Phantom limb pain (PLP) associated neuroplastic changes are partly mediated by excitatory amino acids at NMDA receptor sites. This study was undertaken to deduce if NMDA-receptor antagonists may be effective in patients with chronic PLP. Therefore a four week double-blinded, randomized placebo-controlled trial was performed to evaluate the efficacy of 30 mg memantine/day, an orally administrable NMDA receptor antagonist.Thirty-six patients, 18 per group, with a history of at least 12 months PLP and an average pain of at least 4 on the 11-point numeric rating scale (NRS) were enrolled. The patients completed a standardized questionnaire before the trial. PLP intensity and the level of eight complaints were assessed during the trial. Number needed to treat (NNT) was calculated based on the average PLP during the 3rd week (steady state). In both groups, PLP declined significantly in comparison with the baseline (verum: 5.1 (+/-2.1) to 3,8 (+/-2,3), placebo from 5.1 (+/-2.0) to 3.2 (+/-1,46) NRS) without a re-rising of the PLP during the washout period. Mean pain relief was 47% in the memantine group (10 patients reported more than 50% relief), 40% in the placebo group (6>50%): NNT were 4.5 (KI: 2.1-10.6). Analysis of covariance demonstrated a significant impact only on the prior PLP intensity, but no treatment effect. Two patients have demonstrated long-term pain relief under memantine until now (16 months). The total number of slight adverse events were comparable in both groups, but the overall number of severe events was higher in the memantine group (P<0.05). This trial failed to demonstrate a significant clinical benefit of the NMDA-receptor antagonist memantine in chronic PLP. The administration of a higher dosage is probably not tolerable.

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The central anticholinergic syndrome (CAS) is a rarely observed condition after general anaesthesia. There are no definitive criteria to set the diagnosis of CAS. The syndrome may manifest in clinical neurological signs, such as hyperactive states or a depressed CNS state. The diagnosis usually depends on a process of exclusion of other conditions and is confirmed after rapid recovery following administration of physostigmine. We report on a 34-year-old patient who suddenly lost consciousness and developed respiratory arrest 1 h after general anesthesia and normal postoperative recovery. CAS was considered, although apnea has not been reported as a clinical symptom of this disease up to now and no peripheral signs of CAS were observed. After the administration of 1 mg physostigmine the symptoms resolved immediately and the patient started sufficient spontaneous breathing. However, corresponding to the plasma elimination half-life of the drug, further comatose episodes with apnea occurred. Therefore, the patient was admitted to the ICU and an infusion of physostigmin at a rate of up to 5 mg/h was started. Due to this therapy the patient's state became stable and 15 h after the first manifestation of CAS the infusion of physostigmin was discontinued. The following postoperative course was uneventful. In case of reduced vigilance with apnea after general anaesthesia, central anticholinergic syndrome should be considered. For diagnostic and therapeutic purposes the administration of physostigmine should be attempted.