Neuromuscular Blockade Research Articles

Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure–activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

The impact of sugammadex dosing and administration practices on potential cost savings for pharmacy departments.

Neuromuscular blocking agents (NMBAs) are commonly used during surgery, and restoring neuromuscular function at the end of surgery is vital in preventing complications of residual paralysis. Recent guidelines from the American Society of Anesthesiology recommend using sugammadex over neostigmine; however, sugammadex is significantly more expensive than neostigmine and may increase drug expenditure for pharmacy departments. This review summarizes evidence evaluating sugammadex dose adjustments and the potential of these dose adjustments to lead to cost savings for pharmacy departments. We found evidence suggesting that the manufacturer-recommended sugammadex dose may not be needed in many patients and that dosing based on an adjusted body weight or based on depth of neuromuscular blockade may lead to lower sugammadex usage. Combining sugammadex with neostigmine could also decrease the dose of sugammadex required. We have highlighted the importance of objective neuromuscular monitoring to guide sugammadex dosing and evaluation for residual neuromuscular blockade. Cost savings for pharmacy departments may be realized by these alternative dosing strategies and/or vial-splitting practices. Implementing practices related to sugammadex vial splitting and dose adjustment based on body weight and depth of neuromuscular blockade shows potential benefits in terms of sugammadex cost savings.

A Practical Dosing Algorithm for Deep Neuromuscular Blockade during Total Intravenous Anesthesia: ROCURITHM.

The number of trials investigating the effects of deep neuromuscular blockade (NMB) on surgical conditions and patient outcomes is steadily increasing. Consensus on which surgical procedures benefit from deep NMB (a posttetanic count [PTC] of 1 to 2) and how to implement it has not been reached. The European Society of Anaesthesiology and Intensive Care does not advise routine application but recommends use of deep NMB to improve surgical conditions on indication. This study investigates the optimal dosing strategy to reach and maintain adequate deep NMB during total intravenous anesthesia. Data from three trials investigating deep NMB during laparoscopic surgery with total intravenous anesthesia (n = 424) were pooled to analyze the required rocuronium dose, when to start continuous infusion, and how to adjust. The resulting algorithm was validated (n = 32) and compared to the success rate in ongoing studies in which the algorithm was not used (n = 180). The mean rocuronium dose based on actual bodyweight for PTC 1 to 2 was (mean ± SD) 1.0 ± 0.27 mg · kg-1 ·h-1 in the trials, in which mean duration of surgery was 116 min. An induction dose of 0.6 mg ·kg-1 led to a PTC of 1 to 5 in a quarter of patients after a mean of 11 min. The remaining patients were equally divided over too shallow (additional bolus and direct start of continuous infusion) or too deep; a 15-min wait after PTC of 0 for return of PTC to 1 or higher. Using the proposed algorithm, a mean 76% of all 5-min measurements throughout surgery were on target PTC 1 to 2 in the validation cohort. The algorithm performed significantly better than anesthesiology residents without the algorithm, even after a learning curve from 0 to 20 patients (42% on target, P ≤ 0.001, Cohen's d = 1.4 [95% CI, 0.9 to 1.8]) to 81 to 100 patients (61% on target, P ≤ 0.05, Cohen's d = 0.7 [95% CI, 0.1 to 1.2]). This study proposes a dosing algorithm for deep NMB with rocuronium in patients receiving total intravenous anesthesia.

Systematic review and network meta-analysis on the efficacy and safety of parmacotherapy for hand osteoarthritis.

Hand osteoarthritis poses a significant health challenge globally due to its increasing prevalence and the substantial burden on individuals and the society. In current clinical practice, treatment options for hand osteoarthritis encompass a range of approaches, including biological agents, antimetabolic drugs, neuromuscular blockers, anti-inflammatory drugs, hormone medications, pain relievers, new synergistic drugs, and other medications. Despite the diverse array of treatments, determining the optimal regimen remains elusive. This study seeks to conduct a network meta-analysis to assess the effectiveness and safety of various drug intervention measures in the treatment of hand osteoarthritis. The findings aim to provide evidence-based support for the clinical management of hand osteoarthritis. We performed a comprehensive search across PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials was conducted until September 15th, 2022, to identify relevant randomized controlled trials. After meticulous screening and data extraction, the Cochrane Handbook's risk of bias assessment tool was applied to evaluate study quality. Data synthesis was carried out using Stata 15.1 software. 21 studies with data for 3965 patients were meta-analyzed, involving 20 distinct Western medicine agents. GCSB-5, a specific herbal complex that mainly regulate pain in hand osteoarthritis, showed the greatest reduction in pain [WMD = -13.00, 95% CI (-26.69, 0.69)]. CRx-102, s specific medication characterized by its significant effect for relieving joint stiffness symptoms, remarkably mitigated stiffness [WMD = -7.50, 95% CI (-8.90, -6.10)]. Chondroitin sulfate displayed the highest incidence of adverse events [RR = 0.26, 95% CI (0.06, 1.22)]. No substantial variation in functional index for hand osteoarthritis score improvement was identified between distinct agents and placebo. In summary, GCSB-5 and CRx-102 exhibit efficacy in alleviating pain and stiffness in HOA, respectively. However, cautious interpretation of the results is advised. Tailored treatment decisions based on individual contexts are imperative.

Behavioral control through the direct, focal silencing of neuronal activity

The ability to optically stimulate and inhibit neurons has revolutionized neuroscience research. Here, we present a direct, potent, user-friendly chemical approach for optically silencing neurons. We have rendered saxitoxin (STX), a naturally occurring paralytic agent, transiently inert through chemical protection with a previously undisclosed nitrobenzyl-derived photocleavable group. Exposing the caged toxin, STX-bpc, to a brief (5ms) pulse of light effects rapid release of a potent STX derivative and transient, spatially precise blockade of voltage-gated sodium channels (NaVs). We demonstrate the efficacy of STX-bpc for parametrically manipulating action potentials in mammalian neurons and brain slice. Additionally, we show the effectiveness of this reagent for silencing neural activity by dissecting sensory-evoked swimming in larval zebrafish. Photo-uncaging of STX-bpc is a straightforward method for non-invasive, reversible, spatiotemporally precise neural silencing without the need for genetic access, thus removing barriers for comparative research.

A randomised trial comparing block characteristics of a mixture versus sequential injections of lignocaine and ropivacaine for supraclavicular brachial plexus nerve block in patients undergoing upper limb surgery.

There is no consensus on the appropriate use of mixtures of local anaesthetic drugs in various combinations for nerve blocks. We intended to compare short-acting lignocaine and long-acting ropivacaine as a mixture versus undiluted sequential injections on block characteristics of ultrasound-guided (USG) supraclavicular brachial plexus block for upper limb surgeries. A double-blinded randomised study was conducted on 64 adult patients scheduled for upper limb surgery who received 15 mL each of 2% lignocaine with adrenaline and 0.75% ropivacaine as a 1:1 mixture in the mixed group (Group M) or sequential injections in the sequential group (Group S) by using a USG technique. The primary outcome was the percentage of participants with complete four nerve sensory blocks at 10 minutes post block injection. Secondary outcomes were sensory and motor block characteristics till 30 minutes, total duration of analgesia, sensory and motor block, and complications. Demographic characteristics and time taken for the procedure were similar. The percentage of participants with a complete four-nerve sensory block at 10 minutes was higher in Group S (69%) versus Group M (41%) (P = 0.04). Complete sensory and motor block rates were similar at 30 minutes. The block procedure time, total duration of analgesia, and sensory and motor block were similar in both groups. There were no major complications. Sequential lignocaine-ropivacaine, compared to the mixed injection technique, has a higher initial rate of sensory and motor block onset with a similar total block duration.

Effects Of Low Doses Of Intrathecal Clonidine And Dexmedetomidine With Bupivacaine On The Duration Of Sensory And Motor Block In Abdominal And Lower Limb Surgeries- A Prospective Randomised Double Blinded Study

BACKGROUND: The purpose of this study is to compare the duration of sensory and motor block in elective lower limb and abdominal procedures following intrathecal administration of bupivacaine along with adjuvants either clonidine or dexmedetomidine. METHODS: A prospective randomised double blinded study. 120 study participants were randomly allocated to three groups-Group A was given 12.5 mg of hyperbaric bupivacaine, Group B was given 3 mcg dexmedetomidine along with 12.5 mg hyperbaric bupivacaine and Group C was given 30 mcg of clonidine along with hyperbaric bupivacaine. The duration of sensory and motor block was recorded. RESULTS: Group B and C study participants showed significantly longer duration of sensory and motor block when compared to Group A. The mean duration of sensory block in Group A was 92.5 minutes, Group B 124.5 minutes Group C (119.4 minutes) (A vs B, A vs C p<0.001). The mean duration of motor block in group A 149.1 min, group B 252.5 min, Group C 217 min (A vs B, A vs C, B vs C P<0.001) CONCLUSION: By adding 3 mcg dexmedetomidine or 30 mcg clonidine to hyperbaric bupivacaine duration of sensory and motor block was significantly prolonged.

Cerebral hemodynamics and optic nerve sheath diameter acquired via neurosonology in critical patients with severe coronavirus disease: experience of a national referral hospital in Peru.

We aimed to describe the neurosonological findings related to cerebral hemodynamics acquired using transcranial Doppler and to determine the frequency of elevated ICP by optic nerve sheath diameter (ONSD) measurement in patients with severe coronavirus disease (COVID-19) hospitalized in the intensive care unit of a national referral hospital in Peru. We included a retrospective cohort of adult patients hospitalized with severe COVID-19 and acute respiratory failure within the first 7 days of mechanical ventilation under deep sedoanalgesia, with or without neuromuscular blockade who underwent ocular ultrasound and transcranial Doppler. We determine the frequency of elevated ICP by measuring the diameter of the optic nerve sheath, choosing as best cut-off value a diameter equal to or >5.8 mm. We also determine the frequency of sonographic patterns obtained by transcranial Doppler. Through insonation of the middle cerebral artery. Likewise, we evaluated the associations of clinical, mechanical ventilator, and arterial blood gas variables with ONSD ≥5.8 mm and pulsatility index (PI) ≥1.1. We also evaluated the associations of hemodynamic findings and ONSD with mortality the effect size was estimated using Poisson regression models with robust variance. This study included 142 patients. The mean age was 51.39 ± 13.3 years, and 78.9% of patients were male. Vasopressors were used in 45.1% of patients, and mean arterial pressure was 81.87 ± 10.64 mmHg. The mean partial pressure of carbon dioxide (PaCO2) was elevated (54.08 ± 16.01 mmHg). Elevated intracranial pressure was seen in 83.1% of patients, as estimated based on ONSD ≥5.8 mm. A mortality rate of 16.2% was reported. In the multivariate analysis, age was associated with elevated ONSD (risk ratio [RR] = 1.07). PaCO2 was a protective factor (RR = 0.64) in the cases of PI ≥ 1.1. In the mortality analysis, the mean velocity was a risk factor for mortality (RR = 1.15). A high rate of intracranial hypertension was reported, with ONSD measurement being the most reliable method for estimation. The increase in ICP measured by ONSD in patients with severe COVID-19 on mechanical ventilation is not associated to hypercapnia or elevated intrathoracic pressures derived from protective mechanical ventilation.

Epidural, Inadvertent Subdural, and Combined Epidural-Subdural Anesthesia in Lumbar Spine Surgery: A Retrospective Analysis.

This study aimed to categorize contrast media images associated with epidural, subdural, and combined epidural-subdural anesthesia in patients who had undergone fluoroscopy-guided epidural anesthesia using contrast media combined with monitored anesthesia care (MAC) targeted at deep sedation, incorporating capnography over 5 years. Additionally, a correlation was established between the anesthetic effects and radiographic findings according to the categorized imaging appearances. This study included 628 patients who underwent endoscopic, open, or fusion surgery under epidural anesthesia at Nanoori Hospital in Gangnam between March 2018 and September 2023. Fluoroscopy-guided epidural anesthesia using contrast media combined with MAC and capnography was used. The dataset included detailed radiographic imaging, nursing, and anesthesia records. Distinct patterns of anesthesia administration were observed, with 49%, 19.6%, and 31% of patients receiving epidural, subdural, and combined epidural-subdural anesthesia, respectively. The incidence and duration of motor block were significantly different among the three groups. Additionally, subdural anesthesia displayed a higher incidence of motor block and a prolonged motor deficit duration than epidural anesthesia. Fluoroscopic guidance using a contrast medium for epidural and subdural anesthesia ensures precise space identification and prevents serious anesthetic complications. Our findings suggest the potential to achieve stable anesthesia, particularly using subdural and combined epidural-subdural anesthesia.

Assessing pain in paralyzed critically ill patients receiving neuromuscular blocking agents: A monocenter prospective cohort

IntroductionGiven the absence of established recommendations for pain assessment in pharmacologically paralyzed Intensive-Care-Units (ICU) patients under Neuro-Muscular-Blocking Agents (NMBA), this study assessed the validity of various parameters for evaluating pain in this specific population. Patients and methodsFour electrophysiological parameters (instant-Analgesia-Nociception-Index (ANI), Bispectral index (BIS), Heart Rate (HR) and Mean Arterial Blood Pressure (ABP)) and one clinical parameter (Behavioural-Pain-Scale (BPS)) were recorded during tracheal-suctioning in all consecutive ICU patients who required a continuous infusion of cisatracurium, before and just after paralysis recovery measured by Train-of-Four ratio. The validity of the five pain-related parameters was assessed by comparing the values recorded during different situations (before/during/after the nociceptive procedure) (discriminant-validity, primary outcome), and the effect of paralysis was assessed by comparing values obtained during and after paralysis (reliability, secondary outcome). ResultsTwenty patients were analyzed. ANI, BIS, and HR significantly changed during the nociceptive procedure in both paralysis and recovery, while BPS changed only post-recovery. ANI and HR were unaffected by paralysis, unlike BIS and BPS (mixed-effect model). ANI exhibited the highest discriminant-validity, with values (min 0/max 100) decreasing from 71 [48–89] at rest to 41 [25–72] during tracheal suctioning in paralyzed patients, and from 71 [53–85] at rest to 40 [31–52] in non-paralyzed patients. ConclusionsANI proves the most discriminant parameter for pain detection in both paralyzed and non-paralyzed sedated ICU patients. Its significant and clinically relevant decrease during tracheal suctioning remains unaltered by NMBA use. Pending further studies on analgesia protocols based on ANI, it could be used to assess pain during nociceptive procedures in ICU patients receiving NMBA.

Comparison of Response First Technique with Reversal First Technique for Quality of Extubation in Patients Undergoing Transsphenoidal Pituitary Surgery: A Randomized Clinical Trial.

Early and smooth extubation following anesthesia is an important concern in patients undergoing transsphenoidal pituitary surgery to permit early neurological evaluation and prevent complications. The aim was to compare the RESPONSE FIRST and REVERSAL FIRST techniques for quality of extubation (QOE) in patients undergoing endoscopic transsphenoidal pituitary surgery. Fifty-six patients aged 18-60 years, with American Society of Anesthesiologists Physical Statuses I-II, and undergoing transsphenoidal surgery for pituitary tumors were randomized into either the RESPONSE FIRST group, in which neuromuscular reversal was given following the patient's response to oral commands, or the REVERSAL FIRST group, in which reversal of neuromuscular blockade (NMB) was given at the return of spontaneous respiration. QOE was the primary outcome. Hemodynamic response, jugular venous oxygen saturation (SjVO2), time to extubation, and awareness during emergence were assessed as secondary outcomes. The QOE in the RESPONSE FIRST group was significantly better than the REVERSAL FIRST group (mean (interquartile range (IQR)), 18 (17-19) vs 14 (12-14.75), P < 0.001). Heart rate (HR) and mean arterial pressure (MAP) were better in the RESPONSE FIRST group when compared to the REVERSAL FIRST group at the time of extubation, at 5 minutes, and 15 minutes following extubation (P < 0.05). SjVO2values were higher in the REVERSAL FIRST group as compared to the RESPONSE FIRST group during extubation and at 5 minutes after extubation (P < 0.01). There was no significant difference in the time to extubation between the groups (P = 0.73). The RESPONSE FIRST technique is associated with better QOE and preservation of systemic and cerebral hemodynamics during extubation in patients undergoing transsphenoidal pituitary surgery when compared to the REVERSAL FIRST technique.

Safety and efficacy of dexmedetomidine in combination with local anesthetics for orthopedic nerve blocks: a systematic review and meta-analysis.

Peripheral nerve block, a common technique for managing postoperative pain and providing intraoperative analgesia, often includes adjuncts like dexmedetomidine (DEX) to enhance the effectiveness of local anesthetics. DEX, known for its α2-adrenoceptor agonist properties, extends sensory blockade and improves postoperative analgesia while offering sedative benefits. The objective of this study is to rigorously assess the effectiveness and safety of perineural DEX injection in orthopedic nerve block procedures, focusing on orthopedic surgeries to minimize heterogeneity and provide clearer insights for clinical practice. This meta-analysis, registered on PROSPERO, involved a comprehensive literature search across multiple databases, focusing on RCTs comparing DEX with local anesthetics for peripheral nerve blocks in orthopedic surgery patients. The eligibility criteria included adult participants and various nerve block methods in orthopedic surgeries. Studies were rigorously appraised for methodological quality using Cochrane Handbook guidelines. GRADE profiler 3.6 was used for evidence grading. Among 1391 documents, 21 studies were included, focusing on DEX with local anesthetics in orthopedic nerve blocks. Findings showed significant improvements in analgesia duration, sensory and motor block duration, and reduced postoperative opioid consumption, with an increased risk of bradycardia. Quality assessments indicated moderate bias risk. DEX with local anesthetics significantly enhances nerve block effectiveness, extending analgesia and block durations while reducing opioid need. However, it requires careful monitoring due to increased bradycardia risk. These findings highlight the need for cautious use in clinical practice, considering both potential benefits and adverse effects.

Effect of Neurostimulator Usage on Block Success in Costoclavicular Block: A Randomized Controlled Trial.

The need of a neurostimulator for a successful nerve block was questioned in different block types after ultrasound had become standard. To determine the effect of neurostimulator use on block success in the costoclavicular block (CCB). Sixty patients undergoing upper limb surgery were enrolled in the study. Patients using ultrasound and injection pressure manometer were divided as Group USP, and those using ultrasound, injection pressure manometer, and neurostimulator were divided as Group USPN. After block was applied, sensory and motor block levels were measured on a numeric scale. The block was considered successful when the desired score was reached or general anesthesia was not required intraoperatively. The number of successful and unsuccessful blocks for each group was summed up. The successful block rate was compared as the primary objective. Block application time, time to readiness for surgery, the number of needle passes, diaphragm paralysis rate, and complication rate were compared as secondary goals. Block success rate was 90% (27/30) in Group USP and 96.7% (29/30) in Group USPN. There was no statistical difference in terms of block success rate. Block application time was significantly shorter in Group USP (207.2 ± 32.7 s) when compared to Group USPN (280.9 ± 70.1 s). Other secondary outcomes were similar. Neurostimulator use did not affect block success in the CCB. Neurostimulator utilization prolonged block application time explicitly and did not change the complication rate. Ultrasound and injection pressure manometer are sufficient for a safe and successful CCB.

Effects of avoidance versus use of neuromuscular blocking agents for facilitation of tracheal intubation in children and infants: a protocol for a systematic review, meta-analysis and trial sequential analysis.

The European Society of Anesthesiology and Intensive Care recommends the use of neuromuscular blocking agents (NMBA) in adults, to facilitate tracheal intubation and reduce its associated complications. Children who undergo tracheal intubation may suffer some of the same complications, however, no consensus exists regarding the use of NMBA for tracheal intubation in the pediatric population. We will explore the existing evidence assessing the effects of avoidance versus the use of NMBA for the facilitation of tracheal intubation in children and infants. This protocol follows the preferred reporting items for systematic reviews and meta-analyses protocols recommendations. We will include all randomized controlled clinical trials assessing the effects of avoidance versus the use of NMBA for facilitation of tracheal intubation (oral or nasal) using direct laryngoscopy or video laryngoscopy in pediatric participants (<18 years). Our primary outcome is incidence of difficult tracheal intubation. Secondary outcomes include incidence of serious adverse events, failed intubation, events of upper airway discomfort or injury, and difficult laryngoscopy. We will conduct a thorough database search to identify relevant trials, including CENTRAL, MEDLINE, EMBASE, BIOSIS, Web of Science, CINAHL, and trial registries. Two review authors will independently handle the screening of literature and data extraction. Each trial will be evaluated for major sources of bias with the "classic risk of bias tool" used in the Cochrane Collaboration tool from 2011. We will use Review manager (RevMan) or R with the meta package to perform the meta-analysis. We will perform a trial sequential analysis on the meta-analysis of our primary outcome, providing an estimate of statistical reliability. Two review authors will independently assess the quality of the body of evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. We will use GRADEpro software to conduct the GRADE assessments and to create "Summary of the findings" tables.

Using implementation science to decrease variation and high opioid administration in a surgical ICU.

High doses and prolonged duration of opioids are associated with tolerance, dependence, and increased mortality. Unfortunately, despite recent efforts to curb outpatient opioid prescribing because of the ongoing epidemic, utilization remains high in the intensive care setting, with intubated patients commonly receiving infusions with a potency much higher than doses required to achieve pain control. We attempted to use implementation science techniques to monitor and reduce excessive opioid prescribing in ventilated patients in our Surgical ICU. We conducted a prospective study investigating opioid administration in a closed SICU at an academic medical center over 18 months. Commonly accepted conversions were used to aggregate daily patient opioid use. Patients with a history of chronic opioid use and those being treated with an ICP monitor/drain, neuromuscular blocker, or ECMO were excluded. If the patient spent a portion of a day on a ventilator, that day's total was included in the "vent group." MMEs per patient were collected for each patient and assigned to the on-call intensivist. Intensivists were blinded to the data for the first seven months. They were then provided with academic detailing followed by audit & feedback over the subsequent 11 months, demonstrating how opioid utilization during their time in the SICU compared to the unit average and a blinded list of the other attendings. Student's T-tests were performed to compare opioid utilization before and after initiation of academic detailing and audit & feedback. Opioid utilization in patients on a ventilator decreased by 20.1% during the feedback period, including less variation among all intensivists and a 30.9% reduction by the highest prescribers. Implementation science approaches can effectively reduce variation in opioid prescribing, especially for high outliers in a SICU. These interventions may reduce the risks associated with prolonged use of high-dose opioids. Prospective pre-post-intervention, Level II.

Comparative characteristics of the effectiveness of spinal anesthesia based on bupivacaine in combination with different intrathecal doses of dexmedetomidine

Background. To increase the quality of a block, corresponding adjuvants are used intrathecally. However, currently, the interrelation between different doses of intrathecal dexmedetomidine as an adjuvant, differential analgesia, and the effectiveness of a spinal block is not adequately elucidated. The purpose: to conduct a comparative analysis on the effectiveness of motor (MB) and sensory block (SB), as well as to evaluate the clinical efficiency of analgesia during spinal anesthesia based on bupivacaine in combination with various intrathecal doses of dexmedetomidine. Materials and methods. The study included 150 patients with a mean age of 41.3 ± 8.2 years who underwent biportal endoscopic discectomy. Participants were divided into the following groups: group 1 (n = 30) — intrathecal administration of 2.5 ml bupivacaine combined with intrathecal administration of 2.5 µg dexmedetomidine; group 2 (n = 30) — intrathecal use of 2.5 ml bupivacaine with intrathecal administration of 5 µg dexmedetomidine; group 3 (n = 30) — intrathecal administration of 2.5 ml bupivacaine combined with intrathecal administration of 10 µg dexmedetomidine. In the groups, the sensory and motor status of patients and the level of analgesia were assessed. Results. The time of a SB onset was 22.78 ± 2.04 % higher in group 1 than in group 2 and 37.42 ± 2.75 % higher compared to group 3. The time of a MB onset in group 1 was 9.16 ± 1.32 % higher than in group 2 and 20.17 ± 2.36 % higher compared to group 3. In group 1, the time of a two-segment sensory regression was 21.38 ± 2.18 % lower than in group 2 and 36.40 ± 2.81 % lower than in group 3. The duration of a MB in group 3 was 18.23 ± 2.21 % higher compared to group 2 and 42.39 ± 3.05 % higher than in group 1. In group 3, the indicators of differential analgesia were 110.74 ± 4.53 % higher compared to group 2 and 202.39 ± 5.72 % higher than in group 1. Conclusions. Increasing the intrathecal dose of dexmedetomidine resulted in a reduction in the time of a sensory block onset, while the duration of a motor block increased. The indicators of analgesia duration also directly proportionally increased with the escalation of dexmedetomidine dosage.

Use of sugammadex in prevention of post-operative urinary retention in minimally invasive hernia surgery.

Post-operative urinary retention (POUR) is a known complication of hernia surgery. Minimally invasive inguinal hernia repair (IHR) is typically done under general anesthesia with neuromuscular blockade (NMB), which is commonly reversed with an anticholinesterase inhibitor paired with an anticholinergic agent. Sugammadex is a unique NMB reversal agent that does not have to be paired with an anticholinergic. We sought to explore the role of sugammadex in reducing the rate of POUR following these procedures. Data were collected retrospectively at a single institution between February 2016 and October 2019. We identified and studied patients who underwent minimally invasive IHR and received either sugammadex or neostigmine/glycopyrrolate for NMB reversal. The primary endpoint was POUR requiring bladder catheterization. Secondary endpoints included post-operative and 30-day readmissions. 274 patients were included in this study (143 received neostigmine and glycopyrrolate, 131 sugammadex). The sugammadex patients were on average 5years older than the neostigmine/ glycopyrrolate patients (63.2 vs 58.2, p = 0.003), and received less median intravenous fluids (IVF) (900ml vs 1000ml; p = 0.015). There was a significant difference in the rate of POUR between the sugammadex and neostigmine/glycopyrrolate patients (0.0% vs 8.4%, p ≤ 0.001). The difference remained significant after controlling for age and IVF. The odds of POUR for those who received neostigmine/glycopyrrolate were 25 × higher than the odds of those who received sugammadex. The results of this study reflect the protective role of sugammadex against POUR in minimally invasive IHR cases.

Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta-analytic and meta-regression approach.

Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta-analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients. We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results. We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance. The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.

Effective bolus dose of remimazolam for i-gel® insertion in nonparalyzed patients: a dose-finding study

PurposeRemimazolam is a recently developed ultra-short-acting benzodiazepine used for anesthesia induction and maintenance. Nevertheless, the effective bolus dose of remimazolam for i-gel® (Intersurgical Ltd., Wokingham, Berkshire, UK) insertion without the use of neuromuscular blocking agents (NMBAs) has not been well established.MethodsThis study included 25 adult patients scheduled for surgery under general anesthesia who were eligible for i-gel use. Anesthesia was induced with predetermined bolus doses of remimazolam, starting at 0.3 mg·kg−1 for the first patient, without the use of NMBAs. All patients concurrently received remifentanil using target-controlled infusion (TCI) at a fixed effect-site concentration (Ce) of 3.0 ng·mL−1. Insertion of the i-gel was attempted 90 sec after remimazolam administration, and insertion conditions were assessed. Subsequent doses of remimazolam were decreased or increased by 0.05 mg·kg−1, depending on the success or failure of i-gel insertion.ResultsThe mean (standard deviation) 50% effective dose (ED50) of a remimazolam bolus for successful i-gel insertion as determined by the modified Dixon’s up-and-down method was 0.100 (0.027) mg·kg−1. The ED50 and ED95 estimated by isotonic regression were 0.111 (83% confidence interval [CI], 0.096 to 0.131) mg·kg−1 and 0.182 (95% CI, 0.144 to 0.195) mg·kg−1, respectively. None of the patients required treatment for hypotension or bradycardia during anesthesia induction.ConclusionBased on the ED95 of remimazolam bolus dose determined in our study, we recommend using 0.182 mg·kg−1 of remimazolam in combination with remifentanil TCI at a Ce of 3.0 ng·mL−1 for successful i-gel insertion without NMBAs in adult patients. This regimen seems effective with a low risk of hemodynamic instability during anesthesia induction.Study registrationClinicalTrials.gov (NCT05298228); first submitted 6 March 2022.

Obstructive Sleep Apnea and Risk of Postoperative Complications after Non-Cardiac Surgery.

Obstructive sleep apnea (OSA), a common sleep disorder, poses significant challenges in perioperative management due to its complexity and multifactorial nature. With a global prevalence of approximately 22.6%, OSA often remains undiagnosed, and increases the risk of cardiac and respiratory postoperative complications. Preoperative screening has become essential in many institutions to identify patients at increased risk, and experts recommend proceeding with surgery in the absence of severe symptoms, albeit with heightened postoperative monitoring. Anesthetic and sedative agents exacerbate upper airway collapsibility and depress central respiratory activity, complicating intraoperative management, especially with neuromuscular blockade use. Additionally, OSA patients are particularly prone to opioid-induced respiratory depression, given their increased sensitivity to opioids and heightened pain perception. Thus, regional anesthesia and multimodal analgesia are strongly advocated to reduce perioperative complication risks. Postoperative care for OSA patients necessitates vigilant monitoring and tailored management strategies, such as supplemental oxygen and Positive Airway Pressure therapy, to minimize cardiorespiratory complications. Health care institutions are increasingly focusing on enhanced monitoring and resource allocation for patient safety. However, the rising prevalence of OSA, heterogeneity in disease severity, and lack of evidence for the efficacy of costly perioperative measures pose challenges. The development of effective screening and monitoring algorithms, alongside reliable risk predictors, is crucial for identifying OSA patients needing extended postoperative care. This review emphasizes a multidimensional approach in managing OSA patients throughout the perioperative period, aiming to optimize patient outcomes and minimize adverse outcomes.