Impact of intraoperative dexmedetomidine on postoperative delirium and pro-inflammatory cytokine levels in elderly patients undergoing thoracolumbar compression fracture surgery: A prospective, randomized, placebo-controlled clinical trial.

BACKGROUND: This study evaluates the efficacy of dexmedetomidine (DEX) in reducing postoperative delirium (POD) and modulating pro-inflammatory cytokines in elderly patients undergoing thoracolumbar compression fracture surgery. METHODS: In this randomized, double-blind, placebo-controlled trial conducted from October 2022 to January 2023 at Anting Hospital in Shanghai, 218 elderly patients were randomized into DEX (n = 110) and normal saline (NS, n = 108) groups. The DEX group received 0.5 µg/kg/h DEX, and delirium incidence was assessed using the Confusion Assessment Method (CAM) on days 1 to 3 post-surgery. Levels of interleukins IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured pre-operation (T0) and on postoperative days 1 (T1) and 3 (T3). Preoperative (T0) and postoperative day 1 (T1) cerebrospinal fluid (CSF) samples were treated with varying concentrations of olanzapine or DEX to observe their regulatory effects on the expression of Phospho-ERK1/2 and Phospho-JNK. RESULTS: Dexmedetomidine significantly lowered the incidence of POD to 18.2%, compared to 30.6% in the NS group (P = .033). While all patients showed an initial increase in cytokine levels after surgery, by T3, IL-6 and TNF-α levels notably decreased in the DEX group, with no significant change in IL-1ß levels across groups. The adverse events rate was similar between groups, demonstrating the safety of DEX in this population. In postoperative CSF samples, treatment with 0.5 mM DEX significantly downregulated Phospho-JNK and upregulated Phospho-ERK1/2 expression, demonstrating a dose-dependent modulation of inflammatory responses. CONCLUSION: Dexmedetomidine is effective in reducing early POD in elderly patients post-thoracolumbar compression fracture surgery. It also decreases IL-6 and TNF-α levels, indicating its potential in managing postoperative inflammatory responses. Treatment with 0.5 mM DEX significantly modulated Phospho-ERK1/2 and Phospho-JNK expressions in postoperative CSF samples, indicating a dose-dependent effect on reducing inflammation. This study contributes to understanding DEX's role in improving postoperative outcomes in elderly patients.

Usefulness of Gabapentin as an Alternative/Adjunct Therapy for Delirium: A Retrospective Observational Study.

BACKGROUND: Antipsychotics are commonly used to treat delirium but can adversely affect the extrapyramidal and cardiac conduction systems. Antipsychotic use has also been reported to be associated with increased mortality in older adults. Therefore, alternative and adjunct medications for delirium are necessary. We retrospectively assessed the efficacy and safety of gabapentin (GBP) as an alternative and adjunct medication for delirium. METHODS: We retrospectively investigated the records of patients with delirium treated with GBP (71 patients; median age, 81 years; interquartile range, 76-87.5 years; 54.9% males) at a general hospital. We examined duration to delirium improvement, as assessed by the Intensive Care Delirium Screening Checklist (ICDSC) and DSM-5 criteria, as well as adverse events. RESULTS: The median (interquartile range) GBP dose was 200 mg (150-350 mg) /day. A total of 71.8% and 85.9% of the patients failed to meet the diagnostic criteria for delirium at 2 days and 5 days after initial administration, respectively (p<0.05). In subgroup analysis, patients with a history of epilepsy or cerebrovascular disease responded better to GBP than did those without such histories, suggesting that patients with abnormal/borderline neuronal activity respond to GBP even though they do not exhibit seizures. GBP did not induce extrapyramidal symptoms, cardiac conduction disturbances, hyperglycemia, or epilepsy but caused sleepiness and myoclonus. CONCLUSIONS: GBP may improve delirium with fewer adverse effects and may be a safe alternative or adjunct treatment for delirium. Dosage adjustment may be necessary to prevent sleepiness.

Tocilizumab is associated with reduced delirium and coma in critically ill patients with COVID-19.

Recent preclinical studies demonstrate a direct pathological role for the interleukin-6 (IL-6) pathway in mediating structural and functional delirium-like phenotypes in animal models of acute lung injury. Tocilizumab, an IL-6 pathway inhibitor, has shown reduced duration of ventilator dependency and mortality in critically ill patients with COVID-19. In this study, we test the hypothesis that tocilizumab is associated with reduced delirium/coma prevalence in critically ill patients with COVID-19. 253 patients were included in the study cohort, 69 in the tocilizumab group and 184 in the historical control group who did not receive tocilizumab. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) with a positive score indicating delirium. Coma was defined as a Richmond Agitation-Sedation Scale score of - 4 or - 5. Tocilizumab was associated with significantly greater number of days alive without delirium/coma (tocilizumab [7 days (IQR: 3-9 days)] vs control [3 days (IQR: 1-8 days)]; p < 0.001). These results remained significant after adjusting for age, sex, sepsis, Charlson Comorbidity Index, Sequential Organ Failure Assessment score, and median daily dose of analgesics/sedatives ( ß ^ = 0.671, p = 0.010). There were no significant differences in mortality ( ß ^ = - 0.204, p = 0.561), ventilator duration ( ß ^ = 0.016, p = 0.956), and ICU or hospital length of stay ( ß ^ = - 0.134, p = 0.603; ß ^ = 0.003, p = 0.991, respectively). Tocilizumab use was associated with significantly increased number of days without delirium/coma. Confirmation of these findings in randomized prospective studies may inform a novel paradigm of pharmacological amelioration of delirium/coma during critical illness.

Efficacy and safety of perioperative melatonin for postoperative delirium in patients undergoing surgery: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). METHODS: We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. RESULTS: In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). CONCLUSION: Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.

Listeria brain abscess: a therapeutically challenging rare presentation of listeriosis.

We report a very rare case of Listeria multiple brain abscesses manifested as delirium, which represented diagnostic and therapeutic challenges overcome only by the close cooperation between Infectious Diseases and Neuroradiology, without which a satisfactory outcome would not be achieved.An elderly man presented with confusion and drowsiness with a background of type-II diabetes mellitus. Although computed tomography of the brain only showed frontal lobe oedema, contrast magnetic resonance (MR) imaging showed numerous irregular rim-enhancing lesions containing central diffusion restriction, suggesting multiple pyogenic cerebral abscesses of unclear aetiology. Thereafter, Listeria monocytogenes was isolated from blood cultures, suggesting this as the causative organism. Deemed unsuitable for neurosurgical drainage, the patient received medical management with a protracted course of antibiotics. This case was extremely challenging, due to 1) the impossibility of source control, 2) the small number of effective antibiotics available to treat this condition, and 3) the inevitable antibiotic side-effects, derived from long-term exposure. A successful outcome was only possible thanks to strict close multidisciplinary follow up, requiring frequent MR imaging and a judicious antibiotic choice, including monitoring of their side-effects. Due to the rarity of this condition, there is lack of guidance on its management, hence the importance of multidisciplinary involvement with very close imaging and antibiotic monitoring.

Comparison of Remimazolam and Propofol on Postoperative Delirium in Elderly Patients Undergoing Radical Resection of Colon Cancer: A Single-Center Prospective Randomized Controlled Study.

BACKGROUND We compared the effect of remimazolam and propofol intravenous anesthesia on postoperative delirium in elderly patients undergoing laparoscopic radical resection of colon cancer. MATERIAL AND METHODS One hundred patients undergoing elective radical operation of colon cancer under general anesthesia were divided into a remimazolam group (group R) and propofol group (group P) by a random number table method. During anesthesia induction and maintenance, group R was intravenously injected with remimazolam to exert sedation; however, in group P, propofol was injected instead of remimazolam. The occurrence of postoperative delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit scale and postoperative pain was assessed with the visual analogue score (VAS). The primary outcome measures were the incidence and duration of delirium within 7 days following surgery. Secondary outcome measures included postoperative VAS scores, intraoperative anesthetic drug dosage, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression. RESULTS There was no significant difference in baseline data between the 2 groups (P>0.05). There was no statistically significant difference in the incidence and duration of postoperative delirium between the 2 groups (P>0.05). There were no significant differences in VAS scores, remifentanil consumption, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression between the 2 groups (P>0.05). CONCLUSIONS In elderly patients undergoing radical colon cancer surgery, remimazolam administration did not improve or aggravate the incidence and duration of delirium, compared with propofol.

Efficacy of melatonin in decreasing the incidence of delirium in critically ill adults: a randomized controlled trial.

OBJECTIVE: To determine whether enteral melatonin decreases the incidence of delirium in critically ill adults. METHODS: In this randomized controlled trial, adults were admitted to the intensive care unit and received either usual standard care alone (Control Group) or in combination with 3mg of enteral melatonin once a day at 9 PM (Melatonin Group). Concealment of allocation was done by serially numbered opaque sealed envelopes. The intensivist assessing delirium and the investigator performing the data analysis were blinded to the group allocation. The primary outcome was the incidence of delirium within 24 hours of the intensive care unit stay. The secondary outcomes were the incidence of delirium on Days 3 and 7, intensive care unit mortality, length of intensive care unit stay, duration of mechanical ventilation and Glasgow outcome score (at discharge). RESULTS: We included 108 patients in the final analysis, with 54 patients in each group. At 24 hours of intensive care unit stay, there was no difference in the incidence of delirium between Melatonin and Control Groups (29.6 versus 46.2%; RR = 0.6; 95%CI 0.38 - 1.05; p = 0.11). No secondary outcome showed a statistically significant difference. CONCLUSION: Enteral melatonin 3mg is not more effective at decreasing the incidence of delirium than standard care is in critically ill adults.

Treatment of Anticholinergic Delirium with Oral Rivastigmine: A Case Report.

BACKGROUND: Anticholinergic toxicity is commonly encountered in the emergency department. However, the availability of physostigmine, a central acetylcholinesterase inhibitor used to reverse anticholinergic delirium, has been significantly limited due to national drug shortages in the United States. Several articles have explored the viability of rivastigmine as an alternative treatment in these patients. CASE REPORT: A 33-year-old man presented to the emergency department after a suspected suicide attempt. The patient was found with an empty bottle of diphenhydramine at the scene. On arrival, he was tachycardic and delirious, with dilated and nonreactive pupils and dry skin. As the clinical picture was highly suggestive of anticholinergic toxicity, the patient was treated with oral rivastigmine at a starting dose of 4.5 mg to reverse his anticholinergic delirium. Although a repeat dose was required, his delirium resolved without recurrence. Why Should an Emergency Physician Be Aware of This? Oral rivastigmine has been applied successfully here and in other case reports to reverse anticholinergic delirium with the benefit of prolonged agitation control. Emergency physicians may consider this medication in consultation with a specialist, with initial doses starting at 4.5-6 mg, if encountering anticholinergic delirium when physostigmine is not available.

Fixed dose ketamine for prehospital management of hyperactive delirium with severe agitation.

INTRODUCTION: Patients exhibiting signs of hyperactive delirium with severe agitation (HDSA) may require sedating medications for stabilization and safe transport to the hospital. Determining the patient's weight and calculating the correct weight-based dose may be challenging in an emergency. A fixed dose ketamine protocol is an alternative to the traditional weight-based administration, which may also reduce dosing errors. The objective of this study was to evaluate the frequency and characteristics of adverse events following pre-hospital ketamine administration for HDSA. METHODS: Emergency Medical Services (EMS) records from four agencies were searched for prehospital ketamine administration. Cases were included if a 250 mg dose of ketamine was administered on standing order to an adult patient for clinical signs consistent with HDSA. Protocols allowed for a second 250 mg dose of ketamine if the first dose was not effective. Both the 250 mg initial dose and the total prehospital dose were analyzed for weight based dosing and adverse events. RESULTS: Review of 132 cases revealed 60 cases that met inclusion criteria. Patients' median weight was 80 kg (range: 50-176 kg). No patients were intubated by EMS, one only requiring suction, three required respiratory support via bag valve mask (BVM). Six (10%) patients were intubated in the emergency department (ED) including the three (5%) supported by EMS via BVM, three (5%) others who were sedated further in the ED prior to requiring intubation. All six patients who were intubated were discharged from the hospital with a Cerebral Performance Category (CPC) 1 score. The weight-based dosing equivalent for the 250 mg initial dose (OR: 2.62, CI: 0.67-10.22) and the total prehospital dose, inclusive of the 12 patients that were administered a second dose, (OR: 0.74, CI: 0.27, 2.03), were not associated with the need for intubation. CONCLUSION: The 250 mg fixed dose of ketamine was not >5 mg/kg weight-based dose equivalent for all patients in this study. Although a second 250 mg dose of ketamine was permitted under standing orders, only 12 (20%) of the patients were administered a second dose, none experienced an adverse event. This indicates that the 250 mg initial dose was effective for 80% of the patients. Four patients with prehospital adverse events likely related to the administration of ketamine were found. One required suction, three (5%) requiring BVM respiratory support by EMS were subsequently intubated upon arrival in the ED. All 60 patients were discharged from the hospital alive. Further research is needed to determine an optimal single administration dose for ketamine in patients exhibiting signs of HDSA, if employing a standardized fixed dose medication protocol streamlines administration, and if the fixed dose medication reduces the occurrence of dosage errors.

A joint frailty model for recurrent and competing terminal events: Application to delirium in the ICU.

Joint models linking longitudinal biomarkers or recurrent event processes with a terminal event, for example, mortality, have been studied extensively. Motivated by studies of recurrent delirium events in patients receiving care in an intensive care unit (ICU), we devise a joint model for a recurrent event process and multiple terminal events. Being discharged alive from the ICU or experiencing mortality may be associated with a patient's hazard of delirium, violating the assumption of independent censoring. Moreover, the direction of the association between the hazards of delirium and mortality may be opposite of the direction of association between the hazards of delirium and ICU discharge. Hence treating either terminal event as independent censoring may bias inferences. We propose a competing joint model that uses a latent frailty to link a patient's recurrent and competing terminal event processes. We fit our model to data from a completed placebo-controlled clinical trial, which studied whether Haloperidol could prevent death and delirium among ICU patients. The clinical trial served as a foundation for a simulation study, in which we evaluate the properties, for example, bias and confidence interval coverage, of the competing joint model. As part of the simulation study, we demonstrate the shortcomings of using a joint model with a recurrent delirium process and a single terminal event to study delirium in the ICU. Lastly, we discuss limitations and possible extensions for the competing joint model. The competing joint model has been added to frailtypack, an R package for fitting an assortment of joint models.

Rivastigmine for the management of anticholinergic delirium.

INTRODUCTION: Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural disturbance. Physostigmine is an effective treatment for anticholinergic delirium, but its availability is limited. As rivastigmine is readily available, it has been used to manage anticholinergic delirium; however, there is limited research investigating its use. METHOD: This was a retrospective review of patients with anticholinergic delirium treated in two toxicology units with rivastigmine (oral capsule or transdermal patch) from January 2019 to June 2023. The primary outcome was the use of further parenteral treatment (sedation or physostigmine) for delirium post rivastigmine administration. RESULTS: Fifty patients were administered rivastigmine for the management of anticholinergic delirium. The median age was 36 years (interquartile range: 25-49 years) and 27 (54 per cent) were females. Features consistent with anticholinergic toxicity included tachycardia in 44 (88 per cent) and urinary retention requiring catheterisation in 40 (80 per cent). Forty-three patients (86 per cent) were treated with physostigmine before rivastigmine administration. Twenty-two were managed with transdermal rivastigmine (most commonly 9.5 mg/24 hour patch), and 28 with oral rivastigmine 6 mg. Further parenteral sedation and/or physostigmine treatment were required more often in patients given transdermal than oral rivastigmine [16/22 (73 per cent) versus 9/28 (32 per cent), P = 0.010)]. No patients had bradycardia or gastrointestinal symptoms following rivastigmine administration. One patient with a history of epilepsy had a seizure, 1.5 hours post physostigmine administration and 7 hours post transdermal rivastigmine. DISCUSSION: Rivastigmine has been increasingly used for the management of patients with anticholinergic delirium, due to the lack of availability of physostigmine. In this case series, rivastigmine transdermal patch appeared to be less effective than oral rivastigmine capsules, likely due to its slow onset of action and/or insufficient dose. CONCLUSION: Rivastigmine can be used to treat anticholinergic delirium. In our case series oral rivastigmine appeared more effective than transdermal rivastigmine.

A cluster-randomized controlled trial of a nurse-led artificial intelligence assisted prevention and management for delirium (AI-AntiDelirium) on delirium in intensive care unit: Study protocol.

BACKGROUND: Delirium is a common complication among intensive care unit (ICU) patients that is linked to negative clinical outcomes. However, adherence to the Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PADIS guidelines), which recommend the use of the ABCDEF bundle, is sub-optimal in routine clinical care. To address this issue, AI-AntiDelirium, a nurse-led artificial intelligence-assisted prevention and management tool for delirium, was developed by our research team. Our pilot study yielded positive findings regarding the use of AI-AntiDelirium in preventing patient ICU delirium and improving activities of daily living and increasing intervention adherence by health care staff. METHODS: The proposed large-scale pragmatic, open-label, parallel-group, cluster randomized controlled study will assess the impact of AI-AntiDelirium on the incidence of ICU delirium and delirium-related outcomes. Six ICUs in two tertiary hospitals in China will be randomized in a 1:1 ratio to an AI-AntiDelirium or a PADIS guidelines group. A target sample size of 1,452 ICU patients aged 50 years and older treated in the ICU for at least 24 hours will be included. The primary outcome evaluated will be the incidence of ICU delirium and the secondary outcomes will be the duration of ICU delirium, length of ICU and hospital stay, ICU and in-hospital mortality rates, patient cognitive function, patient activities of daily living, and ICU nurse adherence to the ABCDEF bundle. DISCUSSION: If this large-scale trial provides evidence of the effectiveness of AI-AntiDelirium, an artificial intelligence-assisted system tool, in decreasing the incidence of ICU delirium, length of ICU and hospital stay, ICU and in-hospital mortality rates, patient cognitive function, and patient activities of daily living while increasing ICU nurse adherence to the ABCDEF bundle, it will have a profound impact on the management of ICU delirium in both research and clinical practice. CLINICAL TRIAL REGISTRATION: ChiCTR1900023711 (Chinese Clinical Trial Registry).

Implementing pain, agitation, delirium, and sleep deprivation protocol in critically ill patients: A pilot study on pharmacological interventions.

Critically ill patients frequently experience pain, agitation, delirium, and sleep deprivation, which have been linked to increased mortality and unfavorable clinical outcomes. To address these challenges, the Pain, Agitation, Delirium, and Sleep Deprivation (PADS) protocol was developed, aiming to mitigate mortality and improve clinical outcomes. This study focuses on assessing the protocol's impact using a robust before-and-after study design in the medical and surgical intensive care units (ICUs) at Ramathibodi Hospital. Using an observational approach, this study compares clinical outcomes before and after implementing the PADS protocol in the ICUs. Two patient cohorts were identified: the "before" group, comprising 254 patients with retrospective data collected between May 2018 and September 2019, and the "after" group, consisting of 255 patients for whom prospective data was collected from May to September 2020. Analysis reveals improvements in the after group. Specifically, there was a significant increase in 14-day ICU-free days (9.95 days vs. 10.40 days, p value = 0.014), a decrease in delirium incidence (18.1% vs. 16.1%, p value < 0.001), and a significant reduction in benzodiazepine usage (38.6% vs. 24.6%, p value = 0.001) within the after group. This study emphasizes the protocol's potential to improve patient care and highlights its significance in the ICU context.

Comparison of Pharmacological Treatments for Agitated Delirium in the Last Days of Life.

CONTEXT: Antipsychotics are often used in managing symptoms of terminal delirium, but evidence is limited. OBJECTIVES: To explore the comparative effectiveness of haloperidol with as-needed benzodiazepines (HPD) vs. chlorpromazine (CPZ) vs. levomepromazine (LPZ) for agitated delirium in the last days. METHODS: A prospective observational study was conducted in two palliative care units in Japan. Adult cancer patients who developed agitated delirium with a modified Richmond Agitation-Sedation Scale (RASS-PAL) of one or more were included; palliative care specialist physicians determined that the etiology was irreversible; and estimated survival was 3 weeks or less. Patients treated with HPD, CPZ, or LPZ were analyzed. We measured RASS, NuDESC, Agitation Distress Scale (ADS), and Communication Capacity Scale (CCS) on Days 1 and 3. RESULTS: A total of 277 patients were enrolled, and 214 were analyzed (112 in HPD, 50 in CPZ, and 52 in LPZ). In all groups, the mean RASS-PAL score significantly decreased on Day 3 (1.37 to -1.01, 1.87 to -1.04, 1.79 to -0.62, respectively; P < 0.001); the NuDESC and ADS scores also significantly decreased. The percentages of patients with moderate to severe agitation and those with full communication capacity on Day 3 were not significantly different. The treatments were well-tolerated. While one-fourth of HPD group changed antipsychotics, 88% or more of CPZ and LPZ groups continued the initial antipsychotics. CONCLUSION: Haloperidol with as-needed benzodiazepine, chlorpromazine, or levomepromazine may be effective and safe for terminal agitation. Chlorpromazine and levomepromazine may have an advantage of no need to change medications.

Effect of hospital elder life program on the incidence of delirium: A systematic review and meta-analysis of clinical trials.

OBJECTIVE: This meta-analysis aims to investigate the effect of the Hospital Elder Life Program (HELP) on the incidence of delirium, delirium scores, length of hospital stay, and incidence of falls. METHODS: Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched from inception until January 18, 2024. The search specifically targeted randomized controlled trials (RCTs). Two independent researchers conducted literature screening, quality assessment, and data extraction. The meta-analysis was performed using Review Manager 5.4.1 and Stata 15.1 software. RESULTS: The final analysis included a total of 9 RCTs with 2583 patients. The findings from the meta-analysis indicated that HELP was found to considerably reduce the incidence of delirium and the length of hospital stay when compared to the control group. Nevertheless, no statistically significant differences were observed between the two groups in terms of delirium scores and fall rates. CONCLUSION: In this meta-analysis, HELP can effectively reduce the incidence of delirium and lead to a shorter hospital stay.

Prevention of post-operative delirium using an overnight infusion of dexmedetomidine in patients undergoing cardiac surgery: a pragmatic, randomized, double-blind, placebo-controlled trial.

BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).

The effect of haloperidol's perioperative application on postoperative delirium in elderly patients: a systematic review and meta-analysis.

OBJECTIVES: To systematically review the evidence about the effect of haloperidol on postoperative delirium in elderly patients. METHODS: PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure were used to find concerned studies for meta-analysis. The main outcome was the incidence of postoperative delirium, and the secondary outcomes were side effects of haloperidol and the length of hospital stay. The meta-analyses were conducted using the Review Manager Version 5.1. This study was conducted based on the PRISMA statement. RESULTS: Eight RCTs (1569 patients) were included in the meta-analysis. There was a significant difference in the incidence of postoperative delirium between haloperidol and control groups (OR = 0.62, 95%CI 0.48-0.80, P = 0.0002, I2 = 20%). In addition, side effects of haloperidol and the duration of hospitalization were comparable (OR = 0.58, 95%CI 0.25-1.35, P = 0.21, I2 = 0%; MD =-0.01, 95%CI -0.16-0.15, P = 0.92, I2 = 28%). Subgroup analysis implied the effect of haloperidol on postoperative delirium might vary with the dose (5 mg daily: OR = 0.40, 95%CI 0.22-0.71, P = 0.002, I2 = 0%; <5 mg daily: OR = 0.72, 95%CI 0.42-1.23, P = 0.23, I2 = 0%). CONCLUSIONS: The meta-analysis revealed perioperative application of haloperidol could decrease the occurrence of postoperative delirium without obvious side effects in elderly people, and high-dose haloperidol (5 mg daily) possessed a greater positive effect.

Short-term outcomes of prehospital opioid pain management for older adults with fall-related injury.

BACKGROUND: Opioids are recommended for pain management in patients being cared for and transported by emergency medical services, but no specific guidelines exist for older adults with fall-related injury. Prior research suggests prehospital opioid administration can effectively manage pain in older adults, but less is known about safety in this population. We compared short-term safety outcomes, including delirium, disposition, and length of stay, among older adults with fall-related injury according to whether they received prehospital opioid analgesia. METHODS: We linked Medicare claims data with prehospital patient care reports for older adults (≥65) with fall-related injury in Illinois between January 1, 2014 and December 31, 2015. We used weighted regression models (logistic, multinomial logistic, and Poisson) to assess the association between prehospital opioid analgesia and incidence of inpatient delirium, hospital disposition, and length of stay. RESULTS: Of 28,150 included older adults, 3% received prehospital opioids. Patients receiving prehospital opioids (vs. no prehospital opioids) were less likely to be discharged home from the emergency department (adjusted probability = 0.30 [95% CI: 0.25, 0.34] vs. 0.47 [95% CI: 0.46, 0.48]), more likely to be discharged to a non-home setting after an inpatient admission (adjusted probability = 0.43 [95% CI: 0.39, 0.48] vs. 0.30 [95% CI: 0.30, 0.31]), had inpatient length of stay 0.4 days shorter (p < 0.001) and ICU length of stay 0.7 days shorter (p = 0.045). Incidence of delirium did not vary between treatment and control groups. CONCLUSIONS: Few older adults receive opioid analgesia in the prehospital setting. Prehospital opioid analgesia may be associated with hospital disposition and length of stay for older adults with fall-related injury. However, our findings do not provide evidence of an association with inpatient delirium. These findings should be considered when developing guidelines for prehospital pain management specific to the older adult population.

Inhibition of RXRA-mediated PLA2G2A improves delirium in COPD mice by regulating endoplasmic reticulum stress pathway and inhibiting cell apoptosis.

Delirium is a common psychiatric complication of chronic obstructive pulmonary disease (COPD). The relief of delirium is considered one of the beneficial ways to treat COPD. However, there are currently no specific drugs that alleviate delirium in COPD patients. Our research aimed to elucidate the specific mechanisms underlying delirium in COPD mice, while also seeking more effective therapeutic targets. In our study, bioinformatics analysis and qRT PCR were used to identify key factors in the development of delirium in COPD animal models. Open field and elevated plus maze tests were used to detect delirium in mice. Tunel staining and HE staining were used to analyze the apoptosis of mouse hippocampus cells. EdU and CCK-8 experiments were used to analyze PC-12 cells vitality and proliferation. JASPAR online database, dual luciferase reporting experiments, ChIP experiments, and IF staining were used to analyze the interaction between RXRA and PLA2G2A. RXRA is highly expressed in the brain tissue of COPD mice with delirium symptoms. The downregulation of RXRA inhibits the delirium state in COPD mice. This is mainly due to the reduction of endoplasmic reticulum stress and cell apoptosis by inhibiting the expression of RXRA. In addition, we also confirmed that RXRA is a transcription factor of PLA2G2A. RXRA has an inhibitory effect on the expression of PLA2G2A. In vitro experiments have confirmed that inhibition of the RXRA/PLA2G2A axis reduces cell apoptosis, thereby alleviating the occurrence and development of delirium in COPD mice. Inhibition of the RXRA/PLA2G2A axis reduces endoplasmic reticulum stress and cell apoptosis. This process alleviates the development of delirium in COPD mice.