Dawson Beall

Fibrin sealant foam sprayed directly on liver injuries decreases blood loss in resuscitated rats

OBJECTIVE The majority of early trauma deaths are attributable to uncontrolled hemorrhage from truncal sites. A hemorrhage-control technique that reduced bleeding in the prehospital phase of treatment without requiring manual compression may improve the outcome of these patients. We conducted this preliminary study to determine whether an expanding fibrin sealant foam (FSF) would reduce bleeding from a severe liver injury even during resuscitation. METHODS Rats (n = 31; 291 +/- 5 g; 37.4 +/- 0.3 degrees C; mean +/- SEM), underwent a 60 +/- 5% excision of the median hepatic lobe. The animals received one of three treatments: (1) FSF, (2) immunoglobulin G placebo foam (IgGF), or (3) no treatment. All animals were resuscitated with 40 degrees C lactated Ringers solution at 3.3 mL/ min/kg to a mean arterial pressure of 100 mm Hg. Total blood loss, mean arterial pressure, and resuscitation volume were recorded for 30 minutes. A qualitative measure of foam coverage and adherence to the cut liver edge was recorded. RESULTS The total blood loss was less (p < 0.01) in the FSF group (21.2 +/- 5.0 mL/kg) than in either IgGF (41.4 +/- 4.3 mL/kg) or the no treatment group (44.6 +/- 4.7 mL/kg), which did not differ. The resuscitation volume was not different. The amount of foam used in the treated groups, 9.1 +/- 1.0 g in the FSF group and 10.0 +/- 1.0 g in the IgGF group, did not differ. Survival for 30 minutes was not different among groups. There was no difference in the amount of cut liver covered by either foam, but the clots were more adherent (p < 0.05) in the FSF group than in the IgGF group. CONCLUSION In rats with a severe liver injury, spraying fibrin foam directly on the cut liver surface decreased blood loss when compared with placebo foam and no treatment. This pilot study suggests a future possible treatment for noncompressible truncal hemorrhage.

Does the absorbable fibrin adhesive bandage facilitate partial nephrectomy

PURPOSE To evaluate the ability of the absorbable fibrin adhesive bandage (AFAB), a prototype product comprising lyophilized fibrinogen and thrombin on a VicrylTM mesh backing, to seal the collecting system and control bleeding after partial nephrectomy. MATERIALS AND METHODS Growing female pigs (n = 18) underwent left nephrectomy and a 40% (by length) right lower pole partial nephrectomy. One of three treatments was immediately applied: Conventional-closure of the collecting system, ligation of visible segmental vessels, application of SurgicelTM with bolstering sutures to the renal capsule; AFAB-application of up to two 4 x 4-inch AFABs held under pressure for 60 seconds; Placebo-application of a hemostatically inert VicrylTM bandage, visually identical to the AFAB. Blood loss and ischemic and total operative times were recorded, and abdominal computerized tomography (CT) was performed on postoperative day 6. Animals were sacrificed at 6 weeks to evaluate the remaining renal mass histologically. RESULTS Compared with conventional therapy, use of the AFAB resulted in significantly less bleeding (13 versus 68 ml., p <0.001) and lower operative (7.2 versus 16.3 minutes, p <0.001) and ischemic times (3.4 versus 7.8 minutes, p <0.001). Estimated blood loss in the placebo bandage group was dramatically higher (357 ml., p <0.001). Postoperative CT and histological sectioning suggested that the AFAB produces a stable, durable clot and that healing is at least as successful as with conventional treatment. CONCLUSION Use of the AFAB facilitated performance of partial nephrectomy by reducing blood loss and ischemic and total operative times. The AFAB appears equivalent to conventional surgery in its ability to seal the collecting system.

Treatment of grade 4 renal stab wounds with absorbable fibrin adhesive bandage in a porcine model.

PURPOSE In a porcine model we evaluated the efficacy of the absorbable fibrin adhesive bandage and other novel fibrin products for treating major renal stab wounds. MATERIALS AND METHODS In commercial swine we produced an almost lethal, grade 4 renal stab wound via a 3.5 cm. sagittal, centrally located, through-and-through laceration. Each pig then received treatment in random fashion, including conventional oversewing of capsular defects with absorbable gelatin sponge and horizontal mattress sutures in 6, external absorbable fibrin adhesive bandage that was pressure held for 60 seconds in 6, external and internal absorbable fibrin adhesive bandage that was applied externally, inserted into the renal defect and pressure held for 60 seconds in 6, liquid fibrin sealant that was placed in the laceration and held for 60 seconds in 8, fibrin foam that was applied in the same manner as liquid fibrin in 5 and closing of the peritoneum over the lacerated kidney without further treatment in 6. Blood loss and time to hemostasis were recorded. Animals were sacrificed at 6 weeks to evaluate the injured renal unit. RESULTS Compared with conventional therapy the absorbable fibrin adhesive bandage applied externally alone or externally and internally resulted in significantly less bleeding and significantly less time to hemostasis (p <0.001). Liquid fibrin and fibrin foam did not reliably achieve hemostasis. Postoperatively computerized tomography and histological sectioning suggested that the absorbable fibrin adhesive bandage results in a stable, durable clot and healing is at least as successful as with conventional treatment. CONCLUSIONS The absorbable fibrin adhesive bandage appears to be a safe, rapid means of renal salvage after injury.

Intraoperative use of the absorbable fibrin adhesive bandage: long term effects.

PURPOSE The absorbable fibrin adhesive bandage (AFAB) reduces acute blood loss in experimental trauma models, but the effects on wound healing and subsequent function have heretofore not been investigated. Retropubic prostatectomy was selected to evaluate short and long term effects of using the AFAB intraoperatively. MATERIALS AND METHODS Dogs undergoing prostatectomy were randomly assigned to one of four treatments: CONTROL- sponges and manual pressure were applied after transecting the prostatic pedicles. Sponges were removed when the prostate was delivered. Vessels were isolated and ligated if bleeding continued after removal. AFAB- hemostatically active bandages were applied to the prostatic bed prior to sponges and pressure. Additional bandages were applied at the urethrovesical junction after completing the anastomosis. PLACEBO- visually identical (hemostatically inert) bandages were applied in an identical fashion. LIQUID SEALANT- concentrated thrombin and fibrinogen solution was applied to the vessels prior to sponges and pressure. Additional sealant solution was applied around the anastomosis. RESULTS Blood loss and time to achieve hemostasis were significantly less in the AFAB group compared with the other treatments. There were no differences in days to anastomotic integrity, continence, or intra-abdominal adhesions at necropsy six weeks later. CONCLUSIONS The AFAB can reduce surgery time and blood loss, with no decrement in wound healing or subsequent function.

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.

Metabolic and hemodynamic effects of CO2 pneumoperitoneum in a controlled hemorrhage model.

BACKGROUND Intracavity infusion of fibrin sealant-based agents, as a novel modality to control internal bleeding, is associated with an increase of pneumoperitoneum (PP) pressure. The safe limit of such increase has not been well defined in hypovolemic subjects. The purpose of this study was to evaluate the hemodynamic and metabolic effects of increasing PP pressure and to define the limits of carbon dioxide (CO2) insufflation in a controlled hemorrhage rat model. METHODS Ninety male rats (474 +/- 6 g, 37 degrees +/- 1 degrees C) were anesthetized, and mechanically ventilated. Animals were randomly distributed among 14 groups (n = 6-8) with an increasing amount of blood loss (0, 10, 15, and 17.5 mL/kg) and 15 minutes of CO2 insufflation at 0, 5, 10, and 15 mm Hg starting 15 minutes after hemorrhage, followed by desufflation. Mean arterial pressure (MAP), heart rate, and survival were recorded and arterial and venous blood samples were collected at baseline, at 15 minutes after hemorrhage, after insufflation, and after desufflation procedures to determine arterial blood gases and lactic acid levels. RESULTS In nonhemorrhaged animals, increasing PP pressure up to 15 mm Hg produced only transient changes in MAP and no increase in lactate level. A moderate hemorrhage (10 mL/kg) limited the safe abdominal pressure to 10 mm Hg with metabolic changes that were restored 15 minutes after desufflation. Higher PP pressure (15 mm Hg) at this hemorrhage level produced a significant decline in MAP (42%, p < 0.001) and progressive metabolic acidosis with a 2.1-fold increase (p < 0.01) in lactate level. The more severe hemorrhage (15 mL/kg) further reduced the limits of PP pressure such that 10 and 15 mm Hg resulted in a progressive decline of blood pressures (52% and 54%, respectively; p < 0.001) and severe metabolic acidosis as manifested by 3.3- and 3.1-fold rises in lactate levels, respectively. In the most severe hemorrhaged animals (17.5 mL/kg), the 50% mortality was primarily determined by the severity of the blood loss and the additional PP at 5 mm Hg had no significant impact. CONCLUSION The safe limit of PP pressurization with CO2 is dependent on the amount of blood loss. In this mechanically ventilated rat model, increasing the amount of blood loss from 0 to 15 mL/kg reduces the tolerable level of abdominal insufflation pressure from 15 mm Hg to 5 mm Hg. A 5-mm Hg PP pressure appears safe even in the most severely hemorrhaged animals.

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.

Protein composition of clots detected in pooled cryoprecipitate units.

BACKGROUND: On rare occasions, upon thawing of stored cryoprecipitate components, clots are observed on visual inspection. Although it has been assumed that the clot reflects fibrinogen to fibrin conversion, there are few published studies that document that this assumption is correct. Our studies were conducted to further identify the protein characteristics of the clotted material.