with good outcome, but onset to treatment time and the combined IV thrombolysis was not related to good outcome. After propensity score matching to balance possible confounders between combined and endovascular-only treatment groups, combined treatment did not have beneficial effects than endovascular-only (OR, 0.8; 95% CI, 0.1-2.6). The successful recanalization after endovascular treatment was an independent predictor for good outcome (adjusted OR, 6.8; 95% CI, 1.3-34.5), after controlling age, sex, stroke severity, onset to treatment time, the combined IV therapy, and risk factors. Conclusion: In patients with discrete diffusion-perfusion mismatch, the recanalization after thrombectomy is the most important predictor for good outcomes.