Evaluation of the safety and efficacy of a new hemostatic powder using a quantitative surface bleeding severity scale.

AIMS OF THE STUDY: The safety and efficacy of a hemostatic powder (HP) versus a control agent, absorbable gelatin sponge and thrombin (G + T), were assessed, using a validated, quantitative bleeding severity scale. METHODS: Subjects were randomized to receive HP (256 subjects) or G + T (132 subjects) for treatment of minimal, mild, or moderate bleeding at 20 investigational sites. The primary efficacy endpoint was non-inferiority of HP relative to G + T for success at achieving hemostasis within 6 minutes. Secondary endpoints in rank order included: superiority of HP relative to G + T in mean preparation time; non-inferiority of HP relative to G + T for achieving hemostasis within 3 min; superiority of HP relative to G + T for achieving hemostasis within 6 min; and superiority of HP relative to G + T for success for achieving hemostasis within 3 min. RESULTS: A total of 388 subjects were included in the primary efficacy analysis. At 6 min, hemostasis was achieved in 93.0% (238/256) of the HP group compared to 77.3% (102/132) of the G + T group (non-inferiority P < 0.0001, superiority P < 0.0001). All secondary endpoints were met. Complications were comparable between treatment groups. CONCLUSIONS: HP had superior rates of hemostasis, shorter preparation time, and a similar safety profile compared to G + T in this prospective, randomized trial using quantitative bleeding severity criteria.

The SPOT GRADE: A New Method for Reproducibly Quantifying Surgical Wound Bleeding.

STUDY DESIGN: Benchtop model with prospective surgeon video testing. OBJECTIVE: To create a surface bleeding severity scale, the SPOT GRADE (SG), for quantitative assessment of target bleeding site (TBS) blood loss. This is of particular interest for spinal surgery due to epidural bleeding and an inability to use diathermy and radiofrequency cautery close to nerve roots. SUMMARY OF BACKGROUND DATA: A novel apparatus perfusable at known flow rates and simulating different sized wounds was used to create movies to educate surgeons on specific degrees of bleeding. METHODS: Training (36) and testing (108) videos were created using a benchtop apparatus employing different bleeding severities based on the six-level SG (none, minimal, mild, moderate, severe, and extreme) and TBS sizes (1, 10, and 50 cm). Fourteen surgeons in four specialties (cardiothoracic, abdominal, spine, and orthopedic lower extremity) were trained and tested to evaluate SG characteristics including inter-rater and intrarater reliability. RESULTS: The interclass correlation coefficient was estimated to be 0.89840 (95% confidence interval [CI]: 0.85771, 1), whereas the intraclass correlation coefficient was estimated to be 0.93673 (95% CI: 0.89603, 1). In 98% of cases (95% CI: 0.9736, 0.9927), surgeons correctly identified eligible bleeds for a future clinical trial (scores = 1, 2, or 3) and in 91% of cases (95% CI: 0.8895, 0.9344), surgeons correctly identified noneligible bleeds (scores = 4 or 5). In 98.6% of cases (95% CI: 0.9777, 0.9945), physicians correctly identified true hemostasis (score = 0). Based upon these data the probability of a physician rating a bleed incorrectly as hemostasis (score = 0) is estimated to be 1.51% (95% CI: 0.0061, 0.0363). CONCLUSION: This SG is reproducible and reliable providing a basis for educating surgeons on TBS blood loss. It appears to be a new standard for evaluating wound blood loss. LEVEL OF EVIDENCE: 2.

Enhancing oxygen solubility using hemoglobin- and perfluorocarbon-based carriers.

The objective of this paper is to review the properties of fluids capable to enhance oxygen transport and transfer and recent developments in this field. This paper reviews and compares two different approaches, which could be used to solve the important problem of oxygen supply in some cell and tissue cultures: 1) hemoglobin-based and 2) perfluorocarbon-based (PFC) oxygen carriers. Several types of modified hemoglobin-based oxygen carriers (HBOCs) and their preparation are reviewed, as well as advances in the field of PFC oxygen carriers. Finally, we highlight the advantages and pitfalls, when reported in the literature, associated with each technique.

Physico-chemical properties and cytotoxicity assessment of PEG-modified liposomes containing human hemoglobin.

PEGylated liposomes encapsulating human hemoglobin as oxygen carriers were prepared from purified carbonylhemoglobin (HbCO) solution and a lipid mixture composed of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), cholesterol, 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[poly(ethylene glycol) 2000] (DMPE-PEG(2000)) and palmitic acid. Hemoglobin was extracted and purified from human blood samples. SDS-PAGE was used to assess its purity. Diameter of liposomes containing hemoglobin was controlled to approximately 200 nm using extrusion as measured by dynamic light scattering and transmission electron microscopy. Liposome size distributions were shown to remain unimodal over 14 days, even at different storage temperatures. Zeta potential measurements revealed that liposome containing hemoglobin have a net surface charge of -7.16+/-0.33 mV. Also, hemoglobin encapsulated in liposomes was able to perform several cycles of oxygen loading and unloading using oxygen (O(2)) and carbon monoxide (CO). The hemoglobin vesicle dispersion showed some toxicity as revealed by three in vitro assays in which endothelial cell (HUVECs) monolayers were exposed to these dispersions. Cytotoxicity was function of the liposome concentration in the culture medium.

Perfluorocarbon emulsions cytotoxic effects on human fibroblasts and effect of aging on particle size distribution.

The purpose of this study was to characterize emulsion preparations made of perfluorooctyl bromide (PFOB) and egg yolk phospholipid (EYP) and their cytotoxicity. Dynamic light scattering and transmission electron microscopy revealed that freshly prepared emulsions stored at different temperatures for a 24-h period have a unimodal particle size distribution with an average particle size of ca. 200 nm. The emulsion displayed a broader particle size distribution following a 14-day storage. Primary human fibroblasts exposure to PFOB/EYP emulsions permanently inhibited cell proliferation and decreased mitochondrial activity. Scanning electron microscopy pictures reveal the presence of spherical particles on the fibroblasts following exposure to the emulsions after thorough rinsing with culture media.