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European Journal of Psychotraumatology 2024Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep. In this systematic... (Review)
Review
Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep. In this systematic review, we aimed to summarize the effect of clonidine on sleep quality and duration, nightmares, and PTSD symptom severity in adults with PTSD. PubMed (Medline), Embase, PsycINFO, CINAHL, and clinicaltrials.gov were searched up to April 2023. Studies on clonidine use in adult PTSD patients reporting data on the effect on sleep, nightmares, and PTSD symptoms were included. A narrative summary and a meta-analysis of the study findings are presented. Ten reports, accounting for = 569 patients with PTSD (145 on clonidine and 436 controls), were included in the final selection. There were four case reports, four observational studies, one non-blind clinical trial, and one crossover randomized controlled trial (RCT). Median clonidine dose was 0.15 mg/day (range: 0.1-0.5 mg/day). Median follow-up time was 31 days (range: 3 days to 19 months). The quality of the evidence was rated from very low to low. There was marked between-study heterogeneity and low power in the individual studies, but many reported improved sleep quality, nightmare reduction, and improvement of PTSD symptoms for patients treated with clonidine. Meta-analysis was only possible for two studies reporting the effect of clonidine on nightmares, and showed no difference from the comparator (i.e. prazosin or terazosin) (odds ratio: 1.16; 95% confidence interval: 0.66 to 2.05), potentially pointing towards non-inferiority between these medications. Future research, such as well-powered RCTs, is needed to identify the efficacy in the lower dose range and the most suitable treatment group, and to obtain good evidence on the effects of clonidine in the treatment of sleep disorders related to PTSD.
Topics: Clonidine; Humans; Stress Disorders, Post-Traumatic; Dreams; Sleep Quality; Adrenergic alpha-2 Receptor Agonists
PubMed: 38941125
DOI: 10.1080/20008066.2024.2366049 -
ELife Jun 2024Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these...
Parkinson's disease (PD) is characterized by motor impairments caused by degeneration of dopamine neurons in the substantia nigra pars compacta. In addition to these symptoms, PD patients often suffer from non-motor comorbidities including sleep and psychiatric disturbances, which are thought to depend on concomitant alterations of serotonergic and noradrenergic transmission. A primary locus of serotonergic neurons is the dorsal raphe nucleus (DRN), providing brain-wide serotonergic input. Here, we identified electrophysiological and morphological parameters to classify serotonergic and dopaminergic neurons in the murine DRN under control conditions and in a PD model, following striatal injection of the catecholamine toxin, 6-hydroxydopamine (6-OHDA). Electrical and morphological properties of both neuronal populations were altered by 6-OHDA. In serotonergic neurons, most changes were reversed when 6-OHDA was injected in combination with desipramine, a noradrenaline (NA) reuptake inhibitor, protecting the noradrenergic terminals. Our results show that the depletion of both NA and dopamine in the 6-OHDA mouse model causes changes in the DRN neural circuitry.
Topics: Animals; Dopaminergic Neurons; Serotonergic Neurons; Dorsal Raphe Nucleus; Mice; Disease Models, Animal; Oxidopamine; Parkinsonian Disorders; Male; Mice, Inbred C57BL; Desipramine; Norepinephrine
PubMed: 38940422
DOI: 10.7554/eLife.90278 -
Open Veterinary Journal May 2024The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory...
BACKGROUND
The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory depression in dogs. However, the effects of IM co-administration of medetomidine, butorphanol, and alfaxalone on cardiorespiratory function under inhalation anesthesia have not been studied.
AIM
To assess the cardiorespiratory function following the IM co-administration of 5 μg/kg of medetomidine, 0.3 mg/kg of butorphanol, and 2.5 mg/kg of alfaxalone (MBA) in dogs anesthetized with sevoflurane.
METHODS
Seven intact healthy Beagles (three males and four females, aged 3-6 years old and weighing 10.0-18.1 kg) anesthetized with a predetermined minimum alveolar concentration (MAC) of sevoflurane were included in this study. The baseline cardiorespiratory variable values were recorded using the thermodilution method with a pulmonary artery catheter after stabilization for 15 minutes at 1.3 times their individual sevoflurane MAC. The cardiorespiratory variables were measured again following the IM administration of MBA. Data are expressed as median [interquartile range] and compared with the corresponding baseline values using the Friedman test and Sheff's method. A < 0.05 was considered statistically significant.
RESULTS
The intramuscular administration of MBA transiently decreased the cardiac index [baseline: 3.46 (3.18-3.69), 5 minutes: 1.67 (1.57-1.75) l/minute/m : < 0.001], respiratory frequency, and arterial pH. In contrast, it increased the systemic vascular resistance index [baseline: 5,367 (3,589-6,617), 5 minutes:10,197 (9,955-15,005) dynes second/cm/m : = 0.0092], mean pulmonary arterial pressure, and arterial partial pressure of carbon dioxide.
CONCLUSION
The intramuscular administration of MBA in dogs anesthetized with sevoflurane transiently decreased cardiac output due to vasoconstriction. Although spontaneous breathing was maintained, MBA administration resulted in respiratory acidosis due to hypoventilation. Thus, it is important to administer MBA with caution to dogs with insufficient cardiovascular function. In addition, ventilatory support is recommended.
Topics: Animals; Sevoflurane; Butorphanol; Medetomidine; Dogs; Pregnanediones; Male; Female; Injections, Intramuscular; Anesthetics, Inhalation; Heart Rate; Blood Pressure
PubMed: 38938419
DOI: 10.5455/OVJ.2024.v14.i5.20 -
The Senior Care Pharmacist Jul 2024In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic...
In older inpatients, anticholinergic medications can increase the risk of complications that may increase length of stay (LOS). Cyclobenzaprine is an anticholinergic medication associated with mental status changes, falls, and injuries in older patients. The purpose of this study is to determine whether use of a lower cyclobenzaprine dose (5 mg) compared with higher dosing (10 mg) will affect LOS, 30-day readmission rates, and need for injectable psychotropic agents in inpatients 65 years of age and older. This was a retrospective cohort analysis comparing outcomes in patients 65 years of age and older who received either a 5 mg or 10 mg cyclobenzaprine dose during their inpatient admission over a 2.5-year period. The primary outcome was hospital LOS, adjusted using multivariate linear regression. Secondary outcomes included 30-day readmission rate adjusted using logistic regression and use of injectable antipsychotics or benzodiazepines. A sub-analysis evaluated the impact of the institution's implementation of a geriatric prescribing context (GEM-CON) on cyclobenzaprine dose selection. The adjusted LOS was 32.7% longer (95% CI 25.9%-39.9%) for patients exposed to higher-dose cyclobenzaprine. Use of injectable antipsychotics or benzodiazepines was also significantly greater in the higher-dose group ( < 0.001; = 0.025). Cyclobenzaprine dose was not significantly associated with readmission on multivariate analysis (OR = 0.93, 95% CI 0.45-1.93). After GEM-CON implementation, there was a significant increase in use of the recommended lower cyclobenzaprine dose ( < 0.001). Use of lower cyclobenzaprine dosing in older inpatients is associated with reduced hospital LOS and need for injectable antipsychotics and benzodiazepines.
Topics: Humans; Aged; Retrospective Studies; Male; Female; Aged, 80 and over; Length of Stay; Patient Readmission; Amitriptyline; Dose-Response Relationship, Drug; Inpatients; Cholinergic Antagonists; Cohort Studies; Antipsychotic Agents
PubMed: 38937891
DOI: 10.4140/TCP.n.2024.249 -
Journal of Medical Case Reports Jun 2024We present a unique case of rhinolalia as the first recognizable sign of spontaneous pneumomediastinum and surgical emphysema following drug use.
BACKGROUND
We present a unique case of rhinolalia as the first recognizable sign of spontaneous pneumomediastinum and surgical emphysema following drug use.
CASE PRESENTATION
This case presents a 17-year-old white male experiencing rhinolalia following ecstasy ingestion at a rave. Subsequent chest X-ray revealed extensive surgical emphysema, along with a continuous diaphragm sign indicative of pneumomediastinum. Computed tomography confirmed the diagnosis. The patient was managed conservatively with strict monitoring and 6 hourly electrocardiograms. Follow-up computed tomography on day 3 showed resolution of pneumomediastinum and surgical emphysema, and the patient was safely discharged. Notably, the patient experienced a temporary rhinolalia during the acute phase, which resolved spontaneously as his condition improved.
CONCLUSIONS
This case underscores the importance of considering spontaneous pneumomediastinum and surgical emphysema in the differential diagnosis of young individuals presenting with acute symptoms after drug use.
Topics: Humans; Male; Mediastinal Emphysema; N-Methyl-3,4-methylenedioxyamphetamine; Adolescent; Tomography, X-Ray Computed; Subcutaneous Emphysema; Diagnosis, Differential
PubMed: 38937843
DOI: 10.1186/s13256-024-04618-9 -
Journal of Cardiothoracic Surgery Jun 2024Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of different anesthetic regimens on postoperative cognitive function of elderly patients undergoing thoracic surgery: a double-blinded randomized controlled trial.
OBJECTIVE
Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure.
METHODS
A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively.
RESULTS
POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001).
CONCLUSION
For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane.
Topics: Humans; Aged; Male; Female; Thoracic Surgical Procedures; Postoperative Cognitive Complications; Double-Blind Method; Sevoflurane; Aged, 80 and over; Dexmedetomidine; Propofol; Anesthetics, Inhalation; Cognition; Incidence; Remifentanil; Anesthetics, Intravenous
PubMed: 38937812
DOI: 10.1186/s13019-024-02939-w -
Scientific Reports Jun 2024The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum...
The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum norepinephrine (NE) dosage (MND) and mortality in neonates with septic shock. This retrospective cohort study included neonates with evidence of septic shock and those who received NE infusion. The study included 123 neonates, with 106 in the survival group and 17 in the death group. The death group exhibited significantly lower birth weight (p = 0.022), 1-min Apgar score (p = 0.005), serum albumin (p < 0.001), and base excess (BE) (p = 0.001) levels, but higher lactate (LAC) levels (p = 0.009) compared to the survival group. MND demonstrated an ROC area under the curve of 0.775 (95% CI 0.63-0.92, p < 0.001) for predicting mortality, with an optimal threshold of 0.3 µg/(kg·min), a sensitivity of 82.4%, and a specificity of 75.5%. Multivariate logistic regression indicated that an MND > 0.3 µg/(kg·min) (OR, 12.08, 95% CI 2.28-64.01) was associated with a significantly higher mortality risk. Spearman rank correlation showed a positive correlation between MND and LAC (r = 0.252, p = 0.005), vasoactive-inotropic score (VIS) (r = 0.836, p < 0.001), and a negative correlation with BE (r = - 0.311, p = 0.001). MND > 0.3 µg/(kg min) is a useful predictive marker of mortality in neonatal septic shock.
Topics: Humans; Shock, Septic; Infant, Newborn; Norepinephrine; Male; Female; Retrospective Studies; ROC Curve; Apgar Score
PubMed: 38937631
DOI: 10.1038/s41598-024-65744-4 -
Communications Biology Jun 2024The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative...
The locus coeruleus (LC), our main source of norepinephrine (NE) in the brain, declines with age and is a potential epicentre of protein pathologies in neurodegenerative diseases (ND). In vivo measurements of LC integrity and function are potentially important biomarkers for healthy ageing and early ND onset. In the present study, high-resolution functional MRI (fMRI), a reversal reinforcement learning task, and dedicated post-processing approaches were used to visualise age differences in LC function (N = 50). Increased LC responses were observed during emotionally and task-related salient events, with subsequent accelerations and decelerations in reaction times, respectively, indicating context-specific adaptive engagement of the LC. Moreover, older adults exhibited increased LC activation compared to younger adults, indicating possible compensatory overactivation of a structurally declining LC in ageing. Our study shows that assessment of LC function is a promising biomarker of cognitive aging.
Topics: Locus Coeruleus; Humans; Male; Aging; Magnetic Resonance Imaging; Aged; Female; Adult; Norepinephrine; Middle Aged; Young Adult
PubMed: 38937535
DOI: 10.1038/s42003-024-06446-5 -
In Vivo (Athens, Greece) 2024Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a...
BACKGROUND/AIM
Diabetic retinopathy is a leading cause of blindness worldwide, characterized by neurovascular dysfunction. This study aimed to investigate the impact of brimonidine, a selective adrenoceptor agonist, on diabetic retinal neurodegeneration, recognizing the critical role of neurodegeneration in diabetic retinopathy.
MATERIALS AND METHODS
Streptozotocin-induced diabetes was established in adult male Sprague-Dawley rats to mimic diabetic retinopathy. Rats, except non-diabetic control rats, received topical applications of 0.15% brimonidine tartrate (treatment group) or balanced salt solution (diabetic control group) twice daily following diabetes induction. Each group comprised six randomly assigned animals. Retinal samples were analyzed using immunofluorescence staining, apoptosis assay, and western blot.
RESULTS
Topical brimonidine treatment reduced apoptosis of retinal ganglion cells at 8 weeks after induction of diabetes (p<0.05). Glial activation induced by diabetes was reduced by brimonidine treatment. Immunoblot and immunofluorescence assay revealed that the decrease in phospho- protein kinase B (AKT) level resulting from diabetes was also attenuated by brimonidine (p<0.05). Furthermore, brimonidine alleviated the decrease in anti-apoptotic proteins [BCL2 apoptosis regulator (BCL2) and BCL-xl] induced by diabetes (p<0.05). Elevation of phospho-p38 mitogen-activated protein kinase (p38MAPK) and p53 in diabetic rats were reduced by brimonidine (p<0.05). Additionally, brimonidine treatment attenuated the upregulation of the pro-apoptotic molecule BCL-2 associated X in retinas of diabetic rats (p<0.05).
CONCLUSION
These findings suggest that topical brimonidine treatment may protect retinal ganglion cells in experimental diabetes by modulating the AKT pathway and reducing pro-apoptotic p38MAPK levels. This presents a potential neuroprotective approach in diabetes, offering the advantage of localized treatment without the added burden of oral medication.
Topics: Animals; Diabetic Retinopathy; Brimonidine Tartrate; Neuroprotective Agents; Rats; Apoptosis; Diabetes Mellitus, Experimental; Male; Retinal Ganglion Cells; Administration, Topical; Disease Models, Animal; Rats, Sprague-Dawley; Proto-Oncogene Proteins c-akt; Retina
PubMed: 38936912
DOI: 10.21873/invivo.13611 -
Indian Journal of Dental Research :... Jan 2024Compare the efficacy of 2% lidocaine with adrenaline (1:200,000) and 4% articaine with adrenaline (1:100,000) in inferior alveolar nerve block prior to extraction of... (Comparative Study)
Comparative Study Randomized Controlled Trial
AIMS
Compare the efficacy of 2% lidocaine with adrenaline (1:200,000) and 4% articaine with adrenaline (1:100,000) in inferior alveolar nerve block prior to extraction of bilateral teeth posterior to canine in interval of one week.
METHODS AND MATERIAL
Thirty-five patients were selected for the study. Patients were divided into two different groups: Group 1 - (2% lignocaine with adrenaline (1:200,000)) and Group 2 - (4% articaine with adrenaline (1:100,000)) solution. The study variables for each anaesthetic agent were: onset of action and depth of anaesthesia. A pulp tester was used to demonstrate quantitative values and a visual analogue scale (VAS) was used for qualitative evaluation of the two anaesthetic drugs in 2 min cycle for 10 min with respect to test canine. Anaesthesia was considered successful when pulp tester value 64 was achieved in 10 min for both the anaesthetic agent.
STATISTICAL ANALYSIS USED
The difference in the efficacy of lignocaine and articaine was analysed using Student's t test. Within group comparison of the response to the pulp vitality test and VAS over various time periods was analysed using repeated measures Analysis of Variance (ANOVA) with post-hoc Bonferroni test.
RESULTS
Data analysis showed statistical differences in onset and depth of anaesthesia between the two groups (P < 0.05).
CONCLUSIONS
4% Articaine with adrenaline (1:100,000) onset of action is faster and depth of anaesthesia is better compared to 2% lignocaine with adrenaline (1:200,000). Many previous studies reported onset of anaesthesia, but this study evaluates onset and depth of both the anaesthetic agent quantitatively and qualitatively.
Topics: Humans; Carticaine; Lidocaine; Anesthetics, Local; Nerve Block; Mandibular Nerve; Epinephrine; Adult; Anesthesia, Dental; Young Adult; Male; Dental Pulp Test; Dental Pulp; Pain Measurement; Female; Tooth Extraction; Vasoconstrictor Agents; Adolescent; Cuspid; Time Factors; Treatment Outcome
PubMed: 38934747
DOI: 10.4103/ijdr.ijdr_678_23