Original Article
A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care
N Engl J Med 1999; 340:409-417February 11, 1999
- Abstract
Background
To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction.
Methods
We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter.
Results
Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill — those with an Acute Physiology and Chronic Health Evaluation II score of ≤20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group, P=0.03) — and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.2 percent vs. 28.1 percent, P=0.05).
Conclusions
A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.
Media in This Article
Figure 1
Numbers of Patients Assessed and Enrolled in the Trial.Figure 2
Kaplan–Meier Estimates of Survival in the 30 Days after Admission to the Intensive Care Unit in the Restrictive-Strategy and Liberal-Strategy Groups.Article Activity
- Article
Red-cell transfusions are a cornerstone of critical care practice,1 but there are divergent views on the risks of anemia and the benefits of transfusion in this setting. One important concern is that anemia may not be well tolerated by critically ill patients.2,3 Indeed, two recent studies suggested that anemia increases the risk of death after surgery in patients with cardiac disease2 and in critically ill patients.3 Red-cell transfusions are used to augment the delivery of oxygen in the hope of avoiding the deleterious effects of oxygen debt.4 This view prompted the routine use of transfusion in patients with hemoglobin concentrations that were often more than 10.0 g per deciliter in studies evaluating resuscitation protocols.5,6
Critically ill patients may, however, be at increased risk for the immunosuppressive7,8 and microcirculatory9,10 complications of red-cell transfusions. In addition, concern about the supply and safety of blood has also encouraged a conservative approach to transfusions. For these reasons, the optimal transfusion practice for various types of critically ill patients with anemia has not been established.
To elucidate the potential risks of anemia and possible benefits of transfusions in critically ill patients, we conducted a randomized, controlled, clinical trial to determine whether a restrictive approach to red-cell transfusion that maintains hemoglobin concentrations between 7.0 and 9.0 g per deciliter is equivalent to a more liberal strategy of maintaining hemoglobin concentrations between 10.0 and 12.0 g per deciliter in critically ill patients with euvolemia after initial treatment.
Methods
Study Population
We enrolled patients who were admitted to 1 of 22 tertiary-level and 3 community intensive care units in Canada (see the Appendix) between November 1994 and November 1997. We included patients who were expected to stay in the intensive care unit more than 24 hours, had a hemoglobin concentration of 9.0 g per deciliter or less within 72 hours after admission to the intensive care unit, and were considered to have euvolemia after initial treatment by attending physicians. Patients were excluded for any of the following reasons: an age of less than 16 years; inability to receive blood products; active blood loss at the time of enrollment, defined as evidence of ongoing blood loss accompanied by a decrease in the hemoglobin concentration of 3.0 g per deciliter in the preceding 12 hours or a requirement for at least 3 units of packed red cells during the same period; chronic anemia, defined as a hemoglobin concentration of less than 9.0 g per deciliter on at least one occasion more than one month before admission to the hospital; pregnancy; brain death or imminent death (within 24 hours); a question on the part of attending physicians whether to withhold or withdraw ongoing treatment; and admission after a routine cardiac surgical procedure. The study protocol was approved by the institutional review board of each participating institution, and informed consent was obtained from either the patient or the closest family member before enrollment in the study.
Study Design and Treatment Protocols
Consecutive critically ill patients with normovolemia were assigned to one of two treatment groups, stratified according to center and disease severity (an Acute Physiology and Chronic Health Evaluation [APACHE II] score of 15 or less or a score of more than 15, with higher scores indicating more severe disease),11 and balanced with the use of permuted blocks of four or six.12 Sealed, opaque envelopes arranged in a computer-generated random order were prepared by the data-coordinating center and distributed to each participating institution, where they were opened sequentially to determine the patients' treatment assignments. The envelopes were returned periodically to the coordinating center for auditing.
Transfusion guidelines for both study groups were developed from information obtained in a national survey of critical care practitioners in Canada13 and a pilot study.14 The hemoglobin concentrations of patients assigned to the restrictive strategy of transfusion were maintained in the range of 7.0 to 9.0 g per deciliter, with a transfusion given when the hemoglobin concentration fell below 7.0 g per deciliter. Among patients assigned to the liberal strategy of transfusion, the hemoglobin concentrations were maintained in the range of 10.0 to 12.0 g per deciliter, with a threshold for transfusion of 10.0 g per deciliter. It was not feasible to mask the assigned transfusion strategy from health care providers.
In Canada, red cells are separated from whole blood and stored in citrate–phosphate–dextrose–adenine anticoagulant solution without leukodepletion. The volume of a unit of red cells ranges from 240 to 340 ml, with a hematocrit of approximately 80 percent.15
The physicians caring for the patients were instructed to administer transfusions, one unit at a time, and to measure a patient's hemoglobin concentration after each unit was transfused. Although specific goals for oxygen delivery were not part of the protocol, we provided suggestions for the use of fluids and vasoactive drugs, when necessary, and advice when a transfusion was not indicated by the study protocol. All other management decisions were left to the discretion of the patients' physicians. Adherence to the transfusion protocols was required only during the patient's stay in the intensive care unit. When a patient was discharged from the intensive care unit, a copy of the American College of Physicians guidelines for transfusion16 was placed in his or her medical record.
Compliance with the two transfusion protocols was monitored by daily measurements of hemoglobin concentrations in each patient. In addition, transfusion records were sent regularly to the study coordinating center, which monitored the ability of individual centers to maintain hemoglobin concentrations in the target range.
Base-Line Assessment and Data Collection
At the time of randomization, demographic, diagnostic, and therapeutic information as well as information necessary to determine the severity of illness — including APACHE II scores,11 calculated from data gathered within 24 hours after admission to the intensive care unit, and the multiple-organ-dysfunction score17 — was obtained for each patient. The worst laboratory values recorded during each patient's stay in the intensive care unit were noted for use in assessing organ dysfunction with use of the multiple-organ-dysfunction score17 and the multiple-system organ-failure score.18 Hemoglobin concentrations; the use of red-cell transfusions; medications given, including vasoactive drugs; and the need for mechanical ventilation, dialysis, and surgical intervention were recorded on a daily basis.
The principal reason for admission to the intensive care unit was recorded. We included as many as three secondary diagnoses and eight coexisting conditions. In postoperative patients, the underlying diagnosis and the surgical procedure were recorded. All data were abstracted from clinical records by trained study personnel and coded according to the International Classification of Diseases, 9th Revision, Clinical Modification. All diagnoses were reviewed by two of the four critical care physicians, and disagreements were resolved by consensus.
Outcome Measures
The primary outcome measure was death from all causes in the 30 days after randomization. Secondary outcomes included 60-day rates of death from all causes, mortality rates during the stay in the intensive care unit and during hospitalization, and survival times in the first 30 days. Measures of organ failure and dysfunction, including the number and rates of organ failure as defined previously18 and the multiple-organ-dysfunction score,17 were also assessed. To improve our ability to detect meaningful differences between groups, we used some composite outcomes that included death and organ dysfunction or failure as indicators of morbidity. Patients who died were assigned a multiple-system organ-failure score of 7 and a multiple-organ-dysfunction score of 24, the worst possible values for each scale, as a means of adjusting measures of organ dysfunction and failure for deaths. Lengths of stays in the intensive care unit and the hospital were also recorded.
Statistical Analysis
Since this was an equivalency trial, we used 95 percent confidence intervals to estimate the number of patients necessary for the study to have the power to rule out clinically meaningful differences in outcomes. We estimated that 2300 patients would be needed to rule out an absolute difference of 4 percent in 30-day mortality between the two groups, assuming a combined mortality rate of 18 percent (the rate for a group receiving standard care was estimated to be 20 percent3). An interim analysis conducted in a blinded fashion by the data-monitoring committee after 404 patients had been enrolled revealed that the combined 30-day mortality rate was actually 23 percent. This change increased the detectable difference to 4.5 percent for a sample of 2300 patients. Because of this increase in observed mortality, we decided to decrease the target sample to 1620 patients (primarily on the basis of the hypothesis-testing method, in which the mortality rate for the standard-care group was 26.6 percent, the type 1 and type 2 error rates were 5 percent, and there was no change in the relative risk of 27.5 percent from the original estimate of sample size). The recalculated sample size allowed us to rule out an absolute difference in the 30-day mortality rate of 5.5 percent between groups.
The final analysis was conducted on an intention-to-treat basis. Comparisons of hemoglobin concentrations over time were made with use of analysis of variance with repeated measures, followed by Tukey's honestly-significant-difference test for pairwise comparisons.
Mortality rates, the number of organs that failed per patient, and the rates of multiorgan failure were compared with use of Fisher's exact test. A forward, stepwise logistic-regression procedure was then performed to adjust raw mortality data with use of covariates that were found to be significant predictors of outcomes. Covariates were entered into the logistic model at a P value of ≤0.10. A second logistic regression was performed in which potential confounders, including age, APACHE II score, coexisting illnesses, diagnostic category, and study center, were forced into the model. Kaplan–Meier survival curves for each group were compared with use of a log-rank test statistic. Multiple-organ-dysfunction scores were analyzed with use of an independent t-test. To account for the influence of death on the assessment of organ failure and organ dysfunction, we conducted an additional analysis in which all patients who died were assigned the maximal scores. The complication rates were compared with use of a chi-square test. Lengths of stay in the intensive care unit and the hospital were analyzed with use of the Wilcoxon rank-sum test for independent samples.
A priori subgroup analyses of patients at potential risk for the adverse effects of anemia included patients who were 55 years of age or older, patients with cardiac disease, and patients with APACHE II scores indicating more severe illness. In the final analysis, we increased the threshold value for APACHE II scores from 15 to 20 because less than 20 percent of all patients had an APACHE II score below 15 and because a score of 20 was considered to be a better indicator of severe illness. We also examined patients with systemic infections. Differences in primary outcomes were considered statistically significant when the overall two-sided alpha level was 0.05 or less. No adjustments were made for multiple comparisons. Where appropriate, absolute P values are reported with 95 percent confidence intervals for differences between the groups.
Results
Study Population
A total of 6451 patients were assessed for eligibility (Figure 1Figure 1
Numbers of Patients Assessed and Enrolled in the Trial.). After exclusions for a variety of medical and administrative reasons, 838 patients were enrolled in the study: 418 patients were assigned to a restrictive strategy of transfusion and 420 were assigned to a liberal strategy of transfusion. The consent rate was 41 percent (838 of 2039 patients). As compared with the patients who were enrolled in the study, those who were not enrolled were slightly older (mean [±SD] age, 57.6±18.2 vs. 59.4±18.8 years; P=0.04), but they had similar APACHE II scores (P=0.36) and diagnoses (P=0.26) with the exception of cardiac disease. Twenty-six percent of enrolled patients had cardiac disease, as compared with 20 percent of those who were not enrolled (P<0.01). Nine patients (1 percent) did not complete the trial; four were in the liberal-strategy group and five were in the restrictive-strategy group. Three additional patients were lost to follow-up at 60 days. The executive committee, without foreknowledge of treatment-specific outcomes, decided to terminate the study prematurely because of a decrease in enrollment to below 20 percent of predicted levels over a period of several months.There were no significant differences in any base-line characteristics between the two groups (Table 1Table 1
Base-Line Characteristics of the Study Patients.). The two most common reasons for admission to the intensive care unit were respiratory and cardiac diseases. The average APACHE II score was 21, and more than 80 percent of the patients were receiving mechanical ventilation. A total of 222 patients (26.5 percent) had an infection as either a primary or a secondary diagnosis.Success of Treatment
The average daily hemoglobin concentrations were 8.5±0.7 g per deciliter in the restrictive-strategy group and 10.7±0.7 g per deciliter in the liberal-strategy group (P<0.01). The average hemoglobin concentrations also differed significantly between the groups during each day of the 30-day study (P< 0.01). An average of 2.6±4.1 red-cell units per patient was administered in the restrictive-strategy group, as compared with an average of 5.6±5.3 units per patient in the liberal-strategy group (P<0.01). This equals a relative decrease of 54 percent in the number of transfusions when the lower threshold was used. In addition, 33 percent of the patients in the restrictive-strategy group did not receive any red cells after randomization, as compared with 0 percent of the patients in the liberal-strategy group (P<0.01).
Noncompliance of physicians with the study regimen, as indicated by a finding of hemoglobin concentrations outside the prespecified ranges for at least 48 hours, occurred in 4.3 percent of patients in the liberal-strategy group (18 of 420) and 1.4 percent of patients in the restrictive-strategy group (6 of 418) (P=0.02). A subgroup of these patients were inadvertently crossed over from one group to the other when physicians either administered or withheld red-cell transfusions. The overall rate of crossover was 1.8 percent (15 of 838): 2.6 percent (11) in the liberal-strategy group and 1 percent (4) in the restrictive-strategy group (P=0.12).
Given that the investigators were aware of the patients' treatment assignments, other interventions may have influenced outcomes. The use of medications, including vasoactive drugs; the administration of fluids and daily fluid balance; and the use of pulmonary-artery catheters were similar in both groups throughout the stay in the intensive care unit (P= 0.15). The use of other interventions such as dialysis, mechanical ventilation, and surgical procedures was also similar (P=0.58).
Outcome Measures
The primary outcome — the rate of death from all causes in the 30 days after admission to the intensive care unit — was 18.7 percent in the restrictive-strategy group and 23.3 percent in the liberal-strategy group (95 percent confidence interval for the difference between the groups, –0.84 percent to 10.2 percent; P=0.11) (Table 2Table 2
Outcomes.). The mortality rates during hospitalization were lower in the restrictive-strategy group (22.2 percent vs. 28.1 percent, P=0.05). Other mortality rates including the mortality rate during the entire stay in the intensive care unit (13.9 percent vs. 16.2 percent, P=0.29) and the 60-day mortality rate (22.7 percent vs. 26.5 percent, P=0.23) were also lower in the restrictive-strategy group but not significantly so.Kaplan–Meier survival curves were similar for the patient group as a whole, but they were significantly different in the subgroup of patients with an APACHE II score of 20 or less (P=0.02) and in the subgroup of patients who were younger than 55 years (P=0.02) (Figure 2AFigure 2
Kaplan–Meier Estimates of Survival in the 30 Days after Admission to the Intensive Care Unit in the Restrictive-Strategy and Liberal-Strategy Groups., Figure 2B, and Figure 2C). The unadjusted odds ratio for death within 30 days in the restrictive-strategy group as compared with the liberal-strategy group was 0.75 (P=0.09). Adjustment for the influence of age, APACHE II score, diagnosis, and coexisting illnesses with use of logistic-regression analysis did not change the odds ratio significantly (odds ratio, 0.72; 95 percent confidence interval, 0.50 to 1.07; P=0.07).The number of patients with multiorgan failure (more than three organs), which was analyzed as a dichotomous variable (present or absent) for each of seven organ systems,18 was not significantly different between the restrictive-strategy and liberal-strategy groups (5.3 percent vs. 4.3 percent, P=0.36). The mean multiple-organ-dysfunction score was marginally lower in the restrictive-strategy group than in the liberal-strategy group (8.3±4.6 vs. 8.8±4.4, P=0.10).
We also examined composite outcomes. When organ-failure scores of 7 were assigned to all patients who died within 30 days after admission to the intensive care unit, the number of patients with multiorgan failure was substantially increased in both groups, and the results were marginally better in the restrictive-strategy group (20.6 percent vs. 26.0 percent, P=0.07). Similarly, when all patients who died were given a multiple-organ-dysfunction score of 24, the total scores (P=0.03) and the changes in the scores from base line (P=0.04) were significantly lower in the restrictive-strategy group (Table 2).
Cardiac events, primarily pulmonary edema and myocardial infarction, were more frequent in the liberal-strategy group than in the restrictive-strategy group during the stay in the intensive care unit (P<0.01) (Table 3Table 3
Complications That Occurred during the Patients' Stays in the Intensive Care Unit.). However, there were no significant differences in the rates of cardiac events (41 percent in the restrictive-strategy group and 44 percent in the liberal-strategy group, P=0.86), infectious complications (3 percent and 4 percent, respectively; P=1.00), or multiorgan failure (37 percent and 32 percent, respectively; P=0.59) in the 48 hours preceding death among the patients who died (Table 4Table 4
Characteristics of the 176 Patients Who Died.).Subgroup Analyses
When the patients were analyzed according to age (<55 years vs. ≥55 years) and APACHE II score (≤20 vs. >20), there were no significant differences in base-line characteristics. In the restrictive-strategy group, 173 patients were younger than 55 years, 207 patients had an APACHE II score of 20 or less, 151 patients had cardiac disease, 100 had a traumatic injury, and 114 had a severe infection or septic shock. In the liberal-strategy group, 161 patients were younger than 55 years, 217 had an APACHE II score of 20 or less, 175 had cardiac disease, 100 had a traumatic injury, and 104 had a severe infection or septic shock. All outcomes in the two transfusion-strategy groups were similar for the patients who were older than 55 years and for those with an APACHE II score of more than 20 (P>0.36). However, 30-day mortality was significantly lower in the restrictive-strategy group than in the liberal-strategy group among the patients with an APACHE II score of 20 or less (8.7 percent vs. 16.1 percent; 95 percent confidence interval for the absolute difference, 1.0 to 13.6 percent; P=0.03) and among the patients who were less than 55 years of age (5.7 percent vs. 13.0 percent; 95 percent confidence interval, 1.1 to 13.5 percent; P=0.02). There were no significant differences in 30-day mortality between treatment groups in the subgroup of patients with a primary or secondary diagnosis of cardiac disease (20.5 percent in the restrictive-strategy group and 22.9 percent in the liberal-strategy group; 95 percent confidence interval for the difference, –6.7 to 11.3 percent; P=0.69), in the subgroup of patients with severe infections and septic shock (22.8 percent and 29.7 percent, respectively; P=0.36), or in the subgroup of patients with trauma (10.0 percent and 8.8 percent, respectively; P=0.81).
The results for the rates of organ dysfunction in the subgroups were similar to those for other subgroup analyses. The multiple-organ-dysfunction scores adjusted for patients who died did not differ significantly in the subgroup of patients with an APACHE II score of more than 20, the subgroup more than 55 years of age, and the subgroup with specific diagnoses, including cardiac disease, trauma, and severe infections and septic shock (all P>0.30). However, adjusted multiple-organ-dysfunction scores were significantly lower in the subgroup of patients with an APACHE II score of 20 or less (8.3±6.2 in the restrictive-strategy group and 10.0±7.2 in the liberal-strategy group, P=0.01) and in the subgroup of patients who were younger than 55 years of age (8.8±5.7 and 10.3±6.6, respectively; P=0.03).
Discussion
Our findings indicate that the use of a threshold for red-cell transfusion as low as 7.0 g of hemoglobin per deciliter, combined with maintenance of hemoglobin concentrations in the range of 7.0 to 9.0 g per deciliter, was at least as effective as and possibly superior to a liberal transfusion strategy (threshold, 10.0 g per deciliter; maintenance range, 10.0 to 12.0) in critically ill patients with normovolemia. There was a trend toward decreased 30-day mortality among patients who were treated according to the restrictive transfusion strategy. The significant differences in mortality rates during hospitalization, rates of cardiac complications, and rates of organ dysfunction all favored the restrictive strategy.
We also found that maintaining hemoglobin concentrations in the range of 7.0 to 9.0 g per deciliter decreased the average number of red-cell units transfused by 54 percent and decreased exposure to any red cells after randomization by 33 percent. Concern about exposure to blood products has increased the use of expensive drugs such as epoetin alfa and aprotinin, which reduce perioperative exposure by an average of one to two red-cell units, with little evidence of overall effectiveness. In contrast, a simple and inexpensive intervention that lowers the transfusion threshold improved clinical outcomes and reduced exposure to red cells.
A recent systematic review of transfusion practice19 identified five randomized, controlled clinical trials that compared clinical outcomes after the implementation of two transfusion strategies. The only large trial, in patients with chronic anemia due to sickle cell disease, did not demonstrate decreases in the incidence of sickle cell crises among patients assigned to a liberal transfusion strategy.20 The four other trials were quite small. Two studies in patients undergoing bypass surgery21,22 and our pilot study14 did not find differences between the transfusion strategies but were too small to yield clinically useful inferences. The fifth trial, in patients with nonvariceal gastrointestinal hemorrhage, found that administering transfusions liberally or expectantly resulted not only in increased overall use of transfusions but also in a higher frequency of coagulation abnormalities.23
A number of randomized, controlled clinical trials have addressed the hypothesis that oxygen delivery should be increased or maintained at high levels to minimize the effects of tissue hypoxia caused by disease processes that interfere with oxygen delivery or the body's ability to extract oxygen. One meta-analysis24 found that oxygen delivery was increased when oxygen therapy was initiated preoperatively, but this benefit was not observed in studies that evaluated patients admitted to the intensive care unit. In all the previous studies, the transfusion thresholds exceeded 10.0 g per deciliter; therefore, it was not possible to make inferences about optimal strategies for red-cell transfusion. In our study, red-cell transfusions, used as a means of augmenting oxygen delivery, did not offer any survival advantage in patients with normovolemia when hemoglobin concentrations exceeded 7.0 g per deciliter.
There is also concern about the adverse effects of anemia in patients with ischemic heart disease. Two large cohort studies found that an increasing severity of anemia was associated with a disproportionate increase in mortality rates among patients with ischemic heart disease.2,3 In our study, however, patients with diagnoses of cardiac disease did not have more adverse outcomes when a transfusion threshold of 7.0 g per deciliter was used. The apparent discrepancy between our results and those of previous studies may be the result of confounding3 or an inability to document the negative effects of transfusion2 in the observational studies.
In most clinical trials, there are more patients who are asked to participate than actually agree to participate. There is therefore a possibility that refusals on the part of patients, their surrogates, or their physicians affect the generalizability of the results. A greater proportion of patients with severe cardiac disease than with other types of disease had attending physicians who declined to enroll them in our study. Nevertheless, we believe that a restrictive strategy can be implemented in patients with coronary artery disease but should be considered with caution in patients with acute myocardial infarction and unstable angina.
On the basis of our results, we recommend that critically ill patients receive red-cell transfusions when their hemoglobin concentrations fall below 7.0 g per deciliter and that hemoglobin concentrations should be maintained between 7.0 and 9.0 g per deciliter. The diversity of the patients enrolled in this trial and the consistency of the results suggest that our conclusions may be generalized to most critically ill patients, with the possible exception of patients with active coronary ischemic syndromes.
Supported by the Medical Research Council of Canada and by an unrestricted grant from Bayer. Dr. Hébert is a Career Scientist of the Ontario Ministry of Health.
We are indebted to the members of the Canadian Critical Care Trials Group, Mark Pickett (director of research and development at Bayer), and Bert T. Aye (former director of the Canadian Red Cross Society Blood Services) for their support of the study; to the nurses and critical care teams, which provided outstanding medical care to our patients; and to Christine Niles for secretarial support.
Source Information
From the Critical Care Program (P.C.H., G.P.) and the Clinical Epidemiology Unit (P.C.H, G.W., I.S., E.Y.), University of Ottawa, Ottawa; the Department of Pathology, McMaster University, Hamilton, Ont. (M.A.B.); the Critical Care Program, University of Toronto, Toronto (J.M.); the Critical Care Program, University of Western Ontario, London (C.M.); and the Critical Care Program, University of British Columbia, Vancouver (M.T.) — all in Canada.
Address reprint requests to Dr. Hébert at the Department of Medicine, Ottawa General Hospital, 501 Smyth Rd., Box 205, Ottawa, ON K1H 8L6, Canada.
Study investigators are listed in the Appendix.
Appendix
The following Canadian facilities and persons participated in the study: Ottawa General Hospital, Ottawa — P.C. Hébert, M. Seyidoglu, C. Sexton; Ottawa Civic Hospital, Ottawa — G. Pagliarello, M. Lowen; Toronto Hospital, General Division, Toronto — J. Marshall, M. Steinberg, D. Foster, D. Baptiste; Victoria Hospital, London — C. Martin, J. Kehoe, L. McCarthy, D. Gilliland, B. Martin; Vancouver General Hospital, Vancouver — M. Tweeddale, D. Williams, B. Plumbstead; Health Science Centre, St. John's — S. Peters, D. Gibbons; Victoria General Hospital, Halifax — R. Hall, J. Kearney, G. Williams, V. Nedelcu; Montreal General Hospital, Montreal — D. Fleiszer, L. Perkins; Royal Victoria Hospital, Montreal — S. Magder, D. Jones, S. Bertleff; Jewish General Hospital, Montreal — A. Spanier, D. Collins; St. Michael's Hospital, Toronto — D. Mazer, G. Sloane; Toronto Hospital, Western Division, Toronto — P. Houston, V. Smirnios, C. McKenna, E. Ng; Wellesley Hospital, Wellesley — T. Stewart, D. Schouten; St. Joseph's Hospital, London — A. Kirby, M.-K. Scott; Hamilton General Hospital, Hamilton — T. Hillers, L. Morrison; University Hospital, Saskatoon — J. Pinilla, J. Strickland; Foothills Hospital, Calgary — D. Sandham, L. Crenshaw, L. Knox, J. Lasante; University Hospital, Edmonton — M. van Wijngaarden, E. Merkley, B. Armstrong; St. Paul's Hospital, Vancouver — J.A. Russell, M. Douglas, K. Mulcahy, A. Drummond; Kingston General Hospital, Kingston — G. Wood, D. Heyland, A. Taite; Hôpital Maisonneuve–Rosemont, Montreal — Y. Skrobik, M. Racine; Dr. Everett Chalmers Hospital, Fredericton — N. Mehta, M. Amos; Hôtel Dieu–Grace Hospital, Windsor — J. Muscedere, C. Diemer, P. Oldfield; St. John's Regional Hospital, St. John's — M. Jacka, K. Furlong; Calgary General Hospital–Peter Lougheed Center, Calgary — S. Viner, C. Gunderson; Data Monitoring Committee: St. Joseph's Hospital, London — D. Cook; Hamilton Health Sciences Center, Hamilton — J. Hirsh; University of Waterloo, Waterloo — R. Cook; Toronto General Hospital, Toronto — T. Todd; Data Management Committee: Ottawa General Hospital, Ottawa — P.C. Hébert, I. Schweitzer, E. Yetisir; Ottawa Civic Hospital, Ottawa — G. Wells, M.-L. Tran, F. Daigle-Campbell, A. Gray.
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Citing Articles
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S. KOCSI, G. DEMETER, J. FOGAS, D. ÉRCES, J. KASZAKI, Z. MOLNÁR. (2012) Central venous oxygen saturation is a good indicator of altered oxygen balance in isovolemic anemia. Acta Anaesthesiologica Scandinavican/a-n/a
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Marcella CA Müller, Nicole P Juffermans. (2012) Transfusion-related acute lung injury: a preventable syndrome?. Expert Review of Hematology 5:1, 97-106
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Steven J. Schwulst, John E. Mazuski. (2012) Surgical Prophylaxis and Other Complication Avoidance Care Bundles. Surgical Clinics of North America
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Gregory M. T. Hare, Alexander Mu, Alexander Romaschin, Albert K.-Y. Tsui, Nadine Shehata, W. Scott Beattie, C. David Mazer. (2012) Plasma methemoglobin as a potential biomarker of anemic stress in humans. Canadian Journal of Anesthesia/Journal canadien d'anesthésie
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Marisa B. Marques, Sherry R. Polhill, Michael R. Waldrum, James E. Johnson, Joseph Timpa, Anthony Patterson, Donna Salzman. (2012) How we closed the gap between red blood cell utilization and whole blood collections in our institution. Transfusionno-no
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B. Sorensen, D. Fries. (2012) Emerging treatment strategies for trauma-induced coagulopathy. British Journal of Surgery 99:S1, 40-50
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Russell S. Roberson, Elliott Bennett-Guerrero. (2012) Impact of Red Blood Cell Transfusion on Global and Regional Measures of Oxygenation. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine 79:1, 66-74
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Jared S. Ruckman. (2012) CO-Oximeters. Biomedical Instrumentation & Technology 46:1, 61-63
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K. G. Badami, D. Bruce, D. Whitehead, J. E. Wells. (2012) Haemoglobin triggers and red cell dose in patients with non-acute anaemia. Transfusion Medicineno-no
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Shigetaka Matsunaga, Hiroyuki Seki, Yoshihisa Ono, Hideyoshi Matsumura, Yoshihiko Murayama, Yasushi Takai, Masahiro Saito, Satoru Takeda, Hiroo Maeda. (2012) A Retrospective Analysis of Transfusion Management for Obstetric Hemorrhage in a Japanese Obstetric Center. ISRN Obstetrics and Gynecology 2012, 1-8
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Carson, Jeffrey L., Terrin, Michael L., Noveck, Helaine, Sanders, David W., Chaitman, Bernard R., Rhoads, George G., Nemo, George, Dragert, Karen, Beaupre, Lauren, Hildebrand, Kevin, Macaulay, William, Lewis, Courtland, Cook, Donald Richard, Dobbin, Gwendolyn, Zakriya, Khwaja J., Apple, Fred S., Horney, Rebecca A., Magaziner, Jay, . (2011) Liberal or Restrictive Transfusion in High-Risk Patients after Hip Surgery. New England Journal of Medicine 365:26, 2453-2462
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Barr, Paul J., Bailie, Karen E.M., . (2011) Transfusion Thresholds in FOCUS. New England Journal of Medicine 365:26, 2532-2533
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Stavros G. Memtsoudis, Melanie C. Besculides. (2011) Perioperative comparative effectiveness research. Best Practice & Research Clinical Anaesthesiology 25:4, 535-547
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Brian K. Daines, Raymond H. Kim, Douglas A. Dennis. (2011) Autologous and Allogeneic Blood Transfusions Still Have a Place. Techniques in Knee Surgery 10:4, 211-212
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F. Violi, S. Basili, V. Raparelli, P. Chowdary, A. Gatt, A.K. Burroughs. (2011) Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction?. Journal of Hepatology 55:6, 1415-1427
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A. Shander, M. Javidroozi, S. Ozawa, G. M. T. Hare. (2011) What is really dangerous: anaemia or transfusion?. British Journal of Anaesthesia 107:suppl 1, i41-i59
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K. Mann, I. Sim, T. Ali, P. Chong, P. Leopold, A. Hatrick, D. Gerrard. (2011) Removing the Need for Crossmatched Blood in Elective EVAR. European Journal of Vascular and Endovascular Surgery
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Mervyn Singer. (2011) Management of fluid balance. Current Opinion in Anaesthesiology1
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Paul E. Marik. (2011) The Risks of Blood Transfusion in Patients with Subarachnoid Hemorrhage. Neurocritical Care
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Dieter Mesotten, Greet Van den Berghe. (2011) Glycemic Targets and Approaches to Management of the Patient with Critical Illness. Current Diabetes Reports
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Brodie, Daniel, Bacchetta, Matthew, . (2011) Extracorporeal Membrane Oxygenation for ARDS in Adults. New England Journal of Medicine 365:20, 1905-1914
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Hongmei Zhu, Rahima Zennadi, Bruce X. Xu, Jerry P. Eu, Jordan A. Torok, Marilyn J. Telen, Timothy J. McMahon. (2011) Impaired adenosine-5′-triphosphate release from red blood cells promotes their adhesion to endothelial cells: A mechanism of hypoxemia after transfusion*. Critical Care Medicine 39:11, 2478-2486
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Oliver M. Theusinger, Christian Felix, Donat R. Spahn. (2011) Strategies to reduce the use of blood products. Current Opinion in Anaesthesiology1
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J.M. de Miguel Yanes, J.A. Andueza Lillo, J.C. Cano Ballesteros, S. Gordo Remartínez. (2011) Infecciones sistémicas en Urgencias. Sepsis. Shock séptico. Medicine - Programa de Formación Médica Continuada Acreditado 10:90, 6078-6086
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A. K. Y. Tsui, P. A. Marsden, C. D. Mazer, S. L. Adamson, R. M. Henkelman, J. J. D. Ho, D. F. Wilson, S. P. Heximer, K. A. Connelly, S.-S. Bolz, D. Lidington, M. H. El-Beheiry, N. D. Dattani, K. M. Chen, G. M. T. Hare. (2011) Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia. Proceedings of the National Academy of Sciences 108:42, 17544-17549
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Sarah B Murthi, Lynn G Stansbury, Richard P Dutton, Bennett B Edelman, Thomas M Scalea, John R Hess. (2011) Transfusion medicine in trauma patients: an update. Expert Review of Hematology 4:5, 527-537
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Valeska Balderas, Rafia Bhore, Luis F. Lara, Julia Spesivtseva, Don C. Rockey. (2011) The Hematocrit Level in Upper Gastrointestinal Hemorrhage: Safety of Endoscopy and Outcomes. The American Journal of Medicine 124:10, 970-976
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Bhanu P. Nalla, John Freedman, Gregory M.T. Hare, C. David Mazer. (2011) Update on Blood Conservation for Cardiac Surgery. Journal of Cardiothoracic and Vascular Anesthesia
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Girish Viswanathan, Ananth Kidambi, Adam Nelson, Gnanamoorthy Mayurathan, John Hardy, Patrick Kesteven, Azfar Zaman. (2011) Glycoprotein IIb/IIIa inhibitor associated severe thrombocytopenia in patients with coronary artery disease: Clinical course and outcomes. Platelets1-5
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David Faraoni, Ariane Willems, Philippe Van der Linden. (2011) Erythrocyte Transfusion. Anesthesiology 115:3, 660-661
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John R. Feiner, Heather E. Finlay-Morreale, Pearl Toy, Jeremy A. Lieberman, Maurene K. Viele, Harriet W. Hopf, Richard B. Weiskopf. (2011) High Oxygen Partial Pressure Decreases Anemia-induced Heart Rate Increase Equivalent to Transfusion. Anesthesiology 115:3, 492-498
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R.R. CROSBY-NWAOBI, S. FAITHFULL. (2011) High risk of urinary tract infections in post-operative gynaecology patients: a retrospective case analysis. European Journal of Cancer Careno-no
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Jeffrey Javidfar, Daniel Brodie, Hiroo Takayama, Linda Mongero, Joseph Zwischenberger, Joshua Sonett, Matthew Bacchetta. (2011) Safe Transport of Critically Ill Adult Patients on Extracorporeal Membrane Oxygenation Support to a Regional Extracorporeal Membrane Oxygenation Center. ASAIO Journal 57:5, 421-425
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Todd M. Morgan, Daniel A. Barocas, Sam S. Chang, Sharon E. Phillips, Shady Salem, Peter E. Clark, David F. Penson, Joseph A. Smith, Michael S. Cookson. (2011) The relationship between perioperative blood transfusion and overall mortality in patients undergoing radical cystectomy for bladder cancer. Urologic Oncology: Seminars and Original Investigations
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Michael N. Diringer, Thomas P. Bleck, J. Claude Hemphill, David Menon, Lori Shutter, Paul Vespa, Nicolas Bruder, E. Sander Connolly, Giuseppe Citerio, Daryl Gress, Daniel Hänggi, Brian L. Hoh, Giuseppe Lanzino, Peter Roux, Alejandro Rabinstein, Erich Schmutzhard, Nino Stocchetti, Jose I. Suarez, Miriam Treggiari, Ming-Yuan Tseng, Mervyn D. I. Vergouwen, Stefan Wolf, Gregory Zipfel. (2011) Critical Care Management of Patients Following Aneurysmal Subarachnoid Hemorrhage: Recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference. Neurocritical Care 15:2, 211-240
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Margaret M. Parker. (2011) Transfusion in pediatric sepsis: Less may not be more, but it is at least as good*. Pediatric Critical Care Medicine 12:5, 592-593
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Kristine Weiss Adams, Deborah Tolich. (2011) Original Research: Blood Transfusion: The Patient's Experience. AJN, American Journal of Nursing 111:9, 24-30
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Brian M. Gilliss, Mark R. Looney, Michael A. Gropper. (2011) Reducing Noninfectious Risks of Blood Transfusion. Anesthesiology 115:3, 635-649
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, C. W. Hamm, J.-P. Bassand, S. Agewall, J. Bax, E. Boersma, H. Bueno, P. Caso, D. Dudek, S. Gielen, K. Huber, M. Ohman, M. C. Petrie, F. Sonntag, M. S. Uva, R. F. Storey, W. Wijns, D. Zahger, , J. J. Bax, A. Auricchio, H. Baumgartner, C. Ceconi, V. Dean, C. Deaton, R. Fagard, C. Funck-Brentano, D. Hasdai, A. Hoes, J. Knuuti, P. Kolh, T. McDonagh, C. Moulin, D. Poldermans, B. A. Popescu, Z. Reiner, U. Sechtem, P. A. Sirnes, A. Torbicki, A. Vahanian, S. Windecker, , S. Windecker, S. Achenbach, L. Badimon, M. Bertrand, H. E. Botker, J.-P. Collet, F. Crea, N. Danchin, E. Falk, J. Goudevenos, D. Gulba, R. Hambrecht, J. Herrmann, A. Kastrati, K. Kjeldsen, S. D. Kristensen, P. Lancellotti, J. Mehilli, B. Merkely, G. Montalescot, F.-J. Neumann, L. Neyses, J. Perk, M. Roffi, F. Romeo, M. Ruda, E. Swahn, M. Valgimigli, C. J. Vrints, P. Widimsky. (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal
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Harvey G. Klein. 2011. Red-Cell Transfusion in Clinical Practice. , 213-220.
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A. Y. Mejaddam, G. C. Velmahos. (2011) Randomized controlled trials affecting polytrauma care. European Journal of Trauma and Emergency Surgery
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Yusuf Alper Kılıç, Ali Konan, Volkan Kaynaroğlu. (2011) Resuscitation and monitoring in gastrointestinal bleeding. European Journal of Trauma and Emergency Surgery 37:4, 329-337
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P.H. Pinkerton. (2011) Application of frozen plasma to red cell consumption ratios as a possible indicator for audit of use of frozen plasma in hospital clinical transfusion practice. Transfusion and Apheresis Science
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Marco Ranucci, Solomon Aronson, Wulf Dietrich, Cornelius M. Dyke, Axel Hofmann, Keyvan Karkouti, Marcel Levi, Gavin J. Murphy, Frank W. Sellke, Linda Shore-Lesserson, Christian von Heymann. (2011) Patient blood management during cardiac surgery: Do we have enough evidence for clinical practice?. The Journal of Thoracic and Cardiovascular Surgery 142:2, 249.e1-249.e32
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Yew Y. Ding, Boris Kader, Cindy L. Christiansen, Dan R. Berlowitz. (2011) Patient factors associated with transfusion practices in Veterans Affairs intensive care units: Implications for further research. Journal of Critical Care 26:4, 431.e1-431.e9
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Katerina Pavenski, Elianna Saidenberg, Marianne Lavoie, Melanie Tokessy, Donald R. Branch. (2011) Red Blood Cell Storage Lesions and Related Transfusion Issues: A Canadian Blood Services Research and Development Symposium. Transfusion Medicine Reviews
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Giuseppe Curinga, Amit Jain, Michael Feldman, Mark Prosciak, Bradley Phillips, Stephen Milner. (2011) Red blood cell transfusion following burn. Burns 37:5, 742-752
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Nadine Shehata, Laura Alexandra Burns, Howard Nathan, Paul Hebert, Gregory M.T. Hare, Dean Fergusson, C. David Mazer. (2011) A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery. Transfusionno-no
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P. D. Roux, J. Cooper, K. K. Guntupalli, R. Silbergleit, J. Daily, R. Geocadin, C. A. C. Wijman, J. I. Suarez. (2011) The Critical Care Research Networks Experience. Neurocritical Care
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R. G. Geocadin, T. P. Bleck, W. J. Koroshetz, C. S. Robertson, O. O. Zaidat, P. D. LeRoux, C. A. C. Wijman, J. I. Suarez. (2011) Research Priorities in Neurocritical Care. Neurocritical Care
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Jacques Lacroix, Paul Hébert, Dean Fergusson, Alan Tinmouth, Morris A. Blajchman, Jeannie Callum, Deborah Cook, John C. Marshall, Lauralyn McIntyre, Alexis F. Turgeon. (2011) The Age of Blood Evaluation (ABLE) Randomized Controlled Trial: Study Design. Transfusion Medicine Reviews 25:3, 197-205
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Howard A. Cooper, Sunil V. Rao, Michael D. Greenberg, Maria P. Rumsey, Marcus McKenzie, Kirsten W. Alcorn, Julio A. Panza. (2011) Conservative Versus Liberal Red Cell Transfusion in Acute Myocardial Infarction (the CRIT Randomized Pilot Study). The American Journal of Cardiology
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Marco Ranucci, Maria Teresa La Rovere, Serenella Castelvecchio, Roberto Maestri, Lorenzo Menicanti, Alessandro Frigiola, Andrea Maria D'Armini, Claudio Goggi, Roberto Tramarin, Oreste Febo. (2011) Postoperative Anemia and Exercise Tolerance After Cardiac Operations in Patients Without Transfusion: What Hemoglobin Level Is Acceptable?. The Annals of Thoracic Surgery 92:1, 25-31
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Isabelle Wauters, Johan Vansteenkiste. (2011) Erythropoiesis-stimulating agents in cancer patients: reflections on safety. Expert Review of Clinical Pharmacology 4:4, 467-476
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Richard L. Haspel, Lynne Uhl. (2011) How do I audit hospital blood product utilization?. Transfusionno-no
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Gregory M. T. Hare, James E. Baker, Katerina Pavenski. (2011) Assessment and treatment of preoperative anemia: Continuing Professional Development. Canadian Journal of Anesthesia/Journal canadien d'anesthésie 58:6, 569-581
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Anatole Harrois, Laurent Dupic, Jacques Duranteau. (2011) Targeting the microcirculation in resuscitation of acutely unwell patients. Current Opinion in Critical Care 17:3, 303-307
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Jose P. Sterling, David M. Heimbach. (2011) Hemostasis in burn surgery—A review. Burns 37:4, 559-565
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Leif-Erik Bohman, Gregory G. Heuer, Lukascz Macyszyn, Eileen Maloney-Wilensky, Suzanne Frangos, Peter D. Le Roux, Andrew Kofke, Joshua M. Levine, Michael F. Stiefel. (2011) Medical Management of Compromised Brain Oxygen in Patients with Severe Traumatic Brain Injury. Neurocritical Care 14:3, 361-369
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Natasha Kekre, Andrew Chou, Melanie Tokessey, Steve Doucette, Alan Tinmouth, Jason Tay, David S. Allan. (2011) Storage time of transfused red blood cells and impact on clinical outcomes in hematopoietic stem cell transplantation. Transfusionno-no
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Nicolas M. Van Mieghem, Rutger-Jan Nuis, Apostolos Tzikas, Nicolo Piazza, Carl Schultz, Patrick W. Serruys, Peter P. de Jaegere. (2011) Prevalence and prognostic implications of baseline anaemia in patients undergoing transcatheter aortic valve implantation. EuroIntervention 7:2, 184-191
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B Freidlin, E L Korn. (2011) Assessing causal relationships between treatments and clinical outcomes: always read the fine print. Bone Marrow Transplantation
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Bernadette Paessens, Angela Ihbe-Heffinger, Christoph Schilling, Rita Shlaen, Rudolf Bernard, Christian Peschel, Wolfgang Schramm, Karin Berger. (2011) Blood component use and associated costs after standard dose chemotherapy—a prospective analysis of routine hospital care in lymphoproliferative disorders and NSCLC in Germany. Supportive Care in Cancer
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Maria J. Colomina, Marcos Miguel, Andrés Pelavski, Dolors Castellá. (2011) Appropriateness of red blood cell use in orthopedic surgery and traumatology: analysis of transfusion practice. European Journal of Orthopaedic Surgery & Traumatology
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M. McKenny, T. Ryan, H. Tate, B. Graham, V. K. Young, N. Dowd. (2011) Age of transfused blood is not associated with increased postoperative adverse outcome after cardiac surgery. British Journal of Anaesthesia 106:5, 643-649
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Daniel N. Darlington, Angel V. Delgado, Bijan S. Kheirabadi, Chriselda G. Fedyk, Michael R. Scherer, Anthony E. Pusateri, Charles E. Wade, Andrew P. Cap, John B. Holcomb, Michael A. Dubick. (2011) Effect of Hemodilution on Coagulation and Recombinant Factor VIIa Efficacy in Human Blood In Vitro. The Journal of Trauma: Injury, Infection, and Critical Care1
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Pedro Kurtz, Vincent Fitts, Zeynep Sumer, Hillary Jalon, Joseph Cooke, Vladimir Kvetan, Stephan A. Mayer. (2011) How Does Care Differ for Neurological Patients Admitted to a Neurocritical Care Unit Versus a General ICU?. Neurocritical Care
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Etienne Gayat, Antoine Bodin, Caroline Sportiello, Mireille Boisson, Jean-François Dreyfus, Emmanuel Mathieu, Marc Fischler. (2011) Performance Evaluation of a Noninvasive Hemoglobin Monitoring Device. Annals of Emergency Medicine 57:4, 330-333
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James P. Isbister, Aryeh Shander, Donat R. Spahn, Jochen Erhard, Shannon L. Farmer, Axel Hofmann. (2011) Adverse Blood Transfusion Outcomes: Establishing Causation. Transfusion Medicine Reviews 25:2, 89-101
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J. Lacroix, M. Tucci. (2011) Impact clinique de la durée de conservation des globules rouges avant transfusion. Transfusion Clinique et Biologique 18:2, 97-105
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Katie Grimshaw, Julie Sahler, Sherry L. Spinelli, Richard P. Phipps, Neil Blumberg. (2011) New frontiers in transfusion biology: identification and significance of mediators of morbidity and mortality in stored red blood cells. Transfusion 51:4, 874-880
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Eleftherios C. Vamvakas. (2011) Establishing Causation in Transfusion Medicine and Related Tribulations. Transfusion Medicine Reviews 25:2, 81-88
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S. CARLSEN, A. PERNER, . (2011) Initial fluid resuscitation of patients with septic shock in the intensive care unit. Acta Anaesthesiologica Scandinavica 55:4, 394-400
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Cassandra D. Josephson, Simone A. Glynn, Steve H. Kleinman, Morris A. Blajchman. (2011) A multidisciplinary “think tank”: the top 10 clinical trial opportunities in transfusion medicine from the National Heart, Lung, and Blood Institute-sponsored 2009 state-of-the-science symposium. Transfusion 51:4, 828-841
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Pedro Cabrales, Juan Carlos Briceño. (2011) Delaying Blood Transfusion in Experimental Acute Anemia with a Perfluorocarbon Emulsion. Anesthesiology 114:4, 901-911
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Arash Afshari, Anne Wikkelsø, Jesper Brok, Ann Merete Møller, Jørn Wetterslev, Arash Afshari. 2011. Thrombelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy versus usual care in patients with massive transfusion. .
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Robert I. Parker. (2011) Red blood cell transfusions in children: Treat the child, not the number!*. Pediatric Critical Care Medicine 12:2, 226-228
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Jean-François Hardy, Philippe Linden, Dean Fergusson. (2011) If we have bandwagons, magic bullets, and theoretical constructs, why do we need randomized clinical trials in transfusion medicine and perioperative hemostasis?. Canadian Journal of Anesthesia/Journal canadien d'anesthésie 58:3, 240-245
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Makoto Kobayashi, Masayoshi Ko, Takashi Irinoda, Eiji Meguro, Yoshiro Hayakawa, Yuji Akiyama, Osamu Funato, Akinori Takagane. (2011) Clinical usefulness of continuous central venous oxygen saturation measurement for postoperative management of patients following transthoracic esophagectomy for carcinoma. Esophagus 8:1, 53-58
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George K. Istaphanous, Derek S. Wheeler, Steven J. Lisco, Aryeh Shander. (2011) Red blood cell transfusion in critically ill children: A narrative review*. Pediatric Critical Care Medicine 12:2, 174-183
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Chia-Jung Yang, Kuang-Yu Hsiao, I-Chun Su, I-Chuan Chen. (2011) The Association Between Anemia and the Mortality of Severe Traumatic Brain Injury in Emergency Department. The Journal of Trauma: Injury, Infection, and Critical Care1
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Stefan W. Leichtle, Nicolas J. Mouawad, Richard Lampman, Bonita Singal, Robert K. Cleary. (2011) Does Preoperative Anemia Adversely Affect Colon and Rectal Surgery Outcomes?. Journal of the American College of Surgeons 212:2, 187-194
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Kevin N Sheth, Aaron J Gilson, Yuchiao Chang, Mona A Kumar, Rosanna M Rahman, Natalia S Rost, Kristin Schwab, Lynelle Cortellini, Joshua N Goldstein, Eric E Smith, Steven M Greenberg, Jonathan Rosand. (2011) Packed Red Blood Cell Transfusion and Decreased Mortality in Intracerebral Hemorrhage. Neurosurgery1
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Enrico Vizzardi, Tania Bordonali, Elena Tanghetti, Marco Metra, Livio Dei Cas. (2011) Anaemia and heart failure. Central European Journal of Medicine 6:1, 11-25
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Laurent G. Glance, Andrew W. Dick, Dana B. Mukamel, Fergal J. Fleming, Raymond A. Zollo, Richard Wissler, Rabih Salloum, U. Wayne Meredith, Turner M. Osler. (2011) Association between Intraoperative Blood Transfusion and Mortality and Morbidity in Patients Undergoing Noncardiac Surgery. Anesthesiology 114:2, 283-292
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Jonathan Cohen, Ilya Kagan, Remos Hershcovici, Sylvianne Bursztein-De Myttenaere, Nicola Makhoul, Alexander Samkohvalov, Moshe Hersch, Sharon Einav, Vadim Berezovsky, Daniel Jorge Jakobson. (2011) Red blood cell transfusions—are we narrowing the evidence-practice gap? An observational study in 5 Israeli intensive care units
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W. Eisterer, C. Hussl, H. Erb, F. Haslbauer, S. Sormann, S. Braun, C. Jaeger. (2011) RETRA: evaluating the transfusion rate with darbepoetin alfa 500 µg every 3 weeks in anaemic cancer patients receiving chemotherapy. Current Medical Research and Opinion 27:2, 355-363
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Marta Ulldemolins, Marcos I. Restrepo, Jordi Rello. (2011) Medidas farmacológicas para la prevención de la neumonía asociada a la ventilación mecánica. Medicina Clínica 136:1, 21-25
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Robin Whyte, Haresh Kirpalani, Robin Whyte. 2011. .
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Garth H. Utter, Kiarash Shahlaie, Marike Zwienenberg-Lee, J. Paul Muizelaar. (2011) Anemia in the Setting of Traumatic Brain Injury: The Arguments For and Against Liberal Transfusion. Journal of Neurotrauma 28:1, 155-165
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Kelly L. West, Cory Adamson, Maureane Hoffman. (2011) Prophylactic correction of the international normalized ratio in neurosurgery: a brief review of a brief literature. Journal of Neurosurgery 114:1, 9-18
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Simon J Stanworth, Timothy S Walsh, Robin J Prescott, Robert J Lee, Douglas M Watson, Duncan Wyncoll, . (2011) A national study of plasma use in critical care: clinical indications, dose and effect on prothrombin time. Critical Care 15:2, R108
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Tina L. Palmieri, Soman Sen, Katrina Falwell, David G. Greenhalgh. (2011) Blood Product Transfusion: Does Location Make a Difference?. Journal of Burn Care & Research 32:1, 61-65
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Jason Tay, Alan Tinmouth, Dean Fergusson, David Allan. (2011) Transfusion of red cells in hematopoietic stem cell transplantation (TRIST): study protocol for a randomized controlled trial. Trials 12:1, 207
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Ville Pettilä, Andrew J Westbrook, Alistair D Nichol, Michael J Bailey, Erica M Wood, Gillian Syres, Louise E Phillips, Alison Street, Craig French, Lynnette Murray, Neil Orford, John D Santamaria, Rinaldo Bellomo, David J Cooper, . (2011) Age of red blood cells and mortality in the critically ill. Critical Care 15:2, R116
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Jill M. Cholette, Jeffrey S. Rubenstein, George M. Alfieris, Karen S. Powers, Michael Eaton, Norma B. Lerner. (2011) Children with single-ventricle physiology do not benefit from higher hemoglobin levels post cavopulmonary connection: Results of a prospective, randomized, controlled trial of a restrictive versus liberal red-cell transfusion strategy*. Pediatric Critical Care Medicine 12:1, 39-45
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Elie Azoulay, Marcio Soares, Michael Darmon, Dominique Benoit, Stephen Pastores, Bekele Afessa. (2011) Intensive care of the cancer patient: recent achievements and remaining challenges. Annals of Intensive Care 1:1, 5
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L. T. Goodnough, A. Maniatis, P. Earnshaw, G. Benoni, P. Beris, E. Bisbe, D. A. Fergusson, H. Gombotz, O. Habler, T. G. Monk, Y. Ozier, R. Slappendel, M. Szpalski. (2011) Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines. British Journal of Anaesthesia 106:1, 13-22
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Arasch Wafaisade, Marc Maegele, Rolf Lefering, Maximilian Braun, Sigune Peiniger, Edmund Neugebauer, Bertil Bouillon. (2011) High Plasma to Red Blood Cell Ratios Are Associated With Lower Mortality Rates in Patients Receiving Multiple Transfusion (4 ≤ Red Blood Cell Units < 10) During Acute Trauma Resuscitation. The Journal of Trauma: Injury, Infection, and Critical Care 70:1, 81-89
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K. Huber, C. W. Hamm, J.-P. Bassand, S. Agewall, J. Bax, E. Boersma, H. Bueno, P. Caso, D. Dudek, S. Gielen. (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). European Heart Journal
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M. F. Murphy, S. J. Stanworth, M. Yazer. (2011) Transfusion practice and safety: current status and possibilities for improvement. Vox Sanguinis 100:1, 46-59
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