A retrospective, multi-agency 'target trial emulation' for the comparison of post-resuscitation epinephrine to norepinephrine.

INTRODUCTION: Epinephrine and norepinephrine are the two most commonly used prehospital vasopressors in the United States. Prior studies have suggested that use of a post-ROSC epinephrine infusion may be associated with increased rearrest and mortality in comparison to use of norepinephrine. We used target trial emulation methodology to compare the rates of rearrest and mortality between the groups of OHCA patients receiving these vasopressors in the prehospital setting. METHODS: Adult (18-80 years of age) non-traumatic OHCA patients in the 2018-2022 ESO Data Collaborative datasets with a documented post-ROSC norepinephrine or epinephrine infusion were included in this study. Logistic regression modeling was used to evaluate the association between vasopressor agent and outcome using two sets of covariables. The first set of covariables included standard Utstein factors, the dispatch to ROSC interval, the ROSC to vasopressor interval, and the follow-up interval. The second set added prehospital systolic blood pressure and SpO2 values. Kaplan-Meier time-to-event analysis was also conducted and the vasopressor groups were compared using a multivariable Cox regression model. RESULTS: Overall, 1,893 patients treated by 309 EMS agencies were eligible for analysis. 1,010 (53.4%) received an epinephrine infusion and 883 (46.7%) received a norepinephrine infusion as their initial vasopressor. Adjusted analyses did not discover an association between vasopressor agent and rearrest (aOR: 0.93 [0.72, 1.21]) or mortality (aOR: 1.00 [0.59, 1.69]). CONCLUSIONS: In this multi-agency target trial emulation, the use of a post-resuscitation epinephrine infusion was not associated with increased odds of rearrest in comparison to the use of a norepinephrine infusion.

The association of clinical, treatment, and demographic characteristics with rearrest in a national dataset.

INTRODUCTION: Following initial resuscitation from out-of-hospital cardiac arrest, rearrest frequently occurs and has been associated with adverse outcomes. We aimed to identify clinical, treatment, and demographic characteristics associated with prehospital rearrest at the encounter and agency levels. METHODS: Adult non-traumatic cardiac arrest patients who achieved ROSC following EMS resuscitation in the 2018-2021 ESO annual datasets were included in this study. Patients were excluded if they had a documented DNR/POLST or achieved ROSC after bystander CPR only. Rearrest was defined as post-ROSC CPR initiation, administration of ≥ 1 milligram of adrenaline, defibrillation, or a documented non-perfusing rhythm on arrival at the receiving hospital. Multivariable logistic regression modeling was used to evaluate the association between rearrest and case characteristics. Linear regression modeling was used to evaluate the association between agency-level factors (ROSC rate, scene time, and scene termination rate), and rearrest rate. RESULTS: Among the 53,027 cases included, 16,116 (30.4%) experienced rearrest. Factors including longer response intervals, longer 'low-flow' intervals, unwitnessed OHCA, and a lack of bystander CPR were associated with rearrest. Among agencies that treated ≥ 30 patients with outcome data, the agency-level rate of rearrest was inversely associated with agency-level rate of survival to discharge to home (R2 = -0.393, p < 0.001). CONCLUSIONS: This multiagency retrospective study found that factors associated with increased ischaemic burden following OHCA were associated with rearrest. Agency-level rearrest frequency was inversely associated with agency-level survival to home. Interventions that decrease the burden of ischemia sustained by OHCA patients may decrease the rate of rearrest and increase survival.

A Retrospective Nationwide Comparison of the iGel and King Laryngeal Tube Supraglottic Airways for Out-of-Hospital Cardiac Arrest Resuscitation.

INTRODUCTION: While various supraglottic airway devices are available for use during out-of-hospital cardiac arrest (OHCA) resuscitation, comparisons of patient outcomes by device are limited. In this study, we aimed to compare outcomes of OHCA patients who had airway management by emergency medical services (EMS) with the iGel or King-LT. METHODS: We used the 2018-2021 ESO Data Collaborative public use research datasets for this retrospective study. All patients with non-traumatic OHCA who had iGels or King-LTs inserted by EMS were included. Our primary outcome was survival to discharge to home, and secondary outcomes included first-pass success, return of spontaneous circulation (ROSC), and prehospital rearrest. We examined the association between airway device and each outcome using two-level mixed effects logistic regression with EMS agency as the random effect, adjusted for standard Utstein variables and failed intubation prior to supraglottic airway insertion. Average treatment effects were calculated through propensity score matching. RESULTS: A total of 286,192 OHCA patients were screened, resulting in 93,866 patients eligible for inclusion in this analysis. A total of 9,456 transported patients (59.8% iGel) had associated hospital disposition data. Use of the iGel was associated with greater survival to discharge to home (aOR:1.36 [1.06, 1.76]; ATE: 2.2%[+0.5, +3.8]; n = 7,576), first pass airway success (aOR:1.94 [1.79, 2.09]; n = 73,658), and ROSC (aOR:1.19 [1.13, 1.26]; n = 73,207) in comparison to airway management with the King-LT. iGel use was associated with lower odds of experiencing a rearrest (aOR:0.73 [0.67, 0.79]; n = 20,776). Among patients who received a supraglottic device as a primary airway, use of the iGel was not associated with significantly greater survival to discharge to home (aOR:1.26 [0.95, 1.68]). Among patients who received a supraglottic device as a rescue airway following failed intubation, use of the iGel was associated with greater odds of survival to discharge to home (aOR:2.16 [1.15, 4.04]). CONCLUSION: In this dataset, use of the iGel during adult OHCA resuscitation was associated overall with better outcomes compared to use of the King-LT. Subgroup analyses suggested that use of the iGel was associated with greater odds of achieving the primary outcome than the King-LT when used as a rescue device but not when used as the primary airway management device.

The Association of Combined Prehospital Hypotension and Hypoxia with Outcomes following Out-of-Hospital Cardiac Arrest Resuscitation.

BACKGROUND: Prehospital post-resuscitation hypotension and hypoxia have been associated with adverse outcomes in the context of out-of-hospital cardiac arrest (OHCA). We aimed to investigate the association between clinical outcomes and post-resuscitation hypoxia alone, hypotension alone, and combined hypoxia and hypotension. METHODS: We used the 2018-2021 ESO annual datasets to conduct this study. All EMS-treated non-traumatic OHCA patients who had a documented prehospital return of spontaneous circulation (ROSC) and two or more SpO2 readings and systolic blood pressures recorded were evaluated for inclusion. Patients who were less than 18 years of age, pregnant, had a do-not-resuscitate order or similar, achieved ROSC after bystander CPR only, or had an EMS-witnessed cardiac arrest were excluded. Multivariable logistic regression adjusted for standard Utstein factors and highest prehospital Glasgow Coma Scale (GCS) score was used to investigate the association between hypoxia, hypotension, and outcomes. RESULTS: We analyzed data for 17,943 patients, of whom 3,979 had hospital disposition data. Hypotension and hypoxia were not documented in 1,343 (33.8%) patients, 1,144 (28.8%) had only hypoxia documented, 507 (12.7%) had only hypotension documented, and 985 (24.8%) had both hypoxia and hypotension documented. In comparison to patients who did not have documented hypotension or hypoxia, patients who had documented hypoxia (aOR: 1.76 [1.38, 2.24]), documented hypotension (aOR: 3.00 [2.15, 4.18]), and documented hypoxia and hypotension combined (aOR: 4.87 [3.63, 6.53]) had significantly increased mortality. The relationship between mortality and vital sign abnormalities (hypoxia and hypotension > hypotension > hypoxia) was observed in every evaluated subgroup. CONCLUSIONS: In this large dataset, hypotension and hypoxia were independently associated with mortality both alone and in combination. Compared to patients without documented hypotension and hypoxia, patients with documented hypotension and hypoxia had nearly five-fold greater odds of mortality.

A Retrospective Application of the Arbon and Hartman Models to the Union Cycliste International Mountain Bike World Cup.

INTRODUCTION: Outdoor activities have accelerated in the past several years. The authors were tasked with providing medical care for the Union Cycliste International (UCI) mountain biking World Cup in Snowshoe, West Virginia (USA) in September 2021. The Hartman and Arbon models were designed to predict patient presentation and hospital transport rates as well as needed medical resources at urban mass-gathering events. However, there is a lack of standardized methods to predict injury, illness, and insult severity at rural mass gatherings. STUDY OBJECTIVE: This study aimed to determine whether the Arbon model would predict, within 10%, the number of patient presentations to be expected and to determine if the event classification provided by the Hartman model would adequately predict resources needed during the event. METHODS: Race data were collected from UCI event officials and injury data were collected from participants at time of presentation for medical care. Predicted presentation and transport rates were calculated using the Arbon model, which was then compared to the actual observed presentation rates. Furthermore, the event classification provided by the Hartman model was compared to the resources utilized during the event. RESULTS: During the event, 34 patients presented for medical care and eight patients required some level of transport to a medical facility. The Arbon predictive model for the 2021 event yielded 30.3 expected patient presentations. There were 34 total patient presentations during the 2021 race, approximately 11% more than predicted. The Hartman model yielded a score of four. Based on this score, this race would be classified as an "intermediate" event, requiring multiple Advanced Life Support (ALS) and Basic Life Support (BLS) personnel and transport units. CONCLUSION: The Arbon model provided a predicted patient presentation rate within reasonable error to allow for effective pre-event planning and resource allocation with only a four patient presentation difference from the actual data. While the Arbon model under-predicted patient presentations, the Hartman model under-estimated resources needed due to the high-risk nature of downhill cycling. The events staffed required physician skills and air medical services to safely care for patients. Further evaluation of rural events will be needed to determine if there is a generalized need for physician presence at smaller events with inherently risky activities, or if this recurring cycling event is an outlier.

Stay and play or load and go? The association of on-scene advanced life support interventions with return of spontaneous circulation following traumatic cardiac arrest.

INTRODUCTION: Traumatic out-of-hospital cardiac arrest (tOHCA) has a mortality rate over 95%. Many current protocols dictate rapid intra-arrest transport of these patients. We hypothesized that on-scene advanced life support (ALS) would increase the odds of arriving at the emergency department with ROSC (ROSC at ED) in comparison to performance of no ALS or ALS en route. METHODS: We utilized the 2018-2021 ESO Research Collaborative public use datasets for this study, which contain patient care records from ~2000 EMS agencies across the US. All OHCA patients with an etiology of "trauma" or "exsanguination" were screened (n=15,691). The time of advanced airway management, vascular access, and chest decompression was determined for each patient. Logistic regression modeling was used to evaluate the association of ALS intervention timing with ROSC at ED. RESULTS: 4942 patients met inclusion criteria. 14.6% of patients had ROSC at ED. In comparison to no vascular access, on-scene (aOR: 2.14 [1.31, 3.49]) but not en route vascular access was associated with increased odds of having ROSC at ED arrival. In comparison to no chest decompression, neither en route nor on-scene chest decompression were associated with ROSC at ED arrival. Similarly, in comparison to no advanced airway management, neither en route nor on-scene advanced airway management were associated with ROSC at ED arrival. The odds of ROSC at ED decreased by 3% (aOR: 0.97 [0.94, 0.99]) for every 1-minute increase in time to vascular access and decreased by 5% (aOR: 0.95 [0.94, 0.99]) for every 1-minute increase in time to epinephrine. CONCLUSION: On-scene ALS interventions were associated with increased ROSC at ED in our study. These data suggest that initiating ALS prior to rapid transport to definitive care in the setting of tOHCA may increase the number of patients with a palpable pulse at ED arrival.

A retrospective comparison of the King Laryngeal Tube and iGel supraglottic airway devices: A study for the CARES surveillance group.

OBJECTIVE: Supraglottic airway devices are increasingly used during the resuscitation of out-of-hospital cardiac arrest (OHCA) patients in the United States and worldwide. In this study, we aimed to compare the neurologic outcomes of OHCA patients managed with the King Laryngeal Tube (King LT) to the neurologic outcomes of patients managed with the iGel. METHODS: We used the Cardiac Arrest Registry to Enhance Survival (CARES) public use research dataset for our analysis. Non-traumatic OHCA cases with attempted EMS resuscitation enrolled from 2013-2021 were included. We used two-level mixed effects multivariable logistic regression analyses with treating EMS agency as the random effect to determine the association between supraglottic airway device and outcome. The primary outcome was survival with a Cerebral Performance Category (CPC) score of 1 or 2 at discharge. Secondary outcomes included survival to hospital admission and survival to hospital discharge. Age, sex, calendar year of OHCA, initial ECG rhythm, witnessed status (unwitnessed, bystander witnessed, 9-1-1 responder witnessed), bystander CPR, response interval, and OHCA location (private/home, public, institutional) were used as covariables. RESULTS: In comparison to use of the King LT, use of the iGel was associated with greater neurologically favorable survival (aOR: 1.45 [1.33, 1.58]). In addition, use of the iGel was associated with greater survival to hospital admission (1.07 [1.02, 1.12]) and survival to hospital discharge (1.35 [1.26, 1.46]). CONCLUSIONS: This study adds to the body of literature suggesting that use of the iGel during OHCA resuscitation is associated with better outcomes than use of the King LT.

Association of prehospital post-resuscitation peripheral oxygen saturation with survival following out-of-hospital cardiac arrest.

BACKGROUND: Hypoxia and hyperoxia following resuscitation from out-of-hospital cardiac arrest (OHCA)may cause harm by exacerbating secondary brain injury. Our objective was to retrospectively examine theassociationof prehospital post-ROSC hypoxia and hyperoxia with the primary outcome of survival to discharge home. METHODS: We utilized the 2019-2021 ESO Data Collaborative public use research datasets for this study (ESO, Austin, TX). Average prehospital SpO2, lowest recorded prehospital SpO2, and hypoxia dose were calculated for each patient. Theassociationof these measures with survival was explored using multivariable logistic regression. We also evaluated theassociationof American Heart Association (AHA) and European Resuscitation Council (ERC) recommended post-ROSC SpO2 target ranges with outcome. RESULTS: After application of exclusion criteria, 19,023 patients were included in this study. Of these, 52.3% experienced at least one episode of post-ROSC hypoxia (lowest SpO2 < 90%) and 19.6% experienced hyperoxia (average SpO2 > 98%). In comparison to normoxic patients, patients who were hypoxic on average (AHA aOR: 0.31 [0.25, 0.38]; ERC aOR: 0.34 [0.28, 0.42]) and patients who had a hypoxic lowest recorded SpO2 (AHA aOR: 0.48 [0.39, 0.59]; ERC aOR: 0.52 [0.42, 0.64]) had lower adjusted odds of survival. Patients who had a hyperoxic average SpO2 (AHA aOR: 0.75 [0.59, 0.96]; ERC aOR: 0.68 [0.53, 0.88]) and patients who had a hyperoxic lowest recorded SpO2 (AHA aOR: 0.66 [0.48, 0.92]; ERC aOR: 0.65 [0.46, 0.92]) also had lower adjusted odds of survival. CONCLUSION: Prehospital post-ROSC hypoxia and hyperoxia were associated with worse outcomes in this dataset.

Prehospital time for patients with acute cardiac complaints: A rural health disparity.

OBJECTIVE: Delays in care for patients with acute cardiac complaints are associated with increased morbidity and mortality. The objective of this study was to quantify rural and urban differences in prehospital time intervals for patients with cardiac complaints. METHODS: The ESO Data Collaborative dataset consisting of records from 1332 EMS agencies was queried for 9-1-1 encounters with acute cardiac problems among adults (age ≥ 18) from 1/1/2013-6/1/2018. Location was classified as rural or urban using the 2010 United States Census. The primary outcome was total prehospital time. Generalized estimating equations evaluated differences in the average times between rural and urban encounters while controlling for age, sex, race, transport mode, loaded mileage, and patient stability. RESULTS: Among 428,054 encounters, the median age was 62 (IQR 50-75) years with 50.7% female, 75.3% white, and 10.3% rural. The median total prehospital, response, scene, and transport times were 37.0 (IQR 29.0-48.0), 6.0 (IQR 4.0-9.0), 16.0 (IQR 12.0-21.0), and 13.0 (IQR 8.0-21.0) minutes. Rural patients had an average total prehospital time that was 16.76 min (95%CI 15.15-18.38) longer than urban patients. After adjusting for covariates, average total time was 5.08 (95%CI 4.37-5.78) minutes longer for rural patients. Average response and transport time were 4.36 (95%CI 3.83-4.89) and 0.62 (95%CI 0.33-0.90) minutes longer for rural patients. Scene time was similar in rural and urban patients (0.09 min, 95%CI -0.15-0.33). CONCLUSION: Rural patients with acute cardiac complaints experienced longer prehospital time than urban patients, even after accounting for other key variables, such as loaded mileage.

Point-of-Care Troponin Testing during Ambulance Transport to Detect Acute Myocardial Infarction.

Objective: Use of point-of-care (POC) troponin (cTn) testing in the Emergency Department (ED) is well established. However, data examining POC cTn measurement in the prehospital setting, during ambulance transport, are limited. The objective of this study was to prospectively test the performance of POC cTn measurement by paramedics to detect myocardial infarction (MI) among patients transported to the ED for acute chest pain. Methods: A prospective cohort study of adults with non-traumatic chest pain was conducted in three Emergency Medical Services agencies (December 2016 to January 2018). Patients with ST-elevation MI on ECG were excluded. During ambulance transport paramedics initiated intravenous access, collected blood, and used a POC device (i-STAT; Abbott Laboratories) to measure cTn. Following ED arrival, participants received standard evaluations including clinical blood draws for cTn measurement in the hospital central lab (AccuTnI +3 assay; Beckman Coulter, or cTnI-Ultra assay; Siemens). Blood collected during ambulance transport was also analyzed for cTn in the central lab. Index visit MI was adjudicated by 3 experts using central lab cTn measures from the patient's clinical blood draws. Test characteristics (sensitivity, specificity, and predictive values) for detection of MI were calculated for POC and central lab cTn measurement of prehospital blood and compared with McNemar's test. Results: During the study period prehospital POC cTn results were obtained on 421 patients, of which 5.0% (21/421) had results >99th percentile upper reference limit. MI was adjudicated in 16.2% (68/421) during the index visit. The specificity and positive predictive value of the POC cTn measurement were 99.2% (95% CI 97.5-99.8%) and 85.7% (95% CI 63.7-97.0%) for MI. However, the sensitivity and NPV of prehospital POC cTn were 26.5% (95% CI 16.5-38.6%) and 87.5% (95% CI 83.9-90.6%). Compared to POC cTn, the central lab cTn measurement of prehospital blood resulted in a higher sensitivity of 67.9% (95% CI 53.7-80.1%, p < 0.0001), but lower specificity of 92.4% (95% CI 88.4-95.4%, p = 0.0001). Conclusions: Prehospital POC i-STAT cTn measurement in patients transported with acute chest pain was highly specific for MI but had low sensitivity. This suggests that prehospital i-STAT POC cTn could be useful to rule-in MI, but should not be used to exclude MI.

Mechanisms of intracellular calcium homeostasis in developing and mature bovine corpora lutea.

Although calcium (Ca(2+)) is accepted as an intracellular mediator of prostaglandin F2 alpha (PGF2alpha) actions on luteal cells, studies defining mechanisms of Ca(2+) homeostasis in bovine corpora lutea (CL) are lacking. The increase in intracellular Ca(2+) concentration ([Ca(2+)]i) induced by PGF2alpha in steroidogenic cells from mature CL is greater than in those isolated from developing CL. Our hypothesis is that differences in signal transduction associated with developing and mature CL contribute to the increased efficacy of PGF2alpha to induce a Ca(2+) signal capable of inducing regression in mature CL. To test this hypothesis, major genes participating in Ca(2+) homeostasis in the bovine CL were identified, and expression of mRNA, protein, or activity, in the case of phospholipase Cbeta (PLCbeta), in developing and mature bovine CL was compared. In addition, we examined the contribution of external and internal Ca(2+) to the PGF2alpha stimulated rise in [Ca(2+)]i in LLCs isolated from developing and mature bovine CL. Three differences were identified in mechanisms of calcium homeostasis between developing and mature CL, which could account for the lesser increase in [Ca(2+)]i in response to PGF2alpha in developing than in mature CL. First, there were lower concentrations of inositol 1,4,5-trisphosphate (IP3) after similar PGF2alpha challenge, indicating reduced phospholipase C beta (PLCbeta) activity, in developing than mature CL. Second, there was an increased expression of sorcin (SRI) in developing than in mature CL. This cytoplasmic Ca(2+) binding protein modulates the endoplasmic reticulum (ER) Ca(2+) release channel, ryanodine receptor (RyR), to be in the closed configuration. Third, there was greater expression of ATP2A2 or SERCA, which causes calcium reuptake into the ER, in developing than in mature CL. Developmental differences in expression detected in whole CL were confirmed by Western blots using protein samples from steroidogenic cells isolated from developing and mature CL. Localization of these genes in steroidogenic luteal cells was confirmed by immunohistochemistry. Therefore, it is concluded that the cellular mechanisms that allow PGF2alpha to induce a calcium signal of greater magnitude in mature than in developing CL involve 1) greater PLCbeta activity with enhanced generation of IP3, 2) an enhanced Ca(2+) release from the ER via unrestrained RYR2 due to a decrease in SRI expression, and 3) a reduction in calcium reuptake to the ER due to lower expression of ATP2A2. Accordingly, the increase in [Ca(2+)]i induced by PGF2alpha in mature large steroidogenic cells had less dependency from extracellular calcium than in those isolated from immature CL.