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JAMA Oct 2023Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been...
IMPORTANCE
Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial.
OBJECTIVE
To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction.
DESIGN, SETTING, AND PARTICIPANTS
The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022.
INTERVENTIONS
Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam.
MAIN OUTCOMES AND MEASURES
The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days.
RESULTS
There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]).
CONCLUSIONS AND RELEVANCE
Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05094154.
Topics: Humans; Adult; Female; Middle Aged; Male; Anti-Bacterial Agents; Cefepime; Coma; Piperacillin; Drug Therapy, Combination; Retrospective Studies; Piperacillin, Tazobactam Drug Combination; Sepsis; Acute Kidney Injury; Kidney; Delirium
PubMed: 37837651
DOI: 10.1001/jama.2023.20583 -
European Journal of Anaesthesiology Feb 2024Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role...
Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role in its management. This update to the 2017 ESAIC Guideline on the prevention of POD is evidence-based and consensus-based and considers the literature between 01 April 2015, and 28 February 2022. The search terms of the broad literature search were identical to those used in the first version of the guideline published in 2017. POD was defined in accordance with the DSM-5 criteria. POD had to be measured with a validated POD screening tool, at least once per day for at least 3 days starting in the recovery room or postanaesthesia care unit on the day of surgery or, at latest, on postoperative day 1. Recent literature confirmed the pathogenic role of surgery-induced inflammation, and this concept reinforces the positive role of multicomponent strategies aimed to reduce the surgical stress response. Although some putative precipitating risk factors are not modifiable (length of surgery, surgical site), others (such as depth of anaesthesia, appropriate analgesia and haemodynamic stability) are under the control of the anaesthesiologists. Multicomponent preoperative, intra-operative and postoperative preventive measures showed potential to reduce the incidence and duration of POD, confirming the pivotal role of a comprehensive and team-based approach to improve patients' clinical and functional status.
Topics: Adult; Humans; Emergence Delirium; Anesthesiology; Postoperative Complications; Delirium; Consensus; Critical Care; Risk Factors
PubMed: 37599617
DOI: 10.1097/EJA.0000000000001876 -
Anesthesiology Dec 2023Processed electroencephalography (EEG) is used to monitor the level of anesthesia, and it has shown the potential to predict the occurrence of delirium. While emergence...
BACKGROUND
Processed electroencephalography (EEG) is used to monitor the level of anesthesia, and it has shown the potential to predict the occurrence of delirium. While emergence trajectories of relative EEG band power identified post hoc show promising results in predicting a risk for a delirium, they are not easily transferable into an online predictive application. This article describes a low-resource and easily applicable method to differentiate between patients at high risk and low risk for delirium, with patients at low risk expected to show decreasing EEG power during emergence.
METHODS
This study includes data from 169 patients (median age, 61 yr [49, 73]) who underwent surgery with general anesthesia maintained with propofol, sevoflurane, or desflurane. The data were derived from a previously published study. The investigators chose a single frontal channel, calculated the total and spectral band power from the EEG and calculated a linear regression model to observe the parameters' change during anesthesia emergence, described as slope. The slope of total power and single band power was correlated with the occurrence of delirium.
RESULTS
Of 169 patients, 32 (19%) showed delirium. Patients whose total EEG power diminished the most during emergence were less likely to screen positive for delirium in the postanesthesia care unit. A positive slope in total power and band power evaluated by using a regression model was associated with a higher risk ratio (total, 2.83 [95% CI, 1.46 to 5.51]; alpha/beta band, 7.79 [95% CI, 2.24 to 27.09]) for delirium. Furthermore, a negative slope in multiple bands during emergence was specific for patients without delirium and allowed definition of a test for patients at low risk.
CONCLUSIONS
This study developed an easily applicable exploratory method to analyze a single frontal EEG channel and to identify patterns specific for patients at low risk for delirium.
Topics: Humans; Middle Aged; Anesthesia Recovery Period; Anesthesia, General; Delirium; Propofol; Sevoflurane; Electroencephalography
PubMed: 37616326
DOI: 10.1097/ALN.0000000000004754 -
International Journal of Nursing Studies Dec 2023As advanced age is a major risk factor for confusion status, delirium has become prevalent in the older population, contributing to longer hospital stays, cognitive... (Review)
Review
BACKGROUND
As advanced age is a major risk factor for confusion status, delirium has become prevalent in the older population, contributing to longer hospital stays, cognitive impairment, and higher risks of complications and mortality. Compared with pharmacological methods, non-pharmacological interventions are preferred and are recommended by the National Institute for Health and Care Excellence for the prevention of delirium. Numerous systematic reviews and meta-analyses have been carried out to investigate the effects of non-pharmacological interventions. However, the outcomes were diverse and the quality varied widely, making it challenging to draw firm conclusions from the evidence.
OBJECTIVE
To summarize the contents and evaluate the effects of non-pharmacological interventions to prevent and treat delirium among older people.
DESIGN
Overview of systematic reviews.
METHODS
A comprehensive literature search was conducted in Medline, Cochrane Library, EMBASE, CINAHL, PsycINFO, JBI EBP Database, China's SinoMed, CNKI, and Wangfang databases from inception to 2nd December 2022. Two reviewers performed the study selection, quality appraisal, and data extraction independently. The AMSTAR 2 tool was used to appraise the methodological quality of eligible reviews. The results were presented in narrative synthesis based on types of intervention, including multicomponent and single-component interventions.
RESULTS
Twenty-four systematic reviews were included in this overview, of which four reviews were of high quality. Multicomponent interventions were the most widely disseminated non-pharmacological strategy, which were effective in preventing delirium with 27 %-54 % reduction in delirium incidence. Additionally, the multicomponent strategy also reduced the incidence of falls and pressure ulcers, and showed trends toward shortening the length of stay and improving cognitive function. Among single-component interventions, physical training, geriatric risk assessment, and reorientation protocol revealed positive effects in delirium prevention. However, the effectiveness of non-pharmacological interventions for treating delirium was limited, and while multicomponent methods had inconsistent impacts on the duration and severity of delirium, single-component methods showed no significant impact.
CONCLUSION
Non-pharmacological interventions are effective in reducing the incidence of delirium and improving other health outcomes among older patients. However, the effects on the duration and severity of delirium need more evidence to confirm.
REGISTRATION NUMBER
CRD42022376651 in PROSPERO.
Topics: Humans; Aged; Delirium; Systematic Reviews as Topic; Risk Factors; Length of Stay; Accidental Falls
PubMed: 37826889
DOI: 10.1016/j.ijnurstu.2023.104584 -
Journal of Affective Disorders Oct 2023Major depression (MD) is a well-recognized risk factor for delirium. However, observational studies cannot provide direct evidence of causality between MD and delirium.
BACKGROUND
Major depression (MD) is a well-recognized risk factor for delirium. However, observational studies cannot provide direct evidence of causality between MD and delirium.
METHODS
This study explored the genetic causal association between MD and delirium using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for MD were obtained from the UK Biobank. GWAS summary data for delirium were obtained from the FinnGen Consortium. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were used to perform the MR analysis. In addition, the Cochrane's Q test was used to detect heterogeneity in the MR results. Horizontal pleiotropy was detected using the MR-Egger intercept test and MR pleiotropy residual sum and outliers (MR-PRESSO) test. Leave-one-out analysis was used to investigate the sensitivity of this association.
RESULTS
The IVW method showed that MD was an independent risk factor for delirium (P = 0.013). Horizontal pleiotropy was unlikely to bias causality (P > 0.05), and no evidence of heterogeneity was found between the genetic variants (P > 0.05). Finally, a leave-one-out test showed that this association was stable and robust.
LIMITATIONS
All participants included in the GWAS were of European ancestry. Due to database limitations, the MR analysis did not conduct stratified analyses for different countries, ethnicities, or age groups.
CONCLUSION
We conducted a two-sample MR analysis and found the evidence of genetic causal association between MD and delirium.
Topics: Humans; Depressive Disorder, Major; Mendelian Randomization Analysis; Depression; Genome-Wide Association Study; Delirium
PubMed: 37244544
DOI: 10.1016/j.jad.2023.05.046 -
Anesthesiology Apr 2024The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium....
BACKGROUND
The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium.
METHODS
A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied.
RESULTS
Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each μg/kg increase in the cumulative phenylephrine dose).
CONCLUSIONS
The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.
Topics: Adult; Humans; Phenylephrine; Ephedrine; Vasoconstrictor Agents; Emergence Delirium; Retrospective Studies; Hypotension
PubMed: 37725759
DOI: 10.1097/ALN.0000000000004774 -
British Journal of Anaesthesia Aug 2023Metabolic syndrome and its components are risk factors for cognitive impairment, but their contribution to perioperative neurocognitive disorders is unknown. We examined...
BACKGROUND
Metabolic syndrome and its components are risk factors for cognitive impairment, but their contribution to perioperative neurocognitive disorders is unknown. We examined their associations with the risk of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in older patients.
METHODS
In 765 male and female participants aged ≥65 years, we measured preoperative metabolic parameters and screened for POD for 7 days or until discharge. POCD was defined through comparison of cognitive change on six neuropsychological tests with non-surgical controls. Multiple logistic regression analyses examined the association of metabolic parameters with risk of POD and POCD with adjustment for age, sex, and surgery type.
RESULTS
A total of 149 patients (19.5% of 765) developed POD and 53 (10.1% of 520 attendees) had POCD at 3 months. Patients with metabolic syndrome were at 1.85-fold higher risk of POD (95% confidence interval [CI] 1.26-2.70). Each 1 mM higher high-density lipoprotein cholesterol (HDL-C) was associated with a 0.47-fold lower POD risk (95% CI 0.30-0.74). Each 1 kg m higher body mass index (BMI) was associated with a 1.09-fold higher POCD risk (95% CI 1.02- 1.16).
CONCLUSIONS
Older surgical patients with metabolic syndrome were at increased risk of POD. Only reduced HDL-C was significantly associated with POD. For POCD, a higher preoperative BMI was identified as a risk factor. These findings add to mounting evidence of a distinct epidemiology of POD and POCD. Screening programmes taking advantage of HDL-C and BMI measurements and of metabolic interventions in reducing perioperative neurocognitive disorders should be evaluated.
CLINICAL TRIAL REGISTRATION
NCT02265263.
Topics: Humans; Male; Female; Aged; Emergence Delirium; Postoperative Cognitive Complications; Delirium; Metabolic Syndrome; Cohort Studies; Postoperative Complications
PubMed: 37344340
DOI: 10.1016/j.bja.2023.04.031