Dexmedetomidine Versus Propofol Sedation in Flexible Bronchoscopy: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis

Background:Dexmedetomidine (DEX), is a highly selective alpha2 adrenoceptor (α2-AR) agonist, successfully used in various procedures including flexible bronchoscopy. Randomized controlled trials (RCTs) evaluating DEX sedation during bronchoscopy report equivocal results regarding respiratory and hemodynamic outcomes. Methods We conducted an RCT to evaluate the efficacy of dexmedetomidine compared to propofol for sedation during bronchoscopy. The primary outcome was desaturation events, secondary outcomes were transcutaneous Pco2 level, hemodynamic adverse events and physician and patient satisfaction. We have also conducted A systematic review and meta-analysis of all RCTs evaluating DEX sedation during flexible bronchoscopy, included current study results.ResultsOverall, 63 patients were included, 30 and 33 in the DEX and propofol groups, respectively. The number of desaturation events was similar between groups, median (IQR) 1 (0-1) and 1 (0-2) in the DEX and control groups, respectively (P=0.29). Median desaturation time was 1 (0-2) and 1 (0-3) minutes in the DEX and control groups, respectively (P=0.48). Adverse events included hypotension, 33% vs 21.1% in intervention and control groups, respectively (P=0.04), bradycardia, cough, and delayed recovery from sedation. Total adverse events were 22 and 7 in DEX and propofol groups, respectively (P=0.009). The pooled meta-analysis included 13 trials (1604 participants) showed a significantly lower rate of desaturation events in the DEX group (RR 0.67, 95% CI 0.57 to 0.79) with a significantly higher rate of hypotension and bradycardia events (RR 1.55, 95% CI 1.16 to 2.06 and RR 1.91, 95% CI 1.04 to 3.5, respectively)ConclusionDexmedetomidine sedation resulted in a significantly reduced rate of desaturation events in comparison to propofol, midazolam and fentanyl. However, it was also associated with a higher rate of hypotension and bradycardia.Trial registration : NCT04211298, registration date: 26/12/2019

Efficacy and safety of various brimonidine formulations in the treatment of glaucoma and ocular hypertension

Purpose. To present data on the mechanism of action, efficacy, and side effects of various brimonidine dosage forms in the treatment of glaucoma and ocular hypertension. Material and methods. To perform the review, literature sources were searched through the PubMed and Scopus databases up to and including 2021, using the keywords «brimonidine», «efficacy», «safety», «glaucoma medication». A total of 36 articles related to the topic of the review were selected. The beginning of publications on this topic dates back to 1995. Results. Brimonidine, an alpha2-adrenoceptor agonist, effectively reduces intraocular pressure and can be used as monotherapy, adjuvant and replacement therapy. The effectiveness of brimonidine is similar to that of timolol and prevails over betaxolol but inferior to prostaglandin analogues. The new drug formulation brimonidine-purite 0.15% has a more favorable safety and tolerability profile than the original brimonidine 0.2% while maintaining similar efficacy. However, most patients require two or more hypotensive medications to maintain target IOP. In this context, brimonidine is one of the most appropriate drugs because of its pr oven efficacy when combined with other classes of hypotensive drugs. Conclusion. Brimonidine can be used as monotherapy for glaucoma and ophthalmic hypertension. Experimental and clinical studies have shown a potential neuroprotective effect of brimonidine, which is associated with a direct effect on retinal cells, regardless of the effect of the drug on intraocular pressure. Key words: glaucoma, brimonidine, hypotensive drops, intraocular pressure.

3-Iodothyronamine Induces Diverse Signaling Effects at Different Aminergic and Non-Aminergic G-Protein Coupled Receptors

The thyroid hormone metabolite 3-iodothyronamine (3-T1AM) exerts diverse physiological reactions such as a decrease of body temperature, and negative inotropic and chronotropic effects. This observed pleomorphic effect in physiology can be barely explained by interaction with only one target protein such as the trace-amine receptor 1 (TAAR1), a class A G-protein coupled receptor (GPCR). Moreover, Taar1 knock-out mice still react to 3-T1AM through physiological responses with a rapid decrease in body temperature. These facts propelled our group and others to search for further targets for this molecule.The group of TAARs evolved early in evolution and, according to sequence similarities, they are closely related to adrenoceptors and other aminergic receptors. Therefore, several of these receptors were characterized by their potential to interplay with 3-T1AM. Indeed, 3-T1AM acts as a positive allosteric modulator on the beta2-adrenoceptor (ADRB2) and as a biased agonist on the serotonin receptor 1B (5HT1b) and the alpha2-adrenoceptor (ADRA2A). In addition, 3-T1AM was reported to be a weak antagonist at a non-aminergic muscarinic receptor (M3).These findings impressively reflect that such trace amines can unselectively and simultaneously function at different receptors expressed by one cell or at different tissues. In conclusion, the role of 3-T1AM is hypothesized to concert the fine-tuning of specific cell reactions by the accentuation of certain pathways dependent on distinct receptors. 3-T1AM acts as a regulator of signals by blocking, modulating, or inducing simultaneously distinct intracellular signaling cascades via different GPCRs.

Analgesic Effect of Electroacupuncture on Paclitaxel-Induced Neuropathic Pain via Spinal Opioidergic and Adrenergic Mechanisms in Mice

This study was designed to determine the antinociceptive effect and related neuronal mechanism of electroacupuncture (EA) on paclitaxel (PTX)-induced neuropathic pain in mice. PTX (4 mg/kg, i.p.) was administered once a day for 5 consecutive days to induce neuropathic pain. EA stimulation (2 mA, 2 Hz, 30 min) was applied at the ST36 acupoint bilaterally once in every 2 days. Repeated EA stimulation significantly attenuated PTX-induced mechanical allodynia and thermal hyperalgesia. In a separate set of experiment, the antinociceptive effect of a single EA stimulation 8 days after PTX treatment was reduced by intrathecal pretreatment with naloxone (opioid receptor antagonist), idazoxan (alpha2-adrenoceptor antagonist) or propranolol (beta-adrenoceptor antagonist), but not prazosin (alpha1-adrenoceptor antagonist). Moreover, EA remarkably suppressed the PTX-enhanced phosphorylation of the NMDA receptor NR2B subunit in the spinal dorsal horn, and intrathecal pretreatment of naloxone, idazoxan (IDA) or propranolol blocked the effect of EA. In conclusion, EA stimulation at the ST36 acupoint significantly diminished PTX-induced neuropathic pain in mice via the mediation of spinal opioid receptor, alpha2- and beta-adrenoceptors.