Hyperlactatemia and altered lactate kinetics are associated with excess mortality in sepsis : A multicenter retrospective observational study.

Severe hyperlactatemia (>10mmol/L) or impaired lactate metabolism are known to correlate with increased mortality. The maximum lactate concentration on day 1 of 10,724 septic patients from the eICU Collaborative Research Database was analyzed and patients were divided into three groups based on maximum lactate in the first 24 h (<5mmol/l; ≥5mmol/l & <10mmol/l; ≥10mmol/l). In addition, delta lactate was calculated using the following formula: (maximum lactate day 1 minus maximum lactate day 2) divided by maximum lactate day 1. A multilevel regression analysis was performed, with hospital mortality serving as the primary study end point. Significant differences in hospital mortality were found in patients with hyperlactatemia (lactate ≥10mmol/l: 79%, ≥5mmol/l & <10mmol/l: 43%, <5mmol/l, 13%; p<0.001). The sensitivity of severe hyperlactatemia (≥10mmol/l) for hospital mortality was 17%, the specificity was 99%. In patients with negative delta lactate in the first 24 h, hospital mortality was excessive (92%). In conclusion, mortality in patients with severe hyperlactatemia is very high, especially if it persists for more than 24 h. Severe hyperlactatemia, together with clinical parameters, could therefore provide a basis for setting treatment limits.

Cell-Free Double-Stranded DNA to DNase Ratio Predicts Outcome after Primary Survived Cardiac Arrest.

(1) Double-stranded DNA (dsDNA) and deoxyribonuclease (DNase) as surrogate parameters for accumulating inflammatory hazards are insufficiently studied in resuscitation research. (2) Blood samples of 76 individuals after CA were analyzed 24 and 96 h after ICU admission. Plasma levels of dsDNA, interleukin-8, and monocyte chemoattractant protein-1 and activity of DNase were assessed along with baseline characteristics, intensive care measures, and outcome data. DsDNA/DNase ratio was used as main prognostication parameter. After calculating an optimal empirical cut-off for outcome prediction (death or Cerebral Performance Category ≥3 at 6 months), multivariable logistic regression was applied. (3) Using receiver operating characteristic (ROC) analysis, an area under the curve (AUC) of 0.65 (95% CI 0.50-0.79) was found for dsDNA/DNase after 24 h versus 0.83 (95% CI 0.73-0.92) after 96 h (p = 0.03). The empirical cut-off for dsDNA/DNase ratio after 96 h was 149.97 (Youden). DsDNA/DNase ratio was associated with unfavorable outcome at six months (aOR 1.006, 95% CI 1.0017-1.0094, p = 0.005). In multivariable analysis, the association of dsDNA/DNase ratio independently predicted outcome as a continuous variable (aOR 1.004, 95% CI 1.0004-1.0079, p = 0.029) after adjusting for potential confounders. (4) DsDNA/DNase ratio at 96 h demonstrates good predictive performance for estimating outcome after CA.

Management of intoxicated patients - a descriptive outcome analysis of 4,267 ICU patients.

INTRODUCTION: Intoxications are common in intensive care units (ICUs). The number of causative substances is large, mortality usually low. This retrospective cohort study aims to characterize differences of intoxicated compared to general ICU patients, point out variations according to causative agents, as well as to highlight differences between survivors and non-survivors among intoxicated individuals in a large-scale multi-center analysis. METHODS: A total of 105,998 general ICU patients and 4,267 individuals with the admission diagnoses "overdose" and "drug toxicity" from the years 2014 and 2015 where included from the eICU Collaborative Research Database. In addition to comparing these groups with respect to baseline characteristics, intensive care measures and outcome parameters, differences between survivors and non-survivors from the intoxication group, as well as the individual groups of causative substances were investigated. RESULTS: Intoxicated patients were younger (median 41 vs. 66 years; p<0.001), more often female (55 vs. 45%; p<0.001), and normal weighted (36% vs. 30%; p<0.001), whereas more obese individuals where observed in the other group (37 vs. 31%; p<0.001). Intoxicated individuals had a significantly lower mortality compared to general ICU patients (1% vs. 10%; aOR 0.07 95%CI 0.05-0.11; p<0.001), a finding which persisted after multivariable adjustment (aOR 0.17 95%CI 0.12-0.24; p<0.001) and persisted in all subgroups. Markers of disease severity (SOFA-score: 3 (1-5) vs. 4 (2-6) pts.; p<0.001) and frequency of vasopressor use (5 vs. 15%; p<0.001) where lower, whereas rates of mechanical ventilation where higher (24 vs. 26%; p<0.001) in intoxicated individuals. There were no differences with regard to renal replacement therapy in the first three days (3 vs. 4%; p=0.26). In sensitivity analysis (interactions for age, sex, ethnicity, hospital category, maximum initial lactate, mechanical ventilation, and vasopressor use), a trend towards lower mortality in intoxicated patients persisted in all subgroups. CONCLUSION: This large-scale retrospective analysis indicates a significantly lower mortality of intoxicated individuals compared to general ICU patients.

Dexamethasone Improves Cardiovascular Outcomes in Critically Ill COVID-19, a Real World Scenario Multicenter Analysis.

BACKGROUND: Severe COVID-19 pneumonia requiring intensive care treatment remains a clinical challenge to date. Dexamethasone was reported as a promising treatment option, leading to a reduction of mortality rates in severe COVID-19 disease. However, the effect of dexamethasone treatment on cardiac injury and pulmonary embolism remains largely elusive. METHODS: In total 178 critically ill COVID-19 patients requiring intensive care treatment and mechanical ventilation were recruited in three European medical centres and included in the present retrospective study. One hundred thirteen patients (63.5%) were treated with dexamethasone for a median duration of 10 days (IQR 9-10). Sixty five patients (36.5%) constituted the non-dexamethasone control group. RESULTS: While peak inflammatory markers were reduced by dexamethasone treatment, the therapy also led to a significant reduction in peak troponin levels (231 vs. 700% indicated as relative to cut off value, p = 0.001). Similar, dexamethasone resulted in significantly decreased peak D-Dimer levels (2.16 mg/l vs. 6.14 mg/l, p = 0.002) reflected by a significant reduction in pulmonary embolism rate (4.4 vs. 20.0%, p = 0.001). The antithrombotic effect of dexamethasone treatment was also evident in the presence of therapeutic anticoagulation (pulmonary embolism rate: 6 vs. 34.4%, p < 0.001). Of note, no significant changes in baseline characteristics were observed between the dexamethasone and non-dexamethasone group. CONCLUSION: In severe COVID-19, anti-inflammatory effects of dexamethasone treatment seem to be associated with a significant reduction in myocardial injury. Similar, a significant decrease in pulmonary embolism, independent of anticoagulation, was evident, emphasizing the beneficial effect of dexamethasone treatment in severe COVID-19.

Higher Incidence of Stroke in Severe COVID-19 Is Not Associated With a Higher Burden of Arrhythmias: Comparison With Other Types of Severe Pneumonia.

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins. Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003; newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%). Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.

Soluble suppression of tumorigenicity 2 as outcome predictor after cardiopulmonary resuscitation: an observational prospective study.

Prognostication after cardiopulmonary resuscitation (CPR) is complex. Novel biomarkers like soluble suppression of tumorigenicity 2 (sST2) may provide an objective approach. A total of 106 post-CPR patients were included in this single-center observational prospective study. Serum sST2 levels were obtained 24 h after admission. Individuals were assigned to two groups: patients below and above the overall cohort's median sST2 concentration. Primary outcome was a combined endpoint at 6 months (death or Cerebral Performance Category > 2); secondary endpoint 30-day mortality. A uni- and multivariate logistic regression analysis were conducted. Elevated sST2-levels were associated with an increased risk for the primary outcome (OR 1.011, 95% CI 1.004-1.019, p = 0.004), yet no patients with poor neurological outcome were observed at 6 months. The optimal empirical cut-off for sST2 was 46.15 ng/ml (sensitivity 81%, specificity 53%, AUC 0.69). Levels above the median (> 53.42 ng/ml) were associated with higher odds for both endpoints (death or CPC > 2 after 6 months: 21% vs. 49%, OR 3.59, 95% CI 1.53-8.45, p = 0.003; death after 30 days: 17% vs. 43.3%, OR 3.75, 95% CI 1.52-9.21, p = 0.003). A positive correlation of serum sST2 after CPR with mortality at 30 days and 6 months after cardiac arrest could be demonstrated.

Thinking fast and slow: lactate and MELD-XI (model for end-stage liver disease excluding INR) are useful for estimating mortality after cardiopulmonary resuscitation.

BACKGROUND: Intensivists keep getting challenged with prognostication after cardiopulmonary resuscitation (CPR). The model for end-stage liver disease, excluding INR (MELD-XI) Score has proven valuable for assessing illness severity. Serum lactate is a readily available and established indicator of general stress and tissue hypoxia. We aimed to evaluate the prognostic value of MELD-XI combined with serum lactate in patients after CPR. METHODS: A retrospective analysis on 106 patients after CPR was performed. Multivariable Cox regression was performed to evaluate associations with 30-day mortality and neurological outcome by means of cerebral performance category (CPC). An optimal cut-off was calculated by means of the Youden Index. Patients were then divided into subgroups based on the optimal cut-offs for MELD-XI and serum lactate. RESULTS: MELD-XI and lactate were independently associated with mortality. The respective cut-offs were MELD-XI>12 and lactate ≥2.5 mmol/L. Patients were split into three groups: lactate <2.5 mmol/L and MELD-XI≤12 (low-risk; N.=32), lactate ≥2.5 mmol/L or MELD-XI>12 (medium-risk; N.=39), and lactate ≥2.5 mmol/L and MELD-XI >12 (high-risk; N.=33). The mortality rates were 6%, 26% and 61% in the low, medium and high-risk group. This combined model yielded in the highest predictive abilities (AUC=0.78 95%CI: 0.68-0.85; P=0.03 vs. AUC=0.66 for SOFA Score). Worse neurological outcome (CPC 3 or 4) was more common in the medium and high-risk group (6.25%, 10.3% and 9.1%). CONCLUSIONS: The combination of MELD-XI and lactate concentration at ICU admission was superior to the more complex SOFA Score for prediction of mortality after CPR.

Mortality after cardiopulmonary resuscitation on a medical ICU : A sex-specific outcome analysis.

BACKGROUND: Performing cardiopulmonary resuscitation (CPR) and postresuscitation care in the intensive care unit (ICU) are standardized procedures; however, there is evidence suggesting sex-dependent differences in clinical management and outcome variables after cardiac arrest (CA). METHODS: A prospective analysis of patients who were hospitalized at a medical ICU after CPR between December 2018 and March 2020 was conducted. Exclusion criteria were age < 18 years, hospital length of stay < 24 h and traumatic CA. The primary study endpoint was mortality after 6 months and the secondary endpoint neurological outcome assessed by cerebral performance category (CPC). Differences between groups were calculated by using U­tests and χ2-tests, for survival analysis both univariate and multivariable Cox regression were fitted. RESULTS: A total of 106 patients were included and the majority were male (71.7%). No statistically significant difference regarding 6­month mortality between sexes could be shown (hazard risk, HR 0.68, 95% confidence interval, CI 0.35-1.34; p = 0.27). Neurological outcome was also similar between both groups (CPC 1 88% in both sexes after 6 months; p = 1.000). There were no statistically significant differences regarding general characteristics, pre-existing diseases, as well as the majority of clinical and laboratory parameters or measures performed on the ICU. CONCLUSION: In a single center CPR database no statistically significant sex-specific differences regarding post-resuscitation care, survival and neurological outcome after 6 months were observed.

Heart-Type Fatty Acid-Binding Protein (H-FABP) and its Role as a Biomarker in Heart Failure: What Do We Know So Far?

BACKGROUND: Heart failure (HF) remains one of the leading causes of death to date despite extensive research funding. Various studies are conducted every year in an attempt to improve diagnostic accuracy and therapy monitoring. The small cytoplasmic heart-type fatty acid-binding protein (H-FABP) has been studied in a variety of disease entities. Here, we provide a review of the available literature on H-FABP and its possible applications in HF. Methods: Literature research using PubMed Central was conducted. To select possible studies for inclusion, the authors screened all available studies by title and, if suitable, by abstract. Relevant manuscripts were read in full text. RESULTS: In total, 23 studies regarding H-FABP in HF were included in this review. CONCLUSION: While, algorithms already exist in the area of risk stratification for acute pulmonary embolism, there is still no consensus for the routine use of H-FABP in daily clinical practice in HF. At present, the strongest evidence exists for risk evaluation of adverse cardiac events. Other future applications of H-FABP may include early detection of ischemia, worsening of renal failure, and long-term treatment planning.

Mechanical circulatory support with Impella versus intra-aortic balloon pump or medical treatment in cardiogenic shock-a critical appraisal of current data.

AIMS: Patients suffering from cardiogenic shock (CS) have a high mortality and morbidity. The Impella percutaneous left-ventricular assist device (LVAD) decreases LV preload, increases cardiac output, and improves coronary blood flow. We aimed to review and meta-analyze available data comparing Impella versus intra-aortic pump (IABP) counterpulsation or medical treatment in CS due to acute myocardial infarction or post-cardiac arrest. METHODS AND RESULTS: Study-level data were analyzed. Heterogeneity was assessed using the I2 statistic. Risk rates were calculated and obtained using a random-effects model (DerSimonian and Laird). Four studies were found suitable for the final analysis, including 588 patients. Primary endpoint was short-term mortality (in-hospital or 30-day mortality). In a meta-analysis of four studies comparing Impella versus control, Impella was not associated with improved short-term mortality (in-hospital or 30-day mortality; RR 0.84; 95% CI 0.57-1.24; p = 0.38; I2 55%). Stroke risk was not increased (RR 1.00; 95% CI 0.36-2.81; p = 1.00; I22 0%), but risk for major bleeding (RR 3.11 95% CI 1.50-6.44; p = 0.002; I2 0%) and peripheral ischemia complications (RR 2.58; 95% CI 1.24-5.34; p = 0.01; I2 0%) were increased in the Impella group. CONCLUSION: In patients suffering from severe CS due to AMI, the use of Impella is not associated with improved short-time survival but with higher complications rates compared to IABP and medical treatment. Better patient selection avoiding Impella implantation in futile situations or in possible lower risk CS might be necessary to elucidate possible advantages of Impella in future studies.