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Correspondence  |   February 2014
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Author Affiliations & Notes
  • Andrienn Pongrácz, M.D.
    University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary (B.F.). fulesedi@med.unideb.hu
  • Réka Nemes, M.D.
    University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary (B.F.). fulesedi@med.unideb.hu
  • Béla Fülesdi, M.D., Ph.D., D.Sc.
    University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary (B.F.). fulesedi@med.unideb.hu
  • Edömér Tassonyi, M.D., Ph.D., D.Sc.
    University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary (B.F.). fulesedi@med.unideb.hu
  • (Accepted for publication October 21, 2013.)
    (Accepted for publication October 21, 2013.)×
Article Information
Correspondence
Correspondence   |   February 2014
In Reply
Anesthesiology 02 2014, Vol.120, 508-509. doi:10.1097/ALN.0000000000000090
Anesthesiology 02 2014, Vol.120, 508-509. doi:10.1097/ALN.0000000000000090
In his letter to the Editor, Dr. Carron raises two important issues referring to the published data by Pongrácz et al.1  evaluating low doses of sugammadex to reverse rocuronium-induced neuromuscular blockade (NMB) after the reappearance of four twitches during train-of-four (TOF) stimulation.
First, Dr. Carron emphasizes the importance of having considered a TOF fade ratio of 1.0 or greater as an adequate reversal in our study, unlike 0.9 or greater used by other investigators. Indeed, to date in all published studies investigating sugammadex, the primary outcome parameter was a nonnormalized TOF ratio of 0.9. However, a recorded TOF fade ratio of 0.9 does not equal full recovery of the NMB, because after sugammadex the TOF ratios regularly reach a final value of 1.0 or greater. Therefore, we considered a nonnormalized TOF ratio of 1.0 or greater as an acceptable criterion to exclude a residual NMB.2  Also, we calculated the normalized TOF ratios at recovery, which were around 1.0, as well. Normalization (dividing TOF fade ratios at recovery with those before administration of rocuronium) was necessary because control TOF ratios with acceleromyography often exceeded unity, biasing the results of recovery.3  For instance, when the TOF ratio recovers to 1.0, but the control TOF ratio is 1.18, the normalized TOF ratio will be 0.84 (1.0/1.18), which is insufficient. There is general agreement that a normalized TOF ratio of 0.9 or greater is required to exclude clinically significant residual paralysis.2,3  Furthermore, the changes of single-twitch height should also be measured during neuromuscular monitoring and should exceed a value of 90% of control for neuromuscular recovery to be considered as acceptable.4  However, to date the majority of investigations have not described the changes of T1 single twitches. Considering all these factors, we do agree with Dr. Carron’s suggestion that there is place for improvement of the current practice of neuromuscular monitoring and research.
Second, Dr. Carron estimates that 1.0 mg/kg of sugammadex is not as safe as 2.0 mg/kg in reversing a threshold TOF count 4 residual NMB and therefore suggests the administration of 2.0 mg/kg in this situation. There is no evidence for this suggestion. We have demonstrated that 1.0 mg/kg like 2.0 mg/kg of sugammadex effectively reverses rocuronium-induced NMB when administered at the reappearance of four twitches during TOF stimulation.1  Recurrent muscle paralysis did not occur in our patients. Dr. Carron argues that the safety margin of neuromuscular transmission (70 to 75% of postsynaptic acetylcholine receptors) cannot be liberated from the rocuronium molecules when lower than 2.0 mg/kg sugammadex is administered. This assumption, although attractive, is not supported by any evidence. It is logical that at a TOF count 4 level of block fewer rocuronium molecules are present at the neuromuscular synapse than at a TOF count 2 level of block, where 2.0 mg/kg of sugammadex is the recommended dose. Because the encapsulation of rocuronium by sugammadex is a one-to-one molecular interaction,5  one may hypothesize that the shallower the depth of block the fewer sugammadex molecules are necessary to encapsulate all of the free rocuronium molecules and to relieve the pre- and postsynaptic acetylcholine receptors. Our results support this assumption. However, a caveat is in order: unless the amount of sugammadex is sufficient for the encapsulation of almost all rocuronium molecules, agents that decrease acetylcholine release at the motor nerve terminal (i.e., magnesium or aminoglycoside antibiotics) may cause recurarization. It may therefore be prudent not to give inadequately low doses of sugammadex (0.25 or 0.5 mg/kg) in patients who had received these agents. Quantifying the proportion of receptor occupancy after recommended and lower doses of sugammadex requires further research.
We estimate that adequate use of low doses of sugammadex is safe and may contribute to its widespread use by reducing the expenses of the treatment.
Competing Interests
The authors declare no competing interests.
Andrienn Pongrácz, M.D., Réka Nemes, M.D., Béla Fülesdi, M.D., Ph.D., D.Sc., Edömér Tassonyi, M.D., Ph.D., D.Sc.
University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary (B.F.). fulesedi@med.unideb.hu
References
Pongrácz, A, Szatmári, S, Nemes, R, Fülesdi, B, Tassonyi, E Reversal of neuromuscular blockade with sugammadex at the reappearance of four twitches to train-of-four stimulation.. Anesthesiology. (2013). 119 36–42 [Article] [PubMed]
Capron, F, Alla, F, Hottier, C, Meistelman, C, Fuchs-Buder, T Can acceleromyography detect low levels of residual paralysis? A probability approach to detect a mechanomyographic train-of-four ratio of 0.9.. Anesthesiology. (2004). 100 1119–24 [Article] [PubMed]
Claudius, C, Skovgaard, LT, Viby-Mogensen, J Is the performance of acceleromyography improved with preload and normalization? A comparison with mechanomyography.. Anesthesiology. (2009). 110 1261–70 [Article] [PubMed]
Kopman, AF, Klewicka, MM, Neuman, GG The relationship between acceleromyographic train-of-four fade and single twitch depression.. Anesthesiology. (2002). 96 583–7 [Article] [PubMed]
McIntyre, JA, Castaner, J Sugammadex sodium.. Drugs Fut. (2005). 30 780–4 [Article]