Tranexamic acid in pediatric combat trauma requiring massive transfusions and mortality.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. LEVEL OF EVIDENCE: Evidence (retrospective cohort), Level IV.

Life on the battlefield: Valproic acid for combat applications.

The leading causes of death in military conflicts continue to be hemorrhagic shock (HS) and traumatic brain injury (TBI). Most of the mortality is a result of patients not surviving long enough to obtain surgical care. As a result, there is a significant unmet need for a therapy that stimulates a "prosurvival phenotype" that counteracts the cellular pathophysiology of HS and TBI to prolong survival. Valproic acid (VPA), a well-established antiepileptic therapy for more than 50 years, has shown potential as one such prosurvival therapy. This review details how VPA's role as a nonselective histone deacetylase inhibitor induces cellular changes that promote survival and decrease cellular pathways that lead to cell death. The review comprehensively covers more than two decades worth of studies ranging from preclinical (mice, swine) to recent human clinical trials of the use of VPA in HS and TBI. Furthermore, it details the different mechanisms in which VPA alters gene expression, induces cytoprotective changes, attenuates platelet dysfunction, provides neuroprotection, and enhances survival in HS and TBI. Valproic acid shows real promise as a therapy that can induce the prosurvival phenotype in those injured during military conflict.

Use of ketamine for prehospital pain control on the battlefield: A systematic review.

BACKGROUND: Intravenous ketamine is commonly used for pain management in the civilian prehospital setting. Several studies have evaluated its effectiveness in the military setting. To date, there has been no report reviewing the published data on the use of ketamine in this context. The objective of this systematic review was to analyze the content and quality of published data on the use of ketamine for prehospital pain management in military trauma. METHODS: The MEDLINE database was searched for studies on ketamine use in combat prehospital settings, at point of injury or during evacuation, published between 2000 and 2019. The systematic review was conducted following PRISMA guidelines, and the protocol was registered on PROSPERO (CRD42019115728). Civilian reports and case series lacking systematic data collection were excluded. RESULTS: Eight studies were included with 2029 casualties receiving ketamine. All but one were American reports from Afghanistan and Iraq conflicts. Studies implied retrospective cohorts or prospective observational analysis. Ketamine use rose from 3.9% during the period preceding its addition to the Tactical Combat Casualty Care guidelines in 2012 to 19.8% thereafter. It was the most common analgesic administered (up to 52% of casualties) in one of the studies. Ketamine was more likely given during tactical medical evacuation when no analgesic was provided at the point of injury. The median total intravenous dose was 50 mg. Pain intensity decreased from moderate or severe to mild or none, sometimes after only one dose. In one study, ketamine administration during tactical evacuation was associated with increased systolic blood pressure as opposed to morphine. Incoherent speech, extremity movements, and hallucinations were the main adverse events reported. CONCLUSION: Published data on ketamine use in military trauma are rare and heterogeneous. Though, all studies tend to strengthen the belief in the efficacy and safety of ketamine when given at 50-mg to 100-mg intravenous for prehospital analgesia in combat casualties. LEVEL OF EVIDENCE: Systematic Review, Level IV.

Battlefield pain management: A view of 17 years in Israel Defense Forces.

BACKGROUND: Pain control in trauma is an integral part of treatment in combat casualty care (CCC). More soldiers injured on the battlefield will need analgesics for pain than those who will need lifesaving interventions (LSI). It has been shown that early treatment of pain improves outcomes after traumatic injury, whereas inadequate treatment leads to higher rates of PTSD. The purpose of this article is to report the Israel Defense Forces Medical Corps (IDF-MC) experience with point of injury (POI) use of analgesia. METHODS: All cases documented in the IDF Trauma Registry (ITR) between January 1997 and December 2014 were examined. All cases of POI pain medications were extracted. Data collection included mechanism of injury, wound distribution, pain medication administered, mortality, and provider type. RESULTS: Of 8,576 patients, 1,056 (12.3%) patients who had at least one documented pain management treatment were included in this study. Demographics of the study population included 94.2% men and 5.8% women with a median age of 21 years. Injury mechanisms included 40.3% blast injuries (n = 426) and 29% gunshot injuries (306). Of 1,513 injured body regions reported, 52% (787) were extremity wounds (upper and lower), 23% (353) were truncal wounds, and 17.7% (268) were head and neck injuries. A total of 1,469 episodes of analgesic treatment were reported. The most common types of analgesics were morphine (74.7%, 1,097 episodes), ketamine (9.6%, 141 episodes), and fentanyl (13.6%, 200 episodes). Of the patients, 39% (413) received more than one type of analgesic. In 90.5% of cases, analgesia was administered by a physician or a paramedic. Over the span of the study period (1997-2014), types of analgesics given by providers at POI had changed, as fentanyl was introduced to providers. A total of 801 LSIs were performed on 379 (35.9%) patients receiving analgesia, and no adverse events were found in any of the casualties. CONCLUSION: Most casualties at POI did not receive any analgesics while on the battlefield. The most common analgesics administered at POI were opioids and the most common route of administration was intravenously. This study provides evidence that over time analgesic administration has gained acceptance and has been more common place on the battlefield. Increasingly, more casualties are receiving pain management treatment early in CCC along with LSIs. We hope that this shift will impact CCC by reducing PTSD and overall morbidity resulting from inadequate management of acute pain.