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Context: Pain and symptom management at the end of life (EoL) can pose unique challenges, particularly when symptoms are refractory to conventional methods. Dexmedetomidine, originally approved for sedation in ventilated patients, has been demonstrated to be beneficial in pain management and palliative care settings by functioning as an alpha-2 agonist. Methods: A retrospective review of inpatient palliative care unit (IPU) records from January 2020 to December 2023 was conducted. Twenty-five adult patients receiving continuous dexmedetomidine for refractory pain at the EoL were identified. These patients were further evaluated for concurrent opioid, benzodiazepine, and chlorpromazine usage. Results: Patients experienced predominantly cancer-related pain, and had a median infusion duration of 5 days. Dexmedetomidine's initial dosing differed between the intensive care unit (ICU) and IPU settings. There was a trend toward a decreased opioid requirement 24 hours after initiation. Patients transferred from the ICU showed a progressive increase in opioid use. Conclusion: This study contributes to understanding dexmedetomidine's role in managing refractory symptoms at the EoL in the palliative care setting. [ABSTRACT FROM AUTHOR]

Introduction: At the end of life, the prevalence of delirium and pain is high. Current therapy is not satisfactory. Dexmedetomidine could be useful in the control of delirium and pain but is not approved outside of intensive care setting. Our objectives are to evaluate existing evidence in the literature that assessed the efficacy of dexmedetomidine in pain and delirium control and its safety in palliative care patients outside intensive care units. This systematic review was prospectively registered with PROSPERO and included a risk of bias assessment. Methods: PubMed and SCOPUS were examined for literature published until 2023. Experimental, cohort, cross-sectional, case–control studies, and case series/reports were included if they evaluate the use of dexmedetomidine in delirium and/or pain management in hospitalized palliative care adult patients. Studies were excluded if they were carried out in intensive care units. Results: Of the initial 529 records, 14 were included. Although only two studies were randomized trials, most were small and only one had low risk of bias. In most case reports and in the two retrospective cohort studies, dexmedetomidine appears to be a better option for these symptoms, although differences were not significant in the randomized trials. Discussion: Dexmedetomidine seems to be a promising option for refractory pain and delirium and may contribute to a reduction in opioid administration to control pain. This is the first systematic review of dexmedetomidine in palliative care. Quality evidence is limited, but clinical properties of dexmedetomidine justify the conduction of controlled trials in palliative care. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of radial extracorporeal shock wave therapy (r ESWT) as an additional treatment modality for spastic equinus deformity in chronic hemiplegic patients. Methods: 100 eligible stroke patients with calf muscles spasticity were randomized into 2 groups. Group I: 50 patients exposed to rESWT 1.500 pulses, 0.10 mJ to 0.3mJ/mm2, with a frequency 4 Hz once weekly for one month. Group II: 50 patients exposed to Sham rESWT once weekly for one month. Clinical, electrophysiological & musculoskeletal ultrasound assessments were done for all patients. Results: After controlling baseline as covariate, the trend for modified Ashworth scale (MAS), Passive ankle dorsiflexion motion (PADFM), 10 meters walk test (10-MWT), and Ratio of maximum H reflex to maximum M response (H/M ratio) after one & two months was significantly different between the two groups, with improvement of all clinical and electrophysiological parameters in group I. Conclusion: ESWT represents a useful non-invasive, additional modality for the reduction of foot spasticity and equinus deformity in stroke patients. Implications for Rehabilitation: Extracorporeal shock wave therapy represents a useful non-invasive, additional modality for reduction of foot spasticity and equinus deformity in chronic stroke patients. The application of such a modality improves limb posture, range of motion, and muscle extensibility. Early extracorporeal shock wave rehabilitative intervention in stroke patients reduces fat infiltration and fibrosis replacement of spastic muscle. [ABSTRACT FROM AUTHOR]

The scientific literature contains little reliable data regarding new psychoactive substances and designer drugs, making it difficult to assess toxic blood levels and potentially lethal threshold. Here, we report a fatal co-intoxication involving two uncommon drugs ‒ alpha-methyltryptamine (AMT) and 5-(2-methylaminopropyl)-benzofuran (5-MAPB) ‒ combined with exposure to benzodiazepines, ephedrine, and norephedrine. AMT and 5-MAPB were quantified using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC/MS-MS), revealing concentrations of AMT 4690 ng/mL and 5-MAPB 101 ng/mL in postmortem peripheral blood. We additionally reviewed the literature to help interpret the likely roles of these molecules in the occurrence of death. [ABSTRACT FROM AUTHOR]

Alpha-2 agonists are under-recognized for their class effects yet offer potential benefit in specialty palliative care via decreasing sympathetic output, inducing sedation, and modulating pain. Especially in clinical contexts where agitation predominates and patients are intolerant of oral medication route, transdermal medication delivery is advantageous. We report a case of agitated behaviors in setting of mixed Alzheimer/vascular-type dementia limiting hospital discharge to nursing facility that were ameliorated with transdermal clonidine. We suggest palliative clinicians routinely conceptualize the seemingly disparate alpha-2 agonists as a class for effective symptom palliation especially as new clinical evidence becomes available. [ABSTRACT FROM AUTHOR]

Glaucoma is a leading cause of irreversible blindness which preferentially affects older individuals. No medications or therapies which are currently in our arsenal actually treat glaucoma itself. We know that intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma. The primary treatments for glaucoma include medications, laser therapies, and surgical therapies. The Rho kinase inhibitors are the newest class of medications currently on the market and in development for topical IOP-lowering therapy. Studies have shown their ability to lower eye pressure individually and in combination with other medications. Their ability to potentially provide neuroprotective effects for disease modification also gives this class exciting potential for glaucoma treatment. [ABSTRACT FROM AUTHOR]

Background: Rosacea is a common facial dermatological disease characterized by central erythema and flushing. It is more common in females than males, with a prevalence of approximately 5.5% in the global population and 2.4% among all dermatological outpatients. In 2002, the National Rosacea Society Expert Committee suggested a subtype-based standardized classification system. The most common subtype of rosacea is erythematotelangiectatic rosacea (ETR), followed by papulopustular rosacea (PPR), phymatous rosacea, and ocular rosacea. Current Concepts: Rosacea is characterized by hyperactive innate and neurovascular immune reactions, which lead to altered adaptive immune reactions and hyperreactive inflammation. In 2017, the National Rosacea Society Expert Committee developed a phenotype-based classification system. The diagnostic features include persistent centrofacial erythema and phymatous changes. ETR is associated with sensitive skin and may have a debilitating psychological impact, often leading to psychological conditions such as depression and anxiety. Doxycycline and minocycline are considered the gold-standard oral treatments for rosacea. Topical ivermectin and metronidazole are commonly used to treat PPR. Low-dose isotretinoin is an alternative to avoid long-term chronic antibiotic use. Carvedilol and propranolol are off-label medications used to reduce persistent facial flushing and erythema in rosacea. Some alpha-adrenergic receptor agonists have also been approved for the treatment of persistent erythema in rosacea. Discussion and Conclusion: Rosacea exhibits multiple phenotypic manifestations. The treatment approach is individualized for each patient through the customization of multimodal treatments, including the avoidance of trigger factors and the assessment of comorbid diseases. [ABSTRACT FROM AUTHOR]

Background: The Wide-Awake Local Anesthesia No Tourniquet (WALANT) technique allows intraoperative motor assessment of tendon repair integrity of the hand compared with general anesthesia or brachial plexus block. No studies have tested the effect of adding dexmedetomidine to lidocaine on the analgesic properties of the WALANT technique, which is the aim of our study. Methods: A total of 128 patients aged more than 18 years were scheduled for surgical flexor tendon injury repair using WALANT technique. Patients were divided into two equal groups. Ultrasound-guided subcutaneous injection of lidocaine 1% with dexmedetomidine (1 µg/kg), Group D, or without dexmedetomidine, Group C, was performed at four points: proximal to the wrist joint, the distal forearm, palm region, and proximal phalanges. The primary outcome was total morphine consumption throughout the first postoperative day. Secondary outcomes included number of patients requiring rescue analgesia, time to first analgesic request, and pain score. Results: Total morphine consumption was significantly (P < 0.001) lower in group D (2.66 ± 0.998) than in group C (3.66 ± 1.144) mg. Number of patients requiring rescue analgesia was significantly (P < 0.001) lower in group D (54.7% (35)) than group C (100.0% (64)). The time for first request for analgesia was significantly (P < 0.001) longer in group D (11.31 ± 6.944) than in group C (5.91 ± 4.839) h. Pain score was significantly higher in group C than D at three (P < 0.001), and six (P = 0.001) hours (P = 0.001) postoperatively. Conclusion: Dexmedetomidine significantly improves the analgesic quality of WALANT when added to lidocaine with less opioid consumption. Trial registration: (ID: PACTR202203906027106; Date: 31/07/2023). [ABSTRACT FROM AUTHOR]

Background: The exact median effective dose (ED50) of intranasal dexmedetomidine combined with oral midazolam sedation for magnetic resonance imaging (MRI) examination in children remains unknow and the aim of this study was to determine the ED50 of their combination. Methods: This is a prospective dose-finding study. A total of 53 children aged from 2 months to 6 years scheduled for MRI examination from February 2023 to April 2023 were randomly divided into group D (to determine the ED50 of intranasal dexmedetomidine) and group M (to determine the ED50 of oral midazolam). The dosage of dexmedetomidine and midazolam was adjusted according to the modified Dixon's up-and-down method, and the ED50 was calculated with a probit regression approach. Results: The ED50 of intranasal dexmedetomidine when combined with 0.5 mg∙kg− 1 oral midazolam was 0.39 µg∙kg− 1 [95% confidence interval (CI) 0.30 to 0.46 µg∙kg− 1] while the ED50 of oral midazolam was 0.17 mg∙kg− 1 (95% CI 0.01 to 0.29 mg∙kg− 1) when combined with 1 µg∙kg− 1 intranasal dexmedetomidine. The sedation onset time of children with successful sedation in group D was longer than in group M (30.0[25.0, 38.0]vs 19.5[15.0, 35.0] min, P < 0.05). No other adverse effects were observed in the day and 24 h after medication except one dysphoria. Conclusion: This drug combination sedation regimen appears suitable for children scheduled for MRI examinations, offering a more precise approach to guide the clinical use of sedative drugs in children. Trial registration: Chinese Clinical Trial Registry, identifier: ChiCTR2300068611(24/02/2023). [ABSTRACT FROM AUTHOR]

Introduction: Cataract is one of the most common diseases in the world and the most common cause of vision loss and blindness in the world. Stability of hemodynamic symptoms is one of the most important factors during cataract surgery. Therefore, the aim of this study is to investigate the effect of melatonin and tizanidine on hemodynamic parameters and anxiety in patients undergoing cataract surgery. Materials & Methods: This prospective clinical trial study was conducted on 90 patient's candidates for cataract surgery. Patients into three equal groups; Melatonin, tizanidine and placebo were divided. Hemodynamic parameters were recorded at baseline and every 5 minutes during surgery. After the operation was completed and the patients were transferred to the recovery room, postoperative anxiety in the recovery room and 24 hours after the operation (calling the patient) was checked by means of RASS tools. Results: There was no difference in the variables of age, sex, weight between the studied groups. Heart rate, diastolic and systolic blood pressure decreased over time in all three groups. Diastolic blood pressure in the 10th minute of surgery (late surgery) in the tizanidine group was significantly lower than the control group (P<0.05). Tukey's post hoc test showed that in the recovery room, the level of anxiety in people who received melatonin or tizanidine was significantly lower than the control group (P<0.05). There was no difference between the anxiety levels of the melatonin group and the tizanidine group (P=0.904). Conclusion: The results of this study showed that melatonin and tizanidine can reduce the anxiety of patients in the acute phase after surgery. Since tizanidine may lower blood pressure, melatonin prodrug seems to be a better option for reducing pain and anxiety in patients undergoing cataract surgery. [ABSTRACT FROM AUTHOR]

Randomized controlled trials have shown a higher risk of postoperative hypoxemia and delayed extubation with opioid‐free anesthesia (OFA), compared with opioid anesthesia. The practice of OFA is not standardized. The objective of this study is to investigate the association between the dexmedetomidine administration protocol used and the occurrence of postoperative respiratory complications. This work is a retrospective, propensity score‐adjusted study (inverse probability of treatment weighting) conducted between January 2019 and September 2021 in a French tertiary care university hospital, including 180 adult patients undergoing major digestive surgery. Comparison of 2 anesthesia protocols: with a continuous intravenous maintenance dose of dexmedetomidine following a bolus (group B+M, n = 105) or with a bolus dose alone (group B, n = 75). The main outcome measure was a composite respiratory end point within 24 hours of surgery. There was no significant difference in the incidence of overall respiratory complications, as assessed by the primary end point. Nevertheless, there were more patients with postoperative hypercapnia in group B+M than in group B (16% vs 2.5%, P =.004). Patients in group B+M were extubated later than patients in group B (group B+M, median 40 minutes, IQR 20‐74 minutes; group B, median 20 minutes, IQR 10‐50 minutes; P =.004). Our study showed negative results for the primary end point. However, data on the increased risk of postoperative hypercapnia in patients receiving a maintenance dose of dexmedetomidine are new. Other prospective randomized studies with greater power are necessary to confirm these data and to make OFA safer, by reducing the prescribed doses of dexmedetomidine. [ABSTRACT FROM AUTHOR]

Priapism is a disorder where the penis without sexual stimulation maintains a prolonged rigid erection lasting 4 or more hours. There are two classifications of priapism, ischemic (low flow) or nonischemic high flow, and each have specific etiologies, diagnostic criteria, and management. This presented case study involved a 58-year-old male who experienced an ischemic priapism more than 24 hours after an anterior lumbar interbody fusion (ALIF). A flaccid penis was achieved after the patient received two 400 µg of phenylephrine HCL into the corpora cavernosum. Review of the literature suggests anesthetic medications given during the surgical procedure may have caused the priapism. Lessons that can be learned from this case study highlight that even though the nurse may not expect to see a priapism after an ALIF, the nurse must always be diligent and not become complacent with unexpected findings or assessments that may cause irreparable harm to the patient. [ABSTRACT FROM AUTHOR]

Pediatric regional anesthesia has become an integral part of perioperative pain management strategies in children. Adjuvants play a pivotal role in augmenting the efficacy and prolonging the duration of regional anesthesia techniques, thereby improving postoperative pain control, and reducing opioid consumption. This review provides a comprehensive overview of the various adjuvants utilized in pediatric regional anesthesia, highlighting their mechanisms of action, clinical applications, efficacy, and safety profiles. [ABSTRACT FROM AUTHOR]

Background: The search for the ideal sedative during regional anesthesia continues. Propofol is widely as a sedative intraoperatively. It may cause troublesome hemodynamic changes. Dexmedetomidine is an a2 agonist with sedative, anxiolytic, and analgesic properties. In this study, we compared dexmedetomidine with propofol as sedatives during surgeries under brachial plexus block. Materials and Methods: In our study, 70 American Society of Anesthesiologists I Class and II patients about to undergo upper limb surgeries under brachial plexus block were blinded and randomly allocated to receive either propofol (Group P) or dexmedetomidine (Group D) infusion. Brachial plexus block was performed, and after confirmation of adequate sensory and motor block, an initial loading dose of the drug was administered over 10 min, followed by a maintenance dose till the end of the surgery. Titration of the rate of infusion was done so as to maintain Ramsay Sedation Score (RSS) of 3-4 and Bispectral Index (BIS) of 60-80. Hemodynamic and respiratory parameters were monitored intraoperatively. Adverse effects such as hypotension, bradycardia, respiratory depression, and incidence of oversedation and undersedation were also noted. The collected data were evaluated using appropriate statistical tests in SPSS version 22®. P <0.05 was considered statistically significant. Results: The RSS remained at 4 in Group P from 20 min onward and for Group D, RSS remained at 3 after 30 min. Post-induction, there was a reduction in BIS in both the groups, but patients in Group P showed statistically significant lower values of BIS when compared with Group D. The fall in mean arterial pressure was more in Group P as compared to Group D. Nine (25.71%) incidences of hypotension were seen in Group P and none in Group D. The decrease in heart rate was more profound in Group D as compared with Group P and one incidence of bradycardia observed in Group D. The respiratory rate was relatively stable in Group D as compared to Group P. The oxygen saturation (SpO2) values in the majority of the patients in both groups were above 92%, but three patients in Group P had SpO2 <92%. In Group P, 6 (17.14%) incidences of oversedation and 8 (22.85%) incidences of undersedation were observed. In Group D, 7 (20%) incidences of undersedation with no incidence of oversedation were observed. Conclusion: Dexmedetomidine at recommended doses has a better sedative property with less effect on hemodynamics and respiration as compared to propofol. [ABSTRACT FROM AUTHOR]

Introduction: Rhinoplasty is one of the most common surgeries in the ENT department. Rhinoplasty hemorrhage is one of the complications that different strategies have been used to reduce it. Reduction of bleeding reduces the risk of complications such as hemolytic and non-hemolytic reactions, acute lung damage, viral and bacterial infections, hypothermia and coagulation disorders. Therefore, the aim of this study was to compare the effect of dexmedetomidine, remifentanil and metoral in reducing patient bleeding during rhinoplasty surgery. Materials and Methods: This randomized, double-blind trial was performed on rhinoplasty patients. Rhinoplasty candidates who had the inclusion and exclusion criteria were divided into three groups of remifentanil, metoral and dexmedetomidine according to the random number table. Then 0.5 mg/kg/h of dexmedetomidine in the first group was administered, followed by 100-150 kg/h remifentanil in the second group and 50 mg metoral in the third group. Mean blood pressure, heart rate, mean bleeding and surgeon satisfaction were recorded in designed form. Data were analyzed by Spss-22 software. Results: The mean blood pressure of patients in remifentanil group was lower than the other two groups (P = 0.03). In all three times during surgery, recovery and overall time, the amount of bleeding in the remifentanil group was found to be less than the other two groups. Furthermore, the rate of bleeding in the dexmedetomidine group was found to be less than the metoral group (P = 0.03, P = 0.02). The surgeon's satisfaction score in the remifentanil group was higher than the other two groups. Satisfaction score was higher in dexmedetomidine group than metoral group (P = 0.03). The recovery time in the metoral group was shorter than the other two groups (P = 0.02). Conclusion: Remifentanil caused a good and appropriate reduction of blood pressure in rhinoplasty surgery, causing less bleeding and higher satisfaction. [ABSTRACT FROM AUTHOR]

The article reviews clinical considerations for the treatment and management of xylazine overdoses and xylazine-related wounds. It cautions the overlap in clinical presentation of opioids and xylazine overdoses and suggests intranasal or intravenous naloxine in xylazine overdoses. It discusses the likelihood of the combination of opioids and xylazine to potentiate sedation and respiratory depression and advises taking history of substance use and diagnosis of potential substance use disorder.

Introduction: Hemodynamic disturbance is a common problem in patients undergoing thyroid surgery. It may be due to episodic increases in thyroid hormones (thyroid storm) or stimulation of the carotid sinus baroreflex. The aim of the present study was to investigate effectiveness of the pre-operative oral Clonidine on reducing these hemodynamic changes during total thyroidectomy surgery. Methods: In a prospective, randomized, double-blind study, 80 patients scheduled for elective total thyroidectomy were randomized to receive either 0.2 mg Clonidine (n=40) or a matched placebo (n=40) orally sixty minutes before entering the operating room. Hemodynamic variables, the duration of surgery, estimated amount of blood loss and the dose of administered remifentanil were recorded for further analysis. Results: Oral Clonidine was found to be significantly better in maintaining stable hemodynamics compared to the control group. Also, In the Clonidine group, the estimated amount of blood loss (110.4±10 ml vs. 182.2±11.4 mL, P =0.04), duration of the surgery (78.26±55.2 min vs. 105.16±61.75 min, P =0.027) and administered dose of remifentanil (26.67±6.6 μg vs. 216.2±14.8 μg, P =0.01) were also significantly lower than the control group. Conclusion: Pre-operative administration of 0.2 mg oral Clonidine in patients undergoing total thyroidectomy results in improved perioperative hemodynamic stability and reduced response to perioperative stress. [ABSTRACT FROM AUTHOR]

Children with autism spectrum disorder (ASD) and intellectual disability (ID)/global delay (GD) frequently have symptoms of attention-deficit/hyperactivity disorder (ADHD). We describe the practice patterns of developmental behavioral pediatricians (DBPs) in the treatment of children with ASD and coexisting ADHD and compare medication classes for children with and without intellectual disability. In bivariate analyses, we compared demographic characteristics, co-occurring conditions, and medication classes for children with and without intellectual disability. Significantly more patients with ID/GD were prescribed α-agonists than patients without ID/GD, but the difference was no longer significant when controlling for age in logistic regression children with ID/GD had more comorbidities and were more likely to be prescribed more than on psychotropic medication. In conclusion, age rather than ID/GD was associated with medication choice. [ABSTRACT FROM AUTHOR]

The opioid crisis remains a major public health concern, causing significant morbidity and mortality worldwide. Pain is frequently observed among individuals with opioid use disorder (OUD), and the current opioid agonist therapies (OAT) have limited efficacy in addressing the pain needs of this population. We reviewed the most promising non-opioid analgesic therapies for opioid-dependent individuals synthesising data from randomised controlled trials in the Medline database from December 2022 to March 2023. Ketamine, gabapentin, serotoninergic antidepressants, and GABAergic drugs were found to be the most extensively studied non-opioid analgesics with positive results. Additionally, we explored the potential of cannabinoids, glial activation inhibitors, psychedelics, cholecystokinin antagonists, alpha-2 adrenergic agonists, and cholinergic drugs. Methodological improvements are required to advance the development of novel analgesic strategies and establish their safety profile for opioid-dependent populations. We highlight the need for greater integration of experimental pain methods and abuse liability assessments, more granular assessments of prior opioid exposure, greater uniformity of pain types within study samples, and a particular focus on individuals with OUD receiving OAT. Finally, future research should investigate pharmacokinetic interactions between OAT and various non-opioid analgesics and perform reverse translation basic experiments, particularly with methadone and buprenorphine, which remain the standard OUD treatment. [ABSTRACT FROM AUTHOR]

Objective: Intensive care patients may need sedation for many reasons. The anti-inflammatory effects of different sedation options in sepsis were compared. Although the anti-inflammatory effects of some agents in sepsis have been investigated, there is insufficient evidence about the effects of alpha 2 agonists, especially dexmetatomidine. In this study, the anti-inflammatory effects of midazolam and dexmetatomidine in septic rats were investigated and compared. Methods: Wistar Albino-type male rats with an experimental sepsis model were used in this study. Thirty-two male rats, which had no renal disease or hepatic insufficiency, were randomly divided into 4 groups. Simple laparotomy and placebo surgery were performed in the control group. After laparotomy, cecal ligation and puncture were performed in the septic group. Cecal ligation perforation (CLP) procedure was also applied to the other two groups, but 8 hours after the procedure, dexmetatomidine was given at a dose of 0.01 mg/kg to group dex rats, while midazolam was given 0.01 mg/kg to group midazolam rats. After 24 hours, blood samples were taken from all groups to measure the levels of IL-1, IL-6, and TNF-α, which were considered sepsis precursors, at the end of CLP. In addition, a histopathological examination of liver and kidney tissue was performed. Results: When compared with the control group, TNF-α, IL-1, and IL-6 levels were found to be high in the sepsis group (p=0.002, p=0.027, p=0.017). Significant decreases were observed in both serum and tissue in these parameters in all groups. When these two agents were compared, it was seen that the anti-inflammatory effect was higher in the dexmedetomidine-administered group than in the midazolam administered rats. Conclusion: It has been concluded that dexmedetomidine and midazolam reduce the pro-inflammatory markers that have an important role in the pathophysiology of sepsis. Also, they have immunomodulatory effects. Besides these features, it is seen that dexmetatomidine is superior to midazolam in this respect. [ABSTRACT FROM AUTHOR]

Background: Wen Dan decoction (WDD) has been a famous classic formula for resolving phlegm since ancient times in China. Currently, there are many types of WDD commercial preparations produced through modern technology. However, it is not known whether the holistic quality of WDD commercial preparations is consistent with the traditional decocting method to exert its proper effects. Therefore, the WDD material reference was studied and prepared, which can represent the traditional Chinese formulation WDD. Methods: A method based on UPLC-QTOF-MS was developed to evaluate the quality of WDD material reference and commercial prescriptions. At the same time, the multivariate statistical method was used to compare the differences between the material reference and the commercial prescription by principal component analysis (PCA) and heatmap. Finally, the UPLC-QTOF-MS method was established to quantitatively study 11 representative components, including naringin, hesperidin, neohesperidin, liquiritin, glycyrrhizic acid, adenosine, liquiritigenin, tangeretin, eriocitrin, naringenin and synephrine. Results: A total of 107 compounds were identified in the WDD material reference by comparing the retention time and fragment ion characteristics, including 54 flavonoids, 14 triterpenes, 10 organic acids, 7 alkaloids, 7 coumarins and 15 other components. The samples were almost evenly split into two groups, indicating a difference in quality between the WDD material reference and its commercial preparations in multivariate statistical analysis. Eleven major components of linearity, precision, repeatability, stability and recovery rate met the requirements, which were clearly different in commercial preparations and WDD material references. In terms of the content of 11 components in the commercial preparation, only CP8 is close to the material reference, which is in agreement with the statistical analysis of the heatmap. The concentrations of naringin and neohesperidin from the WDD material reference were higher than those from the commercial preparations. Conclusions: The quality evaluation method established in this study can be used to identify different sources of WDD but also proves that the WDD material reference contains higher naringin. Furthermore, this study confirmed that the preparation technology of WDD commercial prescriptions should be optimized on the basis of WDD material references, producing the closest possible clinical basis for the substance. [ABSTRACT FROM AUTHOR]

Children with autism spectrum disorder are prescribed various medications to address behavior and mood. In clinical trials, individuals taking concomitant psychotropic medications often are excluded to maintain homogeneity and prevent contamination of clinical endpoints. However, this choice may compromise the representativeness of the sample. In a recent study designed to identify biomarkers and endpoints for clinical trials (the Autism Biomarkers Consortium for Clinical Trials), school-age children with autism spectrum disorder were enrolled without excluding for medications, providing the opportunity to examine characteristics of psychotropic medication use and guide future decisions on medication-related inclusion criteria. The aims of the current analysis were (1) to quantify the frequency and type of psychotropic medications reported in school-age children enrolled in the study and (2) to examine behavioral features of children with autism spectrum disorder based on medication classes. Of the 280 children with autism spectrum disorder in the cohort, 42.5% were taking psychotropic medications, with polypharmacy in half. The most commonly reported psychotropic medications included melatonin, stimulants, selective serotonin reuptake inhibitors, alpha agonists, and antipsychotics. Our findings suggest that exclusion of children taking concomitant psychotropic medications could limit the representativeness of the study population, perhaps even excluding children who may most benefit from new treatment options. Children with autism spectrum disorder are prescribed a variety of medications that affect the central nervous system (psychotropic medications) to address behavior and mood. In clinical trials, individuals taking concomitant psychotropic medications often are excluded to maintain homogeneity of the sample and prevent contamination of biomarkers or clinical endpoints. However, this choice may significantly diminish the clinical representativeness of the sample. In a recent multisite study designed to identify biomarkers and behavioral endpoints for clinical trials (the Autism Biomarkers Consortium for Clinical Trials), school-age children with autism spectrum disorder were enrolled without excluding for medications, thus providing a unique opportunity to examine characteristics of psychotropic medication use in a research cohort and to guide future decisions on medication-related inclusion criteria. The aims of the current analysis were (1) to quantify the frequency and type of psychotropic medications reported in school-age children enrolled in the ABC-CT and (2) to examine behavioral features of children with autism spectrum disorder based on medication classes. Of the 280 children with autism spectrum disorder in the cohort, 42.5% were taking psychotropic medications, with polypharmacy in half of these children. The most commonly reported psychotropic medications included melatonin, stimulants, selective serotonin reuptake inhibitors, alpha agonists, and antipsychotics. Descriptive analysis showed that children taking antipsychotics displayed a trend toward greater overall impairment. Our findings suggest that exclusion of children taking concomitant psychotropic medications in trials could limit the clinical representativeness of the study population, perhaps even excluding children who may most benefit from new treatment options. [ABSTRACT FROM AUTHOR]

Dexmedetomidine is a selective alpha-2 receptor agonist which has become increasingly prevalent in the practice of pediatric anesthesia. Its sedative, anxiolytic, sympatholytic, and analgesic properties have made dexmedetomidine an effective drug in pediatric patients to help manage stresses related to surgery. Data for this study were obtained through a retrospective chart review for an 18-month period that identified all patients 18 years of age or younger who underwent surgery at two hospitals in Maine. The study explored the effects of perioperative dexmedetomidine administration on outcomes such as pain scores, analgesic requirements, length of anesthesia time, and postanesthesia care unit (PACU) length of stay. It also compared outcomes between patients that received a low and high dose of dexmedetomidine. While PACU pain scores were comparable between patients who did and did not receive dexmedetomidine, the dexmedetomidine group received significantly lower perioperative doses of all opiates. PACU length of stay was longer for the dexmedetomidine group. Anesthesia times were comparable between the two groups. The group who received a high dose of dexmedetomidine received significantly fewer total opiates than did the low dose group. The PACU length of stay was significantly higher for the high-dose group. [ABSTRACT FROM AUTHOR]

Study objectives: To assess the effect of dexmedetomidine (DEX) on postoperative sleep quality using polysomnography (PSG) to identify possible interventions for postoperative sleep disturbances. Methods: An electronic search of PubMed/MEDLINE, EMBASE, Cochrane Library and Web of Science was conducted from database inception to November 20, 2022. Randomized controlled trials (RCTs) on the effect of DEX administration on postoperative sleep quality using PSG or its derivatives were included. No language restrictions were applied. The sleep efficiency index (SEI), arousal index (AI), percentages of stage N1, N2 and N3 of non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep were measured in our meta-analysis. Results: Five studies, involving 381 participants were included. Administration of DEX significantly improved SEI, lowered AI, decreased the duration of stage N1 sleep and increased the duration of stage N2 sleep compared to placebo groups. There were no significant differences in the duration of stage N3 sleep and REM sleep. DEX administration lowered the postoperative Visual Analogue Scale (VAS) score and improved the Ramsay sedation score with no adverse effect on postoperative delirium (POD). However, high heterogeneity was observed in most of the primary and secondary outcomes. Conclusions: Our study provides support for the perioperative administration of DEX to improve postoperative sleep quality. The optimal dosage and overall effect of DEX on postoperative sleep quality require further investigation using large-scale randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: Anesthesia and surgery can induce perioperative neurocognitive disorders (PND). Mitochondrial dysfunction has been proposed to be one of the earliest triggering events in surgery-induced neuronal damage. Dexmedetomidine has been demonstrated to attenuate the impairment of cognition in aged rats induced by surgery in our previous study. Methods: Male Sprague-Dawley rats underwent hepatic apex resection under anesthesia with propofol to clinically mimic human abdominal surgery. The rats were divided into three groups: Control group, Model group and Dexmedetomidine (Dex) group. Cognitive function was evaluated with the Morris water maze (MWM), Open Field Test (OFT)and Novel object recognition task (NOR). Ultrastructural change in neuronal mitochondria was measured by transmission electron microscopy. Mitochondrial function was measured by mitochondrial membrane potential and activities of mitochondrial complexes. Neuronal morphology was observed with H&E staining and the activation of glial cells was observed by immunohistochemistry in the hippocampus. Protein levels were measured by Western blot (WB) and immunofluorescence at 3 and 7 days after surgery. Results: Surgery-induced cognitive decline lasts three days, but not seven days after surgery in the model group. Transmission electron microscope showed the mitochondrial structure damage in the model group, similar changes were not induced in the Dex group. Dexmedetomidine may reverse the decrease in mitochondrial membrane potential and mitochondrial complex activity. Compared with the Control group, the expression of cytochrome c was significantly increased in model group by Western blot and immunofluorescence on days 3, but not day 7. Rats from the Model group expressed significantly greater levels of Iba-1 and GFAP compared with the Control group and the Dex group. Conclusion: Dexmedetomidine appears to reverse surgery-induced behavior, mitigate the higher density of Iba-1 and GFAP, reduce the damage of mitochondrial structure and function by alleviating oxidative stress and protect mitochondrial respiratory chain, thus increasing cytochrome c oxidase (COX) expression and downregulate the expression of cytochrome c protein in the hippocampus of rats. [ABSTRACT FROM AUTHOR]

We explored the possible utilization of a pure BC3 nanotube and its Au-decorated form (Au@BCNT) for the detection of phenylpropanolamine (PHA) drug. All calculations were performed through TPSS functional using LANL2DZ basis set on the Au atom. For the remaining atoms, we used 6–311++G** basis set. PHA had a weak interaction with the pure BCNT and the binding energy (BE) was − 0.36 eV. PHA did not change the HOMO–LUMO gap and electrical resistivity of the pristine BCNT, and the sensing response is 9.7 at 298 K. PHA interacted via its hexagon with the Au atom and the BE was − 1.49 eV after the Au-decoration on BCNT. Subsequently, the sensing response dramatically improved to 524.6, which is attributed to a great charge transfer. The calculated recovery time was 1.03 s for the PHA desorption from the Au@BCNT surface, which was short. Hence, we can consider Au@BCNT a viable sensor to detect PHA. [ABSTRACT FROM AUTHOR]

Infants might be exposed to pain during their admissions in the neonatal intensive care unit [NICU], both from their underlying conditions and several invasive procedures required during their stay. Considering the particularities of this population, recognition and adequate management of pain continues to be a challenge for neonatologists and investigators. Diverse therapies are available for treatment, including non-pharmacological pain management measures and pharmacological agents (sucrose, opioids, midazolam, acetaminophen, topical agents...) and research continues. In recent years one of the most promising drugs for analgesia has been dexmedetomidine, an alpha-2 adrenergic receptor agonist. It has shown a promising efficacy and safety profile as it produces anxiolysis, sedation and analgesia without respiratory depression. Moreover, studies have shown a neuroprotective role in animal models which could be beneficial to neonatal population, especially in preterm newborns. Side effects of this therapy are mainly cardiovascular, but in most studies published, those were not severe and did not require specific therapeutic measures for their resolution. The main objective of this article is to summarize the existing literature on neonatal pain management strategies available and review the efficacy of dexmedetomidine as a new therapy with increasing use in the NICU. [ABSTRACT FROM AUTHOR]

Background Dexmedetomidine, an alpha-2 agonist, has been widely used as an anesthetic adjunct for transsphenoidal pituitary resection. However, there is no consensus on the appropriate infusion dosage. This study aimed to compare the effects of low (0.2 mcg/kg/h) and intermediate (0.5mcg/kg/h) dexmedetomidine infusions during anesthetic maintenance on blood loss, hemodynamics, and operating time. Methods A randomized controlled trial involving two centers was conducted. Between December 2015 and November 2019, 80 patients (40 in each group) who underwent elective transsphenoidal pituitary tumor resection were recruited. Dexmedetomidine was administered to group I at a loading dose of 0.5 mcg/kg, followed by 0.2 mcg/kg/h, and to group II at the same loading dose, followed by 0.5 mcg/kg/h. Comparative analyses were performed using the Student's t-test, repeated-measures analysis of variance, and Mann-Whitney U test; p-values<0.05 were considered statistically significant. Results Eighty patients were analyzed. Patient demographics were comparable. The difference in intraoperative blood loss between both groups (320 [220-525] vs. 250 [100-487] mL, p=0.070) was not statistically significant. There were no differences in blood pressure or heart rate between the groups. In group II, the procedure took significantly less time (179 vs. 142 minutes, p=0.018), withmore episodes of transient hypotension (p=0.034). Conclusion When maintaining anesthesia for transsphenoidal pituitary resection, dexmedetomidine infusions of 0.2 and 0.5 mcg/kg/h showed the same effect on blood loss and hemodynamics; however, significantly more episodes of transient hypotension and shorter operating times were noted with the latter. [ABSTRACT FROM AUTHOR]

An SPE-GC-MS analytical method using whole blood samples has been developed and validated to detect and quantify nineteen compounds belonging to the Drugs of Abuse (DA) groups of cocaine and metabolites, opiates and new psychoactive substances (NPS). The method detailed here is necessary because the recreational consumption of these DA has increased considerably in recent years and poly-drug-consumption is now very common. The method developed was both specific and selective. Three different working ranges have been defined due to the differences between therapeutic, toxic and lethal concentrations of DA. Linearity was confirmed for the defined working ranges of all DA, except pseudoephedrine, ephedrine, norephedrine, and TFMPP. Since the remaining nineteen substances showed heteroscedasticity, six ponderation factors were studied to find the best fit for each compound. Limits of Detection and Lower Limits of Quantification have been studied and defined. No carryover was noted, with acceptable extraction recoveries. The achievement of all validation criteria according to international guidelines allows the application of the proposed method in routine forensic analysis. Using this method can also significantly reduce response times and GC-MS analysis costs. [ABSTRACT FROM AUTHOR]

The use of recreational drugs like ephedrine, norephedrine, 3,4-methylenedioxymethamphetamine (MDMA), and mescaline can lead to intoxication and, at worst, to death. One reason for a fatal course of intoxication with these drugs might lie in cardiac arrhythmias. To the best of our knowledge, their inotropic effects have not yet been studied in isolated human cardiac preparations. Therefore, we measured inotropic effects of the hallucinogenic drugs ephedrine, norephedrine, mescaline, and MDMA in isolated mouse left atrial (mLA) and right atrial (mRA) preparations as well as in human right atrial (hRA) preparations obtained during cardiac surgery. Under these experimental conditions, ephedrine, norephedrine, and MDMA increased force of contraction (mLA, hRA) and beating rate (mRA) in a time- and concentration-dependent way, starting at 1–3 µM but these drugs were less effective than isoprenaline. Mescaline alone or in the presence of phosphodiesterase inhibitors did not increase force in mLA or hRA. The positive inotropic effects of ephedrine, norephedrine, or MDMA were accompanied by increases in the rate of tension and relaxation and by shortening of time of relaxation and, moreover, by an augmented phosphorylation state of the inhibitory subunit of troponin in hRA. All effects were greatly attenuated by cocaine (10 µM) or propranolol (10 µM) treatment. In summary, the hallucinogenic drugs ephedrine, norephedrine, and MDMA, but not mescaline, increased force of contraction and increased protein phosphorylation presumably, in part, by a release of noradrenaline in isolated human atrial preparations and thus can be regarded as indirect sympathomimetic drugs in the human atrium. [ABSTRACT FROM AUTHOR]

Background: Few studies have compared the efficacy and complications of dexmedetomidine (DEX) and fentanyl (FEN) in extremely preterm infants. Methods: We conducted a single‐institution, retrospective controlled before and after study of preterm infants before 28 weeks of gestation admitted between April 2010 and December 2018 to compare the complications and efficacy of DEX and FEN for preterm infants. Patients were administered FEN prior to 2015 and DEX after 2015 as the first‐line sedative. A composite outcome of death during hospitalization and developmental quotient (DQ) < 70 at a corrected age of 3 years was compared as the primary outcome. Secondary outcomes including postmenstrual weeks at extubation, days of age when full enteral feeding was achieved and additional sedation by phenobarbital (PB) were compared. Results: Sixty‐six infants were enrolled into the study. The only perinatal factor that differed between the FEN (n = 33) and DEX (n = 33) groups was weeks of gestation. The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different. Postmenstrual weeks at extubation did not significantly differ between groups after adjustment for weeks of gestation and being small for gestational age. On the other hand, full feeding was significantly prolonged by DEX (p = 0.031). Additional sedation was less common in the DEX group (p = 0.044). Conclusion: The composite outcome of death and DQ < 70 at a corrected age of 3 years were not significantly different by DEX or FEN for primary sedation. Prospective randomized controlled trials should examine the long‐term effects on development. [ABSTRACT FROM AUTHOR]

Background Dexmedetomidine, an alpha-2 agonist, has been widely used as an anesthetic adjunct for transsphenoidal pituitary resection. However, there is no consensus on the appropriate infusion dosage. This study aimed to compare the effects of low (0.2 mcg/kg/h) and intermediate (0.5 mcg/kg/h) dexmedetomidine infusions during anesthetic maintenance on blood loss, hemodynamics, and operating time. Methods A randomized controlled trial involving two centers was conducted. Between December 2015 and November 2019, 80 patients (40 in each group) who underwent elective transsphenoidal pituitary tumor resection were recruited. Dexmedetomidine was administered to group I at a loading dose of 0.5 mcg / kg, followed by 0.2 mcg / kg / h, and to group II at the same loading dose, followed by 0.5 mcg / kg / h. Comparative analyses were performed using the Student's t -test, repeated-measures analysis of variance, and Mann–Whitney U test; p -values < 0.05 were considered statistically significant. Results Eighty patients were analyzed. Patient demographics were comparable. The difference in intraoperative blood loss between both groups (320 [220–525] vs. 250 [100-487] mL, p = 0.070) was not statistically significant. There were no differences in blood pressure or heart rate between the groups. In group II, the procedure took significantly less time (179 vs. 142 minutes, p = 0.018), with more episodes of transient hypotension (p = 0.034). Conclusion When maintaining anesthesia for transsphenoidal pituitary resection, dexmedetomidine infusions of 0.2 and 0.5 mcg / kg / h showed the same effect on blood loss and hemodynamics; however, significantly more episodes of transient hypotension and shorter operating times were noted with the latter. [ABSTRACT FROM AUTHOR]

Background: Transversus abdominis plane (TAP) block is beneficial for pain management after conducting abdominal surgery. Objective: To compare the outcomes of dexmedetomidine and fentanyl, as adjuvants to bupivacaine, for ultrasound-guided TAP block analgesia among patients undergoing radical cystectomy for postoperative pain management. Methods: This prospective, randomised, comparative study included a total of 60 patients, who underwent radical cystectomy. Participants were randomly divided into three categories with 20 subjects each; group B had patients who received a single shot US-guided TAP block on each side with 20 ml of 0.25% bupivacaine + 2 ml normal saline; group BF had patients who received a single shot US-guided TAP block on each side with 20 ml of 0.25% bupivacaine + 1 µg/kg fentanyl dissolved in 2 ml normal saline and group BD had patients who received a single shot US-guided TAP block on each side with 20 ml of 0.25% bupivacaine + 1 µg/kg dexmedetomidine dissolved in 2 ml normal saline.The researchers recorded the time taken for first rescue analgesia, total analgesic dose in the first 24 h after surgery, patient satisfaction, sedation score, and postoperative complications. Results: The time taken for first rescue analgesia was significantly lengthier in group (BD) (8.90 ± 2.47) than (BF) (6.50 ± 1.43) and (B) (4.40 ± 1.05) groups. The total nalbuphine consumption, during the first 24 h, was significantly lower in (BD) (0.15 ± 0.00) group compared to (BF) (0.20 ± 0.07) and (B) (0.24 ± 0.08) groups. Conclusion: In comparison with fentanyl, as an adjuvant to bupivacaine, dexmedetomidine was found to be associated with prolonged postoperative analgesia, less postoperative pain scores and low opioid consumption. Trial registration: This study was registered at Clinical Trials.gov on 23 March 2020 (registration number: NCT04318158). [ABSTRACT FROM AUTHOR]

Endotracheal tube (ETT) cuff leaks can be encountered in the operating room with variable consequences ranging from a mere annoying bubbling sound to life-threatening respiratory compromise requiring immediate intervention. This scenario becomes more challenging if there is a difficult airway with limited mouth opening and oromaxillofacial surgery where nasal intubation is required with a north pole tube. ETT replacement can expose the patient to airway loss or life-threatening hypoxemia during the ETT exchange. There are no recommended guidelines on how to deal with an ETT cuff leak and no published step-by-step safe management strategy. With the lack of defined protocols and guidelines to manage intraoperative cuff leaks, the presence of mind and ability to make critical decisions by the anesthesiologist cannot be overemphasized. We present a case report of a 40-year-old patient weighing 70 kg diagnosed with carcinoma retromolar trigone posted for wide local excision and posterior segmental mandibulectomy. On airway examination, he had a limited mouth opening of <1 cm, with both nostrils of equal and adequate size. As mask ventilation was not difficult after induction of general anesthesia, we did fiberoptic-guided right nasal intubation with North Pole tube. We were unable to inflate the cuff of ETT and there was a significant leak. Here, we discuss how we exchanged the ETT in this difficult airway scenario. [ABSTRACT FROM AUTHOR]

In this report, we discuss the case of a 9-year-old male with Attention Deficit Hyperactivity Disorder (ADHD) on long-term methylphenidate and guanfacine who experienced acute orofacial dystonia that resolved immediately with the administration of benztropine. Current literature describes various cases of methylphenidate-induced dystonia, but ours appears to be the first reported instance of spontaneous dystonia without a recent change in dose or medication change. This may suggest the possibility of methylphenidate-induced dystonia spontaneously occurring several years after initiation. [ABSTRACT FROM AUTHOR]

Background: Major antihypertensive drug classes (but not Imidazoline Receptor Agonists) have been demonstrated to reduce cardiovascular morbidity and mortality. In 2017, Latvia and Lithuania had the highest cardiovascular mortality among the Eastern, Central, Northern, and Western Member States of the European Union (EU). Cardiovascular mortality in Estonia is much lower than in Lithuania and Latvia. Objective: To evaluate the consumption of Imidazoline Receptor Agonists in the Baltic States and its potential implications. Materials and Methods: The study included data on the sales of Imidazoline Receptor Agonists in Lithuania, Latvia, and Estonia; the marketing authorization databases of the competent authorities; the guidelines on the treatment of hypertension, and the reimbursement conditions. Results: The study showed a very high consumption of the Imidazoline Receptor Agonists in Lithuania and Latvia. From 2016 to 2019, the average consumption of Imidazoline Receptor Agonists in Lithuania was 15.5 times higher than in Estonia; in Latvia, it was 8.9 times higher than in Estonia. The guidelines recommend the use of the Imidazoline Receptors Agonists as one of the last options in hypertension therapy, but the marketing authorizations do not restrict their line of therapy. Conclusions: Consumption of IRAs in Lithuania and Latvia is very high. The authorized use of the IRAs in the EU Member States is not in line with the guidelines on the management of arterial hypertension and therefore patients might be deprived of therapies that reduce the cardiovascular risk. The drug regulatory authorities of the EU should review the data on the safety and efficacy of the IRAs and restrict their therapeutic indications if necessary. [ABSTRACT FROM AUTHOR]

Early diagnosis and prompt treatment of glaucoma are essential to preserve sight. Broadly, three approaches lower intraocular pressure (IOP): laser trabeculoplasty, surgery and drugs. This article briefly introduces the main pharmacological classes that reduce IOP, explores some factors that healthcare professionals (HCPs) should consider when using drugs to protect vision and stresses the importance of vigilance by all HCPs to avoid side effects, including iatrogenic glaucoma. The article also introduces some insights into the biological basis of glaucoma that could result in new drugs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present investigation was to determine whether a 1-h floatation-restricted environmental stimulation therapy (floatation-REST) session could augment recovery from high-intensity resistance exercise (6 × 10 back squats, 2-min rest) known to induce significant metabolic, adrenergic, and mechanical stress. Methods: Eleven healthy resistance-trained males (age, 22.5 ± 2.3 yr; height, 176.4 ± 6.0 cm; weight, 85.7 ± 6.2 kg; back squat one-repetition maximum, 153.1 ± 20.1 kg; strength-to-weight ratio, 1.8 ± 0.2) completed the within-subject, crossover controlled study design. Participants completed two exercise testing blocks separated by a 2-wk washout. In one block, the high-intensity resistance exercise protocol was followed by a 1-h floatation-REST session, whereas recovery in the alternate block consisted of a passive sensory-stimulating control. Markers of metabolic stress, neuroendocrine signaling, structural damage, inflammation, and perceptions of soreness, mood state, and fatigue were assessed over a 48-h recovery window. Results: Floatation-REST significantly attenuated muscle soreness across recovery (P = 0.035) with greatest treatment difference immediately after the intervention (P = 0.002, effect size (ES) = 1.3). Significant differences in norepinephrine (P = 0.028, ES = 0.81) and testosterone (P = 0.028, ES = 0.81) immediately after treatment revealed the modification of neuroendocrine signaling pathways, which were accompanied by greater improvements in mood disturbance (P = 0.029, ES = 0.81) and fatigue (P = 0.001, ES = 1.04). Conclusions: Because no adverse effects and significant and meaningful benefits were observed, floatation-REST may prove a valuable intervention for managing soreness and enhancing performance readiness after exercise. [ABSTRACT FROM AUTHOR]