Neuromuscular Blockade Research Articles

Recovery and immune function after low pressure pneumoperitoneum during robot-assisted radical prostatectomy: a randomised controlled trial.

To compare the effectiveness of low intra-abdominal pressure (IAP) facilitated by deep neuromuscular block (NMB) to standard practice in improving the quality of recovery, preserving immune function, and enhancing parietal perfusion during robot-assisted radical prostatectomy (RARP). In this blinded, randomised controlled trial, 96 patients were randomised to the experimental group with low IAP (8 mmHg) facilitated by deep NMB (post-tetanic count 1-2) or the control group with standard IAP (14 mmHg) and moderate NMB (train-of-four 1-2). Recovery was measured using the 40-item Quality of Recovery questionnaire and 36-item Short-Form Health survey. Immune function was evaluated by plasma damage-associated molecular patterns, cytokines, and ex vivo lipopolysaccharide-stimulated cytokine production. Parietal peritoneum perfusion was measured by analysing the recordings of indocyanine-green injection. Quality of recovery was not superior in the experimental group (n = 46) compared to the control group (n = 50). All clinical outcomes, including pain scores, postoperative nausea and vomiting, and hospital stay were similar. There were no significant differences in postoperative plasma concentrations of damage-associated molecular patterns, cytokines, and ex vivo cytokine production capacity. The use of low IAP resulted in better parietal peritoneum perfusion. Despite better perfusion of the parietal peritoneum, low IAP facilitated by deep NMB did not improve the quality of recovery or preserve immune function compared to standard practice in patients undergoing RARP.

Acute procedural characteristics and safety of pulsed field cryoablation for persistent AF: multicenter results from the first in human PARALELL trial

Abstract Introduction Pulsed Field Cryoablation (PFCA) is dual-energy cardiac ablation modality consisting of short-duration ultra-low temperature cryoablation (ULTC) followed immediately by pulsed electric field ablation (PFA) delivered from the same catheter. It has been hypothesized that it may be beneficial to combine the efficiency of PFA with the contact and stability offered by ULTC. In patients with persistent atrial fibrillation, PFCA could be of particular benefit when creating extended lesion sets beyond pulmonary vein isolation such as posterior wall ablation. By focusing the electric field in high-impedance frozen tissue, PFCA may increase lesion depth and durability despite lower delivered current, while minimizing PFA-related microbubbles and skeletal muscle contraction. Purpose To report the acute outcomes of PFCA observed in the first-in-human PARALELL trial. Methods PFCA was performed using a novel stylet-driven catheter connected to the dedicated ULTC and PFA energy sources. The protocol-defined lesion set included pulmonary vein isolation and posterior wall (PW) ablation, with additional left and right atrial targets per operator discretion. Circular and linear lesions of varying dimensions were created by in-vivo shaping of the flexible, 11 cm-long ablation element of the catheter using exchangeable stylets. The ULTC freeze of 30 second duration was followed immediately by bipolar, biphasic PFA pulse trains delivered sequentially between the pairs of sixteen 3-mm electrodes evenly spaced along the ablation element. Results At 5 European and Canadian sites, 26 patients (age 68±9 years, 88.5% male, median left atrial size 45 mm, IQR [43 mm-48 mm]) underwent PFCA with 22.6 ± 9.6 ablation lesions per patient. The lesion set included 11.9 ± 4.1 lesions to PVs, 7.4 ± 2.7 to the PW, and in 14 patients, 6.6 ± 9.0 lesions to other atrial targets (left atrial roof and floor, PV carinas, mitral and cavotricuspid isthmuses). Isolation was achieved in 94.2% (98 of 104) of PVs and 92.3% (24 of 26) of PWs. The average procedure time was 130.3 ± 40.9 minutes, with catheter dwell time of 78.8 ± 26.0 minutes. Procedure-related groin hematoma at discharge was the only serious adverse event by site adjudication. Intracardiac echocardiography (ICE) performed in 18 patients identified Grade I (FEW) microbubbles in 1.3% (5 of 398) of ablations. Similarly, only faint muscular contractions were observed in 2 of 26 patients, occurring during 1.2% (4 of 339) of lesions placed in 15 patients not receiving any paralytic agents. Conclusions This initial multi-center experience suggests that PFCA can be efficiently performed on multiple atrial targets using a single versatile catheter system, with high acute success and good early safety profile, including minimal occurrence of PFA-related microbubbles and skeletal muscle contractions. The evaluation of the chronic 12-month effectiveness vs ULTC benchmarks and PFA comparators is ongoing.

Oxygen metabolism after cardiac arrest: Patterns and associations with survival

AimWhether changes in oxygen metabolism, as measured by oxygen consumption (VO2), carbon dioxide production (VCO2) and the respiratory exchange ratio (RER), are associated with survival after cardiac arrest is poorly understood. In this prospective observational study, we investigated the association between VO2, VCO2, and RER in the initial 12 and 24 h after return of spontaneous circulation (ROSC) and survival to hospital discharge. MethodsAdults with ROSC after cardiac arrest, admitted to the intensive care unit, requiring mechanical ventilation and treated with targeted temperature management were included. VO2 and VCO2 were measured continuously for 24 h after ROSC, using a noninvasive anesthesia monitor. Area under the curve for VO2, VCO2 & RER was calculated using all available values over 12 and 24 h after ROSC. Using logistic regression, we evaluated the relationship between these metabolic variables and survival to hospital discharge. Analyses were adjusted for temperature, vasopressors, and neuromuscular blockade. ResultsSixty four patients were included. Mean age was 64 ± 16 years, and 59% were women. There was no significant association between the area under the curve of VO2 or VCO2 and survival. A higher RER in the initial 12 h was associated with better survival (aOR = 3.97, 95% CI [1.01,15.6], p = 0.048). Survival was lower in those with median RER < 0.7 in the initial 12 h compared with those with a median RER ≥ 0.7 (25% vs 67%, p = 0.011). ConclusionHigher RER in the initial 12 h was associated with survival after cardiac arrest. The etiology of unusually low RERs in this patient population remains unclear.

Effect of single-dose intravenous lignocaine versus fentanyl on neuromuscular recovery time after general anesthesia in elective pediatric surgery: A randomized controlled pilot study

Abstract Background and Aims: Intravenous (IV) lignocaine is often used to prevent the airway response to extubation, especially in children to prevent respiratory adverse events. It is known to prolong the duration of action of neuromuscular blocking drugs, but data in children are limited. The primary objective of this study was to compare neuromuscular recovery time with IV lignocaine versus fentanyl, in pediatric patients undergoing elective surgery under general anesthesia (GA). Secondary objectives included the comparison of clinical parameters and respiratory complications. Material and Methods: A randomized double-blind pilot study was conducted in 42 children aged 2–8 years undergoing GA with neuromuscular blockade, who received either 1.5 mg/kg of lignocaine or 0.5 mcg/kg of fentanyl IV, just prior to giving reversal at a train of four (TOF) count of 2–3. Time to achieve a TOF ratio of 0.9 and extubation and hemodynamic and respiratory parameters were noted. Incidences of coughing, bucking, laryngospasm, etc., were also noted. P value &lt; 0.05 was considered significant. Results: Demographic and operative data were similar. Time from reversal to TOF ratio of 0.9 was similar with both lignocaine (6.79 ± 3.03 mins) and fentanyl (6.79 ± 3.31 mins), P = 0.99. Time to extubation was also similar in both groups (8.14 ± 3.31 vs 9.19 ± 2.89 min), P = 0.28. Bucking incidence was higher with fentanyl (23.8%) vs lignocaine (9.5%), P = 0.41. Conclusions: Single-dose IV lignocaine administered before reversal did not prolong neuromuscular recovery time compared to fentanyl, with a similar (low) incidence of respiratory events in pediatric patients.

Onset time, duration of action, and intubating conditions after mivacurium in elderly and younger patients.

The neuromuscular blocking agent mivacurium can be used during anesthesia to facilitate tracheal intubation. Data on onset time, duration of action, and effect on intubating conditions in patients 80 years and older are however limited. We hypothesized that onset time and duration of action of mivacurium would be longer in elderly patients than in younger adults. This prospective observational study included 35 elderly (≥80 years) and 35 younger (18-40 years) patients. Induction of anesthesia comprised fentanyl 1-3 μg kg-1 and propofol 1.5-2.5 mg kg-1 and propofol and remifentanil for maintenance. Acceleromyography was used for monitoring neuromuscular blockade. The primary outcome was onset time defined as time from injection of mivacurium 0.2 mg kg-1 to a train-of-four (TOF) count of zero. Other outcomes included duration of action (time to TOF ratio ≥0.9), intubating conditions using the Fuchs-Buder scale and the intubating difficulty scale (IDS), and occurrence of hoarseness and sore throat postoperatively. No difference was found in onset time comparing elderly with younger patients; 219 s (SD 45) versus 203 s (SD 74) (difference: 16 s (95% CI: -45 to 14), p = .30). Duration of action was significantly longer in elderly patients compared with younger patients; 52 min (SD 17) versus 30 min (SD 8) (difference: 22 min [95% CI: 15 to 28], p < .001). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 31/35 (89%) versus 26/35 (74%) (p = .12) or IDS score (p = .13). A larger proportion of younger patients reported sore throat 24 h postoperatively; 34% versus 0%, p = .0002. No difference was found in hoarseness. No difference in onset time of mivacurium 0.2 mg kg-1 was found comparing elderly and younger patients. However, elderly patients had significantly longer duration of action. No difference was found in intubating conditions.

A comparative study between postoperative analgesia of suprainguinal fascia iliaca compartment block (SIFI) and lumbar erector spinae plane block (ESPB) in hip arthroplasty

ABSTRACT Background Suprainguinal fascia iliaca (SIFI) block offers efficient pain relief in total hip arthroplasty, although motor blockage is a common complication. Erector spinae plane block (ESPB) is a promising technique with less motor block; in research, we evaluate the efficacy of both blocks regarding analgesia and early mobilization. Patients and method Fifty-six patients who underwent total hip replacement following spinal anesthesia were divided to either treated with ultrasound guided suprainguinal fascia iliaca (SIFI) block or ultrasound guided ESPB at the end of surgery. The primary measure of interest was the pethidine consumed within a 24-hour period following the surgical procedure. Subordinate outcomes were: first rescue pethidine time, pain scores, and onset of ambulation. Post-operative vomiting, nausea, and other adverse events were recorded. Results Fifty-six patients were involved in the study. No significant statistical variances were found in pethidine consumed at 24 hours (p = 0.122) or pain scores and rescue analgesia timing (p = 0.075). ESPB provided an early onset of ambulation with a highly significant divergence (p < 0.001). Conclusion We concluded that ESPB has a similar analgesic, opioid sparing effect to SIFI block after total hip arthroplasty (THA) and provides early onset of ambulation.

Effects of Maitland mobilization technique on upper extremity function in stroke survivors with spasticity: An experimental study.

The recovery of upper limb function is of great significance for stroke patients to regain their self-care ability, yet it is still a difficult point in clinical practice of neurological rehabilitation. This study aimed to investigate the effect of Maitland joint mobilization technique on the recovery of upper extremity function in patients with spasticity after stroke. From August to December 2023, 71 patients with upper extremity flexor spasm after stroke were recruited and randomly divided into experimental group (n = 35) and control group (n = 36). The control group was given conventional rehabilitation treatment, while the experimental group was treated with Maitland mobilization technique treatment of upper extremity joints on the basis of the control group. The experiment lasted for 8 weeks. Participants of the 2 groups were observed for Fugl-Meyer motor assessment-upper extremity (FMA-UE), box and block test (BBT) and Brunnstrom stage, modified Ashworth scale (MAS), and functional independence measure (FIM) at pre- and post-8 weeks study. There was no significant difference in gender distribution, hemiplegic side, diagnosis, past history, age, duration, body mass index, and mini-mental state examination between the 2 groups (P > .05). After 8 weeks of intervention, both groups showed significant improvement in FMA-UE, Brunnstrom stage, BBT, FIM, and MAS of the shoulder (P < .05); however, there was no significant change in MAS of the elbow, wrist, and finger joints (P > .05). The posttreatment values showed a significant improvement in FMA-UE, BBT, and FIM in the experimental group compared to the control group. Comparing the changes in pretreatment and posttreatment, FMA-UE, BBT, and FIM in the experimental group were significantly improved compared with those in the control group (P < .05). Maitland joint mobilization can improve the motor function of upper extremity and the spasticity of shoulder joint complex in patients with stroke.

Perioperative Management in Neuromuscular Diseases: A Narrative Review.

Patients with neuromuscular diseases are particularly vulnerable in the perioperative period to the development of pulmonary and cardiac complications, or medication side effects. These risks could include hypoventilation, aspiration pneumonia, exacerbation of underlying cardiomyopathy, arrhythmias, adrenal insufficiency, prolonged neuromuscular blockade, issues related to thermoregulation, rhabdomyolysis, malignant hyperthermia, or prolonged mechanical ventilation. Interventions at each of the perioperative stages can be implemented to mitigate these risks. A careful pre-operative evaluation may help identify risk factors so that appropriate interventions are initiated, including cardiology consultation, pulmonary function tests, initiation of noninvasive ventilation, or implementation of preventive measures. Important intraoperative issues include positioning, airway and anesthetic management, and adequate ventilation. The postoperative period may require correction of electrolyte abnormalities, control of secretions with medications, manual or mechanical cough assistance, avoiding the risk of reintubation, judicious pain control, and appropriate medication management. The aim of this review is to increase awareness of the particular surgical challenges in this vulnerable population, and guide the clinician on the various evaluations and interventions that may result in a favorable surgical outcome.

No quadriceps muscle weakness following anterior quadratus lumborum block compared with placebo: a randomized, non-inferiority, blinded, volunteer trial

Background and aimsAnterior quadratus lumborum block is a truncal block, applied in close proximity to the lumbar plexus, potentially causing lower limb weakness. This trial aimed to evaluate whether a...

COMPARISON BETWEEN INTRATHECAL NEOSTIGMINE AND FENTANYL AS ADJUVANT TO HYPERBARIC BUPIVACAINE IN SPINAL ANAESTHESIA FOR POST-OPERATIVE PAIN RELIEF

Objective: Many adjuvants are used during lumbar spinal anaesthesia for lower limb and abdominal surgeries in day-to-day anaesthesia practice. The objectives of the study are to evaluate the time to onset of sensory and motor block, analgesic effect, and side effects of Neostigmine and Fentanyl as an adjuvant to hyperbaric Bupivacaine in spinal anaesthesia. Methods: 80 patients aged 18 to 60 y of either sex, American Society of Anaesthesiologist (ASA) Physical Status I and II, undergoing elective lower limb and abdominal surgeries under lumbar spinal anaesthesia, were randomly divided into two groups-Group N and Group F, with 40 patients each. Group N received 50 µg Neostigmine and Group F received 30 µg Fentanyl with 03 ml of 0.5% hyperbaric Bupivacaine intrathecally. Intraoperative vitals, onset of sensory and motor block, time to first rescue analgesia, and side effects were recorded. Results: There was no significant difference in the time to the onset of sensory block, peak sensory block (T6) and motor block in both groups (p-value&gt;0.05). However, the two-segment block regression was slower, and the time to rescue analgesia was delayed in Group N than in Group F (p-value&lt;0.0001). Except for nausea and vomiting, other side effects like hypotension, bradycardia, etc., were not significant and managed successfully. Conclusion: Both Neostigmine and Fentanyl are safe and effective adjuvant to hyperbaric Bupivacaine in spinal anaesthesia for post-operative analgesic effect. However, due to the higher incidence of nausea and vomiting, the use of Neostigmine as an adjuvant is limited.

0.25% bupivacaine–1% lidocaine vs 0.5% bupivacaine for ultrasound-guided infraclavicular brachial plexus block: a randomized controlled trial

IntroductionIn an effort to shorten onset time, a common practice is to add lidocaine to bupivacaine. In the setting of infraclavicular block, it is unclear what the block characteristics of...

THORACIC SEGMENTAL SPINAL ANAESTHESIA IN UPPER ABDOMINAL SURGERIES AND SIMPLE MASTECTOMY-A CASE SERIES

Objective: To observe safety and efficacy of Segmental thoracic spinal anesthesia (STSA) in upper abdominal and breast surgeries. Methods: 14 cases were selected, out of which 6 laparoscopic cholecystectomy (LC), 4 open cholecystectomy (OC), 3 emergency exploratory laparotomy and 1 simple mastectomy. Under full aseptic precaution, segmental thoracic spinal anesthesia was administered through midline approach in T8-9 space for upper abdominal surgeries and T5-6 space in a simple mastectomy. Using 25G Quincke spinal needle 1.5 ml [7.5 mg] of 0.5% Isobaric Levobupivacaine mixed with 0.4 ml (20µg) Fentanyl was given in abdominal surgeries and 1.2 ml [6 mg] of 0.5% Isobaric Levobupivacaine mixed with 0.4 ml (20µg) Fentanyl in simple mastectomy. Results: Age group of patients ranged from 25 to 65 y, Male: Female ratio of 4:10, Body Mass Index (BMI) range of 22 to 24.9 with physiological status of ASA I to ASA III. Hemodynamically, hypotension was observed in every patient after 5-10 min of STSA well managed with fluid and vasopressors with no bradycardia. Average width of sensory block was T3 to L1-2 in upper abdominal surgeries and T1 to T8 in a simple mastectomy. Motor block was Modified Bromage Scale (MBS) of 0 to 1 during and postoperatively. Regarding analgesia, Visual Analogue Scale (VAS) score was 0 intraoperatively and 0-1 postoperatively. Sedation score was 2 both intraoperatively and postoperatively with no significant complications and good patient and surgeon satisfaction. Conclusion: Segmental thoracic spinal anaesthesia is a safe and effective procedure with good patient and surgeon satisfaction.

The Effect of Phonomyography Prototype for Intraoperative Neuromuscular Monitoring: A Preliminary Study.

Quantitative neuromuscular monitoring, as extolled by clinical guidelines, is advocated to circumvent the complications associated with neuromuscular blockers (NMBs), such as residual neuromuscular block (rNMB). Nonetheless, the worldwide utilization of such methods remains undesirable. Phonomyography (PMG) boasts the advantages of convenience, stability, and multi-muscle recording which may be a promising monitoring method. The purpose of this preliminary study is conducting a feasibility analysis and an effectiveness evaluation of a PMG prototype under general anesthesia. A prospective observational preliminary study was conducted. Twenty-five adults who had undergone none-cardiac elective surgery were enrolled. The PMG prototype and TOF-Watch SX simultaneously recorded the pharmacodynamic properties of single bolus rocuronium at the ipsilateral adductor pollicis for each patient. For the primary outcome, the time duration to 0.9 TOF ratio of the two devices reached no statistical significance (p > 0.05). For secondary outcomes, the multi-temporal neuromuscular-monitoring measurements between the two devices also reached no statistical significance (p > 0.05). What is more, both the Spearman's and Pearson's correlation tests revealed a strong correlation across all monitoring periods between the PMG prototype and TOF-Watch SX. Additionally, Bland-Altman plots demonstrated a good agreement between the two devices. Thus, the PMG prototype was a feasible, secure, and effective neuromuscular-monitoring technique during general anesthesia and was interchangeable with TOF-Watch SX.

Comparison of Suprainguinal Fascia Iliaca Nerve Block and Epidural Analgesia in Patients Undergoing Periacetabular Osteotomy.

Adequate pain control and early mobilization are critical in the postoperative period after periacetabular osteotomy (PAO). Regional anesthesia can reduce postoperative pain, but certain techniques can increase the risk of postoperative motor block and delayed functional recovery. Continuous lumbar epidurals can provide excellent analgesia but also create challenges with early ambulation. Recently, suprainguinal fascia iliaca (SIFI) single-shot blocks have been shown to provide effective analgesia in PAO patients. The goal of this study was to compare opioid use, time to achieve inpatient physical therapy (PT) goals, and length of stay (LOS) between a cohort of patients receiving SIFI blocks and a cohort of patients receiving epidural analgesia (EA). This retrospective single-surgeon comparative cohort study included all patients who underwent a PAO between 2012 and 2022. Regional anesthetic technique (SIFI vs EA), length of hospital stay, intraoperative and postoperative opioid use, pain scores, and time to achievement of PT milestones before discharge were recorded. Patients were excluded if they had any preexisting neuromuscular syndrome or neurosensory deficit. All opioid use was converted to morphine-milligram equivalents using standard conversions. Two hundred four surgeries were done over the study period; 164 patients received EA, and 40 received a SIFI block. The average age of our cohort was 19.5 years (±6 yrs). The SIFI cohort had a significantly shorter mean LOS than the EA cohort (2.9 vs 4.1 days, P < 0.001). Patients in the SIFI cohort achieved all PT ambulation goals significantly sooner than the lumbar epidural group (P < 0.001), with lower total opioid use on each postoperative day. No notable differences were observed in sex, race, BMI, or pain scores at inpatient PT visits before discharge. After PAO surgery, the SIFI block is associated with shorter hospital LOS, reduced postoperative opioid use, and earlier mobilization when compared with those who were managed with an epidural.

Accuracy and Precision of Three Acceleromyographs, Three Electromyographs, and a Mechanomyograph Measuring the Train-of-four Ratio in the Absence of Neuromuscular Blocking Drugs.

The accuracy and precision of currently available, widely used acceleromyograph and electromyograph neuromuscular blockade monitors have not been well studied. In addition, the normalization of the train-of-four ratio from acceleromyography (train-of-four ratio [T4/T1] divided by the baseline train-of-four ratio) has not been validated in comparison to mechanomyography. Enrolled patients had surgery under general anesthesia with a supraglottic airway and without any neuromuscular blocking drugs. Three acceleromyograph monitors, three electromyograph monitors, and a mechanomyograph built in the authors' laboratory were tested. Most patients had an electromyograph and the mechanomyograph on one arm and a third monitor on the contralateral arm. Train-of-four ratios were collected every 12 to 20 s for the duration of the anesthetic. At least 1,000 train-of-four ratios were recorded for each device. Gauge repeatability and reproducibility analysis was performed. Twenty-eight patients were enrolled. In total, 9,498 train-of-four ratio measurements were collected. Since no neuromuscular blocking drugs were used, the expected train-of-four ratio was 1.0. All of the acceleromyograph monitors produced overshoot in the train-of-four ratio (estimated means, 1.10 to 1.13) and substantial variability (gauge SDs, 0.07 to 0.18). Normalization of the train-of-four ratio measured by acceleromyography improved the estimated mean for each device (0.97 to 1.0), but the variability was not improved (gauge SDs, 0.06 to 0.17). The electromyograph and the mechanomyograph monitors produced minimal overshoot (estimated means, 0.99 to 1.01) and substantially less variation (gauge SDs, 0.01 to 0.02). For electromyography and mechanomyography, 0.3% of all train-of-four ratios were outside of the range 0.9 to 1.1. For acceleromyography, 27 to 51% of normalized train-of-four ratios were outside the range of 0.9 to 1.1. Three currently available acceleromyograph monitors produced overshoot and substantial variability that could be clinically significant. Normalization corrected the overshoot in the average results but did not reduce the wide variability. Three electromyograph monitors measured the train-of-four ratio with minimal overshoot and variability, similar to a mechanomyograph.

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.