Efficacy and safety of the second in-hospital dose of tranexamic acid after receiving the prehospital dose: double-blind randomized controlled clinical trial in a level 1 trauma center

Background Prehospital administration of tranexamic acid (TXA) to injured patients is increasing worldwide. However, optimal TXA dose and need of a second infusion on hospital arrival remain undetermined. We investigated the efficacy and safety of the second in-hospital dose of TXA in injured patients receiving 1 g of TXA in the prehospital setting. We hypothesized that a second in-hospital dose of TXA improves survival of trauma patients. Methods A prospective, double-blind, placebo-controlled randomized, clinical trial included adult trauma patients receiving 1 g of TXA in the prehospital settings. Patients were then blindly randomized to Group I (second 1-g TXA) and Group II (placebo) on hospital arrival. The primary outcome was 24-h (early) and 28-day (late) mortality. Secondary outcomes were thromboembolic events, blood transfusions, hospital length of stay (HLOS) and organs failure (MOF). Results A total of 220 patients were enrolled, 110 in each group. The TXA and placebo groups had a similar early [OR 1.000 (0.062–16.192); p = 0.47] and late mortality [OR 0.476 (95% CI 0.157–1.442), p = 0.18].The cause of death (n = 15) was traumatic brain injury (TBI) in 12 patients and MOF in 3 patients. The need for blood transfusions in the first 24 h, number of transfused blood units, HLOS, thromboembolic events and multiorgan failure were comparable in the TXA and placebo groups. In seriously injured patients (injury severity score > 24), the MTP activation was higher in the placebo group (31.3% vs 11.10%, p = 0.13), whereas pulmonary embolism (6.9% vs 2.9%, p = 0.44) and late mortality (27.6% vs 14.3%, p = 0.17) were higher in the TXA group but did not reach statistical significance. Conclusion The second TXA dose did not change the mortality rate, need for blood transfusion, thromboembolic complications, organ failure and HLOS compared to a single prehospital dose and thus its routine administration should be revisited in larger and multicenter studies. Trial registration ClinicalTrials.gov Identifier: NCT03846973.

Clinical and Imaging Indicators of Hemorrhagic Transformation in Acute Ischemic Stroke After Endovascular Thrombectomy

Background and Purpose: Prior studies have investigated the clinical and imaging factors for hemorrhagic transformation (HT), especially symptomatic intracranial hemorrhage (sICH); however, whether alteplase increases the risk of HT after endovascular thrombectomy (EVT) is unknown. This study aimed to assess clinical and imaging features associated with HT, sICH, and parenchymal hematoma (PH) in patients with acute ischemic stroke after EVT, with and without intravenous alteplase in DIRECT-MT (Direct Intraarterial Thrombectomy to Revascularize Acute Ischemic Stroke Patients with Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: a Multicenter Randomized Clinical Trial). Methods: The DIRECT-MT trial is a randomized trial of EVT alone versus intravenous thrombolysis combined with EVT. HT, sICH, and PH was evaluated on follow-up computed tomography. Multivariable ordinal logistic regression analysis was used to test the association of stepwise selected determinants with HT, sICH, and PH. Results: In total, 633 patients were analyzed; 261 (41.2%) had HT; 34 (5.4%) had sICH; and 85 (13.4%) had PH. The median age was 69, and 56.7% were men. The median National Institutes of Health Stroke Scale score was 18, and 320 patients were in combination-therapy group. Symptomatic intracranial hemorrhage was associated with higher baseline National Institutes of Health Stroke Scale score (adjusted odds ratio [OR], 1.06 [95% CI, 1.10–1.12]) and higher glucose level at hospital arrival (adjusted OR, 1.14 [95% CI, 1.00–1.29]). No association was found between alteplase treatment and HT, sICH, or PH. The independent predictor of sICH was higher baseline National Institutes of Health Stroke Scale score (adjusted OR, 1.09 [95% CI, 1.01–1.18]) in EVT alone group, and history of anticoagulant drugs (adjusted OR, 3.75 [95% CI, 1.07–13.06]), higher glucose level at hospital arrival (adjusted OR, 1.19 [95% CI, 1.03–1.38]), >3 passes of device (adjusted OR, 4.42 [95% CI, 1.36–14.32]) in combination-therapy group. Conclusions: In DIRECT-MT, independent predictors of sICH were baseline National Institutes of Health Stroke Scale score and glucose level at hospital arrival. Alteplase treatment did not increase the risk of HT, sICH, or PH after EVT. The independent predictor of sICH was different in EVT alone group and combination-therapy group. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03469206.

Do deaths from road traffic injuries follow a classical trimodal pattern in North West Ethiopia? A hospital-based prospective cohort study

ObjectiveThe objective of this study was to identify timing distribution and predictors of deaths following road traffic injuries among all age groups at Gondar Comprehensive specialised hospital.DesignA single-centre prospective cohort study.SettingThe study hospital is a tertiary hospital in North West Ethiopia.ParticipantsWe enrolled 454 participants who sustained road traffic injuries in to the current study. All age groups and injury severity were included except those who arrived dead, had no attendant and when the injury time was unknown.Primary and secondary outcome measuresThe primary outcome was time to death measured in hours from injury time up to the 30th day of the injuries. Secondary outcomes were prehospital first aid, length of hospital stay and hospital arrival time. The article has been registered, with a unique identification number of research registry 6556.ResultsA total of 454 victims were followed for 275 534 person hours. There were 80 deaths with an overall incidence of 2.90 deaths per 10 000 person hours of observation (95% CI 2.77 to 3.03). The significant predictors of time to death were being a driver (AHR=2.26; 95% CI 1.09 to 4.65, AR=14.8), accident at interurban roads ((AHR (Adjusted HAzard Ratio=1.98; 95% CI 1.02 to 3.82, AR (Attributable Risk)=21%)), time from injury to hospital arrival (AHR=0.41; 95% CI 0.16 to 0.63; AR=3%), systolic blood pressure on admission of <90 mm Hg (AHR=3.66; 95% CI 2.14 to 6.26; AR=57%), Glasgow Coma Scale of <8 (AHR=7.39; 95% CI 3.0819 to 17.74464; AR=75.7%), head injury with polytrauma (AHR=2.32 (1.12774 4.79; AR=37%) and interaction of distance from hospital with prehospital care.ConclusionThough the maturation of trauma centres in many developed countries has changed the temporal pattern of deaths following any trauma, our study demonstrated that trauma deaths follow the traditional trimodal pattern. That implies that potentially preventable causes of death continued in low-resource countries.

Abstract 11243: Novel Peptide for Cardiopulmonary Resuscitation

Introduction: While effective for out-of-hospital cardiac arrest, therapeutic hypothermia can be difficult to timely implement clinically. No drugs exist for improving neurologically intact survival. We have developed a novel peptide (TAT-PHLPP) that inhibits PH domain and Leucine rich repeat Protein Phosphatases (PHLPP), leading to Akt activation and mimicking of the protective effects of therapeutic hypothermia without the need of physical cooling. Hypothesis: We hypothesize that when administered intravenously during CPR, TAT-PHLPP improves neurologically intact survival. Methods: We conducted parallel studies in mouse and swine models. In C57BL6 mice (n = 72), we induced a 8 or 12-min asystolic cardiac arrest with KCl, followed by initiation of CPR and blinded randomized administration of TAT-PHLPP (7.5 mg/kg) or saline placebo. The primary outcomes were 4-h and 5-day survival, mean arterial blood pressure (MAP) and cerebral blood flow (CBF). We assessed PHLPP-NHERF1 binding and glucose utilization (via pyruvate dehydrogenase (PDH) phosphorylation and ATP generation). In 16 swine, we induced 5 min of VF followed by ACLS with vest CPR and administered two doses of TAT-PHLPP or saline. Survival (24 h) and neurological function were assessed. Plasma biomarkers taurine and glutamate levels in mice were measured and validated in CA patients (n=68) with a shockable rhythm at the time of hospital arrival, 6, 24, 48, and 72 h post-hospital arrival. Results: In mice, compared to saline, TAT-PHLPP significantly improved 4-h and 5-day survival, increased post-ROSC MAP and CBF, inhibited PHLPP-NHERF1 binding, increased p-Akt, decreased p-PDH (increased activity) at 15 min post-ROSC, enhanced ATP generation in both heart and brain, and reduced plasma taurine and glutamate levels. In swine, TAT-PHLPP improved 24 h neurologically intact survival (1/9 in control vs. 6/7 with peptide, p < 0.01). In patients, taurine levels were higher in non-survivors (n=44) than survivors (n=24) at 6 h of post-hospital arrival (65.9 ± 34.8 vs. 45.6 ±23.7, p< 0.001). Conclusions: TAT-PHLPP has high translational potential as a first-of-class biologic treatment to reproduce critical outcomes of therapeutic hypothermia and improve cardiac arrest survival.

Abstract 11312: Activation of Citizen Responders to Out-of-Hospital Cardiac Arrest: Temporal Changes During the COVID-19 Outbreak in Denmark 2020

Introduction: Multiple citizen responder (CR) programs worldwide which dispatch laypersons to out-of-hospital cardiac arrest (OHCA) to perform cardiopulmonary resuscitation (CPR) and use of automated external defibrillators (AEDs) were affected by the COVID-19 outbreak in 2020, but little is known about how the pandemic affected CR activation and initiation of bystander CPR and defibrillation. In Denmark, the CR program continued to run during lockdown but with the recommendation to perform chest-compression-only CPR in contrast to standard CPR including ventilations. We hypothesized that bystander interventions as CPR and AED usage decreased during the first COVID-19 lockdown in two regions of Denmark in the spring of 2020. Methods: All OHCAs from January 1, 2020 to June 30, 2020 with CR activation from the Danish Cardiac Arrest Registry and the National Citizen Responder database. Bystander CPR, AED usage, and CRs’ alarm acceptance rate during the national lockdown from March 11, 2020 to April 20, 2020 were compared with the non-lockdown period from January 1, 2020 to March 10, 2020 and from April 21 to June 30, 2020. Results: A total of 6,120 CRs were alerted in 443 (23/100.000 inhabitants) cases of presumed OHCA of which 256 (58%) were confirmed cardiac arrests. Bystander CPR remained equally high in the lockdown period compared with non-lockdown period (99% vs. 92%, p=0.07). Likewise, there was no change in bystander defibrillation (9% vs. 14%, p=0.4). There was a slight increase in the number of CRs who accepted an alarm (7 per alarm, IQR 4) during lockdown compared with non-lockdown period (6 per alarm, IQR 4), p=0.0001. The proportion of patients achieving return of spontaneous circulation at hospital arrival was also unchanged (lockdown 23% vs non-lockdown 23%, p=1.0) (Table 1). Conclusion: Bystander initiated resuscitation rates did not change during the first COVID-19 lockdown in Denmark for OHCAs where CRs were activated through a smartphone app.

Abstract 9450: Shockable Rhythm at Hospital Arrival as the Predictor of Favorable Neurological Outcome in Out-of-Hospital Cardiac Arrest Patients Receiving Extracorporeal Cardiopulmonary Resuscitation

Introduction: For OHCA patients without ROSC under standard ALS, extracorporeal cardiopulmonary resuscitation (ECPR) was the only chance. However, ECPR was invasive and costed tremendous resources. This study aimed to analyze the predictor of favorable neurological outcome at hospital discharge (FO, cerebral performance category 1-2). Hypothesis: In OHCA patients receiving ECPR, shockable rhythm at hospital arrival could serve as predictor of FO. Method: This was a single center retrospective study which enrolled 126 OHCA patients receiving ECPR between January 2012 to December 2019. Primary outcome was FO at hospital discharge. Predictors of FO were assessed by multiple logistic regression. Patients with initial shockable rhythm were analyzed according to the cardiac rhythm at hospital arrival. Result: Among OHCA patients receiving ECPR, FO at hospital discharge was 21%. Certain variables were associated with FO: witnessed collapse (P=0.014), bystander CPR (P=0.05), shorter no flow time(P=0.008), and shockable rhythm at hospital arrival (78% vs. 49%;P=0.009). Initial shockable rhythm did not differ significantly (85% vs. 71% ;P=0.15). Multiple logistic regression showed that shockable rhythm at hospital arrival was the only predictor of FO (OR, 3.012; 95% CI, 1.06-8.53; P=0.038). Patients with initial shockable rhythm represented a heterogenous group. The group with shockable rhythm at hospital arrival had 30% of FO, which was significantly higher than 17% in PEA group, and 6% in asystole group (Graph 1). Patients who remained shockable had higher percentage of witnessed arrest, shorter arrest-hospital time, less metabolic disturbance, and hence higher percentage of FO. Conclusion: In OHCA patients receiving ECPR, shockable rhythm at hospital arrival could predict favorable neurological outcome at discharge more precisely than initial shockable rhythm. ECPR selection criteria should take the rhythm at hospital arrival into consideration.

C.1 Time Metrics and Clinical Outcomes of Thrombectomy in Acute Stroke Patients Before and After Implementation of COVID-19 Infection Protocols in Nine Canadian Stroke Centres

Background: The coronavirus disease 2019 (COVID-19) pandemic has led an implementation of institutional infection control protocols. This study will determine the effects of these protocols on outcomes of acute ischemic stroke (AIS) patients treated with endovascular therapy (EVT). Methods: Uninterrupted time series analysis of the impact of COVID-19 safety protocols on AIS patients undergoing EVT. We analyze data from prospectively collected quality improvement databases at 9 centers from March 11, 2019 to March 10, 2021. The primary outcome is 90-day modified Rankin Score (mRS). The secondary outcomes are angiographic time metrics. Results: Preliminary analysis of one stroke center included 214 EVT patients (n=144 pre-pandemic). Baseline characteristics were comparable between the two periods. Time metrics “last seen normal to puncture” (305.7 vs 407.2 min; p=0.05) and “hospital arrival to puncture” (80.4 vs 121.2 min; p=0.04) were significantly longer during pandemic compared to pre-pandemic. We found no significant difference in 90-day mRS (2.0 vs 2.2; p=0.506) or successful EVT rate (89.6% vs 90%; p=0.93). Conclusions: Our results indicate an increase in key time metrics of EVT in AIS during the pandemic, likely related to infection control measures. Despite the delays, we found no difference in clinical outcomes between the two periods.

Shockable Rhythm at Hospital Arrival as the Predictor of Favourable Neurological Outcome in Patients with Out-of-Hospital Cardiac Arrest (OHCA) Receiving Extracorporeal Cardiopulmonary Resuscitation (ECPR)

Introduction: For patients with out-of-hospital cardiac arrest (OHCA) without return of spontaneous circulation under advanced life support, extracorporeal cardiopulmonary resuscitation (ECPR) is the only lifesaving option. This study aimed to analyse the predictors of favourable neurological outcomes (FO, cerebral performance category 1-2) at hospital discharge among patients with OHCA following ECPR.Methods: In this single-centre retrospective study, 126 patients with OHCA who received ECPR between January 2012 and December 2019 were enrolled. The primary outcome was the FO at hospital discharge. The predictors of FO were assessed using multiple logistic regression analysis. Patients with an initial shockable rhythm were further analysed according to the cardiac rhythm at the time of hospital arrival. Results: Among the patients who received ECPR, the FO at hospital discharge was 21%. Certain resuscitation variables were associated with FO including witnessed collapse (P=0.014), bystander CPR (P=0.05), shorter no-flow time (P=0.008), and a shockable rhythm at hospital arrival (P=0.009). Multiple logistic regression showed that a shockable rhythm at hospital arrival was the only independent predictor of FO at discharge (odds ratio, 3.012; 95% confidence interval, 1.06-8.53; P=0.038). Among patients with an initial shockable rhythm, the group with a shockable rhythm at hospital arrival had a FO of 30%, which was significantly higher than the 11% in the non-shockable rhythm group (P=0.043).Conclusions: In patients with OHCA who received ECPR, a shockable rhythm at the time of hospital arrival was associated with favourable neurological outcomes at discharge. The ECPR selection criteria could consider the rhythm at hospital arrival.

Can Cerebral Regional Oxygen Saturation (rSO2) be used as an Indicator of the Quality of Chest Compressions in Patients with Cardiopulmonary Arrest? A Study Evaluating The Association between rSO2 and Mean Arterial Pressure: The PRESS Study

Background: Sudden cardiac arrest causes numerous deaths worldwide. High-quality chest compressions are important for good neurological recovery. Arterial pressure is considered useful to monitor the quality of chest compressions by the American Heart Association. However, arterial pressure catheter might be inconvenient during resuscitation. Conversely, cerebral regional oxygen saturation (rSO2) during resuscitation may be associated with a good neurological prognosis. Therefore, we aimed to evaluate the correlation between mean arterial pressure and rSO2 during resuscitation to use rSO2 as the indicator of the quality of chest compressions.Methods: This study was a single-centre, prospective, observational study. Patients with out-of-hospital cardiac arrest who were transported to a tertiary care emergency centre between October 2014 and March 2015 in Japan were included. The primary outcome was the regression coefficient between MAP and rSO2. MAP and rSO2 were measured during resuscitation (at hospital arrival [0 min], 3 min, 6 min, 9 min, 12 min, 15 min), and MAP was measured by an arterial catheter inserted into the femoral artery. For analysis, we used the higher value of rSO2 obtained from the left and right forehead of the patient and measured using a near-infrared spectrometer. Regression coefficients were calculated using the generalized estimating equation (GEE) with MAP and SAP as response variables and rSO2 as an explanatory variable, because MAP and rSO2 were repeatedly measured in the same patient. Since the confounding factors between MAP or SAP and rSO2 were not clear clinically or from previous studies, the GEE was analysed using univariate analysis.Results: Thirty-seven patients were analysed. rSO2 and MAP during resuscitation from hospital arrival to 15 min later were expressed as follows (median [interquartile range]): rSO2, 29.5 (24.3–38.8) %, and MAP, 36.5 (26–46) mmHg. The regression coefficient (95% confidence interval) of log-rSO2 and log-MAP was 0.42 (0.03–0.81) (p=0.035).Conclusion: rSO2 and MAP showed a mild but statistically significant association. rSO2 could be used to assess the quality of chest compressions during resuscitation as a non-invasive and simple method.Trial registration: This study was registered in the University hospital Medical Information Network Clinical Trials Registry (UMIN000015479).