Objective: This study aims to identify blood biomarkers of postoperative delirium. Background: Phosphorylated tau at threonine 217 (Tau-PT217) and 181 (Tau-PT181) are new Alzheimer disease biomarkers. Postoperative delirium is associated with Alzheimer disease. We assessed associations between Tau-PT217 or Tau-PT181 and postoperative delirium. Methods: Of 491 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy, 139 participants were eligible and included in the analysis. Presence and severity of postoperative delirium were assessed in the patients. Preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were determined by a newly established Nanoneedle technology. Results: Of 139 participants (73 ± 6 years old, 55% female), 18 (13%) developed postoperative delirium. Participants who developed postoperative delirium had higher preoperative plasma concentrations of Tau-PT217 and Tau-PT181 than participants who did not. Preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were independently associated with postoperative delirium after adjusting for age, education, and preoperative Mini-Mental State score [odds ratio (OR) per unit change in the biomarker: 2.05, 95% confidence interval (CI):1.61-2.62, P < 0.001 for Tau-PT217; and OR: 4.12; 95% CI: 2.55--6.67, P < 0.001 for Tau-PT181]. The areas under the receiver operating curve for predicting delirium were 0.969 (Tau-PT217) and 0.885 (Tau-PT181). The preoperative plasma concentrations of Tau-PT217 or Tau-PT181 were also associated with delirium severity [beta coefficient (β) per unit change in the biomarker: 0.14; 95% CI: 0.09-0.19, P < 0.001 for Tau-PT217; and β: 0.41; 95% CI: 0.12-0.70, P = 0.006 for Tau-PT181). Conclusions: Preoperative plasma concentrations of Tau-PT217 and Tau-PT181 were associated with postoperative delirium, with Tau-PT217 being a stronger indicator of postoperative delirium than Tau-PT181.

Objectives: To describe sedative and analgesic drug utilization in a cohort of critically ill patients with coronavirus disease 2019 and compare standard sedation with an alternative approach using inhaled isoflurane. Design: This was a retrospective cohort study designed to compare doses of sedatives between ICU patients receiving standard IV sedation and patients receiving mixed sedation including inhaled isoflurane. Data were obtained from electronic medical records. Setting: ICU at large academic medical center where mechanical ventilation was delivered with Draeger Apollo (Draeger Medical, Telford, PA) anesthesia machines. Patients: Consecutive adult patients (≥ 18 yr) with confirmed coronavirus disease 2019 admitted to ICU between April 2, 2020, and May 4, 2020. Interventions: None. Measurements and Main Results: Thirty-five mechanically ventilated patients were included in the study, with a mean ( sd ) age of 59.4 (12.8) years. Twenty-three patients (65.7%) were men. Seventeen patients (48.6%) received standard IV sedation, whereas 18 (51.4%) also received isoflurane. The mean duration of mechanical ventilation ( sd ) was 23.3 (11.6) days in the standard sedation group and 23.8 (12.5) days in the isoflurane group. Mean ( sd ) duration of isoflurane exposure was 5.61 (2.99) days, representing 29.1% of total sedation time ( sd , 20.4). Cumulative opioid exposure did not differ between the standard sedation and isoflurane sedation groups (mean morphine milligram equivalent 6668 [ sd , 1,346] vs 6678 [ sd , 2,000] mg). However, the initiation of isoflurane in patients was associated with decreased utilization of propofol (mean daily amount 3,656 [ sd , 1,635] before vs 950 [ sd , 1,804] mg during isoflurane) and hydromorphone (mean daily amount 48 [ sd , 30] before vs 23 [ sd , 27] mg). Conclusions: In the subjects that received isoflurane, its use was associated with significant decreases in propofol and hydromorphone infusions.

Postoperative delirium is a common postoperative complication in older patients, and its pathogenesis and biomarkers remain largely undetermined. The gut microbiota has been shown to regulate brain function, and therefore, it is vital to explore the association between gut microbiota and postoperative delirium. Of 220 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy under general or spinal anesthesia, 86 participants were included in the data analysis. The incidence (primary outcome) and severity of postoperative delirium were assessed for two days. Fecal swabs were collected from participants immediately after surgery. The 16S rRNA gene sequencing was used to assess gut microbiota. Principal component analyses along with a literature review were used to identify plausible gut microbiota, and three gut bacteria were further studied for their associations with postoperative delirium. Of the 86 participants [age 71.0 (69.0–76.0, 25–75% percentile of quartile), 53% female], 10 (12%) developed postoperative delirium. Postoperative gut bacteria Parabacteroides distasonis was associated with postoperative delirium after adjusting for age and sex (Odds Ratio [OR] 2.13, 95% Confidence Interval (CI): 1.09–4.17, P = 0.026). The association between delirium and both Prevotella (OR: 0.59, 95% CI: 0.33–1.04, P = 0.067) and Collinsella (OR: 0.57, 95% CI: 0.27–1.24, P = 0.158) did not meet statistical significance. These findings suggest that there may be an association between postoperative gut microbiota, specifically Parabacteroides distasonis, and postoperative delirium. However, further research is needed to confirm these findings and better understand the gut-brain axis’s role in postoperative outcomes.