Asian Cardiovasc Thorac Ann 2003;11:147-152
© 2003 Asia Publishing EXchange Ltd
Age and Left Ventricular Impairment Predict Reopening for Bleeding
Yongzhi Deng, MD,
Karen Byth, PhD1,
Hugh S Paterson, FRACS
Department of Cardiothoracic Surgery
1 Westmead Millennium Institute, Westmead Hospital, Sydney, Australia
For reprint information contact: Hugh S Paterson, FRACS Tel: 61 2 98457994 Fax: 61 2 98458314 email: patersonh{at}aol.com Department of Cardiothoracic Surgery, Westmead Hospital, Hawkesbury Road, Westmead, NSW, 2145, Australia.
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ABSTRACT
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Statistical analysis of data collected prospectively from all patients undergoing surgery under cardiopulmonary bypass from September 1994 to November 1998 (group 1) was performed to identify preoperative risk factors for reopening for bleeding. Multiple logistic regression analysis of 19 preoperative variables was carried out with reoperation for bleeding as the endpoint. The protocol for intraoperative use of aprotinin was then changed to include high-risk patients. Data collected from all subsequent patients from May 1999 to March 2002 (group 2) were analyzed. Subgroup analyses on primary isolated coronary artery surgery were also performed. Data were obtained from 1,946 patients aged 22 to 88 years (mean, 62.5 years). Older age, severe left ventricular impairment, redo surgery, and chronic renal failure were the independent predictors of reopening for bleeding in group 1. There were no independent predictors of reopening in group 2. Older age and chronic renal failure were the predictors of reexploration for bleeding in patients undergoing primary isolated coronary artery grafting. Prophylactic measures to prevent excessive bleeding should be used in elderly patients and those with severe left ventricular impairment, redo surgery, and chronic renal failure.
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INTRODUCTION
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Bleeding after cardiac surgery is associated with increased risks of perioperative morbidity and mortality. A wide range in the incidence of reoperation for bleeding has been reported but it is usually between 3.6% and 4.4%.1–4 Efforts to reduce postoperative bleeding include the use of prothrombic agents such as aprotinin and lysine analogues. The majority of studies have confirmed the efficacy of antifibrinolytics, but questions of safety and cost effectiveness are unresolved.5–7 Manipulation of hemostasis is balanced by thrombotic complications that may affect graft patency or cerebral, cardiac, and renal function.8–10 The widespread use of prophylactic procoagulants may not be cost effective, and serine protease antagonists such as aprotinin may be associated with adverse reactions.11,12 The purposes of this study were to identify preoperative risk factors that predispose to reexploration for bleeding, to examine the effects of reexploration on perioperative mortality, and to assess the prophylactic effect of selective use of aprotinin in high-risk patients. Procoagulants are most effectively used prophylactically, with high-risk patients being identified preoperatively. Therefore, only preoperative variables were analyzed to identify high-risk patients.
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PATIENTS AND METHODS
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Data were collected prospectively on all patients undergoing surgery under cardiopulmonary bypass (CPB) from September 1994 to November 1998 (group 1) and from May 1999 through March 2002 (group 2), under the care of a single surgeon (HSP). Nineteen preoperative variables (Table 1
) that might predict the need for postoperative reopening for control of bleeding were assessed by multiple logistic regression analysis using reopening for bleeding as the endpoint. The surgical plan was also considered a preoperative variable and included in the analysis. Following analysis of group 1 data (Table 2), the protocol for intraoperative use of aprotinin was revised and applied to patients in group 2. Reopening for bleeding was then included in the analysis as a variable to determine its independent predictive value for perioperative mortality. The same analyses were performed in cases of primary isolated coronary artery bypass grafting (CABG). Twelve patients in group 1 and 5 in group 2 who underwent isolated miscellaneous procedures were excluded from the analysis. A p value less than 0.05 was considered to be statistically significant.
Procedures were routinely performed via a median sternotomy with right atrial and aortic cannulation. A roller pump and hollow fiber oxygenator were used for CPB. Patients were cooled to between 30°C and 32°C. Aortic root cold blood cardioplegia was used in the first 950 patients, with retrograde delivery in selected cases only. Tepid blood cardioplegia via the same delivery system and protocol was used in subsequent patients. No topical solutions were applied. A cardiotomy sucker was employed in all cases. Upon completion of the procedure, the pericardium was approximated at the level of the diaphragm, and the sternum was closed over retrosternal and pleural drains. Postoperatively, the mediastinal shed blood was returned to the patient within 4 hours if greater than 400 mL. Reopening for bleeding was performed when there were signs of cardiac tamponade or there was bleeding via the drains in excess of 1,000 mL within the first 8 hours postoperatively, with no sign of slowing.
Aspirin was routinely stopped 5 to 7 days preoperatively, except in emergency operations. Aprotinin was not used in any patient undergoing non-emergency primary CABG in group 1. Low-dose aprotinin (106 units) was routinely used intraoperatively for non-CABG procedures and in patients with abnormal coagulation profiles. It was also used selectively in redo procedures without a specific protocol, such that 45% of these patients received aprotinin. Postoperative measures used to control bleeding included blood pressure control with vasodilators, positive pressure ventilation, desmopressin acetate, and blood bank products. Aprotinin, aminocaproic acid, and tranexamic acid were not used in the postoperative period prior to reopening. The use of aprotinin was extended in group 2 to include patients over 80 years old, or with a left ventricular (LV) ejection fraction (EF) < 30%, or > 75 years old with LVEF < 50%, those with severe chronic renal failure (serum creatinine > 250 mmol•L-1), and all patients undergoing redo surgery. As in group 1, aprotinin was given as a single dose of 106 units prior to CPB.
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RESULTS
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There was a total of 1,946 patients aged 22–88 years (mean, 62.5 years). The overall rate of reexploration was 5% (97 patients). Group 1 comprised 1,265 patients aged 22–86 years (mean age, 62.0 years) with a male-to-female ratio of 2.6:1, of whom 68 (5.4%) underwent reopening of the sternotomy for control of bleeding in the immediate postoperative period. Forty-eight group 1 patients (3.8%) died in the postoperative period, including 14 of the 68 (20.6%) who had undergone reopening for bleeding. In group 2, there were 681 patients aged 24–88 years (mean age, 63.0 years) with a male-to-female ratio of 2.9:1, of whom 29 (4.3%) underwent reopening of the sternotomy for control of bleeding in the immediate postoperative period. Fifteen patients (2.2%), none of whom had undergone reopening for bleeding, died in the postoperative period.
Older age, severe impairment of LV function (EF < 30%), chronic renal failure, and redo surgery independently predicted postoperative reoperation for control of bleeding in group 1 (Table 2
). The use of intraoperative aprotinin in these high-risk patients in group 2 rendered each risk factor no longer significantly predictive of reopening. However, this reduction in the incidence of reopening associated with each risk factor (interaction) only reached statistical significance in the redo patients (Table 3). Variables not independently predictive of reexploration included gender, symptom class, hypertension, diabetes, smoking history, peripheral vascular disease, hypercholesterolemia, systemic steroid therapy, chronic pulmonary obstructive disease, previous cerebrovascular accidents, urgency, and the type of surgery.
In group 1, a specific site of bleeding associated with the surgery (suture line, cannulation site, or internal mammary artery pedicle) was identified in 39% of reoperations, but no specific site could be found in 42%. Thymic or parasternal bleeding was identified in 14%, and 5% had a severe coagulopathy with multiple bleeding sites. In group 2, 34% had surgical bleeding. Parasternal bleeding was identified in 38% of reoperations. No specific site could be found in 28%.
Multiple logistic regression analysis of the combined groups identified reopening of the sternotomy for control of bleeding as a substantial independent risk factor for perioperative mortality (Table 4). The other risk factors for perioperative mortality were advanced age, female gender, chronic renal failure, severe impairment of LV function, urgency, redo operation, and type of surgical procedure, as well as early period. Thus, the predictors of postoperative mortality are similar to those of reopening for bleeding, but they have an independent effect on mortality over and above that of this variable.
In primary isolated CABG, increased age failed to reach statistical significance in either group, but it was significant for the total cohort. Chronic renal failure did not reach significance. Only 40% of patients in group 2 with severe LV impairment underwent primary isolated CABG, rendering this subgroup too small for analysis (Table 5).
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DISCUSSION
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Some risk factors for reexploration after CPB are well established (Table 6).1–4,12 This study confirmed advanced age, chronic renal failure, and redo surgery to be positive predictors of postoperative bleeding, and also showed severe LV impairment to be an independent predictor. Advanced age is frequently identified as a risk factor for reexploration after cardiac surgery.2,12,13 Sellman and colleagues2 reported a rate of reexploration for bleeding of 4.4% in a group of patients undergoing CABG, and 8.6% in the subset of patients aged 80 and over. Tsai and colleagues12 investigated cardiac surgery in octogenarians and reported mediastinal bleeding necessitating reoperation in 9%, with mortality of 67% in this group. A 15.6% rate of reoperation for bleeding after CABG in patients aged 75 and older has also been reported.13 However, Tuman and colleagues14 found no difference in the rate of reoperation for bleeding among different age groups.
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Table 6. Logistic Regression Analyses of Patient Variables Predicting Risk of Reoperation for Bleeding After Cardiac Surgery
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The role of LV function as a predictor of bleeding was assessed in one previous study, and although there was a trend toward increased need for reexploration with decreasing EF, this did not reach statistical significance; low EF was defined as < 40%, in contrast to our study where preoperative EF < 30% was found to predict reopening.3 It is possible that this reflects poor hemodynamic tolerance of bleeding in patients with significantly impaired LV function, prompting earlier reopening.
Chronic renal insufficiency leads to abnormalities in platelet function that appear to act synergistically with CPB to increase postoperative bleeding. Patients who have undergone previous surgery usually have adhesions which increase the operative and CPB times. Recommendations for the use of aprotinin in these patients have been advanced. Only a few recent studies have systematically investigated reexploration as a multivariate risk factor for certain adverse outcomes (Table 7). Unsworth-White and colleagues4 studied 2,221 patients retrospectively and demonstrated reexploration for bleeding to be a risk factor for operative mortality, increased use of intraaortic balloon pumping, and prolonged intensive care unit stay. Moulton and colleagues1 also identified reexploration as a risk factor for operative death, renal failure, adult respiratory distress syndrome, prolonged mechanical ventilation, sepsis, and atrial arrhythmias. Our results also identified reopening of the sternotomy due to bleeding to be a strong independent risk factor for perioperative death (Table 5). It is considered that the need for reexploration rather than the reexploration itself is a risk factor for perioperative death and therefore, the decision to reexplore should be based on conventional guidelines.1
The importance of minimizing postoperative bleeding is well established because of the associated morbidity and mortality. Modifications in the CPB circuit resulting in less damage to blood components, greater attention to surgical technique aiming for normothermia at separation from CPB, improved techniques for intraoperative cell-saving, and postoperative autotransfusion of shed mediastinal blood have contributed to decreased need for homologous blood products.15 Pharmacological approaches to further decrease transfusion requirements have been developed. Lemmer and colleagues5 reported the results of a multicenter randomized study to investigate the efficacy and safety of aprotinin with 3 different dose regimens and found that there was a lower rate of reopening for bleeding in the groups treated with aprotinin, compared to placebo. When patients were stratified into high and low risk for bleeding, it was seen that limited clinical benefit was conferred by aprotinin in the low-risk group.1 The IMAGE trial raised the question of adverse effects of procoagulant measures, with the finding that saphenous vein graft occlusion was seen in 15.4% of patients treated with aprotinin, compared to 10.9% of patients receiving a placebo.9 Others have shown that high-dose aprotinin in high-risk groups carries a low incidence of graft thrombosis (0.1%).7 Although randomized controlled trials have shown a reduction in blood loss and transfusion requirement, the relatively low blood loss figures in aprotinin and control groups of patients having primary CABG suggests that aprotinin is not of major clinical significance in the management of low-risk patients, with greatest efficacy demonstrated in high-risk groups.16 Also, high-dose aprotinin is expensive and associated with increased risk of anaphylactic reactions with reexposure (2%–4%).
Reopening for bleeding is the clinical endpoint that includes coagulopathic bleeding, surgical bleeding, and a combination of both. The absence of a specific bleeding site may imply a coagulopathy but the identification of a specific site does not imply the absence of coagulopathy. Therefore, reopening for bleeding was used as the endpoint for analysis, regardless of the presence or absence of an identifiable site of bleeding. It was concluded that advanced age, severe impairment of LV function, chronic renal failure, and redo surgery increase the risk of postoperative reopening for control of bleeding. Such reexploration is a predictor of increased perioperative mortality in all patients. The preoperative use of these predictors has allowed the use of prophylactic measures in high-risk patients, such that the incidence of reopening for bleeding in redo surgery, octogenarians, and those with severely impaired LV function has been reduced from 12.1% to 1.9%, 21.7% to 8.0%, and 16% to 5.6% (Table 3), respectively.
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REFERENCES
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ABSTRACT
INTRODUCTION
