The Locus Coeruleus Noradrenaline System in Delirium

Hansen, Niels; Rediske, Alina Isabel

doi:10.3389/fnagi.2021.784356

Cited by 5 publications

(5 citation statements)

References 55 publications

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“…Gao et al demonstrated that transcutaneous electrical acupoint stimulation at bilateral LI4 and PC6 reduced neuroinflammation by lowering the permeability of the blood-brain barrier ( 12 ). Studies reported that one potential mechanism by which auricular acupressure may exert its anti-delirium effect is activating the locus coeruleus noradrenergic system, which is one of the central vagal relay centers and plays a critical role in the generating and regulating of delirium ( 27 , 28 ). By stimulating the ear branch of the vagus nerve, auricular acupressure may exert an add-on neuroprotective effect by direct and indirect modulation of the activity and connectivity of the locus coeruleus noradrenergic system, thus modulating the release and uptake of noradrenaline and dopamine in some key brain regions, including the prefrontal cortex and hippocampus, which are postulated to be associated with attention, memory, and other cognitive dysfunction ( 27 – 29 ).…”

Section: Discussionmentioning

confidence: 99%

“…Studies reported that one potential mechanism by which auricular acupressure may exert its anti-delirium effect is activating the locus coeruleus noradrenergic system, which is one of the central vagal relay centers and plays a critical role in the generating and regulating of delirium ( 27 , 28 ). By stimulating the ear branch of the vagus nerve, auricular acupressure may exert an add-on neuroprotective effect by direct and indirect modulation of the activity and connectivity of the locus coeruleus noradrenergic system, thus modulating the release and uptake of noradrenaline and dopamine in some key brain regions, including the prefrontal cortex and hippocampus, which are postulated to be associated with attention, memory, and other cognitive dysfunction ( 27 – 29 ). As postoperative delirium has been speculated to be a harbinger for postoperative cognitive dysfunction, the mechanism of acupuncture to prevent postoperative delirium may be similar to those of acupuncture to prevent postoperative cognitive dysfunction, which is by attenuating systemic inflammation and neuroinflammation, reducing oxidative stress levels, improving synaptic plasticity, and reducing neuronal injury ( 10 , 12 , 30 ).…”

Section: Discussionmentioning

confidence: 99%

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Transcutaneous Electrical Acupoint Stimulation Combined With Auricular Acupressure Reduces Postoperative Delirium Among Elderly Patients Following Major Abdominal Surgery: A Randomized Clinical Trial

Fan

Lei²,

Wang³

et al. 2022

Front. Med.

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BackgroundPostoperative delirium is common in elderly patients following major surgery. This study aimed to assess the effect of transcutaneous electrical acupoint stimulation combined with auricular acupressure on the incidence of postoperative delirium among older patients undergoing major abdominal surgery.MethodsIn this single-center, randomized controlled clinical trial, 210 patients aged 65 years or older undergoing major abdominal surgery were randomized to receive either intervention treatment (transcutaneous electrical acupoint stimulation started at 30 min before anesthesia until the end of the surgery, followed by intermittent auricular acupressure in the first three postoperative days; n = 105) or standard care (n = 105). The primary outcome was the incidence of delirium at the first seven postoperative days or until hospitalization depended on which came first. Secondary outcomes included delirium severity, opioid consumption, postoperative pain score, sleep quality, length of postoperative hospital stay, and postoperative 30-day complications. Enrollment was from April 2019 to March 2020, with follow-up ending in April 2020.ResultsAll of the 210 randomized patients [median age, 69.5 years, 142 (67.6%) male] completed the trial. The incidence of postoperative delirium was significantly reduced in patients received intervention treatment (19/105 (18.1%) vs. 8/105 (7.6%), difference, –10.5% [95% CI, –1.5% to –19.4%]; hazard ratio, 0.41 [95% CI, 0.18 to 0.95]; P= 0.023). Patients in the control group had a higher postoperative Memorial Delirium Assessment Scale (4 vs. 3; difference, –1; 95% CI, –1 to 0; P = 0.014) and a greater increase in Pittsburgh Sleep Quality Index score from baseline to postoperative day three (2.5 vs. 2.0; difference, –1; 95% CI, –2 to –1; P < 0.001) than patients in the intervention group. No significant difference was observed as of other secondary outcomes.ConclusionIn elderly patients undergoing major abdominal surgery, transcutaneous electrical acupoint stimulation combined with auricular acupressure reduced the incidence of postoperative in-hospital delirium compared with standard care. A multicenter, randomized clinical trial with a larger sample size is necessary to verify these findings.Clinical Trial Registration[https://clinicaltrials.gov], identifier [NCT03726073].

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcutaneous Electrical Acupoint Stimulation Combined With Auricular Acupressure Reduces Postoperative Delirium Among Elderly Patients Following Major Abdominal Surgery: A Randomized Clinical Trial

Fan

Lei²,

Wang³

et al. 2022

Front. Med.

View full text Add to dashboard Cite

show abstract

“…Another acupuncture technique, auricular acupressure, has been reported to exert its neuroprotective and anti-delirium effects by stimulating the auricular branches of the vagus nerve and activating the noradrenergic system of locus locus, one of the central relay centers of the vagus nerve, which plays a key role in the generating and regulation of delirium. [ 43 , 44 ] By directly or indirectly regulating the activity and connectivity of the norepinephrine system in locus locus, auricular acupressure regulates the release and uptake of norepinephrine and dopamine in some key brain regions, including the prefrontal cortex and hippocampus, which are postulated to be associated with attention, memory, and other cognitive dysfunction. [ 45 ] A review article by Hou et al [ 46 ] is consistent with the above views, showing that auricular acupressure can relieve pain, treat insomnia and anxiety, and improve sleep quality, and its mechanism may be achieved by regulating the neuroendocrine system, neuroinflammation and neural reflex, as well as antioxidant effects.…”

Section: Potential Mechanisms Of Acupuncture Against Podmentioning

confidence: 99%

Advances in the prevention and treatment of postoperative delirium by acupuncture: A review

Yang

Wang

Cao³

2023

Medicine

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Postoperative delirium is a common postoperative complication of neurocognitive dysfunction, especially in elderly surgical patients. Postoperative delirium not only damages patients’ recovery but also increases social costs. Therefore, its prevention and treatment has essential clinical and social significance. However, due to its intricate pathogenesis and limited pharmacological interventions, the effective prevention and treatment of postoperative delirium remains a thorny problem. As traditional acupuncture therapy has been shown to be an effective treatment in many neurological disorders, and in recent years, it has begun to be clinically used as an intervention for postoperative delirium. Although most clinical and animal studies confirm that multiple types of acupuncture interventions can alleviate or prevent postoperative delirium by relieving acute postoperative pain, reducing the consumption of anesthetics and analgesics, attenuating neuroinflammation and neuronal lesions, while more evidence-based medical evidence and clinical validation are needed for these encouraging effects.

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“…These agents exert their therapeutic effects by modulating alpha-2A, 2B, and 2C receptors and subsequently inhibit the presynaptic release of norepinephrine (NE) [ 8 , 9 ]. Delirium models have supported an excess of NE, which propagates neuronal damage and cell death, thus worsening symptomatology [ 14 , 18 ]. Additionally, these alpha-2 agonists may inhibit glutamate release via the suppression of voltage-dependent calcium channels and mitogen-activated protein kinase [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

A Retrospective Analysis of Guanfacine for the Pharmacological Management of Delirium

Jiang¹,

Hernandez²,

Burke³

et al. 2023

Cureus

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BackgroundDelirium is a syndrome of acute brain failure that represents a change from an individual's baseline cognitive functioning characterized by deficits in attention and multiple aspects of cognition that fluctuate in severity over time. The symptomatic management of delirium's behavioral manifestations remains difficult. The alpha-2 agonists, dexmedetomidine and clonidine, are efficacious, but their potential cardiovascular adverse effects limit their utilization. Guanfacine is an oral alpha-2 agonist with a lower potential for such adverse outcomes; however, its use in delirium has not been studied. MethodsA retrospective descriptive analysis of guanfacine for managing hyperactive or mixed delirium at Tampa General Hospital from January 2020 to October 2020 was conducted. The primary outcome was the time reduction in acute sedative administration. Secondary outcomes included renewed participation in physical therapy or occupational therapy (PT/OT), decreased opioid use, and an incidence of cardiovascular adverse effects. ResultsOne hundred forty-nine patients were identified as having received guanfacine for managing delirium during the study period. All experienced a reduction in acute sedative use after the initiation of guanfacine. In 93 patients receiving PT/OT and no longer participating due to behavioral agitation, 74% had a documented renewal of services within four days. Of 112 patients on opioids, 70% experienced a 25% reduction in opioid administration within four days. No patients experienced consecutive episodes of hypotension that required a change in their clinical care. Two patients experienced a single episode of consecutive bradycardia that led to the discontinuation of guanfacine. ConclusionsBased on our retrospective study, guanfacine is a well-tolerated medication for the management of delirium. Even in medically and critically ill patients, cardiovascular adverse events were rare with guanfacine. Patients treated with guanfacine experienced decreased acute sedative use for behavioral agitation. Additionally, patients treated with guanfacine received fewer opioids and were better able to participate in PT/OT. Future studies with prospective, randomized, placebo-controlled designs are warranted to evaluate this promising intervention for delirium further.

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The Locus Coeruleus Noradrenaline System in Delirium

Cited by 5 publications

References 55 publications

Transcutaneous Electrical Acupoint Stimulation Combined With Auricular Acupressure Reduces Postoperative Delirium Among Elderly Patients Following Major Abdominal Surgery: A Randomized Clinical Trial

Transcutaneous Electrical Acupoint Stimulation Combined With Auricular Acupressure Reduces Postoperative Delirium Among Elderly Patients Following Major Abdominal Surgery: A Randomized Clinical Trial

Advances in the prevention and treatment of postoperative delirium by acupuncture: A review

A Retrospective Analysis of Guanfacine for the Pharmacological Management of Delirium

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