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Ann Thorac Surg 1996;62:1951-1954
© 1996 The Society of Thoracic Surgeons

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Supplement on Bleeding and Transfusion

Treatment of Excessive Mediastinal Bleeding After Cardiopulmonary Bypass

Department of Anesthesia and Intensive Care Medicine, University Hospital of Liège, Liège, Belgium

Abstract

Background. Excessive mediastinal bleeding after cardiopulmonary bypass is one of the most frequently reported complications of cardiac operations. Appropriate treatment requires a rapid and effective diagnostic work-up, based on the knowledge of the pathophysiology induced by cardiopulmonary bypass.

Methods. Possible causes, diagnostic methods available, and therapeutic approaches are reviewed in the light of the literature published on excessive bleeding after cardiac operations.

Results. When bleeding is massive (>250 to 300 mL/h for the first 2 hours, >150 mL/h thereafter), immediate surgical reexploration is mandatory. When bleeding is less important (50 to 150 mL/h), the decision to reoperate should be based on the presence of hemodynamic compromise or a suspected surgical cause. Otherwise, coagulation testing should allow the correction of hemostatic defects as appropriate with protamine, platelet concentrates, fresh frozen plasma, desmopressin, or antifibrinolytics. Hypothermia and hypotension should be corrected and a trial of positive end-expiratory pressure may be considered if diffuse mediastinal oozing (especially from the bed of the mammary artery) is suspected.

Conclusions. A protocol is suggested to guide treatment, taking into account the rapidity of blood loss and the suspected underlying cause.

Excessive mediastinal bleeding is a significant complication of cardiac operations with cardiopulmonary bypass (CPB). It increases the risks of cardiac failure, dysrrhythmias, and infection [1–3] and, consequently, of postoperative mortality. The incidence of reoperation for hemostasis varies in the literature, ranging from 3% to 14%, with an average of 6.2% [4]. The therapeutic alternatives available to control mediastinal bleeding once it has become excessive will be discussed in light of the known causes of this complication and the diagnostic testing modalities presently available in clinical practice.

Causes of Excessive Bleeding After Cardiac Operations

Coagulopathy Induced by Cardiopulmonary Bypass
Excessive bleeding after a cardiac operation is not usually due to a reduction in the concentration of coagulation factors, nor to activation of fibrinolysis. The most important cause is thought to be altered platelet function. Nonetheless, the reduction in the concentration of coagulation factors induced by hemodilution can be significant in specific patient groups, especially those with preexisting deficits of those factors (eg, those with liver disease, patients receiving oral anticoagulants).

Surgical Trauma
Cardiac operation implies trauma to numerous tissues and structures. The heart itself, the aorta, the coronary arteries, the sternum, and the skin and subcutaneous tissues are all potential sources of intraoperative and postoperative bleeding. The venous and aortic cannulation sites and the area dissected to harvest the mammary artery are also possible origins of surgical bleeding. Adhesions between the heart, the sternum, and other mediastinal tissues can lead to dramatic bleeding during cardiac reoperations.

When mediastinal reexploration is indicated to correct excessive bleeding, the most frequent sources of hemorrhage are the venous and arterial anastomoses, collaterals of the vein grafts, cannulation sites, and the sternum [4]. Obviously, meticulous hemostasis is necessary when closing the chest to avoid reintervention for hemorrhage.

Diagnosis

When confronted with increasing mediastinal drainage, the clinician's first responsibility is to decide whether or not blood loss is pathologic. Second, a decision must be made as to whether or not an indication exists for surgical reexploration, as opposed to medical correction of a bleeding diathesis.

Bleeding after a cardiac operation is generally considered to be abnormal when it exceeds 250 to 300 mL/h for the first 2 hours, or 100 to 150 mL/h thereafter [1, 2]. Bleeding in excess of these volumes usually requires immediate surgical intervention to avoid tamponade or hemorrhagic shock.

When drainage of blood is slight (<50 mL/h), the diagnosis is more difficult. In this case, active bleeding may be present without being exteriorized. The drainage system may be occluded by clots or adhesions isolating the bleeding site. Hemorrhage may also be occurring in a nondrained space (eg, a pleural cavity). Under these conditions, extravasation of even a minimal quantity of blood can have dramatic consequences if not evacuated rapidly (ie, tamponade), well before the hematocrit falls and bleeding is suspected clinically. Careful hemodynamic monitoring and echocardiography are particularly useful in providing an early diagnosis and in making the decision to return to the operating room. Frequent measurements of right- and left-sided filling pressures and of the cardiac output usually suggest the correct diagnosis. A low cardiac output combined with low filling pressures imply a significant volume depletion. On the other hand, an increase in right-sided filling pressures associated with a low-output state suggests a pericardial tamponade. This constellation of findings is not specific, however, as it may reflect right ventricular failure or valvular pathology. Chest roentgenography or, preferably, two-dimensional echocardiography (transthoracic or transesophageal) can be extremely useful to establish the diagnosis.

When blood loss is moderate (50 to 150 mL/h), clinicians must decide whether it is due to a bleeding diathesis amenable to medical treatment or to low-level surgical bleeding requiring reexploration. Observation of the color of the drainage fluid may be helpful; red blood suggests active surgical bleeding, unlikely to respond to the administration of procoagulant factors. Also, if the ratio of the hematocrits of the drained fluid to systemic blood is greater than 0.9, surgical bleeding is likely [4]. On the other hand, when bleeding is diffuse, originating from all surgical sites, a medical source must be suspected. In this case, a careful investigation of hemostatic function must be carried out. When the results of coagulation testing depart significantly from those expected normally after CPB, the coagulation abnormalities can be considered responsible for the increased bleeding, at least in part.

The hemodilution occurring upon initiation of CPB causes an immediate decrease in platelet count to values ranging between 100,000 and 150,000/µL [4–6]. Usually, these levels are not sufficient to compromise hemostasis. It should be noted that this decrease can be more significant in patients with heparin-induced thrombocytopenia [7, 8] or in those undergoing intraaortic balloon counterpulsation [4]. Levels of the coagulation factors themselves decrease by approximately 50% [9]. Despite this, none decrease to levels associated with pathologic bleeding; in essence, normal coagulation is possible with levels of these factors as low as 30% of normal [9, 10]. Levels return to normal within 12 hours after the end of CPB. Fibrinogen and plasminogen concentrations are also halved by hemodilution. These reduced concentrations do not influence hemostasis negatively, and are restored to normal within 12 hours.

A postoperative coagulation profile should include (as a minimum) a platelet count, a bleeding time, a prothrombin time, and an activated partial thromboplastin time. More specialized testing of platelet function may be useful in this context [11], but is not practical in urgent situations. Use of thromboelastography has regained popularity recently [12–14]. This monitoring technique conveys a global perspective of the function of the coagulation and fibrinolytic systems, but can be subject to difficulties in interpretation [15]. Once these preliminary tests have been performed, and as indicated by their results, further testing may be necessary (eg, fibrin and fibrinogen degradation products, D-dimers, fibrinogen levels).

Therapeutic Approach

Decisions concerning therapy for mediastinal bleeding depend on the intensity of the bleeding itself, associated hemodynamic abnormalities, and results of complementary investigations (such as various imaging techniques). A summary of the proposed approach to the treatment of excessive blood loss after an adult cardiac operation is presented in Table 1.

If bleeding is moderate (>100 to 150 mL/h) but continuous, hemostatic defects must be corrected as completely as possible. When bleeding persists despite effective correction of hemostatic abnormalities, the patient should be taken to the operating room for reexploration. Even if no active source of bleeding is found, the clinical experience of most centers is that a majority of patients reexplored for postoperative hemorrhage will, nonetheless, stop bleeding when pericardial clots are removed. This may be due to the elimination of clot-associated localized activation of fibrinolysis, stopping a vicious cycle of bleeding, clot formation, fibrinolysis, and persistent blood loss.

Immediate surgical reexploration is indicated if bleeding is massive (>300 to 400 mL/h), if hemorrhage is moderate but consists of bright red arterial blood, or if signs of tamponade are present clinically or by echography.

Treatment of "Medical" Bleeding

When bleeding is thought to be secondary to defective hemostasis, the abnormalities of coagulation must be corrected, either by administration of fractionated blood products or by use of pharmacologic substances with hemostatic properties.

Because a correlation has been established between postoperative bleeding and both the duration of CPB and the degree of hypothermia [16], every effort must be made to reduce the time spent on bypass and to rewarm patients effectively [17]. Aortic–vein graft anastomoses are particularly vulnerable to low-grade bleeding. Tight control of blood pressure postoperatively to avoid hypertensive episodes should reduce bleeding from stressed suture lines [18]. If the hemodynamic status permits, use of positive end-expiratory pressure has been reported to exert an "internal compression" effect on venous bleeding, especially from the site of mammary artery dissection [19]. However, this observation remains unconfirmed [20].

Pharmacologic intervention to promote hemostasis should be considered under certain circumstances. Additional protamine should be administered only if excess heparin has been shown to be responsible for the bleeding observed. Unfortunately, the activated clotting time and activated partial thromboplastin time can both be prolonged by alterations of the intrinsic coagulation cascade (eg, treatment with aprotinin) [21] as well as by excess heparin. Because excess protamine can, itself, induce a coagulopathy [22], measurement of circulating heparin levels should, ideally, guide the administration of additional protamine. However, this is not always possible, as the whole blood (bedside) monitoring devices required are not available in all centers. Measurement of plasma heparin levels can be performed in the hematology laboratory, but results are not available rapidly enough to be useful for the management of patients. Under these circumstances, the thrombin time or, at the bedside, the activated clotting time performed with test tubes containing protamine, may help diagnose incomplete heparin neutralization in a timely fashion. Alternatively, a shortening of the activated clotting time by more than 10% after the administration of a small dose (eg, 25 mg) of protamine is suggestive of the diagnosis.

The major hemostatic disturbance after a cardiac operation is an alteration of platelet function. If the platelet count is less than 100,000/µL, consideration should be given to immediate transfusion of platelet concentrates [6]. One unit of concentrate per 10 kg of body weight should raise the platelet count by 5,000/µL to 10,000/µL. Even if the count is greater than 100,000/µL, abnormal platelet function may still be responsible for increased bleeding. Indeed, if primary hemostasis is defective, the bleeding time will be abnormally prolonged (>10 minutes) [17, 23]. Under these circumstances, two alternatives can be considered. First, functional exogenous platelets may be transfused as described above. The second option consists of the administration of desmopressin acetate to release von Willebrand factor (factor VIII) and improve defective platelet adhesivity, as discussed in the section on pharmacologic methods to reduce the need for allogeneic blood products. A latency of approximately 20 minutes is necessary before desmopressin becomes effective. If this therapy fails, further administration of the drug is of no benefit, as storage sites of factor VIII will have been depleted after the first injection [24, 25].

Although increased fibrinolysis is not the main hemostatic abnormality after CPB, the use of antifibrinolytic drugs, especially aprotinin, can be of benefit when faced with diffuse postoperative bleeding [26, 27]. Aprotinin has been shown to be effective under these circumstances in a few patients [28], and it may be possible that aprotinin will stop bleeding consistently when the hemorrhage is not of surgical origin. In fact, one study suggests that postoperative aprotinin (2 million kallekrein inhibitor units [280 mg]) reduces blood losses and transfusion requirements comparably with prophylactic high-dose aprotinin [29]. We speculate that aprotinin acts by inhibiting fibrinolysis localized to the pericardium; in any event, the platelet-protective effects of the drug are no longer useful because damage to these elements occurs soon after initiating CPB [30]. Thus, efficacy would depend on the absence of active anastomotic bleeding. If this view is correct, nonresponders must immediately be brought to the operating room for surgical control of bleeding.

Transfusion of fresh frozen plasma or fibrinogen (cryoprecipitates) is only rarely necessary because coagulopathy does not appear before levels of factors decrease to less than 30% of normal (10% to 15% for factor V) [9, 10]. Fibrinogen concentrations greater than 1 g/L are sufficient to allow normal clotting. Therefore, patients with excessive bleeding and a prolongation of the prothrombin time of less than 20% to 30%, or a fibrinogen level greater than 1 g/L, will not respond to administration of these blood products [4]. Fresh frozen plasma may be useful in rare cases such as emergency operations in patients treated with coumarin derivatives or immediately after thrombolysis, or when bleeding is massive, in excess of 1 to 1.5 blood volumes [31].

Summary

Excessive bleeding after cardiac operations is a frequent complication. Prompt and effective treatment may be expected to reduce morbidity and mortality. Short CPB times, meticulous surgical hemostasis, restoration and maintenance of normal body temperature, and close control of postoperative hypertension are simple measures that will help reduce the incidence of this complication and the need for allogeneic blood products.

Surgical reexploration is indicated when bleeding is massive (>250 mL/h), associated with hemodynamic compromise (eg, tamponade), obviously arterial, or not responding to medical correction of a coagulation defect. Occasionally, use of desmopressin or, more frequently, transfusion of platelet concentrates will control excessive bleeding secondary to abnormal platelet count or function. If localized fibrinolysis is suspected, administration of aprotinin may be effective, as long as active anastomotic bleeding is not present. In rare circumstances, administration of fresh frozen plasma or fibrinogen may be necessary to restore normal hemostasis.

Footnotes

Address reprint requests to Dr Hartstein, Département d'Anesthésie-Réanimation, CHU Domaine Universitaire du Sart Tilman, B.35-B4000, Liège 1, Belgium.

References

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