Beeinflussung der Mivacurium-induzierten Muskelrelaxation durch S(+)-Ketamin

General anaesthesia is composed of a cocktail of drugs, including a hypnotic agent, a muscle relaxant and an analgesic. The analgesics belong to the opioid class of drugs (e.g. fentanyl or sufentanil). Alternatively, the opioid may also be replaced by the non-opioid drug, S(+)-ketamine. Studies over the past few years have demonstrated, however, that there may be undesirable interactions between ketamine and a muscle relaxant, leading to excessively prolonged neuromuscular blockage. The aim of this study, therefore, was to evaluate the effects of the muscle relaxant mivacurium in combination with S(+)-ketamine versus sufentanil with respect to muscular relaxation. 120 patients were included in the study who underwent surgery in either trauma or orthopaedic medicine. During the surgical procedures, an intravenous general anaesthesia was administered, with both groups receiving propofol as the hypnotic agent, and mivacurium as the muscle relaxant. As the analgesic, S(+)-ketamine was used in group A (60 patients) and sufentanil was used in group B (60 patients). The patients were randomly allocated to one of group A or group B. Patient exclusion criteria did not apply for this study. The two patient groups do not show differences with regards to biometric data or their distribution into categories according to the ASA. The average time period from the end of muscle relaxant injection to a 25% recovery from the neuromuscular blockage (DUR25) was 22.1 minutes in the ketamine group; this showed significantly increased time when compared with the average time for the sufentanil group, at 19.8 minutes. The relaxation measurement taken as a control of neuromuscular transfer of stimuli to the motor end plate (train-of-four; TOF stimulation) similarly produced a statistically significant increase in the recovery times, on average by 11%. The average TOF-50% value (50% recovery in neuromuscular relaxation) was calculated at 13.4 (for the ketamine group) vs. 11.9 minutes (for the sufentanil group); the average TOF-70% value (70% recovery in neuromuscular relaxation) was 18.8 (for the ketamine group) vs. 16.7 minutes (for the sufentanil group). Finally, the average values for TOF-80% (80% recovery) also showed a significant difference, at 20.2 minutes in the ketamine group, compared with 18.2 minutes in the sufentanil group. It could be proven in this study that there were statistical differences in four of the nine relaxation grades investigated (DUR-25%; TOF-50%; TOF-70%; TOF-80%) between the ketamine-mivacurium group and the sufentanil-mivacurium group. Similarly, there was a statistical trend (p  0.10) with relation to the grade of relaxation T1_5%-25%, T1_25%-75% (recovery index), TOF-90% and TOF-100%. As such, the results provide evidence to support the hypothesis of prolonged neuromuscular block by mivacurium when used in combination with S(+)-ketamine. A positive, additional finding was that of a stable circulatory situation when S(+)-ketamine was used, such that this might represent an advantage over other treatment regimes. Although the findings presented in this paper may not be classified as clinically significant, the possible risk of undesired prolonged neuromuscular blockade or the associated postoperative complications should be pointed out. For this reason, a routine objective measurement of the relaxation in routine clinical practice would be beneficial. Further investigations on the comparability of muscle relaxant effects of the ketamine racemate and its enantiomer S(+)-ketamine represent important future projects. Molecular biological analyses should also to encouraged in order to determine the mechanisms of action of the mivacurium-ketamine interaction in detail.