Daily Anesthesiology Research Analysis

BACKGROUND AND AIMS: High protein nutrition may improve outcomes after critical illness. We recently published the primary frequentist analysis of the PRECISe trial, showing that high (2.0 g/kg/day) compared with standard (1.3 g/kg/day) protein provision led to statistically significant worse health-related quality of life. The study, however, was not powered to draw definitive conclusions about clinical and other functional outcomes under a frequentist framework. We present a pre-planned and pre-specified Bayesian analysis to facilitate the clinical interpretation of these paramount endpoints. METHODS: The trial enrolled 935 patients and used the EQ-5D-5L health utility score as the primary endpoint. We performed Bayesian analyses of the primary and selected secondary endpoints, and relevant subgroups, under weakly informative priors. Sensitivity analyses were performed using skeptical and enthusiastic priors, and informed priors (when available) based on existing literature. Thresholds for clinically relevant differences were predefined. RESULTS: The posterior probability of benefit from high (2.0 g/kg/day) protein targets with respect to the EQ-5D-5L health utility score was 0 %. Concerning 60-day mortality, the posterior probability of any benefit from high protein provision was 8 %, with a posterior probability of clinically important harm (>5 % absolute risk difference) of 47 %, which varied between 1 and 21 % across various sensitivity analyses under reference or literature-based priors. CONCLUSIONS: This pre-planned Bayesian re-analysis of the PRECISe trial shows that high (2.0 g/kg/day) compared to standard (1.3 g/kg/day) protein provision in critically ill patients has a low probability to yield any benefit and results in a high probability of an increase of 60-day mortality. REGISTRATION NUMBER OF CLINICAL TRIAL: NCT04633421.

BACKGROUND: Physiological responses to nociception are complex and involve intricate associations between the central, peripheral, and autonomic nervous systems. To optimize intraoperative analgesic titration, several monitoring devices have been developed, each targeting specific physiologic variables. However, existing devices primarily focus on isolated components of the nociceptive response, such as autonomic or cortical activity, without integrating these perspectives comprehensively. Our aim was to compare the performance of different nociception monitors in response to standardized tetanic stimulation and to investigate the correlation between these monitors' responses and varying concentrations of remifentanil. METHODS: In this study, we evaluated and compared the responses of the Nociception Level index (NOL), Analgesia Nociception Index (ANI), Pupillary Reflex Dilation (PRD) and both raw and processed electroencephalogram (EEG) under varying concentrations of propofol and remifentanil. Standardized tetanic stimuli were administered to patients under general anesthesia with target-controlled infusion of propofol and remifentanil. EEG, PRD, NOL, ANI, heart rate (HR), Bispectral index (BIS), and CONOX monitor indices (qCON and qNOX) were concomitantly recorded. RESULTS: ANI, BIS, HR, NOL, PRD, and qNOX significantly changed after noxious stimulation. In our dataset, PRD had the strongest correlation with varying remifentanil concentrations, while ANI, NOL, and qNOX did not show significant correlations with remifentanil concentrations. Following a noxious stimulus, the raw EEG in patients with low PRD exhibited a significant increase in power in the high EEG frequencies around 25 Hz and decreased power in frequencies corresponding to the alpha range (8-12 Hz) in the power spectral density. CONCLUSIONS: PRD, HR, and BIS correlated with varying levels of remifentanil, with PRD exhibiting the strongest correlation. When CE remifentanil are low, noxious stimuli are more likely to dilate the pupil and be detected in the EEG. Considering the complexity of the nociceptive response, integrating multimodal neurophysiologic monitoring with pharmacological data may improve the anesthesiologist's ability to assess on the nociception-antinociception balance. However, further studies are needed to validate these findings and address the study's limitations.