Sugammadex, the Guardian of Deep Muscle Relaxation During Conventional and Robot-Assisted Laparoscopic Surgery: A Narrative Review.

High intra-abdominal pressure induced by artificial pneumoperitoneum can obviously impair respiratory and circulatory functions and has a negative effect on the prognosis of patients undergoing conventional and robot-assisted laparoscopic surgery. The application of deep neuromuscular blockade during the operation is reported to lower the intra-abdominal pressure and improve patients' outcome. However, concern lies in the risks of postoperative residual muscular paralysis with the use of deep neuromuscular blockade. Sugammadex, a specific antagonist for aminosteroids muscle relaxants, can effectively and rapidly reverse rocuronium and vecuronium induced neuromuscular blockade of different depths. Thus, sugammadex allows the ability to safeguard the application of deep neuromuscular blockade in laparoscopic operations and helps to alleviate the adverse complications associated with pneumoperitoneum. Here, we review the application of deep neuromuscular blockade in different laparoscopic surgeries and discuss the benefits and possible risks of sugammadex administration in the reversal of deep neuromuscular blockade in these operations.

Pharmacokinetics of Sugammadex Dosed by Actual and Ideal Body Weight in Patients With Morbid Obesity Undergoing Surgery.

This analysis of a published study (NCT03346070) evaluated the pharmacokinetics (PKs) of sugammadex dosed by actual body weight (ABW) or ideal body weight (IBW) for reversal of moderate or deep neuromuscular block (M-NMB or D-NMB) in adults with morbid obesity. Adults with body mass index ≥ 40 kg/m2 , ABW ≥ 100 kg, and American Society of Anesthesiologists (ASA) Class 3 were stratified by NMB agent (rocuronium or vecuronium) and randomized 1:1:1:1:1 to (i) M-NMB, sugammadex 2 mg/kg ABW; (ii) M-NMB, sugammadex 2 mg/kg IBW; (iii) M-NMB, neostigmine 5 mg + glycopyrrolate 1 mg; (iv) D-NMB, sugammadex 4 mg/kg ABW; and (v) D-NMB, sugammadex 4 mg/kg IBW. Plasma samples for sugammadex quantification were collected predose, 2, 5, 15, 60, and 120 minutes, and 4, 6 hours postdose. Natural log PK parameters were analyzed using linear fixed effect model with treatment, mode (ABW and IBW), and mode by treatment interaction as fixed terms. The sugammadex PK profile showed rapid distribution followed by monophasic decline consistent with a two-compartment model examined by dose and mode. Absolute sugammadex exposures were ~ 50% higher in the ABW vs. IBW group; dose-independent parameters (clearance and volume of distribution) and terminal half-life remained constant. Sugammadex PK parameter values increased in dose-dependent, linear manner following dosing by ABW or IBW, such that PK continues to be predictive across the clinical dose range. In conjunction with previously published results showing faster recovery with ABW vs. IBW dosing across NMB agent and depth of NMB, these PK findings continue to support dosing by ABW in patients with morbid obesity irrespective of depth of NMB.

Sugammadex Administration in Pregnant Women and in Women of Reproductive Potential: A Narrative Review.

Since its clinical introduction in 2008, sugammadex has demonstrated a high degree of safety and superior effectiveness compared to neostigmine when used to antagonize muscle relaxation produced by steroid nondepolarizing neuromuscular blockers. This includes its use in special populations, such as the elderly, children over 2 years old, and patients with renal, hepatic, or lung disease. In contrast, clinical evidence guiding its use during pregnancy, in women of childbearing potential, and in lactating women, is sparse. An exception is administration at the end of surgery in parturients undergoing cesarean delivery (CD) with general anesthesia (GA), for whom effectiveness and safety evidence is rapidly accumulating. We review evidence regarding sugammadex rescue reversal shortly after high-dose rocuronium in cases of cannot intubate/cannot ventilate (CICV), the extent of placental transfer of maternally administered sugammadex, adverse fetal effects of sugammadex exposure, potential effects on maintenance of early pregnancy, and the extent of transfer to breast milk. Finally, many anesthesiologists appear to heed the manufacturer's warning regarding informing women of childbearing potential regarding the risk of hormone contraceptive failure after sugammadex exposure. We provide a medical ethics analysis of the ex post facto counseling commonly reported after sugammadex administration, which favors either preoperative discussion and shared decision making, or the decision by the physician to use neostigmine. This review highlights the disparity in evidence regarding sugammadex use in various contexts of female reproductive health, including current research gaps that prevent this population from sharing in the benefits of sugammadex enjoyed by most perioperative patients.

Is lower-dose sugammadex a cost-saving strategy for reversal of deep neuromuscular block? Facts and fiction.

BACKGROUND: Sugammadex, a γ-cyclodextrin derivative, belongs to a new class of selective relaxant binding agents. Sugammadex was approved 10-years ago by the European medicines agency and today is used in clinical anesthesia and emergency medicine globally. In this review, indications for neuromuscular block, the challenge of neuromuscular monitoring and the practice of under-dosing of sugammadex as a potential cost-saving strategy are discussed. MAIN BODY: Reversal of neuromuscular block is important to accelerate the spontaneous recovery of neuromuscular function. Sugammadex is able to reverse a rocuronium- or vecuronium-induced neuromuscular block rapidly and efficiently from every depth of neuromuscular block. However, since sugammadex was introduced in clinical anesthesia, several studies have reported administration of a lower-than-recommended dose of sugammadex. The decision to under-dose sugammadex is often motivated by cost reduction concerns, as the price of sugammadex is much higher than that of neostigmine outside the United States. However, under-dosing of sugammadex leads to an increased risk of recurrence of neuromuscular block after an initial successful (but transient) reversal. Similarly, when not using objective neuromuscular monitoring, under-dosing of sugammadex may result in residual neuromuscular block in the postoperative care unit, with its attendant negative pulmonary outcomes. Therefore, an appropriate dose of sugammadex, based on objective determination of the depth of neuromuscular block, should be administered to avoid residual or recurrent neuromuscular block and attendant postoperative complications. Whether the reduction in perioperative recovery time of the patient can be translated into additional procedural cases performed, faster operative turnover times, or improved organizational resource utilization, has yet to be determined in actual clinical practice that includes verification of neuromuscular recovery prior to tracheal extubation. CONCLUSIONS: The current review addresses the indications for neuromuscular block, the challenge of neuromuscular monitoring, the practice of under-dosing of sugammadex as a potential cost-saving strategy in reversal of deep neuromuscular block, the economics of sugammadex administration and the potential healthcare cost-saving strategies.

Effectiveness of sugammadex versus neostigmine on restoration of neuromuscular function in surgical patients with myasthenia gravis undergoing rocuronium-induced neuromuscular blockade: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to identify the effectiveness of sugammadex versus neostigmine on the reversal of rocuronium-induced neuromuscular blockade in surgical patients with myasthenia gravis undergoing general anesthesia.

Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults.

BACKGROUND: Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs have significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety, reduced incidence of residual block on recovery, and more efficient use of healthcare resources. OBJECTIVES: The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents in adults. SEARCH METHODS: We searched the following databases on 2 May 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (WebSPIRS Ovid SP), Embase (WebSPIRS Ovid SP), and the clinical trials registries www.controlled-trials.com, clinicaltrials.gov, and www.centerwatch.com. We re-ran the search on 10 May 2017. SELECTION CRITERIA: We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We included adults, classified as American Society of Anesthesiologists (ASA) I to IV, who received non-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts to identify trials for eligibility, examined articles for eligibility, abstracted data, assessed the articles, and excluded obviously irrelevant reports. We resolved disagreements by discussion between review authors and further disagreements through consultation with the last review author. We assessed risk of bias in 10 methodological domains using the Cochrane risk of bias tool and examined risk of random error through trial sequential analysis. We used the principles of the GRADE approach to prepare an overall assessment of the quality of evidence. For our primary outcomes (recovery times to train-of-four ratio (TOFR) > 0.9), we presented data as mean differences (MDs) with 95 % confidence intervals (CIs), and for our secondary outcomes (risk of adverse events and risk of serious adverse events), we calculated risk ratios (RRs) with CIs. MAIN RESULTS: We included 41 studies (4206 participants) in this updated review, 38 of which were new studies. Twelve trials were eligible for meta-analysis of primary outcomes (n = 949), 28 trials were eligible for meta-analysis of secondary outcomes (n = 2298), and 10 trials (n = 1647) were ineligible for meta-analysis.We compared sugammadex 2 mg/kg and neostigmine 0.05 mg/kg for reversal of rocuronium-induced moderate neuromuscular blockade (NMB). Sugammadex 2 mg/kg was 10.22 minutes (6.6 times) faster then neostigmine 0.05 mg/kg (1.96 vs 12.87 minutes) in reversing NMB from the second twitch (T2) to TOFR > 0.9 (MD 10.22 minutes, 95% CI 8.48 to 11.96; I2 = 84%; 10 studies, n = 835; GRADE: moderate quality).We compared sugammadex 4 mg/kg and neostigmine 0.07 mg/kg for reversal of rocuronium-induced deep NMB. Sugammadex 4 mg/kg was 45.78 minutes (16.8 times) faster then neostigmine 0.07 mg/kg (2.9 vs 48.8 minutes) in reversing NMB from post-tetanic count (PTC) 1 to 5 to TOFR > 0.9 (MD 45.78 minutes, 95% CI 39.41 to 52.15; I2 = 0%; two studies, n = 114; GRADE: low quality).For our secondary outcomes, we compared sugammadex, any dose, and neostigmine, any dose, looking at risk of adverse and serious adverse events. We found significantly fewer composite adverse events in the sugammadex group compared with the neostigmine group (RR 0.60, 95% CI 0.49 to 0.74; I2 = 40%; 28 studies, n = 2298; GRADE: moderate quality). Risk of adverse events was 28% in the neostigmine group and 16% in the sugammadex group, resulting in a number needed to treat for an additional beneficial outcome (NNTB) of 8. When looking at specific adverse events, we noted significantly less risk of bradycardia (RR 0.16, 95% CI 0.07 to 0.34; I2= 0%; 11 studies, n = 1218; NNTB 14; GRADE: moderate quality), postoperative nausea and vomiting (PONV) (RR 0.52, 95% CI 0.28 to 0.97; I2 = 0%; six studies, n = 389; NNTB 16; GRADE: low quality) and overall signs of postoperative residual paralysis (RR 0.40, 95% CI 0.28 to 0.57; I2 = 0%; 15 studies, n = 1474; NNTB 13; GRADE: moderate quality) in the sugammadex group when compared with the neostigmine group. Finally, we found no significant differences between sugammadex and neostigmine regarding risk of serious adverse events (RR 0.54, 95% CI 0.13 to 2.25; I2= 0%; 10 studies, n = 959; GRADE: low quality).Application of trial sequential analysis (TSA) indicates superiority of sugammadex for outcomes such as recovery time from T2 to TOFR > 0.9, adverse events, and overall signs of postoperative residual paralysis. AUTHORS' CONCLUSIONS: Review results suggest that in comparison with neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular block regardless of the depth of the block. Sugammadex 2 mg/kg is 10.22 minutes (˜ 6.6 times) faster in reversing moderate neuromuscular blockade (T2) than neostigmine 0.05 mg/kg (GRADE: moderate quality), and sugammadex 4 mg/kg is 45.78 minutes (˜ 16.8 times) faster in reversing deep neuromuscular blockade (PTC 1 to 5) than neostigmine 0.07 mg/kg (GRADE: low quality). With an NNTB of 8 to avoid an adverse event, sugammadex appears to have a better safety profile than neostigmine. Patients receiving sugammadex had 40% fewer adverse events compared with those given neostigmine. Specifically, risks of bradycardia (RR 0.16, NNTB 14; GRADE: moderate quality), PONV (RR 0.52, NNTB 16; GRADE: low quality), and overall signs of postoperative residual paralysis (RR 0.40, NNTB 13; GRADE: moderate quality) were reduced. Both sugammadex and neostigmine were associated with serious adverse events in less than 1% of patients, and data showed no differences in risk of serious adverse events between groups (RR 0.54; GRADE: low quality).

Reversal of Vecuronium-induced Neuromuscular Blockade with Low-dose Sugammadex at Train-of-four Count of Four: A Randomized Controlled Trial.

BACKGROUND: Rocuronium-induced neuromuscular block that spontaneously recovered to a train-of-four count of four can be reversed with sugammadex 0.5 or 1.0 mg/kg. We investigated whether these doses of sugammadex can also reverse vecuronium at a similar level of block. METHODS: Sixty-five patients were randomly assigned, and 64 were analyzed in this controlled, superiority study. Participants received general anesthesia with propofol, sevoflurane, fentanyl, and vecuronium. Measurement of neuromuscular function was performed with acceleromyography (TOF-Watch-SX, Organon Teknika B.V., The Netherlands ). Once the block recovered spontaneously to four twitches in response to train-of-four stimulation, patients were randomly assigned to receive sugammadex 0.5, 1.0, or 2.0 mg/kg; neostigmine 0.05 mg/kg; or placebo. Time from study drug injection to normalized train-of-four ratio 0.9 and the incidence of incomplete reversal within 30 min were the primary outcome variables. Secondary outcome was the incidence of reparalysis (normalized train-of-four ratio less than 0.9). RESULTS: Sugammadex, in doses of 1.0 and 2.0 mg/kg, reversed a threshold train-of-four count of four to normalized train-of-four ratio of 0.9 or higher in all patients in 4.4 ± 2.3 min (mean ± SD) and 2.6 ± 1.6 min, respectively. Sugammadex 0.5 mg/kg reversed the block in 6.8 ± 4.1 min in 70% of patients (P < 0.0001 vs. 1.0 and 2.0 mg/kg), whereas neostigmine produced reversal in 11.3 ± 9.7 min in 77% of patients (P > 0.05 vs. sugammadex 0.5 mg/kg). The overall frequency of reparalysis was 18.7%, but this incidence varied from group to group. CONCLUSIONS: Sugammadex 1.0 mg/kg, unlike 0.5 mg/kg, properly reversed a threshold train-of-four count of four vecuronium-induced block but did not prevent reparalysis.

The Use of Sugammadex in a Patient With Guillain-Barre Syndrome: A Case Report.

Sugammadex encapsulates and inactivates rocuronium and vecuronium. It is used to reverse neuromuscular blockade from these nondepolarizing agents. The safety of sugammadex in patients with neuromuscular disease has not been established. Guillain-Barre Syndrome (GBS) is a neuromuscular disease characterized by acute inflammatory polyneuropathy. Patients with GBS may exhibit autonomic dysfunction, chronic pain, abnormal reactions to neuromuscular blocking agents, and may require postoperative mechanical ventilation. We report the successful use of sugammadex to reverse rocuronium in a patient with chronic GBS, who presented for a hemicolectomy.

Use of Sugammadex in Patients With Obesity: A Pooled Analysis.

A growing proportion of patients undergoing surgical procedures are obese, providing anesthesiologists with numerous challenges for patient management. The current pooled analysis evaluated recovery times following sugammadex reversal of neuromuscular blockade by body mass index (BMI) in general, and in particular, in patients with BMIs ≥30 kg/m (defined as obese) and <30 kg/m (defined as non-obese). Data were pooled from 27 trials evaluating recommended sugammadex doses for reversal of moderate [reappearance of the second twitch of the train-of-four (TOF); sugammadex 2 mg/kg] or deep (1-2 post-tetanic counts or 15 minutes after rocuronium; sugammadex 4 mg/kg) rocuronium- or vecuronium-induced neuromuscular blockade. All doses of sugammadex were administered based on actual body weight. The recovery time from sugammadex administration to a TOF ratio ≥0.9 was the primary efficacy variable in all individual studies and in the pooled analysis. This analysis comprised a total of 1418 adult patients treated with sugammadex; 267 (18.8%) of these patients had a BMI ≥30 kg/m. The average time to recovery of the TOF ratio to 0.9 was 1.9 minutes for rocuronium-induced blockade and 3.0 minutes for vecuronium-induced blockade. No clinically relevant correlation was observed between BMI and recovery time. The recommended sugammadex doses based on actual body weight provide rapid recovery from neuromuscular blockade in both obese and non-obese patients; no dose adjustments are required in the obese patient.

Speed of reversal of vecuronium neuromuscular block with different doses of neostigmine in anesthetized dogs.

OBJECTIVES: Neostigmine is routinely used to reverse non-depolarizing neuromuscular block. Given its indirect mechanism, a plateau may exist whereby increasing doses of neostigmine do not result in clinical benefit. This study was designed to measure the speed of reversal of vecuronium-induced neuromuscular block in isoflurane-anesthetized dogs after the administration of three doses of neostigmine as used in clinical practice. STUDY DESIGN: Prospective, crossover, randomized study. ANIMALS: Seven adult, mixed-breed dogs with a mean ± standard deviation (SD) age of 2.0 ± 0.8 years and weight of 19.1 ± 9.1 kg. METHODS: Dogs were anesthetized on three occasions with isoflurane and administered vecuronium (0.1 mg kg-1) intravenously (IV). The train-of-four (TOF) ratio was measured on the pelvic limb with acceleromyography. When the second twitch of the TOF had returned spontaneously, atropine (0.03 mg kg-1) and neostigmine (0.02, 0.04 or 0.07 mg kg-1) were administered IV. Time to reach a TOF ratio of ≥0.9 after neostigmine administration was recorded. RESULTS: Increasing the dose of neostigmine from 0.02 mg kg-1 to 0.04 mg kg-1 and 0.07 mg kg-1 resulted in significant reductions in mean ± SD reversal times (10.5 ± 2.3, 7.4 ± 1.1 and 5.4 ± 0.5 minutes, respectively) (p < 0.0001) and smaller coefficients of variation (22%, 15% and 10%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Increasing the dose of neostigmine from 0.02 mg kg-1 to 0.04 mg kg-1 and 0.07 mg kg-1 produced faster and less variable reversal of vecuronium-induced neuromuscular block in isoflurane-anesthetized dogs. No ceiling effect was observed at this dose range.

Efficacy and safety of sugammadex compared to neostigmine for reversal of neuromuscular blockade: a meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: Sugammadex has been introduced for reversal of rocuronium (or vecuronium)-induced neuromuscular blockade (NMB). Although its efficacy has been established, data are conflicting whether it is safer than neostigmine traditionally used for reversing NMB. DESIGN: Meta-analysis of data about effectiveness and safety of sugammadex compared to neostigmine for reversing NMB in adults was performed using the PRISMA methodology. SETTING: University medical hospital. METHODS: A comprehensive search was conducted using PubMed, Web of Science, and Cochrane Library electronic databases to identify English-language randomized controlled trials. Two reviewers independently selected the trials; extracted data on reversal times, incomplete reversals of NMB, and adverse events (AEs); and assessed the trials' methodological quality and evidence level. Only AEs that were related to study drug by a blinded safety assessor were considered for meta-analysis. PATIENTS: A total of 1384 patients from 13 articles were included in this meta-analysis. MAIN RESULTS: Compared to neostigmine, sugammadex was faster in reversing NMB (P<.0001) and more likely to be associated with higher train-of-four ratio values at extubation (mean difference, 0.18; 95% confidence interval [CI], 0.14-0.22; P<.0001) and lower risk of postoperative residual curarization after extubation (odds ratio [OR], 0.05; 95% CI, 0.01-0.43; P=.0068). Compared to neostigmine, sugammadex was associated with a significantly lower likelihood of global AEs (OR, 0.47; 95% CI, 0.34-0.66; P<.0001), respiratory AEs (OR, 0.36; 95% CI, 0.14-0.95; P=.0386), cardiovascular AEs (OR, 0.23; 95% CI, 0.08-0.61; P=.0036), and postoperative weakness (OR, 0.45; 95% CI, 0.21-0.97; P=.0409). Sugammadex and neostigmine were associated with a similar likelihood of postoperative nausea and vomiting (OR, 1.23; 95% CI, 0.70-2.15; P=.4719), pain (OR, 1.06; 95% CI, 0.15-7.36; P=.9559), neurologic AEs (OR, 1.47; 95% CI, 0.52-4.17; P=.4699), general AEs (OR, 0.75; 95% CI, 0.47-1.21; P=.2448), and changes in laboratory tests' values (OR, 0.57; 95% CI, 0.18-1.78; P=.3368). CONCLUSIONS: Results from this meta-analysis suggest that sugammadex is superior to neostigmine, as it reverses NMB faster and more reliably, with a lower risk of AEs.

Clinical pharmacology and efficacy of sugammadex in the reversal of neuromuscular blockade.

INTRODUCTION: Sugammadex is the first clinical representative of a class of drugs called steroidal muscle relaxant encapsulators. Due to its 1:1 binding of rocuronium or vecuronium, sugammadex can reverse any depth of neuromuscular block and has therefore revolutionized the way anesthetists think about drug reversal. AREAS COVERED: This review gives an overview of the clinical pharmacology and efficacy of sugammadex in healthy patients as well as in patients with pre-existing diseases. EXPERT OPINION: After approval in Europe in 2008 and Asia in 2010, sugammadex has recently been approved in the USA and Canada. This will open the field for further research especially for the use in special patient populations and specific diseases. Due to its pharmacodynamic profile, sugammadex in combination with rocuronium might have the potential to displace succinylcholine as the gold standard muscle relaxant for rapid sequence inductions. The use of rocuronium or vecuronium with the potential to reverse its action with sugammadex seems to be safe in patients with impaired neuromuscular transmission, i.e. (neuro)muscular diseases including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence towards an economic advantage of using sugammadex, justifying the relatively high costs for an anesthesia-related drug, is missing.

Comparative Effectiveness of Calabadion and Sugammadex to Reverse Non-depolarizing Neuromuscular-blocking Agents.

BACKGROUND: The authors evaluated the comparative effectiveness of calabadion 2 to reverse non-depolarizing neuromuscular-blocking agents (NMBAs) by binding and inactivation. METHODS: The dose-response relationship of drugs to reverse vecuronium-, rocuronium-, and cisatracurium-induced neuromuscular block (NMB) was evaluated in vitro (competition binding assays and urine analysis), ex vivo (n = 34; phrenic nerve hemidiaphragm preparation), and in vivo (n = 108; quadriceps femoris muscle of the rat). Cumulative dose-response curves of calabadions, neostigmine, or sugammadex were created ex vivo at a steady-state deep NMB. In living rats, the authors studied the dose-response relationship of the test drugs to reverse deep block under physiologic conditions, and they measured the amount of calabadion 2 excreted in the urine. RESULTS: In vitro experiments showed that calabadion 2 binds rocuronium with 89 times the affinity of sugammadex (Ka = 3.4 × 10 M and Ka = 3.8 × 10 M-). The results of urine analysis (proton nuclear magnetic resonance), competition binding assays, and ex vivo study obtained in the absence of metabolic deactivation are in accordance with an 1:1 binding ratio of sugammadex and calabadion 2 toward rocuronium. In living rats, calabadion 2 dose-dependently and rapidly reversed all NMBAs tested. The molar potency of calabadion 2 to reverse vecuronium and rocuronium was higher compared with that of sugammadex. Calabadion 2 was eliminated renally and did not affect blood pressure or heart rate. CONCLUSIONS: Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex. Calabadion 2 is eliminated in the urine and well tolerated in rats.

The use of sugammadex for the reversal of vecuronium-induced neuromuscular block following intracranial surgery.

BACKGROUND: Total intravenous anaesthesia with propofol and remifentanil is widely used in neuroanaesthesiology and enables the quick recovery and early neurological assessment of patients. The administration of muscle relaxants carries a risk of residual relaxation following surgery. The administration of a suitable dose of sugammadex reverses the neuromuscular block irrespective of its depth and has none of the side effects associated with acetylcholinesterase inhibitors. The aim of the present study was to evaluate the usefulness of sugammadex for the reversal of vecuronium-induced effects following intracranial surgery. METHODS: The study involved 38 women who underwent supratentorial tumour removal. These women were randomly divided into two groups. Total intravenous anaesthesia with propofol and remifentanil using target-controlled infusion was administered according to the Schnider and Minto models, respectively. Endotracheal intubation was performed after the target concentrations of propofol and remifentanil reached 4 µg mL⁻¹ and 4 ng mL⁻¹, respectively. Vecuronium (100 µg kg⁻¹) was administered, and no response to TOF stimulation was observed. Relaxation was continued via the continuous infusion of vecuronium (0.8-1.2 µg kg⁻¹ min⁻¹) to provide a TOF of 2 throughout the surgery. In group I, neuromuscular conduction was restored with intravenous sugammadex (2 mg kg⁻¹), whereas in group II, no reversal agents were administered. RESULTS: The times of the return of spontaneous breathing, extubation, eye opening (both spontaneous and in response to a verbal command) were found to be longer in group II than group I. CONCLUSION: The use of sugammadex following craniotomy accelerates the achievement of optimal extubation conditions.

Worldwide experience with sugammadex sodium: implications for the United States.

Sugammadex sodium is a modified γ-cyclodextrin with a very high affinity for rocuronium and, to a lesser extent, vecuronium molecules. In vivo administration results in immediate encapsulation of rocuronium and vecuronium, resulting in termination of neuro- muscular blockade, usually within 3 minutes. This new neuromuscular blocking agent is specific for the aminosteroidal neuromuscular blocking agents rocuronium and vecuronium. Experience gained through worldwide clinical use of sugammadex offers US anesthesia providers the opportunity to better understand this new drug and its clinical applications. The seminal and current literature concerning clinical use of sugammadex is reviewed, and considerations for its incorporation into practice are provided.

The concept behind sugammadex.

Sugammadex is the first selective relaxant binding agent. It allows rapid reversal of any degree of neuromuscular blockade induced by steroidal neuromuscular blocking agents. Sugammadex acts by encapsulation of the neuromuscular blocking agent. This prevents the drug from acting on prejunctional and postjunctional nicotinic receptors, allowing acetylcholine to activate these receptors, and resulting in reversal of the neuromuscular blockade. Objective monitoring of the degree of neuromuscular blockade is strongly recommended to determine the optimal dose of sugammadex. A good understanding of the concept behind sugammadex is essential in order to use this reversal agent in clinical practice.

[Efficacy and safety of sugammadex (Org 25969) in reversing moderate neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 98 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional doses of rocuronium or vecuronium for maintenance of moderate block. At T2 reappearance sugammadex 0-4.0 mg . kg-1 was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 82.1 min in the placebo group to 1.8 min in the 4.0 mg . kg-1 sugammadex group. For the vecuronium-induced neuromuscular block, it decreased from 83.2 min in the placebo group to 2.1 min in the sugammadex 4.0 mg . kg-1 group. Plasma concentrations of sugammadex were approximately dose proportional over the dose range of 0.5 to 4.0 mg . kg-1 and independent of the neuromuscular blocking agents used. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients.

[Efficacy and safety of sugammadex (Org 25969) in reversing deep neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.

A randomised controlled trial comparing sugammadex and neostigmine at different depths of neuromuscular blockade in patients undergoing laparoscopic surgery.

Deep neuromuscular blockade during certain surgical procedures may improve operating conditions. Sugammadex can be used to reverse deep neuromuscular blockade without waiting for spontaneous recovery. This randomised study compared recovery times from neuromuscular blockade induced by rocuronium 0.6 mg.kg(-1), using sugammadex 4 mg.kg(-1) administered at 1-2 post-tetanic count (deep blockade) or neostigmine 50 µg.kg(-1) (plus atropine 10 µg.kg(-1)) administered at the re-appearance of the second twitch of a train-of-four stimulation (moderate blockade), in patients undergoing laparoscopic surgery. The primary efficacy variable was the time from the start of sugammadex/neostigmine administration to recovery of the train-of-four ratio to 0.9. Patients receiving sugammadex recovered 3.4 times faster than patients receiving neostigmine (geometric mean (95% CI) recovery times of 2.4 (2.1-2.7) and 8.4 (7.2-9.8) min, respectively, p<0.0001). Moreover, 94% (62/66) of sugammadex-treated patients recovered within 5 min, vs 20% (13/65) of neostigmine-treated patients, despite the difference in the depth of neuromuscular blockade at the time of administration of both drugs. The ability to provide deep neuromuscular blockade throughout the procedure but still permit reversal at the end of surgery may enable improved surgical access and an enhanced visual field.

Reversal of profound rocuronium or vecuronium-induced neuromuscular block with sugammadex in isoflurane-anaesthetised dogs.

This study evaluated the use of sugammadex for reversal of profound neuromuscular blockade induced with rocuronium or vecuronium in dogs. Anaesthesia was induced and maintained with isoflurane in oxygen in eight dogs on two occasions. Neuromuscular blockade was monitored using peroneal nerve stimulation and acceleromyography. Rocuronium 0.6 mg/kg or vecuronium 0.1mg/kg was administered intravenously (IV), followed 5 min later by sugammadex 8 mg/kg IV. Lag and onset time of rocuronium and vecuronium, lag time from sugammadex injection to recovery of first twitch response, recovery of T1/T0 to 25% and 75%, recovery index, and time to recovery of the train-of-four ratio (T4/T1) to 0.9 were recorded. Cardiovascular and respiratory parameters were also noted. Statistical analysis was performed using one-way ANOVA. Onset time for rocuronium (37 ± 18s; [mean ± SD]) was significantly shorter than for vecuronium (62 ± 15s) (P<0.04). No other significant differences were found between the two groups. After both rocuronium and vecuronium blockade, T4/T1 recovered to 0.9 in under 2 min after sugammadex (58.1 ± 67.8s and 98.1 ± 70.3s, respectively; P<0.32). Sugammadex can reverse profound neuromuscular blockade induced by vecuronium or rocuronium safely and rapidly in isoflurane-anaesthetised dogs.