Discussion

In this case report, we describe a case of rapid arousal form anaesthesia after the reversal of deep rocuronium-induced neuromuscular block with sugammadex despite still significant calculated doses of propofol at the effect site. Signs of light anaesthesia have been reported after sugammadex administration in several dose-finding studies.6 7 Chazot et al reported a case who immediately awoke after sugammadex administration in absence of any stimulation with still adequate anaesthesia under propofol and remifentanil.8 In this patient brain function monitoring was done with Bispectral Index (BIS) (BIS; Aspect Medical System, Norwood, Massachusetts, USA) and Neurosense (Neurowave System, Cleveland, Ohio, USA). In 2020, a randomised clinical trial by Le Guen et al in 51 patients showed that despite constant perfusion with propofol and remifentanil, sugammadex causes signs of awakening in the absence of documented post-operative awareness.9 The BIS monitor was used to monitor anaesthetic depth. Sugammadex is reported in the literature to have a very low affinity for other molecules such as propofol.7 8 Consequently its direct interference with the depth of anaesthesia (in terms of displacement of the hypnotic agent) is considered to be clinically irrelevant. The case presented here differs from the previous ones in that the Sedline Brain function Monitor Masimo was used. This monitor produces a parameter called PSI derived from a proprietary algorithm by processing a high-resolution four-channel EEG with advanced artefact filters.10 The PSI has been clinically validated to measure the depth of anaesthesia and sedation.11 12 The calculation of the PSI takes about 2 min. It uses parallel signal processing engines to extract a clearer EEG signal for computing PSI. It is thus less influenced by artefacts arising from neuromuscular blockade which limit other monitoring techniques as previously demonstrated by Schuller et al.13 In particular, the BIS has been shown to be highly influenced by peripheral electromyography which contributes considerably to the diagnosis of high BIS, and is particularly essential for determining BIS >80.14 The bilateral Masimo Sedline electrodes are radiolucent and were not disturbing during the neuroradiological procedure. The patient underwent 2 hours of general anaesthesia using a Propofol TCI according to the pharmacokinetic model of Schnider et al,4 with a calculated effect site concentration of about 2.6 µg/mL. The patient was kept under deep neuromuscular block (post-tetanic count 2) due to the inherent safety requirements of the neuroradiological intervention. The lecture of the PSI, the interpretation of the bilateral raw EEG and the density spectral array (DSA), allowed us to titrate the anaesthetic drugs to the minimum dosages for effective and safe hypnosis. Intracerebral pathologies might give asymmetric BIS values, but the thresholds at which the extent and type of intracranial pathologies affect BIS are largely unknown.15 16 This should be kept in mind using brain function monitoring in neuroradiological interventions. Our patient had a normal neurological examination before the procedure and the intracerebral bleeding had happened 1 week before the intervention. There was no asymmetry in the DSA. We might, therefore, believe that the calculated PSI correctly reflected anaesthetic depth in this patient. At the end of the procedure, only 2 min after having stopped the propofol perfusion the patient emerged very rapidly and unexpectedly after the administration of sugammadex at a dose of 4 mg/kg. This immediate awakening was documented by Masimo Sedline monitoring. Postmedication excluded signs and symptoms suggestive of awareness. TCI are used routinely to simplify the administration of intravenous drugs during general anaesthesia and to increase its precision but there are large variations in measured serum concentrations.17 One might argue that anaesthetic depth of the patient was already very superficial at the moment we stopped the propofol perfusion, and that the indicated effect site concentrations are calculated and not measured values, but this would have been reflected in a higher PSI value which was about 27 at this moment and which indicated adequate anaesthesia. It is very improbably that the 2 min interruption of the propofol perfusion induced this very rapid arousal (about 2% of total propofol perfusion time). We believe that the observed effect of sugammadex is indirect and might be mainly explained by the afferentation theory. The latter was first described by Lanier et al on a sample of dogs18 and later taken up by Vasella et al.19 The afferentation theory predicts that stimulation of the neuromuscular spindles will produce cerebral stimulation. Cortical activity has therefore a peripheral component deriving from muscular proprioceptive afferences. Neuromuscular block would lead to a ‘peripheral silence’ which sugammadex could interrupt. Compared with previous reports, we used a neuromonitoring method that does not depend on peripheral electromyography, which, therefore, allows us to study more precisely the changes in cortical activity which were observed after the administration of Sugammadex.

In conclusion, this case illustrates the possibility of unexpectedly rapid emergence from effect site-targeted propofol anaesthesia on reversal of neuromuscular blockade with sugammadex. A potential explanation behind this phenomenon could be the sugammadex-induced indirect increase of central stimulation via the reactivation of ascending central pathways originating from neuromuscular spindles. These observations argue for the need of further research between the interaction of neuromuscular blockade and depth of anaesthesia.