A multicenter, prospective, randomized trial evaluating a new hemostatic agent for spinal surgery

STUDY DESIGN: A prospective, randomized trial comparing Proceed, a gelatin-based hemostatic sealant (treatment), with Gelfoam-thrombin (control) in stopping intraoperative bleeding during spinal surgery. OBJECTIVES: To determine the effectiveness and safety of Proceed. SUMMARY OF BACKGROUND DATA: Proceed has been tested in animal models to determine its safety and effectiveness as a hemostatic agent. The current study was conducted under a Food and Drug Administration-approved Investigational Device Exemption to evaluate the effectiveness and safety of Proceed in humans. METHODS: For this study, 127 patients undergoing spinal surgery were randomized into either the treatment or control group after standard surgical means to control bleeding had failed. The bleeding site was evaluated at 1, 2, 3, 6, and 10 minutes after the hemostatic agent was applied. The application was considered successful if the bleeding stopped within 10 minutes. Follow-up evaluation was performed at 12 to 36 hours, then at 6 to 8 weeks after surgery. RESULTS: Proceed stopped bleeding in 98% of the patients (first bleeding site only) within 10 minutes, as compared with 90% of the control patients (P = 0.001). At 3 minutes, successful hemostasis had been achieved in 97% of the Proceed group, as compared with 71% of the control group (P = 0.0001). There was no difference in the adverse event profile between the two groups. CONCLUSIONS: A significantly larger number of bleeding sites had achieved hemostasis with Proceed than with Gelfoam-thrombin at 1, 2, and 3 minutes after application. Proceed was as safe as Gelfoam-thrombin when used for hemostasis during spinal surgery procedures.     

The effects of aprotinin on hemostatic function during cardiac surgery.

The mechanism of action by which large doses of aprotinin decrease blood loss during cardiac surgery is not completely understood. In a prospective, controlled study, 30 patients undergoing cardiac surgery were given high-dose aprotinin in accordance with a commonly used regimen. Twenty untreated but otherwise comparable patients served as the control group. The effects of aprotinin therapy during cardiopulmonary bypass on coagulation parameters, the kallikrein-kinin system, fibrinolysis, platelet stimulation, and the release of elastase from neutrophils were studied. The fibrinolysis parameters were the only measurements that showed clear and significant differences between the two groups. Aprotinin almost completely inhibited the formation of fibrin and fibrinogen degradation products. It is assumed that inhibition of systemic fibrinolysis and suppression of local fibrinolysis contribute to the hemostatic action of aprotinin. The study did not demonstrate a significant protective effect of aprotinin on platelets. In addition, the dose of aprotinin administered did not affect the kallikrein-kinin system of elastase. Therefore, these data suggest that the previously demonstrated hemostatic effects of aprotinin derive primarily from its antifibrinolytic action.     

Prospective, randomized, controlled clinical trial of a novel matrix hemostatic sealant in children undergoing adenoidectomy.

PROBLEM ADDRESSED: Floseal is a novel matrix hemostatic sealant composed of collagen-derived particles and topical bovine-derived thrombin. It is applied as a high-viscosity gel for hemostasis and has been clinically proven to control bleeding. This study is a prospective, randomized, controlled clinical trial of Floseal sealant compared to traditional suction cautery hemostasis in children undergoing adenoidectomy. METHODS AND MEASURES: Seventy patients (mean age 7.0 yrs, 45.7% male) with obstructive sleep apnea underwent traditional cold steel adenoidectomy with an adenoid curette and were then randomized to receive the hemostatic sealant (Floseal) or cautery to obtain hemostasis. Patients were crossed over to the other hemostatic technique if hemostasis was not achieved after more than 100 mL of blood loss or 15 minutes elapsed time. Objective data collected included time to hemostasis and blood loss during hemostasis. Visual analog scales (VAS) were used to record subjective data by the operating surgeon including bleeding following adenoid pack removal (0 = none, 3 = brisk) and ease of operation (1 = extremely easy, 6 = extremely difficult). Parents recorded diet on a journal and were contacted by phone at postoperative day 7 and questioned with regard to return to regular diet and use of narcotics. RESULTS: Compared to patients in the cautery group (n = 35), Floseal patients (n = 35) had significantly shorter times to hemostasis (0.6 +/- 1.3 minutes vs 9.5 +/- 5.4 minutes [mean +/- SD], P < 0.001), less blood loss (2.5 +/- 9.2 mL vs 29.4 +/- 27.1 mL, P < 0.001), less subjective bleeding (0.0 +/- 0.6 vs 2.0 +/- 0.7, [median 4-point VAS +/- SD], P < 0.001), and subjectively easier operations (2.6 +/- 1.0 vs 5.2 +/- 1.0 [mean 6-point VAS +/- SD], P < 0.001). Furthermore, Floseal patients returned to regular diet earlier (2.7 +/- 0.7 vs 4.1 +/- 0.5 days [mean +/- SD], P < 0.001) and had less use of narcotics at 7 days postoperatively (40% vs 69%, P < 0.05). Lastly, three patients in the cautery group were crossed over to the Floseal group, but no Floseal subjects were crossed over to the cautery group. The retail cost of Floseal is US 85 dollars. Operating room costs are estimated at US 12 dollars/minute. Reducing the operative length by 8.9 minutes on average produces a cost savings of US 106.80 dollars per operation. There were no complications in either experimental group including postoperative hemorrhage, hospitalization, blood transfusion, or aspiration. CONCLUSIONS: Floseal matrix hemostatic sealant is a safe, efficacious, easy, and cost-effective technique for obtaining hemostasis in children undergoing adenoidectomy. Limitations of the study include the fact that it is nonblinded, which does allow for some bias in the subjective data recorded. However, utilizing 4 different operating surgeons, 3 of whom were not affiliated with the study, minimized this. CLINICAL SIGNIFICANCE OF STUDY: This study demonstrates the safety and efficacy of a novel hemostatic sealant in children undergoing adenoidectomy. Floseal matrix hemostatic sealant can be used as a first-line hemostatic agent, and it is a good tool in the armamentarium of otolaryngologists who encounter significant bleeding following adenoidectomy.     

Reduction of infection after cardiac surgery: a clinical trial

Between January 1, 1975, and June 1, 1984, 3,275 patients underwent cardiac operations with cardiopulmonary bypass. No operations were performed in 1978. In Phase I of the study, general operating rooms were used for cardiac operations, and standard methods of antisepsis and asepsis were used. Phase II began in January, 1979, with the opening of two specially constructed operating rooms with complete separation of incoming and outgoing personnel and supplies, and with a laminar airflow system. All personnel scrubbed 3 minutes and changed into autoclaved clothing before entering the operating suite, and scrubbed again for 5 minutes before putting on gowns. By Phase III, which began in July, 1982, all additional protocols against infection were in place including strict techniques in the intensive care unit and a continuous antiinfection surveillance program. In Phase I, 7.3% (70% confidence limits [CL] 6.4 to 8.2%) of patients had an infectious complication; in Phase II, 2.7% (CL 2.3 to 3.2%), and in Phase III, 0.8% (CL 0.5 to 1.2%). The reductions were similar in the four subtypes of infection (superficial presternal infection, mediastinitis, endocarditis, and septicemia). The study indicates that improving the surgical environment, improving the surgical and operating room protocols, and increasing the awareness of the dangers of infection among the personnel can strikingly reduce the incidence of infections after cardiac operations.     

Pharmacologic preservation of the hemostatic system during cardiac surgery.

Bleeding after cardiac surgery remains a major potential problem. Numerous pharmacologic approaches to attenuating hemostatic system activation in cardiac surgery patients have been studied to further improve patient management. Therapeutic approaches studied include inhibiting thrombin generation or activation, preserving platelet function, and decreasing the need for transfusion of allogeneic blood products. Pharmacologic approaches to reduce bleeding and transfusion requirements in cardiac surgery patients are based on either preventing or reversing the defects associated with the CPB-induced coagulopathy. The increasing use of platelet inhibitors (clopidogrel and IIb/IIIa receptor antagonists) and new anticoagulants (low-molecular weight heparins, pentasaccharide, recombinant hirudin, bivalirudin, and argatroban) also pose interesting problems in managing cardiac surgery patients. Aprotinin and lysine analogues (epsilon-aminocaproic acid and tranexamic acid) have become mainstay therapeutic agents to prevent bleeding and the potential need for allogeneic transfusion. Newer therapies that are important to consider include the potential of recombinant activated factor VIIa as a therapy for refractory bleeding after cardiac surgery.     

Modifying myocardial management in cardiac surgery: a randomized trial.

Among the 160 patients randomly assigned to one of eight protocols of myocardial management, all of which included controlled aortic root reperfusion, no important differences were found between protocols as to the prevalence of death (0 instances), use of an intra-aortic balloon pump (no instances), use of catecholamines, elaboration of CK-MB isoenzymes, new Q-waves, abnormal wall motion scores, or postoperative atrial fibrillation. Ventricular defibrillation was required more often in patients in the protocol with noncardioplegic blood reperfusate. Cardiac index was highest in the operating room in the group receiving hyperkalemic cold cardioplegia and initial hyperkalemic reperfusion. The reperfusion flow at the controlled pressures had initially a low flow rate (pressure 30 mmHg for 2 min; thereafter 50 mmHg), which increased to reach a peak flow rate at about 3 min after the start of reperfusion, followed by a declining flow rate reflecting changes in coronary resistance. Comparison of the overall randomly assigned group with a historical control group of 100 patients operated upon prior to the randomized trial showed no differences except for a higher rate of postoperative atrial fibrillation (25%) in the historical control group than in the randomized protocols with initial cardioplegic reperfusion (14%). The controlled reperfusion technique was found to be easy to use and is now used routinely.     

The effectiveness of a fibrinogen-thrombin-collagen-based hemostatic agent in an experimental arterial bleeding model.

The hemostyptic agent used in this study is a recently developed material that consists of a collagen fleece containing fibrinogen, thrombin, and aprotinin integrated into its surface (FTCH) with excellent topical hemostyptic properties. The potential use of this substance for cardiovascular surgery was evaluated in a canine arterial bleeding model, which allowed comparison of the new agent with previously used pure collagen (CHF) as well as study of the hemostyptic under elevated blood pressure conditions. The results revealed that FTCH induced reliable hemostasis in 10-mm injuries of the canine hypogastric artery up to a systolic blood pressure of 260 mmHg, whereas bleeding control by CHF alone was impossible. To assess the long-term reliability of FTCH, the dogs were re-explored at intervals of 14 and 31 days after operation. At relaparotomy, the arteries were patent and there was no evidence of recurrent bleeding, thrombosis formation, or aneurysmatic changes. Histologic examinations showed well-healed vascular lesions covered by cell-depleted collagen tissue and a partially resorped hemostyptic. FTCH will not replace adequate surgical techniques but could be useful as a quickly available and easily applicable hemostatic means in otherwise uncontrollable diffuse or acute bleeding in cardiovascular surgery.     

Hextend, a physiologically balanced plasma expander for large volume use in major surgery: a randomized phase III clinical trial. Hextend Study Group.

Hextend (BioTime, Inc., Berkeley, CA) is a new plasma volume expander containing 6% hetastarch, balanced electrolytes, a lactate buffer, and physiological levels of glucose. In preclinical studies, its use in shock models was associated with an improvement in outcome compared with alternatives, such as albumin or 6% hetastarch in saline. In a prospective, randomized, two-center study (n = 120), we compared the efficacy and safety of Hextend versus 6% hetastarch in saline (HES) for the treatment of hypovolemia during major surgery. Patients at one center had a blood sample drawn at the beginning and the end of surgery for thromboelastographic (TEG) analysis. Hextend was as effective as HES for the treatment of hypovolemia. Patients received an average of 1596 mL of Hextend: 42% received >20 mL/kg up to a total of 5000 mL. No patient received albumin. Hextend-treated patients required less intraoperative calcium (4 vs 220 mg; P < 0.05). In a subset analysis of patients receiving red blood cell transfusions (n = 56; 47%), Hextend-treated patients had a lower mean estimated blood loss (956 mL less; P = 0.02) and were less likely to receive calcium supplementation (P = 0.04). Patients receiving HES demonstrated significant prolongation of time to onset of clot formation (based on TEG) not seen in the Hextend patients (P < 0.05). No Hextend patient experienced a related serious adverse event, and there was no difference in the total number of adverse events between the two groups. The results of this study demonstrate that Hextend, with its novel buffered, balanced electrolyte formulation, is as effective as 6% hetastarch in saline for the treatment of hypovolemia and may be a safe alternative even when used in volumes up to 5 L. IMPLICATIONS: Hextend (BioTime, Inc., Berkeley, CA) is a new plasma volume expander containing 6% hetastarch, balanced electrolytes, a lactate buffer, and a physiological level of glucose. It is as effective as 6% hetastarch in saline for the treatment of hypovolemia but has a more favorable side effects profile in volumes of up to 5 L compared with 6% hetastarch in saline.     

Controlled prospective trial of wound management in elective hand surgery.

A total of 33 consecutive patients undergoing elective hand operations were randomly allocated 5 days after the operation either to have all dressings discarded or to continue with an occlusive bandage for a further 2 weeks. Assessments at 2 and 6 weeks showed that wound healing, hand function, symptoms and complications were identical in both groups. It was concluded that for selected patients early removal of hand dressings after surgery does not have any deleterious effects.     

The mechanical bonding of methylmethacrylate to cancellous bone. Effect of a hemostatic agent.

The bonding of methylmethacrylate to cancellous bone was tested in shear both in control specimens and in those in which microfibrillar collagen had been previously used as a hemostatic agent. The breaking load and energy to failure were significantly lowered by the microfibrillar collagen.