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British Journal of Anaesthesia Aug 2023Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common... (Meta-Analysis)
Meta-Analysis Review
Effect of perioperative benzodiazepine use on intraoperative awareness and postoperative delirium: a systematic review and meta-analysis of randomised controlled trials and observational studies.
BACKGROUND
Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits.
METHODS
We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality.
RESULTS
We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I=72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I=13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I=35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I=98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality).
CONCLUSIONS
In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine.
SYSTEMATIC REVIEW PROTOCOL
PROSPERO CRD42019128144.
Topics: Humans; Aged; Benzodiazepines; Emergence Delirium; Dexmedetomidine; Intraoperative Awareness; Delirium; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36621439
DOI: 10.1016/j.bja.2022.12.001 -
Addiction (Abingdon, England) Oct 2022There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW.
METHODS
Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs).
RESULTS
Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR, 0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR, 0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR, 0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = -3.69; 95% CI, -6.21 to -1.17), carbamazepine (d = -2.76; 95% CI, -4.13 to -1.40), fixed-schedule oxazepam (d = -2.55; 95% CI, -4.26 to -0.83), and γ-hydroxybutyrate (d = -1.80; 95% CI, -3.35 to -0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision.
CONCLUSIONS
Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.
Topics: Adult; Alcohol Withdrawal Delirium; Alcoholism; Benzodiazepines; Carbamazepine; Diazepam; Female; Humans; Male; Network Meta-Analysis; Seizures; Substance Withdrawal Syndrome
PubMed: 35194860
DOI: 10.1111/add.15853 -
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 -
Intensive & Critical Care Nursing Apr 2022To assess the evidence for the feasibility and effect of patient and familycentred care interventions provided in the intensive care unit, single or multicomponent,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the evidence for the feasibility and effect of patient and familycentred care interventions provided in the intensive care unit, single or multicomponent, versus usual care, for reducing delirium, anxiety, depression and post-traumatic stress disorder in patients and family-members.
DESIGN
A systematic review and meta-analysis following the PRISMA guidelines and GRADE approach. A systematic literature search of relevant databases, screening and inclusion of studies, data extraction and assessment of risk of bias according to Cochrane methodology. The study is preregistered on PROSPERO (CRD42020160768).
SETTING
Adult intensive care units.
RESULTS
Nine randomised controlled trials enrolling a total of 1170 patients and 1226 family-members were included. We found moderate to low certainty evidence indicating no effect of patient and family centred care on delirium, anxiety, depression, post-traumatic stress disorder, in-hospital mortality, intensive care length of stay or family-members' anxiety, depression and post-traumatic stress disorder. No studies looked at the effect of patient and family centred care on pain or cognitive function in patients. Evaluation of feasibility outcomes was scarce. The certainty of the evidence was low to moderate, mainly due to substantial risk of bias in individual studies and imprecision due to few events and small sample size.
CONCLUSION
It remains uncertain whether patient and family centred care compared to usual care may reduce delirium in patients and psychological sequelae of intensive care admission in patients and families due to limited evidence of moderate to low certainty. Lack of systematic process evaluation of intervention feasibility as recommended by the Medical Research Council to identify barriers and facilitators of patient and family centred care in the adult intensive care unit context, further limits the conclusions that can be drawn.
Topics: Adult; Anxiety; Anxiety Disorders; Critical Care; Humans; Intensive Care Units; Stress Disorders, Post-Traumatic
PubMed: 34753631
DOI: 10.1016/j.iccn.2021.103156 -
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 -
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 -
British Journal of Anaesthesia Nov 2022We conducted a systematic review and meta-analysis of contemporary RCTs to determine the clinical effectiveness of spinal vs general anaesthesia (SA vs GA) in patients... (Meta-Analysis)
Meta-Analysis Review
Clinical effectiveness and safety of spinal anaesthesia compared with general anaesthesia in patients undergoing hip fracture surgery using a consensus-based core outcome set and patient-and public-informed outcomes: a systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
We conducted a systematic review and meta-analysis of contemporary RCTs to determine the clinical effectiveness of spinal vs general anaesthesia (SA vs GA) in patients undergoing hip fracture surgery using a consensus-based core outcome set, and outcomes defined as important by patient and public involvement (PPI) initiatives.
METHODS
RCTs comparing any of the core outcomes (mortality, time from injury to surgery, acute coronary syndrome, hypotension, acute kidney injury, delirium, pneumonia, orthogeriatric input, being out of bed at day 1 postoperatively, and pain) or PPI-defined outcomes (return to preoperative residence, quality of life, and mobility status) between SA and GA were identified from MEDLINE, Embase, Cochrane Library, and Web of Science (2000 to February 2022). Pooled relative risks (RRs) and mean differences (95% confidence intervals [CIs]) were estimated.
RESULTS
There was no significant difference in the risk of delirium comparing SA vs GA (RR=1.07; 95% CI, 0.90-1.29). Comparing SA vs GA, the RR for mortality was 0.56 (95% CI, 0.22-1.44) in-hospital, 1.07 (95% CI, 0.52-2.23) at 30 days, and 1.08 (95% CI, 0.55-2.12) at 90 days. Spinal anaesthesia reduced the risk of acute kidney injury compared with GA: RR=0.59 (95% CI, 0.39-0.89). There were no significant differences in the risk of other outcomes. Few studies reported PPI-defined outcomes, with most studies reporting on one to three core outcomes.
CONCLUSIONS
Except for acute kidney injury, there were no differences between SA and GA in hip fracture surgery when using a consensus-based core outcome set and patient and public involvement-defined outcomes. Most studies reported limited outcomes from the core outcome set, and few reported outcomes important to patients, which should be considered when designing future RCTs.
PROSPERO REGISTRATION
CRD42021275206.
Topics: Humans; Anesthesia, Spinal; Consensus; Quality of Life; Postoperative Complications; Anesthesia, General; Hip Fractures; Treatment Outcome; Delirium; Acute Kidney Injury; Randomized Controlled Trials as Topic
PubMed: 36270701
DOI: 10.1016/j.bja.2022.07.031 -
International Journal of Surgery... Sep 2022Randomized trials have shown conflicting results regarding differences in outcomes according to anesthesia type on the prevalence of postoperative delirium (POD) or... (Meta-Analysis)
Meta-Analysis Review
The impact of regional versus general anesthesia on postoperative neurocognitive outcomes in elderly patients undergoing hip fracture surgery: A systematic review and meta-analysis.
BACKGROUND
Randomized trials have shown conflicting results regarding differences in outcomes according to anesthesia type on the prevalence of postoperative delirium (POD) or postoperative cognitive dysfunction (POCD) in hip surgery patients. The aim of this Meta analysis is to compare the effect of general and regional anesthesia in older patients undergoing hip fracture surgery.
METHODS
A literature search for meta-analysis was performed using Pubmed, The Cochrane Library, Embase and Web of Science citation index for randomized controlled trials (RCTs) to compare the regional anesthesia (RA) to general anesthesia (GA) for postoperative outcomes in elderly undergoing hip fracture surgery till June 2022. The primary outcomes were the incidence of POD or POCD at 24 h, 3 days and 7 days postoperatively. The secondary outcomes were 30 days mortality rate and other adverse events. The risk of bias was assessed using the Cochrane methodology.
RESULTS
Eight studies including 3555 elderly patients over 65 years old showed that there was no significant difference in the prevalence of POD or POCD between RA and GA at 24 h [OR 0.73; 95% coincidence interval (CI) 0.19, 2.71, I = 53%; n = 452; P = 0.63], at 3 days [OR 1.03; 95% CI 0.79, 1.35, I = 0%; n = 1362; P = 0.82], at 7 days [OR 0.79; 95% CI 0.41, 1.52, I = 51%; n = 1336; P = 0.47], respectively. No significant differences were observed in the incidence of other adverse events.
CONCLUSIONS
No significant difference was found in the incidence of cognitive dysfunction after either general or regional anesthesia in elderly patients. Our finding of similar outcomes at 24 h, 3 days and 7 days postoperatively with either technique suggests that anesthesia choices for hip-fracture surgery may be based on the individual characteristics of each patient rather than on anticipated differences in clinical outcomes.
Topics: Aged; Anesthesia, General; Delirium; Hip Fractures; Humans; Postoperative Complications; Postoperative Period
PubMed: 36031067
DOI: 10.1016/j.ijsu.2022.106854 -
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