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Drug Design, Development and Therapy 2023This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients... (Randomized Controlled Trial)
Randomized Controlled Trial
The Effect of Low-Dose Esketamine on Postoperative Neurocognitive Dysfunction in Elderly Patients Undergoing General Anesthesia for Gastrointestinal Tumors: A Randomized Controlled Trial.
PURPOSE
This study aims to evaluate the effects of the intraoperative application of low-dose esketamine on postoperative neurocognitive dysfunction (PND) in elderly patients undergoing general anesthesia for gastrointestinal tumors.
METHODS
Sixty-eight elderly patients were randomly allocated to two groups: the esketamine group (group Es) (0.25 mg/kg loading, 0.125mg/kg/h infusion) and the control group (group C) (received normal saline). The primary outcome was the incidence of delayed neurocognitive recovery (DNR). The secondary outcomes were intraoperative blood loss, the total amount of fluid given during surgery, propofol and remifentanil consumption, cardiovascular adverse events, use of vasoactive drugs, operating and anesthesia time, the number of cases of sufentanil remedial analgesia, the incidence of postoperative delirium (POD), the intraoperative hemodynamics, bispectral index (BIS) value at 0, 1, 2 h after operation and numeric rating scale (NRS) pain scores within 3 d after surgery.
RESULTS
The incidence of DNR in group Es (16.13%) was lower than in group C (38.71%) ( <0.05). The intraoperative remifentanil dosage and the number of cases of dopamine used in group Es were lower than in group C ( <0.05). Compared with group C, DBP was higher at 3 min after intubation, and MAP was lower at 30 min after extubation in group Es (0.05). The incidence of hypotension and tachycardia in group Es was lower than in group C (0.05). The NRS pain score at 3 d after surgery in group Es was lower than in group C ( 0.05).
CONCLUSION
Low-dose esketamine infusion reduced to some extent the incidence of DNR in elderly patients undergoing general anesthesia for gastrointestinal tumors, improved intraoperative hemodynamics and BIS value, decreased the incidence of cardiovascular adverse events and the intraoperative consumption of opioids, and relieved postoperative pain.
Topics: Humans; Aged; Remifentanil; Anesthesia, General; Delirium; Pain, Postoperative; Gastrointestinal Neoplasms
PubMed: 37408867
DOI: 10.2147/DDDT.S406568 -
International Journal of Molecular... Dec 2023The pathogenesis of complex diseases such as pulmonary arterial hypertension (PAH) is entirely rooted in changes in the expression of some vasoactive factors. These play... (Review)
Review
The pathogenesis of complex diseases such as pulmonary arterial hypertension (PAH) is entirely rooted in changes in the expression of some vasoactive factors. These play a significant role in the onset and progression of the disease. Indeed, PAH has been associated with pathophysiologic alterations in vascular function. These are often dictated by increased oxidative stress and impaired modulation of the nitric oxide (NO) pathway. NO reduces the uncontrolled proliferation of vascular smooth muscle cells that leads to occlusion of vessels and an increase in pulmonary vascular resistances, which is the mainstay of PAH development. To date, two classes of NO-pathway modulating drugs are approved for the treatment of PAH: the phosphodiesterase-5 inhibitors (PD5i), sildenafil and tadalafil, and the soluble guanylate cyclase activator (sGC), riociguat. Both drugs provide considerable improvement in exercise capacity and pulmonary hemodynamics. PD5i are the recommended drugs for first-line PAH treatment, whereas sGCs are also the only drug approved for the treatment of resistant or inoperable chronic thromboembolic pulmonary hypertension. In this review, we will focus on the current information regarding the nitric oxide pathway and its modulation in PAH.
Topics: Humans; Pulmonary Arterial Hypertension; Nitric Oxide; Familial Primary Pulmonary Hypertension; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Soluble Guanylyl Cyclase
PubMed: 38203205
DOI: 10.3390/ijms25010036 -
European Heart Journal Apr 2024Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear.
METHODS
From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy.
RESULTS
Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)].
CONCLUSIONS
Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.
Topics: Humans; Renin-Angiotensin System; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Hypertension; Hypotension; Angiotensin Receptor Antagonists
PubMed: 37935833
DOI: 10.1093/eurheartj/ehad716 -
International Journal of Molecular... May 2024Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological... (Review)
Review
Sepsis-associated kidney injury is common in critically ill patients and significantly increases morbidity and mortality rates. Several complex pathophysiological factors contribute to its presentation and perpetuation, including macrocirculatory and microcirculatory changes, mitochondrial dysfunction, and metabolic reprogramming. Recovery from acute kidney injury (AKI) relies on the evolution towards adaptive mechanisms such as endothelial repair and tubular cell regeneration, while maladaptive repair increases the risk of progression to chronic kidney disease. Fundamental management strategies include early sepsis recognition and prompt treatment, through the administration of adequate antimicrobial agents, fluid resuscitation, and vasoactive agents as needed. In septic patients, organ-specific support is often required, particularly renal replacement therapy (RRT) in the setting of severe AKI, although ongoing debates persist regarding the ideal timing of initiation and dosing of RRT. A comprehensive approach integrating early recognition, targeted interventions, and close monitoring is essential to mitigate the burden of SA-AKI and improve patient outcomes in critical care settings.
Topics: Humans; Acute Kidney Injury; Sepsis; Renal Replacement Therapy; Critical Illness
PubMed: 38892111
DOI: 10.3390/ijms25115924 -
Pharmaceuticals (Basel, Switzerland) Aug 2023Normal tension glaucoma (NTG) is defined as a subtype of primary open-angle glaucoma (POAG) in which the intraocular pressure (IOP) values are constantly within the... (Review)
Review
Normal tension glaucoma (NTG) is defined as a subtype of primary open-angle glaucoma (POAG) in which the intraocular pressure (IOP) values are constantly within the statistically normal range without treatment and represents approximately the 30-40% of all glaucomatous cases. The pathophysiology of this condition is multifactorial and is still not completely well known. Several theories have been proposed to explain the onset and progression of this disease, which can be divided into IOP-dependent and IOP-independent factors, suggesting different therapeutic strategies. The current literature strongly supports the fundamental role of IOP in NTG. The gold standard treatment for NTG tends to be based on the lowering IOP even if "statistically normal". Numerous studies have shown, however, that the IOP reduction alone is not enough to slow down or stop the disease progression in all cases, suggesting that other IOP-independent risk factors may contribute to the NTG pathogenesis. In addition to IOP-lowering strategies, several different therapeutic approaches for NTG have been proposed, based on vaso-active, antioxidant, anti-inflammatory and/or neuroprotective substances. To date, unfortunately, there are no standardized or proven treatment alternatives for NTG when compared to traditional IOP reduction treatment regimes. The efficacy of the IOP-independent strategies in decreasing the risk or treating NTG still remains inconclusive. The aim of this review is to highlight strategies reported in the current literature to treat NTG. The paper also describes the challenges in finding appropriate and pertinent treatments for this potentially vision-threatening disease. Further comprehension of NTG pathophysiology can help clinicians determine when to use IOP-lowering treatments alone and when to consider additional or alternatively individualized therapies focused on particular risk factors, on a case-by-case basis.
PubMed: 37631087
DOI: 10.3390/ph16081172 -
MedComm Dec 2023Sepsis is defined as "a life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection." At present, sepsis... (Review)
Review
Sepsis is defined as "a life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection." At present, sepsis continues to pose a grave healthcare concern worldwide. Despite the use of supportive measures in treating traditional sepsis, such as intravenous fluids, vasoactive substances, and oxygen plus antibiotics to eradicate harmful pathogens, there is an ongoing increase in both the morbidity and mortality associated with sepsis during clinical interventions. Therefore, it is urgent to design specific pharmacologic agents for the treatment of sepsis and convert them into a novel targeted treatment strategy. Herein, we provide an overview of the molecular mechanisms that may be involved in sepsis, such as the inflammatory response, immune dysfunction, complement deactivation, mitochondrial damage, and endoplasmic reticulum stress. Additionally, we highlight important targets involved in sepsis-related regulatory mechanisms, including GSDMD, HMGB1, STING, and SQSTM1, among others. We summarize the latest advancements in potential therapeutic drugs that specifically target these signaling pathways and paramount targets, covering both preclinical studies and clinical trials. In addition, this review provides a detailed description of the crosstalk and function between signaling pathways and vital targets, which provides more opportunities for the clinical development of new treatments for sepsis.
PubMed: 38020710
DOI: 10.1002/mco2.418