Assessment of Blood Consumption score for pediatrics (ped-ABC score) predicts transfusion requirements for children with trauma.


 Background

Although transfusion is one of primary life-saving elements, the assessment of requirement for transfusion in children with trauma at an early phase has been challenging. We aimed to develop a scoring system for predicting transfusion requirements in children with trauma.
Methods

This is a retrospective cohort study, which employed a nationwide registry of patients with trauma (Japan Trauma Data Bank) and included the patients aged < 16 years with blunt trauma between 2004 and 2015. An Assessment of Blood Consumption score for pediatrics (ped-ABC score) was developed based on previous literatures and clinical relevance. One point was assigned for each of the following criteria: systolic blood pressure ≤ 90 mmHg; heart rate ≥ 120/min; Glasgow Coma Scale (GCS) < 15; and positive result on focused assessment with sonography for trauma (FAST) scan. For sensitivity analysis, we assessed age-adjusted ped-ABC scores using cut-off points for different ages.
Results

In total, 540 patients had transfusion within 24 hours after trauma among the eligible 5,943 pediatric patients with trauma. The in-hospital mortality rate was 2.6% (145/5,615). Transfusion increased from 7.6% (430/5,631) to 35.3% (110/312) in patients with systolic blood pressure ≤ 90 mmHg (1 point); from 6.1% (276/4,504) to 18.3% (264/1,439) for heart rate ≥ 120/min (1 point); from 4.1% (130/3,198) to 14.9% (410/2,745) for disturbance of consciousness with GCS < 15 (1 point); and from 7.4% (400/5,380) to 24.9% (140/563) for FAST positivity (1 point). The ped-ABC score of 0, 1, 2, 3, and 4 points were associated with the transfusion rates of 2.2% (48/2,210), 7.5% (198/2,628), 19.8% (181/912), 53.3% (88/165), and 89.3% (25/28), respectively. After age adjustment, c-statistic was 0.76 (95% CI, 0.74–0.78).
Conclusions

The ped-ABC score using the vital signs and FAST may be helpful in predicting the transfusion requirements within 24 hours for children with trauma.


Conclusions
The ped-ABC score using the vital signs and FAST may be helpful in predicting the transfusion requirements within 24 hours for children with trauma.

Background
Trauma is a leading cause of death among young populations around the world [1,2]. Even if most of the injuries of children are of mild to moderate severity [3], a rapid evaluation and management for children with serious and life-threating trauma is always needed to avoid preventable trauma death.
Transfusion is one of key life-saving elements for children with trauma. Delay in transfusion is primarily associated with increased mortality [4,5]. However, it has been challenging for a clinician to assess the requirements for transfusion among children with trauma at an early phase [6]. In addition, clinicians may hesitate to use transfusion for children due to the risks of transfusion-related complications such as infection or allergic reaction [7].
Several transfusion prediction scoring systems are available for the patients with trauma [8,9]. Majority of these systems were developed for adults and, subsequently, applied to pediatric populations; however, their effectiveness may be limited for children [10]. Indeed, most transfusions for pediatric patients with trauma were decided without clear indications [11]. There is no prediction scoring system focused on blood transfusion in children with trauma.
Therefore, the objective of this study is to develop a scoring system to predict the requirements for transfusion in children with trauma.

Design and data collection
This is a retrospective cohort study, which employed a nationwide registry of trauma patients in Japan: Japan Trauma Data Bank (JTDB). JTDB is a nationwide trauma registry established in 2003, which is authorized and maintained by the Japanese Association for the Surgery of Trauma and the Japanese Association for Acute Medicine to improve and assure the quality of trauma care in Japan. A total of 272 hospitals, including over 95% of certi ed tertiary emergency medical centers in Japan, contributed to the JTDB in March 2018 [12]. The JTDB collected data regarding patient demographics, trauma cause, Injury Severity Score (ISS), vital signs and emergency procedure at pre-hospital on arrival, and at hospital, and treatment and emergency procedure including transfusion within 24 hours. It also collected outcome data such as emergency department (ED) mortality, in-hospital mortality, and length of stay.

Patient selection
All patients aged < 16 years of age with blunt trauma were included (Fig. 1). Exclusion criteria were: patients who had missing data of age; patients who had trauma mechanisms other than blunt trauma or patients with missing data of trauma mechanism; patients who had no information about transfusion; patients with cardiorespiratory arrest upon arrival at hospital or patients with an Abbreviated Injury Scale (AIS) score of ≤ 2 or 6 (i.e., non-survivable injury) for any reason. We also excluded patients for whom focused assessment with sonography for trauma (FAST) scan was not conducted or data were missing; patients with missing data of systolic blood pressure (SBP), heart rates (HR), and Glasgow Coma Scale (GCS) at ED. Thus, data included in analysis were of those patients who represented the complete datasets for score predictors of SBP, HR, GCS, and FAST.

Development of prediction score
The Assessment of Blood Consumption score for pediatrics (ped-ABC score) was developed based on the previous literatures and clinical relevance ( Table 1). It consists of some components of Assessment of Blood Consumption (ABC) score, which was developed to predict massive transfusion for adult patients with trauma [9], and disturbance of consciousness, which we de ned as GCS < 15. We considered how the association between disturbance of consciousness and transfusion is explained through physiological rationale: severe blood loss decreases cerebral blood ow and perfusion, resulting in the disturbance of consciousness [13]. Finally, 1 point was given for each of the following criteria: SBP ≤ 90 mmHg; heart rate ≥ 120/min; GCS < 15; and positive result on the FAST scan.

Statistical analysis
Continuous variables were presented as median and interquartile range values. These variables were compared by using the Mann-Whitney U test or as mean +/-standard deviation, which was compared by using t-test as appropriately. Categorical variables were presented as numbers and percentages and compared by using either the Chi-square test or Fisher exact test. Scoring items were assessed by using cstatistic with 95% con dence interval (CI), and the characteristics were evaluated by using sensitivity, speci city, and positive and negative predictive values for the score cut-off values of 1, 2, 3, and 4, respectively. For sensitivity analysis, we also assessed the age-adjusted ped-ABC score by using cut-off points for different age categories because the normal range of vital signs among pediatric populations differ as per their age [6,14]. Normal vital signs and cut-off points were based on the published normal ranges compiled from the pediatric textbooks and guidelines [15,16]. In the age-adjusted ped-ABC score, one point was given for each of the following criteria: SBP ≤ 70 mmHg plus child's age multiplied by 2 (age ≤ 10 years) or ≤ 90 mmHg (age > 10 years); heart rate ≥ 160/min (age ≤ 1 years), ≥ 150/min (1 < age ≤ 2 years), ≥ 140/min (3 ≤ age ≤ 5 years), ≥ 120/min (6 ≤ age ≤ 12 years), or ≥ 100/min (age ≥ 13 years); GCS < 15; and positive result on the FAST scan.
We also conducted subgroup analyses that only included patients with ISS ≥ 15; patients without isolated head injury; those without severe isolated head injury (ISS ≥ 3 on head score of AIS). Patients with isolated head injury were considered to have received transfusion mainly for surgical operation.
For all analyses, a p-value < 0.05 was considered to be statistically signi cant. All statistical analyses were performed with EZR (version 1.38; Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (version 3.5.0; The R Foundation for Statistical Computing, Vienna, Austria) [17]. More speci cally, EZR is a modi ed version of R commander designed to apply statistical functions frequently used in biostatistics.

Clinical characteristics
The JTDB enrolled 236,698 patients between January 2004 and December 2015. Of these, 5,943 pediatric patients with trauma (2.5%) were eligible in our study (    Ability of ped-ABC score The transfusion rates of patients in accordance with the ped-ABC score are presented in Table 4. Although the patients with a score of 0 had a transfusion rate of only 2.2%, 89.3% of those with a maximum score of 4 received transfusion. Most patients scored less than 3 (96.7%). The score characteristics for transfusion rates in accordance with the different cut-offs are presented in  Sensitive and subgroup analyses of ped-ABC score Supplemental Table 1 shows the number of patients and transfusion rate for each age category. After age adjustment by using different cut-off points, c-statistic of the score was 0.76 (95% CI, 0.74-0.78), which was similar to score before adjustment. The speci city of score after age adjustment was higher than the score before adjustment (Supplemental Table 2, 3). The other analysis also showed similar test characteristics with respect to the original score (Supplemental Table 4-9).

Brief summary
We developed a scoring system to predict the requirements of transfusion for children with trauma by using a nationwide registry of trauma patients in Japan. It includes results of SBP, HR, GCS and FAST scan. It is helpful for clinicians to make a systematic evaluation with this simpli ed method.

Development of ped-ABC score
We have developed the ped-ABC score, which consisted of vital signs and FAST. Tachycardia and hypotension as well as decreased GCS were associated with poor outcomes in the pediatric patients with trauma [18][19][20]. In addition, positive result of FAST strongly suggests intraabdominal injury that is one of the main reasons for the need of transfusion [21,22]. Scores with multiple combinations of vital sings improve their predictability as compared to the vital signs alone [23].
Indicators that use vital signs tend to be complicated in children because the normal range of vital signs varies with age. In this study, sensitivity analysis performed with age adjustment demonstrated that the test characteristics were equivalent to those before adjustment. Therefore, it is possible to adapt its scoring system more easily in children with trauma without setting different cut-offs for each age. We con rmed that subgroup analyses of patients with ISS ≥ 15, patients without isolated head injury, and patients without severe isolated head injury were also equivalent to the original score. Establishing a scoring system also makes it easier for a clinician to assess the requirement for transfusions in a busy ED.

Comparison with previous studies
Previous studies have reported that shock index (SI), which is calculated by the normal heart rate divided by the SBP, predicted mortality among pediatric patients with trauma and served as a requirement for transfusion [24,25]. The prediction of blood transfusion by using SI may be used for the necessity of transfusion due to its high negative predictive value. The strength of our scoring system lies in the systematic evaluation of the necessity of transfusion according to the score. The ped-ABC score is composed of four points, whereas SI was composed of two choices: "yes" or "no." It could be used not only for rule-out but also for rule-in. Moreover, our scoring system does not require different cut off points according to patient age. In addition, our scoring system is non-invasive and can be used quickly, whereas other studies require laboratory tests [26,27]. Further studies are needed to assess our scoring system.
Ability, utility, and implementation of ped-ABC score The ped-ABC score may be better than the clinical gestalt [28]. Clinicians are sometimes forced to choose between delaying transfusion or risking transfusion-related complications. Indeed, the majority of pediatric arrivals with trauma do not initially show clear indications for transfusion [11]. Our scoring system enables clinicians to evaluate or discuss the need for transfusion by using common criteria. Based on our ped-ABC scores, blood transfusion might be reasonable for patients with a score of 3 or 4.
However, it may be more controversial when a clinician examines patients with a score of 2, though some over-triage for transfusion might be tolerated from the clinical point of view, especially for children.
Delaying transfusion until the worsening of vital signs or coagulopathy in the course of examination would be an alternative to administering transfusion. Ultimately, a nal decision would be needed regarding transfusion. Although the scoring system may not have the ability to predict outcomes perfectly, it can still help clinicians to make a systematic evaluation through a simpli ed method.

Limitations
This study has several limitations. First, approximately 30% of data of FAST scan were not conducted. These might have been the cases where a clinician considered FAST scan unnecessary because of mild state or because they shared a critical status. However, these patients did not need our scoring system to evaluate the requirement of blood transfusion. Second, a validation study is needed since this study was retrospective. Third, there might have been an indication bias of transfusion because we did not have the data of appropriateness of treatments. In 2002, a guideline for trauma care named Japan Advanced Trauma Evaluation and Care was introduced in Japan. It was created with reference to the Advanced trauma life support practice theory. In addition, all participating institutions were national-certi ed emergency centers. Therefore, we believe that most patients received appropriate treatments. Fourth, data about transfusion history is missing in the study; however, as this is a very small proportion (3.9%), we consider it to have little effect on our results. Fifth, the requirement for transfusion is not the same as the urgency or the appropriateness of transfusion. Further studies are warranted to evaluate whether the ped-ABC score could reduce the time to implement transfusion and improve patient outcomes. Sixth, we focused on simplicity when we developed a scoring system to predict the need for transfusion.
Consequently, the scoring system's c-statistic may not be very high. However, we believe that our score is useful in that it makes fast and easy assessment possible at an early phase of trauma survey.

Conclusions
We developed the ped-ABC score: the scoring system to predict requirement for transfusion with 24 hours for children with trauma using vital signs and FAST. > We received the permission to use the data from the steering committee of the JTDB. The study protocol was reviewed and approved by the ethics committees of Juntendo University Hospital. The ethics committees waived the need to obtain informed consent from the study participants, given the retrospective and anonymized nature of this study in the routine care. All methods were carried out in accordance with the relevant guidelines and regulations.

Consent for publication
Not applicable Availability of data and materials The datasets analyzed during the current study is available with the corresponding author on reasonable request.

Figure 1
Flow