Feasibility of Goal-Directed Fluid Therapy in Patients with Transcatheter Aortic Valve Replacement - An Ambispective Analysis.

INTRODUCTION: Goal-directed fluid therapy (GDFT) has been shown to reduce postoperative complications. The feasibility of GDFT in transcatheter aortic valve replacement (TAVR) patients under general anesthesia has not yet been demonstrated. We examined whether GDFT could be applied in patients undergoing TAVR in general anesthesia and its impact on outcomes. METHODS: Forty consecutive TAVR patients in the prospective intervention group with GDFT were compared to 40 retrospective TAVR patients without GDFT. Inclusion criteria were age ≥ 18 years, elective TAVR in general anesthesia, no participation in another interventional study. Exclusion criteria were lack of ability to consent study participation, pregnant or nursing patients, emergency procedures, preinterventional decubitus, tissue and/or extremity ischemia, peripheral arterial occlusive disease grade IV, atrial fibrillation or other severe heart rhythm disorder, necessity of usage of intra-aortic balloon pump. Stroke volume and stroke volume variation were determined with uncalibrated pulse contour analysis and optimized according to a predefined algorithm using 250 ml of hydroxyethyl starch. RESULTS: Stroke volume could be increased by applying GDFT. The intervention group received more colloids and fewer crystalloids than control group. Total volume replacement did not differ. The incidence of overall complications as well as intensive care unit and hospital length of stay were comparable between both groups. GDFT was associated with a reduced incidence of delirium. Duration of anesthesia was shorter in the intervention group. Duration of the interventional procedure did not differ. CONCLUSION: GDFT in the intervention group was associated with a reduced incidence of postinterventional delirium.

Enhanced recovery after surgery in patients with normal pressure hydrocephalus undergoing ventriculoperitoneal shunting procedures.

OBJECTIVE: Patients with idiopathic normal pressure hydrocephalus (iNPH) who undergo ventriculoperitoneal shunt (VPS) placement often belong to an older demographic, putting them at increased risk of postoperative delirium and related complications. Recent literature documenting the use of Enhanced Recovery After Surgery (ERAS) protocols in various disciplines of surgery has shown improved clinical outcomes, faster discharge, and lower readmission rates. Early return to a familiar environment (i.e., discharged home) is a well-known predictor of reduced postoperative delirium. However, ERAS protocols are uncommon in neurosurgery, especially intracranial procedures. We developed a novel ERAS protocol for patients with iNPH undergoing VPS placement to gain further insight regarding postoperative complications, specifically delirium. METHODS: We studied 40 patients with iNPH with indications for VPS. Seventeen patients were selected at random to undergo the ERAS protocol, and twenty-three patients underwent the standard VPS protocol. The ERAS protocol consisted of measures to reduce infection, manage pain, minimize invasiveness, confirm procedural success with imaging, and shorten the length of stay. Pre-operative American Society of Anesthesiologists (ASA) grade was collected for each patient to indicate baseline risk. Rates of readmission and postoperative complications, including delirium and infection, were collected at 48 h, 2 weeks, and 4 weeks postoperatively. RESULTS: There were no perioperative complications among the 40 patients. There was no postoperative delirium in any of the ERAS patients. Postoperative delirium was observed in 10 of 23 non-ERAS patients. There was no statistically significant difference between the ASA grade between the ERAS and non-ERAS groups. CONCLUSIONS: We described a novel ERAS protocol for patients with iNPH receiving VPS focusing on an early discharge. Our data suggest that ERAS protocols in VPS patients might reduce the incidence of delirium without increasing the risk of infection or other postoperative complications.

Elevated neuron-specific enolase level is associated with postoperative delirium and detection of phosphorylated neurofilament heavy subunit: A prospective observational study.

BACKGROUND: Delirium is the most common central nervous system complication after surgery. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage within the central cervous system and is associated with the severity of postoperative delirium. Neuron-specific enolase and S100 calcium-binding protein ß have been identified as possible serum biomarkers of postoperative delirium. This study examined the association of the levels of these markers with incidence of postoperative delirium and detection of phosphorylated neurofilament heavy subunit. METHODS: This study represents a post hoc analysis of 117 patients who participated in a prospective observational study of postoperative delirium in patients undergoing cancer surgery. Patients were clinically assessed for development of postoperative delirium within the first five days of surgery. Serum levels of phosphorylated neurofilament heavy subunit, neuron-specific enolase, and S100 calcium-binding protein ß levels were measured on postoperative day 3. RESULTS: Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Neuron-specific enolase level (P < 0.0001) and the proportion of patients positive for phosphorylated neurofilament heavy subunit (P < 0.0001) were significantly higher in the group of patients with postoperative delirium. Neuron-specific enolase level discriminated between patients with and without clinically diagnosed postoperative delirium with significantly high accuracy (area under the curve [AUC], 0.87; 95% confidence interval [CI], 0.79-0.95; P < 0.0001). Neuron-specific enolase level was associated with incidence of postoperative delirium independently of age (adjusted odds ratio, 8.291; 95% Cl, 3.506-33.286; P < 0.0001). The AUC for the serum neuron-specific enolase level in detecting phosphorylated neurofilament heavy subunit was significant (AUC, 0.78; 95% CI, 0.66-0.90; P < 0.0001). CONCLUSION: Elevated serum neuron-specific enolase was associated with postoperative delirium independent of age as well as detection of phosphorylated neurofilament heavy subunit in serum. Serum neuron-specific enolase and phosphorylated neurofilament heavy subunit might be useful as biomarkers of postoperative delirium. TRIAL REGISTRATION: University Medical Information Network (UMIN) trial ID: UMIN000010329; https://clinicaltrials.gov/.

Functional Outcomes of Frail Patients After Cardiac Surgery: An Observational Study.

BACKGROUND: Although frailty has been associated with major morbidity/mortality and increased length of stay after cardiac surgery, few studies have examined functional outcomes. We hypothesized that frailty would be independently associated with decreased functional status, increased discharge to a nonhome location, and longer duration of hospitalization after cardiac surgery, and that delirium would modify these associations. METHODS: This was an observational study nested in 2 trials, each of which was conducted by the same research team with identical measurement of exposures and outcomes. The Fried frailty scale was measured at baseline. The primary outcome (defined before data collection) was functional decline, defined as ≥2-point decline from baseline in Instrumental Activities of Daily Living (IADL) score at 1 month after surgery. Secondary outcomes were absolute decline in IADL score, discharge to a new nonhome location, and duration of hospitalization. Associations were analyzed using linear, logistic, and Poisson regression models with adjustments for variables considered before analysis (age, gender, race, and logistic European Score for Cardiac Operative Risk Evaluation [EuroSCORE]) and in a propensity score analysis. RESULTS: Data were available from 133 patients (83 from first trial and 50 from the second trial). The prevalence of frailty was 33% (44 of 133). In adjusted models, frail patients had increased odds of functional decline (primary outcome; odds ratio [OR], 2.41 [95% confidence interval {CI}, 1.03-5.63]; P = .04) and greater decline at 1 month in the secondary outcome of absolute IADL score (-1.48 [95% CI, -2.77 to -0.30]; P = .019), compared to nonfrail patients. Delirium significantly modified the association of frailty and change in absolute IADL score at 1 month. In adjusted hypothesis-generating models using secondary outcomes, frail patients had increased discharge to a new nonhome location (OR, 3.25 [95% CI, 1.37-7.69]; P = .007) and increased duration of hospitalization (1.35 days [95% CI, 1.19-1.52]; P < .0001) compared to nonfrail patients. The increased duration of hospitalization, but no change in functional status or discharge location, was partially mediated by increased complications in frail patients. CONCLUSIONS: Frailty may identify patients at risk of functional decline at 1 month after cardiac surgery. Perioperative strategies to optimize frail cardiac surgery patients are needed.

Delirium Severity Post-Surgery and its Relationship with Long-Term Cognitive Decline in a Cohort of Patients without Dementia.

BACKGROUND: Delirium has been associated with more rapid cognitive decline. However, it is unknown whether increased delirium severity is associated with a higher rate of long-term cognitive decline. OBJECTIVE: To evaluate delirium severity and the presence and rate of cognitive decline over 36 months following surgery. METHODS: We examined patients from the Successful Aging after Elective Surgery Study, who were age ≥70 years undergoing major elective surgery (N = 560). Delirium severity was determined by the peak Confusion Assessment Method-Severity (CAM-S) score for each patient's hospitalization and grouped based on the sample distribution: scores of 0-2, 3-7, and 8-19. A neuropsychological composite, General Cognitive Performance (GCP), and proxy-reported Informant Questionnaire for Cognitive Decline (IQCODE) were used to examine cognitive outcomes following surgery at 0, 1, and 2 months, and then every 6 months for up to 3 years. RESULTS: No significant cognitive decline was observed for patients with peak CAM-S scores 0-2 (-0.17 GCP units/year, 95% confidence interval [CI] -0.35, 0.01). GCP scores decreased significantly in the group with peak CAM-S scores 3-7 (-0.30 GCP units/year, 95% CI -0.51, -0.09), and decreased almost three times faster in the highest delirium severity group (peak CAM-S scores 8-19; -0.82 GCP units/year, 95% CI -1.28, -0.37). A similar association was found for delirium severity and the proportion of patients who developed IQCODE impairment over time. CONCLUSION: Patients with the highest delirium severity experienced the greatest rate of cognitive decline, which exceeds the rate previously observed for patients with dementia, on serial neuropsychological testing administered over 3 years, with a dose-response relationship between delirium severity and long-term cognitive decline.

Clinical outcomes in older surgical patients with mild cognitive impairment.

INTRODUCTION: Older adults, including those with mild cognitive impairment (MCI), are increasingly undergoing surgery. METHODS: Relative risks (RRs) of MCI alone or with delirium on adverse outcomes were estimated in an ongoing prospective, observational cohort study of 560 nondemented adults aged ≥70 years. RESULTS: MCI (n = 61, 11%) was associated with increased RR of delirium (RR = 1.9, P < .001) and delirium severity (RR = 4.6, P < .001). Delirium alone (n = 107), but not MCI alone (n = 34), was associated with multiple adverse outcomes including more major postoperative complication(s) (RR = 2.5, P = .002) and longer length of stay (RR = 2.2, P < .001). Patients with concurrent MCI and delirium (n = 27) were more often discharged to a postacute facility (RR = 1.4, P < .001) and had synergistically increased risk for new impairments in cognitive functioning (RR = 3.6, P < .001). DISCUSSION: MCI is associated with increased risk of delirium incidence and severity. Patients with delirium and MCI have synergistically elevated risk of developing new difficulties in cognitively demanding tasks.

Insulin-Like Growth Factor-1, a Potential Predicative Biomarker for Postoperative Delirium Among Elderly Patients with Open Abdominal Surgery.

BACKGROUND: Delirium is commonly observed among elderly surgical subjects during the postoperative period, and the incidence of postoperative delirium (POD) in elderly patients (≥65 years) ranges widely from 10% to 70%. This study aimed at investigating potential serum predicative factors for POD in elderly patients after open abdominal surgery. METHODS: 140 subjects scheduled to undergo elective gastrointestinal tumor resection via laparotomy from March, 2013 to May, 2015 were enrolled in this study. Participants enrolled were evaluated for delirium and delirium severity on preoperative day, postoperative days 2 and 3. Non-fasting blood samples were collected in the morning on the day before surgery for the detection of serum cytokines expressions by enzyme-linked immunesorbent assays (ELISA). RESULTS: A total of 140 patients were finally enrolled in this study and 36 of them occurred POD, with a POD incidence of 25.7%. In comparison with non-POD group, the serum levels of insulin-like growth factor-1 (IGF-1) demonstrated significantly decreased of patients in POD group (P<0.01). The receiver operating characteristic (ROC) curve analysis revealed that serum IGF-1 levels as potential predicative factor for POD with the area under the ROC curve (AUC) values of 0. 805, with 95 % confidence interval (CI) of 0.719-0.891 (P<0.001). Univariate and multivariate logistic regression analysis resulted in serum IGF-1 level as a non-invasive predicative factor for POD (OR=2.52, 95%CI: 1.19-5.43, P=0.019). CONCLUSION: Our results showed that serum IGF-1 level was a potential predicative biomarker for POD among patients undergoing elective gastrointestinal tumor resection via laparotomy.

Postoperative plasma copeptin levels independently predict delirium and cognitive dysfunction after coronary artery bypass graft surgery.

Copeptin can reflect individual's stress state and are correlated with poor outcome of critical illness. The occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD) is associated with worse outcome after coronary artery bypass graft (CABG) surgery. The present study aimed to investigate the ability of postoperative plasma copeptin level to predict POD and POCD in patients undergoing CABG surgery. Postoperative plasma copeptin levels of 108 patients were measured by an enzyme-linked immunosorbent assay. It was demonstrated that plasma copeptin levels were substantially higher in patients with POD than without POD (1.8±0.6 ng/mL vs. 1.1±0.3 ng/mL; P<0.001) and in patients with POCD than without POCD (1.9±0.6 ng/mL vs. 1.1±0.4 ng/mL; P<0.001). Plasma copeptin level and age were identified as independent predictors for POD [odds ratio (OR), 67.386; 95% confidence interval (CI), 12.031-377.426; P<0.001 and OR, 1.202; 95% CI, 1.075-1.345; P=0.001] and POCD (OR, 28.814; 95% CI, 7.131-116.425; P<0.001 and OR, 1.151; 95% CI, 1.030-1.285; P=0.003) using a multivariate analysis. For prediction of POD, the area under receiver operating characteristic curve (AUC) of the copeptin concentration (AUC, 0.883; 95% CI, 0.807-0.937) was markedly higher than that of age (AUC, 0.746; 95% CI, 0.653-0.825; P=0.020). For prediction of POCD, the AUC of the copeptin concentration (AUC, 0.870; 95% CI, 0.792-0.927) was markedly higher than that of age (AUC, 0.735; 95% CI, 0.641-0.815; P=0.043). Thus, postoperative plasma copeptin level may be a useful, complementary tool to predict POD and POCD in patients undergoing CABG surgery.

Preoperative plasma leptin levels predict delirium in elderly patients after hip fracture surgery.

Leptin is considered to be a modulator of the immune response. Hypoleptinemia increases the risk for Alzheimer's disease and vascular dementia. The present study aimed to investigate the ability of plasma leptin level to predict delirium in elderly patients after hip fracture surgery. Postoperative delirium (pod) was evaluated using the Confusion Assessment Method. Prolonged postoperative delirium (ppod) was defined as delirium lasting more than 4 weeks. Plasma leptin levels of 186 elderly patients and 186 elderly controls were measured by an enzyme-linked immunosorbent assay. Plasma leptin level was substantially lower in patients than in controls (4.6±2.2ng/ml vs. 7.5±1.8ng/ml, P<0.001). It was identified as an independent predictor for pod [odds ratio, 0.385; 95% confidence interval (CI), 0.286-0.517; P<0.001] and ppod (odds ratio, 0.283; 95% CI, 0.152-0.527; P<0.001) using a multivariate analysis, and had high area under receiver operating characteristic curve for pod [area under curve (AUC), 0.850; 95% CI, 0.790-0.898] and ppod (AUC, 0.890; 95% CI, 0.836-0.931). The predictive value of leptin was markedly bigger than that of age for pod (AUC, 0.705; 95% CI, 0.634-0.770; P=0.002) and ppod (AUC, 0.713; 95% CI, 0.642-0.777; P=0.019). In a combined logistic-regression model, leptin improved the AUC of age to 0.890 (95% CI, 0.836-0.931) (P<0.001) for pod and 0.910 (95% CI, 0.860-0.947) (P=0.005) for ppod. Thus, preoperative plasma leptin level may be a useful, complementary tool to predict delirium and also prolonged delirium in elderly patients after hip fracture surgery.

α-Synuclein pathology is related to postoperative delirium in patients undergoing gastrectomy.

OBJECTIVE: The clinical characteristics of postoperative delirium are similar to core features of α-synuclein-related cognitive disorders, such as dementia with Lewy bodies or Parkinson disease dementia. We therefore investigated the α-synuclein pathology in patients who experienced postoperative delirium after gastrectomy for stomach cancer. METHOD: Patients with and without postoperative delirium were selected among patients undergoing total gastrectomy for primary gastric cancer from 2007 to 2011 (each n = 16) at the university hospital. Immunohistochemical staining for α-synuclein of both normal and phosphorylated form was performed in the myenteric plexus. A logistic regression analysis was applied to identify independent predictors of postoperative delirium. RESULTS: No significant differences were observed for age, sex, operation time, or onset of delirium after total gastrectomy between patients with and without postoperative delirium. Patients with postoperative delirium had a higher frequency of intensive care unit admissions (43.8 vs 6.3%, p = 0.037) and α-synuclein-positive pathologies of normal (56.3 vs 12.5%, p = 0.023) and phosphorylated form (43.8 vs 6.3%, p = 0.037) compared with those without postoperative delirium. A logistic regression analysis revealed that immunoreactivity for normal α-synuclein (odds ratio [OR] 9.20) and intensive care unit admission (OR 11.97) were independently associated with postoperative delirium. CONCLUSION: These results suggest that underlying α-synuclein pathologies in the stomach are associated with postoperative delirium, implying that postoperative delirium represents a preclinical stage of α-synuclein related to cognitive disorders.