Invited Commentary: Doing It Right Ho, Jessie W; Alam, Hasan B
Journal of the American College of Surgeons,
01/2023, Volume:
236, Issue:
1
Journal Article
ABSTRACT
Introduction
Tranexamic acid (TXA) is a standard component of Tactical Combat Casualty Care. Recent retrospective studies have shown that TXA use is associated with a higher rate of venous ...thromboembolic (VTE) events in combat-injured patients. We aim to determine if selective administration should be considered in the prolonged field care environment.
Materials and Methods
We performed a systematic review using the 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Clinical trials and observational studies of combat casualties published between January 1, 1960, and June 20, 2022, were included. We analyzed survival and VTE outcomes in TXA recipients and non-recipients. We discussed the findings of each paper in the context of current and future combat environments.
Results
Six articles met criteria for inclusion. Only one study was powered to report mortality data, and it demonstrated a 7-fold increase in survival in severely injured TXA recipients. All studies reported an increased risk of VTE in TXA recipients, which exceeded rates in civilian literature. However, five of the six studies used overlapping data from the same registry and were limited by a high rate of missingness in pertinent variables. No VTE-related deaths were identified.
Conclusions
There may be an increased risk of VTE in combat casualties that receive TXA; however, this risk must be considered in the context of improved survival and an absence of VTE-associated deaths. To optimize combat casualty care during prolonged field care, it will be essential to ensure the timely administration of VTE chemoprophylaxis as soon as the risk of significant hemorrhage permits.
The clinical usage of the resuscitative endovascular balloon occlusion of the aorta (REBOA) is limited by distal ischemia resulting from complete aortic occlusion. We hypothesized that animals would ...physiologically tolerate the prolonged partial occlusion using the novel partially occluding REBOA (pREBOA) with survivable downstream injuries.
This study used the pREBOA-PRO catheter in a previously established swine model. Female Yorkshire swine (n = 10) underwent a volume-controlled hemorrhage (40% estimated blood). After 1 hour of shock (mean arterial pressure, 28-32 mm Hg), animals were randomized to partial occlusion for either 2 hours or 4 hours. The pREBOA was inflated in zone 1 to achieve partial occlusion defined as a distal systolic blood pressure (SBP) of 20 ± 2 mm Hg. The balloon was deflated at the end of the occlusion period, and animals were resuscitated for 2 hours. Tissues were examined for gross and histologic injury. The primary endpoint was histologic organ injury, and secondary end points were hemodynamic variables and degree of distal organ ischemia.
All animals survived to the endpoint. Both groups had similar proximal and distal SBP at baseline, with a divergence of pressures ranging from 55 mm Hg to 90 mm Hg on inflation. The lactate levels increased throughout the occlusion and decreased approximately 40% during the observation period. More animals required norepinephrine and fluid in the 4-hour group compared with the 2-hour group. There was no gross small bowel ischemia noted in the 2-hour animals. The 4-hour group had surgically resectable patchy short segment ischemia. Neither group showed nonsurvivable organ ischemia on pathology or laboratory values.
This is the first study showing that the zone 1 aorta can be occluded for over 4 hours using a new pREBOA device without need for balloon titration. In conclusion, simple changes in balloon design offer reliable partial aortic occlusion, with potentially survivable and surgically manageable downstream injuries.
Injuries lead to an early systemic inflammatory state with innate immune system activation. Neutrophil extracellular traps (NETs) are a complex of chromatin and proteins released from the activated ...neutrophils. Although initially described as a response to bacterial infections, NETs have also been identified in the sterile postinjury inflammatory state. Peptidylarginine deiminases (PADs) are a group of isoenzymes that catalyze the conversion of arginine to citrulline, termed citrullination or deimination. PAD2 and PAD4 have been demonstrated to play a role in NET formation through citrullinated histone 3. PAD2 and PAD4 have a variety of substrates with variable organ distribution. Preclinical and clinical studies have evaluated the role of PADs and NETs in major trauma, hemorrhage, burns, and traumatic brain injury. Neutrophil extracellular trap formation and PAD activation have been shown to contribute to the postinjury inflammatory state leading to a detrimental effect on organ systems. This review describes our current understanding of the role of PAD and NET formation following injury and burn. This is a new field of study, and the emerging data appear promising for the future development of targeted biomarkers and therapies in trauma.
It has previously been shown that administration of valproic acid (VPA) can improve outcomes if given within an hour following traumatic brain injury (TBI). This short therapeutic window (TW) limits ...its use in real-life situations. Based upon its pharmacokinetic (PK) data, we hypothesized that TW can be extended to 3 hours if a second dose of VPA is given 8 hours after the initial dose.
Yorkshire swine (40-45 kg; n = 10) were subjected to TBI (controlled cortical impact) and 40% blood volume hemorrhage. After 2 hours of shock, they were randomized to either: 1) normal saline (NS) resuscitation (control), or 2) NS + VPA (150 mg/kg x 2 doses). First dose of VPA was started 3 hours after the TBI, with a second dose 8 hours after the first dose. Neurologic severity scores (NSS) (range, 0-36) were assessed daily for 14 days, and brain lesion size was measured via magnetic resonance imaging (MRI) on post-injury day 3.
Hemodynamic and laboratory parameters of shock were similar in both groups. VPA-treated animals had significantly less neurologic impairment on days 2 (16.3 ± 2.0 vs 7.3 ± 2.8) and 3 (10.9 ± 3.6 vs 2.8 ± 1.1) post-injury and returned to baseline levels 54% faster. MRI showed no differences in brain lesion size on day 3. PK data confirmed neuroprotective levels of VPA in the circulation.
This is the first study to demonstrate that VPA can be neuroprotective even when given 3 hours after TBI. This expanded TW has significant implications for the design of the clinical trial.
N/A (Animal study).
Severe traumatic brain injury (TBI) often initiates a systemic inflammatory response syndrome, which can potentially culminate into multiorgan dysfunction. A central player in this cascade is ...endotheliopathy, caused by perturbations in homeostatic mechanisms governed by endothelial cells due to injury-induced coagulopathy, heightened sympathoadrenal response, complement activation, and proinflammatory cytokine release. Unique to TBI is the potential disruption of the blood-brain barrier, which may expose neuronal antigens to the peripheral immune system and permit neuroinflammatory mediators to enter systemic circulation, propagating endotheliopathy systemically. This review aims to provide comprehensive insights into the "neuroendothelial axis" underlying endothelial dysfunction after TBI, identify potential diagnostic and prognostic biomarkers, and explore therapeutic strategies targeting these interactions, with the ultimate goal of improving patient outcomes after severe TBI.
We have previously shown that partial REBOA (pREBOA) deployment in the thoracic aorta is safe for 2 to 4 hours, but it is unclear whether the distal blood flow after partial aortic occlusion would ...lead to ongoing hemorrhage. The objective of this study was to evaluate the hemostatic efficacy of pREBOA in a model of uncontrolled vascular injury.
Female Yorkshire swine (n = 10, 40 to 45 kg) were anesthetized and instrumented. A through-and-through injury was created in the common iliac artery. The animals were randomly assigned to: (1) pREBOA-PRO deployment after 3 minutes and (2) control. Both groups were given normal saline resuscitation for hypotension. The pREBOA was adjusted to partial occlusion (distal mean arterial pressure of 30 mmHg), and then left without titration for 2 hours. Then, fresh frozen plasma was transfused and the vessel repaired. The balloon was deflated and the animals were monitored for 2 hours. In the critical care period, 2 L of normal saline was infused, norepinephrine was given for mean arterial pressure ≤55, and electrolytes and acidosis were corrected. Organs were examined for gross and histologic evidence of ischemic injuries. The primary endpoint was post-inflation blood loss.
All the pREBOA animals survived until the end, whereas control animals had a mean survival time of 38.2 minutes (p < 0.05). The pREBOA group showed significantly less bleeding after balloon deployment (93.8 vs 1,980.0 mL, p < 0.05), and had appropriate lactate clearance, with minimal histologic distal organ ischemia.
Partial aortic occlusion with the newly designed balloon can achieve the desired balance between effective hemorrhage control and adequate distal flow, without a need for ongoing balloon titration.
