Association between genetic variants of the cholinergic system and postoperative delirium and cognitive dysfunction in elderly patients

Abstract Background Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are frequent and serious complications after surgery. We aim to investigate the association between genetic variants in cholinergic candidate genes according to the Kyoto encyclopedia of genes and genomes - pathway: cholinergic neurotransmission with the development of POD or POCD in elderly patients. Methods This analysis is part of the European BioCog project (www.biocog.eu), a prospective multicenter observational study with elderly surgical patients. Patients with a Mini-Mental-State-Examination score ≤ 23 points were excluded. POD was assessed up to seven days after surgery using the Nursing Delirium Screening Scale, Confusion Assessment Method and a patient chart review. POCD was assessed three months after surgery with a neuropsychological test battery. Genotyping was performed on the Illumina Infinium Global Screening Array. Associations with POD and POCD were analyzed using logistic regression analysis, adjusted for age, comorbidities and duration of anesthesia (for POCD analysis additionally for education). Odds ratios (OR) refer to minor allele counts (0, 1, 2). Results 745 patients could be included in the POD analysis, and 452 in the POCD analysis. The rate of POD within this group was 20.8% (155 patients), and the rate of POCD was 10.2% (46 patients). In a candidate gene approach three genetic variants of the cholinergic genes CHRM2 and CHRM4 were associated with POD (OR [95% confidence interval], rs8191992: 0.61[0.46; 0.80]; rs8191992: 1.60[1.22; 2.09]; rs2067482: 1.64[1.10; 2.44]). No associations were found for POCD. Conclusions We found an association between genetic variants of CHRM2 and CHRM4 and POD. Further studies are needed to investigate whether disturbances in acetylcholine release and synaptic plasticity are involved in the development of POD. Trial registration: ClinicalTrials.gov: NCT02265263.

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Postoperative delirium after cardiac surgery of elderly patients as an independent risk factor for prolonged length of stay in intensive care unit and in hospital

Aging Clinical and Experimental Research ◽

10.1007/s40520-021-01842-x ◽

2021 ◽

Author(s):

Andrea Kirfel ◽

Jan Menzenbach ◽

Vera Guttenthaler ◽

Johanna Feggeler ◽

Andreas Mayr ◽

...

Keyword(s):

Intensive Care Unit ◽

Cardiac Surgery ◽

Intensive Care ◽

Length Of Stay ◽

Elderly Patients ◽

Postoperative Delirium ◽

Confusion Assessment Method ◽

Assessment Method ◽

Hospital Length Of Stay ◽

Confusion Assessment

Abstract Background Postoperative delirium (POD) is a relevant and underdiagnosed complication after cardiac surgery that is associated with increased intensive care unit (ICU) and hospital length of stay (LOS). The aim of this subgroup study was to compare the frequency of tested POD versus the coded International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis of POD and to evaluate the influence of POD on LOS in ICU and hospital. Methods 254 elective cardiac surgery patients (mean age, 70.5 ± 6.4 years) at the University Hospital Bonn between September 2018 and October 2019 were evaluated. The endpoint tested POD was considered positive, if one of the tests Confusion Assessment Method for ICU (CAM-ICU) or Confusion Assessment Method (CAM), 4 'A's Test (4AT) or Delirium Observation Scale (DOS) was positive on one day. Results POD occurred in 127 patients (50.0%). LOS in ICU and hospital were significantly different based on presence (ICU 165.0 ± 362.7 h; Hospital 26.5 ± 26.1 days) or absence (ICU 64.5 ± 79.4 h; Hospital 14.6 ± 6.7 days) of POD (p < 0.001). The multiple linear regression showed POD as an independent predictor for a prolonged LOS in ICU (48%; 95%CI 31–67%) and in hospital (64%; 95%CI 27–110%) (p < 0.001). The frequency of POD in the study participants that was coded with the ICD F05.0 and F05.8 by hospital staff was considerably lower than tests revealed by the study personnel. Conclusion Approximately 50% of elderly patients who underwent cardiac surgery developed POD, which is associated with an increased ICU and hospital LOS. Furthermore, POD is highly underdiagnosed in clinical routine.

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The Effect and Optimal Dosage of Dexmedetomidine Plus Sufentanil for Postoperative Analgesia in Elderly Patients With Postoperative Delirium and Early Postoperative Cognitive Dysfunction: A Single-Center, Prospective, Randomized, Double-Blind, Controlled Trial

Frontiers in Neuroscience ◽

10.3389/fnins.2020.549516 ◽

2020 ◽

Vol 14 ◽

Author(s):

Wenshuai Zhao ◽

Yanan Hu ◽

Hui Chen ◽

Xifan Wang ◽

Liping Wang ◽

...

Keyword(s):

Elderly Patients ◽

Cognitive Dysfunction ◽

Postoperative Analgesia ◽

Postoperative Delirium ◽

Controlled Trial ◽

Postoperative Cognitive Dysfunction ◽

Optimal Dosage ◽

Single Center ◽

Double Blind

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Elevated Procalcitonin and Depression As Risk Factors For Postoperative Delirium In The Elderly After Cardiac Surgery – A Prospective Observational Study.

10.21203/rs.3.rs-94378/v1 ◽

2020 ◽

Author(s):

Anna Kupiec ◽

Barbara Adamik ◽

Natalia Kozera ◽

Waldemar Gozdzik

Keyword(s):

Risk Factors ◽

Cardiac Surgery ◽

Elderly Patients ◽

Postoperative Delirium ◽

Inflammatory Marker ◽

Functional Decline ◽

The Elderly ◽

Confusion Assessment Method ◽

Assessment Method ◽

Multivariable Logistic Regression Model

Abstract Background One of the most common complications after cardiac surgery is delirium. Determining the origin of this complication from possible pathomechanisms is difficult. The activation of an inflammatory response during surgery has been suggested as one possible mechanism of delirium. The usefulness of the inflammatory marker procalcitonin (PCT) as a predictor of delirium after cardiac surgery with cardiopulmonary bypass (CBP) has not yet been investigated. Methods The purpose of this study was to prospectively investigate the risk of developing postoperative delirium in a group of elderly patients using a multivariate assessment of preoperative (PCT, comorbidities, functional decline, depression) and intraoperative risk factors. 149 elderly patients were included. Delirium was assessed using the Confusion Assessment Method for the ICU. Results Thirty patients (20%) developed post-operative delirium: hypoactive in 50%, hyperactive in 33%, mixed in 17%. Preoperative PCT above the reference range (> 0.05 ng/mL) was recorded more often in patients who postoperatively developed delirium than in the non-delirium group (50% vs. 27%, p=0.019). After surgery, PCT was significantly higher in the delirium than the non-delirium group: ICU admission after surgery: 0.08 ng/mL, IQR 0.03-0.15 vs. 0.05 ng/mL, IQR 0.02-0.09, p=0.011), and for consecutive days (day 1: 0.59 ng/mL, IQR 0.25-1.55 vs. 0.25 ng/mL, IQR 0.14-0.54, p=0.003; day 2: 1.21 ng/mL, IQR 0.24-3.29 vs. 0.36 ng/mL, IQR 0.16-0.76, p=0.006; day 3: 0.76 ng/mL, IQR 0.48-2.34 vs. 0.34 ng/mL, IQR 0.14-0.66, p=0.001). Patients with delirium were older (74 years, IQR 70 – 76 vs. 69 years, IQR 67 – 74; p=0.038) and more often had functional decline (47% vs. 28%, p=0.041). There was no difference in comorbidities with the exception of anaemia (43% vs. 19%, p=0.006). Depression was detected in 40% of patients with delirium and in 17% without delirium (p=0.005). In a multivariable logistic regression model of preoperative procalcitonin (OR= 3.05; IQR 1.02-9.19), depression (OR=5.02, IQR 1.67-15.10), age (OR=1.14; IQR 1.02-1.26), functional decline (OR=0.76; IQR 0.63-0.91) along with CPB time (OR=1.04; IQR 1.02-1.06) were significant predictors of postoperative delirium. Conclusion A preoperative PCT test and assessment of functional decline and depression may help identify patients at risk for developing delirium after cardiac surgery.

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Association between baseline cognitive impairment and postoperative delirium in elderly patients undergoing surgery for adult spinal deformity

Journal of Neurosurgery Spine ◽

10.3171/2017.5.spine161244 ◽

2018 ◽

Vol 28 (1) ◽

pp. 103-108 ◽

Cited By ~ 18

Author(s):

Owoicho Adogwa ◽

Aladine A. Elsamadicy ◽

Victoria D. Vuong ◽

Jared Fialkoff ◽

Joseph Cheng ◽

...

Keyword(s):

Risk Factor ◽

Cognitive Impairment ◽

Elderly Patients ◽

Postoperative Delirium ◽

Adult Spinal Deformity ◽

Functional Decline ◽

Confusion Assessment Method ◽

Assessment Method ◽

Degenerative Scoliosis ◽

Patient Reported

OBJECTIVEPostoperative delirium is common in elderly patients undergoing spine surgery and is associated with a longer and more costly hospital course, functional decline, postoperative institutionalization, and higher likelihood of death within 6 months of discharge. Preoperative cognitive impairment may be a risk factor for the development of postoperative delirium. The aim of this study was to investigate the relationship between baseline cognitive impairment and postoperative delirium in geriatric patients undergoing surgery for degenerative scoliosis.METHODSElderly patients 65 years and older undergoing a planned elective spinal surgery for correction of adult degenerative scoliosis were enrolled in this study. Preoperative cognition was assessed using the validated Saint Louis University Mental Status (SLUMS) examination. SLUMS comprises 11 questions, with a maximum score of 30 points. Mild cognitive impairment was defined as a SLUMS score between 21 and 26 points, while severe cognitive impairment was defined as a SLUMS score of ≤ 20 points. Normal cognition was defined as a SLUMS score of ≥ 27 points. Delirium was assessed daily using the Confusion Assessment Method (CAM) and rated as absent or present on the basis of CAM. The incidence of delirium was compared in patients with and without baseline cognitive impairment.RESULTSTwenty-two patients (18%) developed delirium postoperatively. Baseline demographics, including age, sex, comorbidities, and perioperative variables, were similar in patients with and without delirium. The length of in-hospital stay (mean 5.33 days vs 5.48 days) and 30-day hospital readmission rates (12.28% vs 12%) were similar between patients with and without delirium, respectively. Patients with preoperative cognitive impairment (i.e., a lower SLUMS score) had a higher incidence of postoperative delirium. One- and 2-year patient reported outcomes scores were similar in patients with and without delirium.CONCLUSIONSCognitive impairment is a risk factor for the development of postoperative delirium. Postoperative delirium may be associated with decreased preoperative cognitive reserve. Cognitive impairment assessments should be considered in the preoperative evaluations of elderly patients prior to surgery.

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Exploring Postoperative Cognitive Dysfunction and Delirium in Noncardiac Surgery Using MRI: A Systematic Review

Neural Plasticity ◽

10.1155/2018/1281657 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 13

Author(s):

Chenxi Huang ◽

Johan Mårtensson ◽

Ismail Gögenur ◽

Mohammad Sohail Asghar

Keyword(s):

Cognitive Dysfunction ◽

Brain Mri ◽

Postoperative Cognitive Dysfunction ◽

Confusion Assessment Method ◽

Assessment Method ◽

Cognitive Testing ◽

Surgical Patients ◽

Mri Findings ◽

Mri Studies ◽

And Function

Surgical patients are at high risk of developing postoperative cognitive dysfunction (POCD) and postoperative delirium (POD). POCD and POD are associated with increased morbidity and mortality and worsening functional outcomes leading to severe socioeconomic consequences for the patient and the society in general. Magnetic resonance imaging (MRI) offers a unique opportunity to study the anatomy and function of the brain. MRI thus plays an important role in elucidating the neuronal component of POCD and POD. Our aim has been to systematically gather MRI findings that are related to POCD and POD. Systematic searches were conducted in PubMed, EMBASE, and PsycINFO: MRI studies investigating patients with POCD as identified by perioperative cognitive testing or patients with delirium identified postoperatively by the Confusion Assessment Method. A total of ten eligible papers were included with a total of 269 surgical patients, 36 patient controls, and 55 healthy controls who all underwent MRI examination. These studies suggested that reduction of thalamic and hippocampal volumes and reduction of cerebral blood flow may be associated with POCD, while presurgery/preexisting and postoperative white matter pathology may be associated with POD. However, the evidence from these studies is rather weak. Future MRI studies are warranted to verify the current findings.

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