Do we really need sugammadex as an antagonist of muscle relaxants in anesthesia?

PURPOSE OF REVIEW: Sugammadex is a selective relaxant-binding agent that is designed to encapsulate rocuronium and chemically similar steroidal muscle relaxants such as vecuronium. This review summarizes recent information on the use of sugammadex in clinical practice. RECENT FINDINGS: The main advantages of sugammadex when compared with conventional anticholinesterase agents are a much faster recovery time and its unique ability to reverse rapidly and efficiently, for the first time, deep levels of neuromuscular blockade. However, there is paucity of evidence-based studies on the benefit of deep neuromuscular block, and then routine administration of sugammadex to reverse any level of block, for example, during laparoscopic surgery. It appears that reduction of costs depends mainly on organizational factors. Finally it must be remembered that sugammadex only works with steroidal nondepolarizing muscle relaxants; therefore neostigmine should not be withdrawn because it is the only reversal agent effective against atracurium or cisatracurium. SUMMARY: Sugammadex offers a significantly faster and more predictable recovery profile than neostigmine. It is now possible to reverse rapidly and efficiently any level of neuromuscular blockade and to avoid the risk of adverse events because of residual paralysis such as critical respiratory events during recovery from anesthesia.

The influence of unrestricted use of sugammadex on clinical anaesthetic practice in a tertiary teaching hospital.

This retrospective casenote audit involving 374 patients requiring intubation for an anaesthetic found that when the availability of sugammadex became unrestricted, its use increased from 7.1 to 65.3% (P <0.0001) of all muscle relaxant reversals, while neostigmine use decreased from 59.6 to 12.5%. Rocuronium use decreased slightly (90.8 to 79.2%, P=0.006) but vecuronium use increased (2.1 to 8.3%, P=0.02). Cisatracurium and suxamethonium use were unchanged. Total rocuronium dose (55.9 ± 24.1 vs 60.4 ± 22.3 mg) and the number of doses (1.9 ± 1.48 to 1.96 ± 1.27) were unchanged, but the time between the last dose and reversal decreased (91.7 ± 68.1 to 62 ± 52.4 minutes, P=0.0002). There appeared to be no change in postoperative nausea and vomiting, or post-anaesthesia care unit time or oxygen saturation levels. Anaesthetic theatre time fell from 143.5 ± 85.8 to 120 ± 71.2 minutes (P=0.01) and remained significant when adjusted for confounding variables (ratio of means 1.17, 95% confidence interval 1.03 to 1.34, P=0.02), although inferences in relation to causality are limited by the retrospective and observational design of the study. Hospital stay also appeared to fall (4.2 ± 3.5 to 3.4 ± 3.0 days, P=0.035), but was not statistically significant when adjusted for confounding variables (ratio of means 1.04, 95% confidence interval 0.89 to 1.2, P=0.59). These observations suggest that the unrestricted availability of sugammadex will change how steroid-based neuromuscular blocking drugs are used and reversed, but further research is needed to determine if patient outcomes will improve.

Unrestricted access to sugammadex: impact on neuromuscular blocking agent choice, reversal practice and associated healthcare costs.

Sugammadex is known to rapidly and completely reverse the effects of amino-steroidal neuromuscular blocking agents. However, the high costs of sugammadex have so far prevented its introduction as the standard reversal agent in most healthcare systems. At the Royal Perth Hospital, sugammadex was recently introduced as an unrestricted alternative to neostigmine for the reversal of amino-steroidal neuromuscular blocking agents. The aim of this retrospective observational audit was to investigate the impact of this change on clinical practice and associated healthcare costs. Data from all patients intubated during a one-month period in April to May 2010 and for a similar period in 2011 were retrospectively collected and the use of neuromuscular blocking agents and reversal agents were identified and the associated costs were calculated. More steroidal neuromuscular blocking agents and sugammadex (+743%), but less glycopyrrolate and neostigmine (-48%) were used in 2011. Using the manufacturer's list price, muscle relaxation and reversal costs increased from about A$42 per case to about A$127 per case. Between the investigated time periods no differences were found for anaesthesia time, operating time or time spent in the post anaesthesia care unit. However, there was a statistically significant decrease in the time between surgery and discharge (median 2.0 vs 2.2 days). While the design of the audit was such that no inferences can be made about the cause of this change, this is an interesting observation worthy of further investigation.

Is sugammadex economically viable for routine use.

PURPOSE OF REVIEW: Sugammadex belongs to a new class of drugs termed selective relaxant binding agents and is now available for clinical use in over 50 countries. Because of its innovative mechanism of action, reversal of rocuronium or vecuronium becomes independent of the degree of residual neuromuscular blockade. Deep or intense neuromuscular blockade now can rapidly and predictably be reversed. However, compared with the classical acetylcholine esterase inhibitor-based reversal treatment costs are significantly higher. On the basis of the current literature, the cost-effectiveness of sugammadex will be evaluated. RECENT FINDINGS: There is a paucity of evidence-based studies that investigate the pharmacoeconomic aspects of sugammadex reversal. However, several studies assessed the cost-effectiveness of routine reversal with sugammadex compared with cholinesterase inhibitors and one study from the UK analyzed the economic aspects of a rocuronium/sugammadex concept compared with succinylcholine in a 'cannot intubate-cannot ventilate' scenario. The concept of cost reduction by dose reduction of sugammadex is also addressed. SUMMARY: The reduction of recovery times with sugammadex will reduce the incidence of prolonged extubation and may increase patients' throughput. However, the achievable reduction of costs depends on the individual organizational factors, also.

Sugammadex for reversal of neuromuscular block after rapid sequence intubation: a systematic review and economic assessment.

Sugammadex 16 mg kg⁻¹ can be used for the immediate reversal of neuromuscular block 3 min after administration of rocuronium and could be used in place of succinylcholine for emergency intubation. We have systematically reviewed the efficacy and cost-effectiveness and made an economic assessment of sugammadex for immediate reversal. The economic assessment investigated whether sugammadex appears cost-effective under various assumptions about the value of any reduction in recovery time with sugammadex, the likelihood of a 'can't intubate, can't ventilate' (CICV) event, the age of the patient, and the length of the procedure. Three trials were included in the efficacy review. Sugammadex administered 3 or 5 min after rocuronium produced markedly faster recovery than placebo or spontaneous recovery from succinylcholine-induced block. No published economic evaluations were found. Our economic analyses showed that sugammadex appears more cost-effective, where the value of any reduction in recovery time is greater, where the reduction in mortality compared with succinylcholine is greater, and where the patient is younger, for lower probabilities of a CICV event and for long procedures which do not require profound block throughout. Because of the lack of evidence, the value of some parameters remains unknown, which makes it difficult to provide a definitive assessment of the cost-effectiveness of sugammadex in practice. The use of sugammadex in combination with high-dose rocuronium is efficacious. Further research is needed to clarify key parameters in the analysis and to allow a fuller economic assessment.

Sugammadex compared with neostigmine/glycopyrrolate for routine reversal of neuromuscular block: a systematic review and economic evaluation.

The cost-effectiveness of sugammadex for the routine reversal of muscle relaxation produced by rocuronium or vecuronium in UK practice is uncertain. We performed a systematic review of randomized controlled trials of sugammadex compared with neostigmine/glycopyrrolate and an economic assessment of sugammadex for the reversal of moderate or profound neuromuscular block (NMB) produced by rocuronium or vecuronium. The economic assessment aimed to establish the reduction in recovery time and the 'value of time saved' which would be necessary for sugammadex to be potentially cost-effective compared with existing practice. Three trials indicated that sugammadex 2 mg kg⁻¹ (4 mg kg⁻¹) produces more rapid recovery from moderate (profound) NMB than neostigmine/glycopyrrolate. The economic assessment indicated that if the reductions in recovery time associated with sugammadex in the trials are replicated in routine practice, sugammadex would be cost-effective if those reductions are achieved in the operating theatre (assumed value of staff time, £4.44 per minute), but not if they are achieved in the recovery room (assumed value of staff time, £0.33 per minute). However, there is considerable uncertainty in these results. Sugammadex has the potential to be cost-effective compared with neostigmine/glycopyrrolate for the reversal of rocuronium-induced moderate or profound NMB, provided that the time savings observed in trials can be achieved and put to productive use in clinical practice. Further research is required to evaluate the effects of sugammadex on patient safety, predictability of recovery from NMB, patient outcomes, and efficient use of resources.

Sugammadex for the reversal of muscle relaxation in general anaesthesia: a systematic review and economic assessment.

BACKGROUND: Sugammadex (Bridion) is a newly developed agent for the reversal of neuromuscular blockade (NMB) induced by rocuronium or vecuronium. Sugammadex can reverse profound blockade and can be given for immediate reversal and its use would avoid the potentially serious adverse effects of the currently used agent, succinylcholine. Also, sugammadex can reverse NMB more quickly and predictably than existing agents. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of sugammadex for the reversal of muscle relaxation after general anaesthesia in UK practice following routine or rapid induction of NMB. DATA SOURCES: Medical databases [including MEDLINE, EMBASE, CINAHL, Science Citation Index, BIOSIS and Cochrane Central Register of Controlled Trials (CENTRAL), conference proceedings, internet sites and clinical trials registers] were searched to identify published and unpublished studies. The main searches were carried out in May 2008 and supplemented by current awareness updates up until November 2008. REVIEW METHODS: For the clinical effectiveness review, randomised controlled trials of sugammadex against placebo or an active comparator (neostigmine + glycopyrrolate) for the reversal of moderate or profound NMB and for immediate reversal (spontaneous recovery from succinylcholine-induced blockade) were included. The primary effectiveness outcome was speed of recovery from NMB, as measured by objective monitoring of neuromuscular function. For the cost-effectiveness review, a de novo economic assessment considered the routine induction of NMB and the rapid induction and/or reversal of NMB, and threshold analyses were carried out on a series of pairwise comparisons to establish how effective sugammadex needs to be to justify its cost. RESULTS: The review of clinical effectiveness included four randomised active-control trials of sugammadex, nine randomised placebo-controlled trials and five studies in special populations. A total of 2132 titles and abstracts and 265 full-text publications were screened. The included trials indicated that sugammadex produces more rapid recovery from moderate or profound NMB than placebo or neostigmine. Median time to recovery from moderate blockade was 1.3-1.7 minutes for rocuronium + sugammadex, 21-86 minutes for rocuronium + placebo and 17.6 minutes for rocuronium + neostigmine. In profound blockade, median time to recovery was 2.7 minutes for rocuronium + sugammadex, 30 to > 90 minutes for rocuronium + placebo, and 49 minutes for rocuronium + neostigmine. Results for vecuronium were similar. In addition, recovery from NMB was faster with rocuronium reversed by sugammadex 16 mg/kg after 3 minutes (immediate reversal) than with succinylcholine followed by spontaneous recovery (median time to primary outcome 4.2 versus 7.1 minutes). The evidence base for modelling cost-effectiveness is very limited. However, assuming that the reductions in recovery times seen in the trials can be achieved in routine practice and can be used productively, sugammadex [2 mg/kg (4 mg/kg)] is potentially cost-effective at its current list price for the routine reversal of rocuronium-induced moderate (profound) blockade, if each minute of recovery time saved can be valued at approximately 2.40 pounds (1.75 pounds) or more. This is more likely to be achieved if any reductions in recovery time are in the operating room (estimated value of 4.44 pounds per minute saved) rather than the recovery room (estimated value of 0.33 pounds per minute saved). The results were broadly similar for rocuronium- and vecuronium-induced blockade. For rapid reversal of NMB it appeared that any reduction in morbidity from adopting sugammadex is unlikely to result in significant cost savings. LIMITATIONS: The evidence base was not large and many of the published trials were dose-finding and safety studies with very small sample sizes. Also, some relevant outcomes, in particular patient experience/quality of life and resources/costs used, were either not investigated or not reported. In addition, it is likely that the patients included in the efficacy trials were relatively young and in good general health compared with the overall surgical population. Regarding the economic evaluation, there appears to be no evidence linking measures of clinical efficacy to patients' health-related quality of life and mortality risks. CONCLUSIONS: Sugammadex may be a cost-effective option compared with neostigmine + glycopyrrolate for reversal of moderate NMB and also provides the facility to recover patients from profound blockade. Rocuronium + sugammadex could be considered as a replacement for succinylcholine for rapid induction (and reversal) of NMB, although this may not be a cost-effective option in some types of patient at current list prices for sugammadex. Considerable uncertainties remain about whether the full benefits of sugammadex can be realised in clinical practice.

Sensory properties of ginseng solutions modified by masking agents.

Ginseng is one of the most popular functional ingredients found in energy drink formulations. Although ginseng is known for its health benefits, ginseng is also notorious for imparting a bitter taste. Incorporating ginseng into beverages without the bitterness, while still maintaining its health benefits, is necessary for developing an acceptable product. Thus, the objectives of this study were to (1) identify effective treatments for minimizing the bitterness of ginseng in water base and model energy drink base solutions and (2) determine the sensory effects of incorporating different treatment levels to minimize the bitterness of ginseng. A series of pilot studies investigating bitterness reducing treatments were conducted, which included: congruent flavor addition, bitterness blocking agent incorporation, enzymatic modification, ingredient interaction, and complexation. Based on the results of a series of pilot studies, γ-cyclodextrin (γ-CD) and ß-cyclodextrin (ß-CD) complexation agents were identified as having the most potential. Effectiveness of the γ-CDs, ß-CDs, and combinations of γ- and ß-CDs were tested in 100 mL water and in 100 mL model energy drink base solutions containing 0.052 g 80% ginsenosides panax ginseng, using descriptive sensory analysis. Twelve trained panelists evaluated 42 solution treatments (3 treatments × 7 levels × 2 bases) for bitter attributes with and without nose clips. Overall, the most effective treatments were 0.09 g γ-CDs in 100 mL of solution and 1 g ß-CDs in 100 mL solution, which both reduced the bitterness intensity of the solutions by half. Incorporation of these levels of CDs in water and model energy drink base solutions containing ginseng will aid in the development of functional beverages that are more acceptable to a wider range of consumers.

[Sugammadex: something new to improve patient safety or simply a gadget?]. / Le sugammadex : une nouveauté qui s'inscrit dans le cadre de l'amélioration de la sécurité des patients ou un simple gadget ?

The launch on the market of a new compound is always an important event for a specialty, particularly when the mechanism of action is completely new. It is the case with sugammadex, a cyclodextrin able to encapsulate specifically and only nondepolarizing steroidal muscles relaxant, rocuronium or vecuronium. The clinical trials which have been performed for sugammadex approval have demonstrated promising results. Sugammadex is able to rapidly reverse (2-5 min) different levels of neuromuscular blockade: moderate (e.g., T2 recovery), deep (e.g., PTC 1-2 recovery) and also few minutes (3-15) after rocuronium administration. Thus, the sugammadex's onset time is about 10 times more rapid than neostigmine without the need of concomitantly atropine administration. Sugammadex has only been tested in small sample size of patients. Therefore, the exact place in the anesthetic practice, the potential indications, the safety profile on a large-scale, thus remain to determine. In particular, how it will modify our current practices characterized to date by 1) under-use of neuromuscular monitoring, 2) a marginal practice of reversal and 3) a wide use of benzylisoquinolines : atracurium and cis-atracurium? Finally, what will be the medical strategies to justify an additional cost when compared to neostigmine?