Proportion of time spent in blood glucose range 70 to 140 mg/dL is associated with increased survival in patients admitted to ICU after cardiac arrest: A multicenter observational study.

The benefit of any specific target range of blood glucose (BG) for post-cardiac arrest (PCA) care remains unknown.We conducted a multicenter retrospective study of prospectively collected data of all cardiac arrest patients admitted to the ICUs between 2014 and 2015. The main exposure was BG metrics during the first 24 hours, including time-weighted mean (TWM) BG, mean BG, admission BG and proportion of time spent in 4 BG ranges (<= 70 mg/dL, 70-140 mg/dL, 140-180 mg/dL and > 180 mg/dL). The primary outcome was hospital mortality. Multivariable logistic regression, Cox proportion hazard models and generalized estimating equation (GEE) models were built to evaluate the association between the different kinds of BG and hospital mortality.2,028 PCA patients from 144 ICUs were included. 14,118 BG measurements during the first 24 hours were extracted. According to TWM-BG, 9 (0%) were classified into the <= 70 mg/dL range, 693 (34%) into the 70 to 140 mg/dL range, 603 (30%) into the 140 to 180 mg/dL range, and 723 (36%) into the > 180 mg/dL range. Compared with BG 70 to 140 mg/dL range, BG 140 to 180 mg/dL range and > 180 mg/dL range were associated with higher hospital mortality probability. Proportion of time spent in the 70 to 140 mg/dL range was associated with good outcome (odds ratio 0.984, CI [0.970, 0.998], P = .022, for per 5% increase in time), and > 180 mg/dL range with poor outcome (odds ratio 1.019, CI [1.009, 1.028], P< .001, for per 5% increase in time). Results of the 3 kinds of statistical models were consistent.The proportion of time spent in BG range 70 to 140 mg/dL is strongly associated with increased hospital survival in PCA patients. Hyperglycemia (> 180 mg/dL) is common in PCA patients and is associated with increased hospital mortality.

Association of Hospital-Level Acute Resuscitation and Postresuscitation Survival With Overall Risk-Standardized Survival to Discharge for In-Hospital Cardiac Arrest.

Importance: Survival after in-hospital cardiac arrest depends on 2 distinct phases: responsiveness and quality of the hospital code team (ie, acute resuscitation phase) and intensive and specialty care expertise (ie, postresuscitation phase). Understanding the association of these 2 phases with overall survival has implications for design of in-hospital cardiac arrest quality measures. Objective: To determine whether hospital-level rates of acute resuscitation survival and postresuscitation survival are associated with overall risk-standardized survival to discharge for in-hospital cardiac arrest. Design, Settings, and Participants: This observational cohort study included 86 426 patients with in-hospital cardiac arrest from January 1, 2015, through December 31, 2018, recruited from 290 hospitals participating in the Get With The Guidelines-Resuscitation registry. Exposures: Risk-adjusted rates of acute resuscitation survival, defined as return of spontaneous circulation for at least 20 minutes, and postresuscitation survival, defined as survival to discharge among patients achieving return of spontaneous circulation. Main Outcomes and Measures: The primary outcome was overall risk-standardized survival rate (RSSR) for in-hospital cardiac arrest calculated using a previously validated model. The correlation between a hospital's overall RSSR and risk-adjusted rates of acute resuscitation and postresuscitation survival were examined. Results: Of 86 426 patients with in-hospital cardiac arrest, the median age was 67.0 years (interquartile range [IQR], 56.0-76.0 years); 50 665 (58.6%) were men, and 71 811 (83.1%) had an initial nonshockable cardiac arrest rhythm. The median RSSR was 25.1% (IQR, 21.9%-27.7%). The median risk-adjusted acute resuscitation survival was 72.4% (IQR, 67.9%-76.9%), and risk-adjusted postresuscitation survival was 34.0% (IQR, 31.5%-37.7%). Although a hospital's RSSR was correlated with survival during both phases, the correlation with postresuscitation survival (ρ, 0.90; P < .001) was stronger compared with the correlation with acute resuscitation survival (ρ, 0.50; P < .001). Of note, there was no correlation between risk-adjusted acute resuscitation survival and postresuscitation survival (ρ, 0.09; P = .11). Compared with hospitals in the lowest RSSR quartile, hospitals in the highest RSSR quartile had higher rates of acute resuscitation survival (75.4% in quartile 4 vs 66.8% in quartile 1; P < .001) and postresuscitation survival (40.3% in quartile 4 vs 28.7% in quartile 1; P < .001), but the magnitude of difference was larger with postresuscitation survival. Conclusions and Relevance: The findings suggest that hospitals that excel in overall in-hospital cardiac arrest survival, in general, excel in either acute resuscitation or postresuscitation care but not both; efforts to strengthen postresuscitation care may offer additional opportunities to improve in-hospital cardiac arrest survival.

High plasma levels of pro-inflammatory factors interleukin-17 and interleukin-23 are associated with poor outcome of cardiac-arrest patients: a single center experience.

BACKGROUND: Systemic inflammation is an important feature of post-cardiac arrest syndrome (PCAS). This study was designed to determine whether the plasma concentrations of some circulating pro-inflammatory cytokines (interleukin-17 [IL-8], IL-22, IL-23 and IL-33) are of value in predicting the outcome of patients after return of spontaneous circulation (ROSC) during the post-cardiac arrest period. METHODS: This was a prospective observational clinical study. In total, 21 patients (survivors, n = 10; non-survivors, n = 11) who experienced cardiac arrest and successful ROSC with expected survival of at least 7 days were consecutively enrolled from January 2016 to December 2017. Of the 21 enrolled patients, ten survived were designated "survivors". The other eleven patients died between 2 days and 1 months post ROSC. Venous blood was drawn at three time-points: baseline (< 1 h post ROSC), 2 days post ROSC and 7 days post ROSC. Plasma IL-8, IL-22, IL-23 and IL-33 were determined using commercial enzyme-linked immunosorbent assays. RESULTS: Plasma creatinine levels, but aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were elevated in non-survivors compared with survivors. Plasma levels of IL-17, IL-22, IL-23 and IL-33 of the 21 total patients did not change at 2 or 7 days post ROSC compared to baseline. In survivors, the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were lower than baseline. In non-survivors, plasma levels of IL-17 increased compared with baseline. Receiver operating characteristic curve analysis showed that the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were able to predict the mortality of PCAS patients, and positively correlated with Acute Physiology and Chronic Health Evaluation (APACHE)-II score and time to ROSC. CONCLUSION: These results provide the first evidence that the elevated plasma IL-17 and IL-23 levels are associated with poor outcome in PCAS patients. The role of IL-17/IL-23 axis post ROSC is worth paying attention to in PCAS patients. TRIAL REGISTRATION: Clinicaltrial.govNCT02297776, 2014-11-21.

The Sequential Organ Failure Assessment (SOFA) score predicts mortality and neurological outcome in patients with post-cardiac arrest syndrome.

BACKGROUND: Patients experiencing out-of-hospital cardiac arrest (OHCA) and subsequent post-cardiac arrest syndrome are often compromised by multi-organ failure. The Sequential Organ Failure Assessment (SOFA) score has been used to predict clinical outcome of patients requiring intensive care for multi-organ failure. Thus, the assessment of SOFA score is recommended as a criterion for sepsis. Although post-cardiac arrest patients frequently develop sepsis-like status in ICU, there are limited reports evaluating the SOFA score in post-cardiac arrest patients. We investigated the predictive value of the SOFA score in survival and neurological outcomes in patients with post-cardiac arrest syndrome. METHODS: A total of 231 cardiovascular arrest patients achieving return of spontaneous circulation (ROSC) were finally extracted from the institutional consecutive database comprised of 1218 OHCA patients transferred to the institution between January 2015 and July 2018. The SOFA score was calculated on admission and after 48h. Predictors of survival and neurological outcome defined as having cerebral-performance-category (CPC) 1 or 2 at 30 days were determined. RESULTS: SOFA score was lower in survived patients (5.0 vs 10.0, p<0.001) and those with favorable neurological outcome (5.0 vs 8.0, p<0.001) as compared with the counterparts. The SOFA score on admission was an independent predictor of survival (OR 0.68, 95% confidence interval [CI] 0.59-0.78; p<0.001) and favorable neurological performance (OR 0.79; 95% CI 0.69-0.90; p<0.001) at 30 days. Furthermore, a change in SOFA score (48-0h) was predictive of favorable 30-day neurological outcome (OR 0.71, 95% CI 0.60-0.85; p<0.001). CONCLUSIONS: Evaluation of the SOFA score in the ICU is useful to predict survival and neurological outcome in post-cardiac arrest patients.

Acute respiratory failure and inflammatory response after out-of-hospital cardiac arrest: results of the Post-Cardiac Arrest Syndrome (PCAS) pilot study.

BACKGROUND: Although the lungs are potentially highly susceptible to post-cardiac arrest syndrome injury, the issue of acute respiratory failure after out-of-hospital cardiac arrest has not been investigated. The objectives of this analysis were to determine the prevalence of acute respiratory failure after out-of-hospital cardiac arrest, its association with post-cardiac arrest syndrome inflammatory response and to clarify its importance for early mortality. METHODS: The Post-Cardiac Arrest Syndrome (PCAS) pilot study was a prospective, observational, six-centre project (Poland 2, Denmark 1, Spain 1, Italy 1, UK 1), studying patients resuscitated after out-of-hospital cardiac arrest of cardiac origin. Primary outcomes were: (a) the profile of organ failure within the first 72 hours after out-of-hospital cardiac arrest; (b) in-hospital and short-term mortality, up to 30 days of follow-up. Respiratory failure was defined using a modified version of the Berlin acute respiratory distress syndrome definition. Inflammatory response was defined using leukocytes (white blood cells), platelet count and C-reactive protein concentration. All parameters were assessed every 24 hours, from admission until 72 hours of stay. RESULTS: Overall, 148 patients (age 62.9±15.27 years; 27.7% women) were included. Acute respiratory failure was noted in between 50 (33.8%) and 75 (50.7%) patients over the first 72 hours. In-hospital and short-term mortality was 68 (46.9%) and 72 (48.6%), respectively. Inflammation was significantly associated with the risk of acute respiratory failure, with the highest cumulative odds ratio of 748 at 72 hours (C-reactive protein 1.035 (1.001-1.070); 0.043, white blood cells 1.086 (1.039-1.136); 0.001, platelets 1.004 (1.001-1.007); <0.005). Early acute respiratory failure was related to in-hospital mortality (3.172, 95% confidence interval 1.496-6.725; 0.002) and to short-term mortality (3.335 (1.815-6.129); 0.0001). CONCLUSIONS: An inflammatory response is significantly associated with acute respiratory failure early after out-of-hospital cardiac arrest. Acute respiratory failure is associated with a worse early prognosis after out-of-hospital cardiac arrest.

"Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA): Safety and efficacy of low-dose Iloprost, a prostacyclin analogue, in addition to standard therapy, as compared to standard therapy alone, in post-cardiac-arrest-syndrome patients."

OBJECTIVE: An increasingly recognized prognostic factor for out-of-hospital-cardiac-arrest (OHCA) patients is the ischemia-reperfusion injury after restored blood circulation. Endothelial injury is common in patients resuscitated from cardiac arrest and is associated with poor outcome. This study was designed to investigate if iloprost infusion, a prostacyclin analogue, reduces endothelial damage in OHCA patients. METHODS: 50 patients were randomized in a placebo controlled double-blinded trial and allocated 1:2 to 48-hours iloprost infusion, (1 ng/kg/min) or placebo (saline infusion). Endothelial biomarkers (soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), vascular endothelial cadherine (VEcad), nucleosomes) and sympathoadrenal activation (epinephrine/norepinephrine) from baseline to 48 and 96-hours were evaluated. RESULTS: Iloprost infusion did not influence endothelial biomarkers by the 48-hour endpoint. A rebound effect was observed with higher biomarker plasma values in the iloprost group (sTM p=0.02; Syndecan p=0.004; nucleosomes p<0.001; VEcad p<0.03) after 96-hours. There was a significant difference in 180-day mortality in favor of placebo. There was no difference regarding total adverse events between groups (p=0.73). Two patients were withdrawn in the iloprost group due to hypotension. CONCLUSIONS: The administration of low-dose iloprost (1ng/kg/min) to OHCA patients did not significantly influence endothelial biomarkers as measured by the 48- hour endpoint. A rebound effect was however observed in the 96-hour statistical model, with increasing endothelial biomarker levels after cessation of the iloprost-infusion.

Elimination of glutamate using CRRT for 72 h in patients with post-cardiac arrest syndrome: A randomized clinical pilot trial.

AIM: Glutamine and glutamate are major mediators of secondary brain cell death during post-cardiac arrest syndrome. As there is an equilibrium between brain tissue and plasma concentrations of glutamine and glutamate, their elimination from systemic circulation by extracorporeal blood purification may ultimately lead to reduced secondary cell death in the brain. We hypothesized that systemic glutamine and glutamate can be significantly reduced by continuous venovenous hemodiafiltration (CVVHDF). METHODS: This was a prospective, randomized clinical trial in post cardiac-arrest survivors evaluating standard of care or additional CVVHDF over 72 h immediately after admission. Glutamine and glutamate plasma concentrations were analyzed at eight time points in both groups. Primary endpoint was reduction of glutamine and glutamate plasma concentrations. The trial has been registered at clinical trial.gov (NCT02963298). RESULTS: In total, 41 patients were randomized over a period of 12 months (control n = 21, CVVHDF n = 20). The primary aim reduction of glutamine and glutamate plasma concentrations by CVVHDF, was not achieved; both groups-maintained concentrations within a normal range over the study period (glutamate: 4.7-11.1 mg/dL; glutamine: 0.2-3.7 mg/dL). However, post-filter concentrations of glutamine and glutamate in CRRT patients were significantly decreased as compared to pre-filter concentrations (glutamate: pre-filter median 8.85 mg/dL IQR 7.1-9.6; post-filter 0.95 mg/dL IQR 0.5-2; p < 0.001; glutamine: pre-filter 0.7 mg/dL IQR 0.6-1; post-filter 0.2 mg/dL IQR 0-0.2; p < 0.001). CONCLUSION: In this trial, CVVHDF was not able to statistically significantly lower systemic plasma glutamine and glutamate levels. Post-cardiac arrest patients had plasma glutamine and glutamate levels within the normal range.