Impact of Dexmedetomidine on Long-term Outcomes After Noncardiac Surgery in Elderly: 3-Year Follow-up of a Randomized Controlled Trial

Zhang, Danfeng; Su, Xian; Meng, Zhaojun; Li, Hongliang; Wang, Dong‐Xin; Li, Xueying; Maze, Mervyn; Ma, Daqing

doi:10.1097/sla.0000000000002801

Cited by 63 publications

(51 citation statements)

References 36 publications

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“…A randomised control trial by Su et al reported a 60% reduced rate of post-operative delirium after an infusion of dexmedetomidine [ 88 ]. Furthermore, a recent randomised controlled trial discovered improved cognitive function and quality of life in 3-year survivors, as well as increasing survival up to 2-years after a low-dose dexmedetomidine infusion in non-cardiac surgery [ 89 ]. In a meta-analysis of 13 studies with over 1300 patients, Zhou et al estimated an effect size of 40% reduction in the risk of POCD [ 90 ].…”

Section: Therapeutic Options For Post-operative Neurological Complicamentioning

confidence: 99%

Surgery, neuroinflammation and cognitive impairment

et al. 2018

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Trauma experienced during surgery can contribute to the development of a systemic inflammatory response that can cause multi-organ dysfunction or even failure. Post-surgical neuroinflammation is a documented phenomenon that results in synaptic impairment, neuronal dysfunction and death, and impaired neurogenesis. Various pro-inflammatory cytokines, such as TNFα, maintain a state of chronic neuroinflammation, manifesting as post-operative cognitive dysfunction and post-operative delirium. Furthermore, elderly patients with post-operative cognitive dysfunction or delirium are three times more likely to experience permanent cognitive impairment or dementia. We conducted a narrative review, considering evidence extracted from various databases including Pubmed, MEDLINE and EMBASE, as well as journals and book reference lists. We found that further pre-clinical and well-powered clinical studies are required to delineate the precise pathogenesis of post-operative delirium and cognitive dysfunction. Despite the burden of post-operative neurological sequelae, clinical studies investigating therapeutic agents, such as dexmedetomidine, ibuprofen and statins, have yielded conflicting results. In addition, evidence supporting novel therapeutic avenues, such as nicotinic and HMGB-1 targeting and remote ischaemic pre-conditioning, is limited and necessitates further investigation.

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Section: Therapeutic Options For Post-operative Neurological Complicamentioning

confidence: 99%

Surgery, neuroinflammation and cognitive impairment

et al. 2018

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“…The trial demonstrated that low-dose, prophylactic dexmedetomidine in patients > 65 years of age significantly reduced the incidence of postoperative delirium in the first week after surgery [ 102 ]. In the 3-year follow-up study of the trial, we further demonstrated that dexmedetomidine recipients showed significantly improved quality of life, cognitive function and long-term survival [ 103 ]. In a parallel, in a separate randomized trial study, we demonstrated that prophylactic dexmedetomidine in non-cardiac surgery patients increased non-rapid eye movement sleep and improved overall sleep quality, which likely contribute to the lowered incidence of delirium [ 104 ].…”

Section: Elderly and Cognitionmentioning

confidence: 99%

Lasting effects of general anesthetics on the brain in the young and elderly: “mixed picture” of neurotoxicity, neuroprotection and cognitive impairment

Zhao

Weng

et al. 2019

J Anesth

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General anesthetics are commonly used in major surgery. To achieve the depth of anesthesia for surgery, patients are being subjected to a variety of general anesthetics, alone or in combination. It has been long held an illusory concept that the general anesthesia is entirely reversible and that the central nervous system is returned to its pristine state once the anesthetic agent is eliminated from the active site. However, studies indicate that perturbation of the normal functioning of these targets may result in long-lasting desirable or undesirable effects. This review focuses on the impact of general anesthetic exposure to the brain and summarizes the molecular and cellular mechanisms by which general anesthetics may induce long-lasting undesirable effects when exposed at the developing stage of the brain. The vulnerability of aging brain to general anesthetics, specifically in the context of cognitive disorders and Alzheimer’s disease pathogeneses are also discussed. Moreover, we will review emerging evidence regarding the neuroprotective property of xenon and anesthetic adjuvant dexmedetomidine in the immature and mature brains. In conclusion, “mixed picture” effects of general anesthetics should be well acknowledged and should be implemented into daily clinical practice for better patient outcome.

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“…The modi ed Barthel index was sensitive to in-hospital function changes [13,23], and 30-day mRS may re ect longer-term disability recovery after cranial surgery [21]. The postoperative long-term bene cial effects of dexmedetomidine is compatible to those observed among elderly undergoing non-cardiac surgery [27]. However, both mRS and modi ed Barthel index have rarely been applied in previous studies of dexmedetomidine use during cranial surgery.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Intraoperative Dexmedetomidine Infusion Combined With Goal-directed Hemodynamic Therapy for Patients Undergoing Cranial Surgery: A Double-blinded Randomized Controlled Trial

Chen

Lee

Yeh

et al. 2020

Preprint

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BackgroundDespite dexmedetomidine may be neuroprotective in patients undergoing cranial surgery by inhibiting neuroinflammation; however, it reduces cardiac output and cerebral blood flow. We proposed that dexmedetomidine infusion combined with goal-directed hemodynamic therapy (GDHT) could improve cranial surgery neurological outcomes without hemodynamic perturbation.MethodsA randomized, double-blind trial was conducted. One hundred sixty adult patients undergoing elective cranial surgery received either dexmedetomidine (0.5 μg kg−1 h−1) or saline during surgery. The goal-directed hemodynamic therapy was used for stroke volume optimization. The proportion of patients who developed postoperative new neurological deficits was compared. The severities of new neurological deficit were assessed by using in-hospital Barthel index changes and the 30-day modified Rankin Scale (mRS). Postoperative delirium was identified using the Intensive Care Delirium Screening Checklist (ICSDC) criteria. The level of a perioperative serum neuroinflammatory mediator, high motility group box 1 protein (HMGB1), was compared.ResultsThe dexmedetomidine group exhibited a lower cardiac index than did the control group (3.0 ± 0.8 vs. 3.4 ± 1.8 L min−1 m−2; p = 0.0482) without lactate accumulation. Fewer patients in the dexmedetomidine group developed new postoperative deficits (26.3% versus 43.8%; p = 0.031) but numbers of patients remained symptomatic neurological deficit before discharge were comparable between the two groups (23.8% vs. 38.8%; p= 0.060). In addition, an attenuated Barthel index decline (−6.3 ± 20.4 vs. −13.6 ± 24.8; p = 0.043), a more favorable 30-day mRS profile (p = 0.013), and a higher incidence of postoperative delirium-free (ICDSC scored 0: 84.6% versus 64.2%; p = 0.012) were observed in the dexmedetomidine group. Furthermore, dexmedetomidine induced a significant decline in perioperative serum HMGB1 level (222.5 ± 408.3 vs. 152.2 ± 280.0 ng mL−1; p = 0.0033).ConclusionsDexmedetomidine infusion combined with GDHT mitigates neuroinflammation during cranial surgery without hemodynamic perturbation, thus achieving neuroprotective effects.Clinical Trial RegistrationProspectively registered at clinicaltrials.gov. (identifier NCT02878707, date of registration: August 25, 2016)

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Impact of Dexmedetomidine on Long-term Outcomes After Noncardiac Surgery in Elderly: 3-Year Follow-up of a Randomized Controlled Trial

Abstract: For elderly admitted to ICU after noncardiac surgery, low-dose dexmedetomidine infusion did not significantly change 3-year overall survival, but increased survival up to 2 years, and improved cognitive function and quality of life in 3-year survivors.

Cited by 63 publications

References 36 publications

Surgery, neuroinflammation and cognitive impairment

Surgery, neuroinflammation and cognitive impairment

Lasting effects of general anesthetics on the brain in the young and elderly: “mixed picture” of neurotoxicity, neuroprotection and cognitive impairment

Neuroprotective Effects of Intraoperative Dexmedetomidine Infusion Combined With Goal-directed Hemodynamic Therapy for Patients Undergoing Cranial Surgery: A Double-blinded Randomized Controlled Trial

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