Nondepolarizing Neuromuscular Blocking Agents Research Articles

The role of mivacurium in contemporary anesthesiology: a narrative review

Background: Mivacurium is the shortest-acting non-depolarizing neuromuscular blocking agent (NMBA) with a rapid onset of action that is mainly used for short procedures. Despite the fact that mivacurium has a very favorable average 6-minute recovery index after its infusion in comparison to the approximately 15–30 minutes for atracurium, mivacurium is still not really popular among practicing anesthesiologists. Many new studies showing the potential further benefits of implementing mivacurium into daily practice are still being published. Aim of the Study: This study aimed to focus on spreading the common knowledge about the detailed pharmacokinetic and pharmacodynamic properties of mivacurium as a medication that has yet to be used widely by practicing anesthesiologists. Material and methods: The literature review was conducted using the common sources of original articles such as PubMed and Google Scholar from 1975 to September 2022. Results: Based on the literature review, we observed that Mivacurium at a dosage of 6μg produces a lower impact on hemodynamics, shorter intubation and extubation times, faster postoperative recovery, absence of the accumulation of neuromuscular blockade, higher safety, and no significant increase in allergic related adverse events in comparison with other NMBAs.Conclusions: Mivacurium is a muscle relaxant medication that is particularly suited for short-lasting surgical procedures. However, it is important to remember that existing mutations in the butyrylcholinesterase enzyme (BChE) may prolong the effect of the neuromuscular blockade due to significantly reducing plasma cholinesterase activity. Therefore, it is advised to stay cautious during its use as more research needs to be done to be able to thoroughly assess the potential advantages and disadvantages of mivacurium introduction in particular patients

Sugammadex Use Outside of the Postoperative Setting.

Sugammadex rapidly reverses the nondepolarizing neuromuscular blocking agents (NMBAs) rocuronium and vecuronium. The role of sugammadex is not well-defined outside of the postoperative setting. This study aims to describe sugammadex use outside the postoperative setting for the reversal of nondepolarizing NMBAs. This was a single-center, retrospective cohort study conducted in patients who received sugammadex outside of the postoperative setting at an academic medical center between June 2016 and November 2022. The primary outcome was the effect of sugammadex use for rocuronium reversal, defined as any increase in train-of-four (TOF) after sugammadex administration and/or progress note documentation if TOF was unavailable. Secondary outcomes included adverse events and documentation of contraceptive counseling in patients taking hormonal contraceptives with child-bearing ability. A total of 14 383 patients received sugammadex during the study period. Of those patients, 39 (0.3%) were outside of the postoperative setting for the reversal of rocuronium and included in the study. Twenty-nine (74%) patients had an increase in TOF after sugammadex administration and/or progress note documentation if TOF was unavailable. Ten (26%) patients lacked documentation regarding the effect of sugammadex. No adverse reactions were reported. Three (8%) patients included in the study were of child-bearing ability, and 1 of the 3 patients was counseled on using an alternative method of contraception following sugammadex administration. There is a paucity of literature for the use of sugammadex outside of the postoperative setting. This study found that while the use of sugammadex was rare, overall, it was safe and well-tolerated.

Current Practices and Safety of Medication Use During Pediatric Rapid Sequence Intubation

OBJECTIVES This study aimed to characterize medication-related practices during and immediately ­following rapid sequence intubation (RSI) in pediatric care units across the United States and to evaluate adverse drug events. METHODS This was a multicenter, observational study of medication practices surrounding intubation in pediatric and neonatal intensive care unit (NICU) and emergency department patients across the United States. RESULTS A total of 172 patients from 13 geographically diverse institutions were included. Overall, 24%, 69%, and 50% received preinduction, induction, and neuromuscular blockade, respectively. Induction and neuromuscular blocking agent (NMBA) use was low in NICU patients (52% and 23%, respectively), whereas nearly all patients intubated outside of the NICU received both (98% and 95%, respectively). NICU patients who received RSI medications were older and weighed more. Despite infrequent use of atropine (21%), only 3 patients developed bradycardia after RSI. Of the 119 patients who received an induction agent, fentanyl (67%) and midazolam (34%) were administered most frequently. Hypotension and hypertension occurred in 23% and 24% of patients, respectively, but were not associated with a single induction agent. Etomidate use was low and not associated with development of adrenal insufficiency. Rocuronium was the most used NMBA (78%). Succinylcholine use was low (11%) and administered despite hyperkalemia in 2 patients. Postintubation sedation and analgesia were not used or inadequate based on timing of initiation in many patients who received a non-depolarizing NMBA. CONCLUSIONS Medication practices surrounding pediatric RSI vary across the United States and may be influenced by patient location, age, and weight.

Extreme Paralysis Following Rocuronium Administration in a Myasthenia Gravis Patient: A Case Report.

The use of paralytics during rapid sequence intubation (RSI) in patients with myasthenia gravis (MG) remains a controversial topic in emergency medicine. Due to fewer functional acetylcholine receptors, these patients can be both sensitive and resistant to different types of neuromuscular blocking agents (NMBA). Their atypical sensitivity to non-depolarizing NMBAs such as rocuronium can increase both the duration and depth of paralysis after its use at typical RSI doses. However, the extent of rocuronium's prolonged duration of effect in patients with MG has yet to be quantified in an emergency department setting. We describe a case wherein a full RSI dose of 1.2 milligrams per kilogram of rocuronium led to a prolonged 232-minute duration of paralysis in a patient with MG. This sustained paralysis was suspected but only confirmed after the patient received the reversal agent sugammadex. Once administered, an acute change in neurologic function was seen, and the patient was emergently taken to the operating room for neurosurgical intervention. When intubating patients with MG, many emergency physicians are aware that using paralytics during RSI provides several challenges. If not properly dose-reduced, rocuronium may exert its paralytic effects for up to four hours in patients with MG. This unique case highlights the importance of personalizing care for this patient population before, during, and after RSI.

Incidence of postoperative residual neuromuscular blockade - A multicenter, observational study in Portugal (INSPIRE 2).

Although the use of neuromuscular blocking agents (NMBAs) optimizes surgical conditions and facilitates tracheal intubation, it can lead to residual neuromuscular blockade (RNMB), with postoperative complications. This study aimed to assess RNMB incidence and management in Portugal. Prospective observational study of patients admitted for elective surgery requiring general anesthesia with nondepolarizing NMBAs between July 2018 and July 2019 at 10 Portuguese hospitals. The primary endpoint was the proportion of patients arriving at postanesthesia care unit (PACU) with a TOF ratio <0.9. A total of 366 patients were included, with a median age of 59 years, and 89.1% classified as ASA II or III. Rocuronium was the most used NMBA (99.5%). A total of 96.2% of patients received a reversal agent, 96.6% of which sugammadex and 3.4% neostigmine. Twenty patients displayed a TOF ratio <0.9 at PACU arrival, representing an RNMB incidence of 5.5% (95% CI, 3.1%-7.8%). Only two patients displayed a TOF ratio <0.7. RNMB incidence was 16.7% with neostigmine and 5.3% with sugammadex (P = .114). In patients with intraoperative neuromuscular blockade (NMB) monitoring, RNMB incidence was 5% (95% CI, 2%-8%), which varied significantly according to the type of monitoring (P = .018). Incidence of adverse events was 3.3% (2 severe and 10 moderate). The reported overall incidence of 5.5% is numerically lower than results from similar observational studies. An appropriate pharmacological neuromuscular reversal strategy, guided by quantitative neuromuscular monitoring, has the potential to achieve even better results, converting RNMB from an unusual to a very rare or even inexistent event.

Use of NMBA and reversal agent during thyroid surgery with intraoperative neuromonitoring

Neuromuscular blocking agent (NMBA) provides adequate muscle relaxation for intubation and surgery, but their use can interfere with the interpretation of intraoperative neuromonitoring (IONM) signals. Various strategies for the use of NMBA during thyroid surgery with IONM have been proposed for both safe anesthesia and surgery, and adequate quality of IONM. Relaxant-free anesthesia or use of succinylcholine is not recommended as a routine use due to the potential of fatal complications such as laryngeal injury or malignant. Instead, the use of a single dose of rocuronium for intubation with or without a reversal agent has been widely adapted. Though spontaneous recovery of neuromuscular blockade can be achieved without a reversal agent, use of a reversal agent can shorten the time for adequate IONM. Both neostigmine and Sugammadex can be used to reverse the neuromuscular blockade. Neostigmine reverses all types of non-depolarizing NMBA, but can accompany systemic cholinergic effect, and is not effective to deep or higher level of blockade. Sugammadex only reverses the effect of aminosteroid NMBAs, but effective to all levels of blockade. Overall, appropriate strategies for the use of NMBAs and reversal agents are needed to ensure effective IONM without increasing the risk of nerve injury during surgery.

Sugammadex administration in patients with end-stage renal disease: a narrative review with recommendations.

Due to unknown safety concerns, sugammadex should not be administered to patients withend-stage renal disease (ESRD). However, because the supply of benzylisoquinolinium-typeneuromuscular blocking agents (NMBAs) has been discontinued, rocuronium is the onlynon-depolarizing NMBA that can be used in clinical settings in some countries, includingSouth Korea. The administration of sugammadex cannot be avoided to achieve rapid andcomplete neuromuscular recovery in patients with ESRD or renal transplantation after rocuronium administration. Although there has been a limited number of clinical studies involving the use of sugammadex in patients with ESRD, studies have shown that sugammadexcan effectively and safely reverse rocuronium-induced neuromuscular blockade (NMB) inpatients with ESRD, however recovery of neuromuscular function in patients with ESRD isslower than in patients with normal renal function. Nonetheless, safety-concerns are yet tobe addressed. Considering the small number of clinical studies, high heterogeneity amongstudies, and insufficient safety information, more extensive data on the efficacy and safetyof sugammadex in patients with ESRD are needed. In particular, it is important to securedata on safety, including residual NMB after surgery, recurarization and cardiorespiratorycomplications, anaphylactic reactions, and long-term morbidity and mortality. Furthermore,anesthesiologists should remember that performing proper quantitative neuromuscularmonitoring and neuromuscular management based on the monitoring signs are the mostessential requirements when using sugammadex in patients with ESRD.

Nondepolarizing Neuromuscular Blocking Agents Exacerbate Inflammation Response by Antagonizing α7 Nicotinic Acetylcholine Receptors

<p id="p00005">Studies have indicated that Nondepolarizing neuromuscular blocking agents (NMBA) can inhibit α7-nicotinic acetylcholine receptors (α7 nAChR). Our study aimed to determine whether NMBA can enhance the release of tumor necrosis factor TNF-α via α7 nAChR antagonism. In vitro studies showed that primary blood mononuclear cells were stimulated with lipopolysaccharide (LPS)+acetylcholine (Ach). NMBA had been added 5 min before ACh Pre-treat human macrophages, and the supernatant was collected to measure the concentration of TNF-α. In vivo studies indicated that tissue samples were collected from NMBAs pre-treated animal models. The content of TNF-α in blood supernatant as well as in serum, liver, and spleen samples was detected. It can be found that TNF-α release from macrophages was enhanced by NMBA. In addition, rats that were pre-treated with NMBA were also found to have higher levels of TNF-α. Therefore, NMBA can enhance TNF-α releasing from macrophage cells compromised by endotoxin, through actions involving α7 nAChR.

Resistance to non-depolarizing neuromuscular blocking agents

The authors experienced three cases of the resistance to the nondepolarizing neuromuscular blocking agents (NMBAs), rocuronium. There are many factors that affect NMBAs such as steroid, endocrine or autoimmune diseases which are thyroid disease, parathyroid disease, myasthenia gravis and etc., and anticonvulsant medication. However, in these three cases, the patients did not have any neuromuscular disorder, except certain drug administration, smoking, endocrine disorder and fever. In this study, we report three cases of the resistance to rocuronium where the resistance duration was much shorter than known and we should be aware of the importance of neuromuscular monitoring.

Neuromuscular blockade management for intraoperative neural monitoring

This article reviews the literature on development of neuromuscular blockade management in thyroid surgery with intraoperative neural monitoring (IONM) in the past decade. Neuromuscular blockade management includes the choice of neuromuscular blocking agents (NMBAs) and reversal of neuromuscular blockade by sugammadex. A series of animal study and clinical trials showed NMBAs effect on IONM in thyroid surgery. We summarized five NMBA regimens for IONM: (a) relaxant-free regimen, (b) depolarizing NMBA-succinylcholine, (c) titration of nondepolarizing NMBA, and (d) rocuronium combined with sugammadex. The proper management of neuromuscular blockade during IONM has greatly developed over the past decade. The misuse of NMBAs is associated with false IONM interpretations to surgeons. A detailed understanding of NMBAs and neuromuscular blockade management by sugammadex may optimize IONM quality in patients receiving monitored thyroid surgery.

Effect of protracted dexamethasone exposure and its withdrawal on rocuronium-induced neuromuscular blockade and sugammadex reversal: an ex vivo rat study

Studies have reported that protracted dexamethasone treatment induces resistance to nondepolarizing neuromuscular blocking agents (NMBAs) and the association with nicotinic acetylcholine receptors in the diaphragm of rats. Here, we investigated the effect of protracted dexamethasone administration on the sensitivity to rocuronium and the recovery profile when reversed by sugammadex; additionally, we observed the recovery period of pharmacodynamic change after withdrawal. Sprague-Dawley rats received daily intraperitoneal injections of dexamethasone or saline for 14 days. On days 1, 3, and 7 after the last dexamethasone treatment (Dexa1, Dexa3, and Dexa7, respectively) or 1 day after saline (control group), the phrenic nerve-hemidiaphragm preparation was dissected for assay. The dose-response curve of rocuronium in Dexa1 was shifted to the right compared to controls, but curves in Dexa3 and Dexa7 were not significantly different. Groups were not significantly different in attaining the train-of-four ratio ≥ 0.9, but the recovery index in Dexa7 was shorter than that in control and Dexa1. Recovery profiles (period of sugammadex reversal) were not correlated with resistance properties but rather with total administered drugs (binding capacity of NMBAs and sugammadex). Protracted dexamethasone exposure induced resistance to rocuronium but seemed to have no effect on sugammadex reversal in the rat diaphragm.

Lethal self-administration of propofol and atracurium: Two case reports and literature review

Propofol is an intravenous anesthetic agent widely used in the induction and maintenance of general anesthesia. Acute intoxications with propofol are rare and remain primarily related to the acquisition of the product in hospital. If propofol can induce fatal respiratory depression alone, in a number of cases the clinical situation is exacerbated by the presence of other drugs like neuromuscular-blocking agents. Laudanosine, the circulating form of atracurium or cisatracurium, two non-depolarizing neuromuscular-blocking agents, is more frequently observed in toxicology. Such agents are widely used for tracheal intubations. Laudanosine has no pharmacological activity, which is exclusively due to the parent drugs. These agents can be fatal at any concentration, due to respiratory failure. Here, two cases of anesthesiologists’ suicide following self-administration of propofol-atracurium combination are reported. Case 1: a 48-years-old anesthesiologist was found without vital signs at his office. The drugs and paraphernalia used for delivery were discovered at the scene. Case 2: a 61-years-old anesthesiologist was found dead at home with a cannula connected to an infusion set at the bend of the elbow. Next to the body several empty ampoules of Diprivan ® and Atracurium besylate ® were found. For both cases, several biological specimens were collected for toxicological investigation. Comprehensive screenings of drugs and toxic compounds were performed using LC-DAD and GC-MS. Ethanol concentrations were determined using GC-FID. Laudanosine was quantified using LC-DAD. Propofol was quantified using GC-MS and LC-MS/MS. Propofol blood concentrations were 1 and 1.91 mg/L for case 1 and case 2, respectively (therapeutic range: 2–8 mg/L). Laudanosine blood concentrations were 0.13 and 1.18 mg/L for case 1 and case 2, respectively. Paroxetine, N-demethyldiazepam and ethanol were detected in the first case. Hydroxyzine was detected in the second case. In both cases, levels of these substances could not explain the death. Propofol related fatalities are rare, even more when combined with neuromuscular- blocking agents [1] . Propofol and atracurium concentrations documented here, are in agreement with those reported in the literature, these being characterized by a high inter-individual variability [2] . However, the concentrations observed in suicide cases compared to those observed in accidental fatalities (chronic abusers) appear to be much higher. In fact, three manners of death have been described with propofol: suicide, accidental overdose in chronic abusers, and more exceptionally, murder [3] . In the cases described here, circumstances and the use of atracurium suggest suicide. It should be noted that the concentrations of laudanosine and propofol observed here are in the usual anesthetic range. Albeit, it should be pointed out that for anesthetic agents, therapeutic concentrations are established for patients being supported respiratory-wise, while in non-supported or non-intubated patients such concentrations may be fatal. Therefore, the interpretation of the blood concentration in the forensic toxicological analysis must take into account the context and the circumstances of the death.

Effect of intraoperative neuromonitoring on efficacy and safety using sugammadex in thyroid surgery: randomized clinical trial.

PurposeThe use of nondepolarizing neuromuscular blocking agents (NMBAs) may affect intraoperative neuromonitoring (IONM) during anesthesia used during thyroid and parathyroid surgery.MethodsThe use of sugammadex was evaluated in a prospective clinical study during thyroid surgery. Between July 2018 and January 2019, 129 patients were prospectively randomized to either the sugammadex group (group B) or the control group (group A). Group A patients underwent standardized IONM during thyroidectomy, while group B patients used an NMBA-reversal protocol comprised of rocuronium (0.6 mg/kg) in anesthesia induction and sugammadex (2 mg/kg) after first vagal stimulation (V0). A peripheral nerve stimulator was used to monitor the neuromuscular transmission.ResultsIn our clinical study, it took 26.07 ± 3.26 and 50.0 ± 8.46 minutes to reach 100% recovery of laryngeal electromyography at injection of the sugammadex group (2 mg/kg) and the control group, respectively (P < 0.001). The train-of-four ratio recovered from 0 to >0.9 within 4 minutes after administering 2 mg/kg of sugammadex at the beginning of resection. Surgery time was significantly shorter in group B than in group A (P < 0.001). Transient recurrent laryngeal nerve (RLN) paralysis was detected in 4 patients from group A and in 3 patients from group B (P = 0.681). There was no permanent RLN paralysis in the 2 groups.ConclusionOur clinical study showed that sugammadex effectively and rapidly improved the inhibition of neuromuscular function induced by rocuronium. The implementation of the nondepolarizing neuromuscular block recovery protocol may lead to tracheal intubation as well as favorable conditions for IONM in thyroid surgery.

Incidence, risk factors, and consequences of residual neuromuscular block in the United States: The prospective, observational, multicenter RECITE-US study

Study objectiveTo determine the incidence burden and associated risk factors of residual neuromuscular block (rNMB) during routine U.S. hospital care. DesignBlinded multicenter cohort study. SettingOperating and recovery rooms of ten community and academic U.S. hospitals. PatientsTwo-hundred fifty-five adults, ASA PS 1–3, underwent elective abdominal surgery with general anesthesia and ≥1 dose of non-depolarizing neuromuscular blocking agent (NMBA) for endotracheal intubation and/or maintenance of NMB between August 2012 and April 2013. InterventionsTOF measurements using acceleromyography were performed on patients already receiving routine anesthetic care for elective open or laparoscopic abdominal surgery. Measurements allowed assessment of the presence of residual neuromuscular block (rNMB), defined as a train-of-four (TOF) ratio <0.9 at tracheal extubation. We recorded patient and procedural characteristics and assessed TOF ratios (T4/T1) at various times throughout the procedure and at tracheal extubation. Differences in patient and clinical characteristics were compared using Fisher's exact test for categorical variables and t-test for continuous variables. Multivariate logistic regression assessed risk factors associated with rNMB at extubation. Main resultsMost of the study population, 64.7% (n = 165) had rNMB (TOF ratio < 0.9), among them, 31.0% with TOF ratio <0.6. Among those receiving neostigmine and/or qualitative peripheral nerve stimulation per clinical decision, 65.0% had rNMB. After controlling for confounders, we observed male gender (odds ratio: 2.60, P = 0.008), higher BMI (odds ratio: 1.04/unit, P = 0.043), and surgery at a community hospital (odds ratio: 3.15, P = 0.006) to be independently associated with increased odds of rNMB. ConclusionsAssessing TOF ratios blinded to the care team, we found that the majority of patients (64.7%) in this study had rNMB at tracheal extubation, despite neostigmine administration and qualitative peripheral nerve stimulation used for routine clinical care. Qualitative neuromuscular monitoring and clinical judgement often fails to detect rNMB after neostigmine reversal with potential severe consequences to the patient. Our data suggests that clinical care could be improved by considering quantitative neuromuscular monitoring for routine care.

Intraoperative Use of Nondepolarizing Neuromuscular Blocking Agents During Cardiac Surgery and Postoperative Pulmonary Complications: A Prospective Randomized Trial

Nondepolarizing neuromuscular blocking agents (NMBAs) are associated with perioperative complications in noncardiac surgery; however, little is known about their effect on cardiac surgery. This study assessed the effect of neuromuscular blockade (NMB) on the incidence of postoperative pulmonary complications (PPCs) after cardiac surgery and operating conditions. Prospective, randomized clinical trial with blinded outcomes assessment. University hospital, single institution. Adult patients having cardiac surgery requiring cardiopulmonary bypass. One hundred patients were randomized to receive succinylcholine (group SUX) for intubation with no further NMB administered or cisatracurium (group CIS) for intubation and maintenance NMB. The primary outcome was a composite incidence of PPCs in the 72 hours after elective cardiac surgery. PPCs included failure to extubate within 24 hours, need for reintubation, pneumonia, aspiration, unanticipated need for noninvasive respiratory support, acute respiratory distress, and mortality from respiratory arrest. The secondary outcome was the adequacy of operating conditions as assessed by blinded surgeon survey (including a rating of surgical conditions on a Likert scale from 1 = poor to 5 = excellent), anesthesiologist report, and patient questionnaire. The composite incidence of PPCs did not differ between groups (8 of 50 patients in both groups; 16%). Mean surgeon rating of surgical conditions was lower in the SUX group (4.65 ± 0.85 v 4.96 ± 0.20, p = 0.02). Although avoiding nondepolarizing NMBA is feasible, doing so worsened operating conditions and did not reduce the incidence of postoperative pulmonary complications.

Sugammadex: Clinical Pharmacokinetics and Pharmacodynamics

The purpose of this chapter is to provide an evidence based understanding of the pharmacokinetics and pharmacodynamics of sugammadex. Sugammadex is a c-cyclodextrin that rapidly reverses the effect of aminosteroid nondepolarizing neuromuscular blocking agents (NMBAs) rocuronium and vecuronium by forming an inactive 1:1 complex. It is only available in an intravenous form with a bioavailabilty of 100%. It does not bind to plasma proteins and is eliminated unchanged by the kidneys. The type of NMBA used and the degree of the residual neuromuscular blockade at the time of administration determine the dose of sugammadex needed and the speed of reversal. Plasma levels of exogenous compounds with similar steroidal structure, such as some hormones, hormonal contraceptives, and pheromones may also be reduced following administration of sugammadex. While the package insert does not indicate dosage adjustments in elderly patients, or those with hepatic, cardiac, pulmonary comorbidities (not approved in pediatric patients less than 18 years or patients with a creatinine clearance less than 30 ml/min), sugammadex dosing possibly should be adjusted based upon the patient’s age and comorbidities, including liver or kidney failure and morbid obesity. Sugammadex has been shown to be an effective agent in reversing the effects of NMBAs with an acceptable safety and efficacy profile.

Survey of how different groups of veterinarians manage the use of neuromuscular blocking agents in anesthetized dogs

ObjectiveTo analyze practice habits associated with the use, reversal and monitoring of nondepolarizing neuromuscular blocking agents (NMBAs) in dogs by different groups of veterinarians. Study designOnline anonymous survey to veterinarians. PopulationData from 390 answered surveys. MethodsA questionnaire was sent to e-mail list servers of the American College of Veterinary Anesthesia and Analgesia (ACVAA-list), Sociedad Española de Anestesia y Analgesia Veterinaria (SEEAV-list), Colégio Brasileiro de Anestesiologia Veterinária (Brazilian College of Veterinary Anesthesiology; CBAV-list) and American College of Veterinary Ophthalmologists (ACVO-list) to elicit information regarding use of NMBAs and reversal agents, monitoring techniques, criteria for redosing, reversing and assessing adequacy of recovery of neuromuscular function. Binomial logistic regression was used to test for association between responses and group of veterinarians in selected questions. ResultsVeterinarians of the ACVO-list use NMBAs on a higher fraction of their caseload than other groups (all p < 0.0001). Subjective assessment (observation) of spontaneous movement, including spontaneous breathing, is the most common method for assessing neuromuscular function (43% of pooled responses); 18% of participants always reverse NMBAs, whereas 16% never reverse them. Restoration of neuromuscular function is assessed subjectively by 35% of respondents. Residual neuromuscular block is the most common concern regarding the use of NMBAs for all groups of veterinarians. Side effects of reversal agents (anticholinesterases) were of least concern for all groups. Conclusions and clinical relevanceWhile most veterinarians are concerned about residual neuromuscular block, relatively few steps are implemented to reduce the risks of this complication, such as routine use of quantitative neuromuscular monitoring or routine reversal of NMBAs. These results suggest a limitation in transferring information among groups of veterinarians, or in implementing techniques suggested by scientific research.

Mivacurium: a Review

Mivacurium is a short-acting non-depolarizing neuromuscular-blocking agent (NMBA) which has recently been re-released onto the US market. This review provides a brief overview about the pharmacology of mivacurium and discusses its use in recent clinical practice. Mivacurium has been reported to be especially useful in the pediatric population, especially for shorter cases, and infusions can be used for longer cases without inducing tachyphylaxis. As it is rapidly metabolized by pseudocholinesterase (PChE), mivacurium does usually not require a specific reversal agent to offset its actions at the end of surgery. Especially for use in short cases, this makes it a potentially advantageous alternative to the use of other NMBA. However, deficiencies in PChE as well as old age and some drug interactions can be associated with prolonged neuromuscular blockade. The rapid administration of higher doses may provoke significant histamine release leading to hemodynamic compromise. Despite other NMBA being available on the market and its side effects, mivacurium may still be a useful agent in short cases, particularly in the pediatric population.

Effect of anaesthetic and choice of neuromuscular blocker on vagal control of heart rate under laboratory animal experimental conditions.

Neuromuscular-blocking agents are commonly used in laboratory animal research settings. Due to actions of cholinergic receptors at locations other than the motor end-plate, these agents have a strong propensity to modulate autonomic outflow and may therefore not be desirable in studies examining autonomic function. This study aimed to compare the effect of two non-depolarizing neuromuscular-blocking agents, pancuronium and cisatracurium, on blood pressure, heart rate and non-invasive indices of autonomic function (heart rate variability, systolic blood pressure variability and baroreflex sensitivity) under two different types of anaesthesia in Lewis rats. Pancuronium produced a profound vagolytic response characterized by tachycardia, reduction in heart rate variability and baroreflex sensitivity under urethane anaesthesia, and with minimal effect under isoflurane anaesthesia. Conversely, cisatracurium produced no evidence of vagolytic action under either urethane or isoflurane anaesthesia. Therefore, for studies interested in examining autonomic function, particularly baroreflex or vagal function, neuromuscular blockade would be best achieved using cisatracurium.

Anesthetic management of a child with phosphomannomutase-2 congenital disorder of glycosylation (PMM2-CDG)

BackgroundGlycosylation is one of the major posttranslational modifications of proteins and it is essential for proteins to obtain normal biological functions. Congenital disorders of glycosylation (CDGs) are very rare genetic disorders that lack enzymes needed for glycosylation. Phosphomannomutase-2 (PMM2)-CDG is the most common type of CDG. CDGs can cause a wide variety of clinical symptoms in almost every organ system. Muscular hypotonia is often present in patients with CDGs and is one of the most notable problems for anesthetic management because the susceptibility to nondepolarizing neuromuscular blocking agents (NMBAs) in patients with CDGs is unknown.Case presentationThe patient was a 17-month-old boy who weighed 6.5 kg and was 71 cm tall. He presented for strabismus surgery. He had muscular hypotonia, mental retardation, hepatic dysfunction, mild cerebellar hypoplasia, and some dysmorphic features including inverted nipples and abnormal subcutaneous fat distribution of the hips. Gene analysis revealed a compound heterozygous mutation in the gene encoding PMM2 and the patient was diagnosed as having PMM2-CDG. General anesthesia was performed with sevoflurane, nitrous oxide, and rocuronium. Neuromuscular monitoring was performed during anesthesia using train-of-four (TOF)-Watch® (MSD, Japan). As postoperative analgesia, the surgeon performed sub-Tenon’s anesthesia. We did not use any intravenous analgesic. After completion of the operation, residual rocuronium was competed by administration of sugammadex. The patient gained consciousness and spontaneous breathing was established shortly thereafter, and the trachea was smoothly extubated. He was transported to an inpatient ward and was discharged to his home the next day without any complication.ConclusionsWe performed safe anesthetic management in a 17-month-old boy with PMM2-CDG using rocuronium under neuromuscular monitoring.A patient with PMM2-CDG may show nearly normal susceptibility to nondepolarizing NMBAs.