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Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study.

ABSTRACT: Delirium is a common, morbid, and costly postoperative complication. We aimed to identify blood-based postoperative delirium markers in a nested case-control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation.The Successful Aging after Elective Surgery study enrolled dementia-free adults ?70 years old undergoing major scheduled noncardiac surgery (N = 566; 24% delirium). Plasma was collected at four time points: preoperative, postanesthesia care unit, postoperative day 2, and 1 month postoperative. Matched pairs were selected for the independent discovery (39 pairs) and replication cohorts (36 pairs), which were subsequently combined into the pooled cohort (75 pairs). Isobaric tags for relative and absolute quantitation-based relative quantitation mass spectrometry proteomics were performed to identify the strongest delirium-related protein, which was selected for ELISA validation. Using the ELISA results, statistical analyses using nonparametric signed rank tests were performed in all cohorts examining the association between the identified protein and delirium.C-reactive protein emerged from the proteomics analysis as the strongest delirium-related protein. Validation by ELISA confirmed that compared with controls, cases had significantly higher C-reactive protein levels in the discovery, replication, and pooled cohorts at the preoperative (median paired difference [MPD] 1.97 mg/L [p < .05], 0.29 mg/L, 1.56 mg/L [p < .01]), postanesthesia care unit (MPD 2.83 mg/L, 2.22 mg/L [p < .05], 2.53 mg/L [p < .01]) and postoperative day 2 (MPD 71.97 mg/L [p < .01], 35.18 mg/L [p < .05], 63.76 mg/L [p < .01]) time points, but not 1 month postoperative (MPD 2.72 mg/L, -0.66 mg/L, 1.10 mg/L).Elevated preoperative and postoperative plasma levels of C-reactive protein were associated with delirium, suggesting that a preinflammatory state and heightened inflammatory response to surgery are potential pathophysiologic mechanisms of delirium.

SUBMITTER: Dillon ST

PROVIDER: S-EPMC5035711 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study.

Dillon Simon T ST Vasunilashorn Sarinnapha M SM Ngo Long L Otu Hasan H HH Inouye Sharon K SK Jones Richard N RN Alsop David C DC Kuchel George A GA Metzger Eran D ED Arnold Steven E SE Marcantonio Edward R ER Libermann Towia A TA

Biological psychiatry 20160325 2

<h4>Background</h4>Delirium is a common, morbid, and costly postoperative complication. We aimed to identify blood-based postoperative delirium markers in a nested case-control study of older surgical patients using a proteomics approach followed by enzyme-linked immunosorbent assay (ELISA) validation.<h4>Methods</h4>The Successful Aging after Elective Surgery study enrolled dementia-free adults ≥70 years old undergoing major scheduled noncardiac surgery (N = 566; 24% delirium). Plasma was colle ...[more]

PMID: 27160518

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Project description:ImportanceDelirium is a common, serious, and potentially preventable problem for older adults, associated with adverse outcomes. Coupled with its preventable nature, these adverse sequelae make delirium a significant public health concern; understanding its economic costs is important for policy makers and health care leaders to prioritize care.ObjectiveTo evaluate current 1-year health care costs attributable to postoperative delirium in older patients undergoing elective surgery.Design, setting, and participantsThis prospective cohort study included 497 patients from the Successful Aging after Elective Surgery (SAGES) study, an ongoing cohort study of older adults undergoing major elective surgery. Patients were enrolled from June 18, 2010, to August 8, 2013. Eligible patients were 70 years or older, English-speaking, able to communicate verbally, and scheduled to undergo major surgery at 1 of 2 Harvard-affiliated hospitals with an anticipated length of stay of at least 3 days. Eligible surgical procedures included total hip or knee replacement; lumbar, cervical, or sacral laminectomy; lower extremity arterial bypass surgery; open abdominal aortic aneurysm repair; and open or laparoscopic colectomy. Data were analyzed from October 15, 2019, to September 15, 2020.ExposuresMajor elective surgery and hospitalization.Main outcomes and measuresCumulative and period-specific costs (index hospitalization, 30-day, 90-day, and 1-year follow-up) were examined using Medicare claims and extensive clinical data. Total inflation-adjusted health care costs were determined using data from Medicare administrative claims files for the 2010 to 2014 period. Delirium was rated using the Confusion Assessment Method. We also examined whether increasing delirium severity was associated with higher cumulative and period-specific costs. Delirium severity was measured with the Confusion Assessment Method-Severity long form. Regression models were used to determine costs associated with delirium after adjusting for patient demographic and clinical characteristics.ResultsOf the 566 patients who were eligible for the study, a total of 497 patients (mean [SD] age, 76.8 [5.1] years; 281 women [57%]; 461 White participants [93%]) were enrolled after exclusion criteria were applied. During the index hospitalization, 122 patients (25%) developed postoperative delirium, whereas 375 (75%) did not. Patients with delirium had significantly higher unadjusted health care costs than patients without delirium (mean [SD] cost, $146 358 [$140 469] vs $94 609 [$80 648]). After adjusting for relevant confounders, the cumulative health care costs attributable to delirium were $44 291 (95% CI, $34 554-$56 673) per patient per year, with the majority of costs coming from the first 90 days: index hospitalization ($20 327), subsequent rehospitalizations ($27 797), and postacute rehabilitation stays ($2803). Health care costs increased directly and significantly with level of delirium severity (none-mild, $83 534; moderate, $99 756; severe, $140 008), suggesting an exposure-response relationship. The adjusted mean cumulative costs attributable to severe delirium were $56 474 (95% CI, $40 927-$77 440) per patient per year. Extrapolating nationally, the health care costs attributable to postoperative delirium were estimated at $32.9 billion (95% CI, $25.7 billion-$42.2 billion) per year.Conclusions and relevanceThese findings suggest that the economic outcomes of delirium and severe delirium after elective surgery are substantial, rivaling costs associated with cardiovascular disease and diabetes. These results highlight the need for policy imperatives to address delirium as a large-scale public health issue.

Project description:INTRODUCTION:Postoperative delirium (POD) is a common complication in elderly patients, characterised by a fluctuating course of altered consciousness, disordered thinking and inattention. Preliminary research has linked POD with persistent cognitive impairment and decreased quality of life. However, these findings maybe confounded by patient comorbidities, postoperative complications and frailty. Our objective is to determine whether POD is an independent risk factor for persistent impairments in attention and executive function after elective surgery. Our central hypothesis is that patients with POD are more likely to have declines in cognition and quality of life 1?year after surgery compared with patients without POD. We aim to clarify whether these associations are independent of potentially confounding factors. We will also explore the association between POD and incident dementia. METHODS AND ANALYSIS:This study will recruit 200 patients from the ongoing Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study. Patients who live ?45 miles from the study centre or have a planned visit to the centre 10-16 months postoperatively will be eligible. Patients with POD, measured by the Confusion Assessment Method, will be compared with patients without delirium. The primary outcome of cognitive function and secondary outcomes of quality of life and incident dementia will be compared between cohorts. Cognition will be measured by Trails A and B and Stroop Color and Word Test, quality of life with Veteran's RAND 12-item Health Survey and incident dementia with the Short Blessed Test. Multivariable regression analyses and a Cox proportional hazards analysis will be performed. All results will be reported with 95% CIs and ?=0.05. ETHICS AND DISSEMINATION:The study has been approved by the Washington University in St. Louis Institutional Review Board (IRB no 201601099). Plans for dissemination include scientific publications and presentations at scientific conferences. TRIAL REGISTRATION NUMBER:NCT02241655.

Project description:ImportancePostoperative delirium occurs in 10% to 60% of elderly patients having major surgery and is associated with longer hospital stays, increased hospital costs, and 1-year mortality. Emerging literature suggests that dexmedetomidine sedation in critical care units is associated with reduced incidence of delirium. However, intraoperative use of dexmedetomidine for prevention of delirium has not been well studied.ObjectiveTo evaluate whether an intraoperative infusion of dexmedetomidine reduces postoperative delirium.Design, setting, and participantsThis study was a multicenter, double-blind, randomized, placebo-controlled trial that randomly assigned patients to dexmedetomidine or saline placebo infused during surgery and for 2 hours in the recovery room. Patients were assessed daily for postoperative delirium (primary outcome) and secondarily for postoperative cognitive decline. Participants were elderly (>68 years) patients undergoing major elective noncardiac surgery. The study dates were February 2008 to May 2014.InterventionsDexmedetomidine infusion (0.5 µg/kg/h) during surgery and up to 2 hours in the recovery room.Main outcomes and measuresThe primary hypothesis tested was that intraoperative dexmedetomidine administration would reduce postoperative delirium. Secondarily, the study examined the correlation between dexmedetomidine use and postoperative cognitive change.ResultsIn total, 404 patients were randomized; 390 completed in-hospital delirium assessments (median [interquartile range] age, 74.0 [71.0-78.0] years; 51.3% [200 of 390] female). There was no difference in postoperative delirium between the dexmedetomidine and placebo groups (12.2% [23 of 189] vs 11.4% [23 of 201], P = .94). After adjustment for age and educational level, there was no difference in the postoperative cognitive performance between treatment groups at 3 months and 6 months. Adverse events were comparably distributed in the treatment groups.Conclusions and relevanceIntraoperative dexmedetomidine does not prevent postoperative delirium. The reduction in delirium previously demonstrated in numerous surgical intensive care unit studies was not observed, which underscores the importance of timing when administering the drug to prevent delirium.Trial registrationclinicaltrials.gov Identifier NCT00561678.

Project description:BackgroundPostoperative delirium (POD) is common and has negative effects on elderly patients. There is a critical need to identify patients at high risk of POD so that providers can better offer targeted interventions in the preoperative and intraoperative periods. We aimed to characterize the prevalence of preoperative anxiety and investigate whether preoperative anxiety predicted the onset of POD in elderly patients undergoing elective orthopedic surgery.MethodsWe conducted a prospective observational cohort study of elderly patients (aged 65 years or older) undergoing elective orthopedic surgery. Preoperative anxiety was assessed using the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), with clinically significant values defined as HADS-A>7. POD was diagnosed according to the Confusion Assessment Method (CAM) criteria on the 5 postoperative days. To determine the independent risk factors for POD, multivariable logistic regression was conducted, including those variables with a p-value <0.05 at univariate analysis.ResultsThere were 263 patients included in the study. Seventy-three (27.8%) patients were diagnosed to be POD. Median duration of delirium was 2 days. Forty (15.2%) patients were assessed to experience preoperative anxiety. The occurrence of preoperative anxiety in total hip arthroplasty (THA), proximal femoral nail antirotation (PFNA), and total knee arthroplasty (TKA) was 12.5%, 16.1%, and 19.5%, respectively. Based on multivariable analysis, only age (odds ratio [OR]= 1.099, 95% Confidence Interval [CI]: 1.013-1.192; P=0.023), Mini Mental State Examination (MMSE) (OR= 0.603, 95% CI: 0.432-0.842; P=0.003) and preoperative anxiety (OR= 3.119, 95% CI: 1.144-8.500; P=0.026) were independently associated with POD.ConclusionIn conclusion, the current study reveals that preoperative anxiety helps to predict the risk of POD in elderly patients undergoing elective orthopedic surgery. Relieving preoperative anxiety could be a new target for preventive interventions to reduce POD.

Dataset Information

Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study.

Publications

Higher C-Reactive Protein Levels Predict Postoperative Delirium in Older Patients Undergoing Major Elective Surgery: A Longitudinal Nested Case-Control Study.

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