Minimizing blood loss in burn surgery

BACKGROUND: Significant blood loss continues to plague early tangential excision of the burn wound. Although various techniques to reduce intraoperative blood loss have been described, there is an absence of uniformity and consistency in their application. Furthermore, it is unclear whether these techniques compromise intraoperative tissue assessment and wound outcome. The purpose of this study was to evaluate the effects of a comprehensive intraoperative blood conservation strategy on blood loss, transfusion requirements, and wound outcome in burn surgery. METHODS: An intraoperative blood conservation strategy (CONSV) that included donor site and burn wound adrenaline tumescence, donor site and excised wound topical adrenaline, and limb tourniquets was prospectively evaluated and compared with a historical control group (HIST) where only topical adrenaline and thrombin were applied to donor sites and excised wounds. RESULTS: Estimated blood loss was reduced from 211 +/- 166 mL per percentage body surface area excised and grafted in the HIST group to 123 +/- 106 mL in the CONSV group (p = 0.02). Similarly, the intraoperative transfusion requirement in the HIST group was reduced from 3.3 +/- 3.1 units per case to 0.1 +/- 0.3 units per case in the CONSV group (p < 0.001). There was no compromise in wound outcome in the CONSV group, which had a mean skin graft take rate of 96 +/- 4.2%. CONCLUSION: The application of a strict and comprehensive intraoperative blood conservation strategy during burn excision and grafting resulted in a profound reduction in blood loss and transfusion requirements, without compromising wound outcome.     

Efficacy and safety of repeated perioperative doses of recombinant factor VIIa in liver transplantation.

Patients undergoing orthotopic liver transplantation (OLT) have excessive blood loss during surgery that requires blood transfusions, leading to increased postoperative morbidity and mortality. We studied the efficacy and safety of activated recombinant factor VII (rFVIIa) in reducing transfusion requirements in OLT. This multicenter, randomized, double-blind, placebo-controlled trial enrolled patients undergoing OLT because of cirrhosis (Child-Turcotte-Pugh class B or C). Patients received a repeated intravenous bolus regimen of rFVIIa 60 or 120 microg/kg or placebo. The primary efficacy endpoint was the total number of red blood cell (RBC) units transfused during the perioperative period. A total of 182 patients were analyzed for efficacy and 183 for safety. No significant effect of rFVIIa was observed on the number of RBC units transfused or intraoperative blood loss compared with the placebo group. A significantly higher number of patients in the rFVIIa study groups avoided RBC transfusion. Administration of rFVIIa but not placebo restored the preoperative prolonged prothrombin time to normal value during surgery. Patients receiving rFVIIa and placebo did not experience a significant difference in rate of thromboembolic events. Additionally, there was no statistically significant effect of rFVIIa treatment on hospitalization rate, total surgery time, and the proportion of patients undergoing retransplantation. In conclusion, use of rFVIIa during OLT significantly reduced the number of patients requiring RBC transfusion. There was no increase in thromboembolic events with rFVIIa administration compared with placebo.     

不同方法评估重度烧伤清创植皮术患儿术中出血量准确性的比较

目的 比较手术面积和手术面积与血容量乘积(手术面积×血容量)评估重度烧伤清创植皮术患儿出血量的准确性.方法 拟行切削痂、清创植皮手术的重度烧伤患儿20例,年龄7 d～8岁,性别不限,体重4～22 kg,烧伤后5～10 d,烧伤面积15%～50%,手术面积10%～46%.计算术中总出血量,手术面积和手术面积×血容量与总出血量行直线相关和直线回归分析.结果 手术面积和手术面积×血容量与总出血量的相关系数分别为0.776和0.889,比较差异有统计学意义(P＜0.05);总出血量(Y)与手术面积(X1)、手术面积×血容量(X2)直线回归方程分别为:Y=25.094X1-122.431和Y=0.020X2+16.142.结论 与手术面积比较,手术面积×血容量能更准确地评估重度烧伤清创植皮术患儿的术中出血量.

Abstract：

Objective To evaluate the accuracy of different methods for estimating blood loss during burn wound excixion and skin grafting in pediatric patients with severe burn. Methods Twenty pediatric patients of both sexes aged 7 days-8 yr weighing 4-22 kg undergoing burn wound excision and skin grafting were enrolled in this clinical study. Two methods were used for estimating blood loss during operation: Method Ⅰ: surgical surface area (SSA). MethodⅡ: the product of SSA and blood volume (BV). Total blood loss was calculated: total blood loss = BV ( Hct0 - Hctx ) ÷ Hct0 + Tx. Hct0 =Hct before operation. Hctx =Hct at the end of operation. Tx =total amount of blood transfusion. Results The correlation between the total blood loss and SSA was 0.776. The correlation between the total blood loss and the product of SSA and BV was 0.889. The difference was statistically significant. Conclusion The product of SSA and BV is more accurate in estimating blood loss during burn wound excision and skin grafting in children with severe burn.     

Rescue treatment with recombinant factor VIIa is effective in patients with life-threatening bleedings secondary to major wound excision: a report of four cases

Major burn wound excision is associated with excessive perioperative blood loss. Treatment of massive microvascular bleeding represents a special problem in the burn setting, characterized by extensive damage at the capillary level, and resulting in a profound blood loss; which together with the consumptive states makes adequate replacement therapy with coagulation factors and platelets difficult. We described our experience with rescue treatment with rFVIIa in four patients undergoing major wound excision, developing life-threatening perioperative bleeding, and not responding to conventional therapy. Hemostasis was achieved within 15 minutes of intravenous rFVIIa administration, at a dose of 100 microg/kg, in all patients. No treatment-related adverse events, in particular, no thromboembolic events were observed. We conclude that rFVIIa may be an effective hemostatic treatment for patients undergoing major wound excision developing life-threatening bleedings.     

A prospective double blind randomized study comparing the need for blood transfusion with terlipressin or a placebo during early excision and grafting of burns

INTRODUCTION: Early excision and skin grafting has become the standard of good burn management, but it is associated with major blood loss. AIM: To determine the haemostatic effect of terlipressin compared with placebo. MATERIAL AND METHODS: Fifty-one patients with burns of 10-20% total body surface area had early excision and split skin grafting of deep burns. The surface area of the burn wound and of the healed graft were measured by planimetry. The patients were randomly allocated to medication, either terlipressin or placebo. Blood loss and number of transfused units of blood were recorded. RESULTS: Twenty-one patients received terlipressin, 13 received terlipressin late (cross-over) and 17 received placebo. Six out of 21 patients exposed to terlipressin were transfused with eleven units of packed red blood cells. Seven out of 13 patients crossed over from placebo to terlipressin (late terlipressin) were transfused with 17 units of blood. Eight out of 17 patients exposed to the placebo were transfused with 22 units of blood (P < 0.05). Graft healing was 1055 +/- 609 cm2 out of 1452 +/- 11 cm2 in terlipressin and 914 +/- 633 cm2 out of 1288 +/- 720 cm2 in the placebo group (n.s.). CONCLUSION: Terlipressin reduced the need for blood transfusion by a factor of 2.5 compared to a placebo without impairment of graft healing.     

Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials

BACKGROUND: Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma. METHODS: Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose. RESULTS: Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups. CONCLUSION: Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.     

Effect of single dose intravenous tranexamic acid on blood loss in tangential excision of burn wounds — A double blind randomised controlled trial

IntroductionThis study was carried out to evaluate role of intravenous tranexamic acid (TXA) in reducing blood loss during tangential excision of burns.MethodsThis was a single center, prospective double-blinded parallel arm superiority randomized placebo-controlled trial. Patients (15?55 years) with deep dermal thermal burns <30% undergoing tangential excision were randomly assigned (1:1) to TXA and placebo groups. Patients in TXA and placebo groups received injection TXA 15 mg/kg and 10 ml saline respectively, 10 min preoperatively. Primary outcome was volume of blood loss per square centimeter area of burn excised. Secondary outcomes were total volume of blood loss, postoperative hemoglobin, intraoperative fluid requirement, blood transfusion, graft take and length of hospitalization (LOH).ResultsThirty patients were included. Both groups were comparable in terms of Body Mass Index (BMI) preoperative hemoglobin, area of burn excised, duration of surgery and the intraoperative temperature. The average blood loss per square centimeter burn area excised was found to be significantly lower in TXA when compared to placebo group (mean difference: 0.28 ± 0.025 ml/cm²; p = 0.000). The total volume of blood loss was lower in TXA group (258.7 ± 124.10 ml vs 388.1 ± 173.9 ml; p = 0.07). None of the patients required transfusion. The requirement of intra-operative fluids was similar between the two groups (crystalloids: p = 0.236; colloids: p = 0.238). Postoperative hemoglobin, length of hospitalization and graft-take were comparable between the two groups.ConclusionTXA reduced blood loss per unit burn area of tangential excision in <30%TBSA burn, however, we found no significant effect on postoperative Hb and transfusion.     

Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial

BACKGROUND: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy. METHODS: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities. RESULTS: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04). CONCLUSIONS: Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.     

Early versus late recombinant factor VIIa in combat trauma patients requiring massive transfusion

BACKGROUND: Coagulopathy is a consequence of severe trauma, especially in massively transfused patients (>or=10 units of red blood cells in 24 hours), and is associated with increased mortality. We hypothesized that recombinant factor VIIa (rFVIIa) administered to massive transfusion patients before transfusion of 8 units of blood (early) would reduce transfusion requirements compared with rFVIIa after 8 units (late). METHODS: We retrospectively reviewed records for trauma admissions to combat support hospitals in Iraq between January 2004 and October 2005. Patients requiring a massive transfusion and receiving rFVIIa were identified. Groups were divided into those who received rFVIIa early or late. RESULTS: Of 5,334 trauma patients (civilian and military), 365 (6.8%) required massive transfusion. Of these, 117 (32%) received rFVIIa. Complete records for blood transfusions were available for 61 patients: 90% had penetrating trauma, 17 received rFVIIa early, and 44 received it late. At admission, temperature, heart rate, blood pressure, Glasgow Coma Scale score, base deficit, hemoglobin, platelets, prothrombin time/International Normalized Ratio, and Injury Severity Score were similar in both groups as were administered units of fresh frozen plasma, fresh whole blood, cryoprecipitate (cryo), and crystalloid. The early rFVIIa group required fewer units of blood during the first 24-hour period (mean 20.6 vs. 25.7, p=0.048) and fewer units of stored red blood cells (mean 16.7 vs. 21.7, p=0.049). Early and late mortality (33.3% vs. 34.2%, p=NS), acute respiratory distress syndrome (5.9 vs. 6.8%, p=NS), infection (5.9% vs. 9.1%, p=NS), and thrombotic events (0% vs. 2.3%, p=NS) were similar. CONCLUSIONS: Early administration of rFVIIa decreased red blood cell use by 20% in trauma patients requiring massive transfusion.     

Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation: a pilot study

BACKGROUND: Large transfusion requirements, i.e., excessive blood loss, during orthotopic liver transplantation (OLT) are correlated with increased morbidity and mortality. Recombinant factor VIIa (rF-VIIa) has been shown to improve hemostasis in a variety of conditions, but has never been studied in liver transplantation. METHODS: We performed a single-center, open-label, pilot study in adult patients undergoing OLT for cirrhosis Child-Pugh B or C, to assess efficacy and safety of rFVIIa. rFVIIa (80 microg/kg) was administered at the start of the operation, to be repeated according to predefined criteria. Packed red blood cells (RBC), fresh-frozen plasma, and platelet concentrates were administered according to predefined criteria. Perioperative transfusion requirements in study patients were compared with matched controls. RESULTS: Six patients were enrolled in the study. All received a single dose of rFVIIa. Transfusion requirements (given as median, with range in parentheses) were lower in the study group than in matched controls: 1.5 (0-5) vs. 7 (2-18) units of allogeneic RBC (P=0.006), 0 (0-2) vs. 3.5 (0-23) units of autologous RBC (P=0.043), total amount of RBC 3 (0-5) vs. 9 (4-40) units (P=0.002). Transfused fresh-frozen plasma was 1 (0-7) vs. 8 (2-35) units (P=0.011). Blood loss was 3.5 L (1.4-5.3) vs. 9.8 L (3.7-35.0) (P=0.004). One study patient developed a hepatic artery thrombosis at day 1 postoperatively. CONCLUSIONS: A single dose of 80 microg/kg rFVIIa significantly reduced transfusion requirements during OLT. Further study is needed to establish the optimally effective and safe dose of rFVIIa in orthotopic liver transplantation.     

A double-blind, placebo-controlled trial of epsilon-aminocaproic acid for reducing blood loss in coronary artery bypass grafting surgery

BACKGROUND: Epsilon-aminocaproic acid is a plasmin inhibitor that potentially reduces perioperative bleeding when administered prophylactically to cardiac surgery patients. To evaluate the efficacy of epsilon-aminocaproic acid, a prospective placebo-controlled trial was conducted in patients undergoing primary coronary artery bypass grafting surgery. STUDY DESIGN: One hundred patients were randomly assigned to receive either epsilon-aminocaproic acid (100 mg/kg before skin incision followed by 1 g/hour continuous infusion until chest closure, 10 g in cardiopulmonary bypass circuit) or placebo, and the efficacy of epsilon-aminocaproic acid was evaluated by the reduction in postoperative thoracic-drainage volume and in donor-blood transfusion up to postoperative day 12. RESULTS: Postoperative thoracic-drainage volume was significantly lower in the epsilon-aminocaproic acid group compared with the placebo group (epsilon-aminocaproic acid, 649 +/- 261 mL; versus placebo, 940 +/- 626 mL; p=0.003). There were no significant differences between the epsilon-aminocaproic acid and placebo groups in the percentage of patients requiring donor red blood cell transfusions (epsilon-aminocaproic acid, 24%; versus placebo, 18%; p=0.62) or in the number of units of donor red blood cells transfused (epsilon-aminocaproic acid, 2.2 +/- 0.8 U; versus placebo, 1.9 +/- 0.8 U; p=0.29). Epsilon-aminocaproic acid did not reduce the risk of donor red blood cell transfusions compared with placebo (odds ratio: 1.2, 95% confidence interval; 0.4 to 3.2, p=0.63). CONCLUSIONS: Prophylactic administration of epsilon-aminocaproic acid reduces postoperative thoracic-drainage volume by 30%, but it may not be potent enough to reduce the requirement and the risk for donor blood transfusion in cardiac surgery patients. This information is useful for deciding on a therapy for hemostasis in cardiac surgery.     

Rekombinanter Faktor VIIa in der Hämorrhagiebehandlung des Schwerstverletzten

Background

The aim of the study was to assess whether the use of recombinant factor VIIa (rFVIIa) in trauma patients was associated with improved outcome.

Patients and methods

Patients documented in the TraumaRegistry of the German Society for Trauma Surgery (primary admissions; Injury Severity Score, ISS≥?9) who received rFVIIa in the first 6 hours upon admission (rFVIIa?+) were matched with patients that had not received rFVIIa (rFVIIa?).

Results

The matching comparison yielded two identical groups with 100 patients each (rFVIIa+: average age 40.6±18.5 years, ISS 47.1±16.7 versus rFVIIa─: 40.1±19.1 years, ISS 45.1±15.6). Patients were administered an average of 18.3±13.1 (rFVIIa+) versus 19.5±14.0 (rFVIIa─) red blood cell units (p=0.55) and 15.2±13.7 (rFVIIa+) versus 15.0±13.1 (rFVIIa─) units of fresh frozen plasma (p=0.92). Thromboembolisms occurred in 5% (rFVIIa+) versus 2% (rFVIIa─) (p=0.44), multiple organ failure (MOF) in 82% versus 62% (p=0.003) and hospital mortality was 48% versus 43% (p=0.57), respectively.

Conclusion

The early use of rFVIIa in severely injured patients was not associated with either lower transfusion requirements or with mortality reduction but with increased MOF.     

Activated recombinant factor VII after cardiopulmonary bypass reduces allogeneic transfusion in complex non-coronary cardiac surgery: randomized double-blind placebo-controlled pilot study

Background. Receiving an allogeneic transfusion may be an independentpredictor of mortality for patients undergoing cardiac surgery.Furthermore, these patients utilize 15% of all donated bloodin the UK. In our unit, 80% of patients undergoing complex non-coronarycardiac surgery requiring cardiopulmonary bypass (CPB) receivean allogeneic transfusion. Activated recombinant FVII (rFVIIa)may be effective in reducing this need for transfusion. Methods. Twenty patients undergoing complex cardiac surgerywere randomized to receive rFVIIa or placebo after CPB and reversalof heparin. Results. Two patients in the rFVIIa group received 13 unitsof allogeneic red cells and coagulation products compared witheight patients receiving 105 units of allogeneic red cells andcoagulation products in the placebo group (relative risk ofany transfusion 0.26; confidence interval 0.07–0.9; P=0.037).The groups did not differ for adverse events. Conclusion. Despite major limitations (underpowered study andprone to type I error), we have shown that rFVIIa significantlyreduces the need for allogeneic transfusion in complex non-coronarycardiac surgery without causing adverse events.      

Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury

BACKGROUND: Recombinant factor VIIa (rFVIIa) is used for treatment of bleeding episodes in hemophilia patients who develop inhibitors to factors VIII and IX. We tested the hypothesis that administration of rFVIIa early after injury would decrease bleeding and prolong the time from injury to death after experimental hepatic trauma. METHODS: Anesthetized swine were cannulated for blood sampling and hemodynamic monitoring. Avulsion of the left median lobe of the liver induced uncontrolled hemorrhage. After a 10% reduction in mean arterial pressure, animals (n = 8 per group) were blindly randomized to receive intravenous rFVIIa 180 microg/kg, rFVIIa 720 microg/kg, or placebo. Pathologic examination of brain, lung, kidney, heart, and small bowel was performed to assess intravascular thrombosis.RESULTS Mortality during the first hour was 50% (four of eight) in controls versus 0% with rFVIIa 720 microg/kg (p = 0.02, chi2). Blood loss was decreased in the rFVIIa 720 microg/kg group versus the placebo group (13.2 +/- 5.5 mL/kg vs. 21.9 +/- 7.7 mL/kg;p = 0.0223). Time from injury to death was significantly prolonged in the rFVIIa 720 microg/kg group compared with placebo (116 minutes vs. 8.5 +/- 3.5 minutes; p= 0.02). No macro- or microthrombi in vital organs were identified on pathologic examination. CONCLUSION: Intravenous administration of high-dose rFVIIa early after induction of hemorrhage decreased bleeding and prolonged survival. No evidence of thrombosis in vital organs was observed.     

Recombinant Coagulation Factor VIIa in Major Liver Resection: A Randomized, Placebo-controlled, Double-blind Clinical Trial

Background: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.

Methods: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 [mu]g/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.

Results: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26of 63) in the 20-[mu]g/kg group, and 25% (15 of 59) in the 80-[mu]g/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 [mu]g/kg rFVIIa, and 1,036 ml with 80 [mu]g/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 [mu]g/kg rFVIIa, and 1,073 ml with 80 [mu]g/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-[mu]g/kg group, with a significant overall effect of treatment (P = 0.04).     

烧伤患者肢体削痂植皮手术中止血带的应用

目的　探讨烧伤患者肢体削痂植皮手术中止血带的使用方法。方法　 79例拟行肢体削痂植皮手术的烧伤患者随机分为两组 ,A组 (4 1例 )采取持续止血带控制下的削痂植皮 ;B组 (38例 )仅在削痂时使用止血带 ,植皮过程中不使用。观察手术过程中两组的手术失血量、输血量、手术时间和术后创面植皮成活率、有无并发症。　结果　A组手术失血量和输血量比B组分别减少 4 2 %和 5 0 % (P<0 .0 0 1) ,上、下肢手术时间与B组相比缩短了 4 1%和 37% (P <0 .0 0 1) ,两组植皮成活率和皮片下血肿发生率差异无显著性意义 (P >0 .0 5 )。　结论　采用持续止血带技术能有效地控制肢体削痂植皮手术中的失血 ,减少输血量 ,缩短手术时间     

Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease.

Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this double-blind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 microg/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required.     

Safety and hemostatic effect of recombinant activated factor VII in cirrhotic patients undergoing partial hepatectomy: a multicenter, randomized, double-blind, placebo-controlled trial

BACKGROUND: Coagulopathy caused by cirrhosis may contribute to excessive bleeding during hepatectomy. We evaluated the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in cirrhotic patients undergoing partial hepatectomy. METHODS: Patients were randomized to rFVIIa 50 or 100 mug/kg or placebo, administered intravenously 10 minutes before surgery and every second hour during surgery. The primary efficacy end points were the proportion of patients receiving red blood cell (RBC) transfusions and the amount of RBCs transfused. The RBC transfusion trigger was blood loss of 500 mL. Safety end points included thromboembolic and adverse events. RESULTS: No statistically significant effect of rFVIIa treatment on efficacy end points was observed. Serious and thromboembolic adverse events occurred at similar incidences in the study groups. CONCLUSIONS: Using blood loss as a transfusion trigger, the efficacy of rFVIIa in reducing the requirement for RBC transfusion was not established in this study. No safety concerns were identified.     

生长激素在成人大面积深度烧伤的应用

OBJECTIVE: To determine the wound healing effect of rHGH in adult burn patients. METHODS: 16 patients with burn wounds covering over 60% of total body surface (TBSA) were enrolled in this placebo controlled prospective study. They were comparable in nutrient intake, TBSA, and full thickness burn area. rHGH group patients were given rHGH subcutaneously in the dose of 0.3u.Kg-1 at 8 am each morning for 10 days beginning from POD 1. The control group patients were given normal saline as placebo. All the patients received scar excision within 4 days postburn, and the excision wounds were covered with autologous skin pulp grafting. Serum amino acid profile was analyzed at day 1 and day 20 post burn. Healing time of burn wound area and donor site was recorded. Wound healing rate was assessed at day 30 after day. RESULTS: 1. The healing time of autologous skin pulp grafting and donor site, and the length of hospital stay were significantly shorter in GH group patients than control group. 2. The amino acid profile showed no difference between two groups at day 1 and was significantly better in GH group at day 20. CONCLUSION: rHGH could enhance the wound healing rate, improve amino acid profile, and reduce the length of hospital stay of severe burn patients.     

Early burn wound excision and skin grafting postburn trauma restores in vivo neutrophil delivery to inflammatory lesions

This study assessed the effect of early vs delayed postburn wound excision and skin grafting on the in vivo neutrophil delivery to a delayed-type hypersensitivity (DTH) reaction and a bacterial skin lesion (BSL). Male Lewis rats were presensitized to keyhole-limpet hemocyanin. Group 1 comprised sham controls. Groups 2 through 4 were given a 30% 3 degrees scald burn, but the burn wounds were excised, and skin was grafted on days 1, 3, and 7, respectively, after the burn. Group 5 comprised burn controls. Twelve days after burn trauma, all rats were injected at different intervals (during a 24-hour period) with a trio of intradermal injections of keyhole-limpet hemocyanin, Staphylococcus aureus 502A, and saline at different sites. In vivo neutrophil delivery to these dermal lesions was determined by injecting indium in 111 oxyquinoline-labeled neutrophils isolated from similarly treated groups of rats. Neutrophil delivery to DTH and BSL lesions was restored to normal by excision and skin grafting of the burn wound one day after burn trauma. Waiting three days after burn trauma to excise and skin graft the wound partially, but not completely, restored the in vivo neutrophil delivery to DTH and BSL lesions. Waiting one week to excise and skin graft a burn wound resulted in no improvement in neutrophil delivery to DTH and BSL dermal lesions. It was concluded that burn wound excision and skin grafting immediately after burn trauma restored in vivo neutrophil delivery to a BSL and DTH dermal lesion. This may, in part, explain the beneficial effect of early aggressive burn wound debridement in patients with burn injuries.