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Age of transfused blood is an independent risk factor for postinjury multiple organ failure
Age of Transfused Blood Is an Independent Risk Factor for Postinjury Multiple Organ Failure Garret Zallen, MD, Patrick J. Offner, MD, MPH, Ernest E. Moore, MD, John Blackwell, MD, David J. Ciesla, MD, Julie Gabriel, BA, Chris Denny, BA, Christopher C. Silliman, MD, PhD, Denver, Colorado
BACKGROUND: Blood transfusion has repeatedly been demonstrated to be an independent risk factor for postinjury multiple organ failure (MOF). Previously believed to represent a surrogate for shock, packed red blood cell (PRBC) transfusion has recently been shown to result in neutrophil priming and pulmonary endothelial cell activation. We have previously observed that the generation of inflammatory mediators is related to the length of PRBC unit storage. The purpose of this study was to determine if age of transfused PRBC is a risk factor for the development of postinjury MOF. METHODS: Using our prospective database of trauma patients at risk for developing MOF, we identified patients who developed MOF (MOFⴙ) and received 6 to 20 units of PRBCs in the first 12 hours following injury. A similar cohort of patients, matched for ISS and transfusion requirement, who did not develop MOF (MOFⴚ) were also identified. The age of each unit of PRBC transfused in the first 6 hours was determined. Multiple logistic regression was performed to determine if age of transfused blood is an independent risk factor. RESULTS: Sixty-three patients were identified, 23 of whom were MOFⴙ. There was no difference in ISS and transfusion requirement between MOFⴙ and MOFⴚ groups. MOFⴙ patients, however, were significantly older (46 ⴞ 4.7 years versus 33 ⴞ 2.3 years). Moreover, mean age of transfused blood was greater in the MOFⴙ patients (30.5 ⴞ 1.6 days versus 24 ⴞ 0.5 days). Similarly, the mean number of units older than 14 and 21 days old were greater in the MOFⴙ patients. Multivariate analysis identified mean age of
From the Department of Surgery (GZ, PJO, EEM, JB, DJC, JG), Denver Health Medical Center, University of Colorado Health Sciences Center, and the Bonfils Blood Center (CD, CCS), Denver, Colorado. Requests for reprints should be addressed to Patrick J. Offner, MD, MPH, Department of Surgery, MC 0206, Denver Health Medical Center, 777 Bannock Street, Denver, Colorado 80204. Presented at the 51st Annual Meeting of the Southwestern Surgical Congress, Coronado, California, April 18 –21, 1999.
570
© 1999 by Excerpta Medica, Inc. All rights reserved.
blood, number of units older than 14 days, and number of units older than 21 days as independent risk factors for MOF. CONCLUSION: The age of transfused PRBCs transfused in the first 6 hours is an independent risk factor for postinjury MOF. This suggests that current blood bank processing and storage technique should be reexamined. Moreover, fresh blood may be more appropriate for the initial resuscitation of trauma patients requiring transfusion. Am J Surg. 1999;178:570 –572. © 1999 by Excerpta Medica, Inc.
B
lood transfusion has consistently been shown to be a major risk factor for postinjury multiple organ failure (MOF).1 Initially, transfusion requirement was felt to be a surrogate for injury severity, but multiple studies have demonstrated it to be a robust and independent predictor of postinjury MOF.2,3 We have found that the number of packed red blood cell (PRBC) units transfused within 12 hours postinjury can predict adverse outcomes. Current blood banking practices typically fractionate donated blood into PRBCs, fresh frozen plasma (FFP), and cryoprecipitate. The unit of PRBCs contains platelets, white blood cells (WBCs), and plasma. The life span of the platelets and WBC are short, but the units are kept for up to 42 days. When the WBCs die, they release cytotoxic enzymes that can act on fragmented RBC membranes and produce proinflammatory mediators. Plasma obtained from stored PRBCs not only primes neutrophils (PMNs) for enhanced cytotoxicity, but also activates endothelial cells for increased expression of intercellular adhesion molecule-1 (ICAM-1).4 ICAM-1 is the endothelial ligand responsible for PMN adhesion and transmigration.5 The proinflammatory agents responsible for the PMN priming and endothelial activation become significant after 14 days of storage.4 To further characterize the inflammatory potential of old stored blood, we demonstrated that lipids from day 42 PRBC plasma cause acute lung injury in isolated lung models.6 Of note, the policy of most blood banks is to transfuse their oldest units of blood first to avoid losing units to outdate. The purpose of this study was to examine the physiologic effects of the age of stored PRBCs in trauma patients. We hypothesized that the age of the PRBC units is an independent risk factor for the development of MOF in severely injured patients. 0002-9610/99/$–see front matter PII S0002-9610(99)00239-1
AGE OF TRANSFUSED BLOOD A RISK FACTOR FOR MOF/ZALLEN ET AL
MATERIALS AND METHODS
TABLE I
The Colorado Multiple Institutional Review Board approved these studies, and all subjects gave informed consent prior to entry into the study. Patients were eligible for the study if they were aged ⬎17 years, Injury Severity Score (ISS) ⬎15 with at least one extracranial Abbreviated Injury Scale (AIS) ⬎3, evidence of hemorrhagic shock (systolic blood pressure ⬍90 mm Hg), less than 2 hours from their injury, and able to give consent. Age of Blood in Postinjury Patients We maintain a prospective database of trauma patients at risk for developing MOF admitted to our level I trauma center. Patients who developed MOF and received 6 to 20 units of PRBCs in the first 12 hours following injury were identified (n ⫽ 26). A similar cohort of patients, matched for ISS and transfusion requirement, who did not develop MOF were also identified (n ⫽ 42). Using blood bank records, the age of each unit of PRBC transfused in the first 12 hours was determined. MOF Definition MOF was defined using our previously described MOF score.2 In brief, four organs (lungs, kidneys, liver, and heart) were assessed daily for dysfunction and scored from 0 (no dysfunction) to 3 (severe dysfunction). MOF was defined as the sum of the grades simultaneously obtained ⱖ4. Because organ dysfunction scores obtained within the first 48 hours may reflect the primary injury or incomplete resuscitation, MOF was defined only after 48 hours.
Selected Demographic Data Stratified by Multiple Organ Failure (MOF) Status
Age, years Injury Severity Score Transfusion, packed red blood cells
MOF n ⴝ 23
No MOF n ⴝ 40
P Value
46 ⫾ 4.7 29.5 ⫾ 1.6
33 ⫾ 2.3 31.7 ⫾ 1.4
⬍0.05 NS
12.5 ⫾ 1.1
10.6 ⫾ 0.7
NS
NS ⫽ not significant.
Figure 1. The age of transfused blood was analyzed in patients who developed multiple organ failure (MOF⫹) and was compared with patients who did not develop MOF (MOF⫺). The age of transfused blood was significantly older in the MOF⫹ group (P ⬍0.05 compared with MOF⫺).
Statistical Analysis The MOF database is maintained on an IBM-compatible PC using Access 97 (Microsoft Corp, Redmond, Washington). Data were analyzed using SPSS 9.0 for Windows (SPSS Inc., Chicago, Illinois). Chi-square analysis was performed for categorical data. Multiple logistic regression analysis was used to determine if age of transfused blood is an independent risk factor for MOF after controlling for age, base deficit, and serum lactate level. Statistical significance was assigned for P ⬍0.05. Data are shown as mean ⫾ the standard error of the mean.
RESULTS Sixty-three patients were identified, 23 of whom developed MOF (MOF⫹). The mechanism of injury was blunt in 38 patients and penetrating in 25 patients. There was no difference in ISS or transfusion requirement between MOF⫹ patients and patients who did not develop MOF (MOF⫺), but MOF⫹ patients were older (46 ⫾ 4.7 years versus 33 ⫾ 2.3 years, P ⫽ 0.03; Table I). Mean age of transfused blood was significantly greater in the MOF⫹ patients (Figure 1). Similarly, the mean number of units greater than 14 and 21 days old was greater in the MOF⫹ patients (Figure 2). After stratifying by MOF status there was no difference in the age of transfused blood between blunt and penetrating mechanisms. Multivariate analyses identified mean age of blood, number of units older than 14 days, and number of units older than 21 days as independent risk factors for MOF after controlling for patient age, base deficit and serum lactate level (Table II).
Figure 2. Subgroup analysis of the individual units of blood demonstrated that multiple organ failure patients (MOF⫹) received significantly more units of blood ⬎14 days old and ⬎21 days old. *P ⬍0.05 compared with MOF⫺, ⬎14 days. #P ⬍0.05 compared with MOF⫺, ⬎21 days.
COMMENTS Transfusion of blood has been identified to be a robust predictor of postinjury MOF.1,3 Initially, this relationship was felt to reflect a correlation between tissue injury or hemorrhagic shock and blood transfusion requirement. Our subsequent work, however, has shown the number of blood transfusions to be an independent predictor of MOF.3 The recent discovery of the proinflammatory effects of stored blood have provided a possible mechanism for this process. The identification of inflammatory cytokines in stored blood appeared to be a promising target, but the levels of these cytokines are small and of questionable physiologic significance.7 Further investigation by this laboratory has
THE AMERICAN JOURNAL OF SURGERY® VOLUME 178 DECEMBER 1999
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AGE OF TRANSFUSED BLOOD A RISK FACTOR FOR MOF/ZALLEN ET AL
TABLE II Results of Multivariate Analysis of Age of Transfused Blood as a Predictor of Postinjury Multiple Organ Failure Variable Age of blood, days Number of units ⬎14 days old Number of units ⬎21 days old
Odds Ratio
P Value
1.16 (1.02–1.32) 1.16 (1.01–1.34) 1.22 (1.06–1.41)
0.026 0.03 0.006
characterized several lipids in the stored blood that produce lung injury and are associated with transfusion-related lung injury.6,8 The production of these lipids appears to be time dependent with significant biological activity after 14 days of storage. We previously demonstrated that old, but not outdated, PRBC plasma primes PMNs for superoxide production.4 Furthermore, old blood plasma activates endothelial cells in a dose- and age-dependent fashion.9 The concordant activation of both endothelial cells and primed neutrophils is central to the pathogenesis of postinjury MOF.10 Taking this information to the bedside, we performed a multivariate analysis of trauma patients receiving transfusions to examine the effects of the age of stored blood and its concomitant accumulation of proinflammatory mediators on the development of postinjury MOF. We observed that patients who developed MOF received significantly older PRBC units, and furthermore, the age of PRBC units is an independent predictor of MOF. In addition, we have demonstrated that when a similar cohort of patients is transfused with a lipid-free, cytokine-free hemoglobin substitute, the occurrence of MOF is reduced (preliminary data, unpublished). This effect is likely related to an abrogation of transfusion-related PMN priming. Current blood banking standards outdate blood at 42 days. This lifespan is based on the oxygen-binding characteristics of the RBCs. However, PRBC units contain up to 109 WBCs, and the life span of some of these WBCs, most notably the PMNs, is 24 to 72 hours. In normal circulation, these cells undergo apoptosis and are removed by macrophages. In stored units, there is no mechanism for removal of the dead PMNs, and it is likely that they release their lytic enzymes (such as sPLA2) leading to the production of inflammatory mediators. These units are stored at 4°C, which likely slows the enzymatic kinetics, and explains the absence of PMN priming activity until 14 days of storage. Several blood banking techniques may ameliorate this process. Leukoreduction of donor units can remove up to 3 log
572
units of WBCs from the prestorage units. We are currently investigating this technique as a possible mechanism to reduce transfusion-related postinjury MOF. The second option is to wash PRBCs prior to transfusion. We currently use this technique for elective transfusions in at-risk patients at our institution. The time-consuming nature of washing PRBCs and blood bank policy that requires the use of the washed unit within 24 hours of washing, however, makes this option less attractive for massive transfusions in trauma patients. The third option is the transfusion of fresh stored blood. Unfortunately, owing to blood shortages and current blood banking practices, this option is not available at most institutions. Finally, the further development of lipid-free, cytokine-free blood substitutes may obviate the risks associated with traditional PRBC transfusion including disease transmission, immunosuppression and MOF.
REFERENCES 1. Moore FA, Moore EE, Sauaia A. Blood transfusion. An independent risk factor for postinjury multiple organ failure. Arch Surg. 1997;132:620 – 624. 2. Sauaia A, Moore FA, Moore EE, et al. Early predictors of postinjury multiple organ failure. Arch Surg. 1994;129:39 – 45. 3. Sauaia A, Moore FA, Moore EE, et al. Multiple organ failure can be predicted as early as 12 hours after injury. J Trauma. 1998;45: 291–301. 4. Silliman CC, Clay KL, Thurman GW, et al. Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase. J Lab Clin Med. 1994; 124:684 – 694. 5. Liu L, Mul FP, Kuijpers TW, et al. Neutrophil transmigration across monolayers of endothelial cells and airway epithelial cells is regulated by different mechanisms. Ann N Y Acad Sci. 1996;796: 21–29. 6. Silliman CC, Voelkel NF, Allard JD, et al. Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model. J Clin Invest. 1998;101:1458 –1467. 7. Kristiansson M, Soop M, Saraste L, Sundqvist KG. Cytokines in stored red blood cell concentrates: promoters of systemic inflammation and simulators of acute transfusion reactions? Acta Anaesthesiol Scand. 1996;40:496 –501. 8. Silliman CC, Paterson AJ, Dickey WO, et al. The association of biologically active lipids with the development of transfusionrelated acute lung injury: a retrospective study. Transfusion. 1997; 37:719 –726. 9. Silliman C, Hiester AA. Plasma from stored red cells activate human pulmonary endothelial cells. Transfusion. 1998;38(suppl): 96S. 10. Moore FA, Moore EE. Evolving concepts in the pathogenesis of postinjury multiple organ failure. Surg Clin North Am. 1995;75: 257–277.
THE AMERICAN JOURNAL OF SURGERY® VOLUME 178 DECEMBER 1999
BACKGROUND: Blood transfusion has repeatedly been demonstrated to be an independent risk factor for postinjury multiple organ failure (MOF). Previously believed to represent a surrogate for shock, packed red blood cell (PRBC) transfusion has recently been shown to result in neutrophil priming and pulmonary endothelial cell activation. We have previously observed that the generation of inflammatory mediators is related to the length of PRBC unit storage. The purpose of this study was to determine if age of transfused PRBC is a risk factor for the development of postinjury MOF. METHODS: Using our prospective database of trauma patients at risk for developing MOF, we identified patients who developed MOF (MOFⴙ) and received 6 to 20 units of PRBCs in the first 12 hours following injury. A similar cohort of patients, matched for ISS and transfusion requirement, who did not develop MOF (MOFⴚ) were also identified. The age of each unit of PRBC transfused in the first 6 hours was determined. Multiple logistic regression was performed to determine if age of transfused blood is an independent risk factor. RESULTS: Sixty-three patients were identified, 23 of whom were MOFⴙ. There was no difference in ISS and transfusion requirement between MOFⴙ and MOFⴚ groups. MOFⴙ patients, however, were significantly older (46 ⴞ 4.7 years versus 33 ⴞ 2.3 years). Moreover, mean age of transfused blood was greater in the MOFⴙ patients (30.5 ⴞ 1.6 days versus 24 ⴞ 0.5 days). Similarly, the mean number of units older than 14 and 21 days old were greater in the MOFⴙ patients. Multivariate analysis identified mean age of
From the Department of Surgery (GZ, PJO, EEM, JB, DJC, JG), Denver Health Medical Center, University of Colorado Health Sciences Center, and the Bonfils Blood Center (CD, CCS), Denver, Colorado. Requests for reprints should be addressed to Patrick J. Offner, MD, MPH, Department of Surgery, MC 0206, Denver Health Medical Center, 777 Bannock Street, Denver, Colorado 80204. Presented at the 51st Annual Meeting of the Southwestern Surgical Congress, Coronado, California, April 18 –21, 1999.
570
© 1999 by Excerpta Medica, Inc. All rights reserved.
blood, number of units older than 14 days, and number of units older than 21 days as independent risk factors for MOF. CONCLUSION: The age of transfused PRBCs transfused in the first 6 hours is an independent risk factor for postinjury MOF. This suggests that current blood bank processing and storage technique should be reexamined. Moreover, fresh blood may be more appropriate for the initial resuscitation of trauma patients requiring transfusion. Am J Surg. 1999;178:570 –572. © 1999 by Excerpta Medica, Inc.
B
lood transfusion has consistently been shown to be a major risk factor for postinjury multiple organ failure (MOF).1 Initially, transfusion requirement was felt to be a surrogate for injury severity, but multiple studies have demonstrated it to be a robust and independent predictor of postinjury MOF.2,3 We have found that the number of packed red blood cell (PRBC) units transfused within 12 hours postinjury can predict adverse outcomes. Current blood banking practices typically fractionate donated blood into PRBCs, fresh frozen plasma (FFP), and cryoprecipitate. The unit of PRBCs contains platelets, white blood cells (WBCs), and plasma. The life span of the platelets and WBC are short, but the units are kept for up to 42 days. When the WBCs die, they release cytotoxic enzymes that can act on fragmented RBC membranes and produce proinflammatory mediators. Plasma obtained from stored PRBCs not only primes neutrophils (PMNs) for enhanced cytotoxicity, but also activates endothelial cells for increased expression of intercellular adhesion molecule-1 (ICAM-1).4 ICAM-1 is the endothelial ligand responsible for PMN adhesion and transmigration.5 The proinflammatory agents responsible for the PMN priming and endothelial activation become significant after 14 days of storage.4 To further characterize the inflammatory potential of old stored blood, we demonstrated that lipids from day 42 PRBC plasma cause acute lung injury in isolated lung models.6 Of note, the policy of most blood banks is to transfuse their oldest units of blood first to avoid losing units to outdate. The purpose of this study was to examine the physiologic effects of the age of stored PRBCs in trauma patients. We hypothesized that the age of the PRBC units is an independent risk factor for the development of MOF in severely injured patients. 0002-9610/99/$–see front matter PII S0002-9610(99)00239-1
AGE OF TRANSFUSED BLOOD A RISK FACTOR FOR MOF/ZALLEN ET AL
MATERIALS AND METHODS
TABLE I
The Colorado Multiple Institutional Review Board approved these studies, and all subjects gave informed consent prior to entry into the study. Patients were eligible for the study if they were aged ⬎17 years, Injury Severity Score (ISS) ⬎15 with at least one extracranial Abbreviated Injury Scale (AIS) ⬎3, evidence of hemorrhagic shock (systolic blood pressure ⬍90 mm Hg), less than 2 hours from their injury, and able to give consent. Age of Blood in Postinjury Patients We maintain a prospective database of trauma patients at risk for developing MOF admitted to our level I trauma center. Patients who developed MOF and received 6 to 20 units of PRBCs in the first 12 hours following injury were identified (n ⫽ 26). A similar cohort of patients, matched for ISS and transfusion requirement, who did not develop MOF were also identified (n ⫽ 42). Using blood bank records, the age of each unit of PRBC transfused in the first 12 hours was determined. MOF Definition MOF was defined using our previously described MOF score.2 In brief, four organs (lungs, kidneys, liver, and heart) were assessed daily for dysfunction and scored from 0 (no dysfunction) to 3 (severe dysfunction). MOF was defined as the sum of the grades simultaneously obtained ⱖ4. Because organ dysfunction scores obtained within the first 48 hours may reflect the primary injury or incomplete resuscitation, MOF was defined only after 48 hours.
Selected Demographic Data Stratified by Multiple Organ Failure (MOF) Status
Age, years Injury Severity Score Transfusion, packed red blood cells
MOF n ⴝ 23
No MOF n ⴝ 40
P Value
46 ⫾ 4.7 29.5 ⫾ 1.6
33 ⫾ 2.3 31.7 ⫾ 1.4
⬍0.05 NS
12.5 ⫾ 1.1
10.6 ⫾ 0.7
NS
NS ⫽ not significant.
Figure 1. The age of transfused blood was analyzed in patients who developed multiple organ failure (MOF⫹) and was compared with patients who did not develop MOF (MOF⫺). The age of transfused blood was significantly older in the MOF⫹ group (P ⬍0.05 compared with MOF⫺).
Statistical Analysis The MOF database is maintained on an IBM-compatible PC using Access 97 (Microsoft Corp, Redmond, Washington). Data were analyzed using SPSS 9.0 for Windows (SPSS Inc., Chicago, Illinois). Chi-square analysis was performed for categorical data. Multiple logistic regression analysis was used to determine if age of transfused blood is an independent risk factor for MOF after controlling for age, base deficit, and serum lactate level. Statistical significance was assigned for P ⬍0.05. Data are shown as mean ⫾ the standard error of the mean.
RESULTS Sixty-three patients were identified, 23 of whom developed MOF (MOF⫹). The mechanism of injury was blunt in 38 patients and penetrating in 25 patients. There was no difference in ISS or transfusion requirement between MOF⫹ patients and patients who did not develop MOF (MOF⫺), but MOF⫹ patients were older (46 ⫾ 4.7 years versus 33 ⫾ 2.3 years, P ⫽ 0.03; Table I). Mean age of transfused blood was significantly greater in the MOF⫹ patients (Figure 1). Similarly, the mean number of units greater than 14 and 21 days old was greater in the MOF⫹ patients (Figure 2). After stratifying by MOF status there was no difference in the age of transfused blood between blunt and penetrating mechanisms. Multivariate analyses identified mean age of blood, number of units older than 14 days, and number of units older than 21 days as independent risk factors for MOF after controlling for patient age, base deficit and serum lactate level (Table II).
Figure 2. Subgroup analysis of the individual units of blood demonstrated that multiple organ failure patients (MOF⫹) received significantly more units of blood ⬎14 days old and ⬎21 days old. *P ⬍0.05 compared with MOF⫺, ⬎14 days. #P ⬍0.05 compared with MOF⫺, ⬎21 days.
COMMENTS Transfusion of blood has been identified to be a robust predictor of postinjury MOF.1,3 Initially, this relationship was felt to reflect a correlation between tissue injury or hemorrhagic shock and blood transfusion requirement. Our subsequent work, however, has shown the number of blood transfusions to be an independent predictor of MOF.3 The recent discovery of the proinflammatory effects of stored blood have provided a possible mechanism for this process. The identification of inflammatory cytokines in stored blood appeared to be a promising target, but the levels of these cytokines are small and of questionable physiologic significance.7 Further investigation by this laboratory has
THE AMERICAN JOURNAL OF SURGERY® VOLUME 178 DECEMBER 1999
571
AGE OF TRANSFUSED BLOOD A RISK FACTOR FOR MOF/ZALLEN ET AL
TABLE II Results of Multivariate Analysis of Age of Transfused Blood as a Predictor of Postinjury Multiple Organ Failure Variable Age of blood, days Number of units ⬎14 days old Number of units ⬎21 days old
Odds Ratio
P Value
1.16 (1.02–1.32) 1.16 (1.01–1.34) 1.22 (1.06–1.41)
0.026 0.03 0.006
characterized several lipids in the stored blood that produce lung injury and are associated with transfusion-related lung injury.6,8 The production of these lipids appears to be time dependent with significant biological activity after 14 days of storage. We previously demonstrated that old, but not outdated, PRBC plasma primes PMNs for superoxide production.4 Furthermore, old blood plasma activates endothelial cells in a dose- and age-dependent fashion.9 The concordant activation of both endothelial cells and primed neutrophils is central to the pathogenesis of postinjury MOF.10 Taking this information to the bedside, we performed a multivariate analysis of trauma patients receiving transfusions to examine the effects of the age of stored blood and its concomitant accumulation of proinflammatory mediators on the development of postinjury MOF. We observed that patients who developed MOF received significantly older PRBC units, and furthermore, the age of PRBC units is an independent predictor of MOF. In addition, we have demonstrated that when a similar cohort of patients is transfused with a lipid-free, cytokine-free hemoglobin substitute, the occurrence of MOF is reduced (preliminary data, unpublished). This effect is likely related to an abrogation of transfusion-related PMN priming. Current blood banking standards outdate blood at 42 days. This lifespan is based on the oxygen-binding characteristics of the RBCs. However, PRBC units contain up to 109 WBCs, and the life span of some of these WBCs, most notably the PMNs, is 24 to 72 hours. In normal circulation, these cells undergo apoptosis and are removed by macrophages. In stored units, there is no mechanism for removal of the dead PMNs, and it is likely that they release their lytic enzymes (such as sPLA2) leading to the production of inflammatory mediators. These units are stored at 4°C, which likely slows the enzymatic kinetics, and explains the absence of PMN priming activity until 14 days of storage. Several blood banking techniques may ameliorate this process. Leukoreduction of donor units can remove up to 3 log
572
units of WBCs from the prestorage units. We are currently investigating this technique as a possible mechanism to reduce transfusion-related postinjury MOF. The second option is to wash PRBCs prior to transfusion. We currently use this technique for elective transfusions in at-risk patients at our institution. The time-consuming nature of washing PRBCs and blood bank policy that requires the use of the washed unit within 24 hours of washing, however, makes this option less attractive for massive transfusions in trauma patients. The third option is the transfusion of fresh stored blood. Unfortunately, owing to blood shortages and current blood banking practices, this option is not available at most institutions. Finally, the further development of lipid-free, cytokine-free blood substitutes may obviate the risks associated with traditional PRBC transfusion including disease transmission, immunosuppression and MOF.
REFERENCES 1. Moore FA, Moore EE, Sauaia A. Blood transfusion. An independent risk factor for postinjury multiple organ failure. Arch Surg. 1997;132:620 – 624. 2. Sauaia A, Moore FA, Moore EE, et al. Early predictors of postinjury multiple organ failure. Arch Surg. 1994;129:39 – 45. 3. Sauaia A, Moore FA, Moore EE, et al. Multiple organ failure can be predicted as early as 12 hours after injury. J Trauma. 1998;45: 291–301. 4. Silliman CC, Clay KL, Thurman GW, et al. Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase. J Lab Clin Med. 1994; 124:684 – 694. 5. Liu L, Mul FP, Kuijpers TW, et al. Neutrophil transmigration across monolayers of endothelial cells and airway epithelial cells is regulated by different mechanisms. Ann N Y Acad Sci. 1996;796: 21–29. 6. Silliman CC, Voelkel NF, Allard JD, et al. Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model. J Clin Invest. 1998;101:1458 –1467. 7. Kristiansson M, Soop M, Saraste L, Sundqvist KG. Cytokines in stored red blood cell concentrates: promoters of systemic inflammation and simulators of acute transfusion reactions? Acta Anaesthesiol Scand. 1996;40:496 –501. 8. Silliman CC, Paterson AJ, Dickey WO, et al. The association of biologically active lipids with the development of transfusionrelated acute lung injury: a retrospective study. Transfusion. 1997; 37:719 –726. 9. Silliman C, Hiester AA. Plasma from stored red cells activate human pulmonary endothelial cells. Transfusion. 1998;38(suppl): 96S. 10. Moore FA, Moore EE. Evolving concepts in the pathogenesis of postinjury multiple organ failure. Surg Clin North Am. 1995;75: 257–277.
THE AMERICAN JOURNAL OF SURGERY® VOLUME 178 DECEMBER 1999