gms | German Medical Science

Objective: Except of dexamethasone there is a lack of neuroprotective medication in neurosurgical procedures. Several retro- and prospective clinical trials point to a beneficial effect of nimodipine – a well-tolerated calcium antagonist indicated in patients with aneurysmal subarachnoid hemorrhage – on outcome of cranial nerve functions following surgery. In Germany, nimodipine is widely used in VS surgery (off-label use), however, sufficient significant evidence by randomized controlled trials of a clear neuroprotective efficacy is still missing.

Methods: A planned, randomized, two-armed, multicentric phase III trial will investigate the efficacy and safety of prophylactic nimodipine for hearing preservation in VS surgery. Adults with the indication for microsurgical removal of VS will be assigned to either therapy or control group. Patients of the interventional group will be treated with intravenous nimodipine (1–2 mg/h) from the day before surgery until the fifth postoperative day additionally to standard care, the control group will get standard care alone. Hearing function will be determined by pre- and postoperative audiometry with speech discrimination and brainstem auditory evoked potentials, which will be evaluated by a blinded expert reviewer. Furthermore patient-reported outcomes using standardized questionnaires will be analysed.

Results: A previously performed phase III trial on 112 subjects with facial nerve function twelve months after surgery as primary outcome showed no significant effects. However, the risk for postoperative hearing loss was halved in the treatment group compared to the control group (OR: 0.49; 95%-CI: 0.18–1.30; p=0.15), particularly in medium to large sized tumors (Koos III/IV). However, a subsequently performed combined analysis of the phase III trial and its pilot study showed significantly lower risks for hearing loss in the treatment group, for all tumor sizes.

Conclusion: In the future, prophylactic nimodipine treatment may be recommended as a routine medication in VS surgery and possibly in other surgical procedures with nerves at risk. In principle, prophylactic treatment with neuroprotective drugs prior to interventions with nerve tissue at risk seems to be a novel and promising concept. These clinical findings may have a high relevance for fundamental research of the underlying neuroprotective mechanisms.