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      Hypertonic saline for prevention of delirium in geriatric patients who underwent hip surgery

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          Abstract

          Background

          Postoperative delirium (POD) is a common disorder in the elderly patients, and neuroinflammation is the possible underlying mechanism. This study is designed to determine whether or not hypertonic saline (HS) pre-injection can alleviate POD in aged patients.

          Methods

          This prospective study recruited 120 geriatric patients who underwent hip surgery. The patients were randomly divided into two groups: control group (NS group) and HS group. Patients in the NS group were pre-injected with 4 mL/kg isotonic saline, and those in the HS group were pre-injected with 4 mL/kg 7.5% HS. All 120 patients were then subjected to general anesthesia. Blood samples were extracted to detect the concentration of inflammatory factors, namely, IL-1β, IL-6, IL-10, and TNF-α, and the nerve injury factor S100β. Flow cytometry was used to detect the number of monocytes in peripheral venous blood and evaluate the relationship of inflammation to delirium. The nursing delirium screening scale (Nu-DESC) was used to determine cognitive function 1 to 3 days postoperatively.

          Results

          Analysis using random-effect multivariable logistic regression indicated that HS administration before anesthesia was associated with a low risk of POD (odds ratio [OR], 0.13; 95% CI, 0.04 to 0.41; P = 0.001) and few CD14 + CD16+ monocytes (β = − 0.61; 95% CI, − 0.74 to − 0.48; P = 0.000) the following day. When the association between HS and delirium was controlled for CD14 + CD16+ monocytes, the effect size became nonsignificant (odds ratio [OR], 0.86; 95% CI, 0.14 to 5.33; P = 0.874). TNF-α was significantly associated with POD (odds ratio [OR], 1.10; 95% CI, 1.05 to 1.16; P = 0.000). However, IL-1β, IL-6, IL-10, and S100β were not significantly related to POD.

          Conclusion

          HS can alleviate POD in geriatric patients and may inhibit the secretion of inflammatory factors by monocytes.

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          Most cited references38

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          Resolving postoperative neuroinflammation and cognitive decline.

          Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved. C57BL/6J, Ccr2(RFP/+)Cx3cr1(GFP/+), Ikk(F/F) mice and LysM-Cre/Ikk(F/F) mice underwent stabilized tibial fracture operation under analgesia and general anesthesia. Separate cohorts of mice were tested for systemic and hippocampal inflammation, integrity of the blood-brain barrier (BBB), and cognition. The putative resolving effects of the cholinergic pathway on these postoperative responses were also studied. Peripheral surgery disrupts the BBB via release of tumor necrosis factor-alpha (TNFα), which facilitates the migration of macrophages into the hippocampus. Macrophage-specific deletion of Ikappa B kinase (IKK)β, a central coordinator of TNFα signaling through activation of nuclear factor (NF) κB, prevents BBB disruption and macrophage infiltration in the hippocampus following surgery. Activation of the α7 subtype of nicotinic acetylcholine receptors, an endogenous inflammation-resolving pathway, prevents TNFα-induced NF-κB activation, macrophage migration into the hippocampus, and cognitive decline following surgery. These data reveal the mechanisms for bidirectional communication between the brain and immune system following aseptic trauma. Pivotal molecular mechanisms can be targeted to prevent and/or resolve postoperative neuroinflammation and cognitive decline. Copyright © 2011 American Neurological Association.
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            Costs associated with delirium in mechanically ventilated patients.

            To determine the costs associated with delirium in mechanically ventilated medical intensive care unit patients. Prospective cohort study. A tertiary care academic hospital. Patients were 275 consecutive mechanically ventilated medical intensive care unit patients. We prospectively examined patients for delirium using the Confusion Assessment Method for the Intensive Care Unit. Delirium was categorized as "ever vs. never" and by a cumulative delirium severity index. Costs were determined from individual ledger-level patient charges using cost-center-specific cost-to-charge ratios and were reported in year 2001 U.S. dollars. Fifty-one of 275 patients (18.5%) had persistent coma and died in the hospital and were excluded from further analysis. Of the remaining 224 patients, delirium developed in 183 (81.7%) and lasted a median of 2.1 (interquartile range, 1-3) days. Baseline demographics were similar between those with and without delirium. Intensive care unit costs (median, interquartile range) were significantly higher for those with at least one episode of delirium ($22,346, $15,083-$35,521) vs. those with no delirium ($13,332, $8,837-$21,471, p <.001). Total hospital costs were also higher in those who developed delirium ($41,836, $22,782-$68,134 vs. $27,106, $13,875-$37,419, p =.002). Higher severity and duration of delirium were associated with incrementally greater costs (all p <.001). After adjustment for age, comorbidity, severity of illness, degree of organ dysfunction, nosocomial infection, hospital mortality, and other potential confounders, delirium was associated with 39% higher intensive care unit (95% confidence interval, 12-72%) and 31% higher hospital (95% confidence interval, 1-70%) costs. Delirium is a common clinical event in mechanically ventilated medical intensive care unit patients and is associated with significantly higher intensive care unit and hospital costs. Future efforts to prevent or treat intensive care unit delirium have the potential to improve patient outcomes and reduce costs of care.
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              Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability.

              To prospectively develop and validate a predictive model for delirium based on precipitating factors during hospitalization, and to examine the interrelationship of precipitating factors and baseline vulnerability. Two prospective cohort studies, in tandem. General medical wards, university teaching hospital. For the development cohort, 196 patients aged 70 years and older with no delirium at baseline, and for the validation cohort, 312 comparable patients. New-onset delirium by hospital day 9, defined by the Confusion Assessment Method diagnostic criteria. Delirium developed in 35 patients (18%) in the development cohort. Five independent precipitating factors for delirium were identified; use of physical restraints (adjusted relative risk [RR], 4.4; 95% confidence interval [CI], 2.5 to 7.9), malnutrition (RR, 4.0; 95% CI, 2.2 to 7.4), more than three medications added (RR, 2.9; 95% CI, 1.6 to 5.4), use of bladder catheter (RR, 2.4; 95% CI, 1.2 to 4.7), and any iatrogenic event (RR, 1.9; 95% CI, 1.1 to 3.2). Each precipitating factor preceded the onset of delirium by more than 24 hours. A risk stratification system was developed by adding 1 point for each factor present. Rates of delirium for low-risk (0 points), intermediate-risk (1 to 2 points), and high-risk groups (> or equal to 3 points) were 3%, 20%, and 59%, respectively (P < .001). The corresponding rates in the validation cohort, in which 47 patients (15%) developed delirium, were 4%, 20%, and 35%, respectively (P < .001). When precipitating and baseline factors were analyzed in cross-stratified format, delirium rates increased progressively from low-risk to high-risk groups in all directions (double-gradient phenomenon). The contributions of baseline and precipitating factors were documented to be independent and statistically significant. A simple predictive model based on the presence of five precipitating factors can be used to identify elderly medical patients at high risk for delirium. Precipitating and baseline vulnerability factors are highly interrelated and contribute to delirium in independent substantive, and cumulative ways.
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                Author and article information

                Contributors
                xinxi1003@163.com
                15222037573@163.com
                chenxuguangsjz@163.com
                490082645@qq.com
                18332336810@163.com
                huoshup@163.com
                drchangcf@163.com
                18713488965@163.com
                Journal
                J Neuroinflammation
                J Neuroinflammation
                Journal of Neuroinflammation
                BioMed Central (London )
                1742-2094
                14 November 2017
                14 November 2017
                2017
                : 14
                : 221
                Affiliations
                [1 ]GRID grid.452209.8, Department of Anesthesiology, , The Third Hospital of Hebei Medical University, ; No 139, Ziqiang Road, Shijiazhuang, 050051 Hebei People’s Republic of China
                [2 ]ISNI 0000 0000 9792 1228, GRID grid.265021.2, Department of Respiration, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, , Tianjin Medical University, ; Tianjin, 300350 People’s Republic of China
                Author information
                http://orcid.org/0000-0003-3873-9145
                Article
                999
                10.1186/s12974-017-0999-y
                5686947
                29137628
                83a90413-a2a3-4c33-956e-2d38d1c82fd5
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 August 2017
                : 8 November 2017
                Funding
                Funded by: the National Natural Science Foundation of China
                Award ID: 30972832
                Award Recipient :
                Funded by: Hebei Provincial Government Funded Clinical Talents Cultivation and Basic Research Projects
                Award ID: 361005
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Neurosciences
                hypertonic saline,postoperative delirium,elderly,monocytes,cytokines,neuroinflammation
                Neurosciences
                hypertonic saline, postoperative delirium, elderly, monocytes, cytokines, neuroinflammation

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