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Red blood cell transfusion within the first 24 hours of admission is associated with increased mortality in the pediatric trauma population: a retrospective cohort study
© Stone et al; licensee BioMed Central Ltd. 2008
Received: 27 May 2008
Accepted: 20 October 2008
Published: 20 October 2008
Allogeneic red blood cell transfusion is associated with increased morbidity and mortality in adult trauma patients. Although studies have suggested that the adoption of a more restrictive transfusion strategy may be safely applied to critically ill adult and all-cause critically ill pediatric patients, recent developments in our understanding of the negative consequences of red blood cell transfusion have focused almost entirely on adult populations, while the applicability of these findings to the pediatric population remains poorly defined. The object of this study was to evaluate the effect of red blood cell transfusion within the first 24 hours following admission on mortality in pediatric trauma patients treated at our institution.
Age, race, and mechanism of injury did not differ between transfused and non-transfused groups, although there were significantly more female patients in the transfusion group (51 vs. 37%; p < 0.01). Shock index (pulse/systolic blood pressure), injury severity score, and new injury severity score were all significantly higher in the transfused group (1.21 vs. 0.96, 26 vs. 10, and 33 vs. 13 respectively; all p ≤ 0.01). Patients who received a red blood cell transfusion experienced a higher mortality compared to the non-transfused group (29% vs. 3%; p < 0.001). When attempting to control for injury severity, goodness-of-fit analysis revealed a poor fit for the statistical model preventing reliable conclusions about the contribution of red blood cell transfusion as an independent predictor of mortality.
Red blood cell transfusion within the first 24 hours following admission is associated with an increase in mortality in pediatric trauma patients. The potential contribution of red blood cell transfusion as an independent predictor of hospital mortality could not be assessed from our single-institution trauma registry. A review of state-wide or national trauma databases may be necessary to obtain adequate statistical confidence.
Nonoperative management of blunt traumatic injury is now a widely accepted practice in hemodynamically stable patients[1, 2]. The transfusion of allogeneic packed red blood cells (PRBCs) is employed to attenuate reductions in hemoglobin. An increase in serum hemoglobin will increase the oxygen-carrying capacity of the blood, which theoretically provides more oxygen to vital tissues malperfused in the shock state. However, recent studies have associated adverse hospital outcomes with therapeutic blood transfusions in adult patients. Allogeneic blood transfusion has been reported to be an independent predictor of hospital mortality in adult trauma patients [1–4]. Additionally, PRBC transfusion is associated with an increased risk of infection , multisystem organ failure (MSOF),[6, 7] and systemic inflammatory response syndrome (SIRS) in adult trauma patients. Additional studies have suggested that the adoption of a more restrictive transfusion strategy may be safely applied to critically ill adult patients,[8, 9] and all-cause critically ill pediatric patients.
Recent developments in our understanding of the negative consequences of PRBC transfusion have focused almost entirely on adult populations, while the applicability of these findings to the pediatric population remains poorly defined. The purpose of this study was to examine the effect of blood transfusion within the first 24 hours of admission on hospital mortality in the pediatric trauma patient population.
Patient characteristics of transfused and non-transfused groups
7.8 ± 5.0
7.4 ± 5.5
7.8 ± 4.9
Mechanism of Injury
Physiologic and anatomic measures of injury severity
Transfused (n = 106)
Non-Transfused (n = 1533)
Mean ± SD
Mean ± SD
131 ± 35
112 ± 29
10 ± 14
21 ± 11
115 ± 31
123 ± 20
1.2100 ± 0.547
0.961 ± 0.878
2.737 ± 0.921
2.304 ± 0.739
3.413 ± 0.777
3.038 ± 0.887
2.618 ± 0.561
2.498 ± 0.571
1.913 ± 0.596
1.690 ± 0.586
AIS Head and Neck
4.231 ± 0.952
3.162 ± 1.132
1.273 ± 0.550
1.154 ± 0.376
26 ± 13
10 ± 9
33 ± 18
13 ± 13
Transfused (n = 106)
Non-Transfused (n = 1533)
ICU Length of Stay (days)1
6.1 ± 6.7
1.1 ± 3.8
ICU Length of Stay ≥ 1 Day2
Hospital Length of Stay (days)1
12.9 ± 12.3
4.5 ± 7.3
Following trauma, cause of death varies according to the time after the initial insult. In a study looking at the etiologies of traumatic deaths, Sauaia et al, found that 34% of deaths occurred in the pre-hospital setting and 66% occurred in the hospital. Of the patients admitted to the hospital, 81% died within the first 48 hours (acute), 6% within 3–7 days (early), and 14% after seven days (late). While central nervous system injury and exsanguination were the most frequent mechanisms responsible for acute and early deaths, MSOF was the most common cause of late death (61%).
In the acute setting PRBC transfusion can be lifesaving; however, consequences of transfusion may paradoxically result in an increased loss of life from organ failure. PRBC transfusion is often used to attenuate hemoglobin reduction from injury-associated blood loss, but evidence has been accumulating that suggests PRBC transfusion is an independent predictor of post-injury infection and MSOF[6, 7], as well as mortality, in both adult trauma [1–4, 12] and pediatric critically ill patients. In adult ICU patients, a multiple-center protocol that limited blood transfusion demonstrated reduced in-hospital mortality rate, cardiac complication rate, and organ dysfunction compared to a liberal transfusion group, lending evidence that limiting blood transfusion may eliminate some deaths from organ failure. Although a recent study by Lacroix et al. suggests that a restrictive transfusion strategy can safely be employed a pediatric ICU population, no reductions in MSOF or other secondary outcomes were demonstrated over a more liberal transfusion strategy.
Although the hospital mortality rate was significantly higher in our transfused group, patients within this group were more severely injured as measured by physiologic (SI) and anatomic (ISS) measures of injury severity. Over the 8-year study period, only 106 pediatric trauma patients who received a PRBC transfusion within the first 24 hours of admission were identified. Additionally, the removal of patients missing SI or ISS values further reduced the number of observation in this group by approximately 20% (n = 85 patients). All patients having SI and ISS values were included in the final analysis regardless of injury score in order to try to evaluate the effect of transfusion on the entire pediatric trauma population, because we were also interested in outcomes involving lesser injured patients (as determined by the SI and ISS values). However, the small sample size in the transfused group statistically limited our ability to evaluate the independent effects of PRBC transfusion on mortality, as goodness-of-fit analysis on statistical models incorporating SI and/or ISS demonstrated that these models were unreliable. Therefore, a review of state-wide or national trauma databases may be necessary to obtain adequate statistical confidence to determine the independent effects of PRBC on mortality in the pediatric trauma patient population.
Our study suffered from a number of limitations. As a tertiary referral center, many of the patients in this study arrived as transfers from referring institutions. Incomplete transfer records limited our ability to quantify the volume of blood transfused, as well as determine the age of the blood products received. Furthermore the study period also bridged our transition over to exclusively using leukocyte-depleted packed red cells. Age of transfused blood correlates with a higher risk of MOF in trauma patients and also increases mortality in patients with severe sepsis. Stored blood undergoes mechanical changes and older blood may obstruct capillary blood flow, predisposing to tissue ischemia and infection. A previous study at our institution demonstrated that in adult patients, the impact of blood transfusion on mortality is dose dependent, varying as a function of the number of units of PRBCs transfused. These are important variables that have been appreciated in this field of study, which were unable to be addressed directly in this cohort of patients.
Red blood cell transfusion in the first 24 hours following admission is associated with an increase in mortality in pediatric trauma patients. The potential contribution of red blood cell transfusion as an independent predictor of hospital mortality could not be assessed from our single-institution trauma registry. A review of state-wide or national trauma databases may be necessary to obtain adequate statistical confidence. Future research is needed to discover the mechanisms underlying poor transfusion outcomes in both the adult and pediatric populations.
The study was approved by the Institutional Review Board of the University of North Carolina. Over an eight-year period (1998–2006), trauma patient admissions were retrospectively reviewed from an established and verified trauma registry. All pediatric patients (≤ 16 years of age) sustaining blunt or penetrating trauma were included in the analysis and classified into transfused (at least one allogeneic PRBC transfusion within the first 24 hours after admission), and non-transfused groups.
Retrospectively acquired data from the trauma registry included age, gender, race, mechanism of injury (MOI), admission systolic blood pressure (SBP), heart rate (HR), and respiratory rate (RR). The shock index (SI) was calculated using the admission HR and SBP (SI = HR/SBP) and represented admitting physiologic injury. Injury Severity Score (ISS), New Injury Severity Score (NISS), ICU length of stay, hospital length of stay, and hospital mortality were also obtained from registry data. Confirmation of patients identified as having received a blood transfusion within the first 24 hours was performed by reviewing individual patient records.
No specific transfusion protocol was present during the time of this study. Nonoperative management and PRBC transfusion were performed at the discretion of the attending trauma surgeon initially evaluating the patient or the attending intensivist once the patient was transferred to the ICU. In general, hemodynamic instability, failure to respond to resuscitation, and ongoing blood loss were common indications for transfusion.
Univariate analysis was used to identify variables that were associated with blood transfusion, ICU length of stay, hospital length of stay, and hospital mortality. Chi-squared test was used to compare population proportions and two-tailed p values are reported. Student's t test was used for continuous variables. Data are expressed as mean ± standard deviation and comparison between groups is referred to as being statistically significant if p ≤ 0.05. Multivariate logistic regression was used to model the independent effect of blood transfusion on overall hospital mortality. Statistical methods and results were reviewed by an independent statistician.
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