Midazolam 20mg/0.5ml / Lidocaine 10mg/0.5ml nasal solution ampoules

BackgroundProcedural sedation and analgesia is crucial for gastrointestinal endoscopy to improve patient comfort and facilitate procedural success. However, pharmacological agents differ in their efficacy and safety profiles, and the optimal agent to balance these outcomes remains uncertain, creating challenges in clinical decision-making. Therefore, we conducted a network meta-analysis to comprehensively evaluate and compare the efficacy and safety of various pharmacological agents.MethodsWe searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to April 10, 2025. Randomised controlled trials (RCTs) comparing at least two intravenous pharmacological agents in adult patients undergoing gastrointestinal endoscopy were included. Evidence quality was assessed using the Cochrane Risk of Bias 2.0 tool. Efficacy outcomes included sedation success rate and induction time; safety outcomes included time to full alertness, recovery time, and adverse events (hypoxia, hypotension, bradycardia, and postoperative nausea and vomiting [PONV]). A random-effects network meta-analysis was performed. Risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes were calculated, with 95% confidence intervals (CIs). Treatment rankings were presented using surface under the cumulative ranking (SUCRA) curves. The study protocol was registered with PROSPERO (CRD42024572207).FindingsThe network meta-analysis included 152 RCTs with 26,527 patients, evaluating 37 interventions. No regimen demonstrated statistically significant superiority over propofol-opioids in terms of sedation success, which remained the reference standard. However, Etomidate-opioids achieved the highest SUCRA ranking for sedation success (SUCRA = 84.5%) and performed favorably in bradycardia (SUCRA = 79.4%), time to full alertness (SUCRA = 65.3%), and recovery time (SUCRA = 82.8%). Notably, etomidate-opioids significantly reduced the risk of hypoxia compared with propofol-opioids (RR = 0.35, 95% CI 0.16, 0.79; SUCRA = 55.0%), but showed no significant differences in hypotension (SUCRA = 45.5%), bradycardia (SUCRA = 79.4%), time to full alertness (SUCRA = 65.3%), or recovery time (SUCRA = 82.8%). It was, however, associated with an increased the risk of PONV (RR = 2.61, 95% CI 1.13, 6.07, SUCRA = 29.4%). Esketamine-remimazolam demonstrated an excellent safety profile, significantly reducing the risk of hypotension (RR = 0.12, 95% CI 0.06, 0.27; SUCRA = 95.6%) and bradycardia (RR = 0.19, 95% CI 0.06, 0.55; SUCRA = 88.3%) and shortening time to full alertness compared with propofol-opioids (MD = -6.05 min, 95% CI -11.85, -0.24; SUCRA = 92.7%). However, its SUCRA ranking for sedation success was lower than that of etomidate-opioids (63.4% vs. 84.5%), with no statistically significant difference observed between esketamine-remimazolam and etomidate-opioids (RR = 1.29, 95% CI 0.68, 2.45).InterpretationAlthough no pharmacological regimen demonstrates superior sedation success compared with propofol-opioids, which serve as the standard comparator, etomidate-opioids regimens offer a favorable balance between sedation efficacy and safety, though they warrant attention due to an increased risk of PONV. Esketamine-remimazolam demonstrates superior hemodynamic stability and faster recovery but may be less effective in achieving sedation success. Midazolam-based regimens demonstrate lower efficacy and prolonged recovery and are therefore not recommended.FundingNone.

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BackgroundCombining lidocaine with bupivacaine in brachial plexus blocks seeks to blend rapid onset with extended duration; yet, clinical advantages are uncertain. This systematic review assesses their efficacy against bupivacaine alone in ultrasound-guided brachial plexus blocks.MethodsA systematic search of PubMed, EMBASE, and Cochrane databases was conducted in May 2025. Randomized controlled trials (RCTs) comparing lidocaine-bupivacaine mixtures with bupivacaine alone in ultrasound-guided brachial plexus blocks were included. The primary outcome was sensory block onset time. Secondary outcomes included motor block onset time, sensory and motor block durations, and conversion to general anesthesia. Data were analyzed using a random-effects model, with heterogeneity assessed via I² statistics.ResultsOf 1,490 identified articles, 7 RCTs (358 patients) met the inclusion criteria. No significant difference was found in sensory block onset time (mean difference [MD] -1.81 min, 95% confidence interval [CI] -3.92 to 0.29; P = 0.09; I² = 98%) or motor block onset time (MD 0.02 min, 95% CI -2.34 to 2.39; P = 0.99; I² = 95%) between groups. The mixture reduced sensory (MD -172.88 min, 95% CI -215.18 to -130.59; PConclusionsNo clinical benefit was observed from combining lidocaine with bupivacaine, as there was no improvement in block onset times and a reduction in block durations. Given the very low certainty of evidence, these findings should be interpreted with caution, and further high-quality RCTs are needed.

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BackgroundTherapeutic gastrointestinal endoscopy, including endoscopic retrograde cholangiopancreatography and endoscopic submucosal dissection, requires effective sedation strategies to ensure procedural success and patient safety. However, optimal pharmacological regimens remain unclear, particularly for prolonged procedures.MethodsWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomised controlled trials comparing pharmacological sedation strategies in patients undergoing therapeutic gastrointestinal endoscopy. Outcomes included procedural interference events, hypoxia, hypotension, bradycardia, recovery time, induction time, satisfaction, and postoperative nausea and vomiting. Risk of bias was assessed using the Cochrane RoB 2.0 tool, and certainty of evidence was rated using GRADE framework. A frequentist random-effects network meta-analysis was conducted, along with cluster ranking of co-primary outcomes to evaluate benefit-risk trade-offs.ResultsSixty randomised controlled trials involving 7,071 patients and 32 pharmacological regimens were included. Compared with propofol-opioid, which remained the reference standard, no regimen significantly reduced procedural interference events. Ketamine-propofol demonstrated consistent advantages across hypoxia (relative risk [RR] 0.12, 95% confidence interval [CI] 0.03 to 0.59, P = 0.009; moderate certainty), hypotension (RR 0.28, 95% CI 0.09 to 0.83, P = 0.021; low certainty), and bradycardia (RR 0.11, 95% CI 0.01 to 0.86, P = 0.035; moderate certainty). Cluster rank analyses identified ketamine-propofol and lidocaine-midazolam-propofol as the highest-ranking regimens in both efficacy and safety domains. Meta-regression revealed no significant effect modifiers.ConclusionWhile propofol-opioid remains the standard reference, alternative sedation strategies such as ketamine-propofol and lidocaine-midazolam-propofol offer favourable profiles for therapeutic gastrointestinal endoscopy. These findings support individualised regimen selection based on patient and procedural needs.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251018215.

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ObjectivesDexmedetomidine has been increasingly used as an alternative sedative agent during bronchoscopy, but its comparative efficacy and safety remain unclear. This systematic review and meta-analysis aimed to assess the effectiveness and safety of dexmedetomidine compared with other sedative agents in adult bronchoscopy.MethodologyPubMed, Embase, CENTRAL, and Scopus were searched up to 17 December 2025 for randomised controlled trials (RCTs) comparing dexmedetomidine with other sedatives. Procedural success was assessed descriptively, while procedural duration, satisfaction scores, safety and hemodynamic parameters were analyzed quantitatively in a random-effects model.ResultsSeventeen RCTs were included. Qualitative synthesis showed mixed results for the adequacy of sedation between dexmedetomidine and midazolam or propofol. However, studies did note a tendency for better sedation with remimazolam as compared to dexmedetomidine. Compared with midazolam, dexmedetomidine significantly reduced the incidence of hypoxia, but was associated with higher risks of bradycardia and reduced risk of hypotension; no consistent differences were observed in procedure duration or rescue sedation. Compared with propofol, dexmedetomidine was associated with lower rates of hypoxia and hypertension but a higher incidence of bradycardia. Compared with remimazolam, dexmedetomidine was associated with lower patient satisfaction scores and higher rates of hypoxia, whereas other safety outcomes did not show any significant difference. Studies comparing dexmedetomidine with opioids were scarce.ConclusionsEvidence shows dexmedetomidine is an effective sedative for adult bronchoscopy, comparable to midazolam and propofol in sedation levels. It may reduce hypoxia but increases bradycardia. Compared with remimazolam, it seems to offer less favourable sedation with a higher risk of hypoxia. However, data was from a limited number of studies. Registration No.: PROSPERO (CRD420251242030).

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PurposeTo identify and compare anesthetic and analgesic strategies employed during uterine artery embolization for symptomatic leiomyomas, assessing their effectiveness in reducing postoperative pain and opioid use and evaluating complication rates.MethodsA systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Searches were performed in PubMed, Embase, Web of Science, and Scientific Electronic Library Online. Randomized controlled trials and prospective cohort or case-control studies, published in the last 10 years, evaluating pain, opioid consumption, and/or complications, were included.ResultsThe total of 3,433 studies were screened, of which six met eligibility criteria. Superior hypogastric plexus block reduced pain and opioid use. Intra-arterial lidocaine decreased pain within 2-4 h and opioid consumption, with a transient effect; administration after vascular stasis was preferable. Controlled-release oxycodone reduced pain at 24 h and need for rescue medication without lowering mean consumption. Dexamethasone reduced pain at 12-24 h without impacting opioid use. No significant complications were reported.ConclusionIn the ischemic phase of post-uterine artery embolization pain, a superior hypogastric nerve block appears to provide the most consistent relief, with intra-arterial lidocaine representing an alternative when resources are limited. For the inflammatory phase, intravenous dexamethasone is the preferred option, whereas controlled-release oxycodone may be considered only in refractory cases.

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Background/Objectives: Local anaesthetic systemic toxicity (LAST) is a rare but potentially fatal complication of dental and oral and maxillofacial surgical local anaesthesia (LA). Three amide agents are commonly used in the UK: lignocaine (lidocaine) 2% with adrenaline 1:80,000; articaine 4% with adrenaline 1:100,000 (2.2 mL cartridges); and bupivacaine 0.5%. Clinically significant discrepancies between guideline sources for maximum recommended dosages (MRDs) persist, and the additive toxicity of combined amide agents remains underappreciated. The objectives are: to provide clear, evidence-appraised MRD guidance for dental practitioners; to explain safe combination dosing using the fractional dose rule with acknowledgement of its pharmacokinetic limitations; and to outline recognition and management of LAST, including intravenous lipid emulsion (ILE) therapy, setting-stratified response, and differential diagnosis. Methods: These include the following: narrative review of MEDLINE (via PubMed), the Cochrane Library, and Embase (inception to May 2026), supplemented by key regulatory documents (British National Formulary (BNF) 91; US Food and Drug Administration (FDA) prescribing information; UK Summaries of Product Characteristics (SmPCs)); major guideline documents (American Society of Regional Anesthesia and Pain Medicine (ASRA) 2018; Association of Anaesthetists 2021; Resuscitation Council UK 2021); systematic reviews; and peer-reviewed literature, ranked by a jurisdiction-specific UK prescribing and regulatory source hierarchy. Results: BNF 91 and the FDA both support a 7 mg/kg (500 mg) MRD for lignocaine with adrenaline; in practice, the adrenaline ceiling limits administration to 6-7 cartridges (2.2 mL) regardless of the guideline followed. The principal reasons for caution when combining amide agents are; additive systemic toxicity, more complex dose calculation, absence of proven clinical benefit for concurrent mixing, unnecessary drug exposure, and incremental hypersensitivity risk-not metabolic pathway differences. The fractional dose rule is a pharmacologically justified safety heuristic with acknowledged pharmacokinetic limitations. ILE is a specific rescue therapy for severe or cardiovascular LAST; airway support and oxygenation remain the primary interventions. Patient-specific factors substantially lower the effective toxic threshold. Conclusions: Safe LA administration in oral surgery requires systematic MRD calculation, application of the fractional dose rule for combined-agent appointments, attention to patient-specific risk factors, setting-appropriate emergency preparedness, and structured differential diagnosis to distinguish LAST from more common dental emergencies.

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