New hemostatic dressing (FAST Dressing) reduces blood loss and improves survival in a grade V liver injury model in noncoagulopathic swine.

BACKGROUND: We performed this study to evaluate the hemostatic efficacy of the FAST Dressing in treating a grade V liver injury in noncoagulopathic swine. METHODS: Sixteen female splenectomized, noncoagulopathic swine underwent reproducible grade V liver injuries. The animals were blindly randomized to two treatment groups: (1) FAST Dressing (n = 8) or (2) IgG placebo dressing (n = 8). After 30 seconds of uncontrolled hemorrhage, dressings and manual compression were applied at 4-minute intervals. The number of dressings used, time to hemostasis, total blood loss, mean arterial pressure, blood chemistry, and total resuscitation fluid volume were monitored for 2 hours after injury. RESULTS: The mean total blood loss was 412.5 mL (SD 201.3) for the FAST Dressing group compared with 2296.6 mL (SD 1076.0) in the placebo group (p < 0.001). All animals in the FAST Dressing group achieved hemostasis and survived for the duration of the experiment (2 hours) after injury, whereas none of the animals in the placebo group attained hemostasis or survived to 2 hours after injury (p < 0.001). The mean time to hemostasis was 6.6 minutes (SD 2.5). A median of five dressings (mean absolute deviation 1.0, p = 0.007) was sufficient to control hemorrhage in the FAST Dressing group. CONCLUSION: The FAST Dressing reduced blood loss and improved survival compared with placebo in a noncoagulopathic, grade V liver injury swine model.

Clot-inducing minerals versus plasma protein dressing for topical treatment of external bleeding in the presence of coagulopathy.

BACKGROUND: Previous studies identified WoundStat (WS, smectite) and Combat Gauze (CG, kaolin-coated gauze) as the most effective available agents for controlling arterial bleeding with potential utility in casualty care. Tissue sealant properties of WS suggested its potential advantage over clot-promoting CG for treating coagulopathic bleeding. This study compared the efficacy of CG and WS with a fibrinogen-based (FAST) dressing to control bleeding in coagulopathic animals. METHODS: Coagulopathy was induced in pigs (n = 55, 35 kg) by ∼50% isovolemic hemodilution and hypothermia (core temperature, 33°C ± 0.5°C). A 6-mm arteriotomy was made in the femoral artery and free bleeding allowed for 30 seconds. A test agent (n = 13-15 per group) or control product (gauze, GZ, n = 12) was applied to the wounds and compressed with a Kerlix gauze for 2 minutes. Fluid resuscitation was given, titrated to a mean arterial pressure of 65 mm Hg. Animals were observed for 180 minutes or until death. Angiography using the computed tomography method was performed on survivors, and local tissues were collected for histology. RESULTS: No differences were seen in baseline measures. Coagulopathy, confirmed by a 31% increase in prothrombin time and a 28% reduction in clotting strength (maximum amplitude, thrombelastography assay), was similar in all groups before injury. The average pretreatment blood loss was 11.9 mL/kg ± 0.4 mL/kg with no difference among groups. Posttreatment blood loss, however, was significantly different (p = 0.015) ranging from 18.2 mL/kg ± 8.8 mL/kg (FAST) to 63.3 mL/kg ± 10.2 mL/kg (GZ controls). Stable hemostasis was achieved in 10 of 13 (FAST), 5 of 15 (CG), 2 of 15 (WS), and 1 of 12 (GZ) animals in each group, resulting in significantly different survival rates (8-77%; p = 0.001). The average survival times were 145 (FAST), 119 (CG), 75 (WS), and 74 (GZ) minutes for different groups (p < 0.002). The outcomes with the FAST dressing were significantly better than with WS or GZ in this coagulopathic bleeding model. Essentially, no difference was found between WS and GZ control. Computed tomography images showed limited blood flow only through the vessels treated with FAST dressings. Histologic observations of the vessels indicated minimal damage with FAST and CG and greater injury with WS with some residues present on the tissues. CONCLUSION: The tissue sealant property of WS is apparently mediated by clot formation in the wound; therefore, it was ineffective under coagulopathic conditions. CG was partially effective in maintaining blood pressure up to 1 hour after application. FAST dressing showed the highest efficacy because of the exogenous delivery of concentrated fibrinogen and thrombin to the wound, which bypasses coagulopathy and secures hemostasis.

Comparative study of the hemostatic efficacy of a new human fibrin sealant: is an antifibrinolytic agent necessary?

BACKGROUND: Sustained hemostasis by fibrin sealant (FS) is critically important when it is used in trauma surgery. To purportedly delay fibrin degradation and prevent premature hemostatic failure, some FS products added an antifibrinolytic agent (e.g., bovine aprotinin). The purpose of this study was to compare the overall hemostatic efficacy of a new inhibitor-free FS obtained from the American Red Cross (ARC-FS) to a clinically available aprotinin-containing FS preparation (Tisseel). The need for addition of an antifibrinolytic agent was assessed under normal and high-fibrinolytic conditions. METHODS: The abdominal aortas of anesthetized rabbits were transected and anastomosed, end-to end, using only four interrupted sutures. The suture line was covered with approximately 2 mL of either type of FS and blood flow was restored. Blood loss was absorbed by gauze and measured. All rabbits were recovered and underwent histologic examination 4 weeks after operation. The efficacy of FS was also tested under a high-fibrinolytic state by treating the rabbits with human recombinant tissue plasminogen activator (0.15 mg/kg, 3-hour infusion). The investigators were blinded to the treatment groups. RESULTS: The majority (11 of 12) of deaths occurred because of bleeding at the suture line within 7 days of surgery. Sustained hemostasis by FS (>1 week) was required for normal tissue healing and long-term survival of animals. Application of ARC-FS to the suture line produced immediate hemostasis in 43% of animals (three of seven), with mean blood loss of 4.8 +/- 1.8 mL, and 86% long-term survival. Tisseel application produced immediate hemostasis in 13% of animals (one of eight), with mean blood loss of 26.9 +/- 7.0 mL (p < 0.05 vs. ARC-FS) and survival rate of 37% (three of eight). Under high-fibrinolytic conditions, ARC-FS produced immediate and complete hemostasis in seven of eight animals (88%), whereas the Tisseel demonstrated complete hemostasis in one of seven (p < 0.01). The ARC-FS rabbits had a blood loss of 1.9 +/- 1.9 mL and survival rate of 75% (six of eight), whereas the Tisseel animals had a mean blood loss of 30 +/- 6.0 mL and survival rate of 43% (three of seven) (p < 0.01). No detrimental effect on healing was noted with either product. CONCLUSION: ARC-FS provides effective and secure hemostasis against high-pressure arterial bleeding under both normal and high-fibrinolytic conditions. Addition of an antifibrinolytic agent such as aprotinin is not required to sustain the hemostatic function of this fibrin sealant.