An innovated elastic compression hemostasis technique for extremity excision in patients with extensive burns: A prospective clinical randomized controlled trial
OBJECTIVE To introduce an innovative elastic compression hemostasis technique for extremity excision in extensively burnt patients and investigate its effectiveness. METHODS Ten patients were included and divided into 2 groups: the control group (4 patients, 12 extremities) receiving the conventional hemostasis technique and the experimental group (6 patients, 14 extremities) receiving the innovative technique. General data of the patients were collected, excision size measured, hemostasis time recorded, average blood loss per 1% total body surface area of the excised wound calculated, incidence of subcutaneous hematoma and take rate determined. RESULTS The 2 groups had no statistical difference in the baseline data. Average blood loss per 1% total body surface area of the excised wound in the upper and the lower extremities was (62.1 Â± 11.5) mL and (35.6 Â± 11.0) mL in the experimental group, significantly less than (94.3 Â± 6.9) mL and (82.3 Â± 6.2) mL in the control group; a reduction of 34.1% and 56.8% respectively. Hemostasis time in the upper and the lower extremities were (5.0 Â± 0.7) min/1% total body surface area and (2.6 Â± 0.3) min/1% total body surface area, respectively, in the experimental group, significantly less than (7.4 Â± 0.6) min/1% total body surface area and (4.0 Â± 0.9) min/1% total body surface area in the control group; a reduction of 31.8% and 34.9% respectively. The incidences of subcutaneous hematoma were 7.1% and 8.3%, and the take rate (85.9 Â± 6.0)% and (86.5 Â± 4.8)% in the experimental and the control group, respectively, with no statistically significant differences. CONCLUSION The innovative elastic compression hemostasis technique is a reliable new method that significantly reduces blood loss during extremity excision in patients with extensive burns and is worth wider understanding and application.
Bromelain-based enzymatic burn debridement: A systematic review of clinical studies on patient safety, efficacy and long-term outcomes
International wound journal. 2023
In 2012 the European Medicines Agency approved a pineapple stem-derived Bromelain-based debridement concentrate of proteolytic enzymes (NexoBrid®, MediWound Ltd, Yavne, Israel) for adult deep burns. Over 10 000 patients have been successfully treated with NexoBrid® globally, including in the US. The aim of our study is to perform a systematic review of the current literature on Nexobrid® outcomes. We conducted a literature search in PubMed, Google Scholar, Embase, and other search engines (2013-2023). The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. We identified 103 relevant studies of which 34 were found eligible. The included studies report the positive effects of Nexobrid® on burn debridement, functional and cosmetic outcomes, scarring, and quality of life. Also, they validate the high patient satisfaction thanks to enhanced protocols of analgosedation and/or locoregional anaesthesia during Bromelain-based debridement. Two studies investigate potential risks (coagulopathy, burn wound infection) which concluded there is no strong evidence of these adverse events. NexoBrid® is a safe, selective, non-surgical eschar removal treatment modality. The benefits of Bromelain-based debridement are faster debridement and healing times, reduced operations, length of stay, cases of sepsis, blood transfusions, and prevention of compartment syndrome. Existing evidence suggests that the indications and the role of Bromelain-based debridement are expanding to cover "off-label" cases with significant benefits to the global healthcare economy.
Topical Hemostatic Agents in Burn Surgery: A Systematic Review
Journal of burn care & research : official publication of the American Burn Association. 2022
Acute burn surgery has long been associated with significant intra-operative bleeding. Several techniques were introduced to limit hemorrhage, including tourniquets, tumescent infiltration, and topical agents. To date, no study has comprehensively investigated the available data regarding topical hemostatic agents in burn surgery. A systematic review was performed by two independent reviewers using electronic databases (PubMed, Scopus, Web of Science) from first available to September 10, 2021. Articles were included if they were published in English and described or evaluated topical hemostatic agents used in burn excision and/or grafting. Data were extracted on the agent(s) used, their dosage, mode of delivery, hemostasis outcomes, and complications. The search identified 1982 non-duplicate citations, of which 134 underwent full-text review, and 49 met inclusion criteria. In total, 32 studies incorporated a vasoconstrictor agent, and 28 studies incorporated a procoagulant agent. Four studies incorporated other agents (hydrogen peroxide, tranexamic acid, collagen sheets, and TT-173). The most common vasoconstrictor used was epinephrine, with doses ranging from 1:1,000-1:1,000,000. The most common procoagulant used was thrombin, with doses ranging from 10-1,000 IU/mL. Among the comparative studies, outcomes of blood loss were not reported in a consistent manner, therefore meta-analysis could not be performed. The majority of studies (94%) were level of evidence III-V. Determining the optimal topical hemostatic agent is limited by low-quality data and challenges with consistent reporting of intra-operative blood loss. Given the routine use of topical hemostatic agents in burn surgery, high-quality research is essential to determine the optimal agent, dosage, and mode of delivery.
Management of bleeding in major burn surgery
Burns : Journal of the International Society for Burn Injuries. 2018
Major burn surgery is often associated with excessive bleeding and massive transfusion, and the development of a coagulopathy during major burn surgery is associated with increased morbidity and mortality. The aim of this study was to review the literature on intraoperative haemostatic resuscitation of burn patients during necrectomy to reveal strategies applied for haemostatic monitoring and resuscitation. We searched PubMed, EMBASE, and CENTRAL for studies published in the period 2006-2017 concerning bleeding issues related to burn surgery i.e. coagulopathy, transfusion requirements and clinical outcomes. In a broad search, a total of 1375 papers were identified. 124 of these fulfilled the inclusion criteria, and six of these were included for review. The literature confirmed that transfusion requirements increases with burn injury severity and that haemostatic monitoring by TEG((R)) (thrombelastography) or ROTEM((R)) (rotational thromboelastometry) significantly decreased intraoperative transfusions and was useful in predicting and goal-directing haemostatic therapy during excision surgery. Resuscitation of bleeding during major burn surgery in many instances was neither standardized nor haemostatic. We suggest that resuscitation should aim for normal haemostasis during the bleeding phase through close haemostatic monitoring and resuscitation. Randomised controlled trials are highly warranted to confirm the benefit of this concept.
EHTIC study: evaluation of a new hemostatic agent based on tissue factor in skin grafting procedures
Burns : Journal of the International Society for Burn Injuries. 2017;43((4):):780-788
BACKGROUND Excessive bleeding is a major concern in scar debridement and grafting procedures. TT-173 is a new topical hemostatic agent based on recombinant human tissue factor that has shown promising results in patients who underwent tooth extraction. EHTIC study sought to evaluate the efficacy and safety of TT-173 to reduce the bleeding in donor sites of skin grafting procedures. METHODS EHTIC study was a phase II, randomized, parallel, double blind, placebo controlled trial. Patients received TT-173 (n=38) or placebo (n=33) sprayed over donor site after graft harvest. Time to hemostasis and incidence of adverse events were recorded. Systemic absorption of the product and its immunogenicity were also measured during the follow up of the subjects. RESULTS Treatment with TT-173 significantly reduced the bleeding time from 7 to 3min (Log-Rank p<0.0001). Moreover, bleeding stopped within the 10min of evaluation period in all the patients that received TT-173. In contrast, 24.24% of patients from placebo group required additional measures to arrest hemorrhage (Fisher p=0.0013). Product related adverse events, systemic absorption into blood stream, interferences with the healing of the donor site or immunogenic reaction against TT-173 were not observed. CONCLUSION The new hemostatic agent TT-173 has proven efficacious and safe to reduce the bleeding from donor site. This study paves the way for further investigation of the product as topical hemostatic treatment in plastic surgery and other surgical indications.
Controlling intraoperative hemorrhage during burn surgery: a prospective, randomized trial comparing NuStat(R) hemostatic dressing to the historic standard of care
Burns : Journal of the International Society for Burn Injuries. 2016;43((2):):374-378
INTRODUCTION One of the primary intraoperative challenges during burn surgery is to adequately excise the burn while avoiding massive hemorrhage. This has become increasingly important, as we see more burn patients that are older and with more medical comorbidities. While adequate excision down to healthy tissues for deep burns is essential for skin graft to take, it also leads to active bleeding that can be a challenge to control. Good hemostasis is imperative as a hematoma is the most common cause of graft loss. Several new products have become available to help control intraoperative hemorrhage. A new hemostatic dressing, NuStat(R), is available and approved by FDA in United States. METHODS A single institution prospective randomized control trial was completed at Regional Burn Center of the University of South Alabama comparing NuStat(R) with the institutional historic standard of care. Twenty such patients were included in our study. A cost analysis was also completed as part of the study retrospectively. RESULTS For dressings used to treat the burn site, blood loss on the side treated with NuStat(R) was on average less (27g/100cm2) than the side treated with our historic standard of care (31g/100cm2), though it was not statistically significant (p=0.81). Similarly, on the donor site, blood loss on the side treated with NuStat(R) was on average less (14g/100cm2) than the side treated with our historic standard of care (15g/100cm2), but it was also not statistically significant (p=0.92). Average total blood loss from both excision and donor sites was also less with NuStat(R) (10g/100cm2) compared to the historic standard of care (12g/100cm2), but it was also not significant (p=0.77). There was no difference in the number of cycles required to achieve hemostasis for either the burn (1.15 NuStat(R) vs. 1.1 for historic standard of care, p=0.70) or the donor site (1 vs. 1, p=1.0). When comparing the cost of NuStat(R) versus the historic standard of care, the actual costs incurred for the wounds was less for the portion treated with NuStat(R) ($148.43) when compared to the historic standard of care ($186.45) (p<0.001). CONCLUSIONS Based on these findings, NuStat(R) hemostatic action should be comparable to the historic standard of care, and these newer hemostatic agents evaluated further in burn surgery and bleeding during other procedures such as trauma surgery.
Efficacy and safety of a fibrin sealant for adherence of autologous skin grafts to burn wounds: results of a phase 3 clinical study
Journal of Burn Care & Research : Official Publication of the American Burn Association. 2008;29((2):):293-303.
The objective of this phase 3, multicentered, prospective, randomized, evaluator-blinded, clinical study was to compare skin graft adherence utilizing a fibrin sealant containing 4 IU/ml thrombin (FS 4IU VH S/D [FS 4IU VH S/D will be marketed under the trade name ARTISS upon licensure in the United States]) to graft adherence utilizing staples in burn patients requiring wound excision and skin grafting. FS 4IU VH S/D was compared with staples in 138 patients. Patients had burn wounds measuring < or =40% of total body surface area with two comparable test sites measuring between 1 and 4% total body surface area each. Wound closure at day 28 was assessed using test site planimetry and review of day 28 photographs by three independent blinded evaluators (primary endpoint analysis). Secondary efficacy measures included hematoma/seroma on day 1, engraftment on day 5, and wound closure on day 14. Investigator and patient-reported outcomes were also assessed. The proportion of test sites with complete wound closure at day 28 was 70. 3% in FS 4IU VH S/D treated sites and 65. 8% in stapled sites, as assessed by planimetry. Blinded review of day 28 photographs confirmed that the rate of complete wound closure was similar between the two treatments, although the overall assessed rates of closure were lower than those determined by planimetry: FS 4IU VH S/D (43. 3%) and staples (37. 0%). The lower limit of the 97. 5% confidence interval of the difference between FS 4IU VH S/D and staples was -0. 029, which is above the predefined noninferiority margin of -0. 1. Therefore, FS 4IU VH S/D is at least as efficacious as staples at the 97. 5% one-sided level for complete wound closure by day 28. Hematoma/seroma on day 1 occurred at significantly (P < . 0001) fewer FS 4IU VH S/D-treated sites (29. 7% [95% CI 22. 2-38. 1%]) compared with stapled sites (62. 3% [95% CI 53. 7-70. 4%]). Engraftment on day 5 was deemed to be 100% in 62. 3% (95% CI 53. 7-70. 4%) of the FS 4IU VH S/D-treated sites and 55. 1% (95% CI 46. 4-63. 5%) of the stapled sites (P = . 0890). Complete wound closure by day 14 occurred in 48. 8% (95% CI 39. 9-57. 8%) of the FS 4IU VH S/D treated sites and 42. 6% (95% CI 34. 0-51. 6%) of the stapled sites (P = . 2299). FS 4IU VH S/D scored significantly better than staples for all investigator-assessed outcomes, namely quality of graft adherence (P < . 0001), preference for method of fixation (P < . 0001), satisfaction with graft fixation (P < . 0001), and overall quality of healing (P < . 0001). Likewise, FS 4IU VH S/D scored significantly better than staples for all patient-assessed outcomes, namely anxiety about pain (P < . 0001) and treatment preference (P <. 0001). The safety profile of FS 4IU VH S/D was excellent as indicated by the lack of any related serious adverse experiences. These findings demonstrate that FS 4IU VH S/D is safe and effective for attachment of skin grafts, with outcomes at least as good as or better than staple fixation.
Comparison of fibrin sealant and staples for attaching split-thickness autologous sheet grafts in patients with deep partial- or full-thickness burn wounds: a phase 1/2 clinical study
Journal of Burn Care & Research : Official Publication of the American Burn Association. 2007;28((3):):401-8.
We undertook a multicenter, randomized, controlled, phase 1/2 clinical study to investigate the safety and efficacy of a fibrin sealant containing 4 IU/ml thrombin (FS 4IU) for the attachment of autologous sheet grafts in patients with deep partial-thickness or full-thickness burn wounds. Fibrin sealant (FS 4IU) was compared with staples for adherence of sheet grafts in 40 patients. Patients had to have burn wounds measuring 40% TBSA or less with two comparable test sites measuring between 1% and 4% TBSA each. Wound beds were prepared before treatment assignment, which was randomized. Percent area of hematoma/seroma at Day 1 (P = . 0138) and questionable viability at Day 5 (P = . 0182) were significantly less for FS 4IU-treated sites. Median percent area of graft survival on Day 14 was 100% for both treatments (P = . 3525). The percentage of completely closed sites generally was greater for FS 4IU-sites on Days 5 to 91; the maximum difference occurred at Day 28 (79. 5% vs 59%; P = . 0215). The safety profile of FS 4IU was excellent as indicated by the lack of any related serious adverse experiences. These findings indicate that FS 4IU is safe and effective for fixation of skin grafts, with outcomes similar to or better than staple fixation. The data suggest that FS 4IU is a promising candidate for further clinical studies focusing on skin graft adhesion and burn wound healing.
A multicenter clinical trial to evaluate the topical hemostatic efficacy of fibrin sealant in burn patients
Journal of Burn Care & Rehabilitation. 2001;22((2):):99-103.
Current surgical management of deep partial-thickness and full-thickness burn wounds involves early excision and grafting. Blood loss during these procedures can be profound, thus prompting the use of topical hemostatic agents to control and minimize hemorrhage during grafting. The primary endpoint of this multicenter trial was to evaluate the efficacy of fibrin sealant as a topical hemostatic agent during skin grafting. The secondary endpoint was to obtain data to support the existing safety profile of a human fibrin sealant (FS) in participating patients as indicated by the type, severity, and frequency of any adverse events within the 24-hour postoperative period. A multicenter prospective, open label, Phase III multicenter, randomized, comparative clinical trial evaluated the use of fibrin sealant in burn patients undergoing skin graft procedures. Each patient served as his or her own control in this randomized, unblinded study of the effect on time to hemostasis in donor sites treated with the investigational FS product. At operation, 1 contiguous donor skin harvest site was bisected into 2 equal halves, 1 of which was then randomly selected and treated with fibrin sealant. At the end of the fibrin sealant application, the time to hemostasis in each of the donor site halves was identified by the operating surgeon and recorded by the research coordinator. The use of any other topical hemostatic agents was prohibited. A significant difference (P < .001) was demonstrated in the mean time to hemostasis between the fibrin sealant treated donor sites when compared painwise to the control sites. The significant difference was consistent across the 6 participating study centers. There were no adverse events associated with the use of fibrin sealant. The investigational FS product was shown to be efficacious, because it significantly decreases the time to hemostasis at the donor skin harvest site in patients undergoing skin grafting and was noted not to cause any adverse reactions.
Multicenter trial to evaluate the safety and potential efficacy of pooled human fibrin sealant for the treatment of burn wounds
Journal of Trauma-Injury Infection & Critical Care. 1999;46((3):):433-40.
OBJECTIVE The primary purpose of this multicenter study was to evaluate the safety and potential efficacy of a solvent/detergent-treated commercial fibrin sealant (human) for topical hemostasis in skin grafting. METHODS The study involved a prospective evaluation of changes in viral titers in patients with burns less than 15% after treatment with fibrin sealant (human). Each patient served as his/her own control for an unblinded, randomized comparison of donor site hemostasis and healing. Preoperative serum was obtained to screen for viral titers. At autografting, the recipient site and one of two randomly chosen donor sites were treated with fibrin sealant (human). The use of other hemostatic agents, including epinephrine was prohibited. Each donor site was covered with gauze to collect blood for estimation of the relative amount of bleeding. The healing of the graft and donor sites was observed. Viral titers and wounds were checked monthly for 6 months, and at 9 and 12 months postoperatively. RESULTS Viral titers for human immunodeficiency virus; hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus were obtained before and after treatment. Of 47 patients, 34 completed the full year of observation. After treatment, there were no seroconversions to any of the aforementioned viruses. Bleeding at the recipient site appeared well controlled with fibrin sealant (human). Although investigators felt that fibrin sealant (human) improved donor site hemostasis, differences in hemoglobin measurements of blood-soaked dressings failed to reach significance. No differences were noted with regard to acceleration of donor site healing, graft take, or scar maturation at the two groups of donor sites. Anecdotally, the maturation of the recipient site appeared to be accelerated. CONCLUSION Fibrin sealant (human) is safe for use during excision and grafting, and its topical hemostatic potential needs to be examined in patients with larger burns. Its role in scar maturation also needs to be investigated.