Dexmedetomidine for the management of delirium in critically ill patients—A protocol for a systematic review

Maagaard, Mathias; Barbateskovic, Marija; Perner, Anders; Jakobsen, Janus Christian; Wetterslev, Jørn

doi:10.1111/aas.13329

Cited by 7 publications

(6 citation statements)

References 92 publications

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“…DEX is a highly selective α 2 -adrenoceptor (α 2 -AR) and imidazoline receptor agonist, 18 has been widely used for sedation and analgesia in anesthesia as well as antihypertensive, anxiolytic, and anti-delirium. [19][20][21] DEX may lead to the temporary less food intake as a sedation during the initial 7 days posttreatment, after this kind of calming effect gradually reduce and disappear, namely, the mice developed a tolerance to the sedative effects of DEX, food intake will not different between Vehicle-and DEX-treated groups, the body weight continues to decline may be due to the inhibition of liver fatty acid synthesis by DEX, which resulted in a decrease in lipid synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…DEX is a highly selective α 2 -adrenoceptor (α 2 -AR) and imidazoline receptor agonist, 18 has been widely used for sedation and analgesia in anesthesia as well as antihypertensive, anxiolytic, and anti-delirium in the intensive care unit. [19][20][21] DEX can exert its effects via activation of three α 2 -adrenoreceptor subtypes. α2A and α 2C -adrenoreceptor (α 2A -AR and α 2C -AR) located in presynaptic membrane, and regulate the release of neurotransmitter (norepinephrine) in the central nervous system (CNS), cause transient hypertension, hyperglycemia, and tachycardia, which form a negative feedback loop to reduce the release of norepinephrine by inhibiting α 2A -AR.…”

Section: Introductionmentioning

confidence: 99%

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Dexmedetomidine ameliorates high‐fat diet‐induced nonalcoholic fatty liver disease by targeting SCD1 in obesity mice

Tao

Guo

et al. 2020

Pharmacology Res & Perspec

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Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no therapeutic drugs approved for this pathology. Insulin resistance (IR) is implicated both in pathogenesis of nonalcoholic fatty liver disease (NAFLD) and in disease progression from steatosis to nonalcoholic steatohepatitis. In this study, we have characterized effects of an α 2 ‐adrenoceptor agonist, dexmedetomidine (DEX), which can alleviate IR in hepatocytes in high‐fat diet (HFD)‐induced NAFLD mice. The NAFLD mice received a daily intraperitoneal administration of DEX (100 μg·kg ‐1 ) after 16 days exhibited lower body weight, fewer and smaller fat droplets in the liver, markedly reduced the plasma triglyceride levels, accompanied by improvement of liver damage. This inhibition of lipid accumulation activity in obese mice was associated with a robust reduction in the mRNA and protein expression of the lipogenic enzyme stearyl‐coenzyme A desaturase 1 (SCD1), which was probably mediated by the inhibition of C/EBP β, PPAR γ and C/EBP α through suppressing α 2A ‐adrenoceptor ( α 2A ‐AR ) via negative feedback. Additionally, DEX can also improve IR and inflammation by inhibiting the mitogen‐activated protein kinases (MAPK) and nuclear factor kappa beta (NFκB) signaling pathway in vivo. Our findings implicate that DEX may act as a potential anti‐steatotic drug which ameliorates obesity‐associated fatty liver and improves IR and inflammation, probably by suppressing the expression of SCD1 and the inhibition of MAPK/NFκB pathway and suggest the potential adjuvant use for the treatment of NAFLD.

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Section: Discussionmentioning

confidence: 99%

“…DEX is a highly selective α 2 -adrenoceptor (α 2 -AR) and imidazoline receptor agonist, 18 has been widely used for sedation and analgesia in anesthesia as well as antihypertensive, anxiolytic, and anti-delirium in the intensive care unit. [19][20][21] DEX can exert its effects via activation of three α 2 -adrenoreceptor subtypes. α2A and α 2C -adrenoreceptor (α 2A -AR and α 2C -AR) located in presynaptic membrane, and regulate the release of neurotransmitter (norepinephrine) in the central nervous system (CNS), cause transient hypertension, hyperglycemia, and tachycardia, which form a negative feedback loop to reduce the release of norepinephrine by inhibiting α 2A -AR.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine ameliorates high‐fat diet‐induced nonalcoholic fatty liver disease by targeting SCD1 in obesity mice

Tao

Guo

et al. 2020

Pharmacology Res & Perspec

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“…85 86 The method has previously been applied by our group in systematic reviews with meta-analysis on a wide range of healthcare topics. [87][88][89][90][91][92][93][94] A PRISMA-P checklist file is attached (online supplementary additional file 1).…”

Section: Methods and Analysismentioning

confidence: 99%

Effects of adding adjunctive hyperbaric oxygen therapy to standard wound care for diabetic foot ulcers: a protocol for a systematic review with meta-analysis and trial sequential analysis

et al. 2020

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IntroductionDiabetic foot ulcer represents a major health problem globally. Preliminary studies have indicated that systemic treatment of diabetic foot ulcer patients with hyperbaric oxygen therapy have beneficial effects on wound healing, risk of amputation, glycaemic control, atherosclerosis, inflammatory markers and other clinical and laboratory parameters. This protocol for a systematic review aims at identifying the beneficial and harmful effects of adding hyperbaric oxygen therapy to standard wound care for diabetic foot ulcers.Methods and analysisThis protocol was performed following the recommendations of the Cochrane Collaboration and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials assessing the effects of hyperbaric oxygen therapy in the treatment of diabetic foot ulcer versus any control group with any intervention defined as standard wound care or similar, together with sham interventions. Our primary outcome will be: all-cause mortality, serious adverse events and quality of life. Our secondary outcomes will be: healing of index wound, major amputation and wound infection. Any eligible trial will be assessed and classified as either high risk of bias or low risk of bias, and our conclusions will be based on trials with low risk of bias. The analyses of the extracted data will be performed using Review Manager 5 and Trial Sequential Analysis. For both our primary and secondary outcomes, we will create a ‘Summary of Findings’ table and use GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment to assess the quality of the evidence.Ethics and disseminationWe use publicly accessible documents as evidence, there is no participant involvement at an individual level and an institutional ethics approval is not required. The results of the review will be sought published in a peer-reviewed journals, also in the event of insignificant results or null results, and thereby it will be disseminated to clinicians and public available.PROSPERO registration numberCRD42019139256.

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“…On the contrary, other meta-analysis indicated that dexmedetomidine may reduce delirium and duration of MV in patients after cardiac surgery when compared with propofol[47], or in patients undergoing non-invasive ventilation in no-cardiac ICU[48]. According to Maagaard et al[49], the evidence regarding the use of dexmedetomidine in the treatment of ICU-D is conflicting and sparse. As the authors designed an exhaustive protocol for a systematic review, their results could give us valuable information on the real effectiveness of the drug on delirium management[49].…”

Section: Evidence Based Medicine Findings On Pharmacological Preventimentioning

confidence: 99%

“…According to Maagaard et al[49], the evidence regarding the use of dexmedetomidine in the treatment of ICU-D is conflicting and sparse. As the authors designed an exhaustive protocol for a systematic review, their results could give us valuable information on the real effectiveness of the drug on delirium management[49]. Finally, there is more uncertainty on the efficacy of anticholinesterase inhibitors as a systematic review found that these drugs offer no benefit in terms of prophylaxis, or treatment of diagnosed delirium[50].…”

Section: Evidence Based Medicine Findings On Pharmacological Preventimentioning

confidence: 99%

Current controversies and future perspectives on treatment of intensive care unit delirium in adults

Cascella¹,

Fiore²,

Leone³

et al. 2019

WJCCM

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Delirium is the most frequent manifestation of acute brain dysfunction in intensive care unit (ICU). Although antipsychotics are widely used to treat this serious complication, recent evidence has emphasized that these agents did not reduce ICU delirium (ICU-D) prevalence and did not improve survival, length of ICU or hospital stay after its occurrence. Of note, no pharmacological strategy to prevent or treat delirium has been identified, so far. In this scenario, new scientific evidences are urgently needed. Investigations on specific ICU-D subgroups, or focused on different clinical settings, and studies on medications other than antipsychotics, such as dexmedetomidine or melatonin, may represent interesting fields of research. In the meantime, because there is some evidence that ICU-D can be effectively prevented, the literature suggests strengthening all the strategies aimed at prevention through no-pharmacological approaches mostly focused on the correction of risk factors. The more appropriate strategy useful to treat established delirium remains the use of antipsychotics managed by choosing the right doses after a careful case-by-case analysis. While the evidence regarding the use of dexmedetomidine is still conflicting and sparse, this drug offers interesting perspectives for both ICU-D prevention and treatment. This paper aims to provide an overview of current pharmacological approaches of evidence-based medicine practice. The state of the art of the on-going clinical research on the topic and perspectives for future research are also addressed.

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Dexmedetomidine for the management of delirium in critically ill patients—A protocol for a systematic review

Abstract: This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 7 publications

References 92 publications

Dexmedetomidine ameliorates high‐fat diet‐induced nonalcoholic fatty liver disease by targeting SCD1 in obesity mice

Dexmedetomidine ameliorates high‐fat diet‐induced nonalcoholic fatty liver disease by targeting SCD1 in obesity mice

Effects of adding adjunctive hyperbaric oxygen therapy to standard wound care for diabetic foot ulcers: a protocol for a systematic review with meta-analysis and trial sequential analysis

Current controversies and future perspectives on treatment of intensive care unit delirium in adults

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