Clinical Study Assessment of Procalcitonin to Predict Outcome in Hypothermia-Treated Patients after Cardiac Arrest

Objective. Determine the potential of procalcitonin (PCT) to predict neurological outcome after hypothermia treatment following cardiac arrest. Methods. Retrospective analysis of patient data over a 2-year period. Mortality and neurological outcome of survivors were determined 6 months after cardiac arrest using the Cerebral Performance Category (CPC) score. Results. Data from 53 consecutive patients were analyzed. Median age was 63 (54-71) and 79% were male. Twenty-seven patients had good outcome (CPC ≤ 2) whereas 26 had severe neurological sequelae or died (CPC 3-5). At 48 h, after regaining normothermia, PCT was significantly higher in patients with bad outcome compared to those with good outcome: 3.38 (1.10-24.48) versus 0.28 (0-0.75) ng/mL (P < 0.001). PCT values correlated with bad neurological outcome (r = 0.54, P = 0.00004) and predicted outcome with an area under the curve of 0.84 (95% CI 0.73-0.96). A cutoff point of 1 ng/mL provided a sensitivity of 85% and a specificity of 81%. Above a PCT level of 16 ng/mL, no patient regained consciousness. PCT provided an additive value over simplified acute physiology score II. Conclusions. PCT might be an ancillary marker for outcome prediction after cardiac arrest treated by induced hypothermia

Bispectral index to predict neurological outcome early after cardiac arrest.

AIM OF THE STUDY: To address the value of continuous monitoring of bispectral index (BIS) to predict neurological outcome after cardiac arrest. METHODS: In this prospective observational study in adult comatose patients treated by therapeutic hypothermia after cardiac arrest we measured bispectral index (BIS) during the first 24 hours of intensive care unit stay. A blinded neurological outcome assessment by cerebral performance category (CPC) was done 6 months after cardiac arrest. RESULTS: Forty-six patients (48%) had a good neurological outcome at 6-month, as defined by a cerebral performance category (CPC) 1-2, and 50 patients (52%) had a poor neurological outcome (CPC 3-5). Over the 24h of monitoring, mean BIS values over time were higher in the good outcome group (38 +/- 9) compared to the poor outcome group (17 +/- 12) (p<0.001). Analysis of BIS recorded every 30 minutes provided an optimal prediction after 12.5h, with an area under the receiver operating characteristic curve (AUC) of 0.89, a specificity of 89% and a sensitivity of 86% using a cut-off value of 23. With a specificity fixed at 100% (sensitivity 26%) the cut-off BIS value was 2.4 over the first 271 minutes. In multivariable analyses including clinical characteristics, mean BIS value over the first 12.5h was a predictor of neurological outcome (p = 6E-6) and provided a continuous net reclassification index of 1.28% (p = 4E-10) and an integrated discrimination improvement of 0.31 (p=1E-10). CONCLUSIONS: Mean BIS value calculated over the first 12.5h after ICU admission potentially predicts 6-months neurological outcome after cardiac arrest

Late heartbeat-evoked potentials, indicators of cortical representation of interoceptive signal processing, are associated with survival after cardiac arrest

Rationale: Cardiac arrest (CA) is a serious condition characterized by high mortality rates, even after initial successful resuscitation, mainly due to neurological damage. Whether brain-heart communication is associated with outcome after CA is unknown. Heartbeat-evoked brain potentials (HEPs) represent neurophysiological indicators of brain-heart communication, as they reflect cortical representation of interoceptive signal processing. The aim of this study was to address the association between HEPs and survival after CA. Methods: HEPs were calculated from resting EEG/ECG in 55 CA patients 24 h after resuscitation. All patients were treated with targeted temperature management and a standardized sedation protocol during assessment. We investigated the association between HEP amplitude (180{320 ms, 455{595 ms, 860{1000 ms) and 6-month survival. Results: Twenty-five of 55 patients (45%) were still alive at 6-month follow-up. Survivors showed a higher HEP amplitude at frontopolar and frontal electrodes in the late HEP interval than non-survivors. This effect remained significant after controlling for between-group differences in terms of age, Fentanyl dose, and time lag between resuscitation and EEG assessment. There were no group differences in heart rate or heart rate variability. Conclusion: Brain-heart communication, as re ected by HEPs, is associated with survival after CA. Cardiovascular autonomic arousal may not be involved in mediating this effect. Adequate cortical representation of interoceptive signals may be essential to preserve cariovascular health and should be in the focus of prevention strategies. Future studies should address the brain-heart axis in CA

Late heartbeat-evoked potentials, indicators of cortical representation of interoceptive signal processing, are associated with survival after cardiac arrest

Rationale: Cardiac arrest (CA) is a serious condition characterized by high mortality rates, even after initial successful resuscitation, mainly due to neurological damage. Whether brain-heart communication is associated with outcome after CA is unknown. Heartbeat-evoked brain potentials (HEPs) represent neurophysiological indicators of brain-heart communication, as they reflect cortical representation of interoceptive signal processing. The aim of this study was to address the association between HEPs and survival after CA. Methods: HEPs were calculated from resting EEG/ECG in 55 CA patients 24 h after resuscitation. All patients were treated with targeted temperature management and a standardized sedation protocol during assessment. We investigated the association between HEP amplitude (180{320 ms, 455{595 ms, 860{1000 ms) and 6-month survival. Results: Twenty-five of 55 patients (45%) were still alive at 6-month follow-up. Survivors showed a higher HEP amplitude at frontopolar and frontal electrodes in the late HEP interval than non-survivors. This effect remained significant after controlling for between-group differences in terms of age, Fentanyl dose, and time lag between resuscitation and EEG assessment. There were no group differences in heart rate or heart rate variability. Conclusion: Brain-heart communication, as reflected by HEPs, is associated with survival after CA. Cardiovascular autonomic arousal may not be involved in mediating this e ect. Adequate cortical representation of interoceptive signals may be essential to preserve cariovascular health and should be in the focus of prevention strategies. Future studies should address the brain-heart axis in CA

Targeted temperature management at 33°C versus 36°C after cardiac arrest

BACKGROUND: Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS: In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 degrees C or 36 degrees C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS: In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. CONCLUSIONS: In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.)

Efficacy and safety of baricitinib in hospitalized adults with severe or critical COVID-19 (Bari-SolidAct): a randomised, double-blind, placebo-controlled phase 3 trial

International audienceAbstract Background Baricitinib has shown efficacy in hospitalized patients with COVID-19, but no placebo-controlled trials have focused specifically on severe/critical COVID, including vaccinated participants. Methods Bari-SolidAct is a phase-3, multicentre, randomised, double-blind, placebo-controlled trial, enrolling participants from June 3, 2021 to March 7, 2022, stopped prematurely for external evidence. Patients with severe/critical COVID-19 were randomised to Baricitinib 4 mg once daily or placebo, added to standard of care. The primary endpoint was all-cause mortality within 60 days. Participants were remotely followed to day 90 for safety and patient related outcome measures. Results Two hundred ninety-nine patients were screened, 284 randomised, and 275 received study drug or placebo and were included in the modified intent-to-treat analyses (139 receiving baricitinib and 136 placebo). Median age was 60 (IQR 49–69) years, 77% were male and 35% had received at least one dose of SARS-CoV2 vaccine. There were 21 deaths at day 60 in each group, 15.1% in the baricitinib group and 15.4% in the placebo group (adjusted absolute difference and 95% CI − 0.1% [− 8·3 to 8·0]). In sensitivity analysis censoring observations after drug discontinuation or rescue therapy (tocilizumab/increased steroid dose), proportions of death were 5.8% versus 8.8% (− 3.2% [− 9.0 to 2.7]), respectively. There were 148 serious adverse events in 46 participants (33.1%) receiving baricitinib and 155 in 51 participants (37.5%) receiving placebo. In subgroup analyses, there was a potential interaction between vaccination status and treatment allocation on 60-day mortality. In a subsequent post hoc analysis there was a significant interaction between vaccination status and treatment allocation on the occurrence of serious adverse events, with more respiratory complications and severe infections in vaccinated participants treated with baricitinib. Vaccinated participants were on average 11 years older, with more comorbidities. Conclusion This clinical trial was prematurely stopped for external evidence and therefore underpowered to conclude on a potential survival benefit of baricitinib in severe/critical COVID-19. We observed a possible safety signal in vaccinated participants, who were older with more comorbidities. Although based on a post-hoc analysis, these findings warrant further investigation in other trials and real-world studies. Trial registration Bari-SolidAct is registered at NCT04891133 (registered May 18, 2021) and EUClinicalTrials.eu ( 2022-500385-99-00 )