Biochemical and electrophysiological markers predictive of return of spontaneous circulation and post-resuscitation outcome

The majority of patients resuscitated from cardiac arrest (CA) subsequently die due to post-cardiac arrest syndrome (PCAS), whose mechanisms are only partially understood. We adopted an approach of untargeted/targeted plasma metabolomics in rats to identify metabolites involved in the mechanisms of PCAS to be tested as predictors of outcome. Activation of the kynurenine pathway (KP) for tryptophan (TRP) degradation was demonstrated in rats, pigs and in a small cohort of patients. Decreases in TRP occurred during the post-CA period and were accompanied by significant increases in KP metabolites, 3-hydroxyanthranilic acid (3 -HAA) and kynurenic acid in each species, that persisted up to 3-5 days post-CA (p<0.01). KP metabolites changes were significantly related to the severity of myocardial and cerebral injuries and survival. Finally, when tested in 155 patients resuscitated from CA, KP metabolites were significantly higher in patients with poor outcomes. The quality of chest compression (CC) is another major issue for cardiopulmonary resuscitation (CPR) success and survival. The decision whether to interrupt CC to deliver a defibrillation (DF) is difficult. The potential benefit of a DF guided by a real time ventricular fibrillation (YF) waveform analysis would maximize DF success, minimize CC interruptions and myocardial damage by repetitive and unnecessary DFs. We evaluated amplitude spectrum area (AMSA) as predictor of DF outcome in two large databases of out-of-hospital VFs, from US (609 patients) and Italy (1.617 patients). AMSA was significantly higher prior to a successful DF than prior to an unsuccessful one (p<0.0001). Thresholds for prediction of successful and unsuccessful DFs were 16-17 mV-Hz for success and <7 mV-Hz for failure, with a positive predictive value of 80% and a negative predictive value of 97%. AMSA was a better predictor of DF outcome (AUC 0.86, p<0.0001) compared to other VF parameters, i.e. amplitude and frequencies. In conclusion, AMSA would be a useful tool for guiding CPR

2022: Are We Back to the pre-COVID-19 Pandemic Period in the Management of out-of-Hospital Cardiac Arrest?

Introduction: The COVID-19 pandemic caused a significant strain on the Emergency system, particularly for time-dependent diseases like Out of Hospital Cardiac Arrest (OHCA). Studies have shown an increase in the incidence of OHCA during different waves of the pandemic, but there is limited evidence on how survival rates and rescue efforts have been affected in the post-pandemic period. Methods: We performed a retrospective observational cohort study of all OHCA rescues by AREU (Agenzia Regionale Emergenza Urgenza), in the Lombardy region in March in three different years (2019, 2021 and 2022). We used rescue mission data collected in AREU’s database, where logistic information of patient rescue missions managed by the Lombardy Region’s 112 system is recorded.Results: This study was an epidemiology analysis of OHCA after the pandemic. The results showed no significant changes in the probability of receiving bystander cardiopulmonary resuscitation (22.5% vs 24.0%; p=0.41) and public access defibrillation (3.6 vs 3.2; p=0.50) compared to pre-pandemic period. However, there was a decrease in the probability of ROSC (11.5% vs 6.2%; p&lt;0.01).Conclusion: According to our analysis, there appears to be a return to the pre-pandemic phase with regard to the OHCA network. However, it remains to be pointed out that a careful study of disease networks is essential to understand the resilience of our health system and to understand whether we have returned to a system similar to the pre-pandemic phase after the COVID-19 pandemic

Oxygen and carbon dioxide targets during and after resuscitation of cardiac arrest patients

Non peer reviewe

Point-of-care laboratory analyses of intraosseous, arterial and central venous samples during experimental cardiopulmonary resuscitation

Introduction: Screening and correcting reversible causes of cardiac arrest (CA) are an essential part of cardiopulmonary resuscitation (CPR). Point-ofcare (POC) laboratory analyses are used for screening pre-arrest pathologies, such as electrolyte disorders and acid-base balance disturbances. The aims of this study were to compare the intraosseous (10), arterial and central venous POC values during CA and CPR and to see how the CPR values reflect the pre-arrest state. Methods: We performed an experimental study on 23 anaesthetised pigs. After induction of ventricular fibrillation (VF), we obtained POC samples from the 10 space, artery and central vein simultaneously at three consecutive time points. We observed the development of the values during CA and CPR and compared the CPR values to the pre-arrest values. Results: The 10, arterial and venous values changed differently from one another during the course of CA and CPR. Base excess and pH decreased in the venous and 10 samples during untreated VF, but in the arterial samples, this only occurred after the onset of CPR. The 10, arterial and venous potassium values were higher during CPR compared to the pre-arrest arterial values (mean elevations 4.4 mmol/l (SD 0.72), 3.3 mmol/l (0.78) and 2.8 mmol/l (0.94), respectively). Conclusions: A dynamic change occurs in the common laboratory values during CA and CPR. POC analyses of lactate, pH, sodium and calcium within 10 samples are not different from analyses of arterial or venous blood. Potassium values in 10, arterial and venous samples during CPR are higher than the pre-arrest arterial values.Peer reviewe

The effect of 50% compared to 100% inspired oxygen fraction on brain oxygenation and post cardiac arrest mitochondrial function in experimental cardiac arrest

Background and aim: We hypothesised that the use of 50% compared to 100% oxygen maintains cerebral oxygenation and ameliorates the disturbance of cardiac mitochondrial respiration during cardiopulmonary resuscitation (CPR). Methods: Ventricular fibrillation (VF) was induced electrically in anaesthetised healthy adult pigs and left untreated for seven minutes followed by randomisation to manual ventilation with 50% or 100% oxygen and mechanical chest compressions (LUCAS (R)). Defibrillation was performed at thirteen minutes and repeated if necessary every two minutes with 1 mg intravenous adrenaline. Cerebral oxygenation was measured with near-infrared spectroscopy (rSO(2), INVOS (TM) 5100C Cerebral Oximeter) and with a probe (NEUROVENT-PTO, RAUMEDIC) in the frontal brain cortex (PbO2). Heart biopsies were obtained 20 min after the return of spontaneous circulation (ROSC) with an analysis of mitochondrial respiration (OROBOROS Instruments Corp., Innsbruck, Austria), and compared to four control animals without VF and CPR. Brain rSO(2) and PbO2 were log transformed and analysed with a mixed linear model and mitochondrial respiration with an analysis of variance. Results: Of the twenty pigs, one had a breach of protocol and was excluded, leaving nine pigs in the 50% group and ten in the 100% group. Return of spontaneous circulation (ROSC) was achieved in six pigs in the 50% group and eight in the 100% group. The rSO(2) (p = 0.007) was lower with FiO(2) 50%, but the PbO2 was not (p = 0.93). After ROSC there were significant interactions between time and FiO(2) regarding both rSO(2) (p = 0.001) and PbO2 (p = 0.004). Compared to the controls, mitochondrial respiration was decreased, with adenosine diphosphate (ADP) levels of 57 (17) pmol s(-1) mg(-1) compared to 92 (23) pmol s(-1) mg(-1) (p = 0.008), but there was no difference between different oxygen fractions (p = 0.79). Conclusions: The use of 50% oxygen during CPR results in lower cerebral oximetry values compared to 100% oxygen but there is no difference in brain tissue oxygen. Cardiac arrest disturbs cardiac mitochondrial respiration, but it is not alleviated with the use of 50% compared to 100% oxygen (Ethical and hospital approvals ESAVI/1077/04.10.07/2016 and HUS/215/2016, 7 30.3.2016, Funding Helsinki University and others). (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Clinical biomarkers in brain injury: a lesson from cardiac arrest.

Cardiac arrest (CA) is the primary cause of death in industrialized countries. Successful resuscitation rate is estimated of about 40%, but a good neurological outcome remains difficult to achieve. The majority of resuscitated victims suffers of a pathophysiological entity termed as "post resuscitation disease". Today's efforts are mainly pointed to the chain of survival, often devoting less attention to post-resuscitation care. Resuscitated patients are often victims of nihilistic therapeutic approach, with clinicians failing to promptly institute strategies that mitigate the ischemia-reperfusion injury to vital organs. Only after 72 hours prognostication can be realistically attempted. Neurological evaluation relies on a combination of clinical, instrumental and laboratoristic parameters, since no one alone holds a specificity of 100%. Biochemical markers, such as neuron specific enolase and S-100b, may contribute to predict prognosis after CA. To the contrary, when used individually the necessary precision remains poorly characterized. Biochemical studies suffer from substantial methodological differences hampering attempts to summarize their findings. We review the information available on biochemical markers of brain damage for neurological prognostication after CA

Blood pressure variability, heart functionality, and left ventricular tissue alterations in a protocol of severe hemorrhagic shock and resuscitation

Autonomic control of blood pressure (BP) and heart rate (HR) is crucial during bleeding and hemorrhagic shock (HS) to compensate for hypotension and hypoxia. Previous works have observed that at the point of hemodynamic decompensation a marked suppression of BP and HR variability occurs, leading to irreversible shock. We hypothesized that recovery of the autonomic control may be decisive for effective resuscitation, along with restoration of mean BP. We computed cardiovascular indexes of baroreflex sensitivity and BP and HR variability by analyzing hemodynamic recordings collected from five pigs during a protocol of severe hemorrhage and resuscitation; three pigs were sham-treated controls. Moreover, we assessed the effects of severe hemorrhage on heart functionality by integrating the hemodynamic findings with measures of plasma high-sensitivity cardiac troponin T and metabolite concentrations in left ventricular (LV) tissue. Resuscitation was performed with fluids and norepinephrine and then by reinfusion of shed blood. After first resuscitation, mean BP reached the target value, but cardiovascular indexes were not fully restored, hinting at a partial recovery of the autonomic mechanisms. Moreover, cardiac troponins were still elevated, suggesting a persistent myocardial sufferance. After blood reinfusion all the indexes returned to baseline. In the harvested heart, LV metabolic profile confirmed the acute stress condition sensed by the cardiomyocytes. Variability indexes and baroreflex trends can be valuable tools to evaluate the severity of HS, and they may represent a more useful end point for resuscitation in combination with standard measures such as mean values and biological measures. NEW & NOTEWORTHY Autonomic control of blood pressure was highly impaired during hemorrhagic shock, and it was not completely recovered after resuscitation despite global restoration of mean pressures. Moreover, a persistent myocardial sufferance emerged from measured cardiac troponin T and metabolite concentrations of left ventricular tissue. We highlight the importance of combining global mean values and biological markers with measures of variability and autonomic control for a better characterization of the effectiveness of the resuscitation strategy

44 Point-of-care analysis of lactate from intraosseous samples during resuscitation

Aim Intraosseous (IO) access with power-driven devices has become a commonly used method of vascular access during cardiopulmonary resuscitation (CPR). Blood aspirated to confirm correct IO needle position could readily be available for point-of-care (POC) testing. The aim was to investigate how POC lactate levels of intraosseous blood reflect the lactate values in systemic circulation during VF and resuscitation in order to see whether POC IO samples could be used for clinical decision-making during CPR. Methods We conducted an experimental study comparing POC results of lactate from intraosseous, arterial and venous blood of 23 piglets undergoing induced cardiac arrest (VF) and CPR. All blood samples were analysed with i-STAT POC device and the results were compared using Bland-Altman method (ref 1). Results Prior to VF the IO lactate levels were similar to arterial and venous samples (bias [95% CI] between IO and arterial samples was 0.11 mmol/L [−0.02–0.24] and between IO and venous samples 0.03 mmol/L [−0.25–0.31]). Five minutes after onset of VF, intraosseous lactate levels had increased more than arterial and venous values (bias 3.76 mmol/L [1.93–5.59] and 3.52 mmol/L [1.41–5.64] respectively). Five minutes after initiation of CPR with an automatic CPR device (LucasTM) the difference diminished (bias 0.81 mmol/L, [−0.31–1.93] and 1.50 mmol/L [0.07–2.92]). Conclusion Intraosseous lactate values showed good agreement with arterial and venous values before cardiac arrest, but IO values were clearly higher during VF and CPR. During resuscitation IO lactate values seem to represent better the metabolic state at tissue level than arterial or venous lactate. Reference Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet1986;1:307–10 Conflict of interest None declared. Funding None declared

Effectiveness of antiarrhythmic drugs for shockable cardiac arrest : a systematic review

Purpose The purpose of this systematic review is to provide up-to-date evidence on effectiveness of antiarrhythmic drugs for shockable cardiac arrest to help inform the 2018 International Liaison Committee on Resuscitation Consensus on Science with Treatment Recommendations. Methods A search was conducted in electronic databases Medline, Embase, and Cochrane Library from inception to August 15, 2017. Results Of the 9371 citations reviewed, a total of 14 RCTs and 17 observational studies met our inclusion criteria for adult population and only 1 observational study for pediatric population. Based on RCT level evidence for adult population, none of the anti-arrhythmic drugs showed any difference in effect compared with placebo, or with other anti-arrhythmic drugs for the critical outcomes of survival to hospital discharge and discharge with good neurological function. For the outcome of return of spontaneous circulation, the results showed a significant increase for lidocaine compared with placebo (RR = 1.16; 95% CI, 1.03–1.29, p = 0.01). Conclusion The high level evidence supporting the use of antiarrhythmic drugs during CPR for shockable cardiac arrest is limited and showed no benefit for critical outcomes of survival at hospital discharge, survival with favorable neurological function and long-term survival. Future high quality research is needed to confirm these findings and also to evaluate the role of administering antiarrhythmic drugs in children with shockable cardiac arrest, and in adults immediately after ROSC

An Innovative Approach for the Integration of Proteomics and Metabolomics Data in Severe Septic Shock Patients Stratified for Mortality

Abstract In this work, we examined plasma metabolome, proteome and clinical features in patients with severe septic shock enrolled in the multicenter ALBIOS study. The objective was to identify changes in the levels of metabolites involved in septic shock progression and to integrate this information with the variation occurring in proteins and clinical data. Mass spectrometry-based targeted metabolomics and untargeted proteomics allowed us to quantify absolute metabolites concentration and relative proteins abundance. We computed the ratio D7/D1 to take into account their variation from day 1 (D1) to day 7 (D7) after shock diagnosis. Patients were divided into two groups according to 28-day mortality. Three different elastic net logistic regression models were built: one on metabolites only, one on metabolites and proteins and one to integrate metabolomics and proteomics data with clinical parameters. Linear discriminant analysis and Partial least squares Discriminant Analysis were also implemented. All the obtained models correctly classified the observations in the testing set. By looking at the variable importance (VIP) and the selected features, the integration of metabolomics with proteomics data showed the importance of circulating lipids and coagulation cascade in septic shock progression, thus capturing a further layer of biological information complementary to metabolomics information