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Implicating Transfusions in Infections After Cardiac Operations
CORRESPONDENCE
Implicating Transfusions in Infections After Cardiac Operations To the Editor: The article by Dr Horvath and colleagues [1] describes a doserelated association between red blood cell (RBC) transfusion and the hazard of incident infection. The primary study outcome combined a broad group of infections, which may differ substantially by cause. Although the authors acknowledge that their study design did not permit causal inference, we are concerned that factors associated with blood transfusion, independently affecting the risk of infection, have not been considered. For example, the authors note that the relationship between transfusion and infection is especially strong among the patients in whom pneumonia developed, which accounted for over 40% of infections. It is well known that extended ventilator exposure is associated with incident pneumonia [2] and that units of blood transfused are associated with prolonged ventilation [3]; however, the relationship between volume of blood transfused and duration of ventilation is not reported. Blood transfusions may not independently predict incident pneumonia, as is suggested by the authors’ regression model; instead, blood transfusion may be correlated with prolonged ventilation, an independent predictor of pneumonia not included in the authors’ analysis. Furthermore, the presence of chronic obstructive pulmonary disease (COPD) is associated with the hazard of incident infection in the authors’ proportional hazard model; yet, the prevalence of COPD is not described across RBC exposure groups. As presented, the relationship between COPD, which may be associated with both extended ventilation and blood transfusion, and infection cannot be assessed. We encourage the authors to reexamine their outcomes, accounting for possible interactions between infections and factors such as COPD [4] and ventilator time. Blood transfusions may represent a potentially modifiable risk factor for some, but not all, of the infection types reported in this study. Further work is needed to examine causality. Until that time, withholding RBC transfusion to prevent infection may expose some patients to potentially harmful anemia with no proven reduction in infection risk. Rika Ohkuma, MD Eric B. Schneider, PhD Glenn J. R. Whitman, MD Department of Surgery The Johns Hopkins University School of Medicine 1800 Orleans St Baltimore, MD 21287 e-mail: [email protected]
Reply To the Editor: We thank Drs Ohkuma, Schneider, and Whitman for their interest [1] in our article about blood transfusion and infection after cardiac surgery [2]. We are aware that red blood cell transfusion is not only associated in a dose-related manner with infection but also with a number of other adverse events after cardiac surgery, such as risk-adjusted pulmonary complications including respiratory distress, respiratory failure, longer intubation time, adult respiratory distress syndrome, and reintervention [3], as well as renal failure, cardiac complications, and neurologic events [4]. This latter paper also demonstrates an unanticipated doserelated decrement in risk-adjusted late survival. We agree that the mechanism by which the association of transfusion with infection is not known, although certain features of possible mechanisms can be shown in laboratory models. Moreover, we recognize that infection is not the only adverse event associated with transfusion, and that these other adverse events may themselves be associated with infection. We also know from our data that transfusion is not the only risk factor for infection, and we are in the process of publishing these findings. Our findings indicate that these other factors do not supplant transfusion as a risk factor for postoperative infection. As such, we disagree with the word of caution with which you conclude. These other associations with infection do not negate in any way the ever mounting evidence that blood transfusion is associated with morbidity and mortality after cardiac surgery, and suggest that a slightly reduced blood count may be less of a risk to many patients than transfusion [5, 6]. Eugene Blackstone, MD Cleveland Clinic Foundation Cleveland, OH Keith Horvath, MD National Institutes of Health/National Heart, Lung, and Blood Institute Bethesda, MD Alan Moskowitz, MD Health Evidence and Policy Icahn School of Medicine at Mount Sinai 1 Gustave L Levy Pl Box 1077 New York, NY 10029 e-mail: [email protected]
References References
MISCELLANEOUS
1. Horvath KA, Acker MA, Chang H, et al. Blood transfusion and infection after cardiac surgery. Ann Thorac Surg 2013;95: 2194–201. 2. Hortal J, Giannella M, Perez MJ, et al. Incidence and risk factors for ventilator associated pneumonia after major heart surgery. Intensive Care Med 2009;35:1518–25. 3. Cislaghi F, Condemi AM, Corona A. Predictors of prolonged mechanical ventilation in a cohort of 3269 CABG patients. Minerva Anestesiol 2007;73:615–21. 4. Gupta H, Ramanan B, Gupta PK, et al. Impact of COPD on postoperative outcomes: results from a national database. Chest 2013;143:1599–606. Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
1. Ohkuma R, Schneider EB, Whitman GJR. Implicating transfusions in infections after cardiac operations (letter). Ann Thorac Surg 2014;97:1852. 2. Horvath KA, Acker MA, Chang H, et al. Blood transfusion and infection after cardiac surgery. Ann Thorac Surg 2013;95: 2194–201. 3. Koch C, Li L, Figueroa P, Mihaljevic T, Svensson L, Blackstone EH. Transfusion and pulmonary morbidity after cardiac surgery. Ann Thorac Surg 2009;88: 1410–8. 4. Koch CG, Li L, Duncan AI, et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006;34:1608–16. Ann Thorac Surg 2014;97:1852–7 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.02.015
Implicating Transfusions in Infections After Cardiac Operations To the Editor: The article by Dr Horvath and colleagues [1] describes a doserelated association between red blood cell (RBC) transfusion and the hazard of incident infection. The primary study outcome combined a broad group of infections, which may differ substantially by cause. Although the authors acknowledge that their study design did not permit causal inference, we are concerned that factors associated with blood transfusion, independently affecting the risk of infection, have not been considered. For example, the authors note that the relationship between transfusion and infection is especially strong among the patients in whom pneumonia developed, which accounted for over 40% of infections. It is well known that extended ventilator exposure is associated with incident pneumonia [2] and that units of blood transfused are associated with prolonged ventilation [3]; however, the relationship between volume of blood transfused and duration of ventilation is not reported. Blood transfusions may not independently predict incident pneumonia, as is suggested by the authors’ regression model; instead, blood transfusion may be correlated with prolonged ventilation, an independent predictor of pneumonia not included in the authors’ analysis. Furthermore, the presence of chronic obstructive pulmonary disease (COPD) is associated with the hazard of incident infection in the authors’ proportional hazard model; yet, the prevalence of COPD is not described across RBC exposure groups. As presented, the relationship between COPD, which may be associated with both extended ventilation and blood transfusion, and infection cannot be assessed. We encourage the authors to reexamine their outcomes, accounting for possible interactions between infections and factors such as COPD [4] and ventilator time. Blood transfusions may represent a potentially modifiable risk factor for some, but not all, of the infection types reported in this study. Further work is needed to examine causality. Until that time, withholding RBC transfusion to prevent infection may expose some patients to potentially harmful anemia with no proven reduction in infection risk. Rika Ohkuma, MD Eric B. Schneider, PhD Glenn J. R. Whitman, MD Department of Surgery The Johns Hopkins University School of Medicine 1800 Orleans St Baltimore, MD 21287 e-mail: [email protected]
Reply To the Editor: We thank Drs Ohkuma, Schneider, and Whitman for their interest [1] in our article about blood transfusion and infection after cardiac surgery [2]. We are aware that red blood cell transfusion is not only associated in a dose-related manner with infection but also with a number of other adverse events after cardiac surgery, such as risk-adjusted pulmonary complications including respiratory distress, respiratory failure, longer intubation time, adult respiratory distress syndrome, and reintervention [3], as well as renal failure, cardiac complications, and neurologic events [4]. This latter paper also demonstrates an unanticipated doserelated decrement in risk-adjusted late survival. We agree that the mechanism by which the association of transfusion with infection is not known, although certain features of possible mechanisms can be shown in laboratory models. Moreover, we recognize that infection is not the only adverse event associated with transfusion, and that these other adverse events may themselves be associated with infection. We also know from our data that transfusion is not the only risk factor for infection, and we are in the process of publishing these findings. Our findings indicate that these other factors do not supplant transfusion as a risk factor for postoperative infection. As such, we disagree with the word of caution with which you conclude. These other associations with infection do not negate in any way the ever mounting evidence that blood transfusion is associated with morbidity and mortality after cardiac surgery, and suggest that a slightly reduced blood count may be less of a risk to many patients than transfusion [5, 6]. Eugene Blackstone, MD Cleveland Clinic Foundation Cleveland, OH Keith Horvath, MD National Institutes of Health/National Heart, Lung, and Blood Institute Bethesda, MD Alan Moskowitz, MD Health Evidence and Policy Icahn School of Medicine at Mount Sinai 1 Gustave L Levy Pl Box 1077 New York, NY 10029 e-mail: [email protected]
References References
MISCELLANEOUS
1. Horvath KA, Acker MA, Chang H, et al. Blood transfusion and infection after cardiac surgery. Ann Thorac Surg 2013;95: 2194–201. 2. Hortal J, Giannella M, Perez MJ, et al. Incidence and risk factors for ventilator associated pneumonia after major heart surgery. Intensive Care Med 2009;35:1518–25. 3. Cislaghi F, Condemi AM, Corona A. Predictors of prolonged mechanical ventilation in a cohort of 3269 CABG patients. Minerva Anestesiol 2007;73:615–21. 4. Gupta H, Ramanan B, Gupta PK, et al. Impact of COPD on postoperative outcomes: results from a national database. Chest 2013;143:1599–606. Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
1. Ohkuma R, Schneider EB, Whitman GJR. Implicating transfusions in infections after cardiac operations (letter). Ann Thorac Surg 2014;97:1852. 2. Horvath KA, Acker MA, Chang H, et al. Blood transfusion and infection after cardiac surgery. Ann Thorac Surg 2013;95: 2194–201. 3. Koch C, Li L, Figueroa P, Mihaljevic T, Svensson L, Blackstone EH. Transfusion and pulmonary morbidity after cardiac surgery. Ann Thorac Surg 2009;88: 1410–8. 4. Koch CG, Li L, Duncan AI, et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Crit Care Med 2006;34:1608–16. Ann Thorac Surg 2014;97:1852–7 0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2014.02.015