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Ann Thorac Surg 2000;69:1173-1175
© 2000 The Society of Thoracic Surgeons

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ORIGINAL ARTICLES: CARDIOVASCULAR

Bleeding from the sternal marrow can be stopped using vivostat patient-derived fibrin sealant

^a Department of Cardiothoracic Surgery, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark

Address reprint requests to Dr Kjaergard, Department of Cardiothoracic Surgery, Gentofte Hospital, Niels Andersens Vej 65, DK-2900 Hellerup, Denmark
e-mail: hekja{at}gentoftehosp.kbhamt.dk

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Median sternotomy is the most important method of access to the heart. Bleeding from the sternal marrow may become significant, especially in elderly patients. Vivostat (ConvaTec, a Bristol-Myers Squibb Company, Skillman, NJ) patient-derived fibrin sealant is biocompatible and easily applied to the sternal marrow using the Vivostat Spraypen applicator.

Methods. Thirty patients undergoing elective cardiac operation were randomized to receive Vivostat fibrin sealant applied to either the right or left side of the sternum immediately after median sternotomy, with the untreated side serving as control.

Results. The average time to hemostasis was 43 seconds after treatment with Vivostat and 180 seconds on the control sides (p < 0.001). At the end of the operation, complete hemostasis was observed on 24 of 30 sides treated with Vivostat compared with on 4 of 30 of the control sides (p < 0.001). The average volume of sealant used to cover one side of the sternum was 0.9 mL.

Conclusions. Vivostat patient-derived fibrin sealant is a biocompatible alternative to bone wax, with the results of this study showing that it provides effective control of bleeding after median sternotomy.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
Median sternotomy continues to be the most important method of access to the heart. Bleeding from the sternal marrow is enhanced after heparinization and cardiopulmonary bypass, and many surgeons prefer to control this bleeding early in the operative procedure.

The Vivostat System (ConvaTec, a Bristol-Myers Squibb Company, Skillman, NJ) is a novel medical device for the perioperative production and application of patient-derived fibrin sealant. Sealant production does not involve the use of exogenous thrombin or aprotinin, generating up to 5 mL of sealant from 120 mL of the patient’s own blood in approximately 30 minutes. The patient’s blood can be drawn any time during the perioperative period, either on the ward, in a preoperative holding area, or in the operating room during preparation for, or induction of, anesthesia. The blood can be drawn by any qualified phlebotomist or may be taken from an established vascular access line.

A detailed description of the Vivostat System and method of sealant production has been published previously [1]. The system uses batroxobin instead of thrombin as a fibrinogen activator. Batroxobin is a well-documented, safe, and effective human therapeutic [2–4], with a highly specific mechanism of action particularly relevant to fibrin sealant kinetics [5]. The entire process, from the time the patient’s blood is drawn into the preparation unit until the sealant is ready for use, is fully automated and microprocessor controlled. Both the system and biochemical process have excellent reproducibility, ensuring a highly consistent product from patient to patient. The concentration of fibrin in the final sealant is approximately 20 mg/mL [1], and the sealant prepared is stable at room temperature for up to 8 hours (ConvaTec, data on file).

The effectiveness of Vivostat System patient-derived fibrin sealant in stopping bleeding from the sternal marrow after median sternotomy was evaluated in this trial.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Adult patients (>18 years old) who had been admitted for elective cardiac operation requiring median sternotomy were eligible for inclusion into this study. Patients with known bleeding disorders or who had received prior treatment with a fibrin sealant were excluded. Women who were pregnant or lactating were also ineligible for study participation. Patients who had previously consented to participate, and were then withdrawn from the study for any reason before operation, could not be reentered.

Patients were randomized to having Vivostat fibrin sealant applied to either the right or left side of the sternum by drawing a randomization card. In all cases, the other side of the sternum served as the control and was not treated with a special hemostatic agent. Doctor Kjaergard operated on all of the patients. The sternum was divided in the midline with an electrical saw and bleeding vessels in the periosteum were electrocauterized on both sides. The fibrin sealant was applied using the Spraypen applicator (Fig 1) immediately after sternotomy. The whole marrow was covered with sealant, and the volume of sealant used was recorded. The surgeon watched both sides of the sternum for hemostasis for up to 3 minutes. A further assessment of hemostasis was made at the end of the operation, before closure of the sternum. Patients with persistent sternal bleeding received no further treatment.

View larger version (92K): [in this window] [in a new window]   Fig 1. The Spraypen for application of Vivostat patient-derived sealant.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
A total of 30 patients participated in this study. The mean age of the patients was 60 years. Mean weight was 78 kg, mean height was 174 cm, and 8 of 30 of the patients were women. The procedures undertaken were coronary artery bypass grafting (CABG; 20 patients), including two cases of beating heart without cardiopulmonary bypass, valvular operation (3 patients), combined procedures (4 patients), and reoperations (3 patients: 2 re-CABG and 1 redo aortic valve).

The average time to hemostasis was 43 seconds on sides of the sternum treated with Vivostat compared with 180 seconds for control sides (p < 0.001). At the end of the operation, complete hemostasis was observed on 24 of 30 sides treated with Vivostat and on 4 of 30 of the control sides (p < 0.001). Only small bleeding areas (< 1 x 1 cm) were found in the six Vivostat-treated sides in which some residual bleeding was observed. The average volume of sealant used to cover one side of the sternum was 0.9 mL.

There was no 30-day mortality. One patient was readmitted to the hospital with a coliform septicemia and evidence of a sternal wound infection. The wound was opened and debrided. The patient later developed massive rectal bleeding, and at operation required a subtotal colectomy because of extensive colonic necrosis. This patient subsequently developed renal and multiple organ failure and died. We could not positively exclude but did not attribute the wound infection or other elements of this patient’s clinical course to the use of the fibrin sealant. We do not believe that there is any evidence that the use of Vivostat fibrin sealant is associated with any increase in the incidence of sternal wound infection in routine cardiac operations [6].

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
In addition to being the most important approach to the heart, median sternotomy has numerous other applications in general thoracic surgical procedures (including mediastinal tumors, tracheal and cranial resection, and lung volume reduction) [7]. Many opinion leaders in cardiac surgery have recommended the use of bone wax to control sternal bleeding [8–11], although Kirklin and Barratt-Boyes [12] are more reserved, recommending that "a thin layer of bone wax is spread over the marrow only when bleeding is active, because bone wax may result in infection and nonunion. When the sternum is fragile, as in old patients, it is better to avoid wax altogether." Today there is no upper age limit for cardiac operations and many elderly patients with fragile sternums with little spongy bone are operated on. In these patients, bone wax may not be effective, as the marrow cavity may absorb large quantities of wax and still bleed. The reported adverse effects related to the use of bone wax include sternotomy dehiscence and infection [13, 14] and, most particularly, the embolization of bone wax from sternotomy incisions to the lung [15]. Few alternatives to bone wax have been described, none of which is widely accepted [16, 17].

The results of this study suggest that Vivostat System patient-derived fibrin sealant may be an effective alternative to bone wax, although comparative studies are required. This study could not be blinded, and therefore it can be argued that the surgeon was biased when assessing bleeding and time to hemostasis. A further limitation of the study design is the fact that control sides received no treatment, and use of a hemostatically inert substance on the untreated side of the sternum may have been more appropriate. However, it would be easy for any surgeon to use this technique and independently confirm the result. The difference between the sealed and control sides was most striking immediately after sternotomy when the marrow was actively bleeding. At the end of the operation oozing from the marrow had generally diminished, and complete hemostasis had occurred in a number of untreated cases. Small bleeding areas were found in 6 of 30 of the sealed sides at this time, but this was felt to be due most likely to squeezing of the marrow as a result of use of narrow retractors on the sternal edge to permit inspection for bleeding after harvesting of the internal thoracic artery. Less manipulation and more gentle handling of the sternum probably can reduce this occurrence of late bleeding in the sealed marrow. Although patients with persistent sternal bleeding received no further treatment in this study, sufficient Vivostat sealant remained in all cases which easily could have been used to treat these small bleeding sites.

Vivostat sealant is nontoxic and no adverse reactions or safety issues have been identified in this or previous preclinical or clinical studies [6]. Although 1 patient in this study developed sternal wound infection, this was believed to be a random event in a severely disabled patient with occult cancer. We know of no previous reports of the use of other fibrin sealants to control sternal marrow bleeding; however, the number of controlled clinical studies of fibrin sealants is currently increasing, with the majority of articles reporting a beneficial effect of fibrin sealant when it is used as a hemostatic or sealing agent in cardiothoracic surgical procedures [18].

The Vivostat System is expected to be marketed in Europe early in the year 2000. It is an investigational device in the United States. The price of the product has yet to be set by the manufacturer. It is expected that the product will be priced competitively with fibrin sealants that are presently available commercially. The cost of using this product is likely to be higher than the cost of using bone wax; however, sealant not used on the sternal marrow is available for other uses throughout the operation.

In summary, the results of this preliminary study suggest that Vivostat System patient-derived fibrin sealant may be an effective alternative to bone wax for controlling bleeding from the sternum after median sternotomy. Further studies would appear to be merited in this setting, possibly including comparative trials with other fibrin sealants as well as with bone wax.

	Footnotes

 
Doctor Trumbull is Medical Director of Advanced Technology Development for ConvaTec, the Bristol-Myers Squibb Company developing the Vivostat System.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

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2. Aronson D.L. Comparison of the actions of thrombin and the thrombin-like enzymes ancrod and batroxobin. Thromb Haemost 1976;36:9-13.[Medline]
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15. Robicsek F., Masters T.N., Littman L., Born G.V. The embolization of bone wax from sternotomy incisions. Ann Thorac Surg 1981;31:357-359.[Abstract]
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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Henrik K. Kjaergard Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kjaergard, H. K. Articles by Trumbull, H. R. Search for Related Content PubMed PubMed Citation Articles by Kjaergard, H. K. Articles by Trumbull, H. R.