Safe and successful restriction of transfusion
- 1. Safe and Successful Restriction of Transfusion in Burn Patients Peter Kwan, BSc (Eng), MD, Manuel Gomez, MD, MSc, Robert Cartotto, MD, FRCS(C) An acceptable strategy for transfusion of burn patients has not been specifically identified. In 1999, we empirically adopted a hemoglobin (Hb) transfusion trigger of 7.0 g/dl or greater in our burn center. The purpose of this study was to evaluate the effects of this re- strictive transfusion strategy. Retrospective comparison of adults with 20% or greater TBSA treated from 1999 to 2004 (restrictive group; REST) with patients treated before our adoption of the restrictive transfusion strategy (1997–1998: liberal group; LIB). The REST group (n 135, age 42 17 years, %TBSA burn 37 14, and 26% incidence of inhalation injury) did not differ significantly from the LIB group (n 37, age 42 16 years, %TBSA burn 38 17, and 35% inhalation injury). The Hb triggering a transfusion was 7.1 1.2 g/dl in the REST group, compared with 9.2 2.1 g/dl in the LIB group (P < .001). The REST group received significantly fewer units of blood per day than the LIB Group. Pa- tients in the REST group appeared to have significantly better organ function, and there were no differences between the groups in the incidence of acute myocardial infarction. Mortality at 30 days was significantly lower in the REST group (19% vs 38%; P .03), as was overall in-hospital mortality (22% vs 46%; P .003). Transfusion restriction appears to be safe and resulted in fewer transfusions among this group of burn patients. Prospective studies are needed before broadly recommending a transfusion trigger of 7.0 g/dl. (J Burn Care Res 2006;27:826–834) Anemia frequently develops in thermally injured nephrine tumescence and tourniquets have signifi- patients who have sustained burns to more than cantly reduced operative blood loss,9,10 the fact 10% TBSA.1–3 Postburn anemia has a wide variety remains that 100 ml to 250 ml of blood (or 2% to of causes. First, acute erythrocyte destruction from 5% of the circulating blood volume) are shed for thermal and inflammatory insults, combined with every 1% BSA that is excised and grafted.9,11 Fi- sequestration of erythrocytes within the throm- nally, burn patients, especially those that are criti- bosed microcirculation of the burn wound,4 – 6 re- cally ill, are repetitively phlebotomized for labora- sults in a loss of up to 18% of erythrocytes within 24 tory studies and monitoring. Although the amount hours of a 15% to 40% TBSA full-thickness burn.2 of blood drawn from burn patients has not been Second, despite supranormal erythropoietin levels, specifically studied, a recent prospective observa- the marrow response to erythropoietin appears to tional study of more than 1000 critically ill patients be suppressed after burn injury, resulting in slug- in the intensive care unit found that a mean of 41 gish erythrocyte production.7,8 Third, burn pa- ml of blood was drawn in a 24-hour period purely tients are subjected to regular blood loss as they for laboratory investigations.12 It would be reason- undergo staged excisions of the burn wound and able to assume that critically ill burn patients lose at harvesting of skin grafts. Although the use of epi- least this much blood on a daily basis, solely for diagnostic purposes. Consequently, patients with significant burns will From the The Ross Tilley Burn Centre, Sunnybrook and Women’s College Health Sciences Centre, Toronto, Canada. likely develop anemia, which almost certainly will be Address correspondence to Dr. R. Cartotto, Room D710, Ross treated with one or more blood transfusions. Histor- Tilley Burn Centre, Sunnybrook Health Sciences Centre, 2075 ically, the decision as to when to transfuse a patient Bayview Avenue, Toronto, Ontario, Canada M4N 3M5. Copyright © 2006 by the American Burn Association. was largely based on an arbitrary hemoglobin or he- 1559-047X/2006 matocrit level (or “trigger”), and was based to a lesser DOI: 10.1097/01.BCR.0000245494.45125.3E extent on the presence of a clinical hemodynamic 826
- 2. Journal of Burn Care & Research Volume 27, Number 6 Kwan, Gomez, and Cartotto 827 indication, such as myocardial ischemia or acute were identified using our burn center’s computerized blood loss during surgery. The “classic” trigger for database. Charts of eligible subjects were then re- many years was a hemoglobin level less than 10 g/dl trieved from the hospital’s health data records ser- or a hematocrit less than 30%. Recently, Palmieri vices. Transfusion records were retrieved from the et al13,14 conducted multicenter surveys of North hospital blood services laboratory patient database. American burn centers and found that burn physi- Patients with %TBSA burns 20% or greater who sur- cians reported a mean transfusion threshold of 8.1 vived at least 24 hours were eligible for inclusion in g/dl.13 However, on closer examination of data from the study. Exclusion criteria included age younger 666 patients with burns 20% TBSA or greater,14 the than 16 years, presence of associated trauma, known hemoglobin levels at first and last transfusions were diagnosis of chronic anemia at admission (hemoglo- 9.4 g/dl and 9.1 d/l, respectively, suggesting a trans- bin 13.5 g/dl in male patients, 12.0 g/dl in fe- fusion trigger higher than 9 g/dl. male patients), missing or incomplete records, and a These transfusion triggers for burn patients are patient’s declaration of personal or religious reason higher and at odds with transfusion thresholds now for refusing blood transfusions. recommended for other critically ill patients. The Transfusion Requirements in Critical Care (TRICC) Study Groups Trial15 prospectively randomized 838 patients in the Eligible subjects were assigned to one of two study intensive care unit (ICU) to either a restrictive trans- groups based on our adoption of a transfusion trigger fusion strategy using a trigger of 7 g/dl with a goal of 7.0 g/dl in 1999, following publication of the hemoglobin level of 7 to 9 g/dl or to a liberal trans- TRICC Trial.15 Patients treated in the 2 years before fusion strategy using a trigger of 10 g/dl with a goal 1999, during which time we were not using a trans- hemoglobin level of 10 to 12 g/dl. Patients in the fusion trigger of 7.0 g/dl (ie, from January 1, 1997, restricted transfusion group received less blood, ex- to December 31, 1998) formed the liberal transfu- perienced slightly less organ dysfunction, and had sion group (LIB). Patients treated after adoption of comparable mortality with those in the liberal group, the 7.0 g/dl transfusion threshold (ie, from April 1, indicating that the restrictive strategy was at least as 1999, to May 3, 2004), were assigned to the restric- effective as the liberal strategy. tive transfusion group (REST). A 2-year period was The appropriate transfusion trigger for a burn pa- selected for the LIB group because significant changes tient is not known. In 1999, after the publication of in patient care took place in 1996 with the appointment the TRICC trial, we adopted a transfusion trigger of of a new burn director in our unit at that time. Because 7 g/dl for patients in our burn center. This decision we wished to avoid the confounding influence of was done empirically, although there was some lim- changes in practice patterns that took place in 1996, we ited evidence from two small studies to suggest that selected only the 1997 to 1998 period for the LIB transfusion thresholds significantly lower than the 10 group. g/dl or 30% hematocrit level were well tolerated by burn patients.16,17 The purpose of the present study Data Collection was to evaluate the effects of implementing a restric- Data were collected and analyzed during the first 30 tive transfusion strategy with a transfusion trigger of days post burn or until discharge or death if either 7.0 g/dl among adult burn patients treated at our occurred before 30 days after injury. Admission data facility. Specifically, we were interested in whether included age, etiology of burn, %TBSA burns, the intended transfusion threshold was achieved, APACHE II score, and presence of inhalation injury whether less blood was transfused, and whether the diagnosed by bronchoscopic examination.18 Physio- restrictive approach affected outcomes such as organ logic variables were obtained daily and included the function, length of stay, duration of mechanical ven- PaO2/FiO2 ratio, serum creatinine concentration, tilation, and survival. serum bilirubin concentration, and the platelet count. If the variable had been measured more than once on a given day, the value closest to 8 AM on that day was METHODS recorded. Data pertaining to anemia and transfusion included the daily hemoglobin concentration (again, Study Design, Inclusion, and if more than one determination, the value closest to 8 Exclusion Criteria AM was selected), the number of diagnostic blood This study was an Ethics Review Board-approved, draws per day, the number of units of blood trans- retrospective chart review by one researcher at an fused daily in all settings (burn unit and operating adult regional burn center. Eligible study patients room), and the hemoglobin concentration before
- 3. Journal of Burn Care & Research 828 Kwan, Gomez, and Cartotto November/December 2006 transfusion of blood. If a transfusion involved more imum (worst) score of 24 as a means of adjusting the than 1 unit of blood, the hemoglobin before the first measured organ dysfunction for death (“the adjusted unit was recorded as representative of all units given MOD score”). The Delta Multiple Organ Dysfunc- at that transfusion, unless the hemoglobin concentra- tion score ( MOD score) is the difference between tion was specifically measured between units, in the MOD score on admission and the overall worst which case this value also was recorded for the re- MOD score during hospitalization, and was used to maining units that were administered at that transfu- measure the change in organ dysfunction over time. sion. For blood transfused in the operating room, The presence of sepsis, as defined by the ACCP/ the preoperative hemoglobin concentration was re- SCCM Consensus Criteria20 (ie, 2 or more positive corded as the pretransfusion hemoglobin, unless the SIRS signs: temperature 36°C or 38°C, heart rate hemoglobin was measured intraoperatively, in which 90 beats/min, white blood cell count 4000/mm3 case this value also was recorded as a hemoglobin or 11,000/mm3, and respiratory rate 20 breaths/ before transfusion. min or PaCO2 32 mm Hg and the presence of a documented infection), was assessed daily over the en- Transfusion Protocol tire hospital stay for each patient. Because this study was not prospective, patients were not subjected to a rigid transfusion protocol. In the Statistical Analysis LIB group, which was treated before 1999, blood was All values are reported as the mean SD unless oth- transfused at an undefined hemoglobin threshold. In erwise stated. The means of continuous variables be- the REST group, which was treated after 1999, a trans- tween groups were compared using a two-tailed Stu- fusion threshold of 7 g/dl was adopted by the physi- dent’s t-test, whereas categorical variables were cians in our burn center. This threshold was not rigidly compared with the 2 test. A P value .05 was con- enforced but was progressively adopted on an empiric sidered statistically significant. basis after publication of the TRICC trial.15 Single or multiple unit transfusions were allowed, but, unlike the TRICC trial, hemoglobin concentrations were RESULTS not measured before and after each and every unit of blood transfused. Our blood bank supplies units of Study Populations blood, which range in volume between 240 and 340 Between January 1 1997 and December 1998, there ml, with a hematocrit of approximately 80%. Begin- were 59 patients who were potentially eligible for ning in April of 1999, all blood supplied to our facility inclusion in the LIB group. Of these, 6 were excluded by the Canadian Blood Service was in the form of as a result of death within 24 hours of injury, and 16 leuko-reduced packed red blood cells. were excluded because of missing or incomplete records. This left 37 subjects who formed the LIB Outcome Measures group. Between April 1, 1999, and May 3, 2004, Outcome measures included mortality from all causes there were 143 patients who potentially were eligible at 30 days, the in-hospital mortality rate, hospital for inclusion in the REST group. Of these, five were length of stay, and the duration of mechanical venti- excluded because of death within 24 hours of injury, lation. The duration of mechanical ventilation was two were excluded because of presence of associated defined as the time from intubation to the time where polytrauma, and one was excluded because of missing there had been 48 consecutive hours without any records. This left 135 patients who formed the REST mechanical ventilation support, not including oxygen group. The baseline characteristics of the two groups administration by face mask, tracheostomy mask, or are shown in Table 1. There were no significant differ- nasal prongs. ences between the groups with respect to age, total or Organ dysfunction was measured by the raw values full-thickness burn size, presence of inhalation injury, of the PaO2/FiO2 ratio (respiratory system), serum APACHE II score, timing of first wound excision, or creatinine concentration (renal system), serum biliru- total number of operative procedures (Table 1). bin concentration (hepatic system), and the platelet count (hematologic system). The Multiple Organ Anemia and Transfusion Dysfunction Score, defined by Marshall et al,19 as- The mean daily hemoglobin level over the first 30 signs a score of 0 (best) to 4 (worst) to each of 6 organ days after burn was 10.2 2.3 g/dl in the LIB group systems (Appendix 1). A daily MOD score was deter- and 8.6 2.2 g/dl in the REST group (P .001). mined for each patient as described by Marshall et Also, the mean hemoglobin concentration was signif- al,19 and then patients who died were assigned a max- icantly lower in the REST group on each day after the
- 4. Journal of Burn Care & Research Volume 27, Number 6 Kwan, Gomez, and Cartotto 829 Table 1. Baseline comparison of the liberal transfusion group (LIB) and the restrictive transfusion group (REST) with respect to patient age, %TBSA burns, %TBSA full-thickness burns, admission APACHE II score, postburn day of the first burn wound excision, and total number of operations performed in the first 30 days after burn LIB REST P Value N 37 135 Age SD, years 42 16 42 17 .914 %TBSA burn SD 38 17 37 14 .899 %TBSA full thickness SD 19 18 15 18 .323 Admission APACHE II SD 14 9 16 8 .219 Inhalation injury 13/37 (35%) 35/135 (26%) .211 Day first wound excision 4.4 3.6 4.4 4.4 .936 Total trips to operating room per 30 days 2.6 2.6 3.2 2.3 .15 fourth day after burn injury (P .01; Figure 1). The REST group (P .539). Within each group, signif- pretransfusion hemoglobin (ie, the “transfusion trig- icantly more blood was transfused in the burn unit as ger”) was 9.2 2.1 g/dl in the LIB group and 7.1 compared with in the operating room (LIB group: 1.0 in the REST group (P .001). The %TBSA burn 6.3 7.5 units vs 3.1 4.3 units, respectively, P did not affect the transfusion threshold in the REST .03; REST group: 7.1 7.4 units vs 1.6 2.9 units, group. Patients with 40% or greater TBSA (n 51) respectively, P .001). The difference between the had a pretransfusion hemoglobin of 7.0 10.0 g/dl, LIB and REST groups in the number of burn unit whereas those with burns less than 40% TBSA (n transfusions was not significant (P .583), but there 84) had a pretransfusion hemoglobin of 7.1 10.3 were significantly fewer operating room transfusions g/dl (P .350). Conversely, patient age did influ- in the REST group (P .02). A post-hoc subgroup ence the pre-transfusion hemoglobin threshold in the analysis was performed in the REST group to exam- REST Group: 7.4 8.7 g/dl in patients older than ine only patients who always had a pretransfusion 60 years of age (n 23) vs. 6.9 10.0 in patients hemoglobin less than 7.5 g/dl (ie, those that most younger than 60 years of age (n 112; P .001). closely followed the restrictive strategy). There were The mean daily transfusion rate over the first 30 80 patients who always met the criteria of a pretrans- days after burn was significantly greater in the LIB fusion hemoglobin less than 7.5 g/dl. This subgroup group than in the REST group (0.6 0.6 units/ received a mean of 3.9 5.6 units of blood over the patient/day vs 0.4 0.4 units/patient/day, P first 30 days after burn, which was significantly lower .03). The postburn day of the first transfusion was 4.9 than the patients in the LIB group (n 37), who 2.8 days in the LIB group and 5.3 3.1 days in the received 6.3 7.3 units of blood in the first 30 days Figure 1. Mean SD daily hemoglobin concentration over the first 30 days after burn in the restrictive group (closed triangles) and the liberal group (closed circles). The mean daily hemoglobin concentration is significantly lower on all days in the restrictive group after postburn day 4 (P .01).
- 5. Journal of Burn Care & Research 830 Kwan, Gomez, and Cartotto November/December 2006 units transfused to patients in the REST group was 18 8 days. Outcomes The 30-day mortality rate was 38% in the LIB group and 19% in the REST group (P .03). Overall in-hospital mortality also was significantly greater in the LIB group than in the REST group (46% vs 22 %, P .003). The daily % survival rates in each group over the first 30 days after burn are shown in Figure 2. Comparison of demo- Figure 2. Plot of the percent survival on each day post burn graphic data between survivors and nonsurvivors in each in the restrictive group (closed triangles) and the liberal group is provided in Table 2. group (closed circles). The adjusted MOD score was significantly higher (worse) in the LIB Group than in the REST Group (7.9 2.5 vs 6.4 1.0, respectively, P .004), (P .05). Finally, among those patients who had no (Figure 3). However, the MOD score, where a transfusions during the first 30 days after burn, the higher value represents a greater deterioration in or- LIB group had significantly fewer transfusion-free gan function over time, did not differ significantly days than the REST group: in the LIB group, 8 of 37 between the LIB and REST groups (3.5 3.3 vs patients (22%) received no blood whatsoever over 3.7 2.9, respectively, P .614). It was observed 12.6 6.9 days while alive and in hospital, whereas in that despite a 3-fold difference in sample size between the REST group, 35 of 135 patients (26%) received the LIB and REST groups, there was a 6-fold differ- no blood whatsoever over 19.6 8.3 days while alive ence in the number of laboratory measures of vari- and in-hospital (P .03). ables used to determine the MOD score (PaO2/FiO2 ratio, creatinine, platelet count, bilirubin), with 1372 Single vs Multiple Unit Transfusions, measures in the LIB group vs 8000 measures in the Age of Blood REST group. In the LIB group, there were 5.3 8.6 In the LIB group, 18% of all transfusions were single- separate episodes of consensus criteria defined sepsis unit transfusions, whereas 82% were multiple unit over the entire hospital stay, compared to 4.7 5.4 ( 2 unit) transfusions. The mean number of units episodes in the REST group (P .624). transfused at a multiunit transfusion was 2.2 0.4 The incidence of mechanical ventilation was 51% in units. In the REST group, 34% of transfusions were the LIB group and was 74% in the REST group (P single unit, and 66% were multiple-unit transfusions. .004). The duration of mechanical ventilation was The mean number of units transfused at a multiple- 14 11 days in the LIB group and 20 18 days in unit transfusion in the REST group was 2.1 0.2 the REST group (P .151). Overall hospital length units. The difference in proportion of single vs multiple- of stay was not significantly different between the LIB unit transfusions between the LIB and REST groups and REST groups (45 88 days vs 44 38 days, was statistically significant (P .01). Data for the respectively, P .942). The incidence of acute myo- stored age of blood units transfused in the LIB group cardial infarction over the entire hospital stay was 2.7% were not available, but the mean storage age of all in the LIB group and 2.9 % in the REST group. Table 2. Comparison of mean SD age, %TBSA, %BSA full thickness burn (%BSA full), and incidence of smoke inhalation injury in survivors and nonsurvivors in the liberal transfusion group (LIB) and the restrictive transfusion group (REST) LIB Group REST Group Survivors Nonsurvivors Survivors Nonsurvivors Age, years 37 12 49 17 40 15 50 18 %TBSA burn 37 10 44 20 36 14 45 16 %BSA full 11 13 27 18 12 16 26 21 Inhalation injury 5/20 (25%) 8/17 (47%) 22/105 (21%) 13/30 (43%)
- 6. Journal of Burn Care & Research Volume 27, Number 6 Kwan, Gomez, and Cartotto 831 Figure 3. Graph showing the daily adjusted Multiple Organ Dysfunction score in the restrictive group (closed Triangles) and the liberal group (closed circles). DISCUSSION tration of 8.6 1.7 g/dl, suggesting that although transfusion triggers in the critically ill are lower than In 1999, after the publication of the TRICC trial,15 the historical level of 10 g/dl, they have not been which recommended a transfusion threshold of 7.0 uniformly or consistently reduced to the level of 7.0 g/dl for critically ill patients in the intensive care unit, g/dl identified in the TRICC trial. This alone is an we empirically adopted a transfusion trigger of 7.0 interesting observation on the relative success or fail- g/dl in our adult regional burn center. The results of ure of adopting evidence based guidelines in clinical the present study indicate that among adult burn pa- practice. Furthermore, the significant reduction in in- tients with burns 20% or greater TBSA, we success- cidence of multiple-unit transfusions from 82% in the fully achieved a transfusion trigger very close to 7.0 LIB group to 66% in the REST group is further evi- g/dl and that over the first 30 days after burn, this dence of a profound shift in our clinical approach to resulted in a significantly lower daily hemoglobin transfusion of blood. concentration and significantly less transfusion of blood than in the 2-year period before 1999, during The appropriate transfusion trigger for a burn pa- which we did not use a 7.0 g/dl trigger. Further- tient is not known. The recent multicenter study of more, burn patients treated during the period when transfusion among 666 patients with 20% or greater we used a restrictive transfusion protocol demon- TBSA treated in North American Burn Centers re- strated less organ dysfunction and improved survival vealed that the mean hemoglobin concentrations be- compared with their counterparts who were treated fore the first and last transfusions were 9.4 g/dl and with a more liberal transfusion approach. 9.1 g/dl, respectively. Two small studies in burn pa- We were encouraged to find that the transfusion tients have evaluated the use of lower transfusion trigger of 7.0 g/dl was successfully implemented de- thresholds than these. Sittig and Deitch16 prospec- spite the absence of a rigid protocol. This finding is in tively compared a restrictive approach to transfusion contrast to results obtained from two very large pro- (transfusion for hemoglobin 6.0 g/dl) in 14 pa- spective multicenter studies on transfusion in the crit- tients (mean of 28% TBSA burns), with a historical ically ill that were published subsequent to the control group of 38 patients (mean of 26% TBSA TRICC trial. In the Anemia and Blood Transfusion in burns), where a liberal transfusion strategy was ap- Critically Ill Patients (ABC) Ttrial,12 3534 patients in plied (hemoglobin maintained 10 g/dl). The re- Western Europe were transfused for a mean ( SD) strictive strategy significantly reduced blood transfu- pretransfusion hemoglobin concentration of 8.5 sions and did not cause any apparent adverse clinical 1.1 g/dl. In the CRIT study,21 4892 critically ill pa- effects. In a retrospective study by Mann et al,17 41 tients in the United States were transfused blood for patients with burns greater than 10% TBSA treated in at a mean ( SD) pretransfusion hemoglobin concen- 1980 were compared with 38 patients with burns
- 7. Journal of Burn Care & Research 832 Kwan, Gomez, and Cartotto November/December 2006 greater than 10% TBSA treated in 1990. There was a ever, we felt that any clinically relevant change in the significant reduction in blood transfused between the variable would have persisted for more than 24 hours earlier and later time periods. Although transfusion and would have been captured at the next 8 AM re- thresholds were not reported in that study, the au- cording. It should also be noted that this approach thors suggested that the reduction in transfusion was has been used in other well validated studies such as partially related to a reduction in the hematocrit that used to develop the MOD score, by Marshall et transfusion threshold from 30% in the earlier period al.19 Also, the REST group had a disproportionately to 15% to 20% in the later period. Although both of greater number of laboratory values measured relative these studies are limited by small size and their retro- to the LIB group. Although we cannot specifically spective design, they provide an important first step in explain the reason for this, it is possible that patients considering the concept of restricted transfusion in the REST group were being more closely moni- strategies in burn patients. tored, which may have contributed to the improved The results of our study would suggest that for outcomes seen in this group. Also, fewer operating burn patients with burns 20% TBSA, a restrictive room transfusions were given in the REST group transfusion approach using a trigger of 7.0 g/dl is safe than in the LIB group. Therefore, some of the ob- and at least as effective as the previous trigger of 9.2 served reduced transfusion requirements in the REST g/dl, which we used before 1999. It is essential to group may simply have been from less surgical blood emphasize, however, that this approach must be loss. However, because intraoperative transfusion in tested in a randomized prospective fashion because of our institution is based on measured hemoglobin lev- the limitations inherent in a retrospective analysis els rather than on empiric grounds and because there such as this. In particular, the use of a historical con- were no major changes in surgical technique (eg, use trol group, with a relatively limited number of sub- of tumescence and tourniquets) between the LIB and jects and where several cases were excluded because of REST groups, we believe this is a relatively minor missing records, are all important potential sources of consideration. error. In particular, the small sample size in the LIB We cannot rule out the contributory effects of group may have been partly to blame for the relatively changes in ICU care that have taken place duringthe high reported mortality rate in this group. Another 7-year span of this study. The difference in the inci- important consideration in the present study is that dence of mechanical ventilation, for example, might Hb was not measured before and after each and every suggest that the REST group was being managed unit of blood transfused, as was done in the TRICC more aggressively. Also, although there were no spe- trial.15 Thus, the transfusion threshold may actually cific changes in protocol over the study period, there have been greater than that reported because some have been evolving trends in critical care such as use of units of blood could have been transfused at a higher lung protective ventilation, and more restricted se- (but unidentified) threshold. We would expect this rum glucose control, that may well have contributed undermeasurement of the transfusion threshold to to the reported differences in outcomes. Finally, have been more profound in the LIB group since the blood transfused after 1999 (ie, that given to patients vast majority of transfusions in that group (82%) in- in the REST group) was leukoreduced, and it is con- volved two or more units of blood, whereas in the ceivable that this also played a role in the better out- later REST group, we would expect less of an under- come seen in the REST group. measurement of threshold because a significantly lower The much-anticipated randomized prospective study proportion of transfusions (66%) were multiple-unit of restrictive vs liberal approaches to transfusion in burn transfusions. However, the mean number of units patients, currently being organized through the Burn transfused at a multiple-unit transfusion in both Multi-Center Trials Group of the American Burn As- groups was just more than 2 units per transfusion, so sociation, will address the limitations in our study and it seems unlikely that recording of Hb before each will likely provide more definitive guidelines on trans- and every unit of blood would have produced sub- fusion thresholds for burn patients. However, we be- stantially different results. lieve that the findings of this study support the notion Another limitation in this study was that we col- that a more restrictive approach to transfusion is safe lected data closest to 8 AM hours when more than one and well tolerated among adult burn patients. recorded variable was recorded in a 24-hour period. The question of whether a higher transfusion We did this to be as consistent and standardized as threshold should be used in an elderly burn patient or possible, but the potential downside of this approach in a burn patient with a known history of coronary is that we may have not captured deterioration or artery disease has not been answered by this study. Of improvement in a variable in some patients. How- interest was that our transfusion threshold was signif-
- 8. Journal of Burn Care & Research Volume 27, Number 6 Kwan, Gomez, and Cartotto 833 icantly higher in patients older than 60 years of age hours after injury was an independent predictor of compared to those younger than age 60, despite the MOF and that there was a dose-response relationship fact that we did not predefine any specific adjustments between early blood transfusion and the severity of for patient age to our restrictive strategy. Interest- later MOF. Thus, transfusion of blood appears to be ingly, in the TRICC trial,15 neither age older than 55 harmful in many respects and, therefore, the restric- years nor the presence of cardiac disease had any effect tion of transfusion would be expected to be associ- on mortality in patients treated with a restrictive ated with improved outcomes. The results of the transfusion strategy. present study support this concept. Although we can- Blood transfusion is not a benign therapy. The use not directly relate the improved survival and reduced of blood products, specifically whole blood and organ dysfunction to the lower transfusion rate in the packed red blood cells, introduces a variety of risks REST group, our results indicate that a restricted and morbidities. Risks include transfusion reactions, transfusion policy is at least as safe and effective as a transfusion related bacterial sepsis, and infectious dis- liberal approach to transfusion. The improvements in ease transmission from donor to recipient.22–24 The outcome may well have been related to other im- morbidity associated with blood transfusion mainly provements in treatment and accumulation of expe- revolves around immunosuppressive effects on the rience that occurred over the seven year span of this recipient.25–29 Studies in animal burn models and hu- study. Nevertheless, the 7.0 g/dl transfusion thresh- mans with burns demonstrate that blood transfusion old identified in the present study provides an impor- depresses immune function and increases the risks of tant preliminary step which must now be more care- infectious complications.30 –34 There was a statisti- fully scrutinized in a prospective randomized study in cally insignificant trend toward fewer episodes of sepsis in the REST group, which may reflect less burn patients. transfusion-related immunosuppression with the re- strictive transfusion strategy. The development of transfusion-related acute lung injury, defined clini- CONCLUSION cally as a syndrome of acute lung injury that develops during or within 6 hours of transfusion, is also an In this study, a restrictive transfusion strategy resulted emerging potential risk now recognized to be associ- in significant decreases in the number of blood trans- ated with transfusion.35 The potential adverse effects fusions given to burn patients accompanied by a sig- associated with blood transfusion have been demon- nificant decrease in 30-day and overall mortality. The strated in both the ABC trial12 and the CRIT study21 use of a restrictive transfusion strategy for burn pa- which, when combined, involved more than 8000 tients is recommended. Although the results of this ICU patients. In both of these studies, the amount of study support the use of restrictive blood transfusion transfused blood was independently associated with strategies in burn patients, a large-scale randomized increased mortality. Similarly, among trauma pa- controlled trial is needed to definitively study the tients, blood transfusion increases the risk of subse- problem. The resulting outcomes could help deter- quent multiorgan failure (MOF). In a study of 513 mine whether a restrictive strategy is truly beneficial consecutive trauma patients, Moore et al36 demon- for burn patients, and potentially which subgroups of strated that blood transfusion during the first 12 burn patients would most benefit. Appendix 1. The Multiple Organ Dysfunction Score19 SCORE 0 1 2 3 4 PaO2/FiO2 300 226–300 151–225 76–150 75 Creatinine ( mol/l) 100 101–200 201–350 351–500 500 Bilirubin ( mol/l) 20 21–60 61–120 121–240 240 Pulse-adjusted heart rate (PAR) 10 10.1–15.0 15.1–20 20.1–30 30 (heart rate central venous pressure/mean arterial pressure) Platelets/ml, 10–3 120 81–120 51–80 21–50 20 Glasgow Coma Scale 15 13–14 10–12 7–9 6
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