Niche Roles for Dexmedetomidine in the Intensive Care Unit

Wiegand, Alexandra; Behal, Michael L.; Robbins, Blake T.; Bissell, Brittany D; Pandya, Komal; Mefford, Breanne

doi:10.1177/10600280221151170

Cited by 5 publications

(5 citation statements)

References 66 publications

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“…This suggests that when patients developed NOAF without administration of dexmedetomidine, there was an additional risk of mortality beyond the combined risk of no dexmedetomidine and NOAF development. Although we cannot clarify the underlying biological mechanisms based on this study’s results, a possible explanation may be that the pleiotropic effect of dexmedetomidine on immunomodulation, sympatholytic activity, and hemodynamics is synergistic in the presence of NOAF …”

Section: Discussionmentioning

confidence: 68%

“…Although we cannot clarify the underlying biological mechanisms based on this study's results, a possible explanation may be that the pleiotropic effect of dexmedetomidine on immunomodulation, sympatholytic activity, and hemodynamics is synergistic in the presence of NOAF. 35 In contrast, there was no association between dexmedetomidine and in-hospital mortality in the SNUBH-ICU cohort. 36 This could be explained by differences in the baseline risk of death between cohorts.…”

Section: Discussionmentioning

confidence: 86%

“…Although we cannot clarify the underlying biological mechanisms based on this study’s results, a possible explanation may be that the pleiotropic effect of dexmedetomidine on immunomodulation, sympatholytic activity, and hemodynamics is synergistic in the presence of NOAF. 35 …”

Section: Discussionmentioning

confidence: 99%

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Association of Dexmedetomidine With New-Onset Atrial Fibrillation in Patients With Critical Illness

et al. 2023

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ImportanceDexmedetomidine is a widely used sedative in the intensive care unit (ICU) and has unique properties that may be associated with reduced occurrence of new-onset atrial fibrillation (NOAF).ObjectiveTo investigate whether the use of dexmedetomidine is associated with the incidence of NOAF in patients with critical illness.Design, Setting, and ParticipantsThis propensity score–matched cohort study was conducted using the Medical Information Mart for Intensive Care-IV database, which includes records of patients admitted to the ICU at Beth Israel Deaconess Medical Center in Boston dating 2008 through 2019. Included patients were those aged 18 years or older and hospitalized in the ICU. Data were analyzed from March through May 2022.ExposurePatients were divided into 2 groups according to dexmedetomidine exposure: those who received dexmedetomidine within 48 hours after ICU admission (dexmedetomidine group) and those who never received dexmedetomidine (no dexmedetomidine group).Main Outcomes and MeasuresThe primary outcome was the occurrence of NOAF within 7 days of ICU admission, as defined by the nurse-recorded rhythm status. Secondary outcomes were ICU length of stay, hospital length of stay, and in-hospital mortality.ResultsThis study included 22 237 patients before matching (mean [SD] age, 65.9 [16.7] years; 12 350 male patients [55.5%]). After 1:3 propensity score matching, the cohort included 8015 patients (mean [SD] age, 61.0 [17.1] years; 5240 males [65.4%]), among whom 2106 and 5909 patients were in the dexmedetomidine and no dexmedetomidine groups, respectively. Use of dexmedetomidine was associated with a decreased risk of NOAF (371 patients [17.6%] vs 1323 patients [22.4%]; hazard ratio, 0.80; 95% CI, 0.71-0.90). Although patients in the dexmedetomidine group had longer median (IQR) length of stays in the ICU (4.0 [2.7-6.9] days vs 3.5 [2.5-5.9] days; P &lt; .001) and hospital (10.0 [6.6-16.3] days vs 8.8 [5.9-14.0] days; P &lt; .001), dexmedetomidine was associated with decreased risk of in-hospital mortality (132 deaths [6.3%] vs 758 deaths [12.8%]; hazard ratio, 0.43; 95% CI, 0.36-0.52).Conclusions and RelevanceThis study found that dexmedetomidine was associated with decreased risk of NOAF in patients with critical illness, suggesting that it may be necessary and warranted to evaluate this association in future clinical trials.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 86%

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Association of Dexmedetomidine With New-Onset Atrial Fibrillation in Patients With Critical Illness

et al. 2023

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“…In the acute phase, SAP patients usually require admission to the intensive care unit for symptomatic treatment such as mechanical ventilation, fluid resuscitation, or renal replacement therapy ( Yang, et al, 2023 ). Dex reacts with α2 adrenergic receptors in the central nervous system, decreases sympathetic activity, leading to a shift in balance to the parasympathetic nervous system (including the vagus nerve), and is widely used in the intensive care unit ( Wiegand, et al, 2023 ). This study elucidated the remarkable effect of Dex against SAP and investigated the potential mechanism of action by RNA sequencing.…”

Section: Discussionmentioning

confidence: 99%

RNA-sequencing approach for exploring the protective mechanisms of dexmedetomidine on pancreatic injury in severe acute pancreatitis

Yao

Lan

et al. 2023

Front. Pharmacol.

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Background: Severe acute pancreatitis (SAP) is a severe form of acute pancreatitis with the potential to cause life-threatening complications. Patients with acute SAP require surgical intervention and are admitted to the intensive care unit for non-invasive ventilation. Dexmedetomidine (Dex) is currently used by intensive care clinicians and anaesthesiologists as an adjunctive sedative. Therefore, the clinical availability of Dex makes it easier to implement in SAP treatment than developing new drugs.Methods: Randomly dividing thirty rats into sham-operated (Sham), SAP, and Dex groups. The severity of pancreatic tissue injury in each rat was assessed by Hematoxylin and eosin (HE) staining. Serum amylase activity and inflammatory factor levels were measured using commercially available kits. The expressions of necroptosis-related proteins, myeloperoxidase (MPO), CD68, and 4-hydroxy-trans-2-nonenal (HNE) were detected using immunohistochemistry (IHC). Transferase-mediated dUTP nick-end labeling (TUNEL) staining was utilized to identify pancreatic acinar cell apoptosis. The subcellular organelle structure of pancreatic acinar cells was observed using transmission electron microscopy. The regulatory effect of Dex on the gene expression profile of SAP rat pancreas tissue was investigated using RNA sequencing. We screened for differentially expressed genes (DEGs). Quantitative real-time PCR (qRT-PCR) measured critical DEG mRNA expression in rat pancreatic tissues.Results: Dex attenuated SAP-induced pancreatic injury, infiltration of neutrophils and macrophages, and oxidative stress. Dex inhibited the expression of necroptosis-associated proteins RIPK1, RIPK3, and MLKL and alleviated apoptosis in acinar cells. Dex also mitigated the structural damage caused by SAP to mitochondria and endoplasmic reticulum. Dex inhibited SAP-induced 473 DEGs, as determined by RNA sequencing. Dex may regulate SAP-induced inflammatory response and tissue damage by inhibiting the toll-like receptor/nuclear factor κB (TLR/NF-κB) signaling pathway and neutrophil extracellular trap formation.Conclusion: This study elucidated the remarkable effect of Dex against SAP and investigated the potential mechanism of action, providing an experimental base for the future clinical application of Dex in the treatment of SAP.

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“…Similarly, response to norepinephrine decreases following application of lipopolysaccharide and the administration of α2 agonists increases this response in rats (45). Dexmedetomidine (DEX), is one of the most commonly used sedation agents in intensive care (46)(47)(48). As a highly selective α2-adrenoreceptor agonist, DEX serves as an adjunctive therapy through pro-inflammatory downregulation and control of the anti-inflammatory response in patients with sepsis (49).…”

Section: Evaluation Of the Efficacy Of Silymarin And Dexmedetomidine ...mentioning

confidence: 99%

Evaluation of the efficacy of silymarin and dexmedetomidine on kidney and lung tissue in the treatment of sepsis in rats with cecal perforation

Yavuz,

Küçük,

Ergörün

et al. 2024

Exp Ther Med

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Sepsis is a systemic inflammatory response syndrome that develops in the host against microorganisms. This response develops away from the primary infection site and results in end-organ damage. The present study aimed to investigate the protective and therapeutic effects on lung and kidney tissue of silymarin (S) and dexmedetomidine (DEX) applied 1 h before and after sepsis induced by the cecal ligation and puncture (CLP) method in rats. A total of 62 rats was randomly divided into eight groups: i) Control (n=6); ii) cecal perforation (CLP; n=8); iii) S + CLP (n=8; S + CLP; S administered 1 h before CPL); iv) CLP + S (n=8; S administered 1 h after CLP); v) DEX + CLP (n=8; D + CLP; DEX administered 1 h before CLP); vi) CLP + D (n=8; DEX administered 1 h after CLP); vii) SD + CLP (n=8; S and DEX administered 1 h before CLP) and viii) CLP + SD (n=8; S and DEX administered 1 h after CLP). After the cecum filled with stool, it was tied with 3/0 silk under the ileocecal valve and the anterior surface of the cecum was punctured twice with an 18-gauge needle. A total of 100 mg/kg silymarin and 100 µg/kg DEX were administered intraperitoneally to the treatment groups. Lung and kidney tissue samples were collected to evaluate biochemical and histopathological parameters. In the histopathological examination, all parameters indicating kidney injury; interstitial edema, peritubular capillary dilatation, vacuolization, ablation of tubular epithelium from the basement membrane, loss of brush border in the proximal tubule epithelium, cell swelling and nuclear defragmentation; were increased in the CLP compared with the control group. Silymarin administration increased kidney damage, including ablation of tubular epithelium from the basement membrane, compared with that in the CLP group. DEX significantly reduced kidney damage compared with the CLP and silymarin groups. The co-administration of DEX + silymarin decreased kidney damage, although it was not as effective as DEX-alone. To conclude, intraperitoneal DEX ameliorated injury in CLP rats. DEX + silymarin partially ameliorated injury but silymarin administration increased damage. As a result, silymarin has a negative effects with this dosage and DEX has a protective effect. In the present study, it was determined that using the two drugs together had a greater therapeutic effect than silymarin and no differences in the effects were not observed any when the application times of the agents were changed.

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Niche Roles for Dexmedetomidine in the Intensive Care Unit

Cited by 5 publications

References 66 publications

Association of Dexmedetomidine With New-Onset Atrial Fibrillation in Patients With Critical Illness

Association of Dexmedetomidine With New-Onset Atrial Fibrillation in Patients With Critical Illness

RNA-sequencing approach for exploring the protective mechanisms of dexmedetomidine on pancreatic injury in severe acute pancreatitis

Evaluation of the efficacy of silymarin and dexmedetomidine on kidney and lung tissue in the treatment of sepsis in rats with cecal perforation

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