Anesthetic‐Sparing Effect of Dexmedetomidine During Total Intravenous Anesthesia for Children Undergoing Dental Surgery: A Randomized Controlled Trial—In Reply

We thank Dr. Starr and colleagues for their comments [1] on our recent investigation into the propofol- and remifentanil-sparing effects of a bolus dose of dexmedetomidine in pediatric surgery [2]. Their comments echo some limitations we acknowledged in our original publication. For example, they note that our propofol and remifentanil titration rules may not have allowed for a quick enough reduction in infusion rates, likely contributing to our showing less difference than expected. We adjusted these infusions based on the Bispectral Index every 5 min and recognized that more frequent changes (or use of a closed-loop system [3]) may have improved the granularity of our findings. The difference between the percentage changes we reported for propofol (−10.0%) and remifentanil (−13.7%) with a dexmedetomidine bolus dose of 1.0 μg·kg−1 indicates an inconsistency, given that our protocol mandated parallel changes in separate propofol and remifentanil infusions. As Starr et al. note, our aim in synchronizing these infusion changes was to simulate the ‘PR5’ admixture; however, we must clarify that the ratio is 10 mg of propofol to 5 μg of remifentanil (not 100 mg to 5 μg). We believe this discrepancy arose mainly from instances where post-induction propofol boluses were administered without remifentanil or when empty syringes in the pump drivers had to be replaced, which happened more frequently for propofol than remifentanil. Our protocol permitted anesthesiologists to give additional boluses of either drug as needed to ensure an adequate depth of hypnosis. Nevertheless, we do not believe that this discrepancy fundamentally alters the interpretation of our results: that a post-induction 1.0 μg·kg−1 bolus of dexmedetomidine reduced propofol and remifentanil requirements during the maintenance of anesthesia in children, whereas lower doses (0.5 μg·kg−1 and 0.25 μg·kg−1) did not. The primary concern we wish to address is the argument put forward by Starr et al. that our study failed to match the greater anesthetic-sparing effects of dexmedetomidine observed by others [4] because we used a single bolus dose rather than an infusion. This questions the validity of our study design and the practice of administering dexmedetomidine as a bolus. Starr et al. appear to argue that because 1.0 μg·kg−1, 0.5 μg·kg−1, or 0.25 μg·kg−1 dexmedetomidine boluses would result in relatively low peak effect-site concentrations (Ce), insufficient to achieve sedation as a sole agent (which is not how it was used), their effect in combination with propofol-remifentanil will necessarily be negligible. However, as they note themselves, ‘the synergistic effects of dexmedetomidine and propofol/remifentanil are poorly understood’, which provides a succinct justification for our study. Synergistic effects are expected with intravenous anesthetics [3], and while propofol-remifentanil interactions have been most widely studied [5], less is known about the potential combined effect with dexmedetomidine as an additional agent. Starr et al. offer some modeling using iTIVA (Anestesiarte Cali SAS, Cali), where our 1.0 μg·kg−1 dexmedetomidine dose in a child aged 3.3 years and weighing 15 kg would have a peak Ce of 0.86 μg·ml−1, declining to 0.44 μg·ml−1 after 69 min (the median duration of the maintenance period in our study). The fact that the modeled Ce has only declined by 51% after just over an hour speaks to the ongoing pharmacodynamic contribution of dexmedetomidine to the pharmacological milieu, which does have an anesthetic-sparing effect at higher doses. Administering dexmedetomidine as a single bolus dose at the beginning of shorter procedures presents a pragmatic opportunity to harness the benefits of this potential synergy. We hope our findings and this additional discussion will be helpful for physicians aiming to reduce propofol dosing during pediatric anesthesia. Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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