Eur J Cardiothorac Surg 1999;15:266-270
© 1999 Elsevier Science NL
Intraoperative local fibrinolysis as emergency therapy after early coronary artery bypass thrombosis1
Martin Breuer,
Albert Schütz,
Brigitte Gansera,
Walter Eichinger,
Josef Weingartner,
Bernhard Kemkes
Department of Cardiovascular Surgery, Klinikum Bogenhausen, Munich, Germany
Received 22 September 1998;
received in revised form 14 December 1998;
accepted 22 December 1998.
Corresponding author. Tel.: +49-89-9270-2697; fax: +49-89-9270-2605.
 |
Abstract
|
|---|
Objective: Acute graft occlusion early postoperatively after coronary artery bypass grafting (CABG) is a rare but dramatic complication, frequently making resuscitation necessary. Emergency reoperation with reanastomosing of the concerning grafts is the normal procedure to restrict the otherwise unavoidable myocardial damage. Mortality in these cases is up to 50%. Due to this unsatisfying situation, we perform since 1995 in such cases an adjuvant intraoperative intracoronary installed fibrinolysis with recombinant tissue type plasminogen activator (rt-PA; alteplase). Methods: Between 1/1994 and 8/1998, 4231 patients underwent CABG. In 18 of these patients, emergency reoperation within the first 12 h after CABG due to clinical signs of acute myocardial infarction was necessary. In nine of the patients (group II) additionally intraoperative rt-PA lysis of the involved vessel/s has been performed. When the peripheral anastomosis was reopened and the thrombotic material was removed, we inserted for this a left atrial-catheter (LA-catheter) of 1.2 mm in diameter, into the coronary artery. Then we administered within 3–5 min, up to 100 mg rt-PA (t1/2: 5–9 min.) locally into the vessel. All patients were treated postoperatively with acetylsalicyl acid (ASA) and heparine. Results: In group I (n=9; seven males, two females) without thrombolytic therapy, 78% of the patients (n=7) could not have been prevented from large myocardial infarction despite emergency reoperation. Three of these patients died during or early after reintervention. In group II with fibrinolytic therapy (n=9) three of the patients developed Q-wave myocardial infarction following reoperation. None of the patients died. Creatinkinase maximum were in group I significantly higher than in group II (group I: CK=1254 units/l, CK-MB=197 units/l; group II: CK=502 units/l, CK-MB=61 units/l; P<0.01). Postoperative bleeding was considerable elevated in both groups. In group I, 832 ml/24 h (375–1420 ml), in group II 1164 ml/24 h (520–1560 ml). Lysis-associated complications were not observed. Conclusions: Reoperation of patients with acute thrombotic bypass occlusion after CABG is characterized by a high mortality and morbidity. If additionally fibrinolysis is performed, a sufficient myocardial perfusion seems to be restored. A short half-life in combination with the presented non-systemic application technique of rt-PA seem to prevent unpredictable bleeding. Rt-PA lysis apparently contributes very effectively to the restoration of the macro- and microcirculation within the infarct-related area. Thrombolytic therapy during cardiac surgery with rt-PA is feasible, its application easy and harmful complications are not seen.
Key Words: Fibinolytics • Alteplase • Cardiac surgery • Intraoperative application • Bypass thrombosis
|
Introduction
|
|---|
Coronary artery bypass grafting (CABG) is a worldwide established procedure for the treatment of patients with advanced coronary artery disease (CAD). Overall actual mortality should be below 3%. The long-term prognosis after successful surgery is excellent, the complication rate low. Nevertheless complications are possible and in particular acute myocardial infarction is a serious problem after CABG. More than 60% of all early deaths after CABG are due to acute myocardial infarction
[1]. The incidence of acute bypass occlusion resulting in acute myocardial infarction within the first 12 h after surgery is described with up to 10%
[2].
Mostly a technical error during surgery is responsible for the early bypass occlusion. However, a pathological blood clotting or a severe diffuse arteriosclerosis are also possible reasons. The morphological correlate is the thrombosis of the relevant graft and the correspondent coronary artery. With respect to the clinical course of these patients, two different ways are described. For the most part myocardial infarction is detected by significantly elevated CK and CK-MB levels and confirmed by the typical changes in ECG. Mostly hemodynamics are normal in these patients. Urgent catheterization of the coronary arteries as well as the aortocoronary bypasses is mandatory. A speedy stent-implantation or percutaneous transluminal coronary angioplasty (PTCA) usually can remove the causal problem, surgical reintervention and bypass-correction is not required for the most part.
If a strategic important coronary artery is affected by early postoperative bypass occlusion acute cardiogenic shock develops, making cardio-pulmonary resuscitation (CPR) necessary. The prognosis of these patients is very poor even if emergency reoperation is initiated immediately. Despite surgical reoperation with bypass inspection and reanastomosing of the occluded coronary arteries, a lethality of more than 40% must be expected
[3]. A large myocardial infarction with its hemodynamic long-term effects and a harmful reduction of the quality of life are the certain consequences if the event has been survived at least.
With respect to this unsatisfying results under conventional therapy, we started in 1995 with a new therapy regimen in cases of suspected acute postoperative bypass thrombosis. Our intention was to make use of the additive effect of both, a manual removing of accessible thrombi followed by a local fibrinolysis of the remaining thrombotic material. Perhaps like this, a restoration of the macro- and microcirculation of the involved myocardial area would be possible. For this fibrinolytic therapy, we choose rt-PA (recombined tissue type plasminogen activator; ACTILYSETM; Dr. K. Thomae GmbH, Biberach, Germany). The short half-life of rt-PA (5–9 min)
[4] in combination with the non-systemic application technique theoretically should facilitate an intraoperative fibrinolysis during extracorporal circulation (ECC).
|
Materials and methods
|
|---|
All patients since 1994 with ischemia-related changes in ECG and unstable hemodynamics because of suspected bypass thrombosis in the early postoperative course (0–12 h after surgery) were included.
Group I represents the patients who underwent the conventional surgical procedure containing inspection and renewing of both, peripheral and central anatomoses to achieve a sufficient recanalization of the concerning bypasses. At any rate, it was attempted to remove the underlying mostly surgical problem. After a warm reperfusion of at least 30 min weaning from cardio-pulmonary-bypass was initiated.
Since 1995, additionally local fibrinolysis with rt-PA installed directly into the coronary artery was performed (group II). For this we inserted a left-atrial-catheter of 1.2 mm in diameter into the vessel after carefully removing all accessible thrombotic material. Than we administered via this catheter, 100 mg rt-PA within 3–5 min. Reperfusion procedure was the same as described for group I. After this reoperation (6–12 h), all patients were treated with ASA 1000 mg as single bolus and systemic heparine in therapeutical dosage for 2 days.
Data were collected from patients medical records regarding comorbid illness and cardiac history, cardiac catheterization data, intraoperative data and postoperative in-hospital course. In particular perioperative mortality, postoperative bleeding, creatinkinase and creatinkinase-MB levels, ECG-changes and early as well as late complications were observed.
|
Results
|
|---|
From 1/1994 to 10/1998, 18 patients, i.e. 0.4% out of 4502 patients after CABG, underwent emergency reoperation within the first 12 h after bypass surgery on account of acute bypass thrombosis. In 77% of the patients cardio-pulmonary resuscitation was required until ECC could be started. Mean duration of stay at ICU before reoperation was 4.23 h. Preoperative ejection fraction and the number of bypasses/patient were comparable in both groups (group I: EF=53%, 3.4 bypasses/patient; group II: EF=51%, 3.2 bypasses/patient). Mean age ranged between 46 and 73 years (
=68) in group I and 49–77 years (=69) in group II. As risk factors for CAD we detected in group I hypertension (five patients), diabetes (five patients), nicotine (four patients), cholesterol (five patients). In group II hypertension was found in six patients, diabetes in four patients, nicotine in three patients and cholesterol in five patients. One patient of group II underwent a redoing procedure (first CABG 9 years ago).
Aortic cross clamping time represents for this study the time of local rt-PA effectiveness and ranged in group II between 41 and 109 min (=53 min).
Single bypass occlusion because of acute graft thrombosis was found in six patients of group I and five patients of group II. Two patients of group I and three patients of group II had a two-vessel occlusion. A thrombotic occlusion of three grafts was detected in one patient of each group. The distribution of the concerned target vessels is shown in Table 1.
In group I (n=9; seven males, two females) without thrombolytic therapy, 78% of the patients (n=7) could not have prevented a large myocardial infarction despite emergency reoperation. Three of the patients died during or early after reoperation because of low cardiac output syndrome (day 0), severe transmural myocardial infarction of the LAD-artery (day 2) and multi-organ failure (day 12) (
Fig. 1
).
View larger version (37K):
[in this window]
[in a new window]
|
Fig. 1. Remarkably reduced incidence of postoperative myocardial infarction in group II after intraoperative rt-PA lysis. No lethal outcome in this group.
|
|
In group II (n=9; seven males, two females) after additionally intracoronary applied fibrinolytic therapy, 33% of the patients (n=3) developed Q-wave myocardial infarction following reintervention. None of the patients died within the first 4 postoperative weeks (
Fig. 1).
Corresponding to the clinical findings the postoperative CK (6 h postoperative) in group I was significantly higher with =1254 units/l than in group II with =465 units/l (P<0.01) on an average (
Fig. 2
). CK-MB as well, showed significantly different levels between both groups. The maximum levels in group I (=197 units/l) were 6 h after reintervention nearly four-fold higher than in group II (=53 units/l) (P<0.01), (
Fig. 2). Mean duration of stay at ICU of the surviving patients was 8.3 days in group I and 6.4 days in group II, respectively.
View larger version (43K):
[in this window]
[in a new window]
|
Fig. 2. CK and CK-MB levels 6 h after surgical reintervention demonstrate statistically signifcant higher serum levels in group I (no lysis) in comparison to group II (rt-PA lysis).
|
|
The postoperative bleeding (first 24 h) was clearly elevated in both groups. In group I, 832 ml (375–1420 ml), in group II, 1164 ml (520–1560 ml). Nevertheless, in none of the patients a surgical reintervention because of severe bleeding was necessary (
Fig. 3
). Other lysis associated complications were not observed.
View larger version (49K):
[in this window]
[in a new window]
|
Fig. 3. Postoperative bleeding in group II was not significantly enhanced. Other lysis dependent complications could not be observed.
|
|
|
Discussion
|
|---|
This paper presents the first clinical results using an adjuvant fibrinolytic therapy with rt-PA in patients with acute cardiogenic shock after early postoperative coronary artery bypass thrombosis.
It has been demonstrated formerly, that myocardial necrosis in such patients usually involves more than 40% of the left ventricular mass
[5]. The worse results after conventional surgical reintervention clearly demonstrate that the manual extraction of the thrombotic material, by itself is not effective enough to regain a sufficient blood flow.
Clinical use of rt-PA
Up to now there exists only a few experience with the intraoperative use of rt-PA. In ophthalmology, in cases of subretinal hemorrhages and fibrin reactions after cataract operations, the use of rt-PA is described
[14]
[15]. In vascular surgery, the local fibrinolytic therapy of thrombotic occlusions is a meanwhile standardized procedure
[16]. In interventional cardiology, rt-PA gets an increasing importance
[6]
[7]
[8]
[9]
[10]
[11]. Apart from the therapy concept, in cases of myocardial infarction according to the GUSTO-study, there exists some experience with the thrombolysis in cases of thrombotic prosthetic valve obstruction
[10]
[17]. Also in patients with acute pulmonary embolism, fibrinolysis with rt-PA was carried out
[18].
Rt-PA properties
The physiological t-PA is produced of the endothelial cells and is of importance for the dynamic balance between the clotting cascade and the fibrinolytic activity in man. Its so called `fibrin selectivity' is an essential advantage for the intraoperative use. It means that the ability for plasminogen activation of t-PA is necessarily dependent on the presence of fibrin. Thus, the effectiveness of t-PA is directly connected with the existence of fibrin-thrombi. The fibrinolytic effect of rt-PA locally at the thrombus makes a fast reperfusion of the infarct-related coronary artery possible and avoids systemic effects
[12].
Cardiopulmonary bypass results in a major increase of fibrinolytic activity, that has been associated with a higher risk for hemorrhage within the first hours after surgery. However, this fibrinolytic activity is followed by a subsequent phase of a remarkably elevated t-PA-inhibitor activity and a significant decrease in physiological t-PA activity
[13]. This high risk phase for a thromboembolic event in combination with a technical error at the bypass-anastomosis maybe the most frequent reason for early coronary artery thrombosis after CABG.
Intraoperative intracoronary rt-PA-lysis
Fortunately the incidence of early CAB-thrombosis is a scarce event, its outcome however, disastrous. The difference in patient survival between treated and untreated patients in our study and the significantly reduced incidence of postoperative myocardial infarction and CK/CK-MB levels, respectively, suggest that there must be a beneficial additive effect between the conventional manual extraction of thrombotic material and local fibrinolysis of outstanding clinical importance. Rt-PA represents the only highly effective thrombolytic agent providing a concrete solution for the intraoperative use. Its half-life of 5–9 min with a total plasma-clearance of 62 min was the decisive criteria. A strictly local application was guaranteed during cross-clamping of the aorta. The real time of local effectiveness was 30 min at a minimum while the peripheral and central anastomoses were renewed.
We suppose that this non-systemic application technique avoids suspected lysis associated complications. Postoperative bleeding was enlarged, comparable with that of normal redoing procedures in cardiac surgery, but surgical reexploration due to severe bleeding was not necessary.
|
Conclusions
|
|---|
We assume that the intraoperative intracoronary rt-PA lysis in case of early coronary artery bypass thrombosis is a sufficient adjuvant tool to improve the results of surgical reintervention. It seems that the combination of thrombectomie and fibrinolysis is capable of reestablishing nearly the entire macro- and microcirculation of the infarct related myocardium. However, for the long-term outcome of these patients, it is also absolutely required that the underlying, mostly surgical problem could be solved during reintervention. Otherwise early reocclusion of the relevant vessels must be expected.
|
Footnotes
|
|---|
Presented at the 12th Annual Meeting of the European Association for Cardio-thoracic Surgery, Brussels, Belgium, September 20–23, 1998. 
|
References
|
|---|
- Ivert T., Welti R., Eketrom S., Bjork V. Early mortality after 2902 coronary artery bypass operations. Scand J Thorac Cardiovasc Surg 1989;23:3-8.[Medline]
- Backman C., Jacobsson K., Linderholm H., Osterman G. Comparison of some criteria for diagnosing a myocardial infarction after aorto-coronary bypass grafting (CABG). Clin Physiol 1995;15:307-317.[Medline]
- Matsuwaka R., Sakakibara T., Shintani H., Yagura A., Masai T., Mirayama A., Kodama K. Emergency cardiopulmonary bypass support in patients with severe cardiogenic shock after acute myocardial infarction. Heart Vessels 1996;11:27-29.[Medline]
- Gulba D., Bode C., Runge M., Huber K., Roque M. Thrombolytic agents – an overview. Ann Hematol 1996;73(Suppl.):9-27.
- Roque M., Sanz G. Treatment of cardiogenic shock with thrombolysis and coronary angioplasty. Rev Esp Cardiol 1992;45(Suppl. 2):43-49.
- Barbash G., White H., Modan M., Diaz R., Hampton J., Heikkila J., Kristinsson A., Moulopoulos S., Paolasso E., Van der Werf T. Outcome of thrombolytic therapy in relation to hospital size and invasive services. The investigators of the international Tissue Plasminogen Activator/Streptokinase Mortality Trial. Arch Int Med 1994;154:2237-2242.
- Smalling R., Bode C., Kalbfleisch J., Sen S., Limboug P., Forcky F., Habib G., Feldman R., Hohnloser S., Seals A. More rapid complete and stable coronary artery thrombolysis with bolus administration of reteplase compared with alteplase infusion in acute MI. Circulation 1995;91:2725-2732.[Abstract/Free Full Text]
- Prewitt R., Schick U., Ducas J. Optimizing coronary artery thrombolysis with i.v. administration of recombinant tissue plasminogen activator. Single bolus vs. double bolus vs. front-loading. Chest 1996;109:510-515.[Abstract/Free Full Text]
- Mc Neill A., Dickey W., Campbell N., Khan M., Patterson G., Webb S., Adgey A. One-year follow-up after recombinant tissue plasminogen activator administered to patients with acute myocardial infraction. Eur Heart J 1991;12:624-629.[Abstract/Free Full Text]
- GUSTO Angiographic Investigators. The effects of tissue plasminogen activator, streptokinase, or both on coronary-artery patency, ventricular function and survival after acute myocardial infarction. New Engl J Med 1993;329:1615-1622.[Abstract/Free Full Text]
- Van de Werf F., Wilcox R., Barbash G. In-hospital mortality and clinical course of 20 891 patients with suspected acute myocardial infarction randomized between alteplase and streptokinase with or without heparin. Lancet 1990;336:71-75.[Medline]
- Bode C., Smalling R., Berg G., Burnett G., Lorch G., Kalbfleisch J., Chernoff R., Christie L., Feldman R., Seals A., Weaver W. Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase and front loaded, accelerated alteplase in patients with acute myocardial infarction. The RAPID II investigators. Circulation 1996;94:891-898.[Abstract/Free Full Text]
- Chandler W. The effects of CPB on fibrin formation and lysis: is a normal fibrinolytic response essential?. J Cardiovasc Pharmacol 1996;27:63-68.
- Neuhaus K., Essen R., Tebbe U., Vogt A., Roth M., Riess M., Niederer W., Forycki F., Wirtzfeld A., Mäurer W., Limbourg P., Merx W., Haerten K. Improved thrombolysis in acute myocardial infarction with front-loaded administration of alteplase: results of the rt-PA-APSAC patency study. J Am Coll Cardiol 1992;19:885-891.[Abstract]
- Heiligenhaus A., Schilling H., Schilling M., Mellin K. Treatment with tissue plasminogen activator (tPA) in risk patients with fibrin reactions after cataract operations. Ophalmologe 1996;93:49-53.
- Muller-Lung U., Heindel W., Gawenda M., Lachner K. Local fibrinolytic therapy of arterial occlusions of the lower extremity: initial success and clinical outcome. Aktuelle Radiol 1996;6:325-329.[Medline]
- Vitale N., Renzulli A., Cerasuolo F., Caruso A., Festa M., De Luca L., Cotrufo M. Prosthetic valve obstruction: thrombolysis versus operation. Ann Thorac Surg 1994;57:365-370.[Abstract]
- Stock K., Jacob A., Schnabel K. Massive pulmonary embolism: treatment with fragmentation and local fibrinolysis with recombinant human-tissue plasminogen activator. Cardiovasc Intervent Radiol 1997;20:364-368.[Medline]
This article has been cited by other articles:
|
|
|
|
 
M. Thielmann, P. Massoudy, B. R. Jaeger, M. Neuhauser, G. Marggraf, S. Sack, R. Erbel, and H. Jakob
Emergency re-revascularization with percutaneous coronary intervention, reoperation, or conservative treatment in patients with acute perioperative graft failure following coronary artery bypass surgery.
Eur. J. Cardiothorac. Surg.,
July 1, 2006;
30(1):
117 - 125.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
