The available evidence from RCTs suggests that sugammadex produces a substantially faster and more predictable recovery from rocuronium- or vecuronium-induced moderate NMB than neostigmine/glycopyrrolate12,13
and can produce a rapid recovery from profound NMB,14,15
a facility not available with any other drug combination. Thus, sugammadex represents an efficacious and potentially useful new agent for the reversal of NMB. However, the findings are based on limited evidence, and considerable uncertainties remain concerning its clinical effectiveness in practice and especially its cost-effectiveness.
First, the patients in the sugammadex trials were mainly relatively young and in ASA classes I–II, and may not be fully representative of those who would receive sugammadex in routine clinical practice. Secondly, the reductions in recovery time with sugammadex seen in the clinical trials may represent the maximum that can be achieved and the benefits in normal clinical practice will remain uncertain pending wider adoption and evaluation of sugammadex.
Thirdly, the available trials did not compare sugammadex–rocuronium or sugammadex–vecuronium combination with all the commonly used NMBA/reversal agent combinations. Although trials making these direct comparisons are not available, statistical methods have been developed which would have allowed us to combine data from comparisons between other NMB drugs/reversal agent combinations and aminosteroids with sugammadex, namely a mixed treatment comparison.18,19
The application of such methods is, however, subject to certain requirements and unfortunately, due to a lack of access to the necessary data on sugammadex, only limited data being available from older trials that were comparable with those from the newer sugammadex trials, and the nature of the available data (the primary studies elected to report outcomes using a mix of arithmetic mean, geometric mean, and median), we were unable to include this analysis in our review.
To demonstrate cost-effectiveness for sugammadex, two things need to be established. First, that some reduction in patient recovery time can be achieved by using sugammadex compared with neostigmine/glycopyrrolate for the routine reversal of NMB. Secondly, that any such time saving would have value in terms of freeing up staff to work on productive activities. The key economic uncertainties surround the productivity benefits of a reduced time in recovery, that is, the extent to which any time saved in recovery could be put to alternative productive use, for example, in caring for another patient or some other activity. The proportion of recovery time saved which could be put to productive use is ultimately unknown—no evidence was identified in the literature. There is also the possibility that extra operations could be scheduled as a result of any reduced recovery time, but again there is a lack of suitable evidence on the associated impact on costs and health effects. Similarly, there are no data to inform any possible differences between anaesthetic strategies in health-related quality of life and it should also be noted that the estimates reported for this represent the opinion of a single clinical expert only. These and other data weaknesses need to be considered when the results presented here are being interpreted.
The clinical trials of sugammadex were not sufficiently powered to estimate the rates of significant adverse events (including death) with any level of precision, nor were there any observational data to inform these rates. As such, in the absence of clear evidence to the contrary, it was assumed that there were no differences in rates of adverse events between the strategies. This is a limitation of the modelling and should be considered when interpreting the results. One scenario not modelled in the routine setting (due to the lack of available data) is that where a ‘cannot intubate, cannot ventilate’ event occurs. In current practice, such an event has potentially serious consequences (for both patient health and resource use) due to the inability to quickly reverse profound block with neostigmine/glycopyrrolate. It remains unclear whether administering sugammadex 16 mg kg−1
is cost-effective in such circumstances, due to uncertainty over the time it would take to draw up the sugammadex in a high-pressure situation, or alternatively the cost associated with preparing such a dose beforehand for every listed patient.3
If the estimates of the reduction in recovery time derived from the clinical trials were replicated in routine clinical practice, the analysis suggests that sugammadex would be cost-effective if all reductions in recovery time associated with sugammadex were to be achieved in the operating theatre, but not if all reductions in recovery time were to be in the recovery room. Other factors will also affect the cost-effectiveness of sugammadex, for example, where there is additional value in reducing recovery times (e.g. in preventing operations from being delayed or cancelled). The results are broadly similar for rocuronium and vecuronium with any differences driven by the small differences between the prices of these two products and the rates of recurrence of block or residual block.
If sugammadex is to be recommended for wider use in routine surgery, the overall cost of reversal agents would be expected to increase. Also, the use of rocuronium and vecuronium for NMB would increase relative to other non-depolarizing NMBAs. In addition, there would be some requirement for training of staff during the introduction of sugammadex, but this is not expected to involve significant costs.
The implications for the use of objective monitoring if sugammadex was more commonly used in practice are uncertain. In the clinical trials, sugammadex was administered at specific points determined by TOF monitoring and if anaesthetists always follow this practice, the use of monitoring would increase. However, as sugammadex appears effective at all levels of block, anaesthetists may feel able to reduce levels of monitoring as they become more experienced in its use, with resultant savings in equipment costs. There could be an overall deterioration in practice associated with decreased monitoring, although this would be difficult to quantify.
A recently published Cochrane Review20
appears to support the clinical findings of this review, but this review is the first to discuss the cost-effectiveness of sugammadex in UK clinical practice.
In conclusion, the evidence suggests that there are potential benefits of sugammadex in terms of increased patient safety, increased predictability of recovery from NMB, and more efficient use of theatre time and staff. However, whether this potential is realized routinely is unclear: the evidence base is small and the potential benefits of sugammadex have yet to be explored further in clinical practice. A wider range of outcomes, including patient-reported outcomes and effects on costs and resource use (e.g. time in the operating theatre or efficient operating list management), may have to be assessed before the full benefits of sugammadex can be evaluated. These implications relate to UK practice and may not apply to other countries and different health-care systems, and the clinical and economic uncertainties should be taken into consideration when interpreting the findings