Remimazolam vs. propofol for general anaesthesia in elderly patients: a meta-analysis with trial sequential analysis.

BACKGROUND: Elderly patients comprise an increasing proportion of patients undergoing surgery, and they require special attention due to age-related physiological changes. Propofol is the traditional agent for anaesthesia, and recently, remimazolam, a novel ultra-short-acting benzodiazepine, has emerged as an alternative to propofol in general anaesthesia. OBJECTIVES: We aim to compare remimazolam vs . propofol for general anaesthesia in elderly patients regarding hypotension, induction characteristics, haemodynamics and recovery outcomes. DESIGN: Meta-analysis with sensitivity and trial sequential analyses (TSA) to assess inconsistencies. Risk ratios and mean differences with 95% confidence intervals (95% CIs) were computed using a random effects model. Subgroups and meta-regression according to anaesthesia methods were also performed. DATA SOURCES: We systematically searched MEDLINE, Embase and Cochrane for randomised controlled trials (RCTs) up to January 1, 2024. ELIGIBILITY CRITERIA: Patients at least 60 years old, comparing remimazolam vs . propofol for general anaesthesia. RESULTS: Eleven RCTs (947 patients) were included. Compared with propofol, remimazolam was associated with lower postinduction and intra-operative hypotension (RR 0.41, 95% CI 0.27 to 0.62, P  < 0.001) and incidence of bradycardia (risk ratio 0.58, 95% CI 0.34 to 0.98, P  = 0.04), with a higher heart rate ( P  = 0.01). The incidence of injection pain was lower ( P  < 0.001), but remimazolam was associated with a longer time to loss of consciousness ( P  < 0.001) and a higher bispectral index at loss of consciousness ( P  = 0.04). No differences were found for mean arterial pressure, emergence time, extubation time and incidence of emergence agitation. The TSA was consistent and achieved the required information size for hypotension. CONCLUSIONS: Remimazolam significantly reduced the risk of hypotension, bradycardia and injection pain, despite an increase in the time to loss of consciousness. Remimazolam appears to be an effective and well tolerated alternative to propofol in elderly patients undergoing general anaesthesia.

The role of symptoms severity, heart rate, and central sensitization for predicting sleep quality in patients with fibromyalgia.

BACKGROUND: Clinical predictors of sleep quality in patients with fibromyalgia syndrome (FMS) are still unknown. By identifying these factors, we could raise new mechanistic hypotheses and guide management approaches. We aimed to describe the sleep quality of FMS patients and to explore the clinical and quantitative sensory testing (QST) predictors of poor sleep quality and its subcomponents. METHODS: This study is a cross-sectional analysis of an ongoing clinical trial. We performed linear regression models between sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and demographic, clinical, and QST variables, controlling for age and gender. Predictors for the total PSQI score and its seven subcomponents were found using a sequential modeling approach. RESULTS: We included 65 patients. The PSQI score was 12.78 ± 4.39, with 95.39% classified as poor sleepers. Sleep disturbance, use of sleep medications, and subjective sleep quality were the worst subdomains. We found poor PSQI scores were highly associated with symptom severity (FIQR score and PROMIS fatigue), pain severity, and higher depression levels, explaining up to 31% of the variance. Fatigue and depression scores also predicted the subjective sleep quality and daytime dysfunction subcomponents. Heart rate changes (surrogate of physical conditioning) predicted the sleep disturbance subcomponent. QST variables were not associated with sleep quality or its subcomponents. CONCLUSIONS: Symptom severity, fatigue, pain, and depression (but no central sensitization) are the main predictors of poor sleep quality. Heart rate changes independently predicted the sleep disturbance subdomain (the most affected one in our sample), suggesting an essential role of physical conditioning in modulating sleep quality in FMS patients. This underscores the need for multidimensional treatments targeting depression and physical activity to improve the sleep quality of FMS patients.

Comparison of intranasal dexmedetomidine versus oral midazolam for premedication in pediatric patients: an updated meta-analysis with trial-sequential analysis.

BACKGROUND: Midazolam is routinely used as preanesthetic medication in pediatric patients. Recently, dexmedetomidine has emerged as an alternative as a premedicant. We aimed to add more evidence about the efficacy and safety of two common routes of administration for pediatric premedication: oral midazolam versus intranasal dexmedetomidine. METHODS: We systematically searched Randomized Controlled Trials (RCTs) involving patients ≤ 18 years old undergoing preanesthetic medication and comparing intranasal dexmedetomidine with oral midazolam. Risk Ratio (RR) and Mean Difference (MD) with 95% Confidence Intervals (95% CI) were computed using a random effects model. Trial-sequential analyses were performed to assess inconsistency. RESULTS: Sixteen RCTs (1,239 patients) were included. Mean age was 5.5 years old, and most procedures were elective. There was no difference in satisfactory induction or mask acceptance (RR = 1.15, 95% CI 0.97-1.37; p = 0.11). There was a higher incidence of satisfactory separation from parents in the dexmedetomidine group (RR = 1.40; 95% CI 1.13-1.74; p = 0.002). Dexmedetomidine was also associated with a reduction in the incidence of emergence agitation (RR = 0.35; 95% CI 0.14-0.88; p = 0.02). Heart rate and mean arterial pressure were marginally lower in the dexmedetomidine group but without clinical repercussions. CONCLUSION: Compared with oral midazolam, intranasal dexmedetomidine demonstrated better separation from parents and lower incidence of emergence agitation in pediatric premedication, without a difference in satisfactory induction. Intranasal dexmedetomidine may be a safe and effective alternative to oral midazolam for premedication in pediatric patients.

The impact of glucagon-like peptide-1 receptor agonists in the patients undergoing anesthesia or sedation: systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide-1 agonist receptors (GLP-1RAs), medications used for glycemic control and weight loss, are increasing worldwide. In the perioperative period, the major concern related to GLP-1RA is gastric emptying delay and risk of aspiration. This meta-analysis and systematic review compared the risks and benefits of using GLP-1 agonist receptors and control in surgical and nonsurgical procedures under anesthesia or sedation. METHODS: We systematically searched MEDLINE, Embase, and Cochrane for randomized controlled trials and observational studies involving patients > 18 years undergoing elective surgeries or procedures. Outcomes of interest were pre-procedural gastrointestinal (GI) symptoms, residual gastric content assessed by endoscopy, pulmonary aspiration during anesthesia/sedation, perioperative glycemic control, postoperative inotropic support, nausea/vomiting (PONV), atrial fibrillation, and 30-day mortality rate. We used a random effects model, with odds ratio and mean difference computed for binary and continuous outcomes, respectively. RESULTS: Fourteen randomized and observational studies with 2143 adult patients undergoing elective surgeries and procedures were included. GLP-1RA resulted in increased pre-procedural GI symptoms (OR 7.66; 95% CI 3.42, 17.17; p < 0.00001; I2 = 0%) and elevated residual gastric content (OR 6.08; 95% CI 2.86, 12.94; p < 0.00001; I2 = 0%). GLP-1RA resulted in lower glycemic levels (MD - 0.73; 95% CI - 1.13, - 0.33; p = 0.0003; I2 = 90%) and lower rate of rescue insulin administration (OR 0.39; 95% CI 0.23, 0.68 p = 0.0009; I2 = 35%). There was no significant difference in rate of perioperative hypoglycemia (OR 0.60; 95% CI 0.29, 1.24; p = 0.17; I2 = 0%), hyperglycemia (OR 0.89; 95% CI 0.59, 1.34; p = 0.58; I2 = 38%), need for postoperative inotropic support (OR 0.57; 95% CI 0.33, 1.01; p = 0.05; I2 = 0%), atrial fibrillation (OR 1.02; 95% CI 0.52, 2.01; p = 0.95; I2 = 16%), rate of PONV (OR 1.35; 95% CI 0.82, 2.21; p = 0.24; I2 = 0%), and 30-day mortality rate (OR 0.54; 95% CI 0.14, 2.05; p = 0.25; I2 = 0%). CONCLUSION: Compared to control, pre-procedural GLP-1RA increased the rate of GI symptoms and the risk of elevated residual gastric content despite adherence to fasting guidelines. GLP-1RA improved glycemic control and decreased the rate of rescue insulin administration. There was no significant difference in the rates of perioperative hypo or hyperglycemia, postoperative inotropic support, PONV, atrial fibrillation, and 30-day mortality.

Safety of local anesthesia in endovascular treatment of Aneurysms: A systematic review and Meta-Analysis.

BACKGROUND: Endovascular treatment of intracranial aneurysms (EVTIAs) is increasingly popular due to its minimally invasive nature and high success rate. While general anesthesia (GA) has been the historical preference for EVTIAs, there's growing interest in local anesthesia (LA). However, concerns persist about LA safety for EVTIAs. Therefore, we conducted a systematic review and meta-analysis to assess LA safety for EVTIAs. METHODS: Following PRISMA guidelines, we searched PubMed, Embase, and Web of Science databases. Pooled analysis with 95 % confidence intervals (CI) assessed effects, I2 statistics gauged heterogeneity, and a random-effects model was adopted. Conversion to GA, neurological or procedure-related complications, intraoperative intracranial hemorrhagic complications (IIHC), and mortality were assessed. Subanalyses for ruptured and unruptured cases were performed. RESULTS: The analysis included eleven studies, 2,133 patients, and 2,369 EVTIAs under LA. Conversion to GA rate was 1 % (95 %CI: 0 to 2 %). Neurological or procedure-related complications rate was 13 % (95 % CI: 8 % to 17 %). IIHC analysis revealed a rate of 1 % (95 % CI: 1 % to 2 %). The mortality rate was 0 % (95 %CI: 0 % to 0 %). Subanalyses revealed similar rates in ruptured and unruptured subgroups, except for a slightly high rate of complications and IIHC in the ruptured subgroup. CONCLUSION: Findings indicate that EVTIA under LA is safe, with low conversion and mortality rates, even for ruptured aneurysms. Complications rates, also in IIHC rates, are comparable to those reported for GA, emphasizing LA's comparable safety profile in EVTIAs. Considering these promising outcomes, the decision to opt for the LA approach emerges as meaningful and well-suited for the endovascular treatment of aneurysms. Beyond its safety, LA introduces inherent supplementary advantages, including shortened hospitalization periods, cost-effectiveness, and an expedited patient recovery process.

Toluene exposure and changes in platelet count: a narrative review.

Toluene is a widely used solvent whose many toxic effects include neurological and hematological damage. This study reviewed evidence about the effects of toluene exposure on platelet count in humans. Three electronic databases and a digital library of theses and dissertations were searched using a specific strategy, yielding 64 articles, of which 14 were selected. These studies assessed a total of 15,759 participants, including 13,297 exposed individuals, mainly women exposed in an environmental setting. The major findings were: (1) conflicting results (positive, inverse, or no association), (2) cross-contamination with other substances, which impaired assessment of the relationship, and (3) a lack of studies. Thus, further research is needed on this topic, especially toluene exposure in isolation from associated substances.

O tolueno é um solvente amplamente utilizado com múltiplos efeitos tóxicos, sobretudo sobre o sistema nervoso central, assim como efeitos hematológicos. Este estudo foi conduzido para revisar a evidência presente na literatura sobre a exposição humana ao tolueno e seu efeito na contagem de plaquetas. Em 3 bases de dados eletrônicas e 1 biblioteca digital de teses e dissertações foram pesquisadas utilizando uma estratégia de busca específica, da qual resultaram 64 artigos, dos quais 14 foram selecionados. Estes avaliaram 15.759 pessoas, com 13.297 indivíduos expostos, compostos principalmente de mulheres em um cenário ambiental. Foram encontrados 3 grandes resultados, os quais incluem a presença de relações conflitantes (positiva, inversa, sem associação), a presença frequente de outras substâncias afetando a análise da relação, e a falta de estudos. Portanto, nós recomendamos mais pesquisas no tópico, com ênfase na exposição ao tolueno sem substâncias associadas.

Motor cortex inhibition as a fibromyalgia biomarker: a meta-analysis of transcranial magnetic stimulation studies.

Fibromyalgia (FM) is a common and refractory chronic pain condition with multiple clinical phenotypes. The current diagnosis is based on a syndrome identification which can be subjective and lead to under or over-diagnosis. Therefore, there is a need for objective biomarkers for diagnosis, phenotyping, and prognosis (treatment response and follow-up) in fibromyalgia. Potential biomarkers are measures of cortical excitability indexed by transcranial magnetic stimulation (TMS). However, no systematic analysis of current evidence has been performed to assess the role of TMS metrics as a fibromyalgia biomarker. Therefore, this study aims to evaluate evidence on corticospinal and intracortical motor excitability in fibromyalgia subjects and to assess the prognostic role of TMS metrics as response biomarkers in FM. We conducted systematic searches on PubMed/Medline, Embase, and Cochrane Central databases for observational studies and randomized controlled trials on fibromyalgia subjects that used TMS as an assessment. Three reviewers independently selected and extracted the data. Then, a random-effects model meta-analysis was performed to compare fibromyalgia and healthy controls in observational studies. Also, to compare active versus sham treatments, in randomized controlled trials. Correlations between changes in TMS metrics and clinical improvement were explored. The quality and evidence certainty were assessed following standardized approaches. We included 15 studies (696 participants, 474 FM subjects). The main findings were: (1) fibromyalgia subjects present less intracortical inhibition (mean difference (MD) = -0.40, 95% confidence interval (CI) -0.69 to -0.11) and higher resting motor thresholds (MD = 6.90 µV, 95% CI 4.16 to 9.63 µV) when compared to controls; (2) interventions such as exercise, pregabalin, and non-invasive brain stimulation increased intracortical inhibition (MD = 0.19, 95% CI 0.10 to 0.29) and cortical silent period (MD = 14.92 ms, 95% CI 4.86 to 24.98 ms), when compared to placebo or sham stimulation; (3) changes on intracortical excitability are correlated with clinical improvements - higher inhibition moderately correlates with less pain, depression, and pain catastrophizing; lower facilitation moderately correlates with less fatigue. Measures of intracortical inhibition and facilitation indexed by TMS are potential diagnostic and treatment response biomarkers for fibromyalgia subjects. The disruption in the intracortical inhibitory system in fibromyalgia also provides additional evidence that fibromyalgia has some neurophysiological characteristics of neuropathic pain. Treatments inducing an engagement of sensorimotor systems (e.g., exercise, motor imagery, and non-invasive brain stimulation) could restore the cortical inhibitory tonus in FM and induce clinical improvement.

Development of a Clinical Prediction Rule for Treatment Success with Transcranial Direct Current Stimulation for Knee Osteoarthritis Pain: A Secondary Analysis of a Double-Blind Randomized Controlled Trial.

The study's objective was to develop a clinical prediction rule that predicts a clinically significant analgesic effect on chronic knee osteoarthritis pain after transcranial direct current stimulation treatment. This is a secondary analysis from a double-blind randomized controlled trial. Data from 51 individuals with chronic knee osteoarthritis pain and an impaired descending pain inhibitory system were used. The intervention comprised a 15-session protocol of anodal primary motor cortex transcranial direct current stimulation. Treatment success was defined by the Western Ontario and McMaster Universities' Osteoarthritis Index pain subscale. Accuracy statistics were calculated for each potential predictor and for the final model. The final logistic regression model was statistically significant (p < 0.01) and comprised five physical and psychosocial predictor variables that together yielded a positive likelihood ratio of 14.40 (95% CI: 3.66−56.69) and an 85% (95%CI: 60−96%) post-test probability of success. This is the first clinical prediction rule proposed for transcranial direct current stimulation in patients with chronic pain. The model underscores the importance of both physical and psychosocial factors as predictors of the analgesic response to transcranial direct current stimulation treatment. Validation of the proposed clinical prediction rule should be performed in other datasets.

Measuring Contralateral Silent Period Induced by Single-Pulse Transcranial Magnetic Stimulation to Investigate M1 Corticospinal Inhibition.

Contralateral silent period (cSP) is a period of suppression in the background electrical muscle activity captured by electromyography (EMG) after a motor evoked potential (MEP). To obtain this, an MEP is elicited by a suprathreshold transcranial magnetic stimulation (TMS) pulse delivered to the primary motor cortex (M1) of the target muscle selected, while the participant provides a standardized voluntary target muscle contraction. The cSP is a result of inhibitory mechanisms that occur after the MEP; it provides a broad temporal assessment of spinal inhibition in its initial ~50 ms, and cortical inhibition after. Researchers have tried to better understand the neurobiological mechanism behind the cSP to validate it as a potential diagnostic, surrogate, and predictive biomarker for different neuropsychiatric diseases. Therefore, this article describes a method to measure M1 cSP of lower and upper limbs, including a selection of target muscle, electrode placement, coil positioning, method of measuring voluntary contraction stimulation, intensity setup, and data analysis to obtain a representative result. It has the educational objective of giving a visual guideline in performing a feasible, reliable, and reproducible cSP protocol for lower and upper limbs and discussing practical challenges of this technique.