RESUMEN
Postoperative sleep disturbance is a common issue that affects recovery in patients undergoing general anesthesia. Dexmedetomidine (Dex) has a potential role in improving postoperative sleep quality. We evaluated the effects of different doses of Dex on postoperative sleep disturbance and serum neurotransmitters in patients undergoing radical gastrectomy under general anesthesia. Patients were assigned to the control, NS, and Dex (Dex-L/M/H) groups based on different treatment doses [0.2, 0.4, and 0.6 µg/(kg · h)]. The Athens Insomnia Scale (AIS) and ELISA kits were used to assess sleep disturbance and serum neurotransmitter (GABA, 5-HT, NE) levels before surgery and on postoperative days one, four, and seven. The effects of different doses on postoperative sleep disturbance incidence and serum neurotransmitter levels were analyzed by the Fisher exact test and one-way and repeated-measures ANOVA. Patients had no differences in gender, age, body mass index, operation time, and bleeding volume. Different Dex doses reduced the postoperative AIS score of patients under general anesthesia, improved their sleep, and increased serum levels of 5-HT, NE, and GABA. Furthermore, the effects were dose-dependent within the range of safe clinical use. Specifically, Dex at doses of 0.2, 0.4, and 0.6 µg/(kg · h) reduced postoperative AIS score, elevated serum neurotransmitter levels, and reduced postoperative sleep disturbance incidence. Collectively, Dex has a potential preventive effect on postoperative sleep disturbance in patients undergoing general anesthesia for radical gastrectomy. The optimal dose of Dex is between 0.2 and 0.6 µg/(kg · h), which significantly reduces the incidence of postoperative sleep disturbance and increases serum neurotransmitter levels.
Asunto(s)
Anestesia General , Dexmedetomidina , Neurotransmisores , Complicaciones Posoperatorias , Trastornos del Sueño-Vigilia , Humanos , Dexmedetomidina/administración & dosificación , Anestesia General/efectos adversos , Neurotransmisores/sangre , Masculino , Femenino , Trastornos del Sueño-Vigilia/etiología , Trastornos del Sueño-Vigilia/epidemiología , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Incidencia , Anciano , Gastrectomía/efectos adversosRESUMEN
The present study investigated the impact of central α2-adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α2-adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg-1; maintenance infusion of 0.1-0.5 µg kg h-1) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats-1, P = 0.003) most strongly for medium-sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats-1; P < 0.001). Dexmedetomidine progressively de-recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de-recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats-1, P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ -0.09 ± 0.07 to Δ -0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium-sized APs (normalized cluster 2: -6.0 ± 5 to -1.6 ± 2 % mmHg-1; P = 0.008). These data suggest that α2-adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. KEY POINTS: Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear. This microneurographic study investigated the impact of a dexmedetomidine infusion (α2-adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns. Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre. Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre. These data suggest that α2-adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans.
Asunto(s)
Potenciales de Acción , Agonistas de Receptores Adrenérgicos alfa 2 , Dexmedetomidina , Sistema Nervioso Simpático , Humanos , Dexmedetomidina/farmacología , Femenino , Adulto , Masculino , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Sistema Nervioso Simpático/fisiología , Sistema Nervioso Simpático/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Adulto Joven , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Presión Sanguínea/fisiología , Presión Sanguínea/efectos de los fármacos , Músculo Esquelético/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/efectos de los fármacos , Receptores Adrenérgicos alfa 2/fisiología , Receptores Adrenérgicos alfa 2/metabolismoRESUMEN
Dexmedetomidine (DEX) is a highly selective and potent α2-adrenoceptor (α2-AR) agonist that is widely used as a clinical anesthetic to induce anxiolytic, sedative, and analgesic effects. In recent years, a growing body of evidence has demonstrated that DEX protects against acute kidney injury (AKI) caused by sepsis, drugs, surgery, and ischemia-reperfusion (I/R) in organs or tissues, indicating its potential role in the prevention and treatment of AKI. In this review, we summarized the evidence of the renoprotective effects of DEX on different models of AKI and explored the mechanism. We found that the renoprotective effects of DEX mainly involved antisympathetic effects, reducing inflammatory reactions and oxidative stress, reducing apoptosis, increasing autophagy, reducing ferroptosis, protecting renal tubular epithelial cells (RTECs), and inhibiting renal fibrosis. Thus, the use of DEX is a promising strategy for the management and treatment of perioperative AKI. The aim of this review is to further clarify the renoprotective mechanism of DEX to provide a theoretical basis for its use in basic research in various AKI models, clinical management, and the treatment of perioperative AKI.
Asunto(s)
Lesión Renal Aguda , Dexmedetomidina , Daño por Reperfusión , Humanos , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/prevención & control , Transducción de Señal , Inflamación/tratamiento farmacológico , Apoptosis , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & controlRESUMEN
BACKGROUND: Dexmedetomidine (DEX), a highly selective α2-adrenoceptor agonist, can decrease the incidence of arrhythmias, such as catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the underlying mechanisms by which DEX affects cardiac electrophysiological function remain unclear. METHODS: Ryanodine receptor (RyR2) heterozygous R2474S mice were used as a model for CPVT. WT and RyR2R2474S/+ mice were treated with isoproterenol (ISO) and DEX, and electrocardiograms were continuously monitored during both in vivo and ex vivo experiments. Dual-dye optical mapping was used to explore the anti-arrhythmic mechanism of DEX. RESULTS: DEX significantly reduced the occurrence and duration of ISO-induced of VT/VF in RyR2R2474S/+ mice in vivo and ex vivo. DEX remarkably prolonged action potential duration (APD80) and calcium transient duration (CaTD80) in both RyR2R2474S/+ and WT hearts, whereas it reduced APD heterogeneity and CaT alternans in RyR2R2474S/+ hearts. DEX inhibited ectopy and reentry formation, and stabilized voltage-calcium latency. CONCLUSION: DEX exhibited an antiarrhythmic effect through stabilizing membrane voltage and intracellular Ca2+. DEX can be used as a beneficial perioperative anesthetic for patients with CPVT or other tachy-arrhythmias.
Asunto(s)
Arritmias Cardíacas , Calcio , Dexmedetomidina , Canal Liberador de Calcio Receptor de Rianodina , Animales , Dexmedetomidina/farmacología , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/genética , Calcio/metabolismo , Ratones , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/genética , Potenciales de la Membrana/efectos de los fármacos , Isoproterenol/farmacología , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/genética , Taquicardia Ventricular/tratamiento farmacológico , Antiarrítmicos/farmacología , Masculino , Potenciales de Acción/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Glutamate metabolism disorder is an important mechanism of sepsis-associated encephalopathy (SAE). Astrocytes regulate glutamate metabolism. In septic mice, α2A adrenoceptor (α2A-AR) activation in the central nervous system provides neuroprotection. α2A-ARs are expressed abundantly in hippocampal astrocytes. This study was performed to determine whether hippocampal astrocytic α2A-AR activation confers neuroprotection against SAE and whether this protective effect is astrocyte specific and achieved by the modulation of glutamate metabolism. METHODS: Male C57BL/6 mice with and without α2A-AR knockdown were subjected to cecal ligation and puncture (CLP). They were treated with intrahippocampal guanfacine (an α2A-AR agonist) or intraperitoneal dexmedetomidine in the presence or absence of dihydrokainic acid [DHK; a glutamate transporter 1 (GLT-1) antagonist] and/or UCPH-101 [a glutamate/aspartate transporter (GLAST) antagonist]. Hippocampal tissue was collected for the measurement of astrocyte reactivity, GLT-1 and GLAST expression, and glutamate receptor subunit 2B (GluN2B) phosphorylation. In vivo real-time extracellular glutamate concentrations in the hippocampus were measured by ultra-performance liquid chromatography tandem mass spectrometry combined with microdialysis, and in vivo real-time hippocampal glutamatergic neuron excitability was assessed by calcium imaging. The mice were subjected to the Barnes maze and fear conditioning tests to assess their learning and memory. Golgi staining was performed to assess changes in the hippocampal synaptic structure. In vitro, primary astrocytes with and without α2A-AR knockdown were stimulated with lipopolysaccharide (LPS) and treated with guanfacine or dexmedetomidine in the presence or absence of 8-bromo- cyclic adenosine monophosphate (8-Br-cAMP, a cAMP analog). LPS-treated primary and BV2 microglia were also treated with guanfacine or dexmedetomidine. Astrocyte reactivity, PKA catalytic subunit, GLT-1 an GLAST expression were determined in primary astrocytes. Interleukin-1ß, interleukin-6 and tumor necrosis factor-alpha in the medium of microglia culture were measured. RESULTS: CLP induced synaptic injury, impaired neurocognitive function, increased astrocyte reactivity and reduced GLT-1 and GLAST expression in the hippocampus of mice. The extracellular glutamate concentration, phosphorylation of GluN2B at Tyr-1472 and glutamatergic neuron excitability in the hippocampus were increased in the hippocampus of septic mice. Intraperitoneal dexmedetomidine or intrahippocampal guanfacine administration attenuated these effects. Hippocampal astrocytes expressed abundant α2A-ARs; expression was also detected in neurons but not microglia. Specific knockdown of α2A-ARs in hippocampal astrocytes and simultaneous intrahippocampal DHK and UCPH-101 administration blocked the neuroprotective effects of dexmedetomidine and guanfacine. Intrahippocampal administration of DHK or UCPH-101 alone had no such effect. In vitro, guanfacine or dexmedetomidine inhibited astrocyte reactivity, reduced PKA catalytic subunit expression, and increased GLT-1 and GLAST expression in primary astrocytes but not in primary astrocytes that received α2A-AR knockdown or were treated with 8-Br-cAMP. Guanfacine or dexmedetomidine inhibited microglial reactivity in BV2 but not primary microglia. CONCLUSIONS: Our results suggest that neurocognitive protection against SAE after hippocampal α2A-AR activation is astrocyte specific. This protection may involve the inhibition of astrocyte reactivity and alleviation of glutamate neurotoxicity, thereby reducing synaptic injury. The cAMP/protein kinase A (PKA) signaling pathway is a potential cellular mechanism by which activating α2A-AR modulates astrocytic function.
Asunto(s)
Dexmedetomidina , Encefalopatía Asociada a la Sepsis , Sepsis , Masculino , Animales , Ratones , Ratones Endogámicos C57BL , Ácido Glutámico , Astrocitos , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Guanfacina , Lipopolisacáridos , Hipocampo , Sepsis/complicacionesRESUMEN
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that severely affects individuals' daily life and social development. Unfortunately, there are currently no effective treatments for ASD. Dexmedetomidine (DEX) is a selective agonist of α2 adrenergic receptor (α2AR) and is widely used as a first-line medication for sedation and hypnosis in clinical practice. In recent years, there have been reports suggesting its potential positive effects on improving emotional and cognitive functions. However, whether dexmedetomidine has therapeutic effects on the core symptoms of ASD, namely social deficits and repetitive behaviors, remains to be investigated. In the present study, we employed various behavioral tests to assess the phenotypes of animals, including the three-chamber, self-grooming, marble burying, open field, and elevated plus maze. Additionally, electrophysiological recordings, western blotting, qPCR were mainly used to investigate and validate the potential mechanisms underlying the role of dexmedetomidine. We found that intraperitoneal injection of dexmedetomidine in ASD model mice-BTBR T+ Itpr3tf/J (BTBR) mice could adaptively improve their social deficits. Further, we observed a significant reduction in c-Fos positive signals and interleukin-6 (IL-6) expression level in the prelimbic cortex (PrL) of the BTBR mice treated with dexmedetomidine. Enhancing or inhibiting the action of IL-6 directly affects the social behavior of BTBR mice. Mechanistically, we have found that NF-κB p65 is a key pathway regulating IL-6 expression in the PrL region. In addition, we have confirmed that the α2AR acts as a receptor switch mediating the beneficial effects of dexmedetomidine in improving social deficits. This study provides the first evidence of the beneficial effects of dexmedetomidine on core symptoms of ASD and offers a theoretical basis and potential therapeutic approach for the clinical treatment of ASD.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2 , Trastorno del Espectro Autista , Dexmedetomidina , Modelos Animales de Enfermedad , Interleucina-6 , FN-kappa B , Receptores Adrenérgicos alfa 2 , Conducta Social , Animales , Dexmedetomidina/farmacología , Ratones , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/metabolismo , Masculino , Receptores Adrenérgicos alfa 2/metabolismo , Receptores Adrenérgicos alfa 2/efectos de los fármacos , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , FN-kappa B/metabolismo , Interleucina-6/metabolismo , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BL , Conducta Animal/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Inflamación/metabolismo , Inflamación/tratamiento farmacológicoRESUMEN
BACKGROUND: Although it has been established that elevated blood pressure and its variability worsen outcomes in spontaneous intracerebral hemorrhage, antihypertensives use during the acute phase still lacks robust evidence. A blood pressure-lowering regimen using remifentanil and dexmedetomidine might be a reasonable therapeutic option given their analgesic and antisympathetic effects. The objective of this superiority trial was to validate the efficacy and safety of this blood pressure-lowering strategy that uses remifentanil and dexmedetomidine in patients with acute intracerebral hemorrhage. METHODS: In this multicenter, prospective, single-blinded, superiority randomized controlled trial, patients with intracerebral hemorrhage and systolic blood pressure (SBP) 150 mmHg or greater were randomly allocated to the intervention group (a preset protocol with a standard guideline management using remifentanil and dexmedetomidine) or the control group (standard guideline-based management) to receive blood pressure-lowering treatment. The primary outcome was the SBP control rate (less than 140 mmHg) at 1 h posttreatment initiation. Secondary outcomes included blood pressure variability, neurologic function, and clinical outcomes. RESULTS: A total of 338 patients were allocated to the intervention (n = 167) or control group (n = 171). The SBP control rate at 1 h posttreatment initiation in the intervention group was higher than that in controls (101 of 161, 62.7% vs. 66 of 166, 39.8%; difference, 23.2%; 95% CI, 12.4 to 34.1%; P < 0.001). Analysis of secondary outcomes indicated that patients in the intervention group could effectively reduce agitation while achieving lighter sedation, but no improvement in clinical outcomes was observed. Regarding safety, the incidence of bradycardia and respiratory depression was higher in the intervention group. CONCLUSIONS: Among intracerebral hemorrhage patients with a SBP 150 mmHg or greater, a preset protocol using a remifentanil and dexmedetomidine-based standard guideline management significantly increased the SBP control rate at 1 h posttreatment compared with the standard guideline-based management.
Asunto(s)
Antihipertensivos , Presión Sanguínea , Hemorragia Cerebral , Dexmedetomidina , Remifentanilo , Humanos , Dexmedetomidina/uso terapéutico , Dexmedetomidina/administración & dosificación , Remifentanilo/administración & dosificación , Remifentanilo/uso terapéutico , Masculino , Femenino , Estudios Prospectivos , Hemorragia Cerebral/tratamiento farmacológico , Anciano , Persona de Mediana Edad , Método Simple Ciego , Presión Sanguínea/efectos de los fármacos , Antihipertensivos/uso terapéutico , Antihipertensivos/administración & dosificación , Resultado del Tratamiento , Hipnóticos y Sedantes/uso terapéuticoRESUMEN
BACKGROUND: Dexmedetomidine has repeatedly shown to improve anxiety, but the precise neural mechanisms underlying this effect remain incompletely understood. This study aims to explore the role of corticotropin-releasing hormone-producing hypothalamic paraventricular nucleus (CRHPVN) neurons in mediating the anxiolytic effects of dexmedetomidine. METHODS: A social defeat stress mouse model was used to evaluate the anxiolytic effects induced by dexmedetomidine through the elevated plus maze, open-field test, and measurement of serum stress hormone levels. In vivo Ca2+ signal fiber photometry and ex vivo patch-clamp recordings were used to determine the excitability of CRHPVN neurons and investigate the specific mechanism involved. CRHPVN neuron modulation was achieved through chemogenetic activation or inhibition. RESULTS: Compared with saline, dexmedetomidine (40 µg/kg) alleviated anxiety-like behaviors. Additionally, dexmedetomidine reduced CRHPVN neuronal excitability. Chemogenetic activation of CRHPVN neurons decreased the time spent in the open arms of the elevated plus maze and in the central area of the open-field test. Conversely, chemogenetic inhibition of CRHPVN neurons had the opposite effect. Moreover, the suppressive impact of dexmedetomidine on CRHPVN neurons was attenuated by the α2-receptor antagonist yohimbine. CONCLUSIONS: The results indicate that the anxiety-like effects of dexmedetomidine are mediated via α2-adrenergic receptor-triggered inhibition of CRHPVN neuronal excitability in the hypothalamus.
Asunto(s)
Ansiedad , Dexmedetomidina , Neuronas , Núcleo Hipotalámico Paraventricular , Estrés Psicológico , Animales , Masculino , Ratones , Ansiolíticos/farmacología , Ansiedad/tratamiento farmacológico , Hormona Liberadora de Corticotropina/metabolismo , Dexmedetomidina/farmacología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Estrés Psicológico/psicologíaRESUMEN
BACKGROUND: Both dexamethasone and dexmedetomidine increase the duration of analgesia of peripheral nerve blocks. The authors hypothesized that combined intravenous dexamethasone and intravenous dexmedetomidine would result in a greater duration of analgesia when compared with intravenous dexamethasone alone and placebo. METHODS: The authors randomly allocated participants undergoing surgery of the foot or ankle under general anesthesia and with a combined popliteal (sciatic) and saphenous nerve block to a combination of 12 mg dexamethasone and 1 µg/kg dexmedetomidine, 12 mg dexamethasone, or placebo (saline). The primary outcome was the duration of analgesia measured as the time from block performance until the first sensation of pain in the surgical area as reported by the participant. The authors predefined a 33% difference in the duration of analgesia as clinically relevant. RESULTS: A total of 120 participants from two centers were randomized and 119 analyzed for the primary outcome. The median [interquartile range] duration of analgesia was 1,572 min [1,259 to 1,715] with combined dexamethasone and dexmedetomidine, 1,400 min [1,133 to 1,750] with dexamethasone alone, and 870 min [748 to 1,138] with placebo. Compared with placebo, the duration was greater with combined dexamethasone and dexmedetomidine (difference, 564 min; 98.33% CI, 301 to 794; P < 0.001) and with dexamethasone (difference, 489 min; 98.33% CI, 265 to 706; P < 0.001). The prolongations exceeded the authors' predefined clinically relevant difference. The duration was similar when combined dexamethasone and dexmedetomidine was compared with dexamethasone alone (difference, 61 min; 98.33% CI, -222 to 331; P = 0.614). CONCLUSIONS: Dexamethasone with or without dexmedetomidine increased the duration of analgesia in patients undergoing surgery of the foot or ankle with a popliteal (sciatic) and saphenous nerve block. Combined dexamethasone and dexmedetomidine did not increase the duration of analgesia when compared with dexamethasone.
Asunto(s)
Tobillo , Dexametasona , Dexmedetomidina , Pie , Bloqueo Nervioso , Humanos , Dexmedetomidina/administración & dosificación , Dexametasona/administración & dosificación , Bloqueo Nervioso/métodos , Masculino , Femenino , Pie/cirugía , Persona de Mediana Edad , Tobillo/cirugía , Método Doble Ciego , Quimioterapia Combinada/métodos , Anciano , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Nervio Ciático/efectos de los fármacosRESUMEN
BACKGROUND: Dexmedetomidine (Dex), midazolam, and propofol are three distinct sedatives characterized by varying pharmacological properties. Previous literature has indicated the positive impact of each of these sedatives on ICU patients. However, there is a scarcity of clinical evidence comparing the efficacy of Dex, midazolam, and propofol in reducing mortality among people with epilepsy (PWE). This study aimed to assess the impact of Dex, midazolam, and propofol on the survival of PWE. METHODS: The data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC)-IV database (version 2.0). PWE were categorized into Dex, midazolam, and propofol groups based on the intravenously administered sedatives. PWE without standard drug therapy were included in the control group. Comparative analyses were performed on the data among the groups. RESULTS: The Dex group exhibited a significantly lower proportion of in-hospital deaths and a markedly higher in-hospital survival time compared to the midazolam and propofol groups (p < 0.01) after propensity score matching. Kaplan-Meier curves demonstrated a significant improvement in survival rates for the Dex group compared to the control group (p = 0.025). Analysis of Variance (ANOVA) revealed no significant differences in survival rates among the Dex, midazolam, and propofol groups (F = 1.949, p = 0.143). The nomogram indicated that compared to midazolam and propofol groups, Dex was more effective in improving the survival rate of PWE. CONCLUSION: Dex might improve the survival rate of PWE in the ICU compared to no standard drug intervention. However, Dex did not exhibit superiority in improving survival rates compared to midazolam and propofol.
Asunto(s)
Dexmedetomidina , Epilepsia , Hipnóticos y Sedantes , Unidades de Cuidados Intensivos , Midazolam , Propofol , Humanos , Dexmedetomidina/uso terapéutico , Midazolam/uso terapéutico , Midazolam/administración & dosificación , Propofol/administración & dosificación , Propofol/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Hipnóticos y Sedantes/uso terapéutico , Estudios Retrospectivos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Epilepsia/tratamiento farmacológico , Epilepsia/mortalidad , Adulto , Anciano , Bases de Datos Factuales/tendencias , Mortalidad Hospitalaria/tendenciasRESUMEN
BACKGROUND: After cardiac surgery, post-operative delirium (PoD) is acknowledged to have a significant negative impact on patient outcome. To date, there is no valuable and specific treatment for PoD. Critically ill patients often suffer from poor sleep condition. There is an association between delirium and sleep quality after cardiac surgery. This study aimed to establish whether promoting sleep using an overnight infusion of dexmedetomidine reduces the incidence of delirium after cardiac surgery. METHODS: Randomized, pragmatic, multicentre, double-blind, placebo controlled trial from January 2019 to July 2021. All adult patients aged 65 years or older requiring elective cardiac surgery were randomly assigned 1:1 either to the dexmedetomidine group or the placebo group on the day of surgery. Dexmedetomidine or matched placebo infusion was started the night after surgery from 8 pm to 8 am and administered every night while the patient remained in ICU, or for a maximum of 7 days. Primary outcome was the occurrence of postoperative delirium (PoD) within the 7 days after surgery. RESULTS: A total of 348 patients provided informed consent, of whom 333 were randomized: 331 patients underwent surgery and were analysed (165 assigned to dexmedetomidine and 166 assigned to placebo). The incidence of PoD was not significantly different between the two groups (12.6% vs. 12.4%, p = 0.97). Patients treated with dexmedetomidine had significantly more hypotensive events (7.3% vs 0.6%; p < 0.01). At 3 months, functional outcomes (Short-form 36, Cognitive failure questionnaire, PCL-5) were comparable between the two groups. CONCLUSION: In patients recovering from an elective cardiac surgery, an overnight infusion of dexmedetomidine did not decrease postoperative delirium. Trial registration This trial was registered on ClinicalTrials.gov (number: NCT03477344; date: 26th March 2018).
Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Delirio , Dexmedetomidina , Delirio del Despertar , Adulto , Humanos , Delirio del Despertar/inducido químicamente , Delirio del Despertar/tratamiento farmacológico , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Delirio/tratamiento farmacológico , Delirio/etiología , Delirio/prevención & control , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Método Doble CiegoRESUMEN
This study aims to analyze the reversal of lipopolysaccharide (LPS)-induced cardiomyocyte apoptosis via α7nAChR by dexmedetomidine (Dex), so as to provide references for clinical treatment of myocardial disorders in the future. First, the research team divided cardiomyocytes (H9C2) were divided into a control group (normal culture), an LPS group (LPS-induced injury model), and an experimental group (pretreated with Dex before LPS induction). Subsequently, lactate dehydrogenase (LDH) and cell activity were detected, and the research team found that the LDH content of the control, experimental and LPS groups were in ascending order (P<0.05). The cell viability decreased and apoptosis increased in the LPS group, with cells mainly concentrating in the G2-M phase; the viability increased and apoptosis decreased in the experimental group, with blocked G1-G0 phase (P<0.05). This demonstrates that Dex can reverse LPS-induced apoptosis in cardiomyocytes. Subsequently, the research group also detected the expression of α7nAChR and NF-κB/AKT pathway, and it was seen that the expression of α7nAChR in the LPS group was higher than that in the control group, with activated NF-κB/AKT pathway; the α7nAChR expression in the experimental group was further elevated, but the NF-κB/AKT pathway was inhibited (P<0.05). The effects of Dex on cardiomyocytes were seen to be related to the α7nAChR and NF-κB/AKT pathways.
Asunto(s)
Apoptosis , Supervivencia Celular , Dexmedetomidina , Lipopolisacáridos , Miocitos Cardíacos , FN-kappa B , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Receptor Nicotínico de Acetilcolina alfa 7 , Dexmedetomidina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Apoptosis/efectos de los fármacos , Lipopolisacáridos/farmacología , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Línea Celular , L-Lactato Deshidrogenasa/metabolismoRESUMEN
PURPOSE: To investigate whether the effect of intravenous bolus doses of dexmedetomidine on postoperative catheter-related bladder discomfort (CRBD) was dose-dependent in male patients undergoing transurethral resection of bladder tumors (TURBT). METHODS: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR 2,000,034,657, date of registration: July 14, 2020). Adult male patients were randomized to one of four groups: placebo (Group C); dexmedetomidine 0.2 µg/kg (Group D 0.2); dexmedetomidine 0.5 µg/kg (Group D 0.5); or dexmedetomidine 1 µg/kg (Group D 1). The primary outcome was the incidence of moderate-to-severe CRBD at 0, 1, 6, 24, and 48 h postoperatively. RESULTS: The incidence of moderate-to-severe CRBD was significantly lower in Group D 0.5 and Group D 1 than in Group C at 0 h (13% vs. 40%, P = 0.006; 8% vs. 40%, P = 0.001), 1 h (15% vs. 53%, P < 0.001; 13% vs. 53%, P < 0.001), and 6 h (10% vs. 32%, P = 0.025; 8% vs. 32%, P = 0.009) postoperatively. Compared with baseline, both the MAP and HR were significantly lower in Group D 1 at 1 min ([94 ± 15] vs. [104 ± 13] mm Hg, P = 0.003; [64 ± 13] vs. [73 ± 13] bpm, P = 0.001) and 30 min ([93 ± 10] vs. [104 ± 13] mm Hg, P < 0.001; [58 ± 9] vs. [73 ± 13] bpm, P < 0.001) postextubation. CONCLUSION: The effect of intravenous bolus doses of dexmedetomidine on postoperative CRBD was dose-independent, whereas intravenous administration of 0.5 µg/kg dexmedetomidine reduced the early postoperative incidence of CRBD with minimal side effects. TRIAL REGISTRATION: Clinical trial number and registry URL: ChiCTR 2,000,034,657, http://www.chictr.org.cn , date of registration: July 14, 2020.
Asunto(s)
Dexmedetomidina , Neoplasias de la Vejiga Urinaria , Adulto , Humanos , Masculino , Vejiga Urinaria , Resección Transuretral de la Vejiga , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Catéteres Urinarios/efectos adversos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/complicaciones , Método Doble CiegoRESUMEN
BACKGROUND: Information integration and network science are important theories for quantifying consciousness. However, whether these theories propose drug- or conscious state-related changes in EEG during anaesthesia-induced unresponsiveness remains unknown. METHODS: A total of 72 participants were randomised to receive i.v. infusion of propofol, dexmedetomidine, or ketamine at a constant infusion rate until loss of responsiveness. High-density EEG was recorded during the consciousness transition from the eye-closed baseline to the unresponsiveness state and then to the recovery of the responsiveness state. Permutation cross mutual information (PCMI) and PCMI-based brain networks in broadband (0.1-45 Hz) and sub-band frequencies were used to analyse drug- and state-related EEG signature changes. RESULTS: PCMI and brain networks exhibited state-related changes in certain brain regions and frequency bands. The within-area PCMI of the frontal, parietal, and occipital regions, and the between-area PCMI of the parietal-occipital region (median [inter-quartile ranges]), baseline vs unresponsive were as follows: 0.54 (0.46-0.58) vs 0.46 (0.40-0.50), 0.58 (0.52-0.60) vs 0.48 (0.44-0.53), 0.54 (0.49-0.59) vs 0.47 (0.42-0.52) decreased during anaesthesia for three drugs (P<0.05). Alpha PCMI in the frontal region, and gamma PCMI in the posterior area significantly decreased in the unresponsive state (P<0.05). The frontal, parietal, and occipital nodal clustering coefficients and parietal nodal efficiency decreased in the unresponsive state (P<0.05). The increased normalised path length in delta, theta, and gamma bands indicated impaired global integration (P<0.05). CONCLUSIONS: The three anaesthetics caused changes in information integration patterns and network functions. Thus, it is possible to build a quantifying framework for anaesthesia-induced conscious state changes on the EEG scale using PCMI and network science.
Asunto(s)
Dexmedetomidina , Ketamina , Propofol , Humanos , Propofol/farmacología , Ketamina/farmacología , Dexmedetomidina/farmacología , Electroencefalografía , EncéfaloRESUMEN
Dexmedetomidine is increasingly used in paediatric anaesthesia practice. In this issue of the British Journal of Anaesthesia, a retrospective hospital registry study in anaesthetised children showed that intraoperative use of dexmedetomidine was dose-dependently associated with a longer postanaesthesia care unit length of stay. Dexmedetomidine administration was also associated with higher total hospital costs and higher odds of unwarranted haemodynamic effects, while the onset of emergence delirium was not reduced. Although these results could curb enthusiasm for paediatric use of dexmedetomidine, they might also trigger discussion about our approach in the postoperative period to children having received dexmedetomidine intraoperatively.
Asunto(s)
Dexmedetomidina , Hipnóticos y Sedantes , Dexmedetomidina/uso terapéutico , Humanos , Niño , Anestesia/métodos , Delirio del Despertar/prevención & control , Tiempo de Internación/estadística & datos numéricos , Estudios Retrospectivos , Pediatría/métodos , Anestesia PediátricaRESUMEN
BACKGROUND: Dexmedetomidine is increasingly used for surgical patients requiring general anaesthesia. However, its effectiveness on patient-centred outcomes remains uncertain. Our main objective was to evaluate the patient-centred effectiveness of intraoperative dexmedetomidine for adult patients requiring surgery under general anaesthesia. METHODS: We conducted a systematic search of MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to October 2023. Randomised controlled trials (RCTs) comparing intraoperative use of dexmedetomidine with placebo, opioid, or usual care in adult patients requiring surgery under general anaesthesia were included. Study selection, data extraction, and risk of bias assessment were performed by two reviewers independently. We synthesised data using a random-effects Bayesian regression framework to derive effect estimates and the probability of a clinically important effect. For continuous outcomes, we pooled instruments with similar constructs using standardised mean differences (SMDs) and converted SMDs and credible intervals (CrIs) to their original scale when appropriate. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our primary outcome was quality of recovery after surgery. To guide interpretation on the original scale, the Quality of Recovery-15 (QoR-15) instrument was used (range 0-150 points, minimally important difference [MID] of 6 points). RESULTS: We identified 49,069 citations, from which 44 RCTs involving 5904 participants were eligible. Intraoperative dexmedetomidine administration was associated with improvement in postoperative QoR-15 (mean difference 9, 95% CrI 4-14, n=21 RCTs, moderate certainty of evidence). We found 99% probability of any benefit and 88% probability of achieving the MID. There was a reduction in chronic pain incidence (odds ratio [OR] 0.42, 95% CrI 0.19-0.79, n=7 RCTs, low certainty of evidence). There was also increased risk of clinically significant hypotension (OR 1.98, 95% CrI 0.84-3.92, posterior probability of harm 94%, n=8 RCTs) and clinically significant bradycardia (OR 1.74, 95% CrI 0.93-3.34, posterior probability of harm 95%, n=10 RCTs), with very low certainty of evidence for both. There was limited evidence to inform other secondary patient-centred outcomes. CONCLUSIONS: Compared with placebo or standard of care, intraoperative dexmedetomidine likely results in meaningful improvement in the quality of recovery and chronic pain after surgery. However, it might increase clinically important bradycardia and hypotension. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023439896).
Asunto(s)
Teorema de Bayes , Dexmedetomidina , Dexmedetomidina/uso terapéutico , Humanos , Anestesia General/métodos , Atención Dirigida al Paciente , Hipnóticos y Sedantes/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Dolor Postoperatorio/tratamiento farmacológico , Analgésicos no Narcóticos/uso terapéuticoRESUMEN
BACKGROUND: Dexmedetomidine utilisation in paediatric patients is increasing. We hypothesised that intraoperative use of dexmedetomidine in children is associated with longer postanaesthesia care unit length of stay, higher healthcare costs, and side-effects. METHODS: We analysed data from paediatric patients (aged 0-12 yr) between 2016 and 2021 in the Bronx, NY, USA. We matched our cohort with the Healthcare Cost and Utilization Project-Kids' Inpatient Database (HCUP-KID). RESULTS: Among 18 104 paediatric patients, intraoperative dexmedetomidine utilisation increased from 51.7% to 85.7% between 2016 and 2021 (P<0.001). Dexmedetomidine was dose-dependently associated with a longer postanaesthesia care unit length of stay (adjusted absolute difference [ADadj] 19.7 min; 95% confidence interval [CI]: 18.0-21.4 min; P<0.001, median length of stay of 122 vs 98 min). The association was magnified in children aged ≤2 yr undergoing short (≤60 min) ambulatory procedures (ADadj 33.3 min; 95% CI: 26.3-40.7 min; P<0.001; P-for-interaction <0.001). Dexmedetomidine was associated with higher total hospital costs of USD 1311 (95% CI: USD 835-1800), higher odds of intraoperative mean arterial blood pressure below 55 mm Hg (adjusted odds ratio [ORadj] 1.27; 95% CI: 1.16-1.39; P<0.001), and higher odds of heart rate below 100 beats min-1 (ORadj 1.32; 95% CI: 1.21-1.45; P<0.001), with no preventive effects on emergence delirium requiring postanaesthesia i.v. sedatives (ORadj 1.67; 95% CI: 1.04-2.68; P=0.034). CONCLUSIONS: Intraoperative use of dexmedetomidine is associated with unwarranted haemodynamic effects, longer postanaesthesia care unit length of stay, and higher costs, without preventive effects on emergence delirium.
Asunto(s)
Periodo de Recuperación de la Anestesia , Dexmedetomidina , Hemodinámica , Hipnóticos y Sedantes , Tiempo de Internación , Sistema de Registros , Humanos , Dexmedetomidina/uso terapéutico , Preescolar , Lactante , Femenino , Masculino , Niño , Hipnóticos y Sedantes/economía , Hemodinámica/efectos de los fármacos , Tiempo de Internación/estadística & datos numéricos , Recién Nacido , Anestesia/economía , Anestesia/métodos , Estudios Retrospectivos , Costos de la Atención en Salud/estadística & datos numéricos , Relación Dosis-Respuesta a Droga , Anestesia PediátricaRESUMEN
OBJECTIVE: Postoperative delirium is a common and debilitating complication that significantly affects patients and their families. The purpose of this study is to investigate whether there is an effective sedative that can prevent postoperative delirium while also examining the safety of using sedatives during the perioperative period. METHODS: The net-meta analysis was used to compare the incidence of postoperative delirium among four sedatives: sevoflurane, propofol, dexmedetomidine, and midazolam. Interventions were ranked according to their surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 41 RCT studies involving 6679 patients were analyzed. Dexmedetomidine can effectively reduce the incidence of postoperative delirium than propofol (OR 0.47 95% CI 0.25-0.90), midazolam (OR 0.42 95% CI 0.17-1.00), normal saline (OR 0.42 95% CI 0.33-0.54) and sevoflurane (OR 0.39 95% CI 0.18-0.82). The saline group showed a significantly lower incidence of bradycardia compared to the group receiving dexmedetomidine (OR 0.55 95% CI 0.37-0.80). In cardiac surgery, midazolam (OR 3.34 95%CI 2.04-5.48) and normal saline (OR 2.27 95%CI 1.17-4.39) had a higher rate of postoperative delirium than dexmedetomidine, while in non-cardiac surgery, normal saline (OR 1.98 95%CI 1.44-2.71) was more susceptible to postoperative delirium than dexmedetomidine. CONCLUSION: Our analysis suggests that dexmedetomidine is an effective sedative in preventing postoperative delirium whether in cardiac surgery or non-cardiac surgery. The preventive effect of dexmedetomidine on postoperative delirium becomes more apparent with longer surgical and extubation times. However, it should be administered with caution as it was found to be associated with bradycardia.
Asunto(s)
Anestésicos , Delirio del Despertar , Hipnóticos y Sedantes , Humanos , Anestésicos/uso terapéutico , Bradicardia , Dexmedetomidina , Delirio del Despertar/prevención & control , Hipnóticos y Sedantes/uso terapéutico , Midazolam , Propofol , Solución Salina , Sevoflurano , Metaanálisis en RedRESUMEN
BACKGROUND: Radiotherapy is a primary local treatment for tumors, yet it may lead to complications such as radiation-induced heart disease (RIHD). Currently, there is no standardized approach for preventing RIHD. Dexmedetomidine (Dex) is reported to have cardio-protection effects, while its role in radiation-induced myocardial injury is unknown. In the current study, we aimed to evaluate the radioprotective effect of dexmedetomidine in X-ray radiation-treated mice. METHODS: 18 male mice were randomized into 3 groups: control, 16 Gy, and 16 Gy + Dex. The 16 Gy group received a single dose of 16 Gy X-ray radiation. The 16 Gy + Dex group was pretreated with dexmedetomidine (30 µg/kg, intraperitoneal injection) 30 min before X-ray radiation. The control group was treated with saline and did not receive X-ray radiation. Myocardial tissues were collected 16 weeks after X-ray radiation. Hematoxylin-eosin staining was performed for histopathological examination. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining was performed to assess the state of apoptotic cells. Immunohistochemistry staining was performed to examine the expression of CD34 molecule and von Willebrand factor. Besides, western blot assay was employed for the detection of apoptosis-related proteins (BCL2 apoptosis regulator and BCL2-associated X) as well as autophagy-related proteins (microtubule-associated protein 1 light chain 3, beclin 1, and sequestosome 1). RESULTS: The findings demonstrated that 16 Gy X-ray radiation resulted in significant changes in myocardial tissues, increased myocardial apoptosis, and activated autophagy. Pretreatment with dexmedetomidine significantly protects mice against 16 Gy X-ray radiation-induced myocardial injury by inhibiting apoptosis and autophagy. CONCLUSION: In summary, our study confirmed the radioprotective effect of dexmedetomidine in mitigating cardiomyocyte apoptosis and autophagy induced by 16 Gy X-ray radiation.
Asunto(s)
Apoptosis , Autofagia , Dexmedetomidina , Miocitos Cardíacos , Traumatismos Experimentales por Radiación , Animales , Autofagia/efectos de los fármacos , Autofagia/efectos de la radiación , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/efectos de la radiación , Miocitos Cardíacos/metabolismo , Apoptosis/efectos de los fármacos , Masculino , Dexmedetomidina/farmacología , Traumatismos Experimentales por Radiación/prevención & control , Traumatismos Experimentales por Radiación/patología , Traumatismos Experimentales por Radiación/metabolismo , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Protectores contra Radiación/farmacología , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Ratones , Proteínas Relacionadas con la Autofagia/metabolismo , Ratones Endogámicos C57BL , Proteínas Reguladoras de la Apoptosis/metabolismoRESUMEN
Background: Reduction in sedation exposure is an important metric in intensive care unit (ICU) patients. However, challenges arose during the coronavirus disease-2019 (COVID-19) pandemic in adhering to this practice, driven by concerns on transmission and disease severity issues. Accordingly, diverse sedation approaches emerged, although the effect on mortality has not been studied thoroughly. Methods: Retrospective cohort study in the medical ICU of seven hospitals within a major Health System in Northeast Ohio. We included all adult patients admitted with COVID-19 requiring invasive mechanical ventilation (IMV) from March 2020 to December 2021. Results: Study included 2394 COVID-19 patients requiring IMV. Across waves, sample included 55-63% male subjects, with an average age of 61-68 years (P < 0.001), Acute Physiologic and Chronic Health Evaluation (APACHE)-III score 65.8-68.9 (P = 0.37), median IMV duration 8-10 days (P = 0.14), and median ICU duration 9.8-11.6 days (P = 0.084). Propofol remained the primary sedative (84-92%; P = 0.089). Ketamine use increased from the first (9.7%) to fourth (19%) wave (P = 0.002). Midazolam use decreased from the first (27.4%) to third (9.4%) wave (P = 0.001). Dexmedetomidine use declined from 35% to 27-28% (P = 0.002) after the first wave. A multivariable regression analysis indicated clinical variables explained 34% of the variation in hospital mortality (R2). Factors associated with higher mortality included age [aOR = 1.059 (95% CI 1.049-1.069); P < 0.001], COVID-19 wave, especially fourth wave [aOR = 2.147, (95% CI 1.370-3.365); P = 0.001], and higher number of vasopressors [aOR = 31.636, (95% CI 17.603-56.856); P < 0.001]. Addition of sedative medications to a second model led to an increase in the R2 by only 1.6% to 35.6% [aOR = 1 (95% CI 1-1); P > 0.05] for propofol, ketamine, and midazolam. Dexmedetomidine demonstrated a decrease in the odds of mortality [aOR = 0.96 (95% CI 0.94-0.97); P < 0.001]. Conclusion: Mortality in critical COVID-19 patients was mostly driven by illness severity, and the choice of sedation might have minimal impact when other factors are controlled.