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Anesthesiology Nov 2023
Topics: Humans; Hypnotics and Sedatives; Emergence Delirium; Dexmedetomidine; Delirium; Postoperative Complications
PubMed: 37589555
DOI: 10.1097/ALN.0000000000004659 -
International Journal of Surgery... Nov 2023Surgery induces high rates of cognitive disorders, persisting for up to 12 months in elderly adults. This review aimed to assess the currently debated preventive effect... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surgery induces high rates of cognitive disorders, persisting for up to 12 months in elderly adults. This review aimed to assess the currently debated preventive effect of perioperative ketamine on postoperative delirium and postoperative neurocognitive disorders (POND).
MATERIALS AND METHODS
Systematic review and meta-analysis including all randomized controlled trials investigating the effects of perioperative ketamine administration in adult patients compared to placebo or no intervention on postoperative delirium and/or POND between January 2007 and April 2022. Database searches were conducted in PubMed, Medline, Embase, Scopus, and Central. Random effects models were used to pool overall estimates. The GRADE approach was used to assess the quality of the evidence.
RESULTS
From 1379 records screened, 14 randomized controlled trials with 1618 patients randomized met our inclusion criteria with a high level of consensus among reviewers, amongst whom 50% were at low-moderate risk of bias. There was no between-group difference in postoperative delirium [8 trials, 1265 patients, odds ratio (OR) 0.93, 95% CI (0.51-1.70), I2 =28%] and POND [5 trials, 494 patients, OR 0.52, 95% CI (0.15-1.80); I2 =78%]. There was no significant between-group difference in postoperative psychological adverse effects, level of pain, hospital length of stay, or mortality. Between-group subgroup analyses showed no difference in delirium or POND incidence according to surgical setting, ketamine dose, mode of administration, combination or not with other drug(s), and assessment timing or definition of cognitive disorders.
CONCLUSION
Perioperative ketamine does not prevent postoperative delirium or POND. Significant study heterogeneity suggests that standardized measures for POND assessment and a specific focus on patients at high risk for POND should be used to improve the comparability of future studies.
Topics: Adult; Humans; Aged; Ketamine; Emergence Delirium; Cognition Disorders; Cognitive Dysfunction; Randomized Controlled Trials as Topic
PubMed: 37526094
DOI: 10.1097/JS9.0000000000000619 -
Medicina (Kaunas, Lithuania) Sep 2023Delirium is an acute neurological disorder that involves attention and cognition. It is associated with a high risk of morbidity and mortality among older people (>65... (Review)
Review
Delirium is an acute neurological disorder that involves attention and cognition. It is associated with a high risk of morbidity and mortality among older people (>65 years old). In the context of the Emergency Department (ED), it is frequently experienced by patients but often not recognized. Literature studies have identified some screening instruments for an initial evaluation of delirium. Most of these tools have not been validated yet in the context of emergencies, but, in other settings, they were very useful for assessing and maximizing the recognition of this condition among older patients. We conducted a review of the literature, including randomized control trials, clinical and observational studies, and research studies published in recent years, confirming that most of the screening tools for delirium used in the intensive care unit (ICU) or the geriatric department have not been tested in the ED, and the ideal timing and form of the delirium assessment process for older adults have not been defined yet. The aim of our review is to summarize the updated evidence about the screening tools for delirium in the context of the ED, due to the fact that overcrowding of the ED and the stressful condition of emergency situations (that contribute to the onset of delirium) could expose older patients to a high risk of complications and mortality if delirium is not promptly recognized. In conclusion, we support the evidence that delirium is a current and real condition that emergency physicians have to face daily, and we are aware that more research is needed to explore this field in order to improve the overall outcomes of older patients admitted to the ED.
Topics: Humans; Aged; Emergency Service, Hospital; Awareness; Cognition; Hospitalization; Delirium
PubMed: 37763753
DOI: 10.3390/medicina59091634 -
Therapeutic Advances in... 2023Delirium is a serious consequence of many acute or worsening chronic medical conditions, a side effect of medications, and a precipitant of worsening functional and... (Review)
Review
Delirium is a serious consequence of many acute or worsening chronic medical conditions, a side effect of medications, and a precipitant of worsening functional and cognitive status in older adults. It is a syndrome characterized by fluctuations in cognition and impaired attention that develops over a short period of time in response to an underlying medical condition, a substance (prescribed, over the counter, or recreational), or substance withdrawal and can be multi-factorial. We present a narrative review of the literature on nonpharmacologic and pharmacologic approaches to prevention and treatment of delirium with a focus on older adults as a vulnerable population. Older adult patients are most at risk due to decreasing physiologic reserves, with delirium rates of up to 80% in critical care settings. Presentation of delirium can be hyperactive, hypoactive, or mixed, making identification and study challenging as patients with hypoactive delirium are less likely to come to attention in an inpatient or long-term care setting. Studies of delirium focus on prevention and treatment with nonpharmacological or medication interventions, with the preponderance of evidence favoring multi-component nonpharmacological approaches to prevention as the most effective. Though use of antipsychotic medication in delirium is common, existing evidence does not support routine use, showing no clear benefit in clinically significant outcome measures and with evidence of harm in some studies. We therefore suggest that antipsychotics be used to treat agitation, psychosis, and distress associated with delirium at the lowest effective doses and shortest possible duration and not be considered a treatment of delirium itself. Future studies may clarify the use of other agents, such as melatonin and melatonin receptor agonists, alpha-2 receptor agonists, and anti-epileptics.
PubMed: 37701890
DOI: 10.1177/20451253231198462 -
Journal of Psychiatry & Neuroscience :... 2023Delirium is a critically underdiagnosed syndrome of altered mental status affecting more than 50% of older adults admitted to hospital. Few studies have incorporated...
BACKGROUND
Delirium is a critically underdiagnosed syndrome of altered mental status affecting more than 50% of older adults admitted to hospital. Few studies have incorporated speech and language disturbance in delirium detection. We sought to describe speech and language disturbances in delirium, and provide a proof of concept for detecting delirium using computational speech and language features.
METHODS
Participants underwent delirium assessment and completed language tasks. Speech and language disturbances were rated using standardized clinical scales. Recordings and transcripts were processed using an automated pipeline to extract acoustic and textual features. We used binomial, elastic net, machine learning models to predict delirium status.
RESULTS
We included 33 older adults admitted to hospital, of whom 10 met criteria for delirium. The group with delirium scored higher on total language disturbances and incoherence, and lower on category fluency. Both groups scored lower on category fluency than the normative population. Cognitive dysfunction as a continuous measure was correlated with higher total language disturbance, incoherence, loss of goal and lower category fluency. Including computational language features in the model predicting delirium status increased accuracy to 78%.
LIMITATIONS
This was a proof-of-concept study with limited sample size, without a set-aside cross-validation sample. Subsequent studies are needed before establishing a generalizable model for detecting delirium.
CONCLUSION
Language impairments were elevated among patients with delirium and may also be used to identify subthreshold cognitive disturbances. Computational speech and language features are promising as accurate, noninvasive and efficient biomarkers of delirium.
Topics: Humans; Aged; Speech; Language; Cognitive Dysfunction; Delirium
PubMed: 37402579
DOI: 10.1503/jpn.230026 -
BMC Neurology Oct 2023Postoperative delirium (POD) is a frequent neurologic dysfunction that often leads to more negative outcomes. Early identification of patients who are vulnerable to POD... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative delirium (POD) is a frequent neurologic dysfunction that often leads to more negative outcomes. Early identification of patients who are vulnerable to POD and early implementation of appropriate management strategies could decrease its occurrence and improve patient prognosis. Therefore, this meta-analysis comprehensively and quantitatively summarized the prevalence and related predictive factors of POD in head and neck cancer surgical patients.
METHODS
PubMed, Embase, and Cochrane Library were searched for observational studies that reported the prevalence and risk factors for POD after head and neck cancer surgery and were published from their inception until December 31, 2022. Two reviewers independently selected qualified articles and extracted data. The qualities of related papers were assessed using the Newcastle-Ottawa scale (NOS). RevMan 5.3 and Stata 15.0 were applied to analysis the data and conduct the meta-analysis.
RESULTS
Sixteen observational studies with 3289 inpatients who underwent head and neck cancer surgery were included in this review. The occurrence of POD ranged from 4.2 to 36.9%, with a pooled incidence of 20% (95% CI 15-24%, I = 93.2%). The results of this pooled analysis demonstrated that the statistically significant risk factors for POD were increased age (OR: 1.05, 95% CI: 1.03-1.07, P < 0.001), age > 75 years (OR: 6.52, 95% CI: 3.07-13.87, P < 0.001), male sex (OR: 2.29, 95% CI: 1.06-4.97, P = 0.04), higher American Society of Anesthesiologists grade (OR: 2.19, 95% CI: 1.44-3.33, P < 0.001), diabetes mellitus (OR: 2.73, 95% CI: 1.24-6.01, P = 0.01), and history of smoking (OR: 2.74, 95% CI: 1.13-6.65, P = 0.03).
CONCLUSIONS
POD frequently occurs after head and neck cancer surgery. Several independent predictors for POD were identified, which might contribute to identifying patients at high risk for POD and play a prominent role in preventing POD in patients following head and neck cancer surgery.
Topics: Humans; Male; Aged; Emergence Delirium; Delirium; Postoperative Complications; Incidence; Risk Factors; Head and Neck Neoplasms
PubMed: 37848819
DOI: 10.1186/s12883-023-03418-w -
Presence of Preoperative Neurodegeneration Biofluid Markers in Patients with Postoperative Delirium.Anesthesiology Oct 2023The pathophysiology of delirium is incompletely understood, including what molecular pathways are involved in brain vulnerability to delirium. This study examined...
BACKGROUND
The pathophysiology of delirium is incompletely understood, including what molecular pathways are involved in brain vulnerability to delirium. This study examined whether preoperative plasma neurodegeneration markers were elevated in patients who subsequently developed postoperative delirium through a retrospective case-control study.
METHODS
Inclusion criteria were patients of 65 yr of age or older, undergoing elective noncardiac surgery with a hospital stay of 2 days or more. Concentrations of preoperative plasma P-Tau181, neurofilament light chain, amyloid β1-42 (Aβ42), and glial fibrillary acidic protein were measured with a digital immunoassay platform. The primary outcome was postoperative delirium measured by the Confusion Assessment Method. The study included propensity score matching by age and sex with nearest neighbor, such that each patient in the delirium group was matched by age and sex with a patient in the no-delirium group.
RESULTS
The initial cohort consists of 189 patients with no delirium and 102 patients who developed postoperative delirium. Of 291 patients aged 72.5 ± 5.8 yr, 50.5% were women, and 102 (35%) developed postoperative delirium. The final cohort in the analysis consisted of a no-delirium group (n = 102) and a delirium group (n = 102) matched by age and sex using the propensity score method. Of the four biomarkers assayed, the median value for neurofilament light chain was 32.05 pg/ml for the delirium group versus 23.7 pg/ml in the no-delirium group. The distribution of biomarker values significantly differed between the delirium and no-delirium groups (P = 0.02 by the Kolmogorov-Smirnov test) with the largest cumulative probability difference appearing at the biomarker value of 32.05 pg/ml.
CONCLUSIONS
These results suggest that patients who subsequently developed delirium are more likely to be experiencing clinically silent neurodegenerative changes before surgery, reflected by changes in plasma neurofilament light chain biomarker concentrations, which may identify individuals with a preoperative vulnerability to subsequent cognitive decline.
Topics: Humans; Female; Male; Emergence Delirium; Retrospective Studies; Case-Control Studies; Postoperative Complications; Biomarkers
PubMed: 37364279
DOI: 10.1097/ALN.0000000000004666 -
Molecular Psychiatry Nov 2023Neuroinflammatory disorders preferentially impair the higher cognitive and executive functions of the prefrontal cortex (PFC). This includes such challenging disorders... (Review)
Review
Neuroinflammatory disorders preferentially impair the higher cognitive and executive functions of the prefrontal cortex (PFC). This includes such challenging disorders as delirium, perioperative neurocognitive disorder, and the sustained cognitive deficits from "long-COVID" or traumatic brain injury. There are no FDA-approved treatments for these symptoms; thus, understanding their etiology is important for generating therapeutic strategies. The current review describes the molecular rationale for why PFC circuits are especially vulnerable to inflammation, and how α2A-adrenoceptor (α2A-AR) actions throughout the nervous and immune systems can benefit the circuits in PFC needed for higher cognition. The layer III circuits in the dorsolateral PFC (dlPFC) that generate and sustain the mental representations needed for higher cognition have unusual neurotransmission and neuromodulation. They are wholly dependent on NMDAR neurotransmission, with little AMPAR contribution, and thus are especially vulnerable to kynurenic acid inflammatory signaling which blocks NMDAR. Layer III dlPFC spines also have unusual neuromodulation, with cAMP magnification of calcium signaling in spines, which opens nearby potassium channels to rapidly weaken connectivity and reduce neuronal firing. This process must be tightly regulated, e.g. by mGluR3 or α2A-AR on spines, to prevent loss of firing. However, the production of GCPII inflammatory signaling reduces mGluR3 actions and markedly diminishes dlPFC network firing. Both basic and clinical studies show that α2A-AR agonists such as guanfacine can restore dlPFC network firing and cognitive function, through direct actions in the dlPFC, but also by reducing the activity of stress-related circuits, e.g. in the locus coeruleus and amygdala, and by having anti-inflammatory actions in the immune system. This information is particularly timely, as guanfacine is currently the focus of large clinical trials for the treatment of delirium, and in open label studies for the treatment of cognitive deficits from long-COVID.
Topics: Humans; Calcium Signaling; Cognitive Dysfunction; Delirium; Guanfacine; Neuroinflammatory Diseases; Post-Acute COVID-19 Syndrome; Prefrontal Cortex
PubMed: 37029295
DOI: 10.1038/s41380-023-02057-4 -
Ageing Research Reviews Jun 2024Delirium is a common condition across different settings and populations. The interventions for preventing and managing this condition are still poorly known. The aim of... (Review)
Review
Delirium is a common condition across different settings and populations. The interventions for preventing and managing this condition are still poorly known. The aim of this umbrella review is to synthesize and grade all preventative and therapeutic interventions for delirium. We searched five databases from database inception up to March 15th, 2023 and we included meta-analyses of randomized controlled trials (RCTs) to decrease the risk of/the severity of delirium. From 1959 records after deduplication, we included 59 systematic reviews with meta-analyses, providing 110 meta-analytic estimates across populations, interventions, outcomes, settings, and age groups (485 unique RCTs, 172,045 participants). In surgery setting, for preventing delirium, high GRADE evidence supported dexmedetomidine (RR=0.53; 95%CI: 0.46-0.67, k=13, N=3988) and comprehensive geriatric assessment (OR=0.46; 95%CI=0.32-0.67, k=3, N=496) in older adults, dexmedetomidine in adults (RR=0.33, 95%CI=0.24-0.45, k=7, N=1974), A2-adrenergic agonists after induction of anesthesia (OR= 0.28, 95%CI= 0.19-0.40, k=10, N=669) in children. High certainty evidence did not support melatonergic agents in older adults for delirium prevention. Moderate certainty supported the effect of dexmedetomidine in adults and children (k=4), various non-pharmacological interventions in adults and older people (k=4), second-generation antipsychotics in adults and mixed age groups (k=3), EEG-guided anesthesia in adults (k=2), mixed pharmacological interventions (k=1), five other specific pharmacological interventions in children (k=1 each). In conclusion, our work indicates that effective treatments to prevent delirium differ across populations, settings, and age groups. Results inform future guidelines to prevent or treat delirium, accounting for safety and costs of interventions. More research is needed in non-surgical settings.
Topics: Humans; Delirium; Dexmedetomidine; Randomized Controlled Trials as Topic
PubMed: 38677599
DOI: 10.1016/j.arr.2024.102313 -
General Hospital Psychiatry 2023ICU delirium reportedly contributes to increased mortality attributed to underlying diseases, long-term cognitive decline, and increased healthcare costs. Dual orexin... (Observational Study)
Observational Study
Evaluation of the delirium preventive effect of dual orexin receptor antagonist (DORA) in critically ill adult patients requiring ventilation with tracheal intubation at an advanced emergency center: A single-center, retrospective, observational study.
OBJECTIVE
ICU delirium reportedly contributes to increased mortality attributed to underlying diseases, long-term cognitive decline, and increased healthcare costs. Dual orexin receptor antagonists (DORAs), suvorexant and lemborexant, have been suggested for preventing ICU delirium. Although ventilator management is a risk factor for delirium, no study has examined the efficacy of suvorexant and lemborexant in preventing delirium in critically ill patients requiring ventilation. Thus, we retrospectively evaluated the efficacy of DORA in preventing delirium in critically ill adult patients requiring ventilatory management in the emergency room.
METHOD
This retrospective study included patients aged ≥18 years who were admitted to the emergency room and received ventilator support between January 2015 and April 2022. The HR (95% CI) for delirium development in patients taking DORA was estimated using a Cox proportional hazards model, which was adjusted for the patient background and concomitant medications. HRs were calculated for patients taking suvorexant and those taking lemborexant using a stratified analysis.
RESULTS
Of the 297 patients included in the study, 67 were in the DORA group; 50 were on suvorexant and 17 were on lemborexant. The DORA group had a lower incidence of delirium than the control group (p < 0.0001). The risk of delirium was lower in the DORA group compared the control group (HR, 0.22; 95% CI 0.12-0.40).The risk of developing delirium was lower with suvorexant (HR 0.22; 95% CI 0.11-0.41) and lemborexant (HR 0.25; 95% CI 0.08-0.81).
CONCLUSION
DORA is a promising drug that could have the potential to prevent delirium, and its efficacy in preventing delirium should be tested in randomized controlled trials in the future.
Topics: Humans; Adult; Adolescent; Orexin Receptor Antagonists; Retrospective Studies; Critical Illness; Delirium; Intubation, Intratracheal
PubMed: 37182281
DOI: 10.1016/j.genhosppsych.2023.03.010