Abstract Background Postoperative delirium (POD) is the most common neurological adverse event among elderly patients undergoing surgery. POD is associated with an increased risk for postoperative complications, long-term cognitive decline, an increase in morbidity and mortality as well as extended hospital stays. Delirium prevention and treatment options are currently limited. This study will evaluate the effect of transcranial electrical stimulation (tES) on the incidence of POD. Methods We will perform a randomized, double-blind, sham-controlled trial using single-session postoperative application of tES in the recovery room in 225 patients (> 65 years) undergoing elective major surgery. Patients will be randomly allocated (ratio 1:1:1) to one of three study groups: (1) alpha-tACS over posterior parietal cortex [2 mA, 20 min], (2) anodal tDCS over left dorsolateral prefrontal cortex [2 mA, 20 min], (3) sham [2 mA, 30 s]. Delirium will be screened twice daily with the 3-min diagnostic interview Confusion Assessment Method (3D-CAM) in the 5 days following surgery. The primary outcome is the incidence of POD defined as at least one positive screening during the five first postoperative days compared between tACS and sham groups. Secondary outcomes include delirium severity, duration, phenotype, postoperative pain, postoperative nausea and vomiting, electroencephalographic (EEG) markers, and fluid biomarkers. Discussion If effective, tES is a novel, easily applicable, non-invasive method to prevent the occurrence of POD. The comprehensive neurophysiological and biofluid assessments for markers of (neuro-)inflammation and neurodegeneration will shed light on the pathomechanisms behind POD and further elucidate the (after-)effects of tES. The potential implications for the postoperative recovery comprise enhanced patient safety, neurocognitive outcome, perioperative manageability but also reduced healthcare costs. Trial registration German Clinical Trial Registry DRKS00033703. Registered on February 23, 2024.

BackgroundInduction of general anesthesia with propofol induces radical changes in cortical network organization, leading to unconsciousness. While perioperative frontal electroencephalography (EEG) has been widely implemented in the past decades, validated and age-independent EEG markers for the timepoint of loss of consciousness (LOC) are lacking. Especially the appearance of spatially coherent frontal alpha oscillations (8–12 Hz) marks the transition to unconsciousness.Here we explored whether decomposing the EEG spectrum into its periodic and aperiodic components unveiled markers of LOC and investigated their age-dependency. We further characterized the LOC-associated alpha oscillations by parametrizing the adjusted power over the aperiodic component, the center frequency, and the bandwidth of the peak in the alpha range.MethodsIn this prospective observational trial, EEG were recorded in a young (18–30 years) and an elderly age-cohort (≥ 70 years) over the transition to propofol-induced unconsciousness. An event marker was set in the EEG recordings at the timepoint of LOC, defined with the suppression of the lid closure reflex. Spectral analysis was conducted with the multitaper method. Aperiodic and periodic components were parametrized with the FOOOF toolbox. Aperiodic parametrization comprised the exponent and the offset. The periodic parametrization consisted in the characterization of the peak in the alpha range with its adjusted power, center frequency and bandwidth. Three time-segments were defined: preLOC (105 – 75 s before LOC), LOC (15 s before to 15 s after LOC), postLOC (190 – 220 s after LOC). Statistical significance was determined with a repeated-measures ANOVA.ResultsLoss of consciousness was associated with an increase in the aperiodic exponent (young: p = 0.004, elderly: p = 0.007) and offset (young: p = 0.020, elderly: p = 0.004) as well as an increase in the adjusted power (young: p < 0.001, elderly p = 0.011) and center frequency (young: p = 0.008, elderly: p < 0.001) of the periodic alpha peak. We saw age-related differences in the aperiodic exponent and offset after LOC as well as in the power and bandwidth of the periodic alpha peak during LOC.ConclusionDecomposing the EEG spectrum over induction of anesthesia into its periodic and aperiodic components unveiled novel age-independent EEG markers of propofol-induced LOC: the aperiodic exponent and offset as well as the center frequency and adjusted power of the power peak in the alpha range.

Background: Monitoring of pain and nociception in critical care patients unable to self-report pain remains a challenge, as clinical signs are neither sensitive nor specific. Available technical approaches are limited by various constraints. We investigated the electroencephalogram (EEG) for correlates that precede or coincide with behavioural nociceptive re-sponses to noxious stimulation.Methods: In this retrospective study, we analysed frontal EEG recordings of 64 critical care patients who were tracheally intubated and ventilated before, during, and after tracheal suctioning. We investigated EEG power bands for correlates preceding or coinciding with behavioural responses (Behavioural Pain Scale >= 7). We applied the Mann -Whitney U-test to calculate corresponding P-values.Results: Strong behavioural responses were preceded by higher normalised power in the 2.5-5 Hz band (+17.1%; P<0.001) and lower normalised power in the 0.1-1.5 Hz band (-10.5%; P=0.029). After the intervention, strong behavioural re-sponses were associated with higher normalised EEG power in the 2.5-5 Hz band (+16.6%; P=0.021) and lower normalised power in the 8-12 Hz band (-51.2%; P=0.037)Conclusions: We observed correlates in EEG band power that precede and coincide with behavioural responses to noxious stimulation. Based on previous findings, some of the power bands could be linked to processing of nociception, arousal, or sedation effects. The power bands more closely related to nociception and arousal could be used to improve monitoring of nociception and to optimise analgesic management in critical care patients.Clinical trial registration: DRKS00011206.

BACKGROUND:Procedural pain is a common burden in critical care treatment and the prediction of nociceptive reactions remains challenging. Thus, we investigated the Behavioural Pain Scale (BPS), the Critical Pain Observational Tool (CPOT), the nociceptive flexion reflex (NFR), the pupillary dilation reflex (PDR) and the Richmond Agitation-Sedation Scale (RASS) as predictors of behavioural reactions to nociceptive procedures.METHODS:In this monocentric, prospective, observational study, we analysed data of 128 critically ill adults unable to self-report pain to investigate the predictability of behavioural reactions to two procedures: endotracheal suctioning and turning. Next to routine clinical data, CPOT, BPS, PDR, NFR, RASS, propofol and sufentanil doses were recorded before the procedures.RESULTS:For endotracheal suctioning, NFR, BPS, CPOT and RASS showed predictive performances significantly better than chance, but none of them performed significantly better than the sufentanil dose rate. For turning, BPS, CPOT and RASS showed predictive performances significantly better than chance, but only the RASS performed significantly better than the propofol dose rate.CONCLUSIONS:Behavioural reactions to both investigated clinical procedures can be predicted by observational scales or nociceptive reflexes. For endotracheal suctioning, none of the predictors performed superior to using the sufentanil dose rate as a predictor. As using sufentanil as a predictor requires no extra effort in contrast to the other predictors, none of the here investigated tools seem advisable for predicting behavioural reactions to endotracheal suctioning. For patient turning, the RASS predicts reactions better than any other tool.SIGNIFICANCE:In this observational study, we demonstrate that behavioural reactions to potentially nociceptive procedures in critical care treatment can be predicted by observational scales and nociceptive reflexes. However, for endotracheal suctioning, none of the predictors is superior to using the opioid dose rate as a predictor. For patient turning, the RASS predicts reactions better than any other parameters.