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A Comparison Between Enteral and Intravenous Nimodipine in Subarachnoid Hemorrhage: A Systematic Review and Network Meta-Analysis

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Abstract

Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with subarachnoid hemorrhage. We performed a systematic search and a network meta-analysis using the following databases: PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Google Scholar. Risk of Bias 2 tool was used to assess risk of bias of included studies. A ranking among methods was performed on the basis of the frequentist analog of the surface under the cumulative ranking curve. Published studies that met the following population, intervention, comparison, outcomes and study (PICOS) criteria were included: patients with subarachnoid hemorrhage aged 15 years or older (P); nimodipine, intravenous and oral formulation (I); placebo or no intervention (C); poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), case fatality at 3 months, delayed cerebral ischemia, delayed ischaemic neurologic deficit, and vasospasm measured with transcranial Doppler or digital subtraction angiography (O); and randomized controlled trials (S). No language or publication date restrictions were applied. Ten studies were finally included, with a total of 1527 randomly assigned patients. Oral and intravenous nimodipine were both effective in preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. Neither treatment was effective in improving case fatality. Evolving clinical protocols over a 30-year period and the risk of bias of the included studies may limit the strength of our results. Enteral and intravenous nimodipine may have a similar effectiveness in terms of preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. More research may be needed to fully establish the role of intravenous nimodipine in current clinical practice.

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Acknowledgements

We would like to thank Dr. Timo Koivisto and Dr. Aku Kaipainen for providing valuable additional data for our research. We would like to thank Dr. Tommaso Pettenuzzo for his precious input in perfecting our article and for reviewing the statistical analysis.

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Authors and Affiliations

  1. Institute of Anaesthesia and Intensive Care, Padua University Hospital, Via Giustiniani 1, Padua, 35127, Italy

    Federico Geraldini, Alessandro De Cassai, Paolo Diana, Christelle Correale, Annalisa Boscolo, Paolo Navalesi & Marina Munari

  2. Department of Medicine (DIMED), University of Padua, Via Vincenzo Gallucci 13, Padua, 35121, Italy

    Stefano Zampirollo, Laura Disarò, Anna Carere, Nicola Cacco & Paolo Navalesi

Authors
  1. Federico Geraldini
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  2. Alessandro De Cassai
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  5. Annalisa Boscolo
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Contributions

F.G.: conceived the idea with A.D.C., registered the trial on PROSPERO, contacted corresponding authors for missing data, helped with the statistical analysis, and wrote and edited the article. A.D.C.: conceived the idea with F.G., performed the statistical analysis, performed Risk of Bias 2 (ROB2) evaluation, and revised and edited the article. P.D.: supervised the screening phase and resolved disputes involving included studies, screened for duplicates, and helped with the writing of the article. C.C.: Performed the initial search, reviewed full-text articles for potential inclusion, helped with data extraction, and revised and edited the article. A.B.: resolved disputes with ROB2 assessment, performed Grades of Recommendation, Assessment, Development and Evaluation assessment, supervised data extraction, and revised and edited the article. S.Z.: reviewed full-text articles for potential inclusion, helped with data extraction, and revised and edited the article. L.D.: performed the initial screening of abstracts, retrieved the full-text articles of included articles, and revised and edited the article. A.C.: performed the initial screening of abstracts, retrieved full-text articles of included articles, and revised and edited the article. N.C.: performed an additional check on the initial screening phase to evaluate articles, retrieved and analyzed previous systematic reviews potentially of interest, helped with ROB2 evaluation, and helped edit the article. P.N.: supervised the project, helped with the interpretation and contextualization in current literature of the results, and assessed and edited the finalized article. M.M.: helped conceive and plan the idea, assessed it for overall merit, supervised the project, helped with the interpretation and contextualization in current literature of the results, and assessed and edited the finalized article. All authors discussed the results and approved the final manuscript.

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Correspondence to Federico Geraldini.

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Geraldini, F., De Cassai, A., Diana, P. et al. A Comparison Between Enteral and Intravenous Nimodipine in Subarachnoid Hemorrhage: A Systematic Review and Network Meta-Analysis. Neurocrit Care 36, 1071–1079 (2022). https://doi.org/10.1007/s12028-022-01493-4

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