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Bleeding After OPCAB Compared With On-Pump CABG
LETTERS TO THE EDITOR
701
Bleeding After OPCAB Compared With On-Pump CABG To the Editor: We appreciate the opportunity to clarify our views on the important issue of hemostasis after off-pump coronary artery bypass (OPCAB). Dr. Raja’s letter argues that coagulation and platelet function are preserved after OPCAB, based mainly on the fact that the blood transfusions are reduced by OPCAB versus on-pump coronary artery bypass grafting (CABG) in almost every randomized clinical trial performed to date.1-5 As Dr. Raja states, this valuable clinical benefit is one of the more important reasons that have led to a revival of interest in OPCAB. However, preserved hemostasis is not the only factor that would yield an improved transfusion rate in these studies. Avoidance of cardiopulmonary bypass (CPB)-induced hemodilution by OPCAB or established transfusion practice patterns (bias) may have had an underappreciated effect on this observed transfusion “benefit.” Additional studies have demonstrated preserved function of platelets and the coagulation cascade after OPCAB.5,6 While scientifically interesting, most of the assays used in these analyses have not been validated to correlate with clinical hemostasis. The most direct assessment of hemostasis after cardiac surgery is the rate of postoperative hemorrhage (ie, chest tube output) (Table 1). Detailed analysis of the data quoted by Dr. Raja illustrates that only the initial trial by Ascione et al1 showed a significant reduction in chest tube output for off-pump compared with on-pump CABG. This trial was the first published randomized comparison between the on-pump and off-pump techniques, and included restricted entry criteria that limit its current generalizability. Further reports, including one by the same authors in a later follow-up study,2 failed to confirm a reduction in blood loss after OPCAB. In fact, 2 studies showed increased blood loss in the OPCAB group, with statistical significance reached in 1 study.4 Of the 2 meta-analyses quoted by Dr. Raja, Cheng et al7 reported no significant difference in repeat exploration for bleeding within 30 days between the on-pump and off-pump groups. The study by Reston et al8 provided no data relevant to bleeding, and neither study provided information about postoperative chest tube output. This distinction between bleeding rates and transfusion requirements has significant practical implications for managing patients after OPCAB. The a priori preconception that hemostasis is preserved with OPCAB leads to anxiety that the balance of coagulation is tipped toward a postoperative hypercoagulable state.9 As a result, many surgeons use more aggressive antithrombotic regimens10 or have given up on OPCAB for fear of an inevitable increased risk for bypass graft thrombosis. However, we did not find evidence of a hypercoagulable state in the cohort of patients with early vein graft thrombosis after OPCAB. A routine strategy of more aggressive anticoagulation based on the belief of hypercoagulability after OPCAB is likely to have an unfavorable risk-benefit ratio. A more thoughtful analysis of the best available data supports the notion that coronary artery bypass procedures themselves, rather than simply exposure of blood to CPB circuit components, contribute importantly to postoperative coagulopathy and bleeding. In the absence of clinical trials specifically addressing hemostasis after OPCAB, strategies for preventing thrombosis in these patients should follow guidelines established for on-pump CABG. Robert Poston, MD Division of Cardiac Surgery University of Maryland School of Medicine Baltimore, MD Table 1. Postoperative Chest Tube Output in Randomized Clinical Trials Comparing Off-Pump Versus On-Pump CABG Study
BHACAS 11 BHACAS 22 Khan et al3 Octopus study4 Puskas et al5
OPCAB
On-Pump
769 (24 h) 1094 761 (24 h) 822 1031 (24 h) 898 500 (12 h) 400 “. . . chest tube output did not differ between the groups at 4, 8, or 12 hours.”
p
⬍0.05 NS 0.18 ⬍0.02 NS
Abbreviations: CABG, Coronary artery bypass grafting; OPCAB, off-pump coronary artery bypass; BHACAS, Beating Heart and Cardioplegic Arrest Study; NS, not significant.
REFERENCES 1. Ascione R, Williams S, Lloyd CT, et al: Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: A prospective randomized study. J Thorac Cardiovasc Surg 121:689-696, 2001 2. Angelini GD, Taylor FC, Reeves BC, et al: Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): A pooled analysis of two randomised controlled trials. Lancet 359:1194-1199, 2002 3. Khan NE, De Souza AD, Mister R, et al: A randomized comparison of off-pump and on-pump multivessel coronary-artery bypass surgery. N Engl J Med 350:21-28, 2004 4. Van Dijk D, Nierich AP, Jansen EWL, et al: Early outcome after off-pump versus on-pump coronary bypass surgery: Results from a randomized study. Circulation 104:1761-1766, 2001 5. Puskas JD, Williams WH, Duke PG, et al: Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: A prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg 125:797-808, 2003
702
LETTERS TO THE EDITOR
6. Moller CH, Steinbruchel DA: Platelet function after coronary artery bypass grafting: Is there a procoagulant activity after off-pump compared with on-pump surgery? Scand Cardiovasc J 37:149-153, 2003 7. Cheng DC, Bainbridge D, Martin JE, et al: Evidence-Based Perioperative Clinical Outcomes Research Group: Does off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized trials. Anesthesiology 102:188-203, 2005 8. Reston JT, Tregear SJ, Turkelson CM: Meta-analysis of short-term and mid-term outcomes following off-pump coronary artery bypass grafting. Ann Thorac Surg 76:1510-1515, 2003 9. Mariani M, Gu Y, Boonstra P: Procoagulant activity after off-pump coronary operation: Is the current anticoagulation adequate? Ann Thorac Surg 67:1370-1375, 1999 10. D’Ancona G, Donias HW, Karamanoukian RL: OPCAB therapy survey: Off-pump clopidogrel, aspirin or both therapy survey. Heart Surg Forum 4:354-358, 2001 doi:10.1053/j.jvca.2005.03.023
Inaccuracy of Coagulation Studies Performed on Blood Samples Obtained from Arterial Catheter To the Editor: We read the manuscript by Leyvi et al1 with great interest. It reminded us of a case which we present below. Not only during cardiac surgery, but also in the intensive care unit, blood samples for laboratory studies are frequently drawn from arterial catheters. It is usually believed that blood for clotting studies can be drawn from arterial catheters after discarding 5 mL of blood in order that the blood sample not be affected by flush solutions.2 We believe our case is important because it demonstrates the inadequacy of discarding even 10 mL of blood and the inaccuracy of coagulation studies performed on blood samples obtained from arterial catheters. A 23-year-old man with Morque syndrome was admitted to our intensive care unit after orthopedic surgery. Admission coagulation parameters were normal. On the first postoperative day, routine coagulation studies performed on a blood sample obtained from an arterial cannula after 10 mL of discarded volume showed kaolin-activated partial thromboplastin time (APTT) of 111.2 sec (normal, 29-47 sec, determined with STA analyzers; Diagnostica Stago, Stago, France), and international normalized ratio (INR) of 1.61 (normal, 0.75-1.5, determined by STA analyzers; Neoplastine CL PLUS, Diagnostica Stago). After these abnormal results, coagulation studies were repeated with another arterial blood sample and also with a sample from a separate venipuncture site. Extensive physical examination to search for a bleeding site, including the wound, was done repeatedly; additional diagnostic tests including disseminated intravascular coagulation workup, liver function tests, and complete blood cell count were ordered; and vitamin K was administered. The APTT performed on the arterial blood sample was above the measurable limits, and the INR was 1.84. Two units of fresh frozen plasma were given; after which, results of the previously performed coagulation studies from the venipuncture site were found to be normal (APTT, 12.7 sec; INR, 1.28). In this case, we thought coagulation studies performed on blood samples obtained from an arterial cannula gave clinically misleading information (probably because of contamination with small amounts of heparin from the flushes), misguided therapy, and caused misuse of resources. We believe blood samples for clotting studies should not be obtained from arterial catheters, if possible. Arterial and venous thrombelastograph variables can differ during cardiac surgery.3 The coagulation studies performed on blood samples obtained from an arterial catheter can be inaccurate.4-6 It should be remembered that it is clinically wise to repeat coagulation studies from a separate venipuncture site when samples drawn from an arterial cannula show abnormal results even when 10 mL of blood has been discarded. Seda B. Akinci, MD Nevriye Salman, MD Tulay Aykut, MD Meral Kanbak, MD Ulku Aypar, MD Department of Anaesthesiology and Reanimation Faculty of Medicine Hacettepe University Ankara, Turkey REFERENCES 1. Leyvi G, Zhuravlev I, Inyang A, et al: Arterial versus venous sampling for activated coagulation time measurements during cardiac surgery: A comparative study. J Cardiothorac Vasc Anesth 18:573-580, 2004 2. Lew JKL, Hutchinson R, Lin ES: Intraarterial blood sampling for clotting studies. Anaesthesia 46:719-721, 1991 3. Manspeizer HE, Imai M, Frumento RJ, et al: Arterial and venous thrombelastograph variables differ during cardiac surgery. Anesth Analg 93:277-281, 2001
701
Bleeding After OPCAB Compared With On-Pump CABG To the Editor: We appreciate the opportunity to clarify our views on the important issue of hemostasis after off-pump coronary artery bypass (OPCAB). Dr. Raja’s letter argues that coagulation and platelet function are preserved after OPCAB, based mainly on the fact that the blood transfusions are reduced by OPCAB versus on-pump coronary artery bypass grafting (CABG) in almost every randomized clinical trial performed to date.1-5 As Dr. Raja states, this valuable clinical benefit is one of the more important reasons that have led to a revival of interest in OPCAB. However, preserved hemostasis is not the only factor that would yield an improved transfusion rate in these studies. Avoidance of cardiopulmonary bypass (CPB)-induced hemodilution by OPCAB or established transfusion practice patterns (bias) may have had an underappreciated effect on this observed transfusion “benefit.” Additional studies have demonstrated preserved function of platelets and the coagulation cascade after OPCAB.5,6 While scientifically interesting, most of the assays used in these analyses have not been validated to correlate with clinical hemostasis. The most direct assessment of hemostasis after cardiac surgery is the rate of postoperative hemorrhage (ie, chest tube output) (Table 1). Detailed analysis of the data quoted by Dr. Raja illustrates that only the initial trial by Ascione et al1 showed a significant reduction in chest tube output for off-pump compared with on-pump CABG. This trial was the first published randomized comparison between the on-pump and off-pump techniques, and included restricted entry criteria that limit its current generalizability. Further reports, including one by the same authors in a later follow-up study,2 failed to confirm a reduction in blood loss after OPCAB. In fact, 2 studies showed increased blood loss in the OPCAB group, with statistical significance reached in 1 study.4 Of the 2 meta-analyses quoted by Dr. Raja, Cheng et al7 reported no significant difference in repeat exploration for bleeding within 30 days between the on-pump and off-pump groups. The study by Reston et al8 provided no data relevant to bleeding, and neither study provided information about postoperative chest tube output. This distinction between bleeding rates and transfusion requirements has significant practical implications for managing patients after OPCAB. The a priori preconception that hemostasis is preserved with OPCAB leads to anxiety that the balance of coagulation is tipped toward a postoperative hypercoagulable state.9 As a result, many surgeons use more aggressive antithrombotic regimens10 or have given up on OPCAB for fear of an inevitable increased risk for bypass graft thrombosis. However, we did not find evidence of a hypercoagulable state in the cohort of patients with early vein graft thrombosis after OPCAB. A routine strategy of more aggressive anticoagulation based on the belief of hypercoagulability after OPCAB is likely to have an unfavorable risk-benefit ratio. A more thoughtful analysis of the best available data supports the notion that coronary artery bypass procedures themselves, rather than simply exposure of blood to CPB circuit components, contribute importantly to postoperative coagulopathy and bleeding. In the absence of clinical trials specifically addressing hemostasis after OPCAB, strategies for preventing thrombosis in these patients should follow guidelines established for on-pump CABG. Robert Poston, MD Division of Cardiac Surgery University of Maryland School of Medicine Baltimore, MD Table 1. Postoperative Chest Tube Output in Randomized Clinical Trials Comparing Off-Pump Versus On-Pump CABG Study
BHACAS 11 BHACAS 22 Khan et al3 Octopus study4 Puskas et al5
OPCAB
On-Pump
769 (24 h) 1094 761 (24 h) 822 1031 (24 h) 898 500 (12 h) 400 “. . . chest tube output did not differ between the groups at 4, 8, or 12 hours.”
p
⬍0.05 NS 0.18 ⬍0.02 NS
Abbreviations: CABG, Coronary artery bypass grafting; OPCAB, off-pump coronary artery bypass; BHACAS, Beating Heart and Cardioplegic Arrest Study; NS, not significant.
REFERENCES 1. Ascione R, Williams S, Lloyd CT, et al: Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: A prospective randomized study. J Thorac Cardiovasc Surg 121:689-696, 2001 2. Angelini GD, Taylor FC, Reeves BC, et al: Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): A pooled analysis of two randomised controlled trials. Lancet 359:1194-1199, 2002 3. Khan NE, De Souza AD, Mister R, et al: A randomized comparison of off-pump and on-pump multivessel coronary-artery bypass surgery. N Engl J Med 350:21-28, 2004 4. Van Dijk D, Nierich AP, Jansen EWL, et al: Early outcome after off-pump versus on-pump coronary bypass surgery: Results from a randomized study. Circulation 104:1761-1766, 2001 5. Puskas JD, Williams WH, Duke PG, et al: Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: A prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg 125:797-808, 2003
702
LETTERS TO THE EDITOR
6. Moller CH, Steinbruchel DA: Platelet function after coronary artery bypass grafting: Is there a procoagulant activity after off-pump compared with on-pump surgery? Scand Cardiovasc J 37:149-153, 2003 7. Cheng DC, Bainbridge D, Martin JE, et al: Evidence-Based Perioperative Clinical Outcomes Research Group: Does off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized trials. Anesthesiology 102:188-203, 2005 8. Reston JT, Tregear SJ, Turkelson CM: Meta-analysis of short-term and mid-term outcomes following off-pump coronary artery bypass grafting. Ann Thorac Surg 76:1510-1515, 2003 9. Mariani M, Gu Y, Boonstra P: Procoagulant activity after off-pump coronary operation: Is the current anticoagulation adequate? Ann Thorac Surg 67:1370-1375, 1999 10. D’Ancona G, Donias HW, Karamanoukian RL: OPCAB therapy survey: Off-pump clopidogrel, aspirin or both therapy survey. Heart Surg Forum 4:354-358, 2001 doi:10.1053/j.jvca.2005.03.023
Inaccuracy of Coagulation Studies Performed on Blood Samples Obtained from Arterial Catheter To the Editor: We read the manuscript by Leyvi et al1 with great interest. It reminded us of a case which we present below. Not only during cardiac surgery, but also in the intensive care unit, blood samples for laboratory studies are frequently drawn from arterial catheters. It is usually believed that blood for clotting studies can be drawn from arterial catheters after discarding 5 mL of blood in order that the blood sample not be affected by flush solutions.2 We believe our case is important because it demonstrates the inadequacy of discarding even 10 mL of blood and the inaccuracy of coagulation studies performed on blood samples obtained from arterial catheters. A 23-year-old man with Morque syndrome was admitted to our intensive care unit after orthopedic surgery. Admission coagulation parameters were normal. On the first postoperative day, routine coagulation studies performed on a blood sample obtained from an arterial cannula after 10 mL of discarded volume showed kaolin-activated partial thromboplastin time (APTT) of 111.2 sec (normal, 29-47 sec, determined with STA analyzers; Diagnostica Stago, Stago, France), and international normalized ratio (INR) of 1.61 (normal, 0.75-1.5, determined by STA analyzers; Neoplastine CL PLUS, Diagnostica Stago). After these abnormal results, coagulation studies were repeated with another arterial blood sample and also with a sample from a separate venipuncture site. Extensive physical examination to search for a bleeding site, including the wound, was done repeatedly; additional diagnostic tests including disseminated intravascular coagulation workup, liver function tests, and complete blood cell count were ordered; and vitamin K was administered. The APTT performed on the arterial blood sample was above the measurable limits, and the INR was 1.84. Two units of fresh frozen plasma were given; after which, results of the previously performed coagulation studies from the venipuncture site were found to be normal (APTT, 12.7 sec; INR, 1.28). In this case, we thought coagulation studies performed on blood samples obtained from an arterial cannula gave clinically misleading information (probably because of contamination with small amounts of heparin from the flushes), misguided therapy, and caused misuse of resources. We believe blood samples for clotting studies should not be obtained from arterial catheters, if possible. Arterial and venous thrombelastograph variables can differ during cardiac surgery.3 The coagulation studies performed on blood samples obtained from an arterial catheter can be inaccurate.4-6 It should be remembered that it is clinically wise to repeat coagulation studies from a separate venipuncture site when samples drawn from an arterial cannula show abnormal results even when 10 mL of blood has been discarded. Seda B. Akinci, MD Nevriye Salman, MD Tulay Aykut, MD Meral Kanbak, MD Ulku Aypar, MD Department of Anaesthesiology and Reanimation Faculty of Medicine Hacettepe University Ankara, Turkey REFERENCES 1. Leyvi G, Zhuravlev I, Inyang A, et al: Arterial versus venous sampling for activated coagulation time measurements during cardiac surgery: A comparative study. J Cardiothorac Vasc Anesth 18:573-580, 2004 2. Lew JKL, Hutchinson R, Lin ES: Intraarterial blood sampling for clotting studies. Anaesthesia 46:719-721, 1991 3. Manspeizer HE, Imai M, Frumento RJ, et al: Arterial and venous thrombelastograph variables differ during cardiac surgery. Anesth Analg 93:277-281, 2001