Perception of risk in massive transfusion as it relates to fetal outcomes: A survey of surgeons and nurses at one American trauma center.

BACKGROUND: The use of blood products early in the resuscitation of bleeding trauma patients is widely accepted, but made difficult by limited supplies of D- red blood cell (RBC)-containing products. Use of D+ RBC-containing products would alleviate this issue, but could lead to alloimmunization. Risk associated with transfusing D+ RBC in emergency bleeding situations is being reconsidered. The level of concern surrounding emergency transfusion as it relates to future fetal harm was surveyed among surgeons and nurses. METHODS: Faculty and staff in the Departments of Surgery and Nursing were surveyed on the risks of receiving an emergency RBC transfusion and the subsequent potential for fetal harm. Answers were grouped as likely to accept (likely/very likely) or refuse transfusion (unlikely/very unlikely). Participants were compared by sex, and women by child-bearing age, ([15-50 years] vs. [>50 years]). RESULTS: Ninety surveys were initiated with 76 fully completed. Male (n = 39) and female (n = 37) respondents were comparable. Most female respondents (30/37, 81%) were of childbearing age. Overall, both males (38/39, 95%) and females (33/37, 89%; p = .19) were likely to accept a transfusion in an emergency. There was no difference in transfusion acceptance if the risk of fetal harm was presented as 1% (p = .73) or 0.1% (p = .51). Most females (34/37, 92%) were not opposed to transfusion even if there was an unspecified risk of future fetal harm. CONCLUSION: Most of the surgeons and nurses who responded would accept a transfusion in an emergency situation even if it might lead to harming a future fetus.

Impact of Rural Hospital Closures on Health-Care Access.

BACKGROUND: Access to health care is an important issue, particularly in remote areas. Since 2010, 106 rural hospital have closed in the United States, potentially limiting geographic access to health care. The aim of this study was to evaluate the impact of these hospital closures on the proportion of the population who can reach a secondary care facility, by road, within 15, 30, 45, or 60 min. METHODS: Geographical information system analysis, using population data obtained from the 2010 U.S. Census Bureau and hospital data between 2010 and 2019 from the Center for Medicare and Medicaid Services, created 15-, 30-, 45-, and 60-min drive time isochrones (areas from which a central location can be reached within a set time). RESULTS: Rural hospital closures resulted in 0%-0.97% of the population no longer being able to access a hospital within 15 min. The most marked changes were in the East South Central (0.97%, 178,478 residents) and West South Central (0.54%, 197,660 residents) divisions. Lesser degrees of change were noted for longer drive times. The changes were more marked when the rural population was analyzed exclusively. CONCLUSIONS: Recent closures of rural hospitals in the United States have impacted population access to hospital care, although the extent varies. There are regions, such as the Southern and Southeastern United States, which demonstrate greater and potentially more concerning losses in population coverage, probably because of the greater number of closures. Future work should evaluate clinical implications of hospital closures and loss of population coverage.

How Does Mission Ground Time Impact on Population Coverage of Aeromedical Retrieval Systems?

BACKGROUND: Aeromedical retrieval is an essential component of contemporary emergency care systems. However, in many locations, ground emergency medical services are dispatched to the scene of an incident first to assess the patient and then call for a helicopter if needed. The time to definitive care therefore includes the helicopter's flight to the scene, flight to the trauma center, and nonflying time. Mission ground time (MGT) includes the time required to get the helicopter airborne, as well as time spent at the scene, packaging and loading the casualty into the aircraft. Estimates of MGT typically vary from 10 to 30 min. The impact of MGT duration on population coverage-the number of residents that could be taken to a trauma center within a set time-is not known. The aim of this study was to compare population coverage for different durations of MGT in a single state. METHODS: Coverage was calculated using elliptical coverage areas ("isochrones") based on the location of helicopter bases and Level I and Level II trauma centers. The calculations were performed using Microsoft Excel, assuming a cruising speed of 133 knots (246 km/h), and mapped using arcGIS. The access time threshold was set at 60 min, and we evaluated MGTs of 10, 15, 20, 25, and 30 min. RESULTS: MGT has a marked impact on population coverage. The effect is, furthermore, not linear. When considering the state's three Level I trauma centers, decreasing MGT from 30 to 10 min increased population coverage from 61.2% to 84.2%. When also considering Level II centers, decreasing MGT from 30 min to 10 min increased coverage by 20%. CONCLUSIONS: Elliptical isochrones, with allowance for MGT, provide realistic estimates of population coverage. MGT significantly impacts the proportion of the population that can be taken to a Level I and/or Level II Trauma Center within a set time. The impact is not linear, reflecting the uneven distribution of the population. Consideration should be given to minimizing MGT to preserve the benefits of aeromedical retrieval.

Elicitation of prior probability distributions for a proposed Bayesian randomized clinical trial of whole blood for trauma resuscitation.

BACKGROUND: Whole blood trauma resuscitation is conceptually appealing and increasingly used but lacks evidence. A randomized controlled trial is needed but challenging to design. A Bayesian approach might be more efficient and more interpretable than a conventional frequentist design. We report the results on an elicitation meeting to create prior probability distributions to help develop such a trial. METHODS: In-person expert elicitation meeting, based on Sheffield Elicitation Framework methodology. We used an interactive graphical tool to elicit the quantities of interest (24-hour mortality and certainty required). Two rounds were conducted, with an intervening discussion of deidentified responses. Individual responses were aggregated into probability distributions. RESULTS: Fifteen experts participated. The pooled belief was that the median 24-hour mortality of trauma patients with hemorrhagic shock treated with component therapy (the current standard of care) was 19% (95% credible interval [CrI], 6%-45%), and the median 24-hour mortality of those treated with whole blood, 16% (95% CrI, 5%-39%). The pooled prior distribution for the relative risk had a median of 0.84 (95% CrI, 0.26-3.1), indicating that the expert group had a 64% prior belief that whole blood decreases 24-hour mortality compared to component therapy. CONCLUSIONS: Experts had moderately strong beliefs that whole blood reduces the 24-hour mortality of trauma patients with hemorrhagic shock. These data will assist with the design and planning of a Bayesian trial of whole blood resuscitation, which will help to answer a key question in contemporary transfusion practice.

Correction: Role of heme in lung bacterial infection after trauma hemorrhage and stored red blood cell transfusion: A preclinical experimental study.

[This corrects the article DOI: 10.1371/journal.pmed.1002522.].

Older Blood Is Associated With Increased Mortality and Adverse Events in Massively Transfused Trauma Patients: Secondary Analysis of the PROPPR Trial.

STUDY OBJECTIVE: The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion. METHODS: We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in the parent trial included critically injured adult patients admitted to 1 of 12 North American Level I trauma centers who received at least 1 unit of packed RBCs and were predicted to require massive blood transfusion. The primary exposure was volume of packed RBC units transfused during the first 24 hours of hospitalization, stratified by packed RBC age category: 0 to 7 days, 8 to 14 days, 15 to 21 days, and greater than or equal to 22 days. The primary outcome was 24-hour mortality. We evaluated the association between transfused volume of each packed RBC age category and 24-hour survival, using random-effects logistic regression, adjusting for total packed RBC volume, patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, clinical site, and trial treatment group. RESULTS: The 678 patients included in the analysis received a total of 8,830 packed RBC units. One hundred patients (14.8%) died within the first 24 hours. On multivariable analysis, the number of packed RBCs greater than or equal to 22 days old was independently associated with increased 24-hour mortality (adjusted odds ratio [OR] 1.05 per packed RBC unit; 95% confidence interval [CI] 1.01 to 1.08): OR 0.97 for 0 to 7 days old (95% CI 0.88 to 1.08), OR 1.04 for 8 to 14 days old (95% CI 0.99 to 1.09), and OR 1.02 for 15 to 21 days old (95% CI 0.98 to 1.06). Results of sensitivity analyses were similar only among patients who received greater than or equal to 10 packed RBC units. CONCLUSION: Increasing quantities of older packed RBCs are associated with increased likelihood of 24-hour mortality in trauma patients receiving massive packed RBC transfusion (≥10 units), but not in those who receive fewer than 10 units.

Role of heme in lung bacterial infection after trauma hemorrhage and stored red blood cell transfusion: A preclinical experimental study.

BACKGROUND: Trauma is the leading cause of death and disability in patients aged 1-46 y. Severely injured patients experience considerable blood loss and hemorrhagic shock requiring treatment with massive transfusion of red blood cells (RBCs). Preclinical and retrospective human studies in trauma patients have suggested that poorer therapeutic efficacy, increased severity of organ injury, and increased bacterial infection are associated with transfusion of large volumes of stored RBCs, although the mechanisms are not fully understood. METHODS AND FINDINGS: We developed a murine model of trauma hemorrhage (TH) followed by resuscitation with plasma and leukoreduced RBCs (in a 1:1 ratio) that were banked for 0 (fresh) or 14 (stored) days. Two days later, lungs were infected with Pseudomonas aeruginosa K-strain (PAK). Resuscitation with stored RBCs significantly increased the severity of lung injury caused by P. aeruginosa, as demonstrated by higher mortality (median survival 35 h for fresh RBC group and 8 h for stored RBC group; p < 0.001), increased pulmonary edema (mean [95% CI] 106.4 µl [88.5-124.3] for fresh RBCs and 192.5 µl [140.9-244.0] for stored RBCs; p = 0.003), and higher bacterial numbers in the lung (mean [95% CI] 1.2 × 10(7) [-1.0 × 10(7) to 2.5 × 10(7)] for fresh RBCs and 3.6 × 10(7) [2.5 × 10(7) to 4.7 × 10(7)] for stored RBCs; p = 0.014). The mechanism underlying this increased infection susceptibility and severity was free-heme-dependent, as recombinant hemopexin or pharmacological inhibition or genetic deletion of toll-like receptor 4 (TLR4) during TH and resuscitation completely prevented P. aeruginosa-induced mortality after stored RBC transfusion (p < 0.001 for all groups relative to stored RBC group). Evidence from studies transfusing fresh and stored RBCs mixed with stored and fresh RBC supernatants, respectively, indicated that heme arising both during storage and from RBC hemolysis post-resuscitation plays a role in increased mortality after PAK (p < 0.001). Heme also increased endothelial permeability and inhibited macrophage-dependent phagocytosis in cultured cells. Stored RBCs also increased circulating high mobility group box 1 (HMGB1; mean [95% CI] 15.4 ng/ml [6.7-24.0] for fresh RBCs and 50.3 ng/ml [12.3-88.2] for stored RBCs), and anti-HMGB1 blocking antibody protected against PAK-induced mortality in vivo (p = 0.001) and restored macrophage-dependent phagocytosis of P. aeruginosa in vitro. Finally, we showed that TH patients, admitted to the University of Alabama at Birmingham ER between 1 January 2015 and 30 April 2016 (n = 50), received high micromolar-millimolar levels of heme proportional to the number of units transfused, sufficient to overwhelm endogenous hemopexin levels early after TH and resuscitation. Limitations of the study include lack of assessment of temporal changes in different products of hemolysis after resuscitation and the small sample size precluding testing of associations between heme levels and adverse outcomes in resuscitated TH patients. CONCLUSIONS: We provide evidence that large volume resuscitation with stored blood, compared to fresh blood, in mice increases mortality from subsequent pneumonia, which occurs via mechanisms sensitive to hemopexin and TLR4 and HMGB1 inhibition.

Effect of a Strategy of Initial Laryngeal Tube Insertion vs Endotracheal Intubation on 72-Hour Survival in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Emergency medical services (EMS) commonly perform endotracheal intubation (ETI) or insertion of supraglottic airways, such as the laryngeal tube (LT), on patients with out-of-hospital cardiac arrest (OHCA). The optimal method for OHCA advanced airway management is unknown. Objective: To compare the effectiveness of a strategy of initial LT insertion vs initial ETI in adults with OHCA. Design, Setting, and Participants: Multicenter pragmatic cluster-crossover clinical trial involving EMS agencies from the Resuscitation Outcomes Consortium. The trial included 3004 adults with OHCA and anticipated need for advanced airway management who were enrolled from December 1, 2015, to November 4, 2017. The final date of follow-up was November 10, 2017. Interventions: Twenty-seven EMS agencies were randomized in 13 clusters to initial airway management strategy with LT (n = 1505 patients) or ETI (n = 1499 patients), with crossover to the alternate strategy at 3- to 5-month intervals. Main Outcomes and Measures: The primary outcome was 72-hour survival. Secondary outcomes included return of spontaneous circulation, survival to hospital discharge, favorable neurological status at hospital discharge (Modified Rankin Scale score ≤3), and key adverse events. Results: Among 3004 enrolled patients (median [interquartile range] age, 64 [53-76] years, 1829 [60.9%] men), 3000 were included in the primary analysis. Rates of initial airway success were 90.3% with LT and 51.6% with ETI. Seventy-two hour survival was 18.3% in the LT group vs 15.4% in the ETI group (adjusted difference, 2.9% [95% CI, 0.2%-5.6%]; P = .04). Secondary outcomes in the LT group vs ETI group were return of spontaneous circulation (27.9% vs 24.3%; adjusted difference, 3.6% [95% CI, 0.3%-6.8%]; P = .03); hospital survival (10.8% vs 8.1%; adjusted difference, 2.7% [95% CI, 0.6%-4.8%]; P = .01); and favorable neurological status at discharge (7.1% vs 5.0%; adjusted difference, 2.1% [95% CI, 0.3%-3.8%]; P = .02). There were no significant differences in oropharyngeal or hypopharyngeal injury (0.2% vs 0.3%), airway swelling (1.1% vs 1.0%), or pneumonia or pneumonitis (26.1% vs 22.3%). Conclusions and Relevance: Among adults with OHCA, a strategy of initial LT insertion was associated with significantly greater 72-hour survival compared with a strategy of initial ETI. These findings suggest that LT insertion may be considered as an initial airway management strategy in patients with OHCA, but limitations of the pragmatic design, practice setting, and ETI performance characteristics suggest that further research is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT02419573.

A trial of an impedance threshold device in out-of-hospital cardiac arrest.

BACKGROUND: The impedance threshold device (ITD) is designed to enhance venous return and cardiac output during cardiopulmonary resuscitation (CPR) by increasing the degree of negative intrathoracic pressure. Previous studies have suggested that the use of an ITD during CPR may improve survival rates after cardiac arrest. METHODS: We compared the use of an active ITD with that of a sham ITD in patients with out-of-hospital cardiac arrest who underwent standard CPR at 10 sites in the United States and Canada. Patients, investigators, study coordinators, and all care providers were unaware of the treatment assignments. The primary outcome was survival to hospital discharge with satisfactory function (i.e., a score of ≤3 on the modified Rankin scale, which ranges from 0 to 6, with higher scores indicating greater disability). RESULTS: Of 8718 patients included in the analysis, 4345 were randomly assigned to treatment with a sham ITD and 4373 to treatment with an active device. A total of 260 patients (6.0%) in the sham-ITD group and 254 patients (5.8%) in the active-ITD group met the primary outcome (risk difference adjusted for sequential monitoring, -0.1 percentage points; 95% confidence interval, -1.1 to 0.8; P=0.71). There were also no significant differences in the secondary outcomes, including rates of return of spontaneous circulation on arrival at the emergency department, survival to hospital admission, and survival to hospital discharge. CONCLUSIONS: Use of the ITD did not significantly improve survival with satisfactory function among patients with out-of-hospital cardiac arrest receiving standard CPR. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.).

Resuscitation Outcomes Consortium-Amiodarone, Lidocaine or Placebo Study (ROC-ALPS): Rationale and methodology behind an out-of-hospital cardiac arrest antiarrhythmic drug trial.

BACKGROUND: Despite their wide use, whether antiarrhythmic drugs improve survival after out-of-hospital cardiac arrest (OHCA) is not known. The ROC-ALPS is evaluating the effectiveness of these drugs for OHCA due to shock-refractory ventricular fibrillation or pulseless ventricular tachycardia (VF/VT). METHODS: ALPS will randomize 3,000 adults across North America with nontraumatic OHCA, persistent or recurring VF/VT after ≥1 shock, and established vascular access to receive up to 450 mg amiodarone, 180 mg lidocaine, or placebo in the field using a double-blind protocol, along with standard resuscitation measures. The designated target population is all eligible randomized recipients of any dose of ALPS drug whose initial OHCA rhythm was VF/VT. A safety analysis includes all randomized patients regardless of their eligibility, initial arrhythmia, or actual receipt of ALPS drug. The primary outcome of ALPS is survival to hospital discharge; a secondary outcome is functional survival at discharge assessed as a modified Rankin Scale score ≤3. RESULTS: The principal aim of ALPS is to determine if survival is improved by amiodarone compared with placebo; secondary aim is to determine if survival is improved by lidocaine vs placebo and/or by amiodarone vs lidocaine. Prioritizing comparisons in this manner acknowledges where differences in outcome are most expected based on existing knowledge. Each aim also represents a clinically relevant comparison between treatments that is worth investigating. CONCLUSIONS: Results from ALPS will provide important information about the choice and value of antiarrhythmic therapies for VF/VT arrest with direct implications for resuscitation guidelines and clinical practice.

Diagnostic performance of the ABC score in the PROPPR trial.

INTRODUCTION: The Assessment of Blood Consumption (ABC) score is used to predict massive transfusions (MT). However, its diagnostic performance has not been widely examined, especially when used as an objective tool to enroll patients in multi-center clinical trials. The purpose of this study was to evaluate the performance of the ABC score in enrolling patients in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial. We hypothesized the ABC score would have a similar diagnostic performance to predict the need for massive transfusion as previous studies. METHODS: This is a retrospective analysis of the PROPPR trial. Patients were enrolled either on the basis of an ABC score ≥2, or by Physician Gestalt, when the ABC score was <2. We calculated the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios of the ABC score (≥2) for predicting MT (>10 units of red blood cells/24 h or transfusion of >3 units of red blood cells within the first hour). RESULTS: Of the 680 patients, 438 patients (64 %) had an ABC score of ≥2 and 242 (36 %) had an ABC score of <2. An ABC score of ≥2 had 66.8 % sensitivity and 37.0 % specificity for predicting the need for MT, with a PPV of 88.2 % and NPV of 13.1 %. Similarly, an ABC≥2 had 65.6 % sensitivity and 44.6 % specificity for predicting the need for >3 units RBCs in 1 hour, with a PPV of 89.5 % and NPV of 15.3 %. CONCLUSION: The ABC score had lower performance than previously reported for predicting MT, when applied to PROPPR trial patients. The performance for predicting the need for a 3-unit red blood cell transfusion (or more) in the first hour was slightly higher. LEVEL OF EVIDENCE: Level III, Prognostic.

Outcomes of patients enrolled in a prospective and randomized trial on basis of gestalt assessment or ABC score.

BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial rapidly enrolled patients based on an Assessment of Blood Consumption (ABC) ≥ 2 score, or physician gestalt (PG) when ABC score was <2. The objective of this study was to describe what patients were enrolled by the two methods and whether patient outcomes differed based on these enrollments. We hypothesized that there would be no differences in outcomes based on whether patients were enrolled via ABC score or PG. METHODS: Patients were enrolled with an ABC ≥ 2 or by PG when ABC was <2 by the attending trauma surgeon. We compared 1-hour, 3-hour, 6-hour, 12-hour, 18-hour, and 24-hour mortality, 30-day mortality, time to hemostasis, emergent surgical or interventional radiology procedure and the proportion of patients who required either >10 units of blood in 24 hours or >3 units in 1 hour. RESULTS: Of 680 patients, 438 (64%) were enrolled on the basis of an ABC score ≥2 and 242 (36% by PG when the ABC score was <2). Patients enrolled by PG were older (median, 44; interquartile range [IQR], 28-59; p < 0.001), more likely to be White (70.3% vs. 60.3%, p = 0.014), and more likely to have been injured by blunt mechanisms (77.3% vs. 37.2%, p < 0.001). They were also less hypotensive and less tachycardic than patients enrolled by ABC score (both p < 0.001). The groups had similar Injury Severity Scores in the ABC ≥ 2 and PG groups (26 and 27, respectively) and were equally represented (49.1% and 50.8%, respectively) in the 1:1:1 treatment arm. There were no significant differences between the ABC score and PG groups for mortality at any point. Time to hemostasis (108 for patients enrolled on basis of Gestalt, vs. 100 minutes for patients enrolled on basis of ABC score), and the proportion of patients requiring a massive transfusion (>10 units/24 hours) (44.2% vs. 47.3%), or meeting the critical administration threshold (>3 unit/1 hour) (84.7% vs. 89.5%) were similar ( p = 0.071). CONCLUSION: Early identification of trauma patients likely to require a massive transfusion is important for clinical care, resource use, and selection of patients for clinical trials. Patients enrolled in the PROPPR trial based on PG when the ABC score was <2 represented 36% of the patients and had identical outcomes to those enrolled on the basis of an ABC score of ≥2. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

Feasibility of using an automated call service to collect quality of life and functional outcome data in trauma patients.

Objectives: Following up trauma patients after discharge, to evaluate their subsequent quality of life and functional outcomes, is notoriously difficult, time consuming, and expensive. Automated systems are a conceptually attractive solution. We prospectively assessed the feasibility of using a series of automated phone calls administered by Emmi Patient Engagement to survey trauma patients after discharge. Methods: Recruitment into the study was incorporated into the patient discharge process by nursing staff. For this pilot, we included trauma patients discharging home and who were able to answer phone calls. A script was created to evaluate the Extended Glasgow Outcome Scale and the EuroQol EQ-5D to assess functional status and quality of life, respectively. Call attempts were made at 6 weeks, 3 months, 6 months, and 1 year after discharge. Results: A total of 110 patients initially agreed to participate. 368 attempted patient encounters (calls or attempted calls) took place, with 104 (28.3%) patients answering a least one question in the study. 21 unique patients (19.1% of those enrolled) completed 27 surveys. Conclusions: Automated, scripted phone calls to survey patients after discharge are not a feasible way of collecting functional and quality of life data. Level of evidence: Level II/prospective.

Temporal Trends in End-Tidal Capnography and Outcomes in Out-of-Hospital Cardiac Arrest: A Secondary Analysis of a Randomized Clinical Trial.

Importance: While widely measured, the time-varying association between exhaled end-tidal carbon dioxide (EtCO2) and out-of-hospital cardiac arrest (OHCA) outcomes is unclear. Objective: To evaluate temporal associations between EtCO2 and return of spontaneous circulation (ROSC) in the Pragmatic Airway Resuscitation Trial (PART). Design, Setting, and Participants: This study was a secondary analysis of a cluster randomized trial performed at multicenter emergency medical services agencies from the Resuscitation Outcomes Consortium. PART enrolled 3004 adults (aged ≥18 years) with nontraumatic OHCA from December 1, 2015, to November 4, 2017. EtCO2 was available in 1172 cases for this analysis performed in June 2023. Interventions: PART evaluated the effect of laryngeal tube vs endotracheal intubation on 72-hour survival. Emergency medical services agencies collected continuous EtCO2 recordings using standard monitors, and this secondary analysis identified maximal EtCO2 values per ventilation and determined mean EtCO2 in 1-minute epochs using previously validated automated signal processing. All advanced airway cases with greater than 50% interpretable EtCO2 signal were included, and the slope of EtCO2 change over resuscitation was calculated. Main Outcomes and Measures: The primary outcome was ROSC determined by prehospital or emergency department palpable pulses. EtCO2 values were compared at discrete time points using Mann-Whitney test, and temporal trends in EtCO2 were compared using Cochran-Armitage test of trend. Multivariable logistic regression was performed, adjusting for Utstein criteria and EtCO2 slope. Results: Among 1113 patients included in the study, 694 (62.4%) were male; 285 (25.6%) were Black or African American, 592 (53.2%) were White, and 236 (21.2%) were another race; and the median (IQR) age was 64 (52-75) years. Cardiac arrest was most commonly unwitnessed (n = 579 [52.0%]), nonshockable (n = 941 [84.6%]), and nonpublic (n = 999 [89.8%]). There were 198 patients (17.8%) with ROSC and 915 (82.2%) without ROSC. Median EtCO2 values between ROSC and non-ROSC cases were significantly different at 10 minutes (39.8 [IQR, 27.1-56.4] mm Hg vs 26.1 [IQR, 14.9-39.0] mm Hg; P < .001) and 5 minutes (43.0 [IQR, 28.1-55.8] mm Hg vs 25.0 [IQR, 13.3-37.4] mm Hg; P < .001) prior to end of resuscitation. In ROSC cases, median EtCO2 increased from 30.5 (IQR, 22.4-54.2) mm HG to 43.0 (IQR, 28.1-55.8) mm Hg (P for trend < .001). In non-ROSC cases, EtCO2 declined from 30.8 (IQR, 18.2-43.8) mm Hg to 22.5 (IQR, 12.8-35.4) mm Hg (P for trend < .001). Using adjusted multivariable logistic regression with slope of EtCO2, the temporal change in EtCO2 was associated with ROSC (odds ratio, 1.45 [95% CI, 1.31-1.61]). Conclusions and Relevance: In this secondary analysis of the PART trial, temporal increases in EtCO2 were associated with increased odds of ROSC. These results suggest value in leveraging continuous waveform capnography during OHCA resuscitation. Trial Registration: ClinicalTrials.gov Identifier: NCT02419573.

Interactive Media-Based Approach for an Exception From Informed Consent Trial Involving Patients With Trauma.

Importance: Exception From Informed Consent (EFIC) research requires community consultation (CC) and public disclosure (PD). Traditional methods of conducting CC and PD are slow, expensive, and labor intensive. Objective: To describe the feasibility and reach of a novel interactive, media-based approach to CC and PD and to identify the similarities and differences between trial sites in website views, survey responses, online community forum attendance, and opt-out requests. Design, Setting, and Participants: This survey study analyzed the CC and PD campaigns conducted for the TAP trial (Evaluation of BE1116 in Patients With Traumatic Injury and Acute Major Bleeding to Improve Survival), an EFIC trial of the early administration of prothrombin complex concentrate in patients with trauma. The CC and PD campaigns consisted of social media advertisements, linked websites, community surveys, and online community forums. These activities were coordinated from a central site and approved by a central institutional review board. This study focused on the first 52 of 91 TAP trial sites (level I trauma centers) in the US to have completed their CC and PD campaigns. Community members in the catchment areas of the participating trauma centers were targeted. Data analysis was conducted between October 2023 and February 2024. Exposure: Social media advertisements, surveys, and online community meetings conducted as part of the CC and PD campaign for the TAP trial. Main Outcomes and Measures: Social media campaign reach and engagement, web page views, survey results, online community forum attendance, and opt-out requests. Results: Fifty-two trial sites were approved for participant enrollment. Social media advertisements were displayed 92 million times, reaching 11.8 million individuals. The median (IQR) number of people reached in each location was 210 317 (172 068-276 968). Site-specific websites were viewed 144 197 times (median [IQR] viewings per site, 2984 [1267-4038]). A total of 17 206 fully or partly completed surveys were received, and survey respondents had a median (IQR) age of 40.1 (15-65) years and included 10 444 females (60.7%). Overall, 60.6% survey respondents said they would want to be entered into the trial even if they could not give consent, 87.7% agreed that emergency care research was necessary, and 88.0% agreed that the TAP trial should be conducted in their community. Online community forums were attended by a median (IQR) number of 38 (20-63) people. Four opt-out requests were received. Conclusions and Relevance: The interactive media-based approach to CC and PD for the ongoing TAP trial showed the feasibility and benefits of executing an efficient, coordinated, centrally run series of locally branded and geographically targeted CC and PD campaigns for a large EFIC study.

The females have spoken: A patient-centered national survey on the administration of emergent transfusions with the potential for future fetal harm.

BACKGROUND: Traumatic hemorrhage is the leading cause of preventable death. Early in the resuscitation, only RhD-positive red blood cells are likely to be available, which poses a small risk of causing harm to a future fetus if transfused to an RhD-negative females of childbearing age (CBA), that is, 15 to 49 years old. We sought to characterize how the population, in particular females of CBA, felt about emergency blood administration vis-a-vis potential future fetal harm. METHODS: A national survey was performed using Facebook advertisements in three waves from January 2021 to January 2022. The advertisements directed users to the survey site with seven demographic questions and four questions on accepting transfusion with differing probabilities for future fetal harm (none/any/1:100/1:10,000). Acceptance of transfusion questions were scored on 3-point Likert scale (likely/neutral/unlikely). Only completed responses by females were analyzed. RESULTS: Advertisements were viewed 16,600,430 times by 2,169,805 people with 15,396 advertisement clicks and 2,873 surveys initiated. Most (2,256 of 2,873 [79%]) were fully completed. Majority (2,049 of 2,256 [90%]) of respondents were female. Eighty percent of females (1,645 of 2,049) were of CBA. Most females responded "likely" or "neutral" when asked whether they would accept a lifesaving transfusion if the following risk of fetal harm were present: no risk (99%), any risk (83%), 1:100 risk (85%), and 1:10,000 risk (92%). There were no differences between females of CBA versus non-CBA with respect to the likelihood of accepting lifesaving transfusion with any potential for future fetal harm ( p = 0.24). CONCLUSION: This national survey suggests that most females would accept lifesaving transfusion even with the potential low risk of future fetal harm. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Cardiovascular collapse after return of spontaneous circulation in human out-of-hospital cardiopulmonary arrest.

OBJECTIVE: Animal studies describe cardiovascular collapse (CVC; hypotension or reoccurrence of cardiac arrest) after return of spontaneous circulation (ROSC) from cardiopulmonary arrest. Few studies describe CVC in humans. This study aimed to determine the occurrence of CVC in human out-of-hospital cardiopulmonary arrest (OHCA). METHODS: Using observational data from a site of the Resuscitation Outcomes Consortium, the study analysed treated, non-traumatic OHCA achieving initial ROSC. CVC was defined as post-ROSC hypotension (systolic blood pressure ≤80 mm Hg), post-ROSC administration of epinephrine, vasopressin or dopamine, or post-ROSC recurrent cardiac arrest. The time period from initial ROSC to emergency department (ED) arrival was measured. The prevalence of and elapsed time to post-ROSC CVC was determined, censoring cases at the point of ED arrival and comparing clinical characteristics between CVC and non-CVC cases. RESULTS: Of 1081 treated OHCA, ROSC occurred in 58 (5%; 95% CI 4% to 7%). CVC occurred in three cases of 58 ROSC (5%; 95% CI 1% to 14%), all due to recurrent cardiac arrest. The median ROSC to ED arrival time was 6 min (IQR 3-13 min). ROSC to CVC times were 1, 2 and 8 min. Patient sex, age, initial ECG rhythm, endotracheal intubation, bystander cardiopulmonary resuscitation and bystander automated external defibrillation were similar between CVC and non-CVC cases (p=0.11-1.00). CONCLUSIONS: In this series of treated OHCA, only a small fraction of patients experienced CVC after ROSC.

Multicenter social media community consultation for an exception from informed consent trial of the XStat device (PhoXStat trial).

INTRODUCTION: Community consultation (CC) is a key step for exception from informed consent research. Using social media to conduct CC is becoming more widely accepted but has largely been conducted by single sites. We describe our experience of a social media-based CC for a multicenter clinical trial, coordinated by the lead clinical site. METHODS: Multicenter CC was administered by the lead site and conducted in preparation for a three-site prehospital randomized clinical trial. We used Facebook and Instagram advertisements targeted to the population of interest. When "clicked," the advertisements directed individuals to study-specific websites, providing additional information and the opportunity to opt out. The lead institution and one other hospital relied on a single website, whereas the third center set up their own website. Site views were evaluated using Google analytics. RESULTS: The CC took 8 weeks to complete for each site. The advertisements were displayed 9.8 million times, reaching 332,081 individuals, of whom 1,576 viewed one of the study-specific websites. There were no requests to opt out. The total cost was $3,000. The costs per person reached were $1.88, $2.00, and $1.85 for each of the three sites. A number of site-specific issues (multiple languages, hosting of study-specific websites) were easily resolved. CONCLUSION: This study suggests that it is possible for one institution to conduct multiple, simultaneous, social media-based CC campaigns, on behalf of participating trial sites. Our results suggest that this social media CC model reaches many more potential subjects and is economical and more efficient than traditional methods. LEVEL OF EVIDENCE: Epidemiological, level IV.

Understanding the geography of trauma: Combining spatial analysis and funnel plots to create comprehensive spatial injury profiles.

BACKGROUND: Understanding geographic patterns of injury is essential to operating an effective trauma system and targeting injury prevention. Choropleth maps are helpful in showing spatial relationships but are unable to provide estimates of spread or degrees of confidence. Funnel plots overcome this issue and are a recommended graphical aid for comparisons that allow quantification of precision. The purpose of this project was to demonstrate the complementary roles of choropleth maps and funnel plots in providing a thorough representation of geographic trauma data. METHODS: This is a retrospective analysis of emergency medical service transport data of adult patients in Alabama from July 2015 to June 2020. Choropleth maps of case volume and observed-to-expected ratios of incidence were created using US Census Bureau data. Funnel plots were created to relate incidence rate to county population. Subgroup analyses included patients with critical physiology, penetrating, blunt, and burn injuries. RESULTS: We identified 65,247 trauma incidents during the study period. The overall statewide incidence rate was 133 per 10,000 persons. The highest number of incidents occurred in the most populous counties (Jefferson, 10,768; Mobile, 5,642). Choropleth maps for overall incidence and subgroups highlighted that spatial distribution of overall case volume and observed-to-expected ratios are not always congruent. Funnel plots identified possible and probable outliers, and revealed skewed or otherwise unique patterns among injury subgroups. CONCLUSION: This study demonstrates the complementarity of choropleth maps and funnel plots in describing trauma patterns. Comprehensive geospatial analyses may help guide a data-driven approach to trauma system optimization and injury prevention. Combining maps of case counts, incidence, and funnel plots helps to not only identify geographic trends in data but also quantify outliers and display how far results fall outside the expected range. The combination of these tools provides a more comprehensive geospatial analysis than either tool could provide on its own. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level IV.

Airway strategy and ventilation rates in the pragmatic airway resuscitation trial.

BACKGROUND: We sought to describe ventilation rates during out-of-hospital cardiac arrest (OHCA) resuscitation and their associations with airway management strategy and outcomes. METHODS: We analyzed continuous end-tidal carbon dioxide capnography data from adult OHCA enrolled in the Pragmatic Airway Resuscitation Trial (PART). Using automated signal processing techniques, we determined continuous ventilation rates for consecutive 10-second epochs after airway insertion. We defined hypoventilation as a ventilation rate < 6 breaths/min. We defined hyperventilation as a ventilation rate > 12 breaths/min. We compared differences in total and percentage post-airway hyper- and hypoventilation between airway interventions (laryngeal tube (LT) vs. endotracheal intubation (ETI)). We also determined associations between hypo-/hyperventilation and OHCA outcomes (ROSC, 72-hour survival, hospital survival, hospital survival with favorable neurologic status). RESULTS: Adequate post-airway capnography were available for 1,010 (LT n = 714, ETI n = 296) of 3,004 patients. Median ventilation rates were: LT 8.0 (IQR 6.5-9.6) breaths/min, ETI 7.9 (6.5-9.7) breaths/min. Total duration and percentage of post-airway time with hypoventilation were similar between LT and ETI: median 1.8 vs. 1.7 minutes, p = 0.94; median 10.5% vs. 11.5%, p = 0.60. Total duration and percentage of post-airway time with hyperventilation were similar between LT and ETI: median 0.4 vs. 0.4 minutes, p = 0.91; median 2.1% vs. 1.9%, p = 0.99. Hypo- and hyperventilation exhibited limited associations with OHCA outcomes. CONCLUSION: In the PART Trial, EMS personnel delivered post-airway ventilations at rates satisfying international guidelines, with only limited hypo- or hyperventilation. Hypo- and hyperventilation durations did not differ between airway management strategy and exhibited uncertain associations with OCHA outcomes.