Circulatory Failure and Outcome in Out-of-Hospital Cardiac Arrest

Circulatory failure is considered one of the entities of the post cardiac arrest syndrome contributing to poor outcome. It is reported at 15-70% of all patients successfully resuscitated from out-of-hospital cardiac arrest (OHCA). The pathophysiologic mechanism is attributed to limitation of cell metabolism due to inadequate supply of oxygen, caused by pump or conduction failure within the cardiovascular system. The term, however, remains poorly defined and no general consensus on definition exists. Due to the heterogeneity in definition and mechanism, the association with outcome for circulatory failure in cardiac arrest varies, and is partly conflicting. In this thesis we investigate four different surrogate measures of circulatory failure and their association with outcome after out-of-hospital cardiac arrest.Paper I: We conducted a post hoc analysis of adult, unconscious survivors of out-of-hospital included in the TTM- 1 trial, to investigate lactate, a marker of anaerobic metabolism, as a predictor of short-term survival. 877 patients had admission lactate sampled and were included in analyses. Lactate at admission and 12 hours were independently associated with 30-day survival in a model adjusted for known predictors of survival after out-of- hospital cardiac arrest. Estimations of area under the receiver operator curve indicate a poor precision for predicting short time survival, limiting the clinical utility for lactate metrics as a sole predictor of outcome.Paper II: Copeptin, physiologically associated with vasoregulatory status, was analyzed as a marker of severity of circulatory failure, in this post hoc analysis of 690 patients included in the TTM-1 biobank sub study. Copeptin measured at 24 hours was found to be independently associated with 30-day survival, circulatory etiology of death and cardiovascular deterioration.Paper III: In this retrospective registry study of 4004 adult, unconscious patients resuscitated from OHCA, a composite definition of circulatory shock (systolic blood pressure < 90 mmHg, or use of inotropes/vasoactive agents, or clinical signs of hypoperfusion), compared to no circulatory shock on admission was associated with worse odds of good neurological outcome at hospital discharge in an analysis adjusted for baseline comorbidity and predictors of outcome.Paper IV: Patients with moderate vasopressor support (defined as mean arterial pressure < 70 mmHg and/or adrenalin/noradrenaline dose ≤ 0.25 μg/kg/min) treated with target temperature management at 33oC had higher incidence of 6-month mortality compared to patients treated with normothermia, in a post hoc analysis of 1861 OHCA patients included in the TTM-2 trial. No difference in mortality was detected with temperature intervention in patients with no- or high vasopressor support. The increase in mortality seems to be driven by an increase in 30- day incidence of non-neurological death in patients treated at 33oC, compared to normothermia, in the moderate vasopressor support group, while no difference in etiology of death was detected for intervention in the no-, and high vasopressor support group.Conclusion: Circulatory failure after OHCA is associated with outcome, however, the mechanism is complex and probably contains multiple pathways

Assessing left ventricular systolic function in shock: evaluation of echocardiographic parameters in intensive care

Introduction: Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE). Methods: Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI). Results: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively). Conclusions: EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction

Extravascular lung water index improves the diagnostic accuracy of lung injury in patients with shock

Introduction: The diagnosis of acute lung injury (ALI) may be more robust if more accurate physiological markers can be identified. Extravascular lung water (EVLW) is one possible marker, and it has been shown to correlate with respiratory function and mortality in patients with sepsis. Whether EVLW confers diagnostic value in a general population with shock, as well as which index performs best, is unclear. We investigated the diagnostic accuracy of various EVLW indices in patients with shock. Methods: We studied a prospective, observational cohort of 51 patients with shock admitted to a tertiary ICU. EVLW was measured within 6 hours of ICU admission and indexed to actual body weight (EVLW/ABW), predicted body weight (EVLW/PBW) and pulmonary blood volume (EVLW/PBV). The relationship of these indices to the diagnosis and severity of lung injury and ICU mortality were studied. Positive and negative likelihood ratios, pre- and posttest odds for diagnosis of lung injury and mortality were calculated. Results: All EVLW indices were higher among patients with lung injury and significantly correlated with respiratory parameters. Furthermore, all EVLW indices were significantly higher in nonsurvivors. The use of EVLW improves the posttest OR for the diagnosis of ALI, acute respiratory distress syndrome (ARDS) and severe lung injury (sLI) by up to eightfold. Combining increased EVLW and a diagnosis of ALI, ARDS or sLI increases the posttest odds of ICU mortality. EVLW/ABW and EVLW/PBV demonstrated the best diagnostic performance in this population. Conclusions: EVLW was associated with degree of lung injury and mortality, regardless of the index used, confirming that it may be used as a bedside indicator of disease severity. The use of EVLW as a bedside test conferred added diagnostic value for the identification of patients with lung injury

Influence of circulatory shock at hospital admission on outcome after out-of-hospital cardiac arrest

Hypotension after cardiac arrest could aggravate prolonged hypoxic ischemic encephalopathy. The association of circulatory shock at hospital admission with outcome after cardiac arrest has not been well studied. The objective of this study was to investigate the independent association of circulatory shock at hospital admission with neurologic outcome, and to evaluate whether cardiovascular comorbidities interact with circulatory shock. 4004 adult patients with out-of-hospital cardiac arrest enrolled in the International Cardiac Arrest Registry 2006–2017 were included in analysis. Circulatory shock was defined as a systolic blood pressure below 90 mmHg and/or medical or mechanical supportive measures to maintain adequate perfusion during hospital admission. Primary outcome was cerebral performance category (CPC) dichotomized as good, (CPC 1–2) versus poor (CPC 3–5) outcome at hospital discharge. 38% of included patients were in circulatory shock at hospital admission, 32% had good neurologic outcome at hospital discharge. The adjusted odds ratio for good neurologic outcome in patients without preexisting cardiovascular disease with circulatory shock at hospital admission was 0.60 [0.46–0.79]. No significant interaction was detected with preexisting comorbidities in the main analysis. We conclude that circulatory shock at hospital admission after out-of-hospital cardiac arrest is independently associated with poor neurologic outcome.publishedVersio

Status of the Micro Vertex Detector of the Compressed Baryonic Matter Experiment

The CBM experiment will investigate heavy-ion collisions at beam energies from 8 to 45 AGeV at the future accelerator facility FAIR. The goal of the experiment is to study the QCD phase diagram in the vincinity of the QCD critical point. To do so, CBM aims at measuring rare probes among them open charm. In order to identify those rare and short lived particles despite the rich combinatorial background generated in heavy ion collisions, a micro vertex detector (MVD) providing an unprecedented combination of high rate capability and radiation hardness, very light material budget and excellent granularity is required. In this work, we will discuss the concept of this detector and summarize the status of the R&D

Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators

Background: Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation. Methods: Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys® electrochemiluminescence immunoassays on a Cobas e601 instrument. Results: Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0–3 vs. 4–6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95–100% specificities. Conclusions: This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest

The prognostic performance of lactate in out of hospital cardiac arrest, a post hoc analysis of the TTM-trial

The purpose of this studywas to investigate the prognostic value of lactate at admission, 12-h lactate and 12-h lactate clearance for 30-day survival in comatose patients admitted after out of hospi tal cardiac Arrest (OHCA). Although measures of lactate have been successfully implemented in sepsis and trauma care, most OHCA studies are biased due to design and the results are conflicting. This is a post hoc analysis of the TTM-Trial, a multicentre ran domized controlled trial investigating a temperature intervention of 33 C vs. 36 C after OHCA. 939 patients were analysed. 30-day survival was 56%. Median admission lactate was 6.0mmol/l [3.0-9.5]. Survivors at day 30 had lower admission lactate 4.7mmol/l [2.4-8.9] vs. 7.3mmol/l [4.5-10.7] for non-survivors, p < 0.01. The difference inmedian 12-h lactate was 1.4mmol/l [1.0-2.3] vs. 2.0mmol/l [1.2-3.3], p < 0.01. 12-h lactate clearance was 47±70% in survivors vs. 54±46%, p = 0.03. In a mixed model including all sample times, average lactate valueswere higher in the 33C-group (p < 0.001). In an unad justed model the odds ratio (OR) for death by 1mmol/l increase in lactate was 1.1 [1.1-1.2] at admission (p < 0.01), 1.2 [1.1-1.3] at 12-h (p < 0.01) and 1.003 [1.0-1.01] per % decrease in 12-h clear ance (p = 0.03). In a multivariate analysis, admission lactate and 12-h lactate remained independent predictors of 30-day mortality. A receiver operator curve illustrates the prognostic properties of different measures of lactate in this study. Admission lactate and 12-h lactate are associated with 30-day survival after cardiac arrest. The diagnostic value of these lactate measures is of limited use in clinical praxis

Changes in blood lactate predict outcome better than absolute values in severe SIRS

Introduction: Serum lactate is considered to be a marker of tissue hypoxia (1) Cut-off values >4 mM predict poor outcome, yet many patients after resuscitation according Surviving Sepsis Campaign guidelines (SSCG) (2) have high mortality despite decreases in blood lactate. Our hypothesis was that dynamic, rather than absolute blood lactate concentrations predict survival. Further we tested the ability of microdialysis lactate (MD-lac) to follow dynamic changes in blood levels, and whether this was also predictive of survival. Methods: Prospective, observational, single-centre cohort study in a mixed-bed university hospital ICU. About 53 consecutive patients with SIRS and circulatory failure despite adequate fluid resuscitation according to the SSCG were included. Arterial blood lactate (B-lac) was measured 6- hourly and MD-lac in subcutaneous tissue measured 4- hourly. Changes in B- and MD-lac from baseline were also calculated. Results: There were no differences in absolute values of B- lac or MD-lac between survivors and non-survivors during the first 24 h, nor were there differences in the change in MD-lac. In contrast changes in B-lac were greater in survivors. Among patients who reached P-lac > 4 mM during the study period of 7 days, the mortality rate was 37% as compared to 21% in the others, although this did not reach statistical significance. Conclusions: Survivors of severe SIRS were characterized by greater changes in B-lac compared to baseline. This supports the concept of lactate clearance, rather than absolute values, as a useful end point for fluid resuscitation, as opposed to the traditional endpoints used in the SSCG. In contrast MD- lac was not a useful predictor of mortality in this population