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Preoperative medication use and postoperative delirium: a systematic review.

ABSTRACT: Medications are frequently reported as both predisposing factors and inducers of delirium. This review evaluated the available evidence and determined the magnitude of risk of postoperative delirium associated with preoperative medication use.A systematic search in Medline and EMBASE was conducted using MeSH terms and keywords for postoperative delirium and medication. Studies which included patients 18 years and older who underwent major surgery were included. The methodological quality of included studies was assessed independently by two authors using the Newcastle-Ottawa quality assessment scale for cohort studies.Twenty-nine studies; 25 prospective cohort, three retrospective cohort and one post hoc analysis of RCT data were included. Only four specifically aimed to assess medicines as an independent predictor of delirium, all other studies included medicines among a number of potential predictors of delirium. Of the studies specifically testing the association with a medication class, preoperative use of beta-blockers (OR?=?2.06[1.18-3.60]) in vascular surgery and benzodiazepines RR 2.10 (1.23-3.59) prior to orthopedic surgery were significant. However, evidence is from single studies only. Where medicines were included as one possible factor among many, hypnotics had a similar risk estimate to the benzodiazepine study, with one significant and one non-significant result. Nifedipine use prior to cardiac surgery was found to be significantly associated with delirium. The non-specific grouping of psychoactive medication use preoperatively was generally higher with an associated two-to-seven-fold higher risk of postoperative delirium, while only two studies included narcotics without other agents, with one significant and one non-significant result.There was a limited number of high quality studies in the literature quantifying the direct association between preoperative medication use and postsurgical delirium. More studies are required to evaluate the association of specific preoperative medications on the risk of postoperative delirium so that comprehensive guidelines for medicine use prior to surgery can be developed to aid delirium prevention.This systematic review has been registered on PROSPERO International prospective register of systematic reviews (Registration number: CRD42016051245 ).

SUBMITTER: Kassie GM

PROVIDER: S-EPMC5747155 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Preoperative medication use and postoperative delirium: a systematic review.

Kassie Gizat M GM Nguyen Tuan A TA Kalisch Ellett Lisa M LM Pratt Nicole L NL Roughead Elizabeth E EE

BMC geriatrics 20171229 1

<h4>Background</h4>Medications are frequently reported as both predisposing factors and inducers of delirium. This review evaluated the available evidence and determined the magnitude of risk of postoperative delirium associated with preoperative medication use.<h4>Methods</h4>A systematic search in Medline and EMBASE was conducted using MeSH terms and keywords for postoperative delirium and medication. Studies which included patients 18 years and older who underwent major surgery were included. ...[more]

PMID: 29284416

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Project description:BackgroundPostoperative delirium (POD) is a common postoperative complication, characterized by disturbance of attention, perception, and consciousness within 1 week after surgery, and linked to cognitive decline, increased mortality, and other serious surgical outcomes. Early identification and treatment of risk factors for POD could reduce the occurrence of delirium and the related poor outcomes. Malnutrition as a possible precipitating factor, defined as the poor anthropometric, functional, and clinical outcomes of nutrient deficiency, has been investigated. However, the evidence is controversial. The goal of this systematic review and meta-analysis was to comprehensively assess the correlation between preoperative malnutrition and POD.MethodsPubMed, Embase, Cochrane Library, and Web of Science were used to search prospective cohort articles that explored the correlation between preoperative malnutrition and POD from inception until September 30, 2022. Two researchers independently conducted the literature selection and data extraction. The quality of the literature was evaluated according to the Newcastle-Ottawa scale (NOS). Odds ratios (ORs) and 95% confidence intervals (CIs) for POD associated with malnutrition relative to normal nutritional status were calculated.ResultsSeven prospective cohort studies qualified for the meta-analysis, which included 2701 patients. The pooled prevalence of preoperative malnutrition was 15.1% (408/2701), and POD occurred in 428 patients (15.8%). The NOS score was above 7 points in all 7 studies. Our results demonstrated that the pooled OR for malnutrition and POD was 2.32 (95% CI 1.62-3.32) based on a random-effects model. Our subgroup analysis suggested that the relationship between malnutrition and POD was significant in adults following noncardiac surgery (OR = 3.04, 95% CI, 1.99-4.62, P < 0.001), while there was no statistical significance in adults following cardiac surgery (OR = 1.76, 95% CI, 0.96-3.22, P = 0.07). Additionally, in the subgroup analysis based on different malnutrition assessment tools (MNA-SF versus others), a significant association was found in the MNA-SF group (OR = 3.04, 95% CI, 1.99-4.62, P < 0.001), but not in the others group (OR = 1.76, 95% CI, 0.96-3.22, P = 0.07). Other subgroup analyses showed that this association was not significantly affected by evaluation instruments for POD, location of the study, or quality of the article (all P < 0.05).ConclusionsBased on the currently available evidence, our results suggested that preoperative malnutrition was independently associated with POD in adult surgical patients.

Project description:Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with development of postoperative delirium in older surgical patients. We employed a nested case–control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p<0.05). Due to the limited sample size these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identifies 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.

Project description:BackgroundPostoperative delirium (POD) is a common postoperative complication associated with multiple adverse consequences on patient outcomes and higher medical expenses. Preoperative anxiety has been suggested as a possible precipitating factor for the development of POD. As such, we aimed to explore the association between preoperative anxiety and POD in older surgical patients.MethodsElectronic databases including MEDLINE (via PubMed), EMBASE (via Embase.com), Web of Science Core Collection, Cumulative Index to Nursing and Allied Health Literature (CINAHL Complete; via EBSCOhost) and clinical trial registries were systematically searched to identify prospective studies examining preoperative anxiety as a risk factor for POD in older surgical patients. We used Joanna Briggs Institute Critical Appraisal Checklist for Cohort Studies to assess the quality of included studies. The association between preoperative anxiety and POD was summarized with odds ratios (ORs) and 95% confidence intervals (CIs) using DerSimonian-Laird random-effects meta-analysis.ResultsEleven studies were included (1691 participants; mean age ranging between 63.1-82.3 years). Five studies used a theoretical definition for preoperative anxiety, with the Anxiety subscale of Hospital Anxiety and Depression Scale (HADS-A) as the instrument being most often used. When using dichotomized measures and within the HADS-A subgroup analysis, preoperative anxiety was significantly associated with POD (OR = 2.17, 95%CI: 1.01-4.68, I2 = 54%, Tau2 = 0.4, n = 5; OR = 3.23, 95%CI: 1.70-6.13, I2 = 0, Tau2 = 0, n = 4; respectively). No association was observed when using continuous measurements (OR = 0.99, 95%CI: 0.93-1.05, I2 = 0, Tau2 = 0, n = 4), nor in the subgroup analysis of STAI-6 (six-item version of state scale of Spielberger State-Trait Anxiety Inventory, OR = 1.07, 95%CI: 0.93-1.24, I2 = 0, Tau2 = 0, n = 2). We found the overall quality of included studies to be moderate to good.ConclusionsAn unclear association between preoperative anxiety and POD in older surgical patients was found in our study. Given the ambiguity in conceptualization and measurement instruments used for preoperative anxiety, more research is warranted in which a greater emphasis should be placed on how preoperative anxiety is operationalized and measured.

Project description:Objective: To analyze the proteome of preoperative cerebrospinal fluid (CSF) in older orthopedic patients with or without postoperative delirium (POD) using untargeted proteomics. Methods: A prospective cohort study was conducted. Eighty hip fracture patients aged ≥65 years were recruited. After successful spinal anesthesia, CSF was collected. The patients were divided into POD and No-POD groups based on the Confusion Assessment Method, and patients with POD were graded using the Memorial Delirium Assessment Scale (MDAS). Thirty No-POD patients were matched to 10 POD patients by age (±2 years) and Mini-Mental State Examination score (±2 scores). Label-free proteomic analysis was performed using a liquid chromatography coupled to mass spectrometry (LC-MS) workflow. Validation was performed using mass-spectrometry-based parallel reaction monitoring (PRM) for the 30 No-POD and 10 POD patients, as well as for an additional 5 POD patients. Bioinformatics were used to investigate possible relevant pathological mechanisms. Results: The incidence of POD in older orthopedic patients was 18.8% in our cohort of 80 patients. Proteomics results revealed 63 dysregulated CSF proteins, and PRM analysis validated these results. The preoperative CSF levels of both V-set and transmembrane domain-containing protein 2B (VSTM2B) and coagulation factor V (FA5) were positively correlated with MDAS scores on postoperative day 1 (r > 0.8, p < 0.05). Bioinformatic analysis revealed that several nervous-system-related pathways are relevant to POD development. Conclusion: We identified and validated several novel CSF proteins that are dysregulated in POD, and revealed several pathways that are relevant to POD development. Our results not only provide risk biomarkers for POD, but also give clues for further investigations into the pathological mechanisms of delirium. Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR1900021533).

Project description:BackgroundBoth frailty and postoperative delirium (POD) are common in elective surgical patients 65 years of age and older. However, the association between preoperative frailty and POD remains difficult to characterize owing to the large number of frailty and POD assessment tools used in the literature, only a few of which are validated. Furthermore, some validated frailty tools fail to provide clear score cutoffs for distinguishing frail and nonfrail patients. We performed a meta-analysis to estimate the relationship between preoperative frailty and POD.MethodsWe searched several major databases for articles that investigated the relationship between preoperative frailty and POD in patients with mean age ≥65 years who were undergoing elective, nonemergent inpatient surgery. Inclusion criteria included articles published in English no earlier than 1999. Both preoperative frailty and POD must have been measured with validated tools using clear cutoff scores for frailty and delirium. Articles were selected and data extracted independently by 2 researchers. Risk of bias (ROBINS-I) and presence of confounders were summarized. Odds ratios (ORs) for POD associated with frailty relative to nonfrailty were computed with adjusted ORs when available. Original estimates were pooled by random effects analysis. Statistical significance was set at 2-sided P < .05.ResultsNine studies qualified for meta-analysis. The Fried score or a modified version of it was used in 5 studies. Frailty prevalence ranged from 18.6% to 56%. Delirium was assessed with the Confusion Assessment Method (CAM) or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in 7 studies, Delirium Observation Scale in 1 study, and Intensive Care Delirium Screening Checklist in 1 study. The incidence of POD ranged from 7% to 56%. ROBINS-I risk of bias was low in 1 study, moderate in 4 studies, serious in 3 studies, and critical in 1 study. Random effects analysis (n = 794) of the OR for POD in frail versus nonfrail patients based on adjusted OR estimates was significant with an OR of 2.14 and a 95% confidence interval of 1.43-3.19. The I2 value was in the low range at 5.5, suggesting small variability from random effects. Funnel-plot analysis did not definitively support either the presence or absence of publication bias.ConclusionsThis meta-analysis provides evidence for a significant association between preoperative frailty and POD in elective surgical patients age 65 years or older.

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Preoperative medication use and postoperative delirium: a systematic review.

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Preoperative medication use and postoperative delirium: a systematic review.

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