Fibrin tissue sealant and minor skin grafts in burn surgery: A systematic review and meta-analysis
Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2019
BACKGROUND The indications for use of fibrin glue in skin grafting burn patients remains understudied. The purpose of this study is to review the efficacy of fibrin tissue sealant in skin graft adherence, establish guidelines for use of fibrin tissue sealant, and review the cost effectiveness of fibrin glue. METHODS Publications with the following criteria were included: comparative human studies, autologous skin grafts, and autologous or commercial fibrin sealant. Outcomes assessed included evidence of engraftment, wound closure, rates of hematoma/seroma, graft loss and infection. Meta-analysis obtained pooled odds ratios for outcomes of interest. Cost analysis was performed using data available in the literature. RESULTS 7 studies and 751 interventions (fibrin) and controls (staples) were included in the final analysis. 67.6% grafts with fibrin were 100% adherent by one week, vs. 55.5% (OR 1.45, p=0.086). Complete wound closure by one month was 80.2% with fibrin, vs. 73.3% (OR 1.34, p=0.187). Hematoma/seroma occurred 38.2% with fibrin, vs. 64.7% (OR 0.487, p=0.122). Graft loss was higher in the control group, 21% vs. 12.6% (OR 0.891, p=0.604). Average cost of fibrin glue was $50 per ml, and averaged costs of stapler and staple remover was $30 USD ($10-50). CONCLUSION Fibrin glue is as effective as staples for adhering skin grafts, and trends towards lower rates of hematoma/seroma. In topographically complex regions, fibrin glue may be a better choice for adherence of skin grafts.
Pediatric Toxic Shock Syndrome After a 7% Burn: A Case Study and Systematic Literature Review
Annals of plastic surgery. 2019
INTRODUCTION Toxic shock syndrome (TSS) is a life-threatening condition, which occurs in children after sustaining a burn. Often diagnosed retrospectively, many patients may not receive optimal treatment.The primary objective of this study was to evaluate a severe and complex case of TSS at our unit and subsequently conduct a Preferred Reporting for Systematic Reviews and Meta-Analyses-compliant systematic literature review, to identify cases of postthermal injury TSS and evaluate their presentation and management. CASE REPORT A 9-year-old boy with Down syndrome presented with a 7% total body surface area scald to his back and posterior head. Four days after discharge, he developed a fever. The following day, he deteriorated, becoming stridulous and unresponsive. A working diagnosis of TSS was made. The patient's intensive care stay was arduous with multiple complications, including 2 cardiac arrests. METHODS A Preferred Reporting for Systematic Reviews and Meta-Analyses-compliant systematic literature review was conducted. MEDLINE, PubMed, and Web of Science were searched using key terms "burns, thermal injury, scalds, paediatric, child, infant, neonate, toxic shock syndrome" to identify cases. Two authors independently checked each study against inclusion criteria. RESULTS The systematic literature search yielded 9 articles, identifying 40 cases. Ages ranged between 9 months and 8 years. The mean number of days' postburn patients presented with symptoms of TSS was 2.5 days (1-7 days). The most common presenting symptoms were fever (75%), rash (70%), and diarrhea, and/or vomiting (52.5%). Intravenous immunoglobulins were administered in 11 (27.5%) cases. DISCUSSION We have highlighted a case where a possible delayed diagnosis along with the immunodeficiency seen in Down syndrome may have impacted the severity of TSS. The literature review highlighted that a significant proportion of patients do not meet diagnostic criteria. CONCLUSIONS It is fundamental that appropriate diagnostic and management guidelines are developed. Furthermore, this case highlights the importance of educating patient's carers and health professionals of key symptoms to be wary of postburn.
Evaluation of the "early" use of albumin in children with extensive burns: a randomized controlled trial
Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2016;17((6):):e280-6
OBJECTIVE To compare early versus delayed albumin resuscitation in children with burns in terms of clinical outcome and response. DESIGN Randomized controlled trial. SETTING Burn center at a tertiary care teaching hospital. PATIENTS Forty-six children aged 1-12 years with burns greater than 15-45% total body surface area admitted within 12 hours of burn injury. INTERVENTIONS Fluid resuscitation was based on the Parkland formula (3 mL/kg/% total body surface area), adjusted according to urine output. Patients received 5% albumin solution between 8 and 12 hours post burn in the intervention group (n = 23) and 24 hours post burn in the control group (n = 23). Both groups were assessed for reduction in crystalloid fluid infusion during resuscitation, development of fluid creep, and length of hospital stay. MEASUREMENTS AND MAIN RESULTS There was no difference between groups regarding age, weight, sex, % total body surface area, cause of burn, or severity scores. The median crystalloid fluid volume required during the first 3 days post burn was lower in the intervention than in the control group (2.04 vs 3.05 mL/kg/% total body surface area; p = 0.025 on day 1; 1.2 vs 1.71 mL/kg/% total body surface area; p = 0.002 on day 2; and 0.82 vs 1.3 mL/kg/% total body surface area; p = 0.002 on day 3). The median urine output showed no difference between intervention and control groups (2.1 vs 2.0 mL/kg/hr; p = 0.152 on day 1; 2.58 vs 2.54 mL/kg/hr; p = 0.482 on day 2; and 2.9 vs 3.0 mL/kg/hr; p = 0.093 on day 3). Fluid creep was observed in 13 controls (56.5%) and in one patient (4.3%) in the intervention group. The median length of hospital stay was 18 days (range, 15-21 d) for controls and 14 days (range, 10-17 d) in the intervention group (p = 0.004). CONCLUSIONS Early albumin infusion in children with burns greater than 15-45% total body surface area reduced the need for crystalloid fluid infusion during resuscitation. Significantly fewer cases of fluid creep and shorter hospital stay were also observed in this group of patients.
Albumin administration for fluid resuscitation in burn patients: a systematic review and meta-analysis
Burns : Journal of the International Society for Burn Injuries. 2016;43((1):):17-24
OBJECTIVE The objective was to systematically review the literature summarizing the effect on mortality of albumin compared to non-albumin solutions during the fluid resuscitation phase of burn injured patients. DATA SOURCES We searched MEDLINE, EMBASE and CENTRAL and the content of two leading journals in burn care, Burns and Journal of Burn Care and Research. STUDY SELECTION Two reviewers independently selected randomized controlled trials comparing albumin vs. non-albumin solutions for the acute resuscitation of patients with >20% body surface area involvement. DATA EXTRACTION Reviewers abstracted data independently and assessed methodological quality of the included trials using predefined criteria. DATA SYNTHESIS A random effects model was used to assess mortality. We identified 164 trials of which, 4 trials involving 140 patients met our inclusion criteria. Overall, the methodological quality of the included trials was fair. We did not find a significant benefit of albumin solutions as resuscitation fluid on mortality in burn patients (relative risk (RR) 1.6; 95% confidence interval (CI), 0.63-4.08). Total volume of fluid infusion during the phase of resuscitation was lower in patients receiving albumin containing solution -1.00ml/kg/%TBSA (total body surface area) (95% CI, -1.42 to -0.58). CONCLUSION The pooled estimate demonstrated a neutral effect on mortality in burn patients resuscitated acutely with albumin solutions. Due to limited evidence and uncertainty, an adequately powered, high quality trial could be required to assess the impact of albumin solutions on mortality in burn patients.
Albumin in burn shock resuscitation: a meta-analysis of controlled clinical studies
Journal of Burn Care Research. 2016;37((3):):e268-78
Critical appraisal of outcomes after burn shock resuscitation with albumin has previously been restricted to small relatively old randomized trials, some with high risk of bias. Extensive recent data from nonrandomized studies assessing the use of albumin can potentially reduce bias and add precision. The objective of this meta-analysis was to determine the effect of burn shock resuscitation with albumin on mortality and morbidity in adult patients. Randomized and nonrandomized controlled clinical studies evaluating mortality and morbidity in adult patients receiving albumin for burn shock resuscitation were identified by multiple methods, including computer database searches and examination of journal contents and reference lists. Extracted data were quantitatively combined by random-effects meta-analysis. Four randomized and four nonrandomized studies with 688 total adult patients were included. Treatment effects did not differ significantly between the included randomized and nonrandomized studies. Albumin infusion during the first 24 hours showed no significant overall effect on mortality. However, significant statistical heterogeneity was present, which could be abolished by excluding two studies at high risk of bias. After those exclusions, albumin infusion was associated with reduced mortality. The pooled odds ratio was 0.34 with a 95% confidence interval of 0.19 to 0.58 (P < .001). Albumin administration was also accompanied by decreased occurrence of compartment syndrome (pooled odds ratio, 0.19; 95% confidence interval, 0.07–0.50; P < .001). This meta-analysis suggests that albumin can improve outcomes of burn shock resuscitation. However, the scope and quality of current evidence are limited, and additional trials are needed.
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.
Maintenance of serum albumin levels in pediatric burn patients: a prospective, randomized trial
Journal of Trauma-Injury Infection & Critical Care. 1995;39((1):):67-73; discussion 73-4.
A prospective, randomized trial was performed to determine whether maintaining serum albumin levels in burned pediatric patients had any effect on morbidity and mortality. Patients < 19 years of age with burns > 20% total body surface area were randomized to receive supplemental albumin to maintain levels 2.5 to 3.5 g/dL ("High Albumin") or were given albumin only if levels dropped < 1.5 g/dL ("Low Albumin") after completing burn shock resuscitation. The 36 patients in the Low Albumin group were well matched for age, burn size, depth of injury, and inhalation injury when compared with the High Albumin group (34 patients). As expected, serum albumin levels were significantly lower in the Low Albumin group when compared with the High Albumin group. No differences between groups were noted for resuscitation needs, maintenance fluid requirements, urine output, tube feedings received, days of antibiotic treatment, or ventilatory requirements. No differences in hematology, electrolytes, or nutritional laboratories were found. Finally, length of stay, complication rate, and mortality were not affected by albumin treatment. Albumin supplementation to maintain normal serum levels does not seem to be warranted in previously healthy children who suffer severe burns and who receive adequate nutrition.