The onset of action of intravenous rocuronium 1 mg/kg, i.e., the time required to reach the maximal depression of T1 at the adductor pollicis muscle, is 77 s [4]. Rapid onset is a specific characteristic of rocuronium compared to other non-depolarizing neuromuscular blocking agents. However, in our patient, the neuromuscular block developed slowly over 100 min after accidental subcutaneous injection of 1.04 mg/kg rocuronium. The pharmacokinetics of intravenously administered rocuronium can be explained by the three-compartment model [5]. However, because the clearance of subcutaneously administered rocuronium is unknown, it is difficult to predict the real onset and duration of action of rocuronium administered subcutaneously. Molecules of subcutaneously administered drugs might be slowly absorbed into the systemic circulation, taking a longer time to reach the effect sites, resulting in delayed onset and prolonged duration of action as compared to intravenous administration. Since the onset of action depends on the diffusion speed of the drug from extravascular sites, the patient’s health comorbidities might considerably influence the absorption. Patients with peripheral circulatory disturbances and arteriosclerosis might have slow absorption of rocuronium from subcutaneous regions into the blood, and hence, might unexpectedly exhibit slower onset and longer progression of the action of neuromuscular block. Navare and colleagues reported a similar case that had end-stage renal disease and was given an incidental subcutaneous injection of 1.16 mg/kg rocuronium [2]. Unfortunately, although they only observed neuromuscular block qualitatively and assessed TOF counts of the thumb to ulnar nerve TOF stimulation using a peripheral nerve stimulator, it took 39 min for the initial decline in TOF count from 4 to 3 in their patient. As can be expected, peripheral circulatory failure due to diabetes mellitus and arteriosclerosis might significantly slow the absorption of rocuronium from the subcutaneous space. Rocuronium is mainly excreted in bile via the liver [6] and is partially eliminated in urine via the kidneys [3]. Therefore, the clearance of rocuronium decreases by about 20% in patients with chronic renal failure. The slowed elimination of rocuronium from the body might have also been involved in delayed recovery from the rocuronium-induced block in this patient.
Since we quantitatively monitored rocuronium-induced neuromuscular block using acceleromyography, we were able to recognize depressed neuromuscular function, as seen by the TOF count of 2 at the completion of surgery, and could adequately reverse the moderate depth of neuromuscular block with 2 mg/kg of sugammadex. Reportedly, sugammadex 2 mg/kg is sufficient to antagonize rocuronium-induced moderate neuromuscular block in hemodialysis patients [7]. However, it should be remembered that neuromuscular monitoring only indicates the action of rocuronium molecules that have diffused into the neuromuscular junction, and does not demonstrate the amount of rocuronium remaining in a subcutaneous depot. In our case, we administered 4.5 mg/kg of sugammadex, nearly equal to the recommended dose for recovery of a deep neuromuscular blockade, although the TOF count was 2 at the end of surgery. TOF ratio and TOF count continued to decline at that time, so we could not rule out the possibility to change TOF count from 2 to 1 or more deeper level. It would, therefore, be better to administer a larger than usual dose of sugammadex to patients with inadvertent subcutaneous rocuronium injection in order to prevent residual neuromuscular block and recurarization.
In conclusion, because the action of rocuronium injected subcutaneously might vary between patients, making it extremely difficult to predict its onset and duration of action, rigorous quantitative neuromuscular monitoring, adequate dosing with sugammadex, and strict monitoring of respiratory function in the postoperative period can contribute to safe management of patients with inadvertent subcutaneous injection of rocuronium.