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[Hemostatic requirements for the performance of regional anesthesia. Workshop on hemostatic problems in regional anesthesia].

There is uncertainty as to which preoperative examinations are necessary before performing regional anesthesia. Therefore an interdisciplinary consensus conference was established to obtain recommendations on some of the open questions related to this topic. Preoperative laboratory examinations are not necessary prior to peripheral nerve blocks near large vessels if these are easy to compress. In patients on anticoagulant therapy direct puncture of the vessel should be avoided. Prior to spinal or epidural anesthesia, no preoperative laboratory examinations are necessary if no anamnestic or clinical evidence of coagulation disorders exists. Otherwise the following examinations are useful: clotting time, prothrombin time, partial thromboplastin time (PTT), and thrombocyte count. Low-dose heparin prophylaxis is no contraindication to spinal or epidural anesthesia. However, in patients at increased risk of bleeding or with low body weight, PTT and thrombocyte count are necessary. Since at present no definite data exist as to the bleeding risk in patients treated with low-molecular-weight heparin prophylaxis, spinal/epidural anesthesia should be performed in controlled studies only under these conditions. This particular precaution seems to be necessary because low-molecular-weight heparin increases levels of plasminogen activators (t-PA) and therefore has fibrinolytic activity. If plasma expanders are administered perioperatively, the highest bleeding risk exists after dextran infusions. There is also an increased bleeding risk if nonsteroidal anti-inflammatory drugs, especially acetylsalicylic acid, are administered repeatedly within 5 days prior to spinal/epidural anesthesia. In these patients preoperative determination of the clotting time appears necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Conduction↗

Clinical benefits and risk analysis of topical hemostats: a review.

A variety of local hemostats including absorbable gelatin sponge, collagen hemostat, and oxidized cellulose are commercially available. Local hemostats are applied when cautery, ligature, or other conventional hemostatic method is impractical. Proper handling is essential to control bleeding and only the required amount should be used, even though the hemostat is expected to dissolve promptly. A dry local hemostat absorbs body fluid of several times its own weight and expands postoperatively. Therefore, when an absorbable hemostatic agent is retained on or near bony or neural spaces, the minimum amount should be left after hemostasis is achieved. Documentation is important with regard to the hemostat used, including the name of the agent, site, and amount. This information is used as a reference in the interpretation of postoperative diagnostic images, since retained hemostat may sometimes mimic an abscess or recurrent tumor. The antigenicity of collagen is known to be low because of homology. When the safety of collagen was evaluated, the incidence of positive reactions was reported as 3.0%, and collagen may cause allergic reactions. Minimum inflammation without strong foreign body reactions or blockade of healing is desirable after the use of local hemostats. Strong foreign body reactions, chronic inflammation, and infections can cause granuloma formation after local hemostat use. By using local hemostats, it is possible to improve the condition of the patient, reduce complications, and lower direct and indirect costs.

Cellulose, Oxidized↗

The use of hemostatic agents and sealants in urology.

PURPOSE: While hemostatic agents and sealants have long been used in the fields of surgery and urology, confusion persists about their indications for use and the optimal agent choice. We comprehensively defined and evaluated the scientific basis for hemostatic agent and sealant use in urology, and provide a conceptual framework for future research and discussion. MATERIALS AND METHODS: A MEDLINE search of all available literature concerning hemostatic agents in urology was performed, including topical hemostats, anti-fibrinolytics, fibrin sealants and matrix hemostats. Select references were also chosen from the broader surgical literature. Animal studies, case reports, retrospective and prospective studies, and opinion articles were reviewed. RESULTS: Hemostatic agents include a wide range of components. Recent literature has focused on fibrin sealants and matrix agents. Two main indications exist for hemostatic agents, including 1) hemostasis and 2) sealant. The best evidence for efficacy and safety exists for hemostasis, especially for nephrectomy and trauma. Newer data highlight urinary tract reconstruction, fistula and percutaneous tract closure, suture line strengthening and infertility as potential uses. Novel drug delivery and tissue engineering are areas with large clinical potential. CONCLUSIONS: Hemostatic agent use is promising and yet unproven for most conditions currently treated in urology. Hemostasis continues to be the main indication, which is well established. Few trials have examined comparative efficacy among hemostatic agents and further prospective studies are needed to justify additional indications as well as determine the optimal mode of use. Minimally invasive surgery will further drive the use of hemostatic agents and sealants. Cost-effective, evidence based hemostatic agent use will continue to challenge all urologists.

Anastomosis, Surgical↗

[Effects of a hemostatic jelly with polylactic acid on hemostasis of injured cancellous bone].

OBJECTIVE: To prepare a self-made compound, hemostatic jelly with polylactic acid (PLA), which has the hemostatic and absorbable effect on injured cancellous bone. METHODS: Two bone defects of 5 mm in diameter and 4 mm in depth were subjected on 20 health rabbits by drilling through their either outside plate of the iliac, and were filled with hemostatic jelly(group A), bone wax(group B) and blank(group C) respectively. Hemostasis were observed and recorded after 1 and 10 minutes. Five specimens were harvested at 2, 4, 8 and 12 weeks postoperatively for histological observation. RESULTS: (1) Hemostatic effect: Bleeding of injured spongy bone stopped within 10 minutes after the treatment of hemostatic jelly and bone wax, but bleeding of blank did not stop. Hemostatic jelly and bone wax adhered to bone defects firmly within 10 minutes was after the treatment. (2) Absorbable effect: Hemostatic jelly and bone defects have not changed visibly in the first 2 weeks. With histological observation 4 to 8 weeks after the operation, hemostatic jelly was absorbed gradually and replaced by osteogeneous tissue. It was absorbed completely after 8 to 12 weeks. Bone wax was not absorbed after 12 weeks, no new bone tissue was observed at bone wax area. The blank was replaced by connective tissue and osteogeneous tissue partially after 12 weeks. CONCLUSION: The compound hemostatic jelly manifests both hemostatic and absorbable effects on injured cancellous bone and may substitute for bone wax in clinical application.

Animals↗

Evaluation of a new hemostatic agent in experimental splenic laceration.

OBJECTIVES: To compare the effectiveness of several hemostatic agents and to evaluate a new hemostatic agent (ReClot) in controlling splenic hemorrhage. DESIGN: Rabbits were anesthetized and catheters placed. A celiotomy was performed and a splenic injury produced; hemostatic agent and compression were applied. EXPERIMENTAL GROUPS: In group 1 (n = 8), the splenic laceration was compressed with a dry sponge and 75 g of pressure until hemorrhage ceased. In groups 2, 3, and 4 (n = 10 each), splenic injury was treated with Avitene, Collastat, and ReClot, respectively. Hemostatic agent was applied to the splenic laceration and a dry sponge and pressure were applied as described for group 1. In group 5 (n = 9), a splenic laceration was produced, ReClot applied, and aggressive fluid resuscitation was initiated; the volume of crystalloid was adjusted to maintain mean arterial pressure. RESULTS: Application of a hemostatic agent reduced total blood loss compared with that measured in the control group, but there was no difference in blood loss among experimental groups treated with a hemostatic agent. The time required to achieve control of blood loss was less in the ReClot-treated group compared with the Avitene- and Collastat-treated groups. CONCLUSIONS: The hemostatic agent ReClot had a significant advantage over other hemostatic agents for the time required to achieve control of splenic bleeding. Aggressive fluid resuscitation did not limit the ability of ReClot to produce hemostasis.

Acidosis↗

Comparative in vitro analysis of topical hemostatic agents.

Hemostatic agents are broadly utilized across the surgical specialties. While specific characteristics desirable for individual applications may vary, these agents generally are expected to aid the patient's coagulation system in the rapid development of an occlusive clot. Six commonly utilized hemostatic agents were quantitatively compared in terms of their ability to mediate platelet aggregation, deposition and activation, and initiate gross clot formation in a series of in vitro tests. Three types of collagen sponges (Actifoam, Helistat, Instat), microfibrillar collagen (Avitene), a gelatin sponge (Gelfoam), and oxidized regenerated cellulose (Surgicel) were studied. Platelet aggregation: Citrated platelet rich plasma (PRP) was contacted with hemostatic agents both with and without thrombin in a stirred cuvette and the platelet count was measured over 5 min. Platelet deposition: To approximate arterial wounds, PRP was perfused in a controlled manner through hemostatic agents, and the effluent platelet count was measured over time. Platelet activation: ATP secretion from PRP contacted with hemostatic agents in a stirred cuvette was measured at 1 and 5 min. Clot formation: The clotting time of nonanticoagulated whole blood contacted with the hemostatic agents was measured. Materials which depleted platelets most rapidly and effectively in the perfusion system (Avitene, Helistat, and Actifoam) were also the most effective inducers of platelet aggregation and secretion. Clot formation (likely to be platelet dependent) was also more rapid in this group. An overall activity ranking combined the relative performance of each hemostatic agent on the various tests: Actifoam approximately Avitene > Helistat >> Gelfoam > Instat > Surgicel. The activity ranking generally reflects the materials used in these agents (collagen > gelatin > oxidized regenerated cellulose), as well as their processing (chemical crosslinking in collagen sponges may lower activity). Such in vitro assessment of the relative platelet and coagulation activities of hemostatic agents might serve as a useful screening tool before investigating properties which require more expensive animal or clinical testing.

Adenosine Triphosphate↗

Thermal injury resulting from application of a granular mineral hemostatic agent.

BACKGROUND: Uncontrolled hemorrhage accounts for the majority of deaths in combat. Effective topical hemostatic agents suitable for use on the battlefield may be valuable in controlling hemorrhage until definitive surgical intervention is possible. In an effort to identify a hemostatic agent suitable for battlefield use, we evaluated several potential hemostatic agents in a swine injury model and noted thermal injury to tissues with a granular mineral hemostatic agent (QuikClot). METHODS: Anesthetized swine were maintained with a mean arterial pressure in excess of 60 mm Hg. Cutaneous, muscular, hepatic, splenic, venous, and arterial wounds were created in a standardized fashion. Topical hemostatic agents were immediately applied to the wounds and the amount of bleeding and time to hemostasis were noted. RESULTS: The results reported here are part of a larger study in which a variety of hemostatic agents were evaluated. Only the findings related to the granular mineral hemostatic agent are discussed here. Application of the agent resulted in elevated tissue surface temperatures in excess of 95 degrees C and internal tissue temperatures exceeding 50 degrees C, 3 mm deep to the bleeding surface. Necrosis of fat and muscle were noted as well as full and partial thickness cutaneous burns. CONCLUSIONS: Topical administration of a granular mineral hemostatic agent to a variety of wounds in an experimental swine model resulted in thermal tissue injury and necrosis. Suggestions for reducing the extent of injury with this product are offered.

Administration, Cutaneous↗

Application of a zeolite hemostatic agent achieves 100% survival in a lethal model of complex groin injury in Swine.

BACKGROUND: Techniques for better hemorrhage control after injury could change outcome. We have previously shown that a zeolite mineral hemostatic agent (ZH) can control aggressive bleeding through adsorption of water, which is an exothermic process. Increasing the residual moisture content (RM) of ZH can theoretically decrease heat generation, but its effect on the hemostatic properties is unknown. We tested ZH with increasing RM against controls and other hemostatic agents in a swine model of battlefield injury. METHODS: A complex groin injury was created in 72 swine (37 +/- 0.8 kg). This included semitransection of the proximal thigh and complete division of the femoral artery and vein. After 3 minutes, the animals were randomized to 1 of 10 groups: group 1, no dressing (ND); group 2, standard dressing (SD); group 3, SD + 3.5 oz ZH with 1% RM (1% ZH); group 4, SD + 3.5 oz ZH with 4% RM (4% ZH); group 5, SD + 2 oz ZH with 1% RM (1% ZH 2oz); group 6, SD + 3.5 oz ZH with 8% RM (8% ZH); group 7, SD + chitosan-based hemostat, HemCon (HC); group 8, SD + 3.5 oz nonzeolite mineral hemostat, Quick Relief (NZH); group 9, SD + bovine clotting factors-based hemostat, Fast Act (FA); and group 10, SD + 30 g of starch-based hemostat, TraumaDex (TDex). Resuscitation (500 mL of Hespan over 30 minutes) was started 15 minutes after injury and hemodynamic monitoring was performed for 180 minutes. Primary endpoints were survival for 180 minutes and blood loss. In addition, maximum wound temperatures were recorded, and histologic damage to artery, vein, nerve, and muscle was documented. RESULTS: Use of 1% ZH decreased blood loss and reduced mortality to 0% (p < 0.05). Increasing the RM adversely affected efficacy without any significant decrease in wound temperatures. Minimal histologic tissue damage was seen with ZH independent of the percentage of RM. CONCLUSION: The use of zeolite hemostatic agent (1% residual moisture, 3.5 oz) can control hemorrhage and dramatically reduce mortality from a lethal groin wound.

Adsorption↗

Topical hemostatic effect of a common ornamental plant, the geraniaceae Pelargonium zonale.

Geranium has been traditionally used as a local hemostatic medicine in some Andean regions, but this effect has not been tested in controlled experiments. In the present report, the leaves of a geraniaceae (Pelargonium zonale) were tested on a bleeding rat model. The bleeding time was 50% shorter in the geranium leaf juice treatment group (18.10 +/- 2.03 min) and 80% shorter in the geranium crushed-leaf group (7.10 +/- 0.88 min) than in the control (nontreatment) group (37.6 +/- 3.04 min), p < 0.0001. Bleeding time with guava (Psidium guajava) crushed leaves (39.90 +/- 1.54 min) was not different from the control group. A proved hemostatic agent, gelatin sponge, had a similar effect as geranium juice (16.7 +/- 3.32 min) in the same animal model. A buffer solution at pH 3 (the same pH as the geranium leaf extract) did not have any hemostatic effect, and the bleeding time (39.3 +/- 2.71 min) was not different from the control group. The dilution 1:4 geranium leaf juice at pH 3(25.6 +/- 3.08 min) or pH 5 (28.8 +/- 3.98 min) still had a statistically significant hemostatic effect. The results confirm the hemostatic effect of P. zonale leaves and show that it is similar (geranium leaf juice) or better (crushed geranium leaves) than the hemostatic effect of a commercial hemostatic sponge. It seems that the hemostasis caused by P. zonale extract leaves is not due to its low pH. The potential benefits as a new, inexpensive, safe, and easily available natural topical hemostatic agent are discussed.

Administration, Topical↗

Comparison of hemostatic activation created by right- and left-heart radiofrequency catheter ablation.

BACKGROUND: Thromboembolic complications commonly occur in radiofrequency (RF) ablation procedures (0.6-1.3% of cases). Comparison of hemostatic activation between left and right RF ablation is limited. HYPOTHESIS: The purpose of this study was to evaluate platelet and hemostatic activation before, immediately after, and 48 h following left and right myocardial RF ablation procedures. METHODS: The subjects were two groups of patients who underwent right-heart (24 patients) and left-heart (20 patients) RF ablation. Blood samples taken before, immediately after, and 48 h after the procedure were tested for changes in platelet and hemostatic activation. RESULTS: No indication of clinically symptomatic thromboembolism and no major differences in baseline characteristics and procedure were apparent in either group, except for a higher temperature mode setting (p < 0.001) in the left-heart group. The hemostatic evaluation levels increased significantly by the end of the procedure in both groups and the platelet activation level remained elevated for 48 h after the procedure. The platelet activation level increased insignificantly at the end and 48 h after the procedure. Of the other changes in levels of platelet and hemostatic activation, only an increase in one of the hemostatic levels in the right-heart group at 48 h after procedure was significant (p = 0.01). CONCLUSIONS: Our findings suggest that similar hemostatic activation occurred during and immediately after RF ablation in both groups. Sustained elevation of the hemostatic marker after the ablation procedure in the right-heart group was observed as of significant therapeutic and prognostic implications.

Adult↗

Effects of physical training and its cessation on the hemostatic system of obese children.

BACKGROUND: Physical training can improve hemostatic function in adults, thereby reducing heart disease risk, but no information is available in children on whether physical training can enhance hemostatic function. OBJECTIVE: The purpose of this investigation was to examine the effects of a physical training program on hemostatic variables in a biethnic group of obese children. DESIGN: Children were randomly assigned to 2 groups. Group 1 participated in physical training for 4 mo and then ceased physical training for 4 mo, whereas group 2 did no physical training for the first 4 mo and then participated in physical training for 4 mo. Plasma hemostatic variables [fibrinogen, plasminogen activator inhibitor 1 (PAI-1), and D-dimer) were measured at months 0, 4, and 8. RESULTS: Analyses of variance revealed no significant group-by-time interactions for the hemostatic variables. When data from both groups were combined there was a significant decrease in D-dimer after 4 mo of physical training (P < 0.05). Factors explaining individual differences in responsiveness to the physical training revealed that individuals with greater percentage fat before physical training showed greater reductions in fibrinogen and D-dimer, and that blacks showed greater reductions in D-dimer than whites (P < 0.05). Stepwise multiple linear regression showed that only higher prephysical training concentrations of fibrinogen, PAI-1, and D-dimer explained significant proportions of the variation in changes in these variables. CONCLUSIONS: In obese children, 4-mo periods of physical training did not lead to significant changes in hemostatic variables. Children with greater adiposity and concentrations of hemostatic factors before physical training showed greater reductions in hemostatic variables after physical training than did children with lesser values.

Analysis of Variance↗

Chemotherapy-induced activation of hemostasis: effect of a low molecular weight heparin (dalteparin sodium) on plasma markers of hemostatic activation.

PURPOSE: To evaluate the effect of standard chemotherapeutic regimens on the hemostatic profile of patients with breast and lung carcinoma; and to evaluate the effect of a single dose of a low molecular weight (LMW) heparin, dalteparin sodium, administered prior to the chemotherapy on markers of hemostatic activation. PATIENTS AND METHODS: 11 patients with breast cancer and 10 patients with lung cancer receiving systemic chemotherapy were studied. 10 breast cancer patients and 9 lung cancer patients completed at least 1 cycle of treatment and had all hemostatic studies. Patients had a complete hemostatic and prothrombotic profile performed at study initiation. Markers of hemostatic activation consisting of immunoassays for thrombin-antithrombin (TAT) complex and D-dimer were measured in plasma samples obtained prior to chemotherapy and at 1, 24 and 48 h after treatment. A 2500 U dose of dalteparin was given prior to the 2nd cycle of chemotherapy; 5000 U of dalteparin was given prior to the 4th treatment cycle. RESULTS: Chemotherapy resulted in statistically significant increases in TAT and D-dimer for the 1, 24 and 48 h plasma samples in both the breast and lung cancer patients for all cycles of chemotherapy given without LMW heparin. There were statistically significant increases in basal thrombin generation over the 4 cycles of treatment which was unrelated to active cancer. Both pretreatment doses of dalteparin effectively prevented increases in the markers of hemostatic activation. However, in the lung cancer patients, who had significantly increased basal thrombin generation, the 5000 U dose dalteparin was more effective. CONCLUSION: Chemotherapy results in significant hemostatic activation in patients with breast and lung cancer. The effect of treatment appears to be cumulative. A single dose of LMW heparin administered prior to therapy can suppress hemostatic activation.

Adult↗

Comparative evaluation of absorbable hemostats: advantages of fibrin-based sheets.

Bioactive hemostats and wound dressings consist of either inherently active materials or act as delivery vehicles which contain such materials. Fibrin is a natural hemostat and scaffold, guiding the direction of wound contraction and closure. In order to improve the ease of application of liquid fibrin glue, we have made a freeze-dried form of polymerized fibrin that supports hemostasis and wound healing. The bleeding from the middle ear artery of rabbits was found to be arrested instantaneously on application of fibrin sheets, even when the animal was heparinized systemically. As the fibrin sheet was found to be fragile, gelatin was incorporated to the sheet and thus the mechanical stability was improved without compromising the hemostatic effect. The efficacy of the fabricated fibrin and fibrin-gelatin sheets to seal traumatized rat liver was compared with commercially available hemostats, Abgel (cross-linked gelatin) and Surgicel (cross-linked cellulose). Tissue compatibility of all the hemostats was studied by analyzing the liver tissue 15 days after application. While the hemostatic effect was best with fibrin and fibrin-gelatin sheets, both Surgicel and Abgel were not capable of arresting the bleeding quickly. Gross analysis of tissue on the 15th day of application, visibly, Abgel was not only degraded but resulted in severe adhesions of internal organs and histologically capsule formation around the implant was evident. Though Surgicel was also seen as cream soft material on the site of application that joined two pieces of liver, there was no adhesion of other internal organs and histologically, immune reaction and foreign-body-type giant cells were present in large amounts. Fibrin was not found grossly on application site whereas fibrin-gelatin was seen as a small white spot. Granulation tissue formation and cell migration into the fibrin-based sheets were evident, and therefore, fibrin-based sheets are not only efficient hemostats but showed optimum degradation and wound healing.

Animals↗

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.

Adenoidectomy↗