Asian Cardiovasc Thorac Ann 1998;6:270-272
© 1998 Asia Publishing EXchange Pte Ltd
Heparin Dosing and Postoperative Blood Loss in Patients Taking Aspirin
Sandeep Chauhan, MD,
Tushar Kanti Ghosh, MD,
Sushant Srivastava, MCh,
Manoj Sahu, MD,
Smriti Ranjan Mohanty, MS,
Alok Mathur, MS,
Nita Saxena, MD,
Panangipalli Venugopal, MCh
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Department of Cardiothoracic and Vascular Surgery and Department of Cardiac Anaesthesia All India Institute of Medical Sciences New Delhi, India
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For reprint information contact: Sandeep Chauhan, MD Department of Cardiac Anaesthesia All India Institute of Medical Sciences Ansari Nagar New Delhi 110029, India Tel: 91 11 66 1123 Ext. 203 Fax:91 11 686 2663
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ABSTRACT
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A large number of patients scheduled to undergo elective coronary artery bypass grafting continue to take aspirin along with other antianginal medication up to the day of surgery. Patients taking aspirin preoperatively are known to bleed more in the postoperative period than those not taking aspirin. This study was undertaken to determine whether the method of heparin administration (protocol-based bolus dose versus an individualized dose) affected postoperative blood loss or requirements of blood and blood products in patients taking aspirin preoperatively. In this prospective study, 300 consecutive patients taking aspirin prior to coronary artery bypass graft surgery were randomly assigned to receive heparin either as a protocol-based bolus of 400 IU·kg–1 (group A) or according to a dose-response curve to obtain an activated coagulation time of 500 seconds on cardiopulmonarybypass (group B). Group B required significantly less heparin (mean 275 IU·kg–1)and less protamine than group A. Postoperative blood loss, requirement of blood and blood products, and time spent on hemostasis in group B was significantly less at 24 hours than group A. We concluded that individualized dosing of heparin using a dose-response curve is preferable to a protocol-based bolus heparin dose in patients taking preoperative aspirin.
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INTRODUCTION
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After demonstration of the beneficial effects of aspirin on outcome after infarction and on graft patency after coronary artery bypass grafting, many patients with coronary artery disease presenting for elective coronary artery bypass grafting continue taking aspirin along with antianginal medication up to the day of surgery.1,2 Patients taking aspirin preoperatively are known to have greater postoperative blood loss compared to patients not taking aspirin.3 Administration of heparin for cardiopulmonary bypass (CPB) on the basis of a dose-response curve was described by Bull and colleagues4 in 1975. However, protocol-based bolus heparin therapy in various doses is more commonly employed because of its convenience and apparent safety based on the axiom "too much is better than too little."
This study was undertaken to determine whether the basis of heparin administration (protocol-based or an individualized dose) affected postoperative blood lossor blood and blood product requirements.5 A target activated coagulation time (ACT) of 500 seconds was selected in the patients given an individualized heparin dose to avoid the possibility of subclinical coagulation and clotting factor consumption that can occur if the ACT falls below 350 seconds on CPB.6
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PATIENTS AND METHODS
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After approval by the institutional research ethics committee, this study was started in June 1997 at the AllIndia Institute of Medical Sciences. Informed consent was obtained from all patients. Three hundred consecutive patients with coronary artery disease undergoing elective coronary artery bypass grafting were studied. The only inclusion criterion was that the patient was taking aspirin preoperatively up to and including theday before surgery. All operations were performed by the same team. Anesthetic management and conduct of CPB were standardized. The patients were randomly assigned to receive heparin (porcine mucosal; Gland Pharmaceutical, Ameerpet, Hyderabad, India) for CPB, either as a protocol-based bolus of 400 IU·kg–1 with an additional dose of 100 IU·kg–1 after one hour of bypass (group A, n = 150) or as an individualized dose (group B, n = 150). The individual dose was obtained from a modified Bull's dose-response curve as follows. Step 1: baseline ACT; step 2: 100 IU·kg–1 dose of heparin given after sternotomy; step 3: ACT value after this dose; step 4: construction of a dose-response curve; step 5: calculation of dose of heparin sufficient to attain an ACT of 500 seconds on CPB.
Cardiopulmonary bypass was established using a membrane oxygenator (Maxima Plus; Medtronic, Inc., Minneapolis, MN, USA) with moderate hypothermia (28°C). The pump was primed with 20 mL·kg–1 Ringer's lactate solution containing 1 mL·kg–1 sodium bicarbonate (7.5% w/v), 0.5 g·kg–1 mannitol, and 100 IU·kg–1 heparin in both groups of patients. On completion of surgery and termination of bypass, protamine was used to reverse heparin on a weight basis of 5 mg·kg–1 in group A and in group B at a 1.5:1 ratio for residual heparin calculated from the dose-response curve. Time spent on hemostasis and chest closure was noted as an indirect assessmentof the coagulation status.
Postoperative mediastinal chest tube drainage was noted hourly for the first 24 hours. Additional protamine was given if the ACT exceeded 10% of the baseline prebypass value. Packed blood cells were given if the hematocrit fell below 30%, platelet-rich plasma wasgiven for volume replacement when the hematocrit was greater than 30%. Postoperative management was conducted by an intensive care resident blinded to the type of heparin management. Need for reexploration was noted in both groups.
STATISTICAL METHODS
Results were expressed as mean ± standard deviation. Differences between means were interpreted by reference to the standard errors of the differences between means. Values of p < 0.05 (95% confidence limits) were considered significant.
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RESULTS
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The ages of the 300 patients ranged from 29 to 72 years. There were 276 males and 24 females. Table 1
shows the demographic data of the 2 groups. All of the patients were taking aspirin at a dosage of 185 or 375 mg per day up to the day of surgery. Most of the patients had at least one internal mammary artery conduit.
Baseline ACT was similar in both groups of patients as shown in Table 2. Significantly less heparin (mean, 275 ± 50 IU·kg–1) was required when the dose was individualized. The difference in ACT values on CPB at 28°C was also significant. ACT after protamine administration was similar in both groups. However, the amount of protamine needed for reversal of the heparin effect in group B was significantly less than in group A. Consierably less time was required to achieve hemostasis and chest closure after weaning from CPB in group B than in group A.
In the postoperative period, group B patients had significantly less blood loss of 240 ± 40 mL in 24 hours compared to 660 ± 105 mL in group A. Use of blood and blood products were also significantly less in group B compared to group A (Table 3). Lower doses of protamine were required during the intensive care period in group B and the reexploration rate in this group was also lower than in group A (Table 3).
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DISCUSSION
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Aspirin is commonly taken by patients with coronary artery disease. However, preoperative intake of aspirin is known to increase postoperative blood loss. It would be desirable to stop aspirin therapy 7 to 10 days before surgery to reduce blood loss caused by aspirin-induced platelet dysfunction.7 This is frequently not possible because of the short preoperative hospital admission in uncomplicated patients who continue to take aspirin up to the day of surgery.
This study assessed the effect of a small change in bypass management on postoperative blood loss in patients taking aspirin preoperatively. We found that individualization of heparin doses for CPB was an easy and reliable way to reduce postoperative bleeding. Bolus heparin therapy based on protocols delivers higher heparin doses that are known to increase blood loss postoperatively.8 Larger amounts of protamine are required to neutralize heparin after bypass and in the intensive care unit.
Following the dose-response curve for heparin, although a target ACT of 500 seconds was desired, we found ACT values on CPB at 28°C to be much higher (greater than 800 seconds) due to hemodilution and hypothermia. The values with bolus therapy were of course significantly higher. More time was spent on hemostasis after CPB in the group given bolus heparin for CPB. Since all the operations were performed by the same team, variation in surgical techniques was not a cause. Reexploration rates were higher in the group given bolus heparin without any obvious surgical hemorrhage being found.
We concluded from these findings that in patients taking aspirin preoperatively, individualization of heparin dosage to obtain an ACT of 500 seconds on CPB is preferable to protocol-based bolus heparin.
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Acknowledgments
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We wish to thank Mr. Ajay Kumar for secretarial assistance and Dr. S Chaudhary for statistical analysis.
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REFERENCES
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ABSTRACT
INTRODUCTION
