The time from dexamethasone to sugammadex administration was 39.6 ± 17.2 minutes in group D and 36.6 ± 14.6 minutes in group S. We found no significant difference in the time from dexamethasone to sugammadex administration. The time to recovery of the TOF ratio to 0.9 after sugammadex administration was 97.7 ± 23.9 (95% CI, 88.8–106.7) seconds in group D and 91.1 ± 39.5 (95% CI, 76.3–105.8) seconds in group S. The time to extubation after sugammadex administration was 127.9 ± 23.2 (95% CI, 119.2–136.6) seconds and 123.8 ± 38.7 (95% CI, 110.0–137.6) seconds in group D and in group S, respectively. There was no significant difference between groups in time to recovery and time to extubation (P = 0.436; 95% CI, −10.3 to 23.5 and P = 0.612; 95% CI, −11.9 to 20.05 in group D and in group S, respectively) (Fig. 2). One patient in group D and 4 patients in group S experienced nausea. These patients did not require any antiemetic therapy, and their symptoms resolved spontaneously. No side effects were recorded except laryngospasm in 1 patient in group S.
In the present study, we evaluated the reversal time of sugammadex in children administered dexamethasone or saline after the induction of anesthesia. We found that dexamethasone given as a single dose (0.5 mg/kg) does not significantly affect the reversal time of sugammadex in children undergoing adenoidectomy and/or tonsillectomy.
Sugammadex acts by forming a complex with steroidal NMBDs such as rocuronium and vecuronium and reduces their concentrations in the neuromuscular junction. Because of its inert structure, direct drug interactions are rarely expected with sugammadex. Two types of drug interactions may occur with sugammadex by displacement or capturing. Drugs interacting with sugammadex by displacement (i.e., toremifene, fusidic acid, and flucloxacillin) could potentially affect the efficacy of sugammadex due to rocuronium or vecuronium being displaced from sugammadex.23 Capturing interactions may occur if sugammadex binds with other drugs (i.e., hormonal contraceptives), thus sugammadex reduces their free plasma concentration. In addition, sugammadex might have decreased efficacy for rocuronium or vecuronium due to it binding with another drug.24 Therefore, a pharmacokinetic and pharmacodynamic interaction is possible.
Cyclodextrins have been reported to form inclusion complexes with other compounds.23 Zwiers et al.23 investigated clinically relevant displacement interactions between sugammadex and 300 commonly prescribed drugs by using the pharmacokinetic-pharmacodynamic model. The drugs included both steroidal and nonsteroidal drugs acting on steroidal receptors such as the corticosteroids hydrocortisone, prednisolone, and dexamethasone. In that study, dexamethasone was reported to have the lowest association rate constant compared with other corticosteroids used. Furthermore, its low association rate constant showed a small possibility of displacement of the NMBD from sugammadex when using dexamethasone. However, in an in vitro experimental study of innervated human muscle cells, the possible chemical interaction between dexamethasone and sugammadex was documented.25 Recently, in an in vitro experimental model of functionally innervated human muscle cells, Rezonja et al.20 investigated the influence of dexamethasone on sugammadex reversal of rocuronium-induced neuromuscular block and found that dexamethasone led to a dose-dependent inhibition of sugammadex reversal. Considering these data, we also expected that children who receive dexamethasone might show a delayed recovery from rocuronium when receiving sugammadex. However, we failed to demonstrate any inhibitory effect of dexamethasone (0.5 mg/kg) on the reversal time of sugammadex in children. The clinical relevance of the interaction between dexamethasone and sugammadex has not been investigated in humans, and as far as we know, this is the first clinical study evaluating the effect of dexamethasone on sugammadex reversal time.
Another issue that must be further investigated is the dose and the time of administration of dexamethasone. In the literature, there is no reliable way to determine which dose of dexamethasone is required to inhibit sugammadex reversal. In the present study, a single bolus dose of dexamethasone was used intraoperatively to prevent postoperative nausea and vomiting and to improve postoperative pain control at a total dose of 0.5 mg/kg.16 In most studies, although the same dose of dexamethasone was used to treat the inflammatory response during surgery, similar effects have been achieved with a smaller dose of dexamethasone.17,26–32
Time to administration of dexamethasone is also an important issue when rocuronium is used to induce neuromuscular blockade. It is clearly demonstrated that dexamethasone attenuates rocuronium-induced neuromuscular blockade when administered 2 to 3 hours before the induction of anesthesia.33 However, when dexamethasone is given at induction, the duration of neuromuscular blockade is not affected.33 In the present study, this was the main reason why we used dexamethasone at the induction of anesthesia.
The timing of dexamethasone administration may interact with and change the reversal time of sugammadex. Corticosteroids are extensively bound to plasma proteins.34 Thus, sugammadex is probably unable to bind proteins before a rapid distribution to peripheral compartments. Thereby, the inhibitory effect of dexamethasone on sugammadex reversal would be more pronounced when used simultaneously. Further studies are needed to reveal this relation between dexamethasone and sugammadex.
Our study has a number of limitations. First, the study lacks concentration measurements of dexamethasone in the plasma. Second, postoperative side effect assessment was limited to 8 hours because of outpatient conditions. Therefore, we could not show any side effects from the interaction between sugammadex and dexamethasone over a long period of time. Third, the current study was unable to analyze the potential of a dose-response relation of dexamethasone with sugammadex. Fourth, possible age-related differences in this drug-drug interaction were not addressed in this study. Fifth, the study has the possibility of a type II statistical error. Sixth, the lack of T1-25%, T1-75%, and TOF ratio at 80% data limits our study regarding comprehensive evaluation of neuromuscular recovery.
In conclusion, the dose of 0.5 mg/kg dexamethasone during the induction of anesthesia does not substantially affect the reversal time of sugammadex on rocuronium-induced neuromuscular blockade in children.
The authors thank the American Journal of Experts (Certificate Verification Key: 0FD1-F218-BFCA-FB32-C14D) for English editing of this study.
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