© 2005 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
Prevention of pocket related complications with fibrin sealant in patients undergoing pacemaker implantation who are receiving anticoagulant treatment
aVascular Department, Surgical clinic Clinical Center Nis Bulevar Zorana Djindjica 48, Bulevar Nemanjica 72a/25, 18 000 Nis, Serbia, Serbia and Montenegro; bClinic of Cardiovascular Diseases (Pacemaker Center) Clinical Center Nis Bulevar Zorana Djindjica 48, 18 000 Nis, Serbia, Serbia and Montenegro; cInstitute for Blood Transfusion, Nis Bulevar Zorana Djindjica 48, 18 000 Nis, Serbia, Serbia and Montenegro
Manuscript submitted 17 October 2004. Accepted after revision 3 March 2005.
*Corresponding author. Tel.: +381 18 323 979; fax: +381 18 531 950. E-mail addressess: antimon{at}eunet.yu, dmilic{at}ptt.yu (D.J. Milic).
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and methodsResultsReferences |
|---|
AIM: The aim of our study was to establish the efficiency of fibrin sealant in the prevention of pocket related complications in patients undergoing pacemaker implantation who are receiving anticoagulant treatment.
METHODS: The study was performed on 40 and 41 patients prospectively randomized into treatment and control groups who underwent pacemaker implantation procedure between January 2002 and July 2004 at the Pacemaker Center – Clinical Centre Nis, Serbia. Both groups of patients were receiving anticoagulant treatment with either heparin or warfarin. Surgical procedures between the groups differed only in the application of fibrin sealant prior to wound closure in the treatment group.
RESULTS: In the treatment group, there were no pocket related complications while in the control group six patients (14.63%) had minor haematomas that required no treatment. Four patients (9.76%) had significant haematomas (two patients were treated conservatively while the other two needed reintervention). The INR in the treatment group was 2.76 ± 0.85 and in the control group 2.65 ± 0.79 (P = ns). In the follow-up period (2–27 months) no late complications were registered in either group.
CONCLUSION: Fibrin sealant is an effective haemostatic agent. The results obtained in our study show that the administration of fibrin sealant in patients receiving anticoagulant treatment eliminates postoperative haematomas after pacemaker implantation.
Key Words: fibrin sealant, pacemaker implantation, complications, pocket haematoma
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsReferences |
|---|
An increasing number of cardiac patients are receiving anticoagulant treatment in order to reduce the risk of thromboembolism, with the two major indications being atrial fibrillation and the presence of mechanical cardiac valves [1,
2]. Less common, though equally important, are patients receiving anticoagulant treatment for poor left ventricular (LV) systolic function, deep vein thrombosis, pulmonary embolism, or following a thrombotic stroke [3]. The use of intravenous or oral anticoagulation with heparin and warfarin in patients undergoing pacemaker implantation is associated with an increased risk of pocket haematoma formation. On the other hand withholding of anticoagulation, even transiently, may be associated with complications that are more serious than a haematoma, including stroke or valve thrombosis.
Pocket haematoma is an acute, relatively common complication. Usually, haematomas are managed conservatively unless expanding in size, tense or painful. In these cases, reoperation to evacuate the haematoma and identify and arrest the site of bleeding is required. Evacuation was required in 1–2% of implant cases in a recent series [4]. The perioperative use of heparin is associated with a 20% risk of haematoma [5]. A similar risk profile applies to patients receiving warfarin.
The purpose of our study was to establish the efficiency of fibrin sealant (glue) in the prevention of pocket related complications in patients undergoing pacemaker implantation who were receiving anticoagulant treatment with heparin or warfarin. In 1909, fibrin was used for the first time for haemostatic purposes [6]. The spectrum of indications has since been gradually enlarged. However, in the English medical literature the use of fibrin sealant has not previously been reported in patients undergoing pacemaker implantation procedures.
|
Material and methods |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsReferences |
|---|
The subjects of this prospective study were 81 consecutive patients who underwent a permanent pacemaker implantation at the Pacemaker Centre, Clinical Centre, Nis between January 2002 and July 2004. Patients undergoing replacement of a pacemaker generator were excluded. The patients consisted of 50 men and 31 women with a mean age of 65 ± 15 years and mean ejection fraction of 0.38 ± 0.18. Forty-seven percent of patients (38 patients) had coronary artery disease, 41% (33 patients) had no structural heart disease, 6% (five patients) had nonischaemic dilated cardiomyopathy, 3.5% (three patients) had aortic or mitral valve disease and 1.5% (two patients) had hypertrophic cardiomyopathy. Nine patients received a dual-chamber and 72 patients received a single-chamber pacemaker. All pacemakers were implanted in a prepectoral pocket. Surgical procedures in the groups differed only by the application of fibrin sealant prior to wound closure in the treatment group (Figs. 1 and 2). In our study 8 ml homologous fibrin sealant composed of two separate solutions made at the Institute for Blood Transfusion, Nis was used. The first solution is made from cryoprecipitate and it consists of fibrinogen, factor XII, fibronectin and aprotinin. The second solution is made of bovine thrombin (400 IU/mL) and calcium chloride (40 mmol/L).
|
|
All 81 patients had an indication for anticoagulation. Forty-one patients received warfarin for long term while 40 patients were randomized to receive intravenous heparin. Among these 81 patients, five had a mechanical heart valve, 72 had chronic AF and four had a deep venous thrombosis within the previous 2 months. Aspirin therapy was not altered for surgery. All 81 patients were treated with aspirin (mean daily dosage of 220 ± 120 mg/d) at the time of the surgical procedure. There were no identifiable differences in clinical characteristics or type of implanted device between the patients treated with heparin or warfarin.
Study protocol
Treatment with heparin was discontinued 6 h before the pacemaker implantation procedure. All patients receiving warfarin therapy had an international normalized ratio (INR) from 1.8 to 3.8 on the day of surgery. Warfarin therapy was reinstituted the night of the surgical procedure while heparin was reinstituted 8 h following device implantation. Postoperative intravenous heparin was infused at 1000 U/h without a bolus dose or at a previously identified infusion rate that maintained the partial thromboplastin time between 1.5 and 2.2 times the control value. The partial thromboplastin time was measured 6 h after the initiation of heparin therapy and after dosage adjustments, which were made according to a standardized nomogram used at our institution.
Patients were examined daily until hospital discharge, and then one week and every two months after implantation. Systemic thromboembolic events were assessed over the same time period. A pocket haematoma was defined by two investigators as a palpable mass that protruded >2 cm (minor haematoma) or >4 cm (significant haematoma) anterior to the pulse generator and lead. A pocket haematoma was evacuated if tense swelling caused poor capillary perfusion of the overlying skin or severe pain or if the haematoma progressively enlarged. Patients were instructed to contact one of the investigators if a haematoma developed after hospital discharge.
Operative techniques
Under local anaesthesia and following the administration of intravenous prophylactic antibiotics, a small incision was made in the prepectoral region and small subcutaneous pocket was formed. Seventy-six patients (93.82%) underwent lead placement via a cephalic vein cut down approach. Venous access was obtained by subclavian vein puncture in the remaining five patients (6.18%). Under fluoroscopic guidance, a pacing lead was introduced at the right ventricular apex, mid-septum or outflow tract. Sensing and pacing thresholds were measured after the stylet was pulled back. The leads were then sutured using nonabsorbable monofilament sutures at the venous access site. Haemostasis was meticulously secured and homologous fibrin sealant was applied in the pocket prior to connecting and inserting the pulse generator.
The wound was closed in three layers using absorbable sutures, and a sterile pressure dressing was applied.
Postoperative care
A pressure dressing was applied to the wound for 24 h. The patient was transferred to a recovery facility for a few hours, and a chest roentgenogram was obtained. Oral antibiotics and oral pain medications were prescribed for 1–3 days. All cardiac medications were continued.
Statistical analysis
Analysis was made using the Statistical Package for the Social Sciences (SPSS) 9.0 software package (SPSS, Inc., Chicago, IL, USA). Data are expressed as mean ± SD. The two-sided unpaired t-test was used to examine differences between groups. Contingency tables were analyzed using the Fisher's exact test. A P value of 0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsReferences |
|---|
In the treatment group there were no pocket related complications while in the control group a pocket haematoma developed in 10 of 41 examined patients (P < 0.05). In the control group two minor and three significant haematomas were registered in five of 20 patients receiving intravenous heparin (25%) while four minor and one significant haematoma developed in five of 21 patients (23.8%) receiving warfarin (Tables 1 and 2). INR in the treatment group was 2.76 ± 0.85 and in the control group 2.65 ± 0.79 (P = ns). The patients who developed haematomas had an INR of 2.51 ± 0.43 (P = ns).
|
|
Evacuation of a pocket haematoma was necessary in two patients with significant haematomas (both patients were receiving heparin).
The mean time for haematoma formation was 4.4 ± 5.7 days (median, 3 days; range, 1–17 days). Pocket haematoma formation was not associated with age, gender, left ventricular ejection fraction or type of heart disease.
Postoperative days in the hospital
Patients who were treated with heparin remained in the hospital a mean of 4.3 ± 2.8 postoperative days compared with a mean of 2.6 ± 1.3 postoperative days in patients treated with warfarin (t = 3.519; df = 79, P < 0.01). The 10 patients who developed a pocket haematoma remained in the hospital a mean of 5.6 ± 4.1 postoperative days, compared with a mean of 2.9 ± 1.8 days in the 71 patients who did not develop a pocket haematoma (t = 3.654; df = 79, P < 0.01). The five patients treated with heparin who developed a pocket haematoma stayed in the hospital a mean of 6.2 ± 4.5 postoperative days, compared with a mean of 3.7 ± 1.2 postoperative days in 35 patients treated with heparin who did not develop a pocket haematoma (t = 2.828; df = 38, P < 0.01).
Thromboembolic complications
A patient in the control group with AF who received warfarin developed a stroke 2 days postoperatively. No other patients had symptoms or signs of an arterial or venous thromboembolic event.
Discussion
Previous studies
There are published data demonstrating the high risk of developing a pocket haematoma in patients receiving heparin after pacemaker or defibrillator implantation. Pocket haematomas may require surgical drainage and are associated with discomfort and an increased risk of infection [7–9]. The incidence of pocket haematoma formation among patients who did not receive anticoagulation was 2% [10,11]. The risk of an arterial thromboembolic event with a prosthetic heart valve in the absence of anticoagulation is 8% per year [12,13]. The average risk for an arterial thromboembolic event in a patient with nonvalvular atrial fibrillation is 4.5% per year. This risk may be as high as 20% if hypertension, prior stroke, advanced age or congestive heart failure is present [14]. Based on these figures, the calculated daily risk ranges from 0.01% to 0.05%. Heparin would be expected to reduce venous and arterial thromboembolic risk by 66%–80% [15]. Patients who have experienced a deep venous thrombosis or arterial thromboembolism within the past month, however, have a much higher monthly risk of recurrence, 50% and 15%, respectively [15].
Sealing procedures
Sealing procedures with biological materials were introduced in 1909 by Bergel [6]. Following these first experiences, in 1944 Tidrick and Warner [16] reported good clinical results achieved by the application of citrated plasma and thrombin in skin grafting. In 1972 Matras et al. [17] were the first to use highly concentrated fibrinogen solution in combination with bovine thrombin solution to glue tissue. This marked the beginning of the era of modern fibrin sealing [18]. In 1975 first reports on the clinical application of fibrin sealant were published by Spängler [19].
Fibrin glue is composed of two separate solutions of fibrinogen and thrombin. When mixed together, these two solutions mimic the final stages of the clotting cascade to form a fibrin clot. Fibrin glue has been used in a wide variety of surgical procedures to repair, seal, and attach tissues in a variety of anatomic sites. Recent studies have investigated the addition of antibiotics to one of the components of fibrin glue in order to provide a local antimicrobial effect while tissue healing occurs and the fibrin clot resorbs. The addition of antibiotics to one of the components of fibrin glue has been shown to reduce postoperative infections [20,21].
In essence, there are three basic types of fibrin sealants: (1) autologous, (2) homologous (both obtained from cryoprecipitate), and (3) synthetic/commercial. Natural fibrin sealants derived from cryoprecipitate from the patient's plasma (autologous) or from another donor's plasma (homologous), can be used for tissue adhesive purposes. Autologous donation, whether preplanned or at the time of surgery, eliminates the chance of transmission of infectious agents as long as clerical errors have not been made. Ten milliliters of fibrin glue is more than adequate for most clinical applications [22]. Bovine thrombin is added to the cryoprecipitate just before its use to accommodate the formation of the "glue" or "gel." The average cost of autologous cryoprecipitate for fibrin glue purposes is about US$100.00 at most institutions. The two major disadvantages of the use of cryoprecipitate for preparation of fibrin sealants are the possibility of viral transmission and the presence of bovine thrombin. The estimated risk of transfusion transmitted infection from a single unit of a properly screened blood or blood components is reported to be 1:63,000 and 1:103,000 for hepatitis B and C, respectively, and 1:450,000–1:660,000 for HIV [23,24].
Fibrin glue is available in Europe under the brand names Beriplast, Tisseel, and Tissucol. In May 1998, the FDA approved the clinical application of synthetic fibrin sealants in the United States. Currently, the two synthetic fibrin sealants available to surgeons in the United States are Tisseel (Baxter Healthcare, Deerfield, IL) and Hemaseel (Haemacure Corp, Sarasota, FL). Synthetic or commercial fibrin sealants have the following ingredients: (1) vapor-heated, freeze-dried pooled human fibrinogen concentrate and factor XIII, (2) bovine fibrinolysis inhibitor (aprotinin), (3) vapor-heated, freeze-dried pooled human thrombin, and (4) calcium chloride. The major advantage of commercial fibrin sealants is their availability and ease of use. Although these products are slightly more expensive than autologous and homologous fibrin sealants, widespread use of commercial fibrin sealants will undoubtedly reduce their prices in the foreseeable future. The only true contraindications to the use of commercial fibrin sealants are the presence of allergic hypersensitivity to bovine proteins and intravascular application of the product [25].
Conclusion
The use of anticoagulants after pacemaker or defibrillator implantation is associated with a 20%–25% risk of pocket haematoma formation and a longer postoperative hospital stay. Since an increased risk of infection, longer hospital stay and greater postoperative discomfort are trivial compared with a debilitating stroke, patients at the highest risk of thromboembolism should have postoperative anticoagulant treatment initiated after pacemaker or defibrillator implantation. Our study suggests that the application of fibrin sealants could reduce or even eliminate pocket related complications in these patients. The application of fibrin sealant is easy to perform, safe and efficient.
|
References |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsReferences |
|---|
[1] Hirsh J, Dalen JE, Deykin D, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1995; 108: 231–246.
[2] Becker RC and Ansell J. Antithrombotic therapy: an abbreviated reference for clinicians. Arch Intern Med 1995; 155: 149–161.[Abstract]
[3] Al-Khadra AS. Implantation of pacemakers and implantable cardioverter defibrillators in orally anticoagulated patients. Pacing Clin Electrophysiol 2003; 26: 511–514.[CrossRef][Medline]
[4] Kiviniemi M, Pirnes M, Eranen H, et al. Complications related to permanent pacemaker therapy. Pacing Clin Electrophysiol 1999; 22: 711–720.[CrossRef][Medline]
[5] Michaud GF, Pelosi F Jr, Noble MD, et al. A randomized trial comparing heparin initiation 6 h or 24 h after pacemaker or defibrillator implantation. J Am Coll Cardiol 2000; 35: 1915–1948.
[6] Bergel S. Über die Wirkung des Fibrins. Dtsch Med Wochenschr 1909; 35: 663–665.
[7] Castberg T. Complications from the pacemaker pocket: prophylaxis, treatment and results. Acta Med Scand 1976; 596: 51–54.
[8] Cacoub P, Leprince P, Nataf P, et al. Pacemaker infective endocarditis. Am J Cardiol 1998; 82: 480–484.[CrossRef][ISI][Medline]
[9] Bluhm GL. Pacemaker infections: a 2-year follow-up of antibiotic prophylaxis. Scand J Thorac Cardiovasc Surg 1985; 19: 231–235.[Medline]
[10] Pfeiffer D, Jung W, Fehske W, et al. Complications of pacemaker defibrillator devices: diagnosis and management. Am Heart J 1994; 127: 1073–1080.[CrossRef][ISI][Medline]
[11] Chauhan A, Grace AA, Newell SA, et al. Early complications after dual chamber versus single chamber pacemaker implantation. Pacing Clin Electrophysiol 1994; 17: 2012–2015.[CrossRef][Medline]
[12] Mok CK, Boey J, Wang R, et al. Warfarin versus dipyridamole–aspirin and pentoxifylline–aspirin for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial. Circulation 1985; 72: 1059–1063.
[13] Cannegieter SC, Rosendaal FR, Briet E. Thromboembolic and bleeding complications in patients with mechanical heart valve prostheses. Circulation 1994; 89: 635–641.
[14] . Group EAFTS. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke: EAFT (European Atrial Fibrillation Trial) Study Group. Lancet 1993; 342: 1255–1262.[ISI][Medline]
[15] Kearon C and Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997; 336: 1506–1511.
[16] Tidrick RT and Warner ED. Fibrin fixation of skin transplants. Surgery 1944; 15: 90–95.
[17] Matras H, Dinges HP, Lassmann H, et al. Zur nahtlosen interfaszikulären Nerventransplantation im Tierexperiment. Wien Med Wochenschr 1972; 122: 517–523.[Medline]
[18] Gdanietz K and Gutsche I. The use of fibrin sealant in surgery. Acta Chir Austriaca 1991; 3: 95–99.
[19] Spängler HP, Holle J, Moritz E, et al. Experimentelle Untersuchungen und erste klinische Erfahrungen über die totale Blutstillung mittels hochkonzentriertem Fibrin. Österr Ges Chir 1975; 605–610.
[20] Thompson DF, Letassy NA, Thompson GD. Fibrin glue: a review of its preparation, efficacy, and adverse effects as a topical hemostat. Drug Intell Clin Pharm 1988; 22: 946–952.[Abstract]
[21] Senderoff RI, Sheu M-T, Sokoloski TD. Fibrin based drug delivery systems. J Parenter Sci Technol 1991; 45: 2–6.[Medline]
[22] Dresdale A, Rose EA, Jeevanandam V, et al. Preparation of fibrin glue from single-donor fresh-frozen plasma. Surgery 1985; 97: 750.[ISI][Medline]
[23] Schreiber GB, Busch MP, Kleinman S, et al. The risk of transfusion – transmitted viral infections. N Engl J Med 1996; 334: 1685.
[24] Lackritz EM, Satten GA, Aberle-Grasse J, et al. Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States. N Engl J Med 1995; 333: 1721.
[25] Spotnitz WD. Commercial fibrin sealants in surgical care. Am J Surg 2001; 182: 188.[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J.W.M. van Eck, N.M. van Hemel, P. Zuithof, J.P.M. van Asseldonk, T.L.H.M. Voskuil, D.E. Grobbee, and K.G.M. Moons Incidence and predictors of in-hospital events after first implantation of pacemakers Europace, October 1, 2007; 9(10): 884 - 889. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||