Blood transfusion within the first 24 hours after trauma was also an independent predictor of increased hospital LOS by linear regression analysis (Table 7), confirming that transfused patients had greater than 6 more hospital days than nontransfused patients. The mean hospital length of stay for transfused patients was 14 ± 16 days compared with 3 ± 6 days for those patients who were not transfused.
Anemia (hematocrit < 36%) at the time of admission was associated with increased age, increased injury severity (reflected by increased ISS and lower GCS score), and female gender (Table 8). Patients who were anemic at the time of admission had significantly higher serum lactate levels, more abnormal base deficit and shock index scores, and an increased incidence of SIRS (SIRS score ≥ 2). Anemia was an independent predictor of ICU admission, ICU LOS, and hospital LOS, but was not an independent predictor of mortality.
Blood transfusion is presently a major component of the treatment of acute traumatic hemorrhagic shock. The incorporation of blood transfusion in resuscitation protocols for acute trauma is supported in the Advanced Trauma Life Support guidelines of the American College of Surgeons, 18 which are adhered to in trauma treatment centers worldwide. Recent literature has documented severe immunologic responses to blood transfusion with resultant adverse outcomes.
Fransen et al. studied 114 consecutive cardiac surgery patients to evaluate the systemic inflammatory response and outcome associated with blood transfusion. 4 Blood samples were taken at induction of anesthesia; at the start of aortic cross-clamping; at aortic unclamping; and then at 0.5, 4, 8, and 18 hours thereafter. Bactericidal permeability increasing protein and IL-6 serum concentrations were significantly higher in patients who received intraoperative blood transfusions. Furthermore, serum bactericidal permeability increasing protein levels increased with the number of packed cells transfused. Patients who received blood transfusions were also noted to have worse postoperative clinical outcome.
In vitro studies 8 documented that incubation of normal neutrophils with plasma from blood stored for 21 and 42 days induced a significant increase in production of IL-8, IL-1β, tumor necrosis factor-α, and secretory phospholipase compared with plasma from fresh (day 0) blood. Another recent study examined the effect of blood transfusion on immune cells. 9 Neutrophils from healthy volunteers were incubated with plasma from unmodified, leukoreduced, or saline-washed red blood cell units. They documented that neutrophil apoptosis was delayed by blood stored for 21 and 42 days. Furthermore, poststorage washing with saline, but not prestorage leukoreduction, abrogated this effect. These data confirm that stored blood induces an inflammatory response in normal neutrophils.
Additional studies have suggested that universal leukodepletion of packed red blood cells may be a rational approach to preventing the adverse immunologic and inflammatory response to blood transfusion. 20,21 These studies document the deleterious effects of the highly active leukocyte enzymes, including increased in vitro deterioration of red blood cells during storage. These deleterious effects are preventable by prior leukodepletion of the stored blood. Conflicting data exist, however, and the additional costs of leukodepletion may not uniformly be associated with improved clinical outcomes. 22,23
Recent trauma literature has focused extensively on blood transfusion and adverse outcome in trauma. A 55-month inception cohort study evaluating 513 consecutive trauma patients (ISS > 15, survival greater than 48 hours) admitted to the ICU of a Level I trauma center demonstrated a dose-response relationship between blood transfusion and the development of MOF. 16 This effect was present independent of the other indices of shock that were examined. Further evaluation of this finding documented that the age of packed red blood cells transfused within the first 6 hours after trauma, the number of units older than 14 days, and the number of units older than 21 days were independent risk factors for MOF by multiple logistic analysis in trauma patients. 24
Purdy et al. also reported a correlation of mortality with the age of blood transfused in patients admitted to the ICU with a diagnosis of severe sepsis. 25 The median age of blood transfused to survivors was 17 days versus 25 days for nonsurvivors (p < 0.0001). A negative correlation was found between increasing age of blood transfused and survival (r = −0.73). We were unable to evaluate the age of blood as an independent risk factor in this current study, because this information is not currently collected routinely during trauma resuscitation and is not included in our trauma registry information. All future studies investigating blood transfusion and outcome after trauma should therefore include age of blood in the analysis.
Blood transfusion has also been associated with increased risk for bacterial infection in recent studies. A retrospective cohort study of 9,598 consecutive hip fracture patients who underwent surgical repair evaluated the effect of allogeneic blood transfusion on infectious outcomes. 13 Blood transfusion was associated with a 1.35-fold increased risk for bacterial infection and a 1.52-fold increased risk for pneumonia. A dose-response relationship for blood and serious bacterial infection (p = 0.001) and pneumonia (p = 0.001) was established. These investigators concluded that bacterial infection may be the most common life-threatening adverse effect of allogeneic blood transfusion.
Allogeneic blood transfusion was confirmed as an independent predictor for postoperative bacterial infection by multiple logistic regression (p = 0.007) in a prospective analysis of 1,349 patients who underwent colorectal surgery in 11 centers across Canada. 26 There was a higher frequency of wound infections and intra-abdominal sepsis in the 282 patients who had received blood transfusions (25.9 vs. 14.2%, p = 0.001), and a significant dose-response relationship between transfusion and infection was demonstrated. The mortality rate was significantly higher in the transfused group as well.
Most recently, Taylor et al. studied 1,717 patients admitted to a medical-surgical ICU to compare the rates of nosocomial infection between transfused (n = 416) and nontransfused (n = 1,301) patients. 14 Patients were stratified for severity of illness using Mortality Probability Model scores at admission, age, and gender. Nosocomial infection occurred in 5.94% of the entire cohort, but the transfused group had a significantly higher rate (sixfold increase) of nosocomial infection (15.38% vs. 2.92%, p < 0.05). Furthermore, a dose-response relationship between the number of units of red blood cells transfused and risk for nosocomial infection was identified. For each unit of blood administered, the odds of infection were increased by a factor of 1.5 (p < 0.0001). The transfusion group also had a significantly higher mortality rate (24.0% vs. 10.2%, p < 0.05).
Claridge and colleagues examined the relationship between infections in trauma patients and the transfusion of packed red blood cells within the first 48 hours of admission. 15 The overall blood transfusion rate in 1,593 trauma patients was 19.4%, ranging from 0 to 46 units. The infection rate in patients who received at least one blood transfusion was significantly higher (p < 0.0001) at 33.0% versus 7.6% in patients receiving no blood transfusion. This study confirmed a clear dose-dependent correlation between blood transfusion and the development of infection in trauma patients. Multivariate analysis further demonstrated that blood transfusion was an independent risk factor for infection.
We postulate that the increased mortality and ICU resource use identified in transfused trauma patients in this study may, in part, be related to an increased risk for nosocomial infection, but these data were not available for this current study. Future studies that investigate increased mortality and morbidity associated with blood transfusion in trauma should aim to assess this important variable.
The association between blood transfusion and risk for SIRS and worse outcome in trauma patients (n = 9,569) was the focus of a previous study at our institution. 17 Blood transfusion was found to be an independent predictor of mortality, ICU admission, and ICU LOS by logistic regression, with age, ISS, gender, and GCS score held constant. As in the present study, transfused patients were significantly older, had higher ISS, and had lower GCS scores. Patients who received blood transfusions had a 3- to 5-fold increased risk for SIRS, a 10-fold increased risk for mortality, a greater than 3-fold increased risk for ICU admission, and a 6-fold increase in mean ICU LOS. This previous study did not control for indices of shock such as abnormal physiology (represented in this study as shock index [HR/SBP], shown to be more predictive of shock than either HR or SBP alone), base deficit, elevated serum lactate, and anemia, all of which are potential confounding variables.
In the study presented in this article, we sought to validate these previous findings in a larger cohort of trauma patients (n = 15,534) and expanded the analysis to control for race and indices of shock as covariates. This current study confirmed that blood transfusion was a strong independent predictor of SIRS, mortality, ICU admission, ICU LOS, and hospital LOS by multiple logistic and linear regression. Anemia was also examined as an independent outcome variable, and was identified as an independent predictor of ICU admission, ICU LOS, and hospital LOS, but not mortality. Anemic trauma patients were older, had higher ISS, and had lower GCS score, and a higher proportion of anemic patients were female patients. The recognition that anemia, in this study defined as a hematocrit of 36% or hemoglobin concentration < 12 g/dL, was an independent predictor of worse outcome after trauma could lend support to the concept that correction of anemia should be initiated at admission in the acute trauma setting. The question that remains, however, is what hematocrit should be used as the transfusion trigger in the treatment of acute trauma victims, or whether blood transfusion should be reserved only for physiologic indications. A transfusion trigger was not used in the present study but should be considered for future study in trauma when the clinical scenario permits time for hemoglobin measurement.
A randomized, controlled, clinical trial in 25 ICUs (n = 838) randomized patients to a transfusion hemoglobin trigger of 7 g/dL (restrictive strategy) or 10 g/dL (liberal strategy 27). A 54% reduction was achieved in the restrictive group (2.5 vs. 5.6 units of blood). Furthermore, no blood transfusions were required in 33% of the restrictive group. No significant differences in mortality were identified, and organ failure was significantly reduced in the restrictive group. Subgroup analyses favored the restrictive blood transfusion strategy, with a significant decrease in 30-day mortality in patients younger than 55 years (6% vs. 13%, p = 0.02) and less severely ill patients (9% vs. 16%, p = 0.02). This study confirmed that critically ill patients can safely tolerate a lower hemoglobin concentration, and that blood transfusions to achieve a higher transfusion hemoglobin trigger may be associated with worse outcome.
The results of the present study would suggest that although anemia at admission in the acute trauma setting is associated with adverse outcome, blood transfusion for treatment of the anemia may not be the ideal resuscitative fluid with which to correct the deficit in hemoglobin. The hemoglobin concentration used to define anemia in this study is well above the levels defined as the recommended transfusion trigger in most current critical care studies, yet it is clear that this level of anemia at admission after trauma in this study was significantly associated with worse outcome.
Higher hemoglobin levels may indeed be more desirable in the acute trauma scenario for the treatment of hemorrhagic shock, but transfusion of stored blood may not be the best resuscitative fluid for achieving that goal. This finding may support the use of blood or hemoglobin substitutes or other oxygen-carrying fluids such as perfluorocarbons in this clinical scenario.
Initial investigations regarding the utility of human polymerized hemoglobin have been promising. The initial phase II clinical trial (n = 39) using Polyheme (Northfield Labs, Evanston, IL) documented no safety issues related to the use in trauma patients requiring emergent transfusion. 28 The first randomized trial of Polyheme in trauma (mean ISS, 21 ± 10) and emergent surgery documented that Polyheme was safe in acute blood loss, maintained total hemoglobin in lieu of blood despite the marked decrease in red blood cell hemoglobin, and reduced the use of allogeneic blood. 29 Resuscitation with this blood substitute has also been documented to abrogate pathologic postinjury neutrophil cytotoxicity in a recent small study. 30 Injured patients requiring urgent transfusion were given either Polyheme or packed red blood cells, and neutrophils were harvested from peripheral blood. Neutrophils from the patients resuscitated with blood showed increased priming as measured by beta-2 integrin expression, superoxide, and elastase release. In contrast, no such priming was evident with patients resuscitated with the blood substitute Polyheme. 29
In addition, phase III trials with polymerized bovine hemoglobin (hemoglobin-based oxygen carrier; HBOC-201, Biopure, Cambridge, MA) are completed, documenting that infusion of HBOC-201 can avoid or reduce allogeneic blood transfusion needs in specific perioperative settings. 31,32 Recent investigations have documented that hemoglobin-based oxygen carriers are not only simple erythrocyte transfusion substitutes but are highly effective in improving tissue oxygenation. 33 Other studies suggest that leukoreduction of blood (either prestorage at the time of donation or poststorage at the time of administration) or poststorage saline washing of blood may be potential methods for abrogating the adverse effects of blood transfusion.
This current study clearly documents that transfusion of blood in the first 24 hours after injury is associated with worse outcome in trauma after stratification for other factors that affect outcome, including age, gender, race, GCS score, and ISS, and admission shock variables (including admission base deficit, serum lactate, and shock index [HR/SBP]). Two possible explanations of this finding are plausible: blood transfusion increases the trauma patient’s risk of adverse outcome, or trauma patients who require blood transfusion have increased severity of illness that is not reflected in the static measures used in this study, and blood transfusion is simply a marker of increased severity of illness that has been inadequately quantified. Future studies that attempt to further investigate this association between blood transfusions and adverse outcome in trauma should include serial measurements of shock severity, which were not available for analysis in this study.
The results of this current study, and others, urge us to perform future prospective, randomized, clinical trials to investigate modifications (such as leukocyte reduction, saline washing) of blood transfusion and alternatives to blood transfusion in trauma. Furthermore, the development of transfusion protocols based on physiologic indications, to minimize overtransfusion of blood products, should be considered in trauma resuscitation. Future research should be actively engaged in the search for safe, efficacious alternatives to blood transfusion and modification of transfusion practices in the acute treatment and resuscitation of trauma patients.
Dr. Erik S. Barquist (Miami, Florida): In the past 15 years, several critical changes in the management of trauma patients have taken place. These changes include, but of course are not limited to, damage control, open abdomens, much shorter courses of antibiotic therapy, and use of cell scavenging and fewer blood transfusions.
In fact, in the past 6 years, we have reduced red blood cell use in my home trauma center, mostly by changing our transfusion trigger in the ICU, by nearly 50% with no adverse effect on outcomes. This article by Malone et al. suggests that we should be similarly cautious about transfusing our acute trauma patients in the resuscitation bay.
This article used trauma registry data to assess the impact of blood transfusion on mortality in ICU length of stay. It is a well-performed registry study including over 15,000 patients and three years of data.
The data are taken from a previously established trauma registry database. The article is well written and easy to follow. There are many tables that make the data easy to digest. The discussion covers the pertinent articles and the references are complete. Statistical methods included control for covariables such as hypotension, lactate, and base deficit.
The authors tell us that the transfusion patients were older, had a higher ISS and a lower GCS score, and were more likely to have had penetrating trauma and higher SIRS scores. They also had lower admission hematocrits, higher lactates, and more negative base deficits. Risk factors for a transfusion included increasing age, increasing ISS, increased lactate base deficit, shock index, and decreasing GCS score.
Surprisingly, the greatest risk factor was so-called admission anemia, or hematocrit of greater than 36%. Similarly surprising was that female patients seemed to have a lower hematocrit at admission after relatively short transport times than male patients.
The authors report that there was a 22% death rate in those who were transfused early and only a 2.2% death rate in those who were not transfused. Although the authors don’t report the numbers in this fashion, the data aren’t available in the article to determine that of those that died in the ICU after 24 hours, which would presumably exclude those with massive head injury or exsanguination, there was a 14% death rate in those transfused early versus a 9% death rate in those who were not transfused in the first 24 hours. Those are more impressive data.
After stratification for every variable, including shock index, blood pressure, lactate, and base deficit, a statistically significant difference remains. The authors conclude that early blood transfusion is associated in this patient data set with higher mortality and longer lengths of stay.
However, because this is a class II data set, that is, use of a prospectively gathered but retrospectively analyzed trauma data registry, causation remains unclear. Put another way, we know that early blood transfusion in the trauma patient is associated with increased mortality, but we can’t be certain that it was the transfusion that caused the increased mortality.
Transfusion may be a marker for other diseases. A few comments: the extensive tables that accompany the article allow the reader to follow the analysis and conclusions; however, some of the entries are confusing and could be better clarified.
Second, the Materials and Methods section does not clearly state that this is a trauma registry study, and it should. Third, it would be interesting to look at those who died after more than 72 hours in the ICU because, once again, this would eliminate those patients who are destined to die no matter what we do to try and prevent that event from happening. Other than these minor points, however, this is a solid and well-written article, which I enjoyed reading.
Some questions for the authors: did the excess mortality in the early transfusion group occur because of multiple organ disfunction or because of overwhelming infection? Either of these results could be supported by the experimental in vitro data that you listed, supplied by your colleagues at the University of Colorado and other laboratories.
Why were so many patients anemic on presentation to the trauma center? Your trauma center is located in a relatively small state with one of the best prehospital systems in the country. Is this anemia assigned to prolong transporting some patients in hemodilution with crystalloid? Is it a marker of previous disease causing previously existing anemias, or is it perhaps that some sort of patient-aggressive transcapillary refill is a marker of bad disease?
Should transfusion be used if the patient can be volume-resuscitated with other fluids such as crystalloid? How anemic should we allow our acute trauma patients to become before we should worry about them dying from cellular hypoxia rather than in the late stage from multiple organ dysfunction syndrome?
Can you separate out those who are autotransfused using a cell scavenging technology from those who received allogeneic blood transfusion? Does this attenuate the survival disadvantage of transfusion as it has been shown to do in elective surgery?
Finally, have you changed your practice in your busy trauma environment? Do you allow “more anemia” and transfuse for lower hematocrits? Once again, thank you very much. I enjoyed reading the article very much.
Dr. James G. Tyburski (Detroit, Michigan): I want to congratulate Dr. Malone and the group at Maryland for a nice study. I have two questions. Basically, you talk a lot about how the blood would infect the immunologic system in your opening, but you really didn’t talk about infection rate.
Can you break that down a little bit more? Nothing better than infection will increase the length of stay, both in the hospital and in the ICU.
Also, was there any difference in the massive transfusion patients in penetrating trauma? That is, penetrating trauma, again, and the infection rates if there were hollow viscus injuries that could easily influence the lengths of stay. Thank you.
Dr. Carl J. Hauser (Newark, New Jersey): It’s said that there are lies, goddamn lies, and statistics. I would like to suggest that an alternative explanation for the data seen here is that our measurements of shock, things such as shock index, lactate, and base deficit, are just so poor that they don’t really predict the need for transfusion and resuscitation in these patients well.
This is a difficult problem, and I think that we have to be very, very cautious here. I would be very cautious about suggesting withholding transfusions from patients on the basis of the hypothetic danger of inflammation and SIRS associated with old units of blood.
It’s true. It works in the laboratory. It works on neutrophils, but we see a lot of patients here in whom the ongoing resuscitation with blood is necessary. There’s no question about it. If we don’t do it, they won’t live to see SIRS and MOF, so this needs to be looked at with great caution.
Dr. Bill Bromberg (Allentown, Pennsylvania): I had a question about the shock index and the fact that that was a measurement at one point in time. I was wondering whether it’s possible to actually see whether there was more shock over a longer period of time in those people that required transfusion rather than that one point in time. I was wondering whether they looked at that, because if people had ongoing bleeding, obviously, they were going to get transfused.
Dr. Debra L. Malone (closing): Thank you, Dr. Barquist, for your comments and your questions. You wondered, as a few of you other physicians did, what our excess mortality was attributable to.
We, too, wondered that and we have since collected data in that regard. We just have not analyzed that yet statistically, but we are looking at complications, for example, such as infection and now and then how infection may impact on the outcome of mortality.
I don’t know why we have so many anemic patients at shock trauma. I wonder, in part, whether it’s because of the way the main system triages patients and that shock trauma tends to get a greater percentage of sicker patients.
How anemic would I let my patient get before I would transfuse, and would I withhold blood transfusion? No. As of this day, right now, if I had a patient who was hemodynamically unstable because of hemorrhagic shock, I would be the first one in the trauma bay to hang the blood.
However, I would also do that recognizing that I might pay a price down the road. We did look at the number of units that were matched versus unmatched, autotransfused, and so forth.
We have some interesting preliminary data, but before reporting those data we want to perform further analyses. For example, we’re working very closely now with our blood bank, because we would like to know how many of our trauma patients may have received leukodepleted blood and how this may have had an impact on outcome as well.
Dr. Barquist did talk about trauma registry data. Yes, indeed, this is a trauma registry database study. We are in the process of validating our blood transfusion information from the trauma registry with our blood bank.
When I have that information, I will be very quick to pass that along. I cannot tell you statistically what the difference was regarding mechanism of injury in the patients that received massive transfusion. We did not actually break that down. We just saw that those who did receive massive transfusion had worse outcome.
Yes, I think that the measurements of shock are potentially problematic. I think they are limited in their ability at this point in time to assess severity of shock.
I do believe that we need to repeat studies like this and perform other studies so that we can better identify indices that might better clarify patients who are in shock. The shock index is a simple, easily performed, rapidly available tool. It’s a physiologic measure that we find correlates very nicely with the other known indices of shock available to us today.
We have a very busy trauma center, essentially 48 critical care bays that are always full to the brim, and we are always looking for ways to use our resources better. That is why we study shock index, and we hope that with further studies we might be able to quantify its validity as a measurement of shock. Thank you, again, for the opportunity to present this work.
1. Dzik S, Blajchman MA, Blumberg N, et al. Current research on the immunomodulatory effect of allogeneic blood transfusion
. Vox Sang. 1996; 70: 187–194.
2. Innerhofer P, Luz G, Spotl L, et al. Immunologic changes after transfusion of buffy coat-poor versus white cell-reduced blood to patients undergoing arthroplasty. Transfusion. 1999; 39: 1089–1096.
3. Bengtsson A, Avall A, Hyllner M, Bengtson JP. Formation of compliment split products and proinflammatory cytokines by reinfusion of shed autologous blood. Toxicol Lett. 1998; 100–101:129–133.
4. Fransen E, Maessen J, Senden N, et al. Impact of blood transfusions on inflammatory mediator release in patients undergoing cardiac surgery. Chest. 1999; 116: 1233–1239.
5. Avall A, Hyllner M, Bengston JP, et al. Postoperative inflammatory response after autologous and allogeneic blood transfusion
. Anesthesiology. 1997; 87: 511–516.
6. Schmidt H, Bendtzen K, Mortensen PE. The inflammatory cytokine response after autotransfusion of shed mediastinal blood. Acta Anaesthesiol Scand. 1998; 42: 558–564.
7. Haynes SL, Wong JC, Torella F, Dalrymple K, Pilsworth L, McCollum CN. The influence of homologous blood transfusion
on immunity and clinical outcome in aortic surgery. Eur J Vasc Endovasc Surg. 2001; 22: 244–250.
8. Zallen G, Moore EE, Ciesla DJ, et al. Stored red blood cells selectively activate human neutrophils to release IL-8 and secretory PLA-2. Shock
. 2000; 13: 29–33.
9. Biffl WL, Moore EE, Zallen G, et al. Neutrophils are primed for cytotoxicity and resist apoptosis in injured patients at risk for multiple organ failure. Surgery. 1999; 126: 198–202.
10. Makino Y, Yamanoi A, Kimoto T, El-Assal ON, Kohno H, Nagasue N. The influence of perioperative blood transfusion
on intrahepatic recurrence after curative resection of hepatocellular carcinoma. Am J Gastroenterol. 2000; 95: 1294–1300.
11. Mynster T, Nielsen HJ. Storage time of transfused blood and disease recurrence after colorectal cancer surgery. Dis Colon Rectum. 2001; 44: 955–964.
12. Dresner SM, Lamb PJ, Shenfine J, Hayes N, Griffin SM. Prognostic significance of perioperative blood transfusion
following radical resection for oesophageal carcinoma. Eur J Surg Oncol. 2000; 26: 492–497.
13. Carson JL, Altman DG, Duff A, et al. Risk of bacterial infection associated with allogeneic blood transfusion
among patients undergoing hip fracture repair. Transfusion. 1999; 39: 694–700.
14. Taylor RW, Manganaro LA, O’Brien JA, et al. Impact of allogeneic packed red blood cell transfusion on nosocomial infection
rates in the critically ill patient. Crit Care Med. 2002; 30: 2249–2254.
15. Claridge JA, Sawyer RG, Schulman AM, et al. Blood transfusion
correlate with infections in trauma
patients in a dose-dependent manner. Am Surg. 2002; 68: 566–572.
16. Moore FA, Moore EE, Sauaia A. Blood transfusion
: an independent risk factor for postinjury multiple organ failure. Arch Surg. 1997; 132: 620–625.
17. Malone D, Kuhls D, Napolitano LM, McCarter R, Scalea T. Blood transfusion
in the first 24 hours is associated with systemic inflammatory response syndrome (SIRS) and worse outcome in trauma
. Crit Care Med. 2000; 28 (suppl): A138.
18. American College of Surgeons, Committee on Trauma
. Advanced Trauma
Life Support Program for Physicians Manual. 6th ed. Chicago, IL: American College of Surgeons; 1997.
19. Copes WS, Champion H, Sacco WJ, et al. The Injury
Severity Score revisited. J Trauma
. 1988; 28: 69–77.
20. Bratosin D, Leszczynski S, Sartiaux C, et al. Improved storage of erythrocytes by prior leukodepletion: flow cytometric evaluation of stored erythrocytes. Cytometry. 2001; 46: 351–356.
21. Tartter PI, Mohandas K, Azar P, et al. Randomized trial comparing packed red cell blood transfusion
with and without leukocyte depletion for gastrointestinal surgery. Am J Surg. 1998; 176: 462–466.
22. Baron JF, Gourdin M, Bertrand M, et al. The effect of universal leukoreduction of packed red blood cells on postoperative infections in high-risk patients undergoing abdominal aortic surgery. Anesth Analg. 2002; 94: 529–537.
23. Collier AC, Kalish LA, Busch MP, et al. Leukocyte-reduced red blood cell transfusion in patients with anemia
and human immunodeficiency virus infection: the Viral Activation Transfusion study—a randomized controlled trial. JAMA. 2001; 285: 1592–1601.
24. Zallen G, Offner PJ, Moore EE, et al. Age of transfused blood is an independent risk factor for postinjury multiple organ failure. Am J Surg. 1999; 178: 570–572.
25. Purdy FR, Tweeddale MG, Merrick PM. Association of mortality with age of blood transfused in septic ICU patients. Can J Anaesth. 1997; 44: 1256–1261.
26. Chang H, Hall GA, Geerts WH, Greenwood C, McLeod RS, Sher GD. Allogeneic red blood cell transfusion is an independent risk factor for the development of postoperative bacterial infection. Vox Sang. 2000; 78: 13–18.
27. Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999; 340: 409–417.
28. Gould SA, Moore EE, Moore FA, et al. Clinical utility of polymerized hemoglobin as a blood substitute after acute trauma
and emergent surgery. J Trauma
. 1997; 43; 325–331.
29. Gould SA, Moore EE, Hoyt DB, et al. The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma
and emergent surgery. J Am Coll Surg. 1998; 187: 113–122.
30. Johnson JL, Moore EE, Offner PJ, et al. Resuscitation with a blood substitute abrogates pathologic postinjury neutrophil cytotoxic function. J Trauma
. 2001; 50: 449–456.
31. Sprung J, Kindscher JD, Wahr JA, et al. Use of Hemopure in surgical patients: results of a multicenter, randomized single-blinded trial. Anesth Analg. 2002; 94: 799–808.
32. Levy JH, Goodnough LT, Greilich PE, et al. Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: results of a randomized, double-blind trial. J Thorac Cardiovasc Surg. 2002; 124: 35–42.
33. Standl T. Haemoglobin-based erythrocyte transfusion substitutes. Expert Opin Biol Ther. 2001; 1: 831–843.
Keywords:© 2003 Lippincott Williams & Wilkins, Inc.
Blood transfusion; Trauma; Injury; Hemorrhage; Anemia; Shock; Nosocomial infection