Article 1
Impact of Incorporating Whole Blood into Hemorrhagic Shock Resuscitation: Analysis of 1,377 Consecutive Trauma Patients Receiving Emergency-Release Uncrossmatched Blood Products. Brill JB, Tang B, Hatton G, Mueck KM, McCoy CC, Kao LS, Cotton BA. J Am Coll Surg. 2022 Apr 1;234(4):408-418.
Whole blood (WB) transfusion for resuscitation of hemorrhagic shock is not a novel concept being used during both World Wars, the Korean Conflict, and the Vietnam War. However, from the 1970s onwards market forces and logistical/storage issues promulgated the ubiquitous use of fractionated blood in modern day resuscitation. Renewed interest in whole blood has re-emerged due to its robust oxygen-carrying capacity, improve coagulation profile, and increased platelet concentration. While prior RCTs demonstrated some benefit with whole blood resuscitation, these studies were hampered by, amongst other constraints, small sample size. The present study is the largest prospective observational cohort published to date for use of whole blood in hemorrhagic shock.
The authors analyzed 1,377 patients who received any emergency-release, uncrossmatched blood products over a 3-year period and differentiated groups by whether they did or did not receive any whole blood during their resuscitation. This was in additional to component-based therapy. The primary outcome was two-fold: survival to discharge and 24-hour blood product usage. Regression modeling including weighted regression was used between groups to identify predictors of the primary outcomes overall and in several key subgroups including: 1) pre-hospital WB and in-hospital WB only, 2) ISS <15 and ISS >15, and 3) those with or without traumatic brain injury. In general, patients who received WB had worse injuries with a higher ISS and AIS while also having worse physiologic derangements compared to those who received no WB during their resuscitation. Despite these differences, univariate analysis of patients in the WB arm received similar volumes of component therapy compared to patients who received no WB during resuscitation. Following regression modeling with weighted analysis, however, the WB group had a near 60% improvement on 30-day survival (OR 1.59, 95% CI 1.28–1.98) and a 7% decrease in 24-hour blood product usage (OR 0.93, 95% CI 0.91–0.96). Moreover, survival benefit with WB transfusion was seen in three distinct subgroups: patients who received WB pre-hospital (OR 1.50, CI 0.98–2.31) and patients who received WB in-hospital (2.30, CI 1.63–3.26), patients who were both mildly (ISS <15) and severely (ISS >15) injured (OR 3.5, 95% CI 1.8–6.9; 3.7, 95% CI 1.9–7.3, respectively), and whose with or without TBI (with TBI: 1.4, 95% CI 1.0-1.8; without TBI: OR 1.8, 95% CI 1.3-2.5).
The findings from this study are strongly compelling for the incorporation of whole blood into any resuscitation strategy to affect both survival and product usage. Multi-institutional inquiry is needed to better define best practices with regards to WB resuscitation.
Article 2
Prehospital predictors of return of spontaneous circulation in traumatic cardiac arrest. Benhamd A, Canon V, Mercier E, Heidet M, Goosiome A, Savary D, El Khoury C, Gueugniaud P, Hubert H, Tazaourte K. J Trauma Acute Care Surg. 2022 Mar 1;92(3):553-560.
Out of hospital traumatic cardiac arrest (TCA) is associated with high mortality and efforts to garner improved survival along with acceptable neurological outcomes are mixed in the published literature. In distinction from North American based trauma systems where physician-led care predominates within hospital centers, European models of care employ physician-led mobile medical teams into the field to triage and treat the injured prior to hospital arrival. The present study is a retrospective analysis of a large, prospectively maintained French national cardiac arrest registry wherein nearly all out of hospital cardiac arrests (whether medical or traumatic) are captured. The purpose of the study was to assess in a prehospital, physician-led EMS the factors associated with sustained return of spontaneous circulation (ROSC) following TCA, and specifically to gauge the effect of advanced life support procedures barring resuscitative thoracotomy and REBOA.
Over a 9-year period, 4,922 TCAs were eligible for analysis of which 21.1% (n=1,037) patients had on-scene ROSC. Compared to those who did not achieve ROSC, ROSC patients were older, more often had a blunt mechanism of injury, more often had a witnessed TCA, were less likely to be in asystole on initial evaluation, and more likely to have signs of life with pupillary reactivity and agonal respirations. Regarding advanced life support procedures, those with ROSC had more endotracheal intubation vs bag-valve mask ventilation, were more likely to receive intravenous fluids and blood, and more often underwent external hemorrhage control. Notably, patients who did not achieve ROSC more often had finger or needle thoracostomies than those who underwent ROSC. On multivariate logistic regression, predictors of ROSC included any first recorded cardiac rhythm other than asystole, receiving IV fluids or blood, and having undergone external hemorrhage control while resuscitative measures such as finger or needle thoracostomy were predictive of not achieving ROSC. As a secondary outcome, predictors of survival at 30 days in those who achieved ROSC were signs of life at first evaluation including any rhythm other than asystole and signs of agonal respirations while increasing age, penetrating injury, and IV fluid administration were predictive of mortality. Of note, of those who achieved ROSC, only 67 patients (6.5%) survived to 30 days but 72.2% of survivors had acceptable neurological outcomes. Organ donation in decedents was 1.4%.
This study provides insight into not only the factors associated with ROSC in a trauma triage system fundamentally different from its North American counterpart but highlights the overall low survival of out-of-hospital TCA despite advanced life support procedures. Though well designed, it does suffer the design flaws inherent of large, retrospective database analyses and its applicability to North American trauma system design may be difficult to assess.
Article 3
Risk Factors and Prognosis of Early Posttraumatic Seizures in Moderate to Severe Traumatic Brain Injury. Laing J, Gabbe B, Chen Z, Perucca P, Kwan P, O'Brien TJ. JAMA Neurol. 2022 Apr 1;79(4):334-341.
Early posttraumatic seizures (EPS) following a traumatic brain injury (TBI) are associated with increased morbidity, mortality, and posttraumatic epilepsy (PTE). Antiseizure prophylaxis for 7 days following TBI is recommended for EPS prevention, yet seizures occurring outside this window are associated with an 86% prevalence of PTE at 2 years. Lifelong suppression of EPS with antiseizure medication following TBI is not currently supported; however, identifying patients at increased risk could guide antiepileptogenic prescribing. The objective of this study was to identify risk factors for EPS and determine the effect of EPS on short- and long-term outcomes. The authors performed a retrospective review of 15,152 patients aged ≥18 years from 2005 through 2019 who sustained a moderate to severe TBI. Patients were followed for 2 years after injury. Patients who developed EPS during their hospitalization were compared to non-EPS patients to identify EPS risk factors. Short-term outcomes included hospital length of stay (LOS), ICU LOS, ventilated LOS, in-hospital mortality, and discharge disposition. Long-term outcomes assessed at 2-year follow-up included Glasgow Outcome Sale, development of PTE, and use of antiseizure medication (ASM).
Of the 15,152 patients, 416 (2.7%) developed EPS. Significant risk factors for EPS on multivariable regression were increasing a low-height fall, subdural hematoma (SDH), subarachnoid hematoma (SAH), and GCS ≤ 8 as well as increasing age, Charlson Comorbidity Index (CCI), Injury Severity Score, and AIS head severity. Using adaptive least absolute shrinkage and selection operator (LASSO) regression, a CCI > 2, a SDH, and AIS head ≥ 5 contributed most toward EPS association. Patients with EPS had a significantly increased risk of ICU admission and discharge to inpatient rehabilitation as well as longer ICU LOS, ventilator LOS, and hospital LOS. There was no association between EPS and in-hospital mortality. At 2-year follow-up, patients with EPS had a significantly greater risk of severe disability (RR 2.1, p = .001), vegetative state (RR 3.97, p = .046), death (RR 2.14, p = .002), PTE (RR 2.91, p < .001), and ASM use (RR 2.44, p < .001). Predicting which patients are at increased risk for EPS on hospital admission could inform better antiepileptogenic therapies to prevent EPS and its associated adverse outcomes.
Article 4
Assessment of the effect of amantadine in patients with traumatic brain injury: A meta-analysis. Mohamed MS, Sayed IE, Zaki A, Abdelmonem S. J Trauma Acute Care Surg. 2022 Mar 1;92(3):605-614.
Patients with a traumatic brain injury (TBI) are at risk for impairment in cognition and memory. Several pharmacologic treatments have been trialed to improve cognition following TBI, such as amantadine—a dopamine agonist. There is conflicting data about the efficacy of amantadine on improving cognition in this patient population due to varying definitions of TBI and the heterogeneous outcomes evaluated. The goal of this meta-analysis was to estimate the magnitude of efficacy of amantadine on cognitive impairment after TBI. Of the 3,440 records identified, a total of 14 clinical trials, 4 cohort studies, and 2 case-control studies were included in the final analysis. Clinical parameters evaluated were amantadine dose, treatment onset, and treatment duration. The primary outcome was improvement in cognitive function compared attributed to amantadine; secondary outcomes included hospital length of stay (LOS) and adverse events related to amantadine use. Outcomes were measured by the mean difference (MD) between amantadine and comparators: small effect (MD 0.2), medium effect (0.5), and large effect (MD 0.8).
Compared to placebo, amantadine significantly augmented cognitive function (MD 0.5, p < .001). A significant improvement in cognition was observed when amantadine was given within the first week of injury (MD 0.97) and when prescribed for less than a month (MD 0.83). On subgroup analysis, cognitive improvements were significantly improved for patients < 18 years of age (MD 0.66) and among patients with a moderate TBI (MD 0.40). There was no difference in hospital LOS or adverse events when comparing amantadine to placebo. On meta-regression of timing of treatment onset, patient age, and TBI severity, treatment onset had the greatest association with the effect size of amantadine. A major limitation of the study was the measurement of cognition because of the different tools used and different cognitive domains assessed. Nevertheless, amantadine may improve cognitive function in patients with a TBI and larger randomized control trials are warranted to validate these findings.
