Functional Endoscopic Sinus Surgery (FESS) has been performed under controlled hypotension to increase operating field visibility. Intranasal (IN) dexmedetomidine is easy, noninvasive, and possesses lower C max, accompanied by lower pharmacodynamic action, including hypotension, bradycardia, and sedation. This trial aimed to compare IN and intravenous (IV) dexmedetomidine for hypotensive anesthesia during FESS. This randomized, controlled, triple-blinded clinical trial involved sixty cases scheduled for FESS. Patients were divided into two equal groups by random manner. 45-60 min before anesthesia induction, group IN: received 1 µg/kg IN dexmedetomidine diluted in 10 ml of saline 0.9 % intranasally preoperative. Group IV: received 1 µg/kg dexmedetomidine diluted in 10 ml of saline 0.9 % infused over 10 min. The primary outcome was the total amount of administered atropine. The secondary outcomes included hemodynamic, through 1 h before surgery, intraoperatively and postoperatively at different time intervals. The quality of the operative field, sedation, adverse reactions and hemostatic stuffing after FESS were also assessed. The total amount of consumed atropine decreased significantly in group IN compared to group IV. Preoperative Ramsay Sedation scores at T0, T5, T50 and T60 were comparable between the two groups, while at T10, T15, T20, T30, and T40 were lower significantly in the IN group compared with the IV group. Preoperative mean arterial blood pressure at T0, T5 and T60 had comparable differences across both groups while reduced at T10 to T 45 significantly in the IV group than IN group. Both groups had comparable satisfaction, postoperative Ramsey sedation, hemostatic suffering, quality of operative field and complications. In conclusion, IN dexmedetomidine administration is relatively simple and appropriate; moreover, it decreases first-pass metabolism. Onset is prolonged relative to IV dosing; thus, it should be administered nearly 1 h before surgery and recommended in adult patients as they require minor sedation preoperatively.
PURPOSE OF REVIEW: The combination of ketamine with propofol and dexmedetomidine has gained popularity for sedation and general anesthesia in different populations. In our meta-nalysis, we helped the anesthesiologists to know the efficiency and the efficacy of both combinations in adult and pediatric patients. METHODS: We searched PubMed, CENTRAL, Web of Science, and Scopus from inception to August 1, 2023. Our outcome parameters for efficacy were recovery time, pain score, and physician satisfaction while for safety were the related cardiorespiratory, neurological, and gastrointestinal adverse events. RECENT FINDINGS: Twenty-two trials were included with a total of 1429 patients. We found a significantly longer recovery time in the ketadex group of 7.59 min (95% CI, 4.92, 10.26; I2 = 94%) and a significantly less pain score of - 0.72 (95% CI, - 1.10, - 0.34; I2 = 0%). Adults had a significantly better physician satisfaction score with the ketofol group, odds ratio of 0.29 (95% CI, 0.12, 0.71; I2 = 0%). Recovery agitations were higher in the ketofol group with an odds ratio of 0.48 (95% CI, 0.24, 0.98; I2 = 36%). Furthermore, we found a significant difference between the combinations with a higher incidence in the ketadex group with pooled odds ratio of 1.75 (95% CI, 1.06, 2.88; I2 = 15%). Ketadex was associated with lower pain scores, hypoxic events and airway obstruction, and emergence agitation. At the same time, ketofol had much more clinician satisfaction which might be attributed to the shorter recovery time and lower incidence of nausea and vomiting. Therefore, we suppose that ketadex is the better combination in periprocedural sedation for both adult and pediatric patients who are not at greater risk for postoperative nausea and vomiting.
Dexmedetomidine , Ketamine , Propofol , Adult , Humans , Child , Propofol/adverse effects , Ketamine/adverse effects , Anesthesia, General , Vomiting , Pain , Hypnotics and Sedatives/adverse effects
Purpose: of Review: This evidence-based systematic review evaluated the safety of ketamine as regard the potential to provoke epilepsy to help better guide anesthesiologists in their practice. Recent findings: Ketamine, originally developed as a dissociative anesthetic, has gained attention for its potential therapeutic applications in various medical conditions, including epilepsy. Ketamine is generally well-tolerated and widely used in anesthesia, however, conflicting data are confusing the anesthesiologists regarding the potential risk of seizures associated with its use. The literature that claimed the proepileeptic property are inconsistent and the mechanism of action is unclear. Moreover, the case reports had been in same certain contexts, such as procedural sedation where ketamine was used as a single agent. On the other hand, the retrospective data analysis confirmed the positive role ketamine plays as antiepileptic agent. Summary: Many studies have shown promising results for the use of ketamine as antiepileptic agent. In case of epileptic patients, there is no contraindication for using ketamine, however, combining with benzodiazepine or propofol may enhance the safety.
BACKGROUND: Alzheimer's disease (AD) is a neurological disease that causes memory loss over time. Current therapies are limited and frequently inadequate. Epigallocatechin gallate (EGCG), has antioxidant, anti-inflammatory, antifibrosis, anti-remodeling and tissue-protective qualities that may be effective in treatment of different diseases, including AD. Because of nanoparticles' high surface area, they can enhance solubility, stability, pharmacokinetics and biodistribution, and diminish toxicities. Besides, lipid nanoparticles have a high binding affinity that can enhance the rate of drug transport across BBB. So, EGCG nanoparticles represent a promising treatment for AD. OBJECTIVES: This systematic review sought to assess the efficacy of EGCG nanoparticles against AD in rat/mouse models. METHODS: Study was conducted in accordance with PRISMA guidelines, and the protocol was registered in PROSPERO. Electronic databases were searched to discover relevant studies published up to October 2022. RESULTS: Two studies met the inclusion criteria out of 1338 and were included in this systematic review. Collectively, the results indicate that EGCG has a significant potential for reducing AD pathology and improving cognitive deficits in rat/mouse models. The formulated particles were in the nanometer range, as indicated by TEM, with good particle size control and stability. EGCG nanoparticles showed superior pharmacokinetic characteristics and improved blood-brain barrier permeability, and increased brain bioavailability compared to free EGCG. Additionally, nanoEGCG were more effective in modulating oxidative stress than free formulation and decreased AChE in the cortex and hippocampus of AlCl3-treated rats. CONCLUSION: This systematic analysis of the two studies included showed that EGCG nanoparticles are efficacious as a potential therapeutic intervention for AD in rat/mouse models. However, limited number of studies found indicates insufficient data in this research point that requires further investigation by experimental studies.
Gene editing technologies (GETs) could induce gene knockdown or gene knockout for biomedical applications. The clinical success of gene silence by RNAi therapies pays attention to other GETs as therapeutic approaches. This review aims to highlight GETs, categories, mechanisms, challenges, current use, and prospective applications. The different academic search engines, electronic databases, and bibliographies of selected articles were used in the preparation of this review with a focus on the fundamental considerations. The present results revealed that, among GETs, CRISPR/Cas9 has higher editing efficiency and targeting specificity compared to other GETs to insert, delete, modify, or replace the gene at a specific location in the host genome. Therefore, CRISPR/Cas9 is talented in the production of molecular, tissue, cell, and organ therapies. Consequently, GETs could be used in the discovery of innovative therapeutics for genetic diseases, pandemics, cancer, hopeless diseases, and organ failure. Specifically, GETs have been used to produce gene-modified animals to spare human organ failure. Genetically modified pigs are used in clinical trials as a source of heart, liver, kidneys, and lungs for xenotransplantation (XT) in humans. Viral, non-viral, and hybrid vectors have been utilized for the delivery of GETs with some limitations. Therefore, extracellular vesicles (EVs) are proposed as intelligent and future cargoes for GETs delivery in clinical applications. This study concluded that GETs are promising for the production of molecular, cellular, and organ therapies. The use of GETs as XT is still in the early stage as well and they have ethical and biosafety issues.
Gene Editing , Organ Transplantation , Animals , Humans , Swine , Gene Editing/methods , CRISPR-Cas Systems/genetics , Gene Transfer Techniques , Genetic Therapy
This study aims to highlight the potential use of cTNAs in therapeutic applications. The COVID-19 pandemic has led to significant use of coding therapeutic nucleic acids (cTNAs) in terms of DNA and mRNA in the development of vaccines. The use of cTNAs resulted in a paradigm shift in the therapeutic field. However, the injection of DNA or mRNA into the human body transforms cells into biological factories to produce the necessary proteins. Despite the success of cTNAs in the production of corona vaccines, they have several limitations such as instability, inability to cross biomembranes, immunogenicity, and the possibility of integration into the human genome. The chemical modification and utilization of smart drug delivery cargoes resolve cTNAs therapeutic problems. The success of cTNAs in corona vaccine production provides perspective for the eradication of influenza viruses, Zika virus, HIV, respiratory syncytial virus, Ebola virus, malaria, and future pandemics by quick vaccine design. Moreover, the progress cTNAs technology is promising for the development of therapy for genetic disease, cancer therapy, and currently incurable diseases.
BACKGROUND: Tranexamic acid is a well-known antifibrinolytic medication frequently prescribed to individuals with bleeding disorders. Following accidental intrathecal injection of tranexamic acid, major morbidities and fatalities have been documented. The aim of this case report is to present a novel method for management of intrathecal injection of tranexamic acid. CASE PRESENTATION: In this case report, a 400 mg intrathecal injection of tranexamic acid resulted in significant back and gluteal pain, myoclonus of the lower limbs, agitation, and widespread convulsions in a 31-year-old Egyptian male with history of left arm and right leg fracture. Immediate intravenous sedation with midazolam (5 mg) and fentanyl (50 µg) was delivered with no response in seizure termination. A 1000 mg phenytoin intravenous infusion and subsequently, induction of general anesthesia was performed by thiopental sodium (250 mg) and atracurium (50 mg) infusion, and the trachea of the patient was intubated. Maintenance of anesthesia was achieved by isoflurane 1.2 minimum alveolar concentration and atracurium 10 mg every 20 minutes, and subsequent doses of thiopental sodium (100 mg) to control seizures. The patient developed focal seizures in the hand and leg, so cerebrospinal fluid lavage was done by inserting two spinal 22-gauge Quincke tip needles, one on level L2-L3 (drainage) and the other on L4-L5. Intrathecal normal saline infusion (150 ml) was done over an hour by passive flow. After cerebrospinal fluid lavage and the patient's stabilization was obtained, he was transferred to the intensive care unit. CONCLUSIONS: Early and continuous intrathecal lavage with normal saline, with the airway, breathing, and circulation protocol is highly recommended to decrease morbidity and mortality. The selection of the inhalational drug as a sedative and for brain protection in the intensive care unit provided possible benefits in management of this event with medication errors.
Tranexamic Acid , Humans , Male , Adult , Tranexamic Acid/adverse effects , Thiopental , Atracurium , Saline Solution , Injections, Spinal/adverse effects , Seizures/chemically induced , Seizures/drug therapy
