Brain-derived extracellular vesicles as serologic markers of brain injury following cardiac arrest: A pilot feasibility study.

AIM: Assessment of neurologic injury within the immediate hours following out-of-hospital cardiac arrest (OHCA) resuscitation remains a major clinical challenge. Extracellular vesicles (EVs), small bodies derived from cytosolic contents during injury, may provide the opportunity for "liquid biopsy" within hours following resuscitation, as they contain proteins and RNA linked to cell type of origin. We evaluated whether micro-RNA (miRNA) from serologic EVs were associated with post-arrest neurologic outcome. METHODS: We obtained serial blood samples in an OHCA cohort. Using novel microfluidic techniques to isolate EVs based on EV surface marker GluR2 (present on excitatory neuronal dendrites enriched in hippocampal tissue), we employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) methods to measure a panel of miRNAs and tested association with dichotomized modified Rankin Score (mRS) at discharge. RESULTS: EVs were assessed in 27 post-arrest patients between 7/3/2019 and 7/21/2022; 9 patients experienced good outcomes. Several miRNA species including miR-124 were statistically associated with mRS at discharge when measured within 6 hours of resuscitation (AUC = 0.84 for miR-124, p < 0.05). In a Kendall ranked correlation analysis, miRNA associations with outcome were not strongly correlated with standard serologic marker measurements, or amongst themselves, suggesting that miRNA provide distinct information from common protein biomarkers. CONCLUSIONS: This study explores the associations between miRNAs from neuron-derived EVs (NDEs) and circulating protein biomarkers within 6 hours with neurologic outcome, suggesting a panel of very early biomarker may be useful during clinical care. Future work will be required to test larger cohorts with a broader panel of miRNA species.

Cerebral oximetry: a developing tool for monitoring cerebral oxygenation during cardiopulmonary resuscitation.

Despite improvements in cardiopulmonary resuscitation (CPR), survival and neurologic recovery after cardiac arrest remain very poor because of the impact of severe ischemia and subsequent reperfusion injury. As the likelihood of survival and favorable neurologic outcome decreases with increasing severity of ischemia during CPR, developing methods to measure the magnitude of ischemia during resuscitation, particularly cerebral ischemia, is critical for improving overall outcomes. Cerebral oximetry, which measures regional cerebral oxygen saturation (rSO2 ) by near-infrared spectroscopy, has emerged as a potentially beneficial marker of cerebral ischemia during CPR. In numerous preclinical and clinical studies, higher rSO2 during CPR has been associated with improved cardiac arrest survival and neurologic outcome. In this narrative review, we summarize the scientific rationale and validation of cerebral oximetry across populations and pathophysiologic states, discuss the evidence surrounding its use to predict return of spontaneous circulation, rearrest, and neurologic outcome, and provide suggestions for incorporation of cerebral oximetry into CPR practice.

Effect of topography and weather on delivery of automatic electrical defibrillator by drone for out-of-hospital cardiac arrest.

Delivery of automatic electrical defibrillator (AED) by unmanned aerial vehicle (UAV) was suggested for out-of-hospital cardiac arrest (OHCA). The goal of this study is to assess the effect of topographic and weather conditions on call to AED attach time by UAV-AED. We included OHCA patients from 2013 to 2016 in Seoul, South Korea. We developed a UAV-AED flight simulator using topographic information of Seoul for Euclidean and topographic flight pathway including vertical flight to overcome high-rise structures. We used 4 kinds of UAV flight scenarios according to weather conditions or visibility. Primary outcome was emergency medical service (EMS) call to AED attach time. Secondary outcome was pre-arrival rate of UAV-AED before current EMS based AED delivery. Call to AED attach time in topographic pathway was 7.0 min in flight and control advanced UAV and 8.0 min in basic UAV model. Pre-arrival rate in Euclidean pathway was 38.0% and 16.3% for flight and control advanced UAV and basic UAV. Pre-arrival rate in the topographic pathway was 27.0% and 11.7%, respectively. UAV-AED topographic flight took longer call to AED attach time than Euclidean pathway. Pre-arrival rate of flight and control advanced UAV was decreased in topographic flight pathway compared to Euclidean pathway.

Assessment of the evolution of end-tidal carbon dioxide within chest compression pauses to detect restoration of spontaneous circulation.

BACKGROUND: Measurement of end-tidal CO2 (ETCO2) can help to monitor circulation during cardiopulmonary resuscitation (CPR). However, early detection of restoration of spontaneous circulation (ROSC) during CPR using waveform capnography remains a challenge. The aim of the study was to investigate if the assessment of ETCO2 variation during chest compression pauses could allow for ROSC detection. We hypothesized that a decay in ETCO2 during a compression pause indicates no ROSC while a constant or increasing ETCO2 indicates ROSC. METHODS: We conducted a retrospective analysis of adult out-of-hospital cardiac arrest (OHCA) episodes treated by the advanced life support (ALS). Continuous chest compressions and ventilations were provided manually. Segments of capnography signal during pauses in chest compressions were selected, including at least three ventilations and with durations less than 20 s. Segments were classified as ROSC or non-ROSC according to case chart annotation and examination of the ECG and transthoracic impedance signals. The percentage variation of ETCO2 between consecutive ventilations was computed and its average value, ΔETavg, was used as a single feature to discriminate between ROSC and non-ROSC segments. RESULTS: A total of 384 segments (130 ROSC, 254 non-ROSC) from 205 OHCA patients (30.7% female, median age 66) were analyzed. Median (IQR) duration was 16.3 (12.9,18.1) s. ΔETavg was 0.0 (-0.7, 0.9)% for ROSC segments and -11.0 (-14.1, -8.0)% for non-ROSC segments (p < 0.0001). Best performance for ROSC detection yielded a sensitivity of 95.4% (95% CI: 90.1%, 98.1%) and a specificity of 94.9% (91.4%, 97.1%) for all ventilations in the segment. For the first 2 ventilations, duration was 7.7 (6.0, 10.2) s, and sensitivity and specificity were 90.0% (83.5%, 94.2%) and 89.4 (84.9%, 92.6%), respectively. Our method allowed for ROSC detection during the first compression pause in 95.4% of the patients. CONCLUSION: Average percent variation of ETCO2 during pauses in chest compressions allowed for ROSC discrimination. This metric could help confirm ROSC during compression pauses in ALS settings.

The prognostic value of early lactate clearance for survival after out-of-hospital cardiac arrest.

BACKGROUND: Prognostication of survival after out-of-hospital cardiac arrest (OHCA) remains challenging with current guidelines recommending the prognostication no earlier than 72 h after return of spontaneous circulation (ROSC). Prognostic factors that could be used earlier after ROSC, like lactate clearance, are still being studied. OBJECTIVES: This paper aims to investigate the prognostic strength of early lactate clearance for survival after OHCA. METHODS: This retrospective observational single-center study focuses on patients for whom ROSC was achieved after OHCA. Patients ≥18 years admitted between September 2012 and January 2019, for which arterial serum lactate measurements were available immediately at and 3 h after hospital admission (T0 and T3), were included. RESULTS: 192 patients were included. Lactate clearance at T3 (p < 0.001) was identified as an independent predictor for 24 h, 48 h and 72 h survival. Witnessed arrest, bystander CPR and initial shockable rhythm were independent significant predictors for long term survival after ROSC (1 month, 3 months and 1 year; p < 0.05), but not for 24 h survival. Age (above or below 65 years) was not significant for predicting survival. Upon combination of witnessed arrest, bystander CPR and initial shockable rhythm in a multivariate logistic regression model for long term survival, the initial rhythm was the dominant factor in the combined model, making witnessed arrest and bystander CPR redundant. CONCLUSION: Lactate clearance at T3 after ROSC is associated with 24 h, 48 h and 72 h survival. Further research is needed to determine how to incorporate lactate clearance as part of a clinically useful tool to predict long term survival.

Endothelial BMP4 Promotes Leukocyte Rolling and Adhesion and Is Elevated in Patients After Survived Out-of-Hospital Cardiac Arrest.

Leukocyte recruitment is a fundamental step in the inflammatory response during ischemia/reperfusion injury (IRI). Rolling and adhesion of leukocytes to activated endothelium promote tissue inflammation after IRI and require presentation of adhesion molecules E-selectin and ICAM-1 on the endothelial surface. Bone morphogenetic protein (BMP) 4 is a prominent member of the BMP family expressed and secreted by endothelial cells. BMP4 derived from endothelial cells has important functions in vascular disease but its influence on the leukocyte adhesion cascade during inflammation is incompletely understood. In the present study, we challenged mice with an inducible endothelial-specific BMP4 deletion (referred to as EC-BMP4-/- mice) and their control littermates (EC-BMP4+/+) with thioglycollate i.p. and assessed extravasation of different leukocyte subsets during peritonitis. Peritoneal lavages were performed and peritoneal cells were counted. Total cell count in lavages of EC-BMP4-/- mice was markedly reduced compared with lavages of EC-BMP4+/+ mice. FACS analyses of thioglycollate-elicited peritoneal cells revealed that diverse leukocyte subsets were reduced in EC-BMP4-/- mice. Intravital microscopy of cremaster venules demonstrated that rolling and adhesion of leukocytes were significantly diminished in EC-BMP4-/- mice in comparison with control mice in response to TNFα. These observations indicate that endothelial BMP4 is essential for rolling, adhesion, and extravasation of leukocytes in vivo. To understand the underlying mechanisms, levels of endothelial adhesion molecules E-selectin and ICAM-1 were quantified in EC-BMP4-/- and EC-BMP4+/+ mice by quantitative PCR and Western blotting. Interestingly, ICAM-1 and E-selectin expressions were reduced in the hearts of EC-BMP4-/- mice. Next we confirmed pro-inflammatory properties of BMP4 in a gain of function experiments and found that administration of recombinant BMP4 in male C57BL/6 mice increased leukocyte rolling and adhesion in cremaster venules in vivo. To assess the regulation of BMP4 in inflammatory disease in humans, we collected plasma samples of patients from day 0 to day 7 after survived out-of-hospital cardiac arrest (OHCA, n = 42). Remarkably, plasma of OHCA patients contained significantly higher BMP4 protein levels compared with patients with coronary artery disease (CAD, n = 12) or healthy volunteers (n = 11). Subgroup analysis revealed that elevated plasma BMP4 levels after ROSC are associated with decreased survival and unfavorable neurological outcome. Collectively, endothelial BMP4 is a potent activator of inflammation in vivo that promotes rolling, adhesion, and extravasation of leukocyte subsets by induction of E-selectin and ICAM-1. Elevation of plasma BMP4 levels in the post-resuscitation period suggests that BMP4 contributes to pathophysiology and poor outcome of post-cardiac arrest syndrome.

The association of partial pressures of oxygen and carbon dioxide with neurological outcome after out-of-hospital cardiac arrest: an explorative International Cardiac Arrest Registry 2.0 study.

BACKGROUND: Exposure to extreme arterial partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2) following the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) is common and may affect neurological outcome but results of previous studies are conflicting. METHODS: Exploratory study of the International Cardiac Arrest Registry (INTCAR) 2.0 database, including 2162 OHCA patients with ROSC in 22 intensive care units in North America and Europe. We tested the hypothesis that exposure to extreme PaO2 or PaCO2 values within 24 h after OHCA is associated with poor neurological outcome at discharge. Our primary analyses investigated the association between extreme PaO2 and PaCO2 values, defined as hyperoxemia (PaO2 > 40 kPa), hypoxemia (PaO2 < 8.0 kPa), hypercapnemia (PaCO2 > 6.7 kPa) and hypocapnemia (PaCO2 < 4.0 kPa) and neurological outcome. The secondary analyses tested the association between the exposure combinations of PaO2 > 40 kPa with PaCO2 < 4.0 kPa and PaO2 8.0-40 kPa with PaCO2 > 6.7 kPa and neurological outcome. To define a cut point for the onset of poor neurological outcome, we tested a model with increasing and decreasing PaO2 levels and decreasing PaCO2 levels. Cerebral Performance Category (CPC), dichotomized to good (CPC 1-2) and poor (CPC 3-5) was used as outcome measure. RESULTS: Of 2135 patients eligible for analysis, 700 were exposed to hyperoxemia or hypoxemia and 1128 to hypercapnemia or hypocapnemia. Our primary analyses did not reveal significant associations between exposure to extreme PaO2 or PaCO2 values and neurological outcome (P = 0.13-0.49). Our secondary analyses showed no significant associations between combinations of PaO2 and PaCO2 and neurological outcome (P = 0.11-0.86). There was no PaO2 or PaCO2 level significantly associated with poor neurological outcome. All analyses were adjusted for relevant co-variates. CONCLUSIONS: Exposure to extreme PaO2 or PaCO2 values in the first 24 h after OHCA was common, but not independently associated with neurological outcome at discharge.

Mitochondrial dysfunction in adults after out-of-hospital cardiac arrest.

BACKGROUND: While preclinical studies suggest that mitochondria play a pivotal role in ischaemia-reperfusion injury, the knowledge of mitochondrial function in human out-of-hospital cardiac arrest remains scarce. The present study sought to compare oxidative phosphorylation capacity in skeletal muscle biopsies from out-of-hospital cardiac arrest patients to healthy controls. METHODS: This was a substudy of a randomised trial comparing targeted temperature management at 33°C versus 36°C for out-of-hospital cardiac arrest patients. Skeletal muscle biopsies were obtained from adult resuscitated comatose out-of-hospital cardiac arrest patients 28 hours after initiation of targeted temperature management, i.e. at target temperature prior to rewarming, and from age-matched healthy controls. Mitochondrial function was analysed by high-resolution respirometry. Maximal sustained respiration through complex I, maximal coupled respiration through complex I and complex II and maximal electron transport system capacity was compared. RESULTS: A total of 20 out-of-hospital cardiac arrest patients and 21 controls were included in the analysis. We found no difference in mitochondrial function between temperature allocations. We found no difference in complex I sustained respiration between out-of-hospital cardiac arrest and controls (23 (18-26) vs. 22 (19-26) pmol O2/mg/s, P=0.76), whereas coupled complex I and complex II respiration was significantly lower in out-of-hospital cardiac arrest patients versus controls (53 (42-59) vs. 64 (54-68) pmol O2/mg/s, P=0.01). Furthermore, electron transport system capacity was lower in out-of-hospital cardiac arrest versus controls (63 (51-69) vs. 73 (66-78) pmol O2/mg/s, P=0.005). CONCLUSIONS: Mitochondrial oxidative phosphorylation capacity in skeletal muscle biopsies was reduced in out-of-hospital cardiac arrest patients undergoing targeted temperature management compared to age-matched, healthy controls. The role of mitochondria as risk markers and potential targets for post-resuscitation care remains unknown.

Predicting Outcome After Out-of-Hospital Cardiac Arrest: Lactate, Need for Vasopressors, and Cytochrome c.

BACKGROUND: Outcome prediction after out-of-hospital cardiac arrest (OHCA) is difficult. We hypothesized that lactate and need for vasopressors would predict outcome, and that addition of a mitochondrial biomarker would enhance performance of the tool. METHODS: Prospective observational study of OHCA patients presenting to an academic medical center September 2008 to April 2016. We conducted univariate and multivariate logistic regressions. RESULTS: Patients were divided based on 2 variables: vasopressor status and initial lactate (<5 mmol/L, 5-10, ≥10). Three hundred fifty-two patients were evaluated; 249 had a lactate within 3 hours and were included. Patients on vasopressors had higher mortality (74% vs 40%; P < .001). A stepwise increase in mortality is associated with increasing lactate (45% lactate <5, 66% 5-10, and 83% ≥10; P < 001). Multivariable models with lactate group and vasopressors as predictors demonstrated excellent discrimination (area under the receiver operating curve [AUC]: 0.73 [95% confidence interval, CI: 0.66-0.79]; adjusted for additional covariates: AUC: 0.81 [95% CI: 0.75-0.86]). Thirty-six patients had cytochrome c levels available; among these 36, when comparing models with and without cytochrome c, there was no difference (AUC: 0.88 [95% CI: 0.76-1.00] vs AUC: 0.85 [95% CI: 0.73-0.98], respectively; P = .30). CONCLUSION: In this prospective validation, the combination of lactate and vasopressors in the immediate postarrest period is predictive of mortality. Cytochrome c offered minimal additional predictive power.

The complement lectin pathway protein MAp19 and out-of-hospital cardiac arrest: Insights from two randomized clinical trials.

AIM: Activation of the complement system is known to be a potent inducer of systemic inflammation, which is an important component of post-cardiac arrest syndrome. Mannan-binding-lectin associated protein of 19 kDa (MAp19) is suggested to be a regulatory component of the lectin pathway of complement activation. The aims of this study were to describe serial levels of MAp19 protein in comatose survivors of out-of-hospital cardiac arrest (OHCA), to evaluate the effect of two different regimes of targeted temperature management and to investigate the possible association between levels of MAp19 and mortality. METHODS: In this post-hoc study, we analysed data from two large randomized controlled studies: 'Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest' (TTM) and 'Targeted temperature management for 48 versus 24 h and neurological outcome after out-of-hospital cardiac arrest' (TTH). We measured serial levels of MAp19 in 240 patients within 72 h after OHCA and in 82 healthy controls. The effect of targeted temperature management on MAp19 levels was analysed according to temperature allocation in main trials. RESULTS: MAp19 levels were significantly lower in OHCA patients within 48 h after OHCA (p-values <0.001) compared with healthy controls. A target temperature at 33°C compared with 36°C for 24 h was associated with significantly lower levels of MAp19 (-57 ng/mL (95% confidence interval (CI): -97 to -16 mg/mL), p=0.006). Target temperature at 33°C for 48 h compared with 24 h was not associated with a difference in MAp19 levels (-31 ng/mL (95% CI: -120 to 60 mg/mL), p=0.57). Low MAp19 levels at admission were associated with higher 30-day mortality (12% vs. 38%, plog-rank =0.0008), also in adjusted analysis (two-fold higher, hazard ratio =0.48 (95% CI: 0.31 to 0.75), p=0.001). Analysis of MAp19 levels at 24-72 h showed they were not associated with 30-day mortality. CONCLUSION: Survivors after OHCA have lower levels of MAp19 protein compared with healthy controls. A targeted temperature management at 33°C compared with 36°C was associated with significantly lower MAp19 levels, whereas target temperature at 33°C for 48 h compared with 24 h did not influence MAp19 protein levels. Low MAp19 levels at admission were independently associated with increased mortality.

Parameters Influencing Brain Oxygen Measurement by Regional Oxygen Saturation in Postcardiac Arrest Patients with Targeted Temperature Management.

In several studies, regional cerebral oxygen saturation (rSO2) has been measured in patients with postcardiac arrest syndrome (PCAS) to analyze the brain's metabolic status. However, the significance of rSO2 in PCAS patients remains unclear. In the present study, we investigated the relationship between rSO2 and physiological parameters. Comatose survivors of out-of-hospital PCAS with targeted temperature management (TTM) at 34°C for 24 hours were included. All patients were monitored for their rSO2 and additional parameters (arterial oxygen saturation [SaO2], hemoglobin [Hb], mean arterial pressure [MAP], arterial carbon dioxide pressure [PaCO2], and body temperature]) measured at the start of monitoring and 24 and 48 hours after return of spontaneous circulation (ROSC). Patients were divided into favorable and unfavorable groups, and the correlation between rSO2 and these physiological parameters was evaluated by multiple regression analysis. Forty-nine patients were included in the study, with 15 in the favorable group and 34 in the unfavorable group. There was no significant difference in the rSO2 value between the two groups at any time point. The multiple regression analysis of the favorable group revealed a moderate correlation between rSO2 and SaO2, Hb, and PaCO2 only at 24 hours (coefficients: 0.482, 0.422, and 0.531, respectively), whereas that of the unfavorable group revealed moderate correlations between rSO2 and Hb values at all time points, PaCO2 at 24 hours and MAP at 24 and 48 hours. rSO2 was moderately correlated to MAP in unfavorable patients. To optimize brain oxygen metabolic balance for PCAS patients with TTM measuring rSO2, we suggest total evaluation of each parameters of SaO2, Hb, MAP, and PaCO2.

Early blood transcriptomic signature predicts patients' outcome after out-of-hospital cardiac arrest.

BACKGROUND: Early prognostication is a major challenge after out-of-hospital cardiac arrest (OHCA). AIMS: We hypothesized that a genome-wide analysis of blood gene expression could offer new prognostic tools and lines of research. METHODS: Sixty-nine patients were enrolled from an ancillary study of the clinical trial NCT00999583 that tested the effect of erythropoietin (EPO) after OHCA. Blood samples were collected in comatose survivors of OHCA at hospital admission and 1 and 3 days after resuscitation. Gene expression profiles were analyzed (Illumina HumanHT-12 V4 BeadChip; >34,000 genes). Patients were classified into two categories representing neurological favorable outcome (cerebral performance category [CPC] = 1-2) vs unfavorable outcome (CPC > 2) at Day 60 after OHCA. Differential and functional enrichment analyses were performed to compare transcriptomic profiles between these two categories. RESULTS: Among the 69 enrolled patients, 33 and 36 patients were treated or not by EPO, respectively. Among them, 42% had a favorable neurological outcome in both groups. EPO did not affect the transcriptomic response at Day-0 and 1 after OHCA. In contrast, 76 transcripts differed at Day-0 between patients with unfavorable vs favorable neurological outcome. This signature persisted at Day-1 after OHCA. Functional enrichment analysis revealed a down-regulation of adaptive immunity with concomitant up-regulation of innate immunity and inflammation in patients with unfavorable vs favorable neurological outcome. The transcription of many genes of the HLA family was decreased in patients with unfavorable vs favorable neurological outcome. Concomitantly, neutrophil activation and inflammation were observed. Up-stream regulators analysis showed the implication of numerous factors involved in cell cycle and damages. A logistic regression including a set of genes allowed a reliable prediction of the clinical outcomes (specificity = 88%; Hit Rate = 83%). CONCLUSIONS: A transcriptomic signature involving a counterbalance between adaptive and innate immune responses is able to predict neurological outcome very early after hospital admission after OHCA. This deserves confirmation in a larger population.

Lactate, lactate clearance and outcome after cardiac arrest: A post-hoc analysis of the TTM-Trial.

BACKGROUND: Admission lactate and lactate clearance are implemented for risk stratification in sepsis and trauma. In out-of-hospital cardiac arrest, results regarding outcome and lactate are conflicting. METHODS: This is a post-hoc analysis of the Target Temperature Management trial in which 950 unconscious patents after out-of-hospital cardiac arrest were randomized to a temperature intervention of 33°C or 36°C. Serial lactate samples during the first 36 hours were collected. Admission lactate, 12-hour lactate, and the clearance of lactate within 12 hours after admission were analyzed and the association with 30-day mortality assessed. RESULTS: Samples from 877 patients were analyzed. In univariate logistic regression analysis, the odds ratio for death by day 30 for each mmol/L was 1.12 (1.08-1.16) for admission lactate, P < .01, 1.21 (1.12-1.31) for 12-hour lactate, P < .01, and 1.003 (1.00-1.01) for each percentage point increase in 12-hour lactate clearance, P = .03. Only admission lactate and 12-hour lactate levels remained significant after adjusting for known predictors of outcome. The area under the receiver operating characteristic curve was 0.65 (0.61-0.69), P < .001, 0.61 (0.57-0.65), P < .001, and 0.53 (0.49-0.57), P = .15 for admission lactate, 12-hour lactate, and 12-hour lactate clearance, respectively. CONCLUSIONS: Admission lactate and 12-hour lactate values were independently associated with 30-day mortality after out-of-hospital cardiac arrest while 12-hour lactate clearance was not. The clinical value of lactate as the sole predictor of outcome after out-of-hospital cardiac arrest is, however, limited.

Cerebral tissue oximetry levels during prehospital management of cardiac arrest - A prospective observational study.

INTRODUCTION: Near-infrared spectroscopy (NIRS) enables continuous monitoring of regional oximetry (rSO2). The aim of this study was to describe dynamics of regional cerebral oximetry levels during out of hospital cardiac arrest (OHCA) resuscitation, specifically around the time of restoration of spontaneous circulation (ROSC). METHODS: This prospective observational study was performed in the prehospital setting during cardio-pulmonary resuscitation (CPR) of OHCA patients. In the three-year study period, two-hundred eighty OHCA's were responded to; rSO2 was continuously measured throughout CPR and after attaining ROSC. RESULTS: Final data analysis included 53 patients. Continuous rSO2dynamics were described and data was compared amongst ROSC (22 cases) and no-ROSC (31 cases) groups. Initial rSO2levels were below 15% (not detectable) in both groups. With ongoing CPR, rSO2levels were higher in the ROSC group (median 22% vs. 14% in no-ROSC group, p = 0.030). Until ROSC, rSO2levels were higher throughout CPR before ROSC (mean maximal value 47% at ROSC vs. 31% no-ROSC, p < 0.01). Furthermore, we found a pattern of significant, rapid and sustained rise in rSO2levels minutes prior to ROSC and normalization thereafter. CONCLUSIONS: Initial rSO2levels during OHCA are generally undetectable by the time EMS teams initiate CPR. With CPR, rSO2levels rise and are higher during CPR in patients who later achieve ROSC. Patients who achieve ROSC exhibit significant, rapid, and sustained rise in rSO2minutes prior to attaining ROSC, and normalization of rSO2 levels thereafter. Persistently low levels of rSO2 during CPR likely portend poor neurologic outcomes.

Cerebral saturation in cardiac arrest patients measured with near-infrared technology during pre-hospital advanced life support. Results from Copernicus I cohort study.

AIM: To date, monitoring options during pre-hospital advanced life support (ALS) are limited. Regional cerebral saturation (rSO2) may provide more information concerning the brain during ALS. We hypothesized that an increase in rSO2 during ALS in out-of hospital cardiac arrest (OHCA) patients is associated with return of spontaneous circulation (ROSC). METHODS: A prospective, non-randomized multicenter study was conducted in the pre-hospital setting of six hospitals in Belgium. Cerebral saturation was measured during pre-hospital ALS by a medical emergency team in OHCA patients. Cerebral saturation was continuously measured until ALS efforts were terminated or until the patient with sustained ROSC (>20 min) arrived at the emergency department. To take the longitudinal nature of the data into account, a linear mixed model was used. The correlation between the repeated measures of a patient was handled by means of ​a random intercept and a random slope. Our primary analysis tested the association of rSO2 with ROSC. RESULTS: Of the 329 patients 110 (33%) achieved ROSC. First measured rSO2 was 30% ±â€¯18 in the ROSC group and 24% ±â€¯15 in the no-ROSC group (p = .004; mean ±â€¯SD). Higher mean rSO2 values were observed in the ROSC group compared to the no-ROSC group (41% ±â€¯13 versus 33% ±â€¯13 respectively; p < 0.001). The median increase in rSO2, measured from start until two minutes before ROSC, was higher in the ROSC group (ROSC group 17% (IQR 6-29)) than in the no-ROSC group (8% (IQR 2-13); p < 0.001). An increase in rSO2 above 15% was associated with ROSC (OR 4.5; 95%CI 2.747-7.415; p < 0.001). CONCLUSION: Regional cerebral saturation measurements can be used during pre-hospital ALS as an additional marker to predict ROSC. An increase of at least 15% in rSO2 during ALS is associated with a higher probability of ROSC.

Improving the neurological prognosis following OHCA using real-time evaluation of cerebral tissue oxygenation.

BACKGROUND: The neurological prognosis is poor for patients suffering from out-of-hospital cardiac arrest (OHCA), in the absence of bystander cardio pulmonary resuscitation (CPR), and showing asystole as the initial waveform. However, such patients have the potential of resuming social activity if cerebral tissue oxygen saturation can be preserved. CASE PRESENTATION: We recently encountered a 60-year-old man who had suffered an OHCA in the absence of bystander CPR, and who successfully resumed complete social activity despite initial asystole and requiring at least 75min of chest compressions before return of spontaneous circulation (ROSC). In this case, chest compression was appropriately performed concurrently with real-time evaluation of cerebral tissue oxygenation using near-infrared spectroscopy (NIRS). As a result, the cerebral tissue oxygenation was well maintained, leading to resumption of social activity. CONCLUSIONS: Improved neurological prognoses can be expected if OHCA patients with the potential for social activity resumption are identified, using NIRS, and effective cardiopulmonary and cerebral resuscitation is performed while visually checking CPR quality.

Effect of Serum Albumin Concentration on Neurological Outcome After Out-of-Hospital Cardiac Arrest (from the CRITICAL [Comprehensive Registry of Intensive Cares for OHCA Survival] Study in Osaka, Japan).

The aim of this study was to assess whether serum albumin concentration upon hospital arrival had prognostic indications on out-of-hospital cardiac arrest (OHCA). This prospective, multicenter observational study conducted in Osaka, Japan (the CRITICAL [Comprehensive Registry of Intensive Cares for OHCA Survival] study), enrolled all patients with consecutive OHCA transported to 14 participating institutions. We included adult patients aged ≥18 years with nontraumatic OHCA who achieved return of spontaneous circulation and whose serum albumin concentration was available from July 2012 to December 2014. Based on the serum albumin concentration upon hospital arrival, patients were divided into quartiles (Q1 to Q4), namely, Q1 (<2.7 g/dl), Q2 (2.7 to 3.1 g/dl), Q3 (3.1 to 3.6 g/dl), and Q4 (≥3.6 g/dl). The primary outcome was 1-month survival with favorable neurological outcome (cerebral performance category scale 1 or 2). During the study period, a total of 1,269 patients with OHCA were eligible for our analyses. The highest proportion of favorable neurological outcome was 33.5% (109 of 325) in the Q4 group, followed by 13.2% (48 of 365), 5.0% (13 of 261), and 3.5% (11 of 318) in the Q3, Q2, and Q1 groups, respectively. In the multivariable logistic regression analysis, the proportion of favorable neurological outcome in the Q4 group was significantly higher, compared with that in the Q1 group (adjusted odds ratio 8.61; 95% confidence interval 4.28 to 17.33). The adjusted proportion of favorable neurological outcome increased in a stepwise manner across increasing quartiles (p for trend <0.001). Higher serum albumin concentration was significantly and independently associated with favorable neurological outcome in a dose-dependent manner.

MicroRNAs as potential prognosticators of neurological outcome in out-of-hospital cardiac arrest patients.

Out-of-hospital cardiac arrest survival rates have increased due to advancement in resuscitative measures, yet approximately 90% of survivors ultimately die or have severe neurologic dysfunction caused by ischemic injury. Currently, there are few early prognostic indicators of which patients have possibility of meaningful recovery. This leads to uncertainty for families and clinicians, as well as aggressive, invasive and expensive treatments despite medical futility. Several biomarkers investigated in traumatic brain injury have shown prognostication potential in ischemic brain injury. miRNAs, small noncoding RNAs responsible for gene regulation, have been studied in cardiovascular diseases, and have shown prognostication potential due to tissue specificity and stability in circulation. This review discusses available evidence on miRNAs prognosticating neurological outcomes after out-of-hospital cardiac arrest.

Low cerebral blood flow after cardiac arrest is not associated with anaerobic cerebral metabolism.

AIM OF THE STUDY: Estimation of cerebral anaerobic metabolism in survivors and non-survivors after cardiac arrest. METHODS: We performed an observational study in twenty comatose patients after cardiac arrest and 19 healthy control subjects. We measured mean flow velocity in the middle cerebral artery (MFVMCA) by transcranial Doppler. Arterial and jugular blood samples were used for calculation of the jugular venous-to-arterial CO2/arterial to-jugular venous O2 content difference ratio. RESULTS: After cardiac arrest, MFVMCA increased from 26.0[18.6-40.4]cm/sec on admission to 63.9[48.3-73.1]cm/sec after 72h (p<0.0001), with no significant differences between survivors and non-survivors (p=0.4853). The MFVMCA in controls was 59.1[52.8-69.0]cm/sec. The oxygen extraction fraction (O2EF) was 38.9[24.4-47.7]% on admission and decreased significantly to 17.3[12.1-26.2]% at 72h (p<0.0001). The decrease in O2EF was more pronounced in non-survivors (p=0.0173). O2EF in the control group was 35.4[32.4-38.7]%. The jugular bulb-arterial CO2 to arterial-jugular bulb O2 content difference ratio was >1 at all time points after cardiac arrest and did not change during admission, with no differences between survivors and non-survivors. Values in cardiac arrest patients were similar to those in normal subjects. CONCLUSIONS: In this study, low CBF after cardiac arrest is not associated with anaerobic metabolism. Hypoperfusion appears to be the consequence of a decrease of neuronal functioning and metabolic needs. Alternatively, hypoperfusion may decrease cerebral metabolism. Subsequently, metabolism increases in survivors, consistent with resumption of neuronal activity, whereas in non-survivors lasting low metabolism reflects irreversible neuronal damage.

Association of brain metabolites with blood lactate and glucose levels with respect to neurological outcomes after out-of-hospital cardiac arrest: A preliminary microdialysis study.

AIM: Out-of-hospital cardiac arrest (OHCA) is associated with poor prognosis. Cerebral microdialysis (CMD) is an efficient sampling technique to detect neurochemical changes in brain interstitial tissue. In this retrospective study, we hypothesised that there are different CMD levels between patients with favourable and unfavourable neurological outcomes. METHODS: Data of patients with OHCA admitted to Kagawa University Hospital and administered therapeutic hypothermia (TH) were collected. Using a CMD probe, extracellular glucose, lactate and pyruvate levels were measured hourly along with intracranial perfusion pressure (ICP) and cerebral perfusion pressure (CPP) for the initial 72h during TH. The lactate/pyruvate (LP) ratio was calculated. Patients were divided into favourable [Glasgow-Pittsburgh cerebral performance category 1-2 at 30days after cardiac arrest] or unfavourable neurological outcome groups. CMD biochemical markers and blood lactate and glucose levels were compared between two groups. RESULTS: Ten patients were included. ICP was significantly higher in the unfavourable than in the favourable neurological outcome group; there were no significant differences with respect to CPP. The CMD LP ratio in the unfavourable outcome group progressively increased; significant differences were observed on days 2, 3 and 4 (p<0.01). Significant differences in blood lactate levels were observed between the groups only on day 3.5. CMD and blood glucose levels were higher in the unfavourable than in the favourable outcome group during TH. CONCLUSION: The association of CMD levels with long-term outcomes would be better defined in a large randomised prospective study.