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      The Effect and Optimal Dosage of Dexmedetomidine Plus Sufentanil for Postoperative Analgesia in Elderly Patients With Postoperative Delirium and Early Postoperative Cognitive Dysfunction: A Single-Center, Prospective, Randomized, Double-Blind, Controlled Trial

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          Abstract

          Background

          Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common complications after major surgery among elderly patients. Dexmedetomidine (DEX) is less frequently explored for its effects in patients with postoperative neurocognitive disorders. This study investigated the effect and optimal dosage of DEX for patient-controlled analgesia (PCA) on POD and early POCD after major surgery among elderly patients.

          Methods

          Patients in four groups received continuous infusion of DEX 0, 100, 200, and 400 μg with sufentanil 150 μg for PCA immediately after surgery. POD and POCD were assessed on postoperative days 1, 2, 3, and 7 by using the Confusion Assessment Method (CAM) and Mini-Mental State Examination (MMSE) scales. Furthermore, the incidence of POD and POCD of all the four groups in postoperative 7 days classified by high risk factors (age, education, surgical site, and surgical category), sedation level, postoperative pain intensity, and side effects were assessed.

          Results

          The overall incidence rates of POD and early POCD 7 days after surgery were lower in the DEX 200 μg 400 μg groups than in the DEX 0 μg and 100 μg groups ( P < 0.05). Compared with DEX 200 μg, DEX 400 μg reduced early POCD in patients who underwent open surgery ( P < 0.05). There were no intergroup differences in the postoperative sedation level, pain intensity, and side effects.

          Conclusion

          The continuous infusion of DEX 200 μg or DEX 400 μg in PCA significantly decreased the incidence of POD and early POCD after major surgery without increasing any side effects. Compared with DEX 200 μg, DEX 400 μg was preferred for reducing early POCD in patients who underwent open surgery.

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          Most cited references50

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          Delirium in elderly people.

          Delirium is an acute disorder of attention and cognition in elderly people (ie, those aged 65 years or older) that is common, serious, costly, under-recognised, and often fatal. A formal cognitive assessment and history of acute onset of symptoms are necessary for diagnosis. In view of the complex multifactorial causes of delirium, multicomponent non-pharmacological risk factor approaches are the most effective strategy for prevention. No convincing evidence shows that pharmacological prevention or treatment is effective. Drug reduction for sedation and analgesia and non-pharmacological approaches are recommended. Delirium offers opportunities to elucidate brain pathophysiology--it serves both as a marker of brain vulnerability with decreased reserve and as a potential mechanism for permanent cognitive damage. As a potent indicator of patients' safety, delirium provides a target for system-wide process improvements. Public health priorities include improvements in coding, reimbursement from insurers, and research funding, and widespread education for clinicians and the public about the importance of delirium. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Predictors of cognitive dysfunction after major noncardiac surgery.

            The authors designed a prospective longitudinal study to investigate the hypothesis that advancing age is a risk factor for postoperative cognitive dysfunction (POCD) after major noncardiac surgery and the impact of POCD on mortality in the first year after surgery. One thousand sixty-four patients aged 18 yr or older completed neuropsychological tests before surgery, at hospital discharge, and 3 months after surgery. Patients were categorized as young (18-39 yr), middle-aged (40-59 yr), or elderly (60 yr or older). At 1 yr after surgery, patients were contacted to determine their survival status. At hospital discharge, POCD was present in 117 (36.6%) young, 112 (30.4%) middle-aged, and 138 (41.4%) elderly patients. There was a significant difference between all age groups and the age-matched control subjects (P < 0.001). At 3 months after surgery, POCD was present in 16 (5.7%) young, 19 (5.6%) middle-aged, and 39 (12.7%) elderly patients. At this time point, the prevalence of cognitive dysfunction was similar between age-matched controls and young and middle-aged patients but significantly higher in elderly patients compared to elderly control subjects (P < 0.001). The independent risk factors for POCD at 3 months after surgery were increasing age, lower educational level, a history of previous cerebral vascular accident with no residual impairment, and POCD at hospital discharge. Patients with POCD at hospital discharge were more likely to die in the first 3 months after surgery (P = 0.02). Likewise, patients who had POCD at both hospital discharge and 3 months after surgery were more likely to die in the first year after surgery (P = 0.02). Cognitive dysfunction is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 yr or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery.
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              Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit.

              In the intensive care unit (ICU), delirium is a common yet underdiagnosed form of organ dysfunction, and its contribution to patient outcomes is unclear. To determine if delirium is an independent predictor of clinical outcomes, including 6-month mortality and length of stay among ICU patients receiving mechanical ventilation. Prospective cohort study enrolling 275 consecutive mechanically ventilated patients admitted to adult medical and coronary ICUs of a US university-based medical center between February 2000 and May 2001. Patients were followed up for development of delirium over 2158 ICU days using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale. Primary outcomes included 6-month mortality, overall hospital length of stay, and length of stay in the post-ICU period. Secondary outcomes were ventilator-free days and cognitive impairment at hospital discharge. Of 275 patients, 51 (18.5%) had persistent coma and died in the hospital. Among the remaining 224 patients, 183 (81.7%) developed delirium at some point during the ICU stay. Baseline demographics including age, comorbidity scores, dementia scores, activities of daily living, severity of illness, and admission diagnoses were similar between those with and without delirium (P>.05 for all). Patients who developed delirium had higher 6-month mortality rates (34% vs 15%, P =.03) and spent 10 days longer in the hospital than those who never developed delirium (P<.001). After adjusting for covariates (including age, severity of illness, comorbid conditions, coma, and use of sedatives or analgesic medications), delirium was independently associated with higher 6-month mortality (adjusted hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.4-7.7; P =.008), and longer hospital stay (adjusted HR, 2.0; 95% CI, 1.4-3.0; P<.001). Delirium in the ICU was also independently associated with a longer post-ICU stay (adjusted HR, 1.6; 95% CI, 1.2-2.3; P =.009), fewer median days alive and without mechanical ventilation (19 [interquartile range, 4-23] vs 24 [19-26]; adjusted P =.03), and a higher incidence of cognitive impairment at hospital discharge (adjusted HR, 9.1; 95% CI, 2.3-35.3; P =.002). Delirium was an independent predictor of higher 6-month mortality and longer hospital stay even after adjusting for relevant covariates including coma, sedatives, and analgesics in patients receiving mechanical ventilation.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                23 October 2020
                2020
                : 14
                : 549516
                Affiliations
                [1] 1Department of Anesthesiology, The Third Affiliated Hospital, Harbin Medical University , Harbin, China
                [2] 2Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University , Guangzhou, China
                [3] 3Department of Anesthesiology, Heilongjiang Provincial Corps Hospital, Chinese People’s Armed Police Forces , Harbin, China
                Author notes

                Edited by: Divya Vohora, Jamia Hamdard University, India

                Reviewed by: Zhongyong Shi, Tongji University, China; Nilanjan Saha, Jamia Hamdard University, India

                *Correspondence: Fei Han, fh.feih@ 123456yahoo.com

                These authors have contributed equally to this work

                This article was submitted to Neuropharmacology, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2020.549516
                7645155
                33192244
                92d08a79-99fc-4eec-b764-e26a4dbb7c82
                Copyright © 2020 Zhao, Hu, Chen, Wang, Wang, Wang, Wu and Han.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 April 2020
                : 05 October 2020
                Page count
                Figures: 2, Tables: 4, Equations: 0, References: 50, Pages: 11, Words: 0
                Categories
                Neuroscience
                Clinical Trial

                Neurosciences
                dexmedetomidine,patient-controlled analgesia,postoperative delirium,postoperative cognitive dysfunction,elderly patients

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