Intraoperative plasma proteomic changes in cardiac surgery: In search of biomarkers of post-operative delirium.

PURPOSE: Delirium presents a significant healthcare burden. It complicates post-operative care in up to 50% of cardiac surgical patients with worse outcomes, longer hospital stays and higher cost of care. Moreover, the nature of delirium following cardiac surgery with cardiopulmonary bypass (CPB) remains unclear, the underlying pathobiology is poorly understood, status quo diagnostic methods are subjective, and diagnostic biomarkers are currently lacking. OBJECTIVE: To identify diagnostic biomarkers of delirium and for insights into possible neuronal pathomechanisms. EXPERIMENTAL DESIGN: Comparative proteomic analyses were performed on plasma samples from a nested matched cohort of patients who underwent cardiac surgery. Validation by targeted proteomics was performed in an independent set of samples. Biomarkers were assessed for biological functions and diagnostic accuracy. RESULTS: Forty-seven percent of subjects demonstrated delirium. Of 3803 proteins identified from patient samples by multiplexed quantitative proteomics, 16 were identified as signatures of exposure to CPB, and 11 biomarkers distinguished delirium cases from non-cases (AuROC = 93%). Notable among these biomarkers are C-reactive protein, serum amyloid A-1 and cathepsin-B. CONCLUSIONS AND CLINICAL RELEVANCE: The interplay of systemic and central inflammatory markers sheds new light on delirium pathogenesis. This work suggests that accurate identification of cases may be achievable using panels of biomarkers.

Association of Plasma Neurofilament Light with Postoperative Delirium.

OBJECTIVE: To examine the association of the plasma neuroaxonal injury markers neurofilament light (NfL), total tau, glial fibrillary acid protein, and ubiquitin carboxyl-terminal hydrolase L1 with delirium, delirium severity, and cognitive performance. METHODS: Delirium case-no delirium control (n = 108) pairs were matched by age, sex, surgery type, cognition, and vascular comorbidities. Biomarkers were measured in plasma collected preoperatively (PREOP), and 2 days (POD2) and 30 days postoperatively (PO1MO) using Simoa technology (Quanterix, Lexington, MA). The Confusion Assessment Method (CAM) and CAM-S (Severity) were used to measure delirium and delirium severity, respectively. Cognitive function was measured with General Cognitive Performance (GCP) scores. RESULTS: Delirium cases had higher NfL on POD2 and PO1MO (median matched pair difference = 16.2pg/ml and 13.6pg/ml, respectively; p < 0.05). Patients with PREOP and POD2 NfL in the highest quartile (Q4) had increased risk for incident delirium (adjusted odds ratio [OR] = 3.7 [95% confidence interval (CI) = 1.1-12.6] and 4.6 [95% CI = 1.2-18.2], respectively) and experienced more severe delirium, with sum CAM-S scores 7.8 points (95% CI = 1.6-14.0) and 9.3 points higher (95% CI = 3.2-15.5). At PO1MO, delirium cases had continued high NfL (adjusted OR = 9.7, 95% CI = 2.3-41.4), and those with Q4 NfL values showed a -2.3 point decline in GCP score (-2.3 points, 95% CI = -4.7 to -0.9). INTERPRETATION: Patients with the highest PREOP or POD2 NfL levels were more likely to develop delirium. Elevated NfL at PO1MO was associated with delirium and greater cognitive decline. These findings suggest NfL may be useful as a predictive biomarker for delirium risk and long-term cognitive decline, and once confirmed would provide pathophysiological evidence for neuroaxonal injury following delirium. ANN NEUROL 2020;88:984-994.

Usefulness of postoperative serum translocator protein as a predictive marker for delirium after breast cancer surgery in elderly women.

OBJECTIVE: Postoperative delirium (POD) has rarely been investigated in breast cancer patients. Herein, we assessed the association between serum levels of the inflammatory biomarker translocator protein (TP) and the occurrence of POD in breast cancer patients. METHODS: In this prospective, observational study, TP levels were detected in preoperative and postoperative serum samples from 152 elderly breast cancer patients, samples from 152 healthy elderly women, and samples from 152 elderly women with benign breast diseases. The relationship between serum TP levels and POD was investigated using multivariate analysis. RESULTS: TP levels in postoperative patient serum samples were significantly higher than in preoperative patient serum samples and serum from women in the two control groups. Postoperative serum TP levels were independently correlated with serum C-reactive protein levels and the occurrence of POD. Postoperative serum TP levels had a high discriminatory ability for POD under the receiver operating characteristic curve. CONCLUSIONS: Increased postoperative serum TP levels are independently associated with the degree of inflammatory response and the risk of POD in elderly breast cancer patients, substantializing TP as an inflammatory biomarker that can efficiently discriminate POD after breast cancer surgery.

Comparison of the Level of Free Hexafluoro-isopropanol in Adults' Blood and the Incidence of Emergence Agitation After Anesthesia With Different Concentrations of Sevoflurane in Laparoscopic Gastrointestinal Surgery: A Randomized Controlled Clinical Trial.

PURPOSE: The aim of the study is to compare the free hexafluoro-isopropanol (HFIP) concentration in adults' blood and the incidence of emergence agitation (EA) after inhaled different concentrations of sevoflurane. METHODS: Sixty adult patients planning to undergo laparoscopic gastrointestinal surgery were randomly assigned to 3 groups. Each group received sevoflurane as the volatile anesthetic at different concentrations: 0.5 minimum alveolar concentration (MAC), 1.0 MAC, and 1.5 MAC. The use of sevoflurane was continued until the end of surgery. Venous blood samples were obtained at 30, 60, 120, and 180 minutes after starting the use of sevoflurane and subsequently at 60, 180, and 300 minutes after discontinuation of volatile anesthetic administration. Blood concentrations of sevoflurane and free HFIP were determined using gas chromatography. The recovery time and the incidence of EA at different time points were evaluated among the 3 groups. FINDINGS: Changes in the blood concentrations of sevoflurane and free HFIP during and after the use of sevoflurane were similar in all 3 groups. The peak blood concentration of free HFIP occurred 60 minutes after onset of sevoflurane anesthesia in all 3 groups (P < 0.05). The lowest level of free HFIP and the longest recovery time were found in the 1.5-MAC group (P < 0.05). No significant difference was found in the incidence of EA or moderate pain among the 3 groups during recovery. IMPLICATIONS: The generation of HFIP would be inhibited when the inhaled sevoflurane concentration increased to 1.5 MAC. However, the incidence of EA during recovery had nothing to do with the inhaled different sevoflurane concentrations (within 1.5 MAC) in adults. ChicCTR.org identifier: ChiCTR-IPD-17011558.

The effect of the timing and dose of dexmedetomidine on postoperative delirium in elderly patients after laparoscopic major non-cardiac surgery: A double blind randomized controlled study.

STUDY OBJECTIVE: There were few clinical data dosing and timing regimen for preventing postoperative delirium. The present study aimed to investigate the effect of the timing and dose of dexmedetomidine on postoperative delirium in elderly patients after laparoscopic major non-cardiac surgery. PATIENTS AND INTERVENTIONS: A total of 354 patients >65 years of age undergoing laparoscopic major non-cardiac surgery under general anesthesia received a dexmedetomidine 1 µg/kg bolus followed by 0.2-0.7 µg/kg/h infusion from induction of anesthesia to the end of surgery [group D1]); a dexmedetomidine (1 µg/kg bolus [group D2]); or saline (group S) 15 min before the end of surgery. MEASUREMENTS: The incidence and duration of delirium for 5 days after surgery and the cytokine (tumor necrosis factor-alpha TNFα, interleukin [IL]-1 ß, IL-2, IL-6, IL-8, and IL-10) and cortisol levels were measured 1 h and 24 h after surgery. MAIN RESULTS: Group D1 reduced incidence and duration of delirium and group D2 decreased its duration in patients with delirium compared to group S. IL-6 levels were significantly lower at 1 h and 24 h after surgery in group D1 than in group S, and lower at 24 h after surgery than in group D2. IL-6 levels in group D2 were significantly lower only at 1 h after surgery than in group S. However, IL-6 levels in delirious patients in group D2 were significantly lower at 1 h and 24 h after surgery than those in group S. Cortisol levels 1 h after surgery were significantly lower in groups D1 and D2 than in group S. CONCLUSIONS: The dose and timing of dexmedetomidine appeared to be important in preventing delirium. The reduced incidence and duration of delirium by dexmedetomidine was associated with reduced levels of IL-6 24 h after surgery.

Prevalence and risk factors of postoperative delirium in elderly hip fracture patients.

OBJECTIVE: To explore the risk factors associated with postoperative delirium (PD) in elderly patients following total hip arthroplasty (THA) for hip fracture. METHODS: This prospective study enrolled elderly patients (≥ 65 years) with hip fractures who underwent THA under general anaesthesia, and who had a complete set of postoperative observations. Detailed medical history and perioperative characteristics were recorded. During the postoperative period, patients were assessed twice daily for PD using the Confusion Assessment Method. RESULTS: A total of 572 patients were eligible for inclusion in the study. Of these, 120 patients (21.0%) were diagnosed with PD and 452 patients (79.0%) did not experience PD. Multivariate stepwise logistic regression analyses showed that older age, a history of stroke, lower albumin, higher blood glucose, higher total bilirubin, higher C-reactive protein, longer surgery duration and higher volume of red blood cell transfusions were independent risk factors for PD. CONCLUSIONS: Correcting the modifiable risk factors might help prevent PD. Strategies might include nutritional support, tight blood glucose control, improvement of liver function, preoperative infection control and minimizing surgical injury or blood loss.