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Correspondence

Use of rocuronium and sugammadex in renal transplantation

Problems that must be considered

Unterbuchner, Christoph

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European Journal of Anaesthesiology: September 2016 - Volume 33 - Issue 9 - p 690-691
doi: 10.1097/EJA.0000000000000435
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Editor,

Carlos et al.1 reported the successful use of rocuronium, sugammadex and acceleromyography in two paediatric patients after cadaveric renal transplantation. It is an innovative strategy for reversing residual curarisation in this group of patients. However, there are some problems that deserve consideration.

For instance, in patient 1, Carlos et al.1 managed neuromuscular monitoring with uncalibrated acceleromyography. In patient 2, they calibrated the acceleromyograph using 50-Hz tetanic stimulation of the ulnar nerve (TOF-Watch SC; Organon, Dublin, Ireland) (CAL 2 mode) during anaesthesia and rapid sequence induction without a hand adapter.

There is no doubt that calibrated, quantitative neuromuscular monitoring is the gold standard to measure neuromuscular function during anaesthesia and to reduce postoperative residual curarisation. Calibrated acceleromyography is able to identify up to 97% of cases of residual paralysis.2 Nonetheless, in the context of a rapid sequence induction, calibration of the acceleromyograph before injecting the muscle relaxant could lead to a dangerous time delay with the risk of aspiration. A 50-Hz tetanic stimulation before calibration is unnecessary for clinical measurement. It only makes sense for achieving baseline conditions for pharmacokinetic studies to exclude the staircase phenomenon in adults, which affects T1% of TOF stimulation. It is much more important to use the hand adapter of the TOF-Watch device as preload to increase the precision of the acceleromyographic measurement.2 Unfortunately, this preload device is not available for infants. Using the TOF-Watch SX, Carlos et al.1 extubated at a TOF ratio (TOFR) above 1.0. TOF recovery to 1.0 is mandatory at the end of anaesthesia to exclude residual curarisation in uncalibrated acceleromyography.2 Furthermore, end-stage renal disease is often accompanied by uraemic and diabetic polyneuropathy, which can complicate neuromuscular monitoring and interferes with successful calibration of the quantitative, neuromuscular monitoring device.3

Thus, reliable and sufficient reversal of the muscle relaxant becomes tremendously important in end-stage renal patients with renal transplantation to prevent microaspiration because of their immunosuppressed status.

Also, in patients 1 and 2, rocuronium 2.4 and 2.7 mg kg−1, respectively, were administrated. Both the cases were reversed with sugammadex 2 mg kg−1 at moderate neuromuscular block (return of T2). Patient 1 needed another dose of sugammadex 2 mg kg−1 (total dose 71.2 mg) after 7 min at a TOFR of 0.69 for complete recovery.1

Although after a single bolus dose of many nondepolarising muscle relaxants the duration of action is more related to distribution than to elimination, the contribution of renal elimination increases with dosage up to 33% at rocuronium 1 mg kg−1. In patients with end-stage renal disease, the duration of action after rocuronium 0.6 mg kg−1 is significantly increased.4 But, according to my experience, especially during renal transplantation, deep neuromuscular relaxation (post-tetanic count 1 to 2) is necessary to avoid prolapsing of the implanted organ during irritant, retrograde filling of the urinary bladder before ureteroneocystostomy.

In patients with end-stage renal failure, sugammadex 4 mg kg-1 is able to reverse deep neuromuscular blockade clinically and is statistically as rapid as in healthy controls, whereas renal elimination of sugammadex and the rocuronium–sugammadex complex is greatly reduced.5 No case of recurarisation was observed. De Souza et al.6 also demonstrated in patients with renal transplantation that deep neuromuscular block can be reversed reliably with sugammadex 4 mg kg−1. The variability of complete recovery, however, was from 0.5 to 15.3 min.

In addition, high doses of dexamethasone, which are given during renal transplantation, may reduce the efficacy of sugammadex. This was demonstrated in an in-vitro human muscle cell model.7 Maybe patient 1 would have shown a similar variability if the authors had waited a few minutes more.

So if we have unreliable neuromuscular monitoring in combination with prolonged reversal times using sugammadex in end-stage renal failure, it could be an effective method to reverse the complete dose of rocuronium with almost the four-fold dose of sugammadex, because both molecules bind in a 1 : 1 molar ratio.8 This strategy could reduce the danger of underdosing and recurarisation in decreasing the free fraction of rocuronium, which increases the margin of safety at the neuromuscular junction.8

Finally, these two cases underscore the potential of rocuronium and sugammadex to avoid postoperative residual curarisation in end-stage renal failure and renal transplantation, which should be investigated in sufficiently powered, controlled, pharmacokinetic and pharmacodynamic studies.

Acknowledgements related to this article

Assistance with the letter: none.

Financial support and sponsorship: none.

Conflict of interest: none.

Comment from the editor: Dr Carlos and colleagues did not respond to our invitation to reply to this letter.

References

1. Carlos RV, Torres ML, de Boer HD. The use of rocuronium and sugammadex in paediatric renal transplantation: two case reports. Eur J Anaesthesiol 2016; 33:383–385.
2. Fuchs-Buder T, Claudius C, Skovgaard LT, et al. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand 2007; 51:789–808.
3. Unterbuchner C, Fink H, Berthele A, Blobner M. Case scenario: residual curarization in diabetic polyneuropathy. Anesthesiology 2014; 120:474–479.
4. Robertson EN, Driessen JJ, Booij LHDJ. Pharmacokinetics and pharmacodynamics of rocuronium in patients with and without renal failure. Eur J Anaesthesiol 2005; 22:4–10.
5. Panhuizen IF, Gold SJA, Buerkle C, et al. Efficacy, safety and pharmacokinetics of sugammadex 4 mg kg−1 for reversal of deep neuromuscular blockade in patients with severe renal impairment. Br J Anaesth 2015; 114:777–784.
6. De Souza CM, Tardelli MA, Tedesco H, et al. Efficacy and safety of sugammadex in the reversal of deep neuromuscular blockade induced by rocuronium in patients with end-stage renal disease: a comparative prospective clinical trial. Eur J Anaesthesiol 2015; 32:681–686.
7. Rezonja K, Sostaric M, Vidmar G, Mars T. Dexamethasone produces dose-dependent inhibition of sugammadex reversal in in-vitro innervated primary human muscle cells. Anesth Analg 2014; 118:755–763.
8. Donati F. Sugammadex: an opportunity for more thinking or more cookbook medicine? Can J Anaesth 2007; 54:689–695.
© 2016 European Society of Anaesthesiology