Search Results (15)

Medical errors are inevitable and will happen to almost every specialist. In anesthesiology, one of the main concerns is the inappropriate application of muscle relaxants (MRs). As this group of drugs plays a significant role in facilitating endotracheal intubation and optimizing surgical conditions, it is widely and commonly used in the medical field. To prevent residual neuromuscular block, anesthesiologists may pharmacologically reverse the neuromuscular block (NMB) by administering reversal agents. Lately, sugammadex is becoming more popular due to its ability to reverse various levels of NMB more rapidly than traditionally used acetylcholinesterase inhibitors such as neostigmine. The common challenges and errors associated with the administration of neuromuscular blocking agents (NMBAs) and muscle reversal agents include the absence of neuromuscular monitoring, underestimation of the residual block (RB), misinterpretation of DUR25, inappropriate size descriptors for muscle relaxants and reversal agents requiring weight-based dosing, the wrong dosing of rocuronium, poor usage of cisatracurium among patients with renal or hepatic failure, and the wrong usage of succinylcholine. Another source of mistakes may be inaccurate knowledge about the pharmacokinetics and pharmacodynamics of the administered drugs. Medication errors may occur not only when it comes to the usage of muscle relaxants but also with the use of reversal agents, including lack of neuromuscular monitoring, choosing the wrong antagonist strategy, “too early” administration of neostigmine, inappropriate dosing, and insufficient knowledge about drug interactions. Improving the knowledge of administered drugs and adhering to the latest recommendations could prevent many complications. This article aims to review the current challenges in the use of muscle relaxants and reversal agents in anesthesia. Full article

Background/Objectives: Rapid sequence intubation (RSI) involves nearly simultaneous administration of a rapid-acting induction agent and a neuromuscular blocking agent (NMBA) to facilitate ideal intubation conditions. The NMBAs most commonly used for RSI are succinylcholine and rocuronium, which cause paralysis for 5–15 min and 45–70 min, respectively. Awareness with paralysis can occur in patients who are given longer-acting NMBAs with delayed initiation of post-intubation sedation or insufficient sedation depth. The previous literature has associated the use of rocuronium with a significantly longer time to sedation and analgesia. However, a recent study found no difference. The purpose of this study was to assess the association between paralytic agent choice and time to initiation of analgesia and/or sedation after RSI in the emergency department (ED) of a large tertiary care hospital. Methods: This study was an institutional review board (IRB)-approved, single-center, retrospective cohort evaluation of adult patients (≥18 years of age) who received succinylcholine or rocuronium following administration of an induction agent in the ED for RSI during the study time period. The primary outcome was time to initiation of post-intubation analgesia and/or sedation. Continuous data were analyzed by using Mann–Whitney U or Student’s t-test, and categorical data were analyzed using the Chi Square test or Fisher’s Exact test. Results: A total of 400 patients were included in this study. The median time to sedation with succinylcholine was 9 min compared to 14 min with rocuronium (p < 0.01). No significant differences were identified in the baseline characteristics or secondary outcomes related to induction agent choice or ED length of stay. Conclusions: The results of this study further support that the use of rocuronium for RSI is associated with a significantly longer time to sedation and/or analgesia, making emergency medicine provider awareness essential for minimizing the risks associated with inadequate post-intubation sedation. Full article

Neuromuscular blocking agents (NMBAs) are essential in intraocular surgeries to improve surgical conditions and ensure optimal ventilation. However, residual blockade can pose significant risks, particularly in pinnipeds due to their unique diving physiology. This case report describes the use of sugammadex for reversing rocuronium and AMG for monitoring neuromuscular block (NMB) in a California sea lion undergoing lensectomy. The objective is to evaluate the feasibility and safety of sugammadex for reversal of rocuronium-induced neuromuscular blockade and acceleromyography (AMG) for monitoring neuromuscular function in pinnipeds, with the goal of improving anesthetic management and recovery. Rocuronium (0.3 mg/kg IV) was used to achieve complete NMB, and an additional 0.1 mg/kg IV was administered to prolong the block. Sugammadex (1 mg/kg IV) reversed the NMB, with recovery within 90 s. Neuromuscular function was monitored using AMG, with the ulnar nerve of the foreflipper as the stimulation site. AMG allowed for an objective assessment of neuromuscular function, ensuring accurate titration of the NMBA and reversal agent. This is the first report documenting the use of sugammadex for the reversal of rocuronium and AMG for neuromuscular monitoring in a sea lion. This successful application highlights the potential of these techniques to improve anesthesia protocols, patient safety, and welfare in marine mammal medicine. Full article

Neuromuscular blocking agents such as atracurium and rocuronium are commonly used during anesthetic procedures in laboratory pigs. However, species-specific dosing guidelines remain limited, leading to reliance on data extrapolated from other species. This prospective, blinded study aimed to determine the equipotent dose for atracurium (A) and rocuronium (R) in laboratory pigs receiving propofol and to compare their cost-effectiveness. Twelve healthy animals were randomly distributed according to the drug administered (n = 6 per group). For both drugs, the infusion rate was adjusted following an up-and-down titration to maintain a train-of-four count between 3 and 4. Group differences were analyzed using the Wilcoxon signed-rank test. The bolus induction dose (mg/kg) was comparable between atracurium (2.3 [1.8–2.6]) and rocuronium (2 [2]), while atracurium was associated with higher costs (CHF/kg: A, 1.122 [0.878–1.366] versus R, 0.208 [0.208–0.208]; p = 0.002725). The maintenance infusion rate (mg/kg/h) was approximately 40% lower for atracurium (2.7 [2.5–2.8]) than for rocuronium (4.5 [4.4–4.5]; p = 0.004922), yet the maintenance cost (CFH/kg/h) remained higher for atracurium (A: 1.30 [1.22–1.37] versus R: 0.47 [0.45–0.47]; p = 0.0043). This study reports higher doses for anesthetized pigs compared to other species and demonstrates that rocuronium offers superior cost-effectiveness compared to atracurium under these experimental conditions. Full article

Background/Objectives: Neuromuscular blocking agents (NMBAs) are not usually necessary during the induction of general anesthesia in patients using supraglottic airway (SGA) devices. In this study, we assessed the incidences of rocuronium use in adult patients undergoing general anesthesia using SGA devices. Methods: From September 2022 to August 2023, the medical records of adult patients (≥19 years) who underwent orthopedic surgery using SGA devices were retrospectively investigated. The incidences of rocuronium use during anesthetic induction were analyzed according to the anesthetic induction drug. The association of rocuronium use during anesthesia was analyzed in terms of demographic (age, sex, height, and weight), surgical (surgical time), and anesthetic factors (premedication, anesthetic agent, anesthetic time). Results: In total, 321 patients were enrolled. The incidence rate of rocuronium use during anesthetic induction was 28.3%. In the subgroup analysis, patients receiving total intravenous anesthesia (TIVA) with propofol (PPF) and remifentanil showed a markedly lower incidence (14.4%) than the other anesthetic groups. Premedication or short anesthetic duration was associated with lower incidences of rocuronium use. Demographic and other anesthetic factors did not seem to affect the incidences of rocuronium use during anesthesia. Conclusions: The incidence of rocuronium use during anesthetic induction with SGA devices was significantly lower with the PPF-TIVA compared to that using remimazolam-TIVA or inhalational anesthesia. Premedication with midazolam and shorter operation times were associated with a significantly lower incidence of rocuronium use. Full article

Neuromuscular blocking agents (NMBAs) are routinely used during anesthesia to relax skeletal muscle. Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels; NMBAs can induce muscle paralysis by preventing the neurotransmitter acetylcholine (ACh) from binding to nAChRs situated on the postsynaptic membranes. Despite widespread efforts, it is still a great challenge to find new NMBAs since the introduction of cisatracurium in 1995. In this work, an effective ensemble-based virtual screening method, including molecular property filters, 3D pharmacophore model, and molecular docking, was applied to discover potential NMBAs from the ZINC15 database. The results showed that screened hit compounds had better docking scores than the reference compound d-tubocurarine. In order to further investigate the binding modes between the hit compounds and nAChRs at simulated physiological conditions, the molecular dynamics simulation was performed. Deep analysis of the simulation results revealed that ZINC257459695 can stably bind to nAChRs’ active sites and interact with the key residue Asp165. The binding free energies were also calculated for the obtained hits using the MM/GBSA method. In silico ADMET calculations were performed to assess the pharmacokinetic properties of hit compounds in the human body. Overall, the identified ZINC257459695 may be a promising lead compound for developing new NMBAs as an adjunct to general anesthesia, necessitating further investigations. Full article

The use of neuromuscular blocking agents (NMBAs) is common in the intensive care unit (ICU). NMBAs have been used in critically ill patients with lung diseases to optimize mechanical ventilation, prevent spontaneous respiratory efforts, reduce the work of breathing and oxygen consumption, and avoid patient–ventilator asynchrony. In patients with acute respiratory distress syndrome (ARDS), NMBAs reduce the risk of barotrauma and improve oxygenation. Nevertheless, current guidelines and evidence are contrasting regarding the routine use of NMBAs. In status asthmaticus and acute exacerbation of chronic obstructive pulmonary disease, NMBAs are used in specific conditions to ameliorate patient–ventilator synchronism and oxygenation, although their routine use is controversial. Indeed, the use of NMBAs has decreased over the last decade due to potential adverse effects, such as immobilization, venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, ICU-acquired weakness, and residual paralysis after cessation of NMBAs use. The aim of this review is to highlight current knowledge and synthesize the evidence for the effects of NMBAs for critically ill patients with lung diseases, focusing on patient–ventilator asynchrony, ARDS, status asthmaticus, and chronic obstructive pulmonary disease. Full article

(1) Background: The physiological and pharmacological variations between men and women are known to influence drug efficacy. The objective of this study was to determine the 50% and 95% effective doses (ED₅₀ and ED₉₅) of remimazolam required for i-gel supraglottic airway (ISA) insertion under remifentanil infusion without neuromuscular blocking agents (NMBAs) in both males and females. (2) Methods: Patients aged 19–65 years, scheduled for general anesthesia using ISA, were enrolled in this study. Patients were divided into two groups based on their sex. The anesthesia process began with a remifentanil infusion targeting an effect-site concentration of 3.0 ng/mL, accompanied by a remimazolam injection. The initial remimazolam dose was 0.25 mg/kg, and it was adjusted with a step size of 0.05 mg/kg based on the outcome of ISA insertion in the preceding patient. (3) Results: The ED₅₀ of remimazolam (mean ± standard error) was 0.28 ± 0.02 mg/kg in the male group and 0.18 ± 0.02 mg/kg in the female group (p < 0.001). Additionally, ED₉₅, which was calculated using the isotonic regression method, was significantly comparable between the male and female groups (male: 0.35 mg/kg, 95% confidence interval [CI] = 0.34–0.35; female: 0.29 mg/kg, 95% CI = 0.25–0.30). (4) Conclusions: This study showed that both the ED₅₀ and the ED₉₅ of remimazolam for successful ISA insertion was higher for men than that for women. Therefore, while using remimazolam alongside remifentanil infusion without NMBAs for ISA insertion, one should consider the patient’s sex for appropriate dosing. Full article

Background: Neuromuscular blocking agent (NMBA) monitoring and reversals are key to avoiding residual curarization and improving patient outcomes. Sugammadex is a NMBA reversal with favorable pharmacological properties. There is a lack of real-world data detailing how the diffusion of sugammadex affects anesthetic monitoring and practice. Methods: We conducted an electronic health record analysis study, including all adult surgical patients undergoing general anesthesia with orotracheal intubation, from January 2016 to December 2019, to describe changes and temporal trends of NMBAs and NMBA reversals administration. Results: From an initial population of 115,046 surgeries, we included 37,882 procedures, with 24,583 (64.9%) treated with spontaneous recovery from neuromuscular block and 13,299 (35.1%) with NMBA reversals. NMBA reversals use doubled over 4 years from 25.5% to 42.5%, mainly driven by sugammadex use, which increased from 17.8% to 38.3%. Rocuronium increased from 58.6% (2016) to 94.5% (2019). Factors associated with NMBA reversal use in the multivariable analysis were severe obesity (OR 3.33 for class II and OR 11.4 for class III obesity, p-value < 0.001), and high ASA score (OR 1.47 for ASA III). Among comorbidities, OSAS, asthma, and other respiratory diseases showed the strongest association with NMBA reversal administration. Conclusions: Unrestricted availability of sugammadex led to a considerable increase in pharmacological NMBA reversal, with rocuronium use also rising. More research is needed to determine how unrestricted and safer NMBA reversal affects anesthesia intraoperative monitoring and practice. Full article

Acute respiratory distress syndrome (ARDS) accounts for a quarter of mechanically ventilated patients, while during the pandemic, it overwhelmed the capacity of intensive care units (ICUs). Lung protective ventilation (low tidal volume, positive-end expiratory pressure titrated to lung mechanics and oxygenation, permissive hypercapnia) is a non-pharmacological approach that is the gold standard of management. Among the pharmacological treatments, the use of neuromuscular blocking agents (NMBAs), although extensively studied, has not yet been well clarified. The rationale is to minimize the risk for lung damage progression, in the already-injured pulmonary parenchyma. By abolishing rigorous spontaneous efforts, NMBAs may decrease the generation of high transpulmonary pressures that could aggravate patients’ self-inflicted lung injury. Moreover, NMBAs can harmonize the patient–ventilator interaction. Recent randomized controlled trials reported contradictory results and changed the clinical practice in a bidirectional way. NMBAs have not been documented to improve long-term survival; thus, the current guidance suggests their use only in patients in whom a lung protective ventilation protocol cannot be applied, due to asynchrony or increased respiratory efforts. In the present review, we discuss the published data and additionally the clinical practice in the “war” conditions of the COVID-19 pandemic, concerning NMBA use in the management of patients with ARDS. Full article

Objectives: To assess differences in the use of analgesics, sedatives and neuromuscular-blocking agents (NMBA) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19 or other conditions. Methods: Retrospective observational cohort study, single-center tertiary Intensive Care Unit. COVID-19 patients with ARDS (March–May 2020) and non-COVID ARDS patients (2017–2020) on mechanical ventilation and receiving sedation for at least 48 h. Results: A total of 39 patients met the inclusion criteria in each group, with similar demographics at baseline. COVID-19 patients had a longer duration of MV (median 22 (IQRs 16–29) vs. 9 (6–18) days; p < 0.01), of sedatives administration (18 (11–22) vs. 5 (4–9) days; p < 0.01) and NMBA therapy (12 (9–16) vs. 3 (2–7) days; p < 0.01). During the first 7 days of sedation, compared to non-COVID patients, COVID patients received more frequently a combination of multiple sedative drugs (76.9% vs. 28.2%; p < 0.01) and a higher NMBA regimen (cisatracurium: 3.0 (2.1–3.7) vs. 1.3 (0.9–1.9) mg/kg/day; p < 0.01). Conclusions: The duration and consumption of sedatives and NMBA was significantly increased in patients with COVID-19 related ARDS than in non-COVID ARDS. Different sedation strategies and protocols might be needed in COVID-19 patients with ARDS, with potential implications on long-term complications and drugs availability. Full article

COVID-19 patients suffering from severe acute respiratory distress syndrome (ARDS) require mechanical ventilation (MV) for respiratory failure. To achieve these ventilatory goals, it has been observed that COVID-19 patients in particular require high regimens and prolonged use of sedatives, analgesics and neuromuscular blocking agents (NMBA). Withdrawal from analgo-sedation may induce a “drug withdrawal syndrome” (DWS), i.e., clinical symptoms of anxiety, tremor, agitation, hallucinations and vomiting, as a result of adrenergic activation and hyperalgesia. We describe the epidemiology, mechanisms leading to this syndrome and our strategies to prevent and treat it. Full article

Individuals with spastic cerebral palsy (CP) often exhibit altered sensitivities to neuromuscular blocking agents (NMBAs) used for surgical intubation. We assessed usage of the NMBA rocuronium in patients with spastic CP and evaluated potential modifiers of dosing including gross motor function classification system (GMFCS) level, birthweight, gestational age, and the use of anticonvulsant therapy. In a case-control study, surgical patients with spastic CP (n = 64) or with idiopathic or non-neuromuscular conditions (n = 73) were enrolled after informed consent/assent. Patient data, GMFCS level, anticonvulsant use, and rocuronium dosing for intubation and post-intubation neuromuscular blockade were obtained from medical records. Findings reveal participants with CP required more rocuronium per body weight for intubation than controls (1.00 ± 0.08 versus 0.64 ± 0.03 mg/kg; p < 0.0001). Dosing increased with GMFCS level (Spearman’s rho = 0.323; p = 0.005), and participants with moderate to severe disability (GMFCS III-V) had elevated rocuronium with (1.21 ± 0.13 mg/kg) or without (0.86 ± 0.09 mg/kg) concurrent anticonvulsant therapy. Children born full-term or with birthweight >2.5 kg in the CP cohort required more rocuronium than preterm and low birthweight counterparts. Individuals with CP exhibited highly varied and significant resistance to neuromuscular blockade with rocuronium that was related to GMFCS and gestational age and weight at birth. Full article

The diagnostic performance of the bispectral index (BIS) to early predict neurological outcomes in patients achieving return of spontaneous circulation (ROSC) after cardiac arrest (CA) remained unclear. We searched PubMed, EMBASE, Scopus and CENTRAL for relevant studies through October 2019. Methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Meta-analysis was performed using a linear mixed-effects model to the log-transformed data with a logistic distribution assumption. Bivariate meta-regression was performed to explore heterogeneity. In total, 13 studies with 999 CA adult patients were included. At the optimal threshold of 32, BIS obtained within 72 h of ROSC elicits a pooled sensitivity of 84.9% (95% confidence interval (CI), 71.1% to 92.7%), a pooled specificity of 85.9% (95% CI, 71.2% to 93.8%) and an area under the curve of 0.92. Moreover, a BIS cutoff < 12 yielded a pooled specificity of 95.0% (95% CI, 77.8% to 99.0%). In bivariate meta-regression, the timing of neurological outcome assessment, the adoption of targeted temperature management, and the administration of sedative agents or neuromuscular blocking agents (NMBA) were not identified as the potential source of heterogeneity. BIS retains good diagnostic performance during targeted temperature management (TTM) and in the presence of administrated sedative agents and NMBA. In conclusion, BIS can predict poor neurological outcomes early in patients with ROSC after CA with good diagnostic performance and should be incorporated into the neuroprognostication strategy algorithm. Full article

Approximately 60% of perioperative anaphylactic reactions are thought to be immunoglobulin IgE mediated, whereas 40% are thought to be non-IgE mediated hypersensitivity reactions (both considered non-dose-related type B adverse drug reactions). In both cases, symptoms are elicited by mast cell degranulation. Also, pharmacological reactions to drugs (type A, dose-related) may sometimes mimic symptoms triggered by mast cell degranulation. In case of hypotension, bronchospasm, or urticarial rash due to mast cell degranulation, identification of the responsible mechanism is complicated. However, determination of the type of the underlying adverse drug reaction is of paramount interest for the decision of whether the culprit drug may be re-administered. Neuromuscular blocking agents (NMBA) are among the most frequent cause of perioperative anaphylaxis. Recently, it has been shown that NMBA may activate mast cells independently from IgE antibodies via the human Mas-related G-protein-coupled receptor member X2 (MRGPRX2). In light of this new insight into the patho-mechanism of pseudo-allergic adverse drug reactions, in which as drug-receptor interaction results in anaphylaxis like symptoms, we critically reviewed the literature on NMBA-induced perioperative anaphylaxis. We challenge the dogma that NMBA mainly cause IgE-mediated anaphylaxis via an IgE-mediated mechanism, which is based on studies that consider positive skin test to be specific for IgE-mediated hypersensitivity. Finally, we discuss the question whether MRGPRX2 mediated pseudo-allergic reactions should be re-classified as type A adverse reactions. Full article