Article, Pediatrics

An analysis of the pediatric casualties undergoing massive transfusion in Iraq and Afghanistan

a b s t r a c t

Background: Existing data on pediatric massive transfusion as part of trauma resuscitation is limited. We report the characteristics of pediatric casualties associated with undergoing massive transfusion at US military treat- ment facilities during combat operations in Iraq and Afghanistan.

Methods: We queried the Department of Defense Trauma Registry (DODTR) for all pediatric subjects admitted to US and Coalition fixed-facility hospitals in Iraq and Afghanistan from January 2007 to January 2016. We stratified subjects by Centers for Disease Control age groupings: b1, 1-4, 5-9, 10-14, and 15-17 years. We defined a mas- sive transfusion as 40 mL/kg of total blood products or more.

Results: From January 2007 through January 2016 there were 3439 pediatric casualties within the registry, of which 543 (15.7%) met criteria for receiving a massive transfusion. The median age of children undergoing mas- sive transfusion was 9 years (IQR 5-12), male (73.4%), injured in Afghanistan (69.9%) and injured by explosives (60.4%). Compared to other pediatric casualties, subjects undergoing massive transfusion had higher composite injury severity scores (median 17 versus 9), higher incidence of tachycardia (86.8% versus 70.9%), increased in- cidence of hypotension (31.2% versus 7.5%), and decreased survival to hospital discharge (82.6% versus 91.6%). Specific to body regions, casualties undergoing massive transfusion more frequently had Serious injuries to the head/neck (30.0% versus 22.8%), the thorax (22.8% versus 9.9%), abdomen (26.8% versus 6.9%), the extremities (42.1% versus 14.6%), while less frequently had serious injuries to the skin (5.3% versus 8.4%). All findings were significant.

Conclusions: Further research is needed to better translate the lessons learned from pediatric trauma care in the combat setting into the civilian setting in developed countries.

Level of evidence:3

Introduction

Background

Hemorrhage is the leading cause of Preventable death on the battle- field among US military casualties and is associated with the need for massive transfusion [1,2]. Hemorrhage due to trauma is also the leading cause of preventable death worldwide [3]. Massive transfusion specifi- cally refers to the administration of a large volume of blood products over a period of time with various definitions used for clinical and re- search purposes [4]. While massive transfusion occurs in only 3-5% of

* Corresponding author at: 3698 Chambers Pass, JBSA Fort Sam Houston, TX 78234, USA.

E-mail address: [email protected] (S.G. Schauer).

civilian and 8-10% of military trauma patients, these patients consume N70% of the total amount of blood transfused to trauma patients in the military setting [5-7]. Mortality from hemorrhage in this group occurs frequently and early, with a reported mortality rate of 40-60% and most deaths occurring within 3 h of arrival to the hospital [2,7,8]. Recent studies have identified a cut off of 40 ml/kg of all blood products trans- fused as defining a pediatric massive transfusion [9].

Massive transfusion has been extensively studied in combat popula-

tions, in which severely injured casualties experience early coagulopa- thy and greater risk of mortality from hemorrhage [1,10]. Early activation of massive transfusion protocols that include organized ad- ministration of predefined blood products improves survival in these patients [8,11-13]. Consequently, many hospitals have implemented protocols for massive transfusion with varying degrees of success [2,14,15]. In both civilian and combat settings, rapidly and accurately

https://doi.org/10.1016/j.ajem.2019.07.007 0735-6757/

identifying patients that require massive transfusion is vital to effective treatment [2,8]. Clinical criteria that have been consistent in quickly de- termining hemorrhagic patients that are likely to require massive trans- fusion include tachycardia, hypotension, free fluid on ultrasound, and penetrating mechanism of injury [8]. Because prompt treatment with balanced Blood components is critical for survival of patients requiring massive transfusion, early recognition of these predictors is important for successful protocol implementation. Limited data exist regarding the clinical characteristics associated with undergoing massive transfu- sion among pediatric patients [16].

Several studies on pediatric massive transfusion protocols have shown limited success, due in part to limited data to aid providers in identifying those children most likely to benefit from massive transfu- sion [16,17]. The utilization of massive transfusion has not demon- strated a clear Survival benefit in pediatric trauma patients, for which the criteria for protocol activation are less characterized than for adult patients [9]. No consensus exists regarding optimal blood product deliv- ery strategy and clear indicators for pediatric massive transfusion acti- vation. Studies demonstrating increased harm resulting from overly aggressive transfusions and crystalloids in children highlight the impor- tance of identifying such indicators [9,16]. Further characterization of the clinical characteristics associated with pediatric massive transfusion is a necessary first step to reliably determine which pediatric patients will require massive transfusion [16].

Goal of this investigation

We report the characteristics of pediatric casualties associated with undergoing massive transfusion at US military treatment facilities dur- ing combat operations in Iraq and Afghanistan.

Methods

Subjects and setting

This is a secondary analysis of a previously published data in which we sought to describe prehospital and emergency department care of pediatric casualties in Iraq and Afghanistan [18,19]. In this analysis, we focused on pediatric casualties undergoing massive transfusion. The US Army Institute of Surgical Research regulatory office reviewed proto- col H-16-014 and determined it was exempt from institutional review board oversight. We obtained only de-identified data.

Department of Defense Trauma Registry (DODTR) description

We queried the Department of Defense Trauma Registry (DODTR) for all pediatric (age b 18 years) encounters from January 2007 and Jan- uary 2016. The DODTR, formerly known as the Joint Theater Trauma Registry (JTTR), is the data repository for DoD trauma-related injuries [18,20-24]. The DODTR includes documentation regarding demo- graphics, injury-producing incidents, diagnoses, treatments, and out- comes of injuries sustained by US/non-US military and US/non-US civilian personnel in wartime and peacetime from the point of injury to final disposition. The DODTR comprises all patients admitted to a Role 3 (fixed-facility) or forward surgical team (FST) presenting within 72 h of the initial injury who had an injury diagnosis within the follow- ing range of injury codes using the International Classification of Disease 9th Edition (ICD-9) between 800 and 959.9, near-drowning/drowning with associated injury (ICD-9 994.1) or inhalational injury (ICD-9 987.9).

This study comprises a retrospective review of prospectively col-

lected data within the registry. We requested all available documenta- tion of prehospital care and fixed-facility based care.

Dataset development

Though there is variability in the definition of massive transfusion in pediatric patients within the literature, a threshold of 40 mL/kg of all blood products given within the first 24 h has been established as a re- liable indicator of critically injured children at high risk for early death [25]. Data collected included subject age, sex, vital signs, volumes of ad- ministered blood products, location (country) of casualty, mechanism of injury, injury severity score (composite ISS and Abbreviated Injury Scale by body region [AIS version 2005, update 2008, revision 2013]) [26], laboratory values (hematocrit, international normalized ratio [INR], and Base deficit) and survival to discharge. We calculated both composite ISS to take into consideration the totality of each patient’s in- juries as well as body region specific abbreviated injury scales to encap- sulate the severity of injuries to specific anatomic regions (e.g. head/ neck, face, thorax, abdomen, extremities, skin/superficial). We imputed weights using previously described methods based on casualty age [14]. We estimated blood volumes based on the following volumes per unit: Packed red cells (300 mL per unit), fresh frozen plasma (270 mL per unit), platelets (300 mL per unit), cryoprecipitate (10 mL per unit) and whole blood (450 mL per unit). We defined tachycardia based upon a heart rate greater than the 90th percentile for age given that the highest quality data we could retrieve from the peer-reviewed liter- ature regarding ranges of normal for pulse rates reported this threshold [27]. We determined hypotension based upon the estimated weight and lower systolic blood pressure limit on the relevant Broselow reference card. When documentation existed for more than one value for a given variable, we used the highest value for International normalized ratio and heart rate, and the lowest value for base deficit, hemat- ocrit, and systolic blood pressure. We stratified subjects into categories based on Centers for Disease Control age groupings: b1 year, 1-4 years, 5-9 years, 10-14 years, 15-17 years [18,19].

Data analysis

We performed all statistical analysis using Microsoft Excel (version 10, Redmond, Washington) and JMP Statistical Discovery from SAS (version 13, Cary, NC). We compared study variables using a student t-test for continuous variables, Wilcoxon Rank Sum test for ordinal var- iables, and chi-squared test for nominal variables. We defined a serious injury by body region as an abbreviate injury scale of 3 or greater for the respective region [18,19].

Results

From January 2007 through January 2016 there were 42,790 en- counters in the DODTR. Of those, 3439 (8.0%) were pediatric by docu- mented or estimated age. Within the 3439, 543 (15.7%) met criteria for receiving a massive transfusion. The median age of children under- going massive transfusion was 9 years (IQR 5-12), male (73.4%), injured in Afghanistan (69.9%), and injured by explosives (60.4%). The median composite ISS was 17 (IQR 13-25), most frequently with serious inju- ries to the extremities (42.1%). Most survived to hospital discharge (82.6%, Table 1).

Compared to pediatric casualties not undergoing massive transfu- sion, we found no significant differences between age groups. However, there were higher proportions of explosive injuries (60.4% versus 39.8%) and gunshot wounds (25.4% versus 21.4%) and lower propor- tions of patients sustained injuries from Motor vehicle collisions (6.4% versus 12.5%) and other injuries (7.7% versus 26.1%) among patients un- dergoing massive transfusion. Massive transfusion recipients had higher median composite ISS (17 versus 9) and higher proportions of these casualties sustained serious injuries to the extremities (42.1%). Subjects undergoing massive transfusion were more likely to be tachycardic for age (86.8% versus 70.9%, p b 0.001) and hypotensive (31.2% versus 7.5%, p b 0.001). Survival to discharge among massive

Table 1

Demographics of subjects undergoing

massive transfusion.

Total

b1

1-4

5-9

10-14

15-17

(n = 543)

(n = 12)

(n = 100)

(n = 165)

(n = 182)

(n = 84)

Male

73.4% (399)

41.6% (5)

57.0% (57)

72.1% (119)

81.8% (149)

82.1% (69)

Location

Afghanistan

69.9% (380)

50.0% (6)

61.0% (61)

70.9% (117)

79.6% (145)

60.7% (51)

Iraq

30.0% (163)

50.0% (6)

39.0% (39)

29.0% (48)

20.3% (37)

39.2% (33)

Mechanism of injury

Explosive

60.4% (328)

66.6% (8)

52.0% (52)

66.0% (109)

63.1% (115)

52.3% (44)

GSW

25.4% (138)

16.6% (2)

20.0% (20)

17.5% (29)

28.0% (51)

42.8% (36)

MVC

6.4% (35)

8.3% (1)

7.0% (7)

8.4% (14)

6.0% (11)

2.3% (2)

Other

7.7% (42)

8.3% (1)

21.0% (21)

7.8% (13)

2.7% (5)

2.3% (2)

Injury score

Composite

17 (13-25)

16.5 (13.25-21.5)

16.5 (10-25)

18 (13-26)

17 (13-25)

18 (12.5-24.25)

Serious injuries by body region

Head/neck

30.0% (163)

66.6% (8)

44.0% (44)

36.3% (60)

24.1% (44)

8.3% (7)

Face

0.4% (2)

0% (0)

0% (0)

1.2% (2)

0% (0)

0% (0)

Thorax

22.8% (124)

8.3% (1)

15.0% (15)

25.4% (42)

23.6% (43)

27.3% (23)

Abdomen

26.8% (146)

16.6% (2)

15.0% (15)

26.6% (44)

32.9% (60)

29.7% (25)

Extremities

42.1% (229)

16.6% (2)

21.0% (21)

44.8% (74)

46.1% (84)

57.1% (48)

Skin/superficial

5.3% (29)

0% (0)

14.0% (14)

3.0% (5)

3.3% (6)

4.7% (4)

Outcome

Survival to discharge

82.6% (449)

91.6% (11)

78.0% (78)

84.2% (139)

81.8% (149)

85.7% (72)

GSW = gunshot wound.

MVC = motor vehicle collision.

transfusion recipients was lower (82.6% versus 91.6%, p b 0.001, Table 2).

We found no significant difference in maximum INR of casualties un- dergoing massive transfusion versus other pediatric casualties. We found lower mean hematocrits in casualties undergoing massive trans- fusion (29.5 versus 34.1) and lower mean base deficits in casualties un- dergoing massive transfusion (-9.2 versus -4.0, Table 3).

Discussion

In our study focusing on pediatric trauma population in the combat setting, we found a high incidence of casualties (15.7%) receiving a mas- sive transfusion. Of those undergoing massive transfusion, a preponder- ance were older adolescent-aged children. Similar to the adult population, the majority sustained injuries by explosives [10,28]. Labo- ratory values on arrival to the emergency department were not highly associated with the need for massive transfusion. Overall, we found that survival rates were lower for those undergoing massive transfusion compared to our previous report of all children presenting to the ED [19]. Moreover, there also seemed to be a general trend towards higher survival rates as children went up in age with the exception of the

youngest age group (b1 year of age). However, this may be due to the low numbers in this group compared to the other age groups. There is very limited data on massive transfusion in children this young so inter- pretation remains limited.

In a previous study by Edwards et al. found that 224 of 907 (24.7%) pediatric casualties received high-volume resuscitation as defined using the same threshold for massive transfusion used in our analysis (N40 mL/kg) [16]. Additionally, Edwards et al. found that age b 4 years was a predictor for the need of massive transfusion, where as our cohort mostly consisted over older children. There were several differences in methodology that may account for these discrepancies. One third of their patients were excluded for missing weights, and they did not in- clude plasma and platelet volume for their calculation of massive transfusion.

Even though systolic hypotension was associated with massive transfusion, it only occurred in a small proportion of our casualties un- dergoing massive transfusion (31.2%). Consequently, the absence of hy- potension should not lead the clinician to believe a massive transfusion is not necessary. Conversely, we found that tachycardia was frequently present among casualties undergoing massive transfusion (86.8%) but must also note that it was frequently present in those not undergoing

Table 2

A comparison of casualties undergoing massive transfusion compared to the rest of the dataset.

MT recipients (543)

MT non-recipients (2896)

p-Value

Age group

b1

2.2% (12)

2.0% (58)

0.570

1-4

18.4% (100)

18.9% (548)

5-9

30.3% (165)

33.6% (975)

10-14

33.5% (182)

31.1% (903)

15-17

15.4% (84)

14.2% (412)

Mechanism of injury

Explosive

60.4% (328)

39.8% (1153)

b0.001

GSW

25.4% (138)

21.4% (622)

MVC

6.4% (35)

12.5% (363)

Other

7.7% (42)

26.1% (758)

Injury severity score

Composite

17 (13-25)

9 (4-16)

b0.001

Serious injuries by body region

Head/neck

30.0% (163)

22.8% (662)

b0.001

Face

0.3% (2)

0.2% (7)

0.640

Thorax

22.8% (124)

9.9% (288)

b0.001

Abdomen

26.8% (146)

6.9% (200)

b0.001

Extremities

42.1% (229)

14.6% (425)

b0.001

Skin/superficial

5.3% (29)

8.4% (246)

0.012

Vital sign data – age adjusted

Tachycardiaa

86.8% (457)

70.9% (1973)

b0.001

Systolic hypotensiona

31.2% (160)

7.5% (202)

b0.001

Outcome

Survival to discharge

82.6% (449)

91.6% (2654)

b0.001

GSW = gunshot wound; MVC = motor vehicle collision.

a Casualties with missing data were excluded from this. The percentage is based on 3306 children with at least one heart rate documented and 3206 children with at least one systolic pressure documented.

Table 3 A comparison of emergency department laboratory values between the two groups (aver- age, 95% CI)

MT recipients (543) MT non-recipients (2896)

INR 1.73 (1.64-1.83) 1.23 (1.20-1.25)

Hematocrit 29.5 (28.7-30.3) 34.1 (33.8-34.4)

Base excess -9.2 (-9.8 to -8.6) -4.0 (-4.2 to -3.8) INR = international normalized ratio.

massive transfusion (70.9%), and could likely be contributed to pain and other causes. This is consistent with the physiology of other forms of shock in children: they have a robust physiologic reserve with catechol- amine release allowing to compensate for shock states. This suggests that relying on that vital sign only may lead to excessive massive trans- fusion resuscitation. This contrasts with the adult population in which vital signs appear to be a better predictor [2,11,29]. Based on these find- ings, clinicians may have to rely on other predictors when deciding when to activate massive transfusion protocols for pediatric patients such as overall injury severity with special attention to the abdomen or delayed application for hemorrhaging extremities. However, the abil- ity to extrapolate these findings directly to the civilian setting is limited as many of our casualties were injured by way of explosive – which is rare in the developed world. These results can, however, help generate hypotheses for more controlled prospective studies to quickly identify pediatric massive transfusion.

There are several limitations of this study. First, the observational na- ture of our investigation means that we can only demonstrate correla- tion and not causation for why patients underwent particular procedures including massive transfusion. Second, for inclusion within the DODTR, subjects must arrive at the FST or fixed-facility alive or with on-going interventions. As our database excludes all subjects not surviving to fixed-facility unless receiving on-going interventions, we are unable to characterize subjects that died on the battlefield which may result in selection bias. Third, we do not have sufficient data to de- termine transport time or tactical situation which may affect mortality. The time of injury to application of tourniquet was also not captured in this dataset. Fourth, we relied on imputing weights for children which may have an impact on defining the massive transfusion thresholds within the dataset. This limitation is likely more amplified in older chil- dren. A final limitation is that we included data even if it was incomplete in the DODTR [30,31].

Conclusions

Further research is needed to better translate the lessons learned from pediatric trauma care in the combat setting into the civilian setting in developed countries.

Disclosures

We have no relevant disclosures.

Funding

We received no external funding for this study.

Declaration of Competing Interest

We have no conflicts to report.

Acknowledgements

We would like to thank the Joint Trauma system Data Analysis Branch for their efforts with data acquisition.

Disclaimer

Opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Departments of the Army and Air Force, or the Department of Defense.

Ethics

The USAISR regulatory office reviewed protocol H-16-014 and deter- mined it was exempt from IRB oversight. We obtained only de- identified data.

Author contributions

Study conception and design: SGS, MDA, MAB Data acquisition: SGS

Analysis and Data interpretation: SGS, MDA, ARW, TEB, GJH Drafting of the manuscript: SGS, ARW, HLG

Critical revision: SGS, MDA, ARW, HLG, TEB, GJH

References

  1. Schreiber MA, et al. Early predictors of massive transfusion in combat casualties. J Am Coll Surg 2007;205(4):541-5.
  2. Holcomb JB, et al. The prospective, observational, multicenter, major trauma transfu- sion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg 2013;148(2):127-36.
  3. Curry N, et al. The acute management of trauma hemorrhage: a systematic review of randomized controlled trials. Crit Care 2011;15(2):R92.
  4. Stanworth SJ, et al. Reappraising the concept of massive transfusion in trauma. Crit Care 2010;14(6):R239.
  5. Como JJ, et al. Blood transfusion rates in the care of acute trauma. Transfusion 2004; 44(6):809-13.
  6. Holcomb JB, et al. Damage control resuscitation: directly addressing the early coag- ulopathy of trauma. J Trauma Acute Care Surg 2007;62(2):307-10.
  7. Hess JR, Zimrin AB. massive blood transfusion for trauma. Curr Opin Hematol 2005; 12(6):488-92.
  8. Nunez TC, et al. Early prediction of massive transfusion in trauma: simple as ABC (assessment of blood consumption)? J Trauma Acute Care Surg 2009;66(2):346-52.
  9. Neff LP, et al. Clearly defining pediatric massive transfusion: cutting through the fog and friction with combat data. J Trauma Acute Care Surg 2015;78(1):22-9.
  10. McLaughlin DF, et al. A predictive model for massive transfusion in combat casualty patients. J Trauma Acute Care Surg 2008;64(2):S57-63.
  11. Holcomb JB, et al. Increased platelet: RBC ratios are associated with improved sur- vival after massive transfusion. J Trauma Acute Care Surg 2011;71(2):S318-28.
  12. Pidcoke HF, et al. Ten-year analysis of transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: increased plasma and platelet use correlates with im- proved survival. J Trauma Acute Care Surg 2012;73(6):S445-52.
  13. Borgman MA, et al. The ratio of blood products transfused affects mortality in pa- tients receiving massive transfusions at a combat support hospital. J Trauma Acute Care Surg 2007;63(4):805-13.
  14. Riskin DJ, et al. Massive transfusion protocols: the role of aggressive resuscitation versus product ratio in mortality reduction. J Am Coll Surg 2009;209(2):198-205.
  15. Cotton BA, et al. Predefined massive transfusion protocols are associated with a re- duction in organ failure and postinjury complications. J Trauma Acute Care Surg 2009;66(1):41-9.
  16. Edwards MJ, et al. The effects of balanced blood component resuscitation and crys- talloid administration in pediatric trauma patients requiring transfusion in Afghanistan and Iraq 2002 to 2012. J Trauma Acute Care Surg 2015;78(2):330-5.
  17. Chidester SJ, et al. A pediatric massive transfusion protocol. The journal of trauma and acute care surgery 2012;73(5).
  18. Schauer SG, et al. Prehospital interventions performed on pediatric trauma patients in Iraq and Afghanistan. Prehosp Emerg Care 2018:1-6.
  19. Schauer SG, et al. Emergency department resuscitation of pediatric trauma patients in Iraq and Afghanistan. Am J Emerg Med 2018;36(9):1540-4.
  20. Glenn MA, et al. Implementation of a combat casualty trauma registry. J Trauma Nurs 2008;15(4):181-4.
  21. O’Connell KM, et al. Evaluating the Joint Theater Trauma Registry as a data source to benchmark casualty care. Mil Med 2012;177(5):546-52.
  22. Schauer SG, et al. An analysis of casualties presenting to military emergency depart- ments in Iraq and Afghanistan. Am J Emerg Med 2018 https://www.ncbi.nlm.nih. gov/pubmed/29753547.
  23. Schauer SG, et al. Emergency department resuscitation of pediatric trauma patients in Iraq and Afghanistan. Am J Emerg Med 2018.
  24. Schauer SG, et al. Prehospital analgesia for pediatric trauma patients in Iraq and Afghanistan. Prehosp Emerg Care 2018:1-6.
  25. Shroyer MC, et al. Massive transfusion in pediatric trauma: analysis of the National Trauma Databank. J Surg Res 2017;208:166-72.
  26. Gennarelli TA, Wodzin E. AIS 2005: a contemporary injury scale. Injury 2006;37(12):

    1083-91.

    Fleming S, et al. Normal ranges of heart rate and respiratory rate in children from birth to 18 years of age: a systematic review of observational studies. Lancet 2011; 377(9770):1011-8.

  27. Kauvar DS, et al. Fresh whole blood transfusion: a controversial military practice. J Trauma Acute Care Surg 2006;61(1):181-4.
  28. Holcomb JB, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the proppr randomized clinical trial. JAMA 2015;313(5):471-82.
  29. Robinson JB, et al. Battlefield documentation of tactical combat casualty care in Afghanistan. US Army Med Dep J 2016;2-16:87-94.
  30. Schauer SG, et al. A descriptive analysis of data from the Department of Defense Joint Trauma System Prehospital Trauma Registry. US Army Med Dep J 2017(3-17):92-7.