scholarly journals Melatonin for prevention of postoperative delirium after lower limb fracture surgery in elderly patients (DELIRLESS): study protocol for a multicentre randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e053908
Author(s):  
Stéphanie Sigaut ◽  
Camille Couffignal ◽  
Marina Esposito-Farèse ◽  
Vincent Degos ◽  
Serge Molliex ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Lower Limb ◽  
Postoperative Delirium ◽  
Controlled Trial ◽  
Functional Decline ◽  
Assessment Method ◽  
Phase Iii ◽  
Double Blind ◽  
Prolonged Length ◽  
Surgery In Elderly

IntroductionPostoperative delirium (POD) is one of the most frequent complication after surgery in elderly patients, and is associated with increased morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs. Perioperative inflammatory stress is a key element in POD genesis. Melatonin exhibits antioxidative and immune-modulatory proprieties that are promising concerning delirium prevention, but in perioperative context literature are scarce and conflicting. We hypothesise that perioperative melatonin can reduce the incidence of POD.Methods and analysisThe DELIRLESS trial is a prospective, national multicentric, phase III, superiority, comparative randomised (1:1) double-blind clinical trial. Among patients aged 70 or older, hospitalised and scheduled for surgery of a severe fracture of a lower limb, 718 will be randomly allocated to receive either melatonin 4 mg per os or placebo, every night from anaesthesiologist preoperative consultation and up to 5 days after surgery. The primary outcome is POD incidence measured by either the French validated translation of the Confusion Assessment Method (CAM) score for patients hospitalised in surgery, or CAM-ICU score for patients hospitalised in ICU (Intensive Care Unit). Daily delirium assessment will take place during 10 days after surgery, or until the end of hospital stay if it is shorter. POD cumulative incidence function will be compared at day 10 between the two randomised arms in a competing risks framework, using the Fine and Grey model with death as a competing risk of delirium.Ethics and disseminationThe DELIRLESS trial has been approved by an independent ethics committee the Comité de Protection des Personnes (CPP) Sud-Est (ref CPP2020-18-99 2019-003210-14) for all study centres. Participant recruitment begins in December 2020. Results will be published in international peer-reviewed medical journals.Trial registration numberNCT04335968, first posted 7 April 2020.Protocol version identifierN°3–0, 3 May 2021.

The effect of pre-operative methylprednisolone on postoperative delirium in elderly patients undergoing gastrointestinal surgery: a randomized, double-blind, placebo-controlled trial

2021 ◽  
Author(s):  
Xiao-bing Xiang ◽  
Hao Chen ◽  
Ying-li Wu ◽  
Ke Wang ◽  
Xiang Yue ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Heparan Sulfate ◽  
Postoperative Delirium ◽  
Controlled Trial ◽  
Gastrointestinal Surgery ◽  
Assessment Method ◽  
Endothelial Glycocalyx ◽  
Double Blind ◽  
Tnf Α ◽  
Circulating Markers

Abstract Background Pre-operative administration of methylprednisolone reduced circulating markers of endothelial activation. This randomized, double-blind was to evaluate whether a single pre-operative dose of methylprednisolone reduced the rate of postoperative delirium (POD) in older patients undergoing gastrointestinal surgery, and its association with the shedding of endothelial glycocalyx markers. Methods 168 patients, aged 65–80 years and scheduled for laparoscopic gastrointestinal surgery, were randomized to 2 mg·kg -1 methylprednisolone (Group M, n = 84); or equivalent dose of placebo (Group C, n = 84). The primary outcome was the incidence of delirium during the first 5 days after surgery, assessed by the confusion assessment method (CAM). POD severity was rated daily using CAM-Severity (CAM-S). Level of syndecan-1, heparan sulfate, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor (BDNF) were measured at baseline, 1-day, and 3-day after surgery. Results Compared with placebo, methylprednisolone greatly reduced the incidence of delirium at 72 h following surgery [9(10.7%) versus 20(23.8%), P =0.03, OR=2.22(95%CI 1.05-4.59)]. No between-group difference was found in the cumulative CAM-S score (P=0.14). The levels of heparan sulfate, syndecan-1, and TNF-α in Group M were lower than that in Group C (P <0.05 and P <0.01), while the level of BDNF in Group M was higher than that in Group C (P <0.01). Conclusions Pre-operative administration of methylprednisolone does not reduce the severity of POD, but may reduce the incidence of delirium after gastrointestinal surgery in elderly patients, which may be related to a reduction in circulating markers of endothelial degradation, followed by the increase of BNDF level.

scholarly journals Effects of Melatonin on Postoperative Delirium After PCI in Elderly Patients: A Randomized, Single-Center, Double-Blind, Placebo-Controlled Trial

2021 ◽  
Vol 24 (5) ◽  
pp. E893-E897
Author(s):  
Yicheng Shi
Keyword(s):  
Placebo Group ◽  
Elderly Patients ◽  
Postoperative Delirium ◽  
Controlled Trial ◽  
Coronary Intervention ◽  
Assessment Method ◽  
Double Blind ◽  
Significant Difference ◽  
Hospitalization Costs ◽  
To Receive

Background: Experimental evidence has indicated the benefits of melatonin (Mel) for the treatment of delirium. Clinical trials had no definite conclusions concerning Mel on delirium after percutaneous transluminal coronary intervention (PCI) in elderly patients. The present study explored whether acute Mel treatment could reduce the incidence of delirium. Methods: This trial enrolled patients over the age of 60, who were admitted to intensive care units (ICUs) after PCI. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive Mel (3 mg/day) or placebo once daily for up to 7 days. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method (CAM) during the first 7 postoperative days. Analyses were performed using intention-to-treat and safety populations. Results: A total of 297 patients randomly were assigned to receive either placebo (N = 149) or Mel (N = 148). The incidence of postoperative delirium was significantly lower in the Mel group than in the placebo group (27.0% vs. 39.6%, respectively, P = 0.02). There was no significant difference between 30-day all-cause mortality (12.2% vs. 14.1%, P = 0.62) and drug reactions (0 vs. 2.0%, P = 0.25). The length of stay and hospitalization costs in the Mel group were significantly decreased compared with those in the placebo group (P > 0.05). Conclusion: The current study suggests that Mel is safe and effective in the treatment of delirium after PCI. Further investigation is necessary to fully understand the potential usefulness of Mel in older patients via larger randomized, multicenter, double-blind, and placebo-controlled trials.

scholarly journals Elevated Procalcitonin and Depression As Risk Factors For Postoperative Delirium In The Elderly After Cardiac Surgery – A Prospective Observational Study.

2020 ◽  
Author(s):  
Anna Kupiec ◽  
Barbara Adamik ◽  
Natalia Kozera ◽  
Waldemar Gozdzik
Keyword(s):  
Risk Factors ◽  
Cardiac Surgery ◽  
Elderly Patients ◽  
Postoperative Delirium ◽  
Inflammatory Marker ◽  
Functional Decline ◽  
The Elderly ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Multivariable Logistic Regression Model

Abstract Background One of the most common complications after cardiac surgery is delirium. Determining the origin of this complication from possible pathomechanisms is difficult. The activation of an inflammatory response during surgery has been suggested as one possible mechanism of delirium. The usefulness of the inflammatory marker procalcitonin (PCT) as a predictor of delirium after cardiac surgery with cardiopulmonary bypass (CBP) has not yet been investigated. Methods The purpose of this study was to prospectively investigate the risk of developing postoperative delirium in a group of elderly patients using a multivariate assessment of preoperative (PCT, comorbidities, functional decline, depression) and intraoperative risk factors. 149 elderly patients were included. Delirium was assessed using the Confusion Assessment Method for the ICU. Results Thirty patients (20%) developed post-operative delirium: hypoactive in 50%, hyperactive in 33%, mixed in 17%. Preoperative PCT above the reference range (> 0.05 ng/mL) was recorded more often in patients who postoperatively developed delirium than in the non-delirium group (50% vs. 27%, p=0.019). After surgery, PCT was significantly higher in the delirium than the non-delirium group: ICU admission after surgery: 0.08 ng/mL, IQR 0.03-0.15 vs. 0.05 ng/mL, IQR 0.02-0.09, p=0.011), and for consecutive days (day 1: 0.59 ng/mL, IQR 0.25-1.55 vs. 0.25 ng/mL, IQR 0.14-0.54, p=0.003; day 2: 1.21 ng/mL, IQR 0.24-3.29 vs. 0.36 ng/mL, IQR 0.16-0.76, p=0.006; day 3: 0.76 ng/mL, IQR 0.48-2.34 vs. 0.34 ng/mL, IQR 0.14-0.66, p=0.001). Patients with delirium were older (74 years, IQR 70 – 76 vs. 69 years, IQR 67 – 74; p=0.038) and more often had functional decline (47% vs. 28%, p=0.041). There was no difference in comorbidities with the exception of anaemia (43% vs. 19%, p=0.006). Depression was detected in 40% of patients with delirium and in 17% without delirium (p=0.005). In a multivariable logistic regression model of preoperative procalcitonin (OR= 3.05; IQR 1.02-9.19), depression (OR=5.02, IQR 1.67-15.10), age (OR=1.14; IQR 1.02-1.26), functional decline (OR=0.76; IQR 0.63-0.91) along with CPB time (OR=1.04; IQR 1.02-1.06) were significant predictors of postoperative delirium. Conclusion A preoperative PCT test and assessment of functional decline and depression may help identify patients at risk for developing delirium after cardiac surgery.

scholarly journals Association between baseline cognitive impairment and postoperative delirium in elderly patients undergoing surgery for adult spinal deformity

2018 ◽  
Vol 28 (1) ◽  
pp. 103-108 ◽  
Author(s):  
Owoicho Adogwa ◽  
Aladine A. Elsamadicy ◽  
Victoria D. Vuong ◽  
Jared Fialkoff ◽  
Joseph Cheng ◽  
...  
Keyword(s):  
Risk Factor ◽  
Cognitive Impairment ◽  
Elderly Patients ◽  
Postoperative Delirium ◽  
Adult Spinal Deformity ◽  
Functional Decline ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Degenerative Scoliosis ◽  
Patient Reported

OBJECTIVEPostoperative delirium is common in elderly patients undergoing spine surgery and is associated with a longer and more costly hospital course, functional decline, postoperative institutionalization, and higher likelihood of death within 6 months of discharge. Preoperative cognitive impairment may be a risk factor for the development of postoperative delirium. The aim of this study was to investigate the relationship between baseline cognitive impairment and postoperative delirium in geriatric patients undergoing surgery for degenerative scoliosis.METHODSElderly patients 65 years and older undergoing a planned elective spinal surgery for correction of adult degenerative scoliosis were enrolled in this study. Preoperative cognition was assessed using the validated Saint Louis University Mental Status (SLUMS) examination. SLUMS comprises 11 questions, with a maximum score of 30 points. Mild cognitive impairment was defined as a SLUMS score between 21 and 26 points, while severe cognitive impairment was defined as a SLUMS score of ≤ 20 points. Normal cognition was defined as a SLUMS score of ≥ 27 points. Delirium was assessed daily using the Confusion Assessment Method (CAM) and rated as absent or present on the basis of CAM. The incidence of delirium was compared in patients with and without baseline cognitive impairment.RESULTSTwenty-two patients (18%) developed delirium postoperatively. Baseline demographics, including age, sex, comorbidities, and perioperative variables, were similar in patients with and without delirium. The length of in-hospital stay (mean 5.33 days vs 5.48 days) and 30-day hospital readmission rates (12.28% vs 12%) were similar between patients with and without delirium, respectively. Patients with preoperative cognitive impairment (i.e., a lower SLUMS score) had a higher incidence of postoperative delirium. One- and 2-year patient reported outcomes scores were similar in patients with and without delirium.CONCLUSIONSCognitive impairment is a risk factor for the development of postoperative delirium. Postoperative delirium may be associated with decreased preoperative cognitive reserve. Cognitive impairment assessments should be considered in the preoperative evaluations of elderly patients prior to surgery.

scholarly journals Effects of dexmedetomidine on postoperative delirium and expression of IL-1, IL-6, and TNF-α in elderly patients after hip fracture operation

2020 ◽  
Author(s):  
Wenchao Zhang ◽  
Tianlong Wang ◽  
Geng Wang ◽  
Minghui Yang ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Hip Fracture ◽  
Elderly Patients ◽  
Postoperative Delirium ◽  
Early Stage ◽  
Surgical Complication ◽  
Controlled Trial ◽  
Venous Blood ◽  
Inflammatory Factors ◽  
Double Blind ◽  
Tnf Α

Abstract Background: Postoperative delirium (POD) is a common surgical complication in elderly patients. This study investigated the effects of dexmedetomidine on POD and inflammatory factors in elderly patients with hip fracture.Methods: The randomized, double-blind, controlled trial enrolled patients aged ≥65 years who underwent operation for hip fracture in the Department of Anesthesiology in Beijing JiShuiTan Hospital from October 2016 to January 2017. The patients were divided into the DEX group and the NS group and were intravenously infused with dexmedetomidine or an equal volume of normal saline, respectively. After surgery, the incidence of delirium at postoperative day 1 (T1), day 2 (T2) and day 3 (T3) were assessed using the Ramsay score and Confusion Assessment Method (CAM) delirium scale. Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α concentrations in the venous blood of the two groups of patients were detected at T0 (before surgery), T1 and T3.Results: Data from 218 patients were analyzed with 110 patients in the DEX group and 108 in the NS group. Dexmedetomidine decreased POD incidence (18.2% vs. 30.6%, P=0.033). Compared to T0, all three inflammatory factors increased at T1 and then decreased at T3 and changes with time were significant (all P<0.001). IL-6 (P<0.001) and TNF-α (P=0.003) levels were lower in the DEX group, but IL-1 levels were similar. The rate of adverse events was similar in the two groups.Conclusions: Dexmedetomidine reduced the incidence of POD in elderly patients with hip fracture at an early stage, and reduced short-term IL-6 and TNF-α concentrations.

scholarly journals Comparison of postoperative delirium in patients anesthetized with isoflurane versus desflurane during spinal surgery: A prospective randomized controlled trial

2019 ◽  
Vol 10 ◽  
pp. 226
Author(s):  
Steve Joys ◽  
Tanvir Samra ◽  
Vishal Kumar ◽  
Manju Mohanty ◽  
Harsimrat B. S. Sodhi ◽  
...  
Keyword(s):  
Spine Surgery ◽  
Spinal Surgery ◽  
Postoperative Delirium ◽  
Controlled Trial ◽  
Confusion Assessment Method ◽  
Assessment Method ◽  
Double Blind ◽  
Anesthetic Agents ◽  
Number Of Patients ◽  
Severity Scores

Background: Following spine surgery, different types of inhalational anesthetic agents can result in postoperative delirium (POD) that can increase perioperative/postoperative morbidity. Here, we compared the incidence of POD in adults undergoing spine surgery anesthetized with isoflurane versus desflurane. Methods: A prospective randomized double-blind clinical trial for patients undergoing spinal surgery was performed in 60 adults (aged 18–65 years); they were randomized to receive isoflurane or desflurane. On postoperative days 1 and 3, the diagnosis and severity of POD utilized 3D-Confusion Assessment Method (CAM) and CAM-severity delirium severity scores to assess patients’ status. Multiple other variables which may have influenced the frequency/severity of POD were also studied. Results: For the two groups, the incidence of POD utilizing isoflurane and desflurane was similar on postoperative days 1 (10% vs. 13.3%, P > 0.05) and 3 (6.6% vs. 0%, P > 0.05). The severity scores of POD for both anesthetic agents were also similar on postoperative days 1 (1.5 vs. 1) and 3 (0.5 vs. 0.5). In addition, there was no significant association of POD with other perioperative factors. Conclusion: A significant number of patients undergoing spine surgery experience POD. However, the incidence and severity of POD remained similar when utilizing either isoflurane or desflurane.

scholarly journals Serum Biomarkers in Postoperative Delirium after Esophagectomy

2020 ◽  
Vol 3 ◽  
Author(s):  
Azhar Dalal ◽  
Sikandar Khan ◽  
Heidi Lindroth ◽  
Babar Khan
Keyword(s):  
Calcium Binding ◽  
Postoperative Delirium ◽  
Rating Scale ◽  
Controlled Trial ◽  
Assessment Method ◽  
Serum Biomarkers ◽  
University Hospital ◽  
Inflammatory Biomarkers ◽  
Double Blind ◽  
Necrosis Factor Alpha

Background: The pathophysiology of postoperative delirium in patients undergoing esophagectomy is not well understood but has been hypothesized to involve neuroinflammation. Inflammatory biomarkers may therefore be associated with delirium incidence and severity. We conducted this study to measure the association between serum inflammatory biomarkers and postoperative delirium and delirium severity.     Methods: Blood samples were obtained from patients enrolled in a randomized double-blind placebo-controlled trial undergoing elective esophagectomy at Indiana University Health University Hospital. S100 calcium-binding protein B, C-Reactive Protein (CRP), interleukins 8, 10, tumor necrosis factor-alpha, and insulin like growth factor 1 (IGF1) were analyzed at preoperative, and postoperative days 1 and 3 timepoints. Delirium status and severity were assessed using the Confusion Assessment Method for Intensive Care Unit and Delirium Rating Scale (DRS-R-98), respectively.     Results: Samples from 71 patients were included. Higher median CRP values were associated with delirium incidence at post-operative day 1 (no delirium: 22.7 IQR:2.2, 42.7; delirium: 35.4 IQR:25.0, 50.0, p=0.031) but not at post-operative day 3. Median CRP S100B serum values were correlated with mean delirium severity (-0.289, p=0.020). IGF-1 serum values were associated with delirium severity on post-operative day 1 (0.270, p=0.040).     Conclusion: Postoperative delirium incidence was associated with higher median CRP values at POD1. The findings of this study provide evidence for the early measurement of post-operative serum biomarkers to ascertain likely incidence and severity of delirium.  

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