Search

Introduction: Non-depolarizing agents such as rocuronium and vecuronium are frequently used in the emergency department (ED) to facilitate intubation but may lead to delay in neurologic examination and intervention. Sugammadex is used for reversal of neuromuscular blockade by non-depolarizing agents but its role in the reversal of neuromuscular blockade for neurologic examination in the ED is poorly defined.Methods: This was a multicenter cohort study using retrospective chart review. We reviewed all ED encounters from June 21, 2016–February 9, 2024 of the electronic health record of Mass General Brigham, a large multistate health system, and abstracted all ED administrations of sugammadex to facilitate neurologic examination. We calculated descriptive statistics and assessed outcomes.Results: In 3,080,338 ED visits during the study period, 48 patients received sugammadex to facilitate neurologic examination. Of those patients, 23 (47.9%) underwent a procedure within 24 hours. Three (6.3%) had bradycardia, and one (2.1%) had hypotension following sugammadex administration. A total of 23 patients (47.9%) ultimately died during their admission, and 24 (50%) died within 30 days.Conclusion: Patients who received sugammadex in the ED to facilitate neurologic examination during the study period had rare associated adverse effects, high rates of procedures within 24 hours of administration, and significant in-hospital mortality. Prospective data is needed to assess the impact of sugammadex on decision-making.

Concerns regarding residual neuromuscular block (RNMB) have persisted since the introduction of neuromuscular blocking agents, with reported incidences in the 21st century up to 50%. Advances in neuromuscular transmission (NMT) monitoring and the introduction of sugammadex have addressed this issue, but the impact of these developments remains unclear. This prospective observational study evaluated RNMB in 500 surgical patients in a large Dutch teaching hospital with readily available quantitative NMT monitoring and reversal agents. The anaesthetic technique and intraoperative NMT monitoring were independently chosen by the attending anaesthesiologist. Acceleromyography was performed upon arrival in the PACU for patients who received nondepolarising neuromuscular blocking agents. RNMB was defined as a train-of-four ratio (TOFR) <0.9. A systematic review was conducted to analyse trends in RNMB in contemporary practice. Out of 500 patients, 11 (2.2%) had a TOFR <0.9. Intraoperative NMT monitoring was performed in 77.6% of patients, and sugammadex was administered to 38% of patients. No patient received neostigmine. The only difference was an automatically recorded TOFR ≥0.9 at the end of surgery in 61.1% in the non-RNMB group compared with 18.2% in the RNMB group (P =0.009). Our systematic review identified incidences ranging from 3.5% to 53.3% since 2000, with a decreasing trend in Europe and North America. The incidence of residual neuromuscular block in the PACU was 2.2%. This suggests significant improvement in the prevention of residual neuromuscular block and stresses the importance of rigorous neuromuscular transmission monitoring and adequate use of reversal agents. [ABSTRACT FROM AUTHOR]

Background: Neuromuscular blocking agents (NMBAs) are routinely used in anesthesia practice. An undetected, incomplete recovery of neuromuscular function at the end of surgery potentially exposes patients to clinical deterioration in the postoperative period. The aim of this study was to investigate the incidence of postoperative residual neuromuscular blockade (RNMB) in a cohort of patients receiving NMBAs. Methods: We enrolled 90 spontaneously breathing adult patients admitted to the recovery room (RR) after completion of surgeries having received at least 1 dose of NMBA. Anesthesia management, the dosage of NMBA used, and whether monitoring of neuromonitoring function was employed or if a reversal agent was administered were all at the discretion of the attending anesthesiologist, who was unaware that neuromuscular function was going to be monitored in the RR. The primary objective of this study was to determine the incidence of RNMB (defined as a train-of-four ratio ≤ 0.9). The secondary objectives were the number of postoperative adverse respiratory events and, for exploratory purposes, the estimation of potential risk factors through logistic regression analysis. Results: RNMB occurred in 5 (5%) patients who had received only one dose of NMBA at induction of anesthesia. Two patients with RNMB (40%) required O2 supplementation during monitoring in the RR, compared to 11 patients in the rest of the sample (13%). Additionally, 2 of these patients (2%) required O2 supplementation before hospital discharge due to O2 desaturation < 92%. None of the patients with RNMB had received a reversal of neuromuscular blockade at the end of surgery. The association between RNMB and potential risk factors, assessed through multivariable logistic regression did not yield significant results for any of the considered variables. Conclusions: RNMB can occur even when a single dose of NMBAs is administered. Despite decades of extensive literature on the risks of RNMB and recent guidelines, routine monitoring of neuromuscular function and pharmacologic reversal of NMBA is still substandard. Routine monitoring of neuromuscular function is strongly advocated to enhance the level of patient care. Trial registration: The study was registered at ClinicalTrials.gov (NCT06193213, date of registration: 05/01/2024). [ABSTRACT FROM AUTHOR]

Background: Proper anesthesia management is required to maintain immobilization and stable breathing of the patient to improve catheter contact and stability during catheter ablation for PVI. However, it remains unclear whether the depth of neuromuscular blockade affects the results of RFCA under general anesthesia. Methods: The patients were randomly assigned to either the moderate neuromuscular blockade group (Group M, train-of-four 1 to 2) or the deep neuromuscular blockade group (Group D, posttetanic count 1–2). The primary outcome was the 12-month AF recurrence rate using confirmed electrocardiographic diagnosis after the ablation procedure at two different neuromuscular blockade depths. Results: Total 94 patients (47 in each group) were included in the analysis. Recurrence of AF during the A 12-month follow-up was 12 (25%) in group D and 22 (46%) in group M. The AF recurrence rate was significantly higher in group M (p = 0.03). The relative risk (RR) for the risk of 12-month AF recurrence was 0.545 in group D. AF symptom recurrence was observed during the A 12-month follow-up in 12 (25%) and 26 (54%) patients in groups D and M, respectively. Conclusions: Compared to moderate neuromuscular blockade, deep neuromuscular blockade while performing RFCA under general anesthesia reduced 12-month AF recurrence rate. Deep neuromuscular blockade under general anesthesia is thought to increase the success rate by providing a stable surgical environment during the RFCA procedure. Trial registration: Clinical trials of Korea KCT 0003371 [ABSTRACT FROM AUTHOR]

Aiming toward a novel, noninvasive technique, with a real-time potential application in the monitoring of the complexation of steroidal neuromuscular blocker drugs Vecuronium (Vec) and Rocuronium (Roc) with sugammadex (SDX, medication for the reversal of neuromuscular blockade induced by Vec or Roc in general anesthesia), we developed proof-of-principle methodology based on surface-enhanced Raman spectroscopy (SERS). Silver nanoparticles prepared by the reduction of silver ions with hydroxylamine hydrochloride were used as SERS-active substrates, additionally aggregated with calcium nitrate as needed. The Vec and Roc SERS spectra were obtained within the biorelevant 5 × 10−7–1 × 10−4 M range, as well as the SERS of SDX, though the latter was observed only in the presence of the aggregating agent. SDX/drug complexes at a 1/1 molar ratio revealed significant spectral changes in the vibrational bands of the SDX glucose rings and the drug steroid rings, implying that the insertion of Vec and Roc molecules into the SDX cavity was not only driven by attractive electrostatic interactions between the positively charged cyclic unit of the drug and the negative carboxylate groups of cyclodextrin but also supported by hydrophobic interactions between the host cyclodextrin and the guest drug molecule. The observed changes in SERS signals are applicable in biorelevant conditions and support further studies of SDX/drug complexes in vivo. [ABSTRACT FROM AUTHOR]

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 < 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. [ABSTRACT FROM AUTHOR]

Background and Objectives: Neuromuscular blocking agents are essential to ensure optimal surgical conditions during general anesthesia. Sugammadex, a selective binding agent, is widely used to reverse neuromuscular blockade. While weight-based dosing (2 mg/kg for moderate blockade) is recommended, many clinicians administer a fixed dose of 200 mg in clinical practice, potentially leading to overdosing. This study aimed to compare the efficacy and recovery profiles of weight-based and fixed-dose sugammadex in patients undergoing general anesthesia. Materials and Methods: In this randomized controlled trial, 20 patients were divided into two groups: the recommended dose group (R group, 2 mg/kg) and the fixed dose group (F group, 200 mg). Primary outcomes included time to achieve a normalized train-of-four (TOF) ratio of 0.9. Secondary outcomes included recovery time, time to spontaneous respiration, response to verbal commands and extubation, and adverse events. Results: The median time to achieve a normalized TOF ratio of 0.9 was 2.3 min in the R group and 2.0 min in the F group (p = 0.529). Secondary outcomes, including recovery time and time to extubation showed no significant differences. Adverse events were minimal and comparable between groups. Conclusions: The fixed-dose sugammadex (200 mg) demonstrated similar efficacy and safety to weight-based dosing (2 mg/kg) in reversing moderate neuromuscular blockade. These findings do not allow abandoning the recommendation of adjustment for body weight, particularly in patients with low body weight or comorbidities. [ABSTRACT FROM AUTHOR]

Neuromuscular monitoring during general anaesthesia is a crucial practice for the proper management of muscle blocks, allowing the dosage of muscle relaxants to be optimized and adverse effects to be minimized. The use of neuromuscular blocking agents is common in surgery, especially to facilitate intubation and muscle relaxation. However, inappropriate or excessive use of these agents can result in post-operative complications, such as residual muscle weakness, breathing difficulties and delayed recovery. Neuromuscular monitoring has proven to be an essential tool for mitigating these risks. The aim of this study is to evaluate the benefits of neuromuscular monitoring during general anesthesia, with a focus on reducing postoperative complications such as residual muscle weakness, respiratory difficulty and prolonged recovery time. The aim is also to compare the results of patients who receive real-time monitoring with those who do not. This is a qualitative literature review whose aim is to explore the implications of neuromuscular monitoring in anesthetic practices and its effects on postoperative recovery, opioid consumption and residual neuromuscular blockade. To this end, the PubMed, Scopus and Web of Science databases will be used. The review will be refined using health descriptors such as “Neuromuscular Monitoring,” “Residual Paralysis,” “Opioid Consumption,” with a time frame from 1998 to 2020, covering both review articles and clinical studies and randomized trials. Neuromuscular monitoring has shown clear benefits in reducing residual muscle weakness and improving postoperative respiratory function. Studies indicate that patients who use real-time monitoring during general anesthesia have shorter recovery times, lower rates of respiratory complications and less need for assisted ventilation. In addition, monitoring allows for more precise dosing of muscle relaxants, avoiding overuse and the occurrence of adverse effects. When applied correctly, monitoring also contributes to reducing the duration of anesthesia and improves the patient’s post-operative experience. Neuromuscular monitoring during general anesthesia is essential for reducing postoperative complications, especially residual muscle weakness and respiratory difficulty. Its effective use contributes to a faster and safer recovery for patients, allowing healthcare professionals to adjust the dosage of muscle blockers more precisely. The widespread implementation of this practice in surgical centers is recommended to optimize anesthetic management and improve postoperative outcomes. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) presents significant challenges in critical care, primarily due to its inflammatory nature, which leads to impaired gas exchange and respiratory mechanics. While mechanical ventilation (MV) is essential for patient support, the transition from controlled to assisted ventilation is complex and may be associated with intensive care unit-acquired weakness, ventilator-induced diaphragmatic dysfunction and patient self-inflicted lung injury. This paper explores the multifaceted challenges encountered during this transition, with a focus on respiratory effort, sedation management, and monitoring techniques, and investigates innovative approaches to enhance patient outcomes. The key strategies include optimizing sedation protocols, employing advanced monitoring methods like esophageal pressure measurements, and implementing partial neuromuscular blockade to prevent excessive respiratory effort. We also emphasize the importance of personalized treatment plans and the integration of artificial intelligence to facilitate timely transitions. By highlighting early rehabilitation techniques, continuously assessing the respiratory drive, and fostering collaboration among multidisciplinary teams, clinicians can improve the transition from controlled to assisted MV, ultimately enhancing recovery and long-term respiratory health in patients with ARDS. [ABSTRACT FROM AUTHOR]

Background: Establishing a pneumoperitoneum for laparoscopy is common surgical practice, with the goal to create an optimal surgical workspace within the abdominal cavity while minimizing insufflation pressure. Individualized strategies, based on neuromuscular blockade (NMB), pre-stretching routines, and personalized intra-abdominal pressure (IAP) to enhance surgical conditions are strategies to improve surgical workspace. However, the specific impact of each factor remains uncertain. This study explores the effects and side-effects of modifying intra-abdominal volume (IAV) through moderate and complete NMB in a porcine laparoscopy model. Methods: Thirty female Landrace pigs were randomly assigned to groups with complete NMB, regular NMB and a control group. Varying IAP levels were applied, and IAV was measured using CT scans. The study evaluated the maximum attainable IAV (Vmax), the pressure at which the cavity opens (p0), and the ease of expansion (λexp). Cardiorespiratory parameters, including peak inspiratory pressure (PIP), mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO), were continuously recorded to evaluate side-effects. Results: There were no significant weight differences between NMB groups (median 21.1 kg). Observed volumes ranged from 0 to 4.7 L, with a mean Vmax of 3.82 L, mean p0 of 1.23 mmHg, and mean λexp of 0.13 hPa−1. NMB depth did not significantly affect these parameters. HR was significantly increased in the complete NMB group, while PIP, MAP, and CO remained unaffected. Repeated insufflation positively impacted Vmax; ease of opening; and expanding the cavity. Conclusion: In this porcine model, the depth of NMB does not alter abdominal mechanics or increase the surgical workspace. Cardiorespiratory changes are more related to insufflation pressure and frequency rather than NMB depth. Future studies should compensate for the positive effect of repeated insufflation on abdominal mechanics and surgical conditions. [ABSTRACT FROM AUTHOR]

Purpose : This study aimed to assess the effectiveness of monocular and bilateral injections of Dexamethasone-21-acetate (Dex-21-Ac) into the murine fornix twice a week as a glucocorticoid-induced ocular hypertension model and investigated potential systemic side effects. Methods : Dex-21-Ac was administered twice weekly in three groups: bilateral injections, monocular injections, and a control group receiving the vehicle solution bilateral. After 21 days, enucleated eyes were examined using immunocytochemistry (ICC), and organ histology was performed. Results : All groups receiving Dex-21-Ac injections had a significant increase in intraocular pressure (IOP). Monocular injections also resulted in a significant increase in IOP in the fellow eye. The Dex-21-Ac-treated groups showed a bilateral increase in IOP of approximately 8 mmHg, accompanied by elevated expression of alpha smooth muscle actin and fibronectin in the anterior chamber angle. There were no significant changes in weight progression. Hepatic steatosis was observed in all Dex-21-Ac-treated animals, and some suffered from residual neuromuscular blockade under fentanyl anesthesia. Conclusion : Bilateral injections of Dex-21-Ac twice a week lead to a significant increase in daytime IOP and fibrotic changes in the trabecular meshwork. Unilateral application has a significant impact on the fellow eye. Local dexamethasone leads to notable systemic effects independent of changes in animal weight. Considering liver damage and associated influence on metabolization, hepatically eliminated injection anesthetics may lead to overdosing and are not recommended. They should be replaced by inhalation anesthesia. [ABSTRACT FROM AUTHOR]

In the post-anesthesia care unit, there is a high occurrence of residual neuromuscular blockade, which puts patients at risk of negative consequences such as hypoxia. Assessment based on the train-of-four ratio (TOFR) has been used to avoid residual neuromuscular blockade when the TOFR is greater than 0.9, measured at the adductor pollicis muscle (APM). The most commonly used quantitative neuromuscular monitoring (QNM) modalities include acceleromyography (AMG) and electromyography (EMG). However, the poor user-friendliness of current QNM methods hinders their widespread adoption. To overcome this, we developed a new monitoring method using ultra-fast ultrasound imaging to generate a two-dimensional map of muscle transient motion, i.e., sonomechanomyography (SMMG). SMMG of the APM and AMG of the thumb were used to get the TOFR of 20 normal adults. The results showed no significant difference between the left and right hands for both AMG and SMMG TOFR, with p-values larger than 0.05. In addition, the mean accuracy of SMMG TOFR (0.6% relative error) was higher than AMG (1.4% relative error). Moreover, the Bland–Altman plot showed that all the difference values were within the limits of agreement and the mean bias was 0.02, indicating that the two methods had a very good agreement. In particular, using SMMG did not require additional calibration before testing. Overall, the results demonstrated that the method has the potential as a new QNM approach for further clinical studies to benefit patients in need. To demonstrate its clinical potential, further studies are required to evaluate this method in patients during and post-anesthesia. [ABSTRACT FROM AUTHOR]

Background: To investigate feasibility of utilizing enhanced neuromuscular blocking agents with selective recovery protocol during thyroid surgery with intraoperative neuromonitoring (IONM). Methods: Two‐hundred and ninety patients were randomized into two groups: group A 0.3 mg/kg rocuronium and group B 0.6 mg/kg. Sugammadex 2 mg/kg was injected if needed followed initial vagal stimulation (V0). Electromyography signals from vagus and recurrent laryngeal nerves before and after resection were recorded as V1, V2, R1, and R2. Results: In group B, 30 patients (20.7%) had V0 signals <100 μV, compared to 9 (6.2%) in group A. After sugammadex administration, 144 patients (99.3%) in both groups achieved positive V1 signals. Group B demonstrated a shorter surgical time from rocuronium injection to V2 stimulation compared to group A, accompanied by a significantly lower incidence of intraoperative body movement (0 vs. 16 patients). Conclusions: 0.6 mg/kg rocuronium with selective use 2 mg/kg sugammadex for IONM in thyroid surgery can meet both anesthesia and surgery demands. [ABSTRACT FROM AUTHOR]

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four PICO questions (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

Background: Remimazolam is a newly developed benzodiazepine. Early recovery from anesthesia because of its ultra‐short acting effect and less hemodynamic side effects has been reported as the specific advantages of remimazolam. Therefore, the maintenance of anesthesia with propofol may be sometimes switched to remimazolam anesthesia maintenance during surgery because of the risk of delayed awakening and unstable hemodynamics. In the present study, to determine the influence of switching anesthesia from propofol to remimazolam on the baseline TOF ratio, the TOF ratio under remimazolam anesthesia maintenance without any neuromuscular blocking agents was compared to that calibrated after induction of general anesthesia with propofol. Methods: Twelve patients scheduled for elective surgery under general anesthesia in the supine position were investigated. After induction of general anesthesia with remifentanil and propofol, a supraglottic airway was inserted without neuromuscular blockade, and TOF stimulation every 15 s at the adductor pollicis muscle was started with acceleromyography. After stable baseline responses to TOF stimulation being obtained for at least 10 min under propofol anesthesia, the anesthetic agent was switched to remimazolam and TOF stimulation every 15 s was maintained for a further 60 min without any interruption. In each case, the averaged TOF ratio during the last 10 min of TOF monitoring was compared to that during the 10 min immediately before the beginning of remimazolam infusion using a paired t‐test. Results: There were no significant differences in the TOF ratios before and after switching anesthesia to remimazolam (1.07 ± 0.03 vs. 1.07 ± 0.03, p = 0.325). Conclusion: Switching anesthesia from propofol to remimazolam does not affect the baseline TOF ratio. [ABSTRACT FROM AUTHOR]

Summary Introduction Methods Results Discussion Remimazolam is an ultra‐short‐acting benzodiazepine sedative drug. This study aimed to compare the efficacy and safety of remimazolam with propofol for induction and maintenance of general anaesthesia in children undergoing elective surgery.Children (aged 3–6 y, ASA physical status 1 or 2, BMI 14–25 kg.m‐2) undergoing elective surgery under general anaesthesia with tracheal intubation were eligible for inclusion. Children were allocated randomly using a web‐based system to receive either remimazolam or propofol in a 3:1 ratio. After receiving fentanyl 3 μg.kg‐1, children received their allocated drug for both induction and maintenance of general anaesthesia. Induction doses were remimazolam 0.3 mg.kg‐1 or propofol 2.5 mg.kg‐1, with a second dose given should they not achieve loss of consciousness. After neuromuscular blockade and tracheal intubation, maintenance anaesthesia was achieved with an infusion either remimazolam 1–3 mg.kg‐1.h‐1 or propofol 4–12 mg.kg‐1.h‐1, alongside a remifentanil infusion (0.1–0.5 μg.kg‐1.min‐1) titrated to surgical stimulus and haemodynamic parameters. Primary outcomes were the incidence of successful induction and maintenance of anaesthesia. Secondary outcomes included: time to loss of consciousness, awakening and tracheal extubation; incidence of emergence delirium and moderate or severe pain in post‐anaesthesia care unit; incidence of negative behaviour change after surgery at postoperative day 3; and incidence of adverse events.A total of 187 children were analysed (140 allocated to remimazolam and 47 to propofol). All children achieved successful induction of anaesthesia. Successful maintenance of anaesthesia was achieved in 139 (99%) children who received remimazolam compared with 46 (98%) who received propofol (rate difference 1.4%, 95%CI ‐2.9–5.8%, p = 0.441). Adverse events occurred in 27 (19%) children who received remimazolam and 23 (49%) who received propofol.Remimazolam was well tolerated for the induction and maintenance of general anaesthesia in pre‐school‐age children and was non‐inferior to propofol. [ABSTRACT FROM AUTHOR]

Envenomations by snakes represent a neglected health problem in tropical and subtropical countries. In South America, Lachesis muta occasionally causes severe human envenomation, with treatment being conditioned to an unspecific antivenom. In this work, we examined the neutralizing ability of Coutarea hexandra stem bark hydroalcoholic extract (Ch‐E), including the commercial phytochemicals coumarin and quinine, on the neuromuscular blockade induced by L. m. muta venom in mouse phrenic nerve‐diaphragm preparation. Biological assays were performed following conventional myographic technique ex vivo. Ch‐E was phytochemically characterized to detect the presence of coumarin and quinine using analytical methods. Ch‐E and commercial phytochemicals were tested separately or combined under pre‐ and post‐venom incubation protocols. Ch‐E attenuated the venom‐induced neuromuscular blockade only under the pre‐venom incubation protocol. Quinine was not detected in Ch‐E. Commercial coumarin and quinine exhibited a concentration‐dependent counteracting effect on the venom‐induced neuromuscular blockade. The pre‐venom incubation protocol showed to be efficient in attenuating the L. m. muta venom–induced neuromuscular blockade, most likely due to the presence of coumarin derivatives and unknown alkaloids in this extract. [ABSTRACT FROM AUTHOR]

Within biomedical engineering, there has been significant collaboration among clinicians, control engineers, and researchers to tailor treatments to individual patients. Anesthesia is integral to numerous medical procedures, necessitating precise management of hypnosis, analgesia, neuromuscular blockade, and hemodynamic variables. Recent attention has focused on computer-controlled anesthesia and hemodynamic stabilization. This research proposes the integration of a decentralized control strategy for the induction phase with a decoupled control approach for the maintenance phase, aimed at mitigating interactions within the multivariable human system. The proposed strategy is based on fractional-order controllers. The solution is validated using an open-source patient simulator featuring data from 24 virtual patients, demonstrating the efficiency of the proposed approach with respect to decentralized control. [ABSTRACT FROM AUTHOR]

Background: High‐flow nasal oxygenation is reported to prolong duration of apnea while maintaining adequate oxygen saturation with the mouth closed. Also, buccal oxygenation is known to have similar effects in obese adults. We compared the effect of these two methods on prolongation of acceptable apnea time in pediatric patients with their mouth open. Methods: Thirty‐eight patients, aged 0–10 years were randomly allocated to either the high‐flow nasal oxygenation group (n = 17) or the buccal oxygenation group (n = 21). After induction of anesthesia including neuromuscular blockade, manual ventilation was initiated until the expiratory oxygen concentration reached 90%. Subsequently, ventilation was paused, and the patient's head was extended, and mouth was opened. The HFNO group received 2 L·min−1·kg−1 of oxygen, and the BO group received 0.5 L·min−1·kg−1 of oxygen. We set a target apnea time according to previous literature. When the apnea time reached the target, we defined the case as "success" in prolongation of safe apnea time and resumed ventilation. When the pulse oximetry decreased to 92% before the target apnea time, it was recorded as "failure" and rescue ventilation was given. Results: The success rate of safe apnea prolongation was 100% in the high‐flow nasal oxygenation group compared to 76% in the buccal oxygenation group (p =.04). Oxygen reserve index, end‐tidal or transcutaneous carbon dioxide partial pressure, and pulse oximetry did not differ between groups. Conclusion: High‐flow nasal oxygenation is effective in maintaining appropriate arterial oxygen saturation during apnea even in children with their mouth open and is superior to buccal oxygenation. Buccal oxygenation may be a good alternative when high‐flow nasal oxygenation is not available. [ABSTRACT FROM AUTHOR]

Background and Aims: The conventional CE clamp technique may not effectively provide bag-mask ventilation (BMV) in the hands of inexperienced providers. Hence, we compared the efficacy of two-handed CE versus a hybrid technique. Methods: One hundred thirty-two American Society of Anesthesiologists (ASA) I–II adult patients were randomised into groups A and B. After induction of anaesthesia and neuromuscular blockade, Group A received BMV by using the double-handed CE technique. Group B received BMV by using dominant-hand CE and non-dominant-hand thenar eminence (TE) hybrid technique. The primary outcome was two minute (24 breaths) mean exhaled tidal volume. Secondary outcomes were the number of failed breaths and the comfortability level of airway providers using a 5-point Likert scale. Data were analysed using the Mann-Whitney U test, Student t -test, Chi-square test, and Fisher's exact test. Results: The mean exhaled tidal volume and end-tidal carbon dioxide observed in Group A were significantly lower than in Group B (P = 0.001 and P = 0.001, respectively). The number of failed breaths and comfort level of both techniques were comparable in both groups (P = 0.310. and P = 0.584, respectively). Conclusion: The dominant-hand CE and non-dominant-hand TE techniques provide higher exhaled tidal volumes with comparable provider comfortability and may be considered an alternate BMV technique. [ABSTRACT FROM AUTHOR]

Background and Objectives: Metabolic and bariatric surgery (MBS) is practiced worldwide. Sugammadex was proven to have multiple benefits in reversing neuromuscular blockade (NMB) for patients with obesity undergoing MBS, but its effects on complications of various systems are not clear and concrete. Materials and Methods: This systematic review and meta-analysis was conducted as per the PRISMA guidelines and registered on the PROSPERO database (CRD42023491171). A systematic search was conducted in multiple databases for studies comparing sugammadex with neostigmine in MBS. Continuous data are reported as mean differences (MDs) and 95% confidence intervals (CIs). Dichotomous data are reported as relative risks (RRs) and 95% CIs. A two-sided p < 0.05 was considered statistically significant. Trial sequential analysis (TSA) was performed to evaluate the reliability of the conclusions. Results: Nine studies with 633 patients met the inclusion criteria. Compared with those from the neostigmine group, patients from the sugammadex group were characterized by a significantly shorter recovery time from the administration of the study drug to a train-of-four (TOF) ratio of ≥90% (MD [95% CI]: −15.40 [−26.64; −4.15]; I2 = 96.6%; p = 0.0073; n = 380; random effects model), a lower risk of postoperative residual curarization (PORC) (RR [95% CI]: 0.18 [0.09; 0.38]; p < 0.0001; I2 = 27.9%; n = 344; common effect model), postoperative nausea and vomiting (PONV) (RR [95% CI]: 0.67 [0.48; 0.93]; p = 0.0164; I2 = 0%; n = 335; common effect model), and cardiovascular complications (RR [95% CI]: 0.48 [0.26; 0.88]; p = 0.0186; I2 = 14.7%; n = 178; common effect model). TSA confirmed the conclusions regarding the recovery time and PORC risk. Conclusions: In conclusion, our systemic review and meta-analysis with TSA revealed that sugammadex provided a faster and more reliable choice to reverse NMB in patients with obesity undergoing MBS, with a lower risk of PORC. Sugammadex reduced the risk of cardiovascular complications and postoperative nausea and vomiting. However, the conclusions were not confirmed, and, so, further studies may be necessary. [ABSTRACT FROM AUTHOR]

Neuromuscular blocking agents are used commonly to induce skeletal muscle relaxation during surgery. While muscle relaxation facilitates surgical procedures and tracheal intubation, adequate recovery of muscle function after surgery is required to support pulmonary function, and even mild residual neuromuscular block increases the risk of severe postoperative pulmonary complications. While recovery of muscle function after surgery involving neuromuscular blocking agents can be monitored and, in addition, be accelerated by use of current antagonists (reversal agents), there is a clear clinical need for a safe drug to antagonize all types of neuromuscular blocking agents. Here, we show that inhibition of the skeletal muscle-specific chloride ion (Cl-) channel, the ClC-1 channel, markedly accelerates recovery of both single contraction (twitch) and, important physiologically, sustained (tetanic) contractions in a rat model mimicking neuromuscular blocking agent-induced muscle block used during surgery. This suggests ClC-1 inhibition as a mechanism for fast and efficacious recovery of neuromuscular function induced by any neuromuscular blocking agents. Reversal agents are intravenous drugs used to accelerate recovery from neuromuscular block post-surgery. We report that inhibition of ClC-1, a skeletal muscle chloride channel, reverses any nondepolarizing blocking agent, providing a novel reversal (antagonism) mechanism. [ABSTRACT FROM AUTHOR]

Neuromuscular blocking agents (NMBAs), a cornerstone of pediatric anesthesia, facilitate intubation and muscle relaxation during surgery. However, NMBAs can also lead to serious complications including respiratory depression, residual paralysis, and prolonged recovery. Neuromuscular monitoring (NMM) in pediatric patients is therefore essential, as it is in adults, to ensure adequate paralysis during surgery and prompt recovery from NMBA-induced paralysis. This article aimed to provide a comprehensive overview of NMM in pediatric anesthesia including the various available methods, their advantages and disadvantages, and the importance of a standardized NMM approach. [ABSTRACT FROM AUTHOR]

Efficacy and safety of sugammadex for the reversal of neuromuscular blocking agents (NMBAs) in patients with neuromuscular diseases remains unclear. We summarised the available evidence and evaluated the quality of data reporting and the validity of published reports. We searched for reports (any design) on the usage of sugammadex (any regimen) for the reversal of an NMBA in patients (any age) with any neuromuscular disease. We used a modified CARE checklist (maximum score 23) to assess the quality of data reporting and an original specific validity checklist (maximum score 41) that was developed through a Delphi process. We retrieved 126 observational reports (386 patients). Most dealt with myasthenia gravis patients receiving rocuronium. The train-of-four ratio returned to ≥0.9 in 258 of 265 (97.4%) patients in whom neuromonitoring was used. Adverse events occurred in 14 of 332 (4.2%) patients in whom adverse events were reported as present or absent. In 90 case reports, the median score of the 23-point CARE checklist was 13.5 (inter-quartile range [IQR] 11–16). In all 126 reports, the median score of the 41-point validity checklist was 23 (IQR 20–27). Scores were positively correlated. These uncontrolled observations (of mainly low to moderate quality and validity) do not allow confident assessment of the efficacy and safety of sugammadex for the reversal of NMBAs in patients with neuromuscular diseases. Reporting of observational data should follow established guidelines, include specific information to ensure validity, and emphasise what the new data add to current knowledge. PROSPERO 2019 (CRD42019119924). [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate whether liver compression (LC) could increase stroke volume (SV) by more than 15% in healthy, anesthetized dogs with hypovolemia and suggest LC as a novel method to evaluate fluid responsiveness. ANIMALS 6 healthy Beagles. METHODS This prospective, nonrandomized experimental study was conducted from November 2023 to February 2024. The dogs were anesthetized with isoflurane and mechanically ventilated under neuromuscular blockade. After instrumentation, the dogs underwent the following 4 experimental stages in a sequential, nonrandomized manner: stage 1, baseline; stage 2, 30% withdrawal of circulating blood volume; stage 3, 50% infusion of the collected blood; and stage 4, the remaining 50% infusion of the collected blood. At each stage, SV via pulmonary artery thermodilution and hemodynamic variables were measured before, during, and after the LC. RESULTS In stage 2, LC significantly increased mean SV by 30%, from 6.9 to 9 mL/beat. Simultaneously, LC significantly increased mean arterial pressure by 11 mm Hg and mean central venous pressure by 2 mm Hg, while pulse pressure variation significantly decreased from 28% to 22%. In stages 1, 3, and 4, LC did not significantly change mean SV, mean arterial pressure, and pulse pressure variation; however, mean central venous pressure significantly increased during stage 3. CLINICAL RELEVANCE This study demonstrates that LC at 22 mm Hg for 1 minute could increase SV more than 15% in anesthetized, hypovolemic dogs and LC could be used as a novel method to evaluate fluid responsiveness. [ABSTRACT FROM AUTHOR]

Objective Bronchopulmonary dysplasia (BPD) is the most common late morbidity for premature infants. Continuous neuromuscular blockade (CNMB) is suggested for the most unstable phase of BPD, despite no outcome data. We explored the association between duration of CNMB for severe BPD and mortality. Design Medical record review of children <5 years old admitted from 2016 to 2022 with BPD and one or more course of CNMB for ≥14 days. Results Twelve children received a total of 20 episodes of CNMB for ≥14 days (range 14–173 d) during their hospitalization. Most (10/12) were born at <28 weeks' gestation and most (11/12) with birth weight <1,000 g; 7/12 were of Black race/ethnicity. All were hospitalized since birth. Most (10/12) were initially transferred from an outside neonatal intensive care unit (ICU), typically after a >60-day hospitalization (9/12). Half (6/12) of them had a ≥60-day stay in our neonatal ICU before transferring to our pediatric ICU for, generally, ≥90 days (8/12). The primary study outcome was survival to discharge: 2/12 survived. Both had shorter courses of CNMB (19 and 25 d); only one child who died had a course ≤25 days. Just two infants had increasing length Z-scores during hospitalization; only one infant had a final length Z-score > − 2. Conclusion In this case series of infants with severe BPD, there were no survivors among those receiving ≥25 days of CNMB. Linear growth, an essential growth parameter for infants with BPD, decreased in most patients. These data do not support the use of ≥25 days of CNMB to prevent mortality in infants with severe BPD. Key Points This is a case series of neuromuscular blockade for severe BPD. Neuromuscular blockade did not improve linear growth. Ten out of 12 infants who were on prolonged neuromuscular blockade died. [ABSTRACT FROM AUTHOR]

Sugammadex, the first noncompetitive antagonist developed for the reversal of neuromuscular blockade (NMB), is one of the few drugs that has revolutionized anesthetic practice. However, sugammadex use was only recently approved for children aged 2 to 17 years, and it remains unapproved for children under 2. Although the precision and reliability of reversal of NMB with sugammadex are of great benefit in pediatric anesthesia, several important questions remain regarding its use in our youngest patients. In this brief narrative review, we aim to provide an overview of the key considerations and potential challenges that anesthesiologists often face when using sugammadex in pediatric patients. [ABSTRACT FROM AUTHOR]

Purpose 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. Summary 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. Conclusion 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. [ABSTRACT FROM AUTHOR]

Objective: This study functional endoscopic sinus surgery (FESS) is a surgical procedure requiring minimal bleeding to optimize the surgical field. This study aimed to evaluate the effectiveness of magnesium sulfate, lignocaine, and propofol in attenuating hemodynamic response. The primary objective of this study was to compare the efficacy of these agents in reducing hemodynamic response. The secondary objectives included assessing the quality of the surgical field, recovery time, and total neuromuscular dose. Methods: We randomly allocated 105 patients scheduled for FESS into three groups: lignocaine, propofol, and magnesium sulfate. Heart rate and mean arterial pressure were recorded every 5 min for the first 30 min, followed by measurements every 10 min at the end of the procedure. Moreover, recovery time, total neuromuscular blocking dose, and surgical field score were noted upon completion of the procedure. Statistical analysis was conducted using the number cruncher statistical systems version 9.0.8 software. Results: All three groups showed comparable hemodynamic response and surgical field scores. The recovery time was notably longer in the magnesium sulfate group [10.94 min (2.45)] than in the lignocaine [4.37 min (1.03)] [95% confidence interval (CI) -7.32, -5.83; P=0.000] and propofol groups [4.60 min (0.60)] (95% CI 5.60, 7.095; P=0.000). Moreover, the total neuromuscular blocking agent used was significantly lower in the magnesium sulfate group [5.89 mg (0.47)] than in the lignocaine [6.26 mg (0.56)] (95% CI 0.66, 0.03; P=0.035). Conclusion: Propofol, magnesium sulfate, and lignocaine exerted equal efficacy in attenuating hemodynamic responses during surgery and ensuring a satisfactory surgical field. However, magnesium sulfate led to significantly longer recovery times compared with propofol and lignocaine. In addition, magnesium sulfate required a significantly lower total dose of neuromuscular blocking agents than lignocaine. [ABSTRACT FROM AUTHOR]

Background: Neuromuscular blocking agents (NMBAs) are a crucial component of anesthesia and intensive care through the relaxation of skeletal muscles. They can lead to adverse reactions such as postoperative residual neuromuscular block. Only one agent is capable of an instant block reversal in deep block situations, but is restricted to aminosteroid agents. Among animal models, non‐human primates are an essential model for a great diversity of human disease models. The main objective of this study was to establish a model for NMBA monitoring with current available drugs before testing new reversal agents. Methods: Seven healthy male cynomolgus macaques were randomly assigned to this study. Experiments using macaques were approved by the local ethical committee (CEtEA #44). All animals were anesthetized according to institutional guidelines, with ketamine and medetomidine, allowing IV line placement and tracheal intubation. Anesthesia was maintained with isoflurane. Either rocuronium bromine (with or without sugammadex reversal) or atracurium besylate was evaluated. Monitoring was performed with two devices, TOF‐Watch and ToFscan, measuring the T4/T1 and the T4/Tref ratios, respectively. Nonparametric Mann–Whitney statistical analyses were done when indicated. Results: NMBA monitoring required adaptation compared to humans, such as stimulus intensity and electrode placement, to be efficient and valid in cynomolgus macaques. When administered, both NMBAs induced deep and persistent neuro‐muscular block at equivalent doses to clinical doses in humans. The rocuronium‐induced profound neuromuscular block could be reversed using the cyclodextrin sugammadex as a reversal agent. We report no adverse effects in these models by clinical observation, blood chemistry, or complete blood count. Conclusion: These results support the use of non‐human primate models for neuromuscular block monitoring. This represented the first step before the forthcoming testing of new NMBA‐reversal agents. [ABSTRACT FROM AUTHOR]

The article examines the impact of deep neuromuscular blockade (NMB) and low-pressure pneumoperitoneum (PP) on postoperative outcomes in laparoscopic abdominal surgeries. Topics include the longer time to first analgesic administration and lower opioid consumption in the deep NMB group, significantly reduced pain scores at 6, 8, and 12 hours post-surgery, and comparable surgical duration, field quality, and complication rates between the two groups.

Sugammadex, a selective relaxant binding agent, has transformed the management of neuromuscular blockade, offering rapid and safe recovery during various medical and dental procedures. Its applications extend to managing temporomandibular disorders (TMDs) in elderly patients undergoing complex oral rehabilitation. The integration of sugammadex into multidisciplinary treatment protocols--including prosthetic rehabilitation, balneophysiotherapy, and pharmacological therapies--has the potential to improve outcomes significantly. This review examines the pharmacological impact of sugammadex, its commercial formulations, and its role in the holistic management of TMDs in geriatric populations. [ABSTRACT FROM AUTHOR]

Background: COVID-19 patients may exhibit neurological symptoms due to direct viral damage, systemic inflammatory syndrome, or treatment side effects. Mechanical ventilation in patients with severe respiratory failure often requires sedation and neuromuscular blockade, hindering thorough clinical examinations. This study aimed to investigate neurological involvement through clinical and noninvasive techniques and to detect signs of intracranial hypertension in these patients. Method: We conducted a prospective observational study on mechanically ventilated COVID-19 adult patients admitted to our ICU, following standard of care protocols for ventilation and permissive hypercapnia. Data were collected at three time points: admission day (T1), day seven (T7), and day fourteen (T14). At each time point, patients underwent multimodal noninvasive neurological monitoring, including clinical examination, pupillary reactivity, transcranial color doppler of the middle cerebral artery (MCA), and optic nerve sheath diameter (ONSD) assessed via ultrasound (US). Head computer tomography (CT) was performed at T1 and T14. A limited subset of patients had a follow-up examination six months after ICU discharge. Results: Seventy-nine patients were recruited; most were under deep sedation and neuromuscular blockade at T1. Pupillary size, symmetry, and reactivity were normal, as was the MCA mean velocity. However, ONSD, assessed by both US and CT, appeared enlarged, suggesting raised intracranial pressure (ICP). In a subgroup of 12 patients, increased minute ventilation was associated with a significant decrease in US-ONSD, corresponding to a drop in paCO2. At follow-up, twelve patients showed no long-term neurological sequelae, and US-ONSD was decreased in all of them. Discussion and conclusions: In this cohort, enlarged ONSD was detected during non-invasive neurological monitoring, suggesting a raised ICP, with hypercapnia playing a prominent role. Further studies are needed to explore ONSD behavior in other samples of mechanically ventilated, hypercapnic patients. [ABSTRACT FROM AUTHOR]

Background: Improvements in oxygenation and lung mechanics with prone position (PP) in patients with acute respiratory distress syndrome (ARDS) are inconstant. The objectives of the study were (i) to identify baseline variables, including the recruitment-to-inflation ratio (R/I), associated with a positive response to PP in terms of oxygenation (improvement of the ratio of arterial oxygen partial pressure over the inspired oxygen fraction (PaO2/FiO2) ≥ 20 mmHg) and lung mechanics; (ii) to evaluate whether the response to the previous PP session is associated with the response to the next session. Methods: In this prospective, observational, single-center study in patients who underwent PP for ARDS due to COVID-19, respiratory variables were assessed just before PP and at the end of the session. Respiratory variables included mechanical ventilation settings and respiratory mechanics variables, including R/I, an estimate of the potential for lung recruitment compared to lung overinflation. Results: In 50 patients, 201 PP sessions lasting 19 ± 3 h were evaluated. Neuromuscular blockades were used in 116 (58%) sessions. The PaO2/FiO2 ratio increased from 109 ± 31 mmHg to 165 ± 65 mmHg, with an increase ≥ 20 mmHg in 142 (71%) sessions. In a mixed effect logistic regression, only pre-PP PaO2/FiO2 (OR 1.12 (95% CI [1.01–1.24])/every decrease of 10 mmHg, p = 0.034) in a first model and improvement in oxygenation at the previous PP session (OR 3.69 (95% CI [1.27–10.72]), p = 0.017) in a second model were associated with an improvement in oxygenation with PP. The R/I ratio (n = 156 sessions) was 0.53 (0.30–0.76), separating lower- and higher-recruiters. Whereas PaO2/FiO2 improved to the same level in both subgroups, driving pressure and respiratory system compliance improved only in higher-recruiters (from 14 ± 4 to 12 ± 4 cmH2O, p = 0.027, and from 34 ± 11 to 38 ± 13 mL/cmH2O, respectively, p = 0.014). Conclusions: A lower PaO2/FiO2 at baseline and a positive O2-response at the previous PP session are associated with a PP-induced improvement in oxygenation. In higher-recruiters, lung mechanics improved along with oxygenation. Benefits of PP could thus be greater in these patients. [ABSTRACT FROM AUTHOR]

Neuromuscular blocking agents (NMBAs) relax skeletal muscles to facilitate surgeries and ease intubation but can lead to adverse reactions, including complications because of postoperative residual neuromuscular blockade (rNMB) and, in rare cases, anaphylaxis. Both adverse reactions vary between types of NMBAs, with rocuronium, a widely used nondepolarizing NMBA, inducing one of the longest rNMB durations and highest anaphylaxis incidences. rNMB induced by rocuronium can be reversed by the synthetic γ-cyclodextrin sugammadex. However, in rare cases, sugammadex can provoke anaphylaxis. Thus, additional therapeutic options are needed. Rocuronium-induced anaphylaxis is proposed to rely on preexisting rocuronium-binding antibodies. To understand the pathogenesis of rocuronium-induced anaphylaxis and to identify potential therapeutics, we investigated the memory B cell antibody repertoire of patients with suspected hypersensitivity to rocuronium. We identified polyclonal antibody repertoires with a high diversity among V(D)J genes without evidence of clonal groups. When recombinantly expressed, these antibodies demonstrated specificity and low affinity for rocuronium without cross-reactivity for other NMBAs. Moreover, when these antibodies were expressed as human immunoglobulin E (IgE), they triggered human mast cell activation and passive systemic anaphylaxis in transgenic mice, although their affinities were insufficient to serve as reversal agents. Rocuronium-specific, high-affinity antibodies were thus isolated from rocuronium-immunized mice. The highest-affinity antibody was able to reverse rocuronium-induced neuromuscular blockade in nonhuman primates with kinetics comparable to that of sugammadex. Together, these data support the hypothesis that antibodies cause anaphylactic reactions to rocuronium and pave the way for improved diagnostics and neuromuscular blockade reversal agents. Editor's summary: Neuromuscular blocking agents (NMBAs) such as rocuronium are used during anesthesia to assist with surgeries and intubations. Although these agents are effective, they are not without risk. Patients can develop postoperative residual neuromuscular blockade, which can be treated with an NMBA reversal agent, and life-threatening anaphylaxis can occur in rare cases. Here, Dejoux et al. isolated and characterized memory B cells from three individuals who developed reactions to NMBA treatment and had serum antibodies to rocuronium. The authors found that IgE antibodies generated from these memory B cells were sufficient to induce anaphylaxis in mice treated with rocuronium, although they were too low affinity to be used as reversal agents. This led the authors to immunize mice with rocuronium to generate antibodies of higher affinity, which were able to reverse neuromuscular blockade in rocuronium-treated nonhuman primates. Together, these data explain why these three patients had a reaction and offer a therapeutic approach to reversing neuromuscular blockade. —Courtney Malo [ABSTRACT FROM AUTHOR]

Abstract Background Sugammadex is a pharmacologic agent that provides rapid reversal of neuromuscular blockade via encapsulation of the neuromuscular blocking agent (NMBA). The sugammadex-NMBA complex is primarily cleared through glomerular filtration from the kidney, raising the possibility that alterations in renal function could affect its elimination. In pediatric patients, the benefits of sugammadex have led to widespread utilization; however, there is limited information on its application in pediatric renal impairment. This study examined sugammadex use and postoperative outcomes in pediatric patients with severe chronic renal impairment at our quaternary pediatric referral hospital. Methods After IRB approval, we performed a retrospective analysis in pediatric patients with stage IV and V chronic kidney disease who received sugammadex from January 2017 to March 2022. Postoperative outcomes studied included new or increased respiratory requirement, unplanned intensive care unit (ICU) admission, postoperative pneumonia, anaphylaxis, and death within 48 h postoperatively, unplanned deferral of intraoperative extubation, and repeat administrations of NMBA reversal after leaving the operating room. Results The final cohort included 17 patients ranging from 8 months to 16 years old. One patient required new postoperative noninvasive ventilation on postoperative day 2, which was credited to hypervolemia. Another patient had bronchospasm intraoperatively resolving with medication, which could not definitively be associated sugammadex administration. There were no instances of deferred extubation, unplanned ICU or need for supplemental oxygen after tracheal extubation identified. Conclusion No adverse effects directly attributable to sugammadex in pediatric patients with severe renal impairment were detected. There may be a role for utilization of sugammadex for neuromuscular reversal in this population.

Study Objective. Sugammadex is a widely used neuromuscular blockade reversal agent. Cost concerns limit use in pediatric patients for, whom recommended doses are often far less than vial quantities. Therefore, we undertook a quality improvement initiative at a pediatric hospital in which sugammadex vials were fractionated. We hypothesized we would see a decrease in administered dose and waste and improved adherence with dosing guidelines. Methods. Sugammadex vials were fractionated into 25, 50, or 100 mg aliquots, which would be distributed to anesthesia staff by pharmacy staff in approximate 2 mg/kg of actual body weight doses (±10%). We analyzed changes in sugammadex waste and dosing practices 1/1/2019 to 3/15/2023 pre/postintervention (4/1/2021). We gauged dose appropriateness using last train of four (TOF) prior to sugammadex administration. Results. 7,889 patients 2–17 years (4,771 with documented TOF), ASA 1–4 receiving general anesthesia with a steroidal NMB medication and sugammadex reversal. Pre‐ and postintervention mean doses were 2.5 mg/kg (SD: 1.2) and 2.4 mg/kg (SD: 0.96), respectively. A smaller proportion of cases received standard 2 or 4 mg/kg doses (pre: 77.6 vs. post: 66.7%). Mean waste per case declined from 4.2 mg/kg (SD: 4.1) to 0.22 mg/kg (SD: 0.38). Among cases with 0 or 1 measured twitches on TOF that should receive at least 4 mg/kg, fewer received at least 3.6 mg/kg (post: 56.7% vs. pre: 66.8%), and a greater proportion received less than 2.2 mg/kg (post: 27.4% vs. pre: 20.7%). Among cases that should have received at least 2 mg/kg by TOF, the proportion of patients receiving more than 3.6 mg/kg declined from 9.5% to 5.2%. Discussion. Fractionating sugammadex vials was associated with decreases in waste, but not dose, and significant underdosing was more likely to occur. While vial fractionation could enable increased access to sugammadex and other costly medications, it may introduce unintended consequences. [ABSTRACT FROM AUTHOR]

Purpose: Pain is a major physiological stressor that can worsen critical medical conditions in many ways. Currently, there is no reliable monitoring tool which is available for pain monitoring in the deeply sedated ± curarized critically ill patients. This study aims to assess the effectiveness of the multiparameter nociception index (NOL®) in the critical care setting. We compared NOL with traditionally used neurovegetative signs and examined its correlation with sedation depth measured by bispectral index (BIS®) electroencephalographic (EEG) monitoring. Methods: This retrospective monocentric cohort study was conducted in a general intensive care unit, including patients who required moderate-to-deep levels of sedation with or without continuous neuromuscular blockade. The performance of NOL was evaluated both in the entire studied population, as well as in two subgroups: curarized and non-curarized patients. Results: NOL demonstrated greater accuracy than all other indicators in pain detection in the overall population. In the non-curare subgroup, all indices correctly recognized painful stimulation, while in the patients subjected to neuromuscular blocking agent's infusion, only NOL properly identified nociception. In the former group, EEG's relation to nociception was on the border of statistical significance, whereas in the latter BIS showed no correlation with NOL. Conclusion: NOL emerges as a promising device for pain assessment in the critical care setting and exhibits its best performance precisely in the clinical context where reliable pain assessment methods are most lacking. Furthermore, our research confirms the distinction between sedation and analgesia, highlighting the necessity for distinct monitoring instruments to accurately assess them. [ABSTRACT FROM AUTHOR]

Background: We aimed to elucidate the quantitative relationship between the neuromuscular blockade depth and intraoperative motor-evoked potential amplitudes. Methods: This prospective, single-arm, open-label, observational study was conducted at a single university hospital in Seoul, Korea, and included 100 adult patients aged ≥19 years undergoing brain tumor removal surgery under general anesthesia. We measured the neuromuscular blockade degree and motor-evoked potential amplitude in the deltoid, abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles until dural opening. Results: The pharmacokinetic-pharmacodynamic model revealed the exposure-response relationship between the rocuronium effect-site concentration and motor-evoked potential amplitudes. The mean motor-evoked potential amplitudes decreased proportionally with increasing neuromuscular blockade depth. As the mean amplitude increased, the coefficient of variation decreased bi-exponentially. The critical ratio of the first evoked response to the train-of-four stimulation (T1)/control response (Tc) thresholds beyond which the coefficient of variation exhibited minimal change were found to be 0.63, 0.65, 0.68, and 0.63 for the deltoid, abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles, respectively. Conclusions: Our results reveal that the motor-evoked potential amplitude exhibits deterioration proportional to the degree of neuromuscular blockade. In light of the observed bi-exponential decline of the coefficient of variation with the motor-evoked potential amplitude, we recommend maintaining a T1/Tc ratio higher than 0.6 for partial neuromuscular blockade. [ABSTRACT FROM AUTHOR]

Background: 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. Method: 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. 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Low-pressure pneumoperitoneum (LPP) is an attempt to improve laparoscopic surgery. Lower pressure causes lesser inflammation and better hemodynamics. There is a lack of literature comparing inflammatory markers in LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB in laparoscopic cholecystectomy. Methodology: This was a single institutional prospective randomized control trial. Participants included all patients undergoing laparoscopic cholecystectomy for symptomatic gall stone disease. Participants were divided into 2 groups group A and B. Group A—Low-pressure group in which pneumoperitoneum pressure was kept low (8–10 mmHg) with deep Neuromuscular blockade (NMB) and Group B—Normal pressure group (12–14 mmHg) with moderate NMB. A convenience sample size of 80 with 40 in each group was selected. Lab investigations like CBC, LFT, RFT and serum IL-1, IL-6, IL-17, TNF alpha levels were measured at base line and 24 h after surgery and compared using appropriate statistical tests. Other parameters like length of hospital stay, post-operative pain score, conversion rate (low-pressure to standard pressure), and complications were also compared. Results: Eighty participants were analysed with 40 in each group. Baseline characteristics and investigations were statistically similar. Difference (post-operative–pre-operative) of inflammatory markers were compared between both groups. Numerically there was a slightly higher rise in most of the inflammatory markers (TLC, ESR, CRP, IL-6, TNFα) in Group B compared to Group A but not statistically significant. Albumin showed significant fall (p < 0.001) in Group B compared to Group A. Post-operative pain was also significantly less (p < 0.001) in Group A compared to Group B at 6 h and 24 h. There were no differences in length of hospital stay and incidence of complications. There was no conversion from low-pressure to standard pressure. Conclusion: Laparoscopic cholecystectomy performed under low-pressure pneumoperitoneum with deep NMB may have lesser inflammation and lesser post-operative pain compared to standard pressure pneumoperitoneum with moderate NMB. Future studies with larger sample size need to be designed to support these findings. [ABSTRACT FROM AUTHOR]

Background: Prolong effects of non-depolarizing neuromuscular blocking agents after rapid sequence intubation may prevent meaningful neurological examination, delaying appropriate diagnosis and neurosurgical intervention. Sugammadex is indicated for the reversal of neuromuscular blockade induced by rocuronium. Objective: The objective of this study was to evaluate low- (2 mg/kg) vs standard-dose (4 mg/kg) sugammadex for rocuronium-induced deep neuromuscular blockade reversal in the emergency department (ED) by achieving a post-treatment train-of-four (TOF) of 4 to facilitate neurological examination. Methods: This was a single-center, retrospective, cohort study evaluating low-vs standard-dose sugammadex for neuromuscular blockade reversal in the ED. Results: 34 patients were identified within the designated time period, 24 of which were included in the final analysis ([n = 9 low-dose], [n = 15 standard-dose]). Median sugammadex doses were 2.3 mg/kg and 4.1 mg/kg for low- and standard-dose, respectively. The majority of patients presented for intraparenchymal hemorrhage (54.2%). No significant difference in success rate of NMBA reversal was found between low- and standard-dose sugammadex ([100.0% vs 93.3%], P = 1.000). A total of 9 patients had a neurosurgical procedure performed after sugammadex administration. Low-dose sugammadex was associated with significantly less acquisition cost compared to the standard dose (P <.001). Conclusion: Low- (2 mg/kg) and standard-dose (4 mg/kg) sugammadex successfully reversed rocuronium-induced deep neuromuscular blockade in the ED by achieving a post-treatment TOF of 4 to facilitate neurologic examination. Low-dose sugammadex may be a viable option for deep NMBA reversal in the ED and is associated with decreased institutional cost. [ABSTRACT FROM AUTHOR]

Background: Airway pressure release ventilation (APRV) has become increasingly popular for the management of acute respiratory distress syndrome (ARDS); however, its clinical impact remains a topic of debate. Furthermore, there is a gap between the guidelines and the actual clinical practices in mechanical ventilation management for ARDS. This survey aimed to explore the utilization of APRV and mechanical ventilation strategies for ARDS in Chinese intensive care unit (ICU) clinicians. Methods: A comprehensive 34‐item survey was distributed online platforms amongst ICU clinicians across mainland China from June to August 2019. Results: A total of 420 valid responses were collected, with 57.4% (241) originating from academic hospitals and 42.6% (179) from non‐academic hospitals. Of the respondents, 98.6% (414) recognized the significance of low tidal volume ventilation for ARDS prognosis, 85.2% adhered to a tidal volume below 8 mL/kg predicted body weight, and most (46.4%) selected the initial positive end‐expiratory pressure within the range of 5–10 cmH2O based on experience. Among the respondents, 62.1% (261) reported familiarity with APRV and 41.9% (176) had implemented APRV. Of those who had utilized APRV, 93.2% (164) believed in its effectiveness for ARDS patients and 69.3% (122) advocated for early application of APRV. Substantial variations were noted regarding APRV initiation settings and the preservation of spontaneous breathing during APRV. Academic hospitals exhibited higher usage rates of lung recruitment, neuromuscular blockade, prone ventilation, and acquaintance with and utilization of APRV compared to non‐academic hospitals (all p values ≤ 0.001). Conclusions: Our findings highlight opportunities for improvement in mechanical ventilation management for ARDS, particularly in non‐academic hospitals. Additionally, a significant proportion of clinicians demonstrated limited knowledge of APRV, and there was a lack of consensus on its application. Further training and larger‐scale clinical trials are required to validate the efficacy and utilization of APRV in managing ARDS. [ABSTRACT FROM AUTHOR]

Our lab is investigating the efficacy profiles of tropine analogs against opioidinduced respiratory depression. The companion manuscript reports that the cellpermeant tropeine, tropine ester (Ibutropin), produces a rapid and sustained reversal of the deleterious actions of fentanyl on breathing, alveolar-arterial (A-a) gradient (i.e., index of alveolar gas exchange), and arterial blood-gas (ABG) chemistry in freely-moving male Sprague Dawley rats, while not compromising fentanyl analgesia. We report here that in contrast to Ibutropin, the injection of the parent molecule, tropine (200 µmol/kg, IV), worsens the adverse actions of fentanyl (75 µg/kg, IV) on ventilatory parameters (e.g., frequency of breathing, tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives), A-a gradient, ABG chemistry (e.g., pH, pCO2, pO2, and sO2), and sedation (i.e., the righting reflex), while not affecting fentanyl antinociception (i.e., the tail-flick latency) in freely-moving male Sprague Dawley rats. These data suggest that tropine augments opioid receptor-induced signaling events that mediate the actions of fentanyl on breathing and alveolar gas exchange. The opposite effects of Ibutropin and tropine may result from the ability of Ibutropin to readily enter peripheral and central cells. Of direct relevance is that tropine, resulting from the hydrolysis of Ibutropin, would combat the Ibutropin-induced reversal of the adverse effects of fentanyl. Because numerous drug classes, such as cocaine, atropine, and neuromuscular blocking drugs contain a tropine moiety, it is possible that their hydrolysis to tropine has unexpected/unintended consequences. Indeed, others have found that tropine exerts the same behavioral profile as cocaine upon central administration. Together, these data add valuable information about the pharmacological properties of tropine. [ABSTRACT FROM AUTHOR]

A meta-analysis published in the journal Anaesthesia compared the use of remifentanil with neuromuscular blocking (NMB) drugs for tracheal intubation in adults. The study found that a remifentanil bolus provided comparable rates of successful tracheal intubation compared to NMB drugs. However, this conflicts with the findings of a recent trial that found remifentanil to be statistically inferior to NMB drugs. While the use of NMB drugs is widely recommended, the study suggests that tracheal intubation with high doses of remifentanil may be a safe alternative in certain situations. Further research is needed to investigate the efficacy of tracheal intubation without NMB drugs and to improve patient safety during the procedure. [Extracted from the article]