Ann Thorac Surg 2014;98:782–7
Clinical Outcomes Unit American University of Beirut Beirut, Lebanon Sean Neill, MD Department of Anesthesiology University of Michigan Ann Arbor, MI Jennifer Vance, MD Department of Anesthesiology University of Michigan Ann Arbor, MI Donald S. Likosky, PhD Department of Cardiac Surgery University of Michigan Ann Arbor, MI
References 1. Wang S-Y, Xue F-S, Li R-P, Cui X-L. Assessing independent effects of anemia and transfusion on late mortality (letter). Ann Thorac Surg 2014;98:782. 2. Pedersen AB, Baron JA, Overgaard S, Johnsen SP. Short- and long-term mortality following primary total hip replacement for osteoarthritis: a Danish nationwide epidemiological study. J Bone Joint Surg Br 2011;93:172–7. 3. Engoren M, Habib RH, Arslanian-Engoren C, Kheterpal S, Schwann TA. The effect of acute kidney injury and discharge creatinine level on mortality following cardiac surgery. Crit Care Med. In press. PMID 24810529 4. Leslie K, Myles PS, Forbes A, Chan MT. The effect of bispectral index monitoring on long-term survival in the B-aware trial. Anesth Analg 2010;110:816–22. 5. Engoren M, Schwann TA, Habib RH, Neill SN, Vance JL, Likosky DS. The independent effects of anemia and transfusion on mortality after coronary artery bypass. Ann Thorac Surg 2014;97:514–20. 6. Harlaar JJ, Gosselink MP, Hop WC, Lange JF, Busch OR, Jeekel H. Blood transfusions and prognosis in colorectal cancer: long-term results of a randomized controlled trial. Ann Surg 2012;256:681–6.
Clopidogrel After Surgical Coronary Revascularization Increases Venous Graft Patency To the Editor: I read with great interest the article by Ebrahimi and colleagues [1] regarding the effect of the combination of aspirin and clopidogrel on vein graft patency after coronary artery bypass grafting (CABG) surgery. In this observational analysis of data from the Randomized On and Off-Pump Bypass trial, the authors concluded that clopidogrel use after CABG did not significantly reduce the incidence of 1-year venous graft failure. A recent meta-analysis [2] of five randomized controlled studies investigating the effect of single versus dual antiplatelet therapy on early patency of graft conduits after CABG concluded that dual antiplatelet therapy significantly reduced the risk of venous graft occlusion. It is important to note that for vein grafts, single antiplatelet therapy was associated with a significantly increased graft failure rate (91 of 846; 10.8%) versus dual antiplatelet therapy (57 of 860; 6.6%; p ¼ 0.003). Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
783
In the latest guidelines on myocardial revascularization from the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery [3], the task force authors recommend the use of clopidogrel after CABG only in cases of aspirin intolerance because there are no randomized controlled trial comparing the efficacy of clopidogrel plus aspirin versus aspirin alone on graft patency. With the present strong and persuasive scientific evidence, this statement is now outdated. Grafts are especially vulnerable in the early postoperative period, and effective prompt postoperative antiplatelet therapy is paramount to preserve the revascularization benefit [4]. This underscores the importance of rapid identification of patients with aspirin resistance, thus allowing a timely intervention. The beneficial effect of clopidogrel is attributable to the fact that dual antiplatelet therapy overcomes single drug resistances as shown in the CRYSSA (prevention of coronary artery bypass occlusion after off-pump procedures) trial [5]. Jamil Hajj-Chahine, MD Department of Cardio-thoracic Surgery University Hospital of Poitiers 2 Rue de la Miletrie 86021 Poitiers, France e-mail: [email protected]
References 1. Ebrahimi R, Bakaeen FG, Uberoi A, et al. Effect of clopidogrel use post coronary artery bypass surgery on graft patency. Ann Thorac Surg 2014;97:15–21. 2. Nocerino AG, Achenbach S, Taylor AJ. Meta-analysis of effect of single versus dual antiplatelet therapy on early patency of bypass conduits after coronary artery bypass grafting. Am J Cardiol 2013;112:1576–9. 3. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI), Kolh P, Wijns W, Danchin N, et al. Guidelines on myocardial revascularization. Eur J Cardiothorac Surg 2010;38(Suppl):S1–52. 4. Gluckman TJ, McLean RC, Schulman SP, et al. Effects of aspirin responsiveness and platelet reactivity on early vein graft thrombosis after coronary artery bypass graft surgery. J Am Coll Cardiol 2011;57:1069–77. 5. Mannacio VA, Di Tommaso L, Antignan A, De Amicis V, Vosa C. Aspirin plus clopidogrel for optimal platelet inhibition following off-pump coronary artery bypass surgery: results from the CRYSSA (prevention of Coronary arteRY bypass occlusion After off-pump procedures) randomised study. Heart 2012;98:1710–5.
Acute Kidney Injury and Cardiopulmonary Bypass Surgery To the Editor: In a recent issue of The Annals of Thoracic Surgery, Sickeler and colleagues [1] did not confirm any association of cardiac surgery–related acute kidney injury (AKI) risk with the cooccurrence of hypotension and anemia during cardiopulmonary bypass (CPB) relative to anemia alone. Also, they found no association between CPB hypotension (alone) and postoperative AKI. These findings are surprising. However, an important point that should be kept in mind when drawing conclusions from this study is that cerebral 0003-4975/$36.00
MISCELLANEOUS
Robert H. Habib, PhD
CORRESPONDENCE
784
CORRESPONDENCE
outcomes were not evaluated. It is well known that cerebral perfusion is more dependent on mean arterial pressure (MAP), whereas cardiac perfusion is more dependent on diastolic blood pressure and renal perfusion is dependent on both MAP and cardiac output. As a result, the kidney can be hypoperfused at normal MAP if cardiac output compromised, while cerebral and cardiac perfusion is maintained [2, 3]. It has been suggested that maintaining MAP with the autoregulatory range (40–90 mm Hg) for the brain will ensure perfusion to the kidney [4], whose blood flow is also autoregulated [2]. In the present study, although the authors mentioned that target MAP was between 50 and 70 mm Hg, there is no information about the mean MAP values of the study cohort, especially patients who developed AKI. During CPB surgery, MAP values below the optimal renal autoregulation threshold can lead to ischemic kidney damage [5]. Indeed, in patients with hypertension higher MAP values (>50 and 70 mm Hg) may be required to maintain adequate renal perfusion [6]. As a result, the pathogenesis of AKI during CPB is multifactorial and involves hemodynamic, inflammatory and other mechanisms that interact at cellular level [5]. If we consider with a simple logic, the co-occurrence of anemia and hypotension may have more deleterious effects on kidney function, especially in surgical patients. If so or not, we have to explain causality as a major end point with large prospective studies. Yavuzer Koza, MD Ataturk University Faculty of Medicine Department of Cardiology Yakutiye Erzurum, Turkey 25100 e-mail: [email protected]
References 1. Sickeler R, Phillips-Bute B, Kertai MD, et al. The risk of acute kidney injury with co-occurrence of anemia and hypotension during cardiopulmonary bypass relative to anemia alone. Ann Thorac Surg 2014;97:865–71. 2. Rhee CJ, Kibler KK, Easley RB, et al. Renovascular reactivity measured by near-infrared spectroscopy. J Appl Physiol 2012;113:307–14. 3. Michler RE, Sandhu AA, Young WL, Schwartz AE. Low-flow cardiopulmonary bypass: Importance of blood pressure in maintaining cerebral blood flow. Ann Thorac Surg 1995;60: 525–8. 4. Ono M, Brady K, Easley RB, et al. Duration and magnitude of blood pressure below cerebral autoregulation threshold during cardiopulmonary bypass is associated with major morbidity and operative mortality. J Thorac Cardiovasc Surg 2014;147:483–9. 5. Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 2006;1:19–32. 6. Palmer BF. Renal dysfunction complicating the treatment of hypertension. N Engl J Med 2002;347:1256–61.
MISCELLANEOUS
Reply To the Editor: We appreciate the comments of Dr Koza [1] regarding our retrospective analysis [2], which found no change in acute kidney injury (AKI) rates after aortocoronary bypass surgery with the co-occurrence of hypotension and anemia during cardiopulmonary bypass (CPB) relative to anemia alone. Notably, our findings contrast with the post hoc observations of Haase and
Ann Thorac Surg 2014;98:782–7
colleagues [3] in their smaller study (n ¼ 920 versus 3,963 subjects). Interpreting these observations contributes to the ongoing debate over optimal hematocrit and hemodynamics in the cardiac surgery patient. Our original intent was to reconfirm the findings of Haase and colleagues. Notably, the importance of CPB anemia as an AKI risk factor is established; however, studies have not confirmed CPB hypotension as independently important (as long as flow is preserved) [4]. The co-occurrence of these two factors has only been specifically addressed in the two abovementioned papers; we propose that no relationship exists and that the post hoc observations of Haase and colleagues likely reflect a spurious finding. As acknowledged by these authors, type I (false-positive) error is common, and post hoc findings are always deserving of revalidation in a different dataset, particularly when multiple secondary analyses are performed. With regard to Dr Koza’s comments on the effect on renal artery blood flow of myogenic autoregulatory reflexes, we highlight that these are not influenced primarily by the need for oxygen delivery but serve to regulate diversion of systemic blood for renal filtration, while at higher pressures “protecting” the glomeruli from damage by limiting blood flow [5, 6]. Such myogenic reflexes respond to different stimuli than those influencing the tubuloglomerular feedback reflexes that match oxygen supply and demand in the medullary microcirculation within the renal parenchyma, which are poorly understood. In summary, despite employing a much larger sample, rather than confirming the previous study findings, our contradictory analyses lend support to the possibility that Haase and colleagues’ post hoc finding was spurious and suggest that changing current practice based on such findings would be premature. Robert Sickeler, BS Mark Stafford-Smith, MD Department of Anesthesiology Duke University Medical Center Box 3094 DUMC Durham, NC 27710 e-mail: [email protected]
References 1. Koza Y. Acute kidney injury and cardiopulmonary bypass surgery (letter). Ann Thorac Surg 2014;98:783–4. 2. Sickeler R, Phillips-Bute B, Kertai MD, et al. The risk of acute kidney injury with co-occurrence of anemia and hypotension during cardiopulmonary bypass relative to anemia alone. Ann Thorac Surg 2014;97:865–71. 3. Haase M, Bellomo R, Story D, et al. Effect of mean arterial pressure, haemoglobin and blood transfusion during cardiopulmonary bypass on post-operative acute kidney injury. Nephrol Dial Transplant 2012;27:153–60. 4. Stafford-Smith M, Newman MF. What effects do hemodilution and blood transfusion during cardiopulmonary bypass have on renal outcomes? Nat Clin Pract Nephrol 2006;2:188–9. 5. Loutzenhiser R, Griffin K, Williamson G, Bidani A. Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. Am J Physiol Regul Integr Comp Physiol 2006;290: R1153–67. 6. Arendshorst WJ, Br€annstr€ om K, Ruan X. Actions of angiotensin II on the renal microvasculature. J Am Soc Nephrol 1999;(10 Suppl 11):S149–61.
Clinical Outcomes Unit American University of Beirut Beirut, Lebanon Sean Neill, MD Department of Anesthesiology University of Michigan Ann Arbor, MI Jennifer Vance, MD Department of Anesthesiology University of Michigan Ann Arbor, MI Donald S. Likosky, PhD Department of Cardiac Surgery University of Michigan Ann Arbor, MI
References 1. Wang S-Y, Xue F-S, Li R-P, Cui X-L. Assessing independent effects of anemia and transfusion on late mortality (letter). Ann Thorac Surg 2014;98:782. 2. Pedersen AB, Baron JA, Overgaard S, Johnsen SP. Short- and long-term mortality following primary total hip replacement for osteoarthritis: a Danish nationwide epidemiological study. J Bone Joint Surg Br 2011;93:172–7. 3. Engoren M, Habib RH, Arslanian-Engoren C, Kheterpal S, Schwann TA. The effect of acute kidney injury and discharge creatinine level on mortality following cardiac surgery. Crit Care Med. In press. PMID 24810529 4. Leslie K, Myles PS, Forbes A, Chan MT. The effect of bispectral index monitoring on long-term survival in the B-aware trial. Anesth Analg 2010;110:816–22. 5. Engoren M, Schwann TA, Habib RH, Neill SN, Vance JL, Likosky DS. The independent effects of anemia and transfusion on mortality after coronary artery bypass. Ann Thorac Surg 2014;97:514–20. 6. Harlaar JJ, Gosselink MP, Hop WC, Lange JF, Busch OR, Jeekel H. Blood transfusions and prognosis in colorectal cancer: long-term results of a randomized controlled trial. Ann Surg 2012;256:681–6.
Clopidogrel After Surgical Coronary Revascularization Increases Venous Graft Patency To the Editor: I read with great interest the article by Ebrahimi and colleagues [1] regarding the effect of the combination of aspirin and clopidogrel on vein graft patency after coronary artery bypass grafting (CABG) surgery. In this observational analysis of data from the Randomized On and Off-Pump Bypass trial, the authors concluded that clopidogrel use after CABG did not significantly reduce the incidence of 1-year venous graft failure. A recent meta-analysis [2] of five randomized controlled studies investigating the effect of single versus dual antiplatelet therapy on early patency of graft conduits after CABG concluded that dual antiplatelet therapy significantly reduced the risk of venous graft occlusion. It is important to note that for vein grafts, single antiplatelet therapy was associated with a significantly increased graft failure rate (91 of 846; 10.8%) versus dual antiplatelet therapy (57 of 860; 6.6%; p ¼ 0.003). Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
783
In the latest guidelines on myocardial revascularization from the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery [3], the task force authors recommend the use of clopidogrel after CABG only in cases of aspirin intolerance because there are no randomized controlled trial comparing the efficacy of clopidogrel plus aspirin versus aspirin alone on graft patency. With the present strong and persuasive scientific evidence, this statement is now outdated. Grafts are especially vulnerable in the early postoperative period, and effective prompt postoperative antiplatelet therapy is paramount to preserve the revascularization benefit [4]. This underscores the importance of rapid identification of patients with aspirin resistance, thus allowing a timely intervention. The beneficial effect of clopidogrel is attributable to the fact that dual antiplatelet therapy overcomes single drug resistances as shown in the CRYSSA (prevention of coronary artery bypass occlusion after off-pump procedures) trial [5]. Jamil Hajj-Chahine, MD Department of Cardio-thoracic Surgery University Hospital of Poitiers 2 Rue de la Miletrie 86021 Poitiers, France e-mail: [email protected]
References 1. Ebrahimi R, Bakaeen FG, Uberoi A, et al. Effect of clopidogrel use post coronary artery bypass surgery on graft patency. Ann Thorac Surg 2014;97:15–21. 2. Nocerino AG, Achenbach S, Taylor AJ. Meta-analysis of effect of single versus dual antiplatelet therapy on early patency of bypass conduits after coronary artery bypass grafting. Am J Cardiol 2013;112:1576–9. 3. Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI), Kolh P, Wijns W, Danchin N, et al. Guidelines on myocardial revascularization. Eur J Cardiothorac Surg 2010;38(Suppl):S1–52. 4. Gluckman TJ, McLean RC, Schulman SP, et al. Effects of aspirin responsiveness and platelet reactivity on early vein graft thrombosis after coronary artery bypass graft surgery. J Am Coll Cardiol 2011;57:1069–77. 5. Mannacio VA, Di Tommaso L, Antignan A, De Amicis V, Vosa C. Aspirin plus clopidogrel for optimal platelet inhibition following off-pump coronary artery bypass surgery: results from the CRYSSA (prevention of Coronary arteRY bypass occlusion After off-pump procedures) randomised study. Heart 2012;98:1710–5.
Acute Kidney Injury and Cardiopulmonary Bypass Surgery To the Editor: In a recent issue of The Annals of Thoracic Surgery, Sickeler and colleagues [1] did not confirm any association of cardiac surgery–related acute kidney injury (AKI) risk with the cooccurrence of hypotension and anemia during cardiopulmonary bypass (CPB) relative to anemia alone. Also, they found no association between CPB hypotension (alone) and postoperative AKI. These findings are surprising. However, an important point that should be kept in mind when drawing conclusions from this study is that cerebral 0003-4975/$36.00
MISCELLANEOUS
Robert H. Habib, PhD
CORRESPONDENCE
784
CORRESPONDENCE
outcomes were not evaluated. It is well known that cerebral perfusion is more dependent on mean arterial pressure (MAP), whereas cardiac perfusion is more dependent on diastolic blood pressure and renal perfusion is dependent on both MAP and cardiac output. As a result, the kidney can be hypoperfused at normal MAP if cardiac output compromised, while cerebral and cardiac perfusion is maintained [2, 3]. It has been suggested that maintaining MAP with the autoregulatory range (40–90 mm Hg) for the brain will ensure perfusion to the kidney [4], whose blood flow is also autoregulated [2]. In the present study, although the authors mentioned that target MAP was between 50 and 70 mm Hg, there is no information about the mean MAP values of the study cohort, especially patients who developed AKI. During CPB surgery, MAP values below the optimal renal autoregulation threshold can lead to ischemic kidney damage [5]. Indeed, in patients with hypertension higher MAP values (>50 and 70 mm Hg) may be required to maintain adequate renal perfusion [6]. As a result, the pathogenesis of AKI during CPB is multifactorial and involves hemodynamic, inflammatory and other mechanisms that interact at cellular level [5]. If we consider with a simple logic, the co-occurrence of anemia and hypotension may have more deleterious effects on kidney function, especially in surgical patients. If so or not, we have to explain causality as a major end point with large prospective studies. Yavuzer Koza, MD Ataturk University Faculty of Medicine Department of Cardiology Yakutiye Erzurum, Turkey 25100 e-mail: [email protected]
References 1. Sickeler R, Phillips-Bute B, Kertai MD, et al. The risk of acute kidney injury with co-occurrence of anemia and hypotension during cardiopulmonary bypass relative to anemia alone. Ann Thorac Surg 2014;97:865–71. 2. Rhee CJ, Kibler KK, Easley RB, et al. Renovascular reactivity measured by near-infrared spectroscopy. J Appl Physiol 2012;113:307–14. 3. Michler RE, Sandhu AA, Young WL, Schwartz AE. Low-flow cardiopulmonary bypass: Importance of blood pressure in maintaining cerebral blood flow. Ann Thorac Surg 1995;60: 525–8. 4. Ono M, Brady K, Easley RB, et al. Duration and magnitude of blood pressure below cerebral autoregulation threshold during cardiopulmonary bypass is associated with major morbidity and operative mortality. J Thorac Cardiovasc Surg 2014;147:483–9. 5. Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 2006;1:19–32. 6. Palmer BF. Renal dysfunction complicating the treatment of hypertension. N Engl J Med 2002;347:1256–61.
MISCELLANEOUS
Reply To the Editor: We appreciate the comments of Dr Koza [1] regarding our retrospective analysis [2], which found no change in acute kidney injury (AKI) rates after aortocoronary bypass surgery with the co-occurrence of hypotension and anemia during cardiopulmonary bypass (CPB) relative to anemia alone. Notably, our findings contrast with the post hoc observations of Haase and
Ann Thorac Surg 2014;98:782–7
colleagues [3] in their smaller study (n ¼ 920 versus 3,963 subjects). Interpreting these observations contributes to the ongoing debate over optimal hematocrit and hemodynamics in the cardiac surgery patient. Our original intent was to reconfirm the findings of Haase and colleagues. Notably, the importance of CPB anemia as an AKI risk factor is established; however, studies have not confirmed CPB hypotension as independently important (as long as flow is preserved) [4]. The co-occurrence of these two factors has only been specifically addressed in the two abovementioned papers; we propose that no relationship exists and that the post hoc observations of Haase and colleagues likely reflect a spurious finding. As acknowledged by these authors, type I (false-positive) error is common, and post hoc findings are always deserving of revalidation in a different dataset, particularly when multiple secondary analyses are performed. With regard to Dr Koza’s comments on the effect on renal artery blood flow of myogenic autoregulatory reflexes, we highlight that these are not influenced primarily by the need for oxygen delivery but serve to regulate diversion of systemic blood for renal filtration, while at higher pressures “protecting” the glomeruli from damage by limiting blood flow [5, 6]. Such myogenic reflexes respond to different stimuli than those influencing the tubuloglomerular feedback reflexes that match oxygen supply and demand in the medullary microcirculation within the renal parenchyma, which are poorly understood. In summary, despite employing a much larger sample, rather than confirming the previous study findings, our contradictory analyses lend support to the possibility that Haase and colleagues’ post hoc finding was spurious and suggest that changing current practice based on such findings would be premature. Robert Sickeler, BS Mark Stafford-Smith, MD Department of Anesthesiology Duke University Medical Center Box 3094 DUMC Durham, NC 27710 e-mail: [email protected]
References 1. Koza Y. Acute kidney injury and cardiopulmonary bypass surgery (letter). Ann Thorac Surg 2014;98:783–4. 2. Sickeler R, Phillips-Bute B, Kertai MD, et al. The risk of acute kidney injury with co-occurrence of anemia and hypotension during cardiopulmonary bypass relative to anemia alone. Ann Thorac Surg 2014;97:865–71. 3. Haase M, Bellomo R, Story D, et al. Effect of mean arterial pressure, haemoglobin and blood transfusion during cardiopulmonary bypass on post-operative acute kidney injury. Nephrol Dial Transplant 2012;27:153–60. 4. Stafford-Smith M, Newman MF. What effects do hemodilution and blood transfusion during cardiopulmonary bypass have on renal outcomes? Nat Clin Pract Nephrol 2006;2:188–9. 5. Loutzenhiser R, Griffin K, Williamson G, Bidani A. Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. Am J Physiol Regul Integr Comp Physiol 2006;290: R1153–67. 6. Arendshorst WJ, Br€annstr€ om K, Ruan X. Actions of angiotensin II on the renal microvasculature. J Am Soc Nephrol 1999;(10 Suppl 11):S149–61.
