The influence of hemostatic agents on bone healing after sternotomy in a porcine model.

BACKGROUND: Sternotomy is the preferred access to the mediastinum. During sternotomy, trabecular bone is exposed, often resulting in bleeding, which can be treated with mechanical hemostatic agents; however, their influence on the healing process is relatively unexplored. The aim of this study was to investigate the influence of two hemostatic agents: bone wax (BW) and a water-soluble polymer wax, Ostene (WSW), on the mechanical and histologic characteristics of healing sternal bone. METHODS: Twenty-four pigs underwent sternotomy and were randomized into three groups: WSW, BW, or no hemostatic treatment (control). Bone samples were obtained 6 weeks postoperatively. RESULTS: Fracture strength (Fmax) and maximum stiffness (dF/dx) was lower in the BW group than in controls (Fmax: 175.2 vs. 255.8 N, dF/dx: 165.2 vs. 375.4 N/mm,) (p < 0.05). The stiffness did not differ statistically between the WSW and BW groups (298.4 vs 165.2 N/mm) nor did the fracture strength (211.4 vs 175.2 N). The fraction of granulomatous tissue was higher in the BW group compared with both the WSW group (79.1 vs. 16.52%) (p < 0.001) and controls (79.1 vs. 11.2%) (p < 0.001). There was more calcified tissue in controls than in the BW group (23.4 vs. 10.8%) (p < 0.05). CONCLUSIONS: In a porcine model, BW significantly inhibited sternal healing and was associated with chronic inflammation and reduced mechanical integrity. The WSW did not, to the same degree as BW, inhibit bone healing and thus presents an alternative treatment option for sternal bleeding.

The effect of haemostatic devices on bone healing 6 months postoperatively in sternotomized pigs.

OBJECTIVES: Bone wax is frequently used to diminish bleeding after sternotomy. Water-soluble polymer wax has been shown to diminish postoperative bleeding and, unlike traditional bone wax, to be absorbed and removed by the organism in an unchanged state. We have previously shown that bone wax impairs early bone healing after sternotomy, whereas polymer wax does not. This difference was observed 6 weeks postoperatively and questions arose as to whether these effects were long term. Therefore, we hypothesized that bone wax impairs bone healing in sternotomized pigs 6 months postoperatively, whereas polymer wax does not. METHODS: Fourteen Landrace/Yorkshire pigs were sternotomized and then randomly assigned to haemostasis by either bone wax (WAX-group) or water-soluble polymer wax (POL-group). After 6 months, the pigs were euthanized and the sternum was removed and prepared for further assessment. Bone fracture strength and bone stiffness were determined using a modified three-point bending test, whereas bone healing was examined by means of quantitative histology. Six pigs died before the end of the study due to failure to thrive, valve prosthesis endocarditis and coronary artery occlusion. RESULTS: The mechanical testing showed no difference between groups with regard to fracture strength [WAX-group versus POL-group; 214.8 (85.5-478.5) vs 203.8 (90.4-478.5) N, P = 0.986] or maximum stiffness [213.0 (81.5-409.5) vs 348.5 (23.3-689.5) N/mm, P = 0.128]. Histology showed predominance of fibroblast-covered surfaces [10.6% (1.8-23.3%) vs 4.1% (0.0-13.0%), P < 0.001] and fibrous tissue volume [45.4% (6.9-82.0%) vs 17.4% (2.9-55.0%), P < 0.001] in animals treated with bone wax. The volume fraction of calcified bone tended to be higher in the POL-group [26.8% (4.3-35.8%) vs 16.7% (1.5-35.8%), P = 0.065]. Granulomas comprised 12.5% (0.0-78.9%) of the volume fraction in the WAX-group compared with 0.0% (0.0-0.0%) in the POL-group (P < 0.001). CONCLUSION: Bone wax and water-soluble polymer wax had similar long-term effects on bone mechanical properties. Histology confirmed our hypothesis and showed a more extensive foreign body reaction in animals treated with bone wax than in those treated with water-soluble polymer wax.

Gentamicin-enriched, water-soluble polymer wax reduces the burden of infection after sternotomy in pigs.

OBJECTIVES: One of the most frequent complications in cardiac surgery is postoperative bleeding from the sternum. To diminish the risk of bleeding, bone wax is frequently used for haemostasis. However, we have previously shown that bone wax impairs bone healing and induces inflammation in the sternum. A new, water-soluble polymer wax enriched with gentamicin has haemostatic properties similar to bone wax and may diminish the risk of infection. The purpose of this study was to determine whether the gentamicin-enriched, water-soluble polymer wax could reduce infection rates when compared with bone wax in a porcine model. METHODS: Thirty-two Landrace/Yorkshire pigs were sternotomized and randomized to haemostasis by gentamicin-enriched, water-soluble polymer wax (Gen group) or bone wax (Wax group). After 4 weeks the pigs were euthanized. Blood samples were analysed for the fraction and concentration of neutrophil granulocytes and C-reactive protein and the surgical site was biopsied. Stereology was performed on histological samples, and the magnitude of infection was quantified as the areas of microabscesses, granulomas and tissue with acute inflammation compared with the total tissue area. RESULTS: The temperature was 38.2 °C in the Gen group vs 38.6 °C in the Wax group, P < 0.05. No animals in the Gen group and three in the Wax group showed a temperature >39.3 °C. Neutrophil granulocyte concentration was 5.00 × 10(9)/l in the Gen group and 6.92 × 10(9)/l in the Wax group, P = 0.277, with a leucocyte fraction of 20.9% vs 29.3%, P = 0.119. C-reactive protein (CRP) was 142 mg/l in the Gen group compared with 318 mg/l in the Wax group, P = 0.106. Histological samples showed acute inflammatory changes in 5.0% of the tissue in the Gen group vs 18.3% in the Wax group, P < 0.001. Microabscesses were present in 0.3% of the sample tissue in the Gen group vs 2.2% in the Wax group, P < 0.001. Concentrations of gentamicin were >100 mg/l in mediastinal fluid and <2 mg/l in venous blood. CONCLUSIONS: When used for haemostasis after sternotomy in a porcine model, gentamicin-enriched, water-soluble polymer wax reduces sign of infection when compared with bone wax and therefore appears to be a more suitable choice for preventing postoperative, sternal osteomyelitis.

Effect of hemostatic material on sternal healing after cardiac surgery.

BACKGROUND: Postoperative sternal infection and dehiscence cause increased morbidity, mortality, and socioeconomic costs as well as patient discomfort and pain. Some predisposing factors have been uncovered but others remain uninvestigated. Among these are the influence of topical hemostatic agents such as bone wax (BW) and Ostene (Ceremed Inc, Los Angeles, CA) a new, water-soluble polymer wax (WSW). The object of this study was to investigate the impact of topical hemostatic agents on sternal healing in patients. METHODS: In total, 50 patients subjected to elective cardiac surgery and requiring intraoperative hemostatic treatment were randomized to 1 of 2 treatment groups: BW or WSW. Twenty-five patients without need for sternal hemostasis constituted a control group. The doctors analyzing the endpoints were blinded to the treatment. Radiologic bone healing was assessed by a radiologist using computed tomography at 3 and 6 months postoperatively. Quality of life and bodily pain was assessed by questionnaires (Short Form-36 and Visual Analogue Scale). RESULTS: No patients displayed complete radiologic healing at 3 months. Bone healing (evaluated semi-quantitatively at a score from 0 to 10) was significantly impaired in the BW group compared with both the control and WSW groups at both 3 and 6 months postoperatively (p < 0.0001). Radiologic bone healing was positively correlated with physical functioning score (Short Form-36) (p < 0.001). Pain scores were generally low (<1) at both 3 and 6 months with no significant difference between study groups. CONCLUSIONS: The results from this study suggest that WSW provides a useful alternative to BW when topic hemostasis on the sternum is required.

Bone healing after median sternotomy: a comparison of two hemostatic devices.

BACKGROUND: Bone wax is traditionally used as part of surgical procedures to prevent bleeding from exposed spongy bone. It is an effective hemostatic device which creates a physical barrier. Unfortunately it interferes with subsequent bone healing and increases the risk of infection in experimental studies. Recently, a water-soluble, synthetic, hemostatic compound (Ostene®) was introduced to serve the same purpose as bone wax without hampering bone healing. This study aims to compare sternal healing after application of either bone wax or Ostene®. METHODS: Twenty-four pigs were randomized into one of three treatment groups: Ostene®, bone wax or no hemostatic treatment (control). Each animal was subjected to midline sternotomy. Either Ostene® or bone wax was applied to the spongy bone surfaces until local hemostasis was ensured. The control group received no hemostatic treatment. The wound was left open for 60 min before closing to simulate conditions alike those of cardiac surgery. All sterni were harvested 6 weeks after intervention.Bone density and the area of the bone defect were determined with peripheral quantitative CT-scanning; bone healing was displayed with plain X-ray and chronic inflammation was histologically assessed. RESULTS: Both CT-scanning and plain X-ray disclosed that bone healing was significantly impaired in the bone wax group (p < 0.01) compared with the other two groups, and the former group had significantly more chronic inflammation (p < 0.01) than the two latter. CONCLUSION: Bone wax inhibits bone healing and induces chronic inflammation in a porcine model. Ostene® treated animals displayed bone healing characteristics and inflammatory reactions similar to those of the control group without application of a hemostatic agent.