title: Prophylactic nimodipine treatment and improvement in hearing outcome after vestibular schwannoma surgery: a combined analysis of a randomized, multicenter, Phase III trial and its pilot study.
abstract: OBJECTIVE In clinical routines, neuroprotective strategies in neurosurgical interventions are still missing. A pilot study (n = 30) and an analogously performed Phase III trial (n = 112) pointed to a beneficial effect of prophylactic nimodipine and hydroxyethyl starch (HES) in vestibular schwannoma (VS) surgery. Considering the small sample size, the data from both studies were pooled. METHODS The patients in both investigator-initiated studies were assigned to 2 groups. The treatment group (n = 70) received parenteral nimodipine (1-2 mg/hour) and HES (hematocrit 30%-35%) from the day before surgery until the 7th postoperative day. The control group (n = 72) was not treated prophylactically. Facial and cochlear nerve functions were documented preoperatively, during the inpatient care, and 1 year after surgery. RESULTS Pooled raw data were analyzed retrospectively. Intent-to-treat analysis revealed a significantly lower risk for hearing loss (Class D) 12 months after surgery in the treatment group compared with the control group (OR 0.46, 95% CI 0.22-0.97; p = 0.04). After exclusion of patients with preoperative Class D hearing, this effect was more pronounced (OR 0.38, 95% CI 0.17-0.83; p = 0.016). Logistic regression analysis adjusted for tumor size showed a 4 times lower risk for hearing loss in the treatment group compared with the control group (OR 0.25, 95% CI 0.09-0.63; p = 0.003). Facial nerve function was not significantly improved with treatment. Apart from dose-dependent hypotension (p < 0.001), the study medication was well tolerated. CONCLUSIONS Prophylactic nimodipine is safe and may be recommended in VS surgery to preserve hearing. Prophylactic neuroprotective treatment in surgeries in which nerves are at risk seems to be a novel and promising concept. Clinical trial registration no.: DRKS 00000328 ( https://drks-neu.uniklinik-freiburg.de/drks_web/ ).
authors.affiliation: Departments of 1 Neurosurgery and.|Translational Centre for Regenerative Medicine, University of Leipzig.
authors.forename: Christian
authors.initials: C
authors.lastname: Scheller
authors.affiliation: Institute of Medical Epidemiology, Biostatistics, and Informatics, and.
authors.forename: Andreas
authors.initials: A
authors.lastname: Wienke
authors.affiliation: Department of Neurosurgery, University of Tübingen.
authors.forename: Marcos
authors.initials: M
authors.lastname: Tatagiba
authors.affiliation: Department of Neurosurgery, University of Tübingen.
authors.forename: Alireza
authors.initials: A
authors.lastname: Gharabaghi
authors.affiliation: Department of Neurosurgery, University of Tübingen.
authors.forename: Kristofer F
authors.initials: KF
authors.lastname: Ramina
authors.affiliation: Departments of 5 Neurosurgery.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ganslandt
authors.affiliation: Departments of 5 Neurosurgery.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bischoff
authors.affiliation: Otorhinolaryngology, Head and Neck Surgery, and.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zenk
authors.affiliation: Neuroradiology, University of Erlangen-Nuremberg, Erlangen.
authors.forename: Tobias
authors.initials: T
authors.lastname: Engelhorn
authors.affiliation: Department of Neurosurgery, Würzburg University Hospital, Würzburg.
authors.forename: Cordula
authors.initials: C
authors.lastname: Matthies
authors.affiliation: Department of Neurosurgery, Würzburg University Hospital, Würzburg.
authors.forename: Thomas
authors.initials: T
authors.lastname: Westermaier
authors.affiliation: Department of Neurosurgery, Bezirkskrankenhaus Günzburg, University of Ulm, Günzburg.
authors.forename: Gregor
authors.initials: G
authors.lastname: Antoniadis
authors.affiliation: Department of Neurosurgery, Bezirkskrankenhaus Günzburg, University of Ulm, Günzburg.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Pedro
authors.affiliation: Department of Neurosurgery, University of Göttingen; and.
authors.forename: Veit
authors.initials: V
authors.lastname: Rohde
authors.affiliation: Department of Neurosurgery, University of Göttingen; and.
authors.forename: Kajetan
authors.initials: K
authors.lastname: von Eckardstein
authors.affiliation: Department of Neurosurgery, Evangelisches Krankenhaus, University of Oldenburg, Germany ; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kretschmer
authors.affiliation: Neurology.
authors.forename: Malte
authors.initials: M
authors.lastname: Kornhuber
authors.affiliation: Coordination Centre for Clinical Trials, University of Halle-Wittenberg, Halle (Saale).
authors.forename: Jörg
authors.initials: J
authors.lastname: Steighardt
authors.affiliation: Coordination Centre for Clinical Trials, University of Halle-Wittenberg, Halle (Saale).
authors.forename: Michael
authors.initials: M
authors.lastname: Richter
authors.affiliation: Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Fred G
authors.initials: FG
authors.lastname: Barker
authors.affiliation: Departments of 1 Neurosurgery and.
authors.forename: Christian
authors.initials: C
authors.lastname: Strauss
mesh_terms: D000328:Adult; D005260:Female; D006309:Hearing; D034381:Hearing Loss / Q000188:drug therapy / Q000209:etiology / Q000601:surgery*; D006320:Hearing Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D009464:Neuroma, Acoustic / Q000150:complications / Q000188:drug therapy / Q000601:surgery*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019635:Neurosurgical Procedures / Q000379:methods*; D009553:Nimodipine / Q000627:therapeutic use*; D010865:Pilot Projects; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D009553:Nimodipine
keywords: AAO-HNS = American Academy of Otolaryngology–Head and Neck Surgery; HB = House-Brackmann; HES = hydroxyethyl starch; ITT = intent to treat; RCT = randomized controlled trial; VS = vestibular schwannoma; cochlear nerve; facial nerve; hydroxyethyl starch; neuroprotection; nimodipine; vestibular schwannoma