Neostigmine versus   Sugammadex

Abstract

T HERE is convincing evidence that, when reversal of rocuronium-induced neuromuscular paralysis is attempted during deep levels of blockade (posttetanic counts of 1 or 2), sugammadex given in the appropriate dose is a more rapid-acting and reliable antagonist of residual weakness than is neostigmine. 1 The same effect is true at more moderate levels of block (a train-of-four [TOF] count of 1-2) for rocuronium 2 and vecuronium 3 and for rocuronium compared with neostigmine reversal of cisatracurium. 4 The doses of sugammadex required for prompt and effective antagonism of a rocuronium-or vecuronium-induced block at these markers are now well established. However, there is almost no information available regarding how much sugam-madex is needed when the level of block is more modest. In this issue of ANESTHESIOLOGY, Schaller et al. 5 provide dosage suggestions for neostigmine and sugammadex when TOF ratio has recovered spontaneously to a value of 0.50 after the administration of rocuronium. A TOF ratio of 0.50 is an important marker in the recovery process for several reasons. Once a value of 0.50 is reached, subjective (tactile or visual) appreciation that fade exists at all is highly uncertain. 6 Unfortunately, the great majority of anesthetists still do not have access to neuromus-cular monitors that can quantify the evoked response to TOF stimulation. Thus, this level of residual block is easily missed by clinicians. This state of affairs is of concern because a TOF ratio of 0.50 is associated with clear signs of inadequate clinical recovery 7-and potential for adverse clinical consequences. 8,9 It is for this reason that, in the absence of some way of quantifying TOF ratio at the end of surgery, routine reversal of residual block has been advocated. 10 The clinician who cannot detect fade on TOF stimulation after spontaneous recovery from a nondepolarizing block has a dilemma. Is a fully effective dose of neostigmine (50-70 g/kg) still required if recovery to a TOF value of 0.90 within 5-10 min is desired? Recent evidence suggests that this intervention is not necessary. Under these conditions, Fuchs-Buder et al. 11 predicted that as little as 20 g/kg neostigmine would be 100% effective within 10 min, a conclusion given credence by Schaller et al. 5 On the basis of a biexponential model, they calculated that 34 g/kg neostig-mine was required for recovery within 5 min in 95% of patients, but only 10 g/kg would be required for the average patient if a 10-min reversal interval was deemed acceptable. However, a caveat is in order. The conclusions by Schaller et al. 5 do not apply to a TOF count of 4 with detectable fade. When the fourth response to TOF stimulation first becomes detectable, even a 70 g/kg dose of neostigmine cannot guarantee recovery to a TOF ratio of 0.90 with 10 min. 12 Because a TOF count of 1-2 is obviously associated with a higher plasma level (Cp) of blocker than would be found when the TOF count is 4 with minimal fade, it seems only logical that the sugammadex dose requirements usually cited should be less as recovery spontaneously progresses. How much lower is the Cp when the TOF ratio is 0.40-0.50 compared with values at a TOF count of 1-2? It is possible to make some predictions. Tactile appreciation of the first twitch (T 1) to TOF stimulation usually occurs at a T 1 value of approximately 5% of control. 13 By the time the TOF ratio has recovered to 0.40-0.50, T 1 is usually 75% of control. 14 Using a pharmacokinetic/pharmacodynamic model for ve-curonium, 15 this degree of recovery (T 1 at 5-75% of control) is associated with a more than 50% decline in the Cp of the drug. The manufacturer suggested dose of sugammadex for rocuronium (2 mg/kg at a TOF count of 2) is very conservative. It was designed to assure adequate reversal of vecuro-nium as well as rocuronium. However, dose requirements for the latter drug are only half that required for vecuronium. Thus, antagonism of residual rocuronium block at a TOF ratio of 0.50 is unlikely to require doses in excess of 0.50 mg/kg, and perhaps significantly less may prove satisfactory. This is exactly what Schaller et al. 5 observed. They calculated that as little as 0.22 mg/kg was necessary to achieve a TOF ratio of 0.90 within 5 min for 95% of their subjects. This paper by Schaller et al. 5 paper highlights an important gap in our knowledge about how to dose sugammadex. There is little if any information on how to proceed when the TOF count is 4 but there is subjective tactile or visual TOF fade (a ratio of 0.10-0.40). It would not be surprising if a dose of only 1.0 mg/kg proved to provide adequate antago-M: Sugammadex and neostigmine dose-finding study for reversal of shallow residual neuromus-cular block.