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CMAJ : Canadian Medical Association... Nov 2023
Topics: Humans; Nuclear Family; Spouses; Patients; Delirium
PubMed: 37984931
DOI: 10.1503/cmaj.230833-f -
Drug Design, Development and Therapy 2023This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effect of Low-Dose Esketamine on Postoperative Neurocognitive Dysfunction in Elderly Patients Undergoing General Anesthesia for Gastrointestinal Tumors: A Randomized Controlled Trial.
PURPOSE
This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients undergoing general anesthesia for gastrointestinal tumors.
METHODS
Sixty-eight elderly patients were randomly allocated to two groups: the esketamine group (group Es) (0.25 mg/kg loading, 0.125mg/kg/h infusion) and the control group (group C) (received normal saline). The primary outcome was the incidence of delayed neurocognitive recovery (DNR). The secondary outcomes were intraoperative blood loss, the total amount of fluid given during surgery, propofol and remifentanil consumption, cardiovascular adverse events, use of vasoactive drugs, operating and anesthesia time, the number of cases of sufentanil remedial analgesia, the incidence of postoperative delirium (POD), the intraoperative hemodynamics, bispectral index (BIS) value at 0, 1, 2 h after operation and numeric rating scale (NRS) pain scores within 3 d after surgery.
RESULTS
The incidence of DNR in group Es (16.13%) was lower than in group C (38.71%) ( <0.05). The intraoperative remifentanil dosage and the number of cases of dopamine used in group Es were lower than in group C ( <0.05). Compared with group C, DBP was higher at 3 min after intubation, and MAP was lower at 30 min after extubation in group Es (0.05). The incidence of hypotension and tachycardia in group Es was lower than in group C (0.05). The NRS pain score at 3 d after surgery in group Es was lower than in group C ( 0.05).
CONCLUSION
Low-dose esketamine infusion reduced to some extent the incidence of DNR in elderly patients undergoing general anesthesia for gastrointestinal tumors, improved intraoperative hemodynamics and BIS value, decreased the incidence of cardiovascular adverse events and the intraoperative consumption of opioids, and relieved postoperative pain.
Topics: Humans; Aged; Remifentanil; Anesthesia, General; Delirium; Pain, Postoperative; Gastrointestinal Neoplasms
PubMed: 37408867
DOI: 10.2147/DDDT.S406568 -
Annals of Surgery Dec 2023The aim was to determine preoperative gut microbiota metabolites that may be associated with postoperative delirium (POD) development in patients and further study in... (Observational Study)
Observational Study
OBJECTIVE
The aim was to determine preoperative gut microbiota metabolites that may be associated with postoperative delirium (POD) development in patients and further study in rodents.
SUMMARY BACKGROUND DATA
POD occurs in 9% to 50% of older patients undergoing anesthesia/surgery but lacks effective treatments or prevention. High-throughput metabolomics using liquid chromatography with tandem mass spectrometry has accelerated disease-related biomarkers discovery. We performed metabolomic studies in humans to identify potential metabolite biomarkers linked to POD and examined potential mechanisms in rodents.
METHODS
We performed a prospective observational cohort study to examine the metabolomic changes that were associated with the development of POD. Then the gut microbiota-related metabolomic changes were recapitulated by gut microbiota perturbation in rodents. POD was assessed in mice using a battery of behavioral tests including novel objective test, Y-maze test, open-field test, and buried food test. The mechanisms through which gut microbiota-related metabolomic changes influenced POD were examined using chemogenetics.
RESULTS
Indole-3-propionic acid (IPA) is a gut microbiota metabolite that belongs to the indole family. Baseline plasma levels of IPA were significantly inversely correlated with the onset of POD in 103 (17 cases) human individuals. This relationship was validated in preclinical mouse models for POD: reducing IPA levels through gut microbiota perturbation promoted POD-like behavior. More importantly, IPA administration deterred POD-like behavior. Colonization of germ-free mice with mutant Clostridium sporogenes that did not produce IPA-promoted POD-like behavior. Chemogenetic studies revealed that the protective effect of IPA in mice was mediated, in part, by peroxisome proliferator-activated receptor gamma coactivator 1-alpha in hippocampal interneurons.
CONCLUSIONS
Gut microbiota-derived IPA is an important molecule implicated in the pathogenesis of POD, which could potentially be harnessed for POD prevention.
Topics: Humans; Mice; Animals; Gastrointestinal Microbiome; Emergence Delirium; Prospective Studies; Indoles; Biomarkers
PubMed: 37185230
DOI: 10.1097/SLA.0000000000005886 -
Zoological Research Jul 2023Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia. However, given...
Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia. However, given its inherent complexity, few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive. Here, we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors, including anesthesia with surgery (AS), systemic inflammation, and neurotransmission modulation. We found that both bacterial lipopolysaccharide (LPS) and cholinergic receptor antagonist scopolamine (Scop) induction reduced neuronal activities in the delirium-related brain network, with the latter presenting a similar pattern of reduction as found in delirium patients. Consistently, Scop injection resulted in reversible cognitive impairment with hyperactive behavior. No loss of cholinergic neurons was found with treatment, but hippocampal synaptic functions were affected. These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.
Topics: Animals; Mice; Scopolamine; Brain Diseases; Brain; Cognitive Dysfunction; Delirium
PubMed: 37313848
DOI: 10.24272/j.issn.2095-8137.2022.473 -
Clinics in Geriatric Medicine Nov 2023This article covers the epidemiology of delirium and the overlapping condition of altered mental status and encephalopathy that is relevant to those who practice in the... (Review)
Review
This article covers the epidemiology of delirium and the overlapping condition of altered mental status and encephalopathy that is relevant to those who practice in the emergency department.
Topics: Humans; Delirium; Emergency Service, Hospital
PubMed: 37798064
DOI: 10.1016/j.cger.2023.05.006 -
International Psychogeriatrics Aug 2023We examined whether preadmission history of depression is associated with less delirium/coma-free (DCF) days, worse 1-year depression severity and cognitive impairment.
OBJECTIVES
We examined whether preadmission history of depression is associated with less delirium/coma-free (DCF) days, worse 1-year depression severity and cognitive impairment.
DESIGN AND MEASUREMENTS
A health proxy reported history of depression. Separate models examined the effect of preadmission history of depression on: (a) intensive care unit (ICU) course, measured as DCF days; (b) depression symptom severity at 3 and 12 months, measured by the Beck Depression Inventory-II (BDI-II); and (c) cognitive performance at 3 and 12 months, measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) global score.
SETTING AND PARTICIPANTS
Patients admitted to the medical/surgical ICU services were eligible.
RESULTS
Of 821 subjects eligible at enrollment, 261 (33%) had preadmission history of depression. After adjusting for covariates, preadmission history of depression was not associated with less DCF days (OR 0.78, 95% CI, 0.59-1.03 = 0.077). A prior history of depression was associated with higher BDI-II scores at 3 and 12 months (3 months OR 2.15, 95% CI, 1.42-3.24 = <0.001; 12 months OR 1.89, 95% CI, 1.24-2.87 = 0.003). We did not observe an association between preadmission history of depression and cognitive performance at either 3 or 12 months (3 months beta coefficient -0.04, 95% CI, -2.70-2.62 = 0.97; 12 months 1.5, 95% CI, -1.26-4.26 = 0.28).
CONCLUSION
Patients with a depression history prior to ICU stay exhibit a greater severity of depressive symptoms in the year after hospitalization.
Topics: Humans; Delirium; Depression; Prospective Studies; Risk Factors; Intensive Care Units; Cognition
PubMed: 34763741
DOI: 10.1017/S1041610221002556 -
Alzheimer's & Dementia : the Journal of... Jan 2024Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium...
BACKGROUND
Delirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology.
METHODS
The Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts.
RESULTS
Meeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations.
DISCUSSION
The DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes.
HIGHLIGHTS
Delirium features must be clearly defined, standardized, and operationalized. Large datasets incorporating both clinical and biomarker variables should be analyzed together. Delirium screening should incorporate communication and reasoning.
Topics: Humans; Delirium; Research Design; Data Collection; Diagnostic and Statistical Manual of Mental Disorders
PubMed: 37522255
DOI: 10.1002/alz.13419 -
Critical Care (London, England) Nov 2023Despite the extensive volume of research published on checklists in the intensive care unit (ICU), no review has been published on the broader role of checklists within... (Review)
Review
BACKGROUND
Despite the extensive volume of research published on checklists in the intensive care unit (ICU), no review has been published on the broader role of checklists within the intensive care unit, their implementation and validation, and the recommended clinical context for their use. Accordingly, a scoping review was necessary to map the current literature and to guide future research on intensive care checklists. This review focuses on what checklists are currently used, how they are used, process of checklist development and implementation, and outcomes associated with checklist use.
METHODS
A systematic search of MEDLINE (Ovid), Embase, Scopus, and Google Scholar databases was conducted, followed by a grey literature search. The abstracts of the identified studies were screened. Full texts of relevant articles were reviewed, and the references of included studies were subsequently screened for additional relevant articles. Details of the study characteristics, study design, checklist intervention, and outcomes were extracted.
RESULTS
Our search yielded 2046 studies, of which 167 were selected for further analysis. Checklists identified in these studies were categorised into the following types: rounding checklists; delirium screening checklists; transfer and handover checklists; central line-associated bloodstream infection (CLABSI) prevention checklists; airway management checklists; and other. Of 72 significant clinical outcomes reported, 65 were positive, five were negative, and two were mixed. Of 122 significant process of care outcomes reported, 114 were positive and eight were negative.
CONCLUSIONS
Checklists are commonly used in the intensive care unit and appear in many clinical guidelines. Delirium screening checklists and rounding checklists are well implemented and validated in the literature. Clinical and process of care outcomes associated with checklist use are predominantly positive. Future research on checklists in the intensive care unit should focus on establishing clinical guidelines for checklist types and processes for ongoing modification and improvements using post-intervention data.
Topics: Humans; Checklist; Critical Care; Delirium; Intensive Care Units
PubMed: 38037056
DOI: 10.1186/s13054-023-04758-2 -
Annals of Neurology Dec 2023Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative...
OBJECTIVE
Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.
METHODS
Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery. Blood-brain barrier dysfunction was assessed using the cerebrospinal fluid-to-plasma albumin ratio (CPAR).
RESULTS
Of 207 patients (median age = 68 years, 45% female) with complete CPAR and delirium data, 26 (12.6%) developed postoperative delirium. Overall, CPAR increased from before to 24 hours after surgery (median change = 0.28, interquartile range [IQR] = -0.48 to 1.24, Wilcoxon p = 0.001). Preoperative to 24 hours postoperative change in CPAR was greater among patients who developed delirium versus those who did not (median [IQR] = 1.31 [0.004 to 2.34] vs 0.19 [-0.55 to 1.08], p = 0.003). In a multivariable model adjusting for age, baseline cognition, and surgery type, preoperative to 24 hours postoperative change in CPAR was independently associated with delirium occurrence (per CPAR increase of 1, odds ratio = 1.30, 95% confidence interval [CI] = 1.03-1.63, p = 0.026) and increased hospital length of stay (incidence rate ratio = 1.15, 95% CI = 1.09-1.22, p < 0.001).
INTERPRETATION
Postoperative increases in blood-brain barrier permeability are independently associated with increased delirium rates and postoperative hospital length of stay. Although these findings do not establish causality, studies are warranted to determine whether interventions to reduce postoperative blood-brain barrier dysfunction would reduce postoperative delirium rates and hospital length of stay. ANN NEUROL 2023;94:1024-1035.
Topics: Humans; Female; Aged; Male; Delirium; Blood-Brain Barrier; Postoperative Complications; Emergence Delirium; Risk Factors; Organometallic Compounds
PubMed: 37615660
DOI: 10.1002/ana.26771 -
JAMA Network Open Aug 2023The COVID-19 pandemic caused large disruptions to health care for hospitalized older adults. The incidence and management of delirium may have been affected by high...
IMPORTANCE
The COVID-19 pandemic caused large disruptions to health care for hospitalized older adults. The incidence and management of delirium may have been affected by high rates of COVID-19 infection, staffing shortages, overwhelmed hospital capacity, and changes to visitor policies.
OBJECTIVE
To measure changes in rates of delirium and related medication prescribing during the COVID-19 pandemic among hospitalized older adults.
DESIGN, SETTING, AND PARTICIPANTS
This population-based, repeated cross-sectional study used linked databases to measure rates of delirium and related medication prescriptions among adults aged 66 years or older hospitalized before and during the COVID-19 pandemic (January 1, 2017, to March 31, 2022) in Ontario, Canada.
EXPOSURE
The first 2 years of the COVID-19 pandemic (March 1, 2020, to March 31, 2022).
MAIN OUTCOMES AND MEASURES
The main outcomes were weekly rates of delirium per 1000 admitted population and monthly rates of new antipsychotic and benzodiazepine prescriptions per 1000 discharged population. Observed rates were compared with projected rates based on modeling from 3 years before pandemic onset.
RESULTS
Among 2 128 411 hospitalizations of older adults over the 5-year study period (50.7% female; mean [SD] age, 78.9 [8.3] years), absolute rates of delirium increased from 35.9 per 1000 admitted population during the prepandemic period to 41.5 per 1000 admitted population throughout the pandemic. The adjusted rate ratio (ARR) of delirium during the pandemic compared with the projected rate was 1.15 (95% CI, 1.11-1.19). Monthly rates of new antipsychotic prescriptions increased from 6.9 to 8.8 per 1000 discharged population and new benzodiazepine prescriptions from 4.4 to 6.0 per 1000 discharged population and were significantly higher during the pandemic compared with projected rates (antipsychotics: ARR, 1.28; 95% CI, 1.19-1.38; benzodiazepines: ARR, 1.37; 95% CI, 1.20-1.57). Rates were highest during pandemic waves 1 (March to June 2020), 3 (March to June 2021), and 5 (December 2021 to February 2022) and remained elevated above projected levels throughout the first 2 years of the pandemic.
CONCLUSIONS AND RELEVANCE
In this repeated cross-sectional study of hospitalized older adults, there was a temporal association between COVID-19 pandemic onset and significant increases in rates of delirium in the hospital and new antipsychotic and benzodiazepine prescriptions after hospital discharge. Rates remained elevated over 2 years. Pandemic-related changes such as visitor restrictions, staff shortages, isolation practices, and reduced staff time at the bedside may have contributed to these trends.
Topics: Humans; Female; Aged; Male; Benzodiazepines; COVID-19; Antipsychotic Agents; Pandemics; Cross-Sectional Studies; Ontario; Delirium
PubMed: 37548976
DOI: 10.1001/jamanetworkopen.2023.27750