Rocuronium bromide, an intermediate-duration aminosteroidal nondepolarizing neuromuscular blocking agent, displays a dose-response relationship that is predictable in broad terms yet clinically variable in the individual patient. A predictable response guides protocols for its use, with anesthesiologists being able to further titrate according to individual variability; notably, the advent of sugammadex for reversal increases the tolerance for overdosing.
The rocuronium dose producing 95% depression of twitch tension (ED95) is approximately 0.23 to 0.36 mg/kg, and 0.6 mg/kg has become the standard intubating dose, producing onset of maximal block within roughly 40 to 180 seconds and a clinical duration of 15 to 40 minutes (Khuenl-Brady & Sparr, 1996). The rapid onset that makes rocuronium attractive for tracheal intubation is, somewhat paradoxically, a consequence of its comparatively low potency: a larger absolute dose is required to achieve a given degree of block, and this larger dose diffuses to the neuromuscular junction more quickly, shortening the time to maximal effect relative to more potent relaxants such as vecuronium (Khuenl-Brady & Sparr, 1996).
Despite the convenience of fixed weight-based dosing, individual response to a given dose of rocuronium can vary. In a large randomised comparison of 0.6 mg/kg rocuronium in 428 patients, onset time was significantly shorter in women than in men (91.7 versus 108.0 seconds) and clinical duration significantly longer (43.3 versus 31.3 minutes), consistent with greater pharmacodynamic sensitivity to rocuronium in female patients; notably, the same study found no comparable sex-based difference with cisatracurium, a benzylisoquinoline, suggesting the effect is specific to aminosteroidal agents (Adamus et al., 2008).
Renal function similarly modifies the dose-response profile, although rocuronium relies primarily on hepatobiliary elimination, with only 12% to 33% of an administered dose recovered unchanged in urine. In patients with end-stage renal failure given 0.6 mg/kg rocuronium under propofol anaesthesia, clinical duration was significantly prolonged compared with patients with normal renal function (49 versus 32 minutes), as was the time to recovery of the train-of-four ratio to 0.70 (88 versus 55 minutes), corresponding to a 39% reduction in plasma clearance (Robertson et al., 2005). Earlier studies conducted under isoflurane anesthesia had not consistently demonstrated this prolongation, possibly due to a potentiating effect of isoflurane.
Body habitus also bears directly on appropriate dosing strategy. In morbidly obese patients undergoing bariatric surgery, rocuronium 0.6 mg/kg dosed according to ideal body weight produced a significantly shorter duration of action than dosing based on corrected body weight incorporating 40% of excess weight (median 32 versus 42 minutes), without prolonging onset time or compromising intubating conditions, supporting ideal body weight as the preferred basis for dosing in this population (Meyhoff et al., 2009).
Sugammadex reverses rocuronium-induced block in a dose-dependent fashion as well: median time to recovery of the train-of-four ratio to 0.9 fell from 21.0 minutes with spontaneous recovery to 1.1 minutes after sugammadex 4.0 mg/kg, with reversal achieved within three minutes at doses of 2.0 mg/kg or greater (Sorgenfrei et al., 2006).
Although a single weight-based dose of rocuronium is conventionally used to facilitate intubation, the resulting depth and duration of block can differ substantially according to sex, renal function, and body composition. Objective neuromuscular monitoring remains a valuable tool to guide both initial dosing and the timing of and dose for reversal.
References
- Adamus M, Gabrhelik T, Marek O. Influence of gender on the course of neuromuscular block following a single bolus dose of cisatracurium or rocuronium. European Journal of Anaesthesiology. 2008;25(7):589-595. https://doi.org/10.1017/S026502150800402X
- Khuenl-Brady KS, Sparr H. Clinical pharmacokinetics of rocuronium bromide. Clinical Pharmacokinetics. 1996;31(3):174-183. https://doi.org/10.2165/00003088-199631030-00002
- Meyhoff CS, Lund J, Jenstrup MT, et al. Should dosing of rocuronium in obese patients be based on ideal or corrected body weight? Anesthesia & Analgesia. 2009;109(3):787-792. https://doi.org/10.1213/ane.0b013e3181b0826a
- Robertson EN, Driessen JJ, Booij LHDJ. Pharmacokinetics and pharmacodynamics of rocuronium in patients with and without renal failure. European Journal of Anaesthesiology. 2005;22(1):4-10. https://doi.org/10.1017/S0265021505000025
- Sorgenfrei IF, Norrild K, Larsen PB, Stensballe J, Østergaard D, Prins ME, Viby-Mogensen J. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology. 2006;104(4):667-674. https://doi.org/10.1097/00000542-200604000-00009