End-Tidal Carbon Dioxide Measurement in Out-of-Hospital Cardiac Arrest as a Predictor of Return of Spontaneous Circulation: A Literature Review.

INTRODUCTION: One of the leading causes of morbidity and mortality worldwide is out-of-hospital cardiac arrest. Early defibrillation and high-quality cardiopulmonary resuscitation (CPR) have improved survival. The main goal of CPR is to achieve return of spontaneous circulation (ROSC), which is assessed by looking for a pulse, analyzing the heart rhythm, and assessing carbon dioxide levels. The use of cartography during CPR to confirm the correct position of the endotracheal tube during intubation or to assess the effectiveness of chest compressions has increased significantly in the last years. The aim of this review was to identify correlations between end-tidal carbon dioxide levels and the likelihood of ROSC in patients with out-of-hospital cardiac arrest. METHODS: A literature search was performed in MEDLINE (via Pubmed), Scopus, Web of Science, and Google Scholar databases from September to November 2022. Keywords combined with the Boolean operators (AND/OR) were used in both free text and Medical Subject Headings. Studies on adult patients published between 01/01/2016 and 28/09/2022 were searched, with no geographical restrictions. RESULTS: At the end of the selection process, 14 studies were included that investigated capnography in out-of-hospital CPR and reported at least 1 outcome between end-tidal carbon dioxide and ROSC or survival. DISCUSSION: Capnography is an advantageous tool due to its noninvasive characteristics, ease of use, and immediacy of data. In out-of-hospital cardiac arrest, the use of the end-tidal carbon dioxide appears to be an appropriate complementary tool to support clinical decisions, such as correct positioning of the endotracheal tube, optimizing ventilation in CPR, and as a predictor of ROSC.

Circulating glycocalyx shedding products as biomarkers for evaluating prognosis of patients with out-of-hospital cardiac arrest after return of spontaneous circulation.

The endothelial glycocalyx is damaged in postcardiac arrest syndrome (PCAS), but the prognostic value is unknown. We aimed to observe the expression and prognostic value of glycocalyx shedding products, including syndecan-1 (SDC-1), hyaluronan (HA), and heparan sulfate (HS) in PCAS. Data on clinical and 28-day outcomes of seventy-one consecutive patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC) were collected. SDC-1, HA, and HS were measured on days 0, 1, and 3 after ROSC. Thirty healthy individuals were controls. Glycocalyx shedding was observed in human umbilical vein endothelial cells (HUVECs) stimulated during hypoxia and reoxygenation in vitro. Within 4 h of ROSC, SDC-1 and HA levels, significantly increased. In the 28-day non-survivors, HA levels showed a gradual upward trend, SDC-1 remained at a high level, and HS levels first increased, then decreased. Kaplan-Meier curves and binary logistic regression analysis showed the prognostic value of SDC-1 levels on days 0, 1, and 3, HA levels on days 1 and 3, and HS levels on day 1. Only HS levels on day 1 showed a prognostic value for 28-day neurological outcomes. SDC-1 and HA levels were positively correlated with the no-flow time. In vitro, HUVECs showed shedding of SDC-1 and HS during a prolonged duration of hypoxia. After ROSC, SDC-1, HA, and HS levels may predict the 28-day survival after PCAS, and HS levels are associated with functional outcomes.

Effect of cardiopulmonary resuscitation training for layperson bystanders on outcomes of out-of-hospital cardiac arrest: A prospective multicenter observational study.

BACKGROUND: Effective bystander cardiopulmonary resuscitation (CPR) improves outcomes in out-of-hospital cardiac arrest (OHCA) patients. However, the effect of CPR training on the rate of return of spontaneous circulation (ROSC) among laypersons has yet to be thoroughly evaluated. METHODS: This prospective, multicenter observational study was conducted across 42 centers in Japan. We assessed OHCA patients who received bystander CPR from a layperson, excluding those performed by healthcare staff. The primary outcome was the ROSC rate. Secondary outcomes included pre-hospital ROSC, ROSC after hospital arrival, favorable neurological outcomes, and 30-day survival. Propensity score with inverse probability treatment weighting (IPTW) was used to adjust for confounders, including age, sex, presence or absence of witnesses, and past medical history. RESULTS: A total of 969 OHCA patients were included, divided into CPR-trained (n = 322) and control (n = 647). Before adjustment, the ROSC rate was higher in the trained group than the control (40.1% vs. 30.1%, P < 0.01). After IPTW adjustment, the trained group showed a significantly higher ROSC rate (36.7% vs. 30.6%; P = 0.02). All secondary outcomes in the trained group were significantly improved before adjustment. After IPTW adjustment, the trained group showed improved rates of pre-hospital ROSC and ROSC after hospital arrival (30.7% vs. 24.0%; P < 0.01, 23.9% vs. 20.7%; P = 0.04). There were no differences in neurological outcomes and 30-day survival. CONCLUSION: This study demonstrated that CPR training for laypersons was associated with increased ROSC rates in OHCA patients, indicating potential advantages of CPR training for non-healthcare professionals.

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.

The association between serum free fatty acid levels and neurological outcomes in out-of-hospital cardiac arrest patients: A prospective observational study.

Free fatty acids (FFA) are a known risk factor in the development of sudden cardiac death. However, the relationship between FFA and the outcome of out-of-hospital cardiac arrest (OHCA) patients remains unclear. We aimed to examine the association between FFA and neurological outcomes in OHCA patients. This prospective observational study included adult (≥18 years) OHCA patients between February 2016 and December 2022. We measured serial FFA levels within 1 hour after ROSC and at 6, 12, 24, 48, and 72 hours after the return of spontaneous circulation (ROSC). The primary outcome was neurological outcome at 6 months. A poor neurological outcome was defined by cerebral performance categories 3, 4, and 5. A total of 147 patients were included. Of them, 104 (70.7%) had poor neurological outcomes, whereby the median FFA levels within 1 hour after ROSC (0.72 vs 1.01 mol/L), at 6 hours (1.19 vs 1.90 mol/L), 12 hours (1.20 vs 1.66 mol/L), and 24 hours (1.20 vs 1.95 mol/L) after ROSC were significantly lower than in good outcome group. The FFA levels at 6 hours (odds ratio, 0.583; 95% confidence interval, 0.370-0.919; P = .020), and 12 hours (odds ratio, 0.509; 95% confidence interval, 0.303-0.854; P = .011) after ROSC were independently associated with poor neurological outcomes. The lower FFA levels at 6 hours and 12 hours after ROSC were associated with poor neurological outcomes in patients with OHCA. FFA may reflect oxidative metabolism as well as oxidative stress.

Effect of timing of advanced life support on out-of-hospital cardiac arrests at home.

AIM: In cases of out-of-hospital cardiac arrests (OHCA) occurring at home, Japanese emergency medical services personnel decide whether to provide treatment on the scene or during transport based on their judgment. This study aimed to evaluate the association between the timing of advanced life support (ALS) (i.e., endotracheal intubation [ETI] or adrenaline administration) for OHCA at home and prognosis. METHOD: This retrospective cohort study used data from the Japan Utstein Registry and emergency transport data collected from patients who underwent pre-hospital ETI (n = 6806) and received adrenaline (n = 22,636) between 2016 and 2019. The timing of ETI or adrenaline administration was determined as "on the scene" or "in the ambulance." Multiple logistic regression analysis was used to estimate the association among the timing of ALS implementation, pre-hospital return of spontaneous circulation (ROSC), and survival at 1 month. RESULT: ETI on the scene was significantly positively associated with pre-hospital ROSC (adjusted odds ratio [AOR], 1.81; 95% confidence interval [CI], 1.57-2.09) and survival at 1 month (AOR, 1.81; 95% CI, 1.47-2.23). Adrenaline administration on the scene was significantly positively associated with pre-hospital ROSC (AOR, 2.51; 95% CI, 2.33-2.70) and survival at 1 month (AOR, 2.13; 95% CI, 1.89-2.40). CONCLUSION: Our analysis suggests performing ALS on the scene was associated with pre-hospital ROSC and survival at 1 month. Further efforts are needed to increase the rate of ALS implementation on the scene by emergency life-saving technicians.

Neurological prognosis prediction upon arrival at the hospital after out-of-hospital cardiac arrest: R-EDByUS score.

AIM: To develop a new scoring model for patients with cardiogenic out-of-hospital cardiac arrest (OHCA) to facilitate neurological prognosis prediction upon hospital arrival by using prehospital resuscitation features alone. METHODS: Between 2005 and 2019, we enrolled 942,891 adult patients with OHCA of presumed cardiac aetiology from the All-Japan Utstein Registry. Scoring models applied prehospital resuscitation features a priori from the variables the American College of Cardiology algorithm including age, duration to return of spontaneous circulation (ROSC) or hospital arrival, no bystander cardiopulmonary resuscitation (CPR), unwitnessed arrest, and nonshockable rhythm (R-EDByUS score) to predict unfavorable neurological outcomes defined as Cerebral Performance Category 3, 4, or 5 at 1 month. We created nomograms as a "Regression-based model," and created a "Simplified model" in which points were assigned by category for predicting unfavorable neurological outcomes for both the prehospital ROSC cohort (67,064 patients) and the ongoing CPR cohort (875,827 patients). For internal validation, bootstrap optimism-corrected estimates of predictive performance were calculated. RESULTS: A total of 46,971 (70.0%) and 870,991 (99.4%) patients in the prehospital ROSC and ongoing CPR cohorts, respectively, had unfavorable neurological outcomes. In the prehospital ROSC cohort, the C-statistics of the Regression-based and Simplified models were 0.851 and 0.842, and the bootstrap-validated C-statistics were 0.852 and 0.841, respectively. In the ongoing CPR cohort, the C-statistics of the Regression-based and Simplified models were 0.872 and 0.865, and the bootstrap-validated C-statistics were 0.852 and 0.841, respectively. CONCLUSIONS: The R-EDByUS score accurately predicted the neurological prognosis of cardiogenic OHCA upon hospital arrival.

The impact of time to defibrillation on return of spontaneous circulation in out-of-hospital cardiac arrest patients with recurrent shockable rhythms.

OBJECTIVE: Optimal timing for subsequent defibrillation attempts for Out-of-hospital cardiac arrest (OHCA) patients with recurrent VF/pVT is uncertain. We investigated the relationship between VF/pVT duration and return of spontaneous circulation (ROSC) in OHCA patients with recurrent shockable rhythms. METHODS: We analyzed data from the Salt Lake City Fire Department (SLCFD) spanning from 2012 to 2023. The implementation of rhythm-filtering technology since 2011 enabled real-time rhythm interpretation during CPR, with local protocols allowing early defibrillation for recurrent/refractory VF/pVT cases. We included patients experiencing four or five episodes of VF and pVT rhythms and employed generalized estimating equation (GEE) regression analysis to examine the association between VF/pVT durations preceding recurrent defibrillation and return of spontaneous circulation (ROSC). RESULTS: Analysis of 622 appropriate shocks showed that patients achieving ROSC had significantly shorter median VF/pVT duration than those who did not achieve ROSC (0.83 minutes vs. 1.2 minutes, p = 0.004). Adjusted analysis of those with 4 VF/pVT episodes (N = 142) revealed that longer VF/pVT durations were associated with lower odds of achieving ROSC (odds ratio: 0.81, 95% CI: 0.72-0.93, p = 0.005). Every one-minute delay in intra-arrest defibrillation is predicted to decrease the likelihood of achieving ROSC by 19%. CONCLUSION: Every one-minute increase in intra-arrest VF/pVT duration was associated with a statistically significant 19% decrease in the chance of achieving ROSC. This highlights the importance of reducing time to shock in managing recurrent VF/pVT. The findings suggest reevaluating the current recommendations of two minutes intervals for rhythm check and shock delivery.

Infant out-of-hospital cardiac arrest during nights and weekends.

BACKGROUND: A growing body of evidence suggests outcomes for cardiac arrest in adults are worse during nights and weekends when compared with daytime and weekdays. Similar research has not yet been carried out in the infant setting. METHODS: We examined the National Emergency Medical Services Information System (NEMSIS), a database containing millions of emergency medical services (EMS) runs in the United States. Inclusion criteria were infant out-of-hospital cardiac arrests (patients <1 years old) taking place prior to EMS arrival between January 2021 and December 2022 where EMS documented whether return of spontaneous circulation (ROSC) was achieved. Cardiac arrests were classified as occurring during either the day (defined as 0800-1959) or the night (defined as 2000-0759) and weekends (Saturday/Sunday) or weekdays (Monday-Friday). Rates of ROSC achievement were compared. RESULTS: A total of 8549 infant cardiac arrests met inclusion criteria: 5074 (59.4%) took place during daytime compared with 3475 (40.6%) during nighttime, and 5989 (70.1%) arrests occurred on weekdays compared with 2560 (29.9%) on weekends. Rates of ROSC achievement were significantly lower on weekends versus weekdays (16.8% vs. 14.1%; p = 0.00097). A difference in ROSC rates when comparing daytime and nighttime was seen, but this difference was not statistically significant (16.4% vs. 15.3%; p = 0.08076). CONCLUSION: ROSC achievement rates for infant out-of-hospital cardiac arrest are significantly lower on weekends when compared with weekdays. Further study and quality improvement work is needed to better understand this.

External Validation of Updated Prediction Models for Neurological Outcomes at 90 Days in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. METHODS AND RESULTS: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/). CONCLUSIONS: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

Cardiopulmonary Resuscitation Without Aortic Valve Compression Increases the Chances of Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest: A Prospective Observational Cohort Study.

OBJECTIVES: Following current cardiopulmonary resuscitation (CPR) guidelines, which recommend chest compressions at "the center of the chest," ~50% of patients experiencing out-of-hospital cardiac arrest (OHCA) undergo aortic valve (AV) compression, obstructing blood flow. We used resuscitative transesophageal echocardiography (TEE) to elucidate the impact of uncompressed vs. compressed AV on outcomes of adult patients experiencing OHCA. DESIGN: Prospective observational cohort study. SETTING: Single center. PATIENTS: This study included adult OHCA patients undergoing resuscitative TEE in the emergency department. Patients were categorized into AV uncompressed or AV compressed groups based on TEE findings. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was sustained return of spontaneous circulation (ROSC). The secondary outcomes included end-tidal co2 (Et co2 ) during CPR, any ROSC, survival to ICU and hospital discharge, post-resuscitation withdrawal, and favorable neurologic outcomes at discharge. Additional analyses on intra-arrest arterial blood pressure (ABP) were also conducted. The sample size was pre-estimated at 37 patients/group. From October 2020 to January 2023, 76 patients were enrolled, 39 and 37 in the AV uncompressed and AV compressed groups, respectively. Intergroup baseline characteristics were similar. Compared with the AV compressed group, the AV uncompressed group had a higher probability of sustained ROSC (53.8% vs. 24.3%; adjusted odds ratio [aOR], 4.72; p = 0.010), any ROSC (56.4% vs. 32.4%; aOR, 3.30; p = 0.033), and survival to ICU (33.3% vs. 8.1%; aOR, 6.74; p = 0.010), and recorded higher initial diastolic ABP (33.4 vs. 11.5 mm Hg; p = 0.002) and a larger proportion achieving diastolic ABP greater than 20 mm Hg during CPR (93.8% vs. 33.3%; p < 0.001). The Et co2 , post-resuscitation withdrawal, and survival to discharge revealed no significant intergroup differences. No patients were discharged with favorable neurologic outcomes. Uncompressed AV seemed critical for sustained ROSC across all subgroups. CONCLUSIONS: Absence of AV compression during OHCA resuscitation is associated with an increased chance of ROSC and survival to ICU. However, its effect on long-term outcomes remains unclear.

Mortality, morbidity & clinical outcome with different types of vasopressors in out of hospital cardiac arrest patients- a systematic review and meta-analysis.

BACKGROUND & OBJECTIVE: Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of various vasopressors in cardiac arrest patients in terms of clinical, morbidity, and mortality outcomes. METHODS: A comprehensive literature search was performed using online databases (MeSH terms: MEDLINE (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL, Scopus, and Google Scholar) from 1997 to 2023 for relevant English language studies. The primary outcomes of interest for this study included short-term survival leading to death, return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, survival to hospital admission, myocardial infarction, and incidence of arrhythmias. RESULTS: In this meta-analysis, 26 studies, including 16 RCTs and ten non-RCTs, were evaluated. The focus was on the efficacy of epinephrine, vasopressin, methylprednisolone, dopamine, and their combinations in medical emergencies. Epinephrine treatment was associated with better odds of survival to hospital discharge (OR = 1.52, 95%CI [1.20, 1.94]; p < 0.001) and achieving ROSC (OR = 3.60, 95% CI [3.45, 3.76], P < 0.00001)) over placebo but not in other outcomes of interest such as short-term survival/ death at 28-30 days, survival to hospital admission, or neurological function. In addition, our analysis indicates non-superiority of vasopressin or epinephrine vasopressin-plus-epinephrine therapy over epinephrine monotherapy except for survival to hospital admission where the combinatorial therapy was associated with better outcome (0.76, 95%CI [0.64, 0.92]; p = 0.004). Similarly, we noted the non-superiority of vasopressin-plus-methylprednisolone versus placebo. Finally, while higher odds of survival to hospital discharge (OR = 3.35, 95%CI [1.81, 6.2]; p < 0.001) and ROSC (OR = 2.87, 95%CI [1.97, 4.19]; p < 0.001) favoring placebo over VSE therapy were observed, the risk of lethal arrhythmia was not statistically significant. There was insufficient literature to assess the effects of dopamine versus other treatment modalities meta-analytically. CONCLUSION: This meta-analysis indicated that only epinephrine yielded superior outcomes among vasopressors than placebo, albeit limited to survival to hospital discharge and ROSC. Additionally, we demonstrate the non-superiority of vasopressin over epinephrine, although vasopressin could not be compared to placebo due to the paucity of data. The addition of vasopressin to epinephrine treatment only improved survival to hospital admission.

Impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest outcomes in Japan.

This study investigates the impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest (OHCA) outcomes in Japan, aiming to address a critical research gap. Analyzing data from the All-Japan Utstein registry covering pediatric OHCA cases from 2018 to 2021, the study observed no significant changes in one-month survival, neurological outcomes, or overall performance when comparing the pre-pandemic (2018-2019) and pandemic (2020-2021) periods among 6765 cases. However, a notable reduction in pre-hospital return of spontaneous circulation (ROSC) during the pandemic (15.1-13.1%, p = .020) was identified. Bystander-initiated chest compressions and rescue breaths declined (71.1-65.8%, 22.3-13.0%, respectively; both p < .001), while bystander-initiated automated external defibrillator (AED) use increased (3.7-4.9%, p = .029). Multivariate logistic regression analyses identified factors associated with reduced pre-hospital ROSC during the pandemic. Post-pandemic, there was no noticeable change in the one-month survival rate. The lack of significant change in survival may be attributed to the negative effects of reduced chest compressions and ventilation being offset by the positive impact of widespread AED availability in Japan. These findings underscore the importance of innovative tools and systems for safe bystander cardiopulmonary resuscitation during a pandemic, providing insights to optimize pediatric OHCA care.

Use of Initial Endotracheal Versus Intravenous Epinephrine During Neonatal Cardiopulmonary Resuscitation in the Delivery Room: Review of a National Database.

OBJECTIVE: To assess whether initial epinephrine administration by endotracheal tube (ET) in newly born infants receiving chest compressions and epinephrine in the delivery room (DR) is associated with lower rates of return of spontaneous circulation (ROSC) than newborns receiving initial intravenous (IV) epinephrine. STUDY DESIGN: We conducted a retrospective review of neonates receiving chest compressions and epinephrine in the DR from the AHA Get With The Guidelines-Resuscitation registry from October 2013 through July 2020. Neonates were classified according to initial route of epinephrine (ET vs IV). The primary outcome of interest was ROSC in the DR. RESULTS: In total, 408 infants met inclusion criteria; of these, 281 (68.9%) received initial ET epinephrine and 127 (31.1%) received initial IV epinephrine. The initial ET epinephrine group included those infants who also received subsequent IV epinephrine when ET epinephrine failed to achieve ROSC. Comparing initial ET with initial IV epinephrine, ROSC was achieved in 70.1% vs 58.3% (adjusted risk difference 10.02; 95% CI 0.05-19.99). ROSC was achieved in 58.3% with IV epinephrine alone, and 47.0% with ET epinephrine alone, with 40.0% receiving subsequent IV epinephrine. CONCLUSIONS: This study suggests that initial use of ET epinephrine is reasonable during DR resuscitation, as there were greater rates of ROSC compared with initial IV epinephrine administration. However, administration of IV epinephrine should not be delayed in those infants not responding to initial ET epinephrine, as almost one-half of infants who received initial ET epinephrine subsequently received IV epinephrine before achieving ROSC.

Serum urea increase during hospital stay is associated with worse outcomes after in-hospital cardiac arrest.

BACKGROUND: Evaluate the association between serum urea at admission and during hospital stay with return of spontaneous circulation (ROSC) and in-hospital mortality in patients with in-hospital cardiac arrest (IHCA). METHODS: This retrospective study included patients over 18 years with IHCA attended from May 2018 to December 2022. The exclusion criteria were the absence of exams to calculate delta urea and the express order of "do-not-resuscitate". Data were collected from the electronic medical records. Serum admission urea and urea 24 hours before IHCA were also collected and used to calculate delta urea. RESULTS: A total of 504 patients were evaluated; 125 patients were excluded due to the absence of variables to calculate delta urea and 5 due to "do-not-resuscitate" order. Thus, we included 374 patients in the analysis. The mean age was 65.0 ± 14.5 years, 48.9% were male, 45.5% had ROSC, and in-hospital mortality was 91.7%. In logistic regression models, ROSC was associated with lower urea levels 24 hours before IHCA (OR: 0.996; CI95%: 0.992-1.000; p: 0.032). In addition, increased levels of urea 24 hours before IHCA (OR: 1.020; CI95%: 1.008-1.033; p: 0.002) and of delta urea (OR: 1.001; CI95%: 1.001-1.019; p: 0.023) were associated with in-hospital mortality. ROC curve analysis showed that the area under the ROC curve for mortality prediction was higher for urea 24 hours before IHCA (Cutoff > 120.1 mg/dL) than for delta urea (Cutoff > 34.83 mg/dL). CONCLUSIONS: In conclusion, increased serum urea levels during hospital stay were associated with worse prognosis in IHCA.

A retrospective comparison of mechanical cardio-pulmonary ventilation and manual bag valve ventilation in non-traumatic out-of-hospital cardiac arrests: A study from the Belgian cardiac arrest registry.

BACKGROUND: The optimal ventilation modalities to manage out-of-hospital cardiac arrest (OHCA) remain debated. A specific pressure mode called cardio-pulmonary ventilation (CPV) may be used instead of manual bag ventilation (MBV). We sought to analyse the association between mechanical CPV and return of spontaneous circulation (ROSC) in non-traumatic OHCA. METHODS: MBV and CPV were retrospectively identified in patients with non-traumatic OHCA from the Belgian Cardiac Arrest Registry. We used a two-level mixed-effects multivariable logistic regression analysis to determine the association between the ventilation modalities and outcomes. The primary and secondary study criteria were ROSC and survival with a Cerebral Performance Category (CPC) score of 1 or 2 at 30 days. Age, sex, initial rhythm, no-flow duration, low-flow duration, OHCA location, use of a mechanical chest compression device and Rankin status before arrest were used as covariables. RESULTS: Between January 2017 and December 2021, 2566 patients with OHCA who fulfilled the inclusion criteria were included. 298 (11.6%) patients were mechanically ventilated with CPV whereas 2268 were manually ventilated. The use of CPV was associated with greater probability of ROSC both in the unadjusted (odds ratio: 1.28, 95% confidence interval [CI]: 1.01-1.63; p = 0.043) and adjusted analyses (adjusted odds ratio [aOR]: 2.16, 95%CI 1.37-3.41; p = 0.001) but not with a lower CPC score (aOR: 1.44, 95%CI 0.72-2.89; p = 0.31). CONCLUSIONS: Compared with MBV, CPV was associated with an increased risk of ROSC but not with improved an CPC score in patients with OHCA. Prospective randomised trials are needed to challenge these results.

Endotracheal epinephrine at standard versus high dose for resuscitation of asystolic newborn lambs.

INTRODUCTION: Endotracheal (ET) epinephrine administration is an option during neonatal resuscitation, if the preferred intravenous (IV) route is unavailable. OBJECTIVES: We assessed whether endotracheal epinephrine achieved return of spontaneous circulation (ROSC), and maintained physiological stability after ROSC, at standard and higher dose, in severely asphyxiated newborn lambs. METHODS: Near-term fetal lambs were asphyxiated until asystole. Resuscitation was commenced with ventilation and chest compressions. Lambs were randomly allocated to: IV Saline placebo (5 ml/kg), IV Epinephrine (20 micrograms/kg), Standard-dose ET Epinephrine (100 micrograms/kg), and High-dose ET Epinephrine (1 mg/kg). After three allocated treatment doses, rescue IV Epinephrine was administered if ROSC had not occurred. Lambs achieving ROSC were monitored for 60 minutes. Brain histology was assessed for microbleeds. RESULTS: ROSC in response to allocated treatment (without rescue IV Epinephrine) occurred in 1/6 Saline, 9/9 IV Epinephrine, 0/9 Standard-dose ET Epinephrine, and 7/9 High-dose ET Epinephrine lambs respectively. Blood pressure during CPR increased after treatment with IV Epinephrine and High-dose ET Epinephrine, but not Saline or Standard-dose ET Epinephrine. After ROSC, both ET Epinephrine groups had lower pH, higher lactate, and higher blood pressure than the IV Epinephrine group. Cortex microbleeds were more frequent in High-dose ET Epinephrine lambs (8/8 lambs examined, versus 3/8 in IV Epinephrine lambs). CONCLUSIONS: The currently recommended dose of ET Epinephrine was ineffective in achieving ROSC. Without convincing clinical or preclinical evidence of efficacy, use of ET Epinephrine at this dose may not be appropriate. High-dose ET Epinephrine requires further evaluation before clinical translation.

[Analysis of factors affecting the return of spontaneous circulation in elderly patients with out-of-hospital cardiac arrest].

OBJECTIVE: To investigate the factors that influence the return of spontaneous circulation (ROSC) in elderly patients suffering from out-of-hospital cardiac arrest (OHCA). METHODS: A retrospective study was used to collect the clinical data of OHCA patients admitted to the emergency center of Zhengzhou People's Hospital from July 2016 to July 2019 based on the pre-hospital emergency database of Utstein model. Patients' gender, age, cardiac arrest (CA) etiology, presence or absence of bystander cardiopulmonary resuscitation (CPR), emergency response time, initial cardiac rhythm, ventilation method, use of epinephrine, defibrillation and ROSC were included. The patients were divided into elderly and young groups according to whether age ≥ 60 years old, and the differences in various indicators between the two groups were compared. Univariate Logistic regression analysis was used to analyze the relationship between emergency response time and ROSC in elderly patients and multivariate Logistic regression analysis was used to identify factors influencing ROSC in elderly patients. RESULTS: A total of 3 429 adult OHCA patients were enrolled in this study, including 2 105 elderly patients (61.39%), and 1 324 young and middle-aged patients (38.61%). Compared to the young group, the proportion of females, non-cardiac causes and asystole as the initial rhythm was higher in the elderly group, the emergency response time was shorter, the rate of defibrillation and tracheal intubation, and the success rate of ROSC were lower (all P < 0.05). Among them, the proportion of cardiac arrest as the initial rhythm in elderly male patients was significantly higher than that of young male patients (P < 0.05); the proportion of non-cardiac causes in elderly female patients was significantly higher than that of young female patients, and the proportion of defibrillation was significantly lower than that of young female patients (all P < 0.05). Multivariate Logistic regression analysis showed that cardiac arrest as the initial rhythm was strongly associated with ROSC in elderly male patients [odds ratio (OR) = 0.126, 95% confidence interval (95%CI) was 0.045-0.352, P < 0.05]. Univariate Logistic regression analysis of the relationship between emergency response time and ROSC in elderly patients showed that although there was no significant difference in the ROSC success rate among elderly patients with various emergency response times, an emergency response time within 10 minutes was beneficial for ROSC in elderly patients. CONCLUSIONS: The success rate of ROSC is very low in elderly OHCA patients aged ≥60 years. Although the CPR-related indicators of elderly patients are significantly different from those of young patients, there are gender differences. The association between the elderly male patients and cardiac arrest as the initial rhythm is stronger, while OHCA caused by non-cardiac diseases is more common and defibrillable rhythm is less common in elderly female patients. It may be more beneficial for elderly patients to shorten the emergency response time and increase bystander CPR.

The design of the PRINCESS 2 trial: A randomized trial to study the impact of ultrafast hypothermia on complete neurologic recovery after out-of-hospital cardiac arrest with initial shockable rhythm.

BACKGROUND: Delayed hypothermia, initiated after hospital arrival, several hours after cardiac arrest with 8-10 hours to reach the target temperature, is likely to have limited impact on overall survival. However, the effect of ultrafast hypothermia, i.e., delivered intra-arrest or immediately after return of spontaneous circulation (ROSC), on functional neurologic outcome after out-of-hospital cardiac arrest (OHCA) is unclear. In two prior trials, prehospital trans-nasal evaporative intra-arrest cooling was safe, feasible and reduced time to target temperature compared to delayed cooling. Both studies showed trends towards improved neurologic recovery in patients with shockable rhythms. The aim of the PRINCESS2-study is to assess whether cooling, initiated either intra-arrest or immediately after ROSC, followed by in-hospital hypothermia, significantly increases survival with complete neurologic recovery as compared to standard normothermia care, in OHCA patients with shockable rhythms. METHODS/DESIGN: In this investigator-initiated, randomized, controlled trial, the emergency medical services (EMS) will randomize patients at the scene of cardiac arrest to either trans-nasal cooling within 20 minutes from EMS arrival with subsequent hypothermia at 33°C for 24 hours after hospital admission (intervention), or to standard of care with no prehospital or in-hospital cooling (control). Fever (>37,7°C) will be avoided for the first 72 hours in both groups. All patients will receive post resuscitation care and withdrawal of life support procedures according to current guidelines. Primary outcome is survival with complete neurologic recovery at 90 days, defined as modified Rankin scale (mRS) 0-1. Key secondary outcomes include survival to hospital discharge, survival at 90 days and mRS 0-3 at 90 days. In total, 1022 patients are required to detect an absolute difference of 9% (from 45 to 54%) in survival with neurologic recovery (80% power and one-sided α=0,025, ß=0,2) and assuming 2,5% lost to follow-up. Recruitment starts in Q1 2024 and we expect maximum enrolment to be achieved during Q4 2024 at 20-25 European and US sites. DISCUSSION: This trial will assess the impact of ultrafast hypothermia applied on the scene of cardiac arrest, as compared to normothermia, on 90-day survival with complete neurologic recovery in OHCA patients with initial shockable rhythm. TRIAL REGISTRATION: NCT06025123.