-
Anesthesia and Analgesia Aug 2021Both frailty and postoperative delirium (POD) are common in elective surgical patients 65 years of age and older. However, the association between preoperative frailty... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Both 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.
METHODS
We 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.
RESULTS
Nine 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.
CONCLUSIONS
This meta-analysis provides evidence for a significant association between preoperative frailty and POD in elective surgical patients age 65 years or older.
Topics: Age Factors; Aged; Delirium; Elective Surgical Procedures; Female; Frail Elderly; Frailty; Humans; Incidence; Male; Postoperative Cognitive Complications; Prevalence; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 34257192
DOI: 10.1213/ANE.0000000000005609 -
Journal of the American Heart... Nov 2020Background Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However,... (Meta-Analysis)
Meta-Analysis
Background Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer-reviewed, English publications reporting post-CABG delirium or cognitive decline data, for at least one risk factor. Random-effects meta-analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety-seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1-6 months) post-CABG cognitive decline. Conclusions This meta-analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42020149276.
Topics: Cognitive Dysfunction; Coronary Artery Bypass; Coronary Artery Disease; Delirium; Humans; Postoperative Complications; Risk Factors
PubMed: 33164631
DOI: 10.1161/JAHA.120.017275 -
Age and Ageing May 2021Detection of delirium in hospitalised older adults is recommended in national and international guidelines. The 4 'A's Test (4AT) is a short (<2 minutes) instrument for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Detection of delirium in hospitalised older adults is recommended in national and international guidelines. The 4 'A's Test (4AT) is a short (<2 minutes) instrument for delirium detection that is used internationally as a standard tool in clinical practice. We performed a systematic review and meta-analysis of diagnostic test accuracy of the 4AT for delirium detection.
METHODS
We searched MEDLINE, EMBASE, PsycINFO, CINAHL, clinicaltrials.gov and the Cochrane Central Register of Controlled Trials, from 2011 (year of 4AT release on the website www.the4AT.com) until 21 December 2019. Inclusion criteria were: older adults (≥65 years); diagnostic accuracy study of the 4AT index test when compared to delirium reference standard (standard diagnostic criteria or validated tool). Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Pooled estimates of sensitivity and specificity were generated from a bivariate random effects model.
RESULTS
Seventeen studies (3,702 observations) were included. Settings were acute medicine, surgery, a care home and the emergency department. Three studies assessed performance of the 4AT in stroke. The overall prevalence of delirium was 24.2% (95% CI 17.8-32.1%; range 10.5-61.9%). The pooled sensitivity was 0.88 (95% CI 0.80-0.93) and the pooled specificity was 0.88 (95% CI 0.82-0.92). Excluding the stroke studies, the pooled sensitivity was 0.86 (95% CI 0.77-0.92) and the pooled specificity was 0.89 (95% CI 0.83-0.93). The methodological quality of studies varied but was moderate to good overall.
CONCLUSIONS
The 4AT shows good diagnostic test accuracy for delirium in the 17 available studies. These findings support its use in routine clinical practice in delirium detection.
PROSPERO REGISTRATION NUMBER
CRD42019133702.
Topics: Aged; Delirium; Emergency Service, Hospital; Geriatric Assessment; Humans; Mass Screening; Sensitivity and Specificity
PubMed: 33951145
DOI: 10.1093/ageing/afaa224 -
Journal of the American Geriatrics... Nov 2021To determine the associations of delirium with urinary tract infection (UTI) and asymptomatic bacteriuria (AB) in individuals aged 65 and older. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the associations of delirium with urinary tract infection (UTI) and asymptomatic bacteriuria (AB) in individuals aged 65 and older.
METHODS
The protocol for this systematic review and meta-analysis was published on PROSPERO (CRD42020164341). Electronic databases were searched for relevant studies, professional associations and experts in the field were additionally contacted. Studies with control groups reporting associations between delirium and UTI as well as delirium and AB in older adults were included. The random effects model meta-analysis was conducted using odds ratios (ORs) with 95% confidence intervals (CIs) as effect size measures. The Newcastle-Ottawa scale was used to rate the studies' quality. Heterogeneity was assessed using the Q and I tests. The effects of potential moderators were investigated by both subgroup and meta-regression analyses. The risk of publication bias was evaluated using the funnel plot and Egger's test.
RESULTS
Twenty nine relevant studies (16,618 participants) examining the association between delirium and UTI in older adults were identified. The association between delirium and UTI was found to be significant (OR 2.67; 95% CI 2.12-3.36; p < 0.001) and persisted regardless of potential confounders. The association between delirium and AB in older adults in the only eligible study found (192 participants) was insignificant (OR 1.62; 95% CI 0.57-4.65; p = 0.37). All included studies were of moderate quality.
CONCLUSION
The results of this study support the association between delirium and UTI in older adults. Insufficient evidence was found to conclude on an association between delirium and AB in this age group. These findings are limited due to the moderate quality of the included studies and a lack of available research on the association between delirium and AB. Future studies should use the highest quality approaches for defining both delirium and UTI and consider AB in their investigations.
Topics: Aged; Bacteriuria; Delirium; Hospitals; Humans; Nursing Homes; Urinary Tract Infections
PubMed: 34448496
DOI: 10.1111/jgs.17418 -
Anaesthesia Mar 2019Delirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary... (Meta-Analysis)
Meta-Analysis
Delirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary aim of this review was to examine whether dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. We sought randomised clinical trials in MEDLINE, EMBASE, PubMed and CENTRAL from their inception until June 2018. Observational studies, case reports, case series and non-systematic reviews were excluded. Twenty-five trials including 3240 patients were eligible for inclusion in the data synthesis. In the patients who received dexmedetomidine (eight trials, 1425 patients), delirium was reduced, odds ratio (95%CI) 0.36 (0.26-0.51), p < 0.001 and high quality of evidence. The use of dexmedetomidine was associated with a reduced incidence of agitation, OR (95%CI) 0.34 (0.20-0.59), p < 0.001, moderate quality of evidence. Patients who were randomly assigned to dexmedetomidine had a significantly higher incidence of bradycardia, OR (95%CI) 2.18 (1.46-3.24), p < 0.001, moderate quality of evidence; and hypotension, OR (95%CI) 1.89 (1.48-2.41), p < 0.001, high quality of evidence. We found no evidence of an effect on mortality, OR (95%CI) 0.86 (0.66-1.10), p = 0.23, moderate quality of evidence. The trial sequential analyses for the incidence of delirium, bradycardia and hypotension was conclusive but not for the incidence of agitation and mortality. In summary, this meta-analysis suggests that dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. The general quality of evidence ranged from moderate to high.
Topics: Delirium; Dexmedetomidine; Humans; Intensive Care Units; Psychomotor Agitation
PubMed: 30367689
DOI: 10.1111/anae.14472 -
Journal of Critical Care Dec 2020To compare non-pharmacological interventions in their ability to prevent delirium in critically ill patients, and find the optimal regimen for treatment.
OBJECTIVE
To compare non-pharmacological interventions in their ability to prevent delirium in critically ill patients, and find the optimal regimen for treatment.
METHODS
Literature searches were conducted using PubMed, Embase, CINAHL, and Cochrane Library databases until the end of June 2019. We estimated the risk ratios (RRs) for the incidence of delirium and in-hospital mortality and found the mean difference (MD) for delirium duration and the length of ICU stay. The probabilities of interventions were ranked based on clinical outcomes. The study was registered on PROSPERO (CRD42020160757).
RESULTS
Twenty-six eligible studies were included in the network meta-analysis. Studies were grouped into seven intervention types: physical environment intervention (PEI), sedation reducing (SR), family participation (FP), exercise program (EP), cerebral hemodynamics improving (CHI), multi-component studies (MLT) and usual care (UC). In term of reducing the incidence of delirium, the two most effective interventions were FP (risk ratio (RR) 0.19, 95% confidence interval (CI) 0.08 to 0.44; surface under the cumulative ranking curve (SUCRA) = 94%) and MLT (RR 0.43, 95% CI 0.30 to 0.57; SUCRA = 68%) compared with observation. Although all interventions demonstrated nonsignificant efficacy in regards to delirium duration and the length of the patient's stay in the ICU, MLT (SUCRA = 78.6% and 71.2%, respectively) was found to be the most effective intervention strategy. In addition, EP (SUCRA = 97.2%) facilitated a significant reduction in hospital mortality, followed in efficacy by MLT (SUCRA = 73.2%), CHI (SUCRA = 35.8%), PEI (SUCRA = 34.8%), and SR (SUCRA = 31.8%).
CONCLUSIONS
Multi-component strategies are overall the optimal intervention techniques for preventing delirium and reducing ICU length of stay in critically ill patients by way of utilizing several interventions simultaneously. Additionally, family participation as a method of patient-centered care resulted in better outcomes for reducing the incidence of delirium.
Topics: Adult; Aged; Aged, 80 and over; Bayes Theorem; Critical Care; Critical Illness; Delirium; Family; Female; Hospital Mortality; Humans; Incidence; Intensive Care Units; Length of Stay; Male; Middle Aged; Network Meta-Analysis; Young Adult
PubMed: 32919363
DOI: 10.1016/j.jcrc.2020.08.019 -
Intensive Care Medicine Jul 2022Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU).... (Meta-Analysis)
Meta-Analysis
Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU). Dexmedetomidine is an alternative sedative that may achieve lighter sedation, reduce delirium, and provide analgesia. Our objective was to perform a comprehensive systematic review summarizing the large body of evidence, determining if dexmedetomidine reduces delirium compared to conventional sedatives. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and the WHO ICTRP from inception to October 2021. Independent pairs of reviewers identified randomized clinical trials comparing dexmedetomidine to other sedatives for mechanically ventilated adults in the ICU. We conducted meta-analyses using random-effects models. The results were reported as relative risks (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs). In total, 77 randomized trials (n = 11,997) were included. Compared to other sedatives, dexmedetomidine reduced the risk of delirium (RR 0.67, 95% CI 0.55 to 0.81; moderate certainty), the duration of mechanical ventilation (MD - 1.8 h, 95% CI - 2.89 to - 0.71; low certainty), and ICU length of stay (MD - 0.32 days, 95% CI - 0.42 to - 0.22; low certainty). Dexmedetomidine use increased the risk of bradycardia (RR 2.39, 95% CI 1.82 to 3.13; moderate certainty) and hypotension (RR 1.32, 95% CI 1.07 to 1.63; low certainty). In mechanically ventilated adults, the use of dexmedetomidine compared to other sedatives, resulted in a lower risk of delirium, and a modest reduction in duration of mechanical ventilation and ICU stay, but increased the risks of bradycardia and hypotension.
Topics: Adult; Bradycardia; Critical Illness; Delirium; Dexmedetomidine; Humans; Hypnotics and Sedatives; Hypotension; Intensive Care Units; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 35648198
DOI: 10.1007/s00134-022-06712-2 -
Journal of Neuroinflammation Jun 2015Animal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role for microglia in sepsis-associated... (Review)
Review
BACKGROUND
Animal studies show that peripheral inflammatory stimuli may activate microglial cells in the brain implicating an important role for microglia in sepsis-associated delirium. We systematically reviewed animal experiments related to the effects of systemic inflammation on the microglial and inflammatory response in the brain.
METHODS
We searched PubMed between January 1, 1950 and December 1, 2013 and Embase between January 1, 1988 and December 1, 2013 for animal studies on the influence of peripheral inflammatory stimuli on microglia and the brain. Identified studies were systematically scored on methodological quality. Two investigators extracted independently data on animal species, gender, age, and genetic background; number of animals; infectious stimulus; microglial cells; and other inflammatory parameters in the brain, including methods, time points after inoculation, and brain regions.
RESULTS
Fifty-one studies were identified of which the majority was performed in mice (n = 30) or in rats (n = 19). Lipopolysaccharide (LPS) (dose ranging between 0.33 and 200 mg/kg) was used as a peripheral infectious stimulus in 39 studies (76 %), and live or heat-killed pathogens were used in 12 studies (24 %). Information about animal characteristics such as species, strain, sex, age, and weight were defined in 41 studies (80 %), and complete methods of the disease model were described in 35 studies (68 %). Studies were also heterogeneous with respect to methods used to assess microglial activation; markers used mostly were the ionized calcium binding adaptor molecule-1 (Iba-1), cluster of differentiation 68 (CD68), and CD11b. After LPS challenge microglial activation was seen 6 h after challenge and remained present for at least 3 days. Live Escherichia coli resulted in microglial activation after 2 days, and heat-killed bacteria after 2 weeks. Concomitant with microglial response, inflammatory parameters in the brain were reviewed in 23 of 51 studies (45 %). Microglial activation was associated with an increase in Toll-like receptor (TLR-2 and TLR-4), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β) messenger ribonucleic acid (mRNA) expression or protein levels.
INTERPRETATION
Animal experiments robustly showed that peripheral inflammatory stimuli cause microglial activation. We observed distinct differences in microglial activation between systemic stimulation with (supranatural doses) LPS and live or heat-killed bacteria.
Topics: Animals; Delirium; Disease Models, Animal; Escherichia coli; Female; Inflammation; Lipopolysaccharides; Male; Mice; Microglia; Rats; Sepsis
PubMed: 26048578
DOI: 10.1186/s12974-015-0332-6 -
International Journal of Geriatric... Jan 2021Postoperative delirium (POD) is the most common complication in patients after hip fracture surgery, and the incidence of POD is associated with mortality and disability... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Postoperative delirium (POD) is the most common complication in patients after hip fracture surgery, and the incidence of POD is associated with mortality and disability in patients following hip fracture surgery. Therefore, this study aimed to identify the individual as well as anesthetic and operative risk factors associated with the POD in adult patients after hip fracture surgery.
METHODS
We searched relevant articles published to February 2020 in Cochrane Library, PubMed, and Embase. Studies involving adult patients who underwent hip fracture surgery were regarded as relevant if the studies contained the individual or anesthetic and surgical characteristics of participants. The pooled relative risk ratios (RRs) or weight mean difference of the variables were estimated by the Mantel-Haenszel or Inverse-Variance methods.
RESULTS
A total of 44 studies were included, which altogether included 104572 participants with hip fracture surgery (17703 patients with POD and 86869 patients without POD) and the incidence of POD was 16.93%. A total of 14 risk factors, classified into two categories which were individual as well as anesthetic and operative factors, were identified originally, which included age (weight mean difference [WMD]:2.33;95% confidential interval [CI]: 1.64-3.03), sex (RR: 0.89; 95% CI:0.85-0.93), American society of Anesthesiologists classification(RR:0.56; 95%CI:0.51-0.59), body mass index (WMD:-0.62; 95%CI:-0.81 to -0.44), function dependency(RR:1.52; 95% CI:1.24-1.87), visual impairment (RR:1.62; 95% CI: 1.16-2.27), smoking (RR:0.86; 95% CI:0.79-0.94), preoperative delirium (RR: 2.71; 95% CI: 2.50-2.72), dementia (RR:2.60; 95% CI:2.50-2.72), hypertension (RR: 1.10; 95% CI:1.04-1.15), chronic obstructive pulmonary disease (RR:1.08; 95% CI: 1.01-1.16), regional anesthesia (RR:1.20; 95% CI: 1.01-1.43), transfusion (RR: 1.41; 95% CI: 1.22-1.63), and elective surgery (RR: 0.91; 95% CI: 0.84-0.99).
CONCLUSIONS
Patients possessed above risk factors might be high-risk patients. Clinician should maintain keen vigilance at those patients.
Topics: Blood Transfusion; Delirium; Hip Fractures; Humans; Incidence; Postoperative Complications; Risk Factors
PubMed: 32833302
DOI: 10.1002/gps.5408 -
Annals of Internal Medicine Oct 2019Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are...
BACKGROUND
Delirium is common in hospitalized patients and is associated with worse outcomes. Antipsychotics are commonly used; however, the associated benefits and harms are unclear.
PURPOSE
To conduct a systematic review evaluating the benefits and harms of antipsychotics to treat delirium in adults.
DATA SOURCES
PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception to July 2019 without language restrictions.
STUDY SELECTION
Randomized controlled trials (RCTs) of antipsychotic versus placebo or another antipsychotic, and prospective observational studies reporting harms.
DATA EXTRACTION
One reviewer extracted data and assessed strength of evidence (SOE) for critical outcomes, with confirmation by another reviewer. Risk of bias was assessed independently by 2 reviewers.
DATA SYNTHESIS
Across 16 RCTs and 10 observational studies of hospitalized adults, there was no difference in sedation status (low and moderate SOE), delirium duration, hospital length of stay (moderate SOE), or mortality between haloperidol and second-generation antipsychotics versus placebo. There was no difference in delirium severity (moderate SOE) and cognitive functioning (low SOE) for haloperidol versus second-generation antipsychotics, with insufficient or no evidence for antipsychotics versus placebo. For direct comparisons of different second-generation antipsychotics, there was no difference in mortality and insufficient or no evidence for multiple other outcomes. There was little evidence demonstrating neurologic harms associated with short-term use of antipsychotics for treating delirium in adult inpatients, but potentially harmful cardiac effects tended to occur more frequently.
LIMITATIONS
Heterogeneity was present in terms of dose and administration route of antipsychotics, outcomes, and measurement instruments. There was insufficient or no evidence regarding multiple clinically important outcomes.
CONCLUSION
Current evidence does not support routine use of haloperidol or second-generation antipsychotics to treat delirium in adult inpatients.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).
Topics: Antipsychotic Agents; Cognition; Delirium; Electrocardiography; Haloperidol; Heart; Hospital Mortality; Hospitalization; Humans; Length of Stay; Observational Studies as Topic; Palliative Care; Randomized Controlled Trials as Topic; Severity of Illness Index; Time Factors
PubMed: 31476770
DOI: 10.7326/M19-1860