Abstract



 



Purpose   The purpose of this research was to explore whether or not dexamethasone, administered during general anesthesia for the prevention of PONV, affected the ability of sugammadex to reverse rocuronium.



 



Background   Sugammadex was approved by the Food and Drug Administration in late 2015. It’s mechanism of action is to encapsulate the steroidal neuromuscular blocking agents rocuronium and vecuronium, thereby rendering them unable to interact with receptors at the neuromuscular junction. This encapsulation and strong binding allows for the rapid restoration of skeletal muscle function. The steroidal non-depolarizing muscle relaxants rocuronium and vecuronium have a cyclopentanoperhydrophenanthrene structure. It is their structure that allows encapsulation by sugammadex. In vitro interactions between sugammadex and over 300 other molecules were tested; only three compounds appear to have an affinity for the cyclodextrin significant enough to break the bond between sugammadex and rocuronium or vecuronium: toremifene (an oral selective estrogen receptor modulator), fusicid acid (a topical antibiotic cream), and flucloxacillin (a penicillin). Dexamethasone also has a cyclopentanoperhydrophenanthrene structure as well as molecular dimensions that are very much like rocuronium.



 



In 2014, a published in vitro study reported that the efficacy of sugammadex may be diminished in the presence of dexamethasone. Dexamethasone has molecular properties similar to the steroid-based rocuronium molecule. In vitro using innervated primary human muscle cells, dexamethasone inhibited sugammadex’s ability to encapsulate the rocuronium molecule.



 



Methodology   This was a retrospective case-controlled review. The anesthesia records of ASA I or II patients who had elective surgery with general anesthesia that included rocuronium, sugammadex, ondansetron, or dexamethasone; aged 18 years to 65 years; with BMIs between 18 and 30 kg/m2; and with 2 or more risk factors for PONV were analyzed. A total of 813 records were reviewed, but after applying appropriate exclusion criteria 45 records were placed into three mutually exclusive groups:




General anesthesia was standardized, as was the timing of sugammadex administration and the use of acceleromyography for neuromuscular monitoring. The primary outcome variable measured across all three groups included the recovery time to a TOF ratio >0.9 to identify if delayed recovery could be associated with dexamethasone. Additionally, demographic data was extracted to identify confounding variables that may have influenced the results.



 



Result   Demographic and clinical data were no different between the three groups. Recovery times, in seconds using an acceleromygraphy to calculate the quantitative train-of-four ratio, were not significantly different between groups. When sugammadex was administered to antagonize rocuronium blockade, dexamethasone 8 mg IV, given immediately following induction or just prior to administration of sugammadex, did not influence neuromuscular recovery times compared to the control group.



 



Conclusion   The outcome of this small retrospective study did not support the previous results of an in vitro study that suggested dexamethasone used to prevent PONV would impair reversal of rocuronium by sugammadex. These results may not be generalizable to a larger population due to the fact that study patients had only moderate neuromuscular block prior to sugammadex administration.



 



Comment



 



As with any new drug that we use, we must become intimately familiar with its entire profile including possible drug interactions. While sugammadex has been approved for use in Europe for several years and a plethora of research has been published, use in the USA is limited by comparison. Our own clinical involvement is on the up-slope of the learning curve. I also appreciate the explanations offered by the authors regarding the differences in outcomes based on experimental technique, i.e. whether in vitro or in vivo, and how these differences guide us in interpreting results. However, I do agree that conflicting evidence, irrespective of experimental technique, warrants further investigation, and therefore I found this publication extremely useful as I anticipate widespread use of sugammadex. We must understand the clinical relevance of all studies. We certainly are not going to stop treating PONV with dexamethasone since the evidence supports its efficacy, so the probability of using the two drugs during the same anesthetic is high. Now that we have sugammadex available for clinical use we owe it to our patients to understand the drug and its complete profile. I do believe we are going to see massive improvements in outcomes because of sugammadex use; the complications related to neuromuscular blockade use will be problems of the past.