Tranexamic acid (TXA) has been demonstrated to decrease mortality in adult trauma, particularly in those with massive transfusions needs sustained in combat injury. Limited data are available for the ...efficacy of TXA in pediatric trauma patients outside of a single combat support hospital in Afghanistan.
The Department of Defense Trauma Registry was queried for trauma patients younger than 18 years from Iraq and Afghanistan requiring 40 mL/kg or greater of blood product within 24 hours of injury. Burns and fatal head traumas were excluded. Primary outcome was in-hospital mortality. Secondary outcomes were hospital, ventilator, and intensive care unit-free days, as well as total blood product volume.
Among those pediatric patients receiving massive transfusions, those who received TXA were less likely to die in hospital (8.5% vs. 18.3%). Patients who received TXA and those who did not have similar hospital-free days (19 vs. 20), ventilator-free days (27 vs. 27), and intensive care unit-free days (25 vs. 24). Those who received TXA had higher 24-hour blood product administration (100 mL/kg vs. 75 mL/kg). None of our results rose to the level of statistical significance. The TXA administration significantly reduced odds of death on logistic regression (odds ratio, 0.35; 95% confidence interval, 0.123-0.995; p = 0.0488).
Use of TXA in pediatric patients with combat trauma requiring massive transfusions trended toward a significant improvement in in-hospital mortality (p = 0.055). This mortality benefit is similar to that seen in adult studies and a less well characterized cohort in another pediatric study suggesting TXA administration confers mortality benefit in massively transfused pediatric combat trauma victims.
Evidence (retrospective cohort), Level IV.
Tranexamic acid in pediatric hemorrhagic trauma Borgman, Matthew A; Nishijima, Daniel K
The journal of trauma and acute care surgery,
01/2023, Volume:
94, Issue:
1S Suppl 1
Journal Article
Peer reviewed
Open access
There is strong evidence in adult literature that tranexamic acid (TXA) given within 3 hours from injury is associated with improved outcomes. The evidence for TXA use in injured children is limited ...to retrospective studies and one prospective observational trial. Two studies in combat settings and one prospective civilian US study have found association with improved mortality. These studies indicate the need for a randomized controlled trial to evaluate the efficacy of TXA in injured children and to clarify appropriate timing, dose and patient selection. Additional research is also necessary to evaluate trauma-induced coagulopathy in children. Recent studies have identified three distinct fibrinolytic phenotypes following trauma (hyperfibrinolysis, physiologic fibrinolysis, and fibrinolytic shutdown), which can be identified with viscohemostatic assays. Whether viscohemostatic assays can appropriately identify children who may benefit or be harmed by TXA is also unknown.
Massive transfusion (MT) in pediatric patients remains poorly defined. Using the largest existing registry of transfused pediatric trauma patients, we sought a data-driven MT threshold.
The ...Department of Defense Trauma Registry was queried from 2001 to 2013 for pediatric trauma patients (<18 years). Burns, drowning, isolated head injury, and missing Injury Severity Score (ISS) were excluded. MT was evaluated as a weight-based volume of all blood products transfused in the first 24 hours. Mortality at 24 hours and in the hospital was calculated for increasing transfusion volumes. Sensitivity and specificity curves for predicting mortality were used to identify an optimal MT threshold. Patients above and below this threshold (MT+ and MT-, respectively) were compared.
The Department of Defense Trauma Registry yielded 4,990 combat-injured pediatric trauma patients, of whom 1,113 were transfused and constituted the study cohort. Sensitivity and specificity for 24-hour and in-hospital mortality were optimal at 40.1-mL/kg and 38.6-mL/kg total blood products in the first 24 hours, respectively. With the use of a pragmatic threshold of 40 mL/kg, patients were divided into MT+ (n = 443) and MT- (n = 670). MT+ patients were more often in shock (68.1% vs. 47.0%, p < 0.001), hypothermic (13.0% vs. 3.4%, p < 0.001), coagulopathic (45.0% vs. 29.6%, p < 0.001), and thrombocytopenic (10.6% vs. 5.0%, p = 0.002) on presentation. MT+ patients had a higher ISS, more mechanical ventilator days, and longer intensive care unit and hospital stay. MT+ was independently associated with an increased 24-hour mortality (odds ratio, 2.50; 95% confidence interval, 1.28-4.88; p = 0.007) and in-hospital mortality (odds ratio, 2.58; 95% confidence interval, 1.70-3.92; p < 0.001).
Based on this large cohort of transfused combat-injured pediatric patients, a threshold of 40 mL/kg of all blood products given at any time in the first 24 hours reliably identifies critically injured children at high risk for early and in-hospital death. This evidence-based definition will provide a consistent framework for future research and protocol development in pediatric resuscitation.
Diagnostic study, level II. Prognostic/epidemiologic study, level III.
Humanitarian care is a vital component of the wartime mission. Children comprise a significant proportion of casualties injured by explosives and penetrating weapons. Children face a variety of ...unique injury patterns in the combat setting as high-powered firearms and explosives are rarely seen in the civilian setting. We sought to perform a scoping review of pediatric research from the recent US-led wars in Afghanistan, and Iraq conflicts beginning in 2001. We used Google Scholar and PubMed to identify pediatric combat literature published between 2001 and 2022. We utilized the PRISMA-ScR Checklist to conduct this review. We identified 52 studies that met inclusion for this analysis-1 prospective observational study, 50 retrospective studies, and 1 case report. All the original research studies were retrospective in nature except for one. We identified one prospective study that was a post hoc subanalysis from an overall study assessing the success of prehospital lifesaving interventions. Most of the articles came from varying registries created by the United States and British militaries for the purposes of trauma performance improvement. The deployed health service support mission often includes treatment of pediatric trauma patients. The deployed health service support mission often includes treatment of pediatric trauma patients. We found that available literature from this setting is limited to retrospective studies except for one prospective study. Our findings suggest that pediatric humanitarian care was a significant source of medical resource consumption within both of the major wars. Further, many of the lessons learned have directly translated into changes in civilian pediatric trauma care practices highlighting the need for collaborative scientific developments between the military and civilian trauma programs.
Systematic Review/Meta-Analyses; Level III.
It is well known that polytrauma can lead to acute lung injury. Respiratory failure has been previously observed in combat trauma, but not reported in children, who account for over 11% of bed days ...at deployed Military Treatment Facilities (MTFs) using significant resources. We seek to identify risk factors associated with prolonged mechanical ventilation (PMV) which is important in resource planning and allocation in austere environments.
Retrospective review of prospectively collected data within the United States Department of Defense Trauma Registry.
Deployed U.S. MTFs in Iraq and Afghanistan from 2007 to 2016.
All pediatric subjects who required at least 1 day of mechanical ventilation, excluding patients who died on day 0.
PMV was defined using the Youden index for mortality. A multivariable logistic regression model was then performed to identify factors associated with PMV.
The Youden index identified greater than or equal to 6 days as the cutoff for PMV. Of the 859 casualties included in the analysis, 154 (17.9%) had PMV. On univariable analysis, age, severe injury to the thorax and skin, 24-hour volume/kg administration of crystalloids, colloids, platelets, plasma, and packed RBCs was associated with PMV. In the multivariable model, odds ratios (95% CI) associated with PMV were crystalloids 1.04 (1.02-1.07), colloids 1.24 (1.04-1.49), platelets 1.03 (1.01-1.05), severe injury to the thorax 2.24 (1.41-3.48), and severe injury to the skin 4.48 (2.72-7.38). Model goodness-of-fit r2 was 0.14.
In this analysis of factors associated with PMV in pediatric trauma patients in a combat zone, in addition to severe injury to skin and thorax, we found that administration of crystalloids, colloids, and platelets was independently associated with greater odds of PMV. Our findings will help inform resource planning and suggest potential resuscitation strategies for future studies.
Recent data for adult trauma patients suggest improved survival when using hemostatic resuscitation, which includes limiting crystalloids and using closer to 1:1 ratios for both fresh frozen plasma ...(FFP) and platelets (PLTs) relative to packed red blood cells (PRBCs). Pediatric studies have shown similar but mixed results and often lack measuring crystalloids. We seek to evaluate in-hospital survival based on crystalloid administration and different blood product ratios in pediatric casualties during the recent conflicts.
We queried the Department of Defense Trauma Registry for all pediatric encounters in Iraq and Afghanistan from January 2007 to January 2016 and included those with at least 40 mL/kg of total blood products administered provided that they received at least 1 U of PRBC. We grouped children as younger (0-7 years) and older (8-17 years). We grouped low versus high ratios for FFP/PRBC (≤1:2 vs. >1:2) and PLT/PRBC (≤1:6 vs. >1.6). We used a threshold of 40 mL/kg to for high versus low crystalloid resuscitation.
During this time, there were 3,439 encounters in the registry with 521 (15.1%) that met the inclusion criteria. The median age of casualties that met the inclusion was 10 years (interquartile range, 5-13), most were male (73.5%), with a moderate median injury severity score (17; interquartile range, 13-25). We performed regression modeling with adjustments for mechanism of injury, composite injury severity score, and total blood product volume (mL/kg based), grouping children based on high versus low fluid resuscitation. In the low-volume crystalloid group, we found that higher (>1:2) FFP/PRBC was associated with improved survival (odds ratio OR, 3.42). However, in the high fluid crystalloid resuscitation group, we found that that higher ratios for PLT/PRBC (>1:6) overall (OR, 0.46) and the FFP/PRBC (>1:2) in younger children (OR, 0.28) was associated with worse survival. The remaining associations were not statistically significant.
We found an association with survival in massively transfused pediatric trauma patients who received both a high FFP/PRBC ratio and low crystalloid administration. The benefit of this high ratio is negated, in patients receiving high crystalloid volumes, particularly among smaller children. Future studies on hemostatic resuscitation evaluating blood product ratios should also account for crystalloid and colloid administration.
Retrospective, comparative, level III.
Damage control resuscitation including balanced resuscitation with high ratios of plasma (PLAS) and platelets (PLT) to packed red blood cells (PRBC) improves survival in adult patients. We sought to ...evaluate the effect of a high ratio PLAS to PRBC resuscitation strategy in massively transfused pediatric patients with combat injuries.
The Department of Defense Trauma Registry was queried from 2001 to 2013 for pediatric trauma patients (<18 years). Burns, drowning, isolated head trauma, and older teens were excluded. Those who received massive transfusion (≥40 mL/kg total blood products in 24 hours) and early deaths who received any blood products were then evaluated. Primary outcomes were mortality at 24 hours and in-hospital. Secondary outcomes included blood product utilization over 24 hours, ventilator-free days, intensive care unit-free days, and hospital length of stay.
The Department of Defense Trauma Registry yielded 4,980 combat-injured pediatric trauma patients, of whom 364 met inclusion criteria. Analysis of PLAS/PRBC ratios across the entire spectrum of possible ratios in these patients demonstrated no clear inflection point for mortality. Using a division between low (LO) and high (HI) ratios of PLAS/PRBC 1:2, there was no difference in all-cause mortality at 24 hours (LO, 9.2% vs. HI, 8.0%; p = 0.75) and hospital discharge (LO, 21.5% vs. HI, 17.1%; p = 0.39). HI ratio patients received less PRBC but more PLAS and PLT and more total blood products. Those in the HI ratio group also had longer hospital length of stay. Regression analysis demonstrated no associated mortality benefit with a HI ratio (hazards ratio, 2.04; 95% confidence interval, 0.48-8.73; p = 0.34).
In combat-injured children undergoing a massive transfusion, a high ratio of PLAS/PRBC was not associated with improved survival. Further prospective studies should be performed to determine the optimal resuscitation strategy in critically injured pediatric patients.
Therapeutic study, level III.
Damage Control Resuscitation Cap, Andrew P; Pidcoke, Heather F; Spinella, Philip ...
Military medicine,
09/2018, Volume:
183, Issue:
suppl_2
Journal Article
Peer reviewed
Open access
Damage control resuscitation (DCR) is a strategy for resuscitating patients from hemorrhagic shock to rapidly restore homeostasis. Efforts are focused on blood product transfusion with whole blood or ...component therapy closely approximating whole blood, limited use of crystalloid to avoid dilutional coagulopathy, hypotensive resuscitation until bleeding control is achieved, empiric use of tranexamic acid, prevention of acidosis and hypothermia, and rapid definitive surgical control of bleeding. Patients receiving uncrossmatched Type O blood in the emergency department and later receiving cumulative transfusions of 10 or more red blood cell units in the initial 24-hour post-injury (massive transfusion) are widely recognized as being at increased risk of morbidity and mortality due to exsanguination. Ideally, these patients should be rapidly identified, however anticipating transfusion needs is challenging. Useful indicators of massive transfusion reviewed in this guideline include: systolic blood pressure <110 mmHg, heart rate > 105 bpm, hematocrit <32%, pH < 7.25, injury pattern (above-the-knee traumatic amputation especially if pelvic injury is present, multi-amputation, clinically obvious penetrating injury to chest or abdomen), >2 regions positive on Focused Assessment with Sonography for Trauma (FAST) scan, lactate concentration on admission >2.5, admission international normalized ratio ≥1.2-1.4, near infrared spectroscopy-derived StO2 < 75% (in practice, rarely available), BD > 6 meq/L. Unique aspects of out-of-hospital DCR (point of injury, en-route, and remote DCR) and in-hospital (Medical Treatment Facilities: Role 2b/Forward surgical teams - role 3/ combat support hospitals) are reviewed in this guideline, along with pediatric considerations.
Children represent a significant portion of the patient population treated at combat support hospitals. There is significant data regarding post injury seizures in adults but with children it is ...lacking. We seek to describe the incidence of post-traumatic seizures within this population.
This is a secondary analysis of previously described data from the Department of Defense Trauma Registry (DODTR). Within our dataset, we searched for documentation of seizures after admission.
Of the 3439 encounters in our dataset, we identified 37 casualties that had a documented seizure after admission. Most were in the 1-4 year age group (37.8%), male (59.4%), injured by explosive (40.5%), with serious injuries to the head/neck (75.6%). The median ISS was higher in the seizure group (22 versus 10, p<0.001). Most survived to hospital discharge with no statistically significant increased mortality noted in the seizure group (seizure 90.2% versus 91.8%, p = 1.000). In the prehospital setting, the seizure group was more frequently intubated (16.2% versus 6.0%, p = 0.023), received ketamine (20.0% versus 3.2%, p<0.001), and administered an anti-seizure medication (5.4% versus 0.1%, p = 0.001). In the hospital setting, the seizure group was more frequently intubated (56.7% versus 17.7%, p<0.001), had intracranial pressure monitoring (24.3% versus 2.6%, p<0.001), craniectomy (10.8% versus 2.5%, p = 0.014), and craniotomy (21.6% versus 4.7%, p<0.001).
Within our dataset, we found an incidence of 1% of pediatric casualties experiencing a post-traumatic seizure. While this number appears infrequent, there is likely significant under detection of subclinical seizures.
The Joint Theater Trauma Registry database, begun early in Operation Iraqi Freedom and Operation Enduring Freedom, created a comprehensive repository of information that facilitated research efforts ...and produced rapid changes in clinical care. New clinical practice guidelines were adopted throughout the last decade. The damage-control resuscitation clinical practice guideline sought to provide high-quality blood products in support of tissue perfusion and hemostasis. The goal was to reduce death from hemorrhagic shock in patients with severe traumatic bleeding. This 10-year review of the Joint Theater Trauma Registry database reports the military's experience with resuscitation and coagulopathy, evaluates the effect of increased plasma and platelet (PLT)-to-red blood cell ratios, and analyzes other recent changes in practice.
Records of US active duty service members at least 18 years of age who were admitted to a military hospital from March 2003 to February 2012 were entered into a database. Those who received at least one blood product (n = 3,632) were included in the analysis. Data were analyzed with respect to interactions within and between categories (demographics, admission characteristics, hospital course, and outcome). Transfusions were analyzed with respect to time, survival, and effect of increasing transfusion ratios.
Coagulopathy was prevalent upon presentation (33% with international normalized ratio ≥ 1.5), correlated with increased mortality (fivefold higher), and was associated with the need for massive transfusion. High transfusion ratios of fresh frozen plasma and PLT to red blood cells were correlated with higher survival but not decreased blood requirement. Survival was most correlated with PLT ratio, but high fresh frozen plasma ratio had an additive effect (PLT odds ratio, 0.22).
This 10-year evaluation supports earlier studies reporting the benefits of damage-control resuscitation strategies in military casualties requiring massive transfusion. The current analysis suggests that defects in PLT function may contribute to coagulopathy of trauma.
Epidemiologic study, level IV.
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